Steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT), also known as Hashimoto encephalopathy, is a rare complication of autoimmune thyroid disease characterized by a wide range of neurological or psychiatric symptoms, normal or nonspecific brain MRI findings, and elevated serum thyroid peroxidase antibodies regardless of thyroid functional status. Pretreatment diagnostic criteria are not specific but clinical responsiveness to steroid treatment and exclusion of other causes of encephalitis would confirm the diagnosis.
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Epidemiology
The condition is rare and reportedly mostly in adults.
Clinical presentation
Patients present with a wide range of neurologic symptoms, including subacute or fluctuating cognitive impairment or decreased level of consciousness, seizures or new onset status epilepticus, movement disorders (myoclonus, rigidity, cerebellar ataxia, or dyskinesias), or psychiatric disorders (psychosis, depression, tics, or obsessive-compulsive disorder) 1,2,4.
Patients may have mild clinical or subclinical hypothyroidism (elevated serum thyroid-stimulating hormone [TSH] and normal or low serum free thyroxine [T4] levels) 2. However, it is common to have normal thyroid function (normal serum TSH) at the time of neurologic presentation 3. Association with hyperthyroidism (low TSH) is least common 7,8.
Pathology
The pathogenesis is not well understood. It is believed to represent a cross-reaction between autoimmune antithyroid antibodies and neurons resulting in a diffuse central nervous system inflammation 1.
Markers
High serum thyroid peroxidase antibody levels (anti-TPO or TPOAb >200 UI/mL) are required for the diagnosis. However, this marker is not specific for the disease as many healthy persons and patients with other encephalitides harbor the antibody 2.
Neuronal surface antibodies in serum and CSF implicated in autoimmune encephalitis would ideally be excluded (e.g. Hu, Yo, Ri, CRMP5, amphiphysin, Ma2, Tr, GAD, AK5, NMDAR, AMPAR, GABAR, neurexin 3α, IgLON5, CASPR2, LGI1, DPPX, AQP4, mGluR1, mGluR5) 2.
Radiographic features
MRI studies are frequently normal (around 60%). When abnormalities are present, they show non-specific evidence of encephalitis 2,3:
-
T2/FLAIR
- subcortical white matter high signal intensities
- increased signal in medial temporal lobes (amygdala and hippocampus, a limbic encephalitis pattern)
- T1 C+ (Gd): contrast enhancement of the meninges can occur
Treatment and prognosis
Response to glucocorticoid therapy confirms the diagnosis of steroid-responsive encephalopathy associated with autoimmune thyroiditis 4. However, most patients who fulfill pretreatment criteria for Hashimoto encephalopathy do not show a complete clinical response, which raises into question the validity of this disease definition 2. Some patients require other immunosuppressive therapies such as intravenous immunoglobulin or plasmapheresis. Relapses are common and some patients require lifelong therapy 2,4.
History and etymology
Hashimoto thyroiditis was first described in 1912 by Hakaru Hashimoto, a Japanese physician (1881-1934), whilst working in Germany 5,6.
Differential diagnosis
The main differential is antibody-mediated autoimmune encephalitis and infectious encephalitis (such as herpes simplex encephalitis). Other causes of encephalopathy that should be excluded include toxic-metabolic, vascular, and neoplastic processes 2.