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Tendon reflexes for predicting movement recovery

after acute spinal cord injury in humans

Blair Calancie

b,

*, Maria R. Molano

a

, James G. Broton

a a

The Miami Project to Cure Paralysis and Department of Neurological Surgery, University of Miami School of Medicine, Miami, FL, USA b

Department of Neurosurgery, SUNY’s Upstate Medical University, Syracuse, New York, USA

Accepted 25 April 2004 Available online 1 July 2004

Abstract

Objective: Use the tendon reflex to examine spinal cord excitability after acute spinal cord injury (SCI), relating excitability findings to prognosis.

Methods: We conducted repeated measures of reflex responses to mechanical taps at the patellar and Achilles tendons of the lower limbs, and the wrist flexor tendons of the upper limbs in persons with acute SCI, beginning as early as the day of injury. The single largest EMG response (peak-to-peak) for each site was recorded. Subjects were compared based on level of injury and final neurologic status of lower limb motor function (i.e. absence of any voluntary recruitment in a lower limb muscle: motor-complete; voluntary recruitment in 1 or more lower-limb muscles: motor-incomplete).

Results: We studied 229 subjects with acute SCI. Persons with injury to the cervical or thoracic spinal cord and who were (or became) motor-incomplete showed large tendon responses, even at the time of initial evaluation. In combination with larger tendon response amplitudes, the presence of the ‘crossed-adductor’ response to patellar tendon taps at the acute stage was highly predictive of functional motor recovery following SCI. In marked contrast, tendon responses were small (e.g.,0.1 mV) or absent in persons with acute, motor-complete injury (and which remained motor-motor-complete), and the crossed-adductor response was never seen. Reflex amplitudes and the incidence of the crossed-adductor response increased somewhat over time in persons with motor-complete SCI, but did not approach the values seen in motor-incomplete subjects.

Conclusions: Taken together, tendon response amplitude and reflex spread were sensitive and specific indicators of preserved supraspinal control over lower limb musculature in subjects with acute SCI. A simple algorithm using these outcome measures predicted a ‘motor-complete’ status with 100% accuracy, and a motor-incomplete status with accuracy exceeding 91%.

q2004 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved.

Keywords:Spinal cord injury; Human; Prognosis; Tendon reflex; EMG; Acute; Crossed-adductor response

1. Introduction

Severe spinal cord injury (SCI) results in a complete loss of motor and sensory function caudal to the injury site (i.e. category ‘A’ of the American Spinal Injury Association (ASIA) scheme (El Masry et al., 1996; Marino et al., 2003)). It also results in an immediate and prolonged depression of stretch reflex excitability in spinal segments lying caudal to the injury. The term ‘spinal shock’ refers to this condition, defined as a “… state of total abolition of all tendon reflexes and profound depression of other reflex activity below

the level of cord transection which immediately follows such a lesion…” ((Kuhn, 1950), and see (Guttmann, 1976)). A crucial element in Kuhn’s definition of spinal shock is the term ‘transection’, confirming a neurologically-com-plete injury to the spinal cord. Historically, the incidence of ‘complete’ SCI has been 50% or higher (Bracken et al., 1984, 1990; DeVivo, 2002). However, our own work and that of others suggests there is a trend towards increasing numbers of persons with acute, neurologically incomplete SCI (Calancie et al., 2004; National Spinal Cord Injury Statistical Center, 2000). Reflex properties in these cases of less severe SCI have received scant attention at the acute injury stage. It is logical, then, to determine whether such injury results in a profound depression of spinal reflexes at the acute stage comparable to that which occurs with

www.elsevier.com/locate/clinph

1388-2457/$30.00q2004 International Federation of Clinical Neurophysiology. Published by Elsevier Ireland Ltd. All rights reserved. doi:10.1016/j.clinph.2004.04.028

* Corresponding author. Tel.:þ1-315-464-9935; fax:þ1-315-464-9848.

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neurologically complete SCI. If not, then the absence of reflex depression after acute SCI should be associated with a better prognosis for recovery of neurologic function.

Numerous studies have addressed prognosis after SCI in humans, all of which rely heavily upon findings from clinical examinations (Burns et al., 2003; Crozier et al., 1991; Ditunno, 1999; Iseli et al., 1999; Kirshblum and O’Connor, 1998; Poynton et al., 1997; Waters et al., 1998; Wells and Nicosia, 1995). Studies using electrophysiologic approaches or reflex patterns for predicting neurologic recovery are much fewer in number, and most of these concentrate on subjects with complete injury (Curt and Dietz, 1999; Ko et al., 1999; Little et al., 1999; Rutz et al., 2000; Stauffer, 1975). Our goal in this study was to investigate changes in spinal cord reflex behavior in a large population of persons with acute SCI—including persons with incomplete injury—to see whether such testing could complement traditional clinical examination. Such testing might be especially valuable for examining the conse-quences of newly developed interventions designed to treat spinal cord injury, where the sensitivity of traditional testing might be limited for detecting subtle changes in cord function beyond measures of muscle strength and sensory perception (Burns and Ditunno, 2001; Fawcett, 1998). A related paper describes EMG recruitment patterns during recovery in the same sample population (Calancie et al., 2004).

2. Methods

All subject recruitment and examination was carried out at Miami’s Jackson Memorial Hospital, the only Level I Trauma Center in Dade County, FL. Only subjects capable of providing their own consent (for adults) and assent (for children) were recruited. We excluded persons with a diagnosis of traumatic brain injury, or those whose spinal cord dysfunction was due to disease (e.g. neoplasm; autoimmune disorder; chronic canal stenosis and myelo-pathy, etc.). Studies were initiated as early as 8 h following injury, but most subjects were first tested only after they had cleared the ‘Emergency Room’ stage and been admitted. After the initial evaluation, follow-up examinations were scheduled at weeks 1, 2, 4, 8, 12, 26, and 52 post-injury, with yearly examinations beyond this time. At the acute stage, studies were conducted at the subject’s bedside, with the subject lying supine in nearly all cases. The subject’s knee and hip were flexed before applying tendon taps, as described below. After a subject’s discharge, follow-up evaluations were done in a laboratory setting, usually with the subject seated in a dental chair or in his or her wheelchair. In the dental chair, subjects were usually partially reclined, with their hips and knees partially flexed. Subjects tested in their wheelchair were typically in a more traditional sitting posture. We frequently adjusted the inclination of the dental chair and (when possible)

the wheelchair during experiments, in order to minimize the risk of pressure ulceration of weight-bearing areas. Additional able-bodied (AB) subjects were recruited from hospital staff to serve as controls.

Self-adhesive electrodes (Medi-Trace S’Offset) were used to record electromyogram (EMG) from multiple upper- and lower-limb muscles, including wrist flexors (including flexor carpi radialis (FCR)); hip flexors (includ-ing psoas major (‘psoas’)); knee extensors (‘quads’—one lead over rectus femoris and the other over vastus lateralis); knee flexors (‘hams’ —leads placed medially to overlie semimembranosus and semitendinosus); and ankle plantar-flexors (including soleus). Details about the voluntary contraction stage of the study protocol are published elsewhere (Calancie et al., 2004).

EMG signals were preamplified adjacent to the electro-des, and further amplified (gain¼1 or 10 k; Intronix Technologies ‘2024F’) and filtered (100 Hz – 5 kHz), prior to being recorded on digital tape (Vetter ‘4000a’ or MicroData Instruments ‘DT-1600’; sampling rate not less than 2.5 kHz per channel) for later analysis. During acquisition, EMG was passed through audio mixers (Rane ‘RM 26’ or Roland ‘M-120’) for broadcast through a loudspeaker (Yamaha ‘MS 101’), and captured for visual display on a computer monitor (RC Electronics ‘Computer-scope’ or Cambridge Electronics Design ‘Power 1401’). A custom-made tendon hammer was used to deliver tendon taps. This device consisted of a 30 cm steel shaft, at the end of which was a hard plastic impactor mounted on a thin steel plate. The plate was connected to the shaft in a cantilevered manner; the non-fixed end of the plate rested against a micro-switch, which was closed by striking the impactor against a firm object. A 0.2 kg static load was sufficient to close the switch. The micro-switch was connected to a 9 V battery, which provided a voltage transient upon switch closure. This voltage transient was recorded along with EMG records on tape. The total weight of the tendon hammer was 0.5 kg.

Subjects were instructed to make a series of voluntary, isometric contractions of isolated muscles or muscle groups, beginning with left-side muscles. We previously showed a strong relationship between EMG magnitude and manual muscle test scores (Calancie et al., 2001b), allowing us to substitute EMG interference pattern for manual muscle test scores. These contractions also allowed us to stratify subjects into being ‘motor-complete’ (no voluntary con-traction in any lower-limb muscle) or ‘motor-incomplete’ (voluntary contraction in at least one lower-limb muscle; further details of this classification are published elsewhere (Calancie et al., 1999, 2004)).

After testing voluntary contractions, we tested reflex excitability with tendon taps applied to the patellar and Achilles tendons of the lower limbs, and wrist flexor tendons of the upper limbs. Both left- and right-side responses were tested at all 3 sites (knee, ankle, and wrist). Testing of tendon responses was done when

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the subjects were attempting to remain as relaxed as possible. Taps to the patellar and Achilles tendons were done with the knee and ankle positioned at approximately 908. For wrist taps, the forearm was supinated and held from below, with the wrist positioned in ,208 of extension. Between 3 and 5 brisk taps were applied to each site, with at least 3 s between each tap (faster tap rates lead to low-frequency depression of reflex responses (Calancie et al., 1993; Curtis and Eccles, 1960; Magladery et al., 1952; Thompson et al., 1992)). We tried to limit tap-related movement of electrode connecting wires (to minimize movement artifact), but this was not always successful. The same investigator applied tendon taps in most cases; further detail about the confounding risk of variability in applied taps can be found in Section 4.

Subjects were always asked whether or not taps were painful, and were given adequate time between taps to request that we discontinue further taps if pain was excessive. A few subjects injured due to a motor vehicle accident had lacerations of the shin or knee, causing us to sometimes apply less forceful taps during evaluations at the acute stage than we typically used (due to pain, if the subject had retained sensation), or to bypass tap application at that site altogether. In other cases, again at the most acute period following injury, EMG recording sites were sometimes inaccessible due to wound dressings or a limb cast.

Analysis was done offline, from the taped records. To reduce bias, analysis was done by one of the investigators (JGB) who had no interaction with the subjects being tested (i.e. he did not participate in any of the data collection sessions), and no first-hand knowledge of each subject’s neurologic status. Cursors were used to identify the evoked waveforms, limiting possible responses to a particular latency ‘window’ specific to each site of tendon tap. To be considered real, a questionable response needed to repeat at a comparable latency in at least one other trial. Based on peak-to-peak amplitude of the unrectified EMG waveform, the single largest response to each series of tendon taps was determined. Crossed-adductor responses were simply noted as being present or absent, and were not quantified with respect to amplitude. These responses showed considerable size variability from trial to trial, but routinely exceeded 20mV in amplitude. When present at all, they typically were present for each and every tap application, at latencies comparable to those of the ipsilateral patellar tendon response.

Tendon responses were compared between persons with motor-complete versus motor-incomplete injury (based on each subject’s final evaluation) after grouping subjects by region of injury (cervical, thoracic (T2 – T10), and thor-acolumbar (T11 – L5)). These comparisons were made at the acute stage (within 19 days of injury) and at the time of each subject’s final evaluation (a minimum of 4 weeks post-injury, but usually including data collected at much later times following injury, when subjects would typically be considered to have reached a ‘chronic’ stage). Testing of

tendon response amplitudes between groups was performed with ANOVA (Kruskal – Wallis One Way ANOVA on Ranks) followed by Dunn’s pairwise testing, when called for. The rank-based ANOVA was used because tendon response data did not have a normal distribution (i.e. multiple values of zero). Dunn’s test was used due to unequal sample sizes. Results of testing were considered significant forP-values less than .05.

3. Results

Results are based on findings from 229 subjects (40.0^17.5 years of age) with acute SCI. An additional 32 able-bodied subjects (37.2^10.4 years) were included for comparison of patellar and wrist tendon tap findings. The SCI population included 175 males and 54 females. The most common cause of injury was motor vehicle accident (43%), followed by falls (20%) and gunshot (11%). The most common level of spine fracture was at C5. Additional details about the subject population are contained in a separate report which addresses recovery of voluntary contractions in this subject population (Calancie et al., 2004). Results are stratified based on level of spine injury into ‘cervical’ (from C1 – T1, resulting in a ‘pure’ spinal cord injury), ‘thoracic’ (from T2 – T10, also a pure spinal cord injury), and ‘thoracolumbar’ (‘T/L’ from T11 to L5, considered tonotrepresent a pure spinal cord injury, due to the high likelihood of cauda equina involvement).

All subjects gave their informed consent (for adults) and assent (for children) to participate in this study, which was approved by the University of Miami’s Institutional Review Board. A total of 802 evaluations were carried out on subjects in the SCI cohort, and each AB subject was evaluated once. For our SCI subjects, more than 75% of the initial evaluations were conducted within 7 days of the subject’s injury. Fifteen of our 229 subjects (6.6%) were first examined 20 or more days following injury. Reasons for this late recruitment included transfer from another hospital, and medical complications requiring a prolonged period of sedation. These late-recruited subjects were excluded from group comparisons of acute reflex properties. A significant subsetðn¼77Þof our study population was studied only once after SCI, hence sample sizes for our ‘Final’ and ‘Later’ cohorts were almost always smaller than those for the initial measures. A relatively large proportion of our subject population (67%) was comprised of persons with neurologically-incomplete SCI at the time of initial evaluation (ASIA B¼5%; C¼24%; D¼31%; E¼7%). With few exceptions, deep tendon reflex testing at even the most acute stage following SCI revealed marked differences in reflex properties between motor-incomplete versus motor-complete subjects. Fig. 1 illustrates findings from a 24 year old female, injured by a fall 2 days prior to the date of testing. Her neurologic status was ASIA ‘C’ (i.e. she was ‘motor-incomplete’), weakness was evident in all four

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limbs, yet she had no radiologic evidence of spine injury. Panels A – C ofFig. 1illustrate the responses to single taps to wrist flexor (A), patellar (B), and Achilles (C) tendons for the subject’s left and right sides. Taps to flexor tendons at the wrist (1A) caused short-latency, large evoked responses in FCR muscles (asterisk depicts lower gain in this and subsequent traces). There was also ‘spread’ of responses to each of the biceps and triceps brachii muscles, and the ECR, none of which would be considered traditional agonists (or synergists) of the FCR group. Taps to this subject’s patellar (1B) and Achilles (1C) tendons caused large responses in homonymous muscle groups. Lower-limb taps also led to considerable spread (psoas and hamstring groups for patellar taps (1B); hamstring and tibialis anterior for Achilles taps (1C)). In contrast, tendon taps in persons who began (and remained) motor-complete after SCI showed small amplitudes at this acute stage, if a response was present at all, and there was no spread of activity (not shown).

Based on findings at the initial examination, Fig. 2 summarizes the average maximum EMG amplitude (peak-to-peak) of responses to taps at the patellar (panel A), Achilles (panel B) and wrist flexor tendons (panel C), and includes left- and right-side responses from each subject. This figure excludes data from the 15 late-recruited subjects mentioned above. Data are grouped by final neurologic status (motor-complete versus motor-incomplete, based on the latest determination for each subject) and site of spine injury. For purposes of comparison, data from able-bodied Fig. 1. EMG records from muscles indicated in response to single taps of

the wrist flexor tendons (A), patellar tendons (B) and Achilles tendons (C). Each panel shows responses to taps of the left-side (left) and right-side (right) tendons. The tap is applied at the onset of each trace. Data are from a 24 year old female with cervical injury 2 days previously, who has some lower limb voluntary muscle contractions, hence is categorized as ‘motor-incomplete’. Vertical calibration¼1 mV (10 mV for traces with an asterisk).

Fig. 2. Initial evaluation. Average (^standard error) amplitude of the maximum response (peak-to-peak) to taps at the tendon indicated (A, patella; B, Achilles; C, wrist flexor) for the initial evaluation (restricted to ,20 days post-injury) in subjects with injury to the cervical (Cerv), thoracic (Thor), or thoracolumbar spine (T/L). Within each panel, subjects are organized by their final neurologic status into ‘motor-complete’, ‘motor-incomplete’, and ‘able-bodied’ (AB). The sample size for each cohort is indicated at the top of each column. Note that left- and right-side responses from each subject are included.

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subjects for each of the 3 tendon tap sites are included. Each bar shows the standard error and sample size for that cohort. For taps to the patellar and Achilles tendons, reflex amplitudes were, on average, much larger in persons with motor-incomplete SCI (or who becamemotor-incomplete, based on findings from later evaluations) compared to subjects with injury that remained motor-complete, regard-less of the injury level (i.e. cervical, thoracic, or thoraco-lumbar). Table 1 shows that these differences were significant for persons with cervical or thoracic injury, but were non-significant for persons with thoracolumbar injury (note the very small sample size in persons with thoracolumbar, motor-complete SCI).

Responses to wrist flexor tendon taps (Fig. 2C) varied widely. Virtually all subjects with cervical and motor-complete SCI had very small to absent responses to wrist flexor tendon taps compared to subjects with motor-incomplete SCI; this difference was significant. Wrist flexor tendon tap responses in persons with thoracic, motor-complete SCI were much larger, on average, than in subjects with motor-incomplete injury at these levels, but variability of this measure was large, and this difference was not statistically significant. We did not test wrist flexor tendon responses in any of the small cohort of subjects with motor-complete injury to the thoracolumbar region of the spine.

Fig. 3 shows the same comparisons as were made in Fig. 2, but now illustrates the mean tendon response amplitudes at the time of the final evaluation for each subject. Average tendon reflex amplitudes grew for most groups, but the extent of increase tended to be larger for persons with motor-complete injury, consistent with their development of spasticity following injury. Nevertheless, the same relationship seen in Fig. 2 for acute injury was preserved for persons with cervical or thoracic injury tested at much later times: persons with motor-incomplete injury continued to have larger tendon response amplitudes, on average, than persons with motor-complete injury. From a statistical standpoint,Table 1(‘Final’ columns) shows these differences in persons with chronic injury paralleled those for persons with acute injury (‘Initial’ columns), with the sole exception that Achilles tendon taps in motor-complete subjects were no longer significantly smaller than those in motor-incomplete subjects.

For wrist flexor taps, reflex amplitudes at this late stage were larger in motor-incomplete subjects with cervical and thoracic injury compared to motor-complete subjects (Fig. 3C). Differences in these measures were significant for the cervical group, but non-significant for the thoracic and thoracolumbar groups (Table 1).

Note that forFig. 3, we excluded subjects in whom the duration of follow-up from their initial evaluation was very brief (,4 weeks). For most subjects in each of the 6 groups Table 1

Motor-complete versus motor-incomplete comparison of tendon tap response amplitudes at both initial (i.e. acute) and final (i.e. chronic) evaluations for subjects grouped by site of injury

Cervical Thoracic Thoracolumbar Site Initial Final Initial Final Initial Final

Patellar SIG SIG SIG SIG NS NS

Achilles SIG SIG SIG NS NS NS

Wrist SIG SIG NS NS – NS

SIG, significant difference; NS, non-significant difference.

Fig. 3. Final evaluation. Comparable to Fig. 2, except now presenting average tendon response amplitudes measured during each subject’s final evaluation. Data are limited to subjects whose final evaluation was at least 4 weeks following injury. The sample size for each cohort is indicated at the top of each column. The average number of weeks to final evaluation from the time of injury for the motor-complete category was 65, 57 and 96 weeks for subjects with cervical, thoracic, and thoracolumbar injury, respectively (range 4 – 168 weeks). The average number of weeks to final evaluation for the motor-incomplete category was 59, 59, and 53 weeks for subjects with cervical, thoracic, and thoracolumbar injury, respectively (range 4 – 264 weeks).

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examined (motor-complete or motor-incomplete; cervical, thoracic, or thoracolumbar injury), the average follow-up duration was much longer, exceeding one year in all 6 cases; only 5% of subjects contributing data toFig. 3had follow-up durations of only 4 weeks, and all but one of these had motor-incomplete SCI (i.e. reflex amplitudes already high, on average). Note also that many of the subjects contribut-ing data to Fig. 3were taking medications (typically oral baclofen) for managing spasticity at the time of this final evaluation, and we did not attempt to correct for this potential source of variability.

We compared tendon reflex amplitudes for initial versus final evaluations across the different subject groups. Responses to patellar taps showed no significant differences from early to late stages in either complete or motor-incomplete subjects (data not illustrated; statistical outcome of these comparisons in Table 2). Achilles tap responses grew significantly larger at the chronic stage in persons with motor-complete injury to the cervical or thoracic spine, and in persons with motor-incomplete injury to the cervical spine. Wrist tendon response amplitudes grew by significant amounts in persons with cervical injury, whether they were motor-complete or motor-incomplete.

Results to this point have emphasized differences in the absolute amplitude of tendon reflexes between subjects with motor-complete and motor-incomplete SCI, and how these differences persisted over time. These responses were elicited from the muscle whose tendon was tapped.

However, and specifically for taps to the patellar tendon, we saw many trials in which a short-latency contraction in one or more muscles of the contralateral thigh accompanied the ipsilateral quadriceps contraction, leading to a visible adduction of the contralateral thigh (i.e. the crossed-adductor response).

EMG-based examples of the crossed-adductor response to tap of the contralateral patellar tendon are shown inFig. 4. Data in this case were obtained from a 39 year old male who suffered a T9 fracture due to a fall 2 days previously. Taps to the left patellar tendon elicited large responses in his left-side thigh muscles (Fig. 4A, top 3 traces), along with small and large evoked responses in the contralateral psoas and hamstring groups, respectively (angled arrows ofFig. 4A). Fig. 4B shows EMG responses to a tap of this subject’s right-side patellar tendon. In this case, there was recruitment of the right-side (i.e. ipsilateral) psoas, quadriceps, and hamstring groups, as well as recruitment of the left-side (i.e. contralateral) thigh muscles (angled arrows in the upper 3 traces ofFig. 4B).

Fig. 5 summarizes the incidence of a positive crossed-adductor response across all subjects for both early (within the first 20 days;Fig. 5A) and later (.12 weeks;Fig. 5B) time-points following injury. Subjects have been grouped by injury level (cervical; thoracic; thoracolumbar) and their final neurologic status (motor-complete and motor-incom-plete). Crossed-adductor responses to patellar taps were common early after injury in persons with cervical or Table 2

Initial (i.e. acute) versus final (i.e. chronic) comparisons of tendon tap response amplitudes in motor-complete (M-Comp) and motor-incomplete (M-Incomp) subjects grouped by site of injury

Cervical Thoracic Thoracolumbar

M-Comp M-Incomp M-Comp M-Incomp M-Comp M-Incomp

Patellar NS NS NS NS NS NS

Achilles SIG SIG SIG NS NS NS

Wrist SIG SIG NS NS – NS

SIG, significant difference; NS, non-significant difference.

Fig. 4. EMG records following a single tap to the left patellar tendon (A) and the right patellar tendon (B) in a 39 year old male with T9 fracture secondary to a fall, injured 2 days prior to this initial recording session. A tap to the left patellar tendon caused large EMG responses in the subject’s psoas, quadriceps, and hamstring muscles on his left side (upper 3 traces of panel ‘A’), as well as responses in the contralateral psoas and hamstring groups (angled arrows of figure). A tap to the right patellar tendon (B) resulted in large responses in the right-side psoas, quadriceps, and hamstring muscles, and recruitment of all three thigh muscles of the contralateral (i.e. left-side) leg (angled arrows in upper 3 traces of ‘B’). The tap is applied at the onset of each trace. Vertical calibration¼1 mV (or 10 mV for traces with an asterisk).

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thoracic SCI who were (or became) motor-incomplete (incidence of 86 and 75%, respectively). In most of these subjects, both left- and right-side patellar taps elicited crossed-adductor responses. For persons with acute and motor-incomplete injury at thoracolumbar levels, the crossed-adductor response incidence was less common (43%). As shown to the right of Fig. 5A, the crossed-adductor response was present in 8 of the 32 able-bodied subjects tested (i.e. incidence¼25%). However, the response could be elicited from only one of the two tendons tapped (i.e. it was unilateral) in 7 of these 8 subjects.

In stark contrast to findings in subjects with motor-incomplete SCI, the crossed-adductor response to patellar tendon taps wasneverseen at the acute stage in persons who were (and remained) motor-complete (Fig. 5A). There were

no exceptions to this finding, whether a person’s injury was at the cervical, thoracic, or thoracolumbar spine.

Over time, the crossed-adductor response to patellar tendon taps showed only limited recovery in persons with motor-complete SCI, as shown inFig. 5B. It emerged in 5 such subjects with cervical injury (,21%), yet remained absent in all 11 subjects with thoracic injury. Little can be made of the changes in crossed-adductor response prob-ability amongst persons with motor-complete injury to the thoracolumbar spine, as our meager sample size of 3 subjects acutely had declined to only 2 subjects for later follow-up examinations (one of whom now showed a crossed-adductor response to patellar tendon taps).

Data for Fig. 5B include all follow-up evaluations conducted from a time-point of 12 or more weeks post-injury (average follow-up duration ranging from 64 to 141 weeks across all 6 subject categories for this figure). The 12 week minimum was chosen to represent a time when extensor spasticity becomes evident, even in persons with motor-complete SCI. To be considered ‘positive’, it was necessary to see the crossed-adductor response in only 1 follow-up evaluation beyond this 12 week period following injury (that is, a positive response was counted only once per subject for this figure). With this criterion, we are confident that we did not over-represent the incidence of the crossed-adductor response in the motor-complete popu-lation when tested at later times following injury; it remained low, even while ipsilateral tendon reflex ampli-tudes increased considerably, as illustrated inFig. 3.

For subjects with motor-incomplete SCI at the cervical or thoracic levels, the incidence of crossed-adductor responses at later stages following SCI was slightly higher than had been seen acutely. In fact there were only 3 subjects with motor-incomplete and cervical SCI who failed to ever demonstrate the crossed-adductor response when follow-up periods exceeded 12 weeks. Two of these subjects required ventilator support from the time of injury to the point of final follow-up examinations. In spite of this severe injury, both of these subjects recovered volitional recruitment of motor units in the abductor hallucis muscle of one foot. While this movement capability satisfied our criteria for a ‘motor-incomplete’ designation, there was literally no recovery of voluntary contraction in any of the remaining upper- or lower-limb muscles from which we routinely monitored EMG in these subjects.

Our findings indicate a combination of tendon tap amplitude and the presence or absence of the crossed adductor response may be related to the probability that a given subject might have or recover voluntary motor function in one or more lower limb muscles (i.e. be ‘motor-incomplete’) after SCI. Of particular interest is whether or not this relationship holds true at even the most acute stage after injury, at a time when a subject might not have any voluntary recruitment in lower limb muscles, but whom ultimately recovers some contraction ability. An example of such a case is shown inFig. 6, from a 51 year old Fig. 5. Probability of a crossed-adductor response being present to taps of

the patellar tendon for motor-complete, motor-incomplete, and able-bodied subjects. For SCI subjects, data are from the initial evaluation (A), and all evaluations at a post-injury time greater than 12 weeks (B). Incidence is based on the number of subjects tested, rather than the number of tendons tapped, hence each subject can count only once to these totals. A slight negative-going bar was used to signify an incidence of zero. The sample size for each subject cohort is indicated at the top of each column.

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male with a C4 fracture due to a motor vehicle accident. During his first evaluation (second day post-injury (0.3 weeks)), the subject was able to make a weak contraction in only his left wrist extensor and right biceps brachii muscle groups (left-most pies ofFig. 6A). The absence of voluntary contraction in any lower-limb muscle led to his designation as being ‘motor-complete’ at this time. During the same evaluation, responses to taps at the patellar and Achilles tendons were large and well defined bilaterally (left-most columns inFig. 6B). Finally, the crossed-adductor response

was present bilaterally during this initial evaluation (not shown).

Over the next 6 months, the subject recovered contrac-tion in multiple upper- and lower-limb muscles. During this same time period, his patellar reflex amplitudes tended to get smaller, whereas Achilles reflex amplitudes tended to get larger. The crossed-adductor response was present in one or both limbs throughout all of these evaluations. This subject took unassisted steps for the first time on the one-year anniversary of his injury.

Fig. 6. Data from a 51 year old male with C4 fracture due to a motor vehicle accident. (A) EMG scores (0, no contraction; 5, normal interference pattern) during voluntary contractions from 24 muscles, assessed at different times (weeks) post-injury. When depicted in this manner, each circle is divided into 5 ‘slices’. An EMG score of ‘0’ has no fill, an EMG score of ‘5’ leads to a completely filled pie, and scores of 1 – 4 are indicated by progressively more ‘slices’ being filled. During the initial evaluation (at 0.3 weeks), the subject was intubated and on ventilator support. He was able to make a minimal contraction in only 2 of the muscles being tested: left-side wrist extensors, and right-side biceps brachii. This contraction ability extended to additional upper limb muscles by the second evaluation (1.4 weeks post-injury), and now included his hamstring group in the lower limbs bilaterally, making this subject ‘motor-incomplete’. Further evaluations revealed additional muscles now being recruited, while muscles that were already under volitional control tended to show higher levels of recruitment. Note that the evaluation at 7.6 weeks was associated with a marked loss of lower limb contraction ability. The subject had pneumonia at this time, and felt weak and lethargic. (B) Maximal tendon response amplitude (mV) for each of the sites tested, during the same evaluations for which EMG scores from the upper portion of this Figure were derived. Note that even at the most acute stage, when this subject had minimal contraction in upper limbs and no lower limb voluntary contraction, tendon response amplitudes were all 0.5 mV or higher.

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To what extent can the combined use of crossed-adductor presence/absence and tendon reflex amplitude at the acute stage following SCI predict long-term lower limb contrac-tion ability (i.e. motor-complete versus motor-incomplete)? Fig. 7illustrates a simple algorithm that was developed to address this question. Based on results from initial examinations (i.e. subjects first examined within 20 days of injury),Table 3illustrates the accuracy of this algorithm when applied to all subjects in our sample.

The algorithm was 100% accurate in predicting those subjects who remained motor-complete throughout the follow-up evaluations, whether their injury was to the cervical, thoracic, or thoracolumbar region of the spine. The accuracy of this algorithm declined somewhat for predicting motor-incomplete subjects, but was still at or better than 86% for all such subjects regardless of injury level. The subject depicted inFig. 6 was one of 14 in our study who were initially motor-complete (no contractions in

either leg) for at least one evaluation post-injury, but whose tendon response properties accurately predicted their recovery of voluntary contraction in 1 or more lower-limb muscles. These subjects had ASIA classification of ‘A’ or ‘B’ at the initial evaluation following injury.

For the single largest cohort—subjects with motor-incomplete injury to the cervical spine—the algorithm shown in Fig. 7correctly predicted motor outcome for all but 5 of the 101 subjects tested. These 5 ‘exceptions’ either had retained lower limb contraction ability in 1 or more muscles at the initial evaluation ðn¼1Þ; or went on to recover some lower limb contraction ability at some later timeðn¼4Þ;yet had absent crossed-adductor responses and small or absent tendon response amplitudes during the initial (i.e. acute) evaluation. However, three subjects in this group had recovered tendon tap responses that exceeded the criteria for ‘motor-incomplete’ status by the time of the second evaluation (12, 11, and 16 days post-injury). The two remaining subjects of this ‘motor-incomplete’ group that never recovered larger tendon responses or the crossed-adductor response during our follow-up period recovered only minimal lower limb contraction (AbH on one side only) at 12 and 27 weeks post-injury. In other words, there was only scant evidence of retained supraspinal motor influence over their spinal cord caudal to the injury site.

4. Discussion

In persons with acute spinal cord injury, we found that a simple clinical examination of lower limb tendon reflexes revealed dramatic differences between subjects with respect to injury severity and (presumably) long-tract sparing. Patellar tendon response amplitudes in subjects with motor-complete SCI were much smaller, on average, than those from able-bodied subjects during the initial evaluation. Tendon response amplitudes within the motor-complete group only gradually recovered over the ensuing weeks, but were still below AB mean values for taps to the patellar (0.69 mV) and Achilles tendons (3.2 mV) at one year or more post-injury. Our findings are consistent with many other reports of diminished lumbosacral reflexes after severe SCI in humans (Ashby et al., 1974; Calancie et al., 1993; Hiersemenzel et al., 2000; Ko et al., 1999; Leis et al., 1996; Little and Halar, 1985) and higher mammals (Barnes et al., 1962; Fulton et al., 1930; Hunt et al., 1963; McCouch et al., 1971; Weaver et al., 1963), a condition termed spinal shock. We also found that this depression of tendon reflexes extended to the upper limbs in our subjects with neurologically complete injury at the cervical spinal cord. Without stratifying by cervical injury level, though, at least some of this drop could be due to injury to the cervical spinal roots (afferent and efferent) and gray matter mediating this reflex (Berman et al., 1996; Curt and Dietz, 1996; Doherty et al., 2002; Jimenez et al., 2000; Mulcahey et al., 1999; Peckham et al., 1976).

Table 3

Results from application ofFig. 7algorithm for prediction of voluntary contraction in one or more lower limb muscles (i.e. motor-complete versus motor-incomplete) in subjects with acute SCI (limited to initial evaluations ,20 days post-injury)

Category Prediction accuracy (%) Sample size

Cervical, motor-complete 100 40 Thoracic, motor-complete 100 13 Thoracolumbar, motor-complete 100 3 Cervical, motor-incomplete 94 101 Thoracic, motor-incomplete 90 20 Thoracolumbar, motor-incomplete 86 36 Fig. 7. Flowchart for predicting whether or not a subject will have (or recover) voluntary recruitment of at least one lower limb muscle (i.e. be ‘motor-incomplete’) following acute traumatic spinal cord injury. The crossed-adductor response is scored as being either ‘present’ or ‘absent’. Four tendon response amplitudes are evaluated: the left- and right-side patellar responses, and the left- and right-side Achilles responses. If the peak-to-peak amplitude of any 2 of these tendon responses exceeds 0.1 mV at the acute stage, or if the amplitude of any one response exceeds 0.2 mV during this initial evaluation, the subject is predicted to be (or become) ‘motor-incomplete’. In the absence of a crossed-adductor response to taps on either side, and uniformly low-amplitude tendon tap responses, the subject is predicted to remain ‘motor-complete’.

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4.1. Spinal shock

Spinal shock may be due to: (1) a withdrawal of tonic supraspinal facilitation (Chambers et al., 1966; Guttmann, 1970, 1976; Liddell, 1934; Sherrington and Laslett, 1903) and motoneuron hyperpolarization (Barnes et al., 1962; Leis et al., 1996; Schadt and Barnes, 1980); (2) an increase in presynaptic inhibition (Ashby et al., 1974; Ashby and Verrier, 1976; Calancie et al., 1993; Quevedo et al., 1993); or (3) a reduction in fusimotor output to spindle afferents (Barnes, 1964; Gilman et al., 1971; Leis et al., 1996; Weaver et al., 1963; Wolpaw and Lee, 1987), although this last possibility has been challenged (Burke, 1983; Burke et al., 1981; Hunt et al., 1963). Regardless of mechanism, virtually all studies agree that tendon reflexes are depressed after acute, neurologically complete SCI in humans. It is more difficult to establish consensus regarding other lumbosacral reflexes following SCI. One investigator’s interpretation of a present bulbocavernosus reflex (BCR) in persons with complete injury was that this signified the end of spinal shock, and stated that “…in 99% of our patients the bulbocavernosus reflex returned within 24 h.” (Stauffer, 1975). This conclusion is unique, in that many other investigators have stated that spinal shock may persist for weeks or months following severe SCI in man (Ashby et al., 1974; Calancie et al., 1993; Hiersemenzel et al., 2000; Ko et al., 1999).

Confusion about when spinal shock ends after SCI is not helped by a consideration of reflexes other than the tendon reflex. Significant differences were noted in the pattern of tendon and H-reflex recovery compared to F-wave persist-ence after acute SCI (Hiersemenzel et al., 2000). Wide-spread differences in the recovery pattern of the BCR, cremasteric, tendon jerk, and ‘delayed plantar response’ were found in persons with acute SCI (complete or incomplete), prompting Ko, Ditunno and colleagues to call for “…a reconsideration of the term spinal shock…” (page 408), suggesting that the term be ‘discarded’ altogether (Ko et al., 1999).

With a less comprehensive protocol for assessing reflexes after SCI, we are unable to support the suggestion of Ko et al. that the term ‘spinal shock’ be abandoned altogether, since it adequately describes a state of diminished or absent tendon reflexes in persons with acute and neurologically complete SCI. However, we agree that this term fails to accurately capture the state of other lumbosacral reflexes in persons with complete injury, and it certainly fails to accurately predict the state of tendon reflexes—which we found to be anything but depressed—in most persons with acute and neurologicallyincompleteSCI. 4.2. Incomplete SCI and hyperreflexia

Persons with acute, incomplete SCI did not demonstrate signs of spinal shock, at least within the time period in which our initial assessments were made (the majority of

initial evaluations were done within 5 days of injury; 10 of these subjects were first tested within 24 h of their spinal cord injury; further details on the times of testing following injury are published elsewhere (Calancie et al., 2004)). Moreover, these large responses persisted at more chronic stages after injury.

At a more chronic stage, persons with incomplete SCI tend to have enhanced spinal cord excitability, characterized by frequent spasms, enlarged tendon response amplitudes, and recruitment of heteronymous muscles (i.e. ‘spread’) following tendon taps, compared to subjects with complete injury (Hiersemenzel et al., 2000; Maynard et al., 1990). Surprisingly few investigations have examined reflex properties after acute SCI in persons with incomplete injury. In one such study, deep tendon reflexes were noted to be ‘present’ at 2 – 3 days post-injury in 100% of the ASIA ‘D’ subjects, and 75% of the ASIA ‘B’ and ‘C’ subjects (Ko et al., 1999), but response magnitudes were not quantified. Leis and colleagues reported that 4 of the 14 subjects they studied after acute SCI did not show signs of ‘spinal shock’, including the 2 subjects with incomplete (ASIA ‘C’ and ‘D’) status (Leis et al., 1996). Based on our own findings, we think it likely that the two ASIA ‘A’ subjects in that study (Leis et al., 1996) who demonstrated tendon reflexes acutely would have evolved to a motor-incomplete status (ASIA ‘C’ or ‘D’) had a longer follow-up time been utilized. Tator and Rowed wrote that spinal shock varied with injury severity, and might last only minutes to hours in ‘slight’ injuries, but these authors did not elaborate (Tator and Rowed, 1979). 4.3. Corticospinal tract and hyperreflexia

Lateral corticospinal tract fibers originating from upper motoneurons are thought to be responsible for voluntary contraction of both upper and lower limb muscles in the highest primates and man (Burke and Hicks, 1998; Calancie et al., 2001a; Fetz et al., 1976; Jankowska et al., 1975; Kothbauer et al., 1997; Maertens de Noordhout et al., 1999; Olivier et al., 2001; Pechstein et al., 1992; Petersen et al., 2003). Further support for the critical role of corticospinal tract fibers and voluntary movement comes from compari-sons between spinal tract degeneration and movement deficits following selective myelotomy for managing intractable pain in humans (Nathan, 1994). Axons within the lateral corticospinal tracts in humans are especially vulnerable to trauma, based upon histologic findings after relatively mild spinal cord injury resulting in the central cord syndrome (CCS) (Quencer et al., 1992). In an earlier study of subjects with chronic CCS, we showed that evoked motor responses to transcranial magnetic stimulation of motor cortex resulted in delayed EMG response latencies to both upper and lower limb muscles, indicating persistent abnormal conduction within corticospinal tract fibers despite clinical recovery (Alexeeva et al., 1997).

A number of subjects in the present study had symptoms and recovery consistent with the CCS. Overall motor

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recovery in these subjects was typically high, but movement and reflex abnormalities were common (records forFig. 1 were from a subject with CCS), and crossed-adductor responses persisted throughout the follow-up period in each of these subjects.

The close association between slowed central motor conduction and weakness in these individuals, the high likelihood that this weakness was due specifically to corticospinal tract injury, and their hyperreflexia suggest that corticospinal tract (CST) axons play an important role in mediating spinal cord excitability. Indirect evidence supporting this conclusion derives from the high percentage of CST fibers terminating in the intermediate gray and dorsal horn of the mammalian spinal cord (Davidoff, 1990; Phillips and Porter, 1977), implicating these fibers in the modulation of interneuronal excitability (Fetz et al., 2002) and task-specific modulation of segmental reflexes (Capa-day and Stein, 1986; Dietz and Duysens, 2000; Petersen et al., 2003).

4.4. Crossed-adductor response and hyperreflexia

The presence of the crossed-adductor response is typically thought to reflect upper motoneuron (i.e. corti-cospinal tract) damage, as manifest by spinal cord hyperreflexia secondary to chronic spinal myelopathy (Lance and De Gail, 1965). Hyperreflexia and ‘spread’ have been associated with corticospinal damage at a more chronic stage following injury (Teasdall and Van Den, 1981), but we could find no mention of an association between the crossed-adductor response and prognosis in subjects with acute SCI. Subjects in the present study had experienced varying degrees of acute trauma to their spinal cord. The remarkable irony, then, is that the presence of this response amongst these subjects after acute SCI was also strongly predictive of retention or recovery of some volitional movement within lower limb muscles. While the presence of the crossed-adductor response is therefore considered a ‘bad’ sign in the Neurology literature, in this study it successfully predicted the integrity of some supraspinal motor axons (probably within the corticospinal tract) spanning the injury’s epicenter after acute SCI, even in cases when the subject was, for the time-being at least, motor-complete.

Most persons with motor-incomplete SCI showed the crossed-adductor response at the earliest time-points tested (including all 10 such subjects first examined within 24 h of injury). This suggests that this reflex is ‘hard-wired’ in all subjects. Indeed, we saw the crossed-adductor response in 25% of the able-bodied subjects tested, although the probability of seeing this response to taps of both left- and right-side patellar tendons in each subject was low.

Each of the 5 motor-incomplete subjects who did not show the crossed-adductor response during the initial evaluation was receiving narcotics for pain management, and these agents are known to depress spinal cord

excitability (Chabal et al., 1992). The prevalence of the crossed-adductor response was much lower in able-bodied subjects, but still was higher than that for motor-complete subjects at the acute stage (i.e. prevalence of ‘0’). It is also worth noting that only a small number of motor-complete subjects developed the crossed-adductor response at some later time, even when looking 12 or more months post-injury. Its presence acutely therefore appears to depend upon a combination of ‘some’ cord injury, but not ‘too much’ cord injury.

We encountered two subjects whose findings could not be fully reconciled with those from our other subjects. These subjects were initially motor-complete, and over the next few months converted to a ‘motor-incomplete’ status. Both were totally reliant upon mechanical ventilation throughout the follow-up period. Neither subject indicated any sparing of sensation at any level caudal to their cord injury. Despite this evidence of severe cord injury, each recovered the ability to volitionally recruit motor units in an intrinsic muscle in the foot (abductor hallucis), but contraction never recovered in any of the 23 remaining upper and lower limb muscles and muscle groups being monitored. It is interest-ing to note that both subjects had tendon response properties virtually indistinguishable from those with motor-complete injury. That is, reflex amplitudes were markedly attenuated (relative to AB subjects) in both subjects following injury and stayed so throughout the follow-up period, and we never saw a crossed-adductor response following taps to either patellar tendon. Thus in these two subjects with only minimal motor recovery, evidence of axonal continuity across the injury epicenter came from preserved volitional motor function, rather than signs of exaggerated reflex properties.

4.5. Study limitations

A weakness of the present study lies in our use of a manual hammer for delivering tendon taps, potentially introducing variability in the afferent input from trial to trial, and from subject to subject. Ideally, we would have fixed the subject’s lower limb in a motion-stabilizing apparatus and delivered tendon percussions from a rigid, servo-controlled impactor (e.g. Ling Dynamic Systems Model 200). While such an arrangement might have been feasible in the chronic or sub-acute phase following SCI, it was virtually impossible to implement in the acute stage after injury, where subjects were almost always supine on a bedframe, and many had cervical traction applied through tongs fixed to the skull. In other words, subjects were usually tested in the supine position in the first few days and weeks following injury, and in the sitting position at later times. This reveals another potential weakness of the study, in that posture has been shown to influence spinal reflex behavior (Aiello et al., 1992; Chan and Kearney, 1984; Paquet and Hui-Chan, 1997; Perez and Field-Fote, 2003).

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When considering these weaknesses in study design, two points are relevant. First, we attempted to maintain consistency in tendon tap delivery by having the same author (BC) apply the taps whenever possible; this was the case for 829 of the 834 evaluations carried out in this study (i.e..99%). As much as possible, he attempted to apply a comparable tap from trial to trial (with the exceptions as noted earlier). Second, there was nothing we could do about subject positioning during evaluations in the acute stage. Since tendon tap testing made up only a fraction of our entire protocol, even if we had been able to test subjects in the same posture from trial to trial, with limbs rigidly fixed, we would have been unable to carry out additional measures due to limitations of time. These time constraints were especially common during the acute phase, when many other requirements for medical management were ongoing. Because we repeated examinations on the same subjects at all phases following injury, though, we do not believe that the difference in posture introduces as much variability as would have been the case had we made comparisons between entirely different populations of subjects at acute versus chronic stages following injury.

Finally, two conditions associated with chronic SCI may have contributed to differences across all subject categories when comparing findings in acute to those in chronic groups. First, pain (both neuropathic and musculoskeletal) may influence reflex properties, and different forms of this pain are more likely at acute (e.g. trauma-related) and chronic (e.g. musculo-skeletal pain due to overuse syn-dromes; neuropathic pain due to deafferentation) stages following injury (Bockenek and Stewart, 2002). Secondly, atrophy in muscle groups left paretic by the injury may diminish the amplitude of an evoked compound muscle action potential, without influencing the proportion of motoneurons within that muscle’s motoneuron pool recruited by the excitatory input.

4.6. Significance

There have been numerous attempts to relate preser-vation of sensory or motor function after acute SCI with the prospect for motor recovery (Burns et al., 2003; Ditunno, 1999; Waters et al., 1998). Almost without exception, though, these reviews concentrate on persons with motor-complete injury at the time of initial assessment. Fortu-nately, the incidence of motor-complete SCI appears to be declining (National Spinal Cord Injury Statistical Center, 2000), yet persons with motor-incomplete SCI may still have profound neurologic deficits for which there remain no proven and effective therapies. Therefore new investiga-tional strategies now being contemplated for treating persons with complete SCI (Burns et al., 2003; Geller and Fawcett, 2002) may also be applicable to persons with motor-incomplete SCI, provided certain questions about the natural time-course of movement and reflex recovery in this population can be established.

Our premise is that certain electrophysiologic ‘markers’ of spinal cord function—particularly at the acute stage after injury—may improve upon or expand our ability to predict long-term outcome beyond that afforded by more traditional clinical examinations (e.g. ASIA examination (Marino et al., 2003)). We are not suggesting that this form of testing should replace a careful neurologic examination of function after injury, but rather it should complement such testing when subtle changes in spinal cord function may occur.

Results from the present study were reliant upon recordings of multiple EMG channels; this approach may not be called for during routine medical management after SCI, but may have merit for studies requiring greater sensitivity than provided by traditional clinical evaluations. With this approach, we showed that a combination of tendon tap reflex magnitudes and the presence or absence of the crossed-adductor response is 100% accurate in predicting an absence of any lower-limb motor recovery (i.e. whether a subject will remain motor-complete). Clearly this prediction does not have a strong functional value, such as would be the case for predictions of walking capability, for example (Crozier et al., 1991; Daverat et al., 1988; Waters et al., 1989). However, this information can nevertheless be of considerable value for providing a very early indication of whether or not there are any intact motor axons of supraspinal origin traversing a person’s spinal cord injury site, especially in those cases in which subjects appear to be neurologically complete and/or are unable to cooperate with a traditional sensorimotor examination of neurologic function. As we move towards clinical inter-ventions which depend upon reliable and early information about the state of a subject’s spinal cord function, results of these additional tests may be especially valuable for subject selection, and may serve as outcome measures in their own right.

Acknowledgements

This work was supported in part by grants from the National Institutes of Health (NS28059, HD31240, NS36542), by The Miami Project to Cure Paralysis, and by the State University of New York.

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