2017-18Research/HE/HE

Hashimoto encephalopathy (HE), or SREAT, is a rare entity associated with increased anti-thyroid antibodies and autoimmune thyroiditis. Clinicians should have increased suspicion in patients presenting with neurologic and mood symptoms with elevated anti-thyroid antibody levels. The diagnosis can be considered when the patient exhibits rapidly progressing cognitive decline, a negative infectious workup, and a high level of anti-thyroid antibodies. Once SREAT is suspected, aggressive treatment with corticosteroids and immunomodulators can lead to significant improvement in symptoms. IVIG can also be considered.

It is important for clinicians to remember that anti-TPO antibodies are associated with various autoimmune disorders. Not only are anti-TPO antibodies an early predictive marker for thyroid disease, but anti-TPO antibodies have been linked to extra-thyroidal diseases such as vitiligo, orbitopathy, and autoimmune encephalitis. In the setting of an appropriate clinical picture and elevated anti-TPO antibody levels, an extensive evaluation should be pursued to evaluate for autoimmune-related conditions, especially Hashimoto encephalopathy.

ATAbs (anti-thyroglobulin antibodies [TgAb], anti-thyroid peroxidase anti-bodies [TPOAb]) -positive and/or AITD  (Hashimoto’s thyroiditis and Graves’ disease)  patients with symptomatic encephalopathy should undergo proper surveillance for AE. Moreover, low fT3 could serve as a possible predictor of poor short-term outcome in AE, thereby suggesting that monitoring of thyroid function in AE may be necessary.

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This scientific commentary refers to ‘Brain dysfunction and thyroid antibodies: autoimmune diagnosis and misdiagnosis’, by Valencia-Sanchez et al.

In the interest of our patients, we must recognize the new evidence that demonstrates that the diagnostic utility of thyroid antibody testing is limited in the evaluation of autoimmune neurologic conditions. Its role is, at best, limited to demonstrating a potential propensity to systemic autoimmunity. Cessation of thyroid antibody testing in the evaluation of suspected autoimmune encephalitis and encephalopathy will hopefully reduce harm from misdiagnosis and unwarranted treatment, and minimize financial toxicity related to unnecessary interventions.

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We aimed to retrospectively review 144 cases referred with suspected Hashimoto encephalopathy over a 13-year period, and to determine the clinical utility of thyroid antibodies in the course of evaluation of those patients.

In total, 73% of the patients referred with suspected Hashimoto encephalopathy had an alternative non-immune-mediated diagnosis, and more than half had no evidence of a primary neurological disorder. Thyroid antibody prevalence is high in the general population, and does not support a diagnosis of autoimmune encephalopathy in the absence of objective neurological and CNS-specific immunological abnormalities. Thyroid antibody testing is of little value in the contemporary evaluation and diagnosis of autoimmune encephalopathies.

In our experience within our specialty referral practice, the diagnosis of HE/SREAT is assigned to a variety of patients with elevated thyroid antibody values and diverse neuropsychiatric symptomatic presentations, generally without objective demonstration of encephalopathy, CNS inflammation or objective steroid response.

Conclusion

We conclude that thyroid antibodies have served their time as diagnostic biomarkers in autoimmune encephalopathy well, but their role in the evaluation of autoimmune encephalopathy is likely redundant at this point, and certainly less specific than a clinical history of autoimmune disease and neural-specific antibodies. Our experience indicates that a diagnosis of HE/SREAT is often given to patients presenting with cognitive symptoms and a variety of neurological and non-neurological complaints, in the setting of elevated thyroid antibodies in serum without objective cognitive abnormalities. The utility of testing for thyroid antibodies seems questionable in the modern era which has brought availability of validated clinical criteria and advanced neuroimmunologic diagnostics. Over diagnosis of autoimmune encephalopathy brings undesired consequences such as iatrogenic harm, cost of unnecessary immunosuppressive therapies and delayed diagnosis of the correct neurological disorder. As always, test results need to be interpreted in the context of detailed clinical history and examination.

Case study conclusions: HE is rare and can present with a variety of clinical presentations. It should be considered as a differential for a patient presenting with unexplained cognitive impairment. It is crucial to detect and treat HE, as early treatment with steroid therapy has a good prognosis. A screening test of thyroid function test and TPOAb should be incorporated in the confusion screen for patients presenting with acute or subacute cognitive impairment. Other diagnoses should also be excluded with a full workup that includes labs, CSF studies, EEG, and imaging. Treatment with steroids should be considered, especially in patients with seizures that do not respond with anti-epileptics, along with the treatment of underlying thyroid disorder.

Highly Recommended for All Patients who Have received a diagnosis of Hashimoto’s Encephalitis

A retrospective review of cases referred with suspected  Hashimoto encephalopathy, also known as steroid-responsive encephalopathy associated with autoimmune thyroiditis,  over a 13 year period. The final study included 144 patients. After clinical and testing evaluations had been completed, 39/144 patients (27%) were assigned a diagnosis of an autoimmune CNS disorder (Table 2), and 105/144 (73%) were given an alternative clinical diagnosis.

HE, as our case illustrates, can present as progressive EPC with a focal cortical lesion.