Spinal Cord Stimulator Paddle Lead Revision and Replacement for Misplaced or Displaced Electrodes.

OBJECTIVE: Spinal cord stimulators (SCSs) are commonly implanted via a laminotomy or laminectomy. Revision surgery may be necessary in instances of hardware failure or loss of efficacy. It is uncommon for leads to have been initially misplaced in a suboptimal position and revision in these cases necessitates additional dissection for appropriate repositioning. Accordingly, there is concern with a more extensive revision for a potentially higher risk of associated complications. This study aims to describe a series of patients with failed paddle SCS electrodes due to misplacement who underwent revision and replacement. METHODS: Patients who underwent SCS paddle replacement for misplaced paddles between 2021 and 2023 were identified. Medical charts were reviewed for demographic data, operative details, and incidence of complications. RESULTS: Sixteen patients underwent thoracic SCS paddle revision and replacement. The mean age was 59.6 ± 12.6 years, with 11 females and 5 males. Misplaced paddles were too lateral (n = 12), too high (n = 2), or incompletely within the epidural space (n = 2). The mean duration from initial implantation to revision surgery was 44.8 ± 47.5 months. The mean operative duration was 126.1 ± 26.9 minutes and all patients required a "skip" laminectomy or laminotomy. No complications were encountered. The mean length of follow-up was 18.4 ± 7.3 months. Mean preoperative pain intensity was 7.9 ± 1.5 and at last follow-up was 3.6 ± 1.7 (P < 0.001). All but 1 patient continued to use their device in follow-up. CONCLUSIONS: The revision and replacement of misplaced paddle SCS electrodes is a feasible and durable revision strategy, even in long-term implants with extensive scarring.

Division of labor among H3K4 Methyltransferases Defines Distinct Facets of Homeostatic Plasticity.

Heterozygous mutations in any of the six H3K4 methyltransferases (KMT2s) result in monogenic neurodevelopmental disorders, indicating nonredundant yet poorly understood roles of this enzyme family in neurodevelopment. Recent evidence suggests that histone methyltransferase activity may not be central to KMT2 functions; however, the enzymatic activity is evolutionarily conserved, implicating the presence of selective pressure to maintain the catalytic activity. Here, we show that H3K4 methylation is dynamically regulated during prolonged alteration of neuronal activity. The perturbation of H3K4me by the H3.3K4M mutant blocks synaptic scaling, a form of homeostatic plasticity that buffers the impact of prolonged reductions or increases in network activity. Unexpectedly, we found that the six individual enzymes are all necessary for synaptic scaling and that the roles of KMT2 enzymes segregate into evolutionary-defined subfamilies: KMT2A and KMT2B (fly-Trx homologs) for synaptic downscaling, KMT2C and KMT2D (Trr homologs) for upscaling, and KMT2F and KMT2G (dSet homologs) for both directions. Selective blocking of KMT2A enzymatic activity by a small molecule and targeted disruption of the enzymatic domain both blocked the synaptic downscaling and interfered with the activity-dependent transcriptional program. Furthermore, our study revealed specific phases of synaptic downscaling, i.e., induction and maintenance, in which KMT2A and KMT2B play distinct roles. These results suggest that mammalian brains have co-opted intricate H3K4me installation to achieve stability of the expanding neuronal circuits.