Jeffrey A. Pugh

Access to cerebrospinal fluid absorption sites by infusion into vascular channels of the skull diploë

OBJECT The purpose of this human cadaver study was to determine whether or not an intraosseous skull infusion would access the superior sagittal sinus (SSS) via intradural venous channels. The diploic space of the skull bone contains a sinusoidal vascular network that communicates with the underlying dura mater. Diploic veins in the parasagittal area connect with endothelium-lined intradural channels in the subjacent dura and ultimately with the dural venous sinuses. A significant proportion of cerebrospinal fluid (CSF) absorption is thought to occur via arachnoid granulations in the region of the SSS and especially along the parasagittal dura where arachnoid granulations are surrounded by intradural venous channels (lateral lacunae). The CSF is likely to be conducted from the subarachnoid space into the venous system via the fine intradural channels making up the lateral lacunae. METHODS Infusion of vinyl acetate casting material into the diploic space of the human cadaveric skull resulted in complete filling of the lateral lacunae and SSS. Corrosion casting techniques and examination under magnification were used to characterize the anatomical connections between diploic spaces and dural venous sinuses. RESULTS Corrosion casting, performed on five formalin-fixed cadavers, clearly showed the anatomical connections between the diploic infusion site and the venous sinuses in the underlying parasagittal dura where some of the CSF is thought to be absorbed. CONCLUSIONS The diploic vascular channels of the human skull may represent an indirect pathway into the dural venous sinuses. Intraosseous skull infusion may represent another possible strategy for diversion of CSF into the vascular system in the treatment of hydrocephalus.

Pediatric Traumatic Retroclival Epidural Hematoma

A previously healthy ten-year-old girl was involved in a high speed motor vehicle accident (MVA) in which she was the belted front-seat passenger. The patients teeth marks on the dashboard were evidence of a high-velocity impact. Her Glasgow Coma Score on scene was 13, and she was amnestic for the event. She was subsequently transported to the emergency room in full spinal precautions; on arrival she was hemodynamically stable with a Glasgow Coma Score of 14, complaining of neck and jaw pain. Neurological examination revealed impaired abduction of the right eye, with no other focal deficits. She had oral lacerations and bruising over the mandibles bilaterally. Computed tomogram (CT) scan of the head was initially interpreted as normal, but on closer inspection demonstrated a 4mm retroclival hematoma (Figure 1). Sagittal CT through the upper cervical spine revealed the hematoma was epidural, bounded by the spheno-occipital synchondrosis superiorly and by the mid-body of the axis inferiorly (Figure 2). The odontoid was retroflexed (Figure 2). Bilateral mandibular fractures were also uncovered on facial imaging.

Gelastic seizures with dancing arising from the anterior prefrontal cortex

AIM This case report provides insight into the function of the anterior prefrontal cortex (aPFC), specifically Brodmann Area 10 (BA10), and its interconnectivity. METHOD We present a 10-year-old patient with lesional epilepsy and ictal onset, localised to BA10 in the aPFC. RESULTS Thirty-four seizures were recorded. All seizures involved a demonstration of elation with laughter that was associated with a variety of different patterns of complex motor behaviour that included performing specific celebratory movements and acting out a Michael Jackson dance move. Electrographically, the seizures were all stereotyped and arose from the right frontal region, followed by a distinct left temporal ictal rhythm that corresponded with the onset of the behaviours. The lesion in the right aPFC was identified as a mixed lesion with both dysembryoplastic neuroepithelial tumour cells and type II cortical dysplasia. CONCLUSION The electrographic analysis and unique seizure semiology suggest a connection between the aPFC and the contralateral temporal lobe. This neural pathway appears to be involved in the activation of previously formed procedural memories, creating an intensely positive emotional experience.

Immune Cell Infiltrates in Atypical Teratoid/Rhabdoid Tumors

OBJECTIVE Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant tumor of the central nervous system. Its pathogenesis remains unknown. Like glioblastomas, AT/RTs contain brain cancer stem cells (CSCs) that suppress the immunity of patients and are resistant to conventional chemotherapy and radiation therapy. Considerable infiltration of immune cells, including macrophages/microglia, dendritic cells and T-cells, has been noted in glioblastomas, which correlates with poor prognosis. The present study examines the significance of infiltrating immune cells in four cases of AT/RT; including one associated with an autoimmune disease, Henoch-Schonlein purpura. METHODS Tumor tissues from four patients with AT/RT were analyzed and compared with those from four patients with glioblastomas. The frequency of immune cells, including CD68+, CD4+, and CD8+ cells, was assessed by scoring for statistical analysis. RESULTS The infiltration of immune cells was identified in the case of AT/RT associated with HSP and three other cases of infratentorial AT/RTs. Moderate infiltration of CD68+ macrophages/microglia and CD4+ cells was noted in AT/RTs with no significant difference from that in glioblastomas (p > 0.05). However, the infiltration of CD8+ T-cells was significantly higher in AT/RTs than that in glioblastomas (p < 0.05); CD4+/CD8+ ratio was significantly lower in AT/RTs than that in glioblastomas (p < 0.05). In addition, eosinophils were found in all AT/RTs, but not in glioblastomas. CONCLUSIONS These findings suggest an immune microenvironment of AT/RTs with more immune effectors than glioblastomas. Our observation contributes to understanding the growth environment of AT/RTs for which adjuvant immunotherapy may be potentially beneficial.

The first posterior fossa decompression for Chiari malformation: the contributions of Cornelis Joachimus van Houweninge Graftdijk and a review of the infancy of “Chiari decompression”

Over the past several decades, our understanding of the pathophysiology of hindbrain hernias has markedly increased. Additionally, with the advent of MRI, diagnosis of these entities is common. Although the history of the discovery of what are now known as the Chiari malformations is well known, publications regarding the historical surgical treatment of these is, to our knowledge, not extant. Many have attributed the first successful patient series to Gardner in the 1950s. However, and unknown to many, the first description of a hindbrain decompression was in 1930 by the Dutchman Cornelis Joachimus van Houweninge Graftdijk. This neurosurgeon also added to our understanding the pathophysiology of hindbrain herniation and its relationship to raised intracranial pressure. The present paper reviews the contributions of this early pioneer of neurosurgery.

Utility of neurophysiology in the diagnosis of tethered cord syndrome

OBJECT The diagnosis of tethered cord syndrome (TCS) remains difficult, and the decision to operate is even more complex. The objective of this study was to examine how detailed examination of neurophysiological test results can affect the diagnosis for patients undergoing a surgical cord release. METHODS Patients undergoing tethered spinal cord releases were matched by age and sex with control patients undergoing scoliosis correction in the absence of spinal cord pathology. The latency and width of the P37 peak of the posterior tibial nerve somatosensory evoked potential (SSEP) and the motor evoked potential (MEP) latencies were examined. Immediate changes as a result of the surgical procedure were reported. RESULTS The width of the P37 response differed significantly between TCS and control patients and changed significantly during the surgical procedure. Nonsignificant trends were seen in SSEP and MEP latencies. CONCLUSIONS The width of the P37 response may be a useful marker for TCS and may play a role in presurgical decision making.

Global developmental delay, progressive relapsing-remitting parkinsonism, and spinal syrinx in a child with SOX6 mutation.

SOX6, a member of the SOX gene family, plays a key role in the development of several mammalian tissues and organs, including the central nervous system. Specifically, this gene modulates the differentiation and proliferation of interneurons in the medial ganglionic eminence, as well as oligodendrocytes in the spinal cord. We describe the case of a 4-year-old girl with global developmental delay and a spinal cord syrinx who presented with recurrent episodes of parkinsonian symptoms subsequent to febrile illnesses. The symptoms included gait instability, tremor, and dysarthria, with a progressive relapsing-remitting course over the span of 2 years. The patient was later found to have a large deletion-type mutation in the SOX6 gene. This case is the first report in humans implying a role for SOX6 in basal ganglia function, as well as spinal cord development.

Neural activity generated in the neural placode and nerve roots in the neonate with spina bifida

OBJECT The authors conducted a study to determine the neurophysiological capacity of the neural placode in spina bifida neonates and to determine if the spinal nerve roots in these neonates had normal stimulation. METHODS The authors present a case series of 2 neonates born with open neural tube defects who underwent neural tube closure within 24 hours of birth. Neurophysiological monitoring and electrical stimulation of the placode and nerve roots was performed before and after closure of the neural tube. RESULTS Stimulation of nerve roots resulted in evoked electromyographic responses in distinct muscle groups, indicative of the myotome innervation pattern. Stimulation threshold did not change significantly after closure of the placode. Stimulation within the placode generated an alternating pattern of activity in the left and right legs. CONCLUSIONS Closure of the neural tube did not affect the stimulation threshold of the nerve roots, which remained easily excitable. The viability of the nerve roots suggests that they may be candidates for neural prostheses in the future. The neural placode contains basic neural elements for generating a locomotor-like pattern in response to tonic neural inputs.

Eosinophil Infiltrates in Pilocytic Astrocytomas of Children and Young Adults

OBJECTIVE Eosinophils may affect each stage of tumour development. Many studies have suggested that tumour-associated tissue eosinophilia (TATE) is associated with favourable prognosis in some malignant tumours. However, only a few studies exist on TATE in central nervous system (CNS) tumours. Our recent study exhibited eosinophils in atypical teratoid/rhabdoid tumours (AT/RTs), pediatric malignant CNS tumours with divergent differentiation. This study examines eosinophils in pilocytic astrocytomas (PAs). METHODS The study included 44 consecutive cases of patients with PAs and no concurrent CNS inflammatory disease. RESULTS We found eosinophils in 19 (43%) of 44 PAs (patient age range, 0.5-72 years). Eosinophils were intratumoural and clearly distinguishable. The density of eosinophils was rare to focally scattered. PAs containing eosinophils were located throughout the CNS. Furthermore, eosinophilic infiltration was identified in 18 (62%) of 29 pediatric (age range, 0.5-18 years) PAs but only 1 (7%) of 15 (p<0.001, significantly less) adult (age range, 20-72 years) PAs. Eosinophilic infiltration showed no significant differences between PAs with and without MRI cystic formation, surgical procedures, or PAs with and without leptomeningeal infiltration. In comparison, eosinophils were absent in 10 pediatric (age range, 0.5-15 years) ependymomas (or anaplastic ependymomas). CONCLUSIONS These results suggest that eosinophils are common in pediatric PAs but rare in adult PAs. This difference is probably related to the developing immune system and different tumour-specific antigens in children. TATE may play a functional role in the development of pediatric PAs, as well as some other pediatric CNS tumours such as AT/RTs.

Increasing the appeal of neurosurgery to qualified medical students in Canada.

667 The education climate in Canadian medical schools has changed dramatically over the past ten years. A growing and aging population has demanded significant increases in medical school enrollment, with a focus on producing primary care physicians. Despite doubling the number of graduating medical students during this time (Figure 1), the number of candidates applying to Neurosurgery has remained relatively stable. These statistics are concerning when considering five of the past ten years have seen less students rank Neurosurgery as a first choice discipline than the number of Residency positions available, though the overall match rate has remained 1:1 (Figure 2)1. Based on current trends, it is possible that Neurosurgery is failing to appeal to and attract qualified applicants who may otherwise consider a career in this field. This may be inherently limiting the selection process for Neurosurgical programs across the country to only a small cohort of students. Inconsistencies between an increasing number of medical students but relatively stable number of Neurosurgery applicants could be due to both changing student priorities in medical and surgical careers as well as decreased exposure to Neurosurgery in the face of a changing medical curriculum. Both factors should be addressed in order to ensure students well suited for Neurosurgery continue to apply. As of 2010, balance between work and personal life and obtaining sufficient medical competence were cited as the two most important factors for Canadian medical students in determining a satisfying and successful career2. As student priorities continue to change, it is possible students have ruled out Neurosurgery on the basis of expected lifestyle and content difficulty prior to adequate exposure and knowledge of the specialty. Ironically, in the same National Physician Survey, Neurosurgeons report the highest percent of satisfaction compared to all surgical specialties when it comes to balance between personal and professional commitments. Of all respondents, 64.7% were somewhat or very satisfied with this component of their life. In addition, they had comparable results to other competitive surgical specialties when addressing satisfaction of their professional life. It may be beneficial to address student concerns early in training regarding lifestyle and content difficulty, as well as other factors considered important to medical students today, including length of training, job prospects, daily activity, financial remuneration, patient demographics, and the expectations of a Neurosurgical career. Students may also fail to experience adequate exposure to Neurosurgery during their training. In a recent survey of medical students, few agreed that they had a good understanding of the Neurosurgical specialty3. This is especially true for students undergoing their formative pre-clinical years where Increasing the Appeal of Neurosurgery to Qualified Medical Students in Canada