Association of timing of gabapentinoid use with motor recovery after spinal cord injury.

OBJECTIVE: To explore the hypothesis that earlier administration of acute gabapentinoids is beneficial to motor recovery after spinal cord injury in humans. METHODS: This is an observational study using a cohort from the European Multi-Centre Study about Spinal Cord Injury. Patient charts were reviewed to extract information regarding the administration and timing of gabapentinoid anticonvulsants. The primary outcome measure was motor scores, as measured by the International Standards for Neurological Classification of Spinal Cord Injury, collected longitudinally in the first year after injury. Sensory scores (light touch and pinprick) and functional measures (Spinal Cord Independence Measure) were secondary outcomes. Linear mixed effects regression models included a drug-by-time interaction to determine whether exposure to gabapentinoids altered recovery of muscle strength in the first year after injury. RESULTS: A total of 201 participants were included in the study and had a median age of 46 and baseline motor score of 50. Participants were mostly men (85%) with sensory and motor complete injuries (50%). Seventy individuals (35%) were administered gabapentinoids within the first 30 days after injury, and presented with similar demographics. In the longitudinal model, the administration of gabapentinoids within 30 days after injury was associated with improved motor recovery when compared to those who did not receive gabapentinoids during this time (3.69 additional motor points from 4 to 48 weeks after injury; p = 0.03). This effect size increased as administration occurred earlier after injury (i.e., a benefit of 4.68 points when administered within 5 days). CONCLUSIONS: This retrospective, observational study provided evidence of the beneficial effect of gabapentinoid anticonvulsants on motor recovery after spinal cord injury. More critically, it highlighted a potential time dependence, suggesting that earlier intervention is associated with better outcomes. CLASSIFICATION OF EVIDENCE: This study provides Class IV evidence that gabapentinoids improve motor recovery for individuals with acute spinal cord injury.

Acute Traumatic and Ischemic Spinal Cord Injuries Have a Comparable Course of Recovery.

Background. The relative rarity of ischemic compared with traumatic spinal cord injury (SCI) has limited a comparison of the outcomes of these conditions. Objective. To investigate the neurological and functional recovery of ischemic compared with traumatic acute SCI. Methods. Data were derived from the European Multicenter Study Spinal Cord Injury database. Patients with ischemic (iSCI) or traumatic SCI (tSCI), aged 18 years or older were evaluated at different time points from incidence: at about 1 month, 3 months, and 6 months. The neurological status was assessed at each time point by the International Standards for Neurological Classification of Spinal Cord Injury and the functional status by the Spinal Cord Independence Measure. Walking ability was evaluated by Walking Index for Spinal Cord Injury, 10-Meter Walk Test, and 6-Minute Walk Test. Because of the imbalances of the 2 groups in respect to size and lesion severity, a matching procedure according to age, neurological level, and severity of injury was performed. Outcomes evaluation was performed by means of a 2-way repeated-measures ANOVA. Results. The matching procedure resulted in 191 pairs. Both groups significantly improved from about 15 days after the lesion to 6 months. No differences were found in the course of neurological and functional recovery of iSCI compared with tSCI. Conclusions. This analysis from a representative cohort of participants revealed that from 15 days following the cord damage onward, the outcomes after iSCI and tSCI are comparable. This finding supports the potential enrolment of patients with acute iSCI into clinical trials from that point in time after the event and an evaluation up to 6 months afterward.

Comparison of outcomes between people with and without central cord syndrome.

STUDY DESIGN: Retrospective analysis of prospectively collected data. OBJECTIVE: Central cord syndrome (CCS) is reported to have better outcomes than other cervical lesions, especially for ambulation and bladder recovery. However, a formal comparison between patients with CCS and other incomplete cervical spinal cord injuries (iCSCI) is lacking. Aim of the study is to investigate the neurological and functional outcomes in patients with or without CCS. SETTING: European Multicenter Study. METHODS: Data following SCI were derived from the European Multicenter Study about Spinal Cord Injury Database. CCS was diagnosed based on a difference of at least ten points of motor score in favour of the lower extremities. Patients were evaluated at 30 days, 6 months and 1 year from injury. The neurological and functional data were collected at each time point based on the International Standards for Neurological Classification of Spinal Cord injury (ISNSCI) and Spinal Cord Independence Measure (SCIM). Patients were selected with a matching procedure based on lesion severity, neurological level of injury (NLI) and age. Evaluation of the outcomes was performed by means of two-way Anova for repeated measures. RESULTS: The matching produced 110 comparable dyads. At all time points, upper extremity motor scores remained lower than lower extremity motor scores in CCS compared with iCSCI. With regard to daily life independence, both cohorts achieved comparable improvements in self-care sub-scores between T0 and T2 (6.6 ± 6.5 in CCS vs 8.2 ± 6.9 in iCSCI, p = 0.15) but this sub-score was significantly lower in CCS compared with iCSCI (3.6 ± 5.2 in CCS vs 7.3 ± 7.0 in iCSCI at T0, 13.7 ± 6.2 vs 16.5 ± 5.7 at T2), while the other sub-scores were comparable. CONCLUSIONS: In contrast to previous reports, people with CCS have poorer outcomes of self-care ability compared with iCSCI.

Recovery after traumatic thoracic- and lumbar spinal cord injury: the neurological level of injury matters.

STUDY DESIGN: Multicenter prospective cohort. OBJECTIVE: To discern neurological- and functional recovery in patients with a traumatic thoracic spinal cord injury (TSCI), conus medullaris syndrome (CMS), and cauda equina syndrome (CES). SETTING: Specialized spinal cord injury centers in Europe. METHOD: Lower extremity motor score (LEMS) and spinal cord independent measure (SCIM) scores from patients with traumatic TSCI, CMS, and CES were extracted from the EMSCI database. Scores from admittance and during rehabilitation at 1, 3, 6, and 12 months were compared. Linear mixed models were used to statistically analyse differences in outcome, which were corrected for the ASIA Impairment Scale (AIS) in the acute phase. RESULTS: Data from 1573 individuals were analysed. Except for the LEMS in patients with a CES AIS A, LEMS, and SCIM significantly improved over time for patients with a TSCI, CMS, and CES. Irrespectively of the AIS score, recovery in 12 months after trauma as measured by the LEMS showed a statistically significant difference between patients with a TSCI, CMS, and CES. Analysis of SCIM score showed no difference between patients with TSCI, CMS, or CES. CONCLUSION: Difference in recovery between patients with a traumatic paraplegia is based on neurological (motor) recovery. Regardless the ceiling effect in CES patients, patients with a mixed upper and lower motor neuron syndrome (CMS) showed a better recovery compared with patients with a upper motor neuron syndrome (TSCI). These findings enable stratifications of patients with paraplegia according to the level and severity of SCI.

Early Administration of Gabapentinoids Improves Motor Recovery after Human Spinal Cord Injury.

The anticonvulsant pregabalin promotes neural regeneration in a mouse model of spinal cord injury (SCI). We have also previously observed that anticonvulsants improve motor outcomes following human SCI. The present study examined the optimal timing and type of anticonvulsants administered in a large, prospective, multi-center, cohort study in acute SCI. Mixed-effects regression techniques were used to model total motor scores at 1, 3, 6, and 12 months post injury. We found that early (not late) administration of anticonvulsants significantly improved motor recovery (6.25 points over 1 year). The beneficial effect of anticonvulsants remained significant after adjustment for differences in 1-month motor scores and injury characteristics. A review of a subset of patients revealed that gabapentinoids were the most frequently administrated anticonvulsant. Together with preclinical findings, intervention with anticonvulsants represents a potential pharmacological strategy to improve motor function after SCI.

Effects of Pain and Pain Management on Motor Recovery of Spinal Cord-Injured Patients: A Longitudinal Study.

Background Approximately 60% of patients suffering from acute spinal cord injury (SCI) develop pain within days to weeks after injury, which ultimately persists into chronic stages. To date, the consequences of pain after SCI have been largely examined in terms of interfering with quality of life. Objective The objective of this study was to examine the effects of pain and pain management on neurological recovery after SCI. Methods We analyzed clinical data in a prospective multicenter observational cohort study in patients with SCI. Using mixed effects regression techniques, total motor and sensory scores were modelled at 1, 3, 6, and 12 months postinjury. Results A total of 225 individuals were included in the study (mean age: 45.8 ± 18 years, 80% male). At 1 month postinjury, 28% of individuals with SCI reported at- or below-level neuropathic pain. While pain classification showed no effect on neurological outcomes, individuals administered anticonvulsant medications at 1 month postinjury showed significant reductions in pain intensity (2 points over 1 year; P < .05) and greater recovery in total motor scores (7.3 points over 1 year; P < .05). This drug effect on motor recovery remained significant after adjustment for injury level and injury severity, pain classification, and pain intensity. Conclusion While initial pain classification and intensity did not reveal an effect on motor recovery following acute SCI, anticonvulsants conferred a significant beneficial effect on motor outcomes. Early intervention with anticonvulsants may have effects beyond pain management and warrant further studies to evaluate the therapeutic effectiveness in human SCI.