Autoantibody-Associated Movement Disorders

Abstract

Autoantibodies to the extracellular domain of neuronal proteins cause different neurological conditions with movement disorders as a prominent feature. We reviewed the literature of autoantibody-mediated and autoantibody-associated diseases focusing on anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis, autoimmune basal ganglia encephalitis, Sydenham chorea, and the rare syndrome of progressive encephalomyelitis with rigidity and myoclonus. NMDAR encephalitis is a diffuse encephalitis with psychiatric and cognitive features associated with autoantibodies against the NR1 subunit of the NMDAR. The movement disorder phenotype is diverse and often generalized in young children. Although orofacial dyskinesia was the initial movement phenotype, chorea, dystonia, catatonia, and stereotypical movements are now described. The stereotypical movements can be bizarre and include cycling movements and compulsive self-injurious behavior. Autoimmune basal ganglia encephalitis is an inflammatory encephalitis localizing to the basal ganglia that is sometimes associated with serum antibodies against dopamine-2 receptor. Although psychiatric features are common, the dominant problem is a movement disorder, with dystonia-parkinsonism being characteristic. Sydenham chorea is the prototypic poststreptococcal autoimmune neuropsychiatric disorder and several autoantibodies may be involved in disease generation. The syndrome is characterized by a pure chorea, although hypotonia, dysarthria, and emotional lability are common. Progressive encephalomyelitis with rigidity and myoclonus is a rare autoimmune disorder causing rigidity, stimulus sensitive spasms, and myoclonus of nonepileptic origin and is associated with autoantibodies of multiple types including those against the glycine receptor. These disorders are important to recognize and diagnose, as immune therapy can shorten disease duration and improve outcome.

Antibodies to Surface Dopamine-2 Receptor and N-Methyl-D-Aspartate Receptor in the First Episode of Acute Psychosis in Children

“…Flow Cytometry Live Cell-Based Assay for Detection of Antibodies to Cell Surface D2R and NR1 in Serum Flow cytometry live cell-based assay was used to detect immunoglobulin binding from serum to transfected HEK293 cells, as previously described (26)(27)(28)(29). After transfection, cells were cultured for 2 days.…”

“…Cox et al (45) recently reported that a monoclonal IgM antibody derived from a patient with Sydenham chorea bound to human D2R, inducing signaling comparable with that seen after dopamine binding, as measured by levels of cyclic adenosine monophosphate. Furthermore, in the context of autoimmune encephalitis, serum surface D2R and NR1 antibody titers seem to correlate with improvement in clinical status and immunotherapy has proved effective (21,29,46). Existing evidence already suggests that NR1 IgG antibodies are pathogenic in NMDAR encephalitis (15).…”

Mapping autoantigen epitopes: molecular insights into autoantibody-associated disorders of the nervous system

“…The associated autoantibodies can be directed against intracellular or extracellular autoantigens [1–3], and the clinical phenotype of patients is diverse, encompassing movement disorders and neuropsychiatric disorders [4, 5]. Antibodies targeting intracellular antigens are not considered pathogenic but are sometimes believed to be biomarkers of an underlying tumor [6].…”

Movement Disorders in Systemic Diseases

“…Hypotonia is seen in most patients and, when severe, 2% of patients develop a flaccid quadriparesis often labeled as "chorea paralytica." 21 SC is an autoimmune process, a definitive autoantibody has not been found. Sixty percent to 80% of patients have cardiac involvement 22 and half of the patients still have chorea 2 years after onset of symptoms.…”

“…Valproic acid or carbamazepine, rather than neuroleptic therapy, are preferred for symptomatic treatment. 21 Antibiotic prophylaxis following the acute rheumatic fever guidelines until the age of 21 is recommended to avoid rheumatic heart disease. 21 …”