Dyautonomia precedes the onset of motor symptoms in patients with Parkinson’s disease (PD). Therefore, it is useful biomarker predicting disease onset. Accumulating evidence suggests sympathetic nervous system may be a key route for α-synuclein pathology propagation as well as vagus nerve. Cardiovascular autonomic failure includes orthostatic hypotension (OH), postprandial hypotension, supine hypertension and nocturnal hypertension. OH is attributed to both peripheral and central sympathetic nervous failure, and is closely related to the development of cognitive impairment in patients with PD. It is necessary to develop a therapeutic strategy for OH in consideration of supine hypertension. Nonpharmacological treatment such as abdominal compression and head-up sleeping is crucial for the treatment of OH and SH. As for pharmacological treatment, combined treatment of OH with L-noradrenaline precursor and cholinesterase inhibitors seems to be clinically useful because cholinesterase inhibitors enhance the function of sympathetic preganglionic nerve fibers.

Brown adipose tissue (BAT) is a site of adaptive thermogenesis and contributes to the control of body temperature in small rodents. In humans, BAT thermogenesis is acutely activated by cold exposure; moreover, cold exposure generates long-term effects, such as increased BAT activity and mass, involving in cold adaptation. Activation and recruitment of BAT results in an increase in energy expenditure, a decrease in body fat mass, and a concomitant increase in insulin sensitivity in humans. Moreover, recent studies in mice have yielded insights in the regulation of thermogenic activity of BAT. These include identification of branched-chain amino acids as a crucial substrate for BAT thermogenesis as well as phycological stress that is capable of activating BAT thermogenesis. The major challenges remain elucidating of factors that determines metabolic cell fate of brown adipocytes as well as translating these preclinical scientific advances to humans. Pursuing these issues is relevant to discovering novel therapeutic approaches to modulating body temperature and energy homeostasis and to treating insulin resistance and various stress-related disorders..

Amyotrophic lateral sclerosis (ALS) is thought to be a simple disease in which upper and lower motor neurons are selectively involved; however, there are some reports of autonomic dysfunction, which is outside the motor system. However, there is a lack of evidence to clearly explain autonomic neuropathy in ALS pathologically. it is assumed that autonomic dysfunction is caused by the balance between the central autonomic fiber network, including the hypothalamus, and the intermediate lateral nucleus of the spinal cord. The maintenance of lower limb motor function was observed in the cybernic treatment for ALS. The long-term effects including the duration of ADL and prolongation of survival are future issues.

Since around 2000, evidence has been accumulated that Ehlers-Danlos syndrome (EDS) highly co-occurs with postural tachycardia syndrome (PoTS) and/or cerebrospinal fluid (CSF) hypovolemia. The essential matters for discussion on the reason of this comorbidity is as follows: (1) The overwhelming majority cases of EDS are hypermobility type, which exhibit joint hypermobility only. (2) PoTS is characterized by excessive venous blood pooling in the lower part of the body while standing, but typical PoTS patients also exhibit emotional disturbance, e. g. anxiety and depression. Most authors have attributed such emotional disturbance to centripetal input of chronic pain into the central autonomic network (CAN). (3) Most cases of CSF hypovolemia have CSF leak, but decreased production in CSF to compensate the leak is essentially involved in the development of CSF hypovolemia. Concerning the reason of the comorbidity of EDS, PoTS and CSF hypovolemia, some authors have suggested that EDS induces PoTS or CSF hypovolemia; venous hyperextensibility may contribute to the excessive blood pooling, and fragility of the connective tissue may induce CSF leak. However, the majority cases of EDS are lacking venous hyperextensibility and tissue fragility. Recently, Sharp, Critchley, and Eccles (2021) provided a rational hypothesis for the association of EDS and PoTS; patients with both conditions have altered interoception, which produces abnormal emotion and autonomic activities in the CAN. Patients with EDS have altered input of deep sensation into the CAN persistently from periods of development. We suggest that altered interoception is underlying in EDS, PoTS, and CSF hypovolemia.

Autoimmune diseases are among the most common causes of autonomic dysfunction. Autoimmune autonomic ganglionopathy (AAG) is a type of immune-mediated autonomic neuropathy. Around 50% of AAG cases are characterized by high levels of autoantibodies against ganglionic acetylcholine receptor (gAChR). As gAChR is known to mediate synaptic transmission in all autonomic ganglia, anti-gAChR antibodies inhibit this synaptic transmission, resulting in widespread autonomic dysfunction. Flow cytometric analysis of anti-gAChR antibody-mediated immunomodulation and live cell-based assays targeting the extracellular epitopes of the receptor have been reported as new approaches to measure the levels of this antibody and are expected to improve the specificity of antibody detection. The clinical presentation of anti-gAChR antibody-negative AAG cases is similar to that of anti-gAChR antibody-positive cases; however, the underlying mechanisms are still not fully understood. In anti-gAChR antibody-negative cases, intravenous methylprednisolone therapy is more effective than intravenous immunoglobulin therapy or plasma exchange, suggesting the involvement of cell-mediated immunity. Epidemiological studies, including the analysis of treatment efficacy in large numbers of patients, are needed. In this article we provide a review of our current understanding of anti-gAChR antibody-positive and -negative AAG and recent developments in the detection of anti-gAChR antibodies. In addition, acute autonomic and sensory neuropathy, which should be differentiated from AAG, is also outlined.

Manual therapy for the sole of the foot is called by various names such as “reflexology” and “foot zone therapy”, and is performed all over the world as one of complementary and alternative medicines. However, few basic medical studies have been performed on the mechanism of its effect, and the existence of the reflex that is the origin of the name has not been confirmed. Therefore, we performed experiments to confirm the neural mechanism and the existence of specific reflex zones using the response of pressure stimulation to localized parts of the sole to blood pressure, heart rate, and gastric pressure as indexes. From the results of denervation of the afferent and efferent tracts, it was clarified that the sole stimulus was input from the somatosensory nerve and elicited a reflex response with multiple autonomic nerves as the efferent tract. However, the existence of zones could not be clarified.