Last updated:
9/2/2025
Years published: 2018, 2025
NORD gratefully acknowledges Gioconda Alyea, MD (FMG), MS, National Organization for Rare Disorders and Jeehun Lee, MD, Department of Pediatrics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea, for assistance in the preparation of this report.
Summary
Hashimoto encephalopathy is a rare autoimmune neurological disorder characterized by impaired brain function (encephalopathy). Affected people have antithyroid antibodies in their body, especially anti-thyroid peroxidase (TPO) antibodies. Antibodies are part of the immune system; they are specialized proteins that target foreign or invading organisms. Antithyroid antibodies mistakenly target thyroid tissue. However, it is unclear whether these antibodies play any role in the development of Hashimoto encephalopathy or are a coincidental finding.
The main signs and symptoms are related to encephalopathy, a condition that is characterized by cognitive impairment, altered consciousness, psychiatric symptoms and seizures. Progression can be acute, relapsing-remitting, or slowly progressive. Behavioral abnormalities, confusion, hallucinations and sleep disturbances are common. The syndrome is often misdiagnosed as a primary psychiatric disorder or another form of encephalopathy.
Thyroid function in affected individuals varies. While many people have normal thyroid function, some present with an underactive thyroid (hypothyroidism) or less commonly, an overactive thyroid (hyperthyroidism).
Diagnosis requires a combination of clinical assessment, detection of antithyroid antibodies, exclusion of other causes of encephalopathy and often a positive response to corticosteroid treatment. Newer studies also suggest using anti-alpha enolase antibodies as a potentially more specific biomarker.
Treatment typically begins with high-dose corticosteroids, often resulting in rapid clinical improvement. For steroid-refractory or relapsing cases, additional immunosuppressive therapies such as azathioprine, cyclophosphamide, rituximab, intravenous immunoglobulin (IVIG) administration, or a procedure known as plasmapheresis may be used. Anti-seizure and antipsychotic medications are indicated as needed based on individual symptoms.
Introduction
Some researchers think there is a relationship between Hashimoto encephalopathy and Hashimoto thyroiditis, an autoimmune disorder in which antithyroid antibodies mistakenly damage the thyroid. The name Hashimoto encephalopathy is used because antithyroid antibodies and encephalopathy occur together. Whether these two disorders are linked in any way is not fully understood. Because there is no evidence that the antithyroid antibodies in Hashimoto encephalopathy contribute to brain damage, and because most affected individuals have a normal-functioning thyroid, some researchers think these are coincidental findings. Some doctors prefer the name steroid-responsive encephalopathy associated with autoimmune thyroiditis or SREAT instead of Hashimoto encephalopathy.
The most important symptom is impaired brain function (encephalopathy), namely, altered mental status. It is impairment of cognition, attention, orientation, sleep-wake cycle and consciousness.
Although researchers have been able to establish a clear syndrome with characteristic or “core” symptoms, much about the disorder is not fully understood. Several factors including the small number of identified cases and the lack of large clinical studies prevent doctors from developing a complete picture of associated symptoms and prognosis. Therefore, it is important to note that affected individuals may not have all the symptoms discussed below. Affected individuals and families should talk to their doctors and medical team about their specific case, associated symptoms and overall prognosis.
The specific symptoms and severity of the disorder can vary greatly from one person to another. The disorder may follow a relapsing and remitting course, which means that symptoms of cognitive decline and altered consciousness go through cycles where they worsen and improve.
In some people, the disorder will be slowly progressive rather than relapsing and remitting. In these people, there is a progressive pattern of cognitive decline including confusion, hallucinations, dementia and impairment of the sleep-wake cycle including difficulty in maintaining sleep and sleeping for longer periods of time than usual. Depression may be the initial sign in this form.
Although there are two distinct patterns of disease development for Hashimoto encephalopathy, the specific signs and symptoms can overlap. The severity, progression and specific symptoms associated with the disorder can vary greatly from one person to another.
Additional symptoms that can develop include:
Some people may develop tremors, abnormal jerky movements (myoclonus), poor coordination of voluntary movements (ataxia) and slurred speech (dysarthria).
Affected individuals may be inattentive, lack concentration and fail to understand basic concepts. They can also have behavioral changes including depression, anxiety, emotional instability, social withdrawal and changes in personality.
The disorder can follow a limited course that resolves without treatment (self-limited), follow a course where the disease becomes worse over time (progressive), or follow a relapsing and remitting course.
Many people with Hashimoto encephalopathy have a normal-functioning thyroid (euthyroid) despite the presence of antithyroid antibodies. Other individuals may have an underactive thyroid (hypothyroidism) or overactive thyroid (hyperthyroidism). The thyroid is part of the endocrine system, the network of glands that secrete hormones that regulate chemical processes (metabolism) that influence the body’s heart rate, body temperature and blood pressure.
Hashimoto encephalopathy is thought to result from an autoimmune reaction, though the precise mechanism remains unclear. It is associated with the presence of autoantibodies, particularly anti-thyroid peroxidase (TPO), anti-thyroglobulin and anti-NH₂-terminal alpha-enolase antibodies. However, these antibodies do not appear to directly cause brain damage, and their levels do not correlate with the severity of neurological symptoms. Therefore, their presence may simply mean there is a generalized autoimmune predisposition to HE. Anti-NAE antibodies are autoantibodies that target the NH2-terminal of α-enolase, an enzyme found in various tissues including the brain. These antibodies are thought to be involved in the autoimmune process associated with Hashimoto encephalopathy.
Because they are rarely found in other conditions, anti-NAE antibodies are considered highly specific to HE, but they are not always present. Anti-alpha enolase antibodies, which target an enzyme expressed widely in tissues including the brain, have emerged as a potentially useful but not definitive biomarker for HE. Their presence, in combination with antithyroid antibodies, strengthens the case for an active autoimmune process.
In autoimmune diseases, the immune system mistakenly targets the body’s own tissues. In HE, this immune response is thought to lead to disruption of the blood-brain barrier, resulting in localized inflammation and potentially both direct and indirect neuronal injury.
One proposed mechanism is inflammation of blood vessels within the brain (autoimmune cerebral vasculitis), which could account for some of the encephalopathic symptoms observed in HE.
Importantly, HE can occur in individuals with normal thyroid function (euthyroid), and thyroid dysfunction is not required for diagnosis. The presence of antithyroid antibodies in these people suggests that they may not be the underlying cause.
Further research is needed to clarify the exact immunopathogenic mechanisms involved in HE and to identify specific biomarkers that can guide diagnosis and treatment.
Hashimoto encephalopathy is a rare disease that affects females more often than males. The disorder is estimated to affect 2.1 per 100,000 individuals in the general population. It can affect children, but only approximately 60 affected children have been described in the medical literature. Rare disorders often go misdiagnosed or undiagnosed making it difficult to determine the true frequency in the general population.
A diagnosis of Hashimoto encephalopathy is based upon identification of characteristic symptoms, a detailed patient history, a thorough clinical evaluation and a variety of specialized tests. By definition, a person with Hashimoto encephalopathy must have detectable levels of antithyroid antibodies in the body. However, there is no correlation between the amount of antibody levels and the presence or severity of symptoms. Antithyroid antibodies are relatively common in the general population, so this finding must occur in individuals with the characteristic findings associated with Hashimoto encephalopathy and in whom other potential diagnoses have been ruled out.
Clinical Testing and Workup
Blood tests may reveal high levels of antithyroid antibodies. Cerebrospinal fluid, which is the clear fluid that supports and protects the brain and spinal cord, may be studied, which may show nonspecific findings including abnormally high levels of certain proteins. Anti-NAE antibodies are emerging as a helpful marker, with high specificity but limited sensitivity, i.e., they are not present in other diseases (high specificity), but they are not always present in Hashimoto encephalopathy (limited sensitivity).
Doctors may recommend an electroencephalogram (EEG), which is a test that measures the electrical activity of the brain and may show changes in brain function and slowing of background activity. An EEG can also be used to help to detect seizures.
Specialized imaging techniques may be performed including magnetic resonance imaging (MRI). An MRI uses a magnetic field and radio waves to produce cross-sectional images of organs and bodily tissues, including the brain. An MRI is usually normal and is used to exclude other causes of encephalopathy. Rarely, it can show widespread (diffuse) or specific (focal) changes in white matter.
Doctors use a set of criteria to help diagnose Hashimoto encephalopathy. These guidelines are known as the Graus criteria and the revised Graus criteria. They help ensure that other possible conditions are carefully ruled out before a diagnosis is made.
Panel A: original Graus criteria
Panel B: revised Graus criteria
These criteria are used together to guide diagnosis and treatment. Not all people will meet every point, but they help doctors identify when Hashimoto encephalopathy may be the cause of someone’s symptoms.
Treatment
Early recognition and treatment, often with corticosteroids, can lead to significant improvement. Hashimoto encephalopathy is treated with medications known as corticosteroids. Corticosteroids are used to treat inflammation and affected individuals have responded very well to this treatment. The best dose (optimal dose) is unknown and will vary based on several factors including a person’s age, overall health and individual tolerance of the medication. Treatment usually begins with high doses of corticosteroids, which are then slowly lowered (tapered off). Long-term therapy with high doses of corticosteroids is associated with significant side effects, so the high doses are used initially to bring the disorder under control before the doses are lowered. In most people, symptoms usually improve or go away completely within a few months, although some people require treatment for as long as two years.
If corticosteroids are ineffective or cannot be tolerated by an individual, other medications, specifically mediations that suppress the activity of the immune system (immunosuppression), have been tried including azathioprine and cyclophosphamide. In patients who do not fully respond to the corticosteroid therapy, other therapeutic options such as intravenous immune globulin (IVIG) or plasmapheresis could be considered. The mechanism of IVIG is associated with neutralizing circulatory autoantibodies.
Plasmapheresis can remove autoantibodies from the blood. Plasmapheresis is a method for removing unwanted substances (toxins, metabolic substances, autoantibodies) from the blood. During plasmapheresis, blood is removed from the affected individual and blood cells are separated from plasma. The plasma is then replaced with other human plasma, and the blood is transfused back into the affected individual.
Some people with Hashimoto encephalopathy may relapse and require another course of corticosteroid therapy or immunosuppressive therapy.
Management of associated symptoms includes antiepileptics for seizures, antipsychotics for psychiatric symptoms and thyroid hormone therapy for people with hypothyroidism.
Although specific rehabilitation protocols for HE are lacking, treatment strategies for other neuroinflammatory and cognitive disorders are applicable:
Patient education, caregiver training and a multidisciplinary care team are essential for long-term management.
Further research is needed to establish standardized rehabilitation protocols and determine long-term outcomes.
Information on current clinical trials is posted on the Internet at https://clinicaltrials.gov/. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: [email protected]
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact:
https://www.centerwatch.com/
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
JOURNAL ARTICLES
Manocchio N, Magro VM, Massaro L, Sorbino A, Ljoka C, Foti C. Hashimoto’s Encephalopathy: Clinical Features, Therapeutic Strategies, and Rehabilitation Approaches. Biomedicines. 2025; 13(3):726. https://doi.org/10.3390/biomedicines13030726
Croce L, Dal Molin M, Teliti M, Rotondi M. Hashimoto’s encephalopathy: an endocrinological point of view. Front Endocrinol (Lausanne). 2024;15:1367817. Published 2024 Apr 10. doi:10.3389/fendo.2024.1367817
Chaudhuri J, Mukherjee A, Chakravarty A. Hashimoto’s Encephalopathy: Case Series and Literature Review. Curr Neurol Neurosci Rep. 2023;23(4):167-175. doi:10.1007/s11910-023-01255-5
Lee J, Yu HJ, Lee J. Hashimoto encephalopathy in pediatric patients: homogeneity in clinical presentation and heterogeneity in antibody titers. Brain Dev. 2018;40:42-48. https://www.ncbi.nlm.nih.gov/pubmed/28784301
Lee Y, House EM. Treatment of steroid-resistant Hashimoto encephalopathy with misidentification delusions and catatonia. Psychosomatics. 2017;58:322-327. https://www.ncbi.nlm.nih.gov/pubmed/28190544
Dominique Endres, Perlov E, Stich O, Tebartz van Elst L. Steroid response encephalopathy associated with autoimmune thyroiditis (SREAT) presenting as major depression. BMC Psychiatry. 2016;16:184. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4895894/
De Holanda NC, de Lima DD, Cavalcanti TB, Lucena CS, Bandeira F. Hashimoto’s encephalopathy: systemic review of the literature and an additional case. J Neuropsychiatry Clin Neurosci. 2011;23;384-390. https://www.ncbi.nlm.nih.gov/pubmed/22231308
Mocellin R, Walterfang M, Velakoulis D. Hashimoto’s encephalopathy: epidemiology, pathogenesis and management. CNS Drug. 2007;21:799-811. https://www.ncbi.nlm.nih.gov/pubmed/17850170
Taylor SE, Tudor-Williams G, Garalda ME, Martinez-Alier N. Hashimoto’s encephalopathy. Lancet. 2003;361:1912-1913. https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(03)13525-8/fulltext
INTERNET
Rubin DI. Hashimoto Encephalopathy. UpToDate, Inc. Jan 16, 2025. 10. Available at: https://www.uptodate.com/contents/hashimoto-encephalopathy Accessed August 26, 2025.
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