The autonomic nervous system and ischemic stroke: a reciprocal interdependence

Signs and symptoms of autonomic nervous system (ANS) dysfunction are frequently reported after ischemic or haemorrhagic stroke and in many cases they exhibit peculiar patterns in relationship with the site and the extension of brain lesion. However if an ANS disorder can cause or predispose to a stroke is far from being correctly known. Evidences in favor of a pathogenetic mechanism of an ANS dysfunction are reported for myocardial infarction and such data are likely to be appropriate also for atherothrombotic type of ischemic stroke. On the other hand, it is well known that many risk factors for this pathology are strongly correlated with an altered functioning of ANS so that a reciprocal interdependence between ANS and stroke can be hypothesized. This review points to evidence the possible relationship existing between these two conditions and suggests a quite different diagnostic and therapeutic approach to both on the basis of their pathogenetic mechanisms.     

Transient autonomic nervous system dysfunction during hyperacute stroke

Forty-four patients suffering a stroke for the first time were examined within 10 h of the onset of symptoms; the tests performed on their admission to hospital, and thereafter on the third and seventh day, were 24-h Holter EKG with spectral analysis of heart rate variability, evaluation of arterial blood pressure and the levels of catecholamine in the blood and 24-h urine. The dynamic EKG on admission revealed that 31 (70.5%) out of the 44 patients already had arrhythmia. These alterations were observed in 9 (75%) out of 12 haemorrhagic patients with a significant (P < 0.05) prevalence compared to 22 (68.8%) of the 32 ischaemic ones. Arrhythmia showed up in 16 (76.2%) out of 21 cases with right hemisphere lesions and in 12 (63.2%) out of 19 cases of left hemisphere lesions; this difference was also significant (P<0.05). Arrhythmia was still present in 19 (43.2%) patients after 3 days and only in 2 (6.5%) patients after 7 days. The spectral analysis parameters on admission and after 3 days were significantly (P < 0.05) modified in patients with stroke plus arrhythmia, compared to patients with stroke alone and to control subjects, whereas no further differences were observed on the seventh day. Moreover, the percentage of patients with arterial hypertension and high levels of catecholamine greatly decreased from the third day onwards. A transient autonomic nervous system imbalance with prevalent sympathetic activity may justify this cardiovascular impairment during the hyperacute phase of stroke.     

Autonomic nervous system function in myotonic dystrophy

Symptoms suggestive of dysautonomia are often reported in Myotonic Dystrophy (MD) patients. 12 patients with MD underwent cardiovascular function testing with assay of plasma noradrenaline (NA) and adrenaline (A) in supine rest condition and after orthostatic and cold stimulus. Statistical analysis showed no differences between MD patients and an age and sex matched control group.

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Sommario Nei pazienti affetti da Distrofia Miotonica si riscontrano spesso sintomi che suggeriscono un'alterata funzione del Sistema Nervoso Vegetativo. Abbiamo sottoposto a valutazione dei riflessi cardiovascolari e dei livelli ematici di catecolamine (adrenalina e noradrenalina) in condizioni basali, in psizione supina e dopo lo stimolo ortostatico e cold-pressor 12 pazienti affetti da Distrofia Miotonica. L'analisi statistica dei dati non ha mostrato differenze fra i pazienti e un gruppo di controllo comparabile per sesso ed età.

     

Autonomic dysfunction in different subtypes of multiple system atrophy

Multiple system atrophy (MSA) can clinically be divided into the cerebellar (MSA‐C) and the parkinsonian (MSA‐P) variant. However, till now, it is unknown whether autonomic dysfunction in these two entities differs regarding severity and profile. We compared the pattern of autonomic dysfunction in 12 patients with MSA‐C and 26 with MSA‐P in comparison with 27 age‐ and sex‐matched healthy controls using a standard battery of autonomic function tests and a structured anamnesis of the autonomic nervous system. MSA‐P patients complained significantly more often about the symptoms of autonomic dysfunctions than MSA‐C patients, especially regarding vasomotor, secretomotor, and gastrointestinal subsystems. However, regarding cardiovascular, sudomotor pupil, urogenital, and sleep subsystems, there were no significant quantitative or qualitative differences as analyzed by autonomic anamnesis and testing. Our results suggest that there are only minor differences in the pattern of autonomic dysfunction between the two clinical MSA phenotypes. © 2008 Movement Disorder Society     

Autonomic dysfunction in ischemic stroke with carotid stenosis

Xiong L, Leung HW, Chen XY, Han JH, Leung WH, Soo OY, Lau YL, Wong KS. Autonomic dysfunction in ischemic stroke with carotid stenosis.
Acta Neurol Scand: 2012: 126: 122–128.
© 2011 John Wiley & Sons A/S. Objectives – Impaired autonomic function is common in acute ischemic stroke. Previous limited studies have suggested that atherosclerosis may affect the distensibility of the carotid sinus and then impair the cardiovascular autonomic function. This study sought to investigate cardiovascular autonomic function in patients with ischemic stroke with carotid stenosis. Methods – Eighty‐five patients with ischemic stroke (58 ones without carotid stenosis and 27 ones with carotid stenosis, average 6 months after stroke onset) and 37 elderly controls were recruited. All performed Ewing’s battery autonomic function tests. Results – From Ewing’s battery of autonomic function tests, atypical, definite, or severe autonomic dysfunction was identified in 69.0% patients without carotid stenosis and 88.9% with carotid stenosis, with significant difference between the two groups, and the prevalence of autonomic dysfunction in both groups was higher than that in controls (21.6%). Patients with carotid stenosis showed impairment of all parasympathetic tests (all P < 0.05) and one of the sympathetic tests [Mean fall in systolic blood pressure (BP) on standing: P = 0.051], and those without carotid stenosis only showed impairment in two parasympathetic tests (Valsalva ratio: P = 0.014; heart rate response to deep breathing: P < 0.001) in comparison with controls. Patients with carotid stenosis had significantly more impairment than those without carotid stenosis in some autonomic parameters (Valsalva ratio: P < 0.05; mean fall in systolic BP on standing: P < 0.05). Conclusions – Cardiovascular autonomic function is impaired in patients with ischemic stroke, but patients with carotid stenosis show more severely impaired parasympathetic and sympathetic functions.     

Autonomic nervous system laboratories: a European survey

We present a questionnaire-based survey on methods adopted in European autonomic nervous system (ANS) laboratories in the year 2002. Seventy-nine laboratories from 16 countries in Western and Eastern Europe provided information on test methods, equipment, staff, educational programme and research activities. The results confirmed the anticipated heterogeneity of techniques used to investigate ANS disorders. However, cardiovascular (84.8%) and sudomotor (43.0%) tests were the most common. There were no standards regarding equipment, but devices used varied widely, in part commercially available, in part self-developed. Some ANS laboratories performed cardiovascular tests using standard EMG devices with implemented routines to measure heart rate variability. Many investigators used published normative data (75.4%). Most of the responders were involved in scientific work, half were active in education of trainees. A wide variation was found in number and profession of staff members. As more than 60% of questionnaires were returned by neurologists our results may be limited to neurological ANS laboratories. Given the wide variation of methods and equipment used in European ANS laboratories, minimal standards for routine ANS testing are desirable. Standards may help to compare results of diagnostic tests, evaluate equipment and test laboratory methods and commercial devices and set-up educational programmes.     

Autonomic nervous system arousal and cognitive functioning in bipolar disorder

Levy B. Autonomic nervous system arousal and cognitive functioning in bipolar disorder. Bipolar Disord 2012: 00: 000–000. © 2012 John Wiley & Sons A/S.Published by Blackwell Publishing Ltd. Objective: Previous theories about the etiology of cognitive dysfunction in bipolar disorder (BD) emphasized trait factors such as neurological impairment. State factors, other than mood symptoms, that may exacerbate functional deficits have not yet been considered. The purpose of this study was to examine autonomic nervous system (ANS) arousal following cognitive challenge. The study compared patients with BD and healthy controls (HC) in physiological measures and neuropsychological test scores. Methods: Thirty euthymic patients with BD and 22 HC completed the study. Participants completed mood [Beck Depression Inventory‐II (BDI‐II) and Young Mania Rating Scale (YMRS)], anxiety (State–Trait Anxiety Inventory), and substance abuse (Drug Abuse Screening Test–20 item and Alcohol Use Disorders Identification Test) measures. They were connected to an electrogram, a sensitive thermometer for measuring finger temperature, and electrodes that measure galvanic skin response. After a five‐min baseline measurement in a restful state, participants completed a computerized neuropsychological battery (CNS Vital Signs). Results: The group with BD reported significantly more mood symptoms (BDI‐II, t = 3.71, p < 0.001; YMRS, t = 6.73, p < 0.001) and scored higher on a measure of trait‐anxiety (State–Trait Anxiety Inventory, t = 2.91, p < 0.001) than HC. A multivariate analysis of variance revealed higher arousal on all physiological measures in the BD group relative to HC at baseline [F(3,48) = 13.1, p < 0.001] and during cognitive testing [F(3,48) = 11.3, p < 0.001]. The increase in physiological arousal from a restful state to the time of testing was higher for the BD group [F(3,37) = 8.06, p < 0.001]. With respect to cognitive data, HC scored higher than patients with BD across the measures of memory (F = 8.5, p < 0.001), sustained (F = 9.5, p < 0.001) and complex (F = 2.7, p < 0.04) attention, processing speed (F = 10.0, p < 0.001), reaction time (F = 7.8, p < 0.001), cognitive flexibility (F = 19.7, p < 0.001), working memory (F = 10.8, p < 0.001), and social acuity (F = 5.7, p < 0.01), with partial eta‐squared from 0.18 to 0.62. Correlational analysis revealed significant associations between various cognitive test scores and changes in physiological arousal from baseline to testing (?0.59 ≤ r ≤ 0.22). Conclusions: Relative to HC, patients with BD experience larger changes in ANS arousal between a restful baseline and cognitive testing, and achieve lower cognitive test scores. Further research is needed to determine whether acute physiological symptoms of anxiety directly compromise cognitive functioning in BD.     

Autonomic nervous system activity in normotensive subjects with a family history of hypertension

Abstract This study was designed to address alterations in autonomic nervous system activity in normotensive subjects with a family history of hypertension. We compared the autonomic nervous system activity in 59 normotensives with a family history of hypertension and 46 normotensives with no family history of hypertension. Skin blood flow was measured using laser-Doppler method on the nailfold skin in the resting condition, during systemic cooling and during upright tilting. Finger blood pressure, pulse and ECG were monitored by a finapres device. Heart rate, systolic pressure and microvascular flow power spectral analyses were performed using fast Fourier transformation. Baroreflex sensitivity was estimated with the sequence method. Compared to the control group, normotensives with a family history of hypertension showed significantly higher systolic pressure, decreased proportion and area of the high-frequency band of the heart rate variability power spectrum and reduced baroreflex sensitivity in the resting condition as well as a decreased proportion and area of the high-frequency band of the heart rate variability power spectrum during systemic cooling. We also proved a different time course of baroreflex sensitivity during upright tilting in the two groups. In contrast, we did not find any significant differences in the parameters of systolic pressure and microvascular variability power spectra between the two groups. Our results indicate that even normotensives with a family history of hypertension exhibit an increased ratio of sympathetic to parasympathetic activity at the cardiac level; however, they do not show any alteration of the vascular sympathetic reactivity.     

Autonomic nervous system activity and psychiatric severity in schizophrenia

Aims:  Schizophrenia patients have a mortality rate two to three-fold higher than that of the general population. Despite the disorder's widespread recognition, how and to what extent autonomic nervous system (ANS) activity contributes to schizophrenia remains inconclusive. The aim of the present study, therefore, was to determine the extent of ANS activity depression with respect to healthy, well-matched control subjects and the severity of psychiatric disorders as determined using the Global Assessment of Functioning (GAF) scale among schizophrenia patients with special reference to antipsychotic dose.
Methods:  This study included 71 schizophrenia patients and 72 healthy controls. ANS activity was assessed by means of heart rate variability power spectral analysis.
Results:  ANS-related spectral parameters were three–four-fold lower in the patients compared to the control group ( P  < 0.01). Furthermore, when the patients without cardiovascular complications were classified according to GAF score, overall ANS ( P  = 0.033) and parasympathetic nervous system (PNS) activity ( P  = 0.025) were significantly reduced in the low-GAF as compared to the high-GAF group. Partial correlation analyses demonstrated that ANS activity was significantly correlated with GAF score while statistically eliminating the effects of age, gender, body mass index, antipsychotic dose, and lipid profiles of the patient population.
Conclusion:  The significantly lower ANS activity in the low-GAF group suggests that such autonomic functional depression could be associated with the severity of schizophrenia. The present data further imply that schizophrenia patients with more depressed overall ANS and PNS activity might encounter increasing risks for cardiovascular events such as sudden death.     

Autonomic failure: observations of a physician–patient

Here I describe the clinical symptoms of autonomic failure that I began experiencing when I turned 80, a treatment combination that has been remarkably effective, and the recent finding of high titers of antibodies against the ganglionic nicotinic receptor.     

Autonomic nervous system involvement in a new CMT2B family

We describe the first Italian family affected by CMT2B carrying a Val162Met substitution in the RAB7 gene. The clinical and electrophysiological features of our family are similar to those of previously reported families with RAB7 mutations, also for the higher occurrence of ulcers in males. However, in this family we evaluated the autonomic nervous system, never investigated in CMT2B, by means of skin biopsy and sudomotor and cardiovascular tests. Our findings provide both pathological and functional evidence of autonomic nervous system involvement in CMT2B and expand the phenotypic characterization of CMT2B disease.     

The role of microbiome in central nervous system disorders

Mammals live in a co-evolutionary association with the plethora of microorganisms that reside at a variety of tissue microenvironments. The microbiome represents the collective genomes of these co-existing microorganisms, which is shaped by host factors such as genetics and nutrients but in turn is able to influence host biology in health and disease. Niche-specific microbiome, prominently the gut microbiome, has the capacity to effect both local and distal sites within the host. The gut microbiome has played a crucial role in the bidirectional gut–brain axis that integrates the gut and central nervous system (CNS) activities, and thus the concept of microbiome–gut–brain axis is emerging. Studies are revealing how diverse forms of neuro-immune and neuro-psychiatric disorders are correlated with or modulated by variations of microbiome, microbiota-derived products and exogenous antibiotics and probiotics. The microbiome poises the peripheral immune homeostasis and predisposes host susceptibility to CNS autoimmune diseases such as multiple sclerosis. Neural, endocrine and metabolic mechanisms are also critical mediators of the microbiome–CNS signaling, which are more involved in neuro-psychiatric disorders such as autism, depression, anxiety, stress. Research on the role of microbiome in CNS disorders deepens our academic knowledge about host-microbiome commensalism in central regulation and in practicality, holds conceivable promise for developing novel prognostic and therapeutic avenues for CNS disorders.     

The role of IL-15 in central nervous system disorders

IL-15 is a proinflammatory cytokine. It is produced by activated blood monocytes, macrophages, dendritic cells, and activated glial cells. It promotes T-cell proliferation, induction of cytolytic effector cells including natural killer and cytotoxic cells and stimulates B-cell to proliferate and secrete immunoglobulins. Little information is available on the exact role of IL-15 in the neurological diseases. Microglial cells are the main regulators of both innate and adaptive immune responses in the central nervous system (CNS). IL-15 may be involved in the inflammatory reactions and microglial activation of some common CNS disorders such as multiple sclerosis, Alzheimer's and Parkinson's disease, but its exact role in their pathogenesis is not clear.     

Autonomic Dysfunction in Sleep Disorders: From Neurobiological Basis to Potential Therapeutic Approaches

Sleep disorder has been portrayed as merely a common dissatisfaction with sleep quality and quantity. However, sleep disorder is actually a medical condition characterized by inconsistent sleep patterns that interfere with emotional dynamics, cognitive functioning, and even physical performance. This is consistent with sleep abnormalities being more common in patients with autonomic dysfunction than in the general population. The autonomic nervous system coordinates various visceral functions ranging from respiration to neuroendocrine secretion in order to maintain homeostasis of the body. Because the cell population and efferent signals involved in autonomic regulation are spatially adjacent to those that regulate the sleep-wake system, sleep architecture and autonomic coordination exert effects on each other, suggesting the presence of a bidirectional relationship in addition to shared pathology. The primary goal of this review is to highlight the bidirectional and shared relationship between sleep and autonomic regulation. It also introduces the effects of autonomic dysfunction on insomnia, breathing disorders, central disorders of hypersomnolence, parasomnias, and movement disorders. This information will assist clinicians in determining how neuromodulation can have the greatest therapeutic effects in patients with sleep disorders.     

Sexual dysfunction in stroke patients

Objectives – A marked decline in sexual activity has been reported in stroke patients. Little information, however, is available on clinical correlates of sexual dysfunction, changes in the sexual life of spouses of stroke patients, and abnormalities of nocturnal penile erections. Material and methods – In this prospective 6-month follow-up study, we assessed the impact of stroke on libido, sexual arousal, coital frequency and satisfaction with sexual life in 50 stroke patients (38 men, 12 women, aged 32 to 65 years) and in their spouses. We also measured nocturnal penile erections of the male patients using a strain gauge attached around the penis. Results – All the analyzed aspects of sexuality, i.e., libido, coital frequency, erection, ejaculation, vaginal lubrication, orgasm and satisfaction with sexual life, were commonly decreased as a consequence of stroke both in the patients and in their spouses. Fourteen (28%) patients at 2 months post-stroke and 6 (14%) patients at 6 months had ceased having sexual intercourse. Nocturnal erections at 2 months post-stroke were normal in 17 (45%) of the 38 male patients and impaired in 21 (55%) patients, but all of the patients had some nocturnal erections. Sexual dysfunction correlated significantly ( P <0.05) with the presence of the sensory hemisyndrome. Conclusions – Sexual dysfunction and dissatisfaction with sexual life seems to be common both in male and female stroke patients and in their spouses. Decreased libido, sexual arousal and satisfaction are related particularly to the presence of the hemisensory syndrome. The etiology for sexual dysfunction after stroke is multifactorial including both organic and psychosocial factors.     

Autonomic dysfunction in Alzheimer's disease

Twenty-nine patients fitting the NINCDS-ADRDA criteria of Alzheimer's disease participated in a study of autonomic functions. A number of tests on parasympathetic and sympathetic functions were made. Eighteen of the patients were tested a second time one year later. Fifteen healthy subjects with no family history of dementia disorders served as controls. Compared to the controls, the patients showed signs suggesting autonomic dysfunction affecting parasympathetic, as well as vasomotor sympathetic, functions.     

Autonomic function in patients with chronic fatigue syndrome

Subtle signs of autonomic dysfunction and orthostatic intolerance have been reported in patients with chronic fatigue syndrome (CFS). To assess cardiovascular autonomic function noninvasively in an unselected group of patients with CFS, we examined responsiveness to several cardiovascular reflex tests in 37 CFS patients and 38 healthy control subjects. Blood pressure and heart rate (HR) were recorded continuously by a Finapres device before and during forced breathing, standing up, Valsalva maneuver, and sustained handgrip exercise (HG). In addition, a mental arithmetic test was carried out and questionnaires to assess the severity of CFS symptoms were completed. At rest, there were no significant differences in blood pressure or in HR between the two groups. The in- and expiratory difference in HR tended to be lower in CFS patients (28.4±10.5 beats) than in healthy controls (32.2±9.5) (p=0.11). The maximal increase in HR during standing up was not significantly different between the CFS group (37.6±8.9 beats) and the control group (40.2±8.9 beats). There were no significant differences between both groups with regard to the Valsalva ratio, but the systolic and diastolic blood pressure responses were significantly larger in CFS patients, despite the fact that many CFS patients were not able to sustain the Valsalva maneuver. The HR response to MA was significantly less in the CFS group (22.6±9.9) than in the control group (29.5±16.7) (p<0.05), suggesting impaired cardiac sympathetic responsiveness to mental stress. The lower HR responses could not be explained by the level of concentration in the CFS group. During HG exercise, the hemodynamic responses were lower in the CFS group than in the control group, but this might be attributed to the lower level of muscle exertion in CFS patients. There were no significant differences between CFS patients with and without symptoms of autonomic dysfunction regarding the hemodynamic responses to the cardiovascular reflex tests. The findings of the study suggest that there are no gross alterations in cardiovascular autonomic function in patients with CFS.