Background: Temporal lobe epilepsy (TLE) accounts for approximately 20% of pediatric epilepsy cases. Of those, many are considered medically intractable and require surgical interventions. In this study, we hypothesized that mesial temporal sclerosis (MTS) was less common in patients who had undergone surgery for intractable pediatric TLE than in adult series. We further hypothesized that there was a radiological and pathological discordance in identifying the cause of pediatric TLE. Methods: We retrospectively reviewed the charts of pediatric patients with TLE who had undergone surgical treatments as part of the University of Alberta’s Comprehensive Epilepsy Program between 1988 and 2018. Along with preoperative magnetic resonance imaging (MRI) reports, post-surgical pathology results and seizure outcomes were studied Results: Of the 83 pediatric patients who had undergone temporal lobe epilepsy surgery, 28% had tumors, 22% had dual pathologies, 18% had MTS, 11% had focal cortical dysplasia, and 22% had other pathologies. In addition, for 36% of these patients, discordance between their pre-surgical MRI reports and post-surgical pathology reports were found. Conclusions: This was one of the largest retrospective cohort studies of pediatric patients who had undergone surgery for intractable TLE. This study showed that tumors, and not MTS, were the most common pathology in surgical pediatric TLE.

Background: Epileptic encephalopathy (EE) is a severe neurological disorder characterized by treatment-resistant seizures and poor neurodevelopmental outcomes. EE is associated with mutant genes, including those that encode for γ-aminobutyric acid type A (GABAA) receptor subunits. We identified a novel de novo GABRA1 mutation in a patient with EE, characterized its impact on GABAA receptor function, and sought potential therapeutic options. Methods: We described the clinical and electrophysiological features of a patient with a novel de novo GABRA1 (R214C) mutation; performed functional studies; and determined the effect of diazepam and insulin on wild type and mutant GABAA receptors. Results: The patient is a 10-year-old girl with EE, treatment-resistant seizures, intellectual disability and autism. Her GABRA1 (R214C) mutation dramatically decreased whole-cell GABA-evoked currents by reducing GABAA surface receptors, decreasing single channel open time, and altering channel kinetic properties. The combination of diazepam and insulin partially repaired these effects by enhancing channel activity and increasing the number of surface receptors, respectively. Conclusions: Diazepam and insulin partially mitigated a de novo GABRA1 (R214C) mutation’s effects on GABAA receptor number and function. Given the risks of insulin use, pharmacological agents with similar mechanisms of action but fewer side effects, such as IGF-1, should be studied and considered for clinical application.

Background: The goal was to understand factors leading to prolonged wait times for neurological assessment of children with new onset seizures. A second objective was to develop an innovative approach to patient flow through and achieve a reduction in waiting times utilizing limited resources.

Methods:

Audit of the referrals, flow through, wait times

Identification of bottlenecks

Development of triaging strategy:

Suspected Febrile seizures and non-epileptic events;

Suspected benign and absence epilepsies;

Suspected other Focal epilepsies, generalized epilepsies, epilepsy under 2 years

Initiation of early telephone contact and support

Development of a ketogenic diet

Results: Using a triaging strategy and focusing on timely access to investigations, wait times for clinic evaluations were shortened despite larger numbers of referrals (mean wait time reductions from 179 to 91 days). Limiting factors such increase in referral numbers, attrition in support staff, interfered with sustainability of reduced wait times achieved in the initial phase of the program. Conclusions: This pilot study highlights the effectiveness of an innovative triaging strategy and improvements in patient flow through in achieving the goals of reduction in wait times for clinical evaluation and timely investigations to improve care for children with new onset seizures. Insights into limitations of such strategies and factors determining sustainability are discussed.

Background: Forced normalization is the development of psychiatric symptoms in a patient experiencing remission of intractable seizures. The mechanism of this phenomenon is unknown. We present a complex case of Lennox Gastaut syndrome that experiences forced normalization after vagus nerve stimulation (VNS). Methods: This case details a 31-year-old male with seizures since early childhood. The patient has intractable epilepsy and failed AEDs, VNS, and a partial callosotomy. Results: The patient was in remission from 2-12 years old, when seizures returned at a frequency of 2-5 per day. He has multiple types of seizures including drop attacks, absences, and tonic-clonic seizures. Patient experienced status epilepticus multiple times. Twelve AEDs were failed before VNS was started in 2010, which helped curb the severity of seizures and the potential for clusters. Forced normalization developed over the course of treatment with VNS. The patient behavior was characterized by aggression, paranoia, and hallucinations. VNS was turned off late in 2010 and then re-started in January of 2011. Patient proceeded to cycle between several days of seizures without psychiatric symptoms and several days of psychosis without seizures. Conclusions: Vagus nerve stimulation gave way to forced normalization, characterized here as aggressive behaviour and psychosis. Forced normalization is seen commonly after epilepsy surgery, but rarely following VNS.

Background: Multidisciplinary treatment programs benefit headache patients. No evidence exists as to whether they change resource use. A historical prospective cohort study was performed to compare the frequency of ambulatory care and emergency department visits for the purposes of headache by patients seen at the Calgary Headache Assessment and Management Program (CHAMP) in the three years before, and after, their first appointment. Methods: Administrative data from Alberta Health was used. All patients seen by a physician at CHAMP from 2003-2013 were included. Sample characteristics were described and the Wilcoxan signed rank sum test was used to compare the number of ambulatory care and emergency department visits in the three years before and after each patient’s first physician appointment at CHAMP. Follow-up visits at CHAMP were excluded from analyses. Results: The median number of ambulatory care visits over three years changed from 4 to 2 (p<0.001). The median number of emergency department visits was zero before and after assessment at CHAMP. The mean number of emergency department visits changed from 1.5 to 1.2 (p<0.0001). Conclusions: Enrollment in a multidisciplinary headache program reduces the number of ambulatory care visits and emergency department visits for purposes of headache.

Background: Epilepsy aphasia spectrum of disorders is characterized by developmental and language regression with EEG abnormalities that include electrical status epilepticus of sleep (ESES). Landau-Kleffner syndrome (LKS) and epileptic encephalopathy with continuous spike-wave during sleep (CSWS) are the most severe presentations. GRIN2A mutations have been recognized as causative. Methods: we present two sisters with different epilepsy phenotypes. A variant of unknown clinical significance (VUS) in GRIN2A gene was found in one of the sisters and her similarly affected father. Results: The first sister presented with focal onset seizures at the age of 3 years accompanied by language and cognitive regression and EEG features consistent of ESES, meeting criteria for LKS. Multiple anticonvulsants were tried until she responded well to steroids regaining developmental milestones. Her 5-year-old sister recently presented with focal onset seizures. Her language development is appropriate. Her EEG showed independent multifocal spikes but no ESES during sleep. Her seizures were controlled on monotherapy anticonvulsants. Conclusions: We observed a variable EEG-clinical phenotype and different severity among these family members as expected with GRIN2A-related disorders. This report contributes to evidence of the GRIN2A variant pathogenicity.

Background: Childhood primary angiitis of the central nervous system (cPACNS) is a rare inflammatory disease of brain vessels. The small vessel subtype is diagnosed on brain biopsy and often presents with cognitive and behavioural changes, headaches and seizures. However, there are few reported cases of super-refractory status epilepticus. Methods: We present a case of small vessel cPACNS complicated by super-refractory status epilepticus and review the literature. Results: Our patient is a previously healthy 11-year-old boy who presented with new-onset seizures and encephalopathy in the context of fever. He developed super-refractory status epilepticus, requiring burst suppression for four weeks with various IV infusions. During this time, he was on the ketogenic diet and tried eight anti-seizure medications. Extensive investigations included brain biopsy confirming small vessel cPACNS. He was treated with IV methylprednisolone, oral steroids, IVIG, and cyclophosphamide. After prolonged rehabilitation, he recovered almost completely and has a normal neurological examination with no epileptiform activity on EEG. Conclusions: Small vessel cPACNS should be considered in the differential diagnosis of super-refractory status epilepticus. Despite being in SE for four weeks, symptomatic management of seizures and immunosuppression to treat the underlying pathology resulted in favourable neurological outcomes. This is one of the longest cases of SE in small vessel cPACNS in the literature.

Background: Hemifacial Spasm (HFS) is rarely caused by a dolichoectatic vertebrobasilar artery (eVB) compression of the Facial Nerve. This can pose a surgical challenge when performing microvascular decompression as vessel mobilization is often difficult due to atherosclerosis, tethering from brainstem perforators, and large size. These patients are often not considered for surgery. Methods: A retrospective chart review of patients who were surgically treated by the senior author between 2003 and 2017 with an admitting diagnosis of HFS was performed. Patients with preoperative neuroimaging demonstrating eVB compression of their facial nerve/root were included. Results: During the 15-year review, 315 patients underwent microvascular decompression for HFS and 21 (6.7%) had dolichoectactic vertebrobasilar compressions. At final followup (>3 months) 19 patients (90.4%) experienced reduction in symptoms with 15 (71.4%) having complete resolution. One patient required re-operation and benefitted from subsequent symptom relief. The majority of culprit compression was found proximally on the pontine surface. Mobilization of the culprit vessel was achieved successfully in the majority of cases with Teflon pledgets. There were no perioperative strokes or death. Complications are presented Conclusions: Microvascular Decompression for Hemifacial Spasm caused by dolichoectatic vertebrobasilar artery compression can be performed with a high rate of safety and success in the setting of a high case volume centre.

Background: MS related trigeminal neuralgia (MS-TN) is associated with high recurrence and retreatment rates. Optimal treatment and role for partial sensory rhizotomy (PSR) for MS-TN remains to be determined. Methods: We analyzed time to treatment failure (TTF) after PSR (n=14) versus other prior procedures (n=53) among 12 consecutively treated MS-TN patients. Kaplan-Meier curves and Log-Rank tests were utilized to compare BNI pain scores and TTF after PSR vs prior procedures using the same patient cohort as their own control group. Subsequent analysis compared TTF after PSR to other procedures (n=93) among a second cohort of 18 MS-TN patients not undergoing PSR. Results: TTF was significantly longer after PSR compared to prior procedures among the PSR cohort (p<0.0001) with median TTF of 79 vs 10 months respectively. Similarly, there was a longer TTF after PSR compared to prior procedures among the MS-TN cohort with median TTF 79 vs 16 months respectively (p<0.001). PSR resulted in a higher proportion of excellent pain scores when compared to prior procedures in the MS-TN cohort (77% vs 29%, p<0.001). Conclusions: TTF was significantly longer following partial sensory rhizotomy compared to other prior procedures in MS-TN patients. A higher proportion of patients achieved excellent BNI pain scores after PSR.

Background: Migraines are sub-optimally treated, affect millions of Canadians, and are underrepresented in medical training. A study was conducted to identify the needs of Canadian Healthcare Providers (HCPs) for migraine education, with the aim to inform the development of learning activities. Methods: This ethics-approved study was deployed in two consecutive phases using a mixed-methods approach. Phase 1 (qualitative) explored the causes of challenges to migraine care via a literature review, input from an expert working group, and semi-structured interviews with multiple stakeholders. Phase 2 (quantitative) validated these causes using an online survey. Results: The study included 103 participants (28 in phase 1; 75 in phase 2): general practitioners=37; neurologists=24; nurses=14; pharmacists=20; administrators, policy influencers and payers=8. Four areas of sub-optimal knowledge were identified: (1) Canadian guidelines, (2) diagnostic criteria, (3) preventive treatment, and (4) non-pharmacological therapies. Attitudinal issues related to the management of migraine patients were also identified. Detailed data including the frequencies of knowledge gaps among general practitioners and general neurologists will be presented along with qualitative findings. Conclusions: Educational activities for general practitioners and general neurologists who treat patients with migraines should be designed to address the four educational needs described in this study.

Background: Headache is one of the most frequent complaints in primary care. We reviewed headache questions submitted to an electronic consultation service in Ontario to classify the types of headaches and describe the questions being asked. We also identified reasons why answers were not retrievable within UpToDate, an online clinical resource. Methods: 65 headache eConsults were further divided into 85 questions and categorized by headache type and question theme. Questions were manually searched within UpToDate to determine if they could be answered using this resource. The intent to refer the patient for a face-to-face referral after the eConsult was collected. Results: The top classifications were migraine, unclassified headache, and exertional and/or coital headache. The themes -identified were medication questions (41.7%), investigation questions (33.3%), clinical concerns despite normal neurologic exam and/or imaging (15.5%); and abnormal imaging findings (9.5%). Answers to 40.1% of the questions were not retrievable in UpToDate. The main reason for irretrievability was an unusual presentation. Only 33.8% of eConsults resulted in a face-to-face referral to a specialist. Conclusions: Although electronic resources may be useful in some cases, clinical nuances cannot be accounted for. By providing physicians with rapid access to specialists, eConsult services may obviate the need for formal, face-to-face referrals.

Background: Granulomatosis with polyangitis (GPA) is a rare systemic vasculitis with a prevalence of 0.6 per million in the pediatric population. CNS involvement occurs in 7-18% of cases. Pituitary involvement is only noted in 1% of cases. Methods: A 16-year-old girl with newly-diagnosed GPA presented to our hospital with progressive debilitating headaches, polyuria, and polydipsia. Results: Initial MRI showed changes to the pituitary. Lumbar puncture (LP) revealed opening pressure of 26. She developed central diabetes insipidus (DI) and visual changes. Repeat head imaging showed adenohypophysitis. The GPA was previously treated with steroids and cyclophosphamide, followed by Cellcept. Once the pituitary involvement was discovered, she was given re-induction therapy with Rituximab and steroid dose was increased. DI is being treated with DDAVP. Her headaches are improving. Conclusions: CNS inflammatory diseases are rare in childhood. Pituitary involvement is extremely rare in GPA. Induction therapy for adults with GPA and pituitary involvement includes glucocorticoids and cyclophosphamide, which often leads to improvement of MRI abnormalities but is not effective in resolving pituitary dysfunction. Our patient had already received this treatment when she developed the CNS findings. This case demonstrates that cerebral involvement is often resistant to classic therapy, and one should be vigilant in looking for CNS inflammation in these patients.

Background: In RRMS patients with inadequate response to prior therapy, 2 alemtuzumab courses (12 mg/day; baseline: 5 days; 12 months later: 3 days) significantly improved outcomes versus SC IFNB-1a over 2 years (CARE-MS II [NCT00548405]). Efficacy remained durable in a 4-year extension (NCT00930553); patients could receive as-needed alemtuzumab retreatment (≥12 months apart) for disease activity, or another disease-modifying therapy (DMT). Through Year 6, 88% remained on study; 50% received neither alemtuzumab retreatment nor another DMT; 16% received ≥4 courses; 3% received ≥5 courses. We evaluated Course 4 (C4) efficacy in patients receiving ≥4 courses. Methods: Annualized relapse rate (ARR); improved/stable Expanded Disability Status Scale (EDSS) score (versus baseline); 6-month confirmed disability improvement (CDI). 11% of patients met inclusion criteria: ≥4 courses within 60 months of baseline; no DMT. Those receiving C5 were censored at that time. Results: ARR decreased after C4 (12 months pre-C4 [-12M]: 0.75; 12 months post-C4 [+12M]: 0.19; P<0.0001), remaining low (0.23) at Year 3 post-C4. More patients had stable/improved EDSS scores +12M (67.5%) versus at C4 administration (53.5%). Percentage with CDI increased post-C4 (-12M: 10.0%; +12M: 26.7%). Conclusions: C4 reduced relapses and stabilized/improved disability in patients with disease activity after initial treatment (C1, C2) plus one additional course (C3).

Background: The 2005, 2010, and 2017 McDonald diagnostic criteria for multiple sclerosis (MS) were compared at baseline in participants of a Canadian multicentre clinical trial of minocycline in clinically isolated syndrome (CIS). Methods: The cohort included 142 participants. Baseline clinical and imaging data were used to determine if participants met criteria for dissemination in space (DIS) and time (DIT) as required for each version of the criteria. We also explored the impact of permitting a clinical diagnosis of transverse myelitis to represent a spinal cord lesion, and for multifocal clinical onset to represent DIS. Results: The clinical trial excluded patients meeting the 2005 McDonald criteria at baseline. The 2010 criteria were met by 28.9% (41/142) of participants. If a multifocal clinical presentation was considered evidence of DIS 29.6% (42/142) met the 2010 criteria. The 2017 criteria were met by 36.7% (52/142). Allowing a clinical diagnosis of transverse myelitis to confirm a spinal lesion, or multifocal onset to confirm evidence of DIS, led to a diagnosis in 38% (54/142) and 38.7% (55/142), respectively. Conclusions: This study confirms that each revision of the McDonald diagnostic criteria allowed an MS diagnosis in more CIS patients at onset. Exploration of other modifications suggests further improvement may be possible.

Background: Opportunistic infection should be considered when seeing neurological complications in the setting of immunosuppression. Accumulating evidence that enteroviral meningoencephalitis can occur after rituximab administration exists but differentiating it from non-infectious conditions can be challenging. Methods: Case report Results: We describe a 4 year-old-boy with a history of pulmonary capillaritis, treated with immunosuppressive therapy -including steroids, rituximab, and azathioprine. He developed mutism and ataxia after 18 months on rituximab. MRI Brain/Spine revealed extensive T2/FLAIR hyperintensities in the deep subcortical white matter, temporal lobes, globus pallidi, thalami, brainstem, and cerebellum; and swelling of the dorsal cervical cord, showing primarily grey matter involvement. IgG levels had a decreasing trend over the course of Rituximab. CSF, and subsequent brain biopsy, were both positive for enterovirus RNA by RT-PCR. He was thought to have enterovirus encephalitis secondary to rituximab therapy, and was treated with IVIG and fluoxetine. Conclusions: One should consider chronic opportunistic CNS infections in children treated with immunosuppressive therapy, and to consider chronic enterovirus infection when B-cell suppression has occurred. As rituximab is being increasingly used in the pediatric population, and is generally thought to be safe, attention should be paid to any child with chronic neurological signs, particularly younger children who may be at higher risk for chronic enterovirus infection.

Background: Anti-NMDAR Encephalitis is an autoimmune disease of children and adults which most often presents with sub-acute psychiatric disturbance or seizures, but includes a broad group of potential clinical manifestations. Routine neuroimaging, such as cerebral MRI, is often nonspecific or normal. Methods: This study reports a series of retrospectively reviewed pediatric patients with AntiNMDAR encephalitis with emphasis on the evolution of clinical features over time, cerebral MRI, 18-FDG Positron emission tomography (PET) findings, and post illness neurocognitive features. Results: Four cases of Antibody confirmed AntiNMDAR encephalitis were included, two male and two female, of a mean of 13 years of age. Patients had a mean of three symptom categories by presentation, though many of these were subtle, progressing to 6.5 by the end of the first month. MRI, CSF and EEG were abnormal for one, three and all patients, respectively. All patients had abnormal cerebral PET scans, and all displayed some temporal lobe hypermetabolism on either initial or repeat cerebral PET Scan. Conclusions: Anti-NMDAR encephalitis is a variable disorder with an evolving clinical presentation in children. Temporal hypermetabolism on cerebral PET may be a time dependent feature of the disorder.

Background: With few evidence-based disease-modifying therapies being available for patients with progressive multiple sclerosis (PMS), how can neurologists best care for their patients? Little is known about the perspectives of patients with respect to the role they would like their neurologist to play in their care. We hereby report an update to our abstract presented at the Canadian Neurological Sciences Federation’s annual congress in 2016. Methods: Patients with PMS having an Expanded Disability Status Scale (EDSS) score of 6 or more were invited to participate. Semi-structured interviews were conducted with patients and their caregivers, and written questionnaires were completed by all participants. Collected data was subjected to thematic coding. Results: We have now interviewed a total of 18 patients (compared to 10 in 2016) and have reached thematic saturation. The majority of patients identified the neurologist as a useful figure in their care. Three main reasons were identified: (1) The neurologist provides information about new research and therapies (2) The neurologist educates patients about their disease and available services (3) The neurologist is viewed as an important supportive figure. Conclusions: Despite a lack of disease-modifying treatments for progressive multiple sclerosis, patients with PMS view the neurologist as an essential provider of care.

Background: We present a 67-year-old male with a two-week history of progressive double vision. Past medical history included oropharyngeal SCC, T4N2cM0, post-CCRT, and remote sarcoidosis. Clinically, the patient had multiple cranial nerve palsies affecting bilateral occular motor function. Neuroimaging showed an enhancing mass involving the sella and cavernous sinuses. Whole-body PET showed FDG-avid lesions in the sella and liver. Transsphenoidal biopsy of the sellar mass was obtained for tissue diagnosis. Methods: Details of the case were obtained from the patient’s EMR. Neuroimaging and neuropathology were reviewed with the appropriate subspecialists. A literature search was performed using multiple databases (PubMed, Web-of-Science) and relevant articles were included for review. Results: Sellar mass biopsy confirmed p16+ve SCC, identical to the patient’s known primary malignancy. On review of enhanced skull-base images, there was no evidence of direct tumor extension, favouring hematogenous spread. Conclusions: This case demonstrates the localizing potential of cavernous sinus masses. SCC metastases to the cavernous sinus are rare, and confer a poor prognosis.The presence of a p16 mutation has public health implications, as this mutation demonstrates more frequent and aggressive distant metastatic potential, and as a surrogate marker for high-risk HPV infection, represents a preventable risk-factor for a rapidly increasing cause of head and neck cancer in the Western world.

Background: The role of extent of surgical resection (EOR) on clinical outcomes in patients with low-grade glioma requires further examination. Methods: We systematically searched MEDLINE, Embase, and the Cochrane Library for studies published between January 1, 1990 and January 5, 2018 on predefined patient outcomes regarding different EOR of low-grade glioma. Results: Our literature search yielded 60 studies including 13,289 patients. Pooled estimates of overall survival showed an increase from 3.79 years (95% CI, 2.37–5.22) in the biopsy group to 6.68 years (95% CI, 4.19–9.16) in STR to 10.65 years (95% CI, 6.78–14.52) in GTR. When compared to STR, GTR prolonged progression-free survival by 2.08 years (95% CI, 0.26–3.89; P=0.025). Pooled estimates of seizure control showed an improvement from 47.8% (95% CI, 26.7–69.6) with biopsy to 54.2% (95% CI, 48.7–59.6) with STR to 81.0% (95% CI, 74.6–86.2) with GTR. Compared to STR, GTR delayed malignant transformation (RR, 0.43; 95% CI, 0.20–0.93; P=0.032), without increasing postoperative mortality (RR, 0.38; 95% CI, 0.07–1.97; P=0.250) or morbidity (RR, 1.22; 95% CI, 0.65–2.28; P=0.540). Conclusions: Among patients with low grade gliomas, higher degrees of safe EOR, were associated with longer overall and progression-free survival, better seizure control, and delayed malignant transformation, without increased mortality or morbidity.

Background: Supratentorial ventricular hemangioblastoma (HB) associated with Von Hippel Lindau (VHL) are extremely rare. Due to their vascularity and location, their management can be difficult. Methods: A 35 year old female with VHL, has been followed for 25 years with multiple intracranial and spinal tumours. Surgical removal was carried out on one large cystic and solid posterior fossa lesion. In addition, she underwent adrenalectomy for pheochromocytoma. There were no pancreatic or renal lesions. On serial follow up for years, a left frontal ventricular lesion showed increasing size with clinical signs of increased ICP and marked hydrocephalus, requiring shunting procedures, which were carried out 11 years ago. She has been clinically stable since. Results: Hemangioblastomas of the CNS are rare and account for 2% of primary CNS tumours. Supratentorial location is estimated at 4% for sporadic and 13% for HB associated with VHL. The lateral ventricular location is extremely rare. Review of the literature revealed a total of 9 cases of supratentorial ventricular location. The majority of the lesions are associated with VHL and they are solid and vascular lesions. In our cases there was a cystic component. Conclusions: If removal is contemplated, angiography with possible preoperative embolization may be required.