POTENTIATION OF CORTICO-SPINAL OUTPUT VIA TARGETED ELECTRICAL STIMULATION OF THE MOTOR THALAMUS.

Cerebral white matter lesions prevent cortico-spinal descending inputs from effectively activating spinal motoneurons, leading to loss of motor control. However, in most cases, the damage to cortico-spinal axons is incomplete offering a potential target for new therapies aimed at improving volitional muscle activation. Here we hypothesized that, by engaging direct excitatory connections to cortico-spinal motoneurons, stimulation of the motor thalamus could facilitate activation of surviving cortico-spinal fibers thereby potentiating motor output. To test this hypothesis, we identified optimal thalamic targets and stimulation parameters that enhanced upper-limb motor evoked potentials and grip forces in anesthetized monkeys. This potentiation persisted after white matter lesions. We replicated these results in humans during intra-operative testing. We then designed a stimulation protocol that immediately improved voluntary grip force control in a patient with a chronic white matter lesion. Our results show that electrical stimulation targeting surviving neural pathways can improve motor control after white matter lesions.

GABA Increases Sensory Transmission In Monkeys.

Sensory input flow is central to voluntary movements. For almost a century, GABA was believed to modulate this flow by inhibiting sensory axons in the spinal cord to sculpt neural inputs into skilled motor output. Instead, here we show that GABA can also facilitate sensory transmission in monkeys and consequently increase spinal and cortical neural responses to sensory inputs challenging our understanding of generation and perception of movement.

Robot Assisted Neurosurgery for High-Accuracy, Minimally-Invasive Deep Brain Electrophysiology in Monkeys.

Traditional methods to access subcortical structures involve the use of anatomical atlases and high precision stereotaxic frames but suffer from significant variations in implantation accuracy. Here, we leveraged the use of the ROSA One(R) Robot Assistance Platform in non-human primates to study electrophysiological interactions of the corticospinal tract with spinal cord circuits. We were able to target and stimulate the corticospinal tract within the internal capsule with high accuracy and efficiency while recording spinal local field potentials and multi-unit spikes. Our method can be extended to any subcortical structure and allows implantation of multiple deep brain stimulation probes at the same time. Clinical Relevance- Our method will allow us to elucidate further roles of the corticospinal tract and its interactions with other processing centers in intact animals and in motor syndromes in the future.

Long-Term Experience with Occipital and Supraorbital Nerve Stimulation for the Various Headache Disorders-A Retrospective Institutional Case Series of 96 Patients.

OBJECTIVE: We have provided long-term data on clinically meaningful pain alleviation for drug-refractory headache disorders using occipital (ONS) and supraorbital nerve stimulation (SONS). METHODS: We performed a retrospective review of 96 patients with migraine, cervicogenic headache, cluster headache, neuropathic pain of the scalp, tension-type headache, and new daily persistent headache who had undergone ONS (61.5%), SONS (11.5%), or combined ONS plus SONS (27.1%) trial implantation and definitive implantation from 2007 to 2017. Changes in pain perception over time were monitored using the visual analog scale (VAS) for pain. RESULTS: The cohort consisted of 60.4% women and 39.6% men, with a mean age of 46.9 ± 11.5 years and pain duration of 14 ± 14.1 years. Of the 96 patients, 65 (67.7%) were treatment responders to a trial (≥30% amelioration in the average or maximum VAS score for pain and/or number of headache days) that had lasted 22.5 ± 8.8 days. The reduction in their average VAS score for pain was to 37% ± 24.4% of baseline compared with 99.1% ± 24.1% of baseline for those without a response (P < 0.01). Of the 56 patients who had undergone implantation and had long-term follow-up data available for ≤10 years, 32 (57.1%) reported a ≥50% reduction in their average VAS score for pain. Four patients (6.5%) had requested hardware explantation. Stage II complications included 1 infection (1.6%) and 6 electrode dislocations (9.7%). The study limitations included the retrospective nature, lack of controls receiving placebo intervention, and randomization. CONCLUSIONS: After careful patient selection according to a positive response to a trial of ONS and/or SONS, clinically meaningful long-term benefit was achieved in 57.1% of our patients with various chronic headache conditions.

Cranial nerve and intramedullary spinal malignant peripheral nerve sheath tumor associated with neurofibromatosis-1.

Background: Malignant peripheral nerve sheath tumors (MPNSTs) are uncommon but aggressive neoplasms associated with radiation exposure and neurofibromatosis Type I (NF1). Their incidence is low compared to other nervous system cancers, and intramedullary spinal lesions are exceedingly rare. Only a few case reports have described intramedullary spinal cord MPNST. Case Description: We describe the clinical findings, management, and outcome of a young patient with NF1 who developed aggressive cranial nerve and spinal MPNST tumors. This 35-year-old patient had familial NF1 and a history of optic glioma treated with radiation therapy (RT). She developed a trigeminal MPNST that was resected and treated with RT. Four years later, she developed bilateral lower extremity deficits related to an intramedullary cervical spine tumor, treated surgically, and found to be a second MPNST. Conclusion: To the best of our knowledge, this is the first report of cranial nerve and intramedullary spinal MPNSTs manifesting in a single patient, and only the third report of a confined intramedullary spinal MPNST. This unusual case is discussed in the context of a contemporary literature review.