Intravenous Immunoglobulins as Effective Treatment in Sydenham's Chorea
Condition: Sydenham Chorea; Post Streptococcal Movement Disorder
MeSH terms: Movement Disorders; Chorea
Study type: Interventional

Summary: 
      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.
    

Detailed description: 
      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 complications.

      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
      living.

      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
      treatment.

      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.

      ADDENDUM A

      ACUTE SYDENHAM'S CHOREA

      Patient Details

      Present History

      Past history

      Family and Social History

      General examination

      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

      MEDICATION CHART

      Date Medication Dose Side Effects Comments

      PATIENT'S STICKER
    

Intervention name(s): Intravenous immunoglobulin; standard interventions penicillin VK and haloperidol
Intervention type(s): Biological; Drug
Intervention description(s): intravenous immunoglobulin 2g/kg total given over 2 days; Penicillin V K 500mg 12hrly po or 250mg 6 hrly for 10 days IM penicillin to be given at discharge, 1.2 million units if over 30 KG and 600,000 units if weight less than 30 KG haloperidol 0,025mg/kg/day orally in divided doses gradually increasing to a maximum of 0,05mg/kg/day
Intervention MeSH terms: Penicillins; Penicillin V; Haloperidol; Haloperidol decanoate; Immunoglobulins; Immunoglobulins, Intravenous; Antibodies; gamma-Globulins; Rho(D) Immune Globulin
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Double (Participant, Outcomes Assessor)
Primary purpose: Treatment