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Background: According to Braak staging of Parkinson's disease (PD), detection of autonomic dysfunction would help with early diagnosis of PD. Objective: To determine whether the autonomic nervous system is involved in the early stage of PD, we evaluated cardiovascular and sudomotor function in early untreated PD patients. Methods: Orthostatic blood pressure regulation, heart rate variability, skin vasomotor function, and palmar sympathetic sweat responses were examined in 50 early untreated PD patients and 20 healthy control subjects. Results: The mean decrease in systolic blood pressure during head-up tilt in PD patients was mildly but significantly larger than in controls (p = 0.0001). There were no differences between the 2 groups in heart rate variability, with analysis of low frequency (LF; mediated by baroreflex feedback), and high frequency (HF; mainly reflecting parasympathetic vagal) modulation. However, LF/HF, an index of sympatho-parasympathetic balance, was lower in the PD group than in controls (p = 0.02). Amplitudes of palmar sweat responses to deep inspiration (p = 0.004), mental arithmetic (p = 0.01), and exercise (p = 0.01) in PD patients were lower than in controls, with negative correlations with motor severity. Amplitudes of palmar skin vasomotor reflexes in PD patients did not differ from controls. Conclusions: Our study indicates impairment of sympathetic cardiovascular and sudomotor function with orthostatic dysregulation of blood pressure control, reduced LF/HF and reduction in palm sweat responses even in early untreated PD patients. [ABSTRACT FROM AUTHOR]

Postural tachycardia syndrome (POTS) is a poorly understood but important cause of orthostatic intolerance resulting from cardiovascular autonomic dysfunction. PoTS is distinct from the syndromes of autonomic failure usually associated with orthostatic hypotension, such as pure autonomic failure and multiple system atrophy. Individuals affected by PoTS are mainly young (aged between 15 years and 40 years) and predominantly female. The symptoms--palpitations, dizziness and occasionally syncope--mainly occur when the patient is standing upright, and are often relieved by sitting or lying flat. Common stimuli in daily life, such as modest exertion, food ingestion and heat, are now recognized to be capable of exacerbating the symptoms. Onset of the syndrome can be linked to infection, trauma, surgery or stress. PoTS can be associated with various other disorders; in particular, joint hypermobility syndrome (also known as Ehlers- Danios syndrome hypermobility type, formerly termed Ehlers-Danlos syndrome type III). This Review describes the characteristics and neuroepidemiology of POTS, and outlines possible pathophysiological mechanisms of this syndrome, as well as current and investigational treatments. [ABSTRACT FROM AUTHOR]

Abstract: Empathy for the emotions of others may require simulatory engagement of corresponding autonomic arousal states. We tested the hypothesis that disruption of autonomic control impairs the ability to empathize emotionally with others. Fifteen patients with primary autonomic failure showed attenuated scores on the Mehrabian Balanced Emotional Empathy Scale (BEES), compared to both younger and older controls. This effect was not accounted for by age, gender, mood state or functional disability. These early observations provide preliminary evidence for a direct contribution of autonomic responsivity to the ‘higher-order’ social cognitive process of empathy, and may inform the dynamics of supportive care. [Copyright &y& Elsevier]

Neurogenic orthostatic hypotension is a cardinal feature of generalised autonomic failure and commonly is the presenting sign in patients with primary autonomic failure. Orthostatic hypotension can result in considerable morbidity and even mortality and is a major management problem in disorders such as pure autonomic failure, multiple system atrophy and also in Parkinson’s disease. Treatment is ideally two pronged, using non-pharmacological and pharmacological measures. Drug treatment ideally is aimed at restoring adequate amounts of the neurotransmitter noradrenaline. This often is not achievable because of damage to sympathetic nerve terminals, to autonomic ganglia or to central autonomic networks. An alternative is the use of sympathomimetics (that mimic the effects of noradrenaline, but are not identical to noradrenaline), in addition to other agents that target physiological mechanisms that contribute to blood pressure control. L-threo-dihydroxyphenyslerine (Droxidopa) is a pro-drug which has a structure similar to noradrenaline, but with a carboxyl group. It has no pressor effects in this form. It can be administered orally, unlike noradrenaline, and after absorption is converted by the enzyme dopa decarboxylase into noradrenaline thus increasing levels of the neurotransmitter which is identical to endogenous noradrenaline. Experience in Caucasians and in Europe is limited mainly to patients with dopamine beta hydroxylase deficiency. This review focuses on two studies performed in Europe, and provides information on its efficacy, tolerability and safety in patients with pure autonomic failure, multiple system atrophy and Parkinson’s disease. It also addresses the issue of whether addition of dopa decarboxylase inhibitors, when combined with l-dopa in the treatment of the motor deficit in Parkinson’s disease, impairs the pressor efficacy of Droxidopa. [ABSTRACT FROM AUTHOR]

The autonomic nervous system has a craniosacral parasympathetic pathway (fig 1) and supplies every organ in the body. It influences localised organ function and also integrated processes that control vital functions such as arterial blood pres- sure and body temperature. There are specific neurotransmitters in each system that influence ganglionic and post-ganglionic function (fig 2). The symptoms and signs of autonomic disease cover a wide spectrum (table 1) that vary depending upon the aetiology (tables 2 and 3). In some they are localised (table 4). Autonomic disease can result in underactivity or overactivity, sympathetic adrenergic failure causes orthostatic (postural) hypotension and in the male ejaculatory failure, while sympathetic cholinergic failure results in anhidrosis; parasympathetic failure causes dilated pupils, a fixed heart rate, a sluggish urinary bladder, an atonic large bowel and, in the male, erectile failure. With autonomic hyperactivity, the reverse occurs. In some disorders, particularly in neurally mediated syncope, there may be a combination of effects, with bradycardia caused by parasympathetic activity and hypotension resulting from withdrawal of sympathetic activity. The history is of particular importance in the consideration and recognition of autonomic disease, and in separating dysfunction that may result from non-autonomic disorders. [ABSTRACT FROM AUTHOR]

The management of autonomic disease encompasses a number of aspects. Of immediate and practical importance is alleviation of symptoms. The ideal is to rectify the autonomic deficit and cure the underlying disorder. Autonomic disease often involves various systems, and principles in relation to management of the major clinical features are provided. Specific aspects will vary in different diseases and always should be directed to the needs of the individual. [ABSTRACT FROM AUTHOR]

The degree to which perceptual awareness of threat stimuli and bodily states of arousal modulates neural activity associated with fear conditioning is unknown. We used functional magnetic neuroimaging (fMRI) to study healthy subjects and patients with peripheral autonomic denervation to examine how the expression of conditioning-related activity is modulated by stimulus awareness and autonomic arousal. In controls, enhanced amygdala activity was evident during conditioning to both “seen” (unmasked) and “unseen” (backward masked) stimuli, whereas insula activity was modulated by perceptual awareness of a threat stimulus. Absent peripheral autonomic arousal, in patients with autonomic denervation, was associated with decreased conditioning-related activity in insula and amygdala. The findings indicate that the expression of conditioning-related neural activity is modulated by both awareness and representations of bodily states of autonomic arousal. [Copyright &y& Elsevier]

SummaryBackground Syncope is a common disorder that is potentially disabling and affects both young and old. Once neurological, cardiological, and metabolic causes have been excluded, there remains a group in which diagnosis is unclear; some may have an autonomic basis. We therefore did a retrospective study on consecutive patients referred to our tertiary referral autonomic centres between 1992 and 1998 with recurrent syncope and presyncope, in whom non-autonomic causes, before referral, had been sought and excluded. The object was to find out whether autonomic investigation helped diagnosis.Methods Data from case notes and from the autonomic database on 641 patients were analysed. Syncopal patients with a known or provisional diagnosis of autonomic failure were excluded from analysis. The role of screening tests in establishing or excluding an autonomic cause was assessed. Response to additional autonomic tests (such as head-up tilt with or without venepuncture, and food challenge and exercise) was documented. Some patients underwent further testing if non-autonomic neurological, psychiatric, and other disorders were considered.Findings Screening autonomic function tests indicated orthostatic hypotension and confirmed chronic autonomic failure in 31 (4.8%) patients. Neurally mediated syncope was diagnosed in 279 (43.5%) on the basis of clinical features and autonomic testing. Most had vasovagal syncope (227 [35%]); other causes included carotid sinus hypersensitivity (37 [5.8%]), and a group of 15 (2.3%) were associated with rarer causes such as micturition and swallowing. Miscellaneous cardiovascular causes (systemic hypotension, arrhythmias), or drugs, contributed to syncope in 53 (8.3%). Non-autonomic neurological causes included vestibular dysfunction (32 [5%]) and epilepsy (11 [1.7%]). In 56 (8.7%) a psychiatric cause was thought to be contributory. In 179 (27.9%), syncope was of unknown cause.Interpretation In recurrent syncope and presyncope, when cardi... [ABSTRACT FROM AUTHOR]

Offers information about postural hypotension. Definition of postural hypotension; Causes of the condition; Clinical signs of postural hypotension; Pharmacological and nonpharmacological treatment.

Background: The oral ingestion of water increases seated blood pressure in chronic autonomic failure although the mechanisms of this effect remain unclear. Recent studies in normal subjects suggest that oropharyngeal stimulation during swallowing may be of greater importance in causing a rise in blood pressure (BP) than the gastric effects of water. We therefore assessed the haemodynamic effects of water instilled directly into the stomach via a gastrostomy tube in pure autonomic failure (PAF). Methods: The subject had longstanding (>20 years) PAF. A gastrostomy tube had been previously placed because of dysphagia. Distilled water (480 ml) was instilled in the seated position with BP and heart rate (HR) measured over the following 40 min while the subject remained seated. Systolic and diastolic BP (SBP and DBP) and heart rate (HR) were recorded intermittently every 3 min with a Dinamap automated syphgmomanometer and continuously using a Portapres device. Subsequent model flow analysis of the Portapres data provided beat-to-beat estimates of cardiac output, stroke volume, and total peripheral resistance (TPR). Subjective orthostatic symptoms were recorded before and after water. Results: Seated SBP and DBP increased after water instillation with increases first noted between 5 and 8 min after the water had been instilled. The BP remained elevated until 35 min post water increase over baseline being +36.5 mm Hg SBP and +24.3 mm Hg DBP. HR, cardiac output, and stroke volume remained unchanged during the study. Total peripheral resistance (TPR) increased post water. These results are similar to those reported in a recent study involving oral ingestion of 480 ml of water in PAF subjects. Conclusions: Instilling water directly into the stomach in a patient with PAF resulted in similar haemodynamic responses to those seen when water is taken orally. Thus, oropharyngeal factors and swallowing do not appear to be essential in the generation of the water pressor effect in autonomic failure. [Copyright &y& Elsevier]

Nocturnal polyuria is a common symptom in autonomic failure. In patients with urinary bladder involvement nocturia can be troublesome and considerably add to their disabilities. Nocturnal diuresis and natriuresis account for overnight weight loss that appears to worsen the extent of, and symptoms resulting from, orthostatic hypotension in the morning. Some patients are considerably incapacitated and find it difficult to function until late morning; even a light breakfast and minimal exertion can substantially worsen symptoms. This partly may be helped by the use of head-up tilt at night. Nocturnal polyuria probably results in redistribution of body fluids, reducing central filling pressure, stroke volume, cardiac output and thus blood pressure. This is consistent with recent studies confirming that orthostatic hypotension is worse in the morning and indicating that there are greater changes in stroke volume and cardiac output on standing in the morning compared to the evening. The reduction in overnight fluid loss presumably reverses this cycle of events, thus reducing morning orthostatic hypotension.

Focuses on two studies by Jens Jordan and colleagues which report that oral water has substantial pressor effects. Effect that drinking water has on the blood pressures of healthy individuals, as well as those with orthostatic hypotension, Parkinson's disease and autonomic failure; Factors influencing blood pressure; Conclusion that the precise mechanisms causing the pressor response to oral water, especially in patients with sympathetic denervation, still remain to be determined.

Examines the hypotensive and sedative effects of insulin in treating autonomic failure. Rate of blood pressure in patients after insulin administration; Determination of heart rate after hypoglycemia; Standard practice to reverse hypoglycemia.

Abstract: Background: Supine hypertension and post-prandial hypotension are associated with chronic autonomic failure, and may prove resistant to treatment. We determined if the hypotensive effects of food could be utilised to reduce supine hypertension in pure autonomic failure (PAF). Methods: A subject with long-standing PAF, documented supine hypertension and post-prandial hypotension had a gastrostomy tube placed for dysphagia. We compared 24-hour ambulatory blood pressure recordings before and after nocturnal gastrostomy feeding. Results: Gastrostomy feeding was associated with resolution of supine hypertension and normalization of circadian BP rhythm. Conclusions: Gastrostomy feeding at night may help reduce supine hypertension in autonomic failure. [Copyright &y& Elsevier]

Examines the effect of desmopressin on patients with autonomic failure. Reduction of nocturnal polyuria; Decline of overnight weight loss; Increase of supine blood pressure.

Describes a case on therapeutic venous infarction of an aldosterone producing adenoma in a fifty-year-old female. Diagnosis of aldosteronism; Description of treatment; Caution for tumor embolism.

Discusses the occurrence of Reynaud's phenomenon in patients with sympathetic denervation due to primary chronic autonomic failure. Confirmation that Raynaud's phenomenon and cold sensitivity in the hands and feet commonly occur in patients with sympathetic denervation; Link established between sympathetic activation and cold sensitivity in Raynaud's phenomenon.

Reports on the frequency of family history in vasovagal syncope. Details about the study of 132 consecutive patients; The monitoring of continuous blood pressure and heart rate; Age distribution of the onset of patients with vasovagal syncope; The conclusion that family history may be of value in recognition and diagnosis of vasovagal syncope.

A response by Dr. Robert D. Hoeldtke to a letter to the editor about his article "Nitrosative stress in early type I diabetes," in the previous issue is presented.

Background: The cardiomyopathic and neuropathic phenotype of hereditary transthyretin amyloidosis are well recognized. Cardiovascular autonomic dysfunction is less systematically and objectively assessed.Autonomic and clinical features, quantitative cardiovascular autonomic function, and potential autonomic prognostic markers of disease progression were recorded in a cohort of individuals with hereditary transthyretin amyloidosis and in asymptomatic carriers of TTR variants at disease onset (T0) and at the time of the first quantitative autonomic assessment (T1). The severity of peripheral neuropathy and its progression was stratified with the polyneuropathy disability score.A total of 124 individuals were included (111 with a confirmed diagnosis of hereditary transthyretin amyloidosis, and 13 asymptomatic carriers of TTR variants). Symptoms of autonomic dysfunction were reported by 27% individuals at T0. Disease duration was 4.5 ± 4.0 years [mean ± standard deviation (SD)] at autonomic testing (T1). Symptoms of autonomic dysfunction were reported by 78% individuals at T1. Cardiovascular autonomic failure was detected by functional testing in 75% individuals and in 64% of TTR carriers. Progression rate from polyneuropathy disability stages I/II to III/IV seemed to be shorter for individuals with autonomic symptoms at onset [2.33 ± 0.56 versus 4.00 ± 0.69 years (mean ± SD)].Cardiovascular autonomic dysfunction occurs early and frequently in individuals with hereditary transthyretin amyloidosis within 4.5 years from disease onset. Cardiovascular autonomic failure can be subclinical in individuals and asymptomatic carriers, and only detected with autonomic function testing, which should be considered a potential biomarker for early diagnosis and disease progression.Methods: The cardiomyopathic and neuropathic phenotype of hereditary transthyretin amyloidosis are well recognized. Cardiovascular autonomic dysfunction is less systematically and objectively assessed.Autonomic and clinical features, quantitative cardiovascular autonomic function, and potential autonomic prognostic markers of disease progression were recorded in a cohort of individuals with hereditary transthyretin amyloidosis and in asymptomatic carriers of TTR variants at disease onset (T0) and at the time of the first quantitative autonomic assessment (T1). The severity of peripheral neuropathy and its progression was stratified with the polyneuropathy disability score.A total of 124 individuals were included (111 with a confirmed diagnosis of hereditary transthyretin amyloidosis, and 13 asymptomatic carriers of TTR variants). Symptoms of autonomic dysfunction were reported by 27% individuals at T0. Disease duration was 4.5 ± 4.0 years [mean ± standard deviation (SD)] at autonomic testing (T1). Symptoms of autonomic dysfunction were reported by 78% individuals at T1. Cardiovascular autonomic failure was detected by functional testing in 75% individuals and in 64% of TTR carriers. Progression rate from polyneuropathy disability stages I/II to III/IV seemed to be shorter for individuals with autonomic symptoms at onset [2.33 ± 0.56 versus 4.00 ± 0.69 years (mean ± SD)].Cardiovascular autonomic dysfunction occurs early and frequently in individuals with hereditary transthyretin amyloidosis within 4.5 years from disease onset. Cardiovascular autonomic failure can be subclinical in individuals and asymptomatic carriers, and only detected with autonomic function testing, which should be considered a potential biomarker for early diagnosis and disease progression.Results: The cardiomyopathic and neuropathic phenotype of hereditary transthyretin amyloidosis are well recognized. Cardiovascular autonomic dysfunction is less systematically and objectively assessed.Autonomic and clinical features, quantitative cardiovascular autonomic function, and potential autonomic prognostic markers of disease progression were recorded in a cohort of individuals with hereditary transthyretin amyloidosis and in asymptomatic carriers of TTR variants at disease onset (T0) and at the time of the first quantitative autonomic assessment (T1). The severity of peripheral neuropathy and its progression was stratified with the polyneuropathy disability score.A total of 124 individuals were included (111 with a confirmed diagnosis of hereditary transthyretin amyloidosis, and 13 asymptomatic carriers of TTR variants). Symptoms of autonomic dysfunction were reported by 27% individuals at T0. Disease duration was 4.5 ± 4.0 years [mean ± standard deviation (SD)] at autonomic testing (T1). Symptoms of autonomic dysfunction were reported by 78% individuals at T1. Cardiovascular autonomic failure was detected by functional testing in 75% individuals and in 64% of TTR carriers. Progression rate from polyneuropathy disability stages I/II to III/IV seemed to be shorter for individuals with autonomic symptoms at onset [2.33 ± 0.56 versus 4.00 ± 0.69 years (mean ± SD)].Cardiovascular autonomic dysfunction occurs early and frequently in individuals with hereditary transthyretin amyloidosis within 4.5 years from disease onset. Cardiovascular autonomic failure can be subclinical in individuals and asymptomatic carriers, and only detected with autonomic function testing, which should be considered a potential biomarker for early diagnosis and disease progression.Conclusions: The cardiomyopathic and neuropathic phenotype of hereditary transthyretin amyloidosis are well recognized. Cardiovascular autonomic dysfunction is less systematically and objectively assessed.Autonomic and clinical features, quantitative cardiovascular autonomic function, and potential autonomic prognostic markers of disease progression were recorded in a cohort of individuals with hereditary transthyretin amyloidosis and in asymptomatic carriers of TTR variants at disease onset (T0) and at the time of the first quantitative autonomic assessment (T1). The severity of peripheral neuropathy and its progression was stratified with the polyneuropathy disability score.A total of 124 individuals were included (111 with a confirmed diagnosis of hereditary transthyretin amyloidosis, and 13 asymptomatic carriers of TTR variants). Symptoms of autonomic dysfunction were reported by 27% individuals at T0. Disease duration was 4.5 ± 4.0 years [mean ± standard deviation (SD)] at autonomic testing (T1). Symptoms of autonomic dysfunction were reported by 78% individuals at T1. Cardiovascular autonomic failure was detected by functional testing in 75% individuals and in 64% of TTR carriers. Progression rate from polyneuropathy disability stages I/II to III/IV seemed to be shorter for individuals with autonomic symptoms at onset [2.33 ± 0.56 versus 4.00 ± 0.69 years (mean ± SD)].Cardiovascular autonomic dysfunction occurs early and frequently in individuals with hereditary transthyretin amyloidosis within 4.5 years from disease onset. Cardiovascular autonomic failure can be subclinical in individuals and asymptomatic carriers, and only detected with autonomic function testing, which should be considered a potential biomarker for early diagnosis and disease progression. [ABSTRACT FROM AUTHOR]

Editorial. Promotes the recognition of disorders in the autonomic nervous system in light of its effects on every organ in the body through sympathetic and parasympathetic pathways. Awareness as the first step in recognition; Suggested primary investigations when an autonomic disorder is suspected; Question of whether recognition and evaluation influence clinical management; Distinguishing multiple-system atrophy from Parkinson's disease.

Abstract: In pure autonomic failure (PAF) – a rare form of primary dysautonomia – some patients show cerebrovascular lesions usually found in hypertensive subjects. In an autonomic laboratory records of patients with a definitive diagnosis of PAF having had cerebral imaging (cMRI, cCT) were analysed retrospectively. Tilt table data (supine/tilted), 24hour blood pressure recordings (day/night) and serum catecholamine levels were correlated with cerebrovascular lesions and also compared to published normal values. 50 PAF patients (23 female, 27 male) were identified, mean age 67years (sd 9.5). Out of these 35 (70%) had pathologic cerebral scans showing white matter lesions (WML) in 30, lacunar strokes in 5 and hemispheric stroke and microbleeds each in 1. Age and supine systolic blood pressure were significantly elevated in patients with pathologic scans (70 compared to 61years [p=0.007], and 170 compared to 154mmHg [p=0.045]). Out of 28 patients with WML and ambulatory blood pressure recordings available 24 were non-dippers. The data show that the frequency of WML is lower in PAF patients aged 60 to 80years compared to age matched community based samples. Although PAF usually results in hypotension, a frequent complication is supine hypertension. Although the overall frequency of WML seems to be reduced in PAF, a number of patients with elevated supine systolic blood pressure (>160mmHg) develop WML and some of these suffer stroke. [Copyright &y& Elsevier]

Abstract: The autonomic nervous system closely integrates a range of vital processes, including, cardiovascular function. Physical activity, or exercise, requires a range of integrated autonomic and cardiovascular adjustments in order to maintain homeostasis. Pathological conditions that result in dysfunction of the autonomic nervous system, such as autonomic failure, can therefore jeopardize the control of blood pressure resulting in hypotension and have serious implications for health. Exercise induced hypotension, defined as a ≥10mmHg fall in systolic blood pressure during exercise, can be a significant symptom/event for autonomic failure, as well as other autonomic disorder, patients, including, Multiple System Atrophy and Spinal Cord Injury, and can reduce physical capacity, orthostatic tolerance, result in falls, complicate management and reduce quality of life. The likely mechanisms do not appear to be an altered cardiac output or active muscle vasodilation response to exercise, but rather, a lack of and/or a blunted increase in sympathetic nerve activity during exercise and/or excessive vasodilation in the splanchnic circulation. The severity of exercise induced hypotension seems to be higher during dynamic relative to static exercise. The possible management strategies for exercise induced hypotension include both non-pharmacological, e.g., reducing risk factors, and pharmacological measures, such as sympathomimetics, but studies on other pharmacological agents are limited. [Copyright &y& Elsevier]

We interviewed 50 Parkinson's disease (PD) patients using a questionnaire to verify the reliability of orthostatic symptoms in warning the presence of orthostatic hypotension (OH). OH is defined as 20 mm Hg systolic or 10 mm Hg diastolic BP fall within 3 min of tilting or standing but if this fall occurs after 3 min we called it 'late OH' (L-OH). We compared if OH in Parkinson's disease (PD) was more frequent after head-up tilt or on standing and if the period of postural challenge matters in detecting OH. Twenty-one (42%) patients had OH that occurred twice more often after tilting (n = 20) than on standing (n = 10). OH occurred within 3 min of tilting in 9 patients (18%) and appeared beyond the currently recommended 3 min in 11 patients (55%) (L-OH). Ten of the 20 patients developing OH on tilting were symptomatic. The 10 patients who had OH on standing were asymptomatic. Reporting of symptoms was independent of age or severity of BP fall. Most (90%) patients reporting orthostatic symptoms on standing had OH on tilting for 3 min. Orthostatic symptoms in PD have a high specificity but low sensitivity in predicting OH. In Parkinson's disease OH occurs often after tilting than on standing and is delayed (after 3 min). As OH in PD is often asymptomatic and delayed it could contribute to falls and increase morbidity. We suggest routine evaluation of OH in PD by tilting them longer than the recommended 3 minutes to detect delayed OH. © 2009 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Abstract: Neurocardiogenic syncope (NCS, simple fainting) is a common and typically benign familial condition, which rarely may result in traumatic injury or hypoxic convulsions. NCS is associated with emotional triggers, anxiety states and stress. However, the etiology of NCS, as a psychophysiological process, is poorly understood. We therefore investigated the relationship between NCS and brain anatomy. We studied a non-clinical sample of eighteen individuals with histories characteristic of NCS, and nineteen matched controls who had never fainted. We recorded fainting frequency, resting heart rate variability measures and anxiety levels. Structural T1-weighted magnetic resonance images (MRI) were acquired at 1.5 T. Associations between brain morphometry (regional gray and white matter volumes) and NCS, resting physiology and anxiety were tested using voxel-based morphometry (VBM). Compared to controls, NCS participants had lower regional brain volume within medulla and midbrain (a priori regions of interest). Moreover, across NCS individuals, lower gray matter volume in contiguous regions of left caudate nucleus predicted enhanced parasympathetic cardiac tone, fainting frequency and anxiety levels. Our findings provide preliminary evidence for a hierarchical anatomical basis to NCS. First, differences in the volume of brainstem centers supporting cardiovascular homeostasis may relate to constitutional predisposition to NCS. Second, differences in the structural organization of the caudate nucleus in NCS individuals may relate to fainting frequency via interactions between emotional state and parasympathetic control of the heart. These observations highlight the application of VBM to the identification of neurovisceral mechanisms relevant to psychosomatic medicine and the neuroscience of emotion. [Copyright &y& Elsevier]

Local heating of nonglabrous skin increases skin blood flow (SkBF) in two phases. The initial peak (P1) is mediated by a sensory-axon reflex and the plateau phase (P2) by local production of substances such as nitric oxide. We evaluated the SkBF response to local heating in 15 multiple system atrophy (MSA) patients with autonomic failure and 12 age-matched healthy controls. The mean ratio of SkBF at P1 to that at baseline (SkBFP1/SkBFbase ratio) in MSA was significantly lower than that in controls ( P < 0.01). The mean ratio of SkBF at P2 seemed to be slightly reduced in the MSA patients, compared with controls, although there was no significant difference. The P1 phase is thought to be mediated by a sensory-axon reflex modulated by sympathetic nerve activity. These findings are indicative of the skin sympathetic vasomotor dysfunction in MSA. © 2007 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Multiple system atrophy (MSA) and pure autonomic failure (PAF) represent distinct pathological models of autonomic failure in humans. We have investigated the neuroendocrine, behavioural and autonomic cardiovascular responses to the 35% CO2 challenge. Nine patients with MSA, nine with PAF and five control subjects received a single breath of 35% CO2. Peripheral autonomic failure (i.e., PAF) was associated with significantly lower resting noradrenaline levels. All groups demonstrated a significant pressor response to CO2. In controls, the mean pressor response was +60.2 mm Hg, which was significantly smaller in both the PAF (+26.8 mm Hg, P < 0.01) and MSA (+18.3 mm Hg, P < 0.001) patients. In addition, the onset of the response was significantly delayed in both MSA (140.2 s) and PAF (154.2 s) patients compared with controls (32.4 s, P = 0.04 and P = 0.03, respectively). Noradrenaline levels increased only in controls. Central autonomic impairment (i.e., MSA) was associated with lower cortisol release (+8.8% in MSA compared with +35.2% in control and +23.7% in PAF) and fewer somatic symptoms of emotional arousal. Both MSA and PAF exhibit marked sympathetic autonomic impairment, however, residual (albeit differing) sympathetic pathways can still maintain a partial cardiovascular response. A central autonomic lesion, however, also appears to be associated with blunting of both cortisol and emotional responses to this stress paradigm. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study was to evaluate patients with ganglionic acetylcholine receptor antibody (gAChR‐Ab) positive autoimmune autonomic ganglionopathy using a multimodal testing protocol to characterize their full clinical phenotype and explore biomarkers to quantify immunotherapy response. Methods: We conducted a cohort study of 13 individuals (7 women, 21–69 years of age) with autonomic failure and gAChR‐Ab >100 pM identified between 2005 and 2019. From 2018, all patients were longitudinally assessed with cardiovascular, pupillary, urinary, sudomotor, lacrimal and salivary testing, and Composite Autonomic Symptom Score (COMPASS‐31) autonomic symptom questionnaires. The orthostatic intolerance ratio was calculated by dividing change in systolic blood pressure over time tolerated on head‐up tilt. Eleven patients received immunotherapy. Results: At first assessment, all 13 patients had cardiovascular and pupillary impairments, 7 of 8 had postganglionic sudomotor dysfunction, 9 of 11 had urinary retention and xeropthalmia, and 6 of 8 had xerostomia. After immunotherapy, there were significant improvements in orthostatic intolerance ratio (33.3 [17.8–61.3] to 5.2 [1.4–8.2], p = 0.007), heart rate response to deep breathing (1.5 [0.0–3.3] to 4.5 [3.0–6.3], p = 0.02), pupillary constriction to light (12.0 [5.5–18.0] to 19.0 [10.6–23.8]%, p = 0.02), saliva production (0.01 [0.01–0.05] to 0.08 [0.02–0.20] g/min, p = 0.03), and COMPASS‐31 scores (52 to 17, p = 0.03). Orthostatic intolerance ratio correlated with autonomic symptoms at baseline (r = 0.841, p = 0.01) and following immunotherapy (r = 0.889, p = 0.02). Immunofluorescence analyses of skin samples from a patient 32 years after disease onset showed loss of nerve fibers supplying the dermal autonomic adnexa and epidermis, with clear improvements following immunotherapy. Interpretation: Patients with autoimmune autonomic ganglionopathy demonstrated objective evidence of widespread sympathetic and parasympathetic autonomic failure, with significant improvements after immunotherapy. Quantitative autonomic biomarkers should be used to define initial deficits, guide therapeutic decisions, and document treatment response. ANN NEUROL 2021;89:753–768 [ABSTRACT FROM AUTHOR]

Abstract: Aim: A previous study on a small number of patients showed that low skin temperature of the hands, the so called “cold hands sign”, may be useful for distinguishing multiple system atrophy (MSA) from Parkinson''s disease (PD). We have further investigated skin temperature of the hand in a larger number of patients. Methods: Skin temperature on the palm was measured in 50 MSA (11 MSA-P and 39 MSA-C patients) and 50 PD patients, and 25 normal healthy subjects. Results: Palm skin temperature was significantly lower in MSA patients (32.0 ± 2.7 °C) than in controls (34.1 ± 0.9 °C, p = 0.0002), but was not different compared with the PD group (32.9 ± 1.8 °C, p = 0.06). Temperatures of <28 °C were observed in 3 MSA patients (6%) and none of the PD patients and controls. There was no significant difference in palm skin temperature between patients with and without orthostatic hypotension for each patient group, or between MSA-P and MSA-C patients. Conclusion: The cold hand (<28 °C) is a useful marker for distinguishing MSA from PD, but it is not common in MSA patients, and its sensitivity may be low for differentiating between MSA and PD. [Copyright &y& Elsevier]

n effective baroreflex and autonomic pathways normally ensure that blood pressure (BP) is satisfactorily maintained, despite various stimuli in daily life that include postural changes. We describe a 20-year-old man with a cerebellar hematoma and acute hydrocephalus, who had a vermian and partial right cerebellar hemisphere resection followed by orthostatic hypertension (OHT) and mutism. On standing his systolic BP rose over 60 mmHg with a fivefold increase in plasma noradrenaline. After a period of 8 weeks, postural BP regulation improved along with his ability to communicate. We conclude that transient impairment of cerebellar autonomic modulation or dysfunction of the baroreflex medullary circuit, may have resulted in OHT. [ABSTRACT FROM AUTHOR]

Cognitive and emotional processes are influenced by interoception (homeostatic somatic feedback), particularly when physiological arousal is unexpected and discrepancies between predicted and experienced interoceptive signals may engender anxiety. Due to the vulnerability for comorbid psychological symptoms in forms of orthostatic intolerance (OI), this study investigated psychophysiological contributions to emotional symptomatology in 20 healthy control participants (13 females, mean age 36 ± 8 years), 20 postural tachycardia syndrome (PoTS) patients (18 females, mean age 38 ± 13 years) and 20 vasovagal syncope (VVS) patients (15 females, mean age 39 ± 12 years). We investigated indices of emotional orienting responses (OR) to randomly presented neutral, pleasant and unpleasant images in the supine position and during the induced interoceptive threat of symptom provocation of head-up tilt (HUT). PoTS and VVS patients produced greater indices of emotional responsivity to unpleasant images and, to a lesser degree, pleasant images, during interoceptive threat. Our findings are consistent with biased deployment of response-focused emotion regulation (ER) while patients are symptomatic, providing a mechanistic underpinning of how pathological autonomic overexcitation predisposes to anxiogenic traits in PoTS and VVS patients. This hypothesis may improve our understanding of why orthostasis exacerbates cognitive symptoms despite apparently normal cerebral autoregulation, and offer novel therapeutic targets for behavioural interventions aimed at reducing comorbid cognitive-affective symptoms in PoTS and VVS. [ABSTRACT FROM AUTHOR]

Predictive coding models, such as the ‘free-energy principle’ (FEP), have recently been discussed in relation to how interoceptive (afferent visceral feedback) signals update predictions about the state of the body, thereby driving autonomic mediation of homeostasis. This study appealed to ‘interoceptive inference’, under the FEP, to seek new insights into autonomic (dys)function and brain–body integration by examining the relationship between cardiac interoception and autonomic cardiac control in healthy controls and patients with forms of orthostatic intolerance (OI); to (i) seek empirical support for interoceptive inference and (ii) delineate if this relationship was sensitive to increased interoceptive prediction error in OI patients during head-up tilt (HUT)/symptom provocation. Measures of interoception and heart rate variability (HRV) were recorded whilst supine and during HUT in healthy controls (N = 20), postural tachycardia syndrome (PoTS, N = 20) and vasovagal syncope (VVS, N = 20) patients. Compared to controls, interoceptive accuracy was reduced in both OI groups. Healthy controls' interoceptive sensibility positively correlated with HRV whilst supine. Conversely, both OI groups' interoceptive awareness negatively correlated with HRV during HUT. Our pilot study offers initial support for interoceptive inference and suggests OI cohorts share a central pathophysiology underlying interoceptive deficits expressed across distinct cardiovascular autonomic pathophysiology. From a predictive coding perspective, OI patients' data indicates a failure to attenuate/modulate ascending interoceptive prediction errors, reinforced by the concomitant failure to engage autonomic reflexes during HUT. Our findings offer a potential framework for conceptualising how the human nervous system maintains homeostasis and how both central and autonomic processes are ultimately implicated in dysautonomia. [ABSTRACT FROM AUTHOR]

Introduction We investigated the genesis and presentation of previously–reported anxiety in disorders of autonomic overexcitation in relation to interoception, body vigilance and trauma to test our hypothesis that patients with the postural tachycardia syndrome (PoTS), vasovagal syncope (VVS) and essential hyperhidrosis (EH) represent atypical anxiety phenotypes in whom affective symptoms are more related to apprehension and vigilance of physiological (interoceptive) feedback than neurotic or trauma-related factors. Methods The Anxiety Sensitivity Index, Body Vigilance Scale, Self-consciousness Scale, Childhood Traumatic Events Scale and heartbeat tracking tasks were completed by 23 healthy controls, 21 PoTS, 20 EH and 20 VVS patients. Interoceptive accuracy (IA) was assessed during supine rest (9 min), isometric exercise (3 min), cold pressor (90 s) and head up tilt (HUT) (9 min). Results In comparison to controls, PoTS, VVS and EH patients reported increased symptoms of somatic anxiety but not of social anxiety/self-consciousness or trauma. Autonomic patients' IA was diminished and consistently underestimated even during autonomic arousal compared to controls. Controls and EH IA negatively correlated with somatic anxiety/hypervigilance, whereas PoTS and VVS IA and somatic anxiety/vigilance positively correlated. Conclusions Affective symptoms in PoTS, VVS and EH appear to be driven by anxiety and vigilance of physical sensations/symptoms, rather than trauma or neurosis. Increased somatic vigilance/anxiety in PoTS and VVS may be due to interoception being anxiogenic in these cohorts. Diminished interoception may be due to a common central dysregulation, as both sudomotor and cardiovascular forms of autonomic dysfunction had comparable IA deficits. These findings provide a possible therapeutic pathway for psychological symptoms in PoTS, VVS and EH. [ABSTRACT FROM AUTHOR]

The prevalence and costs of the obesity epidemic and obesity-related conditions, including diabetes mellitus, is consistently increasing worldwide. Bariatric medicine is attempting to address this with weight loss and exercise programmes, and with increasing frequency, various forms of bariatric surgery. There has been considerable success reported after bariatric surgery but not without. We describe 14 patients with orthostatic intolerance (OI) post bariatric surgery. We report on OI (postural dizziness, palpitations and fainting), the results of cardiovascular autonomic testing and the associated and/or causative findings as well as reviewing the literature to consider the possible mechanisms. Comprehensive autonomic testing revealed that 35.7% (Buchwald et al., 2004) of these patients fulfilled the criteria for the Postural Tachycardia Syndrome (PoTS), 57.1% (Cremieux et al., 2008) had low levels of basal BP and 42.9% (Cammisotto & Bendayan, 2007) patients were presyncopal and 14.3% (Billakanty et al., 2008) experienced syncope. We propose that the incidence of OI post-bariatric surgery is higher than considered, that certain cohorts may be more susceptible to complications, and that further research is needed to identify the prevalence and, ideally anticipate occurrence. With the increasing prevalence of obesity and required clinical interventions, further understanding of the pathophysiological processes causing autonomic dysfunction after bariatric interventions will aid management, which may differ in those with an underlying disposition to autonomic involvement, such as diabetics, in whom such procedures are increasingly used. [ABSTRACT FROM AUTHOR]

Aim: To clarify the characteristics of hemodynamic responses to exercise and orthostasis in Parkinson's disease patients, especially those with autonomic failure. Methods: Clinical audit of supine cycling exercise test data (with active standing tests pre- and post-exercise) of Parkinson's patients with autonomic dysfunction. 23 patients (71 ± 7 yr, 7 females) with a confirmed diagnosis of Parkinson's were identified. Results: Group mean systolic blood pressure (SBP) fell during pre-exercise standing (−39 ± 29 mmHg, P < 0.001, 17 patients had orthostatic hypotension (OH)), while heart rate (HR) increased (+13 ± 7 beats min−1, P < 0.001). SBP (P < 0.001) increased during exercise with a wide variation in responses. SBP increased in 13 patients (INC; +30 ± 14 mmHg) and either did not change or decreased in 10 patients (DEC −12 ± 11 mmHg, P < 0.001 vs INC). The increase in HR was not different between sub-groups (30 ± 12 vs 25 ± 10 beats min−1, INC vs. DEC, P = 0.29). The size of the pre-exercise stand SBP reduction was greater in DEC vs INC (−64 ± 23 (10 out of 10 had OH) vs −19 ± 16 mmHg (7 out of 13 had OH), respectively, P < 0.001). The HR elevation was not different between sub-groups (13 ± 8 vs 13 ± 4 beats min−1, DEC vs INC, P = 0.94). Post-exercise SBP/DBP were lower for both sub-groups compared to pre-exercise and the standing SBP reduction post-exercise was not greater relative to pre-exercise in either sub-group. Conclusion: Exercise-induced hypotension can occur in Parkinson's disease patients with autonomic failure with the magnitude of the exercise response being related to the severity of autonomic dysfunction. Exercise does not appear to worsen OH in this sample of Parkinson's patients. [ABSTRACT FROM AUTHOR]

Parkinson's disease (PD) is a progressive neurodegenerative disorder characterised by motor dysfunction (parkinsonism) and several non-motor features. Dysautonomia is a significant non-motor feature as well as a neuropsychiatric symptom. Autonomic dysfunction can occur even in the early stages of PD, often preceding the onset of the classic motor symptoms of PD. The patterns of autonomic features in PD are different from other parkinsonian disorders. Detection of autonomic dysfunction may therefore be helpful in diagnosing PD in the early or pre-motor stages, and/or in differentiating it from other parkinsonian disorders, such as multiple system atrophy and progressive supuranuclear palsy. The aim of this review is to describe aspects of autonomic dysfunction, including symptoms, assessment and pathophysiology, resulting from autonomic impairment in PD and other parkinsonian syndromes. [ABSTRACT FROM AUTHOR]

Summary: Background: Multiple system atrophy (MSA) is a fatal and still poorly understood degenerative movement disorder that is characterised by autonomic failure, cerebellar ataxia, and parkinsonism in various combinations. Here we present the final analysis of a prospective multicentre study by the European MSA Study Group to investigate the natural history of MSA. Methods: Patients with a clinical diagnosis of MSA were recruited and followed up clinically for 2 years. Vital status was ascertained 2 years after study completion. Disease progression was assessed using the unified MSA rating scale (UMSARS), a disease-specific questionnaire that enables the semiquantitative rating of autonomic and motor impairment in patients with MSA. Additional rating methods were applied to grade global disease severity, autonomic symptoms, and quality of life. Survival was calculated using a Kaplan-Meier analysis and predictors were identified in a Cox regression model. Group differences were analysed by parametric tests and non-parametric tests as appropriate. Sample size estimates were calculated using a paired two-group t test. Findings: 141 patients with moderately severe disease fulfilled the consensus criteria for MSA. Mean age at symptom onset was 56·2 (SD 8·4) years. Median survival from symptom onset as determined by Kaplan-Meier analysis was 9·8 years (95% CI 8·1–11·4). The parkinsonian variant of MSA (hazard ratio [HR] 2·08, 95% CI 1·09–3·97; p=0·026) and incomplete bladder emptying (HR 2·10, 1·02–4·30; p=0·044) predicted shorter survival. 24-month progression rates of UMSARS activities of daily living, motor examination, and total scores were 49% (9·4 [SD 5·9]), 74% (12·9 [8·5]), and 57% (21·9 [11·9]), respectively, relative to baseline scores. Autonomic symptom scores progressed throughout the follow-up. Shorter symptom duration at baseline (OR 0·68, 0·5–0·9; p=0·006) and absent levodopa response (OR 3·4, 1·1–10·2; p=0·03) predicted rapid UMSARS progression. Sample size estimation showed that an interventional trial with 258 patients (129 per group) would be able to detect a 30% effect size in 1-year UMSARS motor examination decline rates at 80% power. Interpretation: Our prospective dataset provides new insights into the evolution of MSA based on a follow-up period that exceeds that of previous studies. It also represents a useful resource for patient counselling and planning of multicentre trials. Funding: Fifth Framework Programme of the European Union, the Oesterreichische Nationalbank, and the Austrian Science Fund. [Copyright &y& Elsevier]

Summary: Background: Multiple system atrophy (MSA) is a fatal and still poorly understood degenerative movement disorder that is characterised by autonomic failure, cerebellar ataxia, and parkinsonism in various combinations. Here we present the final analysis of a prospective multicentre study by the European MSA Study Group to investigate the natural history of MSA. Methods: Patients with a clinical diagnosis of MSA were recruited and followed up clinically for 2 years. Vital status was ascertained 2 years after study completion. Disease progression was assessed using the unified MSA rating scale (UMSARS), a disease-specific questionnaire that enables the semiquantitative rating of autonomic and motor impairment in patients with MSA. Additional rating methods were applied to grade global disease severity, autonomic symptoms, and quality of life. Survival was calculated using a Kaplan-Meier analysis and predictors were identified in a Cox regression model. Group differences were analysed by parametric tests and non-parametric tests as appropriate. Sample size estimates were calculated using a paired two-group t test. Findings: 141 patients with moderately severe disease fulfilled the consensus criteria for MSA. Mean age at symptom onset was 56·2 (SD 8·4) years. Median survival from symptom onset as determined by Kaplan-Meier analysis was 9·8 years (95% CI 8·1–11·4). The parkinsonian variant of MSA (hazard ratio [HR] 2·08, 95% CI 1·09–3·97; p=0·026) and incomplete bladder emptying (HR 2·10, 1·02–4·30; p=0·044) predicted shorter survival. 24-month progression rates of UMSARS activities of daily living, motor examination, and total scores were 49% (9·4 [SD 5·9]), 74% (12·9 [8·5]), and 57% (21·9 [11·9]), respectively, relative to baseline scores. Autonomic symptom scores progressed throughout the follow-up. Shorter symptom duration at baseline (OR 0·68, 0·5–0·9; p=0·006) and absent levodopa response (OR 3·4, 1·1–10·2; p=0·03) predicted rapid UMSARS progression. Sample size estimation showed that an interventional trial with 258 patients (129 per group) would be able to detect a 30% effect size in 1-year UMSARS motor examination decline rates at 80% power. Interpretation: Our prospective dataset provides new insights into the evolution of MSA based on a follow-up period that exceeds that of previous studies. It also represents a useful resource for patient counselling and planning of multicentre trials. Funding: Fifth Framework Programme of the European Union, the Oesterreichische Nationalbank, and the Austrian Science Fund. [Copyright &y& Elsevier]

Abstract: Post-mortem studies of multiple system atrophy (MSA) patients have shown widespread subcortical neurodegeneration. In this study, we have used 18F-dopa PET, a marker of monoaminergic nerve terminal function, to explore in vivo changes in striatal and extrastriatal dopamine, noradrenaline, and serotonin transmission for a cohort of patients with MSA with predominant parkinsonism. Fourteen patients with MSA, ten patients with idiopathic Parkinson''s disease (PD) matched for disease duration, and ten healthy controls were studied with 18F-dopa PET. Regions of interest (ROIs) were placed to sample 18F-dopa uptake in thirteen structures and mean activity was compared between groups. The MSA patients showed significantly decreased 18F-dopa uptake in putamen, caudate nucleus, ventral striatum, globus pallidus externa and red nucleus compared to controls, whereas PD patients only had decreased 18F-dopa uptake in putamen, caudate nucleus, and ventral striatum. MSA cases with orthostatic hypotension had lower 18F-dopa uptake in the locus coeruleus than patients without this symptom. In conclusion, 18F-dopa PET showed more widespread basal ganglia dysfunction in MSA than in PD with similar disease duration, and extrastriatal loss of monoaminergic innervation could be detected in the red nucleus and locus coeruleus. In contrast to PD, there was no evidence of early compensatory increases in regional 18F-dopa uptake. [Copyright &y& Elsevier]

Postural tachycardia syndrome (PoTS) is a poorly understood but important cause of orthostatic intolerance resulting from cardiovascular autonomic dysfunction. PoTS is distinct from the syndromes of autonomic failure usually associated with orthostatic hypotension, such as pure autonomic failure and multiple system atrophy. Individuals affected by PoTS are mainly young (aged between 15 years and 40 years) and predominantly female. The symptoms--palpitations, dizziness and occasionally syncope--mainly occur when the patient is standing upright, and are often relieved by sitting or lying flat. Common stimuli in daily life, such as modest exertion, food ingestion and heat, are now recognized to be capable of exacerbating the symptoms. Onset of the syndrome can be linked to infection, trauma, surgery or stress. PoTS can be associated with various other disorders; in particular, joint hypermobility syndrome (also known as Ehlers-Danlos syndrome hypermobility type, formerly termed Ehlers-Danlos syndrome type III). This Review describes the characteristics and neuroepidemiology of PoTS, and outlines possible pathophysiological mechanisms of this syndrome, as well as current and investigational treatments. [ABSTRACT FROM AUTHOR]

Abstract: Introduction: Our objective was to assess the usefulness of the Scales for Outcomes in Parkinson’s disease – Autonomic (SCOPA-AUT) in the differential diagnosis of Parkinsonisms and clarify its relation with 123-I-MIBG cardiac scintigraphy. Methods: A total of 112 patients with Parkinson’s disease (PD), 12 with multiple system atrophy parkinsonian variant (MSA-P) and 20 with progressive supranuclear palsy (PSP) participated in the study. The following variables were collected: age, sex, age at onset, length of illness, type and dose of anti-Parkinson medication, and score on the Unified Parkinson’s Disease Rating Scale. The Unified Multiple System Atrophy Rating Scale was administered to patients with MSA and the Progressive Supranuclear Palsy Rating Scale to those with PSP. Finally, the SCOPA-AUT was administered to all the patients. Cardiac 123I-MIBG SPECT scans were performed on a subset of patients (25 with PD and 5 with MSA-P). Results: Statistically significant differences were observed (p < 0.01) in the SCOPA-AUT scores between patients with PD (14.75+/−8.09) and those with MSA (21.07+/−5.56), the latter having higher scores on the bowel function (20.07+/−13.40 vs 34.92+/−14.91) and urinary domains (30.21+/−21.55 vs 49.26+/−21.40) (p < 0.01). No correlation was found between the SCOPA-AUT score and anti-Parkinson’s medication and heart:mediastinum (H/M) MIBG uptake ratio in the cardiac SPECT (at 4 h). Discussion: Severity of dysautonomia as measured by the SCOPA-AUT was not correlated with clinical severity, time since onset or the H/M ratio. In the patients with PD, the only variable associated with the H/M ratio was age at onset of the disease. [Copyright &y& Elsevier]

Abstract: In Parkinsons disease and multiple system atrophy (MSA), cardiovascular dysfunction may occur for a variety of reasons and may manifest itself through inappropriate changes and/or levels in blood pressure, heart rate and/or regional vascular perfusion in a range of situations. The early occurrence of orthostatic hypotension often leads to consideration of MSA, especially in the presence of other features of autonomic failure. Orthostatic hypotension, however, is increasingly recognised in PD, and especially with increasing age, severity of disease and as a result of drug therapy, sometimes for associated disorders. Investigation of cardiovascular autonomic dysfunction in Parkinsonism is therefore important for a variety of reasons, that include determining the precise diagnosis and in predicting prognosis. In Parkinsonian disorders, understanding the pathophysiological basis of the cardiovascular autonomic dysfunction aids targeting of therapy, improves management strategies and provides benefit for such patients. [Copyright &y& Elsevier]

Abstract: The combination of functional brain imaging with measurement of peripheral autonomic responses in humans can provide insight into the embodiment of mental processes and the integration of cognition and emotion with changes in somatic physiology. Initial studies in healthy people and patents validate inferences from more detailed animal experiments regarding the organization of central autonomic control. In particular these have illustrated the coupling of behaviour with sympathetic arousal. Over the last two decades, the growth of emotional neuroscience alongside advances in functional brain imaging has fuelled investigations of relationships between perception, feeling states, somatic and autonomic bodily reactions. These studies have driven a more mechanistic understanding of brain systems through which bodily state is regulated and modified to support adaptive behaviour. In parallel, they have enabled the application of human neuroimaging to autonomic neuroscience. Specific methodological challenges are posed by combining physiological recordings with neuroimaging techniques, particularly functional magnetic resonance brain imaging, which are nevertheless addressable. Using such methods, the neural correlates of dynamic autonomic control has been systematically examined in studies of healthy individuals and patients with specific autonomic dysfunction (including autonomic failure, autonomic (neurally) mediated syncope and the postural tachycardia syndrome). These studies reveal antagonistic interaction of systems underpinning autonomic cardiovascular control (involving mid and subgenual cingulate cortices) and partial organ-specificity of other axes of autonomic response. Current and anticipated technical advances, including the integration of autonomically-focused microneurography and neural stimulation with advanced neuroimaging, will continue to provide detailed insight into dynamics of autonomic control. Translating these insights into clinical benefits remains a priority. [Copyright &y& Elsevier]

Abstract: Objective: To determine if patients with autonomic failure have increased sleep disturbances and if multiple system atrophy (MSA) and pure autonomic failure (PAF) patients have frequent arousals from sleep associated with an attenuated heart rate (HR) response compared to healthy volunteers. Methods: With informed consent, 10 autonomic failure patients and 10 healthy volunteers were studied. Sleep disturbances were scored using standard criteria. Arousals were identified from stage 2 sleep and differences in the R–R interval between groups were tested using a mixed-model regression analysis. Results: Three MSA and one PAF patient had obstructive sleep apnoea compared to one volunteer. One MSA and three PAF patients had periodic limb movements. One MSA patient had REM behaviour disorder. The autonomic patients had significantly reduced total sleep time (p =0.007) and sleep efficiency (p =0.003). The HR response to arousal was smaller in autonomic failure patients compared to volunteers during the early phase of the arousal (p =0.047), but not the later phase (p =0.67). Conclusion: Autonomic failure patients have increased sleep disturbances compared to healthy volunteers. The smaller HR response in autonomic failure patients suggests that an intact sympathetic nervous system is a key component of the HR response associated with arousal from sleep. [Copyright &y& Elsevier]

Children with Congenital Central Hypoventilation Syndrome (CCHS) typically present as newborns with alveolar hypoventilation. With the advent of genetic testing, parents of affected children and other unrelated adults, all heterozygous for the disease-defining PHOX2B polyalanine expansion mutation with the 20/25 genotype, are being identified in adulthood. Though children with PHOX2B mutation-confirmed CCHS demonstrate ANS dysregulation, including altered heart rate and blood pressure control, it is unknown if adults with CCHS have similarly affected autonomic function in blood pressure control. An autonomic profile of blood pressure control has been studied with recording of muscle sympathetic activity and spectral analysis of heart rate and blood pressure variability of one adult patient with alveolar hypoventilation and the 20/25 PHOX2B genotype. All parameters of heart rate variability were reduced. Cardiac baroreflex sensitivity was decreased. Sympathetic responses to Valsalva maneuver, hypoxemia, isometric exercise and cold pressor were blunted. In summary, we found a reduced cardiac baroreflex and a blunted sympathetic mediated response in the individual with adult-onset CCHS, possibly due to dysfunction in the afferent pathway. Our results confirm that PHOX2B affects the development of the autonomic nervous system, possibly causing absence of normal maturation of carotid body and visceral sensory ganglia and leading to autonomic dysfunction in adult-onset CCHS. [ABSTRACT FROM AUTHOR]

We present a preliminary report of the discussion of the joint committee of the American Spinal Injury Association (ASIA) and the International Spinal Cord Society concerning the development of assessment criteria for general autonomic function testing following spinal cord injury (SCI). Elements of this report were presented at the 2005 annual meeting of the ASIA. To improve the evaluation of neurological function in individuals with SCI and therefore better assess the effects of therapeutic interventions in the future, we are proposing a comprehensive set of definitions of general autonomic nervous system dysfunction following SCI that should be assessed by clinicians. Presently the committee recommends the recognition and assessment of the following conditions: neurogenic shock, cardiac dysrhythmias, orthostatic hypotension, autonomic dysreflexia, temperature dysregulation, and hyperhidrosis. [ABSTRACT FROM AUTHOR]

We assessed the effects of clonidine on blood pressure (BP) and heart rate (HR) in multiple system atrophy (MSA), where the autonomic nervous system lesion site is preganglionic, and in pure autonomic failure (PAF), where it is postganglionic. In normal subjects, intravenous infusion of the selective α2-adrenoceptor agonist clonidine reduces BP and plasma noradrenaline (NA) levels by means of central α2-adrenoceptor action, as well as inducing growth hormone (GH) release. Clonidine-induced GH release is impaired in MSA but spared in PAF. However, the hemodynamic effects of clonidine have not been studied extensively in these disorders. We examined intravenous clonidine test results (performed in our autonomic laboratories using the London Autonomic Units protocol) in 58 patients: 39 with probable MSA and 19 with PAF. Systolic BP (SBP), diastolic BP (DBP), HR, and NA levels were measured supine at baseline and for up to 60 minutes after clonidine. Clonidine resulted in a significant BP fall in MSA patients, which occurred earlier (within 15 minutes of clonidine) and to a greater extent than seen in PAF patients. MSA and PAF patients showed reduction in HR after clonidine administration, although this finding was significantly greater in MSA than in PAF patients. NA levels decreased significantly after clonidine administration in both groups. Although basal NA levels were lower in PAF than in MSA patients, there was no difference in NA reduction relative to baseline between groups. MSA patients showed significant negative correlation between basal NA levels and BP response to clonidine. Clonidine infusion reduces BP and HR in both MSA and PAF groups but to a greater extent in MSA patients. The greater vasodepressor action of clonidine in MSA patients suggests that there is partial preservation of brainstem sympathetic outflow pathways in MSA and may reflect its action at sites in the brainstem and spinal cord that were in part functionally preserved in MSA. Despite similar degrees of NA reduction after clonidine administration, the vasodepressor effect of clonidine was attenuated in PAF compared with MSA patients. This attenuation in PAF patients may reflect greater peripheral α2-adrenoceptor denervation supersensitivity due to the postganglionic lesion site. These BP differences, thus, may reflect the underlying lesion site in MSA and PAF, and the hemodynamic data after clonidine infusion may help differentiate these conditions. © 2006 Movement Disorder Society [ABSTRACT FROM AUTHOR]

Psychophysiological science proposes close interactions between cognitive processes and autonomic responses, yet the consequences of autonomic failure on cognitive functioning have not been documented. This pilot study investigates, for the first time, the cognitive profile of 14 patients with Pure Autonomic Failure (PAF). Each patient was administered a comprehensive battery of neuropsychological tests and neuroimaging investigation. A number of patients (n = 6) presented with cognitive impairment. The two most frequent types of impairment were: deficits of speed and attention, and executive functioning. Impairments of free recall memory, intellectual functioning, nominal and calculation functions were also documented, albeit in a much lower frequency. These cognitive changes were not always associated with white matter abnormalities. We speculate that the cognitive impairments associated with PAF represent consequences of systemic hypotension with cerebral underperfusion. However, a failure in integrated bodily arousal responses during cognitive behaviours may also contribute to some of the observed deficits. [ABSTRACT FROM AUTHOR]