Executive functioning (EF) can be one of the earliest, despite under-detected, impaired cognitive domains in patients with multiple sclerosis (pwMS). However, it is still not clear the role of EF on verbal fluency tests given the presence of information processing speed (IPS) deficits in pwMS.

Performance of a group of 43 pwMS without IPS impairment as measured with the Symbol Digit Modalities Test (SDMT) and a group of 32 healthy controls (HC) was compared on the Phonemic and Semantic Fluency Tests. For each group, we scored the number of words generated (i) in the early time interval (i.e., first 15 sec, semi-automatic process) and (ii) in the late time interval (i.e., from 15 to 60 sec, controlled process).

Globally, pwMS produced significantly fewer words than HC on the Phonemic but not on the Semantic Fluency Test. Crucially, in the Phonemic Fluency Test pwMS generated significantly fewer words than HC in the late time interval, whereas no significant difference between the two groups emerged in the early time interval.

These findings suggest that executive dysfunction is the core element on the Phonemic Fluency Test also in pwMS and it deserves attention in both research and clinical practice.

Early and effective treatment of central nervous system (CNS) inflammatory disorders is vital to reduce neurologic morbidity and improve long-term outcomes in affected children. Rituximab is a B-cell-depleting monoclonal antibody whose off-label use for these disorders is funded in the province of Alberta, Canada, by the Short-Term Exceptional Drug Therapy (STEDT) program. This study describes the use of rituximab for pediatric CNS inflammatory disorders in Alberta.

Rituximab applications for CNS inflammatory indications in patients <18 years of age were identified from the STEDT database between January 1, 2012, and December 31, 2019. Patient information was linked to other provincial datasets including the Discharge Abstract Database, Pharmaceutical Information Network, and Provincial Laboratory data. Analysis was descriptive.

Fifty-one unique rituximab applications were identified, of which 50 were approved. New applications increased from one in 2012 to a high of 12 in 2018. The most common indication was autoimmune encephalitis without a specified antibody (n = 16, 31%). Most children were approved for a two-dose (n = 33, 66%) or four-dose (n = 16, 32%) induction regimen. Physician-reported outcomes were available for 24 patients, of whom 14 (58%) were felt to have fully met outcome targets.

The use of rituximab for pediatric CNS inflammatory disorders has increased, particularly for the indication of autoimmune encephalitis. This study identified significant heterogeneity in dosing practices and laboratory monitoring. Standardized protocols for the use of rituximab in these disorders and more robust outcome reporting will help better define the safety and efficacy of rituximab in this population

Innovative shoe insoles, designed to enhance sensory information on the plantar surface of the feet, could help to improve walking in people with Multiple Sclerosis.

To compare the effects of wearing textured versus smooth insoles, on measures of gait, foot sensation and patient-reported outcomes, in people with Multiple Sclerosis.

A prospective, randomised controlled trial was conducted with concealed allocation, assessor blinding and intention-to-treat analysis. Thirty ambulant men and women with multiple sclerosis (MS) (Disease Steps rating 1–4) were randomly allocated to wear textured or smooth insoles for 12 weeks. Self-reported insole wear and falls diaries were completed over the intervention period. Laboratory assessments of spatiotemporal gait patterns, foot sensation and proprioception, and patient-reported outcomes, were performed at Weeks 0 (Baseline 1), 4 (Baseline 2) and 16 (Post-Intervention). The primary outcome was the size of the mediolateral base of support (stride/step width) when walking over even and uneven surfaces. Independent t-tests were performed on change from baseline (average of baseline measures) to post-intervention.

There were no differences in stride width between groups, when walking over the even or uneven surfaces (P ≥ 0.20) at post-intervention. There were no between-group differences for any secondary outcomes including gait (all P values > 0.23), foot sensory function (all P values ≥ 0.08) and patient-reported outcomes (all P values ≥ 0.23).

In our small trial, prolonged wear of textured insoles did not appear to alter walking or foot sensation in people with MS who have limited foot sensory loss. Further investigation is needed to explore optimal insole design.

Australian and New Zealand Clinical Trials Registry (ACTRN12615000421538).

Whether the effects of therapies may wane over time is a matter of debate, especially when considering their long-term cost-effectiveness. Here, we examined how the assumption of the waning of treatment effect was applied across the National Institute for Health and Care Excellence (NICE) appraisals for disease-modifying therapies (DMTs) used in multiple sclerosis.

We undertook a document analysis following a search of the NICE website. The inclusion criteria of the study were as follows: all publicly available documents related to completed appraisals for DMTs (period: January 2000 to July 2021). The exclusion criteria of the study were as follows: all documents that did not meet the inclusion criteria, especially pertaining to drugs used in other disease areas. We extracted information about the waning of treatment effect assumption as considered by companies, assessment groups, and appraisal committees, and we analyzed trends over time.

We reviewed fifteen appraisals that reported guidance on sixteen DMTs. Irrespective of the drugs’ mechanism of action or their pharmaceutical nature, there was substantial variation in the modalities when the assumption of waning was implemented. We noted the recent preference to use all-cause discontinuation as a proxy. This heterogeneity did not appear to affect acceptance of the DMTs (all but one were recommended for use across the National Health System (NHS)).

Modeling the long-term effect of therapies is challenging, especially given the limited follow-up duration of related trials. This generates recurrent debates on the presence of waning of treatment efficacy and heterogeneity across appraisals. More refined recommendations obtained by consensus among stakeholders could help to achieve greater consistency in decision making.

Slowed processing speed impacts employment status in people with multiple sclerosis (PwMS). Studies on the Multiple Sclerosis Functional Composite (MSFC), which includes the Paced Auditory Serial Addition Test (PASAT), have demonstrated that the combined score predicts employment status. Whether PASAT performance alone is associated with employment status is less clear. In addition, no studies have yet evaluated whether cognitive fatigability (CF), as measured with the PASAT, is associated with employment status. The aim of the current study was to examine the association between PASAT performance, CF, and employment status in PwMS.

Hundred and eighty-six PwMS completed the PASAT as part of a larger neuropsychological battery. ANOVAs and chi-squares analyzed group differences between employed and unemployed participants with respect to demographics, PASAT performance scores, and CF. Linear regression determined whether PASAT performance and/or CF scores were associated with employment status.

After controlling for demographic influences, group differences were noted between employed vs. unemployed individuals on PASAT performance scores only. Employment status was associated with PASAT performance scores but not CF.

The current study confirmed that PASAT performance is associated with employment status in MS. Given that CF was not associated, it seems difficulties with information processing speed (IPS) and working memory have more impact on a PwMS’s ability to remain employed rather than within-task performance decline.

Job loss is common in multiple sclerosis (MS) and frequently associated with depression, fatigue, and cognitive dysfunction. Identifying these modifiable risk factors and providing “at-risk” women with a neuropsychologically-based intervention may improve employment outcomes. Our study seeks to investigate the utility of a neuropsychologically-based intervention with varying levels of treatment and follow-up, and evaluate treatment and employment outcomes among groups.

In this longitudinal, quasi-randomized controlled trial, employed women with MS meeting criteria on screening measures were considered “at-risk” for job instability and randomized to one of two neuropsychological testing interventions (standard-care group received testing and phone feedback of results and recommendations; experimental group received testing and in-person feedback with subsequent care-coordinator calls from a nurse to help coordinate recommendation completion). Participants who did not meet criteria were considered “low-risk” and only followed over time.

56 women in the treatment groups (standard-care = 23; experimental = 33) and 63 women in the follow-only group were analyzed at 1 year. Rates of decreased employment were similar between standard-care (17.4%) and experimental (21.2%) groups (OR = .782, 95% CI .200–3.057). However, the experimental group completed significantly more treatment recommendations, t(53) = −3.237, p = .002. Rates of decreased employment were also similar between the “low-risk” (17.5%) and “at-risk” groups (19.6%), (OR = .721, 95% CI .285–1.826).

Employment outcomes were similar at 1 year between treatment groups receiving differing levels of a neuropsychologically-based intervention, however treatment adherence significantly improved in the experimental group. Treatment groups also had similar employment outcomes as compared to a “low-risk,” no intervention group, suggesting that engaging in either neuropsychological intervention may have impacted job stability.

Alexithymia, the lack of words to express emotions, is a common problem in multiple sclerosis (MS) patients.

To investigate the prevalence of alexithymia in patients with MS and to evaluate the factors related to it, including depression.

We conducted a cross-sectional, descriptive and analytical study, which took place in the neurology department in Sfax (Tunisia). It involved MS outpatients in remission phase. Data collection was done using a form exploring sociodemographic, clinical and radiological characteristics. We used the Expanded Disability Status Scale (EDSS) to evaluate neurological impairments, the Toronto Alexithymia Scale (TAS-20) to assess alexithymia, and the Hospital Anxiety and Depression Scale (HADS) to assess depressive symptoms.

Our study included 93 patients. They were married in 57% of cases. The total number of relapses ranged from 1 to 30, with a median of 5. The EDSS score ranged from 0 to 8. A temporal lesion on brain imaging was found in 29% of cases. MS patients had alexithymia in 58.1% of cases and depression in 26.9% of cases. Alexithymia was more frequent in unmarried patients (p = 0.028). Among clinical and radiological factors, the number of relapses was higher (p = 0.035), and temporal lesion was more frequent in alexithymic patients (p = 0.045). In this study, alexithymic patients were more depressed (p < 10-3).

According to our results, depression and alexithymia were found to be significantly inter-related in MS. Future longitudinal studies might better clarify the nature of this relationship in MS patients.

No significant relationships.

Fatigue is one of the most common and disabling symptoms of multiple sclerosis (MS). It can be defined as a subjective lack of physical and mental energy.

To study the prevalence of fatigue in patients with MS and to determine the factors related to it, including depression.

This was a cross-sectional, descriptive and analytical study, which took place in the neurology department in Sfax (Tunisia). It focused on patients with MS in remission phase. We used the Expanded Disability Status Scale (EDSS) to determine the degree of disability caused by MS, the Chalder Fatigue Scale to evaluate the fatigue, and the Hospital Anxiety and Depression Scale (HADS) to assess depressive symptoms.

The 93 patients included in the study had a mean age of 36.59 ± 10.69 years. The socio-economic level was low to medium in 52.7% of cases. The EDSS score ranged from 0 to 8 (median = 3.5). The total number of relapses ranged from 1 to 30 (median = 3.5). MS patients had fatigue in 72.4% of cases and depression in 26.9% of cases. Patients with a low to medium socio-economic level were more fatigued (p=0.027). High number of MS relapses, severity of disability on the EDSS, and presence of depression were associated with fatigue (p=0.014, p<10-3 and p=0.001, respectively).

In MS patients, fatigue is a common symptom. Patients with reduced physical activity and greater MS-related disability have more severe fatigue, which negatively affects psychosocial functioning, increasing the risk of depression.

No significant relationships.

Multiple Sclerosis (MS) is a demyelinating, neurodegenerative, and immune-mediated disease that affects the central nervous system. Usually co-occurs with difficulties in emotional regulation and psychopathology. Anxiety is one of the most common psychiatric manifestations in patients with MS. Nonetheless, empirical evidences on the joint predictive effect of MS clinical conditions and emotion regulation processes on the development of anxiety in MS patients are scarce.

This preliminary study aimed to explore whether fatigue, physical disability (MS clinical conditions) and a low compassionate attitude (maladaptive emotion regulation process based on self-judgment, over-identification, and isolation) predict anxiety symptoms in MS patients.

A convenience sample of 107 patients with MS diagnosis and without other neurological disorders was used in this cross-sectional study. Participants completed the Anxiety Subscale of the Depression, Anxiety and Stress Scales-21, the Analogic Fatigue Scale, the World Health Organization Disability Assessment Schedule, and the Self-judgment, Isolation and Over-identification Subscales of the Self-Compassion Scale.

All potential predictors showed significant correlations with anxiety symptoms and predicted this symptomatology through simple linear regressions. Therefore, they were selected as covariates of the multiple linear regression model, which explained 32% of the variance of anxiety symptoms. This model revealed that fatigue, physical disability, and low compassionate attitude are significant predictors.

The results support the relevance of psychological interventions for MS patients to implement effective strategies to regulate anxiety associated with fatigue and physical disability. Helping patients to adopt a more compassionate attitude toward the self can reduce their anxiety.

No significant relationships.

Many different causes of catatonia are well-documented in medicine. Modern understanding of catatonia has evolved in the last 100 years with the suggestion that there is a root cause in neuroinflammation. This is a case report of a young woman who presented to the emergency department with altered mental status, found to have catatonia responsive to lorazepam, with the underlying etiology being a diagnosis of multiple sclerosis.

A case-based approach is used to support the following learning objectives: - Review the diagnostic criteria for catatonia - Distinguish between simple and malignant catatonia - Review the Bush-Francis Scale - Review available treatment

Mother brings 24-year-old woman into the hospital for altered mental status and changes in behavior including staring spells, periods of withdrawal, refusal to eat, lack of purposeful movement, apraxia, and mutism that worsened 24 hours prior to presentation.

The patient was afebile with negative covid-19 test. Recent diagnosis of Bell’s palsy treated with antivirals and oral steroird, which terminated just prior to presentation. Additionally, patient had outpatient treatment for vertigo. Lumbar puncture was negative for an infectious process. MRI revealed multiple stable white matter lesions in the periventricular, pontine, and subcortical regions, some oriented perpendicular to the corpus callosum.

This case of a 24-year-old woman with catatonia brought an opportunity to retrospectively review a case in detail in order to feature learning objectives that review very important considerations in the evaluation, differential diagnosis, symptom tracking, and treatment of catatonia. The future of research in catatonia is bright and diverse.

No significant relationships.

Schizophrenia (SCZ) is a severe mental disorder that is among the leading causes of disability worldwide. Multiple sclerosis (MS) is a chronic inflammatory neurological disease with a major impact on the quality of life of young adults. Despite the distinct nature of these two disorders, research studies have identified similarities in underlying pathological mechanisms and risk factors.

To illustrate, through a case report, the central role of inflammation in schizophrenia and its relationship with multiple sclerosis.

Case Report of a 31-year-old male patient with schizophrenia who has been diagnosed with multiple sclerosis.

Mr M. is a 31 year old patient who was diagnosed with schizophrenia at age 17. Between the ages of 25 and 27, the patient had two severe psychotic relapses each one requiring inpatient treatment. At that time, he experienced predominantly severe positive symptoms and persistent suicidality. He was initially prescribed amisulpride up to 600mg, followed by haloperidol up to 45mg daily. Due to poor clinical response, the patient was put on clozapine 400mg/d and has been stabilized since 2017, with outpatient checkups. The patient has reported vertigo and trouble walking in August 2021. He has been referred to the Neurology Department. Clinical, biological and imaging findings were highly suggestive of Multiple sclerosis and the patient has received short courses of intravenous corticosteroids.

This case report highlights the possible association between Multiple Sclerosis and schizophrenia. Further research is needed to clarify the role of inflammation in the central nervous system in schizophrenia and the overlap with Multiple Sclerosis.

No significant relationships.