TOPIC: Hashimoto’s encephalopathy
Title: Hashimoto's encephalopathy: epidemiology, pathogenesis and management
Reference: CNS Drugs 21: 799-811, 2007
Hashimoto's encephalopathy is a term used to describe an encephalopathy of presumed autoimmune origin characterised by high titres of antithyroid peroxidase antibodies. In a similar fashion to autoimmune thyroid disease, Hashimoto's encephalopathy is more common in women than in men. It has been reported in paediatric, adult and elderly populations throughout the world.
Clinical presentation & Diagnosis
The clinical presentation may involve a relapsing and remitting course and include seizures, stroke-like episodes, cognitive decline, neuro-psychiatric symptoms and myoclonus. Thyroid function is usually clinically and biochemically normal. Hashimoto's encephalopathy appears to be a rare disorder, but, as it is responsive to treatment with corticosteroids, it must be considered in cases of 'investigation negative encephalopathies'. Diagnosis is made in the first instance by excluding other toxic, metabolic and infectious causes of encephalopathy with neuro-imaging and CSF examination. Neuro-imaging findings are often not helpful in clarifying the diagnosis. Common differential diagnoses when these conditions are excluded are Creutzfeldt-Jakob disease, rapidly progressive dementias, and paraneoplastic and non-paraneoplastic limbic encephalitis. In the context of the typical clinical picture, high titers of thyroid autoantibodies, in particular thyroperoxidase antibodies, are diagnostic. These antibodies, however, can be detected in elevated titres in the healthy general population.
Treatment with corticosteroids is almost always successful, although relapse may occur if this treatment is ceased abruptly. Other forms of immuno-modulation, such as intravenous immunoglobulin and plasma exchange, may also be effective.
Despite the link to autoimmune thyroid disease, the aetiology 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 meningo-encephalopathies. 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 'steroid responsive encephalopathy associated with autoimmune thyroiditis' to better reflect current, if limited, understanding of this condition.
The report does not describe anything new, but provides an excellent summary of this fascinating and serious encephalopathy associated with Hashimoto’s thyroiditis, that responds dramatically to steroids once it is recognized. Although the condition has been known for a decade, it has only recently gained (rather grudgingly) general agreement in the endocrine community that something exists.
The etiology remains obscure. One view is that anti-TPO antibodies may only be markers, but these antibodies are reported to bind to astrocytes. Anti-TPO antibodies from patients with Hashimoto's encephalopathy bind to cerebellar astrocytes. Another hypothesis is that the illness is caused by antibodies developed during Hashimoto’s thyroiditis which crossreact with antigens in the CNS. Several possible target antigens recognized by Hashimoto’s IgG have been recognized, including dimethylargininase-I on endothelial cells, & aldehyde reductase-I, widely distributed on neurons & endothelia ( Gini B et al., Journal of Neuroimmunology, 2008), and alpha-enolase ( Yoneda M et al., Journal of Neuroimmunology, 2007).
Several different clinical presentations have been documented recently, such as acute psychosis, hallucinations, focal seizures, dementia, and several cases in children. While occasional patients enter remission spontaneously, most respond to steroids. The use of IgG (intravenous), plasmapheresis , and thyroidectomy to reduce antigen exposure, have also been employed ( Yuceyar N et al.: Thyrotoxic autoimmune encephalopathy in a female patient: only partial response to typical immunosuppressant treatment and remission after thyroidectomy. Clin Neurol Neurosurg. 109: 458-462, 2007).
This commentary is not meant to provide an exhaustive review of the condition, but rather to interest readers to the problem, its many manifestations, and the need for further research on the pathogenesis.
Summary and commentary prepared by Leslie DeGroot (Related to Chapter 8 of TDM)