Discoveries

Accomplishments in autonomic research:

  • The first neuropathological studies on familial dysautonomia describing the loss of sensory nerves.
  • The first complete neuropathological description of pure autonomic failure, showing Lewy bodies in the peripheral autonomic nerves.
  • The first neuropathological description of patients with Lewy bodies synucleinopathies presenting with long standing isolated autonomic failure.
  • The first reported evidence of end-organ target damage as a consequence of supine hypertension in patients with autonomic failure.
  • Comprehensive study of the vasoactive peptides, endothelin, atrial natriuretic peptide, and vasopressin in autonomic synucleinopathies.
  • A description of the clinical features of familial dysautonomia and the impact of therapeutic interventions
  • The seminal trials of midodrine and droxidopa, the two main drugs used in the treatment of chronic orthostatic hypotension due to autonomic failure.
  • The therapeutic trial of midodrine in patients for the treatment of orthostatic hypotension in patients with familial dysautonomia.
  • Use of fundoplication to prevent aspiration pneumonia, leading to a dramatic increase in life expectancy for patients with familial dysautonomia.
  • A brain MRI-based algorithm for the differential diagnosis of Parkinson disease and multiple system atrophy.
  • Therapeutic trials of botulinum toxin type A in primary palmar hyperhidrosis and the first description of “subclinical” muscle weakness in the hand 
  • The first complete description of a vestibular autonomic reflex in humans.
  • In collaboration with Harvard University researchers, identification of the genetic mutation responsible for familial dysautonomia.
  • The discovery that kinetin (a nutritional supplement) corrects the mis-splicing defect responsible for familial dysautonomia.
  • Study of adaptation to high altitude in Peruvian mountain dwellers.
  • Report of the effect of water in improving blood pressure control.
  • The discovery of the role of vascular sensitivity to hyperventilation in susceptibility to vasovagal syncope.
  • First study describing familial dysautonomia as a disease of afferent baroreflex failure.
  • Description of the neurochemical basis for hypertensive vomiting attacks in familial dysautonomia.
  • Description of the neurohormonal and autonomic profile during seizures in children with benign childhood autonomic seizures (Panayiotopoulos syndrome).
  • First placebo-controlled randomized clinical trial in familial dysautonomia showing carbidopa improves nausea.
  • Description of the lack of proprioception in familial dysautonomia as a cause for gait ataxia.
  • Description of optic neuropathy and progressive neuronal loss in the retinal nerve fiber layer in patients with familial dysautonomia
  • The first study in humans demonstrating that a nutritional supplement can reverse the gene deficit in familial dysautonomia and has potential use as a gene therapy. Description of cardiac sympathetic denervation in a rare genetic form of Parkinson disease.
  • Development and validation of the Orthostatic Hypotension Questionnaire to measure symptoms and monitor the efficacy of therapies.

OrthostaticHypotensionQuestionnaire.pdf