Clinical manifestations, diagnostic criteria and therapy of Hashimoto's encephalopathy: Report of two cases

Abstract

Hashimoto's encephalopathy (HE) is a rare, still not well understood, autoimmune disease with neurological and psychiatric manifestations. and elevated titers of antithyroid antibodies in serum and cerebrospinal fluid (CSF) as a hallmark of the disease. Patients are mostly women. Current diagnostic criteria include corticosteroide responsiveness, but it is the case in only 50% of patients with HE. In steroid non-responders other immunomodulatory therapies or plasmapheresis could be applied. Disease course can be acute, subacute, chronic or relapsing-remitting. Two distinct forms emerged from the reported cases: a vasculitic type characterized by multiple relapsing-remitting stroke-like episodes and mild cognitive impairment and a diffuse progressive type characterized by dementia and psychiatric symptoms. Both forms may be accompanied by depressed level of consciousness (stupor or coma), tremor, seizures, or myoclonus. We present two patients with two distinct forms of HE who had different clinical manifestations and response to therapy.

Introduction

Since the first description of this encephalopathy by Brain et al. [1] 40 years ago, just about 100 cases have been reported [2]. HE is characterized by various neuropsychological symptoms, including cognition and/or consciousness deterioration, personality changes, seizures and myoclonus [3], [4], [5], [6], [7]. Recently, this entity has attracted growing attention because it is included in the group of treatable dementias [5], and [8], it has also been recognized as one of the most important items for differential diagnosis of Creuzfeldt–Jakob disease [9], [10], [11]. Although autoimmune mechanisms are thought to play a pathogenetic role in HE, the etiology of the disease is still incompletely understood. It is closely associated with Hashimoto's thyroiditis (HT) and is thought to be caused by disorders of immune mechanisms. Most recent reports argue in favor of an inflammatory response to antineuronal antibodies [12], [13].

Generally accepted diagnostic criteria are based on the presence of: cognitive impairment with or without neuropsychiatric symptoms; seizures; stroke-like events; focal neurological deficit or movement disorders; elevated antithyroid antibodies; and corticosteroid responsiveness [3]. Approximately 50% of HE cases have focal or diffuse non-enhancing brain magnetic resonance imaging (MRI) abnormalities and 50% respond to corticosteroid therapy.

On neurological examination, pyramidal tract signs without clear focal deficit are frequently found. Investigation of these patients characteristically shows diffuse electroencephalogram (EEG) abnormalities and high CSF protein levels without pleocytosis, although the most relevant issue is the high titre of antithyroid antibodies found in most cases [3]. Since there are no clinical, laboratory or neuroimaging findings that are specific for this entity, the exhaustive exclusion of infectious, metabolic, toxic, vascular, neoplastic and paraneoplastic causes of encephalopathy is mandatory.

We present two new cases with two distinct forms of HE: first with vasculitic or stroke-like type and second with diffuse progressive type.