Περίληψη:
Antibodies against glutamic acid decarboxylase (GAD), originally linked to stiff person syndrome (SPS), now denote the “GAD antibody-spectrum disorders” (GAD-SD) that also include autoimmune epilepsy, limbic encephalitis, cerebellar ataxia and nystagmus with overlapping symptomatology highlighting autoimmune neuronal excitability disorders. The reasons for the clinical heterogeneity among GAD-antibody associated syndromes remain still unsettled, implicating variable susceptibility of GABAergic neurons to anti-GAD or other still unidentified autoantibodies. Although anti-GAD antibody titers do not correlate with clinical severity, very high serum titers, often associated with intrathecal synthesis of anti-GAD-specific IgG, point to in-situ effects of GAD or related autoantibodies within the central nervous system. It remains, however, uncertain what drives these antibodies, why they persist and whether they are disease markers or have pathogenic potential. The review, focused on these concerns, describes the widened clinical manifestations and overlapping features of all GAD-SD; addresses the importance of GAD antibody titers and potential significance of GAD epitopes; summarizes the biologic basis of autoimmune hyperexcitability; highlights the electrophysiological basis of reciprocal inhibition in muscle stiffness; and provides practical guidelines on symptomatic therapies with gamma-aminobutyric acid-enhancing drugs or various immunotherapies. © The Author(s), 2021.
Συγγραφείς:
Tsiortou, P.
Alexopoulos, H.
Dalakas, M.C.
Λέξεις-κλειδιά:
4 aminobutyric acid receptor; alprazolam; autoantibody; azathioprine; baclofen; benzodiazepine; clonazepam; cyclophosphamide; dantrolene; diazepam; gabapentin; glutamate decarboxylase 65; glutamate decarboxylase 67; glutamate decarboxylase antibody; glycine a1 receptor; glycine receptor; granzyme; immunoglobulin; immunoglobulin G; immunosuppressive agent; levetiracetam; lorazepam; methotrexate; mycophenolate mofetil; perforin; rituximab; temazepam; testosterone; thymocyte antibody; tiagabine; tizanidine; unclassified drug; vigabatrin, antibody titer; ataxia; autoimmune epilepsy; autoimmunity; autologous hematopoietic stem cell transplantation; cerebrospinal fluid; clinical feature; cytotoxic T lymphocyte; diagnostic error; disease exacerbation; dysphagia; dystonia; electrophysiology; enzyme linked immunosorbent assay; eye movement disorder; GABAergic transmission; genetic heterogeneity; glutamic acid decarboxylase antibody spectrum disorder; human; immunocytochemistry; immunohistochemistry; immunopathogenesis; immunotherapy; muscle rigidity; muscle spasm; myalgia; nerve cell excitability; neurologic disease; nonhuman; nystagmus; paraneoplastic neuropathy; parkinsonism; phenotype; progressive encephalomyelitis with rigidity and myoclonus; randomized controlled trial (topic); Review; spinal cord disease; stiff man syndrome; systematic review
