Diagnostic and Therapeutic Approach to Autoimmune Neurologic Disorders

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


Semin Neurol. 2018;38(3):392-402. 

In This Article

Abstract and Introduction


The field of autoimmune neurology is evolving rapidly. The discovery of autoantibodies that target neural antigens has expanded swiftly in the last decade. Recognition of the clinical syndromes associated with autoimmune neurologic disorders, and our understanding of the pathophysiology, has progressed significantly. Radiographic, electrophysiological, and laboratory testing (particularly neural autoantibody testing) are fundamental in the diagnosis of autoimmune neurological disorders and in the exclusion of mimics. Furthermore, investigations may serve as a baseline from which objective assessment of improvement or detection of relapse can be made. These disorders can be associated with underlying neoplasms, and screening for malignancy is an essential component of the investigations. Early diagnosis and prompt initiation of immunotherapy can improve neurologic function. The use of immunotherapy, however, can be associated with diverse side effects, and careful monitoring is crucial to prevent complications. Herein the authors address the diagnostic and treatment approach of autoimmune neurologic disorders, with particular focus on antibody-mediated neurologic autoimmunity.


Autoimmune neurological disorders often have multifocal symptoms and typically present subacutely. Multiple structures in the central and peripheral nervous system can be targets of pathogenic autoantibodies, resulting in diverse clinical presentations. Central nervous system (CNS) manifestations include neuropsychiatric symptoms, encephalopathy, seizures, catatonia, chorea, sleep disorders, myoclonus, opsoclonus, optic neuritis, stiff person syndrome, cerebellar ataxia, brainstem syndromes, and myelopathy. Peripheral nervous system symptoms include radiculopathy, plexopathy, neuronopathy, peripheral neuropathy, neuromuscular junction, and muscle disorders. Autonomic nervous system manifestations include anhidrosis, difficulty transitioning from dark to light, orthostasis, cardiac arrhythmias, gastrointestinal dysmotility, and urologic dysfunction.[1]

Traditionally, autoimmune neurologic disorders were often overlooked, but the development of specific neural antibody biomarkers has allowed them to be distinguished from other disorders. This is emphasized by a recent study showing that autoimmune encephalitis was as common as infectious encephalitis at a population level, and the detection of autoimmune encephalitis was increasing over time as more antibody biomarkers were discovered.[2] The unprecedented oncologic success and anticipated increase use of immune checkpoint inhibitors will also increase the number of cases of neurological autoimmunity.[3]

Autoantibody and clinical phenotype associations are summarized in Table 1.