Vertebral pattern and morphology is determined during embryonic segmentation.

BACKGROUND: The segmented nature of the adult vertebral column is based on segmentation of the paraxial mesoderm during early embryogenesis. Disruptions to embryonic segmentation, whether caused by genetic lesions or environmental stress, result in adult vertebral pathologies. However, the mechanisms linking embryonic segmentation and the details of adult vertebral morphology are poorly understood. RESULTS: We induced border defects using two approaches in zebrafish: heat stress and misregulation of embryonic segmentation genes tbx6, mesp-ba, and ripply1. We assayed vertebral length, regularity, and polarity using microscopic and radiological imaging. In population studies, we find a correlation between specific embryonic border defects and specific vertebral defects, and within individual fish, we trace specific adult vertebral defects to specific embryonic border defects. CONCLUSIONS: Our data reveal that transient disruptions of embryonic segment border formation led to significant vertebral anomalies that persist through adulthood. The spacing of embryonic borders controls the length of the vertebra. The positions of embryonic borders control the positions of ribs and arches. Embryonic borders underlie fusions and divisions between adjacent spines and ribs. These data suggest that segment borders have a dominant role in vertebral development.

Utility of Repetitive Nerve Stimulation in the Diagnosis of Myasthenia Gravis in the Inpatient Setting.

Objectives: Sensitivity and specificity of Repetitive Nerve Stimulation (RNS) is typically reported from outpatient centers, and we hypothesized that these values might not apply to hospitalized patients with higher grades of weakness. RNS may be helpful in rapidly confirming diagnosis of myasthenia gravis (MG) in the inpatient setting, as results from confirmatory antibody testing are often delayed. We sought to characterize the sensitivity and specificity of RNS in the inpatient setting to assist in the early diagnosis of MG. Methods: We performed a retrospective analysis of all adult patients who had inpatient RNS at our center from 2016 to 2021. Inclusion criteria included RNS performed at least at one site and a neurological evaluation which prompted an electrodiagnostic study to evaluate for neuromuscular junction (NMJ) pathology. Descriptive statistics and Fisher exact analysis were performed. Results: Of the 32 identified hospitalized patients, 6 had greater than 10% decrement on slow RNS, confirming NMJ dysfunction. Five were diagnosed with MG, and 1 with Lambert-Eaton myasthenic syndrome. Of the 26 patients with normal RNS, 25 ultimately had alternative causes of weakness. One was later diagnosed as seronegative MG based on clinical improvement with acetylcholinesterase inhibitors. In our inpatient population, the overall sensitivity and specificity of RNS were 83.3% and 96.2% respectively. There was a statistically significant association between a positive RNS and diagnosis of MG (P = .0002). Conclusions: RNS is a highly sensitive and specific test for the diagnosis of MG in an inpatient setting, and these results are likely more rapidly available compared to antibody testing.

Disseminated Mycobacterium bovis Infection Complicated by Meningitis and Stroke: A Case Report.

We describe a case of a 19-year-old female presenting with Mycobacterium bovis meningitis, a rarely encountered infection. We discuss the use of pyrosequencing to aid in prompt diagnosis of M. bovis infection, as well as treatment strategies and challenges given the organism's intrinsic resistance to pyrazinamide.

Rescue of Nimodipine-Induced Refractory Vasoplegia With Hydroxocobalamin in Subarachnoid Hemorrhage: A Case Report.

BACKGROUND: We report a case of refractory vasoplegia after nimodipine administration that was unresponsive to triple vasopressor therapy and was rescued by IV hydroxocobalamin. CASE SUMMARY: An 84-year-old male presented comatose from a subarachnoid hemorrhage and developed severe hypotension unresponsive to three vasopressors following a single dose of enteral nimodipine. Multisystem point-of-care ultrasonography ruled out alternate etiologies of shock, indicating that this was likely a vasoplegic state caused by nimodipine. We administered 5 grams of IV hydroxocobalamin over 15 minutes due to the possibility of impaired nitric oxide metabolism as the driver of vasoplegia. This led to immediate improvement in hemodynamics and rapid discontinuation of vasopressors. The patient experienced chromaturia but no other adverse effects due to hydroxocobalamin. CONCLUSIONS: Nimodipine administration is a standard practice for patients with aneurysmal subarachnoid hemorrhage to reduce unfavorable outcomes from cerebral vasospasm. Although mild hypotension is a common side effect of nimodipine, in rare cases, it may become profound, leading to refractory vasoplegia. There is no evidence-base for reversal agents for nimodipine-induced vasoplegia, and this case is the first to demonstrate successful use of hydroxocobalamin as a potential rescue therapy. We also propose an algorithm for treatment of vasoplegia with consideration of medications that act on nitric oxide-mediated vasodilation and their side-effect profiles.

Regional brain volumetric changes despite 2 years of treatment initiated during acute HIV infection.

OBJECTIVE: To assess changes in regional brain volumes after 24 months among individuals who initiated combination antiretroviral therapy (cART) within weeks of HIV exposure. DESIGN: Prospective cohort study of Thai participants in the earliest stages of HIV-1infection. METHODS: Thirty-four acutely HIV-infected individuals (AHI; Fiebig I-V) underwent brain magnetic resonance (MR) imaging and MR spectroscopy at 1.5 T and immediately initiated cART. Imaging was repeated at 24 months. Regional brain volumes were quantified using FreeSurfer's longitudinal pipeline. Voxel-wise analyses using tensor-based morphometry (TBM) were conducted to verify regional assessments. Baseline brain metabolite levels, blood and cerebrospinal fluid biomarkers assessed by ELISA, and peripheral blood monocyte phenotypes measured by flow cytometry were examined as predictors of significant volumetric change. RESULTS: Participants were 31 ±â€Š8 years old. The estimated mean duration of infection at cART initiation was 15 days. Longitudinal analyses revealed reductions in volumes of putamen (P < 0.001) and caudate (P = 0.006). TBM confirmed significant atrophy in the putamen and caudate, and also in thalamic and hippocampal regions. In exploratory post-hoc analyses, higher baseline frequency of P-selectin glycoprotein ligand-1 (PSGL-1)-expressing total monocytes correlated with greater caudate volumetric decrease (ρ = 0.67, P = 0.017), whereas the baseline density of PSGL-1-expressing inflammatory (CD14CD16) monocytes correlated with putamen atrophy (ρ = 0.65, P = 0.022). CONCLUSION: Suppressive cART initiated during AHI may not prevent brain atrophy. Volumetric decrease appears greater than expected age-related decline, although examination of longitudinal change in demographically similar HIV-uninfected Thai individuals is needed. Mechanisms underlying progressive HIV-related atrophy may include early activation and enhanced adhesive and migratory capacity of circulating monocyte populations.

Thymectomy may not be associated with clinical improvement in MuSK myasthenia gravis.

INTRODUCTION: A randomized trial demonstrated benefit from thymectomy in nonthymomatous acetylcholine receptor (AChR)-antibody positive myasthenia gravis (MG). Uncontrolled observational and histologic studies suggest thymectomy may not be efficacious in anti-muscle-specific kinase (MuSK)-MG. METHODS: The therapeutic impact of thymectomy was evaluated from data collected for a multicenter, retrospective blinded review of rituximab in MuSK-MG. RESULTS: Baseline characteristics were similar between thymectomy (n = 26) and nonthymectomy (n = 29) groups, including treatment with rituximab (42% vs. 45%). At last visit, 35% of thymectomy subjects reached the primary endpoint, a Myasthenia Gravis Foundation of America (MGFA) post-intervention status (PIS) score of minimal manifestations (MM) or better, compared with 55% of controls (P = 0.17). After controlling for age at onset of MG, rituximab, prednisone, and intravenous immunoglobulin/plasma exchange treatment, thymectomy was not associated with greater likelihood of favorable clinical outcome (odds ratio = 0.43, 95% confidence interval 0.12-1.53, P = 0.19). DISCUSSION: Thymectomy was not associated with additional clinical improvement in this multicenter cohort of MuSK-MG patients. Muscle Nerve 59:404-410, 2019.

Progressive Brain Atrophy Despite Persistent Viral Suppression in HIV Patients Older Than 60 Years.

BACKGROUND: Current HIV treatments are successful at suppressing plasma HIV RNA to undetectable levels for most adherent patients. Yet, emerging evidence suggests that viral suppression will inadequately control inflammation and mitigate risk for progressive brain injury. We sought to quantify differences in longitudinal brain atrophy rates among older virally suppressed HIV-infected participants compared with that of healthy aging participants. METHODS: We examined longitudinal structural brain magnetic resonance imaging atrophy rates using region of interest assessments and voxel-wise tensor-based morphometry in HIV-infected participants older than 60 years (n = 38) compared with age-matched HIV-uninfected healthy and cognitively normal controls (n = 24). RESULTS: The mean age of participants was 63 years, the mean estimated duration of infection was 21 years, and the median duration of documented viral suppression was 3.2 years. Average proximal and nadir CD4 counts were 550 and 166, respectively; 15/38 (39%) met criteria for HIV-associated neurocognitive disorder. In models adjusting for age and sex, HIV serostatus was associated with more rapid average annualized rates of atrophy in the cerebellum (0.42% vs. 0.02%, P = 0.016), caudate (0.74% vs. 0.03%, P = 0.012), frontal lobe (0.48% vs. 0.01%, P = 0.034), total cortical gray matter (0.65% vs. 0.16%, P = 0.027), brainstem (0.31% vs. 0.01%, P = 0.026), and pallidum (0.73% vs. 0.39%, P = 0.046). Among those with HIV, atrophy rates did not differ statistically by cognitive status. CONCLUSIONS: Despite persistent control of plasma viremia, these older HIV-infected participants demonstrate more rapid progressive brain atrophy when compared with healthy aging. Either HIV or other factors that differ between older HIV-infected participants and healthy controls could be responsible for these differences.