title: Does long-term partial sodium channel blockade alter disease progression in MS? Evidence from a retrospective study.
abstract: BACKGROUND
  There is accumulating evidence that long-term disability and disease progression in multiple sclerosis (MS) are due to prolonged sodium channel opening along demyelinated axons. Despite good evidence in animal models of MS that partial voltage-gated sodium channel (VGSC) blockade reduces disease progression, little is known about its effects in patients, despite widespread use of such agents in the symptomatic management of MS.
  
  
  OBJECTIVE
  To determine if long-term exposure to the VGSC-blocking drug carbamazepine (CBZ) alters disease progression in MS.
  
  
  METHODS
  Using a retrospective chart review of patients diagnosed with MS, we compared progression of disability between patients exposed the VGSC blocker CBZ with those who were not exposed to the drug. Both whole-group and matched case-control analyses were performed after correcting for the influence of age, gender, MS subtype, expanded disability status score at diagnosis, use of disease-modifying therapy, and year of initial therapy. The multiple sclerosis severity scale (MSSS) was used as a measure of disease severity. The primary outcome measure was MSSS score difference between groups.
  
  
  RESULTS
  Four hundred patients were included; 51 received CBZ symptomatic therapy (average duration of therapy 27 months). There was no significant difference in mean MSSS between the two groups in either the whole group comparison (p = 0.63) or the matched analysis (p = 0.12).
  
  
  CONCLUSIONS
  Despite preclinical evidence suggesting a neuroprotective role of VGSC blockers in animal models of MS, this retrospective study suggests that long-term exposure to the VGSC-blocking drug CBZ fails to alter long-term disability and disease progression in MS patients.
authors.affiliation: School of Medicine, National University of Ireland, Galway, Ireland, timothy.counihan@hse.ie.
authors.forename: T J
authors.initials: TJ
authors.lastname: Counihan
authors.forename: J A
authors.initials: JA
authors.lastname: Duignan
authors.forename: G
authors.initials: G
authors.lastname: Gormley
authors.forename: S
authors.initials: S
authors.lastname: Saidha
authors.forename: C
authors.initials: C
authors.lastname: Dooley
authors.forename: J
authors.initials: J
authors.lastname: Newell
mesh_terms: D000328:Adult; D002220:Carbamazepine / Q000627:therapeutic use*; D004185:Disability Evaluation; D018450:Disease Progression; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000175:diagnosis / Q000188:drug therapy* / Q000378:metabolism; D018696:Neuroprotective Agents / Q000627:therapeutic use*; D012189:Retrospective Studies; D012720:Severity of Illness Index; D026941:Sodium Channel Blockers / Q000627:therapeutic use*; D013997:Time Factors; D016896:Treatment Outcome
chemical_list: D018696:Neuroprotective Agents; D026941:Sodium Channel Blockers; D002220:Carbamazepine