Acute pandysautonomia

Alexandru C Barboi MD FACP (Dr. Barboi of NorthShore Medical Group has no relevant financial relationships to disclose.)
Raymond P Roos MD, editor. (Dr. Roos of the University of Chicago owns stock in Amgen, Best Doctors, Express Scripts, Isis, and Merck.)
Originally released May 8, 1995; last updated October 7, 2016; expires October 7, 2019

This article includes discussion of acute pandysautonomia, acute autonomic neuropathy, acute idiopathic autonomic neuropathy, acute idiopathic pandysautonomia, acute panautonomic neuropathy, autoimmune autonomic ganglionopathy, autoimmune autonomic neuropathy, acute autonomic neuropathy with sensory impairment, acute autonomic neuropathy with sensory and motor impairment, idiopathic autonomic neuropathy, and pure pandysautonomia. The foregoing terms may include synonyms, similar disorders, variations in usage, and abbreviations.

Overview

The syndrome of acute pandysautonomia is characterized by acute onset (onset to peak symptoms within 1 month) of severe and disabling autonomic failure affecting sympathetic, parasympathetic, and enteric functions. If initial symptoms are episodic the onset may not be as precise, and for the purpose of this article subacute (1 month to 2 months) presentations are also included. There may be an inciting event which accounts for unrestrained immune activation, such as an acute infection, vaccination, surgery, or an occult cancer. Acute metabolic and toxic exposure can also cause similar manifestations. As noted above, the clinical features consist of variable involvement of sympathetic, parasympathetic, and enteric portions of the autonomic nervous system; however, other portions of the nervous system may be involved less frequently: brain, somatic sensory, and rarer motor nerve fibers. Symptomatic treatment is complex and is helpful in supporting function. If an autoimmune etiology is identified immunomodulatory treatments should be employed early in the course to avoid progressive disability. In this article, the author discusses various clinical presentations with an emphasis on early diagnosis, current pathophysiology, and treatment.

Key points

 

• Acute pandysautonomia is an acquired disorder with widespread but variable sympathetic, parasympathetic, and enteric autonomic dysfunction, including orthostatic hypotension, anhidrosis, unreactive pupils, decreased lacrimation and salivation, gastrointestinal paresis, and impaired genitourinary function.

 

• Clinical variants may include associated encephalitis, sensory or sensorimotor neuropathy, and segmental autonomic disorders such as isolated ileus, unexplained bradycardia, or postural orthostatic tachycardia syndrome.

 

• The acute/subacute clinical course, antecedent immune triggers, elevated CSF protein levels, and frequent association with high titers of ganglionic nicotinic acetylcholine receptor (nAChR) and/or paraneoplastic antibodies suggest that the syndrome is frequently immune-mediated.

 

• In addition to symptomatic and supportive treatment, early immunomodulating therapies should be considered in order to avoid long-term disability.

Historical note and terminology

The syndrome of acute pandysautonomia was first reported in the neurologic literature by Young and colleagues in 1969, and was later discussed in more detail in the same patient as "pure pandysautonomia with recovery" (Young et al 1975). The patient showed "severe postural hypotension without change in heart rate, leading occasionally to fainting, total absence of sweating, extreme dryness of eyes, nasal and oral mucous membranes, midposition nonreactive pupils, absence of bowel sounds and a hypotonic weak bladder." Appenzeller and Kornfeld first coined the term "acute pandysautonomia" (Appenzeller and Kornfeld 1973), and similar cases were also reported later as acute autonomic neuropathy, acute panautonomic neuropathy, acute idiopathic pandysautonomia, and idiopathic autonomic neuropathy (Hopkins et al 1974; Low et al 1983; Suarez et al 1994).

A more heterogeneous picture of the syndrome emerged over the years with reports of variable recovery and associated sensory or sensorimotor symptoms (Appenzeller and Kornfeld 1973; Okada et al 1975; Colan et al 1980; Fagius et al 1983; Low et al 1983; Irioka et al 2001; Ueda et al 2009). A subgroup of patients with pure cholinergic dysautonomia has been described (Harik et al 1977; Inamdar et al 1982), and variable involvement of central nervous system sites may be present (Stoll et al 1991). Some cases have limited autonomic neuropathic features that include postural orthostatic tachycardia syndrome (POTS) (Schondorf and Low 1993). The clinical presentation of acute pandysautonomia is a useful clinical syndromic concept in the sense that it leads to a specific workup and treatment. Careful evaluation of other targeted segments of the nervous system is frequently needed in order to identify encephalitis, acute autonomic and sensory or sensorimotor neuropathy, and Guillain-Barre syndrome with dysautonomia (Low et al 1993; Irioka et al 2001; Ueda et al 2009). Toxic (Stratogianni et al 2012), immune (Yokote et al 2007; McKeon and Benarroch 2016), and metabolic etiologies, such as the autonomic neuropathy described that is induced by treatment of diabetes (Makino et al 2016), should be considered. Of note, the presence of ganglionic acetylcholine receptor antibodies or other paraneoplastic antibodies in patients' sera as well as the generation of an experimental animal model of acute pandysautonomia have led to the concept of autoimmune autonomic ganglionopathy (Klein et al 2003; Vernino et al 2003; Iodice et al 2009; McKeon and Benarroch 2016).

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