Parkinson’s disease (PD) chronic L-Dopa treatment often triggers motor complications, such as L-Dopa-induced dyskinesias (LID). LID are reported to be associated with abnormal glutamatergic activity between the striatum and primary motor cortex (M1), resulting in M1 hyperactivation. Beneficial noninvasive brain stimulation (NIBS) paradigms were reported to normalize glutamatergic activity. The objective of the present study was thus to set up a NIBS paradigm in parkinsonian monkeys to investigate motor behavior under basal conditions and with L-Dopa treatment-inducing dyskinesias.

Motor behavior was investigated in five 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) dyskinetic female Macaca fascicularis monkey models of PD, allowing us to monitor the administration of NIBS and drugs. NIBS used were inhibitory protocols, that is, cathodal transcranial direct current stimulation (c-tDCS) and continuous theta-burst stimulation (cTBS). A procedure of three weeks was developed to progressively acclimate animals to the experimental conditions, equipment and noise of c-tDCS and cTBS before stimulating them with either vehicle or L-Dopa.

One session of c-tDCS with L-Dopa yielded no effect, whereas five sessions briefly reduced LID but decreased the duration of L-Dopa anti-PD effects. cTBS alone improved (decreased) parkinsonian scores as compared to sham stimulation or vehicle alone. Two sessions of cTBS with L-Dopa decreased LID without affecting L-Dopa anti-PD effects.

This is the first study testing c-tDCS and cTBS on the motor behavior of MPTP dyskinetic monkeys. As compared to medicated patients, MPTP monkeys offer the opportunity to evaluate NIBS after-effects in drug-free and LID conditions, which are critical in the search for new PD treatment.

Growing evidence suggests that direct oral anticoagulants (DOACs) may be suitable for cerebral venous thrombosis (CVT). The optimal strategy regarding lead-in parenteral anticoagulation (PA) prior to DOAC is unknown.

In this post hoc analysis of the retrospective ACTION-CVT study, we compared patients treated with DOACs as part of routine care: those given “very early” DOAC (no PA), “early” (<5 days PA) and “delayed” (5–21 days PA). We compared baseline characteristics and outcomes between the very early/early and delayed groups. The primary outcome was a composite of day-30 CVT recurrence/extension, new peripheral venous thromboembolism, cerebral edema and intracranial hemorrhage.

Of 231 patients, 11.7% had very early DOAC, 64.5% early (median [IQR] 2 [1–2] days) and 23.8% delayed (5 [5–6] days). More patients had severe clinical/radiological presentations in the delayed group; more patients had isolated headaches in the very early/early group. Outcomes were better in the very early/early groups (90-day modified Rankin Scale of 0–2; 94.3% vs. 83.9%). Primary outcome events were rare and did not differ significantly between groups (2.4% vs. 2.1% delayed; adjusted HR 1.49 [95%CI 0.17–13.11]).

In this cohort of patients receiving DOAC for CVT as part of routine care, >75% had <5 days of PA. Those with very early/early initiation of DOAC had less severe clinical presentations. Low event rates and baseline differences between groups preclude conclusions about safety or effectiveness. Further prospective data will inform care.

Most patients with internuclear ophthalmoplegia (INO) are orthotropic, although a subset is exotropic. When INO is bilateral, this is termed wall-eyed bilateral internuclear ophthalmoplegia (WEBINO). In 1979, Sharpe described his “first case” of wall-eyed monocular internuclear ophthalmoplegia (WEMINO) as “a unique clinical syndrome” characterized by unilateral INO and ipsilateral exotropia.

WEMINO was clinically identified in seven patients, with oculographic correlation in six and neuropathological confirmation in one. Oculographic features of exotropic INO patients were compared with those of six orthotropic INO patients using magnetic search coil and infrared oculography.

All clinically defined WEMINO patients showed slowed, hypometric ipsilateral saccades by oculography. Six patients had ipsilateral exotropia, and three had ipsilateral hypertropia. Ipsilateral abducting saccades had faster peak velocities for smaller saccades, more so for orthotropic patients. Exotropic patients had normal sinusoidal mean vestibulo-ocular reflex (VOR) gains and phases; orthotropic patients had subnormal mean VOR gains and phase leads.

WEMINO is a clinical ocular motor syndrome characterized by unilateral slow, hypometric adducting saccades with exotropia and hypertropia of the ipsilateral eye. We propose that it results from discrete unilateral damage to burst-tonic fibers in the medial longitudinal fasciculus (MLF) with sparing of the adjacent extrafascicular pathways. Paradoxically, orthotropic INO results from more extensive damage to ascending pathways lateral, ventral and caudal to the MLF. Direct injury to the medial rectus subnucleus is not required. This manuscript was in preparation at the time of Dr Sharpe’s death in 2013 and is an acknowledgement of his forward-thinking, as his hypotheses have stood the test of time.

Understanding post-stroke spasticity (PSS) treatment in everyday clinical practice may guide improvements in patient care.

This was a retrospective cohort study that used population-level administrative data. Adults (aged ≥18 years) who initiated PSS treatment (defined by the first PSS clinic visit, focal botulinum toxin injection, or anti-spasticity medication dispensation [baclofen, dantrolene and tizanidine] with none of these treatments occurring during the 2 years before the stroke) were identified between 2012 and 2019 in Alberta, Canada. Spasticity treatment use, time to treatment start and type of prescribing/treating physician were measured. Descriptive statistics were performed.

Within the cohort (n = 1,079), the most common PSS treatment was oral baclofen (initial treatment: 60.9%; received on/after the initial treatment date up to March 31, 2020: 69.0%), largely prescribed by primary care physicians (77.6%) and started a median of 348 (IQR 741) days after the stroke. Focal botulinum toxin (23.3%; 37.7%) was largely prescribed by physiatrists (72.2%) and started 311 (IQR 446) days after the stroke; spasticity clinic visits (18.6%; 23.8%) were also common.

We found evidence of gaps in provision of spasticity management in persons with PSS including overuse of systemic oral baclofen (that has common adverse side effects and lacks evidence of effectiveness in PSS) and potential underuse of focal botulinum toxin injections. Further investigation and strategies should be pursued to improve alignment of PSS treatment with guideline recommendations that in turn will support better outcomes for those with PSS.

We have updated the migraine prevention guideline of the Canadian Headache Society from 2012, as there are new therapies available, and additionally, we have provided guidelines for the prevention of chronic migraine, which was not addressed in the previous iteration.

We undertook a systematic review to identify new studies since the last guideline. For studies identified, we performed data extraction and subsequent meta-analyses where possible. We composed a summary of the evidence found and undertook a modified Delphi recommendation process. We provide recommendations for treatments identified and additionally expert guidance on the use of the treatments available in important clinical situations.

We identified 61 studies that were included in this evidence update and identified 16 therapies we focused on. The anti-calcitonin gene-related peptide (CGRP) agents were approved by Health Canada between 2018 and 2024 and provide additional options for episodic and chronic migraine prevention. We also summarize evidence for the use of propranolol, topiramate and onabotulinumtoxinA in addition to anti-CGRP agents as treatments for chronic migraine. We have downgraded topiramate to a weak recommendation for use and gabapentin to a weak recommendation against its use in episodic migraine. We have weakly recommended the use of memantine, levetiracetam, enalapril and melatonin in episodic migraine.

Based on the evidence synthesis, we provide updated recommendations for the prevention of episodic and chronic migraine utilizing treatments available in Canada. We additionally provided expert guidance on their use in clinical situations.

Understanding sex differences among persons with moderate-to-severe traumatic brain injury (TBI) is critical to addressing the unique needs of both males and females from acute care through to rehabilitation. Epidemiological studies suggest that 7 of every 10 persons with moderate-to-severe TBI are male, with females representing about 30%–33%.

To examine the proportion of female and male individuals included in randomized controlled trials (RCTs) of interventions for moderate-to-severe TBI.

A systematic review was conducted in line with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines up to and including December 2022 using MEDLINE, PubMed, Scopus, CINAHL, EMBASE and PsycINFO databases. Studies were included if they met the following criteria: (1) human participants with a mean age ≥18 years, (2) ≥50% of the sample had moderate-to-severe TBI and (3) the study design was a RCT. Data extracted included author, year, country, sample size, number of female/male participants and time post-injury.

595 RCTs met the criteria for inclusion, published between 1978 and 2022, totaling 86,662 participants. The average proportion of female participants was 23.14%, and the percentage increased a small but significant amount over time. There was a significantly lower percentage of female participants in RCTs initiated in the acute phase (≤ 1 month) when compared with RCTs conducted in the chronic phase (≥ 6 months) post-injury (p < 0.001).

Female participants are underrepresented in RCTs of moderate-to-severe TBI. Addressing this underrepresentation is critical to establish effective treatments for all persons with TBI.

Patients with stroke while hospitalized experience important delays in symptom recognition. This study aims to describe the overall management of an in-hospital stroke population and how it compares with an out-of-hospital community-onset stroke population.

In this retrospective observational study, we included consecutive patients with in-hospital and out-of-hospital strokes (both ischemic and hemorrhagic) over a period of one year treated at a comprehensive stroke center. Demographic and clinical data were extracted, and patient groups were compared with regard to stroke treatment time metrics.

A total of 362 patients diagnosed with acute stroke were included, of whom 38 (10.5%) had in-hospital and 324 (89.5%) had out-of-hospital strokes. The median delay to stroke recognition (time between the last time seen well and first time seen symptomatic) was significantly longer in in-hospital compared to out-of-hospital strokes (77.5 [0–334.8] vs. 0 [0–138.5] min, p = 0.04). The median time interval from stroke code activation to the arrival of the stroke team at the bedside was significantly shorter in in-hospital versus out-of-hospital cases (10 [6–15] vs. 15 [8–24.8] min, p = 0.01). In-hospital strokes were less likely to receive thrombolysis (12.8% vs. 45.4%, p < 0.01) with significantly higher mortality (18.2% versus 2.6%, p < 0.01) and longer overall median hospital stay (3 [1–7] vs. 12 days [7–23], p < 0.01) compared to out-of-hospital strokes.

This study showed significant delays in stroke symptom recognition and stroke code activation for in-hospital stroke patients despite comparable overall stroke time metrics. Development of in-hospital stroke protocols and systematic staff training on stroke symptom recognition should be implemented to improve care for hospitalized patients.

Many Royal College of Physicians and Surgeons of Canada (RCPSC) graduates in neurosurgery face significant challenges in finding full-time employment. The current study describes the career outcomes of neurosurgery residents from Canadian programs.

All RCPSC neurosurgery graduates (n = 106) who completed their residency between 2015 and 2020 were included in this study. Baseline characteristics were determined for the entire cohort and then stratified by employment status. Several logistic regression models were used to identify predictors of full-time employment after residency.

Overall, 26.4% of neurosurgery graduates from 2015 to 2020 have been underemployed, defined as locum and clinical associate positions (6.6%), the pursuit of multiple fellowships (16%) and career change/nonsurgical career (3.8%). Only 52.0% of graduates were fully employed in Canada, with 30.2% appointed at academic institutions. Skull-base/open vascular (OR: 0.055, 95%CI [<0.01, 0.74]) and general neurosurgery (OR: 0.027, 95% CI [<0.01, 0.61]) fellowships were associated with underemployment. Advanced research degrees (master’s or Ph.D.) and sex were not associated with full-time employment.

Over one-quarter of recent Canadian neurosurgery graduates were underemployed, and nearly half do not find employment in Canada. These results reflect a concerning reality for current and prospective neurosurgery graduates in Canada and will hopefully serve as a call to action for the Canadian neurosurgery community.

Migraine can affect adults during their most productive years, yet few studies in Canada have examined the relationship between migraine-related disability and productivity loss. In particular, the impact of migraine on unpaid productivity loss has not been quantified.

In this cross-sectional study, employed adults living with migraine were recruited from across Canada to complete a web-based questionnaire. Migraine-related disability was assessed using the Migraine Disability Assessment questionnaire, and productivity loss was evaluated using the Valuation of Lost Productivity questionnaire. Multiple regression models were used to quantify the association between migraine-related disability level and productivity loss after adjusting for relevant clinical, occupational and sociodemographic covariates.

There were 441 participants, of which 60.1% were female, and the mean (SD) age was 37.7 (10.9). Compared to participants with little to no migraine-related disability, hours of total productivity loss were higher among those with moderate disability (54.1 [95% CI: 10.2–98.1] adjusted hours per 3 months) and severe disability (110.5 [95% CI: 65.5–155.6] adjusted hours per 3 months); paid productivity loss was higher among participants with moderate disability (32.4 [95% CI: 3.1–61.8] adjusted hours per 3 months) and severe disability (61.6 [95% CI: 31.5–91.7] adjusted hours per 3 months); and unpaid productivity loss was greater in those with severe disability (43.5 [95% CI: 12.7–74.3] adjusted hours per 3 months).

Greater migraine-related disability was associated with more total, paid and unpaid productivity loss among employed adults. These data will be valuable when evaluating the cost-effectiveness of emerging migraine therapies.

Disease-modifying therapies (DMTs) for Alzheimer’s disease (AD) are emerging following successful clinical trials of therapies targeting amyloid beta (Aβ) protofibrils or plaques. Determining patient eligibility and monitoring treatment efficacy and adverse events, such as Aβ-related imaging abnormalities, necessitates imaging with MRI and PET. The Canadian Consortium on Neurodegeneration in Aging (CCNA) Imaging Workgroup aimed to synthesize evidence and provide recommendations on implementing imaging protocols for AD DMTs in Canada.

The workgroup employed a Delphi process to develop these recommendations. Experts from radiology, neurology, biomedical engineering, nuclear medicine, MRI and medical physics were recruited. Surveys and meetings were conducted to achieve consensus on key issues, including protocol standardization, scanner strength, monitoring protocols based on risk profiles and optimal protocol lengths. Draft recommendations were refined through multiple iterations and expert discussions.

The recommendations emphasize standardized acquisition imaging protocols across manufacturers and scanner strengths to ensure consistency and reliability of clinical treatment decisions, tailored monitoring protocols based on DMTs’ safety and efficacy profiles, consistent monitoring regardless of perceived treatment efficacy and MRI screening on 1.5T or 3T scanners with adapted protocols. An optimal protocol length of 20–30 minutes was deemed feasible; specific sequences are suggested.

The guidelines aim to enhance imaging data quality and consistency, facilitating better clinical decision-making and improving patient outcomes. Further research is needed to refine these protocols and address evolving challenges with new DMTs. It is recognized that administrative, financial and logistical capacity to deliver additional MRI and positron emission tomography scans require careful planning.

Self-guided Internet-based cognitive behavior therapy (iCBT) for migraine interventions could improve access to care, but there is poor evidence of their efficacy.

A three-arm randomized controlled trial compared: iCBT focused on psychoeducation, self-monitoring and skills training (SPHERE), iCBT focused on identifying and managing personal headache triggers (PRISM) and a waitlist control. The primary treatment outcome was a ≥ 50% reduction in monthly headache days at 4 months post-randomization.

428 participants were randomized (mean age = 30.1). 240 participants (56.2%) provided outcome data at 4 months. Intention-to-treat (ITT) analysis with missing data imputed demonstrated that the proportion of responders with a ≥ 50% reduction was similar between combined iCBTs and waitlist (48.5/285, 17% vs. 16.6/143, 11.6%, p = 0.20), but analysis of completers showed both iCBT programs to be superior to the waitlist (24/108, 22.2% vs. 13/113, 11.5%, p = 0.047). ITT analysis with missing data imputed showed no difference between the two iCBTs (SPHERE: 24.8/143, 17.3% vs. PRISM: 23.7/142, 16.7%, p = 0.99). Uptake rates of the iCBTs were high (76.9% and 81.69% logged in at least once into SPHERE and PRISM, respectively), but adherence was low (out of those who logged in at least once, 19.01% [21/110] completed at least 50% modules in SPHERE and 7.76% [9/116] set a goal for trying out a given trigger-specific recommendation in PRISM). Acceptability ratings were intermediate.

Self-guided iCBTs were not found to be superior in our primary ITT analysis. Low adherence could explain the lack of effects as completer analysis showed effects for both interventions. Enhancement of adherence should be a focus of future research.