André Rascol

Adrenergic supersensitivity in Parkinsonians with orthostatic hypotension

Abstract. The adrenergic status was studied through evaluation of platelet α2‐adrenoceptor number ([3H]‐yohimbine binding sites), plasma catecholamine levels and blood pressure response to noradrenaline infusion in three groups of subjects (1) Parkinsonians with orthostatic hypotension; (2) Parkinsonians without orthostatic hypotension; and (3) control subjects. In Parkinsonians with orthostatic hypotension, systolic and diastolic blood pressures significantly (P < 0.05) decreased from 144 pM 9 and 76 pM 6 mmHg in the lying position to 95 pM 12 and 60 pM 7 mmHg after 5 min standing. In these patients, noradrenaline plasma levels were significantly low (62 pM 11 pg ml‐1, (P < 0.05) when compared with controls (219 pM 13 pg ml‐1) whereas no difference was noticed in Parkinsonians without orthostatic hypotension (195 pM 14 pg ml‐1). The noradrenaline dose required for a 25 mmHg increase in systolic blood pressure was significantly (P < 0.01) lower in Parkinsonians with orthostatic hypotension (019 pM 0.03 μg kg‐1) when compared with Parkinsonians without orthostatic hypotension (0.86 pM 0.11 μg kg‐1) or with controls (0.68 pM 0.l μg kg‐1). Platelet x2‐adrenoceptor number was higher in Parkinsonians with orthostatic hypotension (313 pM 52 fmol mg‐1 protein) than in Parkinsonians without orthostatic hypotension (168 pM 9 fmol mg‐1 protein) or in controls (175 pM 4 fmol mg‐1 protein) with no change in Kd. This study demonstrates that in patients with Parkinsons disease, orthostatic hypotension is associated with an increase in both vascular sensitivity to noradrenaline and platelet α2‐adrenoceptor number. These observations suggest the existence of an α‐adrenergic supersensitivity in response to the low levels of plasma noradrenaline.

Effect of side and rate of stimulation on cerebral blood flow changes in motor areas during finger movements in humans.

We measured, using single photon emission computed tomography, the regional CBF (rCBF) changes in the motor areas of 24 right-handed normal volunteers during the performance of a motor task consisting of sequential finger-to-thumb opposition. Twelve of them performed the task with their right and their left hands consecutively with a fast frequency and large amplitude. The other 12 subjects performed the task with their right hand only at a slow frequency and small amplitude. The contralateral primary sensorimotor area (S1/M1), supplementary motor area (SMA), and ipsilateral cerebellum were significantly activated during right and left finger movements performed at fast frequency and large amplitude. No significant difference was found between the rCBF changes induced by the right dominant and left nondominant hands. When the task was performed with a slow rate and small amplitude, the SMA was significantly activated while no significant changes were observed in the contralateral S1/M1 or in the ipsilateral cerebellum. These results demonstrate (a) that hand dominance evokes no differences in the activation of the main motor areas and (b) that the frequency and amplitude of the movement have a major effect on the quantitative and qualitative aspect of activation of motor areas in humans.

Ambulatory blood pressure in patients with Parkinson's disease without and with orthostatic hypotension.

Non-invasive ambulatory recordings of blood pressure and heart rate were performed using a Spacelabs device during day and night periods in patients with Parkinsons disease with (n = 19) or without orthostatic hypotension (n = 19). In patients with orthostatic hypotension, the average systolic and diastolic blood pressure during the night (137 ± 5/80 ± 3 mmHg) was higher (p < 0.05) than during the day period (121 ± 3/76 ± 2 mmHg). In patients without orthostatic hypotension, a decrease in blood pressure was recorded during the nocturnal period. In patients with orthostatic hypotension, the blood pressure variability was higher (p < 0.05) during the day (systolic: 14.6 ± 1.3%; diastolic: 16.5 ± 1.0%) than during the night (systolic: 9.1 ± 0.8%; diastolic: 10.8 ± 1.1%). The blood pressure load (percentage of values above 140/90 mmHg) during the night was significantly higher than during the day for both systolic (41.2 ± 8.1 vs. 19.6 ± 4.7%) and diastolic blood pressure (24.9 ± 6.9 vs. 16.3 ± 4.9%). There was a decrease in heart rate in both groups during the night. A fall of 25 mmHg or more in systolic blood pressure after meals occurred in ten patients with orthostatic hypotension and in one patient without orthostatic hypotension. These results indicate that orthostatic hypotension in Parkinsons disease is associated with specific modifications of ambulatory blood pressure including loss of circadian rhythm of blood pressure, increased diurnal blood pressure variability and post-prandial hypotension.

Parkinson's disease and weight loss: A study with anthropometric and nutritional assessment

In order to investigate a putative weight loss in patients with Parkinsons disease, an anthropometric and biochemical study was undertaken. We compared body weight and indexes of fat [body mass index (BMI), tricipital skinfold] and lean [midarm muscle area (MMA), calf circumference] mass in men and women suffering from idiopathic Parkinsons disease with normal controls. We found that women suffering from Parkinsons disease exhibited a significant weight loss (−8.5%) and decreased calf circumference when compared with controls. A decrease (−4.3%) in total body weight was also found in men with Parkinsons disease but the difference did not reach the level of significance. Protein biochemical markers of nutritional status (albumin, prealbumin, retinol binding protein, transferrin) were normal in Parkinsons disease patients. The present study demonstrates the occurrence of weight loss in a large population of patients with Parkinsons disease. The putative mechanisms involved in the weight loss are discussed.

Effects of yohimbine on plasma catecholamine levels in orthostatic hypotension related to Parkinson disease or multiple system atrophy.

Different pathophysiological mechanisms may underly orthostatic hypotension (OH) observed in neurological degenerative disorders. The present study investigates the responses to the pharmacological activation of sympathetic pathways induced by yohimbine (0.2 mg/kg orally) through measurements of plasma catecholamine levels in parkinsonian patients with (n = 9) or without OH (n = 11), in patients with multiple system atrophy (MSA) plus OH (n = 9), and in controls (n = 6). Basal norepinephrine plasma levels in parkinsonian patients with OH (71 +/- 11 pg/ml) were significantly lower (p < 0.05) than in parkinsonian patients without OH (280 +/- 25 pg/ml) or in controls (259 +/- 48 pg/ml). In patients with MSA plus OH, basal catecholamine plasma levels were in the normal range (344 +/- 54 pg/ml). Yohimbine significantly increased norepinephrine (p < 0.05) but not epinephrine plasma levels in all groups. However, the increment obtained in parkinsonian patients with OH (+53 +/- 18 pg/ml) remained significantly lower (p < 0.05) than in parkinsonian patients without OH or in controls (+638 +/- 140 and +457 +/- 103 pg/ml, respectively) as well as in MSA plus OH (+633 +/- 142 pg/ml). Yohimbine failed to modify the blood pressure and heart rate at the dose used. The results suggest that the yohimbine test is useful to elucidate the site of the dysfunction of the efferent sympathetic pathways in these two conditions. In Parkinson disease with OH, the lesion is both central and postganglionnic, whereas in MSA it is only centrally located.

Effects of levodopa and bromocriptine on blood pressure and plasma catecholamines in parkinsonians.

Blood pressure (BP), heart rate (HR), plasma noradrenaline (NA), and adrenaline (A) levels in the lying and standing position were compared in patients with Parkinsons disease (PD) and control subjects. Three groups of PD patients (stage 2 and 3) were investigated: six patients deprived of antiparkinsonian drugs from 48 h, seven levodopa + benserazide-treated patients, and seven bromocriptine-treated patients. BP, HR, NA, and A were similar at rest and in the standing position in controls and in PD patients deprived of antiparkinsonian drugs from 48 h. Chronic treatment with levodopa (+ benserazide) failed to modify BP, HR, NA, and A. Bromocriptine decreased BP, HR, and NA (but not A) at rest. In PD patients treated with levodopa (+ benserazide) or bromocriptine alone, the rise in NA (but not A) elicited by standing up was reduced. These results indicate that (a) stages 2 to 3 of Parkinsons disease are not accompanied by major changes in autonomic cardiovascular function and (b) dopaminergic drugs blunted the sympathetic response to standing up.

Alpha 2-adrenergic sensitivity in Parkinson's disease.

It is now well established that the main symptoms of Parkinsons disease (PD) are related to alterations of dopaminergic pathways in the brain. However, recent studies have shown that the disease is also accompanied by changes in central noradrenergic pathways. The aim of the present study was to investigate whether the altered number of α 2 -adrenoceptors in platelets reflects functional alterations in some other α 2 -mediated physiological responses

Platelet alpha2 adrenoceptors in Parkinson's disease: decreased number in untreated patients and recovery after treatment

Abstract. [3H]‐yohimbine binding sites were quantified in platelets from Parkinsonians with no clinical signs of dysautonomia. Never‐treated Parkinsonians had a lower specific binding than control subjects. This alteration was associated with decreased epinephrine‐induced platelet aggregation. Treatment with dopaminergic agents induced a significant increment of [3H]‐yohimbine binding sites. These results show that Parkinsons disease is associated with a reduced number of peripheral alpha2 adrenoceptors and that dopaminergic agents induce partial recovery.

Cerebral Blood Flow, Cerebral Blood Flow Reactivity to Acetazolamide, and Cerebral Blood Volume in Patients with Leukoaraiosis

We have used single photon emission computed tomography to study cerebral blood flow (CBF), CBF reactivity to acetazolamide, and cerebral blood volume (CBV) in 15 subjects presenting widespread leukoaraiosis, with the aim of answering the question if chronic ischaemia or hypo metabolism is associated with leukoaraiosis. We compared these subjects to 9 controls presenting no leukoaraiosis but with similarly distributed factors for leukoaraiosis. The subjects with leukoaraiosis showed a low regional (r)CBF in their white matter, while CBV and CBF reactivity to acetazolamide were not significantly affected. rCBF, rCBV and rCBF reactivity to acetazolamide did not differ between the cortex of patients and controls. Our results suggest that the low white matter CBF of the patients with leukoaraiosis was related mainly to hypometabolism and not to oligaemia. The capacity of the cerebral vessels to vasodilate does not appear to be affected by leukoaraiosis.

Beta-adrenergic sensitivity in Parkinson's disease: effect of levodopa treatment.

The beta-adrenergic sensitivity in never-treated and levodopa-treated patients with Parkinsons disease (PD) was studied through the evaluation of lymphocyte beta-adrenoceptor number ([125I]cyanopindolol binding sites) and chronotropic and metabolic (plasma nonesterified fatty acids--NEFA) responses to isoproterenol. No change was found in Bmax values or affinity constant Kd between never-treated patients, levodopa-treated patients with PD, and controls. At rest, no difference was observed in heart rate, plasma catecholamine, or NEFA levels between the three groups. Isoproterenol sensitivity (chronotropic response and plasma NEFA increase) was similar in never-treated and treated PD. The results suggest that peripheral beta-adrenergic sensitivity is unaffected either by the pathophysiological process of PD or by levodopa treatment.