There has been considerable attention to immune dysregulation and inflammation in driving the pathology and pathophysiology of multiple sclerosis (MS), leading to advances developing disease-modifying therapies (DMTs). This chapter provides an overview of the role of inflammation and neurodegeneration in MS, which can impact both white matter and gray matter early in MS. It also mentions the examples of advanced MRI techniques and postmortem validation. Previous research which elucidated the role the immune system in MS has greatly impacted the development of highly efficacious therapies which attenuate new inflammatory lesions. Unfortunately, the understanding of the mechanisms underlying the neurodegeneration that contributes to cortical and deep gray matter loss of axons, neurons, and synapses is greatly lacking. Efforts to meet this need will be necessary in developing effective therapies for progressive forms of MS and evaluating the efficacy of neuroprotective strategies in clinical trials.
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In multiple sclerosis (MS), rehabilitation is a component of the comprehensive care approach and is a useful complement to disease-modifying and symptomatic therapies. Even though rehabilitation is integrated as an important component of the comprehensive care of MS, obstacles to its implementation remain, and evidence to guide decision making remains insufficient. This chapter introduces the rehabilitation process, instruments used to measure the rehabilitation results and related conceptual framework, as well as practical applications of rehabilitation in MS. Rehabilitation should be considered in the management of MS at all stages of the disease. The nature, intensity, and setting of rehabilitation interventions are determined on the basis of the patient’s needs and on mutually agreed upon goals. As the success of rehabilitation relies on long-term behavioral modifications, it is important to initiate these interventions early, and to explain to the patient how they fit within the overall management plan for their disease.
Autoimmune encephalitis (AE) describes a group of disorders associated with neural-specific autoantibodies. Understanding the pathophysiology of AE is helpful in guiding diagnostic testing and management. AE describes a heterogeneous group of neurologic disorders associated with neural-specific autoantibodies. AE associated with antibodies targeting extracellular plasma membrane antigens tend to be immunotherapy responsive, as the antibodies themselves are likely pathogenic. Epidemiologic and clinical characteristics, as well as oncologic associations vary among different antibodies and this chapter discusses this in detail. AE can present with distinct clinical syndromes but presentation is heterogeneous and selective antibody testing should be avoided. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis can occur as a postinfectious syndrome following herpes simplex virus encephalitis. Antibodies should be tested in both serum and cerebrospinal fluid. Prompt initiation of immunotherapy improves outcome.
Multiple sclerosis (MS) may sometimes be easy to diagnose but there are also times where the diagnosis is unclear and may take time to make. MS diagnosis is not based on the number of symptoms, but on the pattern of symptoms, neurological findings on exam, MRI features, and sometimes other diagnostic test results (i.e., cerebrospinal fluid [CSF] studies). It requires expertise to make a firm diagnosis of MS. Many other conditions may at times look like MS and should be considered when the history, exam, imaging, or other results suggest other diagnoses. Many people with nonspecific white matter lesions are evaluated for the diagnosis of MS, but often they do not actually have this disease. This chapter attempts to strike a balance between making readers aware of the many red flags and potential alternative diagnoses to MS and highlighting a practical approach to the most commonly seen “possible MS” patient.
Multiple sclerosis (MS) is associated with significant autonomic imbalance, with estimates that up to 90% of patients with MS have symptoms stemming from autonomic dysfunction. Autonomic dysfunction can lead to malfunction of various body systems. Symptoms may manifest clinically as orthostatic intolerance, abnormal sweating, impaired thermoregulation, chronic fatigue, dysfunction of the pupillary reflexes, gastrointestinal symptoms, sleep disturbance, bladder or bowel dysfunction, and sexual dysfunction. Autonomic dysfunction can greatly influence quality of life in patients with MS, and can significantly restrict activities of daily living. Research has demonstrated that ANS imbalance correlates with duration of illness, disease progression, brain lesions, fatigue, inflammatory activity, and disability. This chapter briefly discusses the sexual dysfunction and other autonomic disorders in MS and presents a case example to illustrate sexual dysfunction and other autonomic disorders in MS.
The use of unconventional medicine, also known as complementary and alternative medicine (CAM), is popular among multiple sclerosis (MS) patients yet may not be openly discussed at clinic visits. The remarkable advances in disease-modifying therapies over the past several years have greatly improved treatment options, but the increased complexity of decision making and monitoring associated with some of these therapies may make it even more challenging for clinicians to interact with MS patients about CAM issues. This chapter provides busy clinicians with an easy-to-use, concise guide to CAM therapies they are likely to encounter in practice. It discusses specific CAM therapies include: acupuncture, Chinese herbal medicine, and traditional Chinese medicine; antioxidants; bee venom therapy; cannabis; cooling therapy; cranberry; echinacea and other “immune-stimulating” supplements; fish oil and the swank diet; ginkgo biloba; “gluten sensitivity”; low-dose naltrexone; mindfulness; tai chi; vitamin B12 & vitamin D, and yoga.
Multiple sclerosis (MS) is a chronic, complex illness which can potentially have expansive and profound effects on the entire family. Although caregiving can be greatly rewarding, it also presents challenges. Caregivers can become overburdened with the care of the person with MS and care of the household, finances, and their own self. Caregivers must make it a point to care for themselves emotionally and physically. Although clinical visits are often focused on the MS patient, care providers must make it a point to assess and provide recommendations to the caregiver, particular if that caregiver is experiencing burnout or sometimes even abusing the MS patient. Caregivers commonly report a plethora of their own physical and psychological symptoms. This chapter reviews common caregiver challenges and provide suggestions for how caregivers can more effectively care for themselves while maintaining their responsibility to the MS patient.
Multiple sclerosis (MS) is well known to the general public but was only defined as a separate disorder of the nervous system in the middle of the 19th century. Initially it was thought to be a rare disorder, but soon clinicians became aware that it was the most common serious neurological disorder that occurs in young adults. This brief introduction to the history of MS shows how ideas and knowledge developed and how it moved from a feeling of hopelessness to a now exciting and therapeutic era. Despite the development of elegant investigative techniques for the confirmation of MS, the clinical history and examination continue to be the gold standard for the diagnosis. Therapies for MS have changed dramatically over the last decade with new agents and increased experience. Mitoxantrone was approved for the treatment of MS but reserved for patients who progress rapidly or who fail on other medications.
Although improvements may still be made in the traditional immunologic approach (e.g., development of targeted therapies with more favorable efficacy/risk profiles than present drugs), the next generation of therapeutics will focus largely on mechanisms relevant to progressive multiple sclerosis (MS), with a goal of arresting progression and restoring function. This includes targeting the compartmentalized inflammation that characterizes progressive MS (consisting of diffuse macrophage/microglial activation and leptomeningeal inflammation), as well as strategies to prevent neurodegeneration and induce remyelination. Although more work is needed to elucidate the pathogenesis of progression and to improve the outcome measures used to assess efficacy, many promising agents already exist within the therapeutic pipeline. This chapter reviews some of the most promising therapies and strategies in development, organized as follows: immunologic, neuroprotective, and remyelinating/reparative therapies.
Multiple sclerosis (MS) is the most common progressive neurological disease affecting young men and women with an estimated worldwide prevalence of 2 to 2.5 million people. Both bladder and bowel dysfunction are highly prevalent among both men and women with MS. Bladder and bowel function are integrally related to the patient’s mental, cognitive, and functional status. The evaluation of patients with MS and elimination symptoms should include a detailed history, including prior treatments, a physical examination, assessing cognitive functional status, dexterity and any anatomical abnormalities and a fluid/bladders, and bowel diary. There is limited data on medical therapy for MS related incomplete emptying. Two small studies examined the effect of the alpha-blocker tamsulosin, in MS patients with detrusor sphincter dyssynergia (DSD). It is important that healthcare providers ask about both bowel and bladder complaints as both can be treated and significantly improved with behavioral modifications, medical therapy, and lastly surgery.