ABSTRACTUltrasound (US) imaging of the spinal canal is applied in early infants before formation of posterior spine bony elements. Here, we demonstrate for the first time in adult healthy subjects ...that excellent visualization of intrathecal structures at the level of C1-C2 is possible by transcutaneous US in flexion, extension, and neutral head positions through the soft tissue US window between C1-C2. We show with US that the posterior subarachnoid space increases significantly in head extension. Accordingly, C1-C2 US guidance can facilitate cervical myelography. In addition, we suggest that US of the C1-C2 spine level may offer an adjunct tool to diagnosing structural abnormalities in the setting of traumatic, congenital, or degenerative pathologies of the craniocervical junction.
Oligonucleotide therapeutics offer great promise in the treatment of previously untreatable neurodegenerative disorders; however, there are some challenges to overcome in pre-clinical studies. (1) ...They carry a well-established dose-related acute neurotoxicity at the time of administration. (2) Repeated administration into the cerebrospinal fluid may be required for long-term therapeutic effect. Modifying oligonucleotide formulation has been postulated to prevent acute toxicity, but a sensitive and quantitative way to track seizure activity in pre-clinical studies is lacking. The use of intracerebroventricular (i.c.v.) catheters offers a solution for repeated dosing; however, fixation techniques in large animal models are not standardized and are not reliable. Here we describe a novel surgical technique in a sheep model for i.c.v. delivery of neurotherapeutics based on the fixation of the i.c.v. catheter with a 3D-printed anchorage system composed of plastic and ceramic parts, compatible with magnetic resonance imaging, computed tomography, and electroencephalography (EEG). Our technique allowed tracking electrical brain activity in awake animals via EEG and video recording during and for the 24-h period after administration of a novel oligonucleotide in sheep. Its anchoring efficiency was demonstrated for at least 2 months and will be tested for up to a year in ongoing studies.
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Benatti and colleagues describe novel technique troubleshooting challenges of administering new drugs into the brain of a large animal. The technique consists of single surgical intervention, allowing multiple new drugs infusions over at least 2 months. It allows drug safety assessment by electroencephalography since infusions are made with animals under sedation.
