Sudden-onset Encephalopathy: Do not ignore the Possibility of Hashimoto's Encephalopathy
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/0028-3886.289015
Source of Support: None, Conflict of Interest: None
Keywords: Autoimmune, Hashimoto encephalopathy, hypothyroidism
Hashimoto's encephalopathy (HE) is a complex disorder that is characterized by a heterogeneous clinical clustering of seizures, stroke-like episodes, cognitive and behavioral changes, and neurological features such as myoclonus. A diagnosis is usually made by having a high index of suspicion for the disorder, considering other causes of encephalopathy and detecting high titres of antithyroid antibodies. HE is a rare disease with an estimated prevalence of 2 per 100,000 people. Approximately more than 100 scientific articles on Hashimoto's encephalopathy have been reported and published between 2000 and 2013. Steroids remain the first-line treatment for this condition after the exploration of effective therapies. We report a case of HE, who presented acute generalized tonic-clonic seizure (GTCs) and delirium and who had been diagnosed as HE and treated with steroid, further showing remarkable recovery.
We report a case of a 51-year-old man diagnosed with Hashimoto's encephalopathy, who presented with one episode of GTCs followed by disorientation and agitation. He was healthy in the past and had worked as a chef in a private house. According to his employer, he was perfectly well earlier. On admission, he was severely agitated and disoriented, and was unable to follow commands. His vital signs were stable except body temperature of 38°C; he was moving all four limbs equally, with + 3 deep tendon reflexes, and flexor planters bilaterally. There were no signs of meningeal irritation found. Complete blood count, serum electrolyte, blood urea nitrogen, creatinine, and liver function tests were all normal. His EEG showed generalized slowing, CT scan, and MRI brain were unremarkable and cerebrospinal fluid (CSF) showed protein of 126 (21–41), with normal cell count and negative HSV PCR. TSH was performed as a routine test which came out to be very high 33.23 (0.35–4.94). Repeat TSH test was also high, fT4 was low 0.63 (0.70–1.48 while fT3 was normal 1.84 (1.71–3.71). Antithyroid antibodies titres were significantly high, including antithyroid peroxidase (anti-TPO) level of 83.0 (<5.6) and antithyroglobulin (ATA) level 26 (<4.11). The patient was initially treated with acyclovir but showed no improvement. After all the investigation results were reported, the diagnosis of HE was established. The patient was started on high dose intravenous steroid with remarkable improvement. Steroids were tapered off gradually and later he was started on levothyroxine.
Hashimoto's encephalopathy is a term used to describe an encephalopathy of presumed autoimmune origin characterized by high titres of antithyroid peroxidase antibodies. It was initially described in 1966. Since HE is a treatable disorder, it should be considered in cases of unexplained encephalopathy. Our patient showed hypothyroidism; however, previous studies revealed cases presented with euthyroidism or even hyperthyroidism., Therefore, normal or slightly abnormal thyroid function tests (TFTs) do not exclude the diagnosis.
The clinical presentation may involve a relapsing and remitting course and include seizures, stroke-like episodes, cognitive decline, neuropsychiatric symptoms, and myoclonus. Systemic symptoms such as malaise, myalgia, and fatigue can occur in Hashimoto's encephalopathy, although, fever is rarely described. The mean age of symptoms' onset ranges from 45 to 55 years. The condition is more frequently found in females than in males, with a ratio of ~ 5:1.,
Thyroid function is usually clinically and biochemically normal. Diagnosis is made in the first instance by excluding other toxic, metabolic, and infectious causes of encephalopathy with neuroimaging and CSF examination. Neuroimaging findings are often not helpful in clarifying the diagnosis. Although most of the described cases showed neural symptoms for months before the acute onset, in this case, we acknowledged a dramatic acute onset. Thus, neurologic complications can begin either abruptly, in the form of seizures or agitation, with or without other neurologic complaints, or they can develop gradually, in a relapsing-remitting manner, including, among others, cognitive deterioration and psychiatric illness.
Most cases of Hashimoto's encephalopathy are either clinically euthyroid or subclinically (low thyroid hormone levels without clinical signs) hypothyroid (>60%). CSF is usually examined in cases of encephalopathy. In Hashimoto's encephalopathy, elevated CSF protein was found in 80% of cases., Initially thought to be a diagnostic marker for Creutzfeldt-Jakob disease (CJD), 14-3-3 protein is now known to be a nonspecific marker of diffuse neuronal injury., Elevated 14-3-3 has been reported in a few patients with Hashimoto's encephalopathy and is not of specific diagnostic significance. EEG findings are nonspecific. The most frequently reported abnormalities are slow-wave abnormalities associated with any encephalopathic process. Although abnormalities in computed tomography (CT) scans of the brain have been reported in as many as 50% of cases  findings are generally nonspecific. Initially, both CNS and systemic causes of encephalopathy need to be considered. Systemic disorders such as sepsis, hepatic failure, and renal failure may produce an encephalopathic picture but can be readily excluded on clinical grounds and routine investigations. Infectious CNS causes such as meningitis or encephalitis can be excluded by appropriate CSF analysis; the vascular and neoplastic disease is usually detected with structural or functional neuroimaging techniques; seizure disorders can usually be excluded by single EEG or prolonged EEG monitoring; thyroid hormone studies are not helpful but may identify subclinical thyroid dysfunction. Detection of antithyroid (anti-TPO) antibodies further confirms the diagnosis. Despite the link to autoimmune thyroid disease, the etiology of Hashimoto's encephalopathy is unknown. It is likely that antithyroid antibodies are not pathogenic but titres can be a marker of treatment response. Pathological findings can suggest an inflammatory process but features of a severe vasculitis are often absent. The links between the clinical pictures, thyroid disease, auto-antibody pattern, and brain pathology await further clarification through research. It may be that Hashimoto's encephalopathy will be subsumed into a group of nonvasculitic autoimmune inflammatory meningoencephalopathies. This group may include disorders such as limbic encephalitis associated with voltage-gated potassium channel antibodies. Some authors have suggested abandoning any link to Hashimoto and renaming the condition as “steroid-responsive encephalopathy associated with autoimmune thyroiditis” to better reflect current, if limited, understanding of this condition.
HE is a rare but very serious illness. The incidence is probably underestimated because of the low overall awareness about the disease. [11,12]
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