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Q1: What is the most likely diagnosis?
The combination of delirium, intermittent neurological symptoms, high CSF protein, normal MRI, positive antithyroid antibodies, and reversibility of symptoms with steroids is highly suggestive of Hashimoto's encephalopathy. The differential diagnosis of delirium with a normal MRI includes systemic infection, viral or other infective causes of encephalitis, metabolic disturbance (including hypothyroidism and hyperthyroidism), drug intoxication or withdrawal, or non-convulsive status epilepticus (or postictal or interictal confusion). Rarely, autoimmune disorders such as systemic lupus erythematosus or primary central nervous system vasculitis, and primary CNS tumours such as intravascular lymphoma, may present with a normal MRI.
Q2: Name four other ways in which this disease can present.
The manifestations of Hashimoto's encephalopathy are protean, encompassing virtually any neurological symptom. In a recent survey of reported cases,1 the frequency of symptoms was as follows: epileptic seizures 63%, reduced consciousness 54%, dementia 52%, psychosis 48%, personality change 39%, myoclonus 33%, ataxia 28%, pyramidal signs 28%, stroke-like episodes 26%, hallucinations 19%, extrapyramidal movement disorder 7%, dysarthria 7%.
Q3: What is the likely prognosis?
This has not been definitively studied. Many cases either respond dramatically to steroids or resolve spontaneously. Untreated, the condition can develop into a severe dementia with neurological features. A recent report1 describes seven cases that were initially diagnosed as Creutzfeldt-Jakob disease but subsequently improved or resolved after corticosteroid treatment.
Brain et al first observed the association between encephalopathy and autoimmune thyroid disease in 1966.2 After a report of two cases,3 and the first case series,4 the condition was increasingly recognised in the last decade.1 The mean age of onset is 41 years (range 14 to 78), with a female to male preponderance of 5.6:1. The hallmarks of the condition are:
An encephalopathy presenting as delirium or dementia, usually with neurological signs or seizures as listed above.
Raised serum titres of thyroid microsomal or thyroglobulin antibody, usually in clinically euthyroid patients, but hypothyroid and hyperthyroid cases are reported.
Usually steroid responsive, often dramatically so.
Depression and anxiety are common early symptoms, but psychosis and personality change can also be presenting features. Brain imaging is usually normal although MRI can show high signal lesions on T2 weighted images in the subcortical white matter.5Cerebrospinal fluid protein is raised in 65% of cases and 15% have a CSF pleocytosis (maximum 169 leucocytes/mm3). Thyroid autoantibodies must be raised to make the diagnosis, although it must be remembered that these are raised in 3–4% of the population. Some investigators also suggest ultrasonography of the thyroid to detect a hypoechoic pattern.5 Clearly, with such a wide variety of presentations and no definitive tests the diagnosis must be made with caution, perhaps only after a careful trial of steroids. Spontaneous remissions and other causes of steroid responsive encephalopathy should be taken into account.
The pathogenesis is unknown. Most investigators1-3 assume the presence of a cross reacting antigen in the central nervous system, perhaps producing an immune complex mediated vasculitis. Corticosteroids are the treatment of choice. Prednisolone doses of over 60 mg are usually used, although intravenous methylprednisolone and immunosuppressants such as azathioprine and methotrexate have also been employed successfully.
Hashimoto's encephalopathy is not yet widely known, and may be an underdiagnosed cause of acute confusion in the general medical ward. Given its protean manifestations and reversibility with treatment, a low threshold of suspicion is important. Thyroid autoantibodies should always be checked in cases of confusion where the diagnosis is not clear.
Hashimoto's encephalopathy is an increasingly recognised cause of a wide variety of potentially serious neurological symptoms that usually respond dramatically to steroids.
Patients are mostly clinically euthyroid in the presence of high titres of serum thyroid autoantibody.
MRI of the head is usually normal but CSF protein is often raised. There is sometimes a CSF pleocytosis
Caution must be exercised in keeping a low threshold for the diagnosis but also in not overdiagnosing the condition
Always check serum thyroid autoantibodies in patients with undiagnosed delirium.
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