Joshua A. Cuoco

Operation Frankenstein: Ethical Reflections ofHuman Head Transplantation

Practically every human organ is commonly transplanted providing temporary or permanent relief from a pathologic condition. Although organ transplantation can prolong life, the question arises as to whether it is ethical for any organ of the human body to be transplanted, particularly that of the human head. Plans have recently been announced to perform the first human head transplantation within the next few years; however, the ethics of human head transplantation have not been formally addressed. Here, we present several ethical concerns of a human head transplantation procedure, focusing on bioethical considerations, psychological consequences, and reproductive implications.

Hypothetical Link Between Osteopathic Suboccipital Decompression and Neuroimmunomodulation

Emerging evidence has begun to depict the molecular mechanisms by which inflammation is regulated via the vagus nerve. Specifically, inflammation can be controlled by neuroimmunologic circuitry, dependent upon vagal afferent and efferent fibers, operating in a reflexive continuum. This neuro-immune reflex, known as the inflammatory reflex arc, has some control on serum concentrations of numerous molecular mediators of inflammation such as C-reactive protein and interleukin-6. Importantly, both of these inflammatory proteins are elevated in acute ST-elevation myocardial infarction and are associated with worse cardiac sequelae. Suboccipital decompression by osteopathic manual treatment has been demonstrated to enhance vagal output to the heart, as measured by increased high frequency spectral power of heart rate variability, in a statistically significant manner further supported by a significant decrease in the low-/high frequency spectral power ratio among healthy adults compared to sham treatment and time control. Considering this association, we postulate that suboccipital decompression may stimulate the efferent branch of this vagal-mediated reflex, the cholinergic antiinflammatory pathway, thereby suppressing C-reactive protein and interleukin-6 levels post-ST-elevation myocardial infarction. Furthermore, we provide a detailed clinical study that can determine the validity of our hypothesis.

The Glymphatic-Lymphatic Continuum: Opportunities for Osteopathic Manipulative Medicine.

The brain has long been thought to lack a lymphatic drainage system. Recent studies, however, show the presence of a brain-wide paravascular system appropriately named the glymphatic system based on its similarity to the lymphatic system in function and its dependence on astroglial water flux. Besides the clearance of cerebrospinal fluid and interstitial fluid, the glymphatic system also facilitates the clearance of interstitial solutes such as amyloid-β and tau from the brain. As cerebrospinal fluid and interstitial fluid are cleared through the glymphatic system, eventually draining into the lymphatic vessels of the neck, this continuous fluid circuit offers a paradigm shift in osteopathic manipulative medicine. For instance, manipulation of the glymphatic-lymphatic continuum could be used to promote experimental initiatives for nonpharmacologic, noninvasive management of neurologic disorders. In the present review, the authors describe what is known about the glymphatic system and identify several osteopathic experimental strategies rooted in a mechanistic understanding of the glymphatic-lymphatic continuum.

Microsurgical Clipping of a Giant Middle Cerebral Artery Aneurysm with Successful Postoperative Endovascular Mechanical Thrombectomy for Emergent Treatment of Large Vessel Occlusion

BACKGROUNDnGiant intracranial aneurysms (>25 mm) are uncommon. These lesions typically manifest clinically due to mass effect, acute hemorrhage, or thromboembolic events. To minimize the risk of poor clinical outcome, detailed operative planning and a consideration of all neurosurgical and endovascular techniques are essential before proceeding with microsurgical clipping of ruptured giant aneurysms.nnnCASE DESCRIPTIONnWe describe a case involving a 15-year-old male with a ruptured giant middle cerebral artery aneurysm treated with microsurgical clipping. After clip application, poor distal flow was demonstrated intraoperatively, and emergent angiography demonstrated an M1 occlusion with thrombus. A salvage procedure using endovascular mechanical thrombectomy reestablished distal flow resulting in a good neurologic outcome.nnnCONCLUSIONSnTo our knowledge, this is the first case report to describe microsurgical clipping of an aneurysm followed by successful postoperative endovascular mechanical thrombectomy.

Quantitative Description of Medical Student Interest in Neurology and Psychiatry

CONTEXTnGiven the well-documented shortage of physicians in primary care and several other specialties, quantitative understanding of residency application and matching data among osteopathic and allopathic medical students has implications for predicting trends in the physician workforce.nnnOBJECTIVESnTo estimate medical student interest in neurology and psychiatry based on numbers of applicants and matches to neurology and psychiatry osteopathic and allopathic residency programs. Also, to gauge students previous academic experience with brain and cognitive sciences.nnnMETHODSnThe number of available postgraduate year 1 positions, applicants, and matches from graduating years 2011 through 2015 were collected from the National Matching Services Inc and the American Association of Colleges of Osteopathic Medicine for osteopathic programs and the National Resident Matching Program and the Association of American Medical Colleges for allopathic programs. To determine and compare osteopathic and allopathic medical students interest in neurology and psychiatry, the number of positions, applicants, and matches were analyzed considering the number of total osteopathic and allopathic graduates in the given year using 2-tailed χ2 analyses with Yates correction. In addition, osteopathic and allopathic medical schools websites were reviewed to determine whether neurology and psychiatry rotations were required. Osteopathic medical students reported undergraduate majors were also gathered.nnnRESULTSnCompared with allopathic medical students, osteopathic medical students had significantly greater interest (as measured by applicants) in neurology (χ21=11.85, P<.001) and psychiatry (χ21=39.07, P<.001), and an equal proportion of osteopathic and allopathic medical students matched in neurology and psychiatry residency programs. Approximately 6% of osteopathic vs nearly 85% of allopathic medical schools had required neurology rotations. Nearly 10% of osteopathic applicants and matriculants had undergraduate coursework in brain and cognitive sciences.nnnCONCLUSIONnOsteopathic medical students demonstrated greater interest than allopathic medical students in neurology and psychiatry based on the proportion of residency program applicants but similar interests as measured by matches. Required rotations did not appear to influence students interests.

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.

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

BACKGROUNDnEpidermoid 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.nnnCASE DESCRIPTIONnWe 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 patients symptomatology except for minimal intermittent left-sided facial hypesthesia that remained at her 1-year postoperative visit.nnnCONCLUSIONSnThis 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.

Malformation of the Posterior Cerebellar Vermis Is a Common Neuroanatomical Phenotype of Genetically Engineered Mice on the C57BL/6 Background.

C57BL/6 mice exhibit spontaneous cerebellar malformations consisting of heterotopic neurons and glia in the molecular layer of the posterior vermis, indicative of neuronal migration defect during cerebellar development. Recognizing that many genetically engineered (GE) mouse lines are produced from C57BL/6 ES cells or backcrossed to this strain, we performed histological analyses and found that cerebellar heterotopia were a common feature present in the majority of GE lines on this background. Furthermore, we identify GE mouse lines that will be valuable in the study of cerebellar malformations including diverse driver, reporter, and optogenetic lines. Finally, we discuss the implications that these data have on the use of C57BL/6 mice and GE mice on this background in studies of cerebellar development or as models of disease.

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.