Handbook of clinical neurology最新文献

Treating children and adults with Gilles de la Tourette syndrome (GTS) remains a clinical challenge and typically requires a multidisciplinary approach, owing to the complexity of the disorder and the frequent presence of comorbidities such as obsessive-compulsive disorder and attention-deficit/hyperactivity disorder. This chapter focuses on the pharmacologic management of tics in the context of GTS. It reviews key considerations in the selection of therapeutic agents from the broad range of pharmacologic options available in clinical practice. The strongest evidence supports the use of dopamine receptor antagonists, particularly atypical antipsychotics such as aripiprazole and risperidone. However, other agents - including α-2 adrenergic agonists, vesicular monoamine transporter 2 inhibitors, and topiramate - also play an important role in treatment strategies. Pharmacologic management of GTS should be individualized, taking into account symptom severity, functional impact, and the risk-benefit profile of each therapeutic option.

Sexuality and sexual health are essential for the overall well-being of all individuals. In neurology, research traditionally focused on disorders of sexual function associated with syndromes that present with specific lesions of the spinal cord and brain. In neuropsychiatric tic disorders, however, early research addressed sexuality and sexual behaviors in a wider context and beyond the strict diagnostic categories of sexual dysfunction, including gender identity and sexual orientation. Although these studies provided important insights in the behavioral structure of adults with primary tic disorders and Tourette syndrome, many of these early findings were not replicated subsequently and should, therefore, be critically reconsidered. This chapter provides a comprehensive catalog of existing data on sexuality and sexual health, including gender identity, sexual orientation, sexual dysfunction, adverse sexual experiences, compulsive sexual behaviors, and paraphilic disorders in adults with primary tic disorders. It also discusses the role of comorbidities, particularly attention-deficit/hyperactivity disorder, as well as the impact of neuropsychiatric medication. Additionally, it catalogs, for the first time, different therapeutic approaches that may improve sexual health in adults with primary tic disorders. Finally, knowledge gaps and methodological limitations are also addressed. Ultimately, this chapter's goal is to carefully present existing data, map underexplored needs, and highlight ways to respectfully address them both in clinical practice and through future research.

Traumatic brain injury (TBI) is a serious public health concern and is one of the major causes of death and chronic disability in young individuals. Sleep-wake disturbances are among the most persistent and debilitating consequences of TBI and are reported by 50%-70% of TBI patients regardless of TBI severity. Excessive daytime sleepiness, fatigue, hypersomnia, and insomnia are the most common sleep disturbances in TBI patients. Post-TBI sleep-wake disturbances are often associated with pain, anxiety, depression, and posttraumatic stress disorder. They may exacerbate cognitive impairment following TBI, reduce community integration, and delay recovery and return to normal life. Changes in sleep architecture following TBI have been reported in the literature but cannot fully explain the extent and intensity of the sleep-wake disturbances reported by TBI patients. The alteration in the circadian timing system is another factor that may partially account for the presence of post-TBI sleep-wake disturbances. Current literature supports cognitive behavioral therapy and sleep hygiene education, light therapy, and certain pharmacologic interventions for treating sleep disturbances in TBI patients. Due to heterogeneous consequences of TBI, early screening and individualized approaches to treatment must be prioritized to improve sleep in TBI patients and consequently speed up recovery.

Disorders of consciousness (DoC) are a heterogeneous spectrum of clinical conditions, including coma, unresponsive wakefulness syndrome, and minimally conscious state. DoC are clinically defined on the basis of behavioral cues expressed by the patients, on the assumption that such behavioral responses of the patient are representative of the patient's degree of consciousness impairment. However, many studies have highlighted the issues arising from formulating a DoC diagnosis merely on behavioral assessment. Overcoming the limitations of behavioral assessment, neuroimaging provides a direct window on the cerebral activity of the patient, bypassing the motor, perceptual, or cognitive deficits that might hamper the patient's ability to produce an appropriate behavioral response. This chapter provides an overview of available molecular, functional, and structural neuroimaging evidence in patients with DoC. This chapter introduces the neuroimaging tools available in the clinical settings of nuclear medicine and neuroradiology and presents the evidence on the role of neuroimaging tools to improve the clinical management of DoC patients, from the standpoint of differential diagnosis and prognosis. Last, we outline the open questions in the field, and point at actions that are urgently needed to fully exploit neuroimaging tools to advance scientific understanding and clinical management of DoC.

Sleep deprivation (SD) is an experimental procedure to study the effects of sleep loss on the human brain. Neuroimaging techniques, such as functional magnetic resonance imaging (fMRI) and electroencephalography (EEG), have been pivotal in studying these effects. The present chapter aims to retrace the state of the art regarding the literature that examines the SD effects on the brain through functional connectivity (FC) evaluated in fMRI and EEG settings, separately. Specifically, we focused on the cognitive domains mainly affected by sleep loss and the underlying brain connectivity alterations. SD disrupts homeostatic and circadian processes, negatively affecting cognitive and cerebral functionality explored through FC. All evidence confirms the detrimental role of SD on brain connectivity impacting several resting-state networks and resulting in cognitive impairments. To conclude, SD may offer useful insights into pathogenic mechanisms likely resembling those induced by chronic sleep loss that might find their application in the clinical context.

Historically, the first observations of a lower prevalence of right-handed patients among subjects with schizophrenia led to the hypothesis that brain asymmetry could play a significant role in the etiopathogenesis of the disease. Over the last decades, a growing number of findings obtained through many different techniques such as EEG, MEG, MRI, and fMRI, consistently reported reduction/loss of brain asymmetries as a core feature of schizophrenia, further suggesting such alterations to play a cardinal role in the pathogenesis of the disease. Moreover, several cognitive and psychopathologic dimensions have shown significant correlations with the reduced degree of asymmetry. In particular, the absence or even reversal of structural asymmetries has been documented in language-related brain such as the Sylvian fissure and planum temporale. These findings have been reprocessed within an evolutionary and psychopathologic framework pointing at the loss of asymmetry and the consequent language impairment as primum moves in the pathogenesis of schizophrenia. Overall, despite growing evidence demonstrating a heterogeneous and multifaced etiopathogenesis in schizophrenia, the "old concept" of brain asymmetry still offers intriguing hints and thought-provoking elements for clinicians and researchers who deal with schizophrenia.

The nicotinic acetylcholine receptor (nAChR) is the archetypal neurotransmitter receptor within the superfamily of pentameric ligand-gated ion channels (pLGICs). Typically, it mediates fast synaptic transmission in response to its endogenous ligand, acetylcholine, and can also intervene in slower signaling mechanisms via intracellular metabolic cascades in association with G-protein-coupled receptors. This review covers the structural and functional aspects of the different neuronal nAChR subtypes and their cellular and anatomic distribution in the brain. The significant progress in our knowledge on the topic derives from the successful combination of biochemical, neuroanatomic, pharmacologic, and cell biology approaches, complemented by site-directed mutagenesis, single-channel electrophysiology, and structural biophysical studies. This multipronged approach provides a comprehensive description of nAChR in health and disease, offering improved chances of success in tackling neurologic and neuropsychiatric diseases involving phenotypic alterations of nAChRs, particularly in neurodegenerative diseases.

This chapter provides a concise narrative of the evolution of events that have led to the current widely accepted concept of cholinergic neurotransmission. It recounts the saga of a century of intense research, technologic innovations, and fundamental discoveries, highlighting the contributions of key figures who have provoked ongoing intellectual challenges and scientific disputes regarding the physiologic significance of cholinergic transmission. Additionally, the chapter describes the resolution of decades-old debates surrounding the hypothesis of electrical vs chemical neurotransmission-a debate that has shaped current fundamental concepts and garnered several Nobel Prizes.

Substance use disorders (SUD) remain a major public health concern in which individuals are unable to control their use of substances despite significant harm and negative consequences. Drugs of abuse dysregulate major brain and behavioral functions. Glial cells, primarily microglia and astrocytes, play a crucial role in these drug-induced molecular and behavioral changes. This review explores preclinical and clinical studies of how neuroglia and their associated neuroinflammatory responses contribute to SUD and reward-related properties. We evaluate preclinical and clinical evidence for targeting neuroglia as therapeutic interventions. In addition, we evaluate the literature on the gut microbiome and its role in SUD. Clinical treatments are most effective for reducing drug cravings, and some have yielded promising results in other measures of drug use. N-Acetylcysteine, through modulation of cysteine-glutamate antiporter of glial cells, shows encouraging results across a variety of drug classes. Neuroglia and gut microbiome interactions are important factors to consider with regard to SUD and could lead to novel therapeutic avenues. Age- and sex-dependent properties of neuroglia, gut microbiome, and drug use behaviors are important areas in need of further investigation.

Electroencephalography (EEG) has emerged as a powerful tool in the diagnosis, characterization, and prognostication of patients with disorders of consciousness (DoC). EEG is a well-established monitoring tool for the treatment of specific patient populations with impaired consciousness, such as those with status epilepticus and cardiac arrest. The interrogation of neuronal circuitry using evoked and event-related potentials adds prognostic information in comatose individuals. Novel paradigms integrating transcranial magnetic stimulation may provide insights into the underpinnings of arousal and awareness. Covert consciousness, or willful brain activation to motor commands in behaviorally unresponsive patients, may be diagnosed using EEG recordings and has been linked to better outcomes. These advanced EEG methods are increasingly being explored and integrated into the management of DoC patients.