Alpha-synuclein (αSyn) forms pathologic aggregates in Parkinson’s disease (PD) and is implicated in mechanisms underlying neurodegeneration. While pathologic αSyn has been extensively studied, there is currently no method to evaluate αSyn within the brains of living patients. Patients with PD are often treated with deep brain stimulation (DBS) surgery in which surgical instruments are in direct contact with neuronal tissue; herein, we describe a method by which tissue is collected from DBS surgical instruments in PD and essential tremor (ET) patients and demonstrate that αSyn is detected. 24 patients undergoing DBS surgery for PD (17 patients) or ET (7 patients) were enrolled; from patient samples, 81.2 ± 44.8 µg of protein (n = 15), on average, was collected from surgical instruments. Light microscopy revealed axons, capillaries, and blood cells as the primary components of purified tissue (n = 3). ELISA assay further confirmed the presence of neuronal and glial tissue in DBS samples (n = 4). Further analysis was conducted using western blot, demonstrating that multiple αSyn antibodies are reactive in PD (n = 5) and ET (n = 3) samples; truncated αSyn (1–125 αSyn) was significantly increased in PD (n = 5) compared to ET (n = 3), in which αSyn misfolding is not expected (0.64 ± 0.25 vs. 0.25 ± 0.12, P = 0.046), thus showing that multiple forms of αSyn can be detected from living PD patients with this method.
Reported neuro-modulation schemes in the literature are typically classified as closed-loop or open-loop. A novel group of recently developed neuro-modulation devices may be better described as a neural bypass, which attempts to transmit neural data from one location of the nervous system to another. The most common form of neural bypasses in the literature utilize EEG recordings of cortical information paired with functional electrical stimulation for effector muscle output, most commonly for assistive applications and rehabilitation in spinal cord injury or stroke. Other neural bypass locations that have also been described, or may soon be in development, include cortical-spinal bypasses, cortical-cortical bypasses, autonomic bypasses, peripheral-central bypasses, and inter-subject bypasses. The most common recording devices include EEG, ECoG, and microelectrode arrays, while stimulation devices include both invasive and noninvasive electrodes. Several devices are in development to improve the temporal and spatial resolution and biocompatibility for neuronal recording and stimulation. A major barrier to entry includes neuroplasticity and current decoding mechanisms that regularly require retraining. Neural bypasses are a unique class of neuro-modulation. Continued advancement of neural recording and stimulating devices with high spatial and temporal resolution, combined with decoding mechanisms uninhibited by neuroplasticity, can expand the therapeutic capability of neural bypassing. Overall, neural bypasses are a promising modality to improve the treatment of common neurologic disorders, including stroke, spinal cord injury, peripheral nerve injury, brain injury and more.
28 August 2023 in Journal of Neuropathology & Experimental Neurology
Postoperative pain is the most common undesirable outcome after neurosurgery. Ketorolac is a nonsteroidal anti-inflammatory drug (NSAID) that is administered parenterally and carries a theoretical increased risk of bleeding. Our study aims to determine whether ketorolac after craniotomy for tumor resection significantly changes the rate of postoperative adverse events, adequately controls pain, and decreases concurrent narcotic use. We performed a retrospective chart review of all adult patients who underwent craniotomy for brain tumor resection from 2013 to 2022. Analysis of patients who received ketorolac and those who did not in the postoperative period were compared for adverse events associated with ketorolac use. Secondary outcomes included patient-reported pain scores and postoperative opioid use. In total, 1114 patients were included, of whom 70 received ketorolac in the postoperative period. Ketorolac was typically administered to patients in whom narcotics had failed to provide sufficient pain relief. Patients receiving ketorolac were younger (P = 0.001) and had a lower comorbidity index (P = 0.041) compared with the nonketorolac group. Patients receiving ketorolac did not experience a significantly increased rate of bleeding events (P = 0.850). Patients receiving ketorolac had significantly greater baseline levels of pain (P = 0.018) and opioid use (P = 0.047). When matched for chronic comorbidities including pain disorders, the ketorolac group only displayed greater levels of pain early in the postoperative course (postoperative day 0-1) but not in latter part of the initial postoperative period. Ketorolac is a safe and effective option for pain control after craniotomy for tumor resection. Prospective data are needed to better validate these retrospective observations.