John K. Kramer

Extent of spontaneous motor recovery after traumatic cervical sensorimotor complete spinal cord injury.

Study design:Retrospective, longitudinal analysis of motor recovery data from individuals with cervical (C4–C7) sensorimotor complete spinal cord injury (SCI) according to the International Standards for Neurological Classification of Spinal Cord Injury (ISNCSCI).Objectives:To analyze the extent and patterns of spontaneous motor recovery over the first year after traumatic cervical sensorimotor complete SCI.Methods:Datasets from the European multicenter study about SCI (EMSCI) and the Sygen randomized clinical trial were examined for conversion of American Spinal Injury Association (ASIA) Impairment Scale (AIS) grade, change in upper extremity motor score (UEMS) or motor level, as well as relationships between these measures.Results:There were no overall differences between the EMSCI and Sygen datasets in motor recovery patterns. After 1 year, up to 70% of subjects spontaneously recovered at least one motor level, but only 30% recovered two or more motor levels, with lesser values at intermediate time points. AIS grade conversion did not significantly influence motor level changes. At 1 year, the average spontaneous improvement in bilateral UEMS was 10–11 motor points. There was only moderate relationship between a change in UEMS and a change in cervical motor level (r 2=0.30, P<0.05). Regardless of initial cervical motor level, most individuals recover a similar number of motor points or motor levels.Conclusion:Careful tracking of cervical motor recovery outcomes may provide the necessary sensitivity and accuracy to reliably detect a subtle, but meaningful treatment effect after sensorimotor complete cervical SCI. The distribution of the UEMS change may be more important functionally than the total UEMS recovered.

Characterization of neurological recovery following traumatic sensorimotor complete thoracic spinal cord injury

Study design:Retrospective, longitudinal analysis of sensory, motor and functional outcomes from individuals with thoracic (T2–T12) sensorimotor complete spinal cord injury (SCI).Objectives:To characterize neurological changes over the first year after traumatic thoracic sensorimotor complete SCI.Methods:A dataset of 399 thoracic complete SCI subjects from the European Multi-center study about SCI (EMSCI) was examined for neurological level, sensory levels and sensory scores (pin-prick and light touch), lower extremity motor score (LEMS), ASIA Impairment Scale (AIS) grade, and Spinal Cord Independence Measure (SCIM) over the first year after SCI.Results:AIS grade conversions were limited. Sensory scores exhibited minimal mean change, but high variability in both rostral and caudal directions. Pin-prick and light touch sensory levels, as well as neurological level, exhibited minor changes (improvement or deterioration), but most subjects remained within one segment of their initial injury level after 1 year. Recovery of LEMS occurred predominantly in subjects with low thoracic SCI. The sensory zone of partial preservation (ZPP) had no prognostic value for subsequent recovery of sensory levels or LEMS. However, after mid or low thoracic SCI, ⩾3 segments of sensory ZPP correlated with an increased likelihood for AIS grade conversion.Conclusion:The data suggest that a sustained deterioration of three or more thoracic sensory levels or loss of upper extremity motor function are rare events and may be useful for tracking the safety of a therapeutic intervention in early phase acute SCI clinical trials, if a significant proportion of study subjects exhibit such an ascent.

Feasibility and efficacy of upper limb robotic rehabilitation in a subacute cervical spinal cord injury population

Study design: Multi-center pilot study.Objectives:To investigate the use of an upper limb robotic rehabilitation device (Armeo Spring, Hocoma AG, Switzerland) in a subacute cervical spinal cord injury (SCI) population.Setting: Two Canadian inpatient rehabilitation centers.Methods:Twelve subjects (motor level C4–C6, ASIA Impairment Scale A–D) completed the training, which consisted of 16.1±4.6 sessions over 5.2±1.4 weeks. Two types of outcomes were recorded: (1) feasibility of incorporating the device into an inpatient rehabilitation program (compliance with training schedule, reduction in therapist time required and subject questionnaires) and (2) efficacy of the robotic rehabilitation for improving functional outcomes (Graded and Redefined Assessment of Strength, Sensibility and Prehension (GRASSP), action research arm test, grip dynamometry and range of motion).Results:By the end of the training period, the robot-assisted training was shown to require active therapist involvement for 25±11% (mean±s.d.) of the total session time. In the group of all subjects and in a subgroup composed of motor-incomplete subjects, no statistically significant differences were found between intervention and control limbs for any of the outcome measures. In a subgroup of subjects with partial hand function at baseline, the GRASSP-Sensibility component showed a statistically significant increase (6.0±1.6 (mean±s.e.m.) point increase between baseline and discharge for the intervention limbs versus 1.9±0.9 points for the control limbs).Conclusion:The pilot results suggest that individuals with some preserved hand function after SCI may be better candidates for rehabilitation training using the Armeo Spring device.

Relationship between motor recovery and independence after sensorimotor-complete cervical spinal cord injury

Background. For therapeutics directed to the injured spinal cord, a change in neurological impairment has been proposed as a relevant acute clinical study end point. However, changes in neurological function, even if statistically significant, may not be associated with a functional impact, such as a meaningful improvement in items within the self-care subscore of the Spinal Cord Independence Measure (SCIM). Objective. The authors examined the functional significance associated with spontaneously recovering upper-extremity motor function after sensorimotor-complete cervical spinal cord injury (SCI). Methods. Using the European Multi-center Study about Spinal Cord Injury (EMSCI) data set, a retrospective analysis was undertaken of individuals with cervical sensorimotor-complete SCI (initial motor level, C4-C7). Specifically, changes in upper-extremity motor score (UEMS), motor level, and SCIM (total and self-care subscore) were assessed between approximately 1 and 48 weeks after injury (n = 74). Results. The initial motor level did not significantly influence the total UEMS recovered or number of motor levels recovered. SCIM self-care subscore recovery was significantly greater for those individuals regaining 2 motor levels compared with those recovering only 1 or no motor levels. However, the recovery in the SCIM self-care subscore was not significantly different between individuals recovering only 1 motor level and those individuals who showed no motor-level improvement. Conclusions. A 2 motor-level improvement indicates a clinically meaningful change and might be considered a primary outcome in acute and subacute interventional trials enrolling individuals with cervical sensorimotor-complete SCI.

Challenges for defining minimal clinically important difference (MCID) after spinal cord injury

Study design:This is a review article.Objectives:This study discusses the following: (1) concepts and constraints for the determination of minimal clinically important difference (MCID), (2) the contrasts between MCID and minimal detectable difference (MDD), (3) MCID within the different domains of International Classification of Functioning, disability and health, (4) the roles of clinical investigators and clinical participants in defining MCID and (5) the implementation of MCID in acute versus chronic spinal cord injury (SCI) studies.Methods:The methods include narrative reviews of SCI outcomes, a 2-day meeting of the authors and statistical methods of analysis representing MDD.Results:The data from SCI study outcomes are dependent on many elements, including the following: the level and severity of SCI, the heterogeneity within each study cohort, the therapeutic target, the nature of the therapy, any confounding influences or comorbidities, the assessment times relative to the date of injury, the outcome measurement instrument and the clinical end-point threshold used to determine a treatment effect. Even if statistically significant differences can be established, this finding does not guarantee that the experimental therapeutic provides a person living with SCI an improved capacity for functional independence and/or an increased quality of life. The MDD statistical concept describes the smallest real change in the specified outcome, beyond measurement error, and it should not be confused with the minimum threshold for demonstrating a clinical benefit or MCID. Unfortunately, MCID and MDD are not uncomplicated estimations; nevertheless, any MCID should exceed the expected MDD plus any probable spontaneous recovery.Conclusion:Estimation of an MCID for SCI remains elusive. In the interim, if the target of a therapeutic is the injured spinal cord, it is most desirable that any improvement in neurological status be correlated with a functional (meaningful) benefit.

Dermatomal somatosensory evoked potentials and electrical perception thresholds during recovery from cervical spinal cord injury.

Background. Dermatomal somatosensory evoked potentials (dSSEPs) not only provide a neurophysiological readout comparable with conventional SSEPs but also provide an opportunity to track changes in sensory function corresponding to individual dermatomes (ie, a single spinal segment) above, at, and below the level of spinal cord injury (SCI). Objectives. This study aimed to determine the reliability and responsiveness of dSSEPs and electrical perception thresholds (EPTs) to monitor changes in sensory function after cervical SCI. Methods. Initial and follow-up dSSEPs and EPTs were recorded from cervical dermatomes (C4-C8) of patients with traumatic tetraplegia (C3-C8; ASIA Impairment Scale A-D) during recovery after SCI (n = 18). Results. Follow-up examination of 74 initial dSSEPs unaffected by SCI (n = 18) revealed no significant change in latency (Δ = 0.0 ± 1.4 ms; P = .9) or EPT sensitivity (Δ = 0.1 ± 0.8 mA; P = .3). In 41 dSSEPs initially delayed after SCI (n = 14), latencies significantly decreased on follow-up examination (Δ = -3.1 ± 2.9 ms; P < .01) without a corresponding increase in sensitivity of the EPT (Δ = 0.2 ± 3.4 mA; P = .7). dSSEPs that were not measurable initially were subsequently recorded in 11 dermatomes (n = 5) on follow-up examination. This conversion of abolished-to-recordable dSSEPs was often preceded by the perception of an initial EPT and associated with a concomitant recovery of EPT at follow-up. Conclusion. dSSEPs and EPT can be reliably recorded to monitor changes in sensory function for each individual spinal segment after cervical SCI. dSSEPs may be potentially useful to monitor the safety of a therapeutic drug or cell transplant in early-phase (I/II) clinical trials as well as document the potential efficacy of interventions where the standard neurological assessment might not detect subtle therapeutic effects.

Increased baseline temperature improves the acquisition of contact heat evoked potentials after spinal cord injury.

OBJECTIVE To investigate the effect of increasing the skin surface baseline temperature for contact heat evoked potentials (CHEPs). METHODS CHEPs were studied in healthy subjects and subjects with chronic cervical spinal cord injury (SCI) using a conventional 35°C (condition 1) or increased 42-45°C baseline temperature (condition 2). A third condition was used to standardize the contact heat stimulus duration from the different baseline temperatures. Changes in peak latency and N2P2 amplitude of the CHEPs and rating of perceived intensity were examined between conditions. RESULTS In healthy subjects, increasing the baseline temperature for contact heat stimulation significantly increased the rating of perceived intensity (conditions 2 and 3), as well as the amplitude of CHEPs (condition 2 only). Following SCI, an increased baseline temperature facilitated perception of contact heat stimulation and evoked potentials could be recorded from dermatomes that were insensitive to contact heat from a conventional baseline temperature. CONCLUSIONS Enhancing the acquisition of CHEPs can be achieved by increasing the baseline temperature. This effect can be attributed, in part, to shortening the stimulation duration. SIGNIFICANCE After SCI, increasing the baseline temperature for CHEPs in dermatomes with absent or diminished sensation improved the neurophysiological resolution of afferent sparing.

Association of pain and CNS structural changes after spinal cord injury

Traumatic spinal cord injury (SCI) has been shown to trigger structural atrophic changes within the spinal cord and brain. However, the relationship between structural changes and magnitude of neuropathic pain (NP) remains incompletely understood. Voxel-wise analysis of anatomical magnetic resonance imaging data provided information on cross-sectional cervical cord area and volumetric brain changes in 30 individuals with chronic traumatic SCI and 31 healthy controls. Participants were clinically assessed including neurological examination and pain questionnaire. Compared to controls, individuals with SCI exhibited decreased cord area, reduced grey matter (GM) volumes in anterior cingulate cortex (ACC), left insula, left secondary somatosensory cortex, bilateral thalamus, and decreased white matter volumes in pyramids and left internal capsule. The presence of NP was related with smaller cord area, increased GM in left ACC and right M1, and decreased GM in right primary somatosensory cortex and thalamus. Greater GM volume in M1 was associated with amount of NP. Below-level NP-associated structural changes in the spinal cord and brain can be discerned from trauma-induced consequences of SCI. The directionality of these relationships reveals specific changes across the neuroaxis (i.e., atrophic changes versus increases in volume) and may provide substrates of underlying neural mechanisms in the development of NP.

Relationship between chronic pain and brain reorganization after deafferentation: A systematic review of functional MRI findings

Background Mechanisms underlying the development of phantom limb pain and neuropathic pain after limb amputation and spinal cord injury, respectively, are poorly understood. The goal of this systematic review was to assess the robustness of evidence in support of “maladaptive plasticity” emerging from applications of advanced functional magnetic resonance imaging (MRI). Methods Using MeSH heading search terms in PubMed and SCOPUS, a systematic review was performed querying published manuscripts. Results From 146 candidate publications, 10 were identified as meeting the inclusion criteria. Results from fMRI investigations provided some level of support for maladaptive cortical plasticity, including longitudinal studies that demonstrated a change in functional organization related to decreases in pain. However, a number of studies have reported no relationship between reorganization, pain and deafferentation, and emerging evidence has also suggested the opposite — that is, chronic pain is associated with preserved cortical function. Conclusion Based solely on advanced functional neuroimaging results, there is only limited evidence for a relationship between chronic pain intensity and reorganization after deafferentation. The review demonstrates the need for additional neuroimaging studies to clarify the relationship between chronic pain and reorganization.

Effect of a robotic rehabilitation device on upper limb function in a sub-acute cervical spinal cord injury population

Robotic rehabilitation devices have been suggested as a tool to increase the amount of rehabilitation delivered after a neurological injury. Clinical robotic rehabilitation studies of the upper extremity have generally focused on stroke survivors. We present the results of a multi-center pilot study where an upper-limb robotic rehabilitation device (Armeo Spring®, Hocoma AG) was incorporated into the rehabilitation program of 12 subjects with sub-acute cervical spinal cord injury (motor level C4-C6, AIS A-D). Outcomes were measured using two tests of upper extremity function: ARAT and GRASSP. The change in scores for the arm receiving the Armeo training were not statistically significant when compared to the arm not receiving the Armeo training at discharge from therapy and over follow up assessments (8.7 +/− 2.9 compared to 7.4 +/− 2.5 for ARAT at discharge, p = 0.98, and 13.0 +/− 3.2 compared to 13.3 +/− 3.3 for GRASSP at discharge, p = 0.69). Nevertheless, subjects with some minimal (partial) hand function at baseline had a significantly larger increase in GRASSP scores than subjects with no minimal hand function preserved at baseline (19.3 +/− 2.4 compared to 6.6 +/− 4.7, p = 0.02). This suggests that the initial functional capabilities of patients can influence the benefits measured after robotic rehabilitation training and heterogeneous subject populations should be avoided in early phase studies.