Intravenous Immunoglobulins as Effective Treatment in Sydenham's Chorea
Information source: University of Cape Town
ClinicalTrials.gov processed this data on August 23, 2015
Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Sydenham Chorea; Post Streptococcal Movement Disorder
Intervention: Intravenous immunoglobulin (Biological); standard interventions penicillin VK and haloperidol (Drug)
Sponsored by: University of Cape Town
Official(s) and/or principal investigator(s):
Kathleen Walker, MB ChB, Principal Investigator, Affiliation: Red Cross Children's Hospital, University of Cape Town
Children are at risk of developing an involuntary movement disorder after streptococcal
throat infections. Not all children are affected and the severity is individually variable.
Affected children have alteration in their behaviour and mood and can become quite
compromised in their activities of daily living. The condition is believed to be related to
the body having an over efficient immune response to the infection and some of the
antibodies made in response to the infection also "attack" centres in the brain controlling
movement and mood. Treating these children with immunoglobulins, which "mop up" the
antibodies may reverse or improve affected children. This study hopes to clarify this.
Official title: Intravenous Immunoglobulins as Effective Treatment in Sydenham's Chorea
Study design: Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Double Blind (Subject, Outcomes Assessor), Primary Purpose: Treatment
Primary outcome: improved scores on the sydenham chorea assessment charts
Secondary outcome: improved quality of life
INTRODUCTION Acute Rheumatic Fever (ARF), chronic rheumatic heart disease (RHD) and
neuropsychiatric/ movement disorders related to group A beta haemolytic streptococcal
infections (GABAS) remain major public health problems in South Africa. RHD may require
repeated hospital admissions, invasive surgery and often results in premature death. In
Africa ARF has a mortality of 2-3%. 1 Likewise, neuropsychiatric disorders such as
Sydenham's Chorea (SC) resulting from GABAS result in school difficulties, frequent
absenteeism, behaviour problems such as obsessive compulsive disorder and may progress to
Tourette Syndrome (personal experience). Patients may suffer from disabling neurologic and
psychiatric symptoms many years after their initial episode of ARF (personal experience).
The morbidity from these conditions demands enormous resources from the state in terms of
medical and surgical treatment and we believe results in preventable stress and suffering to
the patient and his or her family. Whilst the ideal goal is primary prevention a measure of
secondary prevention has been attained by the use of monthly prophylactic penilente. In
cases where ARF has occurred, some further intervention is desirable, to prevent the above
At the Rheumatic Fever Clinic (RFC) at Red Cross Hospital patients with established RHD
and old cases of Sydenham's Chorea ( SC) are seen. There are 2-4 new cases of ARF seen per
month. ARF remains a notifiable disease but it appears that these new cases are often not
notified. (personal communication PAWC health officials) SC is a major manifestation of ARF
and following the 1992 update of the modified Jones Criteria, it is sufficient alone to make
a diagnosis of ARF. 2 The duration of SC ranges from a few weeks to 2 years. Recurrences
occur in one third of patients. 3 Current treatment of SC is purely symptomatic and whether
it resolves in 6 weeks or 2 years is dependent on innate healing mechanisms within the
individual. SC is postulated to be mediated through auto- antibodies that mis-recognise
neuronal cell components. These complexes then result in an inflammatory response in the
basal ganglia with the resultant clinical picture of SC. 3 We hypothesise, that the use of
intravenous immunoglobulins ( IVIG) will decrease the number of circulating antibodies
thereby decreasing symptom severity and shortening the course of the illness. Prophylactic
penicillin must be continued to prevent re-exposure and further formation of antibodies.
AIM We aim to determine whether treatment of SC with IVIG expedites recovery and thus cuts
down on morbidity and frequent follow up.
METHOD Our aim is to collect a minimum of 20 patients with acute SC, diagnosed according to
the revised Jones Criteria for ARF and with an absence of indicators of other causes of
chorea. (Table 1) The study would run for 4 years or until the minimum number are recruited.
Patients would be identified and the chorea would be rated as mild, moderate or severe and
all signs of chorea carefully documented as per attached format. (A) Special investigations
would be performed (Table 2). Patients with IgA deficiency would be excluded from the study.
Informed consent would be obtained. Patients would be randomly selected to receive IVIG and
or standard treatment. Each patient will be allocated a code number.
Patients will be admitted to a neurology bed, as usually occurs for the acute management of
moderate and severe SC. Patients will be notified.
Standard pharmacological treatment (Table 3) of haloperidol and or sodium valproate will be
administered, in addition the trial group will receive IVIG. All patients will commence
penicillin prophylaxis. On day two (once the administration of IVIG is complete) the
investigator (KW) and a blinded observer (WM) will examine the patient for signs of chorea
as per addendum A.
The patient will remain hospitalised until he or she can cope with activities of daily
Patients will be reviewed at one month, 3 months, 6 months and 1 year and any other time if
necessary, this being consistent with current management. They will be assessed by a blinded
observer (WM) and by the chief investigator(KW). Follow up will be at the RFC.
IMI penicillin to be given at discharge, 1. 2 million units if over 30 KG and 600,000 units
if weight less than 30 KG NB. Improvement of symptoms with IVIG alone, can only be expected
after the third week post treatment. 5 The aim of this therapy is to shorten the overall
course of the illness and to prevent complications.
SAMPLE SIZE We aim to get a minimum of twenty cases, 10 will receive IVIG and 10 standard
ANALYSIS Aim to get a minimum of 20 new cases. Statistical analysis of the outcome measures
will be undertaken.
ETHICS / CONSENT In recent years IVIG have been used successfully and safely in a number of
auto-immune conditions. 4 Informed consent will be obtained. Parent consent forms will be
available in English, Afrikaans and Xhosa COSTING Salaries. No contract staff or casual
assistants would be employed. Already salaried staff would look after the patients. Patients
with SC are usually admitted to hospital and all the above treatment is administered except
for the administration of IVIG, the assessment of serum gamma-globulins and brain
spectroscopy scans (single photon emission computed tomographic scanning). The department
of Nuclear Medicine has consented to perform these scans. It has been shown that in
hemichorea hypermetabolism occurs in the contralateral basal ganglion and this disappears
with resolution of symptoms. 8 Nursing duties would remain the same as for current admissions
of SC. The only additional nursing duty would be the monitoring of the IV infusion.
The registrars and senior house officers will assist in the management of these patients. As
stated earlier ARF is a public health problem in South Africa. It is important therefore
that health professionals are aware of the preventative and curative treatments available
for the treatment of SC.
ACUTE SYDENHAM'S CHOREA
Family and Social History
Details of CVS
Details of Chorea
To be graded as severe, moderate and mild Severe: unable to ambulate or perform any
activity of daily living (ADL) Moderate: ambulate with assistance and able to perform some
ADLs Mild: ambulate unaided and able to perform most ADLs Minimal: chorea elicited
only during neurological examination (9)
Document whether Hemi-chorea or bilateral
Day 0 = Day of admission Day 1 = treatment commenced
Signs of Chorea Day 0 Day 5 1 mth 3 mth 6 mth 1 year Hypotonia Hungup knee jerks Milkmaid's
Grip Darting Tongue Pronator Sign Dishing Spoon hand Hippus Weakness Emotional lability
Behaviour disturbances Explosive or indistinct speech Facial Grimaces Generalised
restlessness Inappropriate Behaviour eg OCD Shrugging shoulders Writhing TOTAL
(10) Definition of Signs Milkmaid's Grip : inability to maintain contraction when the
patient grasps the examiners fingers Darting Tongue: inability to maintain protrusion of
the tongue Pronator Sign: tendency to pronate one or both hands when they are extended
overhead Dishing Spoon Hand: assumption of a hand posture consisting of wrist flexion,
hyperextension of the metacarpophalangeal joints, finger straightening and thumb abduction
Hippus: reflex constriction and dilation of pupil Hung up knee jerks: slow to return to
pre test position
Date Medication Dose Side Effects Comments
Minimum age: 4 Years.
Maximum age: 16 Years.
- Sydenham chorea moderate to severe (affecting activities of daily living) Raised ASOT
- Mild Sydenham chorea (not affecting activities of daily living)
- Exclusion of systemic lupus erythematosus
- Exclusion of Wilson's disease
- Exclusion of toxin ingestion
Locations and Contacts
Red Cross Children's Hospital, Cape Town, Western Cape 7700, South Africa
Perlmutter SJ, Leitman SF, Garvey MA, Hamburger S, Feldman E, Leonard HL, Swedo SE. Therapeutic plasma exchange and intravenous immunoglobulin for obsessive-compulsive disorder and tic disorders in childhood. Lancet. 1999 Oct 2;354(9185):1153-8.
Swedo SE. Sydenham's chorea. A model for childhood autoimmune neuropsychiatric disorders. JAMA. 1994 Dec 14;272(22):1788-91.
Barron KS, Sher MR, Silverman ED. Intravenous immunoglobulin therapy: magic or black magic. J Rheumatol Suppl. 1992 Apr;33:94-7. Review.
Starting date: May 2002
Last updated: December 3, 2014