Restored Activation of Primary Motor Area from Motor Reorganization and Improved Motor Function after Brain Tumor Resection

N. Shinoura; Y. Suzuki; R. Yamada; T. Kodama; M. Takahashi; K. Yagi

Abstract

BACKGROUND AND PURPOSE: Reorganization of brain function may result in preservation of motor function in patients with brain tumors. The goal of the present study was to investigate whether function of the primary motor area (M1) was restored and whether motor function improved after brain tumor resection.

METHODS: Five patients with metastatic brain tumors located within or near M1 underwent awake surgery with intraoperative cortical mapping and continuous task monitoring. Preoperative and postoperative functional MR imaging (fMRI) was performed during hand clenching, and diffusion tensor imaging (DTI) was performed in 1 case to further characterize the area activated in fMRI.

RESULTS: Preoperative fMRI performed during hand clenching demonstrated reorganization of motor function. In patients with severe paresis (cases 3, 4, and 5), clenching of the affected hand induced a large blood oxygen level–dependent response in the right hemisphere, mainly in the anterior temporal lobe, despite the location site of the tumor. Postoperative fMRI during hand clenching demonstrated activation of the contralateral M1. Furthermore, in case 5, DTI detected tracts, possibly the inferior longitudinal fasciculus, arising from anterior temporal activated area as well as tracts connecting the premotor and M1 activated area. This patient demonstrated mirror movement of the hand during the course of motor function recovery.

CONCLUSIONS: Tumor resection resulted in restoration of M1 function and improved motor function in patients with preoperative reorganization of M1 function. Furthermore, the preoperative reorganization of motor function in cases with severe paresis may be related to changes in the right hemisphere, including the temporal lobe.

Functional MR imaging (fMRI) studies and intraoperative cortical mapping have demonstrated reorganization of the motor area in response to gradual compression of the primary motor cortex (M1) by a tumor.^{^1–4} This reorganization allows for variable preservation of motor function and can occur in one of several patterns, including perilesional extension, shifts from primary to secondary motor areas, or shifts to homologous areas of the unaffected hemisphere.^{^5–11} However, the status of this reorganization after tumor resection is not known. Thus, the goal of the present study was to investigate whether function of the M1 is restored and whether motor function improves after brain tumor resection.

Materials and Methods

Patient

The degree of paresis before and after surgery is indicated by using an objective scale as follows: 5 = normal, contraction against powerful resistance, 5− = between 5 and 4, 4 = good, contraction against gravity and some resistance, 3 = fair, contraction against gravity only, 2 = poor, movement only with gravity eliminated, 1 = trace, flicker of contraction, and 0 = complete paralysis.

Case 1.

A 57-year-old woman with breast cancer experienced onset of right hand paresis (scale 5−) after developing epilepsy 1 month before surgery. MR imaging showed a heterogeneously enhancing tumor within a left frontal lesion (Fig 1A-1).

Fig 1.

Case 1. A 57-year-old woman with metastatic brain tumor located inside the left-sided M1.

A-1, Preoperative MR imaging displays heterogeneously enhancing tumor in the M1.

A-2, Postoperative MR imaging shows ring enhancing lesion, but there was no residual tumor in the M1 according to the intraoperative observation for tumor cavity.

B, fMRI images activated by right hand clenching (B, orange) and right elbow flexion (B, blue) before surgery.

C, fMRI images activated by right hand clenching (orange) and right elbow flexion (blue) after surgery. A relatively small area of the contralateral M1 was activated by right hand clenching before surgery, whereas a large area of the contralateral M1 was activated by right hand clenching after surgery.

Case 2.

A 71-year-old man with lung cancer experienced onset of left-sided hemiparesis (scale 5−) 1 month before surgery. MR imaging demonstrated a heterogeneously enhancing tumor within a right parietal lesion (Fig 2A-1).

Fig 2.

Case 2. A 71-year-old man with metastatic brain tumor located inside the right-sided S1.

A-1, Preoperative MR imaging displays heterogeneously enhancing tumor in the S1.

A-2, Postoperative MR imaging shows no residual tumor in the S1.

B, fMRI images activated by left hand clenching (B, orange) and right hand clenching (B, blue) before surgery.

C, fMRI images activated by left hand clenching (orange) and right hand clenching (blue) after surgery. Left hand clenching (orange area in B) activated the contralateral M1 and S1 areas separately before surgery and (orange area in C) activated the large area of the contralateral M1 and S1, and contralateral supplementary motor area after surgery.

Case 3.

A 49-year-old man with colon cancer experienced onset of right-sided hemiparesis (upper extremity [scale 4] affected more than lower extremity [scale 5−]) and aphasia 1 month before surgery. MR imaging demonstrated a heterogeneously enhancing tumor within a left frontal lesion (Fig 3A-1).

Fig 3.

Case 3. A 49-year-old man with metastatic brain tumor located inside the left-sided premotor area.

A-1, Preoperative MR imaging displays heterogeneously enhancing tumor in the premotor area.

A-2, Postoperative MR imaging shows no residual tumor in the premotor area.

B, fMRI images activated by right hand clenching (B-1, B-3; orange) and left hand clenching (B-2, B-4; blue) before surgery,

C, fMRI images activated by right hand clenching (orange) and left hand clenching (blue) after surgery. The ipsilateral and contralateral M1 and the anterior temporal lobe was activated by right hand clenching before surgery, whereas the contralateral M1 was activated by right hand clenching after surgery. The area in the anterior temporal lobe activated by right hand clenching before surgery (B-1) was not activated by right hand clenching after surgery (C-1).

Case 4.

A 71-year-old woman with colon cancer experienced onset of left-sided hemiparesis (scale 4) 1 month before surgery. MR imaging demonstrated a heterogeneously enhancing tumor within a right frontal lesion (Fig 4A-1).

Fig 4.

Case 4. A 71-year-old woman with metastatic brain tumor located inside the right-sided premotor area.

A-1, Preoperative MR imaging displays heterogeneously enhancing tumor in the premotor area.

A-2, Postoperative MR imaging shows no residual tumor in the premotor area.

B, fMRI images activated by right hand clenching (blue) and left hand clenching (red) before surgery,

C, fMRI images activated by right hand clenching (blue) and left hand clenching (orange) after surgery. Both left and right hand clenching activated the right temporal and frontal lobes before surgery. After surgery, left and right hand clenching activated the anterior temporal lobe (C-1,-2,-3), and left hand clenching activated a relatively small area of contralateral M1 (C-6). Because both preoperative and postoperative fMRI show similar atypical results such as no activation in the left hand M1 during right hand clenching, it seems that this result was not artifactual. It is not clear why there is no activation in the left M1 during right hand clenching, but the right hemisphere might be mainly activated by both right and left hand clenching in the case of severe paresis, possibly because of the preferential processing of spatial information in the right hemisphere.

Case 5.

A 76-year-old man with renal cancer experienced onset of left-sided hemiparesis 1 month before surgery (scale 4). Weakness of the left arm progressed after several episodes of partial seizures involving the left arm. MR imaging showed a heterogeneously enhancing mass within a right frontal lesion (Fig 5A-1).

Fig 5.

Case 5. 76-year-old man with metastatic brain tumor located inside the right-sided M1.

A-1, Preoperative MR imaging displays heterogeneously enhancing tumor in the M1.

A-2, Postoperative MR imaging shows no residual tumor in the M1.

B, fMRI images activated by left hand clenching (orange) before surgery. fMRI by right hand clenching was not performed before surgery.

C, fMRI images activated by left hand clenching (orange) and right hand clenching (blue) after surgery. A relatively small area of the ipsilateral (B-3) and contralateral (B-2) M1 was activated by left hand clenching before surgery. A large portion of the right premotor and M1 were activated by left hand clenching after surgery (C-4, orange). The anterior temporal area was activated by left hand clenching before surgery (B-1) and by right or left hand clenching after surgery (C-1). The right medial M1 was activated by right or left hand clenching (C-3).

Preoperative paresis was relatively severe in cases 3, 4, and 5 compared with cases 1 and 2. Informed consent to perform fMRI, diffusion tensor imaging (DTI), and awake surgery was obtained from each patient.

fMRI and Image Analysis

The fMRI and image analysis was performed as described previously.^¹² In brief, the fMRI was performed with a 1.5T General Electric Signa Horizon LX imager (GE Yokokawa Medical System, Tokyo, Japan) with an acquisition sequence of: gradient-echo–echo-planar imaging (EPI) echo time [TE]/repetition time [TR] = 82.5/3000 ms, 128 × 128 matrix, with a 24 × 24-cm field of view. The reconstructed voxel size was 1.88 × 1.88 × 2.3 mm³. Five-millimeter thickness sections were obtained with 70 repetitions, and a block design of 30-second interval was used. fMRI was performed 1 week before surgery and 1 month after surgery, and the patient was asked to perform repetitive closing of the hand to a fist (hand clenching), because functional hand motor recovery is usually complete at this point in patients who had surgery for brain tumor. The fMRI acquisition time was approximately 3.5 minutes. Anatomic images were acquired with the use of a 3D fast- spoiled gradient echo sequence with TE of 2.4 ms, TR of 26.0 ms, flip angle of 30°, bandwidth of 31.25 kHz, image matrix of 256 × 256, and section thickness of 2.3 mm. After reconstruction, the EPI images were aligned to correct for head motion and were co-registered with anatomic images. EPI images were smoothed by using isotropic Gaussian kernels of 4 mm, and statistical analysis was performed by using the SPM program (London University, London, England).^¹³ The significance of the activations (P value) was less than 0.05, depending on the degree of paresis of patients. When the degree of paresis was severe, we needed to increase P value to detect the activated area. The limitations of fMRI, especially when evaluating individual patients who might be uncomfortable to perform specific tasks because of their handicaps, should be noted.

DTI Image Analysis and Coregistration of fMRI and DTI Images

DTI and image analysis was performed as described previously.^¹² In brief, standard imaging gradients were used with a maximum strength of 22 mT/m and a slew rate of 77 mT/m/ms. All data were acquired by using a birdcage head coil. The DTI acquisition sequence was a single-shot, spin-echo EPI, with TE of 98.6 ms, 128 × 128 acquisition matrix, and a 24 × 24-cm field of view.^¹⁴ Acquisitions of contiguous 5-mm sections were obtained, covering the whole brain, with a b value of 1000 mm²/s in 42 noncollinear directions. The reconstructed voxel size was 1.88 × 1.88 × 4.00 mm³. The DTI acquisition time for 61 images was approximately 10 minutes. The diffusion tensor eigenvalues (λ₁, λ₂, λ₃) and eigenvectors (ε₁, ε₂, ε₃) were calculated from DTI data, and fractional anisotropy (FA) maps were generated according to the Tensorlines algorithm,^{^15,16} which was a combination of the tensor deflection algorithm at low FA and Streamlines tracking at high FA,^{^17–19} with the use of DTI Analyzer (IDL v. 5.6; Research System, Boulder, Colo). Stopping criteria (threshold 0.1) were used for analysis.

Using the highest significantly activated fMRI voxel in each task, coregistration of fMRI and DTI images were used to select the seed points on the FA maps within the white matter adjacent to the activated cortex during fMRI. For the tractography of pathways, the following (regions of interest) ROIs were selected in case 5: the right premotor and M1, and the right anterior temporal lobe.

Mapping and Awake Tumor Resection

Mapping and awake tumor resection was performed as described previously.^²⁰ In brief, the patient was positioned in the supine position and given rigid head fixation (Sugita Headrest; Mizuho Medical Co, Tokyo, Japan) after administration of a local anesthetic agent at the pin sites and regional field block sites. Under general anesthesia with fentanyl and propofol by laryngeal mask airway, the skin was infiltrated with the same local anesthetic agent and incised, and a craniotomy and incision of the dura was performed.

The laryngeal airway was then removed and oxygen was administered via a nasal cannula. Cortical mapping was performed by stimulating the cortex with the modified Ojemann stimulator.^{^21,22} To avoid an intraoperative seizure, a low-stimulus setting (3–5 mA, 60-Hz biphasic square wave pulse of 1 ms/phase for 4 seconds’ duration) was used. Electrocorticography was performed to monitor for after-discharges during stimulations. The patients were observed by the neurosurgeon, and movements of hand clenching were continuously monitored and reported to the operator.

Corticotomy was performed, avoiding the sites identified as eloquent cortex by cortical mapping, and the tumor was removed in the usual fashion. Continuous adequate task judging from the fMRI and DTI images was performed during the removal of tumor near the eloquent motor area responsible for the movement of hand. The patient was performing adequately tasks such as clenching the affected hand, bending the affected elbow, raising the affected arm, or bending the affected knee during the removal of the tumor that was located near the eloquent hand motor area as determined by fMRI and DTI. The fMRI and DTI data combined with a neuronavigation system was available to the neurosurgeon in the operating room, as described before.^²⁰ We have attempted to correlate preoperative fMRI and brain mapping data by using a neuronavigation system. To prevent deterioration of motor function, continuous task under awake anesthesia seems more useful in comparison with electrophysiologic monitoring of the motor strip during general anesthesia, because we could detect subtle deterioration of individual motor function by continuous task.^²⁰ After completion of the tumor resection, the patient was reintubated with a laryngeal airway, and general anesthesia with fentanyl and propofol was administered. After closure of dura, the bone flap was replaced, and the skin was closed in the usual manner.

Results