Efficacy and Safety of Edaravone in Amyotrophic Lateral Sclerosis Patients in Indian Population.

Amyotrophic lateral sclerosis (ALS), is a progressive fatal neurodegenerative disease. It leads to scarring or hardening of Motor neurons. The cause of ALS remains unknown. Oxidative stress caused by free radicals might be an essential factor in the progression of the disease. Edaravone, is a free-radical scavenger, it has been shown to inhibit motor neuron death in animal models by reducing oxidative stress & it has shown efficacy in a small subset of people with ALS. This study was planned to see the efficacy and safety of Edaravone in Indian population. MATERIAL: This study was a single centric observational study, on use of Edaravone in ALS patients. Who were more than 18 years of age and diagnosed to have possible, probable or definite ALS as per the El Escorial Criteria 2014. Total 30 patients were included. All patients had their Revised ALSFRS-R recorded & SFEMG was done at the time of diagnosis then after 6 months of completion of treatment protocol. They were given Edaravone as per as per defined treatment protocol. The treatment protocol consists of 24 weeks (6 cycles). In cycle 1, the study drug was administered for 14 consecutive days followed by a 2 week drug-free period. In cycle 2 and thereafter, the study drug was administered for first 10 days, followed by 18 days drug-free period. The primary efficacy endpoint was a difference in ALSFRS-R score of at least 20% from base line. Secondary endpoints were change in increase in jitter by 10%. Safety endpoints was include the incidence of adverse drug reactions. OBSERVATION: Total of 30 patients were included in the study and 23 patients completed the treatment protocol. 93.3% of patients reported with weakness of limbs while 80% suffered from atrophy of limbs. 96.7% of patients was having fasciculation.2 patients (6.6%) of subjects receiving Edaravone therapy reported with adverse side-effects.After completing the treatment protocol in the study group. On comparing the mean values of ALSFRS-R score at different end-points, no statistical significance was obtained. CONCLUSION: This study failed to demonstrate efficacy of Edaravone to delay the progression of ALS. While the primary desired endpoint was not achieved but there was small improvement in SF-EMG jitter difference of the patients that was not significant statistically. We consider that the study with large sample size results can be helpful to identify the patient population in which Edaravone could be expected to show efficacy.

A Computed Tomography Angiography (CTA): Based score (SGPGI score) to predict level of difficulty, operative, and postoperative outcomes for right-sided radical nephrectomy.

OBJECTIVE: With the advent of laparoscopic approach for the large (T1b-T3a ± N1) right renal masses, higher rates of complications and conversion to open surgery are being reported. The role of preoperative angioembolization (PAE), which has increased cost and inherent morbidity but may help in select circumstances has also not been clearly defined in the literature. We therefore devised a scoring system (SGPGI score) based on pre-operative Computed Tomography Angiography (CTA) to predict the level of difficulty of radical nephrectomy and enhance its safety and efficacy which could also be used for the judicious use of PAE in selected cases. METHODS: In a prospective observational study on 52 patients with right renal masses from January 2014 to July 2018, we calculated a score based on CTA parameters. The patients were stratified for type and duration of surgery, blood loss, postoperative stay, and Clavien-Dindo grade of postoperative complications. RESULTS: Patients were classified into three groups based on our scoring system. Progressively groups with higher score had higher blood loss, operating time, complications and hospital stay, and were more likely to have undergone conversion to open surgery (Area under curve 0.8625 for a cut off score of 10). Intraclass Correlation Coefficient (ICC) was 0.678-1 for the different components of our score. CONCLUSION: The pre-operative CTA based SGPGI score evaluates right renal masses and is able to predict intra-operative difficulties effectively, leading to enhancement of surgery safety and efficacy. It also helps judiciously use PAE.

Glasgow Coma Scale ≤ 12 at Admission is a Predictor of Poor Functional Outcome (mRS 2-6) at One Year in Patients with Cerebral Venous Thrombosis.

OBJECTIVE: To determine factors at hospitalization of cerebral venous thrombosis (CVT) which determine outcome at one year. METHODS: This was an ambispective study with outcome at one year follow up. Patients angiographically proven as CVT were included in study and functional modified Rankin Scale (mRS) determined at one year. They were dichotomized into "good" outcome (mRS 0-1) and "poor" outcome (mRS 2-6). Variables at admission were compared on univariate and then by cox proportional hazard regression for significance. Complications during follow up period were also compared. RESULTS: One hundred and seventy five patients were included, data of 71 was collected prospectively. One hundred and seventeen (66.9%) had "good" outcome while 58 (33.1%) had "poor" outcome. Univariate analysis showed poor outcome associated with age < 30 years, female sex, focal deficit, GCS ≤ 12, ≥3 sinuses involved and intracerebral haemorrhage. On Cox proportional hazard regression only GCS ≤ 12 was significant. Around 96% had complete/ partial recanalization at 6 months. Over one year, the complications included dural AV fistula in 10 (5.7%), intracranial hypertension in 4 (2.3%), venous thromboembolism in 6 (3.4%) and arterial infarct in 4 (2.3%). Proportions with complications in each group were similar. At one year 41 patients (25.2%) were continued on anticoagulation and 97 (55.2%) on antiepileptic drugs. Proportion in each group were similar. CONCLUSION: In patients with CVT, GCS ≤ 12 at admission was a predictor of poor functional outcome (mRS 2-6) at one year. During this period, complications were few and similar in the both the groups.

Multicentric clinical and epidemiological comparison of neuromyelitis optica spectrum disorder with multiple sclerosis from India.

BACKGROUND: In India, Neuromyelitis optica spectrum disorders (NMOSD) can often be misdiagnosed as multiple sclerosis (MS) leading to wrong or delayed treatment. Although diagnostic criteria exist it is important to flag certain highlights in the phenotype by direct comparison which will prompt investigation in the right direction. The aim was to identify distinguishing features, especially differences in disability status and frequency of the optico-spinal syndrome. METHODS: This study was designed as a multicentric, hospital based, ambispective, observational study of patients with primary demyelination due to either NMOSD or MS. Various variables were collected using a data extraction proforma and were compared using statistical means. RESULTS: A total of 212 patients, 166 (78.3%) with MS and 46 (21.7%) with NMOSD, were included from six different cities across India. The male to female ratio was 1:1.3 in MS group and 1:2.3 in NMOSD group. Significant differences on logistic regression included: patients with NMOSD were more disabled despite having a shorter duration of illness with a high progression index (EDSS/ duration of disease in years) of 5.99 vs 0.74 respectively (p = 0.02); in subset of relapsing patients relapsing optico-spinal syndrome (optic neuritis with myelitis) was more common in NMOSD (39.1% vs 0.8%); presence of at least one T2 lesion in the last available MRI brain (78.6% vs 39.1%) and presence of at least one gadolinium enhancing lesion in brain MRI documented during course of illness (30.2% vs 8.7%) was more in MS patients. If the patient with demyelination had a progression index of ≥ 0.39, the Likelihood Ratio (LR) of having NMOSD was 1.32 (95% CI 1.06-1.64), the sensitivity was 0.74 and specificity 0.44. Other notable variables significant on univariate but not on multivariate analysis were: other autoimmune diseases were present more in the NMOSD group (13% vs 2.4%); proportion of patients who had only school education (up to class 12) but not higher were more in NMOSD (67.4% vs 38.5%); the most common clinical presentation in MS patients was either a brainstem or cerebral syndrome (41% vs 21.8%) while it was isolated myelitis in NMOSD patients (37% vs 19.3%). Other findings included: optic neuritis as a presenting feature was common and present in similar proportions in both the groups (around 37%); 50% (23/46) of NMOSD and around 30% (50/166) of MS patients had a single clinical episode during the course of their illness and in the relapsing patients, mean no of relapses (around 2.7) and ARR (MS 0.38, NMOSD 0.54) were similar. Secondary progressive MS was diagnosed in 4.8% (8/166) and primary progressive MS was diagnosed in 3.7% (6/166). CONCLUSION: Index of suspicion for NMOSD should be high in a patient if: the course is relatively short; disability is out of proportion and progression index is ≥0.39 or the patient has had recurrent optico-spinal relapses. It is important to distinguish early in the course NMOSD from MS as timely specific treatment may prevent future disability.

Efficacy and Safety of Supracostal Access for Mini Percutaneous Nephrolithotomy in Pediatric Patients.

OBJECTIVE: To evaluate the efficacy and safety of supracostal percutaneous nephrolithotomy (PCNL) through the 11th intercostal space and compare it with subcostal PCNL in children with renal calculi. MATERIALS AND METHODS: Children with renal calculi who underwent PCNL between January 2010 and December 2017 were divided into 2 groups: supracostal PCNL (group 1) and subcostal PCNL (group 2). Stone location, stone burden, location of the access points, operative time, postoperative visual pain score, success rate, hospital stay, and complications according to the modified Clavien classification were compared. Comparison of medians was done using Mann Whitney U test and the means were compared using t test. RESULTS: Group 1 had 50 patients while group 2 had 60 patients. The stone-free rate was 84.0% and 85.0% in groups 1 and 2, respectively after 1 session of PCNL (P = .885). After auxiliary procedures, it increased to 96.0% and 96.6%, respectively (P = .852). The mean fall in hematocrit was 0.9% in group 1 and 1.5% in group 2 (P = .11) whereas the median pain score was 4 in group 1 and 3 in group 2 (P = .37). In all, 54 complications were recorded the commonest among which were grade I (81.5%). Twenty-nine complications were observed in group 1 while 25 complications were observed in group 2 (P = .088). One patient developed nephropleural fistula while another patient developed hydropneumothorax. Both belonged to group 1. CONCLUSION: Supracostal access for PCNL is an effective and safe alternative to subcostal access for children with renal calculi in terms of stone-free rate and complications.

Breath Rate Variability: A Novel Measure to Study the Meditation Effects.

CONTEXT: Reliable quantitative measure of meditation is still elusive. Although electroencephalogram (EEG) and heart rate variability (HRV) are known as quantitative measures of meditation, effects of meditation on EEG and HRV may well take long time as these measures are involuntarily controlled. Effect of mediation on respiration is well known; however, quantitative measures of respiration during meditation have not been studied. AIMS: Breath rate variability (BRV) as an alternate measure of meditation even over a short duration is proposed. The main objective of this study is to test the hypothesis that BRV is a simple measure that differentiates between meditators and nonmeditators. SETTINGS AND DESIGN: This was a nonrandomized, controlled trial. Volunteers meditate in their natural habitat during signal acquisition. SUBJECTS AND METHODS: We used Photo-Plythysmo-Gram (PPG) signal acquisition system from BIO-PAC and recorded video of chest and abdomen movement due to respiration during a short meditation (15 min) session for 12 individuals (all males) meditating in a relaxed sitting posture. Seven of the 12 individuals had substantial experience in meditation, while others are controls without any experience in meditation. Respiratory signal from PPG signal was derived and matched with that of the video respiratory signal. This derived respiratory signal is used for calculating BRV parameters in time, frequency, nonlinear, and time-frequency domain. STATISTICAL ANALYSIS USED: First, breath-to-breath interval (BBI) was calculated from the respiration signal, then time domain parameters such as standard deviation of BBI (SDBB), root mean square value of SDBB (RMSSD), and standard deviation of SDBB (SDSD) were calculated. We performed spectral analysis to calculate frequency domain parameters (power spectral density [PSD], power of each band, peak frequency of each band, and normalized frequency) using Burg, Welch, and Lomb-Scargle (LS) method. We calculated nonlinear parameters (sample entropy, approximate entropy, Poincare plot, and Renyi entropy). We calculated time frequency parameters (global PSD, low frequency-high frequency [LF-HF] ratio, and LF-HF power) by Burg LS and wavelet method. RESULTS: The results show that the mediated individuals have high value of SDSD (+24%), SDBB (+29%), and RMSSD (+26%). Frequency domain analysis shows substantial increment in LFHF power (+73%) and LFHF ratio (+33%). Nonlinear parameters such as SD1 and SD2 were also more (>20%) for meditated persons. CONCLUSIONS: As compared to HRV, BRV can provide short-term effect on anatomic nervous system meditation, while HRV shows long-term effects. Improved autonomic function is one of the long-term effects of meditation in which an increase in parasympathetic activity and decrease in sympathetic dominance are observed. In future works, BRV could also be used for measuring stress.

Bladder contractility index in posterior urethral valve: A new marker for early prediction of progression to renal failure.

INTRODUCTION: Posterior urethral valve (PUV) is the most common cause of pediatric end stage renal disease (ESRD), imposing a major health burden on medical community caregivers and adversely affecting the quality of life of patients. Chronic kidney disease (CKD) stage III or estimated GFR of <60 mL/min/1.73 m2 is known to be associated with more adverse renal, cardiovascular, and clinical outcomes. Thus, it is desirable to identify factors predicting the rapid and early progression of disease. In the present study, baseline characteristics and urodynamic study (UDS) parameters of boys with PUV are correlated with CKD progression to IIIB or more. AIMS AND OBJECTIVES: To study the correlation of bladder contractility index (BCI) with development of CKD stage IIIB (eGFR of <45 mL/min/1.73 m2) or more in boys with PUV. METHODOLOGY: Baseline characteristics and demographical variables of 270 boys with PUV who underwent valve fulguration at the hospital between 2000 and 2010 were recorded and certain UDS parameters in follow-up were noted such as bladder contractility index (BCI = PdetQmax + 5 Qmax), end filling pressure (EFP), compliance (ΔC), bladder outlet obstruction index (BOOI = Pdet Qmax - 2 Qmax), and bladder volume efficiency (BVE = Voided volume/total capacity). Fate of patients in follow-up was checked in December 2015. RESULTS: Mean follow-up period was 8.5 years (range 5-15) and median age of patients at the time of evaluation was 5.8 years. At the end of the study, 21.8% (59/270) of patients had progressed to CKD stage IIIB or more (primary end point). Cox regression analysis was applied to risk factors predicting development of CKD stage IIIB. In the multivariate model, bladder contractility index (BCI) (HR 0.8; p = 0.004), end filling pressure (EFP) (HR 2.1; p = 0.010), and compliance (ΔC) (p = 0.020) were significantly associated with the event (i.e. an eGFR of <45 mL/min/1.73 m2), whereas BOOI (p = 0.053) and bladder BVE (p = 0.267) were not. ROC cut-off level for BCI predicting the primary end point was 75 (AUC ± SE, 0.73 ± 0.03, sensitivity of 78.2%, and specificity of 62.5%). CONCLUSION: In a well performed UDS, BCI may be a useful tool for early detection of boys with PUV who are likely to progress to CKD stage IIIB or more.

Large Multicystic Dysplastic Kidney Mimicking a Large Cystic Renal Neoplasm.

Multicystic Dysplastic Kidney (MCDK) is one of the most common renal conditions seen in paediatric population. The natural history typically involves involution and many of the patients with unilateral disease may actually never become symptomatic. The initial evaluation is usually done on Ultrasonography (USG) while cross-sectional imaging and nuclear scan are reserved for diagnostic dilemmas. Management is conservative and surgery is done for selected patients with symptomatic cysts or suspicion of neoplasm. We present an interesting case of MCDK in a nine-month-old female hypertensive child presenting with a large abdominal mass increasing in size with imaging features similar to cystic neoplasm and managed with nephrectomy.