Hashimoto Encephalopathy Syndrome Or Myth?
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NEUROLOGICAL REVIEW SECTION EDITOR: DAVID E. PLEASURE, MD Hashimoto Encephalopathy Syndrome or Myth? Ji Y. Chong, MD; Lewis P. Rowland, MD; Robert D. Utiger, MD Background: Hashimoto encephalopathy has been de- Data Synthesis: We identified 85 patients (69 women scribed as a syndrome of encephalopathy and high se- and 16 men; mean age, 44 years) with encephalopathy rum antithyroid antibody concentrations that is respon- and high serum antithyroid antibody concentrations. sive to glucocorticoid therapy, but these could be chance Among these patients, 23 (27%) had strokelike signs, associations. 56 (66%) had seizures, 32 (38%) had psychosis, 66 (78%) had a high cerebrospinal fluid protein concentra- Objective: To study a patient with Hashimoto encepha- tion, and 80 (98%) of 82 had abnormal electroencepha- lopathy and to review the literature to determine whether lographic findings. Thyroid function varied from overt Hashimoto encephalopathy is an identifiable syndrome. hypothyroidism to overt hyperthyroidism; the most common abnormality was subclinical hypothyroidism Data Sources and Extraction: We searched the (30 patients [35%]). Among patients treated with glu- MEDLINE database to June 2002 for “Hashimoto” or “au- cocorticoids, 66 (96%) improved. toimmune thyroiditis” and “encephalopathy” and exam- ined all identified articles and articles referenced therein, Conclusions: The combination of encephalopathy, including all languages. We included all patients with high serum antithyroid antibody concentrations, and noninfectious encephalopathy (clouding of conscious- responsiveness to glucocorticoid therapy seems unlikely ness and impaired cognitive function) and high serum to be due to chance. However, there is no evidence of a antithyroid antibody concentrations. We excluded pa- pathogenic role for the antibodies, which are probably tients if they did not meet these inclusion criteria or if markers of some other autoimmune disorder affecting their symptoms could be explained by another neuro- the brain. logic disorder. We recorded clinical features and the re- sults of imaging, electroencephalographic, thyroid func- tion, and cerebrospinal fluid studies. Arch Neurol. 2003;60:164-171 N 1966, Brain and coworkers1 cases of unexplained encephalopathy described a patient with “Hashi- should show whether we have described a moto’s disease and encephalo- syndrome or a coincidence.” pathy.” The patient was a 49-year- In the intervening 35 years, at least old man with hypothyroidism 105 patients have been reported as hav- Ibeing treated with levothyroxine. He had ing Hashimoto encephalopathy.1-57 The slowly progressive impairment of con- clinical findings have varied, and some cli- sciousness interspersed with episodes of nicians have proposed 2 subtypes of the confusion or coma, often preceded by agi- disorder—a vasculitic type, character- tation, hallucinations, tremor, and cogni- ized by multiple strokelike episodes, and tive loss. He also had recurrent strokelike a diffuse progressive type, characterized episodes involving different vascular beds. by dementia and psychiatric symp- Serum antithyroid microsomal and anti- toms.30 Both forms may be accompanied From the Department of thyroglobulin antibody concentrations were by stupor or coma, tremor, seizures, or my- Neurology, Columbia high, and he had histologically confirmed oclonus.30 University College of Hashimoto thyroiditis. Treatment with The etiology, pathogenesis, histo- Physicians and Surgeons, New York, NY (Drs Chong and prednisone and an anticoagulant for 3 pathologic characteristics, and range of Rowland); and the Department months was ineffective. Subsequently, his clinical features, however, are unclear. Fur- of Medicine, Brigham and neurologic symptoms remitted while he was thermore, the diagnosis, as described by Women’s Hospital, Boston, taking only levothyroxine. Brain et al1(p514) Brain et al,1 depends on the presence of a Mass (Dr Utiger). concluded, “Antibody studies in future high serum concentration of thyroid an- (REPRINTED) ARCH NEUROL / VOL 60, FEB 2003 WWW.ARCHNEUROL.COM 164 ©2003 American Medical Association. All rights reserved. Downloaded From: https://jamanetwork.com/ on 10/05/2021 tibodies, but whether either the antibodies or concomi- ings revealed no evidence of infection, demyelination, or tant thyroid dysfunction contributes to the pathogen- tumor; the only abnormality was small perivascular cuffs esis of the neurologic disorder is not known. Indeed, the of lymphocytic cells. No perivascular demyelination was existence of the disorder itself has been questioned58 be- seen, and axonal staining was normal. cause of the high frequency of high serum antithyroid With glucocorticoid therapy, she gradually im- antibody concentrations in asymptomatic people and be- proved; 15 months later, while taking prednisone (15 mg cause there is no evidence of a causal link between the every other day), she was asymptomatic, and cognitive antibodies and encephalopathy. function was normal. Administration of the same dose We describe a patient with encephalopathy and high of prednisone was continued, and she remained well at serum antithyroid antibody concentrations. We also re- last evaluation (early 2002). view all reported cases to determine whether the disor- der is a definable entity. LITERATURE REVIEW REPORT OF A PATIENT We conducted a MEDLINE search using the words “Hashimoto” or “autoimmune thyroiditis” and “encepha- In 1996, a 63-year-old woman had an episode of pre- lopathy.” We retrieved articles in all languages, and we sumed viral encephalitis with subacute onset of im- reviewed references cited in these articles. We did not paired memory, ataxia, and headache. She had no focal consider patients described in abstracts.59,60 motor, sensory, cranial nerve, or cerebellar abnormali- We diagnosed Hashimoto encephalopathy if pa- ties. Magnetic resonance images of the brain were nor- tients had the following 3 findings: clouding of conscious- mal. Results of cerebrospinal fluid (CSF) studies for vi- ness with reduced wakefulness, attention, or cognitive func- ral and bacterial infection were negative. She was treated tion; no CSF evidence of bacterial or viral infection, as with acyclovir, intravenously, for possible herpes sim- determined by culture or molecular analysis; and posi- plex encephalitis, and she improved. tive test results for or a high serum concentration (or ti- A few months later she developed tremor and cog- ter) of antithyroid microsomal, antithyroid peroxidase, or nitive dysfunction, which subsequently subsided. In 1999, antithyroglobulin antibodies. Patients with strokelike or cognitive dysfunction gradually recurred, she became in- postictal focal signs, seizures, dementia, or psychiatric creasingly confused, and she had a generalized seizure. symptoms were included if consciousness was de- Brain magnetic resonance images were normal. After a pressed. Any CSF abnormality was acceptable as long as second seizure, she was given phosphenytoin, acyclo- viral or bacterial infection was excluded. Any abnormali- vir, and ceftriaxone and was transferred to the Columbia- ties in thyroid function and any thyroid or antithyroid Presbyterian Medical Center, New York. therapy were acceptable as long as there was a high se- On hospital admission, she was comatose. Brain- rum concentration (or titer) of antithyroid antibody. Pa- stem reflexes were present, and painful stimuli resulted tients were excluded if the case report did not contain ad- in extensor posturing of all limbs. Brain magnetic reso- equate information to determine whether the illness met nance images revealed diffuse, nonenhancing white mat- the inclusion criteria or if symptoms could be explained ter hyperintensity, sparing the posterior fossa and deep by brain tumor or stroke, as detected by imaging. gray nuclei (Figure). Treatment with intravenous val- We found studies of 105 patients with brain dys- proic acid, phosphenytoin, mannitol, and methylpred- function associated with possible Hashimoto thyroid- nisolone resulted in rapid improvement. She became ori- itis. We excluded 3 patients who did not have encepha- ented to place and time but was inattentive. Cranial nerve lopathy and in whom CSF was not analyzed19,24,53; 1 patient function was normal except for bilateral sixth nerve palsy. lacking examination of the CSF54; 13 who had no en- Tendon reflexes were brisk, but there were no upper or cephalopathy,16,30,37,41 including 6 patients with a purely lower motor neuron signs, and sensation was normal. cerebellar syndrome42; and 2 in whom serum antithy- Hospital admission laboratory studies revealed a nor- roid antibodies were not measured.40,41 Two patients were mal erythrocyte sedimentation rate; normal serum con- described twice but are included only as single cases.26,48 centrations of lactate, angiotensin-converting enzyme, and Patients who met our criteria for the disorder were complement; and negative test results for antinuclear, divided into subcategories based on the results of thy- anti-DNA, antineutrophilic cytoplasmic, antimyelin- roid function tests (Table 1). associated glycoprotein, anti-Yo, and anti-Hu antibod- ϫ 3 ies. The CSF leukocyte count was 26 10 /µL, the pro- RESULTS tein concentration was 0.098 g/dL, and viral and bacterial culture findings were negative. Serum thyrotropin and We identified 85 patients who met the inclusion crite- thyroxine concentrations were normal on hospital ad- ria, including the patient described herein (Table 2). mission, but