A 16-year-old boy with learning disability presented with nocturnal pharmaco-resistant focal seizures consisting of right arm/axilla pain, sometimes followed by tonic-clonic movements of right arm/leg since 8 years of age. He was on valproate and levetiracetam and had failed multiple drugs in the past. Family history and examination were unremarkable.

Background: To evaluate efficacy, safety, and tolerability of ubrogepant, an oral CGRP receptor antagonist, for acute treatment of a single migraine attack. Methods: Multicenter, randomized, double-blind, placebo-controlled, parallel-group, single-attack, phase 3 study (NCT02828020). Patients randomized 1:1:1 to placebo, ubrogepant 50mg, or ubrogepant 100mg had 60 days to treat one migraine attack (moderate/severe pain intensity). Co-primary efficacy endpoints: pain freedom 2 hours post initial dose and absence of most bothersome migraine-associated symptom (MBS). Results: 1672 patients were randomized (safety population: n=1436; mITT population: n=1327). Mean age: 40.7 years; white (82.4%); female (87.5%). A significantly greater percentage of ubrogepant- than placebo-treated patients achieved pain freedom 2 hours post initial dose (50mg: 19.2%, adjusted P=0.0023; 100mg: 21.2%, adjusted P=0.0003; placebo: 11.8%). A significantly greater percentage of ubrogepant patients achieved absence of MBS (50mg: 38.6%, adjusted P=0.0023, 100mg: 37.7%, adjusted P=0.0023; placebo: 27.8%). The adverse event (AE) profile of ubrogepant was similar to placebo. The most common AEs (incidence ≥2% in any treatment group) within 48 hours of initial or optional second dose were nausea, somnolence, and dry mouth (all with incidence <5%). Conclusions: Both co-primary endpoints were met, with clinically meaningful effects on migraine headache pain and MBS. Ubrogepant was well tolerated, with no identified safety concerns.

A specific mutation (Arg179) of the ACTA2 gene has previously been described to cause a syndrome of multisystemic smooth muscle dysfunction with an extremely characteristic cerebrovascular appearance.1 Accurate neuroimaging diagnosis of this entity is important as this syndrome predisposes to complications such as early-onset ischemic stroke and ascending thoracic aortic aneurysm.2,3 The following case demonstrates a previously undescribed ACTA2 mutation (Met46) with an identical cerebrovascular imaging appearance to that of Arg179 mutations, but a less severe overall phenotype.

This study describes the longitudinal changes of resting motor threshold (RMT) and central motor conduction time (CMCT) in 18 patients with Wilson’s disease (WD). The RMT, CMCT, and Global Assessment Scale for Wilson Disease (GAS-WD) were measured at baseline and at follow-up after 12.94 ± 7.23 months. There was a significant decrease in the RMT (72.11 ± 18.62 vs. 63.7 ± 15.52%; p-value = 0.002) and GAS-WD scores (14.38 ± 5.35 vs. 9.77 ± 6.47 ms; p-value = 0.04). CMCT did not improve despite chelation therapy. Hence, RMT may serve as a marker of chelation efficacy in WD.

A 15-year-old teenager presented with a 2-month history of headache. Neurological examination was normal except for papilledema. Further lumbar puncture indicated intracranial hypertension (330 mm H2O). Brain magnetic resonance imaging (MRI) was normal but phase contrast-magnetic resonance venography (PC-MRV) (Figure 1(A)) suggested possible left transverse-sigmoid sinus thrombosis; subsequent contrast-enhanced 3D fat-saturated T1 volumetric isotropic turbo spin echo acquisition (VISTA) MRI (Figure 1(B)) confirmed the pathology. Hyper-coagulable panel results (including six steroid sex hormones, antithrombin III, protein C, protein S, lupus anticoagulant, and anticardiolipin antibodies) were all within normal range. In further examination, computed tomography (CT) venography images (Figure 1(C) and (D)) showed that the left jugular vein was compressed by the styloid process, consistent with Eagle syndrome.1 The patient who refused the recommended surgical treatment, however, chose anticoagulant therapy consisting of low-molecular weight heparin subcutaneous injection in addition to new oral anticoagulant. At 18-month follow-up, the patient reported no symptoms remained.

There have been significant changes in the diagnostic criteria for diffuse gliomas in the 2016 WHO CNS tumor classification, with the incorporation of molecular criteria into a number of definitions. This has placed a greater emphasis on the availability of key immunohistochemical and molecular tests. In order to determine the effect that these changes have had on neuropathology practice and the access of different centres to these tests, we designed a survey that was sent to all members of the Canadian Association of Neuropathology member list in the fall of 2017. This survey asked a number of questions relating to the approach to glioma diagnosis, immunohistochemical/molecular test ordering patterns, in-house test availability, and need to send out for testing. In this presentation we will present preliminary results from this survey, with a focus on institutional testing capabilities. This provides a valuable resource that could ultimately need to a national database of immunohistochemical and molecular test availability for each neuropathology centre.

We report three brothers born to consanguineous parents of Syrian descent, with a homozygous novel c.324G>A (p.W108*) mutation in PTRH2 that encodes peptidyl-tRNA hydrolase 2, causing infantile-onset multisystem neurologic, endocrine, and pancreatic disease (IMNEPD). We describe the core clinical features of postnatal microcephaly, motor and language delay with regression, ataxia, and hearing loss. Additional features include epileptic seizures, pancreatic insufficiency, and peripheral neuropathy. Clinical phenotyping enabled a targeted approach to the investigation and identification of a novel homozygous nonsense mutation in PTRH2, c.324G>A (p.W108*). We compare our patients with those recently described and review the current literature for IMNEPD.

A 4-year-old boy presented with asymmetric acute flaccid paralysis (AFP) of his right arm and both legs. He was alert with no oculobulbar weakness or incontinence. He had fever and diarrhea 5 days earlier. He was fully immunized with no travel history.

Background: SMA1 is a neurodegenerative disease caused by bi-allelic survival motor neuron 1 gene (SMN1) deletion/mutation. In the phase 1 study, SMN GRT onasemnogene abeparvovec (AVXS-101) improved outcomes of symptomatic SMA1 patients. We report preliminary data of STR1VE, a pivotal study (NCT03306277) evaluating efficacy and safety of a one-time intravenous AVXS-101 infusion. Methods: STR1VE is a phase 3, multicenter, open-label, single-arm study in SMA1 patients aged <6 months (bi-allelic SMN1 loss, 2xSMN2). Primary outcomes: independent sitting for ≥30 seconds (18 months) and survival (14 months). Secondary outcomes: ability to thrive and ventilatory support (18 months). Exploratory outcomes: CHOP-INTEND and Bayley Scales of Infant and Toddler Development scores. Results: Enrollment is complete with 22 patients dosed. Mean age at symptom onset, genetic diagnosis, and enrollment was 1.9 (0–4.0), 2.1 (0.5–4.0), and 3.7 (0.5–5.9) months. At baseline, no patient required ventilatory/nutritional support, and all exclusively fed by mouth. Mean baseline CHOP-INTEND score was 32.6 (17.0–52.0), which increased 6.9 (-4.0–16.0, n=20), 10.4 (2.0–18.0, n=12), and 11.6 (-3.0–23.0, n=9) points at 1, 2, and 3 months; updates provided at congress. Conclusions: Preliminary data from STR1VE show rapid motor function improvements in SMA1 patients, paralleling phase 1 findings.

A 62-year-old male presented to hospital with acute aphasia. His past medical history was significant for a previous left middle cerebral artery stroke, from which he fully recovered, hypertension, dyslipidemia, coronary artery disease, one episode of atrial fibrillation postoperatively, and thalidomide exposure in utero. Although initially he was thought to be aphasic, on further examination, he demonstrated significant abulia. His level of consciousness was normal, and neurological examination was otherwise unremarkable. A CT angiogram of the head and neck was performed. The patient was not a candidate for acute therapy, as he had established stroke on imaging, and the time of onset was unclear.

Background: Preterm infants are at risk for adverse neurodevelopmental outcomes, however studies examining preterm twins are limited. The aim of this study was to examine whether preterm monozygotic (MZ) and dizygotic (DZ) twins have similar morbidities and long-term neurodevelopmental outcomes. Methods: From a cohort of 225 preterm neonates studied with MRI, 24 MZ and 52 DZ twins were included. Outcomes at 1.5-years, 3-years and 4.5-years were assessed with the Bayley-III, Movement Assessment Battery for Children and Wechsler Preschool and Primary Scale of Intelligence. Results: Twin pairs had substantial concordance for retinopathy of prematurity but only moderate-fair concordance for bronchopulmonary dysplasia, infection and brain injury. Differences in cognitive and language scores were stable over time, while motor differences increased. Discordant twins had significantly lower gestational age [Mean1(SD)=26.7(1.38); Mean2(SD)=29.1(2.1); P<0.001] and birth weight [Mean1(SD)=892.2(291.2); Mean2(SD)=1208.0(289.4); P=0.001] and a higher incidence of bronchopulmonary dysplasia and retinopathy of prematurity. In discordant twins, cognitive and language score differences decreased over time while motor differences increased. Conclusions: Preterm twin pairs have similar neurodevelopmental outcomes through early childhood despite poor concordance for perinatal illness. Discordant twins were born earlier and had more morbidities. Increasing concordance in cognitive and language outcomes over time may reflect the positive impact of early intervention programs.

A 59-year-old man presented with confusion, decreased level of consciousness, and generalized tonic–clonic seizures. He was intubated and promptly stabilized on antiepileptic medications. He was not in status epilepticus. He improved after seizure control, though he remained confused. He was neither acutely intoxicated nor were there any substance withdrawal concerns prior to his presentation. Furthermore, no metabolic, electrolyte, or nutritional perturbations were identified. He did, however, have a history of alcoholic hepatitis and was awaiting a liver transplant, but his blood work did not reveal evidence of fulminant hepatic failure at presentation (international normalized ratio – 1.17, platelet count 161,000/µL, ammonia 18 µmol/L, blood urea nitrogen 4.5 mmol/L, and his liver enzymes were only remarkable for an elevated alkaline phosphatase of 143 U/L).

Glioblastoma is the most common primary malignant brain tumour in adults, and remains uniformly lethal. These tumours contain a subpopulation of glioblastoma stem cells (GSCs) that drive tumour recurrence and drug resistance. We find that MacroH2A2 is a histone variant that can stratify glioblastoma patients, with higher levels of this histone variant associated with better patient prognosis. Knockdown of macroH2A2 in GSCs is associated with increased self-renewal and an increased expression of stemness genes by RNA-seq. Our preliminary results suggest that macroH2A2 is a novel biomarker for glioblastoma and that macroH2A2 loss is a marker of GSC stemness and a poor prognostic marker in glioblastoma. This work identifies loss of macroH2A2 as a feature of GSCs and provides a framework for therapeutic modulation of this histone variant.

Community stroke rehabilitation (CSR) is an effective program for survivors to recover at home supported by a multidisciplinary team. A home-based, specialized CSR program was delivered in Windsor, Ontario, to stroke patients who faced barriers to accessing outpatient services following inpatient rehabilitation. Preliminary results show program patients made significant functional improvements from baseline to program discharge. A subgroup analysis revealed that, after adjusting for age and resource intensity, moderate to severe stroke patients made greater functional gains compared to mild stroke patients. The individualized focus of CSR delivered in the home provides an effective model of rehabilitation for continued stroke care in the community.