Paraneoplastic myasthenia gravis: immunological and clinical aspects.
Paraneoplastic myasthenia gravis (MG) is accompanied by a neoplasm, usually thymoma. In patients with thymoma and a specific genetic make-up, the paraneoplastic immune response develops further in thymic remnant or peripheral lymphatic tissue. Paraneoplastic MG and late-onset MG (age >or= 50 years) share a similar immunological profile with high titin and ryanodine receptor (RyR) antibody prevalence. This profile is the most important predictor of clinical outcome in paraneoplastic MG. The presence of a thymoma per se does not cause more severe MG. MG severity is linked to the patient's immunological profile. Paraneoplastic MG causes a distinctive non-limb symptom profile at MG onset, characterized by bulbar, ocular, neck, and respiratory symptoms. When the diagnosis of paraneoplastic MG is established, the neoplasm should be removed surgically. Pre-thymectomy plasmapheresis or iv-IgG should be considered in these patients to minimize post-thymectomy MG exacerbation risk. Paraneoplastic MG usually continues after thymectomy. The pharmacological treatment of paraneoplastic MG does not differ from non-paraneoplastic MG, except for tacrolimus that should be considered in difficult cases. Tacrolimus is an immunosuppressant acting specifically in RyR antibody positive patients through enhancing RyR-related sarcoplasmic calcium release that in theory might be blocked by RyR antibodies, causing symptomatic relief in paraneoplastic MG.
Skeie
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Department of Neurology, Haukeland University Hospital, Bergen, Norway.
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D017668:Age of Onset; D001284:Atrophy; D001323:Autoantibodies / Q000276:immunology; D001324:Autoantigens / Q000276:immunology; D003131:Combined Modality Therapy; D064211:Connectin; D006801:Humans; D006965:Hyperplasia; D007166:Immunosuppressive Agents / Q000627:therapeutic use; D008875:Middle Aged; D009124:Muscle Proteins / Q000276:immunology; D009157:Myasthenia Gravis / Q000188:drug therapy / Q000453:epidemiology / Q000209:etiology* / Q000276:immunology; D009419:Nerve Tissue Proteins / Q000276:immunology; D020364:Paraneoplastic Polyneuropathy / Q000188:drug therapy / Q000209:etiology* / Q000276:immunology; D010956:Plasmapheresis; D011379:Prognosis; D011494:Protein Kinases / Q000276:immunology; D011950:Receptors, Cholinergic / Q000276:immunology; D019837:Ryanodine Receptor Calcium Release Channel / Q000276:immunology; D013934:Thymectomy; D013945:Thymoma / Q000150:complications* / Q000276:immunology / Q000601:surgery; D013950:Thymus Gland / Q000473:pathology; D013953:Thymus Neoplasms / Q000150:complications* / Q000276:immunology / Q000601:surgery
D001323:Autoantibodies; D001324:Autoantigens; D064211:Connectin; D007166:Immunosuppressive Agents; D009124:Muscle Proteins; D009419:Nerve Tissue Proteins; D011950:Receptors, Cholinergic; D019837:Ryanodine Receptor Calcium Release Channel; C577285:TTN protein, human; D011494:Protein Kinases