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Encephalopathy associated with Hashimoto's disease was first reported by Brain et al in 1966.1 Hashimoto's encephalopathy is a steroid responsive relapsing disorder associated with Hashimoto's disease that often presents with stroke-like episodes, myoclonus, and cognitive impairment. Diagnostic testing usually shows a euthyroid state with increased thyroid autoantibodies, increased CSF protein, and EEG abnormalities.2 3 We present the first case of myelopathy associated with Hashimoto's disease, followed 2 months later by encephalopathy.
A 70 year old housewife was admitted to our hospital on 28 July 1997. Her leg had felt heavy for a month, and she was unable to walk for several days before admission due to weakness in the left leg. She had been diagnosed with Hashimoto's disease at the age of 57 and treated with thyroxin. On January 11 1988, she had developed dysesthesia and weakness in the left arm and leg. Brain CT, radiography of the cervical spine, and CSF findings were normal at this time. She gradually recovered after this. On 31 January 1997, she was experiencing weakness in her left leg, which gradually disappeared over 2 months.
On physical examination, the blood pressure was 114/62 mm Hg. She had marked scoliosis. Neurological examination indicated a decrease of pain and temperature sensations on the right side and decrease of position and vibration sensations on the left side of the body below the Th7 level. Her muscle strength was evaluated as 2/5 (grade) in the left lower limb and 3/5 in the right lower limb by manual muscle test. Extensor plantar response was present on the left. Routine haematological and blood chemistry findings were within the normal range except for a mild increase of glutamic oxaloacetic transaminase (46 U/l, normal range 10 to 27), glutamic pyruvic transaminase (45 U/l, normal range 5 to 33) and r-globulin (34%, normal range 9.0 to 18.3). The serum free triiodothyronine, 3.1 pg/ml (normal range 2.4 to 4.5), free thyroxine, 1.2 ng/dl (normal range 0.8 to 1.7), and thyroid stimulating hormone (TSH) concentrations, 4.84 μU/l (normal range 0.3 to 5.0), were normal. The antithyroglobulin antibody titre was 1/409600 and the antithyroid microsomal antibody titre was 1/102400. Serological tests for syphilis and HTLV-I were negative. Vitamin B12, folate, angiotensin converting enzyme, ANA, anti-ds-DNA, ENA complex, and antiphospholipid antibody were normal or negative. Concentrations of circulating immune complexes were raised in blood (3.9 μg/ml, 0 to 2.9). The CSF was under normal pressure and contained 3 lymphocytes/μl, glucose 59 mg/dl, and mildly raised protein concentration at 50 mg/dl. Oligoclonal bands and myelin basic protein were absent. IgG index was normal. Further immunological results showed the titre of antithyroid microsomal antibodies in the CSF to be 1/128 and the titre of antithyroglobulin antibodies in the CSF to be 1/1600. A thoracic spinal MRI examination and myelography showed normal findings. She was given 500 mg intravenous methylprednisolone for 3 days. A few days later she made a marked improvement in muscle strength in her feet.
On 10 August 1997 she developed an abrupt onset of somnolence and disorientation. She was afebrile. Subsequently her respiration became irregular with short apnoeic spells. Funduscopic examination was normal. She had spontaneous myoclonus in her right arm. Repeated CSF investigations showed a predominantly mononuclear pleocytosis (9 cells/μl) and raised protein concentration (74 mg/dl). An EEG showed diffuse slowing of background rhythm with sharp waves in anterotemporal regions. Assuming a meningoencephalitis of possible viral origin, acyclovir was administered intravenously for 10 days. Polymerase chain reaction (PCR) studies for herpes simplex virus and herpes zoster virus were negative. She was given 500 mg intravenous methylprednisolone for 3 days, then oral predonisolone. Her level of consciousness improved rapidly over the next several days. She was fully alert 7 days after initiation of steroid therapy. Steroid dosage was slowly tapered and maintained at 10 mg daily. She remained well for 18 months on steroid therapy. Cerebral MRI disclosed bilateral high signal areas in frontal deep white matter on T2 weighted images. These findings were similar to those seen before her encephalopathy. Repeat spine MRI on 5 September 1997 showed previously unrecognised high intensity area by the T2 weighted image, on the left side of the cord at the level of the fifth and sixth thoracic vertebrae (figure).
Our patient had Hashimoto's disease with a marked increase in antithyroid antibodies. Her thyroid function tests were normal on thyroxin replacement therapy. Diffusely abnormal EEG and high CSF protein were found at her confusional state. Her encephalopathy markedly responded to steroid therapy. Other aetiologies such as infectious, metabolic, toxic, neoplastic, vascular, and paraneoplastic causes had been excluded. These findings are consistent with previously described cases of Hashimoto's encephalopathy.
What is notable in our case is that the myelopathy developed 2 months before encephalopathy. Some diseases, including multiple sclerosis, scoliosis, and vascular accident, are known to cause myelopathy. The lack of typical findings of brain MRI and oligoclonal bands as well as myelin basic protein in CSF, and normal IgG index were not compatible with multiple sclerosis. Findings of myelography and spinal MRI suggested that myelopathy was not associated with scoliosis. Slow progression over a month and the distribution of sensorimotor disturbance were not compatible with vascular accident. We think that her myelopathy was also associated with Hashimoto's disease because she subsequently had encephalopathy and other conditions which could cause myelopathy were excluded. This is the first case of myelopathy associated with Hashimoto's disease.
The aetiology and the pathological basis of Hashimoto's encephalopathy are not known. Brain et al 1described localised cerebral oedema as a possible cause of Hashimoto's encephalopathy. This hypothesis may be supported by reversible MRI abnormalities4 and excellent response to steroid therapy.2 3 Ishii et al 5 postulated that a toxic effect of TRH on the CNS had an important role in Hashimoto's encephalopathy.
In our patient, antithyroid antibodies were detectable not only in serum but also in CSF. Shaw et al 2 reported that antithyroid antibodies were detectable in CSF from one of four patients with Hashimoto's encephalopathy. Marked higher titres of antithyroid antibodies in serum compared with those in CSF in our patient might suggest that antithyroid antibodies in CSF were mainly derived from serum.
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