Varsha Thakur

Seizure activity results in increased tyrosine phosphorylation of the N-methyl-D-aspartate receptor in the hippocampus.

Systemic administration of kainic acid (KA) induces status epilepticus (SE) that causes neurodegeneration and may subsequently lead to spontaneous recurrent seizures. We investigated the effects of KA-induced SE on tyrosine phosphorylation and solubility properties of the NMDA receptor. Following 1 h of SE, total protein tyrosine phosphorylation was elevated in both the hippocampus and frontal cortex relative to controls. Tyrosine phosphorylation of the NMDA receptor subunits NR2A and NR2B was also enhanced following SE. Animals that received KA but did not develop SE, did not exhibit increased tyrosine phosphorylation. SE resulted in a decrease in the solubility of NMDA receptor subunits and of PSD-95 in 1% deoxycholate. In contrast, the detergent solubility of AMPA and kainate receptors was not affected. These findings demonstrate that SE alters tyrosine phosphorylation of the NMDA receptor, and indicate that the interaction of the NMDA receptor with other components of the NMDA receptor complex are altered as a consequence of seizure activity.

Diagnosis and Management of Fetal Heart Failure

Congestive fetal heart failure, defined as inability of the heart to deliver adequate blood flow to organs such as the brain, liver, and kidneys, is a common final outcome of many intrauterine disease states that may lead to fetal demise. Advances in fetal medicine during the past 3 decades now provide the diagnostic tools to detect and also treat conditions that may lead to fetal heart failure. Fetal echocardiographic findings depend on severity of diastolic and systolic dysfunction of both ventricles. At an advanced stage, findings include cardiomegaly; valvar regurgitation; venous congestion; fetal edema and effusions; oligohydramnios; and preferential shunting of blood flow to the brain, heart, and adrenals in the distressed fetus. A useful diagnostic tool to quantify severity of heart failure is the cardiovascular profile score, which is a composite score based on 5 different echocardiographic parameters. To predict outcomes, the score should be interpreted in the context of the underlying disease, as different causes of intrauterine heart failure may have highly variable outcomes. Low fetal cardiac output may result from a myocardial disease (cardiomyopathy, myocarditis, ischemia), abnormal loading conditions (arterial hypertension, obstructive structural heart disease, atrioventricular malformations, twin-to-twin transfusion), arrhythmia, or external cardiac compression (pleural and/or pericardial effusions, cardiac tumours). Treatment options are available for several of these conditions.

A systematic review of the pharmacological management of aortic root dilation in Marfan syndrome.

BACKGROUND Marfan syndrome causes aortic dilation leading to dissection and death. This systematic review examined the use of beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers in the management of aortic dilation in this disease. METHODS We searched four databases--Medline, EMBASE, Web of Science, and The Cochrane Central Register of Controlled Trials--two conference proceedings, references of retrieved articles, and a web-based trial registry. The primary outcome was mortality. The secondary outcomes were aortic dissection, need for elective surgical repair, change in aortic dilation, and adverse events. Two reviewers selected studies, abstracted data, and assessed study quality. Meta-analyses were not performed because of study heterogeneity. RESULTS A total of 18 studies were included--12 completed and six in progress. Of the completed studies, three before-and-after treatment, one prospective cohort, three retrospective cohorts, and two randomised control trials examined beta-blockers; one randomised and one non-randomised trial examined angiotensin-converting enzyme inhibitors; and one retrospective cohort study examined angiotensin II receptor blockers. Studies in progress are all randomised trials. Mortality was not impacted by drug therapy, although studies were underpowered with respect to this outcome. All drug classes were associated with a decrease in the rate of aortic dilation (angiotensin-converting enzyme inhibitors or angiotensin II receptor blockers >beta-blockers); none had an impact on other secondary outcomes. CONCLUSIONS On the basis of existing evidence, beta-blockers, angiotensin-converting enzyme inhibitors, and angiotensin II receptor blockers slow the progression of aortic dilation in Marfan syndrome. Angiotensin-converting enzyme inhibitors and angiotensin II receptor blockers may have more effect than beta-blockers; however, more methodologically rigorous studies currently in progress are needed to evaluate the impact of drug therapy on clinical outcomes.

Does prenatal diagnosis of hypoplastic left heart syndrome make a difference? – A systematic review

Hypoplastic left heart syndrome is frequently diagnosed prenatally with variable benefit. We performed a systematic review to evaluate the impact of fetal diagnosis; the primary objective was to evaluate impact on mortality.

A unique foetal case of left ventricular non-compaction associated with arrhythmia, structural cardiac anomalies, and agenesis of the ductus venosus

A 21-week gestational age foetus was diagnosed with left ventricular non-compaction, Ebsteins anomaly, sinus bradycardia, first-degree heart block, and agenesis of the ductus venosus. The prognosis was guarded given the constellation of findings, and the foetus was monitored closely. Despite a potentially poor outcome, the foetus survived. Prognosis in foetally diagnosed left ventricular non-compaction is usually poor; however, rarely, foetuses can survive postnatally.

An unusual course of anti-Ro antibody-mediated fetal complete heart block

Fetal hydrops is a serious complication of immune-mediated congenital complete atrioventricular block. We present the case of a fetus with severe hydrops and profound bradycardia and an unusual favourable outcome. This case enhances the importance of considering the contribution of ventricular ectopic beats to the cardiac output when counselling and predicting outcome of complete heart block.