Wallach's Interpretation of Diagnostic Tests: Pathways to Arriving at a Clinical Diagnosis (99 page)

Creatine kinase may be elevated up to 1,000 U/L due to denervation.

Evaluation of the CSF may rule out Lyme disease, HIV infection, chronic inflammatory demyelinating polyneuropathy, malignancy, and paraneoplastic syndromes secondary to lymphoma or breast cancer.

Familial ALS genetic testing is commercially available. Mutations occur in the SOD1, TARDBP, FUS, FIG4, ANG, Alsin (ALS2), VAPB, OPTN, and SETX genes (see Chapter
10
Hereditary and Genetic Diseases).

Muscle biopsy may rule out myopathy. In ALS, there is chronic denervation and reinnervation.

AUTOIMMUNE DISORDERS OF THE CNS

PRIMARY AUTOIMMUNE AUTONOMIC FAILURE

   Definition

Primary autoimmune autonomic failure (also known as autoimmune autonomic ganglionopathy, acute panautonomic neuropathy, or acute pandysautonomia) is an autoimmune disorder possibly due to anti-ganglionic acetylcholine receptor antibodies (AChRs) causing dysfunction of efferent sympathetic and parasympathetic pathways.

   Clinical Presentation

Patients present with orthostatic hypotension, anhidrosis, decreased production of saliva and tears, erectile dysfunction, and impaired bladder emptying. This disorder is responsive to plasma exchange. Antibodies to ganglionic AChR are present in about two thirds of all subacute cases and in one third of chronic cases.
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The differential diagnosis should include secondary causes of autoimmune autonomic failure. These are DM, amyloidosis, paraneoplastic syndromes, Lambert-Eaton syndrome, botulism, syphilis, HIV infection, collagen vascular disease, and porphyria.
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   Laboratory Findings

Testing varies according to the presentation and history of autonomic symptoms. Testing should be directed to differentiate between acute inflammatory demyelinating polyneuropathies (Parkinson disease, drug or toxin exposure, and hereditary etiologies) from primary autoimmune autonomic failure. Detection of antibodies binding to ganglionic nicotinic AChRs is performed by radioimmunoprecipitation and is diagnostic.
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There may also be decreased plasma norepinephrine levels.

Tests that rule out disorders that may cause autonomic symptoms include

   Glycosylated hemoglobin to test for diabetes

   Anti-Hu antibody titers, which may be used to test for paraneoplastic syndromes

   Anti-calcium channel antibody titers for Lambert-Eaton myasthenic syndrome

   Stool for botulinum by culture and detection of toxin for botulism

   Serum and urine protein electrophoresis to evaluate myeloma due to amyloidosis, or genetic testing to evaluate for familial amyloidosis

   Rapid plasma reagin (RPR) or syphilis antibody screen

   HIV serology

   ANA levels, ESR, and other autoimmune tests (e.g., rheumatoid factor [RF] and Sjögren syndrome, SS-A and SS-B antibodies) to evaluate for collagen vascular disease