Case Report: Metastatic Bronchopulmonary Carcinoid Tumor to the Pineal Region.

Intracranial spread of a systemic malignancy is common in advanced staged cancers; however, metastasis specifically to the pineal gland is a relatively rare occurrence. A number of primary lesions have been reported to metastasize to the pineal gland, the most common of which is lung. However, metastasis of a bronchial neuroendocrine tumor to the pineal gland is a seldom-reported entity. Here, we present a 53-year-old female who presented with worsening headaches and drowsiness. MRI brain revealed a heterogeneously enhancing partially cystic mass in the pineal region. The patient had an extensive oncologic history consisting of remote stage IIA invasive breast ductal carcinoma as well as a more recently diagnosed atypical bronchopulmonary neuroendocrine tumor with lymph node metastases. She underwent microsurgical volumetric resection of the large pineal mass and a gross total removal of the tumor was achieved. Histopathology confirmed a metastatic tumor of neuroendocrine origin and the immunohistochemical profile was identical to the primary bronchopulmonary carcinoid tumor. Eight weeks after surgery, she underwent stereotactic radiosurgical treatment to the resection cavity. At 1-year follow-up, the patient remains clinically stable without any new focal neurological deficits and without any evidence of residual or recurrent disease on postoperative MRI. Metastatic neuroendocrine tumors should be considered in the differential diagnosis of pineal region tumors and aggressive surgical resection should be considered in selected patients. Gross total tumor resection may afford excellent local disease control. We discuss the relevant literature on neuroendocrine tumors and current treatment strategies for intracranial metastases of neuroendocrine origin.

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.

Corticosteroid-Induced Regression of Glioblastoma: A Radiographic Conundrum.

Corticosteroid-induced regression of lesion contrast enhancement on imaging studies is most commonly appreciated with primary central nervous system lymphoma; however, although exceedingly rare, a limited number of primary and metastatic intracranial lesions have been reported to exhibit similar radiographic changes subsequent to corticosteroid therapy. To date, there have been six cases of glioblastoma reported to exhibit such changes. Lesion transformation on repeat imaging after the initiation of steroids represents a diagnostic dilemma for clinicians when attempting to differentiate between a diagnosis of glioblastoma and lymphoma. Stereotactic biopsy may be inadvertently postponed due to high clinical suspicion for steroid-induced cytotoxicity traditionally seen with lymphomatous cells. To highlight this radiographic conundrum, we present a rare case of corticosteroid-induced regression of glioblastoma and discuss the relevant literature. To our knowledge, this is the first case report to describe the molecular profile of a glioblastoma that underwent corticosteroid-induced regression.

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.

The Effects of 24-Hour Neurosurgical Call on Fine Motor Dexterity, Cognition, and Mood.

BACKGROUND: Concerns regarding the effects of fatigue on physician performance and quality of life lead to the implementation of duty hour restrictions for residents by the Accreditation Council for Graduate Medical Education (ACGME). These restrictions have been met by strong criticism from the neurosurgical community. This is partly due to a lack of objective evidence that fatigue results in decrements in professional function in neurological surgeons. There is also concern that the restrictions have diminished clinical and operative experience as well as the development of professional responsibility in residency. OBJECTIVE:  To evaluate whether 24-hour neurosurgical call has an objective impact on fine motor dexterity, cognitive thinking skills, and mental well-being. METHODS: Subjects were tested before and after taking 24 hours of neurosurgical call. We evaluated fine motor dexterity using the Vienna Test System Motor Performance Series, cognitive thinking abilities using a battery of paper-pencil neuropsychological tests, and mental well-being using the Profile of Mood States.  Results: A total of 27 subjects were included in this study, 12 seasoned to neurosurgical call and 15 naive to neurosurgical call. The seasoned subjects demonstrated no statistically significant change in performance after call on any of the tests for fine motor dexterity or cognitive thinking abilities. The nonseasoned subjects demonstrated multiple decrements in fine motor dexterity and cognitive thinking abilities after taking call. In the Motor Performance Series, they had a statistically significant decrease in the speed of untargeted movements in the nondominant hand during the tapping test (p = 0.002), and a decline in the precision of fine motor movements and information processing as evidenced by an increase in the number of errors of the dominant hand in the line tracking test (p = 0.014). There was a statistically significant decline in their immediate memory during Hopkins Verbal Learning Test (p = 0.025), and complex attention, mental flexibility, and visual-motor speed in the Trail Making Test (p = 0.03). The Profile of Mood States found no difference in feelings of anger (p = 0.54), tension (p = 0.358), or depression (p = 0.65). There were increased feelings of confusion (p < 0.001) and decreased feelings of vigor (p < 0.001) and friendliness (p = 0.001). Nonseasoned subjects had an increase in total mood disturbance (p = 0.012) but seasoned subjects did not (p = 0.083).  Conclusion: Our results suggest that fatigue-induced decrements in professional function can be ameliorated by experience with prolonged duty hours. In contrast to nonseasoned subjects, those who were conditioned to 24-hour neurosurgical call demonstrated resilience in fine motor dexterity and cognitive thinking skills, and exhibited no change in total mood disturbance. An argument can be made that we are turning the neurosurgical training paradigm upside down with the current ACGME duty hour restrictions.

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.

Meckel Cave Epidermoid Cyst Presenting as Multiple Cranial Nerve Deficits Due to Indirect Tumoral Compression of the Cavernous Sinus: A Case Report and Literature Review.

BACKGROUND: Epidermoid cysts in Meckel cave are exceedingly rare. Since 1971, only 17 cases have been reported in the literature, with most patients presenting with trigeminal hypesthesia. However, outgrowth of these lesions from Meckel cave can rarely lead to compression of the proximate cavernous sinus and the neurovascular structures contained within. To date, 2 cases have reported a Meckel cave epidermoid cyst presenting clinically as an intracavernous cranial nerve palsy, presumably a clinical manifestation of cavernous sinus compression from the lesion. CASE DESCRIPTION: We describe a case involving a 51-year-old woman presenting with unilateral refractory trigeminal neuralgia, facial hypesthesia, abducens palsy, plus new-onset partial ptosis. Magnetic resonance imaging revealed a mass in the left Meckel cave that was T1 hypointense, T2 hyperintense, peripherally enhancing, and restricting diffusion. A stereotactic left subtemporal extradural approach was used to resect the lesion, which alleviated most of the patient's symptomatology except for minimal intermittent left-sided facial hypesthesia that remained at her 1-year postoperative visit. CONCLUSIONS: This is a unique report depicting an epidermoid cyst in the Meckel cave causing numerous cranial nerve deficits because of indirect tumoral compression of cranial nerves within the cavernous sinus.

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.

Quantitative Description of Osteopathic Physician Authorship in Prominent Neurosurgery Journals Since 1944: Coming of Age?

Background The Accreditation Council for Graduate Medical Education and the American Osteopathic Association recently agreed to establish a single graduate medical education system for the United States allopathic and osteopathic resident physicians by 2020. Consequential to this merger, new standards will be implemented for academic and research requirements within medical schools as well as residency programs. In the United States, osteopathic medicine is considered to be a parallel profession to allopathic medicine. However, recent studies have revealed that the percentages of United States osteopathic physicians currently in practice are not proportional to the percentages of editorial board member positions they hold in several high-profile medical journals as well as neurosurgical journals. To our knowledge, there is currently no published literature examining osteopathic physician author representation of any neurosurgical journal. In the present study, we analyze the number of osteopathic physicians and osteopathic neurosurgeons serving as authors in prominent neurosurgical journals. Methods American neurosurgical journals with the highest number of citations plus an affiliation with a neurosurgical society open to osteopathic neurosurgeons were used as criteria for journal selection. The Journal of Neurosurgery Publishing Group journals (Journal of Neurosurgery, Journal of Neurosurgery: Spine, Journal of Neurosurgery: Pediatrics, and Neurosurgical Focus) fulfilled these criteria. The number of allopathic and osteopathic physicians who have published at least one manuscript in a Journal of Neurosurgery Publishing Group journal was counted. The specialty of each osteopathic author was examined. Results Our analysis found that allopathic physicians represented 105,157 (99.68%) and osteopathic physicians represented 335 (0.32%) of the 105,492 authorship positions held by these physicians in these journals since 1944. Statistical significance was found comparing the number of allopathic authors versus the number of osteopathic authors (p < 0.0001). The most common specialty represented by osteopathic authors in all journals was neurosurgery (45%). Osteopathic neurosurgeons represented 153 (0.15%) of the total number of allopathic and osteopathic authors. Conclusions These data establish that the percentages of the United States osteopathic physicians and osteopathic neurosurgeons currently in practice are not proportional to the percentages of authorship positions they hold in Journal of Neurosurgery Publishing Group journals. We postulate that this apparent disproportionality may originate from significant differences between allopathic and osteopathic medical school research funding, research opportunities, scholarly activities, and dual-degree programs.

ACTA2 Cerebral Arteriopathy: Not Just a Puff of Smoke.

BACKGROUND: Missense mutations in the gene that codes for smooth muscle actin, ACTA2, cause diffuse smooth muscle dysfunction and a distinct cerebral arteriopathy collectively known as multisystemic smooth muscle dysfunction syndrome (MSMDS). Until recently, ACTA2 cerebral arteriopathy was considered to be a variant of moyamoya disease. However, recent basic science and clinical data have demonstrated that the cerebral arteriopathy caused by mutant ACTA2 exhibits genetic loci, histopathology, neurological sequelae, and radiographic findings unique from moyamoya disease. We conducted a literature review to provide insight into the history, clinical significance, and neurosurgical management of this recently described novel cerebral arteriopathy. SUMMARY: We performed a literature search using PubMed with the key words "ACTA2 mutation," "ACTA2 cerebral arteriopathy," and "multisystemic smooth muscle dysfunction syndrome." Case reports with confirmed ACTA2 mutations and cerebral arteriopathy were included in our review. Our literature search revealed 15 articles (58 cases) of confirmed ACTA2 cerebral arteriopathy. Distinctive features of this arteriopathy included an aberrant internal carotid circulation with dilatation of the proximal segments, occlusive disease at the distal segments, and dolichoectasia. As such, mutant ACTA2 predisposed patients to ischemic strokes as children. Direct and indirect cerebral revascularization procedures are the mainstay treatment options with varying degrees of success. Key Messages: ACTA2 cerebral arteriopathy is a recently described novel cerebrovascular disease seen in patients with MSMDS. Patients currently diagnosed with moyamoya disease who also have dysfunction of smooth muscle organs may benefit from reevaluation by a medical geneticist and ACTA2 genotyping.

Vaccine-Based Immunotherapeutics for the Treatment of Glioblastoma: Advances, Challenges, and Future Perspectives.

Glioblastoma is a highly aggressive neoplasm with an extremely poor prognosis. Despite maximal gross resection and chemoradiotherapy, these grade IV astrocytomas consistently recur. Glioblastoma cells exhibit numerous pathogenic mechanisms to decrease tumor immunogenicity while promoting gliomagenesis, which manifests clinically as a median survival of less than 2 years and few long-term survivors. Recent clinical trials of vaccine-based immunotherapeutics against glioblastoma have demonstrated encouraging results in prolonging progression-free survival and overall survival. Several vaccine-based treatments have been trialed, such as peptide and heat-shock proteins, dendritic cell-based vaccines, and viral-based immunotherapy. In this literature review, we discuss the immunobiology of glioblastoma, significant current and completed vaccine-based immunotherapy clinical trials, and broad clinical challenges and future directions of glioblastoma vaccine-based immunotherapeutics.

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.

Economic Impact of Hospitalization Past Maximal Neurosurgical Inpatient Benefit.

Background The unsustainable cost of healthcare in the United States has made it important for all healthcare professionals to examine their practices for wasteful spending and work to mitigate these costs. When neurosurgical patients remain hospitalized beyond the point of maximum inpatient benefit, this represents a potential source of healthcare economic waste. Objective The objective of this study was to determine the direct and indirect costs to a hospital system when neurosurgical patients remain hospitalized past the maximum inpatient benefit and identify targets to improve this potential wasteful spending.  Methods We performed an extensive chart review of all patients admitted to our neurosurgical service from the months of July to October 2016, who had been deemed medically stable for discharge but remained in the hospital past their ideal date of discharge. We analyzed for significant trends in patient factors, procedural acuity, disposition, funding, and other factors that contributed to the delays in discharge. Results A total of 334 patients were admitted to the Carilion Clinic-Virginia Tech Carilion (CC-VTC) inpatient neurosurgery service, and 50 of these admissions (15%) resulted in medically unnecessary prolonged hospitalizations. These patients were hospitalized for a total of 324 days past the dates of ideal discharge. Elective cases had the maximum number of prolonged hospitalizations, while the emergent cases had the maximum number of prolonged hospitalization days. Patients with private insurance had the shortest number of prolonged hospitalization days, and uninsured patients had the longest. Patients requiring disposition to a rehabilitation or a nursing facility remained in the inpatient setting for longer periods than those destined for home. The most common factors limiting appropriate discharge were related to bed availability at outside facilities, funding issues, and differing opinions on appropriate disposition. The medically unnecessary days accounted for 41% of the total hospitalization but accounted for only 12.9% of the billable charges. The billable cost per medically necessary day was $17,326 in comparison to a medically unnecessary day of $2,070. Indirect costs were inferred from these patients utilizing beds and resources that could have been allocated to others with acute needs, given that our hospital is at capacity and on diversion, a significant percentage of the time. Conclusion Neurosurgical patients remaining hospitalized past their maximal inpatient benefit have a significant economic impact on a hospital system. Identifying patients who are at risk for prolonged hospitalizations may provide us with the targets for improvement to mitigate this healthcare economic waste.