Christopher J. Mathias

Multiple system atrophy (MSA) is now recognized as a sporadic adult onset disease of unknown aetiology with characteristic neuropathological features. Originally three separate disorders were described: ♦ olivopontocerebellar atrophy (OPCA) (Dejerine and Thomas 1900) in which patients manifest predominantly cerebellar symptoms♦ striatonigral degeneration (SND) (...

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.

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.

β-Adrenergic receptor blockers are one of a number of therapeutic agents promoted as having beneficial effects in vasovagal syncope. In this issue of Clinical Science, Eldadah and co-workers have investigated the effect of the β-adrenergic receptor blocker propranolol in preventing syncope in a double-blind cross-over trial in eight subjects with a diagnosis based on tilt table testing and elevated plasma adrenaline levels during syncope. Of these, seven did not respond and the authors therefore suggest that this drug has no role in the management of vasovagal syncope. Their laboratory-based study, however, raises a number of issues regarding terminology, choice of subjects, the value and role of investigations directed towards diagnosis and in understanding pathophysiological mechanisms, and the relevance of such trials to individual subjects with vasovagal syncope.

Multiple system atrophy (MSA) is a sporadic neurodegenerative disorder that affects adults. It is characterised by autonomic failure affecting many systems; cardiovascular, urinary, sexual, gastrointestinal and sudomotor, amongst others. In addition there are motor deficits, resulting in both parkinsonian and/or cerebellar features. This review will outline the clinical features, investigations and management of MSA, with a particular emphasis on autonomic failure.

There are many causes of syncope that include neurological (autonomic and non-autonomic), cardiac and psychiatric causes, amongst others. Disorders of the autonomic nervous system, either intermittent or fixed, are increasingly recognised as contributing to a large proportion of syncope. However, the majority of guidelines focus on cardiological and neurological evaluation in these disorders. In this overview we focus specifically on the role of autonomic evaluation. This has dual purposes; to aid the diagnosis and cause of syncope, and furthermore to provide information to understand the pathophysiological basis of syncope and thus improve management of such disorders.