In
multiple system atrophy (MSA) and
pure autonomic failure (PAF),
orthostatic hypotension (
OH) results from deficient
noradrenaline release from sympathetic nerves during standing. Post-mortem findings have indicated loss of central noradrenergic cells in both diseases. The present study sought in vivo neurochemical evidence for central noradrenergic deficiency in patients with
OH due to MSA or PAF. A total of 28 patients with
OH (18 with MSA; 10 with PAF) had cerebrospinal fluid and blood sampled for levels of
noradrenaline and its neuronal metabolite dihydroxyphenylglycol. A control group of 44 subjects included 10 elderly normal volunteers, 10 patients with
Alzheimer's disease, 18 patients with
dysautonomia (
postural tachycardia syndrome or
neurocardiogenic syncope) and six patients with MSA in the absence of
OH. Patients with
OH had lower cerebrospinal fluid concentrations of
noradrenaline (0.53+/-0.07 nmol/l) and dihydroxyphenylglycol (6.52+/-0.46 nmol/l) than did control subjects (0.90+/-0.09 and 9.64+/-0.46 nmol/l respectively; P =0.0001). The MSA+OH group had higher plasma levels of both
catechols (
noradrenaline, 1.31+/-0.16 nmol/l; dihydroxyphenylglycol, 5.08+/-0.43 nmol/l) than did the PAF group (
noradrenaline, 0.38+/-0.08 nmol/l; dihydroxyphenylglycol, 2.53+/-0.30 nmol/l; P <0.001), despite similarly low cerebrospinal fluid levels. Among MSA patients, those with
OH had lower cerebrospinal fluid levels of
noradrenaline and dihydroxyphenylglycol than those without
OH (
noradrenaline, 1.71+/-0.64 nmol/l; dihydroxyphenylglycol, 10.41+/-1.77 nmol/l respectively; P =0.006). The findings are consistent with central noradrenergic deficiency in both MSA+OH and PAF. In MSA, central noradrenergic deficiency seems to relate specifically to
OH.