Orthostatic hypotension (OH) and cognitive dysfunction impair ADL and QOL in Parkinson’s disease (PD), and many cases of PD with OH exhibit cognitive dysfunction. Postprandial hypotension (PPH), supine hypertension (SH) and nocturnal hypertension (NH) are also related to cognitive dysfunction. Regulation of blood pressure fluctuation is important for preventing deterioration of cognitive dysfunction.
Various autonomic dysfunctions are manifested in Parkinson’s disease (PD). These abnormalities can be detected by various imaging techniques. Recent studies have revealed that many kinds of non-motor symptoms, including autonomic dysfunction, are already present in patients with PD in the so-called premotor phase before the onset of motor symptoms. Advances in imaging techniques have made it possible to detect slight changes in the early phase of PD and these tests may lead to earlier diagnosis prior to the onset of motor symptoms.
The histological hallmark of Lewy body disease (LBD), which encompasses Parkinson’s disease, Parkinson’s disease with dementia, dementia with Lewy body disease, and pure autonomic failure with Lewy bodies, is neuronal α-synuclein aggregates called LBs and Lewy neurites. Neuronal α-synuclein aggregates are distributed throughout the nervous system, including not only the central nervous system (CNS) including sustantia nigra, locus ceruleus, dorsal motor nucleus of the vagus, intermediolateral nucleus of thoracic cord and hypothalamus, but also sympathetic ganglia, enteric nervous system, cardiac and pelvic plexuses, submandibular gland, adrenal medulla and skin. Involvement of central and peripheral autonomic nervous system is characteristic feature of LBD. Non-motor symptoms of LBD closely related to the pathological α-synuclein aggregates in central and peripheral autonomic nervous system. The long duration of pure autonomic failure with Lewy bodies may suggest that development of α-synuclein aggregates from peripheral autonomic nervous system to CNS is not always the same as those among LBD.
This review describes the features of sweating disturbance in Parkinson’s disease (PD) observed in our patients. 1) Sympathetic postganglionic sweating disturbance: Sweating function is less severely disturbed compared to the baroreceptor reflex and cardiac sympathetic nervous functions of patients with PD. 2) The effect of motor complications on sweat volume: the amount of sweat increases during wearing-off or dyskinesia in PD patients. 3) Treatment of paroxysmal excessive sweating: Zonisamide was effective on paroxysmal hyperhidrosis without side-effects in three cases of PD. 4) A case of Lewy body dementia with cold-induced hyperhidrosis: An 80-year-old man was admitted to our hospital. At 70 years old, he noticed paradoxical sweating on the upper body on sudden exposure to cold environments. On admission, he had cortical dysfunction with visual hallucinations and orthostaic hypotension. Hyperhidrosis occurred on the upper limbs and upper part of back when his lower extremities were cooled with cold water. Sweating dysfunction in Parkinson’s disease may be caused by impairment of the thermoregulation system including the hypothalamus.
Acute psychological stress evokes various vital reactions, including autonomic and endocrine responses. The autonomic response is thought to be originated from the defensive reaction and it has been classically reported that the centers for the defensive reaction are located in the lateral hypothalamic area (LHA) and the midbrain periaqueductal gray (PAG). The LHA is further divided into few areas including dorsomedial nucleus (DMN) and perifornical area (PeF) and artificial stimulations of these 2 areas evoke enhancement of respiratory function accompanying with pressor and tachycardic responses. In addition, there are subpopulation neuron groups participating in the autonomic functions in the DMN so that it has been shown that neurons in the DMN are not "command neuron". In contrast, stimulation of neurons in the dorsolateral PAG also increased the phrenic nerve activity and the sympathetic nerve activity (SNA) simultaneously. Furthermore, the increases in the phrenic burst and the SNA evoked by the PAG stimulation are mediated via neurons in the DMN. Thus, it is possible that neurons in the dorsolateral PAG are "command neurons" for the autonomic response evoked by the acute psychological stress.
Transient receptor potential ankyrin 1 (TRPA1), a member of the TRP superfamily, exists in sensory neurons such as trigeminal neurons innervating the nasal cavity and vagal neurons innervating the trachea and the lung. We examined the relative importance of TRPA1 located in the upper airway (nasal) and the lower airway (trachea/lungs) for triggering bradypnea in urethane-anesthetized mice. A vapor of one of the TRPA1-agonists, allyl isothiocyanate (AITC), was introduced by placing a piece of cotton paper soaked with AITC solution into the airline. AITC decreased the respiratory frequency when applied to the upper airway but not to the lower airway. No response was observed in TRPA1 knockout mice. Contribution of the olfactory nerve seemed minimal because olfactory bulbectomized wild-type mice showed a similar response to that of the intact mice. AITC-induced bradypnea seemed to be mediated, at least in part, by the trigeminal nerve because trigeminal ganglion neurons were activated by AITC as revealed by an increase in the phosphorylated form of extracellular signal-regulated kinase in the neurons. These data clearly show that trigeminal TRPA1 in the nasal cavity play an essential role in irritant-induced bradypnea.
It is essential for living organisms to maintain oxygen homeostasis in the body. Augmenting modulation of respiration during hypoxic stress plays an important role in the maintenance of oxygen homeostasis. The mechanism of hypoxic ventilatory responses has been so far investigated focusing on the respiratory neurons in the lower brainstem and the peripheral chemoreceptors as sensors of hypoxia. On the other hand, it has been recently suggested that astrocytes play an essential role in hypoxic ventilatory response as an oxygen sensor. The present article reviews the recent advances in ventilatory responsive mechanisms during hypoxic stress.
Asthma, a heterogeneous disease with varying molecular, biochemical, and cellular inflammatory features, is a respiratory psychosomatic disease, wherein patients can be influenced by psychosocial stress (stress), leading to unstable conditions. Stress is thought to trigger and exacerbate asthma by acting on the neuroendocrine and immune systems via the hypothalamus-pituitary-adrenal axis. Various mechanisms of stress-induced asthma have been proposed, such as the modification of adaptive immune response (T helper type1 cell (TH1) /TH2 imbalance) by stress hormones such as cortisol, adrenalin, and noradrenalin; the induction of airway hyperresponsiveness and mucus hyperproduction by neuropeptides; and steroid resistance due to the reduced expression of glucocorticoid receptors. However, the mechanism of psychosocial stress enhanced allergic inflammation in the airway is still unknown. Chen et al have reported that genomic or epigenomic regulation of ADCYAP1R1, one of the stress resilience-related genes, might be involved in the pathogenesis of childhood asthma. Stress Resilience is to maintain normal psychological and physical functioning, avoiding serious mental illness when exposed to unusual traumatic stress. There might be links between stress resilience and regulation of airway inflammation in asthma. Here, we discuss the future prospects of psychosomatic therapeutic strategies for respiratory psychosomatic disease, such as asthma based on stress resilience.
The storage and elimination of urine depend on the coordinated activity of urinary bladder and urethra. This coordination is mediated by a complex neural control system including the peripheral ganglia, the spinal cord and the brain. In recent year functional brain imaging has made remarkable progress, which made it possible to study the brain control mechanism directly. Healthy volunteers’ study revealed that the brain is activated during bladder filling particularly in the pontine micturition centre, the periaqueductal grey, hypothalamus, the anterior cingulate gyrus, and the prefrontal cortex. Moreover, functional brain imaging has been extended to pathological conditions. These approaches will shed further light on bladder function and dysfunction. In this mini-review, we present recent functional brain imaging findings relevant to micturition reflex, which would facilitate to help patients with bladder dysfunction.
Although micturition reflex is spino-bulbo-spinal reflex, because several higher micturition centers located above brainstem regulate micturition reflex, lower urinary symptoms are common in central nervous system disorders including neurodegenerative disease. It is well known that lower urinary tract symptoms are common in Parkinson’s disease. In this symposium, I will discuss how to treat lower urinary tract symptoms in Parkinson’s disease based on recently published guideline. Lower urinary tract dysfunctions are also prevalent and severe in multiple system atrophy which is usually difficult to differentiate from Parkinson’s disease in the early stage. I will discuss the characteristic features of lower urinary tract dysfunction in multiple system atrophy and utility of measuring post-void residual in differentiating Parkinson’s disease from multiple system atrophy.
The first step in diagnosis of cerebrospinal fluid hypovolemia is detailed hearing of the medical history. In particular, when cerebrospinal fluid hypovolemia has developed on the basis of migraine, tension type headache, medication overuse headache, it persistently listens to the medical history for multiple headaches, it unravels and it newly develops with the headache in the base. It is necessary to doubt the cerebrospinal fluid hypovolemia (usually chronic daily headache with no analgesic effect, orthostatic headache) in the medical history. History is also important in the differentiation of the postural tachycardia syndrome exhibiting orthostatic headache. Rest is necessary at the beginning of the onset of cerebrospinal fluid hypovolemia, but it is necessary to take measures such as to avoid rest as much as possible in the postural tachycardia syndrome, and it is important to differentiate between the two diseases. It is also important to deal with cases that change to postural tachycardia syndrome during the course of cerebrospinal fluid hypovolemia.
Differential diagnosis includes cerebrospinal fluid (CSF) hypovolemia and postural tachycardia syndrome (POTS). The pathomechanism of orthostatic headache due to POTS is still unknown. We performed RI cisternography in 6 POTS patients. All cases showed low CSF pressure. POTS accompanies sympathetic overactivity, which may be a cause of low CSF pressure.
Patients with REM sleep behavior disorder (RBD）had subjective symptoms of autonomic dysfunction compared with normal healthy controls. Scores of autonomic dysfunctions in patients with RBD were similar to those in patients with Parkinson’s disease (PD). Objectively, patients with RBD had orthostatic hypotension and abnormal heart rate variability similar to PD. Also, patients with RBD had similar degree of reduced uptake of MIBG scintigrams to those with PD. Subjective and objective intestinal dysfunction in patients with RBD is reported. The pathological lesion of RBD are thought as locus coeruleus that are associated with control of autonomic function. It is expected whether autonomic dysfunction in patients with RBD is predictive symptoms because it is paid attention to develop synuceinopathies in patients with RBD.
Patients with obstructive sleep apnea syndrome present with snoring, daytime sleepiness and morning headache and show impaired autonomic nervous sysytem activity during sleep, while central sleep apnea syndrome including Cheyne-Stokes respiration is associated with congestive heart failure and the brain lesions involving autonomic controls. Sleep-related breathing disorders are commonly observed in patients with Parkinson’s disease and related disorders showing autonomic symptoms. In this article, I review autonomic impairments in sleep-related breathing disorders with stroke and Parkinson’s disease and related disorders and those without neurological disorders.
We herein provide a historical review on the autonomic control of the cerebrospinal fluid (CSF) production. Benedikt (1875) discovered nerve endings on the choroid plexus of the human fourth ventricle, and traced it to the medulla oblongata, probably nucleus ambiguus. Since then, the dual innervation of the choroid plexus with the sympathetic and parasympathetic fibers was confirmed by means of classical histological staining (Stöhr, 1922; von Bakay, 1941; Tsuker, 1947) . Utilizing histofluorescence technique, Edvinsson et al. (1972, 73) proved that the choroid plexus received both adrenergic and cholinergic fibers. Passing route of the parasympathetic nerves, or cholinergic fibers, is unknown. Accumulated physiological studies revealed transient increase in the CSF production after sympathectomy (von Bakay, 1941; Hegedus et al., 1965; Lindvall et al., 1978) , and reduction in the csf production with stimulation of the sympathetic nerves (Dorigotti et al., 1972; Haywood, 1976; Lindvall et al., 1978) . However, conflicting results were shown in regard to the effects of sympathomimetic drugs on the CSF production, while most authors agreed that cholinergic drugs enhanced the CSF production. The reason why the problem is settled to date is because CSF is mixture of fluid from the choroid plexus and fluid from pia mater. The former is under the direct influence of the autonomic nerves, since the choroid plexus is a secretory organ like the sweat glands and the salivary glands. The latter may strongly depend on blood circulation, since water moves only by osmolar gradient between blood and CSF in the pia mater.
To understand the pathophysiological significance of patchy sweating in the thermoregulatory sweat test (TST), its incidence was assessed in the following disease groups: A, subjects without somatic and autonomic signs (Control: 120); B, idiopathic pure sudomotor failure (6); C, polyneuropathy (85); D, Ross or Adie syndromes (9); E, brainstem lesions (50); F, spinal lesions (51); G, Parkinson’s disease (PD:136); H, multiple system atrophy (MSA:39). Subjects with diabetes mellitus were excluded except in group C. Patchy sweating was not observed in A or E, but it’s incidence was 100 % in B, 63% in C, 78% in D, 2% in E, 51% in G, and 87% in H. These results suggest that patchy sweating in TST may indicate postganglionic sympathetic dysfunction or an impairment of the eccrine sweat glands. Furthermore, postganglionic sympathetic dysfunction may occur with high frequency not only in Parkinson’s disease but also in multiple system atrophy.
We report the case of a 42-year-old woman with gustatory parotid pain. Considering the presence of unilateral Horner and Harlequin syndrome, it was possible that the underlying condition was unilateral cervical sympathetic neuropathy. The patient experienced sharp pain in the region of the parotid gland on the cervical sympathetic neuropathy side immediately after gustatory stimulation using food, immediately followed by a spontaneous remission. Gustatory sweating was noted in the same area. Gustatory parotid pain was caused by denervation hypersensitivity of the sympathetic and parasympathetic receptors of the parotid gland due to cervical sympathetic neuropathy. It is possible that this phenomenon could be etiologically associated with increased pressure in the ducts and induced pain due to increased reflex salivary secretion via gustatory stimulation and strong contraction of myoepithelial cells. MRI revealed no abnormalities in the brain, neck, or chest, and the cause of sympathetic neuropathy remained unknown. Gustatory parotid pain has been reported as the first bite syndrome in the field of otolaryngology. This phenomenon was misquoted in a paper by Haubrich et al. (1986) and should be called “gustatory parotid pain” according to the first paper on this phenomenon by Gardner et al. (1955).