Between July of 2012 and December of 2014, 39 patients were enrolled prospectively to investigate the prevalence of glucose transporter 1 (GLUT1) deficiency in a ketogenic diet clinic. None of them had GLUT1 deficiency. All patients seen in the same clinic within the same period were reviewed retrospectively. A total of 18 of these 85 patients had a genetic diagnosis, including GLUT1 deficiency, pathogenic copy number variants, congenital disorder of glycosylation, neuronal ceroid lipofuscinosis type II, mitochondrial disorders, tuberous sclerosis, lissencephaly, and SCN1A-, SCN8A-, and STXBP1-associated epileptic encephalopathies. The prevalence of genetic diagnoses was 21% and prevalence of GLUT1 deficiency was 2.4% in our retrospective cohort study.

Background: Registered EEG technologists (RETs) are trained in both the technical aspects of EEG and in preliminary EEG interpretation. However, there is little research evaluating the accuracy of EEG interpretation by RETs. Methods: Retrospective study of consecutive routine EEG recordings performed at SickKids Hospital. Preliminary reports by RETs and final reports by neurophysiologists were compared in 5 domains: background activity, focal abnormalities, ictal and inter-ictal epileptiform discharges and summary. Results: 500 EEG recordings were analyzed. Sensitivity and specificity of RET reports was high for the assessment of background (85%, 93%), focal slowing (84%, 93%) and inter-ictal epileptiform discharges (92%, 90%). RET reports identified ictal EEG patterns in 32 cases vs. 29 cases identified by neurophysiologists. RET reports were 100% accurate for noting no EEG change for all of 11 cases with non-epileptic events. Conclusions: Preliminary EEG reports by RETs were sensitive and specific for all EEG domains analyzed. In the majority of cases, the preliminary interpretation made by the RET was concordant with the final report of the neurophysiologist. Given these findings, RETs may be able to participate in the screening of routine EEG recordings in order to enhance the productivity of busy EEG laboratories.

Paraneoplastic syndromes (PNS) are immune-mediated neurologic diseases that occur as an indirect effect of malignancy, and can be challenging to diagnose. Onconeural antibodies have a greater than 95% association with cancer, and their presence in a patient with neurologic symptoms is reportedly highly indicative of PNS. However, we performed a single-centre retrospective review to determine the positive predictive value of onconeural antibody testing, and found it to be concerningly low (39%). Recognising the limitations of onconeural antibody testing is critical to ensure accurate test interpretation, avoid unnecessary repeated malignancy screening and prevent the use of potentially hazardous immunotherapy.

Silent pulmonary embolism (PE) may be associated with acute ischemic stroke (AIS). We identified 10 patients from 3,132 unique patients (3,431 CT scans). We retrospectively examined CT angiogram of patients with AIS to determine the frequency of concurrent PE in AIS. The period prevalence of PE was 0.32. Seven patients had concurrent PE, whereas three had PE diagnosed 2 days after their AIS presentation. We suspected paradoxical embolism via patent foramen ovale as the cause of stroke in three patients and thrombophilia in four patients. Seven patients had poor outcome including four deaths. CT angiogram stroke protocol images from aortic arch to vertex allows visualization of upper pulmonary arteries and PE detection in AIS.

Background. Diffuse low-grade gliomas (LGGs) are infiltrative, slow-growing primary brain tumours that remain relatively asymptomatic for long periods of time before transforming into aggressive high-grade gliomas. Surveillance of tumour stability is performed primarily by serial imaging. Methods. We retrospectively identified LGG patients that were managed by observation with numerous (≥8) serial magnetic resonance imaging (MRI) studies. Tumour volumes were measured by manual segmentation on imaging. Demographic information, tumour histopathological data, and radiological interpretations were collected from electronic medical records. MRI radiology reports of tumour volume stability were classified into "growth" and "no growth" interpretations. Results. Of 74 LGG patients, 10 (13.5%) patients were included in the study. A median of 11 MRIs (range, 8-18) over a median of 79.7 months (range, 39.8-113.8 months) were analyzed per patient. Tumour diameter linearly increased at a median rate of 2.17 mm/year. Cox regression analysis showed that initial tumour volume predicted time to clinical intervention, and Mann-Whitney U test found that tumours of patients diagnosed before age 50 grew more slowly. Radiology interpretations that reported "no growth" (n=66) corresponded to a median measured growth of 3.90 mL and 11.0% compared to the comparison scan. Reports of "growth" (n=36) corresponded to median measured volume increases of 9.36 mL and 20.5%. Conclusion. We retrospectively analyzed the natural history of LGGs in serially-imaged patients at a single institution. Comparisons to the literature suggest that this is a subset of particularly slow-growing and low-risk tumours. We also highlight the clinical value of performing accurate LGG volumetric analyses.

Background: Currently, there is limited insight in to the function of the mesial frontal negative motor area (NMA) and the anatomic structures implicated in its function. Methods: We present a patient with a Rett-like phenotype, refractory frontal lobe epilepsy, and reflexogenic seizures in which backpatting induced atonic seizures with a semiology resembling the patient falling asleep. The patient underwent video EEG monitoring and ictal/interictal SPECT imaging capturing the reflexogenic seizures. Iterative reconstruction was performed, with images co-registered to previously acquired MRI with subtraction Ictal-Interictal imaging co-registered to MRI. Results: Interictally, the patient’s EEG showed a slow background and right frontal spikes. Ictally, the patient had numerous subclinical frontal seizures. The reflexogenic seizures had an ictal pattern at the vertex (Cz) with the ictal SPECT imaging, showing hyperperfusion in the right mesial frontal region, both paramedian precentral and postcentral gyri, and right basal ganglia. Conclusions: Our findings support the hypothesis that the negative motor area may be activated by the primary sensory cortex; moreover, the ictal SPECT now suggests involvement of the basal ganglia in the NMA’s function.

Multiple sclerosis (MS) is a chronic, progressive, autoimmune, neurodegenerative disorder that can interfere with physical and psychological functioning, negatively affecting health-related quality of life (HRQoL). Fostering mindfulness may mitigate the negative consequences of MS on HRQoL. The relationship between mindfulness, mood and MS-related quality of life was investigated. In total, 52 individuals with MS completed questionnaires to examine the relationship between trait mindfulness and wellness. Higher levels of trait mindfulness were associated with better HRQoL, lower depression and anxiety, lower fatigue impact and fewer perceived cognitive deficits. Mindfulness interventions have the potential to enhance wellness in those living with MS.

Some nonmotor symptoms (NMS) of Parkinson’s disease (PD) have been shown to increase the risk of developing dementia. A total of 52 PD patients without dementia at baseline were examined for NMS over 36 months. Mini-Mental State Examination, Dementia Rating Scale–2, and caregiver-derived (Clinical Dementia Rating) scores were employed to rate patients as having either clear progression or not. Some 20 of 48 participants (41.7%) had clear cognitive decline. Univariate binary regression analysis was statistically significant for age (odds ratio [OR] (CI95%)=1.24, 1.07–1.45, p=0.006) and orthostatic hypotension (OH) (OR (CI95%)=4.91, 1.24–19.5, p=0.024). Multivariate analysis showed that only age (OR (CI95%)=1.19, 1.0–1.41, p=0.05) and OH (OR (CI95%)=5.57, 1.0–30.97, p=0.05) were correlated with an increased risk of cognitive decline. The presence of OH at baseline may be a significant predictor of progression to dementia in PD.

Background: Outcomes for patients with melanoma brain metastases (MBM) have been poor. New radiotherapy technologies and systemic agents have improved outcomes. Outcomes have rarely been studied at the population-level. We undertook a population-based study investigating changes in management and outcome for patients with MBM in Ontario from 2007-2016. Methods: This was a retrospective population-based cohort study of patients treated for MBM in Ontario from 2007-2016. Melanoma was identified through the Ontario Cancer Registry. Treatments and outcome were described by era (2007-2009, 2010-2012, 2013-2016). Treatment with cranial radiotherapy and drugs were defined using Cancer Care Ontario data and supplemented by physician billing and drug reimbursement data. Neurosurgery was identified using CIHI hospital records. Time to event was investigated using Kaplan-Meier curves. Results: From January 2007-June 2016, 1096 patients with MBM were treated. Whole brain radiation therapy was the first brain-directed treatment in 75.5% of patients in 2007-2009, dropping to 52.0% for 2013-2016. Patients receiving stereotactic radiation or other conformal techniques as the first brain treatment increased from 3.4% in 2007-2009 to 21.3% 2013-2016. Use of BRAF/MEK inhibitors and immunotherapy increased: <2.0% in 2007-2009 to 40.9% 2013-2016. One-year and two-year overall survival (OS) following first brain-directed treatment was greater in 2013-2016: 21.8% at one year and 13.8% after two years (Wilcoxon p=0.001). This compared to 12.3% and 6.4% 2007-2009, and 10.7% and 5.5% 2010-2012. Conclusion: The advent of new radiation technologies and systemic treatments for MBM was associated with increased survival and greater avoidance of whole brain radiotherapy.

To study the frequency of laboratory test abnormalities, and electrophysiological correlations, we performed a retrospective chart review of 226 patients with polyneuropathy. The frequency of laboratory test abnormalities, and correlations with electrophysiological findings were explored. Abnormal glucose handling tests were the most common findings (54%), followed by paraproteinemia (21%) and anemia (21%). The frequencies of paraproteinemia and anemia in our cohort were significantly higher than previously reported. In addition, several laboratory abnormalities correlated with electrophysiological findings of median neuropathy at the wrist, expanding current knowledge about the deleterious effects of various metabolic and hematologic derangements at this site.

Headache is an uncommon symptom in Guillain–Barré syndrome (GBS). We review four clinical settings related to GBS in which headache may be present. We focus on pathophysiological explanations, alerting the clinician to further potential investigations and treatment. Most reports of headache in GBS occur in the context of the posterior reversible encephalopathy syndrome, an increasingly recognized dysautonomia-related GBS complication. Less frequent is headache in the setting of increased intracranial pressure and papilledema (secondary intracranial hypertension), Miller Fisher syndrome, and cerebral venous sinus thrombosis. Rarely, headache can occur secondary to aseptic meningitis from IVIg use.

We report the clinical and electrophysiological findings in seven patients with orthostatic myoclonus (OM) associated with gait initiation failure and falls. OM is one of the causes of unsteadiness of stance and gait, and it may develop as a symptom of neurodegenerative disorders. Both positive myoclonic bursts and negative myoclonus may be seen in electrophysiological recordings, and electrophysiological analysis suggests a subcortical origin for OM.

Background: NURTURE (NCT02386553) is an ongoing open-label single-arm efficacy/safety study of intrathecal nusinersen in infants who initiate treatment in a presymptomatic stage of spinal muscular atrophy (SMA). Methods: Enrolled infants were age ≤6 weeks at first dose, clinically presymptomatic, had genetically diagnosed SMA, and 2 or 3 copies of SMN2. Primary endpoint is time to death or respiratory intervention (≥6 hours/day continuously for ≥7 days or tracheostomy). Results: As of July 5, 2017, 25 infants (2 copies SMN2, n=15;3 copies, n=10) were enrolled. All infants were alive. Two infants (both with 2 copies SMN2) required respiratory intervention (but not tracheostomy or permanent ventilation) during an acute, reversible viral infection and thus met the primary -endpoint. At last visit, 22/24 (92%) infants had achieved WHO motor milestones sitting without support and 8/16 (50%;2 SMN2, n=3/11;3 SMN2, n=5/5) on study >13 months achieved walking alone. AEs were reported in 24/25 (96%) infants; most 20/25 (80%) had AEs that were mild/moderate in severity; 9 had serious AEs. Four infants had an AE possibly related to study drug, which resolved despite continued treatment. No new safety concerns were identified. Conclusions: Nusinersen continued to benefit infants who initiated treatment in a presymptomatic stage of SMA.

Study Support: Biogen