Orthostatic Hypotension: Mechanisms,Causes, Management

Orthostatic hypotension (OH) occurs when mechanisms for the regulation of orthostatic BP control fails. Such regulation depends on the baroreflexes, normal blood volume, and defenses against excessive venous pooling. OH is common in the elderly and is associated with an increase in mortality rate. There are many causes of OH. Aging coupled with diseases such as diabetes and Parkinson''s disease results in a prevalence of 10-30% in the elderly. These conditions cause baroreflex failure with resulting combination of OH, supine hypertension, and loss of diurnal variation of BP. The treatment of OH is imperfect since it is impossible to normalize standing BP without generating excessive supine hypertension. The practical goal is to improve standing BP so as to minimize symptoms and to improve standing time in order to be able to undertake orthostatic activities of daily living, without excessive supine hypertension. It is possible to achieve these goals with a combination of fludrocortisone, a pressor agent (midodrine or droxidopa), supplemented with procedures to improve orthostatic defenses during periods of increased orthostatic stress. Such procedures include water bolus treatment and physical countermaneuvers. We provide a pragmatic guide on patient education and the patient-orientated approach to the moment to moment management of OH.     

Pyridostigmine treatment trial in neurogenic orthostatic hypotension

BACKGROUND: Midodrine hydrochloride is the only drug demonstrated in a placebo-controlled treatment trial to improve orthostatic hypotension (OH) but it significantly worsens supine hypertension. By enhancing ganglionic transmission, pyridostigmine bromide can potentially ameliorate OH without worsening supine hypertension. OBJECTIVE: To evaluate the efficacy of a single 60-mg dose of pyridostigmine bromide, alone or in combination with a subthreshold (2.5 mg) or suprathreshold (5 mg) dose of midodrine hydrochloride, compared with placebo. DESIGN: We report a double-blind, randomized, 4-way cross-over study of pyridostigmine in the treatment of neurogenic OH. A total of 58 patients with neurogenic OH were enrolled. After 1 day of baseline measurements, patients were given 4 treatments (3 active treatments [60 mg of pyridostigmine bromide; 60 mg of pyridostigmine bromide and 2.5 mg of midodrine hydrochloride; 60 mg of pyridostigmine bromide and 5 mg of midodrine hydrochloride] and a placebo) in random order on successive days. Blood pressure (BP) and heart rate were measured, both supine and standing, immediately before treatment and hourly for 6 hours after the treatment was given. RESULTS: No significant differences were seen in the supine BP, either systolic (P = .36) or diastolic (P = .85). In contrast, the primary end point of the fall in standing diastolic BP was significantly reduced (P = .02) with treatment. Pairwise comparison showed significant reduction by pyridostigmine alone (BP fall of 27.6 mm Hg vs 34.0 mm Hg with placebo; P = .04) and pyridostigmine and 5 mg of midodrine hydrochloride (BP fall of 27.2 mm Hg vs 34.0 mm Hg with placebo; P = .002). Standing BP improvement significantly regressed with improvement in OH symptoms. CONCLUSIONS: Pyridostigmine significantly improves standing BP in patients with OH without worsening supine hypertension. The greatest effect is on diastolic BP, suggesting that the improvement is due to increased total peripheral resistance.     

Acetylcholinesterase inhibition: a novel approach in the treatment of neurogenic orthostatic hypotension

BACKGROUND: Pharmacological treatment of orthostatic hypotension is often limited because of troublesome supine hypertension. OBJECTIVE: To investigate a novel approach to treatment using acetylcholinesterase inhibition, based on the theory that enhanced sympathetic ganglion transmission increases systemic resistance in proportion to orthostatic needs. DESIGN: Prospective open label single dose trial. MATERIAL: 15 patients with neurogenic orthostatic hypotension caused by: multiple system atrophy (n = 7), Parkinson's disease (n = 3), diabetic neuropathy (n = 1), amyloid neuropathy (n = 1), and idiopathic autonomic neuropathy (n = 3). METHODS: Heart rate, blood pressure, peripheral resistance index (PRI), cardiac index, stroke index, and end diastolic index were monitored continuously during supine rest and head up tilt before and one hour after an oral dose of 60 mg pyridostigmine. RESULTS: There was only a modest non-significant increase in supine blood pressure and PRI. In contrast, acetylcholinesterase inhibition significantly increased orthostatic blood pressure and PRI and reduced the fall in blood pressure during head up tilt. Orthostatic heart rate was reduced after the treatment. The improvement in orthostatic blood pressure was associated with a significant improvement in orthostatic symptoms. CONCLUSIONS: Acetylcholinesterase inhibition appears effective in the treatment of neurogenic orthostatic hypotension. Orthostatic symptoms and orthostatic blood pressure are improved, with only modest effects in the supine position. This novel approach may form an alternative or supplemental tool in the treatment of orthostatic hypotension, specially for patients with a high supine blood pressure.     

Carotid artery thickening and neurocirculatory abnormalities in de novo Parkinson disease

Cognitive dysfunction constitutes a major non-motor manifestation of Parkinson disease (PD), but the mechanisms remain incompletely understood. Neurocirculatory abnormalities such as supine hypertension (SH) and orthostatic hypotension (OH), white matter hyperintensities upon magnetic resonance imaging, and dementia are inter-related in PD, even in patients with early, levodopa-untreated disease. These abnormalities might in turn be associated with carotid atherosclerosis which, by a variety of interacting means could contribute to repeated episodes of cerebral hypo- and hyper-perfusion. We investigated inter-correlations among neurocirculatory and carotid sonographic measurements [intimal-medial thickness (IMT) and wall:lumen ratios (WLR)] in 65 patients with levodopa-untreated, de novo PD who underwent tilt table testing and 24-h ambulatory blood pressure monitoring. Increased mean IMT and WLR were associated with OH and supine and overnight blood pressures. Across individuals the orthostatic fall in systolic pressure was correlated with both IMT and WLR. Since arteriosclerosis would be expected to splint carotid sinus baroreceptors, complex positive interactions among carotid wall thickening, SH, and OH may result in myriad episodes of cerebral hypo- and hyper-perfusion, contributing to microvascular injury and consequently to the cognitive dysfunction attending PD.     

The period of hypotension following orthostatic challenge is prolonged in dementia with Lewy bodies

OBJECTIVES: To determine whether orthostatic hypotension (OH) is more common in patients with dementia than in older people without cognitive impairment and to identify key differences in the profile of the orthostatic response and the pulse drive during orthostatic challenge between Alzheimer's disease (AD) and dementia with Lewy bodies (DLB). METHODS: The orthostatic response was evaluated in 235 patients with AD, 52 patients with DLB and 62 elderly controls. The blood pressure and pulse rate were measured in supine position, immediately after standing up and after 1, 3, 5 and 10 min of standing. OH was defined as a reduction of systolic blood pressure (SBP) of at least 20 mm Hg or a reduction of diastolic blood pressure (DBP) of at least 10 mm Hg. RESULTS: OH occurred in 69% of the DLB patients and in 42% of the AD patients, but only in 13% of the controls (p<0.001 controls vs AD and controls vs DLB, p=0.001 AD vs DLB) The DLB patients had a greater drop in SBP than the other study groups during orthostatic challenge and had a more prolonged period of orthostasis. The pulse drive on orthostatic challenge was similar in between groups. However, in the DLB group it was not adequate to restore the blood pressure to supine values. CONCLUSIONS: Patients with DLB react different to orthostatic challenge than patients with AD or controls, with important clinical implications for key disease symptoms and treatment.     

Temporary elimination of orthostatic hypotension by norepinephrine infusion

A cardinal manifestation of chronic autonomic failure is neurogenic orthostatic hypotension (OH), which often is associated with supine hypertension, posing a therapeutic dilemma. We report here success in a first step toward development of a “prosthetic baroreceptor system” to maintain blood pressure during orthostasis without worsening supine hypertension. In all of four patients with neurogenic OH, titrated i.v. NE infusion kept directly recorded intra-arterial pressure at or above baseline during progressive head-up tilt. We conclude that titrated i.v. NE infusion temporarily eliminates OH.     

Treatment of diabetic orthostatic hypotension with Pindolol

The hemodynamic variables, plasma noradrenaline and plasma renin concentrations were studied in a 57-year-old female with insulin-dependent diabetes of long-standing and orthostatic hypotension. For 6 months she had been bedridden because of severe orthostatic symptoms. Reflex responses in the heart rate and blood pressure during the Valsalva manoeuvre as well as beat-to-beat variations in heart rate were absent. Plasma noradrenaline concentrations were subnormal both in the supine and up-right positions.
After treatment with Pindolol 15 mg/day the patient was able to walk around and lead an almost normal life. The orthostatic symptoms recurred after withdrawal of therapy and disappeared on resumption of therapy. Arterial blood pressure measured intra-arterially decreased less in the up-right position during treatment with Pindolol compared to that in the untreated condition. The heart rate did not change during treatment with Pindolol.
Our findings suggest that Pindolol may be an important drug in the treatment of diabetic orthostatic hypotension.     

Ergotamine/caffeine treatment of orthostatic hypotension in parkinsonism with autonomic failure

Eight patients with parkinsonism who developed severe orthostatic sypotension, were treated with oral ergotamine/caffeine. Significant long-term improvement in standing systolic blood pressure and symptoms of syncope and light-headedness were observed in four of these patients. One patient in whom the drug was effective discontinued it because of nausea. Another lost benefit after 2 weeks of sucessful therapy. Significant supine systolic hypertension occureed in only one patient, which was easily managed by nifedipine given at night. Symptoms or signs of ergotism were not observed. Oral ergotamine/caffeine should be considered as a cost-effective teratment for refactory orthostatic hypotension in carefully selected patients with parkinsonism.     

Blood pressure disorders during Parkinson's disease: epidemiology, pathophysiology and management

Blood pressure disorders are highly prevalent in the course of Parkinson's disease (PD). They relate to autonomic failure and are frequently associated with orthostatic hypotension, postprandial hypotension and supine hypertension. Supine hypertension, which may concern up to 50% of patients with PD and autonomic failure, is driven by residual sympathetic activity and changes in sensitivity of vascular adrenergic receptors. It can also be induced or worsened by antihypotensive drugs. Even if little data is available, a set of arguments suggests that supine hypertension sometimes requires treatment. This review will focus on recent data on the pathophysiology and the management of supine hypertension in the context of its association with orthostatic hypotension.     

The Frequency Of Arterial Hypertension Versus Orthostatic Hypotension In Diabetic Patients

Aim: The aim of this study was to assess the relationship between supine high blood pressure and orthostatic hypotension both in Type 1 (T1DM) and Type 2 (T2DM) diabetic patients. Patients and Methods: Our study included 321 T2DM patients (153 M/168 F; mean age 62.3 (14.2 yr; duration of disease 12.1 (7.6 yr) and 116 T1DM patients (65 M/51 F; mean age 39.7 (9.2 yr; duration of diabetes 11.9 (8.1 yr). Patients with orthostatic hypotension were divided into 3 groups: A – without symptoms; B – mild/moderate symptoms (short and tolerable dizziness when standing); C – severe symptoms (persistent and disabling dizziness or even fainting in upright position). Results: Arterial hypertension was registered in 67.6% of T2DM patients (217 from 321 cases) and in 50.0% of T1DM patients (58 from 116 cases). Orthostatic hypotension (defined as a decrease in systolic blood pressure (30 mm Hg)) was encountered in 64.5% in T2DM patients (207 out of 321 cases) and in 60.3% of T1DM patients (70 out of 116 cases). From 207 T2DM patients with orthostatic hypotension, 105 were in Group A (50.7%), 89 in Group B (42.99%) and 13 in Group C (6.28%), while from 70 T1DM patients with orthostatic hypotension 14 were in Group A (20.0%), 51 in Group B (72.8%) and 5 in Group C (7.14%). An association of supine arterial hypertension with orthostatic hypotension was registered in 96 (29.9%) T2DM patients (68 of them receiving antihypertensive treatment) and in 25 (21.5%) T1DM patients (19 of which were on antihypertensive treatment). From the 18 patients with severe orthostatic hypotension (13 T2DM and 5 T1DM), supine arterial hypertension was registered in 5 cases (3 T2DM and 2 T1DM). In 4 of these 5 cases, patients were receiving antihypertensive treatment. Discontinuation of this treatment led to a decrease in the intensity of clinical signs of orthostatic hypotension in 4 out of 5 cases. An improvement of clinical symptoms of orthostatic hypotension was recorded in about 1/3 of hypertensive patients after discontinuation or just lowering of the dose of antihypertensive drugs (26 out of 87 cases). Conclusion: An association between hypertension and orthostatic hypotension is frequent both in T1DM and in T2DM, rising in difficulties for treatment. The treatment of hypertension in diabetic patients should take into account the possible orthostatic hypotension induced by some of the antihypertensive drugs.     

Acetylcholinesterase inhibition in patients with orthostatic intolerance.

The efficacy of current therapeutic measures in orthostatic intolerance (OI) varies among patients and is oftentimes unsatisfactory. New approaches to alleviate symptoms of OI are therefore clearly needed. Recent reports have demonstrated that acetylcholinesterase inhibition is effective in the treatment of orthostatic hypotension with the presumed mechanism of enhancing sympathetic ganglionic transmission. Based on the hypothesis that acetylcholinesterase inhibition, by improving the safety factor of cholinergic transmission, will result in enhanced vascular adrenergic tone and a vagal shift in cardiac sympathovagal balance, we evaluated the role of acetylcholinesterase inhibition in the treatment of patients with OI. We monitored heart rate (HR), blood pressure, and indexes for cardiac output, end-diastolic volume, and systemic resistance continuously in 18 patients with OI during supine rest and during 5 minutes of 70 degrees head-up tilt before and 1 hour after oral administration of 60 mg pyridostigmine. Plasma catecholamines and baroreflex sensitivity were determined for the supine and upright position before and after medication. Patients scored orthostatic symptoms for both tilt studies. The excessive HR response to orthostatic stress was significantly blunted after pyridostigmine administration. HR was significantly lower in the supine and more so in the upright position. Baroreflex sensitivity in the upright position was significantly higher after pyridostigmine. Norepinephrine was increased in both supine and upright position. These changes were associated with significant improvement of orthostatic symptoms. We conclude that pyridostigmine improves orthostatic tolerance in patients with OI. Our findings support the suggested mechanisms of enhanced sympathetic ganglionic neurotransmission and a vagal shift in cardiac sympathovagal balance. Acetylcholinesterase inhibition could be a new useful concept in the treatment of OI.     

Orthostatic Hypotension in Parkinson Disease: How Much You Fall or How Low You Go?

Orthostatic hypotension (OH) is frequent in patients with Parkinson's disease (PD) and can occur with or without symptoms. Pharmacological treatments are effective, but often exacerbate supine hypertension. Guidelines exist for the diagnosis, but not for the treatment of OH. We examined the relationship between blood pressure (BP) and symptoms in a cohort of PD patients with the goal of identifying a hemodynamic target to guide treatment. We measured BP supine and upright (tilt or active standing) and identified the presence or absence of symptomatic OH by using a validated patient‐reported outcome questionnaire in 210 patients with PD. We evaluated the usefulness of the 20/10 and 30/15 mmHg diagnostic criteria (systolic/diastolic) to identify symptomatic OH. Fifty percent of the PD patient cohort met criteria for the 20/10 fall and 30% for the 30/15 BP fall. Among the patients who met either OH criteria, the percentage of those with symptoms was small (33% of those with 20/10 and 44% of those with 30/15 mmHg; 16% and 13%, respectively, overall). Symptomatic OH was associated with an upright mean BP below 75 mmHg. A mean standing BP <75 mmHg had a sensitivity of 97% and a specificity of 98% for detecting symptomatic OH. Although the prevalence of OH in PD is high, not all patients have symptoms of organ hypoperfusion. A mean standing BP below 75 mmHg appears to be a useful benchmark when deciding whether the benefits of initiating pharmacological treatment of OH outweigh the risks of exacerbating supine hypertension. © 2015 International Parkinson and Movement Disorder Society     

Treatment of autonomic dysfunction in Parkinson disease and other synucleinopathies

Dysfunction of the autonomic nervous system afflicts most patients with Parkinson disease and other synucleinopathies such as dementia with Lewy bodies, multiple system atrophy, and pure autonomic failure, reducing quality of life and increasing mortality. For example, gastrointestinal dysfunction can lead to impaired drug pharmacodynamics causing a worsening in motor symptoms, and neurogenic orthostatic hypotension can cause syncope, falls, and fractures. When recognized, autonomic problems can be treated, sometimes successfully. Discontinuation of potentially causative/aggravating drugs, patient education, and nonpharmacological approaches are useful and should be tried first. Pathophysiology‐based pharmacological treatments that have shown efficacy in controlled trials of patients with synucleinopathies have been approved in many countries and are key to an effective management. Here, we review the treatment of autonomic dysfunction in patients with Parkinson disease and other synucleinopathies, summarize the nonpharmacological and current pharmacological therapeutic strategies including recently approved drugs, and provide practical advice and management algorithms for clinicians, with focus on neurogenic orthostatic hypotension, supine hypertension, dysphagia, sialorrhea, gastroparesis, constipation, neurogenic overactive bladder, underactive bladder, and sexual dysfunction. © 2018 International Parkinson and Movement Disorder Society     

Treatment of neurogenic orthostatic hypotension with amezinium metilsulfate, a new indirect sympathomimetic drug

Amezinium metilsulfate is a new, indirectly acting sympathomimetic drug which exclusively affects postganglionic sympathetic neurons and inhibits both intraneuronal monoamine oxidase and norepinephrine reuptake. We examined the short-term effects of amezinium in five patients with severe neurogenic orthostatic hypotension. Single-dose administration of amezinium (10 mg) raised both the supine and sitting mean blood pressures by 15 to 45 mm Hg for 8 hours, with a slight increase in the plasma norepinephrine level. Repeated administration of amezinium (10 to 40 mg/d) produced an increase in sitting blood pressure in three patients and improvement of the orthostatic symptoms in all patients without remarkable recumbent hypertension. The heart rate was increased in two patients. The results indicate that amezinium is of therapeutic value for the treatment of neurogenic orthostatic hypotension. The adrenergic effect of amezinium on the blood pressure and heart rate apparently was related to a slight increase in endogenous norepinephrine in the presence of alpha- and beta-adrenoreceptor supersensitivity.     

Improved orthostatic tolerance in familial amyloidotic polyneuropathy with unnatural noradrenaline precursor l-threo-3,4-dihydroxyphenylserine

Disabling orthostatic hypotension, due to insufficiency of the autonomic nervous system, is a common complication of type I familial amyloidotic polyneuropathy (FAP). We investigated whether oral treatment with l-threo-3,4-dihydroxyphenylserine (l-threo-Dops), a noradrenaline precursor, might be of therapeutical benefit. In twenty untreated FAP patients, aged 33 to 44 years, who, because of severe orthostatic hypotension, were bedridden or constrained to a sitting life, supine and erect blood pressure (BP), plasma noradrenaline and tilting time, defined as the interval (s) between the beginning of a 60° head-up tilt and the occurrence of orthostatic symptoms (dizziness, blurred vision or near syncope) were determined before and at repeated intervals during oral treatment with l-threo-Dops, 100 mg bid, for 6 months. Before treatment supine mean BP was 80 (76–85) mmHg (mean and 95% CI), supine plasma noradrenaline was low, 59 (41–77) pg/ml and tilting time ranged from 38 to 118 s. In response to tilt, mean BP immediately fell by 36 (31–41) mmHg, whereas plasma noradrenaline increased by only 11 (0–21) pg/ml (p=0.05). After 3 to 5 days of treatment with l-threo-Dops all patients experienced marked improvement of their orthostatic tolerance as reflected by their ability to walk freely around. This effect sustained throughout the six months of treatment. Plasma noradrenaline increased moderately by 37 (11–63) pg/ml (p=0.02) and supine mean BP increased by 8.6 (5.8–12.4) mmHg (p<0.001) during chronic treatment. Supine or nocturnal hypertension did not develop, the fall in mean BP in response to tilt diminished by 12.5 (6.5–17.3) mmHg (p<0.001) and tilting time became longer than 600 s in all patients. Because of its efficacy, its sustained duration of action and the lack of side effects, l-threo-Dops is advocated to improve orthostatic tolerance in patients with autonomic insufficiency due to FAP.     

Primary orthostatic hypotension syndromes without somatic neurologic signs--idiopathic orthostatic hypotension and primary sympathicotonic orthostatic hypotension

Idiopathic orthostatic hypotension (IOH) and primary sympathicotonic orthostatic hypotension (PSOH) are conspicuous orthostatic hypotension syndromes without overt somatic neurologic signs. IOH, also referred as pure autonomic failure, is a syndrome of chronic pandysautonomia, and its clinical features include supine hypertension, anhidrosis, impotence, neurogenic urinary and bowel disturbances. PSOH is different from IOH in which it is not accompanied with autonomic features outside of cardiovascular symptoms, and has been most commonly described in German-Scandinavian literatures. The controversy in the nosology of IOH and PSOH has prevented the both concepts from world-wide acceptance, and little has been known about IOH in Japanese population. In the present study, statistical analyses were made to elicit the cases of orthostatic hypotension syndrome without somatic neurologic signs from the pooled results of hemodynamic autonomic functional tests in our laboratory. The subjects were 287 Japanese cases comprising 253 normotensive volunteers and 34 hypertensive patients. Apart from hypertension, none of the subjects exhibited abnormal findings on physical, neurological and routine laboratory examinations. The test of 70 degrees passive head-up tilt and other hemodynamic tests were performed upon the subjects, and the results were pooled by ages. By means of the method of maximum normed residual, statistically screened out were 7 cases with extremely great orthostatic fall in systolic blood pressure (OH-I). Another OH group (OH-II) consisted of 24 cases who showed orthostatic decrease in systolic blood pressure of 30 mmHg or more, but did no fall into the extreme observation. Assuming that the orthostatic regulation mechanism of blood pressure was well maintained in the remaining 256 cases, they were used as the control.(ABSTRACT TRUNCATED AT 250 WORDS)     

Acute orthostatic hypotension when starting dopamine agonists in Parkinson's disease

OBJECTIVE: To study the frequency and severity of acute orthostatic hypotension (OH) in patients with Parkinson's disease who are starting dopamine agonist therapy. PATIENTS AND METHODS: In the context of an outpatient clinical practice, 29 consecutive patients with Parkinson's disease who were starting dopamine agonist therapy were brought into the clinic for their first dose of agonist. After a baseline supine and standing blood pressure assessment, patients were given a test dose of either pergolide mesylate (0.025, 0.05, 0. 125, or 0.25 mg), pramipexole dihydrochloride (0.125 mg), or ropinirole hydrochloride (0.125 or 0.25 mg). At 3 selected times, blood pressure readings were repeated in the supine and standing positions. MAIN OUTCOME MEASURE: Orthostatic hypotension was defined as a drop in either systolic blood pressure of more than 25 mm Hg or diastolic pressure of more than 10 mm Hg. Patients with OH before the administration of the dopamine agonist were excluded. RESULTS: Ten subjects (34%) met the criteria for acute OH. There was no evidence that OH was related to the use of a specific dopamine agonist or the concurrent use of levodopa. Of the patients who met the criteria for OH, only 3 (30%) had symptoms of OH, such as lightheadedness or general malaise. CONCLUSIONS: Acute OH occurs frequently when starting dopamine agonist therapy in Parkinson's disease, but is frequently not appreciated by patients. Knowledge of acute blood pressure responses may be useful when making decisions regarding agonist titration schedules in clinical practice. Arch Neurol. 2000;57:1461-1463     

Prevalence of orthostatic hypotension

Orthostatic hypotension (OH) is defined as a fall in blood pressure of at least 20 mmHg systolic or 10 mmHg diastolic when standing or during head-up tilt testing. The prevalence of OH increases with age, with disorders that affect autonomic nerve transmission, and with increasingly severe orthostatic stress. In normal elderly subjects, the prevalence of OH is reported to be between 5 and 30%. The actual prevalence depends on the conditions during diagnostic testing, such as the frequency of blood pressure recordings, the time of day and the degree of orthostatic stress. Elderly subjects are often taking medications, such as antihypertensives and diuretics that can cause or aggravate OH. Neurological diseases such as diabetic neuropathy, Parkinson’s disease, multiple system atrophy and the autonomic neuropathies further increase the likelihood of OH. The development of OH in normal subjects is associated with an increased mortality rate. OH in diabetes is also associated with a significant increase in mortality rate.     

Pure Autonomic Failure

Pure autonomic failure (PAF) is a rare sporadic neurodegenerative autonomic disorder characterized by slowly progressive pan autonomic failure without other features of neurologic dysfunctions. The main clinical symptoms result from neurogenic orthostatic hypotension and urinary and gastrointestinal autonomic dysfunctions. Autonomic failure in PAF is caused by neuronal degeneration of pre- and postganglionic sympathetic and parasympathetic neurons in the thoracic spinal cord and paravertebral autonomic ganglia. The presence of Lewy bodies and α-synuclein deposits in these neural structures suggests that PAF is one of Lewy body synucleinopathies, examples of which include multiple system atrophy, Parkinson disease, and Lewy body disease. There is currently no specific treatment to stop progression in PAF. Management of autonomic symptoms is the mainstay of treatment and includes management of orthostatic hypotension and supine hypertension. The prognosis for survival of PAF is better than for the other synucleinopathies.     

Neurogenic orthostatic hypotension of Parkinson's disease: What exploration for what treatment?

The aim of this short review is to illustrate, using orthostatic hypotension as an example, the clinical problems related to autonomic features in Parkinson's disease. Orthostatic hypotension is frequently encountered in Parkinson's disease and its diagnosis remains manometric (a fall of at least 20 and/or 10 mmHg in standing blood pressure). It is often associated with supine hypertension to be taken into account before prescribing. To distinguish between the role of disease and of drugs (not only antiparkinsonian drugs), a simple clinical test of autonomic nervous system activity (deep breathing test and standing test with measurement of 30/15 ratio) can be used. When diagnosis with multisystem atrophy is discussed, cardiac [¹²³I]-metaiodobenzylguanidine (MIBG) scintigraphy is of value showing in Parkinson's disease a decreased uptake of the radiopharmaceutical indicating postganglionic sympathetic denervation. Concerning treatment, nonpharmacological methods have to be systematically used since no drug has been specifically evaluated for the treatment of orthostatic hypotension of Parkinson's disease.