Hashimoto's encephalopathy
A rare neurological disorder linked to thyroid autoimmunity.
Hashimoto's encephalopathy, sometimes called steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), is a neurological disorder marked by brain dysfunction, evidence of thyroid autoimmunity, and a strong positive response to corticosteroid treatment. It is linked to Hashimoto's thyroiditis and was first identified in 1966. The NIH Genetic and Rare Diseases Information Center classifies it as a rare disease. Whether it should be considered a neuroendocrine disorder is a matter of debate, as its connection to the endocrine system remains controversial.
By 2005, nearly 200 case reports had been published. From 1990 to 2000, 43 cases appeared in the literature. Since then, research has grown, and scientists worldwide are reporting more cases, suggesting that the condition was likely underdiagnosed in the past. Between 2000 and 2013, over 100 scientific articles on the disorder were published.
Symptoms usually develop gradually, over a period of one to twelve years. They can include personality changes, aggression, delusional behavior, trouble concentrating and remembering, coma, disorientation, headaches, muscle jerks (myoclonus, seen in 65% of cases), lack of coordination (ataxia, also 65%), partial paralysis on the right side, psychosis, seizures (60%), sleep abnormalities (55%), speech problems such as transient aphasia (30-40%), status epilepticus (10-15%), and tremors (30-40%).
The exact mechanism behind the condition is unknown, but it is thought to be autoimmune, much like Hashimoto's thyroiditis. Supporting this idea, autoantibodies against alpha-enolase have been found in association with the disorder. Since enolase is involved in the second-to-last step of glycolysis, if these antibodies inhibit it, each cell would produce less energy. This could lead to shrinkage of affected organs as cells shrink due to the energy deficit, or, in severe cases, cell death through apoptosis or necrosis. This might happen because insufficient ATP is available to maintain basic cellular functions—particularly the sodium-potassium ATPase pump, which helps drive the sodium-calcium exchanger that normally keeps calcium levels low inside cells. Without this gradient, calcium can build up to toxic levels, triggering lysosome rupture and apoptosis.
- First described
- 1966
- Prevalence
- 2.1 per 100,000
- Male to female ratio
- 1:4
- Mean age of onset
- 44
- Field
- Neurology, endocrinology
- Known for
- Encephalopathy with thyroid autoimmunity, responsiveness to corticosteroids
Lore & Background
The first case of Hashimoto's encephalopathy was described by Brain et al. in 1966, involving a 48-year-old man with hypothyroidism, multiple episodes of encephalopathy, stroke-like symptoms, and Hashimoto's thyroiditis confirmed by elevated antithyroid antibodies. Up to 2005, almost 200 case reports were published, with 43 cases between 1990 and 2000. Since then, research has expanded, suggesting the condition was significantly undiagnosed in the past. Over 100 scientific articles on the disease were published between 2000 and 2013.
Symptoms develop gradually over 1–12 years and may include personality changes, aggression, delusional behavior, concentration and memory problems, coma, disorientation, headaches, myoclonus (65% of cases), ataxia (65%), seizures (60%), sleep abnormalities (55%), transient aphasia (30-40%), status epilepticus (10-15%), and tremors (30-40%).
Reader's Guide
Hashimoto's encephalopathy is significant as a rare but treatable cause of encephalopathy, often misdiagnosed due to its diffuse symptoms and gradual onset. Its recognition as a steroid-responsive condition has improved outcomes, though optimal treatment remains uncertain due to a lack of controlled trials. The condition highlights the complex interplay between the immune system and the nervous system, with autoantibodies to alpha-enolase proposed as a key pathogenic mechanism. The high rate of undiagnosed cases suggests that many patients with unexplained neuropsychiatric symptoms may benefit from screening for thyroid antibodies. The disease's disputed relationship to the endocrine system underscores ongoing uncertainty in its classification. Its legacy includes raising awareness of autoimmune encephalopathies and the importance of considering thyroid autoimmunity in patients with cognitive decline, seizures, or psychiatric symptoms. The condition's response to corticosteroids has led to its alternative name, steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT).
Did You Know?
- The first case was described in 1966 in a 48-year-old man with hypothyroidism and stroke-like symptoms.
- Up to 2005, almost 200 case reports of this disease were published.
- Symptoms include myoclonus and ataxia in 65% of cases, and seizures in 60% of cases.
- The condition is recognized as a rare disease by the NIH Genetic and Rare Diseases Information Center.
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