Brain and Nerve最新文献

Cognitive dysfunction, characterized by the deposition of amyloid β (Aβ), such as senile plaque (SP) and cerebral amyloid angiopathy (CAA), and phosphorylated tau are observed in several animal species, including primates, dogs, and cats, suggesting that these disorders are universal age-related phenomena in vertebrates. Additionally, argyrophilic neurofibrillary tangles positive for phosphorylated tau have been observed in primates, marine mammals, and felines. Recent findings regarding the pathology of cognitive dysfunction in aged non-human animals provide valuable information from a comparative perspective for advancing research on the pathogenesis, diagnosis, and treatment of Alzheimer's disease.

Clinical neuropathology was advanced by Charcot at la Salpêtrière Hospital in the 19th century. The lower and upper motor signs of amyotrophic lateral sclerosis were corroborated at autopsy by degeneration of the anterior horns and lateral columns, respectively. The redefinition of paralysis agitans as Parkinson's disease was substantiated in the 20th century through a series of pathological, biochemical, and genetic studies that provided definitive, museum-like evidence of neurological diseases. In contrast to these scientific achievements, the phenomenology of hysteria was publicly evaluated and recognized in front of the audiences that included non-medical professionals. This theater-like format, which encouraged interaction between patients and spectators, might have influenced the clinical presentation of hysteria and complicated its interpretation. Contrary to Charcot's expectations, attempts to identify the causative lesions of hysteria were unsuccessful. Paradoxically, however, this failure paved the way for the development of dynamic psychiatry by Freud and Janet, and later, the conceptualization of functional neurological disorders in the 21st century.

Sleep-waking is regulated by numerous sleep- and wake-promoting nuclei in the brain and biological clocks (suprachiasmatic nucleus). In dementia, organic damage occurs in the brainstem, hypothalamus, and thalamus, where these nuclei and their neural projections are concentrated, resulting in severe insomnia, hypersomnia, and irregular sleep-wake patterns. Numerous cohort studies have strongly suggested that sleep disturbances, such as impaired sleep quality and hypersomnia, may serve as early indicators or risk factors for the onset of dementia. Until recently, the neuropathological mechanisms underlying the association between sleep disturbance and the risk of dementia remained unclear. However, recent advances in research on the glymphatic system and its association with amyloid-beta peptide clearance have begun to elucidate this missing link.

Rapid eye movement (REM) sleep is characterized by an "active brain" and an "immobile body," and its dysregulation has been implicated in disorders such as narcolepsy and REM sleep behavior disorder. In this review, we first provide an overview of the basic features of REM sleep and then introduce the mechanisms by which dopamine signaling in the amygdala induces REM sleep and the inhibitory pathways in the medulla oblongata that mediate muscle atonia. Finally, we discussed how an integrated understanding of these neural circuits will advance our knowledge of the pathophysiology of sleep-related disorders and inform future therapeutic strategies.

This review outlines commonly used self-reporting tools and sleep-related tests for the diagnosis and management of sleep-related disorders. In clinical practice, it is essential to identify multiple potential contributing factors based on the patient's chief complaints and select the most appropriate assessment method accordingly. Each assessment method has its strengths and limitations that must be carefully evaluated when interpreting the results. Notably, while simpler tools offer convenience, their effective clinical use requires a higher level of literacy in sleep physiology and understanding of the characteristics of the measurement devices to ensure appropriate clinical application and result interpretation.

Narcolepsy is primarily characterized by excessive daytime sleepiness, which is the cardinal symptom. Additional associated symptoms include cataplexy, sleep paralysis, hypnagogic hallucinations, and nocturnal sleep fragmentation. Narcolepsy is classified into two subtypes: type 1, which is caused by the loss of orexin-producing neurons, and type 2, the pathophysiology of which remains unclear. Currently, no curative treatment exists; management is limited to symptomatic therapies. Recently, orexin receptor agonists have been developed and are undergoing evaluation in clinical trials.

Narcolepsy is a major central disorder of hypersomnolence that causes excessive daytime sleepiness (EDS), cataplexy, sleep paralysis and hypnagogic hallucinations due to impairment of the orexinergic system. Symptomatic narcolepsy is characterized by persistent EDS and REM sleep-related symptoms due to associated neurological diseases or brain lesions. Hypothalamic lesions due to neurological disorders, including immune-mediated diseases, can cause symptomatic narcolepsy. This review describes symptomatic narcolepsy and EDS associated with neurological disorders.

The discovery of the glymphatic system, a waste clearance pathway in the brain, has drawn increasing attention to the relationship between sleep and neurological diseases such as Alzheimer's disease. Recent studies have revealed the mechanisms of action during sleep in rodents. However, some aspects remain unclear, including their contribution to aging and disease development, and their potential for prevention and early therapeutic intervention.

Restless leg syndrome (RLS) is a sensorimotor disorder characterized by unpleasant sensations in the lower limbs and an urge to move them, which often results in insomnia or difficulty in maintaining sleep. Although RLS is less prevalent in Asian populations than in Western countries, it remains common and often underdiagnosed. The diagnosis is based on international consensus criteria, and its pathophysiology is thought to involve central dopaminergic dysfunction and impaired iron metabolism in the brain. Management strategies include iron supplementation, lifestyle, and pharmacological treatment using dopamine agonists and α2δ ligands. However, drug-induced augmentation remains challenging. The 2024 clinical guidelines published by the Japanese Society of Neurological Therapeutics provide evidence-based recommendations and a treatment algorithm addressing both standard therapy and augmentation. This review summarizes the current knowledge on the epidemiology, diagnosis, pathophysiology, and treatment of RLS, with a focus on the implications of the new guidelines.

Autoimmune encephalitis can cause various sleep disorders. Anti-NMDAR encephalitis often presents with insomnia in the acute phase, which may transition into hypersomnia or confusional arousal during recovery. Anti-LGI1 and anti-CASPR2 encephalitis can also cause Morvan's syndrome. This syndrome is characterized by blurred distinctions between sleep stages, leading to status dissociatus and agrypnia excitata. Anti-IgLON5 disease is associated with parasomnia, sleep apnea, and stridor, all of which can lead to sudden death. NMOSD and anti-Ma2 encephalitis may present as narcolepsy accompanied by hypothalamic lesions, likely due to orexin deficiency.