Anthony Feinstein

Background: Depression is two to three times more common in people with multiple sclerosis (pwMS) than the general population. Objective: To evaluate the efficacy and tolerability of intermittent theta burst stimulation (iTBS) in treating depressive symptoms in pwMS and major depressive disorder (MDD). Methods: Twenty-one pwMS and MDD participated in an open-label 4-week trial of iTBS to the left dorsolateral prefrontal cortex (L-DLPFC). The Hamilton Depression Rating Scale (HAMD-17), California Verbal Learning Test Second Edition Total Learning (CVLT-II-TL), Brief Visuospatial Memory Test – Revised Total Learning (BVMT-R-TL) and Symbol Digit Modalities Test (SDMT) were administered before and after treatment. The primary outcome was response rates on HAMD-17, defined as a >50% reduction from baseline. Results: Depression scores decreased from baseline to post-treatment with a mean reduction of 10.24 points (d = 1.55, 95% CI 0.83 to 2.25, P < .001). Ten (58.8%) pwMS responded to treatment, and seven (41.2%) were non-responders (n = 17). The treatment response group showed lower depression scores post-treatment than non-responders (d = −3.01, 95% CI −4.43 to −1.55, P < .001). Post-treatment, responders showed higher visuospatial memory (d = 1.11, 95% CI 0.06 to 2.14, P = .039) and information processing scores (d = 1.74, 95% CI 0.58 to 2.87, P = .003) compared to non-responders. There were two drop-outs, and two participants were lost to follow-up. There were no serious adverse events. Conclusions: iTBS can improve depressive symptoms in pwMS and MDD and may be associated with cognitive improvement. Clinical trial registration: NCT04621708.

In 334 people with multiple sclerosis, a backward stepwise regression analysis was conducted to identify clinical characteristics that predict who declines neurocognitive testing ( p < 0.05), from demographics, disease-related variables, psychiatric diagnoses, and self-reported cognitive concerns. The mean age was 44.1 years (standard deviation = 11.4), the median Expanded Disability Status Scale was 2.5 (1.5–4.0), 79.8% had relapsing-remitting MS, and 14.7% declined testing. Independent correlates of declining neurocognitive testing included progressive MS (odds ratio = 2.1, 95% confidence interval = [1.0, 4.4], p = 0.046), anxiety-related disorders (odds ratio = 2.5, 95% confidence interval = [1.3, 4.9], p = 0.007), and the absence of self-reported cognitive concerns (odds ratio = 0.3, 95% confidence interval = [0.2, 0.7], p = 0.004). People with multiple sclerosis with these clinical characteristics are more likely to decline neurocognitive testing.

Psychiatric comorbidities are common in people with multiple sclerosis (pwMS). Yet, post-traumatic stress disorder (PTSD) has received little attention to date. Grounded in an emerging literature on the impact of trauma on pwMS, this Topical Review synthesizes current evidence on PTSD in pwMS. Although 5%–16% of pwMS have PTSD, there remains uncertainty about whether the prevalence exceeds that seen in the general population. Nonetheless, PTSD may influence measures of multiple sclerosis (MS)-related disease activity, employment, and participation in healthcare. Preliminary data indicate no sex difference in PTSD in pwMS, in contrast to an elevated risk in females in the general population. Further work is needed to clarify the demographic and disease-related correlates of PTSD, and the effectiveness of potential treatments in pwMS. By summarizing existing knowledge, this review highlights avenues for future research to advance care for people with comorbid PTSD and MS.

Background: Advanced magnetic resonance imaging (MRI) of the cerebellum remains underutilized to detect early microstructural abnormalities associated with multiple sclerosis (MS) clinical disability. Objectives: To examine associations between cerebellar magnetization transfer ratio (MTR) and clinical measures in people with radiologically isolated syndrome (RIS), early relapsing–remitting MS (RRMS), and primary progressive MS (PPMS). Methods: MTR data were acquired at 3.0 T across four sites in 53 RIS, 202 RRMS, 46 PPMS, and 42 control participants, as part of the Canadian Prospective Cohort Study to Understand Progression in MS (CanProCo). Multiple linear regression analyses evaluated associations between cerebellar MTR and clinical measures. Results: Across MS subtypes, lower cerebellar MTR was associated with greater motor disability, most notably with impaired manual dexterity (β = −1.04 to −0.67). After the false discovery rate correction, two associations remained statistically significant ( p < 0.01): lower MTR in the inferior cerebellar peduncles was associated with worse cerebellar function in RRMS, and lower MTR in the anterior lobe was associated with worse manual dexterity in PPMS. Conclusion: This large, multi-center, hypothesis-generating study identified two statistically significant associations between cerebellar MTR and clinical disability, alongside several exploratory findings. These results suggest that cerebellar MTR may capture clinically relevant microstructural abnormalities in early MS.

Smoking nicotine-related substances influences depressive symptoms in people with relapsing-remitting multiple sclerosis (pwRRMS). It remains unknown whether sex impacts this relationship. Addressing this gap, in a consecutive sample of 281 pwRRMS, the mean age was 42.0 years (SD = 11.0), 74.7% were female, 19.9% smoked nicotine-related substances and the mean Hospital Anxiety and Depression Scale depression sub-scale (HADS-D) score was 7.0 (SD = 4.0). Controlling for covariates, sex and smoked nicotine use interacted to influence HADS-D scores ( p = 0.015). In females alone, smoked nicotine use predicted increased HADS-D scores ( p = 0.002). The link between smoked nicotine use and depressive symptoms differs between males and females with relapsing-remitting multiple sclerosis.

Background: Journalists covering war are exposed to grave risk which can cause mental health difficulties. Aims: To determine the long-term psychiatric health of journalists who covered wars in Afghanistan and the Middle East between September 2001 (following 9/11) and 2013 (waning of the Arab Spring uprisings). Method: Observational, qualitative study involving journalists from CNN, The New York Times , the Washington Post , the Associated Press and National Public Radio. Data collected via study website and Zoom interviews. Of 324 journalists identified, 202 (62.3%) were traceable. Of these, 16 (4.9%) were deceased, 156/186 (83.9%) consented and 30/186 (16.1%) declined participation. Of 156 journalists who provided psychometric data, 99 (63.4%) agreed to interview. Duration of exposure to and severity of risk were recorded. Psychometric data included the General Anxiety Disorder seven-item scale, the nine-item Patient Health Questionnaire, the PTSD Checklist for DSM-5 and the Structured Clinical Interview Schedule for DSM-5 to elicit 12-month and lifetime prevalence of psychiatric diagnoses. Results: One hundred and twelve (71.8%) were male, mean age was 57.0 (s.d. = 9.75) years and 77/156 (49.4%) spent more than 3 years in war zones. Time in a war zone correlated with risk severity ( r = 0.476, p < 0.001). Lifetime and 12-month prevalence of post-traumatic stress disorder (PTSD) 27%/6%; major depression 34%/8%; any anxiety disorder 28%/11%; alcohol use disorder 34%/4%; acute stress disorder 6%/0%; dissociative disorder 2%/0%. Severity of risk predicted lifetime PTSD only (odds ratio 2.55, 95% CI: 1.27–5.14, p = 0.009). Counselling was available to 63/156 (40.4%) journalists while covering conflict. Conclusions: Journalists who covered wars in Afghanistan, Iraq and elsewhere that began after 9/11 have a high lifetime prevalence of PTSD, major depression, any anxiety disorder and alcohol use disorder; 12-month prevalence for PTSD and any anxiety disorder remains elevated, albeit less so. War journalism is hazardous, and risk severity predicts PTSD, highlighting the importance of therapy availability.

Objective: There are clinical and radiological sex differences in people with multiple sclerosis (pwMS); however, the influence of sex on the neuropsychiatric symptoms of MS remains unclear. This study aimed to clarify whether there are sex differences in the neuropsychiatric symptoms of MS. Method: A consecutive clinical cohort of 1530 pwMS completed the Hospital Anxiety and Depression Scale for symptoms of anxiety (HADS-A) and depression (HADS-D), the Modified Fatigue Impact Scale (MFIS), the Perceived Deficits Questionnaire (PDQ) for subjective cognitive concerns, and the Minimal Assessment of Cognitive Function in MS neurocognitive battery. Linear regression analyses were undertaken to predict neuropsychiatric raw scores from sex, adjusting for age, educational years, Expanded Disability Status Scale (EDSS) scores, disease duration, and disease subtype. The significance threshold was set at p < .01. Results: Mean age was 43.2 years (SD = 10.6), mean disease duration was 9.7 years (SD = 8.4), and median EDSS was 2.0 (IQR = 1.5–3.5). Seventy-three percent of participants were female. Controlling for covariates, females had higher MFIS, PDQ, California Verbal Learning Test, and Brief Visuospatial Memory Test total learning scores, and lower Judgment of Line Orientation and Paced Auditory Serial Addition Test scores than males, all p < .01. Sex was not independently predictive of scores on the HADS-A, HADS-D, Controlled Oral Word Association Test, Brief Visuospatial Memory Test delayed recall, Symbol Digit Modalities Test, or Delis-Kaplan Executive Function System. Conclusions: Among pwMS, females experience greater fatigue, cognitive complaints, and dysfunction in spatial rotation and working memory than males, while males have elevated learning/memory difficulties. The absence of differences in symptoms of depression and anxiety between males and females contrasts with well-described sex differences in the general population. These data support future research that can explain sex-specific mechanisms of neuropsychiatric symptoms in pwMS.

Background: Physician burnout is highly prevalent in Physical Medicine and Rehabilitation (PM&R), but its origins and drivers remain poorly understood. Objective: This study aims to explore the factors contributing to burnout among Canadian physiatrists. Methods: Using Charmaz’s Constructed Grounded Theory within a qualitative interpretivist paradigm, we interviewed 30 Canadian physiatrists about their experiences with burnout. Analysis was informed by Cooley’s looking-glass self theory. Results: Burnout in PM&R in Canada stems from a medical culture prioritizing academic excellence over compassionate care. Canadian physiatrists report shame and self-criticism when unable to meet these high standards. Retrospective accounts from Canadian physiatrists suggest that burnout peaks during residency, where autonomy is low and demands are high. Participants also described feeling unprepared to handle patients’ emotional needs and experiencing moral distress when necessary care cannot be delivered due to systemic barriers. Health care bureaucracy further compounds burnout. Conclusions: Addressing burnout in PM&R in Canada requires upstream systemic and contemporary cultural change.