Does long-term partial sodium channel blockade alter disease progression in MS? Evidence from a retrospective study

T. J. Counihan, J. A. Duignan, G. Gormley, Shiv Saidha, C. Dooley, J. Newell

Research output: Contribution to journalArticle

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). Conclusion: 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.

Original languageEnglish (US)
Pages (from-to)117-121
Number of pages5
JournalIrish Journal of Medical Science
Volume183
Issue number1
DOIs
StatePublished - Mar 2014

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Sodium Channels
Multiple Sclerosis
Disease Progression
Retrospective Studies
Carbamazepine
Voltage-Gated Sodium Channels
Voltage-Gated Sodium Channel Blockers
Animal Models
Pharmaceutical Preparations
Therapeutics
Axons
Research Design
Outcome Assessment (Health Care)

Keywords

  • Carbamazepine
  • Multiple sclerosis
  • Neuroprotection
  • Sodium channels

ASJC Scopus subject areas

  • Medicine(all)

Cite this

Does long-term partial sodium channel blockade alter disease progression in MS? Evidence from a retrospective study. / Counihan, T. J.; Duignan, J. A.; Gormley, G.; Saidha, Shiv; Dooley, C.; Newell, J.

In: Irish Journal of Medical Science, Vol. 183, No. 1, 03.2014, p. 117-121.

Research output: Contribution to journalArticle

Counihan, T. J. ; Duignan, J. A. ; Gormley, G. ; Saidha, Shiv ; Dooley, C. ; Newell, J. / Does long-term partial sodium channel blockade alter disease progression in MS? Evidence from a retrospective study. In: Irish Journal of Medical Science. 2014 ; Vol. 183, No. 1. pp. 117-121.
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N2 - 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). Conclusion: 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.

AB - 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). Conclusion: 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.

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