Parkinson’s disease (PD) is characterized by the inability of dopamine production from amino acids. Therefore, changes in amino acid profile in PD patients are very critical for understanding disease development. Determination of amino acid levels in PD patients with a cumulative approach may enlighten the disease pathophysiology.

A systematic search was performed until February 2023, resulting in 733 articles in PubMed, Web of Science and Scopus databases to evaluate the serum amino acid profile of PD patients. Relevant articles in English with mean/standard deviation values of serum amino acid levels of patients and their healthy controls were included in the meta-analysis.

Our results suggest that valine, proline, ornithine and homocysteine levels were increased, while aspartate, citrulline, lysine and serine levels were significantly decreased in PD patients compared to healthy controls. Homocysteine showed positive correlations with glutamate and ornithine levels. We also analyzed the disease stage parameters: Unified Parkinson’s Disease Rating Scale III (UPDRS III) score, Hoehn–Yahr Stage Score, disease duration and levodopa equivalent daily dose (LEDD) of patients. It was observed that LEDD has a negative correlation with arginine levels in patients. UPDRS III score is negatively correlated with phenylalanine levels, and it also tends to show a negative correlation with tyrosine levels. Disease duration tends to be negatively correlated with citrulline levels in PD patients.

This cumulative analysis shows evidence of the relation between the mechanisms underlying amino acid metabolism in PD, which may have a great impact on disease development and new therapeutic strategies.

There is limited information on rare spinocerebellar ataxia (SCA) variants, particularly in the Canadian population. This study aimed to describe the demographic and clinical features of uncommon SCA subtypes in Canada and compare them with international data.

We conducted a case series and literature review of adult patients with rare SCA subtypes, including SCA5, SCA7, SCA12, SCA14, SCA15, SCA28, SCA34, SCA35 and SCA36. Data were collected from medical centers in Ontario, Alberta and Quebec between January 2000 and February 2021.

We analyzed 25 patients with rare SCA subtypes, with onset ages ranging from birth to 67 years. Infantile and juvenile-onset cases were observed in SCA5, SCA7, SCA14 and SCA34. Most patients presented with gait ataxia, with no significant differences across groups. Additional common features included saccadic abnormalities (22 of 25), dysarthria (19 of 25) and nystagmus (12 of 22, except in SCA7). Less common findings included dystonia (8 of 25), cognitive impairment (7 of 25), tremor (9 of 25) and parkinsonism (3 of 25).

Our study highlights the heterogeneity of rare SCA subtypes in Canada. Ongoing longitudinal analysis will improve the understanding, management and screening of these disorders.

Spinal CSF leak can cause disabling headaches and neurological symptoms. Lack of awareness, diagnostic delay and treatment inconsistencies affect the quality of CSF leak care globally. This is the first study aiming to identify and assess these challenges in Canada.

A cross-sectional online survey of Canadian patients with spinal CSF leak was designed in collaboration with Spinal CSF Leak Canada, including questions on demographics, headache condition, investigations, treatments, quality of life, financial consequences and out-of-country care.

The survey captured 103 respondents with confirmed spinal CSF leak diagnosis, of whom 56% were still suffering. The majority were female (80%), most being highly educated, with a mean age of 41.8 (SD: 10.37) years at the time of diagnosis. Inconsistencies in care resulted in variable durations for obtaining diagnosis and treatment. The majority of respondents (88%) had seen multiple physicians, and only 50% had seen a CSF leak specialist. Invasive imaging was not performed in 43%. CSF leak relapse after initial successful treatment occurred frequently (43%). The incidence of rebound intracranial hypertension was high (52.5%), and the treatment was difficult to access (77%). Out-of-country care was common (28%), and the impact on financial health was omnipresent (81.5%).

The survey demonstrates significant gaps in spinal CSF leak care in Canada, similar to global observations. Lack of awareness and access, delayed care, and inconsistencies in investigations and management are common. Spinal CSF leak significantly impacts patients’ physical, mental and financial well-being. Increased awareness, referral pathways and standardized treatment algorithms are key factors in optimizing patient care in Canada.

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.

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.