Association of SUMOylation Pathway Genes With Stroke in a Genome-Wide Association Study in India.

OBJECTIVE: To undertake a genome-wide association study (GWAS) to identify genetic variants for stroke in an Indian population. METHODS: In a hospital-based case-control study, 8 teaching hospitals in India recruited 4,088 participants, including 1,609 stroke cases. Imputed genetic variants were tested for association with stroke subtypes using both single-marker and gene-based tests. Association with vascular risk factors was performed with logistic regression. Various databases were searched for replication, functional annotation, and association with related traits. Status of candidate genes previously reported in the Indian population was also checked. RESULTS: Associations of vascular risk factors with stroke were similar to previous reports and show modifiable risk factors such as hypertension, smoking, and alcohol consumption as having the highest effect. Single-marker-based association revealed 2 loci for cardioembolic stroke (1p21 and 16q24), 2 for small vessel disease stroke (3p26 and 16p13), and 4 for hemorrhagic stroke (3q24, 5q33, 6q13, and 19q13) at p < 5 × 10-8. The index single nucleotide polymorphism of 1p21 is an expression quantitative trait locus (p lowest = 1.74 × 10-58) for RWDD3 involved in SUMOylation and is associated with platelet distribution width (1.15 × 10-9) and 18-carbon fatty acid metabolism (p = 7.36 × 10-12). In gene-based analysis, we identified 3 genes (SLC17A2, FAM73A, and OR52L1) at p < 2.7 × 10-6. Eleven of 32 candidate gene loci studied in an Indian population replicated (p < 0.05), and 21 of 32 loci identified through previous GWAS replicated according to directionality of effect. CONCLUSIONS: This GWAS of stroke in an Indian population identified novel loci and replicated previously known loci. Genetic variants in the SUMOylation pathway, which has been implicated in brain ischemia, were identified for association with stroke.

Maternal and Fetal Tuberous Sclerosis: Do We Know Enough as an Obstetrician?

BACKGROUND: Tuberous sclerosis, also known as tuberous sclerosis complex (TSC), is a rare genetic condition that mainly causes hamartomas to develop in different parts of the body. TSC, an autosomal dominant trait with variable penetrance, can adversely affect maternal and fetal outcome. CASE PRESENTATION: In this paper, a case of maternal and fetal tuberous sclerosis having fetal cardiac rhabdomyoma detected in utero at 26 weeks was reported who subsequently had fetal demise at 31 weeks. CONCLUSION: Tuberous sclerosis is a rare genetic condition that mainly causes development of hamartomas. In tuberous sclerosis, a cardiac rhabdomyoma is the only sign that can be detected prenatally. In maternal tuberous sclerosis, fetal ECHO is advisable after 24 weeks. A pregnancy complicated by maternal or fetal tuberous sclerosis deserves careful observation and the fetus should undergo prenatal fetal Doppler echocardiography and if possible magnetic resonance imaging for evaluation of other fetal structures including brain and renal parenchyma, so that parents can be counseled regarding its future prognostic implications. Tuberous sclerosis can lead to poor fetal outcome including intrauterine fetal death; hence regular antenatal follow up is required. Genetic counseling is recommended for couples who have a family history of tuberous sclerosis and who want to have children. Prenatal diagnosis is available for families with a known gene mutation or history of this condition.

Scrub typhus meningoencephalitis, a diagnostic challenge for clinicians: A hospital based study from North-East India.

UNLABELLED: Central nervous system (CNS) involvement is a known complication of scrub typhus which range from mild meningitis to frank meninigoencephalitis. AIMS AND OBJECTIVES: To study the clinical feature, laboratory parameters and response to treatment of scrub typhus meningitis/meningoencephalitis. METHODS AND MATERIALS: This is a hospital based prospective observational study from North Eastern India. Diagnosis was based on clinical features and positive serological test (Weil's Felix test and IgM antibody card test). RESULTS: 13 patients of scrub typhus with features of meningitis/meningoencephalitis were included. The mean duration of fever before presentation was 5.61±3.08 days and 4 (30.76 %) patients had eschar. Altered sensorium, headache, seizure and meningeal sign were present in 13 (100%), 13 (100%), 6 (46.15%) and 10 (76.92%) patients respectively. Mean CSF protein, glucose and Adenosine deaminase was 152.16±16.88mg/dl, 55.23±21.7mg/dl, and 16.98±7.37U/L respectively. Mean total count of CSF leukocyte and lymphocyte percentage was 46.07±131 cell/cumm and 98.66±3.09% respectively. Tablet doxycycline with or without injection azithromycin was used and that shows good response 15.38% of patients died and all of them had multi organ dysfunction. CONCLUSION: Meningoencephalitis is a common manifestation of scrub typhus and diagnosis requires high degree of clinical suspicion which if diagnosed early and specific treatment started, patients usually recover completely with few complications.

Acute subarachnoid hemorrhage as initial presentation of dural sinus thrombosis.

Subarachnoid hemorrhage (SAH) in the older is most often due to aneurismal rupture. Other vascular lesions are known to rarely cause SAH. Cerebral venous thrombosis (CVT) can be difficult to diagnose because of its wide spectrum of clinical manifestations. Its diagnosis can be further complicated when patients initially present with acute SAH. We report a case of dural venous sinus thrombosis with SAH, most probably, due to raised venous pressure draining venous tributaries. A 59-year-old man presented with severe headache. Computerized tomography (CT) scan head was normal. Magnetic resonance imaging (MRI) suggested right parasagittal fronto-parietal hemorrhage. No aneurysm was detected on magnetic resonance angiography (MRA) or digital subtraction angiography (DSA). MRV revealed superior sagittal sinus (SSS) and lateral sinus thrombosis. DSA showed occlusion of intracranial SSS and lateral venous sinus. The patient improved with anticoagulant therapy. This case highlights the fact that SAH may reveal a CVT, and emphasizes on the inclusion of MRV in the diagnostic workup of SAH, particularly in cases in which aneurysm is not detected.