Wednesday, October 12, 2016

Dysautonomia: 1869 - 1999

Dysautonomia: 1869 - 1999

 / By Dr. Margaret Aranda / 

~ October is National Dysautonomia Month ~
~ Series ~
In 1869, the term 'neurasthenia' was popularized by Dr. George Miller Beard (Image 1), primarily as a description to describe women who had the sudden onset of weakness, fatigue, pain and syncope (fainting). 

Image Courtesy Wikipedia

Thought to arise "as a consequence of civilization," the diagnosis could frequently be made after recovery from a brief illness (1). Urbanization stresses in the competitive business environment were thought to contribute to this disease of a "weak nervous system." See Image 2. 

To study the term 'dys - auto - nō - mee - ah' proper, one turns to the Veterinary literature, where the term is well entrenched (2). 

In 1907, dysautonomia was first described in affected Scottish horsesThe major clinical symptoms were dysphagia and gastric dysmotility, resulting in cachectic, severely malnourished horses (Image 3). Horses grazing in the fields seemed prone.

The term "grass sickness" was coined. 

Image 3. Equine Grass Sickness. The prognosis for Equine Grass Sickness was poor, with most horses suffering death or euthanasia.  Image Courtesy 

Survivors were rare and there was no effective treatment. Mortality was estimated at a stunning 95%. Famous thoroughbred racehorses affected by "grass sickness" were Mister Baileys and Dubai Millennium. 

In 1949 Familial Dysautonomia (FDA) was discovered by Drs. Conrad Milton Riley and Richard Lawrence Day, hence ' Riley-Day ' Syndrome was coined (3). From 1949 to 1959, a series of clinical markers were determined: two clinical tests to include the histamine test and Tongue Markers; and two physiologic studies of urine and plasma catecholamine levels and a lack of compensation for conditions of low oxygen and high carbon-dioxide levels (4).

From 1969-1979, Drs. Aguayo and Pearson used electron microscopy to show the defect was decreased small unmyelinated neurons (4). See Image 4.

Image 4 Unmyelinated Nerve Fibers.

In 1982,  Key and Gaskell  rom the University of Bristol reported feline dysautonomia in the veterinary literature. At this time, the diagnosis was prevalent, with hundreds of cases reported by 1985. Cats displayed dry mucous membranes, pupillary dilation and protrusion of the third eyelid (Image 4).  Only about one- quarter of the cases survived. I1983,  Britain described  cat  dysautonomia. In 1991, the United Kingdom reported dysautonomia in the wild hare (Image 5) (2).

Image 5. Feline Dysautonomia. Feline dysautonomia is also known as Key-Gaskell syndrome. 

In 1993, the FDA defect was located on Chromosome 9. Two years later, the FDA clinical trials formed the basis of the pharmacologic agent midodrine being approved by the Federal Drug Administration (4).  

Symptomatic orthostatic intolerance is the presenting complaint of mostly young women who are subsequently diagnosed with Postural Orthostatic Tachycardia Syndrome (POTS). In 1997, Grubb et al. defined the criteria which imposes: an increase in heart rate to 30 beats min/or  an increased heart rate of 120 beats/min or greater when changing from supine to standing position (5,6). 

From 1997 to 1999, the additional neurophysiologic investigations were described to further assess FDA: Cold Face Stimulation, Laser Doppler Flowmeter, and temperature, as correlated with cardiac risk assessment (4). 

In 1999, the precise mapping of the Familial Dysautonomia gene was shown at the 9q31 alleleDysautonomia was reported in the Netherland  llama (4). At the same time, Schondorfer et al estimated the prevalence of orthostatic intolerance with chronic fatigue syndrome at 40% (Schondorfer) (7).

While the initial term 'neurasthenia' as coined by Dr. Beard was not based on autonomic dysfunction per se, Dr. George Miller Beard holds esteem for recognizing a clinical syndrome, going against the grain of science at the time, being a proponent of medical electrical stimulation therapy, as well as being an activist against the use of the death penalty. 

'Dysautonomia' is an original term with a longer history than that reported solely in human literature. 

The veterinarian literature is relevant to dysautonomia. It is the intense and valuable work by Drs. Riley and Day that not only rooted Familial Dysautonomia as an entity, but it entrenched the concept of the autonomic nervous system being assigned its own pathophysiology. 

Great memory in the world of dysautonomia.


( 1) Handbook of Practical Treatment, John H. Musser, MD and O Kelly, MD, 1912.  

(2) Dennis O'Brien. Neurology Department of Veterinary Medicine, Surgery College of Veterinary Medicine University of Missouri, Columbia, MO 65 211.

(3) CM Riley Day RL, WS Greely Dr Langford. Central autonomic dysfunction with defective lacrimation. Pediatrics  3 (4): 468-477, 1949.  PMID 18,118,947.
(4) Kiki MJ e MH. Cecal impaction due to dysautono up of a llama (Lama glama).  1999 Sep; 30 (3): 435-8.Https://  

(5) Grubb BP, Kosinski D., et al. The postural tachycardia syndrome: a neurocardiogenic variant Identified during head-up tilt table testing.  Pacing Clin Electrophysiol , 1997; 20: 2205-2212.

(6) Grubb BP, Kanjwal A. and D. Kosinski The postural tachycardia syndrome: a concise guide to diagnosis and management. J Cardiovasc Electrophysiol , 2006; 17: 108-112.

(7) Schondorfer R Benoit J. and Wei Tu, D. orthostatic intolerance in the chronic fatigue syndrome.  J Auton Nerv Syst  1999; 75: 192-201.

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