Despite its eponym, Hashimoto's Encephalopathy (HE) [2] is only related to Hashimoto's Thyroiditis by the common presence of anti-thyroid antibodies. Clinical manifestations most often consist of an acute to sub-acute onset of confusion associated with an alteration of consciousness, seizure activity, or myoclonus, and may include hallucinations and delusions.
In reviewing the multitude of conditions that may lead to progressive mental status changes in an elderly patient, such conditions as metabolic derangements, autoimmune conditions, paraneoplastic encephalopathy, infection, psychiatric illness, and progressive neurologic conditions must be considered. HE distinguishes itself through its rapid deterioration in mental status, lack of specific electrolyte or radiographic abnormalities, and specific response to immunosuppressive and immunomodulating agents. Although prion-related encephalopathies, such as Creutzfeldt-Jakob Disease (CJD), are considered in the differential diagnosis of HE, the rapid decline in mental status seen in HE distinguishes it from CJD, which causes a slower decline in functional status, and ultimately results in death [3].
The exact etiology for this neurological state is not known. As elevated immunoglobulin levels are usually seen in this condition, an inflammatory state has been conjectured to be pathologically responsible [4]. Given this condition's similarities to non-vasculitic, autoimmune, inflammatory meningoencephalopathies, it has been suggested that this condition's name should be changed to "Steroid Responsive Encephalopathy Associated with Autoimmune Thyroiditis," in order to better characterize what we know about the pathophysiology of this condition [5]. Over the last 40 years, the diagnosis of this condition has been hindered by a lack of universally agreed upon diagnostic features. In response to this ambiguity, more clearly defined criteria have been delineated and include encephalopathy with neuropsychiatric features, seizure activity or focal neurologic deficits; presence of antithyroid antibodies; euthyroid status or mild hypothyroidism; no compelling evidence for a more likely etiology, and reversal of symptoms with steroid administration [6].
Laboratory evaluation is critical to making this diagnosis and will typically show an elevated serum level of anti-thyroperoxidase antibody or anti-thyroglobulin antibody. These antibodies, though frequently present, are not felt to be pathogenic, but simply a marker for an underlying disease, possibly an inflammatory meningoencephalopathy. Since cases of HE have been described in patients with a background metabolic milieu in the euthyroid, hyperthroid, and hypothyroid range, HE is felt not be related to thyroid disease. Cerebrospinal fluid analysis (CSF) is abnormal in approximately 80 percent of patients, usually revealing an elevated CSF protein levels. Other CSF findings include lymphocytic pleocytosis as well as the presence of oligoclonal bands and immune complexes [7, 8]. In the case of our patient, no such abnormalities were discerned. Nonspecific electroencephalographic (EEG) abnormalities are seen in 90 to 98 percent of patients with the most common finding being nonspecific slowing of background activity [9]. Again, in the case of our index patient, no diagnostic abnormalities were found. Magnetic resonance imaging in patients with Hashimoto's encephalopathy is usually normal. In some patients, particularly those with concomitant cerebral atrophy, T2 signal abnormalities of white matter are noted.
Recognizing that the acute confusional state seen in HE is not related to thyroid status and may exacerbate any mental status changes associated with severe hyperthyroidism or hypothyroidism, correction or near correction of thyroid function abnormalities is frequently required for the diagnosis of this condition. This condition must be considered separate from confusion related to thyroid disease since the addition of immunomodulating agents will be required for its specific treatment. Despite the fact that corticosteroids are widely accepted as the standard treatment for HE, there is no consensus on indications for usage or pharmacologic dosing [10]. There appears to be not consensus on the optimal dose or duration of steroid therapy. One approach advocates a dose of oral Prednisone ranging from 50 to 150 mg each day. Another approach recommends the use of high dose, intravenous Methylprednisone, although there are no studies comparing outcomes using the different administration and dosing strategies. In the case series described by Castillo et al., seventeen of twenty patients received a five-day course of Methylprednisolone 1 gram each day for five days followed by oral steroids in six of these patients. The three remaining patients received between ten to thirty days of oral Prednisone, ranging in doses from 60-100 mg. No difference was mentioned in outcomes, and eight of the total twenty patients (40%) followed, were able to discontinue steroid therapy without a relapse in symptoms [6].
In the case of patients who cannot tolerate corticosteroids or who do not respond to corticosteroids, agents such as Azathioprine and Cyclophosphamide have been employed. In other refractory cases, clinical improvement has been documented using either intravenous immunoglobulin or plasmapheresis [11].
