Cerebrospinal fluid levels of catechols in patients with neurogenic orthostatic hypotension.
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.
Goldstein
David S
DS
Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Building 10, Room 6N252, 10 Center Drive, MSC-1620, Bethesda, MD 20892-1620, U.S.A. goldsteind@ninds.nih.gov
Holmes
Courtney
C
Patronas
Nicholas
N
Kopin
Irwin J
IJ
D000368:Aged; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid; D001342:Autonomic Nervous System Diseases / Q000134:cerebrospinal fluid; D016022:Case-Control Studies; D002396:Catechols / Q000134:cerebrospinal fluid*; D002908:Chronic Disease; D006801:Humans; D007024:Hypotension, Orthostatic / Q000134:cerebrospinal fluid*; D016014:Linear Models; D008297:Male; D008734:Methoxyhydroxyphenylglycol / Q000031:analogs & derivatives* / Q000134:cerebrospinal fluid; D019578:Multiple System Atrophy / Q000134:cerebrospinal fluid; D009638:Norepinephrine / Q000134:cerebrospinal fluid
D002396:Catechols; D008734:Methoxyhydroxyphenylglycol; C010117:3,4-dihydroxyphenylglycol; D009638:Norepinephrine