The Uncertain Nosology of Hashimoto Encephalopathy

Abstract

We welcome the review of Hashimoto encephalopathy (HE) by Chong et al 1 and share their concern regarding the indiscriminate use of this poorly defined term. There is sparse evidence for the pathogenicity of antithyroid antibodies in this condition: HE has been associated with variable titers of either thyroglobulin or microsomal antibodies, and these antibodies have different antigenic targets. We agree that HE is likely to represent a heterogeneous group of disorders, probably due to a variety of autoimmune causes, with thyroid antibody elevation being a bystander effect. It is interesting to speculate whether some of the patients might have had the recently described encephalopathy associated with voltage-gated potassium channel antibodies. 2,3Furthermore, not all cases that would meet the criteria of Chong et al 1 for HE have an autoimmune etiology. We cared for a previously healthy 62-year-old woman who had a 4-month history of progressive cognitive and behavioral decline accompanied by extrapyramidal signs and multifocal myoclonus. The level of thyroid-stimulating hormone was mildly raised (10.8 mIU/L; range, 0.3-5.0 mIU/L), and antithyroid microsomal antibodies were present in high titers (1:102400). The cerebrospinal fluid was acellular with no evidence of bacterial or viral infection. There was no response to an empirical trial of steroid therapy, and the patientsubsequentlydied.Postmortemexaminationofthebrain confirmed the diagnosis of sporadic Creutzfeldt-Jakob disease with no evidence of inflammation. This case illustrates the importance of considering histopathologic examination in suspected HE cases, both to exclude alternative diagnoses and to further our understanding of this complex entity. The significance of lymphocytic perivascular infiltration, a nonspecific finding in cerebral vasculitis, remains uncertain in thiscondition. 4 Whereasempiricaluseofcorticosteroidsmay produce clinical improvement in some cases labeled as HE, such treatment is not without its risks and may obscure alternative diagnoses. We suggest that the term Hashimoto encephalopathy be abandoned because implications of causality, which have not been conclusively proved, will remain while this term is in use.

Initial serum thyroid peroxidase antibodies and long-term outcomes in SREAT

“…To date, there is no understanding of how thyroid antibodies may be linked to autoimmune disease. Although abnormal thyroid parameters in serum have been associated with demyelinating diseases of the central nervous system, many authors favor the idea that TPO‐Abs are incidental bystanders in SREAT . The “bystander hypothesis” is supported by epidemiological studies showing that TPO‐Abs have a high prevalence in asymptomatic individuals.…”

Steroid-Responsive Chronic Schizophreniform Syndrome in the Context of Mildly Increased Antithyroid Peroxidase Antibodies

“…Most researchers favor the idea that thyroid antibodies do not play a relevant role in the development of neuropsychiatric symptoms (19, 20). Thyroid antibodies have been found in the serum of 13% of healthy individuals (21, 22).…”

Autoimmune Encephalopathy

“…Screening for evidence of non-organspecific autoimmunity with antinuclear antibody (ANA), antibodies to the extractable nuclear antigen (ENA), and antineutrophil-cytoplasmic antibody (ANCA) is helpful as a marker of nonspecific autoimmunity, but may also suggest CNS involvement of an underlying systemic autoimmune disease, such as systemic lupus erythematosus (SLE), Wegener's granulomatosis, or Sjögren's disease. Thyroid peroxidase (TPO) antibodies are also a useful marker of underlying autoimmunity, but are unlikely to be pathogenic 3 and do not predict treatment response. 9 In general, any autoantibodies may be nonspecifically elevated, even rheumatoid factor and antiphospholipid antibodies.…”