Ekawat Vichayanrat

Autonomic dysfunction in parkinsonian disorders: assessment and pathophysiology

Parkinsons 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.

Cardiovascular autonomic dysfunction in MSA and Parkinson's disease: Similarities and differences

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.

Twenty-Four Hour Non-Invasive Ambulatory Blood Pressure and Heart Rate Monitoring in Parkinson’s Disease

Non-motor symptoms are now commonly recognized in Parkinson’s disease (PD) and can include dysautonomia. Impairment of cardiovascular autonomic function can occur at any stage of PD but is typically prevalent in advanced stages or related to (anti-Parkinsonian) drugs and can result in atypical blood pressure (BP) readings and related symptoms such as orthostatic hypotension (OH) and supine hypertension. OH is usually diagnosed with a head-up-tilt test (HUT) or an (active) standing test (also known as Schellong test) in the laboratory, but 24 h ambulatory blood pressure monitoring (ABPM) in a home setting may have several advantages, such as providing an overview of symptoms in daily life alongside pathophysiology as well as assessment of treatment interventions. This, however, is only possible if ABPM is administrated correctly and an autonomic protocol (including a diary) is followed which will be discussed in this review. A 24-h ABPM does not only allow the detection of OH, if it is present, but also the assessment of cardiovascular autonomic dysfunction during and after various daily stimuli, such as postprandial and alcohol dependent hypotension, as well as exercise and drug induced hypotension. Furthermore, information about the circadian rhythm of BP and heart rate (HR) can be obtained and establish whether or not a patient has a fall of BP at night (i.e., “dipper” vs. non-“dipper”). The information about nocturnal BP may also allow the investigation or detection of disorders such as sleep dysfunction, nocturnal movement disorders, and obstructive sleep apnea, which are common in PD. Additionally, a 24-h ABPM should be conducted to examine the effectiveness of OH therapy. This review will outline the methodology of 24 h ABPM in PD, summarize findings of such studies in PD, and briefly consider common daily stimuli that might affect 24 h ABPM.

SCOPA-AUT scale in different parkinsonisms and its correlation with (123) I-MIBG cardiac scintigraphy.

INTRODUCTION Our objective was to assess the usefulness of the Scales for Outcomes in Parkinsons 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 Parkinsons 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 Parkinsons 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-Parkinsons 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.

Twenty-four-hour ambulatory blood pressure and heart rate profiles in diagnosing orthostatic hypotension in Parkinson's disease and multiple system atrophy.

Twenty‐four‐hour ambulatory blood pressure and heart rate monitoring (24‐h ABPM) can provide vital information on circadian blood pressure (BP) profiles, which are commonly abnormal in Parkinsons disease with and without autonomic failure (PD + AF and PD) and multiple system atrophy (MSA). Twenty‐four‐hour ABPM has not been directly compared between these disorders regarding cardiovascular autonomic function. Our aim was to determine the usefulness of 24‐h ABPM with diary compared to head‐up tilting (HUT) in diagnosing orthostatic hypotension (OH) in these patients.

Sudomotor and cardiovascular dysfunction in patients with early untreated Parkinson's disease.

BACKGROUND According to Braak staging of Parkinsons 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.

Autonomic dysfunction in genetic forms of synucleinopathies: Autonomic Dysfunction in Synucleinopathies

The discovery of genetic links between alpha‐synuclein and PD has opened unprecedented opportunities for research into a new group of diseases, now collectively known as synucleinopathies. Autonomic dysfunction, including cardiac sympathetic denervation, has been reported in familial forms of synucleinopathies that have Lewy bodies at the core of their pathogenesis. SNCA mutations and multiplications, LRRK2 disease with Lewy bodies as well as other common, sporadic forms of idiopathic PD, MSA, pure autonomic failure, and dementia with Lewy bodies have all been associated with dysautonomia. By contrast, in familial cases of parkinsonism without Lewy bodies, such as in PARK2, the autonomic profile remains normal throughout the course of the disease. The degeneration of the central and peripheral autonomic systems in genetic as well as sporadic forms of neurodegenerative synucleinopathies correlates with the accumulation of alpha‐synuclein immunoreactive‐containing inclusions. Given that dysautonomia has a significant impact on the quality of life of sufferers and autonomic symptoms are generally treatable, a prompt diagnostic testing and treatment should be provided. Moreover, new evidence suggests that autonomic dysfunction can be used as an outcome prediction factor in some forms of synucleinopathies or premotor diagnostic markers that could be used in the future to define further research avenues. In this review, we describe the autonomic dysfunction of genetic synucleinopathies in comparison to the dysautonomia of sporadic forms of alpha‐synuclein accumulation and provide the reader with an up‐to‐date overview of the current understanding in this fast‐growing field.

PO189 Autonomic failure caused by adult onset alexander disease with a novel gfap mutation

Slowly progressive autonomic failure in adults presents a diagnostic challenge. Here we describe a patient with slowly progressive autonomic failure present for many years before any other clinically significant symptoms or signs appeared, who underwent detailed autonomic function testing, MR brain imaging and other neurological investigations on several occasions. After she developed bulbar dysfunction (causing two life-threatening choking episodes), pyramidal and sensory dysfunction, and characteristic brain imaging abnormalities were noted, a diagnosis of adult onset Alexander disease was made. GFAP sequencing demonstrated a heterozygous missense mutation (F199S) which has not been previously reported. Relatives affected by similar symptoms (orthostatic syncope and dysphagia) suggest autosomal dominant inheritance. On retrospective review, the imaging abnormalities were present from an early stage of her illness, when autonomic symptoms were present in isolation. We propose that a diagnosis of adult onset Alexander disease should be considered in cases of slowly progressive autonomic failure even in the absence of other clinical manifestations, and that awareness of the characteristic brain imaging abnormalities should allow early diagnosis which can be confirmed with genetic testing.

Plasma noradenaline levels and disease duration in Pure Autonomic Failure

(170.4 ± 34.2 vs 1251 ± 280.1; p = 0.0001) and total power (1045 ± 270.3 vs 4395 ± 848; p = 0.0003) in type 1 diabetic adolescents as compared to healthy controls and the high frequency HF(ms) values showed a decreasing trend (503.8 ± 763.7 vs 1747 ± 1109 ; p = 0.05 ) in the same. Conclusion: This preliminary study shows reduced HRV parameters in asymptomatic type 1 diabetic adolescents as compared to healthy controls. It can be concluded that subclinical cardiac dysautonomia is present in this group of patients.