ArticleAnnals of neurology2026
Cuneiform Nucleus Stimulation Can Assist Gait Training to Promote Locomotor Recovery in Individuals With Incomplete Tetraplegia.
Article in Annals of neurology, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03053791 (A Phase I/II Open-label Multicenter Trial to Evaluate Safety and Preliminary Efficacy of Unilateral Deep Brain Stimulation of the Mesencephalic Locomotor Region in Patients With Incomplete Spinal Cord Injury), which is not on this map. Not yet cited in PubMed.
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A Phase I/II Open-label Multicenter Trial to Evaluate Safety and Preliminary Efficacy of Unilateral Deep Brain Stimulation of the Mesencephalic Locomotor Region in Patients With Incomplete Spinal Cord Injury
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22 authors.
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Abstract
objectiveImpaired ability to induce stepping after incomplete spinal cord injury (SCI) can limit the efficacy of locomotor training, often leaving patients wheelchair-bound. The cuneiform nucleus (CNF), a key mesencephalic locomotor control center, modulates the activity of spinal locomotor centers via the reticulospinal tract. Even with severe corticospinal damage, the widely distributed reticulospinal fibers frequently cross the lesion, and lumbosacral spinal locomotor centers remain responsive. Unilateral deep brain stimulation (DBS) of the CNF (CNF-DBS) can increase modulatory input to sublesional locomotor centers and was shown to induce stepping and promote locomotor recovery in rodent models of severe incomplete SCI. Given the evolutionarily conserved CNF-reticulospinal system, we hypothesize that CNF-DBS can augment training and improve gait in humans with incomplete SCI above the lumbosacral levels.
methodsAiming at bench-to-bedside translation, we investigate CNF-DBS in non-ambulatory patients (clinicaltrials.gov, NCT03053791). Here, we present the first 2 individuals with chronic tetraplegia who underwent 6 months of locomotor training supported by unilateral CNF-DBS, with regular follow-up assessments of adverse and therapeutic effects performed without and with stimulation.
resultsThe walking distance covered during the 6-Minute Walking Test (6MWT) after 6 months compared to baseline served as the primary study end point, which was reached by patient 1 in the off-condition and by patient 2 in the off- and the on-condition. No serious adverse events occurred.
interpretationWe show that the CNF-DBS was well tolerated and had therapeutic potential in the first 2 patients, and discuss the lessons learnt with resulting implementations for the next patients. ANN NEUROL 2026;99:161-177.
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