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  • Updated 11.09.2020
  • Released 05.08.1995
  • Expires For CME 11.09.2023

Acute pandysautonomia

Introduction

Overview

The syndrome of acute pandysautonomia is characterized by acute onset (onset to peak symptoms within one month) of severe and disabling autonomic failure affecting sympathetic, parasympathetic, and enteric functions. If initial symptoms are episodic (syncope) 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 that accounts for unrestrained immune activation, such as an acute infection, vaccination, surgery, or an occult cancer. Acute metabolic disorders and toxic exposures can also cause similar manifestations. The clinical features consist of variable involvement of sympathetic, parasympathetic, and enteric portions of the autonomic nervous system. 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 emphasis on early diagnosis, current pathophysiology, and treatment.

Immune mediated autonomic disorders:

(1) Systemic autoimmune disorders with peripheral autonomic neuropathic manifestations: primary Sjögren syndrome, systemic lupus erythematosus, rheumatoid arthritis

(2) Autoimmune autonomic ganglionopathy with positive or negative serum ganglionic (neuronal) acetylcholine receptor antibodies

(3) Primary autonomic neuropathies:

A. Acute sensory and autonomic neuropathy, idiopathic (ASAN)

B. Acute sensory and autonomic neuronopathy (ASANN)

C. Acute autonomic sensory motor neuropathy (AASMN) (variant of Guillain Barre syndrome)

D. Idiopathic gastrointestinal dysmotility

E. Idiopathic anhidrosis

F. Paraneoplastic autonomic neuropathies: anti-Hu (ANNA-1), anti-CRMP5 (CV-2)

G. Autoimmune neuromuscular disorders with autonomic manifestations: Lambert-Eaton myasthenic syndrome, disorders with positive LGI1 or CASPR2 antibodies, botulism

H. Iatrogenic autonomic neuropathies: chemotherapeutic agents, checkpoint inhibitors

(4) Paraneoplastic autonomic neuropathies: anti-Hu (ANNA-1) and anti-CRMP5 (CV-2)

(5) Autoimmune neuromuscular disorders with autonomic manifestations: Lambert-Eaton myasthenic syndrome, disorders with positive LGI1 or CASPR2 antibodies, Guillain-Barré syndrome

(6) Iatrogenic autonomic neuropathies: chemotherapeutic agents, checkpoint inhibitors

Modified from (19).

Key points

• Acute pandysautonomia is characterized by autonomic failure affecting sympathetic, parasympathetic, and enteric functions.

• In some cases the autoimmune etiology is supported by the presence of antibodies against neuronal antigens.

• Immunomodulating treatments should be employed early in the course to avoid progressive 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" (69). The patient showed "severe postural hypotension without change in heart rate, leading occasionally to fainting without change in heart rate, 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" (02), and similar cases were also reported later as acute autonomic neuropathy, acute panautonomic neuropathy, acute idiopathic pandysautonomia, and idiopathic autonomic neuropathy (31; 51).

A more heterogeneous picture of the syndrome emerged over the years with reports of variable recovery and associated sensory or sensorimotor symptoms (02; 06; 31; 24; 53). A subgroup of patients with pure cholinergic dysautonomia has been described (22), and variable involvement of central nervous system sites may be present (49). Some cases may have limited autonomic neuropathic features to include postural orthostatic tachycardia syndrome (POTS) (45). The clinical presentation of acute pandysautonomia is a useful clinical syndromic concept leading to specific work up and treatment. Careful evaluation of other targeted segments of the nervous system is frequently needed ranging from encephalitis to acute autonomic and sensory or sensorimotor neuropathy to Guillain-Barre syndrome with dysautonomia (Low et al 1993; 24; 53). Toxic immune and metabolic etiologies like treatment induced diabetic autonomic neuropathy should be considered (68; 50; 33; 34). The presence of ganglionic acetylcholine receptor antibodies or other paraneoplastic antibodies (gACHR) in patients’ sera and the development of an experimental animal model of acute pandysautonomia have led to the concept of autoimmune autonomic ganglionopathy (27; 62; 23; 34).

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