Central Nervous System Lymphoproliferative Disorder Secondary to Methotrexate: A Systematic Literature Review and Case Illustration.

BACKGROUND: Methotrexate is an immunosuppressant commonly used to treat inflammatory conditions, such as rheumatoid arthritis. However, albeit exceedingly rare, it can have serious adverse effects within the central nervous system (CNS), such as methotrexate-associated lymphoproliferative disorder (MTX-LPD). Literature describing the natural history, treatment options, and clinical outcomes of patients with CNS MTX-LPD remains sparse. METHODS: We present a systematic literature review following Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and a case illustration of CNS MTX-LPD. RESULTS: A systematic review of the literature revealed 12 published cases of CNS MTX-LPD, plus the case presented herein, for a total of 13 included cases. The most common indication for MTX was rheumatoid arthritis. The most common treatment for the LPD was MTX cessation (12, 92.3%), adjunct chemotherapy (2, 15.4%), total tumor resection (3, 23.1%), or steroid therapy (1, 7.7%). Treatment usually led to improvement of neurological symptoms (9, 69.2%) along with regression of the lesions (3, 23.1%) with no recurrence (6, 46.2%). Death was reported in four cases (30.8%) with a mean time from onset of 11 months. CONCLUSIONS: CNS MTX-LPD should be considered in the differential diagnosis for patients who are taking MTX presenting with neurologic symptoms, as immediate withdrawal of MTX has demonstrated good prognosis.

Pediatric diffuse hemispheric glioma H3 G34-mutant with gains of the BRAF locus: An illustrative case.

Diffuse hemispheric glioma, H3 G34-mutant, is a recently recognized distinct high-grade glioma with a dismal prognosis. In addition to the H3 G34 missense mutation, numerous genetic events have been identified in these malignant tumors, including ATRX, TP53, and, rarely, BRAF genes. There are only a few reports to date that have identified BRAF mutations in diffuse hemispheric glioma, H3 G34-mutant. Moreover, to our knowledge, gains of the BRAF locus have yet to be described. Here, we present a case of an 11-year-old male with a diffuse hemispheric glioma, H3 G34-mutant, found to have novel gains of the BRAF locus. Furthermore, we emphasize the current genetic landscape of diffuse hemispheric glioma, H3 G34-mutant, and implications of an aberrant BRAF signaling pathway.

Successful Treatment of a Balamuthia mandrillaris Cerebral Abscess in a Pediatric Patient With Complete Surgical Resection and Antimicrobial Therapy.

Cerebral amebic encephalitis due to Balamuthia mandrillaris is a rare yet typically fatal disease. As such, identification of the clinical characteristics, appropriate diagnostic workup and commencement of treatment is frequently delayed. Here, we present a case of a 4-year-old male with a B. mandrillaris cerebral abscess successfully treated with expedited neurosurgical resection and broad-spectrum antimicrobial therapy.

Factors affecting R01 grant funding among academic neurosurgeons over the last decade.

BACKGROUND: Recent studies have reported a gender and medical degree disparity for those receiving Research Project Grants in surgical specialties. The aim of the present study is to analyze factors among academics neurosurgeons that correlate to higher amounts of R01 grant monies awarded. MATERIALS AND METHODS: The National Institutes of Health Research Portfolio Online Reporting Tools Expenditures and Results database was queried for neurosurgery funding between 2008 and 2018. Grant recipients were categorized among type of degree, secondary degree(s), professorship, gender, and h - index. Statistical analysis was performed. RESULTS: The National Institutes of Health awarded 480 R01 grants totaling $182,482,644 to 81 allopathic neurosurgeons between 2008 and 2018. No osteopathic neurosurgeons were awarded an R01 grant during this timeframe. There was a significant difference for type of professorship on the total awarded amount at the p < 0.05 level for the three types of professorship [F (2,78) = 4.85, p < 0.01)]. There was a significant difference for magnitude of h - index on total R01 monies (p < 0.00001). Males accounted for the majority of R01 monies (93.99%); however, no significant difference between average amount awarded and gender was identified (p = 0.86). A secondary degree was without significant difference for R01 amount awarded (p = 0.75). CONCLUSIONS: The present study establishes a medical degree disparity for academic neurosurgeons who receive an R01 grant. Statistically significant factors found to affect amount of R01 grant monies awarded were limited to type of professorship and magnitude of h - index.

Neurosurgical Management of Lateral Meningocele Syndrome: A Clinical Update for the Pediatric Neurosurgeon.

BACKGROUND: Lateral meningocele syndrome (LMS) is an exceedingly rare connective tissue disease with phenotypic anomalies similar to those seen in Marfan syndrome, Ehler-Danlos syndrome, and Loeys-Dietz syndrome. However, this syndrome is invariably associated with the presence of multiple lateral thoracolumbar spinal meningoceles: a distinct point of phenotypic divergence from other connective tissue disorders. The etiopathogenesis of this syndrome has recently been linked to truncating mutations within exon 33 of NOTCH3. Despite numerous reports, neurosurgical management of multiple spinal meningoceles remains poorly defined in the literature. We conducted a literature review to provide insight into the nosology, clinical significance, and neurosurgical management strategies of this distinct connective tissue disorder. SUMMARY: Our literature search revealed 11 articles (16 cases) of LMS, which included 9 males and 7 females, belonging to 14 different families. Half of these cases underwent genetic screening: all of which were discovered to exhibit a truncating mutation within exon 33 of NOTCH3. All patients exhibited multiple lateral thoracolumbar spinal meningoceles with craniofacial dysmorphisms. Other clinical characteristics included pathologic changes in spine morphology, Chiari I malformation, syringomyelia, hydrocephalus, and tethered cord. Operative management of multiple spinal meningoceles in LMS is complicated by the presence of such coexisting structural neurologic pathologies, which may alter cerebrospinal fluid flow dynamics and, ultimately, impact operative intervention. Key Messages: LMS is an exceedingly rare connective tissue disorder with severe spinal dural involvement. Neurosurgical management of multiple spinal meningoceles is complex, which is further complicated by the presence of coexisting neuropathology, such as pathologic transformation of spine morphology and Chiari I malformation. Patients with a connective tissue disorder phenotype found to have multiple spinal meningoceles on imaging studies may benefit from evaluation by a medical geneticist and a pediatric neurosurgeon.

The predictive capability of immunohistochemistry and DNA sequencing for determining TP53 functional mutation status: a comparative study of 41 glioblastoma patients.

Tumor protein 53 (p53) regulates fundamental pathways of cellular growth and differentiation. Aberrant p53 expression in glioblastoma multiforme, a terminal brain cancer, has been associated with worse patient outcomes and decreased chemosensitivity. Therefore, correctly identifying p53 status in glioblastoma is of great clinical significance. p53 immunohistochemistry is used to detect pathological presence of the TP53 gene product. Here, we examined the relationship between p53 immunoreactivity and TP53 mutation status by DNA Sanger sequencing in adult glioblastoma. Of 41 histologically confirmed samples, 27 (66%) were immunopositive for a p53 mutation via immunohistochemistry. Utilizing gene sequencing, we identified only eight samples (20%) with TP53 functional mutations and one sample with a silent mutation. Therefore, a ≥10% p53 immunohistochemistry threshold for predicting TP53 functional mutation status in glioma is insufficient. Implementing this ≥10% threshold, we demonstrated a remarkably low positive-predictive value (30%). Furthermore, the sensitivity and specificity with ≥10% p53 immunohistochemistry to predict TP53 functional mutation status were 100% and 42%, respectively. Our data suggests that unless reliable sequencing methodology is available for confirming TP53 status, raising the immunoreactivity threshold would increase positive and negative predictive values as well as the specificity without changing the sensitivity of the immunohistochemistry assay.

Intracranial Squamous Cell Carcinoma Arising From a Cerebellopontine Angle Epidermoid Cyst Remnant Four Decades After Partial Resection.

Intracranial epidermoid cysts are benign lesions that typically remain asymptomatic; however, although histopathologically benign, these cysts can rarely undergo malignant transformation into squamous cell carcinoma. Primary intracranial squamous cell carcinoma carries a poor prognosis as optimal treatment modalities remain unclear due to their low incidence. Here, we present a case of a cerebellopontine angle epidermoid cyst remnant that underwent malignant transformation into squamous cell carcinoma 40 years after partial resection. To our knowledge, this case establishes the longest time interval to date for an intracranial epidermoid cyst to undergo malignant transformation. We also review the relevant literature and discuss recent retrospective clinical studies that have analyzed the effect of multimodal treatment approaches on survival outcomes in patients with these lesions.

Postexercise Death Due to Hemorrhagic Colloid Cyst of Third Ventricle: Case Report and Literature Review.

BACKGROUND: Colloid cysts of the third ventricle are rare, slow-growing lesions of neuroepithelial origin. Although histopathologically benign, third ventricular colloid cysts are a well-known cause of sudden, unexpected coma and death. Several theories have been proposed to describe the rare, sudden onset of severe symptomatology and rapid clinical decline due to colloid cysts. Moreover, there is currently no clear consensus regarding the most suitable neurosurgical technique or the most effective approach for resection, nor do guidelines or standardized clinical indications exist to recommend observation versus intervention and/or resection in the asymptomatic patient. To highlight this conundrum, we present a clinical case of a hemorrhagic colloid cyst that resulted in fatality and discuss the relevant literature. CASE DESCRIPTION: A 21-year-old male presented to an outside hospital with an acute onset of a severe headache, nausea, and vomiting, which started while jogging. A few hours later, he precipitously declined into a comatose state. Radiographic imaging demonstrated a hemorrhagic third ventricular colloid cyst causing acute obstructive hydrocephalus, severe increased intracranial pressure, and downward herniation. He was then transferred to our institution for neurosurgical intervention. Despite aggressive cerebrospinal fluid drainage and medical management, he was declared brain dead several days later. CONCLUSIONS: To our knowledge, this is the only case report to describe sudden-onset coma and death due to a hemorrhagic third ventricular colloid cyst occurring after exercising. We review the literature on fatal colloid cysts emphasizing the proposed mechanisms of sudden death and current neurosurgical management in both asymptomatic and symptomatic patients.

Rapidly Expanding Lateral Ventricular Meningioma Presenting with Intraventricular Hemorrhage following Remote Whole Brain Radiation and Stereotactic Radiosurgery.

Intraventricular meningiomas are uncommon intracranial tumors and infrequently present with hemorrhage. With only 10 reported cases in the literature, it is exceedingly rare for meningiomas of the ventricular system to present with hemorrhage. To our knowledge, this is the first report of a patient presenting with an acute intraventricular hemorrhage in relation to a ventricular meningioma suspected to be radiation induced. In addition, we review the current literature on hemorrhagic intraventricular meningiomas and review the natural history of radiation-induced meningiomas.