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Hashimoto's encephalopathy: myth or reality? An endocrinologist's perspective

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Since the first description of a case of episodic encephalopathy associated with Hashimoto's thyroiditis in 1966, many cases of corticosteroid-responsive encephalopathy associated with positive antithyroid antibodies, clinical Hashimoto's thyroiditis, or spontaneous autoimmune thyroid failure have been reported. These patients have neurologic manifestations of encephalopathy unrelated to other known causes. The condition has thus been termed ‘Hashimoto's encephalopathy’. The literature shows no proven association between thyroid disease and the neurologic process. Although the association of a common endocrinologic condition and a rare neurologic disease may occur by chance, this type of encephalopathy probably has an autoimmune nature and thus is more likely to occur in the background of another autoimmune condition such as autoimmune thyroid disease. Until the pathogenesis of these coincident conditions is better defined, the term ‘corticosteroid-responsive encephalopathy associated with autoimmune thyroiditis' is more accurate and descriptive than Hashimoto's encephalopathy. Advances in the field may clarify this seemingly inconsistent terminology.

Section snippets

Neurologic features

Most reported cases occurred in girls and women (72%). The female-to-male ratio is almost the same as that for Hashimoto's thyroiditis.4 Hashimoto's encephalopathy follows the age and sex distributions of autoimmune thyroid disease5 and occurs in adults5 as well as in children.18, 19, 20, 21

Clinical manifestations are those of fluctuating encephalopathy. Cognitive impairment22, 23, 24, 25, 26 and behavioral changes2, 27 are common. A focal or generalized seizure disorder is also a

Response to immune modulation

This issue is confounded by the fact that, by definition, the condition of almost all the reported patients improved with high-dose corticosteroid therapy, and patients who were non-responsive have been excluded in most case reports and reports of larger series5 (Castillo PR, Woodruff BK, Boeve BF, et al, unpublished data, 2004). Both high doses of oral prednisone and shorter courses of intravenous methylprednisolone have been used.65 Other forms of corticosteroid-sparing immunomodulation—such

Differential diagnosis

Before the diagnosis of Hashimoto's encephalopathy can be made, all other causes of encephalopathy must be excluded. CSF examination, including bacteriologic and virologic evaluations, is necessary. Metabolic and toxic causes of encephalopathy should also be excluded. In patients with overt hypothyroidism, psychological and behavioral abnormalities and neurologic findings may be present that respond to normalization of thyroid function.

Hashimoto's encephalopathy and Creutzfeldt–Jakob disease

Hashimoto's encephalopathy: A Real Clinical Entity but the Wrong Terminology?

There is no question that a syndrome of autoimmune corticosteroid-responsive encephalopathy associated with positive antithyroid antibodies or mild thyroid failure exists. Reported cases of antibrain antibodies71 and pathologic findings identified in brain biopsy and autopsy specimens also suggest an autoimmune source. The presence of antithyroid antibodies in CSF has raised the possibility of intrathecal synthesis of these antibodies.73, 74 However, no evidence, so far, shows that thyroid

The role of the neurologist

Identification of steroid-responsive encephalopathy is a neurologic diagnosis, which should be reached after exclusion of other known causes of encephalopathy.2, 4, 5 The neurologist considers and rules out systemic connective tissue and autoimmune conditions such as lupus erythematosus95, known vasculitis, and Sjögren's syndrome47 that may have CNS involvement. Thyroid function and thyroid antibodies are analyzed, along with other markers of autoimmunity, and if the results are positive, the

The role of the endocrinologist

Endocrinologists are less likely to see typical cases of autoimmune encephalopathy in their practices. Encephalopathy associated with thyroid autoimmunity occurs in patients who have either asymptomatic subclinical hypothyroidism or isolated positive antithyroid antibodies or who are euthyroid and receiving thyroxine therapy. With increasing recognition of autoimmune encephalopathy, and in particular patients with associated thyroid autoimmunity, it is expected that more cases will be

Summary

Since the original description of a patient with hypothyroidism and multiple episodes of reversible stroke-like events and seizure, neurologists have sought evidence of thyroid dysfunction and autoimmunity in patients who have had encephalopathy of uncertain etiology, after exclusion of infectious and other inflammatory encephalopathies. Then, if the patient has positive antithyroid antibodies or mild or treated thyroid failure, the patient is treated with corticosteroids. If the response is

References (101)

  • T. Oide et al.

    Anti-neuronal autoantibody in Hashimoto's encephalopathy: neuropathological, immunohistochemical, and biochemical analysis of two patients

    J Neurol Sci

    (2004)
  • F. Ferracci et al.

    Hashimoto's encephalopathy: epidemiologic data and pathogenetic considerations

    J Neurol Sci

    (2004)
  • P. Saravanan et al.

    Thyroid autoantibodies

    Endocrinol Metab Clin North Am

    (2001)
  • S.G. Ellis et al.

    Central nervous system involvement in systemic lupus erythematosus: a review of neuropathologic findings in 57 cases, 1955–1977

    Semin Arthritis Rheum

    (1979)
  • L. Brain et al.

    Hashimoto's disease and encephalopathy

    Lancet

    (1966)
  • J.Y. Chong et al.

    Hashimoto encephalopathy: syndrome or myth?

    Arch Neurol

    (2003)
  • G.S. Sunil et al.

    Hashimoto's encephalitis

    J Clin Endocrinol Metab

    (2001)
  • A. Chaudhuri et al.

    The clinical spectrum, diagnosis, pathogenesis and treatment of Hashimoto's encephalopathy (recurrent acute disseminated encephalomyelitis)

    Curr Med Chem

    (2003)
  • A.M. Sawka et al.

    Rarity of encephalopathy associated with autoimmune thyroiditis: a case series from Mayo Clinic from 1950 to 1996

    Thyroid

    (2002)
  • G. Zettinig et al.

    Increased prevalence of subclinical brain perfusion abnormalities in patients with autoimmune thyroiditis: evidence of Hashimoto's encephalitis?

    Clin Endocrinol (Oxf)

    (2003)
  • W. Gawron et al.

    Electrophysiological tests of the hearing organ in Hashimoto's disease

    J Pediatr Endocrinol Metab

    (2004)
  • K. Gucuyener et al.

    Tremor and myoclonus heralding Hashimoto's encephalopathy

    J Pediatr Endocrinol Metab

    (2000)
  • S. Fatemi et al.

    Encephalopathy associated with Hashimoto's thyroiditis: use of serum immunoglobulin G as a marker of disease activity

    Thyroid

    (2003)
  • F.H. Mahmud et al.

    Steroid-responsive encephalopathy associated with Hashimoto's thyroiditis in an adolescent with chronic hallucinations and depression: case report and review

    Pediatrics

    (2003)
  • H. Saito et al.

    A case of Hashimoto's encephalopathy associated with Graves' disease [Japanese]

    Rinsho Shinkeigaku

    (2002)
  • I. Kothbauer-Margreiter et al.

    Encephalopathy associated with Hashimoto thyroiditis: diagnosis and treatment

    J Neurol

    (1996)
  • A. Chaudhuri et al.

    Hashimoto's encephalopathy as a cause of steroid responsive symptomatic epilepsy in adults [abstract]

    Epilepsia

    (1999)
  • K.A. Josephs et al.

    Nonvasculitic autoimmune inflammatory meningoencephalitis

    Neuropathology

    (2004)
  • R.J. Caselli et al.

    Nonvasculitic autoimmune inflammatory meningoencephalitis (NAIM): a reversible form of encephalopathy

    Neurology

    (1999)
  • C.A. Sybesma et al.

    Hashimoto encephalopathy in a 12-year-old girl

    Eur J Pediatr

    (1999)
  • N. Watemberg et al.

    Encephalopathy as the presenting symptom of Hashimoto's thyroiditis

    J Child Neurol

    (2000)
  • B. v Maydell et al.

    Hashimoto encephalopathy: is it underdiagnosed in pediatric patients?

    Neuropediatrics

    (2002)
  • C.M. Forchetti et al.

    Autoimmune thyroiditis and a rapidly progressive dementia: global hypoperfusion on SPECT scanning suggests a possible mechanism

    Neurology

    (1997)
  • S. Galluzzi et al.

    Hashimoto's encephalopathy in the elderly: relationship to cognitive impairment

    J Geriatr Psychiatry Neurol

    (2002)
  • Y. Hatano et al.

    A patient with Hashimoto's encephalopathy showing subacute global cognitive dysfunction [Japanese]

    Rinsho Shinkeigaku

    (2003)
  • A.F. Leentjens et al.

    Persistent cognitive defects after corrected hypothyroidism

    Psychopathology

    (1995)
  • M. Seipelt et al.

    Hashimoto's encephalitis as a differential diagnosis of Creutzfeldt–Jakob disease

    J Neurol Neurosurg Psychiatry

    (1999)
  • J.S. Li Voon Chong et al.

    Recurrent encephalopathy and generalised seizures associated with relapses of thyrotoxicosis

    Int J Clin Pract

    (2000)
  • U. Isik et al.

    Recurrent encephalopathy and seizures in an adolescent girl

    Clin Pediatr (Phila)

    (2001)
  • J.C. Erickson et al.

    Palatal tremor and myorhythmia in Hashimoto's encephalopathy

    Neurology

    (2002)
  • G. Taurin et al.

    Choreic syndrome due to Hashimoto's encephalopathy

    Mov Disord

    (2002)
  • T.D. Fife et al.

    Central nystagmus associated with Hashimoto's encephalopathy [abstract]

    Ann Neurol

    (2003)
  • M.U. Manto

    Hashimoto's associated ataxia

    J Neurol Neurosurg Psychiatry

    (2002)
  • M. Selim et al.

    Ataxia associated with Hashimoto's disease: progressive non-familial adult onset cerebellar degeneration with autoimmune thyroiditis

    J Neurol Neurosurg Psychiatry

    (2001)
  • P.R. Castillo et al.

    Undetectable CSF hypocretin-1 in ‘Hashimoto's encephalopathy’ associated with coma

    Neurology

    (2004)
  • A. Ares Luque et al.

    Hashimoto's encephalopathy [Spanish]

    Neurologia

    (2002)
  • D.J. McCabe et al.

    Amnesic syndrome with bilateral mesial temporal lobe involvement in Hashimoto's encephalopathy

    Neurology

    (2000)
  • J. Stone et al.

    A case of reversible amnesia

    Postgrad Med J

    (2001)
  • T. Rekand et al.

    Hashimoto's encephalopathy: a treatable cause of mental impairment, stroke and seizures

    Eur J Neurol

    (2003)
  • L. Brusa et al.

    Hashimoto's encephalopathy presenting with musical hallucinosis

    J Neurol

    (2003)
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