Patients with spastic arm paralysis who received a contralateral C7 nerve graft from their nonparalyzed side to their paralyzed side led to greater improvement in arm function and reduction in spasticity after a year, compared with rehabilitation alone, investigators from Huashan Hospital in China reported online Jan. 3 in the New England Journal of Medicine.
The researchers randomly assigned 36 patients who had unilateral arm paralysis for at least 5 years to either surgical C7 nerve transfer plus rehabilitation or rehabilitation only. Results of the trial’s primary outcome – arm function using the Fugl-Meyer score – showed that those in the surgery group had an average increase of 17.7, while those in the rehabilitation-only group had an average increase of 2.6 (P less than .001). This 15.1-point difference had a 95% confidence interval ranging from 12.2 to 17.9.
To evaluate spasticity, the researchers used the Modified Ashworth Scale, which is a 0-5 scale to score spasticity; a higher score means more spasticity. Surgery patients saw improvement from baseline in all five areas measured across the board, and none saw worsening in scores. The smallest difference between the two groups was in thumb extension, with 15 surgery patients having a 1- and 2-unit improvement and 3 having no change, while 7 controls showed a 1- or 2-unit improvement, another 7 showed no improvement, and 4 had a 1-unit worsening in score (P less than .001). At 1 year, 16 (89%) of surgery patients could accomplish three or more of the functional tasks researchers gave them, whereas none of the controls could.
“The majority of clinical improvements coincided with physiological evidence of connectivity between the hemisphere on the side of the donor nerve and the paralyzed arm,” said lead author Mou-Xiong Zheng, MD, PhD, of the department of hand surgery at Huashan Hospital at Fudan University in Shanghai, and colleagues.
The research by Dr. Zheng and coauthors arises from what is known about hand paralysis after stroke, that damage to the contralateral cerebral hemisphere arises from interruption of the inhibitory activity of upper motor neurons, which causes spasticity, along with hand weakness and loss of fractionated fine motor control. Other studies have noted activity in the cerebral hemisphere on the same side of paralysis during recovery (Neuroimage. 2004;22:1775-83; J Neurophysiol. 2005;93:1209-22; J Neurosci. 2006;26:6096-102; Front Neurol. 2015;6:214), but Dr. Zheng and coauthors noted “sparse” connections between the hand and that part of the brain limit the body’s ability to compensate for spasticity and functional loss.
The latest study followed earlier studies, including one by Dr. Zheng’s coauthors (J Hand Surg Br. 1992;17:518-21), that reported the paralyzed hand could be connected to the unaffected hemisphere by transferring a cervical spine nerve from the nonparalyzed side, a treatment previously reported for injuries of the brachial plexus. Of the five nerves of the brachial plexus, Dr. Zheng and coauthors chose the C7 nerve because it accounts for about 20% of the nerve fibers in the brachial bundle and severing the nerve typically results in transient weakness and numbness in the arm or leg on the same side. Hence, when evaluating the hand on the side of the donor graft, the researchers found no significant changes in power, tactile threshold, or two-point discrimination as a result of surgery.
Their surgical approach was a modification of the C7 nerve transfer method that Dr. Zheng and coauthors had previously reported (Microsurgery. 2011;31:404-8; Neurosurgery. 2015;76:187-95). The operation involved making an incision at the superior aspect of the sternum, mobilizing the donor C7 nerve on the nonparalyzed side, and routing it between the spinal column and esophagus. Then, an anastomosis was performed directly with the C7 nerve on the paralyzed side.
Rehabilitation therapy for both the surgery group and controls was identical, administered four times weekly for 12 months at a single facility, although surgery patients wore an immobilizing cast after their operations.
The nature of the study population – men of varying ages with varying causes of the underlying cerebral lesions – makes it difficult to generalize the findings, Dr. Zheng and coauthors noted. “A larger cohort, followed for a longer period, would be necessary to determine whether cervical nerve transfer results in safe, consistent, and long-term improvements in the function of an arm that is chronically paralyzed as a result of a cerebral lesion,” the authors concluded.
Grants from the following supported the study: National Natural Science Foundation of China; Science and Technology Commission of Shanghai Municipality; Health and Family Planning Commission of Shanghai; and Shanghai Shen-Kang Hospital Development Center.