Summary:
Sydenham’s chorea is an autoimmune neuropsychiatric disorder that may have a prolonged course. In some children, associated psychiatric symptoms unresponsive to neuroleptic therapy may cause a significant disability. Two children with Sydenham’s chorea, a 13-year-old boy with hallucinations and a 14-year-old girl with abulia, who did not respond to psychiatric drugs, were treated with long-term immunosuppression for one year. Hallucinations in the boy resolved following a year-long regimen of corticosteroids and, during a 5-year follow-up, there were no recurrences. Abulia initially resolved after 14 weeks of prednisone treatment. However, symptoms reoccurred several months after the prednisone had been stopped but resolved following prednisone and azathioprine treatment over the next year. Immunosuppressive responsive psychiatric symptoms in Sydenham’s chorea suggests an underlying autoimmune disorder causing behavioral changes and offers a therapeutic option in neuroleptic-resistant cases.
INTRODUCTION
The gold standard treatment in SC includes penicillin prophylaxis and symptomatic treatment. Recommended symptomatic treatment for chorea includes antiepileptic medications and anti-dopaminergic drugs. Immunomodulatory treatments (steroids, IVIG, plasmapheresis)6 are reserved for cases refractory to conventional treatment.4-6 While prospective and retrospective studies demonstrated that short courses of steroid treatment for several weeks, shortens the course of chorea there is no information regarding the impact on recurrence or persistence.6, 7 Moreover, long-term steroid treatment was not reported in Sydenham’s chorea. We report 2 cases of SC treated for disabling psychiatric symptoms that resolved only following long-term immunosuppressive therapy.
CASE REPORTS
Case 1: A 13-year-old boy was referred for chorea in his right limbs following a bout of streptococcal tonsillitis. Laboratory tests demonstrated an elevated antistreptolysin (ASLO) titer (722; Normal <200 IU/ ml), borderline antinuclear antibody titer (1:200) and a positive anti-β-2-glycoprotein 1. CSF was negative for oligoclonal antibodies. There was a mild aortic and mitral regurgitation on echocardiogram and MRI demonstrated a hyperintense T2 lesion in the left caudate.
The chorea responded initially to psychiatric medications (Haloperidol) but was accompanied by psychosis and severe anxiety state. The child started to hear voices, lock doors obsessively, did not go to school nor could he stay in his room alone. Various psychiatric medications were ineffective as well. With the working diagnosis of an autoimmune disorder, most probably Sydenham’s chorea, he was treated with intravenous immunoglobulins (IVIG, 2 gr/kg) without improvement. After 48 hours of high pulse methylprednisone (30 mg/kg/day), the child reported that “this is the first day that thoughts do not enter my head”. Prednisone (1 mg/kg/day) treatment was continued for one year and follow up MRI demonstrated a resolution of the left caudate lesion that became hypointense, compatible with gliosis. During the 5 year follow-up, the diagnosis of SC was seemed most likely and no other signs or symptoms of a different autoimmune disorder, including systemic lupus erythematosus developed.
Case 2: A 14 years old girl was referred for treatment of persistent Sydenham’s chorea and behavioral problems. Three months prior to onset she had recurrent streptococcal infections followed by rheumatic fever (RF) manifested by arthritis, elevated erythrocyte sedimentation rate (ESR) 109 mm/h, C-reactive protein (CRP) 13.66 mg/dL (Normal <0.5) and increased ASLO 493. Echocardiogram showed moderate mitral regurgitation and trace aortic regurgitation. She was treated with penicillin, aspirin and was instructed to stay home and rest until CRP returned to normal and the carditis improved. Two months after onset of RF, changes in the child’s personality and chorea became evident. From being an “easy kid, very mature for her age, and not a complainer” she became “irritable, sensitive and immature”. The most innocuous requests elicited a crisis and she would break down crying even when asked to clear her dinner plate. Valproate improved the chorea but had no effect on the emotional symptoms. Autoimmune workup available at the time that included anti-Glutamic-acid-decarboxylase, Voltage-gated K+ channel and NMDA-receptor antibodies was negative; MRI and MRA were normal.
Psychological follow-up included: At first, a high level of depression (85%). appeared in all subscales (interpersonal-89%; ineffectiveness-96%; anhedonia-90%; negative self esteem-53%). Anxiety was moderate (13/38), inattention was substantially above average (90%) and had oppositional behavior symptoms (5/8). Occasionally she avoided attending school and academic tasks. The general clinical impression is that the child had abulia, defined as apathy with loss of initiative, spontaneous thought, and emotional responses.
Psychological and psychiatric therapy partially improved her symptoms. Disabling emotional symptoms still prevented her from attending school most of the year until Prednisone (2mg/kg/day) was initiated and maintained for 1 month. During the tapering off period, after 3 weeks, the emotional symptoms reemerged and steroids were renewed (2 mg/kg/day) and weaned slowly over 8 weeks. Psychological assessment after steroid treatment demonstrated improvement, with depression levels very much below average (13%) and anxiety (1/38), inattention symptoms (30%) and oppositional behavior resolved (1/8). She was able to express herself and returned to her social and academic function. However, after 12 months, she experienced another bout of disabling emotional symptoms again treated with steroids (prednisone 2 mg/kg/day) for 6 weeks with gradual weaning (1 mg/day) and azathioprine (up to 2 mg/kg/day) as a steroid-sparing maintenance agent for at one year. Evaluation of this regimen demonstrated resolution of all symptoms; she became a straight A student with excellent social relationships and is free of anxiety, depression, inattention or oppositional behavior symptoms.
DISCUSSION
We present 2 cases of children with disabling psychiatric symptoms that were not responsive to conventional neuroleptics who regained normal, baseline function only after long-term immunosuppressive treatment. Resolution of psychiatric symptoms in SC following prolonged steroid treatment, as in these cases, has not been previously described in the literature. While steroids are commonly used for autoimmune-mediated psychiatric illnesses, steroid-induced psychosis is a worrisome adverse effect. The resolution of psychiatric symptoms in SC suggests that the emotional symptoms stem from an autoimmune process which can be reversed both in the acute phase, as seen in case 1, as well as in a recurrent course, such as case 2. While IVIG and steroids were shown as equally effective immune-modulatory treatments for the motor aspects of SC,7 the first case did not respond to IVIG but did to steroids.
Hyperintense lesions have been reported in several cases of SC but they were associated with the motor symptoms (i.e. chorea) and not the behavioral change. In our patient with visual and auditory hallucination, the caudate lesion may be indicative of the pathways responsible for the behavioral changes. The head of the caudate nucleus, injured in case1, is involved in the primates’ emotional pathways8, thus explaining both the right hemichorea and psychiatric symptoms. Moreover, abulia, as described in case 2, is the most common psychiatric manifestation of caudate lesions in adults, suggesting again that injury to this area leads to disabling psychiatric symptoms in SC.9
Motor and non-motor symptoms of SC may persist and reoccur6, 10; but the extent of long-term disability remains unknown. In case 2, the child had a prolonged disabling relapsing-remitting course that responded to immunosuppression. We are aware that only a prolonged follow up of several years will ultimately determine whether the resolution was temporary or whether there will be further relapses. However, our report presents a novel approach suggesting immunosuppressive treatment for resistant psychiatric symptoms. Considering the inflammatory nature of the disease as highlighted by MRI findings, long-term immunosuppressive treatment may prove useful when other conventional treatments have failed. Further studies are needed to study whether immunomodulatory therapy alters the long-term course of SC and reduces persistent or recurrent motor and non-motor sequela of the disease.
A modified summery from our Article in Journal of pediatric neurology: JPN 10(3):211-214 · January 2012
Authours: Ben-Pazi, H, MD, P.J Hashkes, MD, MSc and N. Kroyzer, MA
From the Neuropediatric Unit (H.B.P, N.K), and Pediatric Rheumatologic Unit (P.J.H), Shaare Zedek Medical Center, Jerusalem, Israel
Acknowledgment We thank Angela Vincent MD and the neuroimmunology team at John Radcliffe Hospital, Oxford, UK for neuroimmunological testing.
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