title: Treatment of multiple system atrophy using intravenous immunoglobulin.
abstract: BACKGROUND
  Multiple system atrophy (MSA) is a progressive neurodegenerative disorder of unknown etiology, manifesting as combination of parkinsonism, cerebellar syndrome and dysautonomia. Disease-modifying therapies are unavailable. Activation of microglia and production of toxic cytokines suggest a role of neuroinflammation in MSA pathogenesis. This pilot clinical trial evaluated safety and tolerability of intravenous immunoglobulin (IVIG) in MSA.
  
  
  METHODS
  This was a single-arm interventional, single-center, open-label pilot study. Interventions included monthly infusions of the IVIG preparation Privigen®, dose 0.4 gram/kg, for 6 months. Primary outcome measures evaluated safety and secondary outcome measures evaluated preliminary efficacy of IVIG. Unified MSA Rating Scale (UMSARS) was measured monthly. Quantitative brain imaging using 3T MRI was performed before and after treatment.
  
  
  RESULTS
  Nine subjects were enrolled, and seven (2 women and 5 men, age range 55-64 years) completed the protocol. There were no serious adverse events. Systolic blood pressure increased during IVIG infusions (p<0.05). Two participants dropped out from the study because of a non-threatening skin rash. The UMSARS-I (activities of daily living) and USMARS-II (motor functions) improved significantly post-treatment. UMSARS-I improved in all subjects (pre-treatment 23.9 ± 6.0 vs. post-treatment 19.0±5.9 (p=0.01). UMSARS-II improved in 5 subjects, was unchanged in 1 and worsened in 1 (pre-treatment 26.1±7.5 vs. post-treatment 23.3±7.3 (p=0.025). The MR imaging results were not different comparing pre- to post-treatment.
  
  
  CONCLUSIONS
  Treatment with IVIG appears to be safe, feasible and well tolerated and may improve functionality in MSA. A larger, placebo-controlled study is needed.
authors.affiliation: Department of Neurology, University of Massachusetts Medical School, Worcester, MA 01655, USA. novakp@ummhc.org
authors.forename: Peter
authors.initials: P
authors.lastname: Novak
authors.forename: Arlene
authors.initials: A
authors.lastname: Williams
authors.forename: Paula
authors.initials: P
authors.lastname: Ravin
authors.forename: Omar
authors.initials: O
authors.lastname: Zurkiya
authors.forename: Amir
authors.initials: A
authors.lastname: Abduljalil
authors.forename: Vera
authors.initials: V
authors.lastname: Novak
mesh_terms: D000203:Activities of Daily Living; D004185:Disability Evaluation; D005260:Female; D006801:Humans; D016756:Immunoglobulins, Intravenous / Q000009:adverse effects / Q000627:therapeutic use*; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000188:drug therapy*; D010865:Pilot Projects; D016896:Treatment Outcome
chemical_list: D016756:Immunoglobulins, Intravenous