Handbook of clinical neurology最新文献

Increasing knowledge about the common widespread, distal-predominant polyneuropathies is shifting the standard of care beyond merely palliating symptom toward intervention. This is less advanced for the more prevalent but harder-to-ascertain distal sensory polyneuropathies (DSP) than for motor and demyelinating neuropathies. DSP comprises the sensory-predominant large-fiber axonal/demyelinating neuropathies plus the small-fiber sensory/autonomic axonopathies. Small-fiber disturbances can cause premature fatigue, neuropathic pain and itch, postural orthostasis tachycardia, and gastrointestinal distress. Diagnosis is difficult - screening for classic causes is mandatory but unproductive in a third to a half of patients (initially idiopathic DSP/iiDSP). Multiple large case series and two small passive-transfer studies suggest that autoimmunity may be a prevalent cause of iiDSP, particularly for small-fiber neuropathy. So, despite the knowledge gaps, immunotherapies effective for other neuropathies are increasingly considered for dysimmune iiDSP; particularly in otherwise healthy young patients with impaired life trajectories. To inform these difficult treatment decisions, this chapter summarizes diagnostic requirements for large- and small-fiber iiDSP and evaluates the type and strength of the evidence suggesting autoimmune causality in some. Concomitant rheumatologic conditions including often undiagnosed Sjögren's syndrome, predispose. Youth, abrupt onset, other organ dysimmunity, immune seromarkers, and prior responses to immunotherapy can provide additional evidence, but autoantibody panels are almost never useful. Uncontrolled studies suggest that apparently autoimmune DSP sometimes responds to corticosteroids, intravenous immunoglobulins, and plasmapheresis. However, these cannot be prescribed indiscriminately due to risk, cost/availability, and lack of controlled trials and guidelines. Enough preliminary data may have accrued to permit formulating initial consensus recommendations for selecting the subsets of patients in whom immunotherapy should or should not be considered. Patients, clinicians, and payors would benefit immediately, and highlighting priorities for research could promote long-term advances.

Paraneoplastic neurologic syndromes (PNS) are disorders resulting from an aberrant immune response against the nervous system, triggered by a tumor. Immune checkpoint inhibitor (ICI) cancer immunotherapies, enhance antitumor immunity by targeting immune checkpoint molecules on different cells, including immune and tumor cells. While ICIs improve cancer outcomes, these therapies can lead to immune-related adverse events (irAEs) in several systems including the nervous system. Neurologic irAEs may affect any level of the neuraxis, and, a subset of patients may present with syndromes resembling classic PNS. This chapter will discuss the epidemiology, pathogenesis, clinical manifestation, diagnostic approach, and treatment of PNS and neurologic irAEs.

Functional tics and tic-like behaviors belong to the wide spectrum of functional movement disorders. Until the early 2010s, functional tic disorders were rather uncommon in the differential diagnosis of tics, and only few cases describing their features had been published. However, over the past 10 years there has been a steady increase in the frequency of these cases that peaked throughout the COVID-19 pandemic. On the one hand, the rise in functional tic cases created new challenges of diagnosis and treatment. At the same time, it also pushed the field forward to delineate helpful clinical clues, as well as to work toward specific consensus diagnostic criteria for functional tics and tic-like behaviors. Here, we first provide a historical summary on the debate between neurodevelopmental and functional tics. We then track relevant literature on functional tics and tic-like cases and discuss their salient features, such as an acute onset with severe symptoms and complex repetitive behaviors that typically occur in late adolescence or early adulthood, a large variability of symptoms including spontaneous symptom remissions and re-emergence, and a high prevalence of phonations and vocalizations with the common use of swearwords or variable sentences. In addition, it is common to see an overlap with additional functional neurologic symptoms, such as functional tremor or nonepileptic seizures. In diagnostically challenging cases, neurophysiologic evaluation, including surface electromyography and electroencephalography, may be useful, and markers such as the premotor potential (Bereitschaftspotential) and event-related desynchronization/synchronization may hold promise. Effective management of functional tics begins with an accurate diagnosis and often requires a multidisciplinary approach. Cognitive-behavioral therapy and the Comprehensive Behavioral Intervention for Tics may be particularly useful, alongside addressing comorbid psychiatric conditions. Currently there is an absence of standardized treatment protocols; individualized care plans tailored to each patient's specific needs are generally the most effective approach.

In the past 3 decades, intravenous immunoglobulin (IVIg) - pooled IgG (IgG) obtained from the plasma of several thousands of healthy donors - has had a major impact in the successful treatment of previously poorly controlled autoimmune neurologic disorders. Based on randomized controlled trials, IVIg is approved for the treatment of Guillain-Barré syndrome, chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy (MMN), and dermatomyositis. It has been effective in myasthenia gravis exacerbations and stiff-person syndrome, and exhibits convincing efficacy in autoimmune encephalitides. As maintenance therapy, IVIg and subcutaneous IgG (SCIg) are effective in controlled studies only in CIDP and MMN. The demand for IVIg therapy is ever-growing, resulting in supply shortages, leading to strategies to replace IVIg with recombinant products based on proposed mechanisms that confer its anti-inflammatory activity. This chapter illustrates clinical applications of IVIg in neurologic diseases, discusses the merit of SCIg, and addresses practically important issues, such as the need for dose adjustment, cycling intervals, dependency testing, or treatment discontinuation.

Autoimmune encephalitis (AE) is a heterogeneous inflammatory syndrome caused by autoantibodies targeted at either neuronal cell surface proteins and synaptic receptors, or at intracellular epitopes. Clinical presentation is dependent on the underlying neuronal antigen, typically involving subacute progressive cognitive deficits, psychiatric and behavioral disturbances, seizures, hyperkinesia, and autonomic dysfunction. Prompt diagnosis and treatment of AE can result in clinical remission and favorable long-term prognosis, diminishing risk of relapse, morbidity, and mortality. Current treatment regimens are primarily based on retrospective case studies and expert opinion, as robust randomized-controlled trials are lacking. First-line immunotherapy involves high-dose intravenous glucocorticoids, intravenous immunoglobulins (IVIg) and plasmapheresis, or a combination of these agents. In severe cases or relapsing disease, sequential treatment with second-line therapy with rituximab or cyclophosphamide is indicated. Novel drugs options have been introduced to the field in recent years, although data regarding clinical efficacy is sparse. Maintenance therapy is only indicated for specific antibodies, or in patients with multiple relapses.

Tics are involuntary or semivoluntary, abrupt, brief, nonrhythmic, recurrent movements or sounds. Tourette syndrome (TS) is the most common cause of tics; however, several other disorders have been associated with tics and tic-like movements. Etiologies of secondary tic syndromes and disorders (STS) include hereditary, drug-induced (including tardive), toxins, traumatic, cerebrovascular, infectious, parainfectious, autoimmune, functional disorders, and others. Age at onset after 18 years, lack of comorbid attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, and no family history of tics are considered typical features of STS. Atypical neurologic manifestations such as additional movement disorders, seizures, decreased level of consciousness, and neurologic deficits, temporally related to some triggering event, such as brain trauma, stroke, or drug exposure, should raise suspicion of STS. These patients usually show a more restricted body distribution, less severe and less complex tics compared with patients with TS. Some tics, typically observed in TS, such as eye-blinking, facial grimacing, and complex motor and phonic tics that are preceded by a premonitory urge may not be present in STS. However, there is a substantial overlap of features between patients with TS and STS. Pharmacologic treatment of STS is similar to TS. Additionally, these patients may require specific treatment, such as anticonvulsants, antibiotics, immunotherapy, or drug-discontinuation. Therefore, prompt recognition and early treatment intervention of STS is imperative for a favorable outcome.

Onset of multiple sclerosis (MS) in childhood and adolescence has now been well-recognized over the past 10-15 years. There have been significant advances in the understanding of the disease course of pediatric MS, which is highly inflammatory, with a higher relapse rate than adult MS. High-efficacy, disease-modifying treatments are recommended for the management of pediatric MS, and these treatments have been studied in open-label and retrospective studies, several of which are outlined here. Fingolimod (Gilenya) is approved for pediatric MS in the United States and many world regions. Several treatments used for adult MS are now being trialed in pediatric MS.

Neuromyelitis optica spectrum disorder (NMOSD) and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD) are rare autoimmune neuroinflammatory disorders of the central nervous system (CNS) characterized by recurrent attacks of optic neuritis, transverse myelitis, brainstem, and brain syndromes. In contrast with multiple sclerosis (MS), the accumulation of disability in NMOSD and MOGAD is primarily related to relapses, while accumulation of disability between attacks is less common. Therefore, treatment strategies should mainly focus on effective treatment of acute relapses and relapse prevention. Over the past decade, a better understanding of the underlying pathophysiology of NMOSD and MOGAD has led to newer, more specific treatment approaches, culminating in the first FDA-approved treatments for relapse prevention in NMOSD, while randomized clinical trials in MOGAD are underway. In this review, the current treatment options for NMOSD and MOGAD will be discussed, as well as potential treatments that are expected to become available in the near future.

Acute tic exacerbations in Tourette syndrome (TS) and other tic disorders are influenced by biologic, psychologic, and social factors. Different terms have been used to describe acute tic exacerbations, including tic status, malignant TS, tic attacks, and tic fits. This review traces the evolution of our understanding of acute tic exacerbations and examines the emerging clinical constructs, highlighting the overlapping features and diagnostic ambiguities of such episodes. Common features include repetitive movements lasting from minutes to hours that are rarely suppressible, cause significant distress, functional impairment, and often require medical intervention. The complexity of these conditions and the potential co-occurrence of functional symptoms in some cases can complicate recognition of underlying triggers and appropriate management. Accurate differentiation from other hyperkinetic movement disorders demands a comprehensive assessment encompassing medical, pharmacologic, and psychiatric histories. By synthesizing current literature, this chapter aims to lay the groundwork for improving diagnostic precision and treatment, emphasizing the need for further research into the various mechanisms of acute tic exacerbations.

In the past decades, the connection between the immune system and Tourette syndrome (TS) has been explored as a potential pathophysiologic key aspect. This idea is supported by studies describing the effect of immune cells and inflammatory mediators in neurodevelopment by acting in synaptic arrangement, pruning, and maturation of neural circuitries. Supporting evidence for that correlation is varied, including genome-wide association studies, transcriptome analysis, animal models, and clinical populational-based studies. Moreover, the influence of environmental aspects typically involved in immunologic response and the association of TS with allergies and autoimmune diseases adds to the immune-based neurodevelopment theory. Overall, the research data looking at this association points toward a proinflammatory state, even though there is still uncertainty about the exact role and implication of this immunologic profile in TS, especially due to the lack of robust evidence regarding immunomodulatory treatments. Furthermore, the discrepancy of results in studies shed doubt on the immunologic hypothesis. In this chapter, we summarize the scientific knowledge regarding immunology in TS, discussing it from a historical perspective to more recent studies.