Multiple system atrophy: Building a global community - 30years of advocacy efforts.

Multiple system atrophy (MSA) is a rare, progressive and ultimately fatal neurodegenerative disease with no known cause and no available disease modifying treatment. Known previously by various names including Shy-Drager Syndrome, olivopontocerebellar atrophy (OPCA) and striatonigral degeneration, MSA can be classified simultaneously as a movement disorder, an autonomic disorder, a cerebellar ataxia and an atypical parkinsonian disorder. Despite scholarly attempts to better describe the disease, awareness among medical practitioners about multiple system atrophy as a diagnostic possibility has been slow to catch on. As a result, patients often go undiagnosed for many years or are largely misdiagnosed as Parkinson's disease. The non-homogeneous clinical presentation of MSA and years of confusing nomenclature have all contributed to a lack of awareness of the disease among healthcare professionals as well as the public. This lack of awareness has amplified the unmet needs of MSA patients and other stakeholders. Since the 1980s there has been a growing advocacy effort directed at this rare disease from advocacy groups, grassroots supporters, healthcare professionals and research networks. These stakeholders are beginning to unite their efforts and attack the disease from a global perspective in the hopes of improving outcomes for MSA patients in the future.

Management of non-motor complications in Parkinson's disease.

This paper summarizes the methods we devised for the treatment of psychosis, orthostatic hypotension, and mood disorders among the various non-motor complications of Parkinson's disease. Psychosis may not manifest when a patient believes in his/her delusions. If left untreated over a prolonged period, however, the delusions progress to paranoia that is very difficult to cure. Accordingly, enquiries should be made during routine examinations to detect the presence of psychosis and facilitate early discovery. Atypical antipsychotics are used when psychosis does not improve after reducing the doses of antiparkinson drugs. We achieved favorable results by using mianserin hydrochloride prior to this step, with efficacy being observed for hallucinations and mild delusions that often manifested at night. This drug does not act as a dopamine receptor blocker, so it has the advantage of not aggravating motor symptoms. With this therapy, it is also possible to improve motor symptoms without inducing psychosis by reducing the doses of antiparkinson drugs and locally stimulating the motor loop by deep brain stimulation of the subthalamic nucleus. We previously introduced leg-holding exercises for the treatment of orthostatic hypotension, through which blood pooled in the veins is returned to the systemic circulation by holding the knees. This can be done easily and is free of adverse reactions. Mood disorders are difficult to cope with in patients with Parkinson's disease, but may be treated by selecting an appropriate dopamine agonist while giving consideration to affinity for the dopamine D3 receptor. However, treatment becomes complicated when the dopamine receptor is overstimulated. Here we report on cases of successfully treated pathological gambling and dopamine dysregulation syndrome, which are considered difficult to manage. The solution may differ depending on a patient's environment, and it is not easy to prescribe therapy based on evidence-based medicine. The best therapy should be selected by maintaining communication with the patient and developing a relationship built on trust.

Acute autonomic, sensory and motor neuropathy: successful treatment with IVIg.

Acute autonomic, sensory and motor neuropathy (AASMN) is a rare peripheral nerve disorder characterized by prominent dysautonomia with somatic sensory and motor impairment. Dysautonomia in AASMN is intractable even with corticosteroid therapy or plasmapheresis. Here we report a case of AASMN with severe orthostatic hypotension. Although the effectiveness of corticosteroid was insufficient, high dose intravenous immunoglobulin therapy (IVIg) was effective for not only sensorimotor symptoms but also autonomic symptoms. This is the first case of AASMN showing favorable responses to IVIg treatment, suggesting that IVIg should be considered when corticosteroid therapy or plasmapheresis is ineffective or insufficient.

Parkisonism with Shy-Drager syndrome--a case report.

A previously healthy 60 years old female patient presented with bradykinesia, postural instability and increased rigidity of both upper and lower limbs for 2 years and was diagnosed as Parkinsonism for last years. Later on she developed features of autonomic dysfunction including postural hypotension, hyperhydrosis and urinary incontinence so was diagnosed as Shy-Drager Syndrome. She was treated with fludrocortisone and nefidipine for the management of postural hypotension. Patient developed aspiration pneumonia during oral feeding, despite of ICU management for the same cause patient died of respiratory arrest.

Evaluation and management of autonomic nervous system disorders.

Autonomic nervous system dysfunction may manifest with a variety of symptoms, with orthostatic intolerance (including orthostatic hypotension or tachycardia) and sweating abnormalities (increased or decreased sweating) being common problems requiring medical evaluation and treatment. Determination of the underlying diagnosis for these symptoms is critical in terms of classification of the disorder and its prognosis. Recent advances in evaluation of patients with these conditions and treatment modalities have enabled physicians to improve overall management of patients with these disorders. These advances include testing for ganglionic acetylcholine receptor antibody in patients with suspected autoimmune autonomic neuropathy and use of pyridostigmine for treatment of patients with orthostatic hypotension or tachycardia.

Effects of daily water drinking on orthostatic and postprandial hypotension in patients with multiple system atrophy.

OBJECTIVE: It has been demonstrated that the increased blood pressure (BP) caused by a single dose of water alleviates orthostatic hypotension (OH) and postprandial hypotension (PPH) in patients with autonomic failure (AF). The aim of this study was to evaluate the practical effect of daily water drinking on OH and PPH in the morning when patients with AF are usually most affected. METHODS: In five patients with multiple system atrophy (MSA) characterized by intractable OH and PPH, we measured seated, standing and postprandial BP in the morning without and with ingestion of 350 ml tap water at 07.30 hours for seven successive days. The changes from the basal BP level at 07.30 hours (DeltaBP) were assessed as an index of the effect of water drinking. RESULTS: Water drinking elicited a rapid pressor response in all patients. The DeltaBP during sitting, standing and after a meal following water drinking (day 1 and day 7) was significantly higher than without water drinking (day 0). The effects of reducing OH and PPH on day 7 were equivalent to those on day 1. No adverse effects associated with daily water drinking were observed, except later diuresis, which occurred in one patient. CONCLUSIONS: Daily water drinking demonstrated constant pressor effects in the morning with no severe adverse effects in MSA patients. This finding suggests that water drinking should be tried as a practical measure to prevent or reduce OH and PPH.

Deep brain stimulation improves orthostatic regulation of patients with Parkinson disease.

OBJECTIVE: To evaluate whether subthalamic nucleus (STN) stimulation has an effect on the orthostatic regulation of patients with Parkinson disease (PD), we studied cardiovascular regulation during on and off phases of STN stimulation. METHODS: We examined 14 patients with PD (mean age 58.1 +/- 5.8 years, 4 women, 10 men) with bilateral STN stimulators. Patients underwent 3 minutes of head-up tilt (HUT) testing during STN stimulation and after 90 minutes interruption of stimulation. We monitored arterial blood pressure (BP), RR intervals (RRI), respiration, and skin blood flow (SBF). Baroreflex sensitivity (BRS) was assessed as the square root of the ratio of low-frequency power of RRI to the low-frequency power of systolic BP for coherences above 0.5. RESULTS: During the on phase of the STN stimulation, HUT induced no BP decrease, a significant tachycardia, and a significant decrease of SBF. During the off phase of stimulation, HUT resulted in significant decreases in BPsys and RRI and only a slight SBF decrease. HUT induced no change of BRS during stimulation, but lowered BRS when the stimulator was off (p < 0.05). CONCLUSIONS: STN stimulation of patients with PD increases peripheral vasoconstriction and BRS and stabilizes BP, thereby improving postural hypotension in patients with PD. The results indicate that STN stimulation not only alleviates motor deficits but also influences autonomic regulation in patients with PD.

[Autonomic dysfunction and orthostatic intolerance. Cardiologic diagnosis and treatment options]. / Dysautonomien und orthostatische Intoleranz. Kardiologische Diagnostik und therapeutische Optionen.

Various disorders of autonomic circulatory control are characterized by symptoms of orthostatic intolerance and syncope. Since the introduction of tilt-table testing as a cardiac diagnostic tool by Kenny et al., definition of these disorders has changed significantly. This review summarizes the current knowledge of diagnosis and treatment of the syndromes of orthostatic intolerance.

An ethical dilemma involving a Shy-Drager patient: a case study.

Shy-Drager syndrome, one type of multisystem atrophy, is considered a Parkinson's-plus syndrome. Survival time is less than a decade from the onset of symptoms, and patients usually become physically dependent and wheelchair bound years before death. Ethical dilemmas are very common in health care. In many cases, an ethics consultation is required to resolve complex issues. The ethics committee is guided toward a decision by application of universal ethical principles. Nurses can serve as a patient's advocate, as they are the ones providing direct care and forming relationships with the patient. In many cases, conversations between nurse and patient become pertinent information the ethics team can use to resolve ethical dilemmas.

The effects of water ingestion on orthostatic hypotension in two groups of chronic autonomic failure: multiple system atrophy and pure autonomic failure.

BACKGROUND: Oral ingestion of water increases seated blood pressure in patients with chronic autonomic failure by mechanisms that remain unclear. As orthostatic hypotension is common in chronic autonomic failure, and is not always adequately controlled by medication, the potential benefits of water ingestion on standing blood pressure were studied in two types of autonomic failure: multiple system atrophy (MSA), in which the lesion is central and pre-ganglionic, and pure autonomic failure (PAF), in which the lesion is post-ganglionic. METHODS: In 14 patients with autonomic failure (seven PAF and seven MSA) standing blood pressure and heart rate were measured before, and 15 and 35 minutes after ingestion of 480 ml distilled water. Patients remained seated for 15 minutes after water ingestion, with beat to beat cardiovascular indices measured with the Portapres II device with subsequent Modelflow analysis. RESULTS: Standing prior to water ingestion caused a significant fall in blood pressure in all patients. After water ingestion there was a rise in seated blood pressure. Seated and standing blood pressure at 15 and 35 minutes after water ingestion was significantly higher than before water, with an improvement in orthostatic symptoms. The time to first significant rise in seated blood pressure occurred at 5 minutes post water ingestion in PAF and at 13 minutes in MSA. These increases were accompanied by increases in total peripheral resistance, reaching significance by 5 minutes in PAF and 13 minutes in MSA. There were no significant changes in cardiac output, stroke volume, or ejection fraction. CONCLUSIONS: Water is thus beneficial in improving standing BP in AF, acting within 15 minutes in both MSA and PAF. The earlier onset of the pressor effect in PAF may reflect the differing lesion site and underlying pathophysiology between these conditions.

[Autonomic dysfunction syndromes associated with orthostatic intolerance]. / Síndromes de disfunción autonómica asociados con intolerancia ortostática.

In recent years increased interest has focused on the nature and pathophysiology of orthostatic intolerance and syndromes associated with autonomic disorders. Understanding the pathophysiology underlying these syndromes has led to the recognition of several distinct clinical entities with overlapping features and the associated need to reclassify many of the previously unrecognized syndromes. Among the clinical manifestations, syncope and near syncope are frequently associated with orthostatic intolerance. In addition, however, a wide spectrum of symptoms have been described ranging from chronic fatigue to recurrent neurally mediated vasodepressor reactions. The present review focuses on the pathophysiology and classification of syndromes of autonomic dysfunction associated with orthostatic intolerance. Primary and secondary causes of dysautonomia as well as therapeutic approach to these frequently unrecognized syndromes is presented.

Hypertension in orthostatic hypotension and autonomic dysfunction.

Disabling orthostatic hypotension dominates the clinical picture of autonomic failure. Nonetheless, severe supine hypertension is observed in about 50% of patients. In patients with multiple system atrophy (Shy-Drager syndrome), supine hypertension is explained by residual sympathetic tone because it can be eliminated with the ganglionic blocker trimethaphan. The cause of hypertension in patients with pure autonomic failure is not known and its understanding may be relevant to essential hypertension. Supine hypertension complicates the treatment of these patients but can be managed by overnight administration of antihypertensive medications.

[Three patients with unrecognized orthostatic intolerance]. / Drie patiënten met niet herkende orthostatische intolerantie.

Three patients, men aged 20, 50 and 56 suffered from orthostatic intolerance and syncope for years, despite visits to many doctors. Medical history and cardiovascular reflex investigation revealed problems with the orthostatic blood pressure regulation, caused by initial orthostatic dysregulation, vasovagal syncope and pure autonomic failure, respectively. A structured medical history as well as blood pressure measurements in the supine and standing positions can reveal the diagnosis in many instances of syncope. After confirming the diagnosis, the first concern is a clear explanation of the underlying problems to the patient. Treatment with volume expansion should be considered.

Clinical effects of elastic bandage on neurogenic orthostatic hypotension.

Neurogenic orthostatic hypotension (OH) often causes troublesome symptoms such as dizziness, syncope and falling, interfering active daily life or various therapies in rehabilitation. Nonpharmacologic measures for treating patients with OH include wearing elastic leotard, head-up tilting at night, etc. Elastic garment or antigravity suits is certainly effective, but it may be uncomfortable and not practical. Although elastic bandage (EB) bound on the lower limbs has been thought to be useful, there is few clinical report about its beneficial evidence. We investigated short-term clinical effects of commercially available EB on OH, and estimated the mechanism of its effectiveness by measuring some blood pressure-related humoral variables in neurodegenerative patients with OH.

[Syndromes of autonomic insufficiency associated with orthostatic intolerance: classification, diagnostic and therapeutic approach]. / Syndrome der autonomen Dysfunktion mit orthostatischer Intoleranz: Klassifikation, Diagnostik und Therapie.

Stimulated by the widespread use of tilt table testing, disorders of autonomic function with orthostatic hypotension have recently gained attention by clinical cardiologists. At the same time, improved characterization of the underlying circulatory responses have led to a reclassification of these syndromes. In particular, three subgroups of chronic primary dysautonomia have been defined such as Pure Autonomic Dysfunction, Multiple System Atrophy, and the Postural Orthostatic Tachycardia Syndrome. On the other hand, acute dysautonomias represent a rare yet clinically sometimes dramatic form of autonomic disorders. Several diseases as well as enzymatic disorders, and pharmacological drugs may cause secondary dysautonomia. The clinical correlate of all these forms of dysautonomia is orthostatic hypotension and syncope. Thus, a careful history forms the basis of a successful diagnostic workup of the underlying cause of syncope. This review summarizes the current knowledge of autonomic disorders, their classification and diagnostic and therapy strategies.