Blair Calancie

Comparison of training methods to improve walking in persons with chronic spinal cord injury: a randomized clinical trial.

Abstract Objective To compare two forms of device-specific training – body-weight-supported (BWS) ambulation on a fixed track (TRK) and BWS ambulation on a treadmill (TM) – to comprehensive physical therapy (PT) for improving walking speed in persons with chronic, motor-incomplete spinal cord injury (SCI). Methods Thirty-five adult subjects with a history of chronic SCI (>1 year; AIS ‘C’ or ‘D’) participated in a 13-week (1 hour/day; 3 days per week) training program. Subjects were randomized into one of the three training groups. Subjects in the two BWS groups trained without the benefit of additional input from a physical therapist or gait expert. For each training session, performance values and heart rate were monitored. Pre- and post-training maximal 10-m walking speed, balance, muscle strength, fitness, and quality of life were assessed in each subject. Results All three training groups showed significant improvement in maximal walking speed, muscle strength, and psychological well-being. A significant improvement in balance was seen for PT and TRK groups but not for subjects in the TM group. In all groups, post-training measures of fitness, functional independence, and perceived health and vitality were unchanged. Conclusions Our results demonstrate that persons with chronic, motor-incomplete SCI can improve walking ability and psychological well-being following a concentrated period of ambulation therapy, regardless of training method. Improvement in walking speed was associated with improved balance and muscle strength. In spite of the fact that we withheld any formal input of a physical therapist or gait expert from subjects in the device-specific training groups, these subjects did just as well as subjects receiving comprehensive PT for improving walking speed and strength. It is likely that further modest benefits would accrue to those subjects receiving a combination of device-specific training with input from a physical therapist or gait expert to guide that training.

A Guidance Channel Seeded With Autologous Schwann Cells for Repair of Cauda Equina Injury in a Primate Model

Abstract Background/Objective: To evaluate an implantable guidance channel (GC) seeded with autologous Schwann cells to promote regeneration of transected spinal nerve root axons in a primate model. Methods: Schwann cells were obtained from sural nerve segments of monkeys (Macaca fascicularis; cynomolgus). Cells were cultured, purified, and seeded into a PAN/PVC GC. Approximately 3 weeks later, monkeys underwent laminectomy and dural opening. Nerve roots of the L4 through L7 segments were identified visually. The threshold voltage needed to elicit hindlimb muscle electromyography (EMG) after stimulation of intact nerve roots was determined. Segments of 2 or 3 nerve roots (each ∼8-15 mm in length) were excised. The GC containing Schwann cells was implanted between the proximal and distal stumps of these nerve roots and attached to the stumps with suture. Follow-up evaluation was conducted on 3 animals, with survival times of 9 to 14 months. Results: Upon reexposure of the implant site, subdural nerve root adhesions were noted in all 3 animals. Several of the implanted GC had collapsed and were characterized by thin strands of connective tissue attached to either end. In contrast, 3 of the 8 implanted GC were intact and had white, glossy cables entering and exiting the conduits. Electrical stimulation of the tissue cable in each of these 3 cases led to low-threshold evoked EMG responses, suggesting that muscles had been reinnervated by axons regenerating through the repair site and into the distal nerve stump. During harvesting of the GC implant, sharp transection led to spontaneous EMG in the same 3 roots showing a low threshold to electrical stimulation, whereas no EMG was seen when harvesting nerve roots with high thresholds to elicit EMG. Histology confirmed large numbers of myelinated axons at the midpoint of 2 GC judged to have reinnervated target muscles. Conclusions: We found a modest rate of successful regeneration and muscle reinnervation after treatment of nerve root transection with a Schwann cell-seeded, implanted synthetic GC. Newer treatments, which include the use of absorbable polymers, neurotrophins, and antiscar agents, may further improve spinal nerve regeneration for repair of cauda equina injury.

Intraoperative neuromonitoring: Can the results of direct stimulation of titanium-alloy pedicle screws in the thoracic spine be trusted?

Objective: Intraoperative neuromonitoring of thoracic-level pedicle screw implantation for detecting breaches in the pedicle cortex has adopted methods originally developed in the early 1990s for stainless steel (SS) alloy screws used at lumbosacral levels. In our recent attempts to monitor thoracic-level pedicle screw placement, we were surprised to find that these widely used stimulation parameters were largely ineffectual when stimulating directly through titanium alloy (Ti-alloy) pedicle screws. The objectives of this study, then, were twofold: (1) to report the number of episodes in which intraoperative neuromonitoring of thoracic screw position failed to detect a medially directed breach (or malplacement) in a previously described and limited sample set; and (2) to compare the frequency-specific impedance of a sample of Ti-alloy pedicle screws to comparably sized screws made of SS alloys. We predicted that Ti-alloy screws would demonstrate impairment in conduction properties that could help explain the difficulties we, and others, have recently experienced with neuromonitoring of thoracic pedicle screw placement. Methods: Based on threshold values for train-of-four stimulation of spinal motor pathways, we quantified the incidence of medial breaches of thoracic-level pedicles in a small cohort of subjects. We also evaluated the conductive properties of Ti-alloy pedicle screws and compared these with SS screws. Eleven pedicle screws were examined using energy-dispersive x-ray spectroscopy to identify their alloys, after which DC resistance and AC impedance for each screw was measured. Furthermore, a subset of five screws was used to investigate the current delivery under dynamic testing conditions. Results: Postoperative computed tomography of 6 subjects revealed 10 instances of significant medial screw malpositioning, out of a total of 88 screws placed. In each of these 10 instances, direct stimulation of thoracic pedicle screws at intensities considered in the literature to be clinically significant (i.e., ⩽11 mA) failed to predict these medial pedicle breaches, yet each breach was reliably identified with low-intensity stimulation applied via a ball-tipped probe. For in vitro studies, most screws made of titanium alloys had higher resistance and impedance at tested frequencies compared with their SS counterparts. Moreover, there was widespread variability in conduction properties between Ti-alloy screws, whereas SS screws behaved in a more homogeneous manner. Conclusions: When compared with screws made of SS, most Ti-alloy pedicle screws behaved more like semiconductors, showing conduction properties that were highly frequency dependent. These properties likely contributed to the difficulties we encountered in interpreting thoracic screw placements based on stimulus-evoked electromyography from direct screw stimulation.

Efficacy of QuadroPulse rTMS for improving motor function after spinal cord injury: Three case studies

Context/objective: To examine the effects of repetitive QuadroPulse transcranial magnetic stimulation (rTMSQP) on hand/leg function after spinal cord injury (SCI). Design: Interventional proof-of-concept study. Setting: University laboratory. Participants: Three adult subjects with cervical SCI. Interventions: Repeated trains of magnetic stimuli were applied to the motor cortical hand/leg area. Several exploratory single-day rTMSQP protocols were examined. Ultimately we settled on a protocol using three 5-day trials of (1) rTMSQP only; (2) exercise only (targeting hand or leg function); and (3) rTMSQP combined with exercise. Outcome measures: Hand motor function was assessed by Purdue Pegboard and Complete Minnesota Dexterity tests. Walking function was based on treadmill walking and the Timed Up and Go test. Electromyographic recordings were used for neurophysiological testing of cortical (by single- and double-pulse TMS) and spinal (via tendon taps and electrical nerve stimulation) excitability. Results: Single-day rTMSQP application had no clear effect in the 2 subjects whose hand function was targeted, but improved walking speed in the person targeted for walking, accompanied by increased cortical excitability and reduced spinal excitability. All 3 subjects showed functional improvement following the 5-day rTMSQP intervention, an effect being even more pronounced after the five-day combined rTMSQP + exercise sessions. There were no rTMSQP-associated adverse effects. Conclusion: Our findings suggest a functional benefit of motor cortical rTMSQP after SCI. The effect of rTMSQP appears to be augmented when stimulation is accompanied by targeted exercises, warranting expansion of this pilot study to a larger subject population.

Innervation and function of rat tail muscles for modeling cauda equina injury and repair.

Introduction: The rat tail exhibits functional impairment after cauda equina injury. Our goal was to better understand the innervation and roles of muscles that control the tail. Methods: Adult rats received either: (1) ventral root injury; (2) caudales nerve injury; or (3) mapping of sacrococcygeal myotomes. Activation of small muscles within the tail itself (intrinsics) was compared with that of larger lumbosacral muscles acting on the tail (extrinsics). Behavioral testing of tail movement was done 1 week later. Results: Rats that received ventral root injury exhibited multiple behavioral deficits, whereas rats with injury to caudales nerves maintained more fully preserved tail movement. Mapping studies revealed much broader overlap of myotomes for extrinsic muscles. Conclusions: Extrinsic tail muscles play a greater role in tail movement in the rat than their intrinsic counterparts and are innervated by multiple neurological segments. These findings have major implications for future research on cauda equina injury. Muscle Nerve 52: 94–102, 2015

Recovery of human motoneurons during rotation

During prolonged contractions, few studies have reported rotation among low threshold motoneurons. The question arises whether a motoneuron stops firing due to an increase in firing threshold or whether it is due to regional switching of activity among muscle fascicles. We postulated that if the rest period resulted from an increase in firing threshold, a progressive recovery in the excitability of the motoneuron would be observed during the rest period. The excitability of soleus or tibialis anterior motoneurons was tested during the rest periods. The results showed that a previously tonic motoneuron that had dropped off during rotation, rarely responded to Ia or TMS inputs in the initial parts of the rest period; however, its response probability increased significantly in the second half. Based on these data, we suggest that the observed rotation is due to changes in firing thresholds of motoneurons during prolonged firing.

Intraoperative Neuromonitoring and Alarm Criteria for Judging MEP Responses to Transcranial Electric Stimulation: The Threshold-Level Method.

Summary: The motor evoked potential (MEP) is used in the operating room to gauge—and ultimately protect—the functional integrity of the corticospinal tract (CST). However, there is no consensus as to how to best interpret the MEP for maximizing its sensitivity and specificity to CST compromise. The most common way is to use criteria associated with response magnitude (response amplitude; waveform complexity, etc.). With this approach, should an MEP in response to a fixed stimulus intensity diminish below some predetermined cutoff, suggesting CST dysfunction, then the surgical team is warned. An alternative approach is to examine the minimum stimulus energy—the threshold—needed to elicit a minimal response from a given target muscle. Threshold increases could then be used as an alternative basis for evaluating CST functional integrity. As the original proponent of this Threshold-Level alarm criteria for MEP monitoring during surgery, I have been asked to summarize the basis for this method. In so doing, I have included justification for what might seem to be arbitrary recommendations. Special emphasis is placed on anesthetic considerations because these issues are especially important when weak stimulus intensities are called for. Finally, it is important to emphasize that all the alarm criteria currently in use for interpreting intraoperative MEPs have been shown to be effective for protecting CST axons during surgery. Although differences between approaches are more than academic, overall it is much better for patient welfare to be using some form of MEP monitoring than to use none at all, while you wait for consensus about alarm criteria to emerge.

Cauda equina repair in the rat: Part 3. Axonal regeneration across Schwann cell-Seeded collagen foam: Cauda Equina Repair in the Rat

Introduction: Treatments for patients with cauda equina injury are limited. Methods: In this study, we first used retrograde labeling to determine the relative contributions of cauda equina motor neurons to intrinsic and extrinsic rat tail muscles. Next, we transected cauda equina ventral roots and proceeded to bridge the proximal and distal stumps with either a type I collagen scaffold coated in laminin (CL) or a collagen–laminin scaffold that was also seeded with Schwann cells (CLSC). Regeneration was assessed by way of serial retrograde labeling. Results: After accounting for the axonal contributions to intrinsic vs. extrinsic tail muscles, we noted a higher degree of double labeling in the CLSC group (58.0 ± 39.6%) as compared with the CL group (27.8 ± 16.0%; P = 0.02), but not the control group (33.5 ± 18.2%; P = 0.10). Discussion: Our findings demonstrate the feasibility of using CLSCs in cauda equina injury repair. Muscle Nerve 57: E78–E84, 2018