Task-specific dystonia is characterized by abnormal repetitive movements or postures in a specific body part that is triggered and ends with a task, such as writing. Failing medications, surgery, specifically disruption of key nuclei in the thalamus, can provide excellent symptomatic relief. Transcranial magnetic resonance (MR)-guided focused ultrasound is an emerging incision-less thermoablation technique. We describe MR-guided focused ultrasound tandem ablation of the ventral intermediate and ventralis oralis posterior nuclei in a 60-year-old patient with writer’s cramp. The clinical improvement was immediate with incremental benefit from the latter lesion, which was sustained at 6 months follow-up.

Background: Despite advances in neonatal care, neonates with moderate to severe HIE are at high risk of mortality and morbidity. we report the impact of a dedicated NNCC team on short term mortality and morbidities. Methods: A retrospective cohort study on neonates with moderate to serve HIE between July 1st 2008 and December 31st 2017. primary outcome : a composite of death and/or brain injury on MRI. Secondary outcomes: rate of cooling, length of hospital stay, anti-seizure medication burden, and use of inotropes. A regression analysis was done adjusting for gestational age, birth weight, gender, out-born status, Apgar score at 10 minutes, cord blood pH, and HIE clinical staging Results: 216 neonates were included, 109 before NNCC implementation, and 107 thereafter. NNCC program resulted in reduction in the primary outcome (AOR: 0.28, CI: 0.14-0.54, p<0.001) and brain injury (AOR: 0.28, CI: 0.14-0.55, p<0.001). It decreased average length of stay/infants by 5 days (p=0.03), improved cooling rate (73% compared to 93% , p <0.001), reduced: seizure misdiagnosis (71% compared to 23%, P <0.001), anti-seizure medication burden (P = 0.001), and inotrope use (34% compared to 53%, p=0.004) Conclusions: NNCC program decreased mortality and brain injury , shortened the length of hospital stay and improved care of neonates with significant HIE.

With the financial assistance from two donors, we have established a neurodegenerative disease brain bank at the University of Calgary. At autopsy, tissues from anatomically specific regions are frozen in liquid nitrogen vapour and stored in small, bar-coded cryovials. Cases include patients with dementia, movement disorders, demyelinating diseases, and normal controls. We prepare additional FFPE blocks for diagnosis or banking. Sampling includes all major areas of cortex and most subcortical structures. All brains, including “normal” controls, are characterized with a basic set of stains and major classification schemata are used for Alzheimer and Lewy body diseases. These tissues are available to investigators with IRB-approved research on human tissues

Control tissue is important in the study of age-associated neurodegeneration. We preserve tissues from areas of brain that either are severely or minimally affected by neurodegeneration (e.g. in Alzheimer disease, Brodmann areas 9 and 17, respectively). In our “normal” aging cohort, which includes patients with no described neurodegenerative diseases, we find frequent evidence of low-stage Alzheimer or Lewy body related pathological changes. We also find relatively frequent small vessel disease, which in part relates to our preferential selection of patient’s who died suddenly.

In preliminary studies, we have examined amyloid plaque structure with confocal microscopy using beta-sheet sensitive dyes and have studied the distribution of different chaperones in normal brain.

Purpose: Cranial radiotherapy (CRT) was commonly given for childhood leukemia and brain tumors. Survivors are at risk of late effects including radiation induced meningioma (RIM). Surveillance for RIM is not standardized . We aimed to determine the incidence, latency, and screening patterns for RIM. Materials and Methods: Retrospective chart review of all patients aged <18 years at the time of radiation (RT), treated with CRT for leukemia or a brain tumor in BC between 1981-2006. Patient, tumor, and treatment characteristics were collected. Actuarial statistics were calculated with Kaplan-Meier Curves. Patients were censored at the date of last normal cranial imaging, or development of a RIM. Results: 392 patients were identified. Median age (range) at CRT was 9.6 years. Median CRT dose was 28Gy. The original diagnosis was leukemia in 50%, glioma in 13%, medulloblastoma in 8%, ependymoma in 7%, neuroectodermal tumor in 7%, germ cell tumor in 5%, craniopharyngioma in 4%, and other pathologies in 6%. Median (range) of clinical follow-up (FU) was 13.2 (0-37.5) years. Median (range) of cranial imaging FU was 15.5 (0-21.2) years. There was no documented cranial imaging FU in 144 patients. Forty-eight patients developed a RIM. The median age (range) at RT for patients with RIM was 6.7 years. Only 8 of these cases presented with associated symptoms. The earliest RIM in our cohort occurred 10.2 years after CRT. On actuarial analysis, the median (95% CI) time to development of a meningioma was 29.8 (28.9-30.7) years. Incidence (95% CI) of meningioma at 10 years was 0%, 15 years was 5 (2-9)%, 20 years was 12 (6-18)%, 25 years was 33 (23-43)% and 30 years was 47 (37-68)%. Amongst patients with a RIM, the median dose of CRT was 45 Gy. The lowest dose of RT in a patient who developed RIM was 12 Gy. RT was delivered to the whole brain in 58% and partial brain in 42% of patients with a RIM. Conclusions: After CRT in pediatric patients, there is a significant risk of developing a RIM and a steady increase in this risk with ongoing follow-up. We recommend standardization of surveillance for these patients with screening beginning 10 years after completion of CRT.

The association between environmental exposures and Parkinson’s disease continues to garner interest. In the late 1980s, Barbeau et al. reported in the Canadian Journal of Neurological Sciences a heterogeneous distribution of Parkinson’s disease cases across the province of Québec by hydrographic region. Here we report the findings of a validation study based on data obtained from the Québec medication insurance program–information which was unavailable to the previous group. Similar to Barbeau et al., our analysis showed a heterogeneous distribution of cases across the province with higher prevalence in the same region of interest, in addition to other areas.

The tauopathies are a group of neurodegenerative diseases characterized by abnormal deposition of hyperphosphorylated-tau. The pathogenesis of these changes remains uncertain. In chronic traumatic encephalopathy, tauopathy is hypothesized to occur after repeated mild traumatic brain injury (TBI). Post-traumatic extracellular ATP release and signalling via the P2X purinoceptor 7 (P2RX7) has been shown to be important in mediating pathological changes in TBI. We hypothesized that ATP-P2RX7 is involved in the development of tauopathy.

We injected ATP analogue bzATP or vehicle intraventricularly into C57BL/6 mice, pre-treated with either intraperitoneal P2RX7 antagonist Brilliant Blue G (BBG) or vehicle. At 2 weeks and 3 months, behavioural change was assessed with the tail suspension test, accelerating rotatrod, and fear conditioning; mice were then sacrificed for immunohistochemistry and western blot.

We observed increased immobile time in the tail suspension test for mice treated with bzATP at 3 months. Similarly, for rotarod, mice treated with bzATP showed poorer performance at 3 months. These effects were diminished by BBG pre-treatment. Fear conditioning, however, did not demonstrate a significant difference between groups. Immunohistochemical staining for GFAP showed increased intensity at both 2 weeks and 3 months for bzATP-treated mice compared to those pre-treated with BBG. Levels of phosphorylated tau (AT8) were increased in bzATP-treated mice compared to controls.

In summary, ATP-P2RX7-mediated mechanisms may play a role in the development of behavioural deficits and tauopathy.

Background:ATP8A2 mutations have only recently been associated with human disease. We present the clinical features from the largest cohort of patients with this disorder reported to date. Methods: An observational study of 9 unreported and 2 previously reported patients with biallelic ATP8A2 mutations was carried out at multiple centres. Results: The mean age of the cohort was 9.4 years old (range: 2.5-28 yrs). All patients demonstrated developmental delay, severe hypotonia and movement disorders: chorea/choreoathetosis (100%), dystonia (27%) or facial dyskinesia (18%). Hypotonia was apparent at birth (70%) or before 6 months old (100%). Optic atrophy was observed in 75% of patients who had a funduscopic examination. MRI of the brain was normal for most patients with a small proportion showing mild cortical atrophy (30%), delayed myelination (20%) and/or hypoplastic optic nerves (20%). Epilepsy was seen in two older patients. Conclusions:ATP8A2 gene mutations have emerged as a cause of a novel phenotype characterized by developmental delay, severe hypotonia and hyperkinetic movement disorders. Optic atrophy is common and may only become apparent in the first few years of life, necessitating repeat ophthalmologic evaluation. Early recognition of the cardinal features of this condition will facilitate diagnosis of this disorder.

We report the outcome of 12 patients with inherited neurotransmitter disorders of monoamine, tetrahydrobiopterin and γ amino butyric acid metabolisms from a single Inherited Neurotransmitter Disorder Clinic including tyrosine hydroxylase (n=2), aromatic l-amino acid decarboxylase (n=1), 6-pyruvoyltetrahydropterin synthase, dihydropteridine reductase and succinic semialdehyde dehydrogenase deficiencies. Six patients (with 6-pyruvoyltetrahydropterin synthase, dihydropteridine reductase and tyrosine hydroxylase deficiencies) had normal neurodevelopmental outcome on treatment. Tetrahydrobiopterin loading test in newborns with positive newborn screening for phenylketonuria will identify patients with 6-pyruvoyltetrahydropterin synthase and dihydropteridine reductase deficiencies resulting in abnormal neurotransmitter synthesis in the central nervous system in the neonatal period to initiate disease-specific treatment to improve neurodevelopmental outcome.

At the London Health Sciences Centre Epilepsy Program, stereotactically implanted depth electrodes have largely replaced subdural electrodes in the presurgical investigation of patients with drug-resistant epilepsy over the past 4 years. The rationale for this paradigm shift was more experience with, and improved surgical techniques for, stereoelectroencephalography, a possible lower-risk profile for depth electrodes, better patient tolerability, shorter operative time, as well as increased recognition of potential surgical targets that are not accessible to subdural electrodes.

Canadian contributions to cerebrovascular neurosurgery have been disproportionately large and, with some exceptions, relatively unrecognized. In this review, some of the efforts in the advancement of cerebrovascular neurosurgery by Canadian neurologists and neurosurgeons are described.

CIC, or Capicua, encodes a transcriptional repressor that is itself repressed by RAS/MAPK signalling. CIC is a recurrent target of somatic mutation in type 1 low grade gliomas (LGG), with at least half of the alterations predicted to be deleterious. Type 1 LGGs are a cohort of tumours that are molecularly defined by the loss of heterozygosity of chromosome arms 1p and 19q and the presence of neomorphic IDH1/2 mutations. Despite the high frequency of mutations in CIC within this tumour type, CIC’s putative tumour suppressive role remains to be elucidated. It is also unclear how CIC may cooperate with neomorphic IDH1/2 to promote gliomagenesis. To comprehensively characterize the molecular consequences of CIC loss, we performed RNA-seq, Whole Genome Bisulfite Sequencing, and ChIP-seq on 6 different histone modifications on isogenic CIC-wildtype (WT) and CIC-knockout (KO) normal human astrocytes. To also investigate the collective effects of CIC deficiency and neomorphic IDH1 on the transcriptome and epigenome, we generated the same dataset in isogenic CIC-WT and CIC-KO astrocytes possessing the IDH1 R132H mutation. Analysis of differentially expressed genes illustrates the enrichment of oncogenic pathways in specifically the CIC-KO, IDH1-R132H cells, supporting a synergistic relationship between CIC loss and IDH1-R132H in driving tumour progression. Integrative analyses are ongoing to unveil the epigenetic mechanisms underpinning the regulatory changes in these isogenic cell line models.

BACKGROUND: Meningiomas are the most common primary benign brain tumors in adults. Given the extended life expectancy of most meningiomas, consideration of quality of life (QOL) is important when selecting the optimal management strategy. There is currently a dearth of meningioma-specific QOL tools in the literature. OBJECTIVE: In this systematic review, we analyze the prevailing themes and propose toward building a meningioma-specific QOL assessment tool. METHODS: A systematic search was conducted, and only original studies based on adult patients were considered. QOL tools used in the various studies were analyzed for identification of prevailing themes in the qualitative analysis. The quality of the studies was also assessed. RESULTS: Sixteen articles met all inclusion criteria. Fifteen different QOL assessment tools assessed social and physical functioning, psychological, and emotional well-being. Patient perceptions and support networks had a major impact on QOL scores. Surgery negatively affected social functioning in younger patients, while radiation therapy had a variable impact. Any intervention appeared to have a greater negative impact on physical functioning compared to observation. CONCLUSION: Younger patients with meningiomas appear to be more vulnerable within social and physical functioning domains. All of these findings must be interpreted with great caution due to great clinical heterogeneity, limited generalizability, and risk of bias. For meningioma patients, the ideal QOL questionnaire would present outcomes that can be easily measured, presented, and compared across studies. Existing scales can be the foundation upon which a comprehensive, standard, and simple meningioma-specific survey can be prospectively developed and validated.

In this brief report, computed tomography perfusion (CTP) thresholds predicting follow-up infarction in patients presenting <3 hours from stroke onset and achieving ultra-early reperfusion (<45 minutes from CTP) are reported. CTP thresholds that predict follow-up infarction vary based on time to reperfusion: Tmax >20 to 23 seconds and cerebral blood flow <5 to 7 ml/min−1/(100 g)−1 or relative cerebral blood flow <0.14 to 0.20 optimally predicted the final infarct. These thresholds are stricter than published thresholds.