Handbook of clinical neurology最新文献

Tics, such as those seen in Tourette syndrome (TS), are brief, sudden, and involuntary movements or vocalizations. Although tics are involuntary, most individuals with TS can suppress them on command for short periods of time. This capacity, which is called voluntary tic suppression, is a hallmark feature of TS and differentiates it from most other movement disorders. Several studies have investigated inhibitory control of voluntary actions in TS, given its potential associations with both tic expression and voluntary tic suppression. However, studies on response inhibition in TS have produced quite mixed results. Furthermore, the mechanisms of voluntary tic suppression remain poorly understood. The current chapter offers an overview of the evidence related to inhibitory control of voluntary actions and voluntary tic suppression in TS. It reviews evidence from clinical, behavioral, neuropsychologic, and neurobiologic studies in order to understand to what extent these processes may be similar or different.

Gilles de la Tourette syndrome (GTS) is increasingly conceptualized as a neurodevelopmental network disorder. In this chapter, we have synthesized two decades of neuroimaging findings spanning gray- and white-matter morphology, structural connectivity, and functional network dynamics in GTS across childhood and adulthood. Structural MRI studies using voxel-based morphometry (VBM) have reported heterogeneous volume differences-both decreases and increases-across cortico-striatal-thalamo-cortical regions, motivating the use of meta-analytic approaches to identify more consistent loci, including cingulate, sensorimotor, thalamic, striatal, and insular regions. In contrast, cortical thickness studies more consistently indicate cortical thinning in motor/premotor and prefrontal areas, with links to tic phenomenology and premonitory urges. Diffusion and volumetric white-matter measures further implicate interhemispheric pathways and fronto-striatal projections, with some indices relating to tic severity. At the circuit level, tractography and structural covariance studies support altered connectivity within the cortico-striato-pallido-thalamo-cortical loop and highlight a complementary contribution of cerebello-cortical pathways. Functional MRI studies converge on temporally structured node engagement during tic generation-preceding activity in supplementary motor, cingulate, insular, and opercular regions, followed by sensorimotor, thalamic, and cerebellar involvement-and reveal large-scale reconfiguration of cortico-basal ganglia networks associated with tic severity and comorbid symptoms. Finally, lesion-network mapping and coordinate-based network mapping studies in secondary tics and GTS-related atrophy converge on a common tic-associated network, providing a translational framework to guide neuromodulation and to derive clinically meaningful network biomarkers for treatment targeting.

For many individuals with Tourette, navigating everyday judgments from strangers and peers alike can be as much of a challenge as the tics. Tourette-awareness campaigns and the rise of social media support communities have done significant work to improve the public's understanding and acceptance of tic disorders, but individuals living with it still experience unfortunate misunderstandings about their tics -- sometimes in sensitive environments, like airports -- which makes for a nervous base-pressure that "Touretters" can feel in their day-to-day and which can inflame their ticcing. Social difficulties, and even the fear of the them, are very much a part of the story for people with Tourette and other tic disorders. The science community has done excellent work over the years in reaching out to the Tourette community to consider those daily-life experiences and better align with what people living with Tourette would like to see improve with respect to the disorder.

The spectrum of autoimmune movement disorders is very broad with regard to clinical presentations, associated antibodies, and underlying immunopathophysiology. Early and adequate immunotherapy is key in the management to achieve good outcomes, avoid deterioration, or even death. The rarity of these disorders, however, entails a lack of gold-standard treatment trials we could base our management decisions upon. Here, we summarize existing knowledge about the treatment of autoimmune movement disorders and cerebellar ataxias with neuronal antibodies. We start with a brief introduction of the basic paradigms of neuronal antibody-associated autoimmunity, and of the principles of immune therapy generally applied in antibody-related neurologic disorders, to then discuss in more detail the main movement disorders and cerebellar ataxia related-antibody syndromes and their treatment.

Guillain-Barré syndrome (GBS) and other acute autoimmune neuropathies are rare but severe immune-mediated diseases of the peripheral nervous system. Early diagnosis is important for adequate monitoring and treatment, but it can be complicated by the rarity, heterogeneity in clinical presentation, and extensive differential diagnosis. The current proven effective treatments for GBS are intravenous immunoglobulins administered within 2 weeks and plasma exchange within 4 weeks from the onset of weakness. These therapies are immunomodulatory and aim to prevent further damage of peripheral nerves during the acute stage of the disease. Here we provide an overview of the early presentation of GBS and the required diagnostic workup to discriminate GBS from other causes, including other acute forms of autoimmune polyneuropathies. In addition, the current evidence-based immunotherapies for GBS are discussed along with the presumed pathophysiologic mechanisms of action and practical recommendations for the treatment in clinical practice. Despite current treatment, a substantial proportion of patients with GBS have a poor clinical course and outcome. We will present the latest developments regarding potential new treatments that are currently being evaluated and discuss various opportunities to optimize the design of future treatment trials toward a more effective and personalized treatment of GBS.

Sleep disturbances are highly prevalent in patients with tic disorders and Tourette syndrome, with up to 80% of patients experiencing sleep difficulties. Insomnia is notably present, and pediatric patients often experience parasomnias, including sleepwalking and night terrors. Disruptions in circadian rhythms are also reported, with a pronounced evening chronotype. Concurrently, patients may also suffer from sleep-related movement disorders, and tics are reported to often persist during sleep, further contributing to significant sleep fragmentation. The presence of comorbid attention-deficit hyperactivity disorder may further exacerbate sleep disturbances. Current genetic and neurobiologic evidence suggests shared pathophysiologic mechanisms, particularly involving the dopaminergic system, that underlie both tic manifestations and sleep disruptions. While pharmacologic and nonpharmacologic interventions offer potential therapeutic avenues, their efficacy in a combined tic-sleep disorder context requires further investigation.

Premonitory sensations, or urges, have become a central focus in the study of Gilles de la Tourette syndrome (TS). These bodily sensations, which precede tics, play a crucial role in the clinical manifestations of the syndrome. Tics are often performed to alleviate the discomfort caused by premonitory urges and provide temporary relief. Despite their importance, the causes and mechanisms of premonitory urges remain poorly understood. The severity of tics and an individual's ability to control them are closely related to the intensity and presence of these urges. Current research is actively investigating the neuroanatomic and neurophysiologic basis of premonitory urges, focusing on specific brain regions, neural pathways, and neurotransmitter systems. Understanding premonitory urges is essential for characterizing the clinical phenotype of TS and other neurodevelopmental tic disorders and for developing targeted therapies. By investigating the relationship between premonitory urges, tics, and associated clinical features - such as obsessions, compulsions, and anxiety - researchers aim to improve prognostic tools and refine treatment strategies. Ongoing investigations into these mechanisms hold great promise for improving the care and support of people with TS and, ultimately, their quality of life.

Steroids and immunoglobulins, either intravenous or subcutaneous, have represented the cornerstone treatment of chronic immune-mediated neuropathies for many years. In the last decade, new therapeutic targets are being studied, with the potential to selectively dampen aberrant immune responses, including drugs that act both on the complement pathways and the recycling mechanism of IgG immunoglobulins by the neonatal receptor (FcRn). Among the latter, efgartigimod has recently been approved for the treatment of chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Also rituximab, an anti-CD20 monoclonal antibody mostly used in antimyelin-associated glycoprotein (MAG) antibody neuropathy and in autoimmune nodo-paranodopathies, has been tested both in open and double-blind studies in CIDP, whereas ARGX-117, an antibody targeting the C2 fraction of the complement, is under investigation in multifocal motor neuropathy. In anti-MAG antibody neuropathy, Bruton's tyrosine kinase inhibitors, zanubrutinib and acalabrutinib, are currently tested either as a single agent or in combination with rituximab.

This chapter explores evidence for the effectiveness of noninvasive brain stimulation (NIBS) for tic disorders and explores what the future may hold for these approaches. NIBS can be achieved through several means, including electrical stimulation of peripheral nerves and transcranial cortical stimulation using electrical or magnetic stimulation. Each of these techniques will be discussed with a focus on current evidence of effectiveness in treating tics, benefits, limitations, and current unknowns.

The neonatal Fc receptor (FcRn) is a heterodimeric protein that binds albumin and immunoglobulin G (IgG) to mediate pH-dependent recycling, prevent degradation, and maintain their serum concentrations. The ability to bind IgG means FcRn plays both beneficial and potentially detrimental roles in host immunity. Beneficially, FcRn maintains first-line defenses against invading pathogens by preventing degradation of IgG in mucosal secretions, and is linked with increased tumor protection via IgG immune complex-mediated activation of CD8+ cytotoxic T cells and induction of cytotoxic cytokine secretion. FcRn also maintains serum concentrations of circulating pathogenic IgG autoantibodies associated with neurologic and other autoimmune disorders, including myasthenia gravis, chronic inflammatory demyelinating polyneuropathy, and idiopathic inflammatory myopathies. Traditional immune-based therapies for autoimmune disorders, such as steroidal and nonsteroidal immunosuppressants, intravenous and subcutaneous immunoglobulin therapies, and B cell- and complement-targeting therapies, can be associated with significant side-effects and lack of efficacy in some patients. There is a clear need for alternative strategies to treat antibody-mediated autoimmune diseases. The critical role of FcRn in the pathogenesis of autoimmune disorders makes it an ideal target for novel treatments. Here, we discuss the FcRn receptor, current treatments, and recent clinical developments of FcRn-targeting treatments for autoimmune neurologic disorders.