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Multiple sclerosis (MS) is characterized by focal inflammatory activity in the central nervous system and a diffuse, compartmentalized inflammation that is the primary driver of neuroaxonal damage and worsening disability. It is now recognized that higher-efficacy disease-modifying therapies (HE-DMT) are often required to treat the complex neuropathological changes that occur during the disease course and improve long-term outcomes. The optimal use of HE-DMTs in practice was addressed by a Canadian panel of 12 MS experts who used the Delphi method to develop 27 consensus recommendations. The HE-DMTs that were considered were the monoclonal antibodies (natalizumab, ocrelizumab, ofatumumab) and the immune reconstitution agents (alemtuzumab, cladribine). The issues addressed included defining aggressive/severe disease, patient selection of the most appropriate candidates for HE-DMTs, baseline investigations and efficacy monitoring, defining suboptimal treatment response, use of serum neurofilament-light chain in evaluating treatment response, safety monitoring, aging and immunosenescence and when to consider de-escalating or discontinuing treatment. The goals of the consensus recommendations were to provide guidelines to clinicians on their use of HE-DMTs in practice and to improve long-term outcomes in persons with MS.
People with multiple sclerosis (pwMS) commonly describe cognitive decline later in the day, but few studies have evaluated this perception’s validity. In a consecutive sample of 791 pwMS, this study evaluated whether time-of-testing predicted Minimal Assessment of Cognitive Function in MS raw scores, accounting for age, sex, educational years, disease duration, disability and disease-modifying therapy use. The mean age was 43.76 years (SD = 11.30), 76.74% were female and most had mild disability. Later time-of-testing independently predicted reduced Judgment of Line Orientation scores (p < 0.01), but not other cognitive variables. In pwMS, there is a diurnal decline in visuospatial cognitive test performance.
Cognitive impairment is a common feature of multiple sclerosis (MS), and its severity may be influenced by several factors, such as biological sex and levels of cognitive reserve (CR). The relationship between sex, CR, and cognition has not yet been fully investigated. Therefore, the present study aimed to explore sex differences in CR building and the effect of sex and CR on cognitive performance in MS.
Method:
233 participants underwent the Brief Repeatable Battery of Neuropsychological Tests (BRB-N), the Stroop test, and the Cognitive Reserve Scale. The t-test was performed to compare sociodemographic variables, Italian adaptation of the Cognitive Reserve Scale, and cognitive test scores between sexes. To evaluate the effect of CR and sex and their interaction on cognitive performance several models of multivariate analyses of covariance were performed (dependent variables: all subtests of Brief Repeatable Battery of Neuropsychological Tests and Stroop scores; independent variables: sex and CR). Covariates included age, Expanded Disability Status Scale, and BDI-II scores.
Results:
Women showed higher levels of CR, particularly in daily activities (t = −5.848, p<.001), hobbies (t = −2.591, p = .010), and social life (t = −2.362, p = .011). Sex differences were noted in verbal memory and fluency (with women outperforming men) and processing speed (with men performing better than women). Multivariate analyses revealed a nonsignificant interaction between CR and sex on cognition (Λ=.950, F(10,260)=.813, p = .617, ηp2 = .050).
Conclusions:
CR and sex seemed to affect cognitive performance independently in pwMS. This highlights the importance of considering both factors in cognitive assessment, and that both sexes may benefit from specific psychoeducational training aimed at increasing CR levels.
Cognitive impairment is prevalent, disabling, and poorly managed in multiple sclerosis (MS). Physical activity, often expressed as steps/day, has been associated with cognitive function in this population. This brief report examined the possibility of a (1) steps/day threshold associated with absence of cognitive impairment or (2) dose-response relationship between steps/day and cognitive function in MS.
Method:
The sample included 358 persons with MS who provided demographic (age, sex, race) and clinical (MS type, disease duration, disability status) information, and completed the Symbol Digit Modalities Test (SDMT) and California Verbal Learning Test-Second Edition (CVLT-II). Participants wore an ActiGraph GT3X+ accelerometer above the non-dominant hip during waking hours of the day over a 7-day period for measuring steps/day.
Results:
The receiver operating characteristic (ROC) curve analysis did not identify a steps/day threshold associated with cognitive impairment on SDMT (area under the curve [AUC] ranged between 0.606 and 0.691). The ROC curve analysis further did not identify a threshold of steps/day associated with cognitive impairment based on CVLT-II (AUC range 0.606 to 0.691). The regression analysis indicated significant linear relationships between steps/day and SDMT (R2 = .06; β=.251; p < .001) and CVLT-II (R2 = .06; β=.247; p < .001) z-scores.
Conclusion:
The observed linear relationship suggests that focusing on increasing steps/day across all levels of physical activity might have benefits for cognitive function in MS.
Edited by
Dharti Patel, Mount Sinai West and Morningside Hospitals, New York,Sang J. Kim, Hospital for Special Surgery, New York,Himani V. Bhatt, Mount Sinai West and Morningside Hospitals, New York,Alopi M. Patel, Rutgers Robert Wood Johnson Medical School, New Jersey
Disorders of the neuromuscular system have significant consequences for the anesthetic provider. A thorough knowledge of inheritance patterns, diagnosis, symptomatology, treatment, and pathophysiology is paramount in providing safe anesthetic care. Here we provide a review of the commonly encountered neuromuscular disorders and highlight the most salient features of each. The broad range of demyelinating diseases, myotonias, channelopathies, myasthenic syndromes, and mitochondrial diseases that affect the neuromuscular system will be presented.
Edited by
Dharti Patel, Mount Sinai West and Morningside Hospitals, New York,Sang J. Kim, Hospital for Special Surgery, New York,Himani V. Bhatt, Mount Sinai West and Morningside Hospitals, New York,Alopi M. Patel, Rutgers Robert Wood Johnson Medical School, New Jersey
Disorders of the neuromuscular system have significant consequences for the anesthetic provider. A thorough knowledge of inheritance patterns, diagnosis, symptomatology, treatment, and pathophysiology is paramount in providing safe anesthetic care. Here we provide a review of the commonly encountered neuromuscular disorders and highlight the most salient features of each. The broad range of demyelinating diseases, myotonias, channelopathies, myasthenic syndromes, and mitochondrial diseases that affect the neuromuscular system will be presented.
Limited access to multiple sclerosis (MS)-focused care in rural areas can decrease the quality of life in individuals living with MS while influencing both physical and mental health.
Methods:
The objectives of this research were to compare demographic and clinical outcomes in participants with MS who reside within urban, semi-urban and rural settings within Newfoundland and Labrador. All participants were assessed by an MS neurologist, and data collection included participants’ clinical history, date of diagnosis, disease-modifying therapy (DMT) use, measures of disability, fatigue, pain, heat sensitivity, depression, anxiety and disease activity.
Results:
Overall, no demographic differences were observed between rural and urban areas. Furthermore, the categorization of primary residence did not demonstrate any differences in physical disability or indicators of disease activity. A significantly higher percentage of participants were prescribed platform or high-efficacy DMTs in semi-urban areas; a higher percentage of participants in urban and rural areas were prescribed moderate-efficacy DMTs. Compared to depression, anxiety was more prevalent within the entire cohort. Comparable levels of anxiety were measured across all areas, yet individuals in rural settings experienced greater levels of depression. Individuals living with MS in either an urban or rural setting demonstrated clinical similarities, which were relatively equally managed by DMTs.
Conclusion:
Despite greater levels of depression in rural areas, the results of this study highlight that an overall comparable level and continuity of care is provided to individuals living with MS within rural and urban Newfoundland and Labrador.
Indigenous Peoples in Canada are comprised of First Nations, Inuit and Métis and are the youngest and fastest growing population in the country. However, there is limited knowledge of how they are affected by multiple sclerosis (MS), the most common nontraumatic neurological disease of young adults, with Canada having one of the highest prevalences in the world. In this narrative review, we outline the limited studies conducted with Indigenous Peoples living with MS in Canada and the gaps in the literature. From the limited data we have, the prevalence of MS in Indigenous Peoples is lower, but the disease appears to be more aggressive. Given the dearth of Canadian data, we explore the worldwide MS studies of Indigenous populations. Lastly, we explore ways in which we can improve our understanding of MS among Indigenous Peoples in Canada, which entails building trust and meaningful relationships with these communities and acknowledging past and ongoing injustices. Furthermore, healthcare professionals conducting research with Indigenous Peoples should undergo training in cultural safety and data sovereignty, including principles of ownership, control, access and possession to have greater engagement with Indigenous communities to conduct more relevant research. With joint efforts between healthcare professionals and Indigenous communities, the scientific research community can be positioned to conduct better, more appropriate and desperately needed research, ultimately with improvements in the delivery of care to Indigenous Peoples living with MS in Canada.
The outcomes of radiosurgery for trigeminal neuralgia (TN) in patients with multiple sclerosis (MS) are not as extensively assessed as those for idiopathic or classical TN cases.
Objective:
Evaluate the safety and efficacy of radiosurgery for TN in MS patients and identify potential predictors of successful outcomes.
Methods:
A retrospective single-institution cohort study with patients treated between 2009 and 2022 was performed. Fifty patients were included, and a total of 68 radiosurgical interventions were delivered. Outcomes included the maintenance of pain relief assessed using Kaplan–Meier curves and treatment-related complications. Cox regression analyses were used to identify potential predictors of better pain relief.
Results:
Following the first radiosurgical treatments, the initial pain relief rate was 86% after a median latency period of 14 days. Adequate pain relief rates at 6, 12, 36 and 60 months were 86%, 52%, 35% and 24%, respectively. Adequate pain relief was sustained for an actuarial median of 12.7 months. After initial relief, pain recurrence occurred in 68% of patients. No statistical difference was seen in the duration of pain relief after initial or repeat radiosurgery (p = 0.368). The most frequent complication was facial hypesthesia (Barrow Neurological Institute facial hypesthesia scale grade II: 10%; III: 6%; IV: 0%). Ipsilateral vascular compression was predictive of better efficacy (p = 0.024).
Conclusion:
Radiosurgery for TN in patients with MS appears to be safe and to provide effective pain relief. Notably, radiological identification of vascular compression may predict more sustained pain relief.
To describe and compare the prevalence of psychosocial and psychiatric disorders among veterans with multiple sclerosis (MS) and a propensity-score-matched group of veterans without MS, and to identify sociodemographic and clinical characteristics associated with comorbid psychosocial and psychiatric problems among veterans with MS.
Methods
Data were linked and extracted from the Veterans Affairs (VA) Homeless Operations Management and Evaluation System and the Corporate Data Warehouse. The total sample comprised 27,342 veterans in the VA healthcare system between January 1, 2022, and June 30, 2023, who met eligibility criteria for an MS diagnosis (n=13,671) and 1:1 propensity-score-matched sample of veterans who did not have MS (n=13,671). MS diagnosis, substance use disorder (SUD), mental illness, and homelessness were defined using standard ICD-10 codes. Covariates included sex, age, Charlson Comorbidity Index (CCI), and VA service-connected disability rating.
Results
A higher prevalence of mental illness among veterans with MS (33%) was found compared with those without MS (31%). Multivariable logistic regression models indicated MS was negatively associated with diagnoses of alcohol use disorder, stimulant use disorders, posttraumatic stress disorder, and schizophrenia/schizoaffective disorder but positively associated with diagnoses of cannabis use disorder and major depressive disorder. MS was not significantly related to homelessness. Disparities in psychosocial and psychiatric disorders among veterans with MS are described.
Conclusion
This study provides novel insights regarding rates of homelessness, SUD, and mental illnesses among veterans with MS. Interdisciplinary approaches to identification and management of mental illness, SUD, and homelessness among veterans with MS are critically needed.
Self-management practices can contribute to the lives of patients with multiple sclerosis. The aim of this study is to improve patients’ self-management abilities through a multidisciplinary developed module.
Methods:
This prospective, randomized controlled trial was conducted between January 2020 and November 2021 at a university hospital in Ankara, Turkiye. The self-management module was implemented by a clinical pharmacist with the aim of enhancing self-management capabilities through an educational approach, with a focus on medication adherence, management of drug-related problems, follow-ups and self-directed activities. The intervention group completed the self-management module, while the control group received usual outpatient care. To evaluate the impact of the module, the Multiple Sclerosis Self-Management Revised scale was administered to the patients. Interviews were conducted at 4-month intervals.
Results:
Study (n = 102) and control group (n = 98) patients were followed up for 8 months, and the median duration of intervention was 11 minutes. The mean (± SD) self-management scores of the study group increased from 68.9 (± 9.3) to 79.0 (± 9.4) at the end of the interviews, and this increase was found to be significant compared to the control group (p < 0.001). The self-management module has been shown to improve self-management, medication adherence, perception of care and patient engagement in treatment (p < 0.001).
Conclusions:
This single-center randomized controlled trial suggests that a pharmacist-implemented self-management module increased patient engagement and medication adherence. The self-management interventions could be tailored to groups that tend to have lower self-management abilities, such as older individuals, and those who have lower educational attainment, health engagement or medication adherence.
Pediatric-onset multiple sclerosis (POMS) accounts for approximately 2 to 5% of all individuals with MS and is associated with an increased risk for cognitive impairment. In recent years, neuropsychological screening questionnaires have been increasingly utilized for pediatric populations in multidisciplinary settings. This study examines the clinical utility of the Colorado Learning Difficulties Questionnaire (CLDQ) and Pediatric Perceived Cognitive Functioning (Peds PCF) screening measures for identifying cognitive impairment in persons with POMS during a target neuropsychological evaluation.
Method:
Retrospective data was gathered from electronic medical records at a single pediatric hospital.
Results:
Forty-nine participants were included (69% female; 43% Hispanic/Latinx; mean age = 16.1 years old, range = 9.9 to 20.6 years old). Correlation analyses demonstrated strong interrelatedness between caregiver ratings on screening measures and performance on traditional neuropsychological measures. Effect sizes were medium across comparisons (CLDQ: Spearman’s rho = −.321 to −.563; PedsPCF: Spearman’s rho = .308 to .444). Exploratory cut-points using receiver operating characteristic analysis and Youden indices are also discussed.
Conclusions:
Comparison of scores across caregiver rating questionnaires and on a targeted neuropsychological battery suggests that the screening surveys alone may not be sensitive enough to identify children with cognitive impairments, but ratings may provide qualitatively meaningful information along with neuropsychological testing. This study illustrates how pediatric neuropsychologists can leverage screening tools to focus consultative interviews and effectively triage referrals for evaluation within an academic medical setting.
The rising burden of neurological disorders poses significant challenges to healthcare systems worldwide. There has been an increasing momentum to apply integrated approaches to the management of several chronic illnesses in order to address systemic healthcare challenges and improve the quality of care for patients. The aim of this paper is to provide a narrative review of the current landscape of integrated care in neurology. We identified a growing body of research from countries around the world applying a variety of integrated care models to the treatment of common neurological conditions. Based on our findings, we discuss opportunities for further study in this area. Finally, we discuss the future of integrated care in Canada, including unique geographic, historical, and economic considerations, and the role that integrated care may play in addressing challenges we face in our current healthcare system.
Edited by
David Kingdon, University of Southampton,Paul Rowlands, Derbyshire Healthcare NHS foundation Trust,George Stein, Emeritus of the Princess Royal University Hospital
Neuropsychiatry has a long and fascinating history as a discipline at the interface between neurology and psychiatry that combines clinical observations with modern investigational techniques. Historically, organic psychiatry has focused on clinical syndromes with regional connections affecting the four cortical lobes and the corpus callosum. Behavioural neurology has developed from early observations of classical neurocognitive syndromes, including aphasia, alexia, apraxia, agnosia and Gerstmann syndrome. A number of common neurological conditions often present with specific psychiatric symptoms: traumatic brain injury, cerebrovascular disease, brain tumours, epilepsy, movement disorders, infectious diseases and autoimmune neurological disorders such as multiple sclerosis, systemic lupus erythematosus and autoimmune encephalopathies. The differential diagnosis between delirium, dementia and pseudodementia can pose significant challenges. Finally, several toxic, metabolic and endocrine disorders can have clinically relevant neuropsychiatric manifestations.
Understanding disease-modifying therapy (DMT) use and healthcare resource utilization by different geographical areas among people living with multiple sclerosis (pwMS) may identify care gaps that can be used to inform policies and practice to ensure equitable care.
Methods:
Administrative data was used to identify pwMS on April 1, 2017 (index date) in Alberta. DMT use and healthcare resource utilization were compared between those who resided in various geographical areas over a 2-year post-index period; simple logistic regression was applied.
Results:
Among the cohort (n = 12,338), a higher proportion of pwMS who resided in urban areas (versus rural) received ≥ 1 DMT dispensation (32.3% versus 27.4%), had a neurologist (67.7% versus 63.9%), non-neurologist specialist (88.3% versus 82.9%), ambulatory care visit (87.4% versus 85.3%), and MS tertiary clinic visit (59.2% versus 51.7%), and a lower proportion had an emergency department (ED) visit (46.3% versus 62.4%), and hospitalization (20.4% versus 23.0%). Across the provincial health zones, there were variations in DMT selection, and a higher proportion of pwMS who resided in the Calgary health zone, where care is managed by MS tertiary clinic neurologists, had an outpatient visit to a neurologist or MS tertiary clinic versus those who resided in other zones where delivery of MS-related care is more varied.
Conclusions:
Urban/rural inequalities in DMT use and healthcare resource utilization appear to exist among pwMS in Alberta. Findings suggest the exploration of barriers with consequent strategies to increase access to DMTs and provide timely outpatient MS care management, particularly for those pwMS residing in rural areas.
Restriction of dietary carbohydrates, fat and/or protein is often used to reduce body weight and/or treat (metabolic) diseases. Since diet is a key modulator of the human gut microbiome, which plays an important role in health and disease, this review aims to provide an overview of current knowledge of the effects of macronutrient-restricted diets on gut microbial composition and metabolites. A structured search strategy was performed in several databases. After screening for inclusion and exclusion criteria, thirty-six articles could be included. Data are included in the results only when supported by at least three independent studies to enhance the reliability of our conclusions. Low-carbohydrate (<30 energy%) diets tended to induce a decrease in the relative abundance of several health-promoting bacteria, including Bifidobacterium, as well as a reduction in short-chain fatty acid (SCFA) levels in faeces. In contrast, low-fat diets (<30 energy%) increased alpha diversity, faecal SCFA levels and abundance of some beneficial bacteria, including Faecalibacterium prausnitzii. There were insufficient data to draw conclusions concerning the effects of low-protein (<10 energy%) diets on gut microbiota. Although the data of included studies unveil possible benefits of low-fat and potential drawbacks of low-carbohydrate diets for human gut microbiota, the diversity in study designs made it difficult to draw firm conclusions. Using a more uniform methodology in design, sample processing and sharing raw sequence data could foster our understanding of the effects of macronutrient restriction on gut microbiota composition and metabolic dynamics relevant to health. This systematic review was registered at https://www.crd.york.ac.uk/prospero as CRD42020156929.