C7 Nerve Transfer May Reduce Spastic Arm Paralysis

Patients with spastic arm paralysis who receive a contralateral C7 nerve graft from their nonparalyzed side to their paralyzed side may have greater improvement in arm function and reduction in spasticity after a year, compared with patients who undergo rehabilitation alone, according to research published January 4 in the New England Journal of Medicine.

The researchers randomly assigned 36 patients who had had unilateral arm paralysis for at least five years to either surgical C7 nerve transfer plus rehabilitation or rehabilitation alone. Participants in the surgery group had an average increase of 17.7 points on the Fugl-Meyer score, while those in the rehabilitation-only group had an average increase of 2.6 points.

To evaluate spasticity, the researchers used the Modified Ashworth Scale, which is scored from 0 to 5. A higher score indicates greater spasticity. Patients who received surgery had improvement from baseline in all five areas measured, and none worsened. The smallest difference between the two groups was in thumb extension. On this measure, 15 surgery patients had a one- or two-unit improvement and three had no change, while seven controls had a one- or two-unit improvement, seven had no improvement, and four had a one-unit worsening. At one year, 16 (89%) patients in the surgery group were able to accomplish three or more of the functional tasks that researchers gave them, whereas none of the controls could do so.

“The majority of clinical improvements coincided with physiologic 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, a hand surgeon at Huashan Hospital at Fudan University in Shanghai, and colleagues.

A Modification to a Previous Surgical Method

Damage to the contralateral cerebral hemisphere after stroke arises from interruption of the inhibitory activity of upper motor neurons. This interruption causes spasticity, along with hand weakness and loss of fractionated fine motor control. In previous studies, researchers have observed activity in the cerebral hemisphere on the same side of paralysis during stroke recovery, but Dr. Zheng and coauthors asserted that connections between the hand and that part of the brain are “sparse,” thus limiting the body’s ability to compensate for spasticity and functional loss.

The latest findings are consistent with those of earlier studies, including one by Dr. Zheng’s coauthors that suggested that the paralyzed hand could be connected to the unaffected hemisphere by transferring a cervical spine nerve from the nonparalyzed side. Researchers previously found this treatment effective 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. Severing the nerve typically results in transient weakness and numbness in the arm or leg on the same side. When they evaluated 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.

The authors’ surgical approach was a modification of the C7 nerve transfer method that Dr. Zheng and coauthors had previously reported. 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 the surgery group and controls was identical. Rehabilitation sessions took place 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 (ie, men of various ages with various causes of the underlying cerebral lesions) makes it difficult to draw general conclusions from 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.

Results Need Clarification

The results that Dr. Zheng and coauthors reported “are exciting, but need clarification and confirmation,” said Robert J. Spinner, MD, Chair of the Department of Neurologic Surgery; Alexander Y. Shin, MD, Consultant in the Department of Orthopedic Surgery; and Allen T. Bishop, MD, Consultant in the Department of Orthopedic Surgery; all at the Mayo Clinic in Rochester, Minnesota, in an accompanying editorial.

Among the questions Dr. Spinner and coauthors raised about the study are whether distal muscles can functionally reinnervate in a year, and whether C7 neurotomy on the paralyzed side led to improvements in spasticity and function. “The C7 neurotomy itself, associated with an immediate reduction in spasticity, represents a major advance for some patients with brain injury who have poor function and spasticity,” they noted. Improvement of the damaged motor cortex, which ongoing physical therapy may enhance, may also contribute to a reduction in spasticity.

Dr. Spinner and coauthors also cited a previous trial by some of Dr. Zheng’s colleagues in which 49% of patients with brachial plexus injury had motor recovery within seven years. “The presence of physiological connectivity observed in the trials does not necessarily equate with functional recovery,” the authors stated.

Future studies of surgical C7 nerve transfer in patients with one-sided arm paralysis should include patients who have C7 neurotomy without nerve transfer, said Dr. Spinner and colleagues. They also noted that because Dr. Zheng and colleagues perform a relatively high volume of these operations, their results might not be easy to reproduce elsewhere.

“Factors other than technical ones, including differences in BMI and limb length across different populations, may lead to different surgical outcomes,” said Dr. Spinner and coauthors. Future research should focus on ways to enhance or speed up nerve regeneration, improve plasticity, and maximize rehabilitation, they added.

—Richard Mark Kirkner

Suggested Reading

Spinner RJ, Shin AY, Bishop AT. Rewiring to regain function in patients with spastic hemiplegia. N Engl J Med. 2018;378(1):83-84.

Zheng MX, Hua XY, Feng JT, et al. Trial of contralateral seventh cervical nerve transfer for spastic arm paralysis. N Engl J Med. 2018;378(1):22-34.