Neurologic Clinics

The unprecedented scope of the coronavirus disease 2019 (COVID-19) pandemic resulted in numerous disruptions to daily life, including for people with multiple sclerosis (PwMS). This article reviews how disruptions in multiple sclerosis (MS) care prompted innovations in delivery of care (eg, via telemedicine) and mobilized the global MS community to rapidly adopt safe and effective practices. We discuss how our understanding of the risks of COVID-19 in PwMS has evolved along with recommendations pertaining to disease-modifying therapies and vaccines...

Multiple sclerosis has historically been characterized as a disease that affects young women of European ancestry, but recent studies indicate that the incidence and prevalence of the disease is much higher in Black and Hispanic populations than previously recognized. There is evidence that there is a more severe disease course in these populations. , but the intersection of genetic underpinnings and social determinants of health (SDOH) is poorly understood due to the lack of diversity in clinical research...

Multiple sclerosis has a 3:1 female-to-male predominance and commonly presents in young adult women. The hormonal changes in women throughout their lifetime do affect the underlying pathology of multiple sclerosis, and the needs of women therefore change with age. Although multiple sclerosis does not adversely affect fertility or pregnancy, there are many factors to consider when caring for women throughout family planning, pregnancy, and the postpartum period. The care of these women and complex decisions regarding disease-modifying therapy use in family planning should be individualized and comprehensive...

Chronologic aging is associated with multiple pathologic and immunologic changes that impact the clinical course of multiple sclerosis (MS). Clinical phenotypes evolve across the lifespan, from a highly inflammatory course in the very young to a predominantly neurodegenerative phenotype in older patients. Thus, unique clinical considerations arise for the diagnosis and management of the two age extremes of pediatric and geriatric MS populations. This review covers epidemiology, diagnosis, and treatment strategies for these populations with nuanced discussions on therapeutic approaches to effectively care for patients living with MS at critical transition points during their lifespan...

Multiple sclerosis (MS) is a disease of the central nervous system characterized by inflammatory demyelination and neurodegeneration. Numerous disease-modifying therapies for MS exist but are only partially effective, making it essential to optimize all factors that may influence the course of the disease. This includes conscientious management of both mental and physical comorbidities, as well as a comprehensive strategy for promoting wellness in patients with MS. Thoughtful engagement of those living with MS through shared decision making and involvement of a multidisciplinary team that includes primary care, relevant specialists, psychology, and rehabilitation is likely to lead to better outcomes...

Randomized controlled trials (RCTs) are essential for regulatory approval of disease-modifying therapies (DMTs), yet their strict selection criteria often lead to limited generalizability. Observational studies using real-world data (RWD) allow for more inclusive heterogeneous cohorts resulting in higher external validity to inform treatment practices. As reviewed in this article, well-designed comparative effectiveness studies are an important application of RWD. Although, like RCTs, observational studies have their own set of limitations, including various biases that may confound results, advanced statistical methods can mitigate many of these limitations...

Treatment options for patients newly diagnosed with multiple sclerosis (MS) are expanding with the continuous development and approval of new disease-modifying therapies (DMTs). The optimal initial treatment strategy, however, remains unclear. The 2 main treatment paradigms currently employed are the escalation (ESC) approach and the early highly effective treatment (EHT) approach. The ESC approach consists of starting a lower- or moderate-efficacy DMT, which offers a potentially safer approach, while the EHT approach favors higher-efficacy treatment early in the disease course, despite a potential increase in risk...

In aggregate, the available data suggest autologous hematopoietic stem cell transplantation (AHSCT) has potent, durable efficacy to treat relapsing multiple sclerosis (MS). Safety issues and financial costs are significant but largely associated with the procedure itself. AHSCT is a reasonable option for patients with highly active relapsing MS and an inadequate response to the available disease therapies. The key question is where to place AHSCT in the overall relapsing MS algorithm relative to other high-efficacy therapies...

Multiple sclerosis (MS) can cause significant disability to patients via relapse-associated worsening and progression independent of relapses. The causes of neuronal and myelin damage can include lymphocyte-mediated inflammation and microglial activation. Bruton's tyrosine kinase (BTK) is an enzyme that mediates B cell activation and the proinflammatory phenotype of microglia. Inhibiting BTK provides a novel therapeutic target for MS but also has a complicated pharmacology based on binding specificity, CNS penetration, half-life, and enzyme inhibition characteristics...

Multiple sclerosis (MS) is a highly heterogeneous disease. Currently, a combination of clinical features, MRI, and cerebrospinal fluid markers are used in clinical practice for diagnosis and treatment decisions. In recent years, there has been considerable effort to develop novel biomarkers that better reflect the pathologic substrates of the disease to aid in diagnosis and early prognosis, evaluation of ongoing inflammatory activity, detection and monitoring of disease progression, prediction of treatment response, and monitoring of disease-modifying treatment safety...

Depletion of circulating B lymphocytes using anti-CD20 monoclonal antibodies (mAbs) greatly reduces inflammatory activity in relapsing multiple sclerosis (RMS); it reduces progression to a lesser extent in nonrelapsing progressive MS. Mechanisms whereby anti-CD20 mAbs reduce MRI and clinical relapse activity in people with RMS are still being elucidated. Anti-CD20 agents do not fully protect from nonrelapsing disease progression, possibly due to their inability to cross the blood-brain barrier and inability to ameliorate the full extent of biology of MS progression...

The treatment of patients with relapsing multiple sclerosis (MS) has advanced tremendously over the past few decades. More efficacious therapies have been approved, which can significantly reduce the inflammatory process of relapsing MS. Neuroprotection by controlling this pathophysiology is important given our current limitations to control progressive MS and induce neurorepair. Here, the authors discuss the current landscape of neurotherapeutics for relapsing MS focusing on newer disease-modifying treatments and their use...

Multiple sclerosis (MS) misdiagnosis in the form of an incorrect diagnosis of MS, as well as delayed diagnosis in patients who do have MS, both influence patient clinical outcomes. Contemporary studies have reported data on factors associated with these diagnostic challenges and their frequency. Expediting diagnosis in patients with MS and reducing MS misdiagnosis in patients who do not have MS may be aided by educational efforts surrounding early MS symptoms and proper application of MS diagnostic criteria...

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Sexual and gender minority (SGM) people can face unique stressors and structural discrimination that result in higher rates of neuropsychiatric symptoms, such as depression, anxiety, and suicidality. Although more rigorous studies are needed, emerging data suggest a possible higher prevalence of functional neurological disorder and other brain-mind-body conditions in SGM people. Representation and iterative feedback from affected community members is critical to the process of developing affirming environments...

The fifth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-5) Somatic Symptom Disorder (SSD) and Illness Anxiety Disorder (IAD) replaced the diagnostic entities of the fourth edition of the Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) somatoform disorders and hypochondriasis. SSD turns away from specifying the presence or absence of a medical condition for presented symptoms and instead focuses on excessive symptom-related affects, cognitions, and behaviors. People with pathological health anxiety can be diagnosed with SSD or IAD, depending on the intensity of accompanying somatic symptoms...

Functional neurologic disorder (FND) is commonly encountered across outpatient and inpatient medical settings. Given the potential for a high burden of disability in some patients and mounting evidence for the efficacy of FND-specific multidisciplinary treatment services, expanding clinical services for this population is a necessity. In this perspective article, we discuss considerations for creating FND services, including the types of services that exist, how to start, how to identify appropriate referrals, and how to develop and monitor individualized treatment plans...

Functional neurologic disorder (FND) is a common condition for which neurology residents often receive little to no formal teaching. Using a question-and-answer format, this article puts forward a case for why an FND curriculum is needed and aims to provide guidance on possible curricular content including medical knowledge, clinical skills, communication, and team-based collaboration. The authors also discuss methods for teaching and evaluating this knowledge and associated clinical skills, linking this to current Accreditation Council for Graduate Medical Education neurology milestones...

Occupational therapy (OT) is an important treatment modality for patients with paroxysmal functional neurologic disorder (FND) symptoms. In our clinical experience, an outpatient, OT-based sensory modulation treatment can address sensory processing difficulties often endorsed by patients with paroxysmal motor FND and functional seizures. This article aims to describe in detail the goals and treatment strategies for occupational therapists to replicate this approach. This article is also an important first step in aiding the development and execution of clinical trials to further evaluate the effectiveness of sensory-based treatment in patients with FND...

Functional neurological disorder (FND) is a neuropsychiatric condition. In this field, prospective psychotherapy trials and consensus recommendations for physiotherapy, occupational therapy, and speech language therapy have been published. However, significant clinical complexities remain. "Rule in" signs - while critical for making a positive diagnosis - do not equate to a personalized treatment plan in many instances. Here, we propose that the neuropsychiatric assessment and real-time development of a work-in-progress biopsychosocial clinical formulation aids the development of a patient-centered outpatient treatment plan...