Plasma Exchange and Intravenous Immunoglobulin Efficacy Study (PIES) in Acute Central Nervous System Demyelinating Disease

Study ID
STU 052012-080

Cancer Related
No

Healthy Volunteers
No

Study Sites

Contact
Samuel Hughes
214-645-7977
samuel.hughes@utsouthwestern.edu

Principal Investigator
Benjamin Greenberg

Summary

- Day one: Diagnosis of aDeM or TM x patient is enrolled in study. Patient is assessed with a complete comprehensive neurologic exam and assessed according to age with the eDSS scale (ages 5+), MSFC scale (ages 8+), Hauser's ambulation scale (ages 2+), WeeFiM (ages 2-7 years), or a modified Denver ii developmental index scale (ages 2-5 years).
- Day 1-5: Patient receives high-dose steroids for 5 days once daily. in addition, on day 2-3, the patient is randomized to receive either intravenous immunoglobulin or plasma exchange.
- Day 5 - Patient is assessed with a complete comprehensive neurologic exam and assessed according to age with the eDSS scale (ages 5+), MSFC scale (ages 8+), Hauser's ambulation scale (ages 2+), WeeFiM (ages 2-7 years), or a modified Denver ii developmental index scale (ages 2-5 years).
- Day 7-15: Pt re-assessed at day 10 and day 15 (if the subject is still hospitalized) with a comprehensive neurologic examination and according to age with the eDSS scale (ages 5+), MSFC scale (ages 8+), Hauser's ambulation scale (ages 2+), WeeFiM (ages 2-7 years), or a modified Denver ii developmental index scale (ages 2-5yrs). Decision made according to presence of significant neurologic deficits of continuing with further treatment. The decision to cross over to the other therapy modality is based on the following: 1) if the Hauser ambulation scale was worse than 3 at the onset, an inability to achieve a 2-point improvement results in cross-over to the other therapy oR 2) if the Hauser ambulation scale is 3 or better at onset, an inability to improve by at least one point results in cross-over oR 3) a motor score less than 4-/5 in at least 50% or more of muscle groups in TWo limbs anD any muscle groups with a 0-1/5 score in any muscle group will result in cross-over to the other therapy oR 4) vision is worse than 20/60 in either eye would constitute a decision to proceed with further therapy.
- Special cases:
o at days 2-12+, the patients will be reviewed and evaluated by an independent neurologist for their entire course of care. Should their be particular concern by said neurologist because of the aggressive nature of their course or progression of symptoms, other adjuvant therapies may be considered outside of the study protocol. These patients will still be included in the final analysis and will follow-up with the study team after discharge.
o Patients will automatically receive plasma exchange as initial therapy if they require mechanical ventilation at onset or within first few days of treatment and are not already receiving plasma exchange.
- upon completion of hospitalization, patients will follow-up in clinic in 3-6
months, and will receive a comprehensive neurologic examination and the
eDSS scale (ages 5+), MSFC scale (ages 8+), Hauser's ambulation scale
(ages 2+), WeeFiM (ages 2-7 years), or a modified Denver ii
developmental index scale (ages 2-5 years).

Participant Eligibility

Individuals from both genders, ages: 2 years-18 years of age, and patients from all ethnicities and cultural backgrounds will be recruited from Children[Single Quote]s Medical Center Dallas to participate in this study. The patients will enter based on their diagnosis of acute disseminated encephalomyelitis or acute transverse myelitis. The diagnostic criteria for acute disseminated encephalomyelitis is the following:
Of these first 5 criteria, at least 4 must be met
1. First clinical attack of inflammatory or demyelinating disease in the CNS
2. Acute or subacute onset
3. Affects multifocal areas of the CNS
4. Polysymptomatic presentation
5. Must include encephalopathy: acute behavioral change such as confusion or irritability and/or alteration in consciousness ranging from somnolence to coma.

Their radiologic criteria are the following:
Of these criteria (after 4 of 5 above are met), #1 MUST be met and either one of the next 2 criteria

1. Large (>1 to 2 cm in size) multifocal, hyperintense, bilateral, asymmetric lesions in the supratentorial or infratentorial white matter. Rarely, brain MRI shows a single large ([greater than or equal to]1 to 2 cm) lesion predominantly affecting white matter.
2. Gray matter, especially basal ganglia and thalamus, may be involved
3. Spinal cord MRI may show confluent intramedullary lesion(s) with variable enhancement, in addition to the abnormalities on brain MRI
No radiologic evidence of previous destructive white matter changes


The criteria for acute transverse myelitis is the following:
The bolded criteria are MANDATORY criteria (all 4) and non-bolded are not mandatory but will be included in reporting

1. Development of sensory, motor or autonomic dysfunction attributable to the spinal cord (BOLD)
2. Bilateral signs and/or symptoms (though not necessarily symmetric)
3. Clearly-defined sensory level
4. Exclusion of extra-axial compressive etiology by neuroimaging (MRI or myelography; CT of spine not adequate) (BOLD)
5. Inflammation within the spinal cord demonstrated by CSF pleocytosis or Elevated IgG index/synthesis rate or gadolinium enhancement. If none of the inflammatory criteria is met at symptom onset, repeat MRI and LP evaluation between 2-7 days following symptom onset meets criteria** (BOLD)
6. Progression to nadir between 4 hours to 21 days following the onset of symptoms. If patient awakens with symptoms, symptoms must become more pronounced from point of awakening. (BOLD)

** - Sometimes evidence of inflammation only noted on an elevated IgG index or synthesis rate, however, this laboratory test is not resulted for a few days. Should patient meet 3 of 4 criteria and we are waiting on results of this test because no pleocytosis or gadolinium enhancement is noted at onset, the patient will be enrolled in study and, if later found to not meet this criteria, pt will be removed from the study and treated according to best practice.