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The relationship between locomotor disability, autonomic dysfunction, and the integrity of the striatal dopaminergic system in patients with multiple system atrophy, pure autonomic failure, and Parkinson's disease, studied with PET.

18F-dopa and S-11C-nomifensine (NMF) are positron emitting tracers whose caudate and putamen uptake reflects striatal dopamine storage capacity and the integrity of dopamine reuptake sites, respectively. Using these two tracers, the integrity of the presynaptic striatal dopaminergic system has been studied with positron emission tomography (PET) in 10 subjects with multiple system atrophy (MSA, Shy-Drager syndrome) who had an akinetic-rigid syndrome that was poorly responsive to L-dopa, autonomic failure, and cerebellar ataxia. PET findings for the 10 MSA patients were compared with those for 13 age-matched controls, 8 subjects with L-dopa responsive Parkinson's disease (PD), and 7 subjects with pure autonomic failure (PAF). Influx constants, Ki, reflecting specific 18F-dopa uptake into striatal tissue, were severely reduced in the putamen and caudate of the 10 MSA subjects (mean putamen Ki 0.005 min-1 MSA vs 0.013 min-1 controls; mean caudate Ki 0.007 min-1 MSA vs 0.013 min-1 controls). Reduction of putamen, but not caudate, 18F-dopa uptake correlated with severity and duration of locomotor disability. Eight patients with PD, and a similar degree and duration of locomotor disability to the patients with MSA, demonstrated equal impairment of mean putamen 18F-dopa uptake, but significant preservation of mean caudate function. The 7 PAF patients had normal mean levels of putamen and caudate 18F-dopa uptake, although 1 individual PAF patient had significantly impaired striatal function. The MSA and PD groups of subjects both showed significantly reduced levels of specific striatal S-11C-NMF binding, again caudate function being relatively preserved in PD. It is concluded that in both MSA and PD there is a parallel decline of striatal dopamine storage capacity and reuptake site integrity, probably reflecting a loss of nigrostriatal nerve terminals. Caudate function is relatively preserved in PD compared with MSA. The majority of PAF patients have an intact nigrostriatal dopaminergic system, suggesting that PAF is a condition distinct from PD and MSA in spite of some pathological similarities. PET is capable of detecting subclinical nigrostriatal involvement in PAF patients when this is present.

Adult

Autonomic dysfunction in recent onset and advanced Parkinson's disease.

Cardiovascular autonomic nerve function and its relation to the clinical variables of untreated recent onset and levodopa-treated advanced disease parkinsonian patients were studied. Heart rate variations were diminished in both groups when compared with age-matched controls. An orthostatic blood pressure drop was found in both disease groups. The drop was stronger and related to the levodopa dose in the advanced disease group. In conclusion, 1) in Parkinson's disease a parasympathetic damage occurs which worsens during the course of the disease, 2) the orthostatic fall in blood pressure, indicating a sympathetic dysfunction, is partly due to the disease itself and partly due to levodopa treatment.

Aged

Autonomic dysfunction in the Landry-Guillain-Barre syndrome.

Tests of autonomic function have been performed on 7 patients with the Landry-Guillain-Barre syndrome and 5 control subjects. These included a sweat test, and measurement of both postural hypotension and baroreflex sensitivity. Sweating was definitely abnormal in 5 patients. Postural hypotension was present in 4 patients. The baroreflex sensitivity was significantly reduced (p less than 0.01) in the patients when compared with the control group. The results demonstrate that both the sympathetic and parasympathetic nervous systems may be affected in the Landry-Guillain-Barre syndrome.

Adult

Control of nausea and autonomic dysfunction with terfenadine, a peripherally acting antihistamine.

Terfenadine (Seldane) was administered to 14 male subjects in a randomized, double-blinded, and crossed-over design to assess the efficacy of this peripherally active antihistamine as an anti-motion sickness drug. Terfenadine possesses practically no central side effects. A Staircase Profile Test was administered 4 h following placebo or a single oral dose of terfenadine (300 mg). The study revealed a statistically significant therapeutic effect from terfenadine (p less than 0.05). This led us to conclude that because the drug does not or only poorly crosses the blood-brain barrier, a selective peripheral antihistamine (H1) action may be sufficient in the control of motion sickness induced through cross-coupled accelerative semicircular canal stimulation using a rotating chair. This finding implies that other peripherally acting agents might be found that possess even greater anti-motion sickness efficacy. The present research raises additional questions regarding current theories on the etiology of motion sickness, its associated autonomic system dysfunction, and the validity of assumptions that effective pharmacological agents must act centrally.

Autonomic Nervous System

[Autonomic dysfunction in patients with temporal lobe epilepsy].

In 102 patients with temporal epilepsy autonomic (tone, responses, effectiveness) and sympathoadrenal (urine excretion of catecholamines and its changes under effects of epinephrine, insulin and L-DOPA administration) systems were investigated. Some of the indices under study showed reliable correlations with clinical data. Pronounced alterations of autonomic functions were found. The data suggest an important role of catecholamines in the pathogenesis of temporal epilepsy.

Adolescent

Age-dependent occurrence of autonomic dysfunction in chronic uraemia.

A battery of cardiovascular reflex tests were performed in twenty patients with chronic renal failure on intermittent haemodialysis. Using age-adjusted confidence limits, old-aged uraemics showed more extensive parasympathetic and sympathetic dysfunction than middle-aged patients. The results suggest that autonomic nervous system in the elderly is more susceptible to uraemic toxins than in the middle age. This should lead to better preventive and therapeutic strategies in older uraemics.

Adult

Occurrence of uraemic autonomic dysfunction in relation to age.

A battery of cardiovascular reflex tests were performed on 20 patients with chronic renal failure on intermittent haemodialysis, to assess occurrence of parasympathetic and sympathetic abnormalities. Using age-adjusted confidence limits, elderly uraemics showed more extensive parasympathetic and sympathetic dysfunction than middle-aged patients. The results suggest that the autonomic nervous system in the elderly is more susceptible to uraemic toxins than in the middle aged. This should lead to better preventive and therapeutic strategies for older uraemics.

Adult

[Autonomic dysfunction in metabolic diseases].

Among many metabolic disorders, porphyrias and Fabry disease are known to affect autonomic nervous system. In patients with acute intermittent porphyria, hereditary coproporphyria, and variegate porphyria, autonomic symptoms such as abdominal pain, vomiting, hypertension and tachycardia are among the most prominent clinical manifestations. Fabry disease is clinically characterized by severe limb pain, hypohidrosis, angiokeratomas and various autonomic symptoms. In both porphyrias and Fabry disease, pathological changes in the central and peripheral autonomic nervous system have been documented. In porphyrias, a loss of myelinated fibers, axonal degeneration, and segmental demyelination in peripheral autonomic nerves as well as chromatolysis of several brain stem nuclei have been found. In Fabry disease, abnormal amount of the substrates of alpha-galactosidase, i.e. ceramide di- and trihexoside, are found to be accumulated in the central and peripheral autonomic nerves.

Autonomic Nervous System Diseases

Cardiac autonomic dysfunction during sleep in some neurological diseases.

The most widely used tests for the investigation of the autonomic nervous system (ANS) functioning measure the heart rate (HR) variations during wakefulness. Most tests have some limitations: they require patient collaboration and can be modified by his or her emotional status. We studied HR variability in relation to body movements during sleep in some neurological diseases. Our method seems to be better than the traditional tests in detecting early cardiac ANS damage, especially when the patient is non-co-operative for ANS evaluation during wakefulness after various stimuli.

Adult

Autonomic dysfunction in botulism B: a clinical report.

Nine cases of botulism B with preponderant effects upon cholinergic autonomic innervation are presented. Blurred vision and dry mouth were constant symptoms. Impairment of salivary and lacrimal secretion were detectable for months. In the absence of clinical signs, electromyographic studies did not reveal neuromuscular involvement. Administration of antitoxin in the late course of such cases is not recommended, but guanidine can be used. Doubt is cast upon a new clinical entity called "acute autonomic neuropathy."

Adult