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David S. Hersh, Katherine N. Sanford, Kenneth Moore and Frederick A. Boop

Dorsally exophytic brainstem tumors arise from within the brainstem itself. As the tumor grows, it pulls eloquent tissue with it, resulting in a shape that is analogous to the sides of a volcano. Rather than a resection that is flush with the brainstem being performed, this functional tissue on the lateral edges of the tumor must be identified and preserved in order to avoid postoperative deficits. The authors describe a midline, suboccipital approach with the use of intraoperative direct stimulation to identify and preserve functional tissue innervating the palate during the resection of a dorsally exophytic medullary tumor.

The video can be found here: https://youtu.be/qbk2DvInO8o.

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Paul D. Sawin, Vincent C. Traynelis, Gretchen Rich, Bruce A. Smith, Timothy J. Maves, Kenneth A. Follett and Steven A. Moore

✓ The mechanism of action underlying chymopapain (Chymodiactin) chemonucleolysis remains obscure. Radiographic studies suggest that chymopapain does not alter disc fragment size acutely; nonetheless, patients often report symptom resolution within a few days, even hours, of treatment. The authors postulate that, in addition to its chemonucleolytic action, chymopapain may possess antiinflammatory properties. To test this hypothesis, the authors assessed the ability of chymopapain to modulate the activity of the proinflammatory enzyme phospholipase A2 (PLA2) and to ameliorate behavioral changes associated with inflammatory neuropathy in an in vivo model of sciatica.

Thirty-nine male Fischer rats were randomly assigned to one of three treatment groups: 1) saline, 2) betamethasone, or 3) chymopapain. All of the rats underwent unilateral sciatic nerve ligation with loose chromic gut suture to induce inflammatory mononeuropathy. The animals were tested for thermal and mechanical hyperalgesia on Days 0 (preoperation), 7 (pretreatment), and 14 (prior to death). Three animals were killed on Day 0 to determine the baseline PLA2 activity within unmanipulated rat sciatic nerves. On Day 7, three animals from each group were killed to assess PLA2 activity prior to treatment. The remainder were given a single infusion of saline, betamethasone (0.3 mg/kg), or chymopapain (100 pKat U) around the inflamed nerve. On Day 14, the remaining animals were killed and their sciatic nerves were removed. The tissue was homogenized and the PLA2 activity was determined using [14C]arachidonate—labeled Escherichia coli phospholipid membrane as a substrate. Lipids were extracted and separated by thin-layer chromatography.

All animals developed behavioral changes consistent with inflammatory mononeuropathy 24 to 72 hours postoperatively; these included gait disturbance, flexion deformity, and hyperalgesia of the involved hindlimb. The degree of mechanical and thermal hyperalgesia was comparable between groups at Day 7. By Day 14, the thermal hyperalgesia had resolved; the mechanical hyperalgesia was less evident in the betamethasone- and chymopapain-treated groups than in the saline-treated controls (p = 0.003; saline- vs. chymopapain-treated groups p = 0.004; saline- vs. betamethasone-treated groups p = 0.008). The mean PLA2 activity at baseline (Day 0) was 11.6 ± 4.9 nmol phospholipid hydrolyzed per minute per milligram of protein. The PLA2 activity at Day 7 was 74.4 ± 18.2 (ligated side) and 21.2 ± 11.7 (nonligated side). At Day 14, PLA2 activity was reduced in the chymopapain- (47.8 ± 12.3) and betamethasone- (39.7 ± 9.5) treated groups compared with the saline control group (62.3 ± 11.2), (saline- vs. chymopapain-treated groups p < 0.05; saline- vs. betamethasone-treated groups p < 0.01). The PLA2 activity in nonligated specimens was 18.6 ± 10.1.

These data indicate that chymopapain exhibits antiinflammatory properties in vivo, reducing PLA2 activity and ameliorating mechanical hyperalgesia in this model of inflammatory sciatic neuropathy.

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David S. Hersh, Kenneth Moore, Vincent Nguyen, Lucas Elijovich, Asim F. Choudhri, Jorge A. Lee-Diaz, Raja B. Khan, Brandy Vaughn and Paul Klimo Jr.

OBJECTIVE

Stenoocclusive cerebral vasculopathy is an infrequent delayed complication of ionizing radiation. It has been well described with photon-based radiation therapy but less so following proton-beam radiotherapy. The authors report their recent institutional experience in evaluating and treating children with radiation-induced cerebral vasculopathy.

METHODS

Eligible patients were age 21 years or younger who had a history of cranial radiation and subsequently developed vascular narrowing detected by MR arteriography that was significant enough to warrant cerebral angiography, with or without ischemic symptoms. The study period was January 2011 to March 2019.

RESULTS

Thirty-one patients met the study inclusion criteria. Their median age was 12 years, and 18 (58%) were male. Proton-beam radiation therapy was used in 20 patients (64.5%) and photon-based radiation therapy was used in 11 patients (35.5%). Patients were most commonly referred for workup as a result of incidental findings on surveillance tumor imaging (n = 23; 74.2%). Proton-beam patients had a shorter median time from radiotherapy to catheter angiography (24.1 months [IQR 16.8–35.4 months]) than patients who underwent photon-based radiation therapy (48.2 months [IQR 26.6–61.1 months]; p = 0.04). Eighteen hemispheres were revascularized in 15 patients. One surgical patient suffered a contralateral hemispheric infarct 2 weeks after revascularization; no child treated medically (aspirin) has had a stroke to date. The median follow-up duration was 29.2 months (IQR 21.8–54.0 months) from the date of the first catheter angiogram to last clinic visit.

CONCLUSIONS

All children who receive cranial radiation therapy from any source, particularly if the parasellar region was involved and the child was young at the time of treatment, require close surveillance for the development of vasculopathy. A structured and detailed evaluation is necessary to determine optimal treatment.

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David S. Hersh, Rahul Kumar, Kenneth A. Moore, Luke G. F. Smith, Christopher L. Tinkle, Jason Chiang, Zoltan Patay, Amar Gajjar, Asim F. Choudhri, Jorge A. Lee-Diaz, Brandy Vaughn and Paul Klimo Jr.

OBJECTIVE

Biopsies of brainstem lesions are performed to establish a diagnosis in the setting of an atypical clinical or radiological presentation, or to facilitate molecular studies. A better understanding of the safety and diagnostic yield of brainstem biopsies would help guide appropriate patient selection.

METHODS

All patients who underwent biopsy of a brainstem lesion during the period from January 2011 to June 2019 were reviewed. Demographic, radiological, surgical, and outcome data were collected.

RESULTS

A total of 58 patients underwent 65 brainstem biopsies during the study period. Overall, the median age was 7.6 years (IQR 3.9–14.2 years). Twenty-two of the 65 biopsies (34%) were open, 42 (65%) were stereotactic, and 1 was endoscopic. In 3 cases (5%), a ventriculoperitoneal shunt was placed, and in 9 cases (14%), a posterior fossa decompression was performed during the same operative session as the biopsy. An intraoperative MRI (iMRI) was performed in 28 cases (43%). In 3 of these cases (11%), the biopsy was off target and additional samples were obtained during the same procedure. New neurological deficits were noted in 5 cases (8%), including sensory deficits, ophthalmoparesis/nystagmus, facial weakness, and hearing loss; these deficits persisted in 2 cases and were transient in 3 cases. A pseudomeningocele occurred in 1 patient; no patients developed a CSF leak or infection. In 8 cases (13%) an additional procedure was needed to obtain a diagnosis.

CONCLUSIONS

Brainstem biopsies are safe and effective. Target selection and approach should be a collaborative effort. iMRI can be used to assess biopsy accuracy in real time, thereby allowing any adjustment if necessary.