Hashimoto's Encephalopathy—Steroid Responsive Syndrome
Abstract & Commentary
By Matthew E. Fink, MD, Vice Chairman, Professor of Clinical Neurology, Weill Cornell Medical College, Chief, Division of Stroke and Critical Care Neurology, NewYork-Presbyterian Hospital. Dr. Fink reports no financial relationship relevant to this field of study.
Synopsis: Subacute encephalopathy associated with thyroid antibodies and a history of autoimmune thyroid disease may respond dramatically to high-dose corticosteroid therapy.
Source: Castillo P, et al. Steroid-Responsive Encephalopathy Associated with Autoimmune Thyroiditis. Arch Neurol. 2006;63:197-202.
Acute and subacute encephalopathy is a common reason for neurological consultation in the hospital, but often, a specific etiology is not forthcoming. A family of autoimmune encephalopathy syndromes, some associated with underlying malignancies, have been described in recent years, and some have had specific anti-neuronal antibodies identified to aid in diagnosis. The existence of the syndrome first described by Lord Brain in 1966 (Brain L, et al. Lancet. 1966;2:512-514) and termed Hashimoto's encephalopathy, has been debated in the literature and has not been well characterized. Castillo and colleagues, at the Mayo Clinic, have done an admirable job of characterizing a recognizable syndrome, and have further defined it by a dramatic response to corticosteroids.
In a review of 20 patients followed at the Mayo Clinic, a diagnosis of SREAT (steroid-responsive encephalopathy associated with auto-immune thyroiditis) was based on the following criteria— encephalopathy with cognitive impairment and neuropsychiatric features, presence of serum thyroid antibodies, euthyroid or mildly hypothyroid state, no evidence of other infectious, toxic, metabolic, neoplastic, or vascular process, no serologic evidence of paraneoplastic autoantibodies, and complete or near-complete return of baseline neurological status after treatment with corticosteroids.
All but one patient required acute hospitalization because of the severity of the illness. The median age at onset was 56 years (range, 27-84) and 70% were female. The most common clinical features at presentation were behavioral-cognitive abnormalities (100%), tremor (80%), transient aphasia (80%), myoclonus (65%), gait ataxia (65%), seizures (60%), and sleep abnormalities (55%). Misdiagnoses were common, with the most frequent being Creutzfeldt-Jakob disease, viral encephalitis, and degenerative dementias. A history of hypothyroidism or euthyroid goiter was present in 11 patients, and 5 additional patients were diagnosed with hypothyroidism after resolution of the encephalopathy. Eight patients were diagnosed with other autoimmune disorders in addition to thyroid disease. Serologic studies revealed that 13/13 patients tested positive for thyroperoxidase antibodies, 7/7 patients tested positive for thyroid microsomal antibodies, and 6/10 were positive for thyroglobulin antibodies. Liver AST/ALT levels were elevated in 11/20 patients but other autoantibodies (ANA, ENA, RF, Gliadin) were present in less than half of the patients. CSF had elevated protein in 17/20 and elevated white count in 5/20, but only 2 patients had increases of IgG or oligoclonal bands. EEG testing in 19/20 patients showed generalized slowing that resolved after treatment in the 17 patients who had follow-up studies. Cerebral angiography in 5 patients, and meningeal and brain biopsy in 2 patients did not reveal any significant abnormalities. Brain MRI in 4 patients revealed diffuse increased signal on T2-weighted and FLAIR images in the cerebral white matter that normalized after treatment with corticosteroids.
The SREAT syndrome is defined by its response to therapy, and all of the reported patients received high-dose corticosteroid therapy, 1 gm/day of intravenous methylprednisolone for 5 days, followed by oral prednisone 60-100 mg/day for 10-30 days. Fifteen patients returned to their normal neurological baseline status and 5 had residual symptoms.
Commentary
Castillo et al have done an admirable job of further defining and characterizing the syndrome of Hashimoto's encephalopathy, with particular emphasis on a therapeutic response to high-dose corticosteroids. In a clinically similar group of 12 patients who did not respond to corticosteroids, there was progression of disease in all cases, and 4 autopsy examinations revealed Creutzfeldt-Jakob disease in 2, Lewy body disease in one, and neurofilament inclusion body disease in one. It is likely that the others had a progressive neurodegenerative or prion disease. Therefore, the importance of a therapeutic trial of high-dose corticosteroids cannot be overemphasized, since the alternative diagnoses are progressive, fatal conditions that have no effective treatment. In an appropriate clinical setting, corticosteroid therapy is warranted. However, we do not know what the natural history of SREAT would be in the absence of therapy. It is plausible that there might be spontaneous remission of this encephalopathy, as occurs in other autoimmune conditions. So, there is still much to learn. In order to more clearly define and understand this syndrome, we hope that further studies of Hashimoto's encephalopathy, as well as the broader group of nonvasculitic autoimmune meningoencephalitis (Caselli RJ, et al. Neurology.1999;53:1579-1581) will be investigated for evidence of biologically-active, anti-neuronal antibodies that might lead us to the pathophysiology of these mysterious disorders.
Subacute encephalopathy associated with thyroid antibodies and a history of autoimmune thyroid disease may respond dramatically to high-dose corticosteroid therapy.You have reached your article limit for the month. Subscribe now to access this article plus other member-only content.
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