Diagnostic and Therapeutic Approach to Autoimmune Neurologic Disorders

A. Sebastian López-Chiriboga, MD; Eoin P. Flanagan, MD

Disclosures

Semin Neurol. 2018;38(3):392-402. 

In This Article

Electrophysiologic Studies

Electroencephalogram

EEG should be performed to evaluate abnormal epileptiform activity, a common feature of antibody-associated neurologic disorders. Beyond supporting the diagnosis of epilepsy, it can also help evaluate the response to immunotherapy with normalization of EEG patterns.[38] Multiple electroencephalography patterns have been reported in patients with autoimmune epilepsy and encephalitis; extreme delta brush seems to be particularly specific for NMDA-R encephalitis and can predict worse outcomes.[39] Many autoimmune epilepsies target the deep structures of the brain, and thus a normal EEG does not exclude autoimmune epilepsy; special attention to subtle abnormalities on EEG is warranted (in the context of the phenotype of the clinical spell) in suspected autoimmune epilepsy.

Electromyography

Nerve conduction and electromyographic testing can be helpful to evaluate for large-fiber involvement typical of ANNA1 and CRMP-5 paraneoplastic syndromes and peripheral nerve hyperexcitability that can be seen in patients with CASPR2 autoantibodies.[40] Repetitive stimulation demonstrates a compound muscle action potential decrement in myasthenia gravis, and an increment in Lambert–Eaton syndrome.

Dysautonomia Evaluation

Multiple neural autoantibodies are associated with autonomic disorders (ganglionic nicotinic acetylcholine receptor antibody, ANNA-1, P/Q and N-type VGCCs, NMDA, CASPR2, DPPX).

Autonomic testing helps support the diagnosis, defines severity, and helps evaluate response to immunotherapy. Autonomic testing includes quantitative sudomotor axon reflex test, thermoregulatory sweat test (Figure 1H), heart rate response to Valsalva, blood pressure, and heart rate response to passive head-up tilt.[41] Gastrointestinal transit studies can also be helpful to establish a diagnosis of gastrointestinal dysmotility and monitor response to immunotherapy.[42] A wide variety of medications can cause abnormalities in the aforementioned autonomic testing, and clinicians should keep that in mind when interpreting results.

Visual-evoked Potentials—Optical Coherence Tomography

These studies are helpful to assist in the clinical examination of the optic pathways (VEP) and to evaluate extent of damage and possibly response to immunotherapy (OCT), particularly for patients with AQP4 and MOG antibodies.[43] Electroretinogram is usually abnormal in patients with cancer-associated retinopathy and autoimmune retinopathies.[44]

Movement Disorders Laboratory Evaluation

Ataxia, chorea, myoclonus, dystonia, hyperekplexia, and other movement disorders have been associated with antibodies targeting neural antigens. Surface EMG and movement disorder laboratory evaluation helps characterize tremors further and confirm the diagnosis of hyperexcitability, myoclonus, and stiff person syndrome[45] (GAD65, glycine receptor ab, and amphiphysin) to confirm the diagnosis.

Neuropsychometric Testing

Validated bedside cognitive tests should be performed as a helpful objective assessment of cognition. In selected patients, formal neuropsychological testing is a valuable tool for assessment of the extent of cognitive damage, and can be used to evaluate immunotherapy response.[46]

Polysomnography

Polysomnography is useful in patients with antibodies that are associated with sleep disorders, including those with the following antibodies CASPR2, DPPX, IgLON5, anti-Ma2, AQP4, and ANNA-2 antibodies.[47] Abnormalities can include sleep-disordered breathing, REM sleep behavior disorder, and abnormal NREM sleep architecture. Polysomnogram is critical in patients with ANNA-2, as these patients can develop laryngospasm and require prophylactic tracheostomy.[48] Profound insomnia is a characteristic feature of Morvan's syndrome, associated with CASPR2 or LGI-1 autoantibodies.[40] Narcolepsy-cataplexy can be seen in patients with anti-Ma2 antibodies and AQP4 autoimmunity when either disorder is accompanied by diencephalic and hypothalamic involvement.[49] IgLON5 also appears to be associated with a risk of sudden death in sleep.[50]

Pathologic Analysis

In rare instances and when the diagnosis is unclear, tissue biopsy can be helpful to establish a diagnosis and rule out a competing etiology (e.g., glioma, lymphoma, or opportunistic infection).

Emerging Laboratory Techniques

Next-generation sequencing for rapid identification of pathogens and other new techniques in the fields of metagenomics and proteomics are arising as promising future methods of antibody detection and exclusion of alternative etiologies.[51]

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