Using positron emission tomography (PET), we studied regional striatal 18F-dopa uptake in 16 patients with L-dopa-responsive Parkinson's disease (PD), 18 patients with multiple system atrophy, and 10 patients with progressive supranuclear palsy. Results were compared with those of 30 age-matched normal volunteers. The patients with PD showed significantly reduced mean uptake of 18F-dopa in the caudate and putamen compared to controls, but while function in the posterior part of the putamen was severely impaired (45% of normal), function in the anterior part of the putamen and in the caudate was relatively spared (62% and 84% of normal). Mean 18F-dopa uptake in the posterior putamen was depressed to similar levels in all patients. Unlike patients with PD, the patients with progressive supranuclear palsy showed equally severe impairment of mean 18F-dopa uptake in the anterior and posterior putamen. Caudate 18F-dopa uptake was also significantly lower in patients with progressive supranuclear palsy than in patients with PD, being depressed to the same level as that in the putamen. Mean 18F-dopa uptake values in the anterior putamen and caudate in patients with multiple system atrophy lay between PD and progressive supranuclear palsy levels. Locomotor disability of individual patients with PD or multiple system atrophy correlated with decline in striatal 18F-dopa uptake, but this was not the case for the patients with progressive supranuclear palsy. We conclude that patients with PD have selective nigral pathological features with relative preservation of the dopaminergic function in the anterior putamen and caudate, whereas there is progressively more extensive nigral involvement in multiple system atrophy and progressive supranuclear palsy.(ABSTRACT TRUNCATED AT 250 WORDS)

Equilibrium striatal: cerebellar 11C-raclopride (RAC) uptake ratios reflect the density of striatal dopamine D2 binding sites. Using positron emission tomographic scanning we have measured striatal RAC uptake in 6 untreated patients with Parkinson's disease (PD), 5 chronically treated patients with PD and a fluctuating response to L-dopa, 10 patients with striatonigral degeneration (SND), and 9 patients with progressive supranuclear palsy (PSP). Regional cerebral blood flow was determined also, with C15O2. Mean striatal: cerebellar RAC uptake was not significantly different from normal in untreated patients with PD, though 2 of these 6 patients showed significantly increased putamen tracer binding. Mean caudate and putamen: cerebellar RAC uptake ratios of the group with PD and a fluctuating response to L-dopa were significantly reduced by 30% and 18%, respectively. The patients with SND had lesser, but significant, 10% and 11% decreases in mean caudate and putamen: cerebellar RAC uptake ratios, respectively, whereas patients with PSP showed 24% and 9% reductions in caudate and putamen: cerebellar RAC binding. Striatal and frontal blood flow were significantly reduced in patients with PSP, but not in patients with PD or SND. In conclusion, striatal D2 binding potential is normal or raised in untreated patients with PD, but reduced in patients with PD and a fluctuating response to L-dopa. Patients with SND and PSP show a decrease in striatal RAC binding, but to a lesser extent than patients with PD and a fluctuating response to treatment.(ABSTRACT TRUNCATED AT 250 WORDS)

We have monitored ambulant intra-arterial blood pressure with the Oxford system in six subjects with autonomic failure who exhibited postural hypotension. Plotting pooled hourly mean values we have demonstrated a consistent circadian trend in blood pressure that was the inverse of the normal pattern, with the highest pressures at night and the lowest in the morning. In four subjects, confinement to bed did not substantially alter this pattern. Heart rate variability was much reduced in four of the subjects, but relatively normal in two in whom blood pressure variation was also less abnorrnal. There was a correlation of the nadir of the blood pressure measurements with the reported time of peak incidence of orthostatic symptoms. These findings are of importance in both the management and physiologic testing of patients with this condition. Circulation 68, No. 3, 477-483, 1983. THE PRINCIPAL cardiovascular abnormalities found in subjects with autonomic failure are an unvarying heart rate and orthostatic hypotension, 1-1 the latter producing the disabling postural dizziness associated with the condition. Such large swings of blood pressure might be expected to obscure trends due to factors other than posture, although supine blood pressure measurements in such patients are also known to be highly variable,6 7 often showing hypertensive levels8'9 that may be exacerbated by treatment. 101 I Several of the many case reports of this condition" 7 8. [12][13][14] comment on the greater severity of postural symptoms in the morning, with improvement during the afternoon and evening. This observation has suggested the presence of important circadian periodicity.We have previously reported circadian trends in blood pressure in normal and hypertensive subjects,'5' 16 the highest levels occurring in the morning and the lowest during sleep at night. Although some controversy exists over the physiologic mechanisms producing this pattern,'7-20 the basic day-night change is undisputed. We have demonstrated its reproducibility2l' 22 and independence of physical activity23 but,

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.

We conclude that atrial natriuretic peptide can induce a gradual decrease in blood pressure, sometimes followed by symptomatic hypotension, which occurs suddenly. This phenomenon depends on the duration of the infusion as well as the dose. Moreover, the dose effect is enhanced during low sodium intake. This warrants careful observation of patients with essential hypertension who are given infusions of atrial natriuretic peptide over longer periods. The effect ofdesmopressin on nocturnal polyuria, overnight weight loss, and morning postural hypotension in patients with autonomic failure CHRISTOPHER J MATHIAS, PAUL FOSBRAEY, DAVID F DA COSTA, ANDREW THORNLEY, ROGER BANNISTER Abstract Day and night urine volume, morning and evening body weight, and supine and sitting blood pressure were measured in five patients with chronic autonomic failure who were not receiving treatment with drugs. AU had nocturnal polyuria, overnight weight loss, and a pronounced postural fall in blood pressure, with lowest levels in the morning. Desmopressin (24 ,ug given intramuscularly at 8 pm) reduced nocturnal polyuria, diminished overnight weight loss, raised supine blood pressure, and reduced the postural fail, especially in the morning, when patients were often at their worst.

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