Clinical and neuropathological findings in Hashimoto’s encephalopathy: a case report

Abstract

Hashimoto’s encephalopathy (HE) is a controversial autoimmune condition of the central nervous system (CNS) characterized by focal and/or diffuse symptoms concomitant with raised levels of anti-thyroid antibodies, in particular anti-thyroperoxidase (TPO) and/or anti-thyroglobulin (TG) antibodies [1]. Hereby, we provide the full clinical and neuropathological description of an HE patient with a rapid and fatal course. A 67-year-old man with autoimmune hypothyroidism taking L-thyroxine 100 lg/day came to our observation because of 1-month history of apathy and speech difficulties. At admission in the neurological ward, fluent aphasia, disorientation, and spontaneous diffuse myoclonic jerks were present. Cranial CT and brain MRI were unremarkable. EEG evidenced rare diffuse theta-delta bursts. On laboratory investigations, we detected only a markedly raised titer of serum anti-TPO antibodies (3,790 UI/ml). CSF analysis disclosed very high protein concentration (126 mg/dL) with moderate alteration of blood–brain barrier permeability. Virological analyses were all negative. Total tau CSF concentration was normal, whereas the 14-33 protein was present in traces. To rule out a neurological paraneoplastic syndrome, the patient’s serum was analyzed by an indirect immunofluorescence assay on monkey cerebellum slides. We evidenced a Tr-like pattern, characterized by a prominent staining of cytoplasm and dendrites of Purkinje cells, but with no positive dots in the molecular layer (Fig. 1). No paraneoplastic antibody specificity (Hu, Yo, Ri, amphiphysin, Ma2, Ta) was detected by dot blot. Serum anti-VGKC and anti-NMDA-R antibodies were absent. A total body contrast-enhanced CT ruled out occult neoplasms. Given the subacute encephalopathy picture with no evident causes and the very raised serum titer of anti-TPO antibodies, a presumptive diagnosis of HE was made. A high-dose systemic methylprednisolone pulse (1,000 mg/ day) was started. After 5 days from steroid initiation, the patient was intubated and transferred to the intensive care unit (ICU) because of a refractory convulsive status epilepticus. Thiopentone was administered to get a suppression-burst pattern on EEG recordings. After 1 week the patient’s clinical conditions markedly ameliorated and no seizure relapses were observed. Therefore, he was readmitted to our neurologic ward. In the following 5 days, diffuse myoclonic jerks progressively increased, leading to convulsive status epilepticus. The patient entered again the ICU to employ intravenous thiopentone. A new brain MRI study evidenced diffuse hyperintensity of cortical white matter of parietal lobes in T2 and FLAIR scans with no contrast enhancement in T1 sequences. MRI signs of bilateral hippocampal sclerosis were also present. The patient’s neurologic status deteriorated in spite of a 10-day systemic methylprednisolone (1,000 mg/day) and 5-day intravenous human immunoglobulin pulse (400 mg/kg/ day). Exitus occurred from a multiorgan failure syndrome after 3 weeks. The autopsy procedure was limited to the intracranial content, since the remote suspect of a prion disease. On gross inspection, cortical gyri were slightly flattened. On microscopic examination, areas of neuropil vacuolation with congestion and swollen endothelial cells D. Imperiale (&) R. Testi A. Romito S. Taraglio Centro Regionale Diagnosi ed Osservazione Malattie Prioniche DOMP, ASL To2, Via Cibrario 72, 10144 Turin, Italy e-mail: daniele.imperiale@aslto2.piemonte.it