ABSTRACT
Riluzole is a sodium-glutamate antagonist that attenuates neurodegeneration in amyotrophic lateral sclerosis (ALS). It has shown favorable results in promoting recovery in pre-clinical models of traumatic spinal cord injury (tSCI) and in early phase clinical trials. This study aimed to evaluate the efficacy and safety of riluzole in acute cervical tSCI. An international, multi-center, prospective, randomized, double-blinded, placebo-controlled, adaptive, Phase III trial (NCT01597518) was undertaken. Patients with American Spinal Injury Association Impairment Scale (AIS) A-C, cervical (C4-C8) tSCI, and <12 h from injury were randomized to receive either riluzole, at an oral dose of 100 mg twice per day (BID) for the first 24 h followed by 50 mg BID for the following 13 days, or placebo. The primary efficacy end-point was change in Upper Extremity Motor (UEM) scores at 180 days. The primary efficacy analyses were conducted on an intention to treat (ITT) and completed cases (CC) basis. The study was powered at a planned enrolment of 351 patients. The trial began in October 2013 and was halted by the sponsor on May 2020 (and terminated in April 2021) in the face of the global COVID-19 pandemic. One hundred ninety-three patients (54.9% of the pre-planned enrolment) were randomized with a follow-up rate of 82.7% at 180 days. At 180 days, in the CC population the riluzole-treated patients compared with placebo had a mean gain of 1.76 UEM scores (95% confidence interval: -2.54-6.06) and 2.86 total motor scores (CI: -6.79-12.52). No drug-related serious adverse events were associated with the use of riluzole. Additional pre-planned sensitivity analyses revealed that in the AIS C population, riluzole was associated with significant improvement in total motor scores (estimate: standard error [SE] 8.0; CI 1.5-14.4) and upper extremity motor scores (SE 13.8; CI 3.1-24.5) at 6 months. AIS B patients had higher reported independence, measured by the Spinal Cord Independence Measure score (45.3 vs. 27.3; d: 18.0 CI: -1.7-38.0) and change in mental health scores, measured by the Short Form 36 mental health domain (2.01 vs. -11.58; d: 13.2 CI: 1.2-24.8) at 180 days. AIS A patients who received riluzole had a higher average gain in neurological levels at 6 months compared with placebo (mean 0.50 levels gained vs. 0.12 in placebo; d: 0.38, CI: -0.2-0.9). The primary analysis did not achieve the predetermined end-point of efficacy for riluzole, likely related to insufficient power. However, on pre-planned secondary analyses, all subgroups of cervical SCI subjects (AIS grades A, B and C) treated with riluzole showed significant gains in functional recovery. The results of this trial may warrant further investigation to extend these findings. Moreover, guideline development groups may wish to assess the possible clinical relevance of the secondary outcome analyses, in light of the fact that SCI is an uncommon orphan disorder without an accepted neuroprotective treatment.
ABSTRACT
STUDY DESIGN: This was a survey of the surgeon members of the Lumbar Spine Research Society (LSRS). OBJECTIVE: The purpose of this study was to assess trends in surgical practice and patient management involving elective and emergency surgery in the early months of the coronavirus pandemic. SUMMARY OF BACKGROUND DATA: The novel coronavirus has radically disrupted medical care in the first half of 2020. Little data exists regarding the exact nature of its effect on spine care. METHODS: A 53-question survey was sent to the surgeon members of the LSRS. Respondents were contacted via email 3 times over a 2-week period in late April. Questions concentrated on surgical and clinical practice patterns before and after the pandemic. Other data included elective surgical schedules and volumes, as well as which emergency cases were being performed. Surgeons were asked about the status of coronavirus disease 2019 (COVID-19) virus testing. Circumstances for performing surgical intervention on patients with and without testing as well as patients testing positive were explored. RESULTS: A total of 43 completed surveys were returned of 174 sent to active surgeons in the LSRS (25%). Elective lumbar spine procedures decreased by 90% in the first 2 months of the pandemic, but emergency procedures did not change. Patients with "stable" lumbar disease had surgeries deferred indefinitely, even beyond 8 weeks if necessary. In-person outpatient visits became increasingly rare events, as telemedicine consultations accounted for 67% of all outpatient spine appointments. In total, 91% surgeons were under some type of confinement. Only 11% of surgeons tested for the coronavirus on all surgical patients. CONCLUSIONS: Elective lumbar surgery was significantly decreased in the first few months of the coronavirus pandemic, and much of outpatient spine surgery was practiced via telemedicine. Despite these constraints, spine surgeons performed emergency surgery when indicated, even when the COVID-19 status of patients was unknown. LEVEL OF EVIDENCE: Level IV.