Background: Phantogeusia associated with Parkinson Disease has not heretofore been reported. Methods: A 59 year old right handed female presented with a four year history of a bitter, sour and sweet taste on her entire tongue and roof of her mouth, 8/10 intensity, constant, persistent, without any external stimuli. Drinking water tasted bitter and sour. The phantogeusia was unresponsive to dietary changes, gabapentine, and allergy medications. Results: Abnormalities in Neurological examination: Decreased blink frequency. Hypokinetic. Hypomimetic face. Mood appears sad. Cranial Nerve (CN) examination: CN lll, lV, Vl: Saccadization of horizontal eye movements. Motor Examination: Pill rolling tremor in right hand. 1+ cogwheel rigidity in left upper extremity. Gait: 2+ retropulsion. Chemosensory testing: Olfactory: Alcohol Sniff Test: 6 (anosmia). SNAP Phenylethyl Alcohol Threshold Testing left -2.5 (hyposmia) & right > -2.0 (anosmia). Gustatory testing: Propylthiouracil Disc Taste test: 10 (normogeusia). Taste Testing Threshold: normogeusia to NaCl, Sucrose, HCl, Urea, and PTC. Other: DOPAPET: positive for Parkinson disease. Upper endoscopy: normal. Conclusions: Investigation for the presence of parkinsonian features in those with phantogeusia is warranted and chemosensory dysfunction including phantogeusia in those who presents with Parkinson’s disease is worthy of exploration.

Orbital lymphaticovenous malformations (LVM) are congenital vascular lesions that are typically infiltrative in nature. There have been reports of orbital LVMs extending intracranially through orbital fissures, but there have been no reports of intradural extension that we are aware of. We present the case of an otherwise healthy 25-year-old female with an orbital LVM extending intradurally. Imaging revealed an intraorbital lesion extending through a bony defect in the medial orbital roof to the orbitofrontal cortex. A modified orbitozygomatic approach was used to obliterate this lesion. A durotomy was created to examine the intradural extension of the lesion, which appeared as a lobulated red vascular structure emanating from the dura along the roof of the orbit. This was gradually and comprehensively bipolar coagulated and subsequently obliterated. Neurosurgical and ophthalmological collaboration was used in the surgical management of this case. In summary, we report the first case of an orbital LVM extending intradurally, and provide pre and post-operative imaging as well as images captured through the intraoperative microscope. Through this case we highlight the importance of an interdisciplinary approach when managing orbital LVMs, as both ophthalmological and neurosurgical expertise were critical in the success of the surgery.

Background: Post-craniotomy pain can be severe and undermanaged. While opioids are the mainstay treatment, they have the potential to interfere with neurological monitoring. The objectives of this review are: 1) to identify measures to provide opioid-free analgesia 2) to compare the effectiveness of non-opioid to opioid analgesia in post-craniotomy pain. Methods: A comprehensive search of EMBASE, MEDLINE, and the Cochrane Central Registry of Controlled Trials (CENTRAL) databases was conducted for RCTs evaluating the effect of opioid vs non-opioid pain control strategies in patients undergoing supratentorial craniotomy. Results: The literature search yielded 462 citations, 5 RCTs that met the inclusion criteria for a total of 250 patients. Scalp infiltration/block was found to provide equivalent analgesia to morphine1 and fentanyl.2 Morphine was associated with slightly higher postoperative nausea and vomiting. Paracetamol was less likely to induce nausea and vomiting,3,4 but provided inadequate pain relief compared to nalbuphine,3 tramadol,3 morphine4 and sufentanil.4 Dexmedetomidine5 provided similar analgesia to remifentanil but did delay the time to first dose of rescue analgesia with similar side effects. Conclusions: Based on the limited number of RCTs comparing opioid to non-opioid techniques, no definite recommendations can be made with regards to the optimal management of post-craniotomy pain. Considerations should be made for use of multimodal analgesia-including adjuvant analgesics.

Background: The trigemino-cardiac reflex (TCR) is a sudden onset of bradycardia, hypotension, apnea or gastric hypermotility during stimulation of the trigeminal nerve. Methods: We conducted a MEDLINE search for surgical cases of TCR and herein describe a case seen recently at our institution. Results: A 60 year-old female underwent a left orbitozygomatic craniotomy for resection of a skull-base tumor. Pre-operative anesthesia evaluation was unremarkable and negative for a history of cardiovascular disease. Intra-operatively, retraction with moderate force of the temporalis muscle consistently produced asystole. Cessation of retraction resulted in immediate return of sinus rhythm. Otherwise, intra-operative heart rate was 60-90 BPM. Post-operatively, vital signs and clinical course were unremarkable. The patient experienced a similar phenomenon during an operation 6 years earlier, when manipulation of tumor near cranial nerves IX/X resulted in bradycardia. TCR is the result of a polysynaptic brainstem network involving the afferent trigeminal sensory nucleus, the reticular formation, and the efferent vagal motor nucleus. Conclusions: This is a case of exaggerated vagal response following manipulation of the temporalis muscle. Our report emphasizes the importance for neurosurgeons and anesthesiologists alike to be wary of TCR in order to avoid deleterious consequences when operating on structures associated with the trigeminal nerve.

Background: The 2013 Physician Payments Sunshine Act mandates that all US drug and device manufacturers disclose payments to physicians annually in the Open Payments Database (OPD). We aimed to determine the prevalence, magnitude and nature of these payments to neurological surgery in 2015. Methods: Records of payments to physicians identified by the ‘neurological surgery’ taxonomy code in 2015 were accessed via the OPD. The data were analyzed in terms of the type and amounts of payments, companies making payments, and in comparison to previous studies. Results: In 2015, 330 companies made 83,690 payments ($99,048,607) to 7,613 physicians. The mean payment ($13,010) was substantially greater than the median ($114). Royalties and licensing accounted for the largest proportion of total payment value (74.2%), but only 1.7% of the total number. Food and beverage payments were the most commonly reported transaction (75%), but only 2.5% of the total value. Neurological surgery had the second highest average total payment per physician of any specialty. Conclusions: The overall value of payments to the neurological surgery specialty is driven by a small number of payments that may represent appropriate compensation for novel device development. The OPD provides an opportunity for increased transparency and for the interpretation of research in light of potential conflicts of interest.

Background: Industry funding of neurosurgery research is on the rise and this creates a conflict of interest (COI) with the potential to bias results. The reporting and handling of COI is impacted by the variation in policies and definitions between journals. In this study we sought to evaluate the prevalence and comprehensiveness of COI policies amongst leading neurosurgical journals. Methods: We conducted a cross-sectional study of publicly available online disclosure policies in the 20 highest-ranking neurosurgical journals, as determined by Google Scholar Metrics, in July of 2016. Results: Eighteen (89.5%) of the top neurosurgical journals included COI policy statements. Ten journals requested declaration of non-financial conflicts, while two journals defined a time period of interest for conflicts. Sixteen journals required declaration from the corresponding author, 13 from all authors, six from reviewers and five from editors. Five journals included COI declaration verification, management or enforcement. Journals with more comprehensive COI policies were significantly more likely to have higher h5-indices (p=0.003) and higher impact factors (p=0.01). Conclusions: In 2016, the majority of high-impact neurosurgical journals had publicly available COI disclosure policies. Policies varied substantially across neurosurgical journals; but COI comprehensiveness was associated with impact factor and h5-index. More comprehensive and consistent COI policies will facilitate increased transparency in neurosurgery research.

Background: Inadequate postoperative pain control is common and is associated with negative clinical outcomes. The objective is to identify preoperative predictors of poor postoperative pain control in the adult population undergoing inpatient surgery. Methods: Meta-analysis was performed according to MOOSE guidelines. Studies were included if they evaluated postoperative pain using a validated instrument in adults undergoing inpatient surgery and reported a measure of association between poor postoperative pain control and at least one preoperative predictor. Measures of association were pooled using random effects models. Results: A total of 33 studies representing 59,259 patients were included. Significant preoperative predictors of poor postoperative pain included sleeping difficulties (OR 2.32 [95% CI 1.46-3.69]), history of depressive symptoms (OR 1.71 [95% CI 1.32-2.22]), use of preoperative analgesia (OR 1.54 [95% CI 1.18-2.03]), smoking (OR 1.33 [95% CI 1.09-1.61]), -female sex (OR 1.29 [95% CI 1.17-1.43]), presence of preoperative pain (OR 1.21 [95% CI 1.10-1.32]], history of anxiety symptoms (OR 1.22 [95% CI 1.09-1.36)], younger age (OR 1.18 [95% CI 1.05-1.32)], and higher BMI (OR 1.02 [95% CI 1.01-1.03]). Conclusions: Nine significant predictors of poor postoperative pain control were identified and these should be recognized as important factors when developing pre- and peri-operative strategies to improve pain outcomes.

Background: A surgical technique for foramen magnum decompression of Chiari malformation I in 11 patients is described. Methods: We used minimally invasive tubular retractors (METRx Quadrant) attached to a flexible arm to keep the retractor in a fixed position, while allowing flexible angulation under fluoroscopic guidance. Despite the small surgical opening, this approach allowed access to a wide working area, minimized soft tissue exposure, and optimized extent of decompression. For some patients, only the outer layer of dura was opened, but in cases where clinically indicated, a duraplasty was performed. Results: Postoperative CT head demonstrated satisfactory bony removal, and MRI with CSF flow study showed restoration, or significant improvement to CSF flow around the foramen magnum. There was a low incidence of post-operative complications, and the average length of hospital stay was around 1 day (1.2). For 10 out of 11 patients; their symptoms completely resolved on last follow-up, and for those who had syringomyelia, they demonstrated a radiological evidence of syrinx reduction or resolution. Conclusions: Based on our experience with this technique in foramen magnum decompression of Chiari malformation I, minimally invasive tubular retractor is a useful tool, providing the surgeon with enhanced visualization of the operative field, while reducing potential damage to tissue, and optimizing surgical outcomes.

Background: Limited information exists in neurosurgery regarding the association between functional status at hospital discharge and adverse events following discharge. Methods: A retrospective cohort study included all adults in one Boston teaching hospital who underwent neurosurgery between 2000-2012, survived hospitalization and had a Physical Therapist functional status assessment within 48-hours of discharge. 90-day post-discharge all-cause mortality was obtained from the US Social Security Administration Death Master File. Logistic regression analysis was used. Results: 2,369 patients were included, comprising 65% cranial and 35% spinal. Malignancy and trauma was 47% and 13%, respectively. 238 patients had independent functional status. 90-day mortality and readmission was 8.3% and 28%, respectively. Second, third and lowest quartile of functional status was associated with a 3.16 (95%CI 1.08-9.24), 6.00 (2.11-17.04) and 6.26 (2.16-18.16) respective increased odds of 90-day post-discharge mortality compared to patients with independent functional status, adjusting for age, gender, race, length of stay, presence of malignancy and Deyo-Charlson comorbidity. Good discrimination (AUC 0.82) and calibration (Hosmer-Lemeshow χ2 P = 0.23) were demonstrated. Adjusted odds of 90-day readmission in patients with the lowest quartile of functional status was 1.89 (1.28-2.80) higher than patients with independent functional status. Conclusions: Lower functional status at hospital discharge following neurosurgery is associated with increased post-discharge mortality and hospital readmission.

Background: One aspect of idiopathic normal pressure hydrocephalus (iNPH) that has garnered interest is whether it can be familial. Thus far, the literature consists of several case reports, and two larger pedigree cohorts. Our objective is to highlight key deficiencies in such studies so far, illustrating them through a family case study of our own, and to propose a set of criteria that studies on familial iNPH should incorporate. Methods: Our case study is a retrospective chart review of three siblings, two male and one female, who were diagnosed with iNPH after the age of 60, and whose symptoms improved with cerebrospinal fluid (CSF) shunting. An interview with them revealed that their mother also exhibited symptoms of iNPH, but was never treated with a shunt. Results: Our family case is reflective of several deficiencies of familial iNPH research as a whole—unconfirmed diagnosis, especially confirmation with shunt responsiveness, and lack of measures of symptom improvement. Conclusions: Research on familial iNPH should focus on patients whose diagnosis is confirmed by shunt responsiveness, and should involve a system to objectively measure signs of NPH. Studies should also compare the prevalence of iNPH among first degree relatives of NPH patients to that in the general population.

Background: External ventricular drain (EVD) insertion is a common neurosurgical procedure performed in patients with life-threatening conditions, but can be associated with complications. The objectives of this study are to evaluate data on national practice patterns and complications rates in order to optimize clinical care Methods: The Canadian Neurosurgery Research Collaborative conducted a prospective multi-centre registry of patients undergoing EVD insertions at Canadian residency programs Results: In this interim analysis, 4 sites had recruited 46 patients (mean age: 53.9 years, male:female 2:1). Most EVD insertions occurred outside of the operating theatre, using free-hand technique, and performed by junior neurosurgery residents (R1-R3). The catheter tip was in the ipsilateral frontal horn or body of the lateral ventricle in 76% of cases. Suboptimally placed catheters did not have higher rates of short-term occlusion. EVD-related hemorrhage occurred in 6.5% (3/45) with only 1 symptomatic patient. EVD-related infection occurred in 13% (6/46) at a mean of 6 days and was associated with longer duration of CSF drainage (P=0.039; OR: 1.13) Conclusions: Interim results indicate rates of EVD-related complications may be higher than previously thought. This study will continue to recruit patients to confirm these findings and determine specific risk factors associated with them

Background: Ventriculoperitoneal (VP) shunts are an established treatment modality for CSF diversion. An alternative to VP shunting is lumboperitoneal (LP) shunting. There is a paucity of evidence on LP shunt use in the literature, but available studies demonstrate that it is a safer and similarly efficacious method for conditions such as normal pressure hydrocephalies (NPH) and idiopathic -intracranial hypertension (IIH). Methods: Ventriculoperitoneal (VP) shunts are an established treatment modality for CSF diversion. An alternative to VP shunting is lumboperitoneal (LP) shunting. There is a paucity of evidence on LP shunt use, but available studies demonstrate that it is a safer and similarly efficacious method for conditions such as normal pressure hydrocephalies (NPH) and idiopathic intracranial hypertension (IIH). Results: 95 patients were treated with lumboperitoneal shunt, 71 of which were for hydrocephalus and 24 for IIH. 39 male and 58 female patients were included with mean age 55 (range from 20 to 96 years old). 26 patients had laparoscopic placement of the peritoneal catheter. Mechanical issues with distal end was less with laparoscopic approach. Conclusions: We will review disease-specific scores for NPH and IIH, and compare laparoscopic with non-laparoscopic placement of peritoneal catheter. We will also compare outcomes and complications with rates for VP shunting.

Background: Reversible splenial lesion syndrome (RESLES) is a rare clinico-radiological entity associated with multiple etiologies including infection, metabolic, and epileptic disorders. We describe the case of a child with a reversible splenial lesion who presented with encephalopathy and prior history of episodic ataxia. Methods: A 3-year-old girl presented to the Stollery Children’s hospital with three days of respiratory symptoms followed by acute onset ataxia and encephalopathy. Blood, respiratory samples, and cerebral spinal fluid (CSF) were drawn to investigate for infectious, autoimmune, and metabolic causes. Magnetic resonance imaging (MRI) brain was done and repeated. Results: A respiratory panel tested positive for respiratory syncytial virus (RSV), enterovirus, and rhinovirus. CSF analysis revealed elevated white blood cell count (283). MRI brain demonstrated diffusion restriction involving the posterior body and splenium of the corpus callosum and bilateral middle cerebral peduncles, which resolved nine days later. The patient received high-dose steroids with gradual improvement in the encephalopathy and ataxia. Conclusions: This report contributes to the complexities in clinical understanding of RESLES, as it highlights a novel presentation with ataxia and encephalopathy. The patient’s diagnosis was complicated by previous ataxic episodes of unknown etiology, which allows further consideration of a metabolic or genetic ataxic syndrome and its relationship to encephalopathy.

Background: Worster-Drought syndrome (WDS) is a congenital, pseudobulbar paresis. Patients show oromotor apraxia causing impaired speech, drooling, dysphagia and varying degrees of cognitive impairment. Familial cases are reported although causative genes have not been identified. LINS mutations have recently been reported in patients with severe cognitive and language impairment. Methods: The proband was diagnosed with WDS at 8 years old because of longstanding drooling, dysphagia and impaired tongue movement. At 14 years old, he remains aphonic, using sign language and typing on a smart-tablet to communicate. Neurological examination including facial and extraocular movement was otherwise unremarkable. MRI brain revealed no heterotopia or atrophy. Results: An expanded intellectual disability panel at GeneDx identified nonsense mutations in LINS alleles: c.1096; p.Glu366X and c.1178 T>G, p.Lys393X. Neuropsychological testing at 14 years old noted nonverbal reasoning skills at 5 year old level with relative sparing of his receptive vocabulary and visual attention. Compared to prior testing at 9 years his receptive language improved from a 6 year old to an 8.5 year old level. Conclusions: Nonsense mutations of LINS have been identified in a patient with WDS. Despite his severe and persistent aphonia, improvements in receptive language were observed with global intellectual functioning better than expected.

Background: Long-term EEG monitoring (LTEM), including amplitude-integrated (aEEG) or conventional EEG (cEEG), is increasingly being used in critically ill neonates. Despite an abundance of studies regarding the clinical utility of LTEM, much is unknown regarding provider attitudes toward this tool. We aimed to evaluate neurologist and neonatologist opinions regarding LTEM in the NICU and describe current Canadian practices. Methods: A 15-item questionnaire was developed with input from neonatologists and pediatric neurologists at two Canadian centres. The questionnaire was piloted at our hospital and subsequently distributed to Canadian neonatologists and pediatric neurologists. Results: All 16 local respondents use LTEM in the NICU. Neonatologists were more likely to combine aEEG and cEEG, and monitor for longer durations than pediatric neurologists. However, most pediatric neurologists would like to monitor more (71%), compared to neonatologists who were more likely to say that current monitoring practices are sufficient. High rates of neonatologists (88%) and neurologists (85%) are interested in attending an education session on LTEM. Conclusions: Preliminary data suggests neonatologists and pediatric neurologists differ in their approach to LTEM. Results from our national questionnaire will be analyzed shortly, and may inform the development of educational materials as well as future studies that involve multi-centre efforts.

Background: Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta (PIK3CB) is a member of the PI3K complex. This complex has two p110 members; PIK3CA (p110a) and PIK3CB (p110b) which are both ubiquitously expressed. PI3K complex functions to phosphorylate PIP2 to PIP3 which activates AKT and subsequently mTOR. PIK3CA mutations have been previously linked with macrocephaly and developmental delay. Methods: An 18 month old girl was investigated for severe hypotonia, developmental delay and macrocephaly. Head circumference was >97%ile at birth and 53.0 cm (>99%ile, +5.4 SD) at 13 months old. She had no hydrocephalus or epilepsy. MRI brain (18 months old) re-identified megalencephaly and diffuse polymicrogyria. Symmetric signal abnormality was noted in the periventricular white matter, unchanged between 8 and 18 month images. MR spectroscopy was unrevealing. At 18 months she remains unable to sit independently. Exome sequencing was performed and functional studies to further support variant pathogenicity. Results: Exome sequencing identified de novo variant in PIK3CB: c.1735G>T; p.Asp579Tyr. No mutations were noted in other genes known to cause developmental delay, macrocephaly or overgrowth syndromes. Functional studies in patient cells showed dysregulation of PIK3CB and downstream signalling, providing support for causality of this novel disease gene. Conclusions: We believe that our patient’s macrocephaly (+5.4 SD) and diffuse polymicrogyria results from altered PIK3CB function.

Background: Neuropsychological assessments are used in hospitals to examine brain-behaviour relationships, and are an integral part of care for medically complex patients. Unfortunately, waitlists can be lengthy. We gathered information regarding best-practice guidelines and physician referral patterns in an effort to better manage the neuropsychology waitlist at a pediatric hospital. Methods: We conducted: 1) A semi-structured telephone survey with 4 Canadian, pediatric, hospital-based neuropsychology services; 2) An electronic survey distributed to referring physicians at CHEO; 3) A focus group for CHEO neurologists and neurosurgeons. Results: The telephone survey indicated that there are no clear, best-practice guidelines for pediatric neuropsychologists working in a tertiary, pediatric hospital. The electronic survey revealed some confusion about neuropsychology services and indicated the need for better communication between neuropsychology and referral sources. The focus group revealed that demand for neuropsychology services far outstrips supply and confirmed the need for better communication. Conclusions: The results confirmed the need for best-practice guidelines to be developed around delivering neuropsychology services within a pediatric tertiary care setting, as well as continuing to work closely with neurology and neurosurgery to ensure that the neuropsychological needs of their patients are met.

Background: Children with biallelic mutations in TRNT1 have multi-organ involvement with congenital sideroblastic anemia, -B-cell immunodeficiency, periodic fevers, and developmental delay (SIFD) as well as seizures, ataxia and sensorineural hearing loss. The TRNT1 gene encodes the CCA-adding enzyme essential for maturation of both nuclear and mitochondrial transfer RNAs accounting for phenotypic pleitropy. Neurodegenerative Leigh syndrome has not been previously reported. Methods:Case summary: A Portuguese boy presented with global developmental delay, 2 episodes of infantile Leigh encephalopathy at 8 mo and 4 yr responsive to high-dose steroids, slow neurodegeneration of cognitive, language and motor functions with optic atrophy, pigmentary retinopathy, spasticity, dystonia, and focal dyscognitive seizures, pancytopenia, transfusion dependent sideroblastic anemia, recurrent febrile infections (pulmonary, gastrointestinal), hypernatremia, with tracheostomy dependence at age 5 yr, malabsorption and TPN dependence at 9 yr, and survival to early adulthood. Neuroimaging showed symmetric hemorrhagic lesions in the thalamus, brain stem (periaqueductal grey) and cerebellum consistent with Leigh syndrome but no lactate peak on MRS. Results: Whole exome sequencing identified a homozygous missense pathogenic variant in TRNT1, c.668T>C (p.I223T) in the affected individual. Conclusions: This report expands the neurological phenotype of TRNT1 mutations and highlights the importance of considering this gene in the evaluation of Leigh syndrome.

Background: We report three brothers born to consanguineous parents of Syrian descent with a novel homozygous c.324G>A (p.W108*) mutation in PTRH2 that encodes mitochondrial peptidyl-tRNA hydrolase 2. Mutations in PTRH2 have recently been identified in the autosomal recessive condition, Infantile Onset Multisystem Neurologic, Endocrine and Pancreatic Disease (IMNEPD). To our knowledge, this is the first case of IMNEPD described in a Canadian centre. Methods: Clinical phenotyping enabled a targeted approach in which all exons of PTRH2 were sequenced. We identified a novel mutation and compared our patients with those recently described. Results: We identified a homozygous nonsense mutation in PTRH2, c.324G>A (p.W108*). This G to A mutation results in a premature stop at codon 108 that produces a truncated protein, removing most of the amino acids at the enzymatic active site. This mutation is not listed in the human Gene Mutation Database Cardiff, NCBI dbSNP, 1000 Genomes, Exome Variant Server or ClinVar and is a rare variant listed in gnomAD. Conclusions: In IMNEPD, nonsense mutations in PTRH2 appear to cause severe disease with postnatal microcephaly, neurodevelopmental regression, and ataxia with additional features of seizures, peripheral neuropathy, and pancreatic dysfunction, whereas missense mutations may produce a milder phenotype. The spectrum exhibited by our patients suggests variable expressivity with PTRH2 mutations.

Background: Heterozygous loss-of-function mutations in the synaptic scaffolding gene SHANK2 are strongly associated with autism spectrum disorder (ASD). However, their impact on the function of human neurons is unknown. Derivation of induced pluripotent stem cells (iPSC) from affected individuals permits generation of live neurons to answer this question. Methods: We generated iPSCs by reprogramming dermal fibroblasts of neurotypic and ASD-affected donors. To isolate the effect of SHANK2, we used CRISPR/Cas9 to knock out SHANK2 in control iPSCs and correct a heterozygous nonsense mutation in ASD-affected donor iPSCs. We then derived cortical neurons from SOX1+ neural precursor cells differentiated from these iPSCs. Using a novel assay that overcomes line-to-line variability, we compared neuronal morphology, total synapse number, and electrophysiological properties between SHANK2 mutants and controls. Results: Relative to controls, SHANK2 mutant neurons have increased dendrite complexity, dendrite length, total synapse number (1.5-2-fold), and spontaneous excitatory postsynaptic current (sEPSC) frequency (3-7.6-fold). Conclusions: ASD-associated heterozygous loss-of-function mutations in SHANK2 increase synaptic connectivity among human neurons by increasing synapse number and sEPSC frequency. This is partially supported by increased dendrite length and complexity, providing evidence that SHANK2 functions as a suppressor of dendrite branching during neurodevelopment.