The term “Hashimoto encephalopathy” (HE) was used perhaps for the first time in 1991 by Shaw (1), who collected five cases with similar symptoms such as seizures, disorientation, frequent episodes of alternating hemiparesis, high protein levels in the cerebrospinal fluid and electrocardiographic abnormalities. However, these patients also had hypothyroidism and positive thyroid antibodies. However, in 1966, a case was described of a 63-year-old man who had seizures, disorientation, frequent episodes of alternating hemiparesis, high protein levels in the cerebrospinal fluid, electrocardiographic abnormalities and biopsy-confirmed Hashimoto thyroiditis (2) Because several cases were later published that showed a similar outcome but with entirely different clinical presentations, the question has been raised whether HE is a true syndrome. The same authors concluded that several patients presented with various signs of encephalopathy and high thyroid antibody levels together with the responsiveness to glucocorticoid therapy and that such convergence seems unlikely to result from chance (3). There also appears to be no evidence of any specific pathogenic role for thyroid antibodies in the origin of such encephalopathy, and several authors hypothesized that these antibodies are only markers of a possibly unrelated autoimmune disease affecting the brain. The term HE is now commonly used for the few hundred patients published so far, whereas some other terms such as “myxedema madness” (4), “encephalopathy associated to autoimmune thyroid disease” (5) or “steroid-responsive encephalopathy with antibodies to thyroperoxidase” (SREAT) (6) have been mostly abandoned.
HE is a relatively rare condition with a broad range of clinical presentation. Thus, there is a high risk that patients with this serious disease will be misdiagnosed and thus even mistreated, sometimes for a considerably long time. Because the finding of TPOab in blood is one of the most frequent signs accompanying HE, it is generally recommended as a powerful diagnostic tool in all cases of unexplained fluctuating encephalopathy. The most frequently observed signs include epilepsy-like seizures resistant to anticonvulsive treatment, confusion, headaches, hallucinations, stroke-like episodes, coma, impairment of cognitive function, behavioral and mood disturbance, focal neurological deficits, disturbance of consciousness, ataxia, and presenile dementia.
Although the majority of described cases showed neural symptoms for months before the acute onset, in some cases a dramatic acute onset appeared. A review of 30 patients revealed two types of clinical presentation, e.g., that with acute or insidious onset (21). In general, this view seems to be supported by an overview of several patients as summarized below. However, a third type of onset and clinical course of a variety of neurologic complications was recently defined as “relapsing-remitting manner including cognitive deterioration and psychiatric illness” (8).
HE appears in all age groups including children (22), and as much as approximately 70 to 80 percent of the patients are women and girls. It was repeatedly underlined that, especially in children, several cases of such encephalopathy remained unrecognized for a considerable time (8, 23, 24). However, in several cases, a clear thyroid disorder, mostly presenting as hypofunction, could provide useful streamlining diagnostic guidance in patients with various neuropsychiatric signs. Such signs usually continue after the thyroid treatment or even show a worsening that is generally considered to be one of the most important signs of HE, as the specific neuropsychiatric problems usually accompanying each thyroid disorder disappear after treatment with thyroxine.
Some useful reports have appeared regarding the frequency of individual symptoms and/or laboratory findings in patients with HE. Chong et al. (3) summarized 105 cases and concluded that in most cases, the diagnosis was based on the disturbed consciousness, negative finding of bacterial or viral infection in the cerebrospinal fluid, and high level of thyroid antibodies, with latter found in 100% of the cases, although the antibody level usually did not appear to be correlated with the severity of the illness. Moreover, a high protein level in the cerebrospinal fluid appeared in 78% of cases, abnormal electroencephalography in 98% and various mostly nonspecific abnormalities on magnetic resonance imaging in approximately 50%. Magnetic resonance revealed ischemic areas, multiple tumors, granulomas or various degenerative processes in 60% of the cases, and SPECT examinations showed decreased perfusion in the cortical areas or basal ganglia (25). From 1995 to 2003, 20 patients with Hashimoto encephalopathy were examined (26) and tremor was found in 16, transient aphasia in 16, myoclonus in 13, walking impairments in 13, seizures in 12 and sleeping disorders in 11 of them.
=== CSF Analysis
Cerebrospinal fluid analysis, electroencephalography, and neuroimaging studies do not show consistent findings to support the diagnosis. Physicians’ awareness of this complication is of great importance because most patients respond dramatically to corticosteroid therapy. Moreover, early recognition might also prevent a costly diagnostic work-up in patients with unexplained encephalopathy. In one patient, a follow-up for the IgG level in the CSF was found to be useful; after the IgG was found to be increased, the treatment was repeated with a partial clinical improvement and decline in the CSF level of IgG. Following high-dose steroid treatment, the patients’ clinical condition stabilized and a CSF analysis showed even further IgG decline (27). Thus far, approximately 150 cases have been published, although this disease probably remains under-diagnosed because it is not yet generally known and there were also presumably several additional cases that simply were not published at all. As clearly follows from the literature, an unusually wide variety of symptoms at presentation effectively obscures the basic pathogenetic process of HE. Because thyroid antibodies recently became considered as a useful marker for HE, it is recommended to check for their elevation not only in the blood but also in the CSF, particularly in cases presenting the triad of encephalopathy with EEG slowing and increased protein level in the CSF as well as in all unexplained cases with a variety of nonspecific neuropsychiatric symptoms, generalized or partial seizures, hallucinations, or status epilepticus.
The MRI manifestations of HE can vary from normal appearance, ischemic lesions, demyelination, and vasogenic edema to atrophy. The diverse MRI features of HE reported in the literature make it difficult to understand the pathological process and monitor the prognosis. To investigate the dynamic changes of MRI manifestations in HE, two cases of HE were retrospectively analyzed with a series of longitudinal MRI data. Although similar acute ischemic manifestations were observed at the onset of HE in both cases, at follow-up, we observed different evolutions of HE on MRI between the two cases, which might partially account for the diversity of MRI findings (for example, a certain stage of HE). The clinical and MRI findings at follow-up also indicated that early treatment contributed to the recovery of the lesions (28).
Once a firm HE diagnosis is made, corticosteroid treatment usually provides a dramatic recovery, but several adverse outcomes, relapses and temporary or permanent spontaneous remissions have also been reported. At the same time, the high effectiveness of corticoid treatment in nearly all HE patients strongly supports an common autoimmune origin. Even in the absence of diagnostic serological findings, clinical improvement with corticosteroids may be provide the only evidence of autoimmune encephalopathy (29). However, it is always necessary to consider the possible adverse effects of corticosteroid therapy (30). Additionally, a case of HE was described that improved only after intravenous immunoglobulin treatment (31).
International Journal of Endocrinology and Metabolism. 2012 December; 10(2): 506-514. , DOI: 10.5812/ijem.4174