Horacio Kaufmann

Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome

Roy Freeman • Wouter Wieling • Felicia B. Axelrod • David G. Benditt • Eduardo Benarroch • Italo Biaggioni • William P. Cheshire • Thomas Chelimsky • Pietro Cortelli • Christopher H. Gibbons • David S. Goldstein • Roger Hainsworth • Max J. Hilz • Giris Jacob • Horacio Kaufmann • Jens Jordan • Lewis A. Lipsitz • Benjamin D. Levine • Phillip A. Low • Christopher Mathias • Satish R. Raj • David Robertson • Paola Sandroni • Irwin Schatz • Ron Schondorff • Julian M. Stewart • J. Gert van Dijk

Consensus statement on the definition of orthostatic hypotension, neurally mediated syncope and the postural tachycardia syndrome.

Roy Freeman • Wouter Wieling • Felicia B. Axelrod • David G. Benditt • Eduardo Benarroch • Italo Biaggioni • William P. Cheshire • Thomas Chelimsky • Pietro Cortelli • Christopher H. Gibbons • David S. Goldstein • Roger Hainsworth • Max J. Hilz • Giris Jacob • Horacio Kaufmann • Jens Jordan • Lewis A. Lipsitz • Benjamin D. Levine • Phillip A. Low • Christopher Mathias • Satish R. Raj • David Robertson • Paola Sandroni • Irwin Schatz • Ron Schondorff • Julian M. Stewart • J. Gert van Dijk

L-DOPS therapy for refractory orthostatic hypotension in autoimmune autonomic neuropathy

The authors report a 46-year-old woman with antibodies to the nicotinic acetylcholine receptor (NiAchR) of the autonomic ganglia. She presented with severe orthostatic intolerance refractory to treatment with midodrine, fludrocortisone, erythropoietin, vasopressin, salt, and fluid loading. Addition of l-threo-3,4-dihidroxyphenylserine (l-DOPS) substantially improved blood pressure and orthostatic tolerance. l-DOPS may benefit patients with severe orthostatic intolerance and be particularly effective in patients with ganglionic NiAchR antibodies.

Familial Dysautonomia (Riley–Day Syndrome)

Publisher Summary Familial dysautonomia (FD), also known as Riley–Day syndrome or hereditary sensory and autonomic neuropathy type III, is an autosomal recessive disease caused by mutations in the gene that encodes for I-κ-B kinase complex associated protein (IKAP). Typically, affected patients present at birth with hypotonia, episodic skin blotching and irritability. Infants do not respond to pain or cold stimuli. Oral incoordination and abnormal swallowing reflexes lead to feeding difficulties and recurrent bouts of aspiration pneumonia. Blood pressure instability occurs in all patients from birth. Cortical arousal results in hypertension and tachycardia. Patients with FD have blunted baroreceptor afferents and, as a consequence, their blood pressure is extremely labile. Although reduced in number, efferent sympathetic nerves are functional. Supine plasma norepinephrine levels are normal in FD. Stimuli that activate efferent sympathetic neurons, independently of baroreceptor afferent pathways, such as cognitive tasks and emotional arousal, dramatically increase blood pressure, heart rate and circulating norepinephrine levels. Pharmacologic treatment of the labile blood pressure in patients with FD is complex and frequently unsuccessful, because drugs that increase standing blood pressure worsen hypertension and drugs that lower blood pressure may worsen orthostatic hypotension.

Supine plasma NE predicts the pressor response to droxidopa in neurogenic orthostatic hypotension.

Objective To test whether the plasma levels of norepinephrine (NE) in patients with neurogenic orthostatic hypotension (nOH) predict their pressor response to droxidopa. Methods This was an observational study, which included patients with nOH. All patients had standardized autonomic function testing including determination of venous plasma catecholamine levels drawn through an indwelling catheter while resting supine. This was followed by a droxidopa titration with 100 mg increments in successive days until relief of symptoms, side effects, or the maximum dose of 600 mg was reached. No response was defined as an increase of <10 mm Hg in systolic blood pressure (BP) after 3-minute standing 1 hour after droxidopa administration. Nonlinear regression models were used to determine the relationship between BP response and plasma NE levels. Results We studied 20 patients with nOH due to Parkinson disease, pure autonomic failure, multiple system atrophy, or autoimmune autonomic neuropathies. Their supine plasma NE levels ranged from 44 to 850 pg/mL. Lower supine plasma NE levels were associated with greater pressor effect 1 hour after dose (R2 = 0.49) and higher standing BP (R2 = 0.45). Patients with no pressor response to droxidopa had higher NE levels (382 ± 100 vs 115 ± 20 pg/mL, p = 0.0014). A supine NE level of <219.5 pg/mL had 83% sensitivity and 93% specificity to predict a pressor response (area under the curve = 0.95, p = 0.0023). Conclusions In patients with nOH, lower supine resting plasma NE levels are associated with a greater pressor effect of droxidopa treatment. This finding should help identify patients with nOH most likely to respond to standard doses of droxidopa. Classification of evidence This study provides Class I evidence that lower supine plasma NE levels accurately identify patients with nOH more likely to have a greater pressor effect from droxidopa.