Background: Microvascular decompression (MVD) is commonly used in the treatment of trigeminal neuralgia with positive clinical outcomes. Fully endoscopic microvascular decompression (E-MVD) has been proposed as a minimally invasive, effective alternative, but a comparative review of the two approaches in the literature has not been conducted. Methods: We performed a meta-analysis comparing patient outcome rates and complications for both techniques. From a pool of 1,039 studies, 22 articles were selected for review: 12 open MVD and 10 E-MVD. The total number of patients was 6,734. Results: Good pain relief was achieved in 81% of MVD and 88% of E-MVD patients, with a mean recurrence rate of 14% and 9% respectively. Average rates of complications in MVD versus E-MVD included facial paresis or weakness, 9%, 3%; -hearing loss, 4%, 1%; cerebrospinal leak, both 3%; cerebellar damage and infection, 2%, <1%; and mortality <1%, 0% respectively. Conclusions: The reviewed literature revealed similar clinical outcomes with respect to pain relief for both approaches. Recurrence rate and incidence of complications, notably facial paresis and hearing loss were higher for MVD. We concluded that E-MVD appears to offer at least as good a surgical outcome as MVD, with possibly a shorter operative time, smaller craniectomy and lower recurrence rates.

Background: We aimed to identify preoperative predictors of survival in Metastatic Epidural Spinal Cord Compression (MESCC) patients surgically treated, examine how these predictors relate to eight prognostic models, and to perform the first full external validation of these models in accordance with the TRIPOD statement. Methods: 142 surgically treated MESCC patients were enrolled in a prospective, multicenter cohort study and followed for 12 months or until death. Cox proportional hazards (PH) regressions were used. Non-collinear predictors with <10% missing data, ≥10 events per stratum and p<0.05 in univariable analysis were tested through a backward stepwise selection. For the original and revised Tokuhashi, Tomita, modified Bauer, van der Linden, Bartels, OSRI, Bartels and Bollen, we examined calibration and discrimination; survival stratified by risk groups with the Kaplan-Meier method and log-rank test. Results: Primary tumor, organ metastasis and SF-36v2 PC were associated with survival in multivariable analysis; corrected discrimination was 0.68. These three predictors were common to most current prognostic models. However, calibration was poor overall while discrimation was possibly helpful. Conclusions: Primary tumor type (breast, prostate and thyroid), absence of organ metastasis, and a lower degree of physical disability are preoperative predictors of longer survival in surgical MESCC patients. Clinicians should use these 8 prognostic models with caution.

Background: There remains an important role for consolidating evidence on the utility of image guidance (IG) in neurosurgery. In 1963, Ayub Ommaya proposed a surgical technique for the -placement of a subcutaneous reservoir and pump to allow access to intraventricular cerebrospinal fluid. In this study, we sought to compile evidence from the literature about surgical outcome in ORI with and without IG. Methods: A systematic review was conducted in accordance with PRISMA guidelines. Overall surgical complication rate was considered a primary outcome and further classified into specific complication categories. Results: 40 studies were identified, including our own series, for a total of 1947 independent ORI procedures. Pooled rates of outcome for IG compared to non-IG were 6.0% versus 13.6% for overall complications; 2.0% versus 2.8% for catheter malfunction; 1.9% versus 2.3% for catheter malposition; 0.5% versus 4.0% for early infection; 4.3% versus 9.4% for any infection; and 0.4% versus 1.4% for mortality. Conclusions: We observed that IG ORI resulted in improved accuracy and decreased complications compared to non-IG. To our knowledge, this study comprises the largest observational analysis of operative outcomes demonstrating evidence for the utility of IG.

Background: Although surgery is the mainstay of treatment for most pituitary adenomas, post-operative radiotherapy has been shown to be of benefit in improving tumor control and recurrence-free survival. To understand potential side effects of radiotherapy we performed a systematic review and meta-analysis to determine the efficacy and safety of post-operative radiotherapy for pituitary adenoma. Methods: A systematic review was performed according to the Meta-analysis Of Observational Studies in Epidemiology (MOOSE) guidelines. We searched PubMed, MEDLINE and Cochrane databases with no language or publication date restrictions. Outcomes included 5- and 10-year progression-free survival and adverse events rates. Results: A total of 48 studies from 1986-2016 met the inclusion criteria, with 7551 cumulative patients. The cumulative 5- and 10-year s progression-free survival rates were 90.8% (95% CI 86-94%) and 88.6% (95% CI 81-93%), respectively. The overall adverse events rate was 8% (95% CI 5-12%). All outcomes were associated with significant heterogeneity (I2 ≥ 70%). No differences in survival rates or adverse events in relation to study date, tumor pathology, radiosurgery system used or dose of radiation. Conclusions: Post-operative radiotherapy for pituitary adenomas is effective and safe. Because of the significant heterogeneity and lack of matched controls in the literature, optimum timing and dosage are still unclear. Further prospective studies are needed.

Background: Venous thromboembolism (VTE) is a serious complication following severe TBI, however, anticoagulant prophylaxis is often withheld over concerns of intracranial hemorrhage (ICH) progression. We analyzed practice patterns and outcomes among severe TBI patients and systematically reviewed the literature for studies of anticoagulant prophylaxis after severe TBI. Methods: We prospectively screened consecutive patients with severe TBI (highest GCS≤8 from time of injury to ICU admission) admitted to a Level-I trauma centre between Oct 1,2015–Sept 30,2016 to assess type/timing of anticoagulant prophylaxis, rates of new VTE and ICH progression. Results: We identified 64 eligible patients with severe TBI. Most (53;83%) received anticoagulant prophylaxis, initiated ≥3d after TBI in 67%. Ten (16%) developed VTE during hospitalization; 8 started prophylaxis prior to VTE. No significant difference was observed in VTE incidence or ICH progression between patients with early prophylaxis (<3d) vs.later (≥3d). Our systematic review identified 5 studies of heterogeneous quality/design, with reported VTE incidence of 11-30% in patients without anticoagulant prophylaxis and 5-10% in patients with prophylaxis. Conclusions: VTE is a common complication after severe TBI despite routine use of anticoagulant prophylaxis. Anticoagulant prophylaxis is often started late (≥3d) post-injury. The relative benefits of early prophylaxis versus possible risks of ICH progression should be directly compared in an appropriately powered RCT.

Background: After correlating in vivo macrostimulation-induced pain or temperature sensation during percutaneous cervical cordotomy with simultaneous CT imaging of the electrode tip location, we present a modern description of the somatotopy of the human cervical spinothalamic tract Methods: Twenty patients with medically refractory, unilateral, nociceptive pain due to malignancy received contralateral cervical percutaneous cordotomy. In a post-hoc analysis of the data, each individual’s cervical spinal cord was measured from the CT image using PACS software. The location of the electrode tip during each stimulation-induced response was then superimposed on a diagram of their cord Results: The lower limb responses were found more superficial and posterior to those of the upper limb. Interestingly, the region for upper limb responses surrounded that for lower limb primarily anteriorly and medially (deep) but also posteriorly Conclusions: This work simultaneously combined awake physiologic localization of fibers within the human -spinothalamic tract (STT) with neuroimaging documenting their precise anatomical localization within the spinal cord. The resultant map of the STT demonstrates, for the first time, that fibers from the lower limb are located superficially and posteriorly within the anterolateral spinal cord with the fibers from the upper limb surrounding them primarily deep and anteriorly but also posteriorly

Background: The effectiveness of the Hydrocephalus Research Network (HCRN) shunt protocol has not been validated in a non-HCRN, small-to-medium volume pediatric neurosurgery center. This study evaluates whether the 9-step Calgary Shunt Protocol (CSP) adapted from the HCRN shunt protocol reduced shunt infections. Methods: The CSP was prospectively applied at Alberta Children’s Hospital from May 23rd, 2013 to all children undergoing any shunt procedure. Children undergoing shunt surgery before CSP implementation acted as a control-cohort. The strict HCRN definition of shunt infection was applied. Results: A total of 268 shunt procedures were performed. There was a significant absolute risk reduction of 10.0% ([95%CI 3.9%-15.9%], p=0.004) in shunt infections after implementation of the CSP. In univariate analyses, chlorhexidine compared to povidone skin prep reduced shunt infection by 8.2% ([95%CI 1.84-14.6%], p=0.02) and waiting ≥ 20 min between receiving preoperative antibiotics and skin incision reduced shunt infections by 9.6% ([95%CI 2.4%-16.9%], p=0.02). In multivariate analysis, only protocol implementation independently reduced shunt infections (OR 0.19 [95%CI 0.06-0.67], p=0.004). Conclusions: This study externally validates the published HCRN protocol for reducing shunt infection in an independent, non-HCRN, and small-to-medium volume neurosurgery setting. Chlorhexidine skin prep and waiting ≥ 20 min between preoperative antibiotic and skin incision may have contributed to the protocol’s quality improvement success.

Background: A will, power of attorney and advanced healthcare directive are critical to guide decision-making in people with cognitive decline. We identified characteristics that are associated with the existence of these documents in patients who presented to a rural and remote memory clinic (RRMC). Methods: 95 consecutive patients were included in this study. Patients and caregivers completed questionnaires on initial presentation to the RRMC and patients were asked if they have legal documents. Patients also completed neuropsychological testing. Statistical analysis (t-test and χ2 test) was performed to identify significant variables. Results: 70 patients had a will, 62 had a power of attorney and 21 had an advanced healthcare directive. Having a will was associated with good quality of life (p=0.001), living alone (p=0.034), poor verbal fluency (p=0.055) and European ethnicity (p=0.028). Factors associated with having a power of attorney included good quality of life (p=0.031), living alone (p=0.053) and poor verbal fluency (p=0.015). Old age (p=0.015), poor verbal fluency (p=0.023) and severity of cognitive and functional impairment (p=0.023) were associated with having an advanced healthcare directive. Conclusions: Our results indicate that poor quality of life, good verbal fluency, non-European ethnicity and living with others are associated with a lower likelihood of creating legal documents in patients with cognitive decline

Background: To determine whether exosomal microRNAs (miRNAs) in CSF of patients with FTD can serve as diagnostic biomarkers, we assessed miRNA expression in the Genetic FTD Initiative (GENFI) cohort and in sporadic FTD. Methods: GENFI participants were either carriers of a pathogenic mutation or at risk of carrying a mutation because a first-degree relative was a symptomatic mutation carrier. Exosomes were isolated from CSF of 23 -pre-symptomatic and 15 symptomatic mutation carriers, and 11 healthy non-mutation carriers. Expression of miRNAs was measured using qPCR arrays. MiRNAs differentially expressed in symptomatic compared to pre-symptomatic mutation carriers were evaluated in 17 patients with sporadic FTD, 13 patients with sporadic Alzheimer’s disease (AD), and 10 healthy controls (HCs). Results: In the GENFI cohort, miR-204-5p and miR-632 were significantly decreased in symptomatic compared to pre-symptomatic mutation carriers. Decrease of miR-204-5p and miR-632 revealed receiver operator characteristics with an area of 0.89 [90% CI: 0.79-0.98] and 0.81 [90% CI: 0.68-0.93], and when combined an area of 0.93 [90% CI: 0.87-0.99]. In sporadic FTD, only miR-632 was significantly decreased compared to sporadic AD and HCs. Decrease of miR-632 revealed an area of 0.89 [90% CI: 0.80-0.98]. Conclusions: Exosomal miR-204-5p and miR-632 have potential as diagnostic biomarkers for genetic FTD and miR-632 also for sporadic FTD.

Background: The NIH Toolbox - Cognition Battery (NIHTB-CB) is a computerized cognitive assessment designed for clinical research that is administered in-person. Here, we explored the feasibility and validity of a novel video-conference protocol for administering the NIHTB-CB. Since our protocol required repeated assessments, we further explored the NIHTB-CB’s practice effect. Methods: Twenty-five healthy participants completed the NIHTB-CB under two separate conditions four weeks apart. The standard condition followed the recommended administration protocol, whereas the video-conference condition had the examiner and participant in separate rooms but able to communicate over video-conference. A linear mixed-model analysis was performed to explore the fixed effect of testing condition and time on NIHTB-CB performance. Results: Across all three NIHTB-CB composite scores (total, fluid and crystallized cognition) no significant fixed effect of administration condition was found. A significant practice effect was observed for the fluid and total cognition composite scores over a 29.0 (± 2.1) day test-retest interval. Conclusions: Our novel video-conference protocol for the NIHTB-CB is equivalent to the standard protocol in healthy participants, and may provide a solution for researchers seeking to engage study participants at remote sites. If the NIHTB-CB is used longitudinally to monitor patients, corrections for repeated measures may be required.

Background: Neurogenic orthostatic hypotension (NOH) is characterized by a reduction in systolic blood pressure of ≥20 mmHg or diastolic blood pressure of ≥10 mmHg within three minutes of upright posture. NOH is prevalent in the elderly population who is at increased risk for cognitive decline, therefore it is imperative to investigate if there is a relationship between NOH and impaired cognition. Methods: Currently, 9 control subjects and 4 NOH patients have been recruited. Cognitive function is assessed using the symbol digit modalities test (SDMT) which assesses information processing speed and the Stroop test which measures response inhibition. SDMT and Stroop test are administered when the table is supine and during tilt. Results: NOH patients scored significantly worse on SDMT when lying (p=0.018) and standing (p=0.004) compared to the control group. Control subjects performed significantly better when standing for both SDMT (p=0.008) and Stroop (p=0.026), whereas NOH patients had similar scores when lying and standing for SDMT and Stroop. Conclusions: Preliminary results show that information processing speed is slower in NOH patients than controls in both the supine and standing positions. NOH patients have a more difficult time inhibiting unwanted responses compared to controls when standing, which is represented by a greater interference score in NOH patients.

Background: Lisdexamfetamine has not heretofore been reported to cause pathological gambling. Such a case is presented. Methods: A middle-aged woman, without past interest in gambling, gaming, or risk taking behavior, with childhood history of attention deficit hyperactivity disorder presented with difficulty focusing and concentrating. Lisdexamfetamine was started at 20 mg daily and gradually escalated due to lack of efficacy. At 70 mg daily, she began binging on sweets and gambling all day, every day at nearby riverboats, which she had never frequented previously. Upon reduction to 60 mg daily, the gambling resolved. Ritalin 20 mg every morning and 50 mg every afternoon was used without gambling reoccurrence. Results: Mental Status Examination: Alert, cooperative and oriented x 3 with good eye contact. Euthymic, without mania, thoughts logical and goal directed. Conclusions: Enhanced dopamine in the nucleus accumbens may induce hedonic activities including gambling, binging on sweets, or sexual activity (Moore et al. 2014). Lisdexamfetamine has been described to induce mania, and pathological gambling may have been an isolated manifestation of early mania. In those who have recently begun lisdexamfetamine, query should be made regarding change in gambling behavior and in those who are pathologically gambling, investigation should be entertained as to whether they are taking lisdexamfetamine.

Background: We present a case of a previously well 71-year-old woman who developed rapidly progressive dementia. She had several prolonged hospital admissions and extensive investigations were performed. Her illness was steroid-responsive with clinical features suggestive of Hashimoto’s Encephalopathy (HE). However, multiple thyroid antibody panels acquired were initially normal, becoming elevated during subsequent relapses that occurred 3 years after initial presentation. The case signifies the importance of repeating antithyroid antibody levels in a patient with a clinical picture suggestive of HE. Methods: Case report. Results: The diagnosis of HE was established because of a compatible clinical picture including a relapsing encephalopathy with motor involvement and steroid responsiveness. In addition, although initial antithyroid antibody testing was negative, subsequent attacks were associated with significant elevations and reverted to normal with resolution of the attacks. Conclusions: In a patient with normal levels of antithyroid antibodies and a clinical presentation suggestive of HE, we recommend repeat antithyroid antibody testing to confirm diagnosis. Further studies are necessary to clarify the pathogenic role of elevated antithyroid antibodies in the mechanism of HE.

Background: Idiopathic Normal-pressure hydrocephalus (iNPH) is characterized by cognitive impairment, gait disturbance, enlarged ventricles with/without cerebral atrophy, with/without urinary incontinence, and normal cerebrospinal fluid pressure. Familial iNPH is very rarely described in the literature. A Canadian family with more than one generation of iNPH has never been described. Methods: Patient 1: 50-year-old female presented with wide-based and magnetic gait, multiple falls with subsequent freezing. LP with large volume tap was performed. Patient had ventriculo peritoneal (VP) shunt surgery. Patient 2: 52 year male (brother): Presented with long-standing cognitive impairment and fatigue. Montreal Cognitive Assessment (MOCA) was performed. Whole exome sequencing(WES) of both siblings as well as an unaffected first cousin was done. The father and grandmother of both patients was diagnosed with iNPH. Results: Patient 1: Opening pressure on LP was 22 cm-H2O. She responded well to large volume tap. She had VP shunt resulting in improved gait. Patient 2: Opening pressure on LP was 16cm-H2O. CSF flow study was slow for age indicative of NPH. MoCA score was 25/30. WES of patients and unaffected first cousin is underway. Conclusions: We present an undescribed Canadian family with iNPH in more than one generation. WES is underway for better understanding of genetic predesposition and inheritance of familial iNPH

Background: Transient neurological symptoms in patients with subdural hematoma (SDH) are often attributed to secondary epilepsy despite a negative workup. We believe a significant proportion of these patients could rather suffer from cortical spreading depolarization (CSD). Methods: We performed a retrospective case-control study of patients with transient neurological symptoms post-SDH evacuation between 1996 and 2017. The clinical features of patients with negative EEG were compared to those with positive EEG (ictal or interictal abnormalities) and a clinical scoring system was created. Results: 59 patients were included, 20 (34%) with a positive EEG. Speech-related symptoms (OR 4.8, p=0.018) and prolonged episodes (OR 23.1, p=0.001) were associated with a negative EEG. Clonic movements (OR 0.014, p<0.0005), impaired awareness (OR 0.013, p<0.0005), positive symptoms (OR 0.05, p<0.0001), complete response to standard antiepileptic drugs (OR 0.06, p=0.007) and mortality (OR 0.021, p=0.003) were associated with a positive EEG. We built a clinical score based on these features, which showed a 90% sensitivity and 100% specificity. Conclusions: We believe that the differences observed between both groups were driven by the presence of CSD rather than seizure in the case group. Our proposed scoring system can help predict EEG results and may be useful to identify CSD in future trials.

Background: Infantile spasms (IS) is a seizure disorder in young children which can be challenging to recognize. Early diagnosis and treatment of IS is critical for prevention of developmental delay. At the Hospital for Sick Children, rule-out IS accounts a large percentage of outpatient EEG referrals, while few result in a diagnosis. The goal of this study was to characterize the seizure semiology and source of referral, in order to explore ways in which triaging of these referrals may be improved. Methods: A retrospective review was done on all 84 rule-out IS EEG referrals within the last year at the Hospital for Sick Children. Source of referral, description of episodes, and result of EEG was extracted and data qualitatively analyzed. Results: Neurologists at Hospital for Sick Children accounted for the least number of referrals however contributed the greatest percentage of IS diagnoses. Non-neurologists contributed the most referrals, however 75% of these EEGs were normal. Common semiologies as described by referring physicians are discussed. Conclusions: Improved triaging of EEG referrals may be achieved through screening of referrals by paediatric neurologists, clarification of event semiology, and better IS education. This represents a critical opportunity for improvement of resource allocation as well as patient care and outcomes within all major referral centres.

Background: Post-hypoxic myoclonus is broadly divided into myoclonic status epilepticus (MSE) and Lance-Adams syndrome (LAS), where diagnosis depends on clinical and electroencephalographic (EEG) findings. Positive rolandic sharp waves (PRS) are a classic EEG finding in pre-term infants with white matter necrosis, but they are not known to be epileptogenic and have never been described in adults. Methods: We report a unique case of PRS correlated with myoclonic seizures in a post-hypoxic adult patient. Results: Shortly after cardiac arrest, a 21-year-old woman developed multifocal post-hypoxic myoclonus. Early development of myoclonus suggested MSE, but her EEG findings were atypical for MSE; initially, the only notable feature on EEG were subtle PRS. LAS did not fit the clinical picture or EEG findings. As myoclonus persisted over the following weeks, PRS evolved on EEG into positive rolandic predominant generalized polyspike-wave complexes that became definitively time-locked to each myoclonic jerk. PRS were diagnosed as epileptogenic and frequent myoclonic jerks were diagnosed as continuous myoclonic seizure. Myoclonus resolved to medication and mental status returned to baseline. Conclusions: We report for the first time that PRS can appear in adult patients and be epileptogenic, and produce a non-classical variant of post-hypoxic myoclonus that carries good prognosis.

Background: We evaluate long-term post-operative hippocampal volume (HV) on non-epileptic hippocampus using MR volumetry as well as the neuropsychological outcome in patients with surgery for unilateral mesial temporal lobe epilepsy (MTLE) and achieved seizure-freedom. Methods: We studied 1.5-Tesla MRI before and after epilepsy surgery in 24 patients with MTLE. Serial MRI studies were scheduled at 4 post-operative consecutive periods; 6m-1y; 1-2y; 2-3y; 3-5y. We compared neuropsychological outcomes for memory and estimated IQ at the same periods with serial MRI up to 3 years. Results: The pre-operative non-epileptic HV was significantly smaller than HV in age-matched controls (n=14) (p<0.05). The HV became progressively atrophic after the surgery (p<0.05), correlating with the age at surgery (p<0.05) and pre-operative larger non-epileptic HV (p<0.05), but not with seizure duration. In 14 patients with non-dominant MTLE, the smaller dominant HV at 2-3y period correlated with decline of verbal memory (p<0.05). Conclusions: Post-operative progression of non-epileptic hippocampal atrophy was found with significantly more pronounce in patients with older age at surgery and larger pre-operative non-epileptic hippocampus. After the epileptogenic hippocampus is resected, the remaining hippocampus alone might exhaust to maintain the memory, especially in elders.

Background: Intracranial hypotension (IH) is typically characterized by an orthostatic headache. There have been limited case reports describing iatrogenic IH presenting with seizures. Methods: Case report. Results: A 71-year-old woman with chronic back pain developed convulsive status epilepticus (SE), characterized by generalized clonic seizures, immediately following scoliosis surgery. She had no history of seizures or seizure risk factors. Despite treatment with Midazolam, Phenytoin and Lacosamide, seizures recurred five times over three hours. Thus, Propofol and Midazolam infusions were initiated. An electroencephalogram revealed burst suppression and bilateral hemispheric epileptiform discharges. MRI brain was consistent with IH without cortical vein thrombosis. Fluid from the surgical drains was positive for Beta-2 transferrin, indicating cerebral spinal fluid. Her intracranial hypotension was likely due to an -intraoperative dural tear causing SE. Over two weeks, she remained on bedrest, sedation was weaned, and Phenytoin and Lacosamide were tapered and discontinued. She had no further seizures. Conclusions: IH is an under recognized cause of seizure following spinal or cranial surgery, lumbar puncture, or spinal anaesthesia. Proposed mechanisms include traction on cortical structures, increased cerebral blood flow and cortical irritation secondary to subdural hygromas.

Background: Epilepsy/seizure awareness is improving across Canada. With the formation of a Comprehensive Epilepsy Program in Manitoba (including a new Pediatric Epilepsy Monitoring Unit), a provincial strategy has been proposed outlining a path towards improved access to epilepsy care. We now sought to qualify the current state of clinician knowledge and comfort towards diagnosis and management of this condition. Methods: A qualitative online survey, comprised of 36 short-answer questions, was delivered to primary care and specialist physicians in Manitoba. Results:108 subjects responded, across varying medical disciplines. 101 (93.5%) have previously managed epilepsy patients, and 87 (80.6%) have previously ordered an EEG. A total of 63 (59.4%) have referred to a neurologist, with a lower proportion (30, 28.3%) referring specifically to an epileptologist. 36 respondents (33.3%) have heard of the ILAE guidelines, with 43 (63.2%) reporting refractory epilepsy to be -defined by the failure of 3 (or more) medications. 61 (56.5%) were unaware of invasive EEG techniques. Most (85, 78.7%) understood a role for surgery in treating epilepsy, with 12 (11.1%) unaware of surgical therapies beyond VNS. Conclusions: SESAME successfully identified strong awareness towards epilepsy, with small lapses in knowledge that will benefit from a formal provincial-wide educational curriculum.