THE NEUROLOGIC LEVEL after spinal cord injury (SCI)

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1 389 Recovery of Upper-Extremity Strength in Complete and Incomplete Tetraplegia: A Multicenter Study John F. Ditunno, Jr., MD, Michelle E. Cohen, PhD, Walter W. Hauck, PhD, Amie B. Jackson, MD, Marca L. Sipski, MD ABSTRACT. Ditunno JF Jr, Cohen ME, Hauck WW, Jackson AB, Sipski ML. Recovery of upper-extremity strength in complete and incomplete tetraplegia: a multicenter study. Arch Phys Med Rehabil 2000;81: Objective: To examine upper-extremity motor recovery of subjects with tetraplegia with both complete and incomplete injuries, to predict which patients and at what time they would recover a motor level. Design: Prospective, multicenter clinical study of upperextremity motor recovery in subjects with acute traumatic spinal cord injury. Setting: Three regional spinal cord injury centers. Subjects: One hundred sixty-seven individuals with acute traumatic tetraplegia (144 males [86%], and 23 females [14%]) between the ages of 15 and 75 years (mean age, 35.5 yrs). Methods: Subjects were examined and classified using sequential manual muscle tests performed on admission, 72 hours, 1, 2, and 3 weeks, and 1, 2, 3, 6, 12, 18, and 24 months postinjury. C5 biceps, C6 extensor carpi radialis, C7 triceps, and C8 flexor digitorum profundus were evaluated using a 0 5 scale. Analyses of the right motor levels used a series of logistic regression models, and for multiple measurements on each subject, models were estimated using generalized estimating equations. Results: The analysis for recovery of the biceps for the C4 group showed 70% of complete compared with 90% of incomplete injuries recovered ( p.001); of the extensor carpi radialis in the C5 group, 75% complete and 90% incomplete recovered ( p.002); and of the triceps in the C6 group, 85% of complete and 90% of incomplete injuries recovered ( p.16). Conclusion: Predicting future potential for upper-extremity motor recovery and for independence in self-care in groups of patients at a specific motor level is possible within the first week of injury. Key Words: Spinal cord injuries; Tetraplegia; Self-care; Arm; Motor activity. From the Department of Rehabilitation Medicine (Dr. Ditunno), the Department of Occupational Therapy, College of Health Professions (Dr. Cohen), and the Department of Clinical Pharmacology (Dr. Hauck), Thomas Jefferson University, Philadelphia, PA; University of Alabama at Birmingham, Birmingham, AL (Dr. Jackson); and the Kessler Institute for Rehabilitation, West Orange, NJ (Dr. Sipski). Submitted for publication February 18, Accepted in revised form July 19, Supported in part by Regional Spinal Cord Injury Center of Delaware Valley Model SCI Systems grant H133N50021 to Thomas Jefferson University from the National Institute on Disability and Rehabilitation Research. No commercial party having a direct financial interest in the results of the research supporting this article has or will confer a benefit upon the authors or upon any organization with which the authors are associated. Reprint requests to John F. Ditunno, Jr., MD, Department of Rehabilitation Medicine, Regional Spinal Cord Injury Center of Delaware Valley, Thomas Jefferson University Hospital, South 10th Street, Suite 375, Main Building, Philadelphia, PA by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation /00/ $3.00/0 doi: /mr by the American Congress of Rehabilitation Medicine and the American Academy of Physical Medicine and Rehabilitation THE NEUROLOGIC LEVEL after spinal cord injury (SCI) to the cervical area is the major factor that determines independence in self-care. 1-3 The ability to predict this recovery and function in the days immediately after injury has become increasingly important in rehabilitation planning. Patients and their families wish to know how much recovery and function, and the medical/rehabilitation staff must know, to set goals with their patients, and insurance companies require justification for payment for rehabilitation services. In addition to the need for early prognosis, the extent and the duration of the recovery is important for planning longer-term interventions such as the use of neuroenhancing agents, 4,5 muscle transfers, 6 and functional electrical stimulation systems. 7 In recent years, several studies 8-14 have examined the rate and extent of recovery of neurologic function after SCI. Although most of the studies reported results from a single center and, therefore, a limited number of patients, one multicenter study 11 from 4 SCI centers reported on 150 subjects with complete tetraplegia. This latter study did not use a mathematical model and could not predict recovery of strength for discrete motor levels within the first week of injury. In fact, the use of mathematical models has been limited, 14,15 and only one has been used in motor recovery for the upper extremities. 14 Several multicenter studies have correlated the neurologic level 16 or motor scores 17 with self-care function. In cervical injuries, however, the single neurologic level is determined by the sensory level approximately 50% of the time, and the motor level determines the remainder. 18 It is the motor level, however, that best correlates with self-care function, and it has been shown to be superior to the single neurologic level. 19 In fact, in a recent report, 20 early prediction of neurologic recovery correlated with function for SCI has been emphasized as a rehabilitation imperative for purposes of health care planning. It is for these reasons that we chose to perform the following multicenter study using a mathematical model. The purpose of the study, therefore, was to examine the recovery of muscle strength of the upper extremities of subjects with tetraplegia with both complete and incomplete injuries, to predict which patients and at what time they would recover a motor level. The hypothesis was that incomplete injuries would recover a function level (3/5 muscle strength or greater) of the impaired muscles sooner and in a higher percentage than complete injuries. METHODS Subjects The subjects in this study were patients admitted within 1 week of injury to 1 of 3 model SCI centers from September 1990 to September Individuals were included in the study if they had complete or incomplete injuries (American Spinal Injury Association [ASIA] grades A to D) at neurologic levels C4 to C8 and consented to participate in the study. Patients were

2 390 RECOVERY OF UPPER-EXTREMITY STRENGTH, Ditunno excluded from the study if their concomitant injuries or diseases during the acute phase of injury made classification of the spinal cord difficult (ie, fractures of the extremities, brain injury, or preexisting neurologic disorders). One hundred sixty-seven individuals with acute traumatic tetraplegia (144 males [86%], and 23 females [14%]) between the ages of 15 and 75 years (mean age, 35.5 yrs) served as the subjects in this study. Over one third of the injuries were caused by vehicular crashes (30.4% automobile, 3.1% motorcycle, 0.4% other vehicles), 20.5% were the result of falls, 17.4% resulted from violence (11.8% gun shots, 3.7% person-toperson contact, 1.9% other penetrating wounds), 13.7% resulted from diving accidents, and 12.3% stemmed from other causes. The lead center provided 121 subjects, Center A 29 subjects, and Center B 17 subjects. Procedures All subjects were examined and classified using the ASIA Standards. 21 Subjects had sequential manual muscle tests performed on admission, 72 hours, 1, 2, and 3 weeks, and 1, 2, 3, 6, 12, 18, and 24 months postinjury. Upper-extremity muscles (C5 biceps, C6 extensor carpi radialis, C7 triceps, and C8 flexor digitorum profundus) were evaluated using a scale of 0to5. 21 Several examiners performed the sequential examinations, and interrater reliability was analyzed separately for each center. Weighted Kappa s between.64 and.99 showed substantial agreement between the examiners. The lead center was responsible for storing, verifying (the process of checking for discrepancies and coding errors), and analyzing all data. An investigator from each center or a designee was responsible for the accuracy of all data submission. Data Analysis Subjects injuries were classified separately for right and left motor levels at C4, C5, and C6. This classification was based on the ASIA standards in which the C4 motor level was determined by a sensory level at C4 and a biceps at grade 0 to 2/5. The C5, C6, and C7 motor levels were determined based on the respective key muscles of the biceps, wrist extensors, and Table 1: Classification of Subjects by Level and Grade of Injury Level ASIA Grade A B C D Total C C C Total triceps, which tested grade 3/5 or greater provided the level above was normal. The data were analyzed to determine the percentage of key muscles for the motor levels C5, C6, and C7 that recovered from a grade 0 to 2/5 to a grade 3/5 or greater at each evaluation period. Preliminary analyses were performed to determine if there were significant differences between the right and left motor levels in the percentage of key muscle recovery at each evaluation period. McNemars analyses showed no differences between the right and left motor levels for the percentage of recovered key muscles (C4, C5, and C6) in complete (A and B) or incomplete (C and D). Subsequent analyses of the right motor levels were performed using a series of logistic regression models. To accommodate for multiple measurements on each subject, the models were estimated using generalized estimating equations (GEE). 22 The method of fractional polynomials 23 was used to fit smooth curves for the proportion of key muscles recovered over time. An advantage of the fractional polynomials is that they show fewer artifact bends than standard polynomials in regression models. However, using fractional polynomials to approximate an asymptote over time results in fitted curves, which bend slightly downward at the later time periods. This is an artifact; the curves should be thought of as flat. All curves shown include linear and square-root terms for time in months and a term for ASIA impairment grade. RESULTS Of the 167 subjects in this study (table 1), 40 were classified as having injuries at the C4 right motor level (16.2% [27] A and Fig 1. Recovery of right biceps muscles (%) in subjects classified as C4 right motor level. Percentage of subjects (, motor complete;, motor incomplete) whose biceps muscles recovered to grade 3/5 over time postinjury. The curves represent recovery models generated by GEE analyses.

3 RECOVERY OF UPPER-EXTREMITY STRENGTH, Ditunno 391 Fig 2. Recovery of right wrist muscle (%) in subjects classified as C5 right motor level. Percentage of subjects (, motor complete;, motor incomplete) whose wrist muscles recovered to grade 3/5 over time postinjury. The curves represent recovery models generated by GEE analyses. B and 7.8% [13] C and D), 90 at the C5 right motor level (37.7% [63] A and B, and 6.2% [27] C and D), and 37 at the C6 right motor level (13.1% [22] A and B, and 9% [15] C and D). Figures 1, 2, and 3, show the actual percentage of key muscles recovered at each of the 11 evaluation periods (72 hours to 24 months postinjury) and the fitted model for complete (A and B) and incomplete (C and D) C4, C5, and C6 right motor levels. In all 3 cases (C4, C5, C6), there were no important or statistically significant interactions between time and ASIA grade. All 3 cases, however, had significant nonlinear trends in recovery (figs 1 and 2, p.01; fig 3, p.05). The analysis for recovery of the biceps from a grade 0 2/5 (C4 motor level) to a grade 3/5 or better (C5 motor level) for the C4 group (fig 1) showed that although both the incomplete and the complete injuries recovered over time, there were significant differences between the complete and incomplete injuries in the proportion of key muscles that recovered ( p.001). Approximately 70% of complete injuries recovered, compared with 90% of incomplete injuries. Analysis for recovery of the extensor carpi radialis from a grade 0 to 2/5 (C5 motor level) to a grade 3/5 or better (C6 motor level) in the C5 group (fig 2) showed the same overall recovery trend with significant differences between the complete and incomplete injuries in the proportion of key muscles that recovered (approximately 75% complete and 90% incomplete recovered, p.002). Although analyses for recovery of the triceps in the C6 group (fig 3) Fig 3. Recovery of right triceps muscles (%) in subjects classified as C6 right motor level. Percentage of subjects (, motor complete;, motor incomplete) whose triceps muscles recovered to grade 3/5 over time postinjury. The curves represent recovery models generated by GEE analyses.

4 392 RECOVERY OF UPPER-EXTREMITY STRENGTH, Ditunno showed significant overall recovery, there was no significant difference between the complete and incomplete injuries in the proportion of key muscles that recovered to a grade 3/5 or better (approximately 85% of complete injuries and 90% of incomplete injuries recovered, p.16). DISCUSSION Incomplete injuries of the cervical spinal cord recover to a greater extent than complete injuries, a finding that has been reported previously in a large study from the Model SCI Systems 16 and multicenter drug trials. 17,24 Our hypothesis is that the recovery of nonfunctional muscles to a functional level in the area of injury to the cervical spinal cord in incomplete injuries occurs to a greater extent and sooner compared with complete injuries, and this is supported by the results. The recovery patterns show that in figures 1 and 2, 90% or more of patients with an incomplete injury at the C4 and C5 levels will gain a neurologic level, and this is significantly improved over complete lesions, whereas the improvement at C6 (fig 3), while better, is not statistically significant. This difference in outcome at different levels has not been previously reported because of limited sample size and the method of analysis. However, these results represent recovery of patients from 3 model system centers, with the same phases of rehabilitation care. Although we showed a significant difference in motor recovery between complete and incomplete injuries in an earlier study, the sample size was smaller, limited to one center, and was only carried out to 2 months. 9 Another report 13 on motor recovery in incomplete tetraplegia compared the subjects to a previous report 12 of complete tetraplegia over a 2-year period and indicated the recovery was twice as great. The initial observational point was 30 days compared with 7 days, however, and also differs because of the use of motor scores rather than motor levels, which makes comparison with our study difficult. Although we have not analyzed the results in this study to determine the extent of recovery above grade 3, the muscles, which recovered sooner in a previous study, 11 also recovered to grade 4 or 5. In addition, we did not analyze our data for change in motor scores, so our results cannot be compared with those of recent drug trials. 17,24 Analysis of changes in aggregate motor scores in incomplete lesions, however, presents a problem as pointed out by Holford and Bracken, 15 because the improvement in the total motor score may reflect both upper- and lower-extremity improvement. Although Marino 25 has compared upper-extremity motor scores and neurologic levels to self-care function in complete injuries and showed a good correlation, there has been no effort to equate specific motor scores with specific activities of daily living. Neurologic levels, on the other hand, have been used by rehabilitation clinicians for over 40 years 1 and are the most frequently cited impairment level when discussing potential self-care function. Although considerable variance has been reported over the years, much of this has been due to lack of precision in the definition of levels, such as the distinction between motor levels and the single neurologic level, and the self-care instruments. 26 Welch s study 3 on the comparison of the C6 and C7 levels using the ASIA neurologic standards and Weingarden s report 27 on the decline of independence in self-care are illustrations of the importance of correlating self-care with neurologic levels. In the former study, the advantages of becoming independent in self-care were demonstrated in patients with a C7 neurologic level. Based on this, 80% to 90% of patients with an initial C6 level and nonfunctional triceps in our study should achieve this level of function whether they have incomplete or complete injuries. The latter study shows that patients may decrease their function without a corresponding neurologic loss. In the interest of efficiency, patients who had achieved independence in some dressing activities spent their time on other activities. This alerts the clinician to prognosticate only to the function a patient may achieve, yet allows for individual patient variance. The importance of predicting future recovery and potential for independence in self-care as early as possible has become essential in the current health care reform climate. Accuracy for the potential of upper-extremity motor recovery in groups of patients at a specific neurologic level is now possible within the first week of injury. It is important to recognize that persons with incomplete injuries may achieve not only an earlier improvement, but also overall improvement that results in a much higher level of function. 16 Individuals with complete injuries may require a longer period to achieve a similar functional level in the upper extremity, but the potential is real, and the timing and intensity of the rehabilitation intervention should be based on the predictive pattern of recovery. Last, after initial discharge, periodic reassessments by the rehabilitation clinician are necessary to assure that the patient achieves his or her ultimate functional level. The mechanisms for recovery of the upper-extremity strength following injury to the cervical spinal cord are poorly understood. The complexity of the lesion and the multiple possible sites that may be damaged make it difficult to localize the injury. Direct trauma and or secondary ischemia 28 may involve upper and lower motoneurons and possibly roots or spinal nerves. Curt and Dietz 29 attempted to determine differences by electroneuromyography between intramedullary damage of motoneurons and the anterior nerve roots. Although they stated that the prognosis for recovery of hand function can be determined by this method, they did not offer an explanation of mechanisms. Marino 30 reported on increased density of the motor territory based on peripheral sprouting in upperextremity muscles recovering from SCI. Others have demonstrated unmasking and other evidence of central nervous system plasticity based on changes in territory of motor-evoked potentials, but this has recently been challenged. 31 An interesting case report 32 on profound neuronal loss in the face of good hand function in a posttraumatic cervical syrinx suggested axonal sprouting directly to the motor neuron and reactive synaptogenesis as reasons for minimal loss of strength. Clearly, more research is needed to elucidate strategies for therapeutic interventions based on a better understanding of the underlying mechanisms. References 1. Long C, Lawton EB. Functional significance of spinal cord lesion level. Arch Phys Med Rehabil 1955;36: Bedbrook GM. Spinal injuries with tetraplegia and paraplegia. J Bone Joint Surg Br 1979;61: Welch RD, Lobley SJ, O Sullivan SB, Freed MM. Functional independence in quadriplegia. Arch Phys Med Rehabil 1986;67: Hayes KC, Blight AR, Potter PJ, Allatt RD, Hsieh JT, Wolfe DL, et al. 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