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J Neurol Neurosurg Psychiatry 68:102-103 doi:10.1136/jnnp.68.1.102
  • Letters to the editor

Hashimoto's encephalopathy presenting as “myxoedematous madness”

  1. P GARRARD,
  2. J R HODGES
  1. University of Cambridge Neurology unit, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
  2. University of Cambridge Department of Psychiatry, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
  3. MRC Cognition and Brain Sciences Unit, 15 Chaucer Road, Cambridge CB2 2EF, UK
  4. Department of Nuclear Medicine, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
  1. Dr P Garrard, University of Cambridge Neurology Unit, Box 165, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK email garrard{at}cnbc.cmu.edu
  1. P J DE VRIES,
  2. N HUNT
  1. University of Cambridge Neurology unit, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
  2. University of Cambridge Department of Psychiatry, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
  3. MRC Cognition and Brain Sciences Unit, 15 Chaucer Road, Cambridge CB2 2EF, UK
  4. Department of Nuclear Medicine, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
  1. Dr P Garrard, University of Cambridge Neurology Unit, Box 165, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK email garrard{at}cnbc.cmu.edu
  1. A CRAWFORD,
  2. J R HODGES
  1. University of Cambridge Neurology unit, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
  2. University of Cambridge Department of Psychiatry, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
  3. MRC Cognition and Brain Sciences Unit, 15 Chaucer Road, Cambridge CB2 2EF, UK
  4. Department of Nuclear Medicine, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
  1. Dr P Garrard, University of Cambridge Neurology Unit, Box 165, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK email garrard{at}cnbc.cmu.edu
  1. K BALAN
  1. University of Cambridge Neurology unit, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
  2. University of Cambridge Department of Psychiatry, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
  3. MRC Cognition and Brain Sciences Unit, 15 Chaucer Road, Cambridge CB2 2EF, UK
  4. Department of Nuclear Medicine, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK
  1. Dr P Garrard, University of Cambridge Neurology Unit, Box 165, Addenbrooke's Hospital, Cambridge CB2 2QQ, UK email garrard{at}cnbc.cmu.edu

    The neuropsychiatric sequelae of hypothyroidism range from lethargy and mental slowing to the florid psychotic illness referred to as “myxoedematous madness”. The last condition is characterised by frank hypothyroidism accompanied by psychosis, and may respond completely to thyroxine.1 More recently described is a syndrome of subacute encephalopathy, associated with high titres of thyroid autoantibodies, raised CSF protein, EEG abnormalities, and perfusion deficits in the presence of normal structural neuroimaging.2-4 In most cases, the encephalopathy occurs without any gross change in circulating concentrations of thyroid hormones, suggesting that an inflammatory process is responsible for the cerebral dysfunction. In the absence of pathological data, the evidence for a specific pathogenetic mechanism is largely circumstantial: a small vessel vasculitis and immune complex deposition have both been suggested.3 4

    Although none of the published cases of Hashimoto's encephalopathy has described psychosis as a primary feature, it is possible that “myxoedematous madness”, a condition first described in detail by Asher in 19491 lies in a range of encephalopathic phenomena mediated by autoimmune mechanisms. This suggestion would certainly be consistent with the range of clinical presentations of other autoimmune cerebral vasculitides.5 As autoimmune thyroiditis is the commonest cause of thyroid failure in this country,6 it is likely to have been present in at least some of Asher's original 14 cases. Although most had florid myxoedematous features at psychiatric presentation, this may simply reflect the difficulty of diagnosing subclinical thyroid disease before rapid laboratory assays became widely available. Many features of the present case, however, favoured an endocrine rather than an inflammatory mechanism, suggesting that the condition of “myxoedematous madness”, though rare, remains a valid diagnostic entity.

    A 63 year old market stallholder without medical or psychiatric history was brought to a local psychiatric hospital by the police. His business had been in decline for several months, and his family had noticed uncharacteristic emotional lability. In the weeks preceding admission he had experienced delusions and hallucinations, and exhibited uncharacteristic behaviour. He had reported a vision of the crucifixion, and hearing the voice of his dead mother. He claimed that his house was occupied by the devil, drove around aimlessly in his car, and appeared constantly fearful and withdrawn. On the day of admission he had made a bonfire in the garden and burned his wife's clothes, family photographs, furniture, and business papers. When his wife and son tried to intervene he became aggressive and threatened them with a saw. The general practitioner was called and suspected either an acute psychosis or a severe depressive illness. Police assistance was requested because of the patient's continuing violent behaviour.

    On admission he was unkempt but cooperative and apparently euthymic. He denied depression, but displayed no insight into the irregularity of his behaviour. No psychotic features were seen, although during the admission he consistently rationalised all reported psychotic phenomena. He was aggressive towards staff and made repeated attempts to abscond. General physical examination was unremarkable. Neurological examination was normal except for spoken language, which was fluent and grammatical, but contained word finding pauses, circumlocutions, and occasional semantic errors (for example, “I just want to get my feet back on the table”). Formal neuropsychological testing, and a screen of laboratory tests for reversible causes of encephalopathy, were performed on admission, and results are presented below (column A). Attention is drawn to his mild naming deficit, and poor performance on the Rey figure, which was due to planning rather than visuospatial errors, suggesting a predominantly “dysexecutive” pattern. CT and EEG were both normal, and SPECT disclosed widespread but mild cortical hypoperfusion. Trifluoperazine (2 mg twice daily) was started on admission, and thyroxine (75 μg once daily) added 1 week later. His mental state and behaviour stabilised, leading to discharge after 2 months.

    At 6 month follow up the patient had stopped neuroleptic drugs, but continued taking thyroxine. He reported feeling “back to normal”, had bought a new house, and was working as a part time shop assistant. He still had subtle word finding difficulties, and was referred to the regional memory clinic for further evaluation, which took place 6 months later. Behavioural assessment showed persisting deficits in delayed recall of verbal material, verbal fluency, and visuospatial function. Formal psychometric testing, blood tests, and SPECT were repeated, 1 year after the original examinations. Laboratory and neuropsychological results are presented in the table. It is of note that, whereas his naming ability had improved, performance on frontal executive tasks remained impaired. The appearance of the follow up SPECT differed minimally, if at all, from the first examination.

    In summary, therefore, this patient presented in clear consciousness with a first episode of acute psychosis, and evidence of subtle executive and linguistic neuropsychological disturbance, on the background of gradual behavioural and affective change. He was profoundly hypothyroid due to an autoimmune thyroiditis, but there was no clinical evidence of thyroid failure other than the abnormal mental state. The psychiatric component of his illness recovered fully, and the antithyroid microsomal antibody titre fell markedly after thyroxine replacement, although his mild neuropsychological deficits remained unchanged. Corticosteroids were not used at any stage.

    The response to thyroxine does not, in itself, imply that the cerebral illness had an endocrine origin; a recent report described a patient with a subacute encephalopathic illness and compensated hypothyroidism in the presence of increased antimicrosomal antibodies, all of which responded to thyroxine replacement alone.4 In that case, however, both EEG and SPECT were abnormal, the SPECT showing multiple areas of severely reduced perfusion, which normalised with treatment. By contrast, in the present case the EEG was normal and the SPECT abnormality was marginal and changed little, if at all, with treatment. The evidence for a significant vasculitic component to the illness is, therefore, unconvincing.

    The mild and relatively circumscribed neuropsychological deficits coupled with florid psychotic phenomena, also contrast with the profound global disturbance of cognition usually associated with Hashimoto's encephalopathy.3 This distinction suggests that microvascular disruption and thyroid hormone depletion may emphasise different aspects of the clinical range in Hashimoto's encephalopathy. Although the present case would support Asher's conclusion that the psychiatric features of Hashimoto's encephalitis typically respond to thyroid replacement, it additionally suggests that subtle neuropsychological deficits may be apparent even in the absence of obvious cerebral perfusion deficits, and that these may not be fully reversible.

    References

    Table 1

    Laboratory and neuropsychological results at presentation (A) and at 12 month follow up (B)

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