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Background: Multiple sclerosis (MS) is an inflammatory and degenerative disease of the central nervous system. More than 90,000 Canadians are affected; a cure is yet to be found. Available treatments to manage the disease course are only partially effective. For many years, persons with MS (PwMS) have used cannabis to relax, to reduce pain and spasticity, or to improve sleep and daily functioning, despite the lack of scientific evidence on the efficacy of specific cannabinoids [i.e., tetrahydrocannabinol (THC) and cannabidiol (CBD)] on these MS symptoms. The purpose of this clinical trial is to assess the effectiveness of different doses of these cannabinoids, alone or combined, on spasticity relief, compared to placebo. Moreover, we aim to determine which treatment is best effective to address other key MS conditions. Methods: A double-blinded, randomized, factorial, placebo-controlled trial will be performed. We intend to include up to 250 PwMS aged over 21 recruited from the Centre hospitalier de l'Université de Montréal MS Clinic. PwMS will be randomly assigned on a 1:1:1:1 ratio to one of the trial arms: THC alone, CBD alone, THC/CBD combination, or placebo, using stratified blocked randomization, with random blocks within each stratum. The primary outcome is a self-assessment of spasticity using the mean Numeric Rating Scale score over 7 days. The main outcome will be the difference in this score at 4 weeks compared to baseline. Secondary outcomes include assessments of spasticity as measured by a clinician, pain, fatigue, sleep, bowel, bladder, and sexual dysfunction, restless legs syndrome, mental health, quality of life, mobility, cognitive functioning, and adverse events. Treatment responders are eligible for a 12-week extension phase, using the same treatment allocation and assessments. Discussion: Previous clinical studies examined the efficacy of cannabis-based medicines in PwMS, mostly using products with 1:1 THC/CBD ratio. The major barrier to effectively use cannabis in real-world clinical settings is the lack of evidence on benefits of specific cannabinoids and information on possible related risks. The CANSEP study will contribute to overcome these limitations and identify the risks and benefits of cannabis-based treatments in PwMS. Clinical trial registration: ClinicalTrials.Gov, NCT05092191.

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(1) Background: This article discusses the first two phases of development and validation of the Three Domains of Judgment Test (3DJT). This computer-based tool, co-constructed with users and capable of being administered remotely, aims to assess the three main domains of judgment (practical, moral, and social) and learn from the psychometric weaknesses of tests currently used in clinical practice. (2) Method: First, we presented the 3DJT to experts in cognition, who evaluated the tool as a whole as well as the content validity, relevance, and acceptability of 72 scenarios. Second, an improved version was administered to 70 subjects without cognitive impairment to select scenarios with the best psychometric properties in order to build a future clinically short version of the test. (3) Results: Fifty-six scenarios were retained following expert evaluation. Results support the idea that the improved version has good internal consistency, and the concurrent validity primer shows that 3DJT is a good measure of judgment. Furthermore, the improved version was found to have a significant number of scenarios with good psychometric properties to prepare a clinical version of the test. (4) Conclusion: The 3DJT is an interesting alternative tool for assessing judgment. However, more studies are needed for its implementation in a clinical context.

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OBJECTIVE: Ictal semiology interpretation for differentiating psychogenic nonepileptic seizures (PNESs) and epileptic seizures (ESs) is important for the institution of appropriate treatment. Our objective was to assess the ability of different health care professionals (HCPs) or students to distinguish PNES from ES based on video-recorded seizure semiology. METHODS: This study was designed following the Standards for Reporting of Diagnostic Accuracy Studies (STARD) guidelines. We showed in a random mix 36 videos of PNES or ES (18 each) and asked 558 participants to classify each seizure. The diagnostic accuracy of various groups of HCPs or students for PNES versus ES was assessed, as well as the effect of patient age and sex. Measures of diagnostic accuracy included sensitivity, specificity, and area under the curve (AUC). RESULTS: The descending order of diagnostic accuracy (AUC) was the following (p ≤ 0.001): (1) neurologists and epileptologists; (2) neurology residents; (3) other specialists and nurses with experience in epilepsy; and (4) undergraduate medical students. Although there was a strong trend toward statistical difference, with AUC 95% confidence intervals (CIs) that were not overlapping, between epileptologists (95% CI 93, 97) compared to neurologists (95% CI 88, 91), and neurologists compared to electroencephalography technicians (95% CI 82, 87), multiple pairwise comparisons with the conservative Tukey-Kramer honest significant difference test revealed no statistical difference (p = 0.25 and 0.1, respectively). Patient age and sex did not have an effect on diagnostic accuracy in neurology specialists. CONCLUSION: Visual recognition of PNES by HCPs or students varies overall proportionately with the level of expertise in the field of neurology/epilepsy.

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Patients presenting with acute or chronic hepatopathy can develop altered mental status with psychomotor slowing, most commonly indicating encephalopathy. We present the case of a 56-year-old patient who developed subacute atypical neuropsychiatric symptoms including cognitive and behavioural disorganization, manic-like state, and lateralized parkinsonian syndrome. The sequence of events, complete work-up, and detailed neuropsychiatric examination were not compatible with hepatic encephalopathy or delirium; therefore we extended our differential diagnosis and suggested the pathophysiological process described below.

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OBJECTIVES: Although multiple sclerosis (MS) has long been considered to primarily affect white matter, it is now recognized that cognitive deficits in MS are also related to neocortical, thalamic and hippocampal damage. However, the association between damage to these structures and memory deficits in MS is unclear. This study examines whether MS patients with cognitive impairment have a reduction of hippocampal and/or thalamic volumes compared to cognitively intact patients, and whether these volume reductions correlate with various aspects of memory function. METHODOLOGY: Volumetric MRI measures of thalamus and hippocampus of forty-one patients with MS were performed. The patients were divided in two groups depending on the presence or absence of cognitive impairment, based on their neuropsychological tests scores. RESULTS: Right hippocampal volume was found to be associated with learning, and the left thalamic volume was found to predict performance in verbal memory. Cognitively impaired patients had a tendency to have a reduced left thalamic volume compared to cognitively intact patients. CONCLUSIONS: This study does not support a direct relationship between hippocampal atrophy and verbal memory. These results add to the growing evidence of the involvement of thalamus in cognitive impairment in MS and its association with verbal memory deficits.

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AIM: To document perceptions of circumstances spontaneously associated with the occurrence of the stroke on that particular day. BACKGROUND: Known triggers of stroke include birthday or negative emotions. However, specific circumstances relating to that birthday or emotion have not yet been documented. DESIGN: Phenomenological perspective where data were collected between October 2011-June 2012. METHOD: In-depth interviews conducted 5-8 weeks post stroke with 37 participants, with a mean age of 56·3 years (sd 11·9) and 40·5% (14/37) of whom were female. An interview guide composed of open-ended questions and developed with experts was used to explore in detail free associations surrounding the stroke. All interviews were audiotaped and transcribed. Data were rigorously analysed by two team members and discussed in team meetings until reaching consensus on essential themes. FINDINGS: Relationships emerged as being the overarching theme related to stroke triggers with the interrelated subthemes of: (1) birthday or anniversary; (2) parenting; (3) being sick seen as a benefit; and (4) alcohol or drug abuse. The stroke happened on a day which was related in some way to a relationship with a significant other affected by tension, a lack of transparency or an overinvestment of emotional/affective state. CONCLUSIONS: There is a need to address individuals' beliefs as a part of secondary prevention interventions to be truly client-centred, which the phenomenological perspective allows. Relationships as a potential source of stress should be added as a theme to discuss with patients for a holistic approach to stroke prevention including psychosocial factors.

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OBJECTIVE: Since a large proportion of multiple sclerosis (MS) patients exhibit cognitive deficits, it is important to have reliable and cost-effective screening measures that can be used to follow patients effectively. the objective of this study was to evaluate the clinical value of the Montreal Cognitive Assessment (MoCA) test in detecting cognitive deficits in MS patients. METHODS: Forty-one (70.1% women, mean age 44.51 ±7.43) mildly impaired (EDSS: 2.26 ±1.87) MS patients were recruited for this study. In addition to the MoCA, they were administered the MSNQ-P (patient version) and the MSNQ-I (informant version), the bDI-FS and a comprehensive neuropsychological test battery. RESULTS: there were significant correlations between the MoCA test and the three factors derived from the neuropsychological evaluation (Executive/speed of processing, Learning, Delayed recall). the MoCA test was correlated with the MSNQ-I but only marginally with the MSNQ-P. In addition, there was no significant correlation between the MSNQ-P and the neuropsychological factors, whereas significant correlations were found between two of those factors (Learning and Delayed recall) and the MSNQ-I, suggesting that the informant version is more reliable than the patient version for the presence of cognitive deficits. CONCLUSION: the results obtained in the present study support the value of the MoCA test as a screening tool for the presence of cognitive dysfunction in MS patients, even in patients with mild functional disability (EDSS).

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Pseudobulbar affect (PBA) is defined as episodes of involuntary crying, laughing, or both in the absence of a matching subjective mood state. This neuropsychiatric syndrome can be found in a number of neurological disorders including multiple sclerosis (MS). The aim of this study was to identify neuroanatomical correlates of PBA in multiple sclerosis (MS) using a case-control 1.5T MRI study. MS patients with (n = 14) and without (n = 14) PBA were matched on demographic, disease course, and disability variables. Comorbid psychiatric disorders including depressive and anxiety disorders were absent. Hypo- and hyperintense lesion volumes plus measurements of atrophy were obtained and localized anatomically according to parcellated brain regions. Between-group statistical comparisons were undertaken with alpha set at 0.01 for the primary analysis. Discrete differences in lesion volume were noted in six regions: Brainstem hypointense lesions, bilateral inferior parietal and medial inferior frontal hyperintense lesions, and right medial superior frontal hyperintense lesions were all significantly higher in the PBA group. A logistic regression model identified four of these variables (brainstem hypointense, left inferior parietal hyperintense, and left and right medial inferior frontal hyperintense lesion volumes) that accounted for 70% of the variance when it came to explaining the presence of PBA. In conclusion, MS patients with PBA have a distinct distribution of brain lesions when compared to a matched MS sample without PBA. The lesion data support a widely-dispersed neural network involving frontal, parietal, and brainstem regions in the pathophysiology of PBA.

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The effect of major depression on subjective and objective cognitive deficits 6 months following mild to moderate traumatic brain injury (TBI) was assessed in 63 subjects. Patients with subjective cognitive complaints (n=63) were more likely to be women, with higher Glasgow Coma Scale (GCS) scores and have a diagnosis of major depression. They also performed significantly more poorly on various measures of memory, attention and executive functioning. Group differences on most but not all cognitive measures disappeared in a multivariate analysis when controlling for depression. In mild to moderate TBI, subjective cognitive deficits are linked in large measure to comorbid major depression. However, other mechanisms may also account for these deficits.

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OBJECTIVE: In multiple sclerosis (MS), magnetic resonance imaging (MRI) predictors of cognitive impairment are based on sophisticated computer-generated analyses that are difficult to apply in clinical settings. This study investigated the clinical usefulness of a new visual rating scale, the Cholinergic Pathways Hyperintensities Scale (CHIPS), in detecting cognitive dysfunction. METHODS: Forty clinically definite MS patients underwent a brain MRI. Based on the CHIPS, cholinergic pathway hyperintensities were rated in 10 regions on four axial slices. Computerized hyperintense lesion volumes were also obtained. For cognitive testing, The Neuropsychological Screening Battery for Multiple Sclerosis was used. "Low" and "High" lesion score groups were computed based on the mean of the total CHIPS score. Optimal sensitivity and specificity of the total CHIPS score in detecting cognitive impairment were determined using a receiver operator characteristic curve. RESULTS: Despite a similar demographic profile, subjects with a "High" lesion score performed significantly worse than the "Low" lesion score group on verbal (P = .007) and visuospatial (P = .02) memory, and on a global index of cognitive functioning (P = .001). Optimal sensitivity (82%) and specificity (83%) were reached with a threshold total CHIPS score of 18 points. Total CHIPS score and total hyperintense lesion load were correlated (sigma = 0.82, P < .0001). CONCLUSION: CHIPS is helpful in clinically predicting cognitive impairment in MS.

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The possession of at least one APOE-epsilon4 allele may be linked to poor outcome in patients with predominantly severe traumatic brain injury (TBI). In mild TBI, which accounts for approximately 85% of all cases, the role of the APOE-epsilon4 allele is less clear. Studies completed to date have relied on brief cognitive assessments or coarse measures of global functioning, thereby limiting their conclusions. Our study investigated the influence of the APOE-epsilon4 allele in a prospective sample of 90 adults with mild to moderate TBI in whom neuropsychiatric outcome 6 months after injury was assessed as follows: (i) a detailed neuropsychological battery; (ii) an index of emotional distress (General Health Questionnaire); (iii) a diagnosis of major depression (Structured Clinical Interview for DSM-IV); (iv) a measure of global functioning (Glasgow Outcome Scale); (v) an index of psychosocial outcome (Rivermead Head Injury Follow-up Questionnaire); and (vi) symptoms of persistent post-concussion disorder (Rivermead Post-Concussion Symptoms Questionnaire). No association was found between the presence of the APOE-epsilon4 allele and poor outcome across all measures. Given the homogeneous nature of our sample (mild to moderate injury severity), the uniform follow-up period (6 months) and the comprehensive markers of recovery used, our data suggest that the APOE-epsilon4 allele does not adversely impact outcome in this group of TBI patients.

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OBJECTIVE: To assess the specific effect of dizziness on psychosocial outcome after mild to moderate traumatic brain injury (TBI). DESIGN: Six-month cross-sectional study. Setting An outpatient TBI clinic in a tertiary care referral center. Participants A consecutive sample of 207 adults with mild to moderate TBI, 138 (66.7%) of whom had subjective complaint of posttraumatic dizziness. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Psychosocial indices (Glasgow Outcome Scale [GOS], General Health Questionnaire [GHQ], Rivermead Head Injury Follow-Up Questionnaire [RHFUQ], return to work status) were collected from dizzy and nondizzy patients. RESULTS: Despite similar demographic, TBI, and global disability (GOS) profiles of both groups, psychosocial functioning (GHQ, RHFUQ, return to work) was significantly worse in dizzy subjects ( P <.01 for all indices). A logistic regression analysis identified dizziness ( P =.006), total GHQ ( P =.001), and psychotropic and analgesic use ( P =.05) as significant independent predictors of reemployment. CONCLUSIONS: Although dizziness was closely linked to psychologic distress at 6 months after head injury, it also emerged as an independent predictor of failure to return to work, suggesting that not all its adverse effects on outcome are psychologically mediated. Clinicians need to be alert to the presence of dizziness as an adverse prognostic indicator after mild to moderate TBI.

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