ABSTRACT
BACKGROUND: Diagnosis of lateral medullary syndrome (LMS) is often delayed due to elusive clinical presentations and frequently non-revealing neuroimaging tests. We aimed to investigate the use of ipsilateral vocal cord paresis (VCP) identified on neck computed tomography angiography (CTA) as an early diagnostic sign for LMS. METHODS: Medical records were queried for patients admitted with LMS between 1/2012 and 10/2020. A control group of patients undergoing CTA for transient or no neurological symptoms was matched for sex and age. Clinical data were collected by a stroke neurologist. Two neuroradiologists independently and blindly assessed CTA images for radiological signs of VCP. RESULTS: Fifteen LMS and 15 control patients were included in the analysis. Median time from arrival to LMS diagnosis was 29.4â¯h [IQR 7,47] and twice as long in patients who suffered aspiration pneumonia. Thrombolysis rate was 0% in LMS patients versus 14.5% in general stroke patients. Dysphonia was noted in the emergency department in three (20%) patients, whereas all 15 patients had radiological signs of VCP on CTA. Medialization of a true vocal cord was the most sensitive (100%) and specific (80-87%) sign for LMS, with good inter-rater agreement (kappa 0.66). Timely detection of VCP on CTA could have shortened median time to LMS diagnosis by 14â¯h and enabled thrombolytic therapy in 3 (20%) patients. CONCLUSIONS: VCP on CTA is a valuable sign for the diagnosis of LMS. If detected early, it may enable reperfusion therapy and prevent aspiration pneumonia, consequently saving life and diminishing disability.
Subject(s)
Lateral Medullary Syndrome , Stroke , Vocal Cord Paralysis , Cerebral Angiography , Computed Tomography Angiography , Humans , Lateral Medullary Syndrome/complications , Lateral Medullary Syndrome/diagnostic imaging , Stroke/drug therapy , Thrombolytic Therapy , Vocal Cord Paralysis/diagnostic imagingABSTRACT
Prenatal hypoxia ischemia is a major cause of neurodevelopmental impairment in the newborn, associated with risk for motor, behavioral and cognitive impaired outcomes. We used an established mouse model of maternal hypoxia to examine the immediate molecular responses of signaling pathways associated with both cell death and neurogenesis. We also characterized responses to maternal pre-treatment with MgSO(4). Maternal hypoxia at embryonic day 17 (E17) failed to trigger inflammation or cell death in fetal brain at 24 h after hypoxia. However, maternal hypoxia decreased levels of neuronal migration signaling: Reelin (53% of control), Disabled 1 (Dab1, 77% of control), and amyloid precursor protein (APP, 64% of control) 2 h after the insult. These changes persisted for 24 h. At later times, Reelin levels in hippocampi of newborns in the maternal hypoxia-treated group increased compared to controls. Full protection from maternal hypoxia effects on hippocampal Reelin levels resulted from maternal pre-treatment with MgSO(4). Hypoxia and MgSO(4) increased radial and lateral migration distance in the CA1 four days after the insult, while in the DG the hypoxia treatment alone increased migration. Maternal hypoxia and MgSO(4) pre-treatment also stimulated hippocampal expression of genes related to neurogenesis, such as BDNF and NeuroD4. Taken together, the long-term neurodevelopmental outcome of prenatal and perinatal hypoxia may depend on perturbation of developmental signals that affect neuronal migration.
Subject(s)
Cell Movement/physiology , Fetal Hypoxia/physiopathology , Hippocampus/embryology , Hippocampus/physiopathology , Hypoxia, Brain/embryology , Hypoxia, Brain/physiopathology , Neurons/physiology , Amyloid beta-Protein Precursor/metabolism , Animals , Animals, Newborn , Cell Adhesion Molecules, Neuronal/metabolism , Cell Death/physiology , Cell Movement/drug effects , Central Nervous System Agents/pharmacology , Dentate Gyrus/drug effects , Dentate Gyrus/embryology , Dentate Gyrus/physiopathology , Disease Models, Animal , Encephalitis/embryology , Encephalitis/physiopathology , Extracellular Matrix Proteins/metabolism , Fetal Hypoxia/drug therapy , Hippocampus/drug effects , Hypoxia, Brain/drug therapy , Magnesium Sulfate/pharmacology , Mice , Mice, Inbred C57BL , Nerve Tissue Proteins/metabolism , Neurogenesis/drug effects , Neurogenesis/genetics , Neurogenesis/physiology , Neurons/drug effects , Random Allocation , Reelin Protein , Serine Endopeptidases/metabolism , Signal Transduction , Time FactorsABSTRACT
The fetal and newborn brain is particularly susceptible to hypoxia, which increases the risk for neurodevelopmental deficits, seizures, epilepsy and life-span motor, behavioral and cognitive disabilities. Here, we report that prenatal hypoxia at gestation day 17 in mice caused an immediate decrease in fetal cerebral cortex levels of glutamate decarboxylase, a key proteins in the GABA pathway. While maternal MgSO4 treatment prior to hypoxia did not have an early effect, it did accelerate maturation at a later stage based on the observed protein expression profile. In addition, MgSO4 reversed the hypoxia-induced loss of a subpopulation of inhibitory neurons that express calbindin in cortex at postnatal day 14. In the hippocampus, responses to prenatal hypoxia were also evident 4 days after the hypoxia. However, in contrast to the observations in cerebral cortex, hypoxia stimulated key protein expression in the hippocampus. The hippocampal response to hypoxia was also reversed by maternal MgSO4 treatment. The data presented here suggests that decreased levels of key proteins in the GABA pathway in the cerebral cortex may lead to high susceptibility to seizures and epilepsy in newborns after prenatal or perinatal hypoxia and that maternal MgSO4 treatment can reverse the hypoxia-induced deficits in the GABA pathway.
