Hashimoto’s encephalopathy (HE): an under diagnosed autoimmune-mediated encephalopathy

Excerpt

Hashimoto’s encephalopathy (HE) is a rare autoimmune-mediated encephalopathy characterized by high serum levels of thyroid autoantibodies and no evidence of infection or other well-defined cerebral disorders [1]. Classically the clinical manifestations include acute to sub acute onset of confusion with alteration of consciousness, rarely myoclonus [2]. Serum autoantibodies against the amino terminal of alpha enolase (anti-NAE Abs) have been discovered, with high specificity as sierological markers for HE [3]. We report, the unusual case of a 40-year-old patient who was referred to our Emergency room because of marked asthenia associated to nausea, vomiting, and ataxia. On examination ataxia, myoclonic tremor and cerebellar dysmetria were present. He was then referred to Neurologic Unit for suspected encephalitis. History revealed familiarity for thyroid disease: mother underwent thyroid surgery for thyroid neoplasia and brother was affected from hypothyroidism. Laboratory showed: leucocytosis, increased values of creatine phospho kinase (CPK) and antithrombin III (AT III). Autoimmune hypothyroidism was present: TSH: 21.1 mUI/mL, FT4: 0.7 ng/mL, antithyroglobulin autoantibodies (Abtg): 3712 UI/mL, antithyroperoxidase autoantibodies (TPOAb): 2000 U/L e anti TSH-receptor autoantibodies (TRab) < 0.5UI/mL. Hyposurrenalism was than excluded and l-thyroxine therapy was started. A double mutation methylenetetrahydrofolate reductase (MTHFR) C677T in eterozigosis is present. EEG, TSA eco color Doppler, and ECG were negative. NMR revealed a diffuse leucopathic hyperintensity of peritrigonal area and semioval centres (Fig. 1). Ultrasound imaging of thyroid showed an increased gland with marked hypoechogenicity and increased vascularization on eco color Doppler. Cerebrospinal fluid (CSF) study showed normal cytology and increased glucose and protein, with the presence of Ab TPO (66 UI/mL) and Ab Tg (34 UI/mL) and negative anti-virus neurotropic antibodies. For this reason an autoimmune encephalopathy was suspected and methylprednisolone was started (16 mg/die) with remission of syndrome. The alterations of CSF associated to mild autoimmune hypothyroidism and NMR imaging results suggested the diagnosis of HE. Hashimoto’s encephalopathy is a rare steroid responsive neuropsychiatric syndrome which could be considered when other causes of encephalopathy have been excluded and thyroid autoantibodies are present. The physiopathological mechanisms proposed are an autoimmune cerebral vasculitis, a toxic effect of thyroid stimulating hormone on central nervous system and a neuronal reaction mediated by thyroid autoantibodies [3]. Although the pathogenesis remains unclear, some studies have demonstrated brain vasculitis or lymphocyte infiltration in many small vessels of biopsied or post-mortem brains, suggesting that an insufficiency of cerebral blood flow due to vasculitis causes the neuropsychiatric syndrome. HE is distinct from myxedema’s encephalopathy caused by hypothyroidism and can be effectively treated, not only with thyroid hormone replacement therapy but with immunotherapy. Even if in this case anti-NAE Abs were not searched HE has been diagnosed on the basis of the presence of thyroid autoantibodies and the responsiveness to corticosteroid treatment. Infact HE is as an underdiagnosed treatable condition, which has to be considered in patients with a neuropsychiatric syndrome suggestive for an encephalitis when other causes of SNC damage have been excluded, in presence of antithyroid antibodies and/or anti-NAE Abs.

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