Background: The Canadian Stroke Best Practice Recommendations target a median door-to-needle time of 30 minutes. However, brain tissue becomes damaged with any delay from symptom onset. Efficiencies may be gained prior to hospital arrival, by evaluating the timeliness of patient access to hospital from symptom onset, as well as by improving healthcare provider communication, prior to arrival of the patient. Methods: We engaged with hospital administration, paramedic services, allied health colleagues, physicians, and engineers, to develop Kairos, a secure online platform that healthcare providers can utilize to track progress en route to hospital, as well as to share pertinent stroke patient information, prior to arrival. Results: Kairos is built on React Native, allowing users to access it on android or iOS devices. Paramedics select patient identification, symptom onset time, and associated symptoms. The receiving hospital can add doctors to the patient’s thread, and the stroke team can prepare for patient arrival. Conclusions: We plan to measure the median symptom onset-to-hospital time in patients with strokes, and monitor the change in door-to-needle time following implementation at an Ontario Regional Stroke Centre.

Background: This is the first report of Heparin induced thrombocytopenia (HIT) presenting as bilateral carotid thrombi and multiple cerebral infarcts. Methods: 54 year old woman presented with sudden onset of right arm numbness and weakness two days after discharge from hospital. During her hospitalization 9 days prior, she underwent colovesicular fistula repair, received heparin subcutaneously for DVT prophylaxis and had normal platelet counts. Results: On this admission, MRI Brain showed scattered multiple acute infarcts within the cortex of bilateral cerebral hemispheres. CT angiography head /neck showed non-occlusive thrombi at the carotid bifurcations bilaterally. Platelet count on admission was 267 K/uL q which decreased to 125 K/uL the next day, after which heparin was started for the carotid thrombi. The platelet count rapidly decreased further to 79 K/uL leading to suspicion for HIT and switching to Argatroban. HIT and serotonin release assay were positive confirming the diagnosis of HIT. CT chest and tranthoracic echocardiogram was normal. Venous Duplex of bilateral upper and lower extremities were negative for DVTs.Hypercoaguable evaluation was negative. Conclusions: This case highlights the importance of identifying HIT as a cause of arterial thrombosis and stroke even with normal platelet counts in the clinical setting of recent heparin use.

Background: Many guidelines in neurology encompass the principles of Choosing Wisely Canada (CWC): resource stewardship, patient safety, and high value care. There are currently 49 medical societies with CWC recommendations excluding the Canadian Neurologic Society (CNS). Methods: A descriptive process for list generation is outlined. A review of the American Choosing Wisely recommendations was undertaken to generate an adapted list of ten recommendations. CNS board members vetted this list and an online survey was sent to each CNS member. Results: A short list of recommendations endorsed by the CNS membership at large will be presented according to the survey results. CWC promotion of the list will take place to reach specialists, primary care providers, and trainees to ensure high value neurological care delivery is the standard across Canada. Conclusions: The process to delineate CWC recommendations for neurology is outlined. Participating in the CWC movement is an important leadership initiative for the CNS. It demonstrates the commitment of Canadian neurologists to the principles of high value patient care in neurology.

Background: Postural Orthostatic Tachycardia Syndrome (POTS) causes excessive heart rate and orthostatic intolerance on standing. About 25% patients have refractory POTS. Saline infusions reduce improve quality of life in such patients. Intravenous albumin expands circulatory volume by increasing plasma oncotic pressure. Efficacy of albumin infusions in POTS has not been studied. Methods: To assess the efficacy of albumin infusions in refractory POTS we treated patients with weekly or biweekly intravenous infusions of either 5% albumin in normal saline (n=16) or normal saline alone (n=7) in this open label comparative study. Most patients had failed multiple treatments. Serial clinical evaluations with individual symptom scores were the primary outcome measure of efficacy. Results: Mean follow up was 2 years (range 4 weeks - 5 years). 14/16 patients on albumin and 4/7 patients on saline infusions improved. Significantly more patients (7 vs. 1) on albumin showed marked improvement from baseline with more prominent reduction in orthostatic heart rate (mean reduction 19 vs. 14 beats minute). Albumin was well tolerated. More patients on saline (3/7 vs. 2/16) discontinued infusions due to lack of efficacy. Some patients required a permanent venous catheter. Conclusions: Intravenous albumin infusions are well tolerated and more effective than normal saline in refractory POTS.

Background: Calcium (Ca) and magnesium (Mg) are crucial in metabolism, excitability and neuroglial plasticity. Our aim was to evaluate whether Mg (20 mg/kg) or Ca (100 mg/kg) could improve the memory prognosis in the kainic model of mesial temporal epilepsy. Methods: Seizures were induced by systemic injection of kainate (8mg/kg) and mice were then treated by ions every 48 hours. A placebo (physiological solution) replaced kainate or ions in specific groups. Six cohorts were studied for seven weeks: control group (G0: no kainate and no ion, only placebo); untreated reference group (GR: kainate and then placebo); G1 groups were treated from the third day (G1m, G1c: kainate and then Mg/Ca); G2 groups were treated from the third week (G2m, G2c: kainate and then Mg/Ca). Radial maze and a classic maze were used for cognition evaluation. Results: The memory (short/long term) was differently affected by kainate or improved by Mg/Ca. The treated groups performed better than GR mice, but Mg was more effective. In addition, Mg demonstrated an increasing therapeutic effect over time while Ca showed an acute and apparently decreasing action in the G1c group. Conclusions: Mg should be considered for a clinical evaluation of its effect on epileptic disorders.

Background: There are few published reports on the safety and efficacy of stereoelectroencephalography (SEEG) in the presurgical evaluation of pediatric drug-resistant epilepsy. Our objective was to describe institutional experience with pediatric SEEG in terms of (1) insertional complications, (2) identification of the epileptogenic zone and (3) seizure outcome following SEEG-tailored resections. Methods: Retrospective review of 29 patients pediatric drug resistant epilepsy patients who underwent presurgical SEEG between 2005 – 2018. Results: 29 pediatric SEEG patients (15 male; 12.4 ± 4.6 years old) were included in this study with mean follow-up of 6.0 ± 4.1 years. SEEG-related complications occurred in 1/29 (3%)—neurogenic pulmonary edema. A total of 190 multi-contact electrodes (mean of 7.0 ± 2.5per patient) were implanted across 30 insertions which captured 437 electrographic seizures (mean 17.5 ± 27.6 per patient). The most common rationale for SEEG was normal MRI with surface EEG that failed to identify the EZ (16/29; 55%). SEEG-tailored resections were performed in 24/29 (83%). Engel I outcome was achieved following resections in 19/24 cases (79%) with 5.9 ± 4.0 years of post-operative follow-up. Conclusions: Stereoelectroencephalography in presurgical evaluation of pediatric drug-resistant epilepsy is a safe and effective way to identify the epileptogenic zone permitting SEEG-tailored resection.

Background: Cannabis has been shown to be an effective therapy for epilepsy in children with Dravet and Lennox-Gastaut syndrome. Despite the fact that many pediatric epilepsy patients across Canada are currently being treated with cannabis, little is known about pediatric neurologists’ attitudes towards it. Methods: A 26-item online survey was distributed to 148 pediatric neurologists across Canada. Results: 56/148 neurologists responded and reported that over 600 children with epilepsy are currently taking cannabinoids. 34% of neurologists authorized cannabis to children, 38% referred children for authorization, and 29% did not authorize or refer their patients. Of those neurologists who referred, 76% referred to a community-based non-neurologist. The majority of physicians authorized cannabis to patients with Dravet syndrome (68%) and Lennox-Gastaut syndrome (64%). Cannabis was never authorized as a first-line treatment. 54% of neurologists stated that their patients were taking CBD alone, despite this option not being available in Canada. All physicians reported having at least one hesitation regarding cannabis, the most common ones being poor evidence (66%), poor quality control (52%), and cost (50%). Conclusions: The majority of Canadian pediatric neurologists use cannabis as a treatment for epilepsy in children. However, there appear to be knowledge gaps and hesitations.

Background: The classic ketogenic diet is the main non-pharmacological treatment for refractory epilepsy; however, adherence is often challenging. The low glycemic index diet (LGID) is less strict, almost equally effective, and associated with improved adherence. Little is known about the quality of life of children treated with LGID. The objective of this study was to explore changes in the quality of life of children with epilepsy transitioning to the LGID. Methods: Patients on LGID and their parents filled out Pediatric Quality of Life Epilepsy Module questionnaires; one while being on the LGID, and one retrospectively for the time prior to starting the LGID. Results: Data was collected from five children ages 3-13 and their parents. Complete seizure control was seen in two children, >50% seizure reduction in one, and no change in two children. Parental reported quality of life while on the LGID increased with two participants but decreased in all child self reports. Conclusions: Although the LGID led to improved seizure control in three out of five patients, the child-reported quality of life decreased in all children. Larger prospective studies are warranted to reliably assess the impact of the LGID on the quality of life in children with epilepsy.

Background: Topiramate is an antiepileptic frequently used in pediatrics with multiple mechanisms of action. This includes carbonic anhydrase inhibition, which has unclear relevance to its antiepileptic effect. Metabolic acidosis, hypocitraturia and nephrolithiasis are known side-effects of carbonic anhydrase inhibition and can limit therapeutic effect. Alkali therapy may normalize acidosis, increase urinary citrate, and reduce nephrolithiasis risk. We hypothesize that provision of sodium bicarbonate supplementation to patients with topiramate-induced acidosis will mitigate these side-effects without worsening seizure frequency or severity. Methods: Pediatric patients on antiepileptic therapy with topiramate are being recruited from outpatient pediatric neurology clinics at McMaster Children’s Hospital. We aim to recruit 20 patients with metabolic acidosis and 20 control patients. Measures include blood gas, electrolytes, urine electrolytes and citrate. Patients with metabolic acidosis will be given daily sodium bicarbonate for one month, followed by repeat bloodwork. Seizure frequency will be prospectively documented in all participants throughout the three-month period. Results: Recruitment is ongoing, and three patients (1 with acidosis) have been recruited thus far. Results will be analyzed with chi-squared and paired T tests. Conclusions: This pilot study is the first to evaluate the safety and efficacy of sodium bicarbonate supplementation in patients receiving topiramate for seizure control.

Background: Non-convulsive seizures are common in critically ill patients and are best detected by continuous EEG (cEEG) monitoring. A recent consensus statement from the American Clinical Neurophysiology Society (ACNS) outlines the indications for EEG monitoring in critically ill patients. Our aim was to assess adherence to these indications, barriers to cEEG utilization as well as to optimize cEEG monitoring in critically ill children. Methods: We conducted a retrospective review of electronic medical records, analyzing patients admitted to the PICU from January 1st until June 23rd 2018, followed by an 8-week mentorship period, consisting of educational interventions as well as daily patient rounds to help identify patients meeting cEEG monitoring criteria. Results: Prevalence of patients meeting cEEG monitoring indications were similar in both the retrospective and mentorship period (18% vs. 23%). During the retrospective period, 23% of patients received cEEG monitoring, reaching 100% at the end of the mentorship period. The median delay for initiation of monitoring was 17 hours, largely due to restrictions in the availability of technologists. All cEEGs performed informed anti-convulsive management. Conclusions: An educational intervention was effective in increasing PICU cEEG monitoring. However, limited hours of technologist availability represented the largest barrier to timely cEEG monitoring.

Background: When compared to the general population, researchers have reported elevated rates of mental health issues in the pediatric epilepsy population. These issues have been found to be especially problematic around the time of transition from pediatric to adult care. This is significant because depression and/or anxiety have been found to be directly related to worsened seizure outcomes and quality of life. Despite this, no known Canadian pediatric epilepsy centers have integrated mental health assessment into mainstream practice. Methods: To explore the importance of mental health assessments, we looked at the prevalence rates of both depression and anxiety in 91 adolescents with epilepsy aged 14 to 18 (M=16.3, 51 males, 41 females) enrolled into an epilepsy transition clinic. Results: 58.3% of adolescents showed signs of depression (28.6% mild, 21.4% moderate, 6.0% moderately-severe, 2.4% severe), and 51.8% of adolescents showed signs of anxiety (31.8% mild, 10.6% moderate, 9.4% severe). Remarkably, 54.8% of patients presenting with moderate to severe depression and/or anxiety had not been previously identified Conclusions: These results suggest that in order to ensure the best possible outcomes for patients, mental health assessments should be integrated into the standard model of care for transition-aged adolescents with epilepsy.

Background: Focal cortical dysplasias (FCDs) are congenital structural abnormalities of the brain, and represent the most common cause of medication-resistant focal epilepsy in children and adults. Recent studies have shown that somatic mutations (i.e. mutations arising in the embryo) in mTOR pathway genes underlie some FCD cases. Specific therapies targeting the mTOR pathway are available. However, testing for somatic mTOR pathway mutations in FCD tissue is not performed on a clinical basis, and the contribution of such mutations to the pathogenesis of FCD remains unknown. Aim: To investigate the feasibility of screening for somatic mutations in resected FCD tissue and determine the proportion and spatial distribution of FCDs which are due to low-level somatic mTOR pathway mutations. Methods: We performed ultra-deep sequencing of 13 mTOR pathway genes using a custom HaloPlexHS target enrichment kit (Agilent Technologies) in 16 resected histologically-confirmed FCD specimens. Results: We identified causal variants in 62.5% (10/16) of patients at an alternate allele frequency of 0.75–33.7%. The spatial mutation frequency correlated with the FCD lesion’s size and severity. Conclusions: Screening FCD tissue using a custom panel results in a high yield, and should be considered clinically given the important potential implications regarding surgical resection, medical management and genetic counselling.

Background: Childhood absence epilepsy is a common generalized epilepsy in pediatric patients. Although this was considered a “benign” syndrome, new data suggests there are associated neurocognitive effects. This is the first study comparing quality of life and social functioning in those with absence epilepsy to those with other types of epilepsy. Methods: This observational study recruited patients from six Canadian academic centers. 106 patients had absence seizures, and 219 had other seizures. Established measures of depression, anxiety, social skills, social support, participation, quality of life, and epilepsy severity were assessed. MANCOVA was used to evaluate differences in social function, quality of life, and epilepsy severity measures, while accounting for age and gender. Results: This yielded a statistically significant result (Wilk’s lambda <0.05), with partial eta squared of 0.163. Follow up of between subjects tests revealed lower health related quality of life interpersonal/ social subscale and close friend social support scores in those with absence epilepsy, while other measures were not significant. Conclusions: Children with absence epilepsy have similar social function, quality of life and epilepsy severity measures compared to those with other types of epilepsy. This indicates that any dysfunction in these domains is similar to those with other types of epilepsy.

Background: Sotos syndrome is a genetic condition caused by NSD1 alterations, characterized by overgrowth, macrocephaly, dysmorphic features, and learning disability. Approximately half of children with Sotos syndrome develop seizures. We investigated the spectrum of seizure phenotypes in these patients. Methods: Patients were recruited from clinics and referral from support groups. Those withclinical or genetic diagnosis of Sotos syndrome and seizures were included. Phenotyping data was collected via structured clinical interview and medical chart review. Results: 25 patients with typical Sotos syndrome features were included. Of 14 tested patients, 64% (n=9) had NSD1 alterations. Most had developmental impairment (80%, n=20) and neuropsychiatric comorbidities (68%, n=17). Seizure onset was variable (2 months to 12 years). Febrile and absence seizures were the most frequent types (64%, n=16). Afebrile generalized tonicclonic (40%, n=10) and atonic (24%, n=6) seizures followed. Most patients (60%, n=15) had multiple seizure types. The majority (72%, n=18) was controlled on a single antiepileptic, or none; 4% (n=1) remained refractory to antiepileptics. Conclusions: The seizure phenotype in Sotos syndrome most commonly involves febrile convulsions or absence seizures. Afebrile tonic-clonic or atonic seizures may also occur. Seizures are typically well-controlled with antiepileptics. The rate of developmental impairment and neuropsychiatric comorbidities is high.

Background: This study sought to examine the association between early life stressors and adolescent headache and the potential mediating influence of internalizing psychopathology. Methods: This study used data from 2,313 respondents of the National Longitudinal Survey of Children and Youth, followed prospectively from age 0-1 years at baseline (1994/1995) until age 14-15 years (2008/2009). The relationships between four measures of early life family level stressors, and outcomes of incident health professional diagnosed migraine and self-reported, unclassified frequent headache (>1 per week) were examined using multivariable logistic regression. Mediation analyses of the indirect effect of internalizing psychopathology (i.e., depression and anxiety symptoms) were examined using a regression-based path analytical framework. Results: There were 81 adolescents with incident migraine and 231 with frequent headache. There were no direct associations between early life family level factors and adolescent headache (p > .05). Internalizing psychopathology mediated relationships between family dysfunction (indirect effect [IE] 0.0181, 95% bias-corrected confidence interval [CIBC] 0.0001-0.0570), punitive parenting (IE 0.0241, 95% CIBC 0.0015-0.0633), parental depressive symptomatology (IE 0.0416, 95% CIBC 0.0017-0.0861), and incident migraine, but not frequent headache. Conclusions: Findings provide support for the influence of early life family level factors on prospective risk of developing migraine through internalizing psychopathology.

Background: Benign spasms of infancy (BSI), previously described as benign non-epileptic infantile spasms or benign myoclonus of early infancy, are non-epileptic movements manifesting during the first year of life and spontaneously resolving in the second year of life. BSI are characterized by spasms typically lasting 1-2 seconds, involving to varying degrees the head, neck, trunk, shoulders and upper extremities. Ictal and interictal EEG recordings are normal. BSI are not associated with developmental retardation and do not require treatment. Distinction between BSI and infantile epileptic disorders, such as epileptic spasms or myoclonic epilepsy of infancy, can be challenging given the clinical similarities. Moreover, interictal EEGs can be normal in all conditions. Epileptic spasms and myoclonic epilepsy require timely treatment to improve neurodevelopmental outcomes. Methods: We describe a 6-month old infant presenting with spasm-like movements. His paroxysms as well as a positive family history for epileptic spasms were in keeping with a likely diagnosis of West syndrome. Results: Surprisingly, ictal video EEG did not reveal epileptiform activity, and suggested a diagnosis of BSI. Conclusions: We emphasize that ictal EEG is the gold standard for classification of infantile paroxysms as either epileptic or non-epileptic, thereby avoiding overtreatment of BSI and facilitating timely targeted treatment of infantile epilepsies.

Background: Dystonia is a hyperkinetic condition that produces abnormal movements or postures. Its diagnostic procedure is often challenging and time consuming. Genetic testing provides an effective approach for diagnosis, but currently only very few dystonia genes have been identified. We propose that studying early-onset forms of dystonia with the use of whole-genome sequencing (WGS) will improve the identification of dystonia-relevant genes and mutations. Methods: We performed deep WGS using the Illumina HiSeq X technology in a mother-proband pair with dystonia. The mother has generalized dystonia (age of onset: 15) and the proband has myoclonic dystonia (age of onset: 11). Results: No pathogenic mutation was identified in any of the known dystonia genes. However, we identified a rare heterozygous frameshift mutation (p.K342fs*7) at LMNB1 that was shared between the mother and the proband. Duplication of LMNB1 is known to cause Adult-onset Demyelinating Leukodystrophy. A heterozygous deletion of LMNB1 has been reported in a patient with microcephaly and global developmental disorder. Conclusions: Further characterization of phenotypes in the participants and their family members is needed to confirm the relationship between mutation in LMNB1 and dystonia. This work provides a proof-of-principle that novel disease-relevant genes can potentially be identified using the proposed approach.

Background: Electroconvulsive therapy (ECT) involves the induction of a generalized seizure with an electrical current and has been used worldwide when treating medically refractory psychiatric illness. Here we describe a patient with no prior history or risk factors for epilepsy who developed temporal lobe epilepsy after chronic treatment of ECT. Methods: A 16-year-old right-handed boy with severe refractory depression received ECT treatment every 10 days for 8 months. Six months into his ECT treatment, the patient developed seizures and was admitted to a pediatric epilepsy monitoring unit. Results: Initial clinical events included lightheadedness, diaphoresis, and nausea with associated kaleidoscopic vision changes. Seizures progressed to confusion, fear and paranoia by the time the patient was admitted for monitoring. Long-term video EEG captured many focal seizures with impaired awareness, all originating from both temporal lobes. MRI was normal. ECT was terminated and the patient started on carbamazepine. He has been seizure free for the past 2 years on medication Conclusions: While rare, we present a case of a patient with no prior risk factors for epilepsy who developed temporal lobe epilepsy after chronic ECT treatment. Although ECT is an indispensable treatment for many medically refractory psychiatric illnesses, we suggest caution in young patient undergoing ECT.

Background: overtreatment of neonatal seizures may result in neurological morbidity. aEEG, despite low sensitivity, is widely used, for ease of bedside interpretation. vEEG, is a limited resource needing expert interpretation. We hypothesize that using aEEG combined with vEEG will increase the sensitivity and specificity of seizure detection and reduce anti-convulsants use compared to aEEG alone. Methods: Prospective cohort of neonates admitted to CHEO NICU with suspected seizures between April 1st 2018 to present. Seizures (clinical/aEEG) were documented by bedside clinicians and compared to the vEEG. Bedside clinicians could call a neurologist for remote review of the vEEG. Outcomes include concordance of aEEG and vEEG events and number of episodes where management was changed based on both readings Results: 27 patients had both modalities recording simultaneously. No seizure was identified by either modality in 23 recordings. Seizures were identified in 4 vEEG recordings; the aEEG partially identified these seizures.

• aEEG specificity of 0.87, negative predictive value 0.8, sensitivity 0.44 and positive predictive value 0.57

• Bedside clinician contacted a neurologist 9 times; in 2 cases, this prevented unnecessary treatment.

Conclusions: In this small sample, aEEG had good specificity for ruling out seizures, but low sensitivity for detecting them. The new combined pathway may prevent unnecessary treatment.

Background: Seizure monitoring via amplitude-integrated EEG (aEEG) is standard of care in many NICUs; however, conventional EEG (cEEG) is the gold standard for seizure detection. We compared the diagnostic yield of aEEG interpreted at the bedside, aEEG interpreted by an expert, and cEEG. Methods: Neonates received aEEG and cEEG in parallel. Clinical events and aEEG were interpreted at bedside and subsequently independently analyzed by experienced neonatology and neurology readers. Sensitivity and specificity of bedside aEEG as compared to expert aEEG interpretation and cEEG were evaluated. Results: Thirteen neonates were monitored for an average duration of 33 hours (range 15-94). Fourteen seizure-like events were detected by clinical observation, and 12 others by bedside aEEG analysis. None of the bedside aEEG events were confirmed as seizures on cEEG. Expert aEEG interpretation had a sensitivity of 13% with 46% specificity for individual seizure detection (not adjusting for patient differences), and a sensitivity of 50% with 46% specificity for detecting patients with seizures. Conclusions: Real-world bedside aEEG monitoring failed to detect seizures evidenced via cEEG, while misclassifying other events as seizures. Even post-hoc expert aEEG interpretation provided limited sensitivity and specificity. Considering the poor sensitivity and specificity of bedside aEEG interpretation, combined monitoring may provide limited clinical benefit.