Brain and Nerve最新文献

Postural abnormalities are relatively common in Parkinson's disease (PD), affecting roughly 20-30% of patients. These abnormalities include camptocormia, Pisa syndrome, and dropped head syndrome, but the mechanisms of these abnormalities remain poorly understood and are likely multifactorial. The reported risk factors for postural abnormalities in PD include long disease duration, older age, medication exposure, and musculoskeletal comorbidities, though causality is unclear. Diagnosis is complicated by variations in definitions and measurement techniques, although standardized angle-based methods have increased consistency. Central factors, such as dystonia, sensory integration deficits, and altered postural perception, as well as peripheral factors, such as paraspinal muscle changes, are thought to contribute to Postural abnormalities. Treatments involve medication adjustments, local injections of botulinum toxin or lidocaine, targeted rehabilitation strategies, and surgical approaches such as deep brain stimulation or spinal correction, but the results are unpredictable and often temporary. Large-scale research using consistent diagnostic methods and neurophysiological assessments is needed to further understand these postural disorders and develop more effective, evidence-based interventions.

The timing of dementia onset in patients with Parkinson's disease varies significantly. Predictors of the early development of dementia include postural instability, gait disturbance, REM sleep behavior disorder, and visuo-spatial impairment. The main neuropathological basis of dementia in Parkinson's disease involves the co-occurrence of α-synuclein pathology in the cerebral cortex and Alzheimer's disease co-pathology. Cholinergic system degeneration significantly affects symptom expression, making cholinesterase inhibitors effective for alleviating visual hallucinations and cognitive deficits.

Insomnia, one of the non-motor symptoms of Parkinson's disease (PD), affects approximately 80% of patients with advanced-stage PD. In such cases, it is necessary to evaluate and treat the condition with the understanding that various factors may be involved, such as side effects or complications of medications and comorbid conditions and diseases, including primary sleep disorders and motor symptoms of PD. The principles of treatment include sleep hygiene education, control of nocturnal motor symptoms through adjustment of anti-parkinsonian medications with consideration of continuous dopaminergic stimulation (CDS), treatment of non-motor symptoms that interfere with sleep, discontinuation of medications that disturb sleep, and management of primary sleep-related disorders. Insomnia in PD can affect not only patient quality of life but also motor functions, making individualized and appropriate assessment and management essential.

Although traditionally classified as a movement disorder due to nigrostriatal dopamine loss, Parkinson's disease also manifests a wide range of psychiatric symptoms across the disease course from prodromal phase to advanced stages. These psychiatric symptoms include depression, anxiety, apathy, impulse control disorders, hallucinations, and delusions. The emergence of psychiatric symptoms reflects the dysfunction of the dopaminergic system and multiple neurotransmitter systems (e.g., serotonergic, noradrenergic, and cholinergic systems) and disruption of large-scale brain networks. Providing optimal care requires stage- and symptom-specific strategies, such as optimizing dopaminergic therapy, judiciously using atypical antipsychotics, and considering acetylcholinesterase inhibitors when appropriate. This review summarizes the epidemiology, pathophysiology, and treatment of the psychiatric symptoms in Parkinson's disease, highlighting individualized management strategies that align with the underlying mechanisms.

Patients with Parkinson's disease (PD) often develop hypersexuality. Hypersexuality occurs in impulse control disorders (ICD), which are caused by dopamine replacement therapy. Hypersexuality becomes a burden for patients, their spouses, and caregivers and worsens their quality of life. Hypersexuality occurs in approximately 3-8% of patients with PD and tends to occur in young male patients. Other risk factors for hypersexuality in PD include cognitive impairment, a history of depression or pathological gambling, and impulsive or novelty-seeking personality traits. Dopamine agonists are more likely to cause hypersexuality; however, levodopa can also cause hypersexuality. The average duration of medication use in patients with PD with hypersexuality is 6.5years. Treatment for hypersexuality involves reducing, switching, or discontinuing dopamine replacement therapy, particularly dopamine agonists. Drugs must be carefully selected for young male patients at high risk of developing hypersexuality.

Autophagy is an essential degradation mechanism that maintains intracellular homeostasis. In recent years, an increasing number of cases with mutations in autophagy-related genes, such as ATG7, have been reported. These findings highlight the crucial role of autophagy in human neurodevelopment. However, the severity of clinical symptoms does not always correlate with the degree of autophagy impairment observed in patient-derived cells, and phenotypic manifestations can vary widely. These findings indicate that autophagy dysfunction alone does not fully explain disease mechanisms, even in neurological disorders directly associated with mutations in autophagy-related genes. Currently, no established methods exist to quantitatively assess autophagy activity in vivo, making it challenging to determine whether autophagy dysfunction serves as a primary driver of disease pathogenesis in adult-onset neurodegenerative diseases, such as Alzheimer's and Parkinson's disease. Although several lines of indirect evidence indicate impaired autophagy in these conditions, it remains uncertain whether such changes are causative or secondary to the disease process. Further research is warranted to elucidate the precise role of autophagy in both developmental and degenerative neurological disorders and to determine whether targeting autophagy holds promise as a therapeutic strategy.

Falls represent critical clinical events in older people, leading to functional decline, fractures, and deterioration in their ability to perform activities of daily living and decreased cognitive abilities, resulting in a bedridden state. Progression of Parkinson's disease (PD) causes postural instability, gait disturbances, gait freezing, and cognitive dysfunction, which markedly elevate the risk of falling compared with that of the general older adult population. Kempster et al. revealed that patients with PD frequently fall, reaching major milestones in PD such as dementia or institutionalization within only a few years; therefore, falls directly influence the prognosis of those with PD. In addition, falls in those with PD are related to not only motor dysfunction but also nonmotor features, including orthostatic hypotension and cognitive decline. Age-related sarcopenia, comorbidities, polypharmacy, and environmental factors further increase the risk of falls; as such, these underlying factors must be understood, and targeted preventive strategies must be implemented for patient management.

Orthostatic hypotension (OH) is a major problem in patients with Parkinson's disease (PD), necessitating careful management by neurologists. Furthermore, understanding the relationship between OH and other non-motor symptoms provides valuable insight into the pathological progression associated with α-synuclein and the clinical subtypes for PD. This study explains the physiological mechanisms of blood pressure regulation and the pathogenesis and management of OH in PD. It also discusses the relationship between OH and other non-motor symptoms, particularly cognitive decline, including verification of the α-synuclein propagation hypothesis.

John Hughlings Jackson (1835-1911) was a British neurologist renowned for his research on epilepsy. Beyond his work as a clinician, his overall intuitive grasp of neuroscience is particularly remarkable-he consistently proposed foundational concepts. This essay explains the theoretical aspects of Jackson's work that influenced contemporary neuroscience. It focuses specifically on his theoretical challenge to transcend both localizationism and holism within his extensive body of work and on his proposed duality of neural processes, which emerged as he sought to identify evolutionary hierarchies.

Wilder Penfield (1891-1976) was a Canadian neurosurgeon whose pioneering work left a lasting mark on neuroscience and epilepsy surgery. He advanced knowledge of cortical localization by electrically stimulating the brain under local anesthesia, allowing patients to report sensations and movements. From these observations, he created the famous "homunculus," a functional map of motor and sensory areas. Penfield also developed the Montreal Procedure, a groundbreaking surgical approach for intractable epilepsy. By stimulating the cortex during awake operations, he identified and preserved critical regions for speech and movement while safely removing epileptic foci. His studies also revealed that cortical stimulation could evoke vivid memories and experiences, contributing to research on memory and consciousness. In 1934, Penfield founded the Montreal Neurological Institute (MNI), the first center to integrate clinical care, research, and education in neuroscience. This interdisciplinary model fostered collaboration among neurosurgeons, neurologists, psychologists, and basic scientists, becoming the prototype for modern neuroscience institutes. Through his surgical innovations, scientific insights, and commitment to education, Penfield trained generations of specialists and shaped the field of translational medicine. His legacy continues to influence epilepsy surgery, cortical mapping, and the study of brain-mind relationships.