Adeno-associated viral vector 9 (AAV9) has recently been shown to penetrate the blood--brain barrier via intravascular administration, making it a good candidate for diffuse gene delivery. However, the potential side effects of systemic delivery are unknown. Intrathecal viral vector administration may be more invasive than intravenous injections, but it requires far less vector and it can be performed on an outpatient basis, making it an ideal route of delivery for clinical translation. A total of 12 domestic farm pigs (o20 kg) underwent a single-level lumbar laminectomy with intrathecal catheter placement for AAV9 delivery. Animals were perfused and the tissue was harvested 30 days after treatment. Gene expression was assessed by anti-green fluorescent protein immunohistochemistry. Although a single lumbar injection resulted in gene expression limited to the lumbar segment of the spinal cord, three consecutive boluses via a temporary catheter resulted in diffuse transduction of motor neurons (MNs) throughout the cervical, thoracic and lumbar spinal cords. We now present the first successful robust transduction of MNs in the spinal cord of a large animal via intrathecal gene delivery using a self-complementary AAV9. These promising results can be translated to many MN diseases requiring diffuse gene delivery.
In environments in which opioids are increasingly abused for recreation, children are becoming more at risk for both accidental and nonaccidental intoxication. In toxic doses, opioids can cause potentially lethal acute leukoencephalopathy, which has a predilection for the cerebellum in young children. The authors present the case of a 2-year-old girl who suffered an accidental opioid overdose, presenting with altered mental status requiring cardiorespiratory support. She required emergency posterior fossa decompression, partial cerebellectomy, and CSF drainage due to cerebellar edema compressing the fourth ventricle. To the authors’ knowledge, this is the first report of surgical decompression used to treat cerebellar edema associated with opioid overdose in a child.
BACKGROUND: The coronavirus identified in 2019 (COVID-19) pandemic effectively ended all major spine educational conferences in the first half of 2020. In response, the authors formed a "virtual" case-based conference series directed at delivering spine education to health care providers around the world. We herein share the technical logistics, early participant feedback, and future direction of this initiative.-METHODS: The Virtual Global Spine Conference (VGSC) was created in April 2020 by a multiinstitutional team of spinal neurosurgeons and a neuroradiologist. Biweekly virtual meetings were established wherein invited national and international spine care providers would deliver casebased presentations on spine and spine surgeryLrelated conditions via teleconferencing. Promotion was coordinated through social media platforms such as Twitter.-RESULTS: VGSC recruited more than 1000 surgeons, trainees, and other specialists, with 50e100 new registrants per week thereafter. An early survey to the participants, with 168 responders, indicated that 92% viewed the content as highly valuable to their practice and 94% would continue participating post COVID-19. Participants from the United States (29%), Middle East (16%), and Europe (12%) comprised the majority of the audience. Approximately 52% were neurosurgeons, 18% orthopedic surgeons, and 6% neuroradiologists. A majority of participants were physicians (55%) and residents/fellows (21%).-CONCLUSIONS: The early success of the VGSC reflects a strong interest in spine education despite the COVID-19 pandemic and social distancing guidelines. There is widespread opinion, backed by our own survey results, that many clinicians and trainees want to see "virtual" education continue post COVID-19.
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