Nerve Transfers in Post-stroke Spasticity

Stroke is nowadays a leading cause of disability with devastating sequelae. Upper limb spasticity is one of them. Nevertheless, not all the muscles are equally affected, as some may turn spastic or paretic and other remain intact. This unique pathophysiological mosaic dictates a precise therapeutic plan. Existing spasticity treatment has significant drawbacks due to its unspecific targeting and short duration. A causal, life-lasting treatment, precisely adapted to every single patient's needs and to disease pattern, is currently missing. Hyperselective muscle denervation and subsequent cognitive reinnervation with appropriate unaffected donor nerves may break the pathological spastic circuit and provide volitional muscle control. With this pioneering study we will perform cognitive nerve transfers to spastic muscles and will prospectively investigate their effects on clinical, electrophysiological, molecular-biological and histological level. Accurate donor nerve selection will be for the first time quantified through motor unit number estimation with high-density needle electromyography. This revolutionary concept can open the window to a new era of therapeutic possibilities for stroke victims.

Patients with post-stroke upper limb spasticity will be operated for cognitive nerve transfers to spastic muscles to allow for volitional muscle reinnervation and disrupture of spasticity. Adequate healthy nerve donors from the ipsilateral arm will be determined clinically and electrophysiologically.

Based on the fact that upper motor neuron syndrome after stroke is presented with variable clinical features, usually without affecting in the same way the entire upper extremity, we aim to investigate the efficacy of nerve transfers to spastic muscles after stroke using as donor nerves that innervate unaffected ipsilateral volitionally controlled muscles.

A score of 1 indicates no resistance, and 5 indicates rigidity. A 1+ scoring category indicates resistance through less than half of the movement. Scores range from 0-4, with 6 choices .

Changes in muscle satellite cell population (%) in spastic muscles and comparison with healthy control group

Muscle biopsies from spastic muscles will be obtained during the surgery of nerve transfers. The muscle satellite cell population (%) will be calculated with the use of Flow Cytometry and be compared to the one of healthy muscles of control group. There will be no recruitment procedure for the control group. Routinely, when we carry out surgery for ulnar nerve release in the elbow and nerve transposition, a part of the flexor carpi ulnaris muscle needs to be excised and discarded. After obtaining informed consent from patients for further use of their biological material, we will collect these muscles and use them as control group.

The total score on the ARAT ranges from 0 to 57, with the lowest score indicating that no movements can be performed, and the upper score indicating normal performance.

High density electromyography with fine needle electrodes will be applied to allow an accurate estimation of motor units (absolute number) in donor muscles, in spastic muscles and in newly-innervated muscles

Muscle biopsies from spastic muscles will be obtained during the surgery of nerve transfers. Collagen content of spastic muscles (%) will be calculated with the use of Picrosirius red staining and bright field light microscopy and be compared with healthy muscles of control group. There will be no recruitment procedure for the control group. Routinely, when we carry out surgery for ulnar nerve release in the elbow and nerve transposition, a part of the flexor carpi ulnaris muscle needs to be excised and discarded. After obtaining informed consent from patients for further use of their biological material, we will collect these muscles and use them as control group.

Biopsy of a muscle fascicle from spastic muscles will be obtained during the surgery of nerve transfers with the use of dedicated clamps and will be fixed in formalin. The sarcomere length will be calculated with the use of fractional laser. The sarcomere length of spastic muscles will be compared with the sarcomere length of healthy control group muscles.

Inclusion Criteria: Are undergoing nerve transfers Age from 18 to 75 years old Minimum of 1 year interval after stroke Are able to understand German or English Medical Research Council (MRC) Muscle scale for donor nerves: M4 or M5 Walking patients, with or without crutches Good general health condition and social support For the control group: Age 18-75 years old Indication for ulnar nerve release and submuscular transposition for compression neuropathy in the elbow No other neurological disorders Exclusion Criteria: Stroke earlier than 3 years at the time of first consultation Lower limb spasticity and patients mobile with wheel chair

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