Niranjan Khandelwal

Albendazole therapy in children with focal seizures and single small enhancing computerized tomographic lesions : a randomized placebo-controlled double blind trial

BACKGROUND Single small enhancing computerized tomographic (CT) lesions (SSECTLs) are common in children with focal seizures. These are considered to represent solitary cysticercus granulomas. Controversy exists regarding their treatment. OBJECTIVE To evaluate the efficacy of albendazole in cases of focal seizures with SSECTLs. DESIGN Randomized, placebo-controlled, double blind trial. SETTING Pediatric service of Nehru Hospital, PGIMER, an urban tertiary care teaching hospital. SUBJECTS 63 children between 2 and 12 years of age with focal seizures for <3 months and SSECTLs. INTERVENTION All children were randomly assigned to receive either albendazole (15 mg/kg/ day) or placebo for 28 days. CT scan was done at 1 and 3 months after beginning treatment. Codes opened after 6 months of inclusion in the study showed that 31 had received albendazole and 32 had received placebo. All children were followed up for at least 15 months. RESULTS Disappearance of lesions on CT scan was noted in 41% of albendazole vs. 16.2% of placebo patients after 1 month of follow-up (P < 0.05) and 64.5% of albendazole- vs. 37.5% of placebo-treated patients after 3 months of follow-up (P < 0.05). During the first 4 weeks of therapy seizure recurrence was seen in 9.7% of albendazole vs. 3.2% of placebo-treated children (odds ratio, 3.32; 95% confidence interval, 0.33 to 33.8). After 4 weeks seizure recurrence was seen in 31.3% of placebo-treated children vs. 12.9% of albendazole-treated children (odds ratio, 3.07; 95% confidence interval, 1.18 to 11.15). CONCLUSIONS Albendazole therapy results in significantly faster and increased resolution of solitary cysticercus lesions (SSECTLs) and appears to reduce the risk of late seizure recurrences.

Clinical Spectrum of 500 Children With Neurocysticercosis and Response to Albendazole Therapy

Neurocysticercosis is a major cause of neurologic illness worldwide. Its manifestations are variable, and somewhat different when it occurs in children. Controversy exists regarding anticysticercal therapy. The clinical, laboratory, and radiographic features of 500 consecutive children with neurocysticercosis were studied; the children were then followed prospectively and their response to albendazole therapy was analyzed. Diagnosis of neurocysticercosis was based primarily on neuroimaging. Computed tomographic (CT) scans, neurocysticercosis serology, chest radiographs, and Mantoux tests were done in all children, and magnetic resonance imaging scans in 10%. All children with multiple lesions, and some randomly allocated children with single, small, enhancing CT lesions received albendazole. CT scans were repeated after 3 to 6 months. There were 272 boys and 228 girls, age range 16/12 to 126/12 years. Seizures were present in 94.8% of cases; 83.7% had focal seizures. Features of raised intracranial pressure were seen in 30% of patients and focal neurodeficit in 4%. Single lesions were seen in 76% of the children, with perilesional edema in 57.4%. Thirty-four children who had multiple cysts and received albendazole underwent serial CT evaluation. Four showed disappearance of lesions and 22 had reductions in the size or number, to give an overall improvement rate of 76%. Serial CT studies were available on 176 children with single lesions, 90 of whom received albendazole. Improvement (disappearance or reduction in the size of lesions) was observed in 91% (82 of 90) of albendazole-treated children versus 85% (73 of 86) of untreated children. This difference was not significant. No significant side-effects of albendazole were reported. These data indicate that partial seizures and single parenchymal cysts are the most frequent clinical and neuroradiographic manifestations of neurocysticercosis in children. Although albendazole therapy should be considered, especially in children with multiple lesions, many children with isolated neurocysticercosis will improve without antiparasitic therapy. (J Child Neurol 2000;15:207-213).

Intravenous Autologous Bone Marrow Mononuclear Stem Cell Therapy for Ischemic Stroke: A Multicentric, Randomized Trial

Background and Purpose— Pilot studies have suggested benefit from intravenous administration of bone marrow mononuclear stem cells (BMSCs) in stroke. We explored the efficacy and safety of autologous BMSCs in subacute ischemic stroke. Methods— This was a phase II, multicenter, parallel group, randomized trial with blinded outcome assessment that included 120 patients. Patients with subacute ischemic stroke were randomly assigned to the arm that received intravenous infusion of autologous BMSCs or to control arm. Coprimary clinical efficacy outcomes were Barthel Index score and modified Rankin scale at day 180. Secondary outcomes were change in infarct volume, National Institute of Health Stroke Scale (NIHSS) at day 90 and 180. Main safety outcomes were adverse events, any new area of 18fluorodeoxyglucose positron emission tomography uptake in any body part over 365 days. Results— Fifty-eight patients received a mean of 280.75 million BMSCs at median of 18.5 days after stroke onset. There was no significant difference between BMSCs arm and control arm in the Barthel Index score (63.1 versus 63.6; P=0.92), modified Rankin scale shift analysis (P=0.53) or score >3 (47.5% versus 49.2%; P=0.85), NIHSS score (6.3 versus 7.0; P=0.53), change in infarct volume (−11.1 versus −7.36; P=0.63) at day 180. Adverse events were also similar in the 2 arms, and no patient showed any new area of 18fluorodeoxyglucose uptake. Conclusions— With the methods used, results of this hitherto first randomized controlled trial indicate that intravenous infusion of BMSCs is safe, but there is no beneficial effect of treatment on stroke outcome. Clinical Trial Registration— URLs: http://ctri.nic.in/Clinicaltrials and http://www.clinicaltrials.gov. Unique identifiers: CTRI-ROVCTRI/2008/091/0004 and NCT0150177.

Early results of core decompression and autologous bone marrow mononuclear cells instillation in femoral head osteonecrosis: a randomized control study.

Fifty-one osteonecrotic hips in 40 patients were randomly divided into 2 treatment groups. Patients in group A (25 hips) were treated with core decompression, and those in group B (26 hips) received autologous bone marrow mononuclear cell instillation into the core tract after core decompression. Outcome between the 2 groups were compared clinically (Harris Hip score), radiographically (x-ray and magnetic resonance imaging), and by Kaplan-Meier hip survival analysis after 12 and 24 months of surgical intervention. The clinical score and mean hip survival were significantly better in group B than in group A (P < .05). Patients with adverse prognostic features at initial presentation, that is, poor Harris Hip score, x-ray changes, edema, and/or effusion on magnetic resonance imaging had significantly better clinical outcome and hip survival in group B than in group A.

Comparison of CT venography with MR venography in cerebral sinovenous thrombosis

OBJECTIVE The purpose of this study was to compare cerebral CT venography with MR venography and determine the reliability of CT venography in the diagnosis of cerebral sinovenous thrombosis. SUBJECTS AND METHODS Fifty patients who were clinically suspected of having cerebral sinovenous thrombosis, irrespective of age and sex, underwent cerebral CT venography and MR venography. Projection venograms were displayed using maximum-intensity-projection images for both CT venography and MR venography. The CT venograms were also displayed using the integral algorithm, which depicts the average intensity value of the first five voxels deep in relation to the model surface that is nearest the viewer, allowing direct visualization of the thrombus in the sinuses. All CT venograms and MR venograms were independently evaluated by experienced neuroradiologists. RESULTS Of these 50 patients, 30 patients were diagnosed as having cerebral sinovenous thrombosis on both CT venography and MR venography. The total numbers of sinuses involved were 81 and 77 (CT venography and MR venography). When MR venography was used as the gold standard, CT venography was found to have both a sensitivity and a specificity of 75-100%, depending on the sinus and vein involved. CONCLUSION CT venography is as accurate as MR venography for diagnosing cerebral sinovenous thrombosis.

A novel content-based active contour model for brain tumor segmentation

Brain tumor segmentation is a crucial step in surgical and treatment planning. Intensity-based active contour models such as gradient vector flow (GVF), magneto static active contour (MAC) and fluid vector flow (FVF) have been proposed to segment homogeneous objects/tumors in medical images. In this study, extensive experiments are done to analyze the performance of intensity-based techniques for homogeneous tumors on brain magnetic resonance (MR) images. The analysis shows that the state-of-art methods fail to segment homogeneous tumors against similar background or when these tumors show partial diversity toward the background. They also have preconvergence problem in case of false edges/saddle points. However, the presence of weak edges and diffused edges (due to edema around the tumor) leads to oversegmentation by intensity-based techniques. Therefore, the proposed method content-based active contour (CBAC) uses both intensity and texture information present within the active contour to overcome above-stated problems capturing large range in an image. It also proposes a novel use of Gray-Level Co-occurrence Matrix to define texture space for tumor segmentation. The effectiveness of this method is tested on two different real data sets (55 patients - more than 600 images) containing five different types of homogeneous, heterogeneous, diffused tumors and synthetic images (non-MR benchmark images). Remarkable results are obtained in segmenting homogeneous tumors of uniform intensity, complex content heterogeneous, diffused tumors on MR images (T1-weighted, postcontrast T1-weighted and T2-weighted) and synthetic images (non-MR benchmark images of varying intensity, texture, noise content and false edges). Further, tumor volume is efficiently extracted from 2-dimensional slices and is named as 2.5-dimensional segmentation.

MDCT in the Staging of Gallbladder Carcinoma

OBJECTIVE The purpose of our study was to determine the utility of dual-phase MDCT with 3D reconstruction in the staging and resectability of gallbladder carcinoma. SUBJECTS AND METHODS Twenty-seven consecutive patients with suspected gallbladder carcinoma on clinical examination and routine sonography were prospectively analyzed with dual-phase MDCT. Of these patients, only 20 who underwent a laparotomy for extended cholecystectomy or a palliative surgery were included in the study. Three-dimensional volume-rendered reconstruction was used for evaluation of the vascular invasion and anatomy. The staging and resectability as determined on CT were compared with preoperative findings. RESULTS On the basis of the CT findings, eight tumors were resectable and 12 were unresectable. On surgery, 11 tumors were found to be resectable and the remaining were unresectable. Overstaging by CT occurred in three patients due to overassessment of duodenal infiltration. CT had a sensitivity of 72.7%, a specificity of 100%, and an accuracy of 85% for determining resectability of gallbladder carcinoma. For the diagnosis of hepatic and vascular invasion by the tumor, there was 100% correlation between CT and surgery. Vascular variations were found in six of the 11 patients who underwent radical cholecystectomy. CONCLUSION Dual-phase MDCT with 3D reconstruction is a comprehensive imaging technique for staging gallbladder carcinoma and determining the vascular road map before surgery.

Efficacy of Autologous Bone Marrow–Derived Stem Cell Transplantation in Patients With Type 2 Diabetes Mellitus

Progressive and inexorable beta-cell dysfunction is the hallmark of type 2 diabetes mellitus (T2DM) and beta-cell regeneration using stem cell therapy may prove to be an effective modality. A total of 10 patients (8 men) with T2DM for >5 years, failure of triple oral antidiabetic drugs, currently on insulin (> or = 0.7 U/kg/day) at least for 1 year, and glutamic acid decarboxylase antibody negative were included. Patients on stable doses of medications for past 3 months were recruited. Primary end points were reduction in insulin requirement by > or = 50% and improvement in glucagon-stimulated C-peptide levels at the end of 6 months of autologous bone marrow-derived stem cell transplantation (SCT), while secondary end points were a change in weight and HbA1c and lipid levels as compared to baseline. Seven patients were responders and showed a reduction in insulin requirement by 75% as compared to baseline. Mean duration to achieve the primary objective was 48 days. Three patients were able to discontinue insulin completely, although it was short-lived in one. Mean HbA1c reduction was 1% and 3 of the 7 responders had HbA1c value <7%. A significant weight loss of 5.5 kg was noted in the responders, whereas, nonresponders gained 2.2 kg of weight. However, weight loss did not correlate with reduction in insulin requirement (r = 0.68, P = 0.06). There was a significant improvement in both fasting and glucagon-stimulated C-peptide level in the group (P = 0.03) and responders (P = 0.03). HOMA-B increased significantly in the whole group (P = 0.02) and responders (P = 0.04) whereas, HOMA-IR did not change significantly (P = 0.74). Reduction in insulin doses correlated with stimulated C-peptide response at the baseline (r = 0.83, P = 0.047) and mononuclear cell count of infused stem cells (r = 0.57, P = 0.04). No serious adverse effects were noted. Our observations indicate that SCT is a safe and effective modality of treatment to improve beta-cell function in patients with T2DM. However, further large-scale studies are needed to substantiate these observations.

Neural network based focal liver lesion diagnosis using ultrasound images.

Present study proposes a computer-aided diagnostic system to assist radiologists in identifying focal liver lesions in B-mode ultrasound images. The proposed system can be used to discriminate focal liver diseases such as Cyst, Hemangioma, Hepatocellular carcinoma and Metastases, along with Normal liver. The study is performed with 111 real ultrasound images comprising of 65 typical and 46 atypical images, which were taken from 88 subjects. These images are first enhanced and then regions of interest are segmented into 800 non-overlapping segmented regions-of-interest. Subsequently 208-texture based features are extracted from each segmented region-of-interest. A two step neural network classifier is designed for classification of five liver image categories. In the first step, a neural network classifier gives classification among five liver image categories. If neural network decision is for more than one class as obtained from the first step, binary neural network classifiers are used in the second step for crisp classification between two classes. Test results of two-step neural network classifier showed correct decisions of 432 out of 500 segmented regions-of-interest in test set with classification accuracy of 86.4%. The classifier has given correct diagnosis of 90.3% (308/340) in the tested segmented regions-of-interest from typical cases and 77.5% (124/160) in tested segmented regions-of-interest from atypical cases.

Enhancement of the ultrasound images by modified anisotropic diffusion method

Speckle is a primary factor which degrades the contrast resolution and masks the meaningful texture information present in an ultrasound image. Its presence severely hampers the interpretation and analysis of ultrasound images. When speckle reduction technique is applied for visual enhancement of ultrasound images, it is to be kept in mind that blurring associated with speckle reduction should be less and fine details are properly enhanced. With these points in consideration, the modified speckle reduction anisotropic diffusion (MSRAD) method is proposed in the present study to improve the visual quality of the ultrasound images. In the proposed MSRAD method, the four neighboring pixel template in speckle reduction anisotropic diffusion (SRAD) method of Yu and Acton (IEEE Trans Image Process 11:1260–1270, 2002) have been replaced by a new template of larger number of neighboring pixels to calculate the diffusion term. To enhance visual quality of ultrasound images, nonquadratic regularization (Yu and Yadegar, Proceedings of the IEEE international conference on image processing, 2006) is incorporated with MSRAD method and accordingly changes in parameter settings have been made. The performance of MSRAD method was evaluated using clinical ultrasound images, interpretation by the medical experts and results of MSRAD method by subjective and objective criteria.