Anti-Thyroid Peroxidase/Anti-Thyroglobulin Antibody-Related Neurologic Disorder Responsive to Steroids Presenting with Pure Acute Onset Chorea

Background: Pure acute onset chorea without encephalopathy has rarely been reported in anti-thyroid peroxidase (anti-TPO)/anti-thyroglobulin (anti-TG) antibody-related neurologic disorders responsive to steroids (ATANDS). Case report: We report a 16-year-old female who presented with acute chorea without encephalopathy. Anti-TPO antibodies were found to be strongly positive (>1200 IU/ml) along with anti-thyroglobulin and anti-thyroid stimulating hormone receptor antibodies. After pulse intravenous methylprednisolone therapy (1 g/day for five consecutive days), all the movements seized, and she was discharged with oral prednisolone 30 mg/day with gradual tapering over next three months. After one year of follow-up, she is stable, drug-free, and never had any other problems. Discussion: Anti-thyroid antibodies testing should be included in routine/conventional panel that is done for elucidating causes of chorea as ATANDS can be easily missed and is treatable with widely available, relatively low-cost drugs like steroids with a promising outcome.

steroids [10,11]. Despite this, response to steroids seems to be the only partially consistent feature of this disorder hence renamed as "steroid responsive encephalopathy associated with autoimmune thyroiditis" (SREAT) [12], but neither response to steroids nor association with thyroiditis is steadfast [13]. Termasarasab et al., [14] have recently proposed "anti-TPO/TG antibody-related neurologic disorders responsive to steroids (ATANDS)" to be the renamed entity that would include the complete spectrum. Reported movement disorders that have been associated with ATANDS can be either "encephalopathic" or "non-encephalopathic" [5][6][7]14].
We had treated a patient with pure acute chorea who rapidly improved with corticosteroids. Here, we describe the case with a complete report. We also provide a review of the literature, which was performed to collect and summarize the present state of knowledge on movement disorders associated with ATANDS. A 16-year-old female presented to the neurology outpatient department with complaint of acute onset involuntary weird and quirky movements of all four limbs for last four days, which were irregular, asymmetric, rapid, unpredictable, purposeless, jerky and flowing from distal to proximally and that disappeared completely during sleep. Her past medical history was unremarkable. No associated febrile episode, seizure, headache, visual disturbances, behavioral changes, personality changes, forgetfulness, attention problems, or self-care inadequacy were noted. She had no history of any drug intake for any disease or substance abuse in recent past. No history was suggestive of any connective tissue disorder or thyroid dysfunction. Nobody in family had any neurological disease. On completion of an unremarkable general survey, detailed neurological examination revealed generalized chorea involving all extremities (right > left) with classic Jack in the box tongue and Milkman's grip signs. Precise and meticulous cognitive assessment failed to unveil any impairment. Neither motor weakness, nor sensory deficits, nor signs of meningeal irritation and cranial nerve deficits were noted. Slit lamp examination ruled out Kayser-Fleischer ring.
Complete hemogram, thyroid, liver, kidney functions, electrolytes, arterial blood gas analysis and HbA1C were normal. A urine beta human chorionic gonadotropin and abdominal ultrasound ruled out any pregnancy. Serologies for human immunodeficiency virus, hepatitis C, and hepatitis B were negative. 24 hours urinary copper and serum ceruloplasmin levels were within normal range. Echocardiography, serial anti-streptolysin O titers, and anti-DNase B antibodies levels ruled out possibility of Sydenham's chorea. Anti-Nuclear Antibody (ANA) screening using HEp-2 cells, ANA profile, antiphospholipid antibodies, and antineutrophil cytoplasmic antibodies (cANCA and pANCA) were found to be negative. Autoantibodies directed against voltage gated potassium channel and anti-N-methyl-D-aspartate receptor antibodies were also negative. Magnetic resonance imaging of brain, electroencephalogram and cerebrospinal fluid analyses were otherwise normal.
Serum anti-TPO antibodies were found to be strongly positive (>1200 IU/ml) along with anti-TG and anti-thyroid stimulating hormone receptor antibodies. Patient was put on pulse intravenous methylprednisolone therapy (1 g/day for five consecutive days). All the movements seized and she was discharged with oral prednisolone 30 mg/day with gradual tapering over next three months. Tests were rerun with similar results, but anti-thyroid stimulating hormone receptor antibodies, which were within normal range this time around. At present, after one year of followup, she remains stable, drug-free and without any other problems.

Discussion
ATANDS with associated movement disorders have been described previously (Table 1) . We have reported a 16-year-old female with ATANDS who presented with acute pure chorea without encephalopathy. ATANDS presenting with chorea is exceedingly rare. For example, Miranda et al., [47] described a middle-aged female with acute onset rapidly worsening choreo-athetosis with dystonia and slurred speech which came out to be a case of ATANDS. Sharan A et al., [41] reported an aged female with ATANDS, who developed abrupt onset behavioral changes along with asymmetric florid chorea. Taurin G et al., [19] narrated behavioral abnormality with psychotic features along with bilateral and axial choreic movements in an elderly female. Our patient had no behavioral abnormalities or any other extrapyramidal or cerebellar features unlike those previously mentioned cases [19,41,47]. In all those cases steroid resulted in good yield alike our patient [19,41,47].
Etiopathogenetic factors for chorea are believed to be a) a hypersensitivity of dopaminergic receptors to dopamine due to a thyrotoxic state; [17,51] b) derangements in cerebral perfusion as reported in cases of acute onset chorea associated with other etiologies [27,52,53] and substantiated by single-photon emission computed tomography and positron emission tomography imaging; [54,55] c) autoimmune central nervous system vasculitis; [8,56] and d) antithyroid antibody mediated effects on neurons [7,[57][58][59]. However, for neurological manifestations like chorea, antithyroid antibodies are extremely sensitive, but lack specificity [60]. And whether they are pathogenic or just a marker   Art. 19, page 7 of 10 Ghosh et al: Anti-Thyroid Peroxidase/Anti-Thyroglobulin Antibody-Related Neurologic Disorder Responsive to Steroids Presenting with Pure Acute Onset Chorea of the disease or just an epiphenomenon, remains elusive [6,7,60,61]. Presence of anti-thyroid antibodies in general population is well established even in absence of neurologic disorders and usually acting as a confounding factor in diagnosis [60]. Further, levels of anti-thyroid antibodies do not correlate well with disease severity and often persist in high levels after the treatment and clinical response [6,62,63].
In conclusion, our experience with the current case and our review of the literature strongly suggest that ATANDS/SREAT can rarely present with movement disorders alone and may be a definite separate entity. Anti-thyroid antibody testing should be included in routine/conventional panel that is done for elucidating causes of chorea as this disorder can be easily missed and is treatable with widely available, relatively low-cost drugs like steroids with a promising outcome.