Table 3:

Relevant literature review of CNS HLH cases with brainstem or cerebellitis patterns with available MR imaging and genetic data

Literature Review	Imaging Pattern	Genetic Variants	Age of Onset, Relation to Systemic HLH	Imaging Findings
Benson et al²3 cases	Brainstem–predominant pattern (CLIPPERS- like)	1 disruptive, 2 with missense mutations and absent protein expression Pt 1: PRF1 c.452A>T (p.H151L) and c.666C>A (H222Q), Perforin expression 0% Pt 2: PRF1 c.443C>G (p.A148G) and c.666C>A (H222Q), Perforin expression 0% Pt 3: UNC13D c.2346_2349delGGAG(p.R782fs), c.2588G>A (p.G863D)	5–7 yr, all 3 CNS-restricted HLH	CLIPPERS MR imaging criteria NA
Taieb et al²⁸4 patients	Brainstem–predominant pattern (CLIPPERS- like)	4 cases, all with missense mutations and retained-but-decreased protein expression Pt 1: PRF1 c.272C>T(p.A91V) homozygous, perforin expression 38% Pt 2: UNC13D c.919C>T (p.Q307) and c.2038C>T (p.R680W), not applicable Pt 3: PRF1* c.116C>A (p.P39H) and c.272C>T (p.A91V), perforin expression 25% Pt 4: PRF1 c.82C>T (p.R28C) and c.272C>T (p.A91V), perforin expression 38%	Adults (42–73 yr), all had CNS-restricted HLH	Three-fourths had atypical MR imaging CLIPPERS features (confluent contrast-enhancing lesions)
Bhoopalan et al²⁶ 1 patient	Cerebellitis	1 patient with compound heterozygous PRF1 gene mutations with at least 1 disruptive mutation PRF1: c.50delT (p.L17fs) and c.527G>A(p.C176Y))	8 yr, CNS-restricted HLH	Cerebellitis, tonsillar herniation, no multifocal lesions
Khan et al²⁷1 patient	Cerebellitis	1 patient with homozygous missense mutation c. 173T > C (p.L58P) in STX11 (syntaxin 11) gene	2 yr 7 months, systemic HLH already present	Cerebellitis, tonsillar herniation, diffuse-to-multifocal lesions already present
Astigarraga et al³ 1 patient	Cerebellitis	1 patient with compound heterozygous missense PRF mutations PRF1: c.643C>A (p.L215I) and c.785C>A (p.Ala262Asp) (perforin expression data NA)	3 yr, preceded systemic HLH	Recurrent cerebellitis, tonsillar herniation, subsequently multifocal lesions
Taieb et al²⁸1 patient	Cerebellitis	Patient 3’s (in CLIPPERS series) brother’s; granddaughter, monoallelic PRF1 mutation (genetic variant NA)	Not specified, self-limited CNS-restricted presentation	NA
Chiapparini et al²⁹ 1 patient	Cerebellitis	1 patient with homozygous missense PRF1 mutation c.673C>T (p.Arg225Trp) (perforin expression data NA)	13 yr, preceded systemic HLH	Cerebellitis, tonsillar herniation followed by multifocal lesions

Note:—NA indicates not available; Pt, patient.