The Laryngoscope C 2014 The American Laryngological, V
Rhinological and Otological Society, Inc.
Timing of Nimodipine Therapy for the Treatment of Vocal Fold Paralysis Shaum S. Sridharan, MD; Clark A. Rosen, MD; Libby J. Smith, DO; VyVy N. Young, MD; Michael C. Munin, MD Objectives/Hypothesis: To retrospectively determine optimal timing for initiation of nimodipine within a cohort of patients with acute vocal fold paralysis (VFP). Study Design: Retrospective patient review. Methods: Subjects were divided into three groups: initiation within 15 days postinjury (n 5 19), between 15 and 30 days postinjury (n 5 23), or greater than 30 days postinjury (n 5 11). Results: Fifty-one patients (53 paralyzed vocal folds [VFs]) met entrance criteria and were offered and started off-label nimodipine treatment. Thirty-six of 53 VFs recovered purposeful motion (67.9%). There was no significant difference in the rate of VF recovery among patients who began nimodipine within 15 days (68.4%), patients who started nimodipine between 15 and 30 days (73.9%) of nerve injury (P 5.1405), and patients who initiated nimodipine after 30 days postinjury (54.5%). Conclusions: Nimodipine treatment for acute VFP yielded equal VF motion recovery rates regardless of when the medication was initiated. Time to recovery of motion was not different between groups studied. Key Words: Nimodipine, vocal cord paralysis, laryngeal electromyography, laryngeal muscle innervation, nerve regeneration/drug effects, timing. Level of Evidence: 4 Laryngoscope, 125:186–190, 2015
INTRODUCTION Recent efforts in the care of vocal fold paralysis (VFP) have focused on specific interventions that could promote the recovery of purposeful vocal fold motion (VFM) in the acutely injured recurrent laryngeal nerve (RLN) without transection.1–3 Nimodipine, an L-type voltage-gated calcium channel blocker, has been utilized in an attempt to improve functional recovery after peripheral nerve injury.2,4,5 It is postulated that by blocking the transient intracellular influxes of Ca11 ions within neurons, propagation of the growth cones in the injured nerve is improved.6 There are currently no randomized clinical studies available that definitively prove the effectiveness of nimodipine in restoring VFM after paralysis. However, previous nonrandomized clinical investigations into the use of nimodipine in acute VFP have demonstrated significant VFM recovery rates From the Department of Otolaryngology, University of Pittsburgh Voice Center (S.S.S., C.A.R., L.J.S., V.N.Y.), Department of Physical Medicine and Rehabilitation (M.C.M.), and Department of Otolaryngology (M.C.M.), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A. Editor’s Note: This Manuscript was accepted for publication August 4, 2014. Presented at the American Laryngological Association 135th Annual Meeting at COSM, Las Vegas, Nevada, U.S.A., May 14, 2014. The authors have no funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Clark A. Rosen, MD, University of Pittsburgh Voice Center, Department of Otolaryngology, UPMC Mercy Building B, Suite 11500, 1400 Locust Street, Pittsburgh, PA 15219. E-mail: [email protected] DOI: 10.1002/lary.24903
Laryngoscope 125: January 2015
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compared to historical control groups.2,7 Increases in nerve fiber growth rate and size have been confirmed by animal studies after crush injury to the RLN and facial nerve.8,9 Moreover, improved nerve growth was observed in rats with transection injury to the RLN with reanastomosis.10 Animal studies suggest that the earlier nimodipine was started, the greater the chance for VFP recovery following injury.8,10 In the clinical setting, starting nimodipine therapy immediately after RLN injury can be challenging. Hydman et al. were able to start nimodipine on six of their patients immediately after iatrogenic nerve injury. The three patients who remained on the nimodipine therapy all had return of VFM.2 In our previous cohort of 28 patients enrolled in our treatment protocol, patients were started on nimodipine therapy if they were evaluated anytime within 4 months of RLN injury. Recovery rates for purposeful VFM in patients taking nimodipine after paralysis was 60% compared to 400
Rhinological and Otological Society, Inc.
Timing of Nimodipine Therapy for the Treatment of Vocal Fold Paralysis Shaum S. Sridharan, MD; Clark A. Rosen, MD; Libby J. Smith, DO; VyVy N. Young, MD; Michael C. Munin, MD Objectives/Hypothesis: To retrospectively determine optimal timing for initiation of nimodipine within a cohort of patients with acute vocal fold paralysis (VFP). Study Design: Retrospective patient review. Methods: Subjects were divided into three groups: initiation within 15 days postinjury (n 5 19), between 15 and 30 days postinjury (n 5 23), or greater than 30 days postinjury (n 5 11). Results: Fifty-one patients (53 paralyzed vocal folds [VFs]) met entrance criteria and were offered and started off-label nimodipine treatment. Thirty-six of 53 VFs recovered purposeful motion (67.9%). There was no significant difference in the rate of VF recovery among patients who began nimodipine within 15 days (68.4%), patients who started nimodipine between 15 and 30 days (73.9%) of nerve injury (P 5.1405), and patients who initiated nimodipine after 30 days postinjury (54.5%). Conclusions: Nimodipine treatment for acute VFP yielded equal VF motion recovery rates regardless of when the medication was initiated. Time to recovery of motion was not different between groups studied. Key Words: Nimodipine, vocal cord paralysis, laryngeal electromyography, laryngeal muscle innervation, nerve regeneration/drug effects, timing. Level of Evidence: 4 Laryngoscope, 125:186–190, 2015
INTRODUCTION Recent efforts in the care of vocal fold paralysis (VFP) have focused on specific interventions that could promote the recovery of purposeful vocal fold motion (VFM) in the acutely injured recurrent laryngeal nerve (RLN) without transection.1–3 Nimodipine, an L-type voltage-gated calcium channel blocker, has been utilized in an attempt to improve functional recovery after peripheral nerve injury.2,4,5 It is postulated that by blocking the transient intracellular influxes of Ca11 ions within neurons, propagation of the growth cones in the injured nerve is improved.6 There are currently no randomized clinical studies available that definitively prove the effectiveness of nimodipine in restoring VFM after paralysis. However, previous nonrandomized clinical investigations into the use of nimodipine in acute VFP have demonstrated significant VFM recovery rates From the Department of Otolaryngology, University of Pittsburgh Voice Center (S.S.S., C.A.R., L.J.S., V.N.Y.), Department of Physical Medicine and Rehabilitation (M.C.M.), and Department of Otolaryngology (M.C.M.), University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania, U.S.A. Editor’s Note: This Manuscript was accepted for publication August 4, 2014. Presented at the American Laryngological Association 135th Annual Meeting at COSM, Las Vegas, Nevada, U.S.A., May 14, 2014. The authors have no funding, financial relationships, or conflicts of interest to disclose. Send correspondence to Clark A. Rosen, MD, University of Pittsburgh Voice Center, Department of Otolaryngology, UPMC Mercy Building B, Suite 11500, 1400 Locust Street, Pittsburgh, PA 15219. E-mail: [email protected] DOI: 10.1002/lary.24903
Laryngoscope 125: January 2015
186
compared to historical control groups.2,7 Increases in nerve fiber growth rate and size have been confirmed by animal studies after crush injury to the RLN and facial nerve.8,9 Moreover, improved nerve growth was observed in rats with transection injury to the RLN with reanastomosis.10 Animal studies suggest that the earlier nimodipine was started, the greater the chance for VFP recovery following injury.8,10 In the clinical setting, starting nimodipine therapy immediately after RLN injury can be challenging. Hydman et al. were able to start nimodipine on six of their patients immediately after iatrogenic nerve injury. The three patients who remained on the nimodipine therapy all had return of VFM.2 In our previous cohort of 28 patients enrolled in our treatment protocol, patients were started on nimodipine therapy if they were evaluated anytime within 4 months of RLN injury. Recovery rates for purposeful VFM in patients taking nimodipine after paralysis was 60% compared to 400
