Unfavourable outcome of Hashimoto encephalopathy due to status epilepticus

Abstract

Sirs: A 27-year-old woman with a history of Hashimoto’s thyroiditis presented with psychotic symptoms and myoclonus. Four months earlier, her relatives had noticed myoclonic jerks in the four limbs and depression. During the following weeks, the patient also manifested visual hallucinations and generalized tonic-clonic seizures. In addition, progressive cognitive deterioration and slowed psychomotor activity became evident. One month later, she experienced two episodes of convulsive status epilepticus lasting over 50 minutes that resolved after intravenous lorazepam and phenobarbital had been given. On admission to our department, neurological examination revealed disorientation, fine finger tremor and spontaneous and stimulus-induced myoclonus at the four limbs. Neuropsychological evaluation showed Mini-Mental Status Examination’s score of 23/30, verbal memory deficit, frontal dysfunction and impaired attention. The patient was taking L-thyroxine, 100 μg/day, valproate, 750 mg/day and phenobarbital, 100 mg/day. Laboratory analysis demonstrated high titres of thyroid microsomal antibodies (1781 IU/ml; normal < 60) antithyreoglobulin antibodies (127.5 IU/ml; normal < 28.7) and TSH (40.9 μU/ml; normal < 4.2 μU/ml). FT3 and FT4 were within the normal limits. Antinuclear and antiDNA antibodies were normal. Serological test for syphilis and HIV were negative. CSF examination showed slightly elevated protein levels (55 mg/dl, normal < 40) and two oligoclonal bands. 14-3-3 protein was absent and there was no evidence of bacterial or viral infection. EEG showed diffuse slowing of background activity and bifrontal theta activity. Photic stimulation induced massive myoclonus in the four limbs (Figure). Brain MRI and 99Tc SPECT were unremarkable. Genetic study excluded Unverricht-Lundborg and Lafora disease, and MERRF. As diagnosis of Hashimoto encephalopathy (HE) was made, intravenous treatment with methylprednisolone 1 g followed by prednisolone 40 mg/day was started. No significant improvement was observed and, 6 days later, the patient manifested progressively increasing massive myoclonus, culminating in convulsive status epilepticus. Intravenous benzodiazepines failed to interrupt status epilepticus and pentothal anesthesia was initiated. Ictal activity was never fully suppressed at EEG prolonged monitoring. The patient died after a prolonged comatose state from cardiac failure two weeks later. Autopsy was performed. Microscopic examination revealed focal infiltration of thyroid by lymphocytes. Fixed brain tissue was paraffin-processed, and 10 μm sections were obtained. Gross examination revealed few hemorrhagic areas in the pons. Immunohistochemical staining by using the avidin-biotinperoxidase complex method for assessment of astrocytes (glial fibrillary acid protein), microglia (HLA-DR) and T cells (CD3, CD4, CD8, CD19, CD45), did not show lymphocytic infiltrates. PrPSc staining was negative and no evidence of PAS+ inclusion bodies was found in the cerebral parenchyma. The clinical picture of our patient suggested the diagnosis of diffuse (type II) HE [1, 2]. HE is defined by the association of encephalopathy with the presence of antithyroid antibodies [1, 2]. Steroid treatment is usually effective but refractory cases have been reported [2]. Accordingly, clinical LETTER TO THE EDITORS