Handbook of clinical neurology最新文献

Stroke, ischemic or hemorrhagic, triggers a complex and coordinated glial response, which, to a large extent, defines the progression and outcome of this focal damage of the nervous tissue. Massive cell death in the infarction core results in a release of damage-associated molecular patterns, which, together with blood-borne factors entering the brain through either ruptured vessels or through compromised blood-brain barrier, trigger reactive gliosis. Microglia are the first to migrate toward the lesion, proliferate, and phagocytose cellular debris in and around the infarct core. Reactive astrogliosis occurs around the margins of the infarct core and is characterized by astrocytic proliferation, morphologic remodeling with loss of territorial domain segregation, and transcriptional reprogramming into wound repair astrocytes that form a periinfarct border that protects the healthy tissue and assists postlesional regeneration.

The nonvisual effects of light in humans are mainly conveyed by a subset of retinal ganglion cells that contain the pigment melanopsin which renders them intrinsically photosensitive (= intrinsically photosensitive retinal ganglion cells, ipRGCs). They have direct connections to the main circadian clock in the suprachiasmatic nuclei (SCN) of the hypothalamus and modulate a variety of physiological processes, pineal melatonin secretion, autonomic functions, cognitive processes such as attention, and behavior, including sleep and wakefulness. This is because efferent projections from the SCN reach other hypothalamic nuclei, the pineal gland, thalamus, basal forebrain, and the brainstem. The ipRGCs also directly impact the prefrontal cortex and the perihabenular nucleus (mood). In particular, light suppresses the secretion of melatonin in a dose-dependent manner, mainly depending on irradiance and spectral composition of light. There is evidence that exposure to light-emitting devices from luminaires and screens before bedtime can impact on sleep onset latency, sleep duration, and sleep quality. Likewise, light exposure during daytime modulates sleep architecture, duration, and sleep quality during the subsequent night. Therefore, the integration of acute, circadian, and long-term effects of light together influence sleep-wake quality and behavior in healthy individuals, as well as in patients with psychiatric or medical disorders.

Sleep and circadian dysfunction are common nonmotor symptoms in patients with Parkinson disease (PD). Sleep and circadian dysfunction usually have a significant negative impact on quality of life and may also serve as markers to identify patients in the preclinical stage of PD. Sleep disturbances have different types in PD such as insomnia, excessive daytime sleepiness, rapid eye movement sleep behavior disorders, restless legs syndrome, and sleep-disordered breathing. Because PD has a variety of clinical manifestations, sleep disorders and circadian dysfunction are most easy to be overlooked. The management of sleep and circadian dysfunction in patients with PD is complex as these conditions are heterogeneous; therefore, treatment plans must be individualized and directed at the underlying cause(s). Therefore, screening for and managing sleep and circadian dysfunction are important in clinical practice, and looking for new perspective and opportunities for treatment of them may improve the quality of life of PD patients. Therefore, screening for and managing sleep and circadian dysfunction are important in clinical practice. Looking for new perspective and opportunities for treatment will likely improve the quality of life of PD patients.

The study of blood and cerebrospinal fluid biomarkers is a promising and rapidly advancing field in the research of disorders of consciousness (DoC). The use of advanced biochemical and analytic techniques in biomarker research has improved our ability to identify new biomarkers that can aid in the diagnosis, prognosis, and treatment of patients with brain injury. However, the use of biomarkers in clinical practice is limited by several challenges, including the lack of standardization in test and research methodologies. Despite this, identifying the most promising biomarkers and supporting their findings with strong evidence can improve their clinical utility. This chapter discusses the most promising biomarkers for DoC, which fall into four categories: neuronal, glial, inflammatory, and metabolic biomarkers. Understanding the role of each category in DoC can provide valuable insights into the mechanisms of brain injury and inform the development of more effective diagnostic and treatment strategies. By integrating biomarker research with clinical practice, we can improve our understanding of DoC and provide better care for these patients.

The blood-brain barrier (BBB) is a highly dynamic and complex structure, present throughout the brain vasculature, that safeguards the brain against blood-borne insults. Neuroglial cells play a major role in its development, function, and homeostasis of the BBB by establishing intricate interactions via direct cell-cell contacts and paracrine signaling. Astrocytes, pericytes, oligodendrocytes, and microglia, alongside specialized brain endothelial cells, orchestrate key events in the brain in health and disease, which can be partially recapitulated by in vitro and in vivo models for biomedical research. This chapter presents a detailed description of the main cellular and molecular mechanisms that govern the neuroglia-BBB crosstalk and the available models for its investigation, emphasizing the importance of each cell population and the synergistic roles they play in the brain.

The nonimage-forming effects of light are pivotal in regulating cognitive functions, including alertness, sustained attention, and higher-order cognitive processes. These cognitive domains are deeply influenced by the sleep-wake cycle, which are governed by two key processes: the homeostatic process, which builds sleep pressure during wakefulness, and the circadian process, which aligns with environmental light cues to regulate wakefulness and sleep. When these processes fall out of sync-a condition known as circadian misalignment-alertness, sustained attention, and cognitive performance can suffer significantly. This misalignment is often observed in shift workers, individuals experiencing jet lag, and those with circadian rhythm sleep disorders. However, strategic light exposure can help mitigate these cognitive impairments by realigning circadian rhythms, enhancing wakefulness during desired periods, and facilitating sleep when needed. This chapter examines the complex interplay between light, circadian rhythms, the sleep-wake cycle, and cognitive functioning, offering a comprehensive exploration of how these factors shape cognitive performance throughout the day and under conditions of circadian misalignment. It also discusses the broader implications of these interactions for cognitive health and performance.

The advancements in understanding hemispheric specialization of language (HSL) have been following two primary avenues: the development of neuroimaging techniques and the study of its reorganizations in patients with various neuropathologic conditions. Hence, the objectives of this chapter are twofold. First, to provide an overview of the key neuroimaging techniques employed to investigate HSL, along with the notable findings derived from them in the healthy population. Second, it focuses on the reorganization of HSL in physiologic (healthy aging) and pathologic (poststroke aphasia and temporal lobe epilepsy) conditions. The chapter emphasizes the importance of employing multimodal methodologies to comprehend the complex relationship between underlying HSL mechanisms affected by disease and resulting language impairments. Combining the neuroimaging techniques can help us understand how different characteristics of language networks combine into general mechanisms that support their plasticity. Nevertheless, it highlights the need for standardized HSL metrics, as the absence of such metrics poses challenges in synthesizing findings across studies. Additionally, while HSL findings are being accumulated, albeit multimodal, there is a lack of integration within a robust theoretical framework. In conclusion, there is a need for novel models acknowledging multimodal aspects of HSL while positioning it within the context of other cognitive functions.

Disorder of consciousness (DoC) are the shared clinical manifestation of severe brain injuries resulting from a variety of etiologies. The nosology of DoC, as well as the armamentarium of methods available to diagnose it, has rapidly evolved. As a result, the diagnosis of DoC is complex and dynamic. We offer an evidence-based approach to DoC diagnosis, highlighting the challenges and pitfalls therein. Accordingly, we summarize the contemporary taxonomy of DoC and its development. We discuss the standardized behavioral diagnostic tools that form the foundation of DoC diagnosis, the evidence for their use, and their limitations. We also highlight recent advances in functional MRI (fMRI) and electroencephalography (EEG) techniques to increase the sensitivity and specificity of DoC diagnosis. We discuss the concept of covert consciousness (i.e., cognitive motor dissociation) as a discrete diagnostic category of DoC, as well as its diagnostic implications. Finally, we underscore issues of neuroethics and equity raised by contemporary models of DoC.