Reverse End-to-Side Nerve Transfer for Severe Ulnar Nerve Injury: A Western Canadian Multicentre Prospective Nonrandomized Cohort Study.

BACKGROUND: Reverse end-to-side (RETS) nerve transfer has become increasingly popular in patients with severe high ulnar nerve injury, but the reported outcomes have been inconsistent. OBJECTIVE: To evaluate the "babysitting effect," we compared outcomes after anterior interosseous nerve RETS transfer with nerve decompression alone. To evaluate the source of regenerating axons, a group with end-to-end (ETE) transfer was used for comparisons. METHODS: Electrophysiology measures were used to quantify the regeneration of anterior interosseous nerve (AIN) and ulnar nerve fibers while functional recovery was evaluated using key pinch and Semmes-Weinstein monofilaments. The subjects were followed postsurgically for 3 years. RESULTS: Sixty-two subjects (RETS = 25, ETE = 16, and decompression = 21) from 4 centers in Western Canada were enrolled. All subjects with severe ulnar nerve injury had nerve compression at the elbow except 10 in the ETE group had nerve laceration or traction injury. Postsurgically, no reinnervation from the AIN to the abductor digiti minimi muscles was seen in any of the RETS subjects. Although there was no significant improvement in compound muscle action potentials amplitudes and pressure detection thresholds in the decompression and RETS group, key pinch strength significantly improved in the RETS group ( P < .05). CONCLUSION: The results from published clinical trials are conflicting in part because crossover regeneration from the donor nerve has never been measured. Unlike those with ETE nerve transfers, we found that there was no crossover regeneration in the RETS group. The extent of reinnervation was also no different from decompression surgery alone. Based on these findings, the justifications for this surgical technique need to be carefully re-evaluated.

Microglia response following acute demyelination is heterogeneous and limits infiltrating macrophage dispersion.

Microglia and infiltrating macrophages are thought to orchestrate the central nervous system (CNS) response to injury; however, the similarities between these cells make it challenging to distinguish their relative contributions. We genetically labeled microglia and CNS-associated macrophages to distinguish them from infiltrating macrophages. Using single-cell RNA sequencing, we describe multiple microglia activation states, one of which was enriched for interferon associated signaling. Although blood-derived macrophages acutely infiltrated the demyelinated lesion, microglia progressively monopolized the lesion environment where they surrounded infiltrating macrophages. In the microglia-devoid sciatic nerve, the infiltrating macrophage response was sustained. In the CNS, the preferential proliferation of microglia and sparse microglia death contributed to microglia dominating the lesion. Microglia ablation reversed the spatial restriction of macrophages with the demyelinated spinal cord, highlighting an unrealized macrophages-microglia interaction. The restriction of peripheral inflammation by microglia may be a previously unidentified mechanism by which the CNS maintains its "immune privileged" status.