Regenerative Medicine and Stem Cells Technologies

13 young adults with tetraplegia are able to feed themselves, hold a drink, brush their teeth, and write as a result of a novel surgical technique which connects functioning nerves with injured nerves to restore power in paralysed muscles Nerve transfer surgery has enabled 13 young adults with complete paralysis to regain movement and function in their elbows and hands, according to the largest case series of this technique in people with tetraplegia (paralysis of both the upper and lower limbs), published in The Lancet.

During the surgery, Australian surgeons attached functioning nerves above the spinal injury to paralysed nerves below the injury. Two years after surgery, and following intensive physical therapy, participants were able to reach their arm out in front of them and open their hand to pick up and manipulate objects. Restoring elbow extension improved their ability to propel their wheelchair and to transfer into bed or a car.

They can now perform everyday tasks independently such as feeding themselves, brushing teeth and hair, putting on make-up, writing, handling money and credit cards, and using tools and electronic devices.

The findings suggest that nerve transfers can achieve similar functional improvements to traditional tendon transfers, with the benefit of smaller incisions and shorter immobilisation times after surgery.

In 10 participants, nerve transfers were uniquely combined with tendon transfers allowing different styles of reconstruction to be performed in each hand, and enabling participants to benefit from the innate strengths of both tendon and nerve transfers. Nerve transfers restored more natural movement and finer motor control in one hand, and tendon transfers restored more power and heavy lifting ability in the other hand.

While only a small study, researchers say that nerve transfers are a major advance in the restoration of hand and arm function, and offer another safe, reliable surgical option for people living with tetraplegia.

Nevertheless, four nerve transfers failed in three participants and the authors conclude that more research will be needed to determine which people are the best candidates to select for nerve transfer surgery to minimise the incidence of failure.

"For people with tetraplegia, improvement in hand function is the single most important goal. We believe that nerve transfer surgery offers an exciting new option, offering individuals with paralysis the possibility of regaining arm and hand functions to perform everyday tasks, and giving them greater independence and the ability to participate more easily in family and work life," says Dr Natasha van Zyl from Austin Health in Melbourne, Australia who led the research.

"What"s more, we have shown that nerve transfers can be successfully combined with traditional tendon transfer techniques to maximise benefits. When grasp and pinch was restored using nerve transfers in one hand and tendon transfers in the other, participants consistently reporting that they liked both hands for different reasons and would not choose to have two hands reconstructed in the same way."

Traditionally, upper limb function has been reconstructed using tendon transfer surgery, during which muscles that still work, but are designed for another function, are surgically re-sited to do the work of muscles that are paralysed. In contrast, nerve transfers allow the direct reanimation of the paralysed muscle itself. Additionally, nerve transfers can re-animate more than one muscle at a time, have a shorter period of immobilisation after surgery (10 days in a sling vs 6-12 weeks in a brace for a nerve transfer for elbow extension), and avoid the technical problems associated with of tendon transfer surgery including tendon tensioning during surgery and mechanical failure (stretch or rupture) after surgery.

Previous single case reports and small retrospective studies have shown nerve transfer surgery to be feasible and safe in people with tetraplegia. But this is the first prospective study to use standardised functional outcome measures and combinations of multiple nerve and tendon transfer surgeries.

In total the study recruited 16 young adults (average age 27 years) with traumatic, early (less than 18 months post injury) spinal cord injury to the neck (C5-C7), who were referred to Austin Health in Melbourne for restoration of function in the upper limb. Most were the result of motor vehicle accidents or sports injuries.

Participants underwent single or multiple nerve transfers in one or both upper limbs to restore elbow extension, grasp, pinch, and hand opening. This involved taking working nerves to expendable muscles innervated above the spinal injury and attaching them to the nerves of paralysed muscles innervated below the injury to restore voluntary control and reanimate the paralysed muscle.

For example, the surgeons selected the nerve supplying the teres minor muscle in the shoulder as a donor nerve and attached it to the nerve supplying the triceps that activates the muscles that extend (straighten) the elbow. To restore grasp and pinch the nerve to a spare wrist extensor muscle was transferred to the anterior interosseous nerve.

In total, 59 nerve transfers were completed in 16 participants (13 men and three women; 27 limbs). In 10 participants (12 limbs), nerve transfers were combined with tendon transfers to improve hand function.

Participants completed assessments on their level of independence related to activities of daily living (e.g., self-care, toilet, upper limb function, muscle power, grasp and pinch strength, and hand opening ability) before surgery, one year after surgery, and again two years later. Two participants were lost to follow up, and there was one death (unrelated to the surgery).

At 24 months, significant improvements were noted in the hands ability to pick up and release several objects within a specified time frame and independence. Prior to surgery, none of the participants were able to score on the grasp or pinch strength tests, but 2 years later pinch and grasp strength were high enough to perform most activities of daily living.

Three participants had four failed nerve transfers __ two had a permanent decrease in sensation, and two had a temporary decrease in wrist strength that resolved by 1 year after surgery. Overall, surgery was well tolerated. Five serious adverse events were recorded (including a fall from a wheelchair with femur fracture), but none were related to the surgery.

Despite these achievements, nerve transfer surgery still has some limitations. For the best results nerve transfers should ideally be performed within 6-12 months of injury. Additionally, it can take months after nerve transfer for nerve regrowth into the paralysed muscle to occur and for new movement to be seen, and years until full strength is achieved. However, the authors note that one of the benefits of nerve transfers is that most movements not successfully restored by nerve transfers can still be restored using tendon transfers.

Discussing the implications of the findings in a linked comment, Dr Ida Fox from Washington University in the USA writes, "Stem cells and neuroprostheses could change the landscape of regenerative medicine in the future. For now, nerve transfers are a cost-effective way to harness the body"s innate capability to restore movement in a paralysed limb. As nerve transfers are adopted and their uses adapted, careful ongoing outcomes research __ including comparison of nerve versus tendon transfer outcomes, which nerve transfers produce the greatest functional improvements, and optimal timings for surgery after injury __ is paramount to advancing the field. Detailed study of the reasons for nerve transfer failure is also required, as is improving our understanding of the effects of biopsychosocial factors (including access to information and care, psychological readiness, and social support) on patient decision making and outcomes."

Reference:https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(19)31143-2/fulltext