HASHIMOTO S ENCEPHALOPATHY

1. HASHIMOTO�S ENCEPHALOPATHY ??? ?????????????? ????????

2. Case Report This 38 y/o female was a case of ITP diagnosed in 1996 and received splenectomy due to poor medical control in 1999. Memory impairment and fatigue for a month Acute onset of self talking, incoherent speech, irritable, crying out and agitation were noted in February 2000.

3. Case Report CSF analysis showed lymphocytic pleocytosis and elevated protein (WBC: 90/ml lymphocyte: 62%, T.P: 97 mg/dl) Brain CT showed no obvious focal lesion. Under the impression of TB meningitis or aseptic meningitis, She was admitted to our Neurology service

4. Case Report After admission, anti-TB medication was given, but her clinical condition didn�t improve Brain MRI showed no obvious focal lesion EEG showed diffuse delta wave Routine hematologic and biochemical blood tests, culture of blood and CSF, HIV, VDRL, CMV, HSV antibodies were negative

5. Case Report Her general condition became worse and was intubated due to CO2 retention Seizure was noted during ICU care Thrombocytopenia was noted again and solumedrol 40 mg bid for two days and qd for 12 days was given Her condition improved gradually, and was discharged

6. Case Report But decrease of her mentality was noted and she had intermittent incoherent speech Puffy face was noted during OPD follow up and thyroid function was checked Hypothyroidism was noted (T4: 3.4 �g/dl, T3: 59.8 ng/dl, TSH: 85.59 �U/ml) and thyroxine was given Microsomal Ab: 1:25600(+), thyroglobulin Ab: 1:100(+)

7. Case Report In November 2002, gradual onset of dysarthria and difficult writing were noted She came to our hospital for help and admission. But her condition didn�t improve and frequent seizure attacked, then her consciousness became confused.

8. Case Report Brain MRI: no obvious focal lesion EEG: diffuse continuous slow waves CSF analysis: mild elevation of protein (T.P.: 48 mg/dl),IgG: 6.03, Albumin: 26.5 Serum IgG: 1110, albumin: 3.5 Brain SPECT: hypoperfusion in the left temporal area, left cerebellum, and hyperperfusion in the left fronto-parietal areas

9. Case Report T4: 3.89 T3: 56.98 TSH: 12.31 Thyroxin was increased to 150 �g/day and Hashimoto�s encephalopathy was suspected Solu-medrol 500 mg ivd bid for 3 days and then received Prednisolone 60 mg/day Her condition got improvement day by day and was discharged two weeks later

10. Case Report Thyroglobulin Ab: 1: 100 (-) Microsomal Ab: 1: 25600 (+) Anti- TSH receptor Ab: 43% T4: 5.93 T3: 64.25 TSH: 2.78

11. Hashimoto�s Encephalopathy The neurologic complication of hypothyroidism, such as dementia, psychosis, ataxia, and seizure are well established and resolve when thyroxine replacement is started Hashimoto�s encephalopathy persists even after thyroid function normalizes, sometimes responding only to immunosuppression

12. Hashimoto�s Encephalopathy Patients with Hashimoto�s thyroiditis may have widespread extrathyroid abnormal immune activity Becker et al reviewed 153 patients with Hashimoto�s thyroiditis. Thirty-six (23.5%) had associated illnesses, including rheumatoid arthritis, pernicious anemia, myasthenia gravis, Addison disease, lupus erythematosus, and ulcerative colitis

13. Hashimoto�s Encephalopathy The possibility of an autoimmune encephalopathy associated with Hashimoto�s disease was first suggested by Brain et al in 1966 It is a subacute process that responds to immunosuppression and not to thyroxine Hashimoto�s encephalopathy is rare, and approximately 30 cases have been reported

14. Hashimoto�s Encephalopathy The average age of onset in reported cases is 47 years ( range from 14 to 78 years) Approximately 85% of the patients are women

15. Pathogenesis The pathogenesis of Hashimoto�s encephalopathy is unknown Hypothyroidism can be excluded, since Hashimoto�s encephalopathy is seen in the euthyroid state of after the correction of hypothyroidism

16. Pathogenesis Current evidence suggests that the encephalopathy results from an autoimmune process, though the exact mechanism has not been elucidated Some findings suggest acute disseminated encephalomyelitis as a potential model, while others favor cerebral angiitis as a paradigm

17. Pathogenesis The antithyroid antibodies are unlikely to be the culprit in the CNS, since no shared antigen between the thyroid gland and the brain has been identified Antithyroid antibody titers do not correlate with disease severity The thyroiditis and the encephalopathy both may represent the casaualty of an overly aggressive immune system

18. Clinical Presentation The first type is characterized by acute stroke-like episodes with transient focal neurologic deficits and even epileptic seizures The second type has a more insidious onset, progressing to dementia, psychosis, and coma over several weeks

19. Diagnosis Thyrotropin and FT4 levels are relatively normal or mild hypothyroidism A positive antithyroid antibody titer is necessary but not sufficient in making the diagnosis of Hashimoto�s encephalopathy In about 75% of reported cases, the CSF reveals an elevated protein level (range from 48 to 298 mg/dL)

20. Diagnosis Of these, 25% also have mononuclear pleocytosis ( range, 8 to 169 cells) Oligoclonal bands are detected in 4 of 15 patients Glucose level is always normal A normal examination may be present in up to 25% of cases and does not rule out Hashimoto�s encephalopathy

21. Diagnosis Electroencephalography is abnormal in more than 90% of cases Typically, the EEG shows nonspecific, intermittent slow wave activity These abnormalities do not improve and even worsen after initiation of anticonvulsant therapy

22. Diagnosis Cranial CT is usually normal in patients of all ages, but may reveal cerebral atrophy or ventricular dilatation Cranial MRI is more sensitive but not more specific Cerebral isotope studies or brain scans: 50% manifested abnormalities consisting of global, focal, or symmetric multifocal areas of decreased perfusion

23. Diagnostic Criteria of HE (A) Unexplained episodes of relapsing myocloni, generalized seizures, focal neurological deficits or psychiatric disorders (B) At least 3 of the following Abnormal EEG Elevated AMAs Elevated CSF protein and /or oligoclonal bands Excellent response to steroids Unrevealing cerebral MRI

24. Treatment Patients with Hashimoto�s encephalopathy respond dramatically to steroid therapy The initial dose of steroids varies between 50 mg and 150 mg of prednisone daily, slowly decreased over weeks to months Rapid improvement can be observed within 1 to 3 days, the average time from start of therapy to significant clinical improvement is 4 to 6 weeks

25. Prognosis Most patients (90%) stay in remission even after treatment has been discontinued

26. Clinical Suggestion Any neuropsychiatric condition that is not responding to conventional therapy, especially probable or known autoimmune thyroiditis, should raise suspicion for Hashimoto�s encephalopathy The presence of goiter or a positive family history for thyroid dysfunction warrants testing for thyroid function and antithyroid antibody titer

27. Clinical Suggestion Additional studies such as EEG, MRI, and lumbar puncture should be done not only to look for supporting evidence for Hashimoto�s encephalopathy, but also to rule out other etiologies of encephalopathy More common causes of encephalopathy, such as infections, electrolyte imbalance, toxins, and neoplasm must be excluded before steroid therapy is initiated