Comparative Analysis of Tenecteplase versus Alteplase in Acute Ischemic Stroke: A Multicentric Observational Study from Eastern India.

BACKGROUND: Tenecteplase is used as an alternative to alteplase and is considered noninferior for thrombolysis in acute ischemic stroke. OBJECTIVES: To compare the effectiveness and adverse effects of tenecteplase and alteplase in the real-world management of acute ischemic stroke. MATERIALS AND METHODS: In this retrospective observational study, we collected data from acute ischemic stroke patients admitted in six hospitals in West Bengal, India, and were thrombolysed with tenecteplase or alteplase between July 2021 and June 2022. Demographic data, baseline parameters, hospital course, and 3-month follow-up data were collected. The percentage of patients achieving a score of 0-2 in the modified Ranking scale at 3 months, rate of symptomatic intracranial hemorrhage, and all-cause mortality within 3 months were the main parameters of comparison between the two thrombolytic agents. RESULTS: A total of 162 patients were initially included in this study. Eight patients were excluded due to unavailability of follow-up data. Among the remaining patients, 71 patients received tenecteplase and 83 patients received alteplase. There was no statistically significant difference between tenecteplase and alteplase with respect to the percentage of patients achieving functional independence (modified Rankin scale score 0-2) at 3 months (53.5% vs. 60.2%, P = 0.706), rate of symptomatic intracranial hemorrhage (5.6% vs. 10.8%, P = 0.246), and all-cause mortality at 3 months (11.3% vs. 15.7%, P = 0.628). CONCLUSION: The effectiveness of tenecteplase is comparable to alteplase in the real-world management of acute ischemic stroke. Symptomatic intracranial hemorrhage and all-cause mortality rates are also similar in real-world practice.

Spectrum of Posterior Cerebral Artery Dissection: A Retrospective Observational Study and a Critical Review.

Background and Aims: Intracranial arterial dissections commonly involve the vertebrobasilar system leading to subarachnoid hemorrhage (SAH) or cerebral infarction attributable to a dissecting aneurysm of the vessel or occlusion of the lumen depending on the depth of dissection. However, isolated posterior cerebral artery dissections (PCADs) are rare and sparsely reported in the literature. Methodology: A retrospective multicentric observational study was carried out after collecting data from 14 patients admitted with PCAD in three hospitals of Kolkata, Jaipur, and Patna within the period of July 2021 to June 2022. Results: The median age of the population was 48.5 years, and 64.28% were females. SAH was the most common presentation with dissecting aneurysms in all patients barring one, who presented with a left occipital infarct consequent to ipsilateral PCAD. Among the 14 patients, three patients denied endovascular intervention and were lost to follow-up; one patient with an occipital infarct and another patient with a dissecting left P3 aneurysm, which underwent spontaneous thrombosis, were managed conservatively. Among the nine patients scheduled for endovascular coiling, one patient succumbed before intervention and one patient succumbed to sepsis in the postoperative period. A complete recovery was noted in six patients, whereas residual neurodeficits were present in three patients. Among the six patients who had an uneventful recovery at the end of 3 months, five patients had an endovascular intervention. Conclusion: PCAD may present with large-scale neurodeficits and is associated with high morbidity and mortality, hence necessitating prompt management. Conservative management is preferable for consequent infarcts, whereas endovascular management is desirable in cases of dissecting aneurysms, which usually tend to have a favorable outcome if intervened early.

Post-Varicella Neurological Complications: A Preliminary Observation from a Tertiary Care Centre of Eastern India.

Objectives: The objective of this study is to analyse detailed clinical presentations, imaging findings, and outcome in a series of 17 cases (n = 17) with neurological complications following acute varicella infection. Methods: It is an observational study on the patients who presented to the neurology outpatient department of our institute with neurological abnormalities following acute varicella infection within the last 3 months. Results: Neuroimaging, either computed tomography or magnetic resonance imaging, cerebrospinal fluid analysis, electroencephalography and nerve conduction studies were performed in all the patients along with other specialized investigations as per clinical context. The age of presentation varied from childhood to middle age (median age was 23 years) and range of clinical spectrum was also wide. Peripheral nervous system involvement was more common in the form of Guillain-Barré syndrome (29.4%) and isolated lower motor neuron facial nerve palsy (23.5%) compared to central nervous system (CNS) involvement. CNS involvement was documented in the form of ataxia (11.76%), myelopathy (17.6%), stroke (5.88%) and encephalitis (5.88%). Conclusion: Chickenpox is a common viral disease and most patients recover without any complication. Although rare, neurological complications following acute varicella infection may have myriad presentations ranging from lower motor neuron facial palsy to life-threatening encephalitis. Compared to other studies, varicella encephalitis and ataxia were not so common in our study group. Response to therapy was uniformly good except in the patients presenting with ataxia. Response was particularly good to central and peripheral demyelinating disorders.

Spectrum of Neurological Illnesses in Pregnancy - An Observational Study from a Tertiary Care Centre of Eastern India.

INTRODUCTION: Neurological disorders in pregnancy may be observed in patients with a pre-existing neurological disorder; patients developing a primary neurological disorder during the course of pregnancy or puerperium; and in patients with primary medical disorders presenting with neurological manifestations. OBJECTIVES: The objectives of the study were to find out the magnitude of neurological disorders in pregnancy in a tertiary care hospital along with assessment of proportion of women with particular disorders among total number of neurological disorders during the course of pregnancy or puerperium (6 weeks after child birth) and also to elicit the effect of neurological disorders on pregnancy outcome, if any. METHODS: A prospective observational longitudinal study was carried out in a tertiary care centre of Eastern India from July 2018 to June 2020 including all pregnant women attending the department of Obstetrics and Gynaecology. We screened 886 pregnant women, out of which 91 cases were identified and investigated. For the purpose of comparison of fetal and maternal outcome, 91 control subjects were chosen from the screened patients in a randomized fashion, so that the baseline characteristics of the two groups were comparable Results: In our study, 10.3% population had neurological disorders, among which 30.8% had primary headache, 3.2% had secondary headache, 8.5% had neurological low back pain, 19.1% had epilepsy, 6.4% had cerebrovascular disorders, 27.6% had peripheral neuropathy, 4.2% had other disorders such as neuropsychiatric Wilson's disease, myasthenia gravis and compressive myelopathy. Moreover, 10.2% of the total study population was hypertensive and 2.9% were diabetic. CONCLUSION: 10.3% mothers did have some neurological disorder, the commonest of which was migraine (primary headache) followed by carpal tunnel syndrome (peripheral neuropathy) and neurological low back pain. Overall fetomaternal outcomes were favorable barring cerebro-vascular disorder and Posterior reversible encephalopathy syndrome (PRES). We recommend screening for neurological disorder from early pregnancy for early detection and appropriate management of that condition.

Repurposing monoamine oxidase inhibitors (MAOI) for the treatment of rheumatoid arthritis possibly through modulating reactive oxidative stress mediated inflammatory cytokines.

Monoamine oxidase inhibitors (MAOI) are presently used to treat depression, parkinsonian, and other psychiatric disorders. The present study was aimed to repurpose the use of MOAI in Rheumatoid Arthritis (RA). The animal model of RA was developed using collagen type II (CII) in Freund's complete adjuvant (FCA) followed by lipopolysaccharide (LPS) and a booster dose of CII in FCA. The effect of MAOI, Selegiline was evaluated whereas the indicators like paw thickness, arthritic score, and the splenic index were measured and compared with the standard drug Methotrexate. Further to explore the molecular mechanism, the expression of serum inflammatory cytokines (IL-6 and TNF-α), radiographical and histopathological study of hind paw were also checked and analyzed. Treatment with MAOI, Selegiline not only reduced the paw thickness, arthritic score, and the splenic index, but also greatly improved the inflammatory biochemical and hematologic parameters and improved the arthritis score. The serum level of IL-6 and TNF-α are considerably decreased dose dependently, however, the notable significant effect (**p < 0.01) observed at concentration of 30 mg/kg b.w. when the RA animals treated by Selegiline. Collectively, Selegiline improved the progression of RA possibly via decreased catecholamine breakdown at synovial fluid resulting decrease hydrogen peroxide (H2O2) generation and inhibition of pro-inflammatory cytokines in situ. Thus, the finding support and indicate the repurposing of MAOI for the treatment of RA meriting further studies on synovial monoamine oxidase as a new therapeutic target to design a new drug for RA.

Successful closure of trigemino-cavernous fistula with minimally invasive approach.

A male in his early teens presented with redness of the right eye following a fall. This redness was progressive and increased suddenly over the week prior to presentation. Fundus evaluation revealed an exudative retinal detachment, and a bruit was audible over the right eye. A digital subtraction angiogram revealed the cause to be a ruptured persistent trigeminal artery aneurysm causing a carotid-cavernous fistula like haemodynamic situation with a massively dilated superior ophthalmic vein. Curative embolisation was done using both vertebrobasilar and carotid approach, and the aneurysm as well as the fistula was occluded using detachable coils and n-butyl cyanoacrylate glue. Patient made a complete recovery in his proptosis and chemosis over 8 weeks, with significant improvement of his visual acuity. The key to successful outcome in this case was a complete occlusion with thrombosis of the fistula bed that can only be achieved using a combination of coils and liquid embolic agents.

A Unique Brain Connectome Fingerprint Predates and Predicts Response to Antidepressants.

More than six decades have passed since the discovery of monoaminergic antidepressants. Yet, it remains a mystery why these drugs take weeks to months to achieve therapeutic effects, although their monoaminergic actions are present rapidly after treatment. In an attempt to solve this mystery, rather than studying the acute neurochemical effects of antidepressants, here we propose focusing on the early changes in the brain functional connectome using traditional statistics and machine learning approaches. Capitalizing on three independent datasets (n = 1,261) and recent developments in data and network science, we identified a specific connectome fingerprint that predates and predicts response to monoaminergic antidepressants. The discovered fingerprint appears to generalize to antidepressants with differing mechanism of action. We also established a consensus whole-brain hierarchical connectivity architecture and provided a set of model-based features engineering approaches suitable for identifying connectomic signatures of brain function in health and disease.

Influence of Fano resonance on SERS enhancement in Fano-plasmonic oligomers.

Plasmonic oligomers can provide profound Fano resonance in their scattering responses. The sub-radiant mode of Fano resonance can result in significant near-field enhancement due to its light trapping capability into the so-called hotspots. Appearance of these highly localized hotspots at the excitation and/or Stokes wavelengths of the analytes makes such oligomers promising SERS active substrates. In this work, we numerically and experimentally investigate optical properties of two disk-type gold oligomers, which have different strength and origin of Fano resonance. Raman analysis of rhodamine 6G and adenine with the presence of the fabricated oligomers clearly indicates that an increment in the strength of Fano resonance can improve the Raman enhancement of an oligomer significantly. Therefore, by suitable engineering of Fano lineshape, one can achieve efficient SERS active substrates with spatially localized hotspots.

Regional default mode network connectivity in major depressive disorder: modulation by acute intravenous citalopram.

The relationship between altered default mode network (DMN) connectivity and abnormal serotonin function in major depressive disorder (MDD) has not been investigated. Using intravenous citalopram and resting-state fMRI, we investigated DMN intra-network connectivity and serotonin function in 77 healthy controls and patients with MDD. There were no significant main effects of MDD or citalopram on DMN intra-network connectivity; however, significant interactions indicated that group differences under saline were modified by citalopram. In MDD patients during saline infusion, in contrast with controls, the DMN (i) did not include the precuneus that was instead part of an anti-correlated network but (ii) did include amygdala that was part of the anti-correlated network in controls. Citalopram infusion in MDD patients restored the pattern seen in controls under saline. In healthy controls, citalopram infusion disengaged the precuneus from the DMN and engaged the amygdala, partially reproducing the abnormalities seen under saline in MDD. In exploratory analyses within the MDD group, greater rumination self-ratings were associated with greater intra-network connectivity of the anterior cingulate cortex with the DMN. We hypothesise that, in MDD, disengagement of the precuneus from the DMN relates to overgeneral memory bias in rumination. The opposite effect, with greater engagement of the amygdala in the DMN, reflects the negative valence of rumination. Reversal of these abnormalities by citalopram suggests that they may be related to impaired serotonin function. That citalopram engaged the amygdala in the DMN in controls may relate to the paradoxical effects on aversive processing seen with acute SSRIs in healthy subjects.

Ketamine, but Not the NMDAR Antagonist Lanicemine, Increases Prefrontal Global Connectivity in Depressed Patients.

BACKGROUND: Identifying the neural correlates of ketamine treatment may facilitate and expedite the development of novel, robust, and safe rapid-acting antidepressants. Prefrontal cortex (PFC) global brain connectivity with global signal regression (GBCr) was recently identified as a putative biomarker of major depressive disorder (MDD). Accumulating evidence have repeatedly shown reduced PFC GBCr in MDD, an abnormality which appears to normalize following ketamine treatment. METHODS: Fifty-six unmedicated participants with MDD were randomized to intravenous placebo (normal saline; n = 18), ketamine (0.5mg/kg; n = 19) or lanicemine (100mg; n = 19). PFC GBCr was computed using time series from functional magnetic resonance imaging (fMRI) scans that were completed at baseline, during infusion, and 24h post-treatment. RESULTS: Compared to placebo, ketamine significantly increased average PFC GBCr during infusion (p = 0.01) and 24h post-treatment (p = 0.02). Lanicemine had no significant effects on GBCr during infusion (p = 0.45) and 24h post-treatment (p = 0.23), compared to placebo. Average delta PFC GBCr (during minus baseline) showed a pattern of positively predicting depression improvement in participants receiving ketamine (r = 0.44; p = 0.06; d = 1.0) or lanicemine (r = 0.55; p = 0.01; d = 1.3), but not those receiving placebo (r = -0.1; p = 0.69; d = 0.02). Follow-up vertex-wise analyses showed ketamine-induced GBCr increases in the dorsolateral, dorsomedial, and frontomedial PFC during infusion, and in the dorsolateral and dorsomedial PFC 24h post-treatment (corrected p < 0.05). Exploratory vertex-wise analyses examining the relationship with depression improvement showed positive correlation with GBCr in the dorsal PFC during infusion and 24h post-treatment, but negative correlation with GBCr in the ventral PFC during infusion (uncorrected p < 0.01). CONCLUSIONS: In a randomized placebo-controlled approach, the results provide the first evidence in MDD of ketamine-induced increases in PFC GBCr during infusion, and suggests that ketamine's rapid-acting antidepressant properties are related to its acute effects on prefrontal connectivity. Overall, the study findings underscore the similarity and differences between ketamine and another N-methyl-D-aspartate receptor (NMDAR) antagonist, while proposing a pharmacoimaging paradigm for optimization of novel rapid-acting antidepressants prior to testing in costly clinical trials.