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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
TREATMENT
Masking
NONE
Enrollment
20
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.
General Hospital of Vienna
Vienna, Austria
Chedoke Arm and Hand Activity Inventory (CAHAI-9) score
Patients can reach a score for CAHAI 9 between 9 to 63. The lower the score, the greater impairment.
Time frame: 0-24 months
Modified Ashworth Scale
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 .
Time frame: 0-24 months
Changes in electrophysiological muscle activity after nerve transfers
Low frequency-dependent depression of H-wave (in mV)
Time frame: 0-24 months
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.
Time frame: During surgery- 24 months
The Action Research Arm Test (ARAT)
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.
Time frame: 0-24 months
The Disabilities of the Arm, Shoulder and Hand (DASH) score
Scores range from 0 (no disability) to 100 (most severe disability).
Time frame: 0-24 months
Motor Unit Number Estimation of donor and spastic muscles
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
Time frame: 0-24 months
Comparison of collagen content between spastic and healthy 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.
Time frame: During surgery- 12 months
Changes in sarcomere length (μm) in spastic muscles
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.
Time frame: During surgery- 12 months
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