Abstract
Hashimoto’s encephalopathy (HE) is a rare neurological disorder with a heterogeneous group of neurological symptoms associated with high titres of anti-thyroid antibodies. Clinical manifestations may include encephalopathic features such as seizures, behavioural and psychiatric manifestations, movement disorders and coma. The objective of this presentation is to describe a patient with this rare and controversial clinical syndrome mimicking Creutzfeldt–Jakob disease, associated with a Hashimoto euthyroid thyroiditis and with a significant response to high dose intravenous prednisone. The responsiveness of this syndrome to steroids suggests that this disorder involves immune pathogenic mechanisms, as previous reviews reported.
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Introduction
Hashimoto’s encephalopathy (HE) is a rare neurological disorder with a heterogeneous group of neurological symptoms associated with high titres of anti-thyroid antibodies. Clinical manifestations include seizures, behavioural and psychiatric manifestations, movement disorders and coma [1]. HE is also named steroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT).
Case report
We describe a 66 year-old patient with this rare and controversial clinical syndrome.
He was admitted to our ER department for acute onset of confusion, speech and comprehension disturbances followed by a generalised tonic-clonic seizure with prolonged coma requiring assisted ventilation after i.v. diazepam. Two days before admission, he had had fever up to 39.2°C. He had been in Australia 1 month before and had undergone a flu vaccination 10 days before admission. Past medical history revealed mild hypertension and dilated cardiomyopathy.
In the ER department, a lumbar puncture showed mild increase in proteins (70 mg/dL), with normal cell count and glycorrhachia. EEG showed diffuse slow theta–delta activity. Brain CT scan was unremarkable. Brain MRI showed a left white-matter subcortical hyperintense lesion in long-TR weighed sequences, with an altered diffusion. Proton density images revealed mild bilateral hyperintensity of the frontal and insular grey matter. No contrast-enhanced alterations were evident (Fig. 1). Intracranial angio-MRI was normal. Even if CSF count was normal, in the hypothesis of an early phase central nervous system infection, we started i.v. antiviral and antibiotic therapy with Acyclovir, 350 mg t.i.d., and i.v. Ceftriaxone, 2 g b.i.d. The following day, brain MRI disclosed bilateral frontal and temporo-insular cortical hyperintensities in DWI and proton density images with no enhancement after gadolinium [2].
In our Neurology Unit, where he was admitted 4 days after onset, neurological examination documented decreased alertness and attention, disorientation to place and time, poor speech production, and frequent paraphasic errors. Comprehension for simple requests was mildly altered. EEG activity was slow (4–5 Hz) and discontinuous, with occasional fronto-temporal delta pattern and interposed sharp-waves.
We observed alertness fluctuations and psychomotor agitation with akineto-rigid extrapyramidal signs and ataxia.
Over the following 10 days, he became more confused, agitated, with visual hallucinations and aggressive behaviour. We observed action tremor, speech worsening, generalised myoclonic jerks with sub-continuous clonic movement of the right arm. We started sodium valproate, titrated to 800 mg × 2/days with subsequent improvement of both paroxysmal movements and EEG.
Autoantibodies (ANA, ENA, dsDNA, ANCA, LLAC, aPL), virological/bacteriological screening and paraneoplastic antibodies (Yo, Hu, Ri, CV2) were negative as well as an in-depth cancer screening.
Alertness and speech kept worsening with persistence of visual hallucinations, aggressive behaviour and myoclonic jerks. He had a second generalised tonic-clonic seizure.
In the hypothesis of a Creutzfeldt–Jakob disease with acute onset, we performed a second lumbar puncture with a search for 14.3.3 Protein, which was absent. CSF was normal.
Ten days after admission to our department, we discovered a high titre of anti-thyroglobulin antibodies (465 UI/m) with normal thyroid hormones, TSH and anti-TPO antibodies. A diagnosis of thyroiditis was made at thyroid echography. In the hypothesis of Hashimoto euthyroid thyroiditis, treatment with i.v. methylprednisolone 1 g once a day was given for 3 days followed by an oral taper. A progressive clinical improvement was observed over the following 3 days. A positron emission tomography showed a diffusely reduced cerebral metabolism, particularly evident in the left frontal lobe as reported in HE cases [3].
When discharged, 15 days later after steroid treatment, the patient was confused no more and had a normal behaviour; he was independent in self-care and aphasia was improving, though with residual verbal fluency impairment. EEG and MRI also showed mild improvement (Fig. 2).
In conclusion, we report a new case of a patient with acute onset of a rapidly progressive euthyroid SREAT mimicking Creutzfeldt–Jakob disease [4, 5].
Discussion
Encephalopathy with positivity of anti-thyroid antibodies was originally described by Brain et al. [6], though without a good response to steroid therapy. Recently (2004), Ghika-Schmid et al. [7], reported two cases of Hashimoto thyroiditis with high titres of anti-thyroglobulin antibodies and clinical features similar to our patient. Both patients did not respond to anticonvulsant medication, but exhibited rapid neurological improvement following steroid treatment. EEG delta activity was paradoxically increased by anticonvulsant treatment, as we observed in our patient who had an increased susceptibility to Diazepam.
HE typically affects patients when they are euthyroid and in an appropriate clinical situation; anti-thyroid autoantibodies are the main indicators of the encephalopathy [8]. Two types of initial clinical presentation were differentiated: (1) a vasculitis type with stroke-like episodes and mild cognitive impairment and (2) a diffuse progressive type with dementia, seizures, psychotic episodes, or altered consciousness. These types may overlap, particularly over the long-term course in untreated patients. The EEG was abnormal in 90% of cases; it showed unspecific changes and the condition was steroid-responsive [7]. The MRI white-matter subcortical hyperintense lesion in long-TR-weighed sequences observed in our patient are in accordance with previously reported diffuse white-matter signal abnormalities [1, 9]. Though status epilepticus (SE) can be responsible for the presence of MRI cortical hyperintensities, we excluded this hypothesis because EEG never indicated SE and because MRI abnormalities in our patient were both cortical and subcortical.
At present, it is still not clear whether anti-thyroid antibodies are an immune epiphenomenon in some patients with encephalopathic processes or whether they are really implicated in the pathogenic mechanisms of the disorder [10]. In our opinion, the responsiveness of this syndrome to steroids supports the hypothesis that this disorder involves immune pathogenic mechanisms, as previous reviews reported [1].
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Conflict of interest
The authors declare no conflicts of interest or commercial relationships including Grants, honoraria, speaker’s lists, significant ownership, and/or support from pharmaceutical or other companies such as manufactures of equipment, diagnostic or other laboratories whose products are directly or indirectly involved or affected by the article.
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D. Santoro and I. Colombo equally contributed to the manuscript.
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Santoro, D., Colombo, I., Ghione, I. et al. Steroid-responsive Hashimoto encephalopathy mimicking Creutzfeldt–Jakob disease. Neurol Sci 32, 719–722 (2011). https://doi.org/10.1007/s10072-011-0610-8
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DOI: https://doi.org/10.1007/s10072-011-0610-8