1naresh2naresh<pre>Array
(
    [urn:ac.highwire.org:guest:identity] => Array
        (
            [runtime-id] => urn:ac.highwire.org:guest:identity
            [type] => guest
            [service-id] => ajnr-ac.highwire.org
            [access-type] => Controlled
            [privilege] => Array
                (
                    [urn:ac.highwire.org:guest:privilege] => Array
                        (
                            [runtime-id] => urn:ac.highwire.org:guest:privilege
                            [type] => privilege-set
                            [privilege-set] => GUEST
                        )

                )

            [credentials] => Array
                (
                    [method] => guest
                )

        )

    [aa56b651-27a9-40e6-bd82-9673dfe5add2] => Array
        (
            [runtime-id] => aa56b651-27a9-40e6-bd82-9673dfe5add2
            [type] => toll-free-key
            [service-id] => ajnr-ac.highwire.org
            [access-type] => Controlled
            [privilege] => Array
                (
                    [de52ec1f-fbb3-4423-ac0b-df80744b73b9] => Array
                        (
                            [runtime-id] => de52ec1f-fbb3-4423-ac0b-df80744b73b9
                            [type] => toll-free-key
                        )

                )

            [credentials] => Array
                (
                    [method] => toll-free-key
                    [value] => tf_ipsecsha;ce5e04dada54959d69614cb3dd5eaaaad3a94ef9
                )

        )

)
1naresh2naresh<pre>Array
(
    [urn:ac.highwire.org:guest:identity] => Array
        (
            [runtime-id] => urn:ac.highwire.org:guest:identity
            [type] => guest
            [service-id] => ajnr-ac.highwire.org
            [access-type] => Controlled
            [privilege] => Array
                (
                    [urn:ac.highwire.org:guest:privilege] => Array
                        (
                            [runtime-id] => urn:ac.highwire.org:guest:privilege
                            [type] => privilege-set
                            [privilege-set] => GUEST
                        )

                )

            [credentials] => Array
                (
                    [method] => guest
                )

        )

    [aa56b651-27a9-40e6-bd82-9673dfe5add2] => Array
        (
            [runtime-id] => aa56b651-27a9-40e6-bd82-9673dfe5add2
            [type] => toll-free-key
            [service-id] => ajnr-ac.highwire.org
            [access-type] => Controlled
            [privilege] => Array
                (
                    [de52ec1f-fbb3-4423-ac0b-df80744b73b9] => Array
                        (
                            [runtime-id] => de52ec1f-fbb3-4423-ac0b-df80744b73b9
                            [type] => toll-free-key
                        )

                )

            [credentials] => Array
                (
                    [method] => toll-free-key
                    [value] => tf_ipsecsha;ce5e04dada54959d69614cb3dd5eaaaad3a94ef9
                )

        )

)
1naresh2naresh<pre>Array
(
    [urn:ac.highwire.org:guest:identity] => Array
        (
            [runtime-id] => urn:ac.highwire.org:guest:identity
            [type] => guest
            [service-id] => ajnr-ac.highwire.org
            [access-type] => Controlled
            [privilege] => Array
                (
                    [urn:ac.highwire.org:guest:privilege] => Array
                        (
                            [runtime-id] => urn:ac.highwire.org:guest:privilege
                            [type] => privilege-set
                            [privilege-set] => GUEST
                        )

                )

            [credentials] => Array
                (
                    [method] => guest
                )

        )

    [aed575e6-c40c-4231-aa8a-2d925f21fe55] => Array
        (
            [runtime-id] => aed575e6-c40c-4231-aa8a-2d925f21fe55
            [type] => toll-free-key
            [service-id] => ajnr-ac.highwire.org
            [access-type] => Controlled
            [privilege] => Array
                (
                    [938414e2-9685-44fa-9d29-ebd08c90445a] => Array
                        (
                            [runtime-id] => 938414e2-9685-44fa-9d29-ebd08c90445a
                            [type] => toll-free-key
                        )

                )

            [credentials] => Array
                (
                    [method] => toll-free-key
                    [value] => tf_ipsecsha;ce5e04dada54959d69614cb3dd5eaaaad3a94ef9
                )

        )

)
1naresh2naresh<pre>Array
(
    [urn:ac.highwire.org:guest:identity] => Array
        (
            [runtime-id] => urn:ac.highwire.org:guest:identity
            [type] => guest
            [service-id] => ajnr-ac.highwire.org
            [access-type] => Controlled
            [privilege] => Array
                (
                    [urn:ac.highwire.org:guest:privilege] => Array
                        (
                            [runtime-id] => urn:ac.highwire.org:guest:privilege
                            [type] => privilege-set
                            [privilege-set] => GUEST
                        )

                )

            [credentials] => Array
                (
                    [method] => guest
                )

        )

    [050b9729-90f1-4d0f-b8c7-2d7b333462dc] => Array
        (
            [runtime-id] => 050b9729-90f1-4d0f-b8c7-2d7b333462dc
            [type] => toll-free-key
            [service-id] => ajnr-ac.highwire.org
            [access-type] => Controlled
            [privilege] => Array
                (
                    [dea708c0-14c4-4ae9-a4cb-ddbb217b64cd] => Array
                        (
                            [runtime-id] => dea708c0-14c4-4ae9-a4cb-ddbb217b64cd
                            [type] => toll-free-key
                        )

                )

            [credentials] => Array
                (
                    [method] => toll-free-key
                    [value] => tf_ipsecsha;ce5e04dada54959d69614cb3dd5eaaaad3a94ef9
                )

        )

)
1naresh2naresh<pre>Array
(
    [urn:ac.highwire.org:guest:identity] => Array
        (
            [runtime-id] => urn:ac.highwire.org:guest:identity
            [type] => guest
            [service-id] => ajnr-ac.highwire.org
            [access-type] => FreeToRead
            [privilege] => Array
                (
                    [urn:ac.highwire.org:guest:privilege] => Array
                        (
                            [runtime-id] => urn:ac.highwire.org:guest:privilege
                            [type] => privilege-set
                            [privilege-set] => GUEST
                        )

                )

            [credentials] => Array
                (
                    [method] => guest
                )

        )

    [e819bf74-424f-4c8e-8402-8f86803a9c5b] => Array
        (
            [runtime-id] => e819bf74-424f-4c8e-8402-8f86803a9c5b
            [type] => toll-free-key
            [service-id] => ajnr-ac.highwire.org
            [access-type] => FreeToRead
            [privilege] => Array
                (
                    [c42c2f10-c3dc-4b2f-a49d-75a5ba5b4816] => Array
                        (
                            [runtime-id] => c42c2f10-c3dc-4b2f-a49d-75a5ba5b4816
                            [type] => toll-free-key
                        )

                )

            [credentials] => Array
                (
                    [method] => toll-free-key
                    [value] => tf_ipsecsha;ce5e04dada54959d69614cb3dd5eaaaad3a94ef9
                )

        )

)
1naresh2naresh<pre>Array
(
    [urn:ac.highwire.org:guest:identity] => Array
        (
            [runtime-id] => urn:ac.highwire.org:guest:identity
            [type] => guest
            [service-id] => ajnr-ac.highwire.org
            [access-type] => FreeToRead
            [privilege] => Array
                (
                    [urn:ac.highwire.org:guest:privilege] => Array
                        (
                            [runtime-id] => urn:ac.highwire.org:guest:privilege
                            [type] => privilege-set
                            [privilege-set] => GUEST
                        )

                )

            [credentials] => Array
                (
                    [method] => guest
                )

        )

    [e819bf74-424f-4c8e-8402-8f86803a9c5b] => Array
        (
            [runtime-id] => e819bf74-424f-4c8e-8402-8f86803a9c5b
            [type] => toll-free-key
            [service-id] => ajnr-ac.highwire.org
            [access-type] => FreeToRead
            [privilege] => Array
                (
                    [c42c2f10-c3dc-4b2f-a49d-75a5ba5b4816] => Array
                        (
                            [runtime-id] => c42c2f10-c3dc-4b2f-a49d-75a5ba5b4816
                            [type] => toll-free-key
                        )

                )

            [credentials] => Array
                (
                    [method] => toll-free-key
                    [value] => tf_ipsecsha;ce5e04dada54959d69614cb3dd5eaaaad3a94ef9
                )

        )

)
1naresh2naresh<pre>Array
(
    [urn:ac.highwire.org:guest:identity] => Array
        (
            [runtime-id] => urn:ac.highwire.org:guest:identity
            [type] => guest
            [service-id] => ajnr-ac.highwire.org
            [access-type] => Controlled
            [privilege] => Array
                (
                    [urn:ac.highwire.org:guest:privilege] => Array
                        (
                            [runtime-id] => urn:ac.highwire.org:guest:privilege
                            [type] => privilege-set
                            [privilege-set] => GUEST
                        )

                )

            [credentials] => Array
                (
                    [method] => guest
                )

        )

    [aa56b651-27a9-40e6-bd82-9673dfe5add2] => Array
        (
            [runtime-id] => aa56b651-27a9-40e6-bd82-9673dfe5add2
            [type] => toll-free-key
            [service-id] => ajnr-ac.highwire.org
            [access-type] => Controlled
            [privilege] => Array
                (
                    [de52ec1f-fbb3-4423-ac0b-df80744b73b9] => Array
                        (
                            [runtime-id] => de52ec1f-fbb3-4423-ac0b-df80744b73b9
                            [type] => toll-free-key
                        )

                )

            [credentials] => Array
                (
                    [method] => toll-free-key
                    [value] => tf_ipsecsha;ce5e04dada54959d69614cb3dd5eaaaad3a94ef9
                )

        )

)
1naresh2naresh<pre>Array
(
    [urn:ac.highwire.org:guest:identity] => Array
        (
            [runtime-id] => urn:ac.highwire.org:guest:identity
            [type] => guest
            [service-id] => ajnr-ac.highwire.org
            [access-type] => Controlled
            [privilege] => Array
                (
                    [urn:ac.highwire.org:guest:privilege] => Array
                        (
                            [runtime-id] => urn:ac.highwire.org:guest:privilege
                            [type] => privilege-set
                            [privilege-set] => GUEST
                        )

                )

            [credentials] => Array
                (
                    [method] => guest
                )

        )

    [aa56b651-27a9-40e6-bd82-9673dfe5add2] => Array
        (
            [runtime-id] => aa56b651-27a9-40e6-bd82-9673dfe5add2
            [type] => toll-free-key
            [service-id] => ajnr-ac.highwire.org
            [access-type] => Controlled
            [privilege] => Array
                (
                    [de52ec1f-fbb3-4423-ac0b-df80744b73b9] => Array
                        (
                            [runtime-id] => de52ec1f-fbb3-4423-ac0b-df80744b73b9
                            [type] => toll-free-key
                        )

                )

            [credentials] => Array
                (
                    [method] => toll-free-key
                    [value] => tf_ipsecsha;ce5e04dada54959d69614cb3dd5eaaaad3a94ef9
                )

        )

)
1naresh2naresh<pre>Array
(
    [urn:ac.highwire.org:guest:identity] => Array
        (
            [runtime-id] => urn:ac.highwire.org:guest:identity
            [type] => guest
            [service-id] => ajnr-ac.highwire.org
            [access-type] => Controlled
            [privilege] => Array
                (
                    [urn:ac.highwire.org:guest:privilege] => Array
                        (
                            [runtime-id] => urn:ac.highwire.org:guest:privilege
                            [type] => privilege-set
                            [privilege-set] => GUEST
                        )

                )

            [credentials] => Array
                (
                    [method] => guest
                )

        )

    [aa56b651-27a9-40e6-bd82-9673dfe5add2] => Array
        (
            [runtime-id] => aa56b651-27a9-40e6-bd82-9673dfe5add2
            [type] => toll-free-key
            [service-id] => ajnr-ac.highwire.org
            [access-type] => Controlled
            [privilege] => Array
                (
                    [de52ec1f-fbb3-4423-ac0b-df80744b73b9] => Array
                        (
                            [runtime-id] => de52ec1f-fbb3-4423-ac0b-df80744b73b9
                            [type] => toll-free-key
                        )

                )

            [credentials] => Array
                (
                    [method] => toll-free-key
                    [value] => tf_ipsecsha;ce5e04dada54959d69614cb3dd5eaaaad3a94ef9
                )

        )

)
1naresh2naresh<pre>Array
(
    [urn:ac.highwire.org:guest:identity] => Array
        (
            [runtime-id] => urn:ac.highwire.org:guest:identity
            [type] => guest
            [service-id] => ajnr-ac.highwire.org
            [access-type] => Controlled
            [privilege] => Array
                (
                    [urn:ac.highwire.org:guest:privilege] => Array
                        (
                            [runtime-id] => urn:ac.highwire.org:guest:privilege
                            [type] => privilege-set
                            [privilege-set] => GUEST
                        )

                )

            [credentials] => Array
                (
                    [method] => guest
                )

        )

    [aa56b651-27a9-40e6-bd82-9673dfe5add2] => Array
        (
            [runtime-id] => aa56b651-27a9-40e6-bd82-9673dfe5add2
            [type] => toll-free-key
            [service-id] => ajnr-ac.highwire.org
            [access-type] => Controlled
            [privilege] => Array
                (
                    [de52ec1f-fbb3-4423-ac0b-df80744b73b9] => Array
                        (
                            [runtime-id] => de52ec1f-fbb3-4423-ac0b-df80744b73b9
                            [type] => toll-free-key
                        )

                )

            [credentials] => Array
                (
                    [method] => toll-free-key
                    [value] => tf_ipsecsha;ce5e04dada54959d69614cb3dd5eaaaad3a94ef9
                )

        )

)
1naresh2naresh<pre>Array
(
    [urn:ac.highwire.org:guest:identity] => Array
        (
            [runtime-id] => urn:ac.highwire.org:guest:identity
            [type] => guest
            [service-id] => ajnr-ac.highwire.org
            [access-type] => Controlled
            [privilege] => Array
                (
                    [urn:ac.highwire.org:guest:privilege] => Array
                        (
                            [runtime-id] => urn:ac.highwire.org:guest:privilege
                            [type] => privilege-set
                            [privilege-set] => GUEST
                        )

                )

            [credentials] => Array
                (
                    [method] => guest
                )

        )

    [aa56b651-27a9-40e6-bd82-9673dfe5add2] => Array
        (
            [runtime-id] => aa56b651-27a9-40e6-bd82-9673dfe5add2
            [type] => toll-free-key
            [service-id] => ajnr-ac.highwire.org
            [access-type] => Controlled
            [privilege] => Array
                (
                    [de52ec1f-fbb3-4423-ac0b-df80744b73b9] => Array
                        (
                            [runtime-id] => de52ec1f-fbb3-4423-ac0b-df80744b73b9
                            [type] => toll-free-key
                        )

                )

            [credentials] => Array
                (
                    [method] => toll-free-key
                    [value] => tf_ipsecsha;ce5e04dada54959d69614cb3dd5eaaaad3a94ef9
                )

        )

)
1naresh2naresh<pre>Array
(
    [urn:ac.highwire.org:guest:identity] => Array
        (
            [runtime-id] => urn:ac.highwire.org:guest:identity
            [type] => guest
            [service-id] => ajnr-ac.highwire.org
            [access-type] => Controlled
            [privilege] => Array
                (
                    [urn:ac.highwire.org:guest:privilege] => Array
                        (
                            [runtime-id] => urn:ac.highwire.org:guest:privilege
                            [type] => privilege-set
                            [privilege-set] => GUEST
                        )

                )

            [credentials] => Array
                (
                    [method] => guest
                )

        )

    [ab7611fe-20ad-4bb1-b228-884233831cef] => Array
        (
            [runtime-id] => ab7611fe-20ad-4bb1-b228-884233831cef
            [type] => toll-free-key
            [service-id] => ajnr-ac.highwire.org
            [access-type] => Controlled
            [privilege] => Array
                (
                    [66a64291-e572-45e0-894e-4674bba1e163] => Array
                        (
                            [runtime-id] => 66a64291-e572-45e0-894e-4674bba1e163
                            [type] => toll-free-key
                        )

                )

            [credentials] => Array
                (
                    [method] => toll-free-key
                    [value] => tf_ipsecsha;ce5e04dada54959d69614cb3dd5eaaaad3a94ef9
                )

        )

)
<!DOCTYPE html>
<html lang="en" dir="ltr" 
  xmlns="http://www.w3.org/1999/xhtml"
  xmlns:mml="http://www.w3.org/1998/Math/MathML">
  <head prefix="og: http://ogp.me/ns# article: http://ogp.me/ns/article# book: http://ogp.me/ns/book#" >
    <!--[if IE]><![endif]-->
<link rel="dns-prefetch" href="//securepubads.g.doubleclick.net" />
<link rel="dns-prefetch" href="//scholar.google.com" />
<link rel="dns-prefetch" href="//cdn.jsdelivr.net" />
<link rel="dns-prefetch" href="//www.google.com" />
<link rel="dns-prefetch" href="//www.googletagmanager.com" />
<meta http-equiv="Content-Type" content="text/html; charset=utf-8" />
<link rel="shortlink" href="/node/111459" />
<meta name="Generator" content="Drupal 7 (http://drupal.org)" />
<link rel="shortcut icon" href="http://ajnr-stage2.stage.highwire.org/sites/default/files/images/favicon.ico" type="image/vnd.microsoft.icon" />
<meta name="article_thumbnail" content="http://ajnr-stage2.stage.highwire.org/content/ajnr/45/11/1791/embed/mml-math-1.gif" />
<meta name="issue_cover_image" content="http://ajnr-stage2.stage.highwire.org/sites/default/files/highwire/ajnr/45/11.cover-source.jpg" />
<meta name="type" content="article" />
<meta name="category" content="research-article" />
<meta name="HW.identifier" content="/ajnr/45/11/1791.atom" />
<meta name="HW.pisa" content="ajnr;45/11/1791" />
<meta name="DC.Format" content="text/html" />
<meta name="DC.Language" content="en" />
<meta name="DC.Title" content="Enzyme Replacement Therapy for CLN2 Disease: MRI Volumetry Shows Significantly Slower Volume Loss Compared with a Natural History Cohort" />
<meta name="DC.Identifier" content="10.3174/ajnr.A8408" />
<meta name="DC.Date" content="2024-11-01" />
<meta name="DC.Publisher" content="American Journal of Neuroradiology" />
<meta name="DC.Rights" content="© 2024 by American Journal of Neuroradiology" />
<meta name="DC.AccessRights" content="restricted" />
<meta name="DC.Description" content="BACKGROUND AND PURPOSE: Neuronal ceroid lipofuscinoses are a group of neurodegenerative disorders. Recently, enzyme replacement therapy (ERT) was approved for neuronal ceroid lipofuscinosis type 2 (CLN2), a subtype of neuronal ceroid lipofuscinoses. The aim of this study was to quantify brain volume loss in CLN2 disease in patients on ERT in comparison with a natural history cohort using MRI.

MATERIALS AND METHODS: Nineteen (14 female, 5 male) patients with CLN2 disease at 1 UK center were studied using serial 3D T1-weighted MRI (follow-up time, 1–9 years). Brain segmentation was performed using FreeSurfer. Volume measurements for supratentorial gray and white matter, deep gray matter (basal ganglia/thalami), the lateral ventricles, and cerebellar gray and white matter were recorded. The volume change with time was analyzed using a linear mixed-effects model excluding scans before treatment onset. Comparison was made with a published natural history cohort of 12 patients (8 female, 4 male), which was re-analyzed using the same method.

RESULTS: Brain volume loss of all segmented brain regions was much slower in treated patients compared with the natural history cohort. For example, supratentorial gray matter volume in treated patients decreased by a mean of 3% (SD, 0.74%) ( P &lt; .001) annually compared with an annual volume loss of a mean of 16.8% (SD, 1.5%) ( P &lt; .001) in the natural history cohort.

CONCLUSIONS: Our treatment cohort showed a significantly slower rate of brain parenchymal volume loss compared with a natural history cohort in several anatomic regions. Our results complement prior clinical data that found a positive response to ERT. We demonstrate that automated MRI volumetry is a sensitive tool to monitor treatment response in children with CLN2 disease.

CLN2
:   neuronal ceroid lipofuscinosis type 2
ERT
:   enzyme replacement therapy
ICV
:   intracerebro-ventricular
NCL
:   neuronal ceroid lipofuscinosis
TPP1
:   tripeptidyl peptidase 1" />
<meta name="DC.Contributor" content="Pritika Gaur" />
<meta name="DC.Contributor" content="Paul Gissen" />
<meta name="DC.Contributor" content="Asthik Biswas" />
<meta name="DC.Contributor" content="Kshitij Mankad" />
<meta name="DC.Contributor" content="Sniya Sudhakar" />
<meta name="DC.Contributor" content="Felice D’Arco" />
<meta name="DC.Contributor" content="Angela Schulz" />
<meta name="DC.Contributor" content="Jens Fiehler" />
<meta name="DC.Contributor" content="Jan Sedlacik" />
<meta name="DC.Contributor" content="Ulrike Löbel" />
<meta name="article:published_time" content="2024-11-01" />
<meta name="article:section" content="Pediatric Neuroimaging" />
<meta name="citation_title" content="Enzyme Replacement Therapy for CLN2 Disease: MRI Volumetry Shows Significantly Slower Volume Loss Compared with a Natural History Cohort" />
<meta name="citation_abstract" lang="en" content="&lt;h3&gt;BACKGROUND AND PURPOSE:&lt;/h3&gt;
&lt;p&gt;Neuronal ceroid lipofuscinoses are a group of neurodegenerative disorders. Recently, enzyme replacement therapy (ERT) was approved for neuronal ceroid lipofuscinosis type 2 (CLN2), a subtype of neuronal ceroid lipofuscinoses. The aim of this study was to quantify brain volume loss in CLN2 disease in patients on ERT in comparison with a natural history cohort using MRI.&lt;/p&gt;&lt;h3&gt;MATERIALS AND METHODS:&lt;/h3&gt;
&lt;p&gt;Nineteen (14 female, 5 male) patients with CLN2 disease at 1 UK center were studied using serial 3D T1-weighted MRI (follow-up time, 1–9 years). Brain segmentation was performed using FreeSurfer. Volume measurements for supratentorial gray and white matter, deep gray matter (basal ganglia/thalami), the lateral ventricles, and cerebellar gray and white matter were recorded. The volume change with time was analyzed using a linear mixed-effects model excluding scans before treatment onset. Comparison was made with a published natural history cohort of 12 patients (8 female, 4 male), which was re-analyzed using the same method.&lt;/p&gt;&lt;h3&gt;RESULTS:&lt;/h3&gt;
&lt;p&gt;Brain volume loss of all segmented brain regions was much slower in treated patients compared with the natural history cohort. For example, supratentorial gray matter volume in treated patients decreased by a mean of 3% (SD, 0.74%) (&lt;i&gt;P&lt;/i&gt; &amp;lt; .001) annually compared with an annual volume loss of a mean of 16.8% (SD, 1.5%) (&lt;i&gt;P&lt;/i&gt; &amp;lt; .001) in the natural history cohort.&lt;/p&gt;&lt;h3&gt;CONCLUSIONS:&lt;/h3&gt;
&lt;p&gt;Our treatment cohort showed a significantly slower rate of brain parenchymal volume loss compared with a natural history cohort in several anatomic regions. Our results complement prior clinical data that found a positive response to ERT. We demonstrate that automated MRI volumetry is a sensitive tool to monitor treatment response in children with CLN2 disease.&lt;/p&gt;" />
<meta name="citation_journal_title" content="American Journal of Neuroradiology" />
<meta name="citation_publisher" content="American Journal of Neuroradiology" />
<meta name="citation_publication_date" content="2024/11/01" />
<meta name="citation_mjid" content="ajnr;45/11/1791" />
<meta name="citation_id" content="45/11/1791" />
<meta name="citation_public_url" content="http://ajnr-stage2.stage.highwire.org/content/45/11/1791" />
<meta name="citation_abstract_html_url" content="http://ajnr-stage2.stage.highwire.org/content/45/11/1791.abstract" />
<meta name="citation_full_html_url" content="http://ajnr-stage2.stage.highwire.org/content/45/11/1791.full" />
<meta name="citation_pdf_url" content="http://ajnr-stage2.stage.highwire.org/content/ajnr/45/11/1791.full.pdf" />
<meta name="citation_issn" content="0195-6108" />
<meta name="citation_issn" content="1936-959X" />
<meta name="citation_doi" content="10.3174/ajnr.A8408" />
<meta name="citation_pmid" content="38977290" />
<meta name="citation_volume" content="45" />
<meta name="citation_issue" content="11" />
<meta name="citation_article_type" content="Research Article" />
<meta name="citation_section" content="Pediatric Neuroimaging" />
<meta name="citation_firstpage" content="1791" />
<meta name="citation_lastpage" content="1797" />
<meta name="citation_author" content="Pritika Gaur" />
<meta name="citation_author_institution" content="aFrom the Department of Radiology (P. Gaur, A.B., K.M., S.S., F.D., U.L.), Great Ormond Street Hospital, London, UK" />
<meta name="citation_author_orcid" content="https://orcid.org/0000-0002-6286-9655" />
<meta name="citation_author" content="Paul Gissen" />
<meta name="citation_author_institution" content="bNational Institute for Health Research (P. Gissen), Great Ormond Street Hospital Biomedical Research Centre, University College London, London, UK" />
<meta name="citation_author" content="Asthik Biswas" />
<meta name="citation_author_institution" content="aFrom the Department of Radiology (P. Gaur, A.B., K.M., S.S., F.D., U.L.), Great Ormond Street Hospital, London, UK" />
<meta name="citation_author_orcid" content="https://orcid.org/0000-0003-2010-9524" />
<meta name="citation_author" content="Kshitij Mankad" />
<meta name="citation_author_institution" content="aFrom the Department of Radiology (P. Gaur, A.B., K.M., S.S., F.D., U.L.), Great Ormond Street Hospital, London, UK" />
<meta name="citation_author_orcid" content="https://orcid.org/0000-0001-5979-9337" />
<meta name="citation_author" content="Sniya Sudhakar" />
<meta name="citation_author_institution" content="aFrom the Department of Radiology (P. Gaur, A.B., K.M., S.S., F.D., U.L.), Great Ormond Street Hospital, London, UK" />
<meta name="citation_author_orcid" content="https://orcid.org/0000-0002-7632-9705" />
<meta name="citation_author" content="Felice D’Arco" />
<meta name="citation_author_institution" content="aFrom the Department of Radiology (P. Gaur, A.B., K.M., S.S., F.D., U.L.), Great Ormond Street Hospital, London, UK" />
<meta name="citation_author" content="Angela Schulz" />
<meta name="citation_author_institution" content="cDepartment of Paediatrics (A.S.), University Medical Center Hamburg-Eppendorf, Hamburg, Germany" />
<meta name="citation_author_institution" content="gGerman Center for Child and Adolescent Health (A.S.), Partner Site Hamburg, Hamburg, Germany" />
<meta name="citation_author" content="Jens Fiehler" />
<meta name="citation_author_institution" content="dDepartment of Diagnostic and Interventional Neuroradiology (J.F.), University Medical Center Hamburg-Eppendorf, Hamburg, Germany" />
<meta name="citation_author_orcid" content="https://orcid.org/0000-0001-8533-7478" />
<meta name="citation_author" content="Jan Sedlacik" />
<meta name="citation_author_institution" content="eRobert Steiner MR Facility (J.S.), Medical Research Council Laboratory of Medical Sciences, Hammersmith Hospital Campus, London, UK" />
<meta name="citation_author_institution" content="fMansfield Centre for Innovation (J.S.), Imaging Sciences, Institute of Clinical Sciences, Imperial College London, Hammersmith Hospital Campus, London, UK" />
<meta name="citation_author_orcid" content="https://orcid.org/0000-0003-3125-1083" />
<meta name="citation_author" content="Ulrike Löbel" />
<meta name="citation_author_institution" content="aFrom the Department of Radiology (P. Gaur, A.B., K.M., S.S., F.D., U.L.), Great Ormond Street Hospital, London, UK" />
<meta name="citation_author_orcid" content="https://orcid.org/0000-0001-9844-3464" />
<meta name="citation_reference" content="citation_journal_title=Epileptic Disord;citation_author=DA. Nita;citation_author=SE. Mole;citation_author=BA. Minassian;citation_title=Neuronal ceroid lipofuscinoses;citation_pages=73-88;citation_volume=18;citation_year=2016;citation_pmid=27629553;citation_doi=10.1684/epd.2016.0844" />
<meta name="citation_reference" content="citation_journal_title=Int J Mol Sci;citation_author=K. Kaminiów;citation_author=S. Kozak;citation_author=J. Paprocka;citation_title=Recent insight into the genetic basis, clinical features, and diagnostic methods for neuronal ceroid lipofuscinosis;citation_pages=5729;citation_volume=23;citation_year=2022;citation_pmid=35628533;citation_doi=10.3390/ijms23105729" />
<meta name="citation_reference" content="citation_journal_title=Science;citation_journal_abbrev=Science;citation_author=DE. Sleat;citation_author=RJ. Donnelly;citation_author=H. Lackland;citation_title=Association of Mutations in a Lysosomal Protein with Classical Late-Infantile Neuronal Ceroid Lipofuscinosis;citation_pages=1802-1805;citation_volume=277;citation_year=1997;citation_issue=5333;citation_pmid=9295267;citation_doi=10.1126/science.277.5333.1802" />
<meta name="citation_reference" content="citation_journal_title=Mol Neurodegener;citation_author=AB. Mukherjee;citation_author=AP. Appu;citation_author=T. Sadhukhan;citation_title=Emerging new roles of the lysosome and neuronal ceroid lipofuscinoses;citation_volume=14;citation_year=2019;citation_pmid=30651094;citation_doi=10.1186/s13024-018-0300-6" />
<meta name="citation_reference" content="citation_journal_title=N Engl J Med;citation_author=CLN2 Study Group;citation_title=Study of intraventricular cerliponase alfa for CLN2 disease;citation_pages=1898-907;citation_volume=378;citation_year=2018;citation_pmid=29688815;citation_doi=10.1056/NEJMoa1712649" />
<meta name="citation_reference" content="citation_journal_title=AJNR Am J Neuroradiol;citation_author=U. Löbel;citation_author=J. Sedlacik;citation_author=M. Nickel;citation_title=Volumetric description of brain atrophy in neuronal ceroid lipofuscinosis, 2: supratentorial gray matter shows uniform disease progression;citation_volume=37;citation_year=2016;citation_pmid=27231226;citation_doi=10.3174/ajnr.A4816" />
<meta name="citation_reference" content="citation_journal_title=Neurological sciences :  official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology;citation_journal_abbrev=Neurol Sci;citation_author=L. D'Incerti;citation_title=MRI in neuronal ceroid lipofuscinosis.;citation_pages=S71-S73;citation_volume=21;citation_year=2000;citation_issue=3 Suppl;citation_pmid=11073231;citation_doi=10.1007/s100720070043" />
<meta name="citation_reference" content="citation_journal_title=Eur J Paediatr Neurol;citation_author=K. Aydın;citation_author=C. Havali;citation_author=A. Kartal;citation_title=MRI in CLN2 disease patients: subtle features that support an early diagnosis;citation_pages=228-36;citation_volume=28;citation_year=2020;citation_pmid=32855042;citation_doi=10.1016/j.ejpn.2020.07.009" />
<meta name="citation_reference" content="citation_journal_title=Journal of Child Neurology;citation_journal_abbrev=J Child Neurol;citation_author=SL. Vanhanen;citation_author=R. Raininko;citation_author=P. Santavuori;citation_title=MRI Evaluation of the Brain in Infantile Neuronal Ceroid-Lipofuscinosis. Part 1: Postmortem MRI With Histopathologic Correlation;citation_pages=438-443;citation_volume=10;citation_year=1995;citation_issue=6;citation_pmid=8576552;citation_doi=10.1177/088307389501000603" />
<meta name="citation_reference" content="citation_journal_title=AJNR Am J Neuroradiol;citation_author=A. Biswas;citation_author=P. Krishnan;citation_author=A. Amirabadi;citation_title=Expanding the neuroimaging phenotype of neuronal ceroid lipofuscinoses;citation_volume=41;citation_year=2020;citation_pmid=32855186;citation_doi=10.3174/ajnr.A6726" />
<meta name="citation_reference" content="citation_journal_title=Journal of Child Neurology;citation_journal_abbrev=J Child Neurol;citation_author=SL. Vanhanen;citation_author=R. Raininko;citation_author=T. Autti;citation_title=MRI Evaluation of the Brain in Infantile Neuronal Ceroid-Lipofuscinosis: Part 2: MRI Findings in 21 Patients;citation_pages=444-450;citation_volume=10;citation_year=1995;citation_issue=6;citation_pmid=8576553;citation_doi=10.1177/088307389501000604" />
<meta name="citation_reference" content="citation_journal_title=Neuroradiology;citation_journal_abbrev=Neuroradiology;citation_author=T. Autti;citation_author=R. Joensuu;citation_author=L. Aberg;citation_title=Decreased T2 signal in the thalami may be a sign of lysosomal storage disease.;citation_pages=571-578;citation_volume=49;citation_year=2007;citation_issue=7;citation_pmid=17334752;citation_doi=10.1007/s00234-007-0220-6" />
<meta name="citation_reference" content="citation_journal_title=Molecular therapy :  the journal of the American Society of Gene Therapy;citation_journal_abbrev=Mol Ther;citation_author=M. Chang;citation_author=JD. Cooper;citation_author=DE. Sleat;citation_title=Intraventricular enzyme replacement improves disease phenotypes in a mouse model of late infantile neuronal ceroid lipofuscinosis.;citation_pages=649-656;citation_volume=16;citation_year=2008;citation_issue=4;citation_pmid=18362923;citation_doi=10.1038/mt.2008.9" />
<meta name="citation_reference" content="citation_journal_title=Mol Genet Metab;citation_author=BR. Vuillemenot;citation_author=D. Kennedy;citation_author=JD. Cooper;citation_title=Nonclinical evaluation of CNS-administered TPP1 enzyme replacement in canine CLN2 neuronal ceroid lipofuscinosis;citation_pages=281-93;citation_volume=114;citation_year=2015;citation_pmid=25257657;citation_doi=10.1016/j.ymgme.2014.09.004" />
<meta name="citation_reference" content="citation_journal_title=Lancet Neurol;citation_author=A. Schulz;citation_author=N. Specchio;citation_author=E. de Los Reyes;citation_title=Safety and efficacy of cerliponase alfa in children with neuronal ceroid lipofuscinosis type 2 (CLN2 disease): an open-label extension study;citation_pages=60-70;citation_volume=23;citation_year=2024;citation_pmid=38101904;citation_doi=10.1016/S1474-4422(23)00384-8" />
<meta name="citation_reference" content="Batten Disease Family Association. http://www.bdfa-uk.org.uk/research-and-resources/brineura-for-cln2/-. Accessed February 25, 2024" />
<meta name="citation_reference" content="citation_journal_title=AJNR Am J Neuroradiol;citation_author=JP. Dyke;citation_author=D. Sondhi;citation_author=HU. Voss;citation_title=Brain region-specific degeneration with disease progression in late infantile neuronal ceroid lipofuscinosis (CLN2 disease);citation_volume=37;citation_year=2016;citation_pmid=26822727;citation_doi=10.3174/ajnr.A4669" />
<meta name="citation_reference" content="citation_journal_title=Neuroradiology;citation_author=JN. Hochstein;citation_author=A. Schulz;citation_author=M. Nickel;citation_title=Natural history of MRI brain volumes in patients with neuronal ceroid lipofuscinosis 3: a sensitive imaging biomarker;citation_pages=2059-67;citation_volume=64;citation_year=2022;citation_pmid=35699772;citation_doi=10.1007/s00234-022-02988-9" />
<meta name="citation_reference" content="citation_journal_title=Sci Rep;citation_author=K. Knoernschild;citation_author=HJ. Johnson;citation_author=KE. Schroeder;citation_title=Magnetic resonance brain volumetry biomarkers of CLN2 Batten disease identified with miniswine model;citation_pages=5146;citation_volume=13;citation_year=2023;citation_pmid=36991106;citation_doi=10.1038/s41598-023-32071-z" />
<meta name="citation_reference" content="citation_journal_abbrev=NeuroImage;citation_author=B. Fischl;citation_title=FreeSurfer.;citation_pages=774-781;citation_volume=62;citation_year=2012;citation_issue=2;citation_pmid=22248573;citation_doi=10.1016/j.neuroimage.2012.01.021" />
<meta name="citation_reference" content="citation_journal_title=J Stat Soft;citation_author=D. Bates;citation_author=M. Mächler;citation_author=B. Bolker;citation_title=Fitting linear mixed-effects models using lme4;citation_pages=1-48;citation_volume=67;citation_year=2015;citation_pmid=23757445;citation_doi=10.18637/jss.v067.i01" />
<meta name="citation_reference" content="citation_journal_title=Commun Stat Appl Methods;citation_author=S. Kim;citation_title=ppcor: an r package for a fast calculation to semi-partial correlation coefficients;citation_pages=665-74;citation_volume=22;citation_year=2015;citation_pmid=26688802;citation_doi=10.5351/CSAM.2015.22.6.665" />
<meta name="citation_reference" content="citation_journal_title=Lancet Child Adolesc Health;citation_author=M. Nickel;citation_author=A. Simonati;citation_author=D. Jacoby;citation_title=Disease characteristics and progression in patients with late-infantile neuronal ceroid lipofuscinosis type 2 (CLN2) disease: an observational cohort study;citation_pages=582-90;citation_volume=2;citation_year=2018;citation_pmid=30119717;citation_doi=10.1016/S2352-4642(18)30179-2" />
<meta name="citation_reference" content="citation_journal_title=AJNR Am J Neuroradiol;citation_author=EH. Baker;citation_author=SW. Levin;citation_author=Z. Zhang;citation_title=MRI brain volume measurements in infantile neuronal ceroid lipofuscinosis;citation_volume=38;citation_year=2017;citation_pmid=27765741;citation_doi=10.3174/ajnr.A4978" />
<meta name="citation_reference" content="citation_journal_title=AJNR Am J Neuroradiol;citation_author=Alzheimer’s Disease Neuroimaging Initiative;citation_title=Comparing 3T and 1.5T MRI for mapping hippocampal atrophy in the Alzheimer’s Disease Neuroimaging Initiative;citation_volume=36;citation_year=2015;citation_pmid=25614473;citation_doi=10.3174/ajnr.A4228" />
<meta name="twitter:title" content="Enzyme Replacement Therapy for CLN2 Disease: MRI Volumetry Shows Significantly Slower Volume Loss Compared with a Natural History Cohort" />
<meta name="twitter:card" content="summary_large_image" />
<meta name="twitter:image" content="http://ajnr-stage2.stage.highwire.org/sites/default/files/highwire/ajnr/45/11.cover-source.jpg" />
<meta name="twitter:description" content="BACKGROUND AND PURPOSE: Neuronal ceroid lipofuscinoses are a group of neurodegenerative disorders. Recently, enzyme replacement therapy (ERT) was approved for neuronal ceroid lipofuscinosis type 2 (CLN2), a subtype of neuronal ceroid lipofuscinoses. The aim of this study was to quantify brain volume loss in CLN2 disease in patients on ERT in comparison with a natural history cohort using MRI.

MATERIALS AND METHODS: Nineteen (14 female, 5 male) patients with CLN2 disease at 1 UK center were studied using serial 3D T1-weighted MRI (follow-up time, 1–9 years). Brain segmentation was performed using FreeSurfer. Volume measurements for supratentorial gray and white matter, deep gray matter (basal ganglia/thalami), the lateral ventricles, and cerebellar gray and white matter were recorded. The volume change with time was analyzed using a linear mixed-effects model excluding scans before treatment onset. Comparison was made with a published natural history cohort of 12 patients (8 female, 4 male), which was re-analyzed using the same method.

RESULTS: Brain volume loss of all segmented brain regions was much slower in treated patients compared with the natural history cohort. For example, supratentorial gray matter volume in treated patients decreased by a mean of 3% (SD, 0.74%) ( P &lt; .001) annually compared with an annual volume loss of a mean of 16.8% (SD, 1.5%) ( P &lt; .001) in the natural history cohort.

CONCLUSIONS: Our treatment cohort showed a significantly slower rate of brain parenchymal volume loss compared with a natural history cohort in several anatomic regions. Our results complement prior clinical data that found a positive response to ERT. We demonstrate that automated MRI volumetry is a sensitive tool to monitor treatment response in children with CLN2 disease.

CLN2
:   neuronal ceroid lipofuscinosis type 2
ERT
:   enzyme replacement therapy
ICV
:   intracerebro-ventricular
NCL
:   neuronal ceroid lipofuscinosis
TPP1
:   tripeptidyl peptidase 1" />
<meta name="og-title" property="og:title" content="Enzyme Replacement Therapy for CLN2 Disease: MRI Volumetry Shows Significantly Slower Volume Loss Compared with a Natural History Cohort" />
<meta name="og-url" property="og:url" content="http://ajnr-stage2.stage.highwire.org/content/45/11/1791" />
<meta name="og-site-name" property="og:site_name" content="American Journal of Neuroradiology" />
<meta name="og-description" property="og:description" content="BACKGROUND AND PURPOSE: Neuronal ceroid lipofuscinoses are a group of neurodegenerative disorders. Recently, enzyme replacement therapy (ERT) was approved for neuronal ceroid lipofuscinosis type 2 (CLN2), a subtype of neuronal ceroid lipofuscinoses. The aim of this study was to quantify brain volume loss in CLN2 disease in patients on ERT in comparison with a natural history cohort using MRI.

MATERIALS AND METHODS: Nineteen (14 female, 5 male) patients with CLN2 disease at 1 UK center were studied using serial 3D T1-weighted MRI (follow-up time, 1–9 years). Brain segmentation was performed using FreeSurfer. Volume measurements for supratentorial gray and white matter, deep gray matter (basal ganglia/thalami), the lateral ventricles, and cerebellar gray and white matter were recorded. The volume change with time was analyzed using a linear mixed-effects model excluding scans before treatment onset. Comparison was made with a published natural history cohort of 12 patients (8 female, 4 male), which was re-analyzed using the same method.

RESULTS: Brain volume loss of all segmented brain regions was much slower in treated patients compared with the natural history cohort. For example, supratentorial gray matter volume in treated patients decreased by a mean of 3% (SD, 0.74%) ( P &lt; .001) annually compared with an annual volume loss of a mean of 16.8% (SD, 1.5%) ( P &lt; .001) in the natural history cohort.

CONCLUSIONS: Our treatment cohort showed a significantly slower rate of brain parenchymal volume loss compared with a natural history cohort in several anatomic regions. Our results complement prior clinical data that found a positive response to ERT. We demonstrate that automated MRI volumetry is a sensitive tool to monitor treatment response in children with CLN2 disease.

CLN2
:   neuronal ceroid lipofuscinosis type 2
ERT
:   enzyme replacement therapy
ICV
:   intracerebro-ventricular
NCL
:   neuronal ceroid lipofuscinosis
TPP1
:   tripeptidyl peptidase 1" />
<meta name="og-type" property="og:type" content="article" />
<meta name="og-image" property="og:image" content="http://ajnr-stage2.stage.highwire.org/sites/default/files/highwire/ajnr/45/11.cover-source.jpg" />
<meta name="viewport" content="width=device-width, initial-scale=1" />
<link rel="alternate" type="application/vnd.ms-powerpoint" title="Powerpoint" href="/content/45/11/1791.ppt" />
<link rel="alternate" type="text/plain" title="Full Text (Plain)" href="/content/45/11/1791.full.txt" />
<link rel="alternate" type="application/pdf" title="Full Text (PDF)" href="/content/45/11/1791.full.pdf" />
<link rel="canonical" href="http://ajnr-stage2.stage.highwire.org/content/45/11/1791" />
<script>window.dataLayer = window.dataLayer || [];window.dataLayer.push({"page":{"hwTitle":"Enzyme Replacement Therapy for CLN2 Disease: MRI Volumetry Shows Significantly Slower Volume Loss Compared with a Natural History Cohort","hwUrl":"http://ajnr-stage2.stage.highwire.org/content/45/11/1791","hwPath":"/content/45/11/1791","hwType":"journal page"},"user":{"hwMemberID":"","hwLoggedIntoInstitutionID":"","hwLoggedIntoInstitution":"","hwAccessUsageTerms":"guest","hwRegisteredUser":"no","hwHasFullTextAccess":"no","hwEntitled":"no"},"content":{"hwIssueDate":"2024-11-01","hwIssueDateTime":"2024-11-01 00:00:00","hwPublicationDate":"2024-11-07","hwPublicationDateTime":"2024-11-07 15:14:12","hwNlmArticleType":"research-article","hwDOI":"10.3174/ajnr.A8408","hwAuthors":"Pritika Gaur,Paul Gissen,Asthik Biswas,Kshitij Mankad,Sniya Sudhakar,Felice D\u2019Arco,Angela Schulz,Jens Fiehler,Jan Sedlacik,Ulrike L\u00f6bel","hwContributors":"","hwIsEarlyRelease":"no","hwEissn":"1936-959X","hwPissn":"0195-6108","hwVolume":"45","hwIssue":"11","hwArticleType":"Pediatric Neuroimaging","hwTabView":"main_tab","hwViewType":"","hwAccessType":"Paywall","hwOpenAccess":"no","hwFreeAccess":"no","hwTaxonomy":"","hwCorpusCode":"ajnr","hwType":"article","hwSubtitle":null,"hwOverline":null,"hwPisaId":"ajnr;45/11/1791","hwFirstPage":"1791","hwLastPage":"1797","hwIsLatestVersion":"yes","hwIsCurrentIssue":"no","hwIsOpenIssue":"no","hwHasFullText":"yes","hwHasPDF":"yes","hwParentTitle":"American Journal of Neuroradiology: 45 (11)","hwElectronicPubDate":"2024-11-07","hwElectronicPubDateTime":"2024-11-07 15:14:12"}});
//--><!]]></script>
    <title>Enzyme Replacement Therapy for CLN2 Disease: MRI Volumetry Shows Significantly Slower Volume Loss Compared with a Natural History Cohort | American Journal of Neuroradiology</title>  
    <link type="text/css" rel="stylesheet" href="/sites/default/files/advagg_css/css__BJ6Ou6QsBRtnFTmxaakamOIS8n4QswDP2XnnZ1sxtaM__NBuvkP6eInGIkb1aJvUHx5PX79XApuxBDkk_77W5tYk__Op4k-kV4DoWc7bsUP7umKmZ0WXfmoYdRDoZFPNSd-oM.css" media="all" />
<link type="text/css" rel="stylesheet" href="/sites/default/files/advagg_css/css__azeXjFYQUa4gTbdEg4sgM2osudOlAYwVv6vNmRXI3ac__zr83wx5lNxUVx-jSIFm8RDKOeMAB7RbaBxriFHS3dt4__Op4k-kV4DoWc7bsUP7umKmZ0WXfmoYdRDoZFPNSd-oM.css" media="all" />
<link type="text/css" rel="stylesheet" href="/sites/default/files/advagg_css/css__Ep75tNOnm8H2Mejav16FnGCfM1sLwyporbQrCIgwg3g__vXGjszfa0bvxzymQ8Cfns-o2huFvm80jp3igN8XcYeI__Op4k-kV4DoWc7bsUP7umKmZ0WXfmoYdRDoZFPNSd-oM.css" media="all" />
<link type="text/css" rel="stylesheet" href="/sites/default/files/advagg_css/css__TKi6DXKzgLPdEthh1Tnc63zY1QF4rLZHoM06Xy7VN6g__zaEHphFiBcrl8WVy_4n080y02dQ7HKxd_aqZbYgQ5Z0__Op4k-kV4DoWc7bsUP7umKmZ0WXfmoYdRDoZFPNSd-oM.css" media="all" />
<link type="text/css" rel="stylesheet" href="/sites/all/modules/highwire/highwire/highwire.style.highwire.css?sycxuq" media="all" />
<link type="text/css" rel="stylesheet" href="/sites/default/files/advagg_css/css__BX3nCkChknRoE-aDbdxprlFaypp4fXWeczbX7JvfqrM__NtFlOF_CU23QNMU5lA_arwbEf0O6qOCUd0hDjDpj968__Op4k-kV4DoWc7bsUP7umKmZ0WXfmoYdRDoZFPNSd-oM.css" media="all" />
<link type="text/css" rel="stylesheet" href="//cdn.jsdelivr.net/qtip2/2.2.1/jquery.qtip.min.css" media="all" />
<link type="text/css" rel="stylesheet" href="/sites/default/files/advagg_css/css__JnM-0sgpwKaRZfZwuqss_otkHPbNak1GxbxWZGNp2wo__ZeyEyuNcSNDfCqRmRUW_NahTWs9Wd-k1qLvZUB0phNg__Op4k-kV4DoWc7bsUP7umKmZ0WXfmoYdRDoZFPNSd-oM.css" media="all" />
<style type="text/css" media="all">
/* <![CDATA[ */
#sliding-popup.sliding-popup-bottom,#sliding-popup.sliding-popup-bottom .eu-cookie-withdraw-banner,.eu-cookie-withdraw-tab{background:#000000;}#sliding-popup.sliding-popup-bottom.eu-cookie-withdraw-wrapper{background:transparent}#sliding-popup .popup-content #popup-text h1,#sliding-popup .popup-content #popup-text h2,#sliding-popup .popup-content #popup-text h3,#sliding-popup .popup-content #popup-text p,.eu-cookie-compliance-secondary-button,.eu-cookie-withdraw-tab{color:#ffffff !important;}.eu-cookie-withdraw-tab{border-color:#ffffff;}.eu-cookie-compliance-more-button{color:#ffffff !important;}

/* ]]> */
</style>

<!--[if lte IE 7]>
<link type="text/css" rel="stylesheet" href="/sites/default/files/advagg_css/css__ElJr3PIJEvw3qLXc1cnYiLj2G4KgDPSXFOfm6Phf8hw__JdWGm15cDWjsK6KrFlQVXQix9YgNeYysf22XZHj-Y-c__Op4k-kV4DoWc7bsUP7umKmZ0WXfmoYdRDoZFPNSd-oM.css" media="all" />
<![endif]-->
<link type="text/css" rel="stylesheet" href="/sites/default/files/advagg_css/css__Wnlyen9qEpwh_Qaf9okEu4QdVGM0BDothxeqA6Nbvo8__EJmw6SZD9bYoS8jocCpPYS3JFRURpdzmuvJoAUNiI-g__Op4k-kV4DoWc7bsUP7umKmZ0WXfmoYdRDoZFPNSd-oM.css" media="all" />
<link type="text/css" rel="stylesheet" href="/sites/default/files/advagg_css/css__nv7Hafs9UucfV8bmT4epWF4zWAFU2G9JLHVgOOHDqbA__k9QUw6MohZGXV0YlzqvUpPTbyzhbizsKOi4x3aA7Tx0__Op4k-kV4DoWc7bsUP7umKmZ0WXfmoYdRDoZFPNSd-oM.css" media="all" />

<!--[if (lt IE 9)&(!IEMobile)]>
<link type="text/css" rel="stylesheet" href="/sites/default/files/advagg_css/css__XH6bpcI0f2dImc-p674DLCZtWBGb-QwxJK1YexVGtno__vUceGprdo5nIhV6DH93X7fI3r8RcTJbChbas9TQXeW4__Op4k-kV4DoWc7bsUP7umKmZ0WXfmoYdRDoZFPNSd-oM.css" media="all" />
<![endif]-->

<!--[if gte IE 9]><!-->
<link type="text/css" rel="stylesheet" href="/sites/default/files/advagg_css/css__2WBMox6sOrN42ss5lCnH7WWVRdFdJCxtTKnQJYRwTE4__yqNvNYLvMpjy3ffuJrjjm9uW2i-Me1c23KLYuWHaqio__Op4k-kV4DoWc7bsUP7umKmZ0WXfmoYdRDoZFPNSd-oM.css" media="all" />
<!--<![endif]-->
<link type="text/css" rel="stylesheet" href="/sites/default/files/advagg_css/css__wxg7u6KrkAKrph8zjmzjNAiqxtVP2vhMWX2NZ6DPPZE__ECvRNuvDf2Tm_Pc-j1mEkt48QjmIz2s2CyWDspWAhhI__Op4k-kV4DoWc7bsUP7umKmZ0WXfmoYdRDoZFPNSd-oM.css" media="all" />
    <script type="text/javascript">
<!--//--><![CDATA[//><!--
/*!
 * yepnope1.5.4
 * (c) WTFPL, GPLv2
 */
(function(a,b,c){function d(a){return"[object Function]"==o.call(a)}function e(a){return"string"==typeof a}function f(){}function g(a){return!a||"loaded"==a||"complete"==a||"uninitialized"==a}function h(){var a=p.shift();q=1,a?a.t?m(function(){("c"==a.t?B.injectCss:B.injectJs)(a.s,0,a.a,a.x,a.e,1)},0):(a(),h()):q=0}function i(a,c,d,e,f,i,j){function k(b){if(!o&&g(l.readyState)&&(u.r=o=1,!q&&h(),l.onload=l.onreadystatechange=null,b)){"img"!=a&&m(function(){t.removeChild(l)},50);for(var d in y[c])y[c].hasOwnProperty(d)&&y[c][d].onload()}}var j=j||B.errorTimeout,l=b.createElement(a),o=0,r=0,u={t:d,s:c,e:f,a:i,x:j};1===y[c]&&(r=1,y[c]=[]),"object"==a?l.data=c:(l.src=c,l.type=a),l.width=l.height="0",l.onerror=l.onload=l.onreadystatechange=function(){k.call(this,r)},p.splice(e,0,u),"img"!=a&&(r||2===y[c]?(t.insertBefore(l,s?null:n),m(k,j)):y[c].push(l))}function j(a,b,c,d,f){return q=0,b=b||"j",e(a)?i("c"==b?v:u,a,b,this.i++,c,d,f):(p.splice(this.i++,0,a),1==p.length&&h()),this}function k(){var a=B;return a.loader={load:j,i:0},a}var l=b.documentElement,m=a.setTimeout,n=b.getElementsByTagName("script")[0],o={}.toString,p=[],q=0,r="MozAppearance"in l.style,s=r&&!!b.createRange().compareNode,t=s?l:n.parentNode,l=a.opera&&"[object Opera]"==o.call(a.opera),l=!!b.attachEvent&&!l,u=r?"object":l?"script":"img",v=l?"script":u,w=Array.isArray||function(a){return"[object Array]"==o.call(a)},x=[],y={},z={timeout:function(a,b){return b.length&&(a.timeout=b[0]),a}},A,B;B=function(a){function b(a){var a=a.split("!"),b=x.length,c=a.pop(),d=a.length,c={url:c,origUrl:c,prefixes:a},e,f,g;for(f=0;f<d;f++)g=a[f].split("="),(e=z[g.shift()])&&(c=e(c,g));for(f=0;f<b;f++)c=x[f](c);return c}function g(a,e,f,g,h){var i=b(a),j=i.autoCallback;i.url.split(".").pop().split("?").shift(),i.bypass||(e&&(e=d(e)?e:e[a]||e[g]||e[a.split("/").pop().split("?")[0]]),i.instead?i.instead(a,e,f,g,h):(y[i.url]?i.noexec=!0:y[i.url]=1,f.load(i.url,i.forceCSS||!i.forceJS&&"css"==i.url.split(".").pop().split("?").shift()?"c":c,i.noexec,i.attrs,i.timeout),(d(e)||d(j))&&f.load(function(){k(),e&&e(i.origUrl,h,g),j&&j(i.origUrl,h,g),y[i.url]=2})))}function h(a,b){function c(a,c){if(a){if(e(a))c||(j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}),g(a,j,b,0,h);else if(Object(a)===a)for(n in m=function(){var b=0,c;for(c in a)a.hasOwnProperty(c)&&b++;return b}(),a)a.hasOwnProperty(n)&&(!c&&!--m&&(d(j)?j=function(){var a=[].slice.call(arguments);k.apply(this,a),l()}:j[n]=function(a){return function(){var b=[].slice.call(arguments);a&&a.apply(this,b),l()}}(k[n])),g(a[n],j,b,n,h))}else!c&&l()}var h=!!a.test,i=a.load||a.both,j=a.callback||f,k=j,l=a.complete||f,m,n;c(h?a.yep:a.nope,!!i),i&&c(i)}var i,j,l=this.yepnope.loader;if(e(a))g(a,0,l,0);else if(w(a))for(i=0;i<a.length;i++)j=a[i],e(j)?g(j,0,l,0):w(j)?B(j):Object(j)===j&&h(j,l);else Object(a)===a&&h(a,l)},B.addPrefix=function(a,b){z[a]=b},B.addFilter=function(a){x.push(a)},B.errorTimeout=1e4,null==b.readyState&&b.addEventListener&&(b.readyState="loading",b.addEventListener("DOMContentLoaded",A=function(){b.removeEventListener("DOMContentLoaded",A,0),b.readyState="complete"},0)),a.yepnope=k(),a.yepnope.executeStack=h,a.yepnope.injectJs=function(a,c,d,e,i,j){var k=b.createElement("script"),l,o,e=e||B.errorTimeout;k.src=a;for(o in d)k.setAttribute(o,d[o]);c=j?h:c||f,k.onreadystatechange=k.onload=function(){!l&&g(k.readyState)&&(l=1,c(),k.onload=k.onreadystatechange=null)},m(function(){l||(l=1,c(1))},e),i?k.onload():n.parentNode.insertBefore(k,n)},a.yepnope.injectCss=function(a,c,d,e,g,i){var e=b.createElement("link"),j,c=i?h:c||f;e.href=a,e.rel="stylesheet",e.type="text/css";for(j in d)e.setAttribute(j,d[j]);g||(n.parentNode.insertBefore(e,n),m(c,0))}})(this,document);

//--><!]]>
</script>
<script type="text/javascript" src="/sites/all/libraries/modernizr/modernizr.min.js?sycxuq"></script>
<script type="text/javascript">
<!--//--><![CDATA[//><!--
yepnope({
  test: Modernizr.matchmedia,
  nope: '/sites/all/libraries/media-match/media.match.min.js'
});
//--><!]]>
</script>
<script type="text/javascript" src="/sites/default/files/advagg_js/js__wH8myWXKi4A-QKdUKDXzJAnGs-FRS1A2ZzTTNzjRAdI__4MCtOZK_Ov0QKyRlXNLGQ2LRlYRGWj9ArT-NpFox3QA__Op4k-kV4DoWc7bsUP7umKmZ0WXfmoYdRDoZFPNSd-oM.js"></script>
<script type="text/javascript">
<!--//--><![CDATA[//><!--
var googletag = googletag || {};
googletag.cmd = googletag.cmd || [];
googletag.slots = googletag.slots || {};
//--><!]]>
</script>
<script type="text/javascript" src="//securepubads.g.doubleclick.net/tag/js/gpt.js"></script>
<script type="text/javascript" src="/sites/default/files/advagg_js/js__9ici6QMeDS-cROq8R0RhuICsMGMP2wcJZNQQFsqQi44__kScSwG4RXGl1LXnj4qqt0ZxtNX4Gh2TK5W-o8Uup4SA__Op4k-kV4DoWc7bsUP7umKmZ0WXfmoYdRDoZFPNSd-oM.js"></script>
<script type="text/javascript" src="/sites/default/files/advagg_js/js__fwhbnUWIxW-jFl55E2mBYVtZTjGhJ1JWyZYAJ2cEd3A__jCrCuWCJIPYPe1FzZoUvsJWEjkNMmRIQHYek1h7idBE__Op4k-kV4DoWc7bsUP7umKmZ0WXfmoYdRDoZFPNSd-oM.js"></script>
<script type="text/javascript">
<!--//--><![CDATA[//><!--
googletag.slots["rhs"] = googletag.defineSlot("/446583111/RHS_300x250", [300, 250], "dfp-ad-rhs")
  .addService(googletag.pubads());
//--><!]]>
</script>
<script type="text/javascript" src="/sites/default/files/advagg_js/js__UR8BHznwml64Vq0ijSGFwlm-xe9ttj1aripHInFCOLw__irCalsu-H_fRTOPqjyCv1O8Ax7fqY6DDf-uMOV1dvGY__Op4k-kV4DoWc7bsUP7umKmZ0WXfmoYdRDoZFPNSd-oM.js"></script>
<script type="text/javascript">
<!--//--><![CDATA[//><!--
var mapping = googletag.sizeMapping()
  .addSize([768, 0], [728, 90])
  .addSize([0, 0], [300, 50])
  .build();
googletag.slots["bottom_leaderboard"] = googletag.defineSlot("/446583111/Bottom_Banner_728x90", [[728, 90], [300, 50]], "dfp-ad-bottom_leaderboard")
  .addService(googletag.pubads())
  .defineSizeMapping(mapping);
//--><!]]>
</script>
<script type="text/javascript" src="/sites/default/files/advagg_js/js__bQc6kyz_Gw2afC1F6wguCBh8Z8nev-hxX6F2Tw4bq6k__CO2faEsYCquY82rVj6as9HScSnogGHeR-oh5fSQydG0__Op4k-kV4DoWc7bsUP7umKmZ0WXfmoYdRDoZFPNSd-oM.js"></script>
<script type="text/javascript">
<!--//--><![CDATA[//><!--
var mapping = googletag.sizeMapping()
  .addSize([768, 0], [728, 90])
  .addSize([0, 0], [300, 50])
  .build();
googletag.slots["top_leaderboard"] = googletag.defineSlot("/446583111/Top_Leaderboard_728x90", [[728, 90], [300, 50]], "dfp-ad-top_leaderboard")
  .addService(googletag.pubads())
  .defineSizeMapping(mapping);
//--><!]]>
</script>
<script type="text/javascript" src="/sites/default/files/advagg_js/js__wS6WUeF11NLeJgCqxc-dMvjhALAMQG1jlaeWdG8yVZc__CPiombDS21ooaYdmqHXdcMoJwB2FMn18JzO97LewQxc__Op4k-kV4DoWc7bsUP7umKmZ0WXfmoYdRDoZFPNSd-oM.js"></script>
<script type="text/javascript">
<!--//--><![CDATA[//><!--
document.createElement( "picture" );
//--><!]]>
</script>
<script type="text/javascript" src="/sites/default/files/advagg_js/js__UK1ygaa8bCfT-jsjqYRdRLDZ5N17950T7K5WPC9XtpI__NqLYT1T1SMBsKukLWIe82VgCZYYCMHZX_f609-a1rj8__Op4k-kV4DoWc7bsUP7umKmZ0WXfmoYdRDoZFPNSd-oM.js"></script>
<script type="text/javascript">
<!--//--><![CDATA[//><!--
googletag.cmd.push(function() {
  googletag.pubads().enableAsyncRendering();
  googletag.pubads().enableSingleRequest();
  googletag.pubads().collapseEmptyDivs();
  googletag.pubads().addEventListener("slotRenderEnded", function (event) {
    if (event.isEmpty) {
      var id = event.slot.getSlotElementId();
      var x = document.getElementById(id);
      if (x.parentElement.classList.contains("dfp-tag-wrapper")) {
        x.parentElement.style.display = "none";
      }
    }
  });
  googletag.pubads().setTargeting("page:hwTitle", "Enzyme Replacement Therapy for CLN2 Disease: MRI Volumetry Shows Significantly Slower Volume Loss Compared with a Natural History Cohort");
  googletag.pubads().setTargeting("page:hwUrl", "http://ajnr-stage2.stage.highwire.org/content/45/11/1791");
  googletag.pubads().setTargeting("page:hwPath", "/content/45/11/1791");
  googletag.pubads().setTargeting("page:hwType", "journal page");
  googletag.pubads().setTargeting("user:hwAccessUsageTerms", "guest");
  googletag.pubads().setTargeting("user:hwRegisteredUser", "no");
  googletag.pubads().setTargeting("user:hwHasFullTextAccess", "no");
  googletag.pubads().setTargeting("user:hwEntitled", "no");
  googletag.pubads().setTargeting("content:hwIssueDate", "2024-11-01");
  googletag.pubads().setTargeting("content:hwIssueDateTime", "2024-11-01 00:00:00");
  googletag.pubads().setTargeting("content:hwPublicationDate", "2024-11-07");
  googletag.pubads().setTargeting("content:hwPublicationDateTime", "2024-11-07 15:14:12");
  googletag.pubads().setTargeting("content:hwNlmArticleType", "research-article");
  googletag.pubads().setTargeting("content:hwDOI", "10.3174/ajnr.A8408");
  googletag.pubads().setTargeting("content:hwAuthors", ["Pritika Gaur","Paul Gissen","Asthik Biswas","Kshitij Mankad","Sniya Sudhakar","Felice D’Arco","Angela Schulz","Jens Fiehler","Jan Sedlacik","Ulrike Löbel"]);
  googletag.pubads().setTargeting("content:hwIsEarlyRelease", "no");
  googletag.pubads().setTargeting("content:hwEissn", "1936-959X");
  googletag.pubads().setTargeting("content:hwPissn", "0195-6108");
  googletag.pubads().setTargeting("content:hwVolume", "45");
  googletag.pubads().setTargeting("content:hwIssue", "11");
  googletag.pubads().setTargeting("content:hwArticleType", "Pediatric Neuroimaging");
  googletag.pubads().setTargeting("content:hwTabView", "main_tab");
  googletag.pubads().setTargeting("content:hwAccessType", "Paywall");
  googletag.pubads().setTargeting("content:hwOpenAccess", "no");
  googletag.pubads().setTargeting("content:hwFreeAccess", "no");
  googletag.pubads().setTargeting("content:hwCorpusCode", "ajnr");
  googletag.pubads().setTargeting("content:hwType", "article");
  googletag.pubads().setTargeting("content:hwPisaId", "ajnr;45/11/1791");
  googletag.pubads().setTargeting("content:hwFirstPage", "1791");
  googletag.pubads().setTargeting("content:hwLastPage", "1797");
  googletag.pubads().setTargeting("content:hwIsLatestVersion", "yes");
  googletag.pubads().setTargeting("content:hwIsCurrentIssue", "no");
  googletag.pubads().setTargeting("content:hwIsOpenIssue", "no");
  googletag.pubads().setTargeting("content:hwHasFullText", "yes");
  googletag.pubads().setTargeting("content:hwHasPDF", "yes");
  googletag.pubads().setTargeting("content:hwParentTitle", "American Journal of Neuroradiology: 45 (11)");
  googletag.pubads().setTargeting("content:hwElectronicPubDate", "2024-11-07");
  googletag.pubads().setTargeting("content:hwElectronicPubDateTime", "2024-11-07 15:14:12");
});

googletag.enableServices();
//--><!]]>
</script>
<script type="text/javascript" src="/sites/default/files/advagg_js/js__3vwOA0BwlnyBkt9H4CLg6FgNyKAh--OmfOxFOIu_5S4__EXTgktcHbQ7BQfelY6CnrqgPRc4i4eD6XcZ4i3xs5RU__Op4k-kV4DoWc7bsUP7umKmZ0WXfmoYdRDoZFPNSd-oM.js"></script>
<script type="text/javascript" async="async" src="https://scholar.google.com/scholar_js/casa.js"></script>
<script type="text/javascript" src="/sites/default/files/advagg_js/js__11OTRBANYp_FPYy8gxuWv8XYK780LivNl9ef5qg3rfw__TEVdNksA7-zrPiZwnenYHdToBjuVChsDlzQL_vP4NkY__Op4k-kV4DoWc7bsUP7umKmZ0WXfmoYdRDoZFPNSd-oM.js"></script>
<script type="text/javascript" src="//cdn.jsdelivr.net/qtip2/2.2.1/jquery.qtip.min.js"></script>
<script type="text/javascript" src="/sites/default/files/advagg_js/js__yiXGyyzC1oV2sZBtAUN2DFoM2mAH5KP0iYCqS1dmafE__UiTPqZo1iNHqhqhx1lKGu2xkUGpxmin5ny6_22C53JA__Op4k-kV4DoWc7bsUP7umKmZ0WXfmoYdRDoZFPNSd-oM.js"></script>
<script type="text/javascript">
<!--//--><![CDATA[//><!--
if(typeof window.MathJax === "undefined") window.MathJax = { menuSettings: { zoom: "Click" } };
//--><!]]>
</script>
<script type="text/javascript" src="/sites/default/files/advagg_js/js__gzglMimeshoybn5FdOUfx5zFIzXjSZCarAdAqdFwzb0__XnS2ZmP_Eu1FvGruois2GWaJM4qn-3H8Rt4VF8dvyrA__Op4k-kV4DoWc7bsUP7umKmZ0WXfmoYdRDoZFPNSd-oM.js"></script>
<script type="text/javascript" src="https://www.google.com/recaptcha/api.js?hl=en&amp;render=explicit&amp;onload=drupalRecaptchaOnload"></script>
<script type="text/javascript" src="/sites/default/files/advagg_js/js__4ykqVVdSaGtVGauctG3E3Uojp_237f35KQ7wMtKX9S4__4JHByHSitU6UdWxmWARTSoZyB2PFgzkw__raxGdvbvk__Op4k-kV4DoWc7bsUP7umKmZ0WXfmoYdRDoZFPNSd-oM.js"></script>
<script type="text/javascript">
<!--//--><![CDATA[//><!--

      $(document).ready(function() {
          $.getJSON("//www.deepdyve.com/rental-link?docId=10.3174/ajnr.A8408&journal=1936-959X&fieldName=journal_doi&affiliateId=asnr&format=jsonp&callback=?", function(data) {
            if (data.status === "ok") {
              // Update the href url so it goes straight to the article page
              $(".js-deepdyve-link a").attr("href", data.url);
              $(".js-deepdyve-link").show();
            } else if (data.status === "not_found") {
              $(".js-deepdyve-link").hide();
            }
          });
        });
//--><!]]>
</script>
<script type="text/javascript" src="/sites/default/files/advagg_js/js__4lG8Nd_Z78ebRQwNtbOlh_jt-whQYFW5Try6DwQUwAM__8EEmyuTE_JxYCL1fbIkxkI5UUKYRtta33k484QkazhA__Op4k-kV4DoWc7bsUP7umKmZ0WXfmoYdRDoZFPNSd-oM.js"></script>
<script type="text/javascript" async="async" src="https://www.googletagmanager.com/gtag/js?id=G-4CRTLTY8KW"></script>
<script type="text/javascript">
<!--//--><![CDATA[//><!--
window.dataLayer = window.dataLayer || [];function gtag(){dataLayer.push(arguments)};gtag("js", new Date());gtag("set", "developer_id.dMDhkMT", true);gtag("config", "G-4CRTLTY8KW", {"groups":"default","anonymize_ip":true});
//--><!]]>
</script>
<script type="text/javascript" src="/sites/default/files/advagg_js/js__xwmR_XUqgIHdKocIkn2GiqYMVWJ0gY7OwpoARPRxEYM__CdSkXbn46iKUJfVct1nUx50N8MQ35eZOCMya9EuGbeU__Op4k-kV4DoWc7bsUP7umKmZ0WXfmoYdRDoZFPNSd-oM.js"></script>
<script type="text/javascript" src="/sites/default/files/advagg_js/js__156__G_TX0wWbp2x4EuISKOgbs4NaeHZ2KmXq85T6UI__w2izI_4UeJKq2XZJo79kNkQyxp_-2ptYjzA3YJcr-tg__Op4k-kV4DoWc7bsUP7umKmZ0WXfmoYdRDoZFPNSd-oM.js"></script>
<script type="text/javascript" src="/sites/default/files/advagg_js/js__az53Pz-SG0wejB-7UDzC-AbKqNFb4dAiZbq9Ymbj0sY__8FyXs8A34T1jX6OUXsgX27-4ASoy8QDncslXiOc2PK4__Op4k-kV4DoWc7bsUP7umKmZ0WXfmoYdRDoZFPNSd-oM.js"></script>
<script type="text/javascript">
<!--//--><![CDATA[//><!--
jQuery.extend(Drupal.settings, {"basePath":"\/","pathPrefix":"","ajaxPageState":{"theme":"jcore_1","theme_token":"A0tTqWm2Nuhp5eHKw3qFUGCBPvnr29FfE5Y1hEXnHNo","js":{"sites\/all\/libraries\/modernizr\/modernizr.min.js":1,"sites\/all\/modules\/contrib\/jquery_update\/replace\/jquery\/1.8\/jquery.min.js":1,"misc\/jquery-extend-3.4.0.js":1,"misc\/jquery.once.js":1,"misc\/drupal.js":1,"sites\/all\/modules\/contrib\/jquery_update\/replace\/ui\/ui\/minified\/jquery.ui.core.min.js":1,"sites\/all\/modules\/contrib\/jquery_update\/replace\/ui\/ui\/minified\/jquery.ui.widget.min.js":1,"sites\/all\/modules\/contrib\/jquery_update\/replace\/ui\/ui\/minified\/jquery.ui.button.min.js":1,"sites\/all\/modules\/contrib\/jquery_update\/replace\/ui\/ui\/minified\/jquery.ui.mouse.min.js":1,"sites\/all\/modules\/contrib\/jquery_update\/replace\/ui\/ui\/minified\/jquery.ui.draggable.min.js":1,"sites\/all\/modules\/contrib\/jquery_update\/replace\/ui\/ui\/minified\/jquery.ui.position.min.js":1,"sites\/all\/modules\/contrib\/jquery_update\/replace\/ui\/ui\/minified\/jquery.ui.resizable.min.js":1,"sites\/all\/modules\/contrib\/jquery_update\/replace\/ui\/ui\/minified\/jquery.ui.dialog.min.js":1,"sites\/all\/modules\/contrib\/jquery_update\/replace\/ui\/ui\/minified\/jquery.ui.tooltip.min.js":1,"sites\/all\/modules\/contrib\/jquery_update\/replace\/ui\/ui\/minified\/jquery.ui.accordion.min.js":1,"sites\/all\/libraries\/jquery.bgiframe\/jquery.bgiframe.js":1,"sites\/all\/libraries\/jquery.hoverIntent\/jquery.hoverIntent.js":1,"sites\/all\/libraries\/superfish\/superfish.js":1,"sites\/all\/modules\/contrib\/nice_menus\/js\/nice_menus.js":1,"sites\/all\/modules\/contrib\/eu_cookie_compliance\/js\/jquery.cookie-1.4.1.min.js":1,"sites\/all\/modules\/highwire\/highwire\/js\/highwire.equal-heights.js":1,"sites\/all\/modules\/highwire\/highwire\/js\/highwire.panels-ajax-tab.js":1,"sites\/all\/libraries\/colorbox\/jquery.colorbox-min.js":1,"sites\/all\/modules\/contrib\/colorbox\/js\/colorbox.js":1,"sites\/all\/modules\/contrib\/colorbox\/styles\/default\/colorbox_style.js":1,"https:\/\/scholar.google.com\/scholar_js\/casa.js":1,"sites\/all\/modules\/highwire\/highwire\/highwire_log\/highwire_log.js":1,"sites\/all\/modules\/highwire\/highwire\/highwire_user\/js\/highwire_user_meta.js":1,"sites\/all\/modules\/contrib\/panels_ajax_tab\/js\/panels_ajax_tab.js":1,"\/\/cdn.jsdelivr.net\/qtip2\/2.2.1\/jquery.qtip.min.js":1,"sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_article_reference_popup.js":1,"sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_at_symbol.js":1,"sites\/all\/modules\/contrib\/captcha\/captcha.js":1,"misc\/textarea.js":1,"sites\/all\/modules\/contrib\/recaptcha\/js\/recaptcha.js":1,"https:\/\/www.google.com\/recaptcha\/api.js?hl=en\u0026render=explicit\u0026onload=drupalRecaptchaOnload":1,"sites\/all\/modules\/highwire\/highwire\/highwire_citation\/plugins\/content_types\/js\/highwire_citation_export.js":1,"sites\/all\/modules\/highwire\/highwire\/plugins\/content_types\/js\/minipanel_dialog_link.js":1,"sites\/all\/modules\/highwire\/highwire\/plugins\/content_types\/js\/highwire_share_dialog.js":1,"sites\/all\/modules\/highwire\/highwire\/plugins\/content_types\/js\/clipboard.min.js":1,"sites\/all\/modules\/highwire\/highwire\/plugins\/content_types\/js\/highwire_clipboard.js":1,"sites\/all\/modules\/contrib\/service_links\/js\/twitter_button.js":1,"sites\/all\/modules\/contrib\/service_links\/js\/facebook_like.js":1,"sites\/all\/modules\/contrib\/service_links\/js\/google_plus_one.js":1,"sites\/all\/modules\/highwire\/highwire\/plugins\/content_types\/js\/highwire_article_nav.js":1,"sites\/all\/modules\/highwire\/highwire\/plugins\/content_types\/js\/highwire_nav_float.js":1,"sites\/all\/modules\/highwire\/highwire\/plugins\/content_types\/js\/highwire_citing_links.js":1,"sites\/all\/modules\/highwire\/highwire\/highwire_search\/plugins\/content_types\/js\/highwire_search_similar_articles.js":1,"sites\/all\/modules\/contrib\/panels_accordion\/js\/panels_accordion.js":1,"sites\/all\/modules\/highwire\/highwire\/js\/highwire.article-citation-access.js":1,"sites\/all\/modules\/highwire\/highwire\/js\/highwire.article-citation-author-tooltip.js":1,"sites\/all\/modules\/highwire\/highwire\/highwire_responsive\/plugins\/styles\/highwire_responsive_toggle\/highwire_responsive_toggle.js":1,"sites\/all\/modules\/contrib\/google_analytics\/googleanalytics.js":1,"https:\/\/www.googletagmanager.com\/gtag\/js?id=G-4CRTLTY8KW":1,"sites\/all\/themes\/highwire\/jcore_1\/js\/theme-scripts.js":1,"sites\/all\/modules\/highwire\/highwire\/highwire_responsive\/js\/highwire-mediaqueries.js":1,"sites\/all\/libraries\/enquire.js\/enquire.min.js":1,"sites\/all\/modules\/contrib\/picture\/picturefill2\/picturefill.min.js":1,"sites\/all\/modules\/contrib\/picture\/picture.min.js":1,"sites\/all\/modules\/highwire\/highwire\/plugins\/content_types\/js\/highwire_panels_ajax_tab.js":1,"sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_openurl.js":1,"sites\/all\/modules\/highwire\/highwire\/plugins\/highwire_markup_process\/js\/highwire_google_scholar_sprinkle.js":1,"sites\/all\/modules\/highwire\/highwire\/plugins\/content_types\/js\/highwire_article_trendmd.js":1,"sites\/all\/modules\/highwire\/highwire\/highwire_user\/plugins\/content_types\/js\/highwire_user_salutation.js":1,"sites\/all\/modules\/contrib\/eu_cookie_compliance\/js\/eu_cookie_compliance.js":1,"http:\/\/securepubads.g.doubleclick.net\/tag\/js\/gpt.js":1,"sites\/all\/modules\/highwire\/highwire\/js\/highwire.gtranslate.js":1,"sites\/all\/modules\/highwire\/highwire\/highwire_datalayer\/js\/highwire_datalayer.js":1,"sites\/all\/themes\/contrib\/omega\/omega\/js\/jquery.formalize.js":1,"sites\/all\/themes\/contrib\/omega\/omega\/js\/omega-mediaqueries.js":1,"sites\/all\/themes\/contrib\/omega\/omega\/js\/omega-equalheights.js":1},"css":{"modules\/system\/system.base.css":1,"modules\/system\/system.menus.css":1,"modules\/system\/system.messages.css":1,"modules\/system\/system.theme.css":1,"misc\/ui\/jquery.ui.core.css":1,"misc\/ui\/jquery.ui.theme.css":1,"misc\/ui\/jquery.ui.button.css":1,"misc\/ui\/jquery.ui.resizable.css":1,"misc\/ui\/jquery.ui.dialog.css":1,"misc\/ui\/jquery.ui.tooltip.css":1,"misc\/ui\/jquery.ui.accordion.css":1,"sites\/all\/modules\/contrib\/date\/date_api\/date.css":1,"sites\/all\/modules\/contrib\/date\/date_popup\/themes\/datepicker.1.7.css":1,"modules\/field\/theme\/field.css":1,"sites\/all\/modules\/highwire\/highwire\/highwire_draw\/css\/highwire-draw.css":1,"sites\/all\/modules\/highwire\/highwire\/highwire_folders\/highwire_folders.css":1,"sites\/all\/modules\/highwire\/highwire\/highwire_responsive\/css\/highwire-responsive.css":1,"sites\/all\/modules\/highwire\/highwire\/highwire_saved_searches\/highwire_saved_searches.css":1,"sites\/all\/modules\/highwire\/highwire\/highwire_user\/highwire_user.css":1,"modules\/node\/node.css":1,"sites\/all\/modules\/contrib\/picture\/picture_wysiwyg.css":1,"modules\/search\/search.css":1,"modules\/user\/user.css":1,"sites\/all\/modules\/contrib\/views\/css\/views.css":1,"sites\/all\/modules\/contrib\/ckeditor\/css\/ckeditor.css":1,"sites\/all\/modules\/contrib\/colorbox\/styles\/default\/colorbox_style.css":1,"sites\/all\/modules\/contrib\/ctools\/css\/ctools.css":1,"sites\/all\/modules\/contrib\/google_admanager\/google_admanager.css":1,"sites\/all\/modules\/highwire\/highwire\/highwire.style.highwire.css":1,"sites\/all\/modules\/highwire\/highwire\/css\/nlm-elements.css":1,"sites\/all\/modules\/contrib\/panels\/css\/panels.css":1,"public:\/\/ctools\/css\/263bfdb18936424f0ade19d6bd885f37.css":1,"sites\/all\/modules\/contrib\/panels_ajax_tab\/css\/panels_ajax_tab.css":1,"sites\/all\/modules\/highwire\/highwire\/plugins\/content_types\/css\/highwire_corrections.css":1,"\/\/cdn.jsdelivr.net\/qtip2\/2.2.1\/jquery.qtip.min.css":1,"sites\/all\/modules\/highwire\/highwire\/plugins\/layouts\/highwire_2col_stacked\/highwire-2col-stacked.css":1,"sites\/all\/modules\/contrib\/forward\/forward.css":1,"sites\/all\/modules\/highwire\/highwire\/plugins\/content_types\/css\/highwire_share_link.css":1,"sites\/all\/modules\/highwire\/highwire\/plugins\/content_types\/css\/highwire_copy_permalink.css":1,"sites\/all\/modules\/highwire\/highwire\/highwire.style.markup.css":1,"sites\/all\/modules\/highwire\/highwire\/plugins\/content_types\/css\/highwire_citing_links.css":1,"sites\/all\/modules\/highwire\/highwire\/plugins\/content_types\/css\/highwire_reports_feed.css":1,"sites\/all\/modules\/highwire\/highwire\/css\/highwire-article-citation-list.css":1,"sites\/all\/modules\/highwire\/highwire\/highwire_responsive\/plugins\/styles\/highwire_responsive_toggle\/highwire_responsive_toggle.css.less":1,"sites\/all\/modules\/contrib\/nice_menus\/css\/nice_menus.css":1,"sites\/all\/modules\/contrib\/nice_menus\/css\/nice_menus_default.css":1,"sites\/all\/modules\/contrib\/panels\/plugins\/layouts\/onecol\/onecol.css":1,"sites\/all\/modules\/contrib\/eu_cookie_compliance\/css\/eu_cookie_compliance.css":1,"sites\/all\/modules\/highwire\/highwire\/css\/highwire.gtranslate.css":1,"sites\/all\/modules\/highwire\/highwire\/highwire_theme_tools\/css\/font-hwicons.css":1,"sites\/all\/modules\/highwire\/highwire\/highwire_theme_tools\/css\/font-hwicons-glyphs.css":1,"sites\/all\/themes\/highwire\/jcore_1\/eu_cookie_compliance.css":1,"sites\/all\/themes\/highwire\/jcore_1\/css\/font-awesome-ie7.css":1,"sites\/all\/themes\/contrib\/omega\/alpha\/css\/alpha-reset.css":1,"sites\/all\/themes\/contrib\/omega\/alpha\/css\/alpha-mobile.css":1,"sites\/all\/themes\/contrib\/omega\/alpha\/css\/alpha-alpha.css":1,"sites\/all\/themes\/contrib\/omega\/omega\/css\/formalize.css":1,"sites\/all\/themes\/contrib\/omega\/omega\/css\/omega-text.css":1,"sites\/all\/themes\/contrib\/omega\/omega\/css\/omega-branding.css":1,"sites\/all\/themes\/contrib\/omega\/omega\/css\/omega-menu.css":1,"sites\/all\/themes\/contrib\/omega\/omega\/css\/omega-forms.css":1,"sites\/all\/modules\/highwire\/highwire\/css\/highwire-forms.css":1,"sites\/all\/themes\/highwire\/jcore_1\/css\/mobile-reset.css":1,"sites\/all\/themes\/highwire\/jcore_1\/css\/font-awesome.css":1,"sites\/all\/themes\/highwire\/jcore_1\/css\/forms.css":1,"sites\/all\/themes\/highwire\/jcore_1\/css\/global.css":1,"sites\/all\/themes\/highwire\/jcore_1\/css\/jquery-ui-elements.css":1,"sites\/all\/themes\/highwire\/jcore_1\/css\/text.css":1,"sites\/all\/themes\/highwire\/jcore_1\/css\/eletters.css":1,"sites\/all\/themes\/highwire\/jcore_1\/css\/colors.css.less":1,"ie::normal::sites\/all\/themes\/highwire\/jcore_1\/css\/jcore-1-jcore-default.css":1,"ie::normal::sites\/all\/themes\/highwire\/jcore_1\/css\/jcore-1-jcore-default-normal.css":1,"ie::normal::sites\/all\/themes\/highwire\/jcore_1\/css\/grid\/jcore_default\/normal\/jcore-default-normal-30.css":1,"narrow::sites\/all\/themes\/highwire\/jcore_1\/css\/jcore-1-jcore-default.css":1,"narrow::sites\/all\/themes\/highwire\/jcore_1\/css\/jcore-1-jcore-default-narrow.css":1,"sites\/all\/themes\/highwire\/jcore_1\/css\/grid\/jcore_default\/narrow\/jcore-default-narrow-30.css":1,"normal::sites\/all\/themes\/highwire\/jcore_1\/css\/jcore-1-jcore-default.css":1,"normal::sites\/all\/themes\/highwire\/jcore_1\/css\/jcore-1-jcore-default-normal.css":1,"sites\/all\/themes\/highwire\/jcore_1\/css\/grid\/jcore_default\/normal\/jcore-default-normal-30.css":1,"wide::sites\/all\/themes\/highwire\/jcore_1\/css\/jcore-1-jcore-default.css":1,"wide::sites\/all\/themes\/highwire\/jcore_1\/css\/jcore-1-jcore-default-wide.css":1,"sites\/all\/themes\/highwire\/jcore_1\/css\/grid\/jcore_default\/wide\/jcore-default-wide-30.css":1,"sites\/all\/modules\/shared\/jnl_ajnr_styles\/css\/jnl-ajnr-styles.css.less":1,"sites\/all\/modules\/shared\/jnl_ajnr_styles\/css\/jnl-ajnr-breakpoints.css.less":1}},"colorbox":{"opacity":"0.85","current":"{current} of {total}","previous":"\u00ab Prev","next":"Next \u00bb","close":"Close","maxWidth":"98%","maxHeight":"98%","fixed":true,"mobiledetect":true,"mobiledevicewidth":"480px"},"highwire":{"markup":[{"requested":"short-text","variant":"abstract","view":"abstract","pisa":"ajnr;45\/11\/1791"},{"requested":"short-text","variant":"abstract","view":"abstract","pisa":"ajnr;45\/11\/1791"},{"requested":"index","variant":"index","view":"full","pisa":"ajnr;ajnr.A8408\/DCSupplemental"},{"requested":"long","variant":"abstract","view":"abstract","pisa":"ajnr;45\/11\/1791"},{"requested":"full-text","variant":"full-text","view":"full","pisa":"ajnr;45\/11\/1791"},{"requested":"index","variant":"index","view":"full","pisa":"ajnr;ajnr.A8408\/DCSupplemental"}],"nid":"111459","apath":"\/ajnr\/45\/11\/1791.atom","pisa":"ajnr;45\/11\/1791","ac":{"\/ajnr\/45\/11\/1791.atom":{"access":{"full":false,"reprint":false,"abstract":true},"pisa_id":"","apath":"\/ajnr\/45\/11\/1791.atom","jcode":"ajnr"},"ajnr;45\/11\/1791":{"access":{"full":false},"pisa_id":"ajnr;45\/11\/1791","apath":"","jcode":"ajnr"}},"processed":["highwire_math"],"trendmd":{"trendmd-suggestions":"{\u0022element\u0022:\u0022#trendmd-suggestions\u0022,\u0022track_id\u0022:\u0022null\u0022}"},"modal_window_width":"560","share_modal_width":"560","share_modal_title":"Share this Article","dataLayer":"{\u0022page\u0022:{\u0022hwTitle\u0022:\u0022Enzyme Replacement Therapy for CLN2 Disease: MRI Volumetry Shows Significantly Slower Volume Loss Compared with a Natural History Cohort\u0022,\u0022hwUrl\u0022:\u0022http:\\\/\\\/ajnr-stage2.stage.highwire.org\\\/content\\\/45\\\/11\\\/1791\u0022,\u0022hwPath\u0022:\u0022\\\/content\\\/45\\\/11\\\/1791\u0022,\u0022hwType\u0022:\u0022journal page\u0022},\u0022user\u0022:{\u0022hwMemberID\u0022:\u0022\u0022,\u0022hwLoggedIntoInstitutionID\u0022:\u0022\u0022,\u0022hwLoggedIntoInstitution\u0022:\u0022\u0022,\u0022hwAccessUsageTerms\u0022:\u0022guest\u0022,\u0022hwRegisteredUser\u0022:\u0022no\u0022,\u0022hwHasFullTextAccess\u0022:\u0022no\u0022,\u0022hwEntitled\u0022:\u0022no\u0022},\u0022content\u0022:{\u0022hwIssueDate\u0022:\u00222024-11-01\u0022,\u0022hwIssueDateTime\u0022:\u00222024-11-01 00:00:00\u0022,\u0022hwPublicationDate\u0022:\u00222024-11-07\u0022,\u0022hwPublicationDateTime\u0022:\u00222024-11-07 15:14:12\u0022,\u0022hwNlmArticleType\u0022:\u0022research-article\u0022,\u0022hwDOI\u0022:\u002210.3174\\\/ajnr.A8408\u0022,\u0022hwAuthors\u0022:\u0022Pritika Gaur,Paul Gissen,Asthik Biswas,Kshitij Mankad,Sniya Sudhakar,Felice D\\u2019Arco,Angela Schulz,Jens Fiehler,Jan Sedlacik,Ulrike L\\u00f6bel\u0022,\u0022hwContributors\u0022:\u0022\u0022,\u0022hwIsEarlyRelease\u0022:\u0022no\u0022,\u0022hwEissn\u0022:\u00221936-959X\u0022,\u0022hwPissn\u0022:\u00220195-6108\u0022,\u0022hwVolume\u0022:\u002245\u0022,\u0022hwIssue\u0022:\u002211\u0022,\u0022hwArticleType\u0022:\u0022Pediatric Neuroimaging\u0022,\u0022hwTabView\u0022:\u0022main_tab\u0022,\u0022hwViewType\u0022:\u0022\u0022,\u0022hwAccessType\u0022:\u0022Paywall\u0022,\u0022hwOpenAccess\u0022:\u0022no\u0022,\u0022hwFreeAccess\u0022:\u0022no\u0022,\u0022hwTaxonomy\u0022:\u0022\u0022,\u0022hwCorpusCode\u0022:\u0022ajnr\u0022,\u0022hwType\u0022:\u0022article\u0022,\u0022hwSubtitle\u0022:null,\u0022hwOverline\u0022:null,\u0022hwPisaId\u0022:\u0022ajnr;45\\\/11\\\/1791\u0022,\u0022hwFirstPage\u0022:\u00221791\u0022,\u0022hwLastPage\u0022:\u00221797\u0022,\u0022hwIsLatestVersion\u0022:\u0022yes\u0022,\u0022hwIsCurrentIssue\u0022:\u0022no\u0022,\u0022hwIsOpenIssue\u0022:\u0022no\u0022,\u0022hwHasFullText\u0022:\u0022yes\u0022,\u0022hwHasPDF\u0022:\u0022yes\u0022,\u0022hwParentTitle\u0022:\u0022American Journal of Neuroradiology: 45 (11)\u0022,\u0022hwElectronicPubDate\u0022:\u00222024-11-07\u0022,\u0022hwElectronicPubDateTime\u0022:\u00222024-11-07 15:14:12\u0022}}"},"highwire_panel_tabs":[{"panel_name":"jnl_ajnr_tab_pdf","panel_ajax_tab":"jnl_ajnr_tab_pdf"}],"panel_ajax_tab":{"path":"sites\/all\/modules\/contrib\/panels_ajax_tab"},"instances":"{\u0022highwire_abstract_tooltip\u0022:{\u0022content\u0022:{\u0022text\u0022:\u0022\u0022},\u0022style\u0022:{\u0022tip\u0022:{\u0022width\u0022:20,\u0022height\u0022:20,\u0022border\u0022:1,\u0022offset\u0022:0,\u0022corner\u0022:true},\u0022classes\u0022:\u0022qtip-custom hw-tooltip hw-abstract-tooltip qtip-shadow qtip-rounded\u0022,\u0022classes_custom\u0022:\u0022hw-tooltip hw-abstract-tooltip\u0022},\u0022position\u0022:{\u0022at\u0022:\u0022right center\u0022,\u0022my\u0022:\u0022left center\u0022,\u0022viewport\u0022:true,\u0022adjust\u0022:{\u0022method\u0022:\u0022shift\u0022}},\u0022show\u0022:{\u0022event\u0022:\u0022mouseenter click \u0022,\u0022solo\u0022:true},\u0022hide\u0022:{\u0022event\u0022:\u0022mouseleave \u0022,\u0022fixed\u0022:1,\u0022delay\u0022:\u0022100\u0022}},\u0022highwire_author_tooltip\u0022:{\u0022content\u0022:{\u0022text\u0022:\u0022\u0022},\u0022style\u0022:{\u0022tip\u0022:{\u0022width\u0022:15,\u0022height\u0022:15,\u0022border\u0022:1,\u0022offset\u0022:0,\u0022corner\u0022:true},\u0022classes\u0022:\u0022qtip-custom hw-tooltip hw-author-tooltip qtip-shadow qtip-rounded\u0022,\u0022classes_custom\u0022:\u0022hw-tooltip hw-author-tooltip\u0022},\u0022position\u0022:{\u0022at\u0022:\u0022top center\u0022,\u0022my\u0022:\u0022bottom center\u0022,\u0022viewport\u0022:true,\u0022adjust\u0022:{\u0022method\u0022:\u0022\u0022}},\u0022show\u0022:{\u0022event\u0022:\u0022mouseenter \u0022,\u0022solo\u0022:true},\u0022hide\u0022:{\u0022event\u0022:\u0022mouseleave \u0022,\u0022fixed\u0022:1,\u0022delay\u0022:\u0022100\u0022}},\u0022highwire_reflinks_tooltip\u0022:{\u0022content\u0022:{\u0022text\u0022:\u0022\u0022},\u0022style\u0022:{\u0022tip\u0022:{\u0022width\u0022:15,\u0022height\u0022:15,\u0022border\u0022:1,\u0022mimic\u0022:\u0022top center\u0022,\u0022offset\u0022:0,\u0022corner\u0022:true},\u0022classes\u0022:\u0022qtip-custom hw-tooltip hw-ref-link-tooltip qtip-shadow qtip-rounded\u0022,\u0022classes_custom\u0022:\u0022hw-tooltip hw-ref-link-tooltip\u0022},\u0022position\u0022:{\u0022at\u0022:\u0022bottom left\u0022,\u0022my\u0022:\u0022top left\u0022,\u0022viewport\u0022:true,\u0022adjust\u0022:{\u0022method\u0022:\u0022flip\u0022}},\u0022show\u0022:{\u0022event\u0022:\u0022mouseenter \u0022,\u0022solo\u0022:true},\u0022hide\u0022:{\u0022event\u0022:\u0022mouseleave \u0022,\u0022fixed\u0022:1,\u0022delay\u0022:\u0022100\u0022}}}","qtipDebug":"{\u0022leaveElement\u0022:0}","urlIsAjaxTrusted":{"\/content\/45\/11\/1791":true},"ws_fl":{"width":100,"height":21},"ws_gpo":{"size":"","annotation":"","lang":"","callback":"","width":300},"highwire_search_similar_articles":{"highwire-search-similar-articles-list-1":{"conf":{"context":"requiredcontext_entity:node_1","override_title":1,"override_title_text":"\u003Ci class=\u0022icon-caret-right\u0022\u003E\u003C\/i\u003E Similar Articles","number_per_page":"5","show_pager":0,"more_link_path":"similar\/articles","more_link":1,"empty_message":"No similar articles are available.","citation_style":"jcore_standard","title_type":"prefer_short","title_as_link":0,"display_subtitle":0,"choose_pubdate":"ppubdate","display_markup_snippet":"","display_original_link":0,"display_access_indicator":0,"display_cme_link":0,"display_access_indicator_text":0,"display_highlight_image":"0","display_variants":0,"display_supplements":0,"display_abstract_tooltip":0,"display_author_tooltip":0,"override_title_heading":"h2","citation_settings_source":"citation_manager","citation_manager_wrapper":{"citation_manager_citation":"jcore_list_title_only"},"corpus_config_wrapper":{"corpus_config_citation_context":[]},"cache_enabled":1,"cache_time":"600","short_title_options":{"char_count":"50","add_ellipsis":0},"access_indicator_settings":{"open_access":{"icon":"icon-unlock","title":"Open Access"},"user_access":{"icon":"icon-ok-sign","title":"You have access"},"no_access":{"icon":"icon-lock","title":"Restricted access"}},"pdf_download":{"display_pdf_download":0,"pdf_download_icon":"icon-cloud-download","pdf_download_text":"PDF"},"include_on_behalf":1,"show_mark_citation":0,"display_infotrieve_link":0,"infotrieve_link_settings":{"icon":"icon-usd","link_caption":"Order full text via Infotrieve"},"highlight_image_style":"","featured_image_variant":"large","featured_image_click_image":"colorbox","display_google_scholar_tooltip":1,"display_pubmed_tooltip":1,"display_advanced_search_tooltip":1,"display_author_landing_page_tooltip":1,"display_orcid_tooltip":0,"display_ads_search_tooltip":0,"display_agricola_tooltip":0,"author_site_search_path":"","display_translations":0,"display_translations_text":"","display_translations_text_icon":"","bundle_overrides_checkboxes":{"highwire_book_fragment":{"selector":0},"highwire_news_story":{"selector":0},"highwire_book_edition":{"selector":0},"highwire_article":{"selector":0},"highwire_issue":{"selector":0},"highwire_comment":{"selector":0},"highwire_fragment":{"selector":0},"highwire_book_section":{"selector":0},"highwire_journal":{"selector":0}},"bundle_overrides":{"highwire_book_fragment":{"selector":0,"citation_style":"jcore_title_and_author","cache_enabled":1,"cache_time":"600","title_type":"full","short_title_options":{"char_count":"50","add_ellipsis":0},"title_as_link":0,"display_subtitle":0,"choose_pubdate":"ppubdate","display_markup_snippet":"","highlight_image_toggle":0,"display_original_link":0,"display_access_indicator":"0","access_indicator_settings":{"open_access":{"icon":"icon-unlock","title":"Open Access"},"user_access":{"icon":"icon-ok-sign","title":"You have access"},"no_access":{"icon":"icon-lock","title":"Restricted access"}},"display_variants":0,"display_supplements":0,"pdf_download":{"display_pdf_download":0,"pdf_download_icon":"icon-cloud-download","pdf_download_text":"PDF"},"include_on_behalf":1,"cpath_prefix":"\/content","show_mark_citation":0,"display_infotrieve_link":0,"infotrieve_link_settings":{"icon":"icon-usd","link_caption":"Order full text via Infotrieve"},"display_highlight_image":0,"highlight_image_style":"thumbnail","display_fragment_caption":1,"display_parent_citation":1,"parent_citation_type":"highwire_book_section","parent_citation_settings":{"citation_style":"folio_book_sections_standard","cache_enabled":1,"cache_time":"600","title_type":"full","short_title_options":{"char_count":"50","add_ellipsis":0},"title_as_link":0,"display_subtitle":0,"choose_pubdate":"ppubdate","display_markup_snippet":"","highlight_image_toggle":0,"display_original_link":0,"display_access_indicator":0,"access_indicator_settings":{"open_access":{"icon":"icon-unlock","title":"Open Access"},"user_access":{"icon":"icon-ok-sign","title":"You have access"},"no_access":{"icon":"icon-lock","title":"Restricted access"}},"display_variants":0,"display_supplements":0,"pdf_download":{"display_pdf_download":0,"pdf_download_icon":"icon-cloud-download","pdf_download_text":"PDF"},"include_on_behalf":1,"cpath_prefix":"\/content","show_mark_citation":0,"display_infotrieve_link":0,"infotrieve_link_settings":{"icon":"icon-usd","link_caption":"Order full text via Infotrieve"},"display_highlight_image":0,"highlight_image_style":"","display_abstract_tooltip":0,"display_author_tooltip":0,"display_google_scholar_tooltip":1,"display_pubmed_tooltip":1,"display_advanced_search_tooltip":1,"display_author_landing_page_tooltip":0,"author_site_search_path":"search\/"}},"highwire_news_story":{"selector":0,"citation_style":"mla","cache_enabled":1,"cache_time":"600","title_type":"full","short_title_options":{"char_count":"50","add_ellipsis":0},"title_as_link":0,"display_subtitle":0,"choose_pubdate":"ppubdate","display_markup_snippet":"","highlight_image_toggle":0,"display_original_link":0,"display_access_indicator":0,"access_indicator_settings":{"open_access":{"icon":"icon-unlock","title":"Open Access"},"user_access":{"icon":"icon-ok-sign","title":"You have access"},"no_access":{"icon":"icon-lock","title":"Restricted access"}},"display_variants":0,"display_supplements":0,"pdf_download":{"display_pdf_download":0,"pdf_download_icon":"icon-cloud-download","pdf_download_text":"PDF"},"include_on_behalf":1,"cpath_prefix":"\/content","show_mark_citation":0,"display_infotrieve_link":0,"infotrieve_link_settings":{"icon":"icon-usd","link_caption":"Order full text via Infotrieve"},"display_highlight_image":"0","highlight_image_style":"","featured_image_click_image":"nothing","display_author_tooltip":0,"display_google_scholar_tooltip":0,"display_pubmed_tooltip":0,"display_advanced_search_tooltip":0},"highwire_book_edition":{"selector":0,"citation_style":"folio_books_standard","cache_enabled":1,"cache_time":"600","title_type":"full","short_title_options":{"char_count":"50","add_ellipsis":0},"title_as_link":0,"display_subtitle":0,"choose_pubdate":"ppubdate","display_markup_snippet":"","highlight_image_toggle":0,"display_original_link":0,"display_access_indicator":0,"access_indicator_settings":{"open_access":{"icon":"icon-unlock","title":"Open Access"},"user_access":{"icon":"icon-ok-sign","title":"You have access"},"no_access":{"icon":"icon-lock","title":"Restricted access"}},"display_variants":0,"display_supplements":0,"pdf_download":{"display_pdf_download":0,"pdf_download_icon":"icon-cloud-download","pdf_download_text":"PDF"},"include_on_behalf":1,"cpath_prefix":"\/content","show_mark_citation":0,"display_infotrieve_link":0,"infotrieve_link_settings":{"icon":"icon-usd","link_caption":"Order full text via Infotrieve"},"display_highlight_image":0,"highlight_image_style":"","display_author_tooltip":0,"display_google_scholar_tooltip":1,"display_pubmed_tooltip":1,"display_advanced_search_tooltip":1,"display_author_landing_page_tooltip":1,"display_orcid_tooltip":1,"author_site_search_path":"search\/"},"highwire_article":{"selector":0,"citation_style":"mla","cache_enabled":1,"cache_time":"600","title_type":"full","short_title_options":{"char_count":"50","add_ellipsis":0},"title_as_link":0,"display_subtitle":0,"choose_pubdate":"ppubdate","display_markup_snippet":"","highlight_image_toggle":0,"display_original_link":0,"display_access_indicator":0,"access_indicator_settings":{"open_access":{"icon":"icon-unlock","title":"Open Access"},"user_access":{"icon":"icon-ok-sign","title":"You have access"},"no_access":{"icon":"icon-lock","title":"Restricted access"}},"display_variants":0,"display_supplements":0,"pdf_download":{"display_pdf_download":0,"pdf_download_icon":"icon-cloud-download","pdf_download_text":"PDF"},"include_on_behalf":0,"cpath_prefix":"\/content","show_mark_citation":0,"display_infotrieve_link":0,"infotrieve_link_settings":{"icon":"icon-usd","link_caption":"Order full text via Infotrieve"},"display_highlight_image":"0","highlight_image_style":"","featured_image_variant":"large","featured_image_click_image":"nothing","display_cme_link":0,"display_abstract_tooltip":0,"display_author_tooltip":0,"display_google_scholar_tooltip":1,"display_pubmed_tooltip":1,"display_advanced_search_tooltip":1,"display_author_landing_page_tooltip":1,"display_orcid_tooltip":1,"display_ads_search_tooltip":0,"display_agricola_tooltip":0,"author_site_search_path":"search\/","display_translations":0,"display_translations_text":"Translations Available","display_translations_text_icon":"icon-globe"},"highwire_issue":{"selector":0,"citation_style":"mla","cache_enabled":1,"cache_time":"600","title_type":"full","short_title_options":{"char_count":"50","add_ellipsis":0},"title_as_link":0,"display_subtitle":0,"choose_pubdate":"ppubdate","display_markup_snippet":"","highlight_image_toggle":0,"display_original_link":0,"display_access_indicator":0,"access_indicator_settings":{"open_access":{"icon":"icon-unlock","title":"Open Access"},"user_access":{"icon":"icon-ok-sign","title":"You have access"},"no_access":{"icon":"icon-lock","title":"Restricted access"}},"display_variants":0,"display_supplements":0,"pdf_download":{"display_pdf_download":0,"pdf_download_icon":"icon-cloud-download","pdf_download_text":"PDF"},"include_on_behalf":1,"cpath_prefix":"\/content","show_mark_citation":0,"display_infotrieve_link":0,"infotrieve_link_settings":{"icon":"icon-usd","link_caption":"Order full text via Infotrieve"},"display_highlight_image":0,"highlight_image_style":"","featured_image_click_image":"nothing","display_author_tooltip":0,"display_google_scholar_tooltip":1,"display_pubmed_tooltip":1,"display_advanced_search_tooltip":1,"display_author_landing_page_tooltip":0,"display_orcid_tooltip":1,"author_site_search_path":"search\/"},"highwire_comment":{"selector":0,"citation_style":"highwire_comment","show_title":0,"title_as_link":0,"title_as_link_type":"tab_view","author_format_type":"fullname","author_format_custom":"","author_list_separator":", ","date_format":"(j F Y)","display_comment_body":1,"display_attachment":1,"display_conflict_of_interest":1},"highwire_fragment":{"selector":0,"citation_style":"jcore_title_and_author","cache_enabled":1,"cache_time":"600","title_type":"full","short_title_options":{"char_count":"50","add_ellipsis":0},"title_as_link":0,"display_subtitle":0,"choose_pubdate":"ppubdate","display_markup_snippet":"","highlight_image_toggle":0,"display_original_link":0,"display_access_indicator":"0","access_indicator_settings":{"open_access":{"icon":"icon-unlock","title":"Open Access"},"user_access":{"icon":"icon-ok-sign","title":"You have access"},"no_access":{"icon":"icon-lock","title":"Restricted access"}},"display_variants":0,"display_supplements":0,"pdf_download":{"display_pdf_download":0,"pdf_download_icon":"icon-cloud-download","pdf_download_text":"PDF"},"include_on_behalf":1,"cpath_prefix":"\/content","show_mark_citation":0,"display_infotrieve_link":0,"infotrieve_link_settings":{"icon":"icon-usd","link_caption":"Order full text via Infotrieve"},"display_highlight_image":0,"highlight_image_style":"","display_fragment_caption":1,"fragment_image_settings":{"fragment_image_variant":"medium","fragment_click_image":"colorbox","show_download_links":1},"display_parent_citation":1,"parent_citation_type":"highwire_article","parent_citation_settings":{"citation_style":"mla","cache_enabled":1,"cache_time":"600","title_type":"full","short_title_options":{"char_count":"50","add_ellipsis":0},"title_as_link":0,"display_subtitle":0,"choose_pubdate":"ppubdate","display_markup_snippet":"","highlight_image_toggle":0,"display_original_link":0,"display_access_indicator":0,"access_indicator_settings":{"open_access":{"icon":"icon-unlock","title":"Open Access"},"user_access":{"icon":"icon-ok-sign","title":"You have access"},"no_access":{"icon":"icon-lock","title":"Restricted access"}},"display_variants":0,"display_supplements":0,"pdf_download":{"display_pdf_download":0,"pdf_download_icon":"icon-cloud-download","pdf_download_text":"PDF"},"include_on_behalf":0,"cpath_prefix":"\/content","show_mark_citation":0,"display_infotrieve_link":0,"infotrieve_link_settings":{"icon":"icon-usd","link_caption":"Order full text via Infotrieve"},"display_highlight_image":"0","highlight_image_style":"","featured_image_variant":"large","featured_image_click_image":"nothing","display_cme_link":0,"display_abstract_tooltip":0,"display_author_tooltip":0,"display_google_scholar_tooltip":1,"display_pubmed_tooltip":1,"display_advanced_search_tooltip":1,"display_author_landing_page_tooltip":1,"display_orcid_tooltip":1,"display_ads_search_tooltip":0,"display_agricola_tooltip":0,"author_site_search_path":"search\/","display_translations":0,"display_translations_text":"Translations Available","display_translations_text_icon":"icon-globe"}},"highwire_book_section":{"selector":0,"citation_style":"folio_book_sections_standard","cache_enabled":1,"cache_time":"600","title_type":"full","short_title_options":{"char_count":"50","add_ellipsis":0},"title_as_link":0,"display_subtitle":0,"choose_pubdate":"ppubdate","display_markup_snippet":"","highlight_image_toggle":0,"display_original_link":0,"display_access_indicator":0,"access_indicator_settings":{"open_access":{"icon":"icon-unlock","title":"Open Access"},"user_access":{"icon":"icon-ok-sign","title":"You have access"},"no_access":{"icon":"icon-lock","title":"Restricted access"}},"display_variants":0,"display_supplements":0,"pdf_download":{"display_pdf_download":0,"pdf_download_icon":"icon-cloud-download","pdf_download_text":"PDF"},"include_on_behalf":1,"cpath_prefix":"\/content","show_mark_citation":0,"display_infotrieve_link":0,"infotrieve_link_settings":{"icon":"icon-usd","link_caption":"Order full text via Infotrieve"},"display_highlight_image":0,"highlight_image_style":"","display_abstract_tooltip":0,"display_author_tooltip":0,"display_google_scholar_tooltip":1,"display_pubmed_tooltip":1,"display_advanced_search_tooltip":1,"display_author_landing_page_tooltip":0,"author_site_search_path":"search\/"},"highwire_journal":{"selector":0,"citation_style":"mla","cache_enabled":1,"cache_time":"600","title_type":"full","short_title_options":{"char_count":"50","add_ellipsis":0},"title_as_link":0,"display_subtitle":0,"choose_pubdate":"ppubdate","display_markup_snippet":"","highlight_image_toggle":0,"display_original_link":0,"display_access_indicator":0,"access_indicator_settings":{"open_access":{"icon":"icon-unlock","title":"Open Access"},"user_access":{"icon":"icon-ok-sign","title":"You have access"},"no_access":{"icon":"icon-lock","title":"Restricted access"}},"display_variants":0,"display_supplements":0,"pdf_download":{"display_pdf_download":0,"pdf_download_icon":"icon-cloud-download","pdf_download_text":"PDF"},"include_on_behalf":1,"cpath_prefix":"\/content","show_mark_citation":0,"display_infotrieve_link":0,"infotrieve_link_settings":{"icon":"icon-usd","link_caption":"Order full text via Infotrieve"},"display_highlight_image":0,"highlight_image_style":"","display_author_tooltip":0,"display_google_scholar_tooltip":1,"display_pubmed_tooltip":1,"display_advanced_search_tooltip":1,"display_author_landing_page_tooltip":0,"display_orcid_tooltip":1,"author_site_search_path":"search\/"}},"cpath_prefix":"\/content","ajax_loading_icon_classes":"icon-spinner icon-spin icon-2x","ajax_loading_text":"","highlight_image_toggle":0,"more_link_label":"See more","url_parameters":{"q":"node\/111459"}},"nid":"111459"}},"panels_accordion":{"highwire_article_accordion_container":{"heightStyle":"content","autoHeight":false,"collapsible":0,"region_accordion_id":"highwire_article_accordion_container","active":0,"animated":"slide"}},"color":{"logo":"http:\/\/ajnr-stage2.stage.highwire.org\/sites\/default\/files\/ajnr-web-logo_0.png"},"nice_menus_options":{"delay":800,"speed":"fast"},"highwireResponsive":{"enquire_enabled":1,"breakpoints_configured":1,"breakpoints":{"zero":"all and (min-width: 0px)","xsmall":"all and (min-width: 380px)","narrow":"all and (min-width: 768px) and (min-device-width: 768px), (max-device-width: 800px) and (min-width: 768px) and (orientation:landscape)","normal":"all and (min-width: 980px) and (min-device-width: 980px), all and (max-device-width: 1024px) and (min-width: 1024px) and (orientation:landscape)","wide":"all and (min-width: 1220px)"}},"eu_cookie_compliance":{"popup_enabled":1,"popup_agreed_enabled":0,"popup_hide_agreed":false,"popup_clicking_confirmation":true,"popup_scrolling_confirmation":false,"popup_html_info":"\u003Cdiv\u003E\n  \u003Cdiv class=\u0022popup-content info\u0022\u003E\n    \u003Cdiv id=\u0022popup-text\u0022\u003E\n      \u003Cp\u003EWe use cookies on this site to enhance your user experience. By clicking any link on this page you are giving your consent for us to set cookies.\u003C\/p\u003E\n    \u003C\/div\u003E\n    \u003Cdiv id=\u0022popup-buttons\u0022\u003E\n      \u003Cbutton type=\u0022button\u0022 role=\u0022dialog\u0022 aria-labelledby=\u0022Continue\u0022\n        class=\u0022agree-button eu-cookie-compliance-default-button\u0022\u003EContinue\u003C\/button\u003E\n                  \u003Cbutton type=\u0022button\u0022 role=\u0022dialog\u0022 aria-labelledby=\u0022Find out more\u0022\n        class=\u0022find-more-button eu-cookie-compliance-more-button\u0022\u003EFind out more\u003C\/button\u003E\n          \u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E","use_mobile_message":false,"mobile_popup_html_info":"\u003Cdiv\u003E\n  \u003Cdiv class=\u0022popup-content info\u0022\u003E\n    \u003Cdiv id=\u0022popup-text\u0022\u003E\n          \u003C\/div\u003E\n    \u003Cdiv id=\u0022popup-buttons\u0022\u003E\n      \u003Cbutton type=\u0022button\u0022 role=\u0022dialog\u0022 aria-labelledby=\u0022Continue\u0022\n        class=\u0022agree-button eu-cookie-compliance-default-button\u0022\u003EContinue\u003C\/button\u003E\n                  \u003Cbutton type=\u0022button\u0022 role=\u0022dialog\u0022 aria-labelledby=\u0022Find out more\u0022\n        class=\u0022find-more-button eu-cookie-compliance-more-button\u0022\u003EFind out more\u003C\/button\u003E\n          \u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E","mobile_breakpoint":"768","popup_html_agreed":"\u003Cdiv\u003E\n  \u003Cdiv class=\u0022popup-content agreed\u0022\u003E\n    \u003Cdiv id=\u0022popup-text\u0022\u003E\n      \u003Cp\u003EThank you for accepting cookies. You can now hide this message or find out more about cookies.\u003C\/p\u003E\n    \u003C\/div\u003E\n    \u003Cdiv id=\u0022popup-buttons\u0022\u003E\n      \u003Cbutton type=\u0022button\u0022 class=\u0022hide-popup-button eu-cookie-compliance-hide-button\u0022\u003EHide\u003C\/button\u003E\n              \u003Cbutton type=\u0022button\u0022 class=\u0022find-more-button eu-cookie-compliance-more-button-thank-you\u0022 \u003EFind out more\u003C\/button\u003E\n          \u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E","popup_use_bare_css":false,"popup_height":"auto","popup_width":"100%","popup_delay":1000,"popup_link":"\/help\/cookie-policy","popup_link_new_window":1,"popup_position":null,"popup_language":"en","store_consent":false,"better_support_for_screen_readers":0,"reload_page":0,"domain":"","popup_eu_only_js":0,"cookie_lifetime":365,"cookie_session":false,"disagree_do_not_show_popup":0,"method":"default","whitelisted_cookies":"","withdraw_markup":"\u003Cbutton type=\u0022button\u0022 class=\u0022eu-cookie-withdraw-tab\u0022\u003EPrivacy settings\u003C\/button\u003E\n\u003Cdiv class=\u0022eu-cookie-withdraw-banner\u0022\u003E\n  \u003Cdiv class=\u0022popup-content info\u0022\u003E\n    \u003Cdiv id=\u0022popup-text\u0022\u003E\n      \u003Cp\u003E\u0026lt;h2\u0026gt;We use cookies on this site to enhance your user experience\u0026lt;\/h2\u0026gt;\u0026lt;p\u0026gt;You have given your consent for us to set cookies.\u0026lt;\/p\u0026gt;\u003C\/p\u003E\n    \u003C\/div\u003E\n    \u003Cdiv id=\u0022popup-buttons\u0022\u003E\n      \u003Cbutton type=\u0022button\u0022 class=\u0022eu-cookie-withdraw-button\u0022\u003EWithdraw consent\u003C\/button\u003E\n    \u003C\/div\u003E\n  \u003C\/div\u003E\n\u003C\/div\u003E\n","withdraw_enabled":false},"googleanalytics":{"account":["G-4CRTLTY8KW"],"trackOutbound":1,"trackMailto":1,"trackDownload":1,"trackDownloadExtensions":"7z|aac|arc|arj|asf|asx|avi|bin|csv|doc(x|m)?|dot(x|m)?|exe|flv|gif|gz|gzip|hqx|jar|jpe?g|js|mp(2|3|4|e?g)|mov(ie)?|msi|msp|pdf|phps|png|ppt(x|m)?|pot(x|m)?|pps(x|m)?|ppam|sld(x|m)?|thmx|qtm?|ra(m|r)?|sea|sit|tar|tgz|torrent|txt|wav|wma|wmv|wpd|xls(x|m|b)?|xlt(x|m)|xlam|xml|z|zip","trackColorbox":1},"omega":{"layouts":{"primary":"normal","order":["narrow","normal","wide"],"queries":{"narrow":"all and (min-width: 768px) and (min-device-width: 768px), (max-device-width: 800px) and (min-width: 768px) and (orientation:landscape)","normal":"all and (min-width: 980px) and (min-device-width: 980px), all and (max-device-width: 1024px) and (min-width: 1024px) and (orientation:landscape)","wide":"all and (min-width: 1220px)"}}}});
//--><!]]>
</script>
    <!--[if lt IE 9]><script src="http://html5shiv.googlecode.com/svn/trunk/html5.js"></script><![endif]-->
  </head>
  <body class="html not-front not-logged-in page-node page-node- page-node-111459 node-type-highwire-article context-content hw-default-jcode-ajnr hw-article-type-research-article hw-article-category-pediatric-neuroimaging">
<!-- Google Tag Manager -->
<noscript><iframe src="//www.googletagmanager.com/ns.html?id=GTM-MXP45WNH" height="0" width="0" style="display:none;visibility:hidden"></iframe></noscript>
<script type="text/javascript">(function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0];var j=d.createElement(s);var dl=l!='dataLayer'?'&l='+l:'';j.src='//www.googletagmanager.com/gtm.js?id='+i+dl;j.type='text/javascript';j.async=true;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-MXP45WNH');</script>
<!-- End Google Tag Manager -->
    <div id="skip-link">
      <a href="#main-content" class="element-invisible element-focusable">Skip to main content</a>
    </div>
    <div class="region region-page-top" id="region-page-top">
  <div class="region-inner region-page-top-inner">
      </div>
</div>    <div class="page clearfix footer-borders panels-page panels-layout-jcore_2col" id="page">
      <header id="section-header" class="section section-header">
  <div id="zone-advertising-top-wrapper" class="zone-wrapper zone-advertising-top-wrapper clearfix">  
  <div id="zone-advertising-top" class="zone zone-advertising-top clearfix container-30">
    <div class="grid-28 suffix-1 prefix-1 region region-ad-top" id="region-ad-top">
  <div class="region-inner region-ad-top-inner">
    <div class="block block-panels-mini mobile-hiddens rtecenter block-jnl-ajnr-ad-leaderboard block-panels-mini-jnl-ajnr-ad-leaderboard odd block-without-title" id="block-panels-mini-jnl-ajnr-ad-leaderboard">
  <div class="block-inner clearfix">
                
    <div class="content clearfix">
      <div class="panel-display panel-1col clearfix" id="mini-panel-jnl_ajnr_ad_leaderboard">
  <div class="panel-panel panel-col">
    <div><div class="panel-pane pane-dfp-pane text-center" >
  
      
  
  <div class="pane-content">
    <div id="dfp-ad-top_leaderboard-wrapper" class="dfp-tag-wrapper">
<div class="slug">Advertisement</div>
<div  id="dfp-ad-top_leaderboard" class="dfp-tag-wrapper">
  <script type="text/javascript">
    googletag.cmd.push(function() {
      googletag.display("dfp-ad-top_leaderboard");
    });
  </script>
</div>
</div>  </div>

  
  </div>
</div>
  </div>
</div>
    </div>
  </div>
</div>  </div>
</div>  </div>
</div><div id="zone-superheader-wrapper" class="zone-wrapper zone-superheader-wrapper clearfix mobile-only print-hidden">  
  <div id="zone-superheader" class="zone zone-superheader clearfix mobile-only print-hidden container-30">
    <div class="grid-30 region region-superheader" id="region-superheader">
  <div class="region-inner region-superheader-inner">
    <div class="block block-panels-mini block-responsive-menu block-panels-mini-responsive-menu odd block-without-title" id="block-panels-mini-responsive-menu">
  <div class="block-inner clearfix">
                
    <div class="content clearfix">
      <div class="panel-display panel-1col clearfix" id="mini-panel-responsive_menu">
  <div class="panel-panel panel-col">
    <div><div id="unique-id3" class="highwire-responsive-toggle-group"><div class="panel-pane pane-panels-mini pane-responsive-menu-main-menu" >
  
        <h2 class="pane-title"><span class="icon-reorder"></span><span class="element-invisible">Main menu</span></h2>
    
  
  <div class="pane-content">
    <div class="panel-display panel-1col clearfix" id="mini-panel-responsive_menu_main_menu">
  <div class="panel-panel panel-col">
    <div><div class="panel-pane pane-menu-tree pane-main-menu" >
  
      
  
  <div class="pane-content">
    <div class="menu-block-wrapper menu-block-ctools-main-menu-1 menu-name-main-menu parent-mlid-main-menu:0 menu-level-1">
  <nav class="menubar-nav"><ul class="menu" role="menu"><li class="first leaf menu-mlid-772" role="menuitem"><a href="/" class="" data-icon-position="" data-hide-link-title="0">Home</a></li>
<li class="expanded active-trail menu-mlid-773" role="menuitem"><a href="/content/current" data-hide-link-title="0" class="active active-trail" data-icon-position="">Content</a><nav class="menubar-nav"><ul class="menu" role="menu"><li class="first expanded menu-mlid-774" role="menuitem"><a href="/content/current" data-hide-link-title="0" class="" data-icon-position="">Current Issue</a></li>
<li class="leaf menu-mlid-1747" role="menuitem"><a href="/content/early/preprint" data-hide-link-title="0" class="" data-icon-position="">Publication Preview--Preprint</a></li>
<li class="leaf menu-mlid-775" role="menuitem"><a href="/content/early/recent" data-hide-link-title="0" class="" data-icon-position="">Publication Preview--Ahead of Print</a></li>
<li class="leaf menu-mlid-776" role="menuitem"><a href="/content/by/year" data-hide-link-title="0" class="" data-icon-position="">Past Issue Archive</a></li>
<li class="leaf menu-mlid-900" role="menuitem"><a href="/cow/by/year" data-hide-link-title="0" class="" data-icon-position="">Case of the Week Archive</a></li>
<li class="leaf menu-mlid-1006" role="menuitem"><a href="/cc/by/year" data-hide-link-title="0" class="" data-icon-position="">Classic Case Archive</a></li>
<li class="leaf menu-mlid-901" role="menuitem"><a href="/com/by/year" data-hide-link-title="0" class="" data-icon-position="">Case of the Month Archive</a></li>
<li class="last leaf menu-mlid-1334" role="menuitem"><a href="http://www.ajnr.org/content/covid-19-content-and-resources" data-hide-link-title="0" class="" data-icon-position="">COVID-19 Content and Resources</a></li>
</ul></nav></li>
<li class="expanded menu-mlid-784" role="menuitem"><a href="/content/about-us" class="" data-icon-position="" data-hide-link-title="0">About Us</a><nav class="menubar-nav"><ul class="menu" role="menu"><li class="first leaf menu-mlid-785" role="menuitem"><a href="/page/content/About" data-hide-link-title="0" class="" data-icon-position="">About AJNR</a></li>
<li class="leaf menu-mlid-899" role="menuitem"><a href="https://www.ajnr.org/page/content/Ed-Board" data-hide-link-title="0" class="" data-icon-position="">Editorial Board</a></li>
<li class="last leaf menu-mlid-864" role="menuitem"><a href="http://www.asnr.org" data-hide-link-title="0" target="_blank" class="" data-icon-position="">American Society of Neuroradiology</a></li>
</ul></nav></li>
<li class="expanded menu-mlid-1746" role="menuitem"><a href="/" class="" data-icon-position="" data-hide-link-title="0">For Authors</a><nav class="menubar-nav"><ul class="menu" role="menu"><li class="first leaf menu-mlid-1725" role="menuitem"><a href="https://www.ajnr.org/content/author-policies" data-hide-link-title="0" class="" data-icon-position="">Author Policies</a></li>
<li class="leaf menu-mlid-1856" role="menuitem"><a href="https://www.ajnr.org/preprint_publishing" data-hide-link-title="0" class="" data-icon-position="">Preprint Publishing</a></li>
<li class="last leaf menu-mlid-1726" role="menuitem"><a href="https://www.ajnr.org/content/manuscript-submission-guidelines" data-hide-link-title="0" class="" data-icon-position="">Manuscript Submission Guidelines</a></li>
</ul></nav></li>
<li class="leaf menu-mlid-862" role="menuitem"><a href="https://mc.manuscriptcentral.com/ajnr" data-hide-link-title="0" target="_blank" class="" data-icon-position="">Submit a Manuscript</a></li>
<li class="expanded menu-mlid-1184" role="menuitem"><a href="/content/about-us" data-hide-link-title="0" class="" data-icon-position="">Special Collections</a><nav class="menubar-nav"><ul class="menu" role="menu"><li class="first leaf menu-mlid-1733" role="menuitem"><a href="http://www.ajnr.org/cc/CSF-Spinal-Leak" data-hide-link-title="0" class="" data-icon-position="">Spinal CSF Leak Articles (Jan 2020-June 2024)</a></li>
<li class="leaf menu-mlid-1185" role="menuitem"><a href="http://www.ajnr.org/cc/most-impactful-ajnr-articles" data-hide-link-title="0" class="" data-icon-position="">Most Impactful AJNR Articles</a></li>
<li class="last leaf menu-mlid-1896" role="menuitem"><a href="http://www.ajnr.org/cc/2024-Awards" data-hide-link-title="0" class="" data-icon-position="">2024 AJNR Journal Awards</a></li>
</ul></nav></li>
<li class="last expanded menu-mlid-788" role="menuitem"><a href="/content/advertising" class="" data-icon-position="" data-hide-link-title="0">More</a><nav class="menubar-nav"><ul class="menu" role="menu"><li class="first leaf menu-mlid-780" role="menuitem"><a href="/content/subscriber-help-and-services" data-hide-link-title="0" class="" data-icon-position="">Subscribers</a></li>
<li class="leaf menu-mlid-863" role="menuitem"><a href="https://marketplace.copyright.com/rs-ui-web/mp/details/journal/122810747" data-hide-link-title="0" class="" data-icon-position="">Permissions</a></li>
<li class="leaf menu-mlid-782" role="menuitem"><a href="/page/content/Ads" data-hide-link-title="0" class="" data-icon-position="">Advertisers</a></li>
<li class="leaf menu-mlid-790" role="menuitem"><a href="/alerts" data-hide-link-title="0" class="" data-icon-position="">Alerts</a></li>
<li class="last leaf menu-mlid-791" role="menuitem"><a href="/feedback" class="" data-icon-position="" data-hide-link-title="0">Feedback</a></li>
</ul></nav></li>
</ul></nav></div>
  </div>

  
  </div>
</div>
  </div>
</div>
  </div>

  
  </div>
<div class="panel-pane pane-panels-mini pane-responsive-menu-user-menu" >
  
        <h2 class="pane-title"><span class="icon-gear"></span><span class="element-invisible">User menu</span></h2>
    
  
  <div class="pane-content">
    <div class="panel-display panel-1col clearfix" id="mini-panel-responsive_menu_user_menu">
  <div class="panel-panel panel-col">
    <div><div class="panel-pane pane-menu-tree pane-user-menu" >
  
      
  
  <div class="pane-content">
    <div class="menu-block-wrapper menu-block-ctools-user-menu-1 menu-name-user-menu parent-mlid-user-menu:0 menu-level-1">
  <nav class="menubar-nav"><ul class="menu" role="menu"><li class="first leaf menu-mlid-801" role="menuitem"><a href="/content/subscriber-help-and-services" data-hide-link-title="0" class="" data-icon-position="">Subscribe</a></li>
<li class="leaf menu-mlid-802" role="menuitem"><a href="/alerts" data-hide-link-title="0" class="" data-icon-position="">Alerts</a></li>
<li class="leaf menu-mlid-803" role="menuitem"><a href="/user/login?destination=/content/45/11/1791" class="" data-icon-position="" data-hide-link-title="0">Log in</a></li>
<li class="last leaf menu-mlid-17" role="menuitem"><a href="/user/logout?current=node/111459" class="" data-icon-position="" data-hide-link-title="0">Log out</a></li>
</ul></nav></div>
  </div>

  
  </div>
<div class="panel-separator"></div><div class="panel-pane pane-highwire-user-identities" >
  
      
  
  <div class="pane-content">
    <div class="highwire-user-message" data-separator="|"><span class="highwire-user-institution" data-id-type="institution" data-identity="a%3A2%3A%7Bs%3A4%3A%22show%22%3Bi%3A1%3Bs%3A7%3A%22message%22%3Bs%3A50%3A%22Institution%3A%20%5Bidentity%3Ainstitutional_display_name%5D%22%3B%7D"></span></div>  </div>

  
  </div>
</div>
  </div>
</div>
  </div>

  
  </div>
<div class="panel-pane pane-panels-mini pane-responsive-menu-search" >
  
        <h2 class="pane-title"><span class="icon-search"></span><span class="element-invisible">Search</span></h2>
    
  
  <div class="pane-content">
    <div class="panel-display panel-1col clearfix" id="mini-panel-responsive_menu_search">
  <div class="panel-panel panel-col">
    <div><div class="panel-pane pane-highwire-seach-qsearch-nocontext" >
  
      
  
  <div class="pane-content">
    <form class="highwire-quicksearch button-style-mini button-style-mini" action="/content/45/11/1791" method="post" id="highwire-search-qsearch-nocontext-form" accept-charset="UTF-8"><div><div class="form-item form-item-label-invisible form-type-textfield form-item-keywords">
  <label class="element-invisible" for="quick_search_header_keywords_1196494910">Search for this keyword </label>
 <input placeholder="Search..." type="text" id="quick_search_header_keywords_1196494910" name="keywords" value="" size="60" maxlength="128" class="form-text" />
</div>
<div class="button-wrapper button-mini"><span class="icon-search"></span><input data-icon-only="1" data-font-icon="icon-search" data-icon-position="after" type="submit" id="quick_search_header_submit_1922655596" name="op" value="Search" class="form-submit" /></div><input type="hidden" name="form_build_id" value="form-pSVZ2j9qUPEwjiOZ7Y1ICsTGsdQZ7Bb-jHMY63Nz0k4" />
<input type="hidden" name="form_id" value="highwire_search_qsearch_nocontext_form" />
</div></form>  </div>

  
  </div>
<div class="panel-separator"></div><div class="panel-pane pane-custom pane-1 highwire-responsive-advanced-search-link pane-menu-tree" >
  
      
  
  <div class="pane-content">
    <ul class="menu">
  <li><a href="/search" title="Advanced search">Advanced search</a></li>
  </ul>  </div>

  
  </div>
</div>
  </div>
</div>
  </div>

  
  </div>
</div></div>
  </div>
</div>
    </div>
  </div>
</div><div class="block block-panels-mini block-hw-small-logo block-panels-mini-hw-small-logo even block-without-title" id="block-panels-mini-hw-small-logo">
  <div class="block-inner clearfix">
                
    <div class="content clearfix">
      <div class="panel-display panel-1col clearfix" id="mini-panel-hw_small_logo">
  <div class="panel-panel panel-col">
    <div><div class="panel-pane pane-small-logo" >
  
      
  
  <div class="pane-content">
    <a href="/" class="" data-icon-position="" data-hide-link-title="0"><img src="http://ajnr-stage2.stage.highwire.org/sites/default/files/ajnr-logo.png" alt="American Journal of Neuroradiology" title="American Journal of Neuroradiology" /></a>  </div>

  
  </div>
</div>
  </div>
</div>
    </div>
  </div>
</div>  </div>
</div>  </div>
</div><div id="zone-user-wrapper" class="zone-wrapper zone-user-wrapper clearfix mobile-hidden print-hidden">  
  <div id="zone-user" class="zone zone-user clearfix equal-height-container mobile-hidden print-hidden container-30">    
  	    <div class="grid-30 region region-user-second equal-height-element" id="region-user-second">
  <div class="region-inner region-user-second-inner">
    <div class="block block-panels-mini text-right no-margin-bottom block-jnl-ajnr-uid-strng block-panels-mini-jnl-ajnr-uid-strng odd block-without-title" id="block-panels-mini-jnl-ajnr-uid-strng">
  <div class="block-inner clearfix">
                
    <div class="content clearfix">
      <div class="panel-display panel-1col clearfix" id="mini-panel-jnl_ajnr_uid_strng">
  <div class="panel-panel panel-col">
    <div><div class="panel-pane pane-highwire-user-identities" >
  
      
  
  <div class="pane-content">
    <div class="highwire-user-message" data-separator=" | "><span class="highwire-user-institution" data-id-type="institution" data-identity="a%3A2%3A%7Bs%3A4%3A%22show%22%3Bi%3A1%3Bs%3A7%3A%22message%22%3Bs%3A85%3A%22%3Cspan%20class%3D%22narrow-hidden%22%3EInstitution%3A%20%3C%2Fspan%3E%5Bidentity%3Ainstitutional_display_name%5D%22%3B%7D"></span></div>  </div>

  
  </div>
</div>
  </div>
</div>
    </div>
  </div>
</div>  </div>
</div>  </div>
</div>  
  <div id="zone-branding" class="zone zone-branding clearfix mobile-hidden print-display-block container-30">
    <div class="grid-19 prefix-1 region region-branding print-display-block" id="region-branding">
  <div class="region-inner region-branding-inner">
        <div class="branding-data clearfix">
            <div class="logo-img">
        <a href="/" rel="home" class="" data-icon-position="" data-hide-link-title="0"><img alt="American Journal of Neuroradiology" src="http://ajnr-stage2.stage.highwire.org/sites/default/files/ajnr-web-logo_0.png" /></a>      </div>
                        <hgroup class="site-name-slogan element-invisible">        
                                <h2 class="site-name element-invisible"><a href="/" title="Home" class="" data-icon-position="" data-hide-link-title="0">American Journal of Neuroradiology</a></h2>
                              </hgroup>
          </div>
          </div>
</div><div class="grid-9 suffix-1 region region-branding-second print-hidden" id="region-branding-second">
  <div class="region-inner region-branding-second-inner">
    <div class="block block-panels-mini text-right no-margin-bottom block-jnl-ajnr-user-menu block-panels-mini-jnl-ajnr-user-menu odd block-without-title" id="block-panels-mini-jnl-ajnr-user-menu">
  <div class="block-inner clearfix">
                
    <div class="content clearfix">
      <div class="panel-display panel-1col clearfix" id="mini-panel-jnl_ajnr_user_menu">
  <div class="panel-panel panel-col">
    <div><div class="panel-pane pane-block pane-system-user-menu links inline pane-system" >
  
      
  
  <div class="pane-content">
    <nav class="menubar-nav"><ul class="menu" role="menu"><li class="first leaf" role="menuitem"><a href="/content/subscriber-help-and-services" data-hide-link-title="0" class="" data-icon-position="">Subscribe</a></li>
<li class="leaf" role="menuitem"><a href="/alerts" data-hide-link-title="0" class="" data-icon-position="">Alerts</a></li>
<li class="leaf" role="menuitem"><a href="/user/login?destination=/content/45/11/1791" class="" data-icon-position="" data-hide-link-title="0">Log in</a></li>
<li class="last leaf" role="menuitem"><a href="/user/logout?current=node/111459" class="" data-icon-position="" data-hide-link-title="0">Log out</a></li>
</ul></nav>  </div>

  
  </div>
</div>
  </div>
</div>
    </div>
  </div>
</div><div class="block block-panels-mini block-jnl-ajnr-search-box block-panels-mini-jnl-ajnr-search-box even block-without-title" id="block-panels-mini-jnl-ajnr-search-box">
  <div class="block-inner clearfix">
                
    <div class="content clearfix">
      <div class="panel-display panel-1col clearfix" id="mini-panel-jnl_ajnr_search_box">
  <div class="panel-panel panel-col">
    <div><div class="panel-pane pane-highwire-seach-quicksearch no-margin-bottom" >
  
      
  
  <div class="pane-content">
    <form class="highwire-quicksearch button-style-mini button-style-mini" action="/content/45/11/1791" method="post" id="highwire-search-quicksearch-form-0" accept-charset="UTF-8"><div><div class="form-item form-item-label-invisible form-type-textfield form-item-keywords">
  <label class="element-invisible" for="search_rightsidebar_keywords_1025285001">Search for this keyword </label>
 <input placeholder="search" type="text" id="search_rightsidebar_keywords_1025285001" name="keywords" value="" size="60" maxlength="128" class="form-text" />
</div>
<div class="button-wrapper button-mini"><span class="icon-search"></span><input data-icon-only="1" data-font-icon="icon-search" data-icon-position="after" type="submit" id="search_rightsidebar_submit_1864835820" name="op" value="Search" class="form-submit" /></div><input type="hidden" name="form_build_id" value="form-Z4TJ0Xy1pIEaeCCfD3Txb3aSnpolih2wnZjFhpjTPE0" />
<input type="hidden" name="form_id" value="highwire_search_quicksearch_form_0" />
</div></form>  </div>

  
  </div>
<div class="panel-separator"></div><div class="panel-pane pane-custom pane-2" >
  
      
  
  <div class="pane-content">
    <p><a href="/search">Advanced Search</a></p>  </div>

  
  </div>
</div>
  </div>
</div>
    </div>
  </div>
</div>  </div>
</div>  </div>
  
  <div id="zone-menu" class="zone zone-menu clearfix mobile-hidden container-30">
    <div class="grid-28 suffix-1 prefix-1 region region-menu region-menu-bg-opaque region-menu-no-border" id="region-menu">
  <div class="region-inner region-menu-inner">
        <div class="block block-nice-menus block-1 block-nice-menus-1 odd block-without-title" id="block-nice-menus-1">
  <div class="block-inner clearfix">
                
    <div class="content clearfix">
      <nav class="menubar-nav"><ul class="nice-menu nice-menu-down nice-menu-main-menu" id="nice-menu-1" role="menu"><li class="menu-772 menu-path-front first odd " role="menuitem"><a href="/" class="" data-icon-position="" data-hide-link-title="0">Home</a></li>
<li class="menu-773 menuparent  menu-path-content-current active-trail  even " role="menuitem"><a href="/content/current" data-hide-link-title="0" class="active" data-icon-position="">Content</a><ul role="menu"><li class="menu-774 menu-path-content-current first odd " role="menuitem"><a href="/content/current" data-hide-link-title="0" class="" data-icon-position="">Current Issue</a></li>
<li class="menu-1747 menu-path-content-early-preprint  even " role="menuitem"><a href="/content/early/preprint" data-hide-link-title="0" class="" data-icon-position="">Publication Preview--Preprint</a></li>
<li class="menu-775 menu-path-content-early-recent  odd " role="menuitem"><a href="/content/early/recent" data-hide-link-title="0" class="" data-icon-position="">Publication Preview--Ahead of Print</a></li>
<li class="menu-776 menu-path-content-by-year  even " role="menuitem"><a href="/content/by/year" data-hide-link-title="0" class="" data-icon-position="">Past Issue Archive</a></li>
<li class="menu-900 menu-path-cow-by-year  odd " role="menuitem"><a href="/cow/by/year" data-hide-link-title="0" class="" data-icon-position="">Case of the Week Archive</a></li>
<li class="menu-1006 menu-path-cc-by-year  even " role="menuitem"><a href="/cc/by/year" data-hide-link-title="0" class="" data-icon-position="">Classic Case Archive</a></li>
<li class="menu-901 menu-path-com-by-year  odd " role="menuitem"><a href="/com/by/year" data-hide-link-title="0" class="" data-icon-position="">Case of the Month Archive</a></li>
<li class="menu-1334 menu-path-ajnrorg-content-covid-19-content-and-resources  even last" role="menuitem"><a href="http://www.ajnr.org/content/covid-19-content-and-resources" data-hide-link-title="0" class="" data-icon-position="">COVID-19 Content and Resources</a></li>
</ul></li>
<li class="menu-784 menuparent  menu-path-node-7  odd " role="menuitem"><a href="/content/about-us" class="" data-icon-position="" data-hide-link-title="0">About Us</a><ul role="menu"><li class="menu-785 menu-path-node-935 first odd " role="menuitem"><a href="/page/content/About" data-hide-link-title="0" class="" data-icon-position="">About AJNR</a></li>
<li class="menu-899 menu-path-sajnrorg-page-content-ed-board  even " role="menuitem"><a href="https://www.ajnr.org/page/content/Ed-Board" data-hide-link-title="0" class="" data-icon-position="">Editorial Board</a></li>
<li class="menu-864 menu-path-asnrorg  odd last" role="menuitem"><a href="http://www.asnr.org" data-hide-link-title="0" target="_blank" class="" data-icon-position="">American Society of Neuroradiology</a></li>
</ul></li>
<li class="menu-1746 menuparent  menu-path-front  even " role="menuitem"><a href="/" class="" data-icon-position="" data-hide-link-title="0">For Authors</a><ul role="menu"><li class="menu-1725 menu-path-sajnrorg-content-author-policies first odd " role="menuitem"><a href="https://www.ajnr.org/content/author-policies" data-hide-link-title="0" class="" data-icon-position="">Author Policies</a></li>
<li class="menu-1856 menu-path-sajnrorg-preprint-publishing  even " role="menuitem"><a href="https://www.ajnr.org/preprint_publishing" data-hide-link-title="0" class="" data-icon-position="">Preprint Publishing</a></li>
<li class="menu-1726 menu-path-sajnrorg-content-manuscript-submission-guidelines  odd last" role="menuitem"><a href="https://www.ajnr.org/content/manuscript-submission-guidelines" data-hide-link-title="0" class="" data-icon-position="">Manuscript Submission Guidelines</a></li>
</ul></li>
<li class="menu-862 menu-path-smcmanuscriptcentralcom-ajnr  odd " role="menuitem"><a href="https://mc.manuscriptcentral.com/ajnr" data-hide-link-title="0" target="_blank" class="" data-icon-position="">Submit a Manuscript</a></li>
<li class="menu-1184 menuparent  menu-path-node-7  even " role="menuitem"><a href="/content/about-us" data-hide-link-title="0" class="" data-icon-position="">Special Collections</a><ul role="menu"><li class="menu-1733 menu-path-ajnrorg-cc-csf-spinal-leak first odd " role="menuitem"><a href="http://www.ajnr.org/cc/CSF-Spinal-Leak" data-hide-link-title="0" class="" data-icon-position="">Spinal CSF Leak Articles (Jan 2020-June 2024)</a></li>
<li class="menu-1185 menu-path-ajnrorg-cc-most-impactful-ajnr-articles  even " role="menuitem"><a href="http://www.ajnr.org/cc/most-impactful-ajnr-articles" data-hide-link-title="0" class="" data-icon-position="">Most Impactful AJNR Articles</a></li>
<li class="menu-1896 menu-path-ajnrorg-cc-2024-awards  odd last" role="menuitem"><a href="http://www.ajnr.org/cc/2024-Awards" data-hide-link-title="0" class="" data-icon-position="">2024 AJNR Journal Awards</a></li>
</ul></li>
<li class="menu-788 menuparent  menu-path-node-9  odd last" role="menuitem"><a href="/content/advertising" class="" data-icon-position="" data-hide-link-title="0">More</a><ul role="menu"><li class="menu-780 menu-path-node-960 first odd " role="menuitem"><a href="/content/subscriber-help-and-services" data-hide-link-title="0" class="" data-icon-position="">Subscribers</a></li>
<li class="menu-863 menu-path-smarketplacecopyrightcom-rs-ui-web-mp-details-journal-122810747  even " role="menuitem"><a href="https://marketplace.copyright.com/rs-ui-web/mp/details/journal/122810747" data-hide-link-title="0" class="" data-icon-position="">Permissions</a></li>
<li class="menu-782 menu-path-node-937  odd " role="menuitem"><a href="/page/content/Ads" data-hide-link-title="0" class="" data-icon-position="">Advertisers</a></li>
<li class="menu-790 menu-path-alerts  even " role="menuitem"><a href="/alerts" data-hide-link-title="0" class="" data-icon-position="">Alerts</a></li>
<li class="menu-791 menu-path-node-10  odd last" role="menuitem"><a href="/feedback" class="" data-icon-position="" data-hide-link-title="0">Feedback</a></li>
</ul></li>
</ul></nav>
    </div>
  </div>
</div><div class="block block-menu text-right block-menu-social-media block-menu-menu-social-media even block-without-title" id="block-menu-menu-social-media">
  <div class="block-inner clearfix">
                
    <div class="content clearfix">
      <nav class="menubar-nav"><ul class="menu" role="menu"><li class="first leaf" role="menuitem"><a href="http://www.twitter.com/TheAJNR" target="_blank" class="link-icon-only link-icon"><span class="hw-icon-x-twitter"></span> <span class="title element-invisible">Follow AJNR on Twitter</span></a></li>
<li class="leaf" role="menuitem"><a href="http://www.facebook.com/AmJNeuroradiol" target="_blank" class="link-icon-only link-icon"><span class="icon-facebook-sign icon-2x"></span> <span class="title element-invisible">Visit AJNR on Facebook</span></a></li>
<li class="leaf" role="menuitem"><a href="https://www.instagram.com/the_ajnr/?hl=en" class="link-icon-only link-icon"><span class="icon-instagram icon-2x"></span> <span class="title element-invisible">Follow AJNR on Instagram</span></a></li>
<li class="leaf" role="menuitem"><a href="https://www.linkedin.com/company/american-journal-of-neuroradiology" class="link-icon-only link-icon"><span class="icon-linkedin icon-2x"></span> <span class="title element-invisible">Join AJNR on LinkedIn</span></a></li>
<li class="last leaf" role="menuitem"><a href="/rss" class="link-icon-only link-icon"><span class="icon-rss icon-2x"></span> <span class="title element-invisible">RSS Feeds</span></a></li>
</ul></nav>    </div>
  </div>
</div>  </div>
</div>
  </div>
  
  <div id="zone-header" class="zone zone-header clearfix container-30">
  	      </div>
</header>    
      <section id="section-content" class="section section-content">
    
  <div id="zone-content" class="zone zone-content clearfix container-30">    
        
    <div class="grid-28 suffix-1 prefix-1 region region-content" id="region-content">
  <div class="region-inner region-content-inner">
    <a id="main-content"></a>
                        <div class="block block-system block-main block-system-main odd block-without-title" id="block-system-main">
  <div class="block-inner clearfix">
                
    <div class="content clearfix">
      <div class="panel-display panels-960-layout jcore-2col-layout" >
	  <div class="panel-row-wrapper panel-row-first clearfix">
		
		<div class="top-wrapper">
			<div class="panel-panel panel-region-top">
			  <div class="inside"><div class="panel-pane pane-highwire-article-citation" >
  
      
  
  <div class="pane-content">
    <div class="highwire-article-citation highwire-citation-type-highwire-article node111459--5" data-node-nid="111459" id="top-node-111459--61081363309" data-pisa="ajnr;45/11/1791" data-pisa-master="ajnr;ajnr.A8408" data-apath="/ajnr/45/11/1791.atom" data-hw-author-tooltip-instance="highwire_author_tooltip"><div class="highwire-cite highwire-cite-highwire-article highwire-citation-jcore-article-title-complete clearfix has-author-tooltip highwire-citation-highwire-article-top-a">
  
  
      <div class="highwire-cite-overline"><span  class="highwire-cite-metadata-article-type highwire-cite-metadata">Research Article</span><span class="separator-pipe"></span><span  class="highwire-cite-metadata-art-cat highwire-cite-metadata"><span class="wrapper">Pediatric Neuroimaging</span></span></div>
  
      <div class="highwire-cite-access"><span class="highwire-citation-access highwire-citation-access-check" data-pisa-id="ajnr;ajnr.A8408" data-atom-uri="/ajnr/45/11/1791.atom" data-request-view="full"></span></div>
  
      <h1 class="highwire-cite-title" id="page-title">Enzyme Replacement Therapy for CLN2 Disease: MRI Volumetry Shows Significantly Slower Volume Loss Compared with a Natural History Cohort</h1>  
    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0">Pritika Gaur</span>, <span class="highwire-citation-author" data-delta="1">Paul Gissen</span>, <span class="highwire-citation-author" data-delta="2">Asthik Biswas</span>, <span class="highwire-citation-author" data-delta="3">Kshitij Mankad</span>, <span class="highwire-citation-author" data-delta="4">Sniya Sudhakar</span>, <span class="highwire-citation-author" data-delta="5">Felice D’Arco</span>, <span class="highwire-citation-author" data-delta="6">Angela Schulz</span>, <span class="highwire-citation-author" data-delta="7">Jens Fiehler</span>, <span class="highwire-citation-author" data-delta="8">Jan Sedlacik</span> and <span class="highwire-citation-author" data-delta="9">Ulrike Löbel</span></span></div>
  
    	<div class="highwire-cite-metadata"><span  class="highwire-cite-metadata-journal highwire-cite-metadata">American Journal of Neuroradiology </span><span  class="highwire-cite-metadata-date highwire-cite-metadata">November 2024,  </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">45 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(11) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">1791-1797; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata">DOI: https://doi.org/10.3174/ajnr.A8408 </span></div>
  
  
  
</div>
<div id="hw-article-author-popups-top-node-111459--61081363309" style="display: none;"><div class="author-tooltip-0"><div class="author-tooltip-name">Pritika Gaur </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Department of Radiology (P. Gaur, A.B., K.M., S.S., F.D., U.L.), Great Ormond Street Hospital, London, UK</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=Pritika%2BGaur%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Gaur%20P&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3APritika%2BGaur%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="https://orcid.org/0000-0002-6286-9655" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for Pritika Gaur</a></li></ul></div><div class="author-tooltip-1"><div class="author-tooltip-name">Paul Gissen </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>b</span>National Institute for Health Research (P. Gissen), Great Ormond Street Hospital Biomedical Research Centre, University College London, London, UK</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=Paul%2BGissen%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Gissen%20P&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3APaul%2BGissen%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-2"><div class="author-tooltip-name">Asthik Biswas </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Department of Radiology (P. Gaur, A.B., K.M., S.S., F.D., U.L.), Great Ormond Street Hospital, London, UK</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=Asthik%2BBiswas%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Biswas%20A&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AAsthik%2BBiswas%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="https://orcid.org/0000-0003-2010-9524" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for Asthik Biswas</a></li></ul></div><div class="author-tooltip-3"><div class="author-tooltip-name">Kshitij Mankad </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Department of Radiology (P. Gaur, A.B., K.M., S.S., F.D., U.L.), Great Ormond Street Hospital, London, UK</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=Kshitij%2BMankad%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Mankad%20K&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AKshitij%2BMankad%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="https://orcid.org/0000-0001-5979-9337" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for Kshitij Mankad</a></li></ul></div><div class="author-tooltip-4"><div class="author-tooltip-name">Sniya Sudhakar </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Department of Radiology (P. Gaur, A.B., K.M., S.S., F.D., U.L.), Great Ormond Street Hospital, London, UK</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=Sniya%2BSudhakar%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Sudhakar%20S&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3ASniya%2BSudhakar%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="https://orcid.org/0000-0002-7632-9705" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for Sniya Sudhakar</a></li></ul></div><div class="author-tooltip-5"><div class="author-tooltip-name">Felice D’Arco </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Department of Radiology (P. Gaur, A.B., K.M., S.S., F.D., U.L.), Great Ormond Street Hospital, London, UK</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=Felice%2BD%E2%80%99Arco%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=D%E2%80%99Arco%20F&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3AFelice%2BD%25E2%2580%2599Arco%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-6"><div class="author-tooltip-name">Angela Schulz </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>c</span>Department of Paediatrics (A.S.), University Medical Center Hamburg-Eppendorf, Hamburg, Germany</div><div class='author-affiliation'><span class='nlm-sup'>g</span>German Center for Child and Adolescent Health (A.S.), Partner Site Hamburg, Hamburg, Germany</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=Angela%2BSchulz%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Schulz%20A&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link last"><a href="/search/author1%3AAngela%2BSchulz%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li></ul></div><div class="author-tooltip-7"><div class="author-tooltip-name">Jens Fiehler </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>d</span>Department of Diagnostic and Interventional Neuroradiology (J.F.), University Medical Center Hamburg-Eppendorf, Hamburg, Germany</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=Jens%2BFiehler%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Fiehler%20J&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AJens%2BFiehler%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="https://orcid.org/0000-0001-8533-7478" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for Jens Fiehler</a></li></ul></div><div class="author-tooltip-8"><div class="author-tooltip-name">Jan Sedlacik </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>e</span>Robert Steiner MR Facility (J.S.), Medical Research Council Laboratory of Medical Sciences, Hammersmith Hospital Campus, London, UK</div><div class='author-affiliation'><span class='nlm-sup'>f</span>Mansfield Centre for Innovation (J.S.), Imaging Sciences, Institute of Clinical Sciences, Imperial College London, Hammersmith Hospital Campus, London, UK</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=Jan%2BSedlacik%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=Sedlacik%20J&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AJan%2BSedlacik%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="https://orcid.org/0000-0003-3125-1083" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for Jan Sedlacik</a></li></ul></div><div class="author-tooltip-9"><div class="author-tooltip-name">Ulrike Löbel </div><div class="author-tooltip-affiliation"><span class="author-tooltip-text"><div class='author-affiliation'><span class='nlm-sup'>a</span>From the Department of Radiology (P. Gaur, A.B., K.M., S.S., F.D., U.L.), Great Ormond Street Hospital, London, UK</div></span></div><ul class="author-tooltip-find-more"><li class="author-tooltip-gs-link first"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=author&amp;author%5B0%5D=Ulrike%2BL%C3%B6bel%2B" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on Google Scholar</a></li><li class="author-tooltip-pubmed-link"><a href="/lookup/external-ref?access_num=L%C3%B6bel%20U&amp;link_type=AUTHORSEARCH" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Find this author on PubMed</a></li><li class="author-site-search-link"><a href="/search/author1%3AUlrike%2BL%25C3%25B6bel%2B" rel="nofollow" class="" data-icon-position="" data-hide-link-title="0">Search for this author on this site</a></li><li class="author-orcid-link last"><a href="https://orcid.org/0000-0001-9844-3464" target="_blank" class="" data-icon-position="" data-hide-link-title="0">ORCID record for Ulrike Löbel</a></li></ul></div></div></div>  </div>

  
  </div>
</div>
			</div>
		</div>
	
	</div> <!-- /.panel-row-wrapper -->	
	  
  <div class="panel-row-wrapper clearfix">
		
		<div class="main-content-wrapper grid-17 suffix-1 alpha">
			<div class="panel-panel panel-region-content">
			  <div class="inside"><div class="panel-pane pane-highwire-panel-tabs pane-panels-ajax-tab-tabs" >
  
      
  
  <div class="pane-content">
    <div class="item-list"><ul class="tabs inline panels-ajax-tab"><li class="first"><a href="/content/45/11/1791" class="panels-ajax-tab-tab" data-panel-name="jnl_ajnr_tab_art" data-target-id="highwire_article_tabs" data-entity-context="node:111459" data-trigger="" data-url-enabled="1">Article</a><a href="/panels_ajax_tab/jnl_ajnr_tab_art/node:111459/1" rel="nofollow" style="display:none" class="js-crawler-link"></a></li><li><a href="/content/45/11/1791/tab-figures-data" class="panels-ajax-tab-tab" data-panel-name="jnl_ajnr_tab_data" data-target-id="highwire_article_tabs" data-entity-context="node:111459" data-trigger="tab-figures-data" data-url-enabled="1">Figures &amp; Data</a><a href="/panels_ajax_tab/jnl_ajnr_tab_data/node:111459/1" rel="nofollow" style="display:none" class="js-crawler-link"></a></li><li><a href="/content/45/11/1791/tab-supplemental" class="panels-ajax-tab-tab" data-panel-name="jnl_ajnr_tab_supp" data-target-id="highwire_article_tabs" data-entity-context="node:111459" data-trigger="tab-supplemental" data-url-enabled="1">Supplemental</a><a href="/panels_ajax_tab/jnl_ajnr_tab_supp/node:111459/1" rel="nofollow" style="display:none" class="js-crawler-link"></a></li><li><a href="/content/45/11/1791/tab-references" class="panels-ajax-tab-tab" data-panel-name="jnl_ajnr_tab_refs" data-target-id="highwire_article_tabs" data-entity-context="node:111459" data-trigger="tab-references" data-url-enabled="1">References</a><a href="/panels_ajax_tab/jnl_ajnr_tab_refs/node:111459/1" rel="nofollow" style="display:none" class="js-crawler-link"></a></li><li><a href="/content/45/11/1791/tab-article-info" class="panels-ajax-tab-tab" data-panel-name="jnl_ajnr_tab_info" data-target-id="highwire_article_tabs" data-entity-context="node:111459" data-trigger="tab-article-info" data-url-enabled="1">Info &amp; Metrics</a><a href="/panels_ajax_tab/jnl_ajnr_tab_info/node:111459/1" rel="nofollow" style="display:none" class="js-crawler-link"></a></li><li class="last"><a href="/content/ajnr/45/11/1791.full.pdf" class="panels-ajax-tab-tab" data-panel-name="jnl_ajnr_tab_pdf" data-target-id="highwire_article_tabs" data-entity-context="node:111459" data-trigger="tab-pdf" data-url-enabled="1"><i class="icon-file-alt"></i> PDF</a><a href="/panels_ajax_tab/jnl_ajnr_tab_pdf/node:111459/1" rel="nofollow" style="display:none" class="js-crawler-link"></a></li></ul></div>  </div>

  
  </div>
<div class="panel-separator"></div><div class="panel-pane pane-highwire-panel-tabs-container" >
  
      
  
  <div class="pane-content">
    <div data-panels-ajax-tab-preloaded="jnl_ajnr_tab_art" id="panels-ajax-tab-container-highwire_article_tabs" class="panels-ajax-tab-container"><div class="panels-ajax-tab-loading" style ="display:none"><img class="loading" src="http://ajnr-stage2.stage.highwire.org/sites/all/modules/contrib/panels_ajax_tab/images/loading.gif" alt="Loading" title="Loading" /></div><div class="panels-ajax-tab-wrap-jnl_ajnr_tab_art"><div class="panel-display panel-1col clearfix" >
  <div class="panel-panel panel-col">
    <div><div class="panel-pane pane-snippet pane-article-access-text" >
  
      
  
  <div class="pane-content">
    <div class="snippet article-access-text" id="article-access-text">
  
      
  <div class="snippet-content">
    <p>This article requires a subscription to view the full text. If you have a subscription you may use the login form below to view the article. Access to this article can also be purchased.</p>  </div>

</div>
  </div>

  
  </div>
<div class="panel-separator"></div><div class="panel-pane pane-highwire-markup" >
  
      
  
  <div class="pane-content">
    <div class="highwire-markup"><div xmlns="http://www.w3.org/1999/xhtml" data-highwire-cite-ref-tooltip-instance="highwire_reflinks_tooltip" class="content-block-markup" xmlns:xhtml="http://www.w3.org/1999/xhtml"><div class="article abstract-view "><span class="highwire-journal-article-marker-start"></span><div class="section abstract" id="abstract-1"><h2>Abstract</h2><div id="sec-1" class="subsection"><p id="p-1"><strong>BACKGROUND AND PURPOSE:</strong> Neuronal ceroid lipofuscinoses are a group of neurodegenerative disorders. Recently, enzyme replacement therapy (ERT) was approved for neuronal ceroid lipofuscinosis type 2 (CLN2), a subtype of neuronal ceroid lipofuscinoses. The aim of this study was to quantify brain volume loss in CLN2 disease in patients on ERT in comparison with a natural history cohort using MRI.</p></div><div id="sec-2" class="subsection"><p id="p-2"><strong>MATERIALS AND METHODS:</strong> Nineteen (14 female, 5 male) patients with CLN2 disease at 1 UK center were studied using serial 3D T1-weighted MRI (follow-up time, 1–9 years). Brain segmentation was performed using FreeSurfer. Volume measurements for supratentorial gray and white matter, deep gray matter (basal ganglia/thalami), the lateral ventricles, and cerebellar gray and white matter were recorded. The volume change with time was analyzed using a linear mixed-effects model excluding scans before treatment onset. Comparison was made with a published natural history cohort of 12 patients (8 female, 4 male), which was re-analyzed using the same method.</p></div><div id="sec-3" class="subsection"><p id="p-3"><strong>RESULTS:</strong> Brain volume loss of all segmented brain regions was much slower in treated patients compared with the natural history cohort. For example, supratentorial gray matter volume in treated patients decreased by a mean of 3% (SD, 0.74%) (<em>P</em> &lt; .001) annually compared with an annual volume loss of a mean of 16.8% (SD, 1.5%) (<em>P</em> &lt; .001) in the natural history cohort.</p></div><div id="sec-4" class="subsection"><p id="p-4"><strong>CONCLUSIONS:</strong> Our treatment cohort showed a significantly slower rate of brain parenchymal volume loss compared with a natural history cohort in several anatomic regions. Our results complement prior clinical data that found a positive response to ERT. We demonstrate that automated MRI volumetry is a sensitive tool to monitor treatment response in children with CLN2 disease.</p></div></div><div class="section glossary" id="glossary-1"><h2 class="">ABBREVIATIONS:</h2><dl id="def-list-1"><dt id="def-item-1">CLN2<span class="def-item-dt-sep"></span></dt><dd>neuronal ceroid lipofuscinosis type 2<span class="def-item-dd-sep"></span></dd><dt id="def-item-2">ERT<span class="def-item-dt-sep"></span></dt><dd>enzyme replacement therapy<span class="def-item-dd-sep"></span></dd><dt id="def-item-3">ICV<span class="def-item-dt-sep"></span></dt><dd>intracerebro-ventricular<span class="def-item-dd-sep"></span></dd><dt id="def-item-4">NCL<span class="def-item-dt-sep"></span></dt><dd>neuronal ceroid lipofuscinosis<span class="def-item-dd-sep"></span></dd><dt id="def-item-5">TPP1<span class="def-item-dt-sep"></span></dt><dd>tripeptidyl peptidase 1</dd></dl></div><ul class="copyright-statement"><li class="fn" id="copyright-statement-1">© 2024 by American Journal of Neuroradiology</li></ul><span class="highwire-journal-article-marker-end"></span></div><span class="related-urls"></span></div><a href="http://ajnr-stage2.stage.highwire.org/content/45/11/1791.full" class="hw-link hw-link-article-full-text" data-icon-position="" data-hide-link-title="0">View Full Text</a></div>  </div>

  
  </div>
<div class="panel-separator"></div><div class="panel-pane pane-panels-mini pane-jnl-ajnr-challenge pane-style-alt-content" >
  
      
  
  <div class="pane-content">
    <div class="panel-display highwire-1col-stacked-layout" id="mini-panel-jnl_ajnr_challenge">
	  
  <div class="panel-row-wrapper clearfix">
		
		<div class="content-wrapper">
			<div class="panel-panel panel-region-content">
			  <div class="inside"><div class="panel-pane pane-highwire-opportunity-challenge" >
  
      
  
  <div class="pane-content">
    <div class='opportunity-challenge-login'><h3>Log in using your username and password</h3><div class="drupal-login compact"><form action="/content/45/11/1791" method="post" id="highwire-user-login" accept-charset="UTF-8"><div><div class="form-item form-item-label-invisible form-type-textfield form-item-name">
  <label class="element-invisible" for="edit-name">Username <span class="form-required" title="This field is required.">*</span></label>
 <input placeholder="Username" type="text" id="edit-name" name="name" value="" size="30" maxlength="60" class="form-text required" />
</div>
<div class="form-item form-item-label-invisible form-type-password form-item-pass">
  <label class="element-invisible" for="edit-pass">Password <span class="form-required" title="This field is required.">*</span></label>
 <input placeholder="Password" type="password" id="edit-pass" name="pass" size="30" maxlength="128" class="form-text required" />
</div>
<input type="hidden" name="form_build_id" value="form-dDQ9nBD11V0eh75DiH-tmiKR6BGh1pTNnaVfNzGTxkU" />
<input type="hidden" name="form_id" value="highwire_user_login" />
<div class="form-actions form-wrapper" id="edit-actions"><input type="submit" id="edit-submit" name="op" value="Log in" class="form-submit" /></div><div class="reset-password"><a href="/user/password" class="" data-icon-position="" data-hide-link-title="0">Forgot</a> your user name or password?</div></div></form></div></div>  </div>

  
  </div>
</div>
			</div>
		</div>
	
	</div> <!-- /.panel-row-wrapper -->	
	
	</div>

  </div>

  
  </div>
<div class="panel-separator"></div><div class="panel-pane pane-highwire-article-trendmd" >
  
      
  
  <div class="pane-content">
    <div id="trendmd-suggestions"></div>  </div>

  
  </div>
</div>
  </div>
</div>
</div></div>  </div>

  
  </div>
<div class="panel-separator"></div><div class="panel-pane pane-highwire-node-pager" >
  
      
  
  <div class="pane-content">
    <div class="pager highwire-pager pager-mini clearfix highwire-node-pager highwire-article-pager"><span class="pager-prev"><a href="/content/45/11/1784" title="Arterial Spin-Labeling Perfusion Lightbulb Sign: An Imaging Biomarker of Pediatric Posterior Fossa Hemangioblastoma" rel="prev" class="pager-link-prev link-icon"><span class="icon-circle-arrow-left"></span> <span class="title">Previous</span></a></span><span class="pager-next"><a href="/content/45/11/1798" title="Probabilistic Presurgical Language fMRI Atlas of Patients with Brain Tumors" rel="next" class="pager-link-next link-icon-right link-icon"><span class="title">Next</span> <span class="icon-circle-arrow-right"></span></a></span></div>  </div>

  
  </div>
<div class="panel-separator"></div><div class="panel-pane pane-highwire-back-to-top" >
  
      
  
  <div class="pane-content">
    <a href="#page" class="back-to-top" data-icon-position="" data-hide-link-title="0"><span class="icon-chevron-up"></span> Back to top</a>  </div>

  
  </div>
</div>
			</div>
		</div>
		
		<div class="sidebar-right-wrapper grid-10 omega">
			<div class="panel-panel panel-region-sidebar-right">
			  <div class="inside"><div class="panel-pane pane-panels-mini pane-jnl-ajnr-art-issue pane-style-alt-content" >
  
        <h2 class="pane-title">In this issue</h2>
    
  
  <div class="pane-content">
    <div class="panel-display panel-1col clearfix" id="mini-panel-jnl_ajnr_art_issue">
  <div class="panel-panel panel-col">
    <div><div class="panel-pane pane-highwire-article-citation" >
  
      
  
  <div class="pane-content">
    <div class="highwire-article-citation highwire-citation-type-highwire-issue node111440" data-node-nid="111440" id="node-111440--21722530323" data-pisa="ajnr;45/11" data-pisa-master="ajnr;45/11" data-apath="/ajnr/45/11.atom"><div class="highwire-cite highwire-cite-highwire-issue highwire-citation-jcore-issue-widget clearfix">
    
      <div class="highwire-cite-highlight"><a href="/content/45/11"  class="highlight-image-linked"><img class="highlight-image" src="http://ajnr-stage2.stage.highwire.org/sites/default/files/styles/medium/public/highwire/ajnr/45/11.cover-source.jpg?itok=9FRhlSZb" alt="American Journal of Neuroradiology: 45 (11)" /></a></div>
  
  <div class="highwire-cite-col">
      
      
          <a href="/content/45/11" class="highwire-cite-linked-title" data-icon-position="" data-hide-link-title="0"><span class="highwire-cite-title">American Journal of Neuroradiology</span></a>      
      
        	<div class="highwire-cite-metadata"><span  class="highwire-cite-metadata-volume highwire-cite-metadata">Vol. 45</span>, <span  class="highwire-cite-metadata-issue highwire-cite-metadata">Issue 11 </span><div  class="highwire-cite-metadata-pubdate highwire-cite-metadata">1 Nov 2024 </div></div>
      
      
        	<div class="highwire-cite-extras"><div class='highwire-article-citation-variant-list'><ul class="links variants-list"><li class="toc first"><a href="/content/45/11.toc" class="highwire-variant-link variant-toc " title="Table of Contents" rel="alternate" type="text/html" data-icon-position="" data-hide-link-title="0">Table of Contents</a></li><li class="index-by-author"><a href="/content/45/11.index-by-author" class="highwire-variant-link variant-index-by-author " title="Index by author" rel="alternate" data-icon-position="" data-hide-link-title="0">Index by author</a></li><li class="enclosure-complete-issue last"><a href="/content/ajnr/45/11/local/complete-issue.pdf" class="highwire-variant-link variant-enclosure" title="Complete Issue (PDF)" rel="alternative" data-icon-position="" data-hide-link-title="0">Complete Issue (PDF)</a></li></ul></div></div>
      </div>

</div></div>  </div>

  
  </div>
</div>
  </div>
</div>
  </div>

  
  </div>
<div class="panel-separator"></div><div class="panel-pane pane-panels-mini pane-jnl-ajnr-ad-rhs" >
  
      
  
  <div class="pane-content">
    <div class="panel-display panel-1col clearfix" id="mini-panel-jnl_ajnr_ad_rhs">
  <div class="panel-panel panel-col">
    <div><div class="panel-pane pane-dfp-pane text-center" >
  
      
  
  <div class="pane-content">
    <div id="dfp-ad-rhs-wrapper" class="dfp-tag-wrapper">
<div class="slug">Advertisement</div>
<div  id="dfp-ad-rhs" class="dfp-tag-wrapper">
  <script type="text/javascript">
    googletag.cmd.push(function() {
      googletag.display("dfp-ad-rhs");
    });
  </script>
</div>
</div>  </div>

  
  </div>
</div>
  </div>
</div>
  </div>

  
  </div>
<div class="panel-separator"></div><div class="panel-pane pane-panels-mini pane-jnl-ajnr-art-tools" >
  
      
  
  <div class="pane-content">
    <div id="mini-panel-jnl_ajnr_art_tools" class="highwire-2col-stacked panel-display">
	  
  <div class="panel-row-wrapper clearfix">
		<div class="content-left-wrapper content-column">
          <div class="panel-panel panel-region-content-left">
            <div class="inside"><div class="panel-pane pane-highwire-variant-link" >
  
      
  
  <div class="pane-content">
    <a href="/content/ajnr/45/11/1791.full-text.print" target="_blank" rel="nofollow" class="link-icon"><span class="icon-print"></span> <span class="title">Print</span></a>  </div>

  
  </div>
<div class="panel-pane pane-highwire-variant-link text-no-wrap" >
  
      
  
  <div class="pane-content">
    <a href="/content/ajnr/45/11/1791.full-text.pdf" target="_blank" class="link-icon"><span class="icon-download-alt"></span> <span class="title">Download PDF</span></a>  </div>

  
  </div>
<div class="panel-pane pane-minipanel-dialog-link pane-jnl-ajnr-art-email" >
  
      
  
  <div class="pane-content">
    <div class='minipanel-dialog-wrapper'><div class='minipanel-dialog-link-link'><a href="/" oncontextmenu="javascript: return false;" class="minipanel-dialog-link-trigger link-icon" title="Email this Article"><span class="icon-envelope"></span> <span class="title">Email Article</span></a></div><div class='minipanel-dialog-link-mini' style='display:none'><div class="panel-display panel-1col clearfix" id="mini-panel-jnl_ajnr_art_email">
  <div class="panel-panel panel-col">
    <div><div class="panel-pane pane-block pane-forward-form pane-forward" >
  
      
  
  <div class="pane-content">
    <form action="/content/45/11/1791" method="post" id="forward-form" accept-charset="UTF-8"><div><div id="edit-instructions" class="form-item form-item-label-before form-type-item">
 <p>Thank you for your interest in spreading the word on American Journal of Neuroradiology.</p><p>NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.</p>
</div>
<div class="form-item form-item-label-before form-type-textfield form-item-email">
  <label for="edit-email">Your Email <span class="form-required" title="This field is required.">*</span></label>
 <input type="text" id="edit-email" name="email" value="" size="58" maxlength="256" class="form-text required" />
</div>
<div class="form-item form-item-label-before form-type-textfield form-item-name">
  <label for="edit-name--2">Your Name <span class="form-required" title="This field is required.">*</span></label>
 <input type="text" id="edit-name--2" name="name" value="" size="58" maxlength="256" class="form-text required" />
</div>
<div class="form-item form-item-label-before form-type-textarea form-item-recipients">
  <label for="edit-recipients">Send To <span class="form-required" title="This field is required.">*</span></label>
 <div class="form-textarea-wrapper resizable"><textarea id="edit-recipients" name="recipients" cols="50" rows="5" class="form-textarea required"></textarea></div>
<div class="description">Enter multiple addresses on separate lines or separate them with commas.</div>
</div>
<div id="edit-page" class="form-item form-item-label-before form-type-item">
  <label for="edit-page">You are going to email the following </label>
 <a href="/content/45/11/1791" class="active" data-icon-position="" data-hide-link-title="0">Enzyme Replacement Therapy for CLN2 Disease: MRI Volumetry Shows Significantly Slower Volume Loss Compared with a Natural History Cohort</a>
</div>
<div id="edit-subject" class="form-item form-item-label-before form-type-item">
  <label for="edit-subject">Message Subject </label>
 (Your Name) has sent you a message from American Journal of Neuroradiology
</div>
<div id="edit-body" class="form-item form-item-label-before form-type-item">
  <label for="edit-body">Message Body </label>
 (Your Name) thought you would like to see the American Journal of Neuroradiology web site.
</div>
<div class="form-item form-item-label-before form-type-textarea form-item-message">
  <label for="edit-message--2">Your Personal Message </label>
 <div class="form-textarea-wrapper resizable"><textarea id="edit-message--2" name="message" cols="50" rows="10" class="form-textarea"></textarea></div>
</div>
<input type="hidden" name="path" value="node/111459" />
<input type="hidden" name="path_cid" value="" />
<input type="hidden" name="forward_footer" value="" />
<input type="hidden" name="form_build_id" value="form-SjNtnUk-qik4zTPji8wCF1yazP5Yq--mx-BnTa5Mg5g" />
<input type="hidden" name="form_id" value="forward_form" />
<fieldset class="captcha form-wrapper"><legend><span class="fieldset-legend">CAPTCHA</span></legend><div class="fieldset-wrapper"><div class="fieldset-description">This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.</div><input type="hidden" name="captcha_sid" value="108731650" />
<input type="hidden" name="captcha_token" value="ddcb8819192b1222584930418427e478" />
<input type="hidden" name="captcha_response" value="Google no captcha" />
<div class="g-recaptcha" data-sitekey="6LfnJVIUAAAAAE-bUOMg0MJGki4lqSvDmhJp19fN" data-theme="light" data-type="image"></div></div></fieldset>
<div class="form-actions form-wrapper" id="edit-actions--2"><input type="submit" id="edit-submit--2" name="op" value="Send Message" class="form-submit" /></div></div></form>  </div>

  
  </div>
</div>
  </div>
</div>
</div></div>  </div>

  
  </div>
<div class="panel-pane pane-minipanel-dialog-link pane-jnl-ajnr-cite-tool" >
  
      
  
  <div class="pane-content">
    <div class='minipanel-dialog-wrapper'><div class='minipanel-dialog-link-link'><a href="/highwire/citation/111459/download" oncontextmenu="javascript: return false;" class="minipanel-dialog-link-trigger link-icon" title="Citation Tools"><span class="icon-globe"></span> <span class="title">Citation Tools</span></a></div><div class='minipanel-dialog-link-mini' style='display:none'><div class="panel-display panel-1col clearfix" id="mini-panel-jnl_ajnr_cite_tool">
  <div class="panel-panel panel-col">
    <div><div class="panel-pane pane-highwire-citation-export" >
  
      
  
  <div class="pane-content">
    <div class="highwire-citation-export">  
  <div class="highwire-citation-info">
      <div class="highwire-article-citation highwire-citation-type-highwire-article cite-tool-node111459" data-node-nid="111459" id="citation-node-111459--286987054" data-pisa="ajnr;45/11/1791" data-pisa-master="ajnr;ajnr.A8408" data-apath="/ajnr/45/11/1791.atom"><div class="highwire-cite highwire-cite-highwire-article highwire-citation-jcore-standard clearfix">
  
  
  
  
      <div class="highwire-cite-title">CLN2 Therapy: MRI Volumetry Findings</div>  
    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0"><span class="nlm-given-names">Pritika</span> <span class="nlm-surname">Gaur</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">Paul</span> <span class="nlm-surname">Gissen</span></span>, <span class="highwire-citation-author" data-delta="2"><span class="nlm-given-names">Asthik</span> <span class="nlm-surname">Biswas</span></span>, <span class="highwire-citation-author" data-delta="3"><span class="nlm-given-names">Kshitij</span> <span class="nlm-surname">Mankad</span></span>, <span class="highwire-citation-author" data-delta="4"><span class="nlm-given-names">Sniya</span> <span class="nlm-surname">Sudhakar</span></span>, <span class="highwire-citation-author" data-delta="5"><span class="nlm-given-names">Felice</span> <span class="nlm-surname">D’Arco</span></span>, <span class="highwire-citation-author" data-delta="6"><span class="nlm-given-names">Angela</span> <span class="nlm-surname">Schulz</span></span>, <span class="highwire-citation-author" data-delta="7"><span class="nlm-given-names">Jens</span> <span class="nlm-surname">Fiehler</span></span>, <span class="highwire-citation-author" data-delta="8"><span class="nlm-given-names">Jan</span> <span class="nlm-surname">Sedlacik</span></span>, <span class="highwire-citation-author" data-delta="9"><span class="nlm-given-names">Ulrike</span> <span class="nlm-surname">Löbel</span></span></span></div>
  
    	<div class="highwire-cite-metadata"><span  class="highwire-cite-metadata-journal highwire-cite-metadata">American Journal of Neuroradiology </span><span  class="highwire-cite-metadata-date highwire-cite-metadata">Nov 2024, </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">45 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(11) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">1791-1797; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="label">DOI:</span> 10.3174/ajnr.A8408 </span></div>
  
  
  
</div>
</div>  </div>
  <div class="highwire-citation-formats">
  	      <h2>Citation Manager Formats</h2>
        <div class="highwire-citation-formats-links">
      <span class="Z3988" title="ctx_ver=Z39.88-2004&amp;rft_val_fmt=info%3Aofi%2Ffmt%3Akev%3Amtx%3Ajournal&amp;rft.spage=1791&amp;rft.epage=1797&amp;rft.atitle=Enzyme%20Replacement%20Therapy%20for%20CLN2%20Disease%3A%20MRI%20Volumetry%20Shows%20Significantly%20Slower%20Volume%20Loss%20Compared%20with%20a%20Natural%20History%20Cohort&amp;rft.volume=45&amp;rft.issue=11&amp;rft.date=2024-11-01%2000%3A00%3A00&amp;rft.stitle&amp;rft.jtitle=American%20Journal%20of%20Neuroradiology&amp;rft.au=Gaur%2C+Pritika&amp;rft.au=Gissen%2C+Paul&amp;rft.au=Biswas%2C+Asthik&amp;rft.au=Mankad%2C+Kshitij&amp;rft.au=Sudhakar%2C+Sniya&amp;rft.au=D%E2%80%99Arco%2C+Felice&amp;rft.au=Schulz%2C+Angela&amp;rft.au=Fiehler%2C+Jens&amp;rft.au=Sedlacik%2C+Jan&amp;rft.au=L%C3%B6bel%2C+Ulrike"></span><ul class="hw-citation-links inline button button-alt button-grid clearfix"><li class="bibtext first"><a href="/highwire/citation/111459/bibtext" class="hw-download-citation-link" data-icon-position="" data-hide-link-title="0">BibTeX</a></li><li class="bookends"><a href="/highwire/citation/111459/bookends" class="hw-download-citation-link" data-icon-position="" data-hide-link-title="0">Bookends</a></li><li class="easybib"><a href="/highwire/citation/111459/easybib" class="hw-download-citation-link" data-icon-position="" data-hide-link-title="0">EasyBib</a></li><li class="endnote-tagged"><a href="/highwire/citation/111459/endnote-tagged" class="hw-download-citation-link" data-icon-position="" data-hide-link-title="0">EndNote (tagged)</a></li><li class="endnote-8-xml"><a href="/highwire/citation/111459/endnote-8-xml" class="hw-download-citation-link" data-icon-position="" data-hide-link-title="0">EndNote 8 (xml)</a></li><li class="medlars"><a href="/highwire/citation/111459/medlars" class="hw-download-citation-link" data-icon-position="" data-hide-link-title="0">Medlars</a></li><li class="mendeley"><a href="/highwire/citation/111459/mendeley" class="hw-download-citation-link" data-icon-position="" data-hide-link-title="0">Mendeley</a></li><li class="papers"><a href="/highwire/citation/111459/papers" class="hw-download-citation-link" data-icon-position="" data-hide-link-title="0">Papers</a></li><li class="refworks-tagged"><a href="/highwire/citation/111459/refworks-tagged" class="hw-download-citation-link" data-icon-position="" data-hide-link-title="0">RefWorks Tagged</a></li><li class="reference-manager"><a href="/highwire/citation/111459/reference-manager" class="hw-download-citation-link" data-icon-position="" data-hide-link-title="0">Ref Manager</a></li><li class="ris"><a href="/highwire/citation/111459/ris" class="hw-download-citation-link" data-icon-position="" data-hide-link-title="0">RIS</a></li><li class="zotero last"><a href="/highwire/citation/111459/zotero" class="hw-download-citation-link" data-icon-position="" data-hide-link-title="0">Zotero</a></li></ul>    </div>
  </div>
</div>
  </div>

  
  </div>
</div>
  </div>
</div>
</div></div>  </div>

  
  </div>
</div>
          </div>
        </div>
        
        <div class="content-right-wrapper content-column">
          <div class="panel-panel panel-region-content-right">
            <div class="inside"><div class="panel-pane pane-highwire-share-link highwire_clipboard_link_ajax"  id="shareit">
  
      
  
  <div class="pane-content">
    <a href="/" class="link-icon"><span class="icon-share-alt"></span> <span class="title">Share</span></a>  </div>

  
  </div>
<div class="panel-pane pane-panels-mini pane-jnl-ajnr-share highwire_clipboard_form_ajax_shareit" >
  
      
  
  <div class="pane-content">
    <div class="panel-display panel-1col clearfix" id="mini-panel-jnl_ajnr_share">
  <div class="panel-panel panel-col">
    <div><div class="panel-pane pane-highwire-article-citation large-margin-bottom" >
  
      
  
  <div class="pane-content">
    <div class="highwire-article-citation highwire-citation-type-highwire-article node111459--3" data-node-nid="111459" id="share-node-111459--41869426058" data-pisa="ajnr;45/11/1791" data-pisa-master="ajnr;ajnr.A8408" data-apath="/ajnr/45/11/1791.atom"><div class="highwire-cite highwire-cite-highwire-article highwire-citation-jcore-standard clearfix">
  
  
  
  
      <div class="highwire-cite-title">CLN2 Therapy: MRI Volumetry Findings</div>  
    	<div class="highwire-cite-authors"><span  class="highwire-citation-authors"><span class="highwire-citation-author first" data-delta="0"><span class="nlm-given-names">Pritika</span> <span class="nlm-surname">Gaur</span></span>, <span class="highwire-citation-author" data-delta="1"><span class="nlm-given-names">Paul</span> <span class="nlm-surname">Gissen</span></span>, <span class="highwire-citation-author" data-delta="2"><span class="nlm-given-names">Asthik</span> <span class="nlm-surname">Biswas</span></span>, <span class="highwire-citation-author" data-delta="3"><span class="nlm-given-names">Kshitij</span> <span class="nlm-surname">Mankad</span></span>, <span class="highwire-citation-author" data-delta="4"><span class="nlm-given-names">Sniya</span> <span class="nlm-surname">Sudhakar</span></span>, <span class="highwire-citation-author" data-delta="5"><span class="nlm-given-names">Felice</span> <span class="nlm-surname">D’Arco</span></span>, <span class="highwire-citation-author" data-delta="6"><span class="nlm-given-names">Angela</span> <span class="nlm-surname">Schulz</span></span>, <span class="highwire-citation-author" data-delta="7"><span class="nlm-given-names">Jens</span> <span class="nlm-surname">Fiehler</span></span>, <span class="highwire-citation-author" data-delta="8"><span class="nlm-given-names">Jan</span> <span class="nlm-surname">Sedlacik</span></span>, <span class="highwire-citation-author" data-delta="9"><span class="nlm-given-names">Ulrike</span> <span class="nlm-surname">Löbel</span></span></span></div>
  
    	<div class="highwire-cite-metadata"><span  class="highwire-cite-metadata-journal highwire-cite-metadata">American Journal of Neuroradiology </span><span  class="highwire-cite-metadata-date highwire-cite-metadata">Nov 2024, </span><span  class="highwire-cite-metadata-volume highwire-cite-metadata">45 </span><span  class="highwire-cite-metadata-issue highwire-cite-metadata">(11) </span><span  class="highwire-cite-metadata-pages highwire-cite-metadata">1791-1797; </span><span  class="highwire-cite-metadata-doi highwire-cite-metadata"><span class="label">DOI:</span> 10.3174/ajnr.A8408 </span></div>
  
  
  
</div>
</div>  </div>

  
  </div>
<div class="panel-separator"></div><div class="panel-pane pane-highwire-article-clipboard-copy large-margin-bottom" >
  
      
  
  <div class="pane-content">
    <div class = "clipboard-copy">
  <span class="label-url">
    <label for="dynamic">Share This Article:</label>
  </span>
  <span class="input-text-url">
    <input type="text" id="dynamic" value="http://ajnr-stage2.stage.highwire.org/content/45/11/1791" size="50"/>
  </span>
  <span class="copy-button button">
    <button id="copy-dynamic" class="clipboardjs-button" data-clipboard-target="#dynamic" data-clipboard-alert-style="tooltip" data-clipboard-alert-text="Copied!">Copy</button>
  </span>
</div>
  </div>

  
  </div>
<div class="panel-separator"></div><div class="panel-pane pane-service-links" >
  
      
  
  <div class="pane-content">
    <div class="service-links"><a href="http://del.icio.us/post?url=http%3A//ajnr-stage2.stage.highwire.org/content/45/11/1791&amp;title=Enzyme%20Replacement%20Therapy%20for%20CLN2%20Disease%3A%20MRI%20Volumetry%20Shows%20Significantly%20Slower%20Volume%20Loss%20Compared%20with%20a%20Natural%20History%20Cohort" id="delicious" title="Bookmark this post on del.icio.us" class="service-links-delicious" rel="nofollow" target="_blank" data-icon-position="" data-hide-link-title="0"><img src="http://ajnr-stage2.stage.highwire.org/sites/all/modules/highwire/highwire/images/delicious-32.png" alt="del.icio.us logo" /></a> <a href="http://twitter.com/share?url=http%3A//ajnr-stage2.stage.highwire.org/content/45/11/1791&amp;text=Enzyme%20Replacement%20Therapy%20for%20CLN2%20Disease%3A%20MRI%20Volumetry%20Shows%20Significantly%20Slower%20Volume%20Loss%20Compared%20with%20a%20Natural%20History%20Cohort" id="twitter" title="Share this on Twitter" class="service-links-twitter" rel="nofollow" target="_blank" data-icon-position="" data-hide-link-title="0"><img src="http://ajnr-stage2.stage.highwire.org/sites/all/modules/highwire/highwire/images/twitter.png" alt="Twitter logo" /></a> <a href="http://www.facebook.com/sharer.php?u=http%3A//ajnr-stage2.stage.highwire.org/content/45/11/1791&amp;t=Enzyme%20Replacement%20Therapy%20for%20CLN2%20Disease%3A%20MRI%20Volumetry%20Shows%20Significantly%20Slower%20Volume%20Loss%20Compared%20with%20a%20Natural%20History%20Cohort" id="facebook" title="Share on Facebook" class="service-links-facebook" rel="nofollow" target="_blank" data-icon-position="" data-hide-link-title="0"><img src="http://ajnr-stage2.stage.highwire.org/sites/all/modules/highwire/highwire/images/fb-blue.png" alt="Facebook logo" /></a> <a href="http://www.mendeley.com/import/?url=http%3A//ajnr-stage2.stage.highwire.org/content/45/11/1791&amp;title=Enzyme%20Replacement%20Therapy%20for%20CLN2%20Disease%3A%20MRI%20Volumetry%20Shows%20Significantly%20Slower%20Volume%20Loss%20Compared%20with%20a%20Natural%20History%20Cohort" id="mendeley" title="Share on Mendeley" class="service-links-mendeley" rel="nofollow" target="_blank" data-icon-position="" data-hide-link-title="0"><img src="http://ajnr-stage2.stage.highwire.org/sites/all/modules/highwire/highwire/images/mendeley.png" alt="Mendeley logo" /></a></div>  </div>

  
  </div>
</div>
  </div>
</div>
  </div>

  
  </div>
<div class="panel-pane pane-service-links" >
  
      
  
  <div class="pane-content">
    <div class="service-links"><div class="item-list"><ul><li class="first"><a href="http://twitter.com/share?url=http%3A//ajnr-stage2.stage.highwire.org/content/45/11/1791&amp;count=horizontal&amp;via=&amp;text=Enzyme%20Replacement%20Therapy%20for%20CLN2%20Disease%3A%20MRI%20Volumetry%20Shows%20Significantly%20Slower%20Volume%20Loss%20Compared%20with%20a%20Natural%20History%20Cohort&amp;counturl=http%3A//ajnr-stage2.stage.highwire.org/content/45/11/1791" class="twitter-share-button service-links-twitter-widget" id="twitter_widget" title="Tweet This" rel="nofollow" target="_blank" data-icon-position="" data-hide-link-title="0"><span class="element-invisible">Tweet Widget</span></a></li><li><a href="http://www.facebook.com/plugins/like.php?href=http%3A//ajnr-stage2.stage.highwire.org/content/45/11/1791&amp;layout=button_count&amp;show_faces=false&amp;action=like&amp;colorscheme=light&amp;width=100&amp;height=21&amp;font=&amp;locale=" id="facebook_like" title="I Like it" class="service-links-facebook-like" rel="nofollow" target="_blank" data-icon-position="" data-hide-link-title="0"><span class="element-invisible">Facebook Like</span></a></li><li class="last"><a href="http://ajnr-stage2.stage.highwire.org/content/45/11/1791" id="google_plus_one" title="Plus it" class="service-links-google-plus-one" rel="nofollow" target="_blank" data-icon-position="" data-hide-link-title="0"><span class="element-invisible">Google Plus One</span></a></li></ul></div></div>  </div>

  
  </div>
</div>
          </div>
        </div>
	</div> <!-- /.panel-row-wrapper -->	
	
	</div>

  </div>

  
  </div>
<div class="panel-separator"></div><div class="panel-pane pane-jnl-ajnr-rental" >
  
      
  
  <div class="pane-content">
    <span class="js-deepdyve-link">
            <a class="button btn btn-primary btn-sm" role="button"  href="https://www.deepdyve.com/doc-view?docId=10.3174/ajnr.A8408&fieldName=journal_doi&affiliateId=asnr"><i class="icon-usd"> </i> Purchase</a>  </div>

  
  </div>
<div class="panel-separator"></div><div class="panel-pane pane-highwire-article-nav mobile-hidden pane-style-alt-content" >
  
        <h2 class="pane-title">Jump to section</h2>
    
  
  <div class="pane-content">
    <div class="highwire-list-wrapper highwire-article-nav highwire-nav-float"><div class="highwire-list"><ul data-highwire-float="1" data-highwire-float-class="grid-10 alpha omega"><li class="parent first odd"><a href="/content/45/11/1791" class="highwire-article-nav-jumplink" data-panel-ajax-tab="jnl_ajnr_tab_art" data-is-tab-link="true" data-icon-position="" data-hide-link-title="0">Article</a><div class="highwire-list"><ul><li class="first odd"><a href="#abstract-1" class="highwire-article-nav-jumplink first" data-panel-ajax-tab="jnl_ajnr_tab_art" data-icon-position="" data-hide-link-title="0">Abstract</a></li><li class="even"><a href="#glossary-1" class="highwire-article-nav-jumplink" data-panel-ajax-tab="jnl_ajnr_tab_art" data-icon-position="" data-hide-link-title="0">ABBREVIATIONS:</a></li><li class="odd"><a href="#sec-8" class="highwire-article-nav-jumplink" data-panel-ajax-tab="jnl_ajnr_tab_art" data-icon-position="" data-hide-link-title="0">MATERIALS AND METHODS</a></li><li class="even"><a href="#sec-12" class="highwire-article-nav-jumplink" data-panel-ajax-tab="jnl_ajnr_tab_art" data-icon-position="" data-hide-link-title="0">RESULTS</a></li><li class="odd"><a href="#sec-13" class="highwire-article-nav-jumplink" data-panel-ajax-tab="jnl_ajnr_tab_art" data-icon-position="" data-hide-link-title="0">DISCUSSION</a></li><li class="even"><a href="#sec-14" class="highwire-article-nav-jumplink" data-panel-ajax-tab="jnl_ajnr_tab_art" data-icon-position="" data-hide-link-title="0">CONCLUSIONS</a></li><li class="odd"><a href="#ack-1" class="highwire-article-nav-jumplink" data-panel-ajax-tab="jnl_ajnr_tab_art" data-icon-position="" data-hide-link-title="0">Acknowledgments</a></li><li class="even"><a href="#fn-group-1" class="highwire-article-nav-jumplink" data-panel-ajax-tab="jnl_ajnr_tab_art" data-icon-position="" data-hide-link-title="0">Footnotes</a></li><li class="last odd"><a href="#ref-list-1" class="highwire-article-nav-jumplink last" data-panel-ajax-tab="jnl_ajnr_tab_art" data-icon-position="" data-hide-link-title="0">References</a></li></ul></div></li><li class="even"><a href="/content/45/11/1791/tab-figures-data" class="highwire-article-nav-jumplink" data-panel-ajax-tab="jnl_ajnr_tab_data" data-is-tab-link="true" data-icon-position="" data-hide-link-title="0">Figures &amp; Data</a></li><li class="odd"><a href="/content/45/11/1791/tab-supplemental" class="highwire-article-nav-jumplink" data-panel-ajax-tab="jnl_ajnr_tab_supp" data-is-tab-link="true" data-icon-position="" data-hide-link-title="0">Supplemental</a></li><li class="even"><a href="/content/45/11/1791/tab-references" class="highwire-article-nav-jumplink" data-panel-ajax-tab="jnl_ajnr_tab_refs" data-is-tab-link="true" data-icon-position="" data-hide-link-title="0">References</a></li><li class="odd"><a href="/content/45/11/1791/tab-article-info" class="highwire-article-nav-jumplink" data-panel-ajax-tab="jnl_ajnr_tab_info" data-is-tab-link="true" data-icon-position="" data-hide-link-title="0">Info &amp; Metrics</a></li><li class="last even"><a href="/content/45/11/1791.full.pdf" class="highwire-article-nav-jumplink" data-icon-position="" data-hide-link-title="0"><i class="icon-file-alt"></i> PDF</a></li></ul></div></div>  </div>

  
  </div>
<div class="panel-separator"></div><div class="panel-pane pane-panels-mini pane-jnl-ajnr-accordion" >
  
      
  
  <div class="pane-content">
    <div class="panel-display panel-1col clearfix" id="mini-panel-jnl_ajnr_accordion">
  <div class="panel-panel panel-col">
    <div><div id="highwire_article_accordion_container"><h3 ><i class="icon-caret-right"></i> Related Articles</h3><div><div class='highwire-list-footer'><div class="highwire-related-articles-footer"><ul class="links inline"><li class="related-pubmed first"><a href="/lookup/external-ref?link_type=MED_NBRS&amp;access_num=38977290" target="_blank" class="" data-icon-position="" data-hide-link-title="0">PubMed</a></li><li class="related-google-scholar last"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=related&amp;author%5B0%5D=Pritika%2BGaur&amp;author%5B1%5D=Paul%2BGissen&amp;author%5B2%5D=Asthik%2BBiswas&amp;author%5B3%5D=Kshitij%2BMankad&amp;author%5B4%5D=Sniya%2BSudhakar&amp;author%5B5%5D=Felice%2BD%E2%80%99Arco&amp;author%5B6%5D=Angela%2BSchulz&amp;author%5B7%5D=Jens%2BFiehler&amp;author%5B8%5D=Jan%2BSedlacik&amp;author%5B9%5D=Ulrike%2BL%C3%B6bel&amp;title=Enzyme%2BReplacement%2BTherapy%2Bfor%2BCLN2%2BDisease%3A%2BMRI%2BVolumetry%2BShows%2BSignificantly%2BSlower%2BVolume%2BLoss%2BCompared%2Bwith%2Ba%2BNatural%2BHistory%2BCohort&amp;publication_year=2024&amp;path=content/45/11/1791" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Google Scholar</a></li></ul></div></div></div><h3 ><i class="icon-caret-right"></i> Cited By...</h3><div><div class="highwire-list highwire-cited-by"><ul><li class="first last odd"><div class="no-results">No citing articles found.</div></li></ul></div><div class='highwire-list-footer'><ul class="links inline"><li class="citing-cross-ref first"><a href="/crossref-forward-links/ajnr/45/11/1791#crossref" class="hw-crossref hw-crossref-link-ajax" data-list-wrapper="hw-crossref-list-wrapper" target="_blank" data-icon-position="" data-hide-link-title="0">Crossref</a></li><li class="citing-google-scholar last"><a href="/lookup/google-scholar?link_type=googlescholar&amp;gs_type=citedby&amp;path=content/45/11/1791" target="_blank" class="" data-icon-position="" data-hide-link-title="0">Google Scholar</a></li></ul></div><div title="Crossref Cited-by Linking Search Results" style="display:none;" class="hw-crossref-list-wrapper"><p class = "hw-crossref-message">This article has not yet been cited by articles in journals that are participating in Crossref Cited-by Linking.</p></div></div><h3 ><i class="icon-caret-right"></i> More in this TOC Section</h3><div><div class="highwire-list highwire-article-citation-list"><ul><li class="first odd"><div class="highwire-article-citation highwire-citation-type-highwire-article node112503" data-node-nid="112503" id="node-112503--2985182551" data-pisa="ajnr;ajnr.A8450v2" data-pisa-master="ajnr;ajnr.A8450" data-apath="/ajnr/early/2024/12/26/ajnr.A8450.atom"><div class="highwire-cite highwire-cite-highwire-article highwire-citation-jcore-standard-title-only clearfix">
  
  
  
  
      <a href="/content/early/2024/12/26/ajnr.A8450" class="highwire-cite-linked-title" data-icon-position="" data-hide-link-title="0"><span class="highwire-cite-title">Neuroradiologic, Clinical, and Genetic Characterization of Cerebellar Heterotopia: A Pediatric Multicentric Study</span></a>  
  
  
  
  
</div>
</div></li><li class="even"><div class="highwire-article-citation highwire-citation-type-highwire-article node112055" data-node-nid="112055" id="node-112055--211024843" data-pisa="ajnr;45/12/1895" data-pisa-master="ajnr;ajnr.A8414" data-apath="/ajnr/45/12/1895.atom"><div class="highwire-cite highwire-cite-highwire-article highwire-citation-jcore-standard-title-only clearfix">
  
  
  
  
      <a href="/content/45/12/1895" class="highwire-cite-linked-title" data-icon-position="" data-hide-link-title="0"><span class="highwire-cite-title">Anomalous Pontine Cranial Nerves in Children</span></a>  
  
  
  
  
</div>
</div></li><li class="last odd"><div class="highwire-article-citation highwire-citation-type-highwire-article node112061" data-node-nid="112061" id="node-112061--21547757551" data-pisa="ajnr;45/12/S64" data-pisa-master="ajnr;45/12/S64" data-apath="/ajnr/45/12/S64.atom"><div class="highwire-cite highwire-cite-highwire-article highwire-citation-jcore-standard-title-only clearfix">
  
  
  
  
      <a href="/content/45/12/S64" class="highwire-cite-linked-title" data-icon-position="" data-hide-link-title="0"><span class="highwire-cite-title">Cerebellar Tonsillar Position on MR</span></a>  
  
  
  
  
</div>
</div></li></ul></div><div class='highwire-list-footer'><a href="/content/by/section/Pediatric%20Neuroimaging" class="" data-icon-position="" data-hide-link-title="0">Show more <span class="wrapper">PEDIATRIC NEUROIMAGING</span></a></div></div><h3 ><i class="icon-caret-right"></i> Similar Articles</h3><div><div class="highwire-search-similar-ajax-wrapper" id="highwire-search-similar-articles-list-1"><div class="highwire-ajax-loading"><span class="icon-spinner icon-spin icon-2x"></span></div></div></div></div></div>
  </div>
</div>
  </div>

  
  </div>
</div>
			</div>
		</div>
	
	</div> <!-- /.panel-row-wrapper -->	
	
	</div>

    </div>
  </div>
</div><div class="block block-panels-mini more-padding-top mobile-hiddens block-jnl-ajnr-ad-bot-leaderboard block-panels-mini-jnl-ajnr-ad-bot-leaderboard even block-without-title" id="block-panels-mini-jnl-ajnr-ad-bot-leaderboard">
  <div class="block-inner clearfix">
                
    <div class="content clearfix">
      <div class="panel-display panel-1col clearfix" id="mini-panel-jnl_ajnr_ad_bot_leaderboard">
  <div class="panel-panel panel-col">
    <div><div class="panel-pane pane-dfp-pane text-center" >
  
      
  
  <div class="pane-content">
    <div id="dfp-ad-bottom_leaderboard-wrapper" class="dfp-tag-wrapper">
<div class="slug">Advertisement</div>
<div  id="dfp-ad-bottom_leaderboard" class="dfp-tag-wrapper">
  <script type="text/javascript">
    googletag.cmd.push(function() {
      googletag.display("dfp-ad-bottom_leaderboard");
    });
  </script>
</div>
</div>  </div>

  
  </div>
</div>
  </div>
</div>
    </div>
  </div>
</div>      </div>
</div>  </div>
</section>    
  
      <footer id="section-footer" class="section section-footer">
    
  <div id="zone-postscript" class="zone zone-postscript clearfix container-30">
    <div class="grid-28 suffix-1 prefix-1 region region-postscript-fourth" id="region-postscript-fourth">
  <div class="region-inner region-postscript-fourth-inner">
    <div class="block block-panels-mini block-jnl-ajnr-footer block-panels-mini-jnl-ajnr-footer odd block-without-title" id="block-panels-mini-jnl-ajnr-footer">
  <div class="block-inner clearfix">
                
    <div class="content clearfix">
      <div class="panel-display panels-960-row jcore-row-4col clearfix" id="mini-panel-jnl_ajnr_footer">
  <div class="panel-panel panel-region-col-1 grid-7 alpha">
    <div class="inside"><div class="panel-pane pane-block pane-menu-navigate pane-menu" >
  
        <h2 class="pane-title">News and Updates</h2>
    
  
  <div class="pane-content">
    <nav class="menubar-nav"><ul class="menu" role="menu"><li class="first leaf" role="menuitem"><a href="https://www.ajnr.org/cc/2024-Awards" data-hide-link-title="0" class="" data-icon-position="">2024 Journal Award Winners</a></li>
<li class="last leaf" role="menuitem"><a href="/page/content/Reviewer-Recognition" data-hide-link-title="0" class="" data-icon-position="">Thanks to our 2023 Distinguished Reviewers</a></li>
</ul></nav>  </div>

  
  </div>
</div>
  </div>
  <div class="panel-panel panel-region-col-2 grid-7">
    <div class="inside"><div class="panel-pane pane-block pane-menu-more-information pane-menu" >
  
        <h2 class="pane-title">Resources</h2>
    
  
  <div class="pane-content">
    <nav class="menubar-nav"><ul class="menu" role="menu"><li class="first leaf" role="menuitem"><a href="/page/content/EBM" data-hide-link-title="0" class="" data-icon-position="">Evidence-Based Medicine Level Guide</a></li>
<li class="leaf" role="menuitem"><a href="/content/browse-podcast-archives" data-hide-link-title="0" class="" data-icon-position="">AJNR Podcast Archive</a></li>
<li class="leaf" role="menuitem"><a href="/content/institutional-subscriptions" data-hide-link-title="0" class="" data-icon-position="">Librarian Resources</a></li>
<li class="last leaf" role="menuitem"><a href="http://www.ajnr.org/page/content/Terms-and-Conditions" data-hide-link-title="0" class="" data-icon-position="">Terms and Conditions</a></li>
</ul></nav>  </div>

  
  </div>
</div>
  </div>
  <div class="panel-panel panel-region-col-3 grid-7">
    <div class="inside"><div class="panel-pane pane-block pane-menu-add-journals pane-menu" >
  
        <h2 class="pane-title">Opportunities</h2>
    
  
  <div class="pane-content">
    <nav class="menubar-nav"><ul class="menu" role="menu"><li class="first last leaf" role="menuitem"><a href="/page/content/Publons" data-hide-link-title="0" class="" data-icon-position="">Get Peer Review Credit from Publons</a></li>
</ul></nav>  </div>

  
  </div>
</div>
  </div>
  <div class="panel-panel panel-region-col-4 grid-7 omega">
    <div class="inside"><div class="panel-pane pane-block pane-menu-other-services pane-menu" >
  
        <h2 class="pane-title">American Society of Neuroradiology</h2>
    
  
  <div class="pane-content">
    <nav class="menubar-nav"><ul class="menu" role="menu"><li class="first leaf" role="menuitem"><a href="http://www.neurographics.org/" data-hide-link-title="0" class="" data-icon-position="">Neurographics</a></li>
<li class="leaf" role="menuitem"><a href="http://www.asnr.org/index.php/education/fellowship-portal/" data-hide-link-title="0" class="" data-icon-position="">Fellowship Portal</a></li>
<li class="last leaf" role="menuitem"><a href="https://www.asnr.org/membership-types/" data-hide-link-title="0" class="" data-icon-position="">Not an ASNR Member? Join Now</a></li>
</ul></nav>  </div>

  
  </div>
</div>
  </div>
</div>    </div>
  </div>
</div>  </div>
</div>  </div>
  
  <div id="zone-footer" class="zone zone-footer clearfix container-30">
    <div class="grid-28 suffix-1 prefix-1 region region-footer-first" id="region-footer-first">
  <div class="region-inner region-footer-first-inner">
    <div class="block block-panels-mini block-jnl-ajnr-foot-info block-panels-mini-jnl-ajnr-foot-info odd block-without-title" id="block-panels-mini-jnl-ajnr-foot-info">
  <div class="block-inner clearfix">
                
    <div class="content clearfix">
      <div class="panel-display panel-1col clearfix" id="mini-panel-jnl_ajnr_foot_info">
  <div class="panel-panel panel-col">
    <div><div class="panel-pane pane-page-logo-footer" >
  
      
  
  <div class="pane-content">
    <img class="footer-logo" src="http://ajnr-stage2.stage.highwire.org/sites/default/files/ajnr-logo.png" alt="" />  </div>

  
  </div>
<div class="panel-separator"></div><div class="panel-pane pane-snippet pane-footer-copyright-text" >
  
      
  
  <div class="pane-content">
    <div class="snippet footer-copyright-text" id="footer-copyright-text">
  
      
  <div class="snippet-content">
    <p>&copy; 2025 by the <a href="http://www.asnr.org">American Society of Neuroradiology</a> All rights, including for text and data mining, AI training, and similar technologies, are reserved.<br />
Print ISSN: 0195-6108 Online ISSN: 1936-959X</p>
  </div>

</div>
  </div>

  
  </div>
<div class="panel-separator"></div><div class="panel-pane pane-highwire-branding" >
  
      
  
  <div class="pane-content">
    <a href="http://home.highwire.org" target="_blank" class="highwire-branding-link" data-icon-position="" data-hide-link-title="0"><img class="logo-highwire" src="http://ajnr-stage2.stage.highwire.org/sites/all/modules/highwire/highwire/plugins/content_types/images/logo_small_hw_white.png" width="190" height="31" alt="Powered by HighWire" /></a>  </div>

  
  </div>
</div>
  </div>
</div>
    </div>
  </div>
</div>  </div>
</div>  </div>
</footer>  </div>    <div class="region region-page-bottom" id="region-page-bottom">
  <div class="region-inner region-page-bottom-inner">
      </div>
</div><script type="text/javascript" src="/sites/default/files/advagg_js/js__bnwyEQSuZLC-kZnFqCi5iE02nOCzM7DjY7zYxcN9nsQ__VBiBT_qq_eHMMO2Q1rXK1u-hHff31XLUkmi9dgjuPeY__Op4k-kV4DoWc7bsUP7umKmZ0WXfmoYdRDoZFPNSd-oM.js"></script>
<script type="text/javascript" src="/sites/default/files/advagg_js/js__GM3GJPR36rRIz0TRkjC5OQwrioSyN9aoYRivDhCO_AM__qAl84FcCv2jyN22yFGS5Oc85cjd9zKX6p_cFNLGhe-M__Op4k-kV4DoWc7bsUP7umKmZ0WXfmoYdRDoZFPNSd-oM.js" async="async"></script>
<script type="text/javascript" src="/sites/default/files/advagg_js/js__puuQ6qZuZflSOzhCnY-jgY7Fv9AlRwAQ8SzEc4pSqOs__QdvWVdmkPpxtURk1sK0nHm-KZ4OJQjVuYZTnLqK1Isw__Op4k-kV4DoWc7bsUP7umKmZ0WXfmoYdRDoZFPNSd-oM.js"></script>
<script type="text/javascript">
<!--//--><![CDATA[//><!--
function euCookieComplianceLoadScripts() {}
//--><!]]>
</script>
<script type="text/javascript">
<!--//--><![CDATA[//><!--
var eu_cookie_compliance_cookie_name = "";
//--><!]]>
</script>
<script type="text/javascript" src="/sites/default/files/advagg_js/js__WcTpt-w0y1FyXrxZNriX8Ts1KjsFTDpdvZaw9yhRn24__aFJpdvsZPb1v9rWrq-WXbz_WQ9IThQN-mFTCdm1cfXc__Op4k-kV4DoWc7bsUP7umKmZ0WXfmoYdRDoZFPNSd-oM.js"></script>
  </body>
</html>