Mesenchymal Stromal Cell Implants for Chronic Motor Deficits After Traumatic Brain Injury: Post Hoc Analysis of a Randomized Trial.

BACKGROUND AND OBJECTIVES: Traumatic brain injury (TBI) is frequently characterized by chronic motor deficits. Therefore, this clinical trial assessed whether intracranial implantation of allogeneic modified mesenchymal stromal (SB623) cells can improve chronic motor deficits after TBI. METHODS: Post hoc analysis of the double-blind, randomized, prospective, surgical sham-controlled, phase 2, STEMTRA clinical trial (June 2016 and March 2019) with 48 weeks of follow-up was conducted. In this international, multicenter clinical trial, eligible participants had moderate-to-severe TBI, were ≥12 months postinjury, and had chronic motor deficits. Participants were randomized in a 1:1:1:1 ratio to stereotactic surgical intracranial implantation of SB623 cells (2.5 × 106, 5.0 × 106, 10 × 106) or surgical sham-controlled procedure. The prespecified primary efficacy end point was significantly greater change from baseline of the Fugl-Meyer Motor Scale (FMMS) score, a measure of motor status, for the SB623 pooled vs control arm at 24 weeks. RESULTS: A total of 211 participants were screened, 148 were excluded, and 63 underwent randomization, of which 61 (97%; mean age, 34 [SD, 12] years; 43 men [70.5%]) completed the trial. Single participants in the SB623 2.5 × 106 and 5.0 × 106 cell dose groups discontinued before surgery. Safety and efficacy (modified intent-to-treat) were assessed in participants who underwent surgery (N = 61; SB623 = 46, controls = 15). The primary efficacy end point (FMMS) was achieved (least squares mean [SE] SB623: +8.3 [1.4]; 95% CI 5.5-11.2 vs control: +2.3 [2.5]; 95% CI -2.7 to 7.3; p = 0.04), with faster improvement of the FMMS score in SB623-treated groups than in controls at 24 weeks and sustained improvement at 48 weeks. At 48 weeks, improvement of function and activities of daily living (ADL) was greater, but not significantly different in SB623-treated groups vs controls. The incidence of adverse events was equivalent in SB623-treated groups and controls. There were no deaths or withdrawals due to adverse events. DISCUSSION: Intraparenchymal implantation of SB623 cells was safe and significantly improved motor status at 24 weeks in participants with chronic motor deficits after TBI, with continued improvement of function and ADL at 48 weeks. Cell therapy can modify chronic neurologic deficits after TBI. TRIAL REGISTRATION INFORMATION: ClinicalTrials.gov Identifier: NCT02416492. Submitted to registry: April 15, 2015. First participant enrolled: July 6, 2016. Available at: classic.clinicaltrials.gov/ct2/show/NCT02416492. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that intracranial implantation of allogeneic stem (SB623) cells in adults with motor deficits from chronic TBI improves motor function at 24 weeks

MR Imaging of the Cavernous Sinus

Due to hs unique location lateral to the phuhary fossa, inferior to the optic chiasm, and encasing cranial nerves Ill, IV, V1, V2, and VI, the cavernous sinus region has held great interest to the neuro-ophthalmologist. Recent ad vances in neurosurgical technique allowing microsurgical dissection within the sinus its~ make Identification and exact location of lesions increasingly important. While dynamic CT scanning has added significantly to the non Invasive evaluation of the cavernous sinus, MR Imaging promises to further enhance our ability to accurately in age the cavernous sinus and its contents. MRI has several obvious advantages, including the absence of radiation, direct multiplanar images, the absence of bone and dental artifact, and the avoidance of iodinated contrast

MR Imaging of the Cavernous Sinus

Due to its unique location lateral to the pituitary fossa, inferior to the optic chiasm, and encasing cranial nerves III, IV, V1, V2, and VI, the cavernous sinus region has held great interest to the neuro-ophthalmologist. Recent advances in neurosurgical technique allowing microsurgical dissection within the sinus itself make identification and exact location of lesions increasingly important

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Headache is one of the most common disorders presenting to the physicians office. Epidemiologic studies show that in a given year, the majority of people within the United States will have headache, and approximately 5% will seek medical attention. It is estimated that 25% of all new visits in a neurologists office is for headache. Over 90% of headaches are primary headache disorders that are they have no underlying secondary cause. As physicians, our main concern is finding the underlying disease or disorder that is causing headache. The primary headache disorders by definition have no significant abnormalities on their examination, nor relevant findings on neuroimaging. The key to making a diagnosis in the primary headache disorders taking a thorough history

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curriculum_fellow; KBDneurodismigrain