A Multicentre randomiSed Controlled TRial of IntraVEnous Immunoglobulin Versus Standard Therapy for Transverse Myelitis

Inclusion Criteria:

• Diagnosis of EITHER acute first onset transverse myelitis (using the TM Consortium Working Group 2002criteria) - patients must fulfill all of the following criteria:

• Sensory, motor, or autonomic dysfunction attributable to spinal cord disease

• Bilateral signs and/or symptoms (not necessarily symmetric)

• Sensory level (except in young children <5 years where this is difficult to evaluate)

• Lack of MRI brain criteria consistent with multiple sclerosis

• Progression to nadir between 4 h and 21 days OR first presentation of neuromyelitis optica (using standardised criteria) - patients mustfulfil both absolute criteria:

• Optic neuritis

• Acute myelitis, plus two out of three supportive criteria (as Aquaporin 4 antibody (AQP4) is often not available acutely, only the first two supportive criteria would beapplied),

• Brain MRI not meeting criteria for Multiple Sclerosis (MS) at disease onset

• Spinal cord MRI with contiguous T2-weighted signal abnormality extending over three ormore vertebral segments, indicating a relatively large lesion in the spinal cord

• AQP4 seropositive status

• ASIA Impairment Score of A-C

• Randomisation to occur no later than day 5 of steroids, and, if definitely known,within 21 days from symptom onset.

• Give assent (8-16 years)/consent to participate in the trial

Exclusion Criteria:

• Contraindication to IVIG as stated in the summary of product characteristics (SmPC),or receiving IVIG for other reasons

• Previously known systemic autoimmune disease (e.g. systemic lupus erythematosus) orany evidence of systemic inflammation during current presentation.

• Direct infectious aetiology (e.g. varicella zoster)

• Previous episode of central nervous system (CNS) inflammatory demyelination

• Acute disseminated encephalomyelitis (ADEM)

• Other causes of myelopathy not thought to be due to myelitis (e.g. nutritional,ischaemic, tumour etc.)

• Other disease which would interfere with assessment of outcome measures

• Known pregnancy

• Circumstances which would prevent follow-up for 12 month