Hereditary spastic paraplegia (HSP) is a heterogeneous neurodegenerative disorder with lower-limb spasticity and weakness. Different patterns of inheritance have been identified in HSP. Most autosomal-dominant HSPs (AD-HSPs) are associated with mutations of the SPAST gene (SPG4), leading to a pure form of HSP with variable age-at-onset (AAO). Anticipation, an earlier onset of disease, as well as aggravation of symptoms in successive generations, may be correlated to SPG4. Herein, we suggested that anticipation might be a relatively common finding in SPG4 families.

Whole-exome sequencing was done on DNA of 14 unrelated Iranian AD-HSP probands. Data were analyzed, and candidate variants were PCR-amplified and sequenced by the Sanger method, subsequently checked in family members to co-segregation analysis. Multiplex ligation-dependent probe amplification (MLPA) was done for seven probands. Clinical features of the probands were recorded, and the probable anticipation was checked in these families. Other previous reported SPG4 families were investigated to anticipation.

Our findings showed that SPG4 was the common subtype of HSP; three families carried variants in the KIF5A, ATL1, and MFN2 genes, while five families harbored mutations in the SPAST gene. Clinical features of only SPG4 families indicated decreasing AAO in affected individuals of the successive generations, and this difference was significant (p-value <0.05).

It seems SPAST will be the first candidate gene in families that manifests a pure form of AD-HSP and anticipation. Therefore, it may be a powerful situation of genotype–phenotype correlation. However, the underlying mechanism of anticipation in these families is not clear yet.

This research aimed to study the short-term seizure outcomes following treatment with 8 mg/kg/day prednisolone in children with infantile spasms (IS) refractory to vigabatrin. We hypothesized that high-dose prednisolone may result in similar rates of electroclinical remission when compared to published ACTH rates.

All consecutive children with hypsarrhythmia or hypsarrhythmia variant on EEG with/without IS, who had been treated with vigabatrin as first-line anti-seizure medication (ASM) followed by high-dose oral prednisolone (8 mg/kg/day; maximum 60 mg/day) in cases who did not respond to vigabatrin, were included. Clinical and electroclinical response (ECR) at 2 weeks following initiation of treatment and adverse effects were assessed.

Sixty-five children were included. A genetic etiology was seen in 38.5% cases. Complete ECR was seen in 30.8% (20/65) of the patients 2 weeks after vigabatrin. Complete ECR was noted in 77.8% (35/45) of the patients, 2 weeks after prednisolone initiation in children who failed vigabatrin, and this was sustained at 6 weeks in 66.7% (30/45) patients. Prednisolone was generally well tolerated.

High-dose (8 mg/kg/day) oral prednisolone resulted in sustained complete ECR (at 6 weeks) in two-thirds of the children with hypsarrhythmia or hypsarrhythmia variant on EEG with/without parentally reported IS. It was generally well tolerated and found to be safe.

Health utility instruments are increasingly being used to measure impairment in health-related quality of life (HRQoL) after stroke. Population-based studies of HRQoL after stroke and assessment of differences by age and functional domain are needed.

We used the Canadian Community Health Survey linked with administrative databases to determine HRQoL using the Health Utilities Index Mark 3 (HUI3) among those with prior hospitalization or emergency department visit for stroke and compared to controls without stroke. We used multivariable linear regression to determine the difference in HUI3 between those with stroke and controls for the global index and individual attributes, with assessment for modification by age (<60, 60–74, and 75+ years) and sex, and we combined estimates across survey years using random effects meta-analysis.

Our cohort contained 1240 stroke survivors and 123,765 controls and was weighted to be representative of the Canadian household population. Mean health utility was 0.63 (95% confidence interval [CI] 0.58, 0.68) for those with stroke and 0.83 (95% CI 0.82, 0.84) for controls. There was significant modification by age, but not sex, with the greatest adjusted reduction in HUI3 among stroke respondents aged 60–74 years. Individual HUI3 attributes with the largest reductions in utility among stroke survivors compared to controls were mobility, cognition, emotion, and pain.

In this population-based study, the reduction in HUI3 among stroke survivors compared to controls was greatest among respondents aged 60–74, and in attributes of mobility, cognition, emotion, and pain. These results highlight the persistent impairment of HRQoL in the chronic phase of stroke and potential targets for community support.

Status epilepticus (SE) has traditionally been thought to cause cerebrospinal fluid (CSF) pleocytosis. However, attributing CSF pleocytosis solely to SE without addressing the underlying etiology may lead to poor outcomes. Leukocyte recruitment to CSF has been shown to peak around 24 hours after prolonged seizures in animal studies, suggesting that CSF pleocytosis within the first 24 hours of SE onset may be due to underlying causes. The goal of this study is to assess if SE is associated with CSF pleocytosis, independent of other causes within the first 24 hours of onset.

We completed a historical cohort study of adult patients with SE admitted to the intensive care unit of Vancouver General Hospital between March 2010 and May 2019.

Of the 441 patients admitted with SE during the study period, 107 met our inclusion criteria leading to 111 lumbar punctures (LPs), with 4 patients receiving two LPs. CSF pleocytosis was seen in 12 of 72 patients who underwent an LP within the first 24 hours of SE onset. In all 12 patients, a secondary etiology for the pleocytosis was observed aside from SE. Of the six CSF samples collected after 24 hours of onset that demonstrated pleocytosis, four had no cause for pleocytosis other than SE.

In all 12 patients with CSF pleocytosis in the first 24 hours of onset of SE, an underlying etiology was identified. Therefore, any pleocytosis noticed within the first 24 hours of onset of refractory SE should not be attributed solely to SE.

In January 2020, the first case of Guillain Barre syndrome (GBS) due to COVID-19 was documented in China. GBS is known to be postinfectious following several types of infections. Although causality can only be proven through large epidemiological studies, we intended to study this association by a thorough review of the literature.

We searched PubMed, EMBASE, and Google scholar and included all papers with English or Spanish full text and original data of patients with GBS and recent COVID infection. Variables of interest were demographics, diagnostic investigations, and the latency between arboviral and neurological symptoms. Further variables were pooled to identify GBS clinical and electrophysiological variants, used treatments, and outcomes. The certainty of GBS diagnosis was verified using Brighton criteria.

We identified a total of 109 GBS cases. Ninety-nine cases had confirmed COVID-19 infection with an average age of 56.07 years. The average latency period between the arboviral symptoms and neurologic manifestations for confirmed COVID-19 cases was 12.2 d. The predominant GBS clinical and electromyography variants were the classical sensorimotor GBS and acute demyelinating polyneuropathy respectively. Forty cases required intensive care, 33 cases required mechanical ventilation, and 6 cases were complicated by death.

Studies on COVID-19-related GBS commonly reported sensorimotor demyelinating GBS with frequent facial palsy. The time between the onset of infectious and neurological symptoms suggests a postinfectious mechanism. Early diagnosis of GBS in COVID-19 patients is important as it might be associated with a severe disease course requiring intensive care and mechanical ventilation.

Survivors of patients with artery of Percheron infarction (API) often have a prolonged and disabling form of cognitive impairment that remains insufficiently characterized. We aimed to examine the clinical and cognitive features of API in the short and long term after stroke.

We reviewed 6400 patients with a first-ever stroke included in the Stroke Registry between 2011 and 2021. The diagnosis of API was based on clinical diagnosis and imaging confirmation. All patients underwent neuropsychological assessment at hospital stay and 1 year after stroke. A z-score of each patients’ cognitive test point was calculated, and a z-score inferior to 2 was considered as pathological.

Of the 10 patients enrolled, all had cognitive impairment, consciousness, and behavioral disorders at stroke onset. Six patients had pure bilateral thalamic involvement while four had bilateral thalamic and rostral midbrain involvement. At 12 months, 50% of patients had global mental state scores 2 SD below the population mean (z-score mean ± SD, −2.17 ± 0.4). Most of the prefrontal cortex cognitive processes including executive functions such as planning and cognitive control (z-score mean ± SD, −3.92 ± 0.3), processing speed (−4.42 ± 0.5), working memory (−3.97 ± 0.3) were severely impaired at stroke onset. Especially in patients with thalamic and rostral midbrain involvement, deficiencies in executive function (z-score mean ± SD, −2.60 ± 0.4), processing speed (−2.22 ± 0.5), working (−3.76 ± 0.4), and episodic memory (−2.23 ± 0.3) continued 12 months after stroke.

The occlusion of the artery of Percheron results in severe behavioral and cognitive disorders in the short and long term after stroke.

To investigate the relative contributions of cerebral cortex and basal ganglia to movement stopping, we tested the optimum combination Stop Signal Reaction Time (ocSSRT) and median visual reaction time (RT) in patients with Alzheimer’s disease (AD) and Parkinson’s disease (PD) and compared values with data from healthy controls.

Thirty-five PD patients, 22 AD patients, and 29 healthy controls were recruited to this study. RT and ocSSRT were measured using a hand-held battery-operated electronic box through a stop signal paradigm.

The mean ocSSRT was found to be 309 ms, 368 ms, and 265 ms in AD, PD, and healthy controls, respectively, and significantly prolonged in PD compared to healthy controls (p = 0.001). The ocSSRT but not RT could separate AD from PD patients (p = 0.022).

Our data suggest that subcortical networks encompassing dopaminergic pathways in the basal ganglia play a more important role than cortical networks in movement-stopping. Combining ocSSRT with other putative indices or biomarkers of AD (and other dementias) could increase the accuracy of early diagnosis.

The PREDICT study assessed real-world, long-term health-related quality of life in adults with chronic migraine (CM) receiving onabotulinumtoxinA.

Canadian, multicenter, prospective, observational study in adults naïve to onabotulinumtoxinA for CM. OnabotulinumtoxinA (155–195 U) was administered every 12 weeks over 2 years (≤7 treatment cycles). Primary endpoint: mean change in Migraine-Specific Quality of Life Questionnaire (MSQ) at treatment 4 (Tx4) versus baseline. Secondary endpoints: mean change in MSQ at final visit versus baseline, and headache days.

184 participants (average age 45 years; 84.8% female; 94.6% Caucasian) received ≥1 onabotulinumtoxinA treatment; 150 participants completed 4 treatments (1 year) and 123 completed all 7 treatment cycles (2 years). Mean (SD) onabotulinumtoxinA dose per treatment cycle was 171 (18) U and treatment interval was 13.2 (1.8) weeks. Baseline mean (SD) 20.9 (6.7) headache days/month decreased (Tx1: −3.5 [6.3]; Tx4: −6.5 [6.6]; p < 0.0001 versus baseline). Mean (SD) increased from baseline in MSQ at Tx4 (restrictive: 21.5 [24.3], preventive: 19.5 [24.7], emotional: 22.9 [32.9]) and the final visit (restrictive: 21.3 [23.0], preventive: 19.2 [23.7], emotional: 27.4 [30.7]), exceeding minimal important differences (all p < 0.0001). Seventy-seven (41.8%) participants reported 168 treatment-emergent adverse events (TEAEs); 38 TEAEs (12.0%) were considered treatment-related. Four (2.2%) participants reported six serious TEAEs; none were considered treatment-related. No new safety signals were identified.

Real-world evidence from PREDICT demonstrates that onabotulinumtoxinA for CM in Canada improved MSQ scores and reduced headache frequency and severity, adding to the body of evidence on the long-term safety and effectiveness of onabotulinumtoxinA for CM.

The effectiveness of mechanical thrombectomy (MT) in elderly stroke patients remains debated. We aimed to describe outcomes and their predictors in a cohort of patients aged ≥ 85 years treated with MT.

Data from consecutive patients aged ≥ 85 years undergoing MT at two stroke centers between January 2016 and November 2019 were reviewed. Admission National Institutes of Health Stroke Scale (NIHSS), pre-stroke, and 3-month modified Rankin scale (mRS) were collected. Successful recanalization was defined as modified thrombolysis in cerebral ischemia score ≥ 2b. Good outcome was defined as mRS 0–3 or equal to pre-stroke mRS at 3 months.

Of 151 included patients, successful recanalization was achieved in 74.2%. At 3 months, 44.7% of patients had a good outcome and 39% had died. Any intracranial hemorrhage (ICH) and symptomatic ICH occurred in 20.3% and 3.6%, respectively. Logistic regression analysis identified lower pre-stroke mRS score (adjusted odds ratio [aOR], 0.52; 95% CI, 0.36–0.76), lower admission NIHSS score (aOR, 0.90; 95% CI, 0.83–0.97), successful recanalization (aOR, 3.65; 95% CI, 1.32–10.09), and absence of ICH on follow-up imaging (aOR, 0.42; 95% CI, 0.08–0.75), to be independent predictors of good outcome. Patients with successful recanalization had a higher proportion of good outcome (45.3% vs 34.3%, p = 0.013) and lower mortality at 3 months (35.8% vs 48.6%, p = 0.006) compared to patients with unsuccessful recanalization.

Among patients aged ≥ 85 years, successful recanalization with MT is relatively common and associated with better 3-month outcome and lower mortality than failed recanalization. Attempting to achieve recanalization in elderly patients using MT appears reasonable.

Several guidelines currently recommend acute diffusion weighted imaging (DWI) for the detection of ischemia in transient ischemic attack (TIA). However, DWI hyperintensities resolve early and only 30%–50% with clinically defined TIA show acute DWI positivity. A recent meta-analysis reported an unexplained 7-fold variation in DWI positivity in TIA across studies, concluding that DWI does not provide a consistent basis for defining ischemia. Intracortical excitability, measured using transcranial magnetic stimulation (TMS), has previously been shown to be altered after TIA and associated with ABCD2 scores; however, whether altered cortical excitability is associated with clinical and DWI-based definitions of TIA remains unclear.

Individuals with TIA symptoms (N = 23; mean age = 61 ± 12) were prospectively recruited and underwent DWI and paired-pulse TMS. Multivariate linear regression was used to estimate associations between TMS-derived excitability thresholds, and clinical TIA diagnosis, and imaging-based evidence of cerebral ischemia (DWI positivity). Area under the curve (AUC) analyses was used to compare the discriminability of TMS-derived thresholds and clinical TIA diagnoses.

Thresholds for intracortical inhibition in the TIA-unaffected hemisphere were significantly associated with the clinical diagnosis of TIA. No associations between TMS-derived thresholds and DWI positivity were observed. TMS thresholds showed low-moderate discriminability and values differed by age (65+) and sex.

In this small sample, TMS-derived markers of intracortical excitability were associated with clinical TIA diagnoses but not DWI positivity. Our results provide preliminary evidence for the potential discriminative utility of TMS for the diagnosis of TIA and highlight the need for future work in larger cohorts.

This study seeks to determine the prevalence and nature of cannabis use in patients with headache in a tertiary headache clinic and to explore patients’ empiric experience in using cannabinoids therapeutically.

Many patients with headache report cannabinoid use as an effective abortive and/or preventive therapy. Mounting evidence implicates cannabinoids in pain mechanisms pertaining to migraine and other headache types.

A cross-sectional study surveyed 200 patients presenting with any headache disorder to a tertiary headache clinic in Calgary, Alberta. Descriptive analyses were applied to capture information about headache diagnoses and the frequency, doses and methods of cannabinoid delivery employed, as well as patients’ perceptions of therapeutic benefit and selected negative side effects.

Active cannabinoid users comprised 34.0% of respondents. Approximately 40% of respondents using cannabinoids engaged in very frequent use (≥300 days/year). Of cannabinoid modalities, liquid concentrates were most popular (39.2%), followed by smoked cannabis (33.3%). Patients endorsed cannabinoid use for both prevention and acute therapy of headaches, often concurrently. Sixty percent of respondents felt cannabinoids reduced headache severity, while 29.2% perceived efficacy in aborting headaches. Nearly 5% of respondents volunteered that they had encountered a serious problem such as an argument, fight, accident, or work issue as a result of their cannabis use. Approximately 35.4% of users had attempted to reduce their use.

This survey shows that over one-third of patients with headache disorders in a tertiary headache clinic use cannabis as a treatment for their headaches. Of these, about 25% and 60% perceive improvements in headache frequency and severity, respectively. The results of this survey will aid neurologists and headache specialists in understanding the landscape of cannabinoid use in a more severely affected population and inform future-controlled studies of cannabinoids in headache patients.

Essential tremor (ET) is a common movement disorder with ˜5% prevalence in individuals above the age of 65, but in rare cases, it arises during childhood. Growing evidence suggests the role of cerebellum in the disease mechanism. ET is highly heritable, however, poor replication of risk loci point to its significant heterogeneity. Thus, it is important to genetically investigate kindreds with a strong aggregation of ET.

We conducted a clinical and whole-genome investigation of a large Caucasian Canadian family, in which six out of eight patients are affected by childhood-onset ET in four consecutive generations. Eight family members were available for study, including three patients affected by ET. Whole-genome sequencing (WGS) was conducted for the four most informative individuals, followed by Sanger sequencing in the entire kindred.

We searched for rare variants absent in the eldest unaffected individual, but present in the patients (two siblings and their third-degree relative). Our stringent whole-genome filtering approach revealed a rare heterozygous p. Arg90Gln substitution in TCP10L (rs151233771) in all three investigated patients. Sanger sequencing confirmed the p. Arg90Gln variant and revealed its absence in the rest of the family members.

Whole-genome data of the family with ET resulted in a single candidate gene mapped to 21q22.11 locus (TCP10L) with the highest brain expression in cerebellum. Our study encourages future replication studies to validate the genetic link between TCP10L and ET, and suggests the p. Arg90Gln variant for functional investigation.

Rapid eye movement sleep behaviour disorder (RBD) is considered to be one of the most frequent and important prodromal symptoms of Parkinson’s disease (PD). We aimed to study the neurophysiological abnormalities in patients of PD-RBD and PD without RBD (PD-nRBD) using transcranial magnetic stimulation (TMS).

Twenty patients each of PD-RBD and PD-nRBD were included in the study in addition to 20 age and gender-matched healthy controls. RBD was identified using the RBD screening questionnaire (RBDSQ). All the subjects were evaluated with single and paired-pulse TMS and parameters such as resting motor threshold (RMT), central motor conduction time (CMCT), silent period (SP), short-interval intracortical inhibition (SICI) and intracortical facilitation (ICF) were recorded.

The mean age of the controls and PD patients with and without RBD was comparable. There were no significant differences in RMT, CMCT and silent period between the two patient groups. SICI was present in all the three groups with significant inhibition noted in PD-RBD group (p < 0.001). ICF was absent in patients of PD-RBD (0.19 ± 0.11) and PD-nRBD (0.7 ± 0.5) when compared to controls (1.88 ± 1.02) with profound impairment in patients with PD-RBD (p < 0.001). The mean MoCA score was found to be significantly different in all the three groups with a worse score in patients with RBD (23.10 ± 2.55; p < 0.001).

PD-RBD patients have significantly greater inhibition and reduced intracortical facilitation suggesting enhanced GABAergic and reduced glutaminergic transmission. These abnormalities may underlie the different pathophysiological process observed in these patients.

Symptomatic carotid near-occlusion is often described as rare. Recent studies have shown that near-occlusions are overlooked, especially near-occlusion without full collapse (with a small but normal-appearing distal internal carotid artery).

To assess the prevalence of near-occlusion among symptomatic ≥50% carotid stenosis, incidence of symptomatic near-occlusion, and review the literature.

Prospective controlled single-center cross-sectional study. Consecutive cases with symptomatic ≥50% carotid stenosis were examined with computed tomography angiography (CTA). The CTAs were assessed for near-occlusion by two observers. A systematic literature review was performed with emphasis on how study design affects prevalence estimate.

Totally, 186 patients with symptomatic ≥50% carotid stenosis were included, 34% (n = 63, 95% CI 27, 41) had near-occlusion. The incidence of symptomatic near-occlusion was 3.4 (95% CI 2.5, 4.2) per 100,000 person-years. Inter-rater κ was 0.71. The average prevalence of near-occlusion among symptomatic ≥50% carotid stenosis was higher in studies with good design (30%, range 27%–34%) than studies without good design (9%, range 2%–10%).

Near-occlusion is common variant of symptomatic ≥50% carotid stenosis, both in the current study and in all previous studies of good design. Studies that suggest that near-occlusion is rare have had methodological issues.

Stroke survivors may be at higher risk of incident cancer, although the magnitude and the period at risk remain unclear. We conducted a retrospective cohort study to compare the risk of cancer in stroke survivors to that of the general population.

The Canadian Longitudinal Study on Aging is a large population-based cohort of individuals aged 45–85 years when recruited (2011–2015). We used data from the comprehensive subgroup (n = 30,097) to build a retrospective cohort with individual exact matching for age (1:4 ratio). We used Cox proportional hazards models to estimate hazard ratios of new cancer diagnosis with and without a prior stroke.

We respectively included 920 and 3,680 individuals in the stroke and non-stroke groups. We observed a higher incidence of cancer in the first year after stroke that declined afterward (p-value = 0.030). The hazard of new cancer diagnosis after stroke was significantly increased (hazard ratio: 2.36; 95% CI: 1.21, 4.61; p-value = 0.012) as compared to age-matched non-stroke participants after adjustments. The most frequent primary cancers in the first year after stroke were prostate (n = 8, 57.1%) and melanoma (n = 2, 14.3%).

The hazard of new cancer diagnosis in the first year after an ischemic stroke is about 2.4 times higher as compared to age-matched individuals without stroke after adjustments. Surveillance bias may explain a portion of post-stroke cancer diagnoses although a selection bias of healthier participants likely led to an underestimation of post-stroke cancer risk. Prospective studies are needed to confirm the potentially pressing need to screen for post-stroke cancer.

There is international variability in whether neurological determination of death (NDD) is conceptually defined based on permanent loss of brainstem function or “whole brain death.” Canadian guidelines are not definitive. Patients with infratentorial stroke may meet clinical criteria for NDD despite persistent cerebral blood flow (CBF) and relative absence of supratentorial injury.

We performed a multicenter cohort study involving patients that died from ischemic or hemorrhagic stroke in Alberta intensive care units from 2013 to 2019, focusing on those with infratentorial involvement. Medical records were reviewed to determine the incidence and proportion of patients that met clinical criteria for NDD; whether ancillary testing was performed; and if so, whether this demonstrated the absence of CBF.

There were 95 (27%) deaths from infratentorial and 263 (73%) from supratentorial stroke. Sixteen patients (17%) with infratentorial stroke had neurological examination consistent with NDD (0.55 cases per million per year). Among patients that underwent confirmatory evaluation for NDD with an apnea test, ancillary test (radionuclide scan), or both, ancillary testing was more common with infratentorial compared with supratentorial stroke (10/12 (85%) vs. 25/47 (53%), p = 0.04). Persistent CBF was detected in 6/10 (60%) patients with infratentorial compared with 0/25 with supratentorial stroke (p = 0.0001).

Infratentorial stroke leading to clinical criteria for NDD occurs with an annual incidence of about 0.55 per million. There is variability in clinicians’ use of ancillary testing. Persistent CBF was detected in more than half of patients that underwent radionuclide scans. Canadian consensus is needed to guide clinical practice.