Brain and nerve = Shinkei kenkyū no shinpo
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Central nervous system hyperexcitability disorders, known as stiff-man/person syndrome (SPS), are thought to be related to the regulatory disturbance of inhibitory synaptic transmission of motor neurons in the brainstem and spinal cord. SPS is characterized by stiffness and spasms of the axis and limbs and is divided into two clinical subgroups: classic SPS, which affects the lumbar, trunk, and proximal limb muscles, and SPS-plus syndrome. The latter comprises (1) the stiff-limb subtype, in which symptom is limited to the lower limbs; (2) jerking stiff-man syndrome, characterized by chronically progressive stiffness and myoclonus; and (3) acute-onset and progressive encephalomyelitis with rigidity and myoclonus. ⋯ In paraneoplastic SPS, anti-amphiphysin antibodies have been shown in patients with breast cancer or small cell lung cancer. One case of mediastinal tumor with anti-gephyrin antibodies has also been reported. However, the roles of these autoantibodies in the pathomechanisms of SPS have not yet been elucidated.
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Alzheimer's disease (AD) is the most common type of dementia in the elderly and has multiple causes. The amyloid precursor protein (APP), presenilin1 (PSEN1), and presenilin2 (PSEN2) genes were identified as causative genes in a small number of families with autosomal dominant early-onset forms of AD (ADEOAD). However, many AD cases are sporadic and the late-onset type, which develops after 65 years of age. ⋯ Mutations in the causative genes of ADEOAD have been also observed in both familial LOAD and sporadic EOAD. Furthermore, new causative genes have been identifies in some families by whole genome or exome analyses. Considering the new common disease-rare variants hypothesis, personal genome sequence analysis is a potential strategy for identifying AD risk or protective genes.
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Compared to young people, elderly people are more likely to develop cognitive impairments associated with medications. Dementia and delirium (acute confusional state) are known to be associated with drug toxicity. ⋯ In addition, non-psychoactive drugs such as histamine H2 receptor antagonists, cardiac medications, and antibiotics may cause acute and chronic cognitive impairments. Early diagnosis and withdrawal of the offending agent is essential for treating drug-induced dementia and delirium.
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Pain is a common reason for seeking health care and chronic pain is a common comorbidity in psychiatric disorders. In clinical practice, we encounter many patients with chronic pain; however, before initiating pain treatment, we should conduct detailed analysis of psychiatric symptoms, such as perception, memory, thought and mood disturbances or behavioral problems. We should also determine the frequency of occurrence of mental disorders in patients with pain, especially those with chronic pain, such as in mood, anxiety, pain, personality, and developmental disorders, and dementia. Current understanding of the intricate relationship between chronic pain and psychiatric issues not only provides opportunities for designing appropriate treatment but also raises good and new questions for future pain research.
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Neuropathic pain syndromes are clinically characterized by spontaneous pain and evoked pain (hyperalgesia and allodynia). The optimal treatment approach for neuropathic pain is still under development because of the complex pathological mechanisms underlying this type of pain. ⋯ Central sensitization represents enhancement of the function of neuronal circuits in nociceptive pathways and is a manifestation of the remarkable plasticity of the somatosensory nervous system after nerve injury. This review highlights the pathological features of central sensitization, which develops because of (1) injury-induced abnormal inputs from primary afferents, (2) increase in the excitability of dorsal horn neurons, and (3) activated glial cell-derived signals.