Dr. Patterson of Hospital of the University of Pennsylvania has no relevant financial relationships to disclose.)
Dr. Lancaster of the University of Pennsylvania received a speaker’s fee and research grant from Grifols and consulting fees from Merck and Novartis.)
Hashimoto encephalopathy is a controversial and poorly understood diagnosis classically defined as a steroid-responsive encephalopathy associated with thyroid autoimmunity (Montagna et al 2016; Zhou et al 2017). The key features are: (1) altered level of consciousness and (2) presence of anti-thyroid peroxidase (anti-TPO) or anti-thyroglobulin (anti-TG) antibodies. It is distinct from alterations in mentation that may occur due to severe hyper- or hypothyroidism, and severe abnormalities in thyroid hormone levels should be excluded when making the diagnosis. Symptoms can vary considerably though commonly include cognitive deficits, behavioral changes, myoclonus, or stroke-like episodes.
Thyroid antibodies are relatively common in the general population and can coexist with other autoimmune responses, which may better explain some patients symptoms (Hollowell et al 2002). Thyroid antibodies are not thought to directly affect the brain. With the increasing recognition of pathogenic or potentially pathogenic antibodies to brain proteins, such as the N-methyl-D-aspartate receptor (NMDAR) or leucine-rich, glioma-inactivated 1 (LGI1), some patients have been reclassified as having these specific autoimmune brain diseases. Given the diverse clinical presentations, those diagnosed with Hashimoto encephalopathy may have a variety of unrecognized CNS autoimmune diseases.
Patients with suspected Hashimoto encephalopathy require careful evaluation for autoimmune and nonautoimmune causes of encephalopathy.
• Hashimoto encephalopathy is a poorly understood syndrome of reversible cognitive impairment in the setting of thyroid autoantibodies.
• Thyroid antibodies are relatively common in the general population and may also be found in patients with other, better-defined types of autoimmune encephalitis and in persons without autoimmune brain disease. Thorough testing for other causes of encephalopathy is necessary.
• There is no Class 1 evidence for treatment of Hashimoto encephalopathy. Most treatment protocols include intravenous or oral steroids. Most patients respond at least partially to steroids or other forms of immune therapy.
Historical note and terminology
In 1966, Brain and colleagues reported the initial case of Hashimoto encephalopathy, a 40-year-old man with thyroid antibodies who had multiple stroke-like episodes and periods of profound confusion (Brain et al 1966). He eventually had excellent recovery (although he did not obviously respond to steroids). Although he had thyroid disease, this was well controlled during most of his clinical course. The authors concluded that he may have had an autoimmune disease but doubted that the thyroid antibodies were directly pathogenic.
Hashimoto encephalopathy is referred to by the National Institutes of Health as Hashimoto encephalitis. In the last decade, alternative names for Hashimoto encephalopathy have been proposed, including steroid-responsive encephalopathy associated with thyroiditis (SREAT) and encephalopathy associated with autoimmune thyroid disease (EAATD) (Schiess and Pardo 2008).
Hashimoto encephalopathy should not be confused with Hashimoto thyroiditis. Hashimoto thyroiditis was first described in 1912 as a form of thyroid disease with lymphomatous infiltrates (Hiromatsu et al 2013). Unlike Hashimoto encephalopathy, humoral factors such as antibodies to thyroid peroxidase, thyroglobulin, and other thyroid antibodies are thought to directly contribute to the pathogenesis of Hashimoto thyroiditis, along with cellular immunity, genetic risk, and other factors (Ajjan and Weetman 2015).
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