KMT2B-Related Dystonia in Indian Patients With Literature Review and Emphasis on Asian Cohort

Objective@#aaMutations in the KMT2B gene have been identified in patients previously diagnosed with idiopathic dystonia. Literature on KMT2B-related dystonia is sparse in the Indian and Asian populations. @*Methods@#aaWe report seven patients with KMT2B-related dystonia studied prospectively from May 2021 to September 2022. Patients underwent deep clinical phenotyping and genetic testing by whole-exome sequencing (WES). A systematic literature search was performed to identify the spectrum of previously published KMT2B-related disorders in the Asian subcontinent. @*Results@#aaThe seven identified patients with KMT2B-related dystonia had a median age at onset of four years. The majority experienced onset in the lower limbs (n = 5, 71.4%), with generalization at a median duration of 2 years. All patients except one had complex phenotypes manifesting as facial dysmorphism (n = 4), microcephaly (n = 3), developmental delay (n = 3), and short stature (n = 1). Magnetic resonance imaging (MRI) abnormalities were present in four cases. WES revealed novel mutations in the KMT2B gene in all patients except one. Compared to the largest cohort of patients with KMT2B-related disorders, the Asian cohort, comprising 42 patients, had a lower prevalence of female patients, facial dysmorphism, microcephaly, intellectual disability, and MRI abnormalities. Protein-truncating variants were more prevalent than missense variants. While microcephaly and short stature were more common in patients with missense mutations, facial dysmorphism was more common in patients with truncating variants. Deep brain stimulation, performed in 17 patients, had satisfactory outcomes. @*Conclusion@#aaThis is the largest series of patients with KMT2B-related disorders from India, further expanding the clinico-genotypic spectrum. The extended Asian cohort emphasizes the unique attributes of this part of the world.

Diode laser – A cure for obstinate oral lichen planus: A case series and review of the literature

Oral lichen planus (OLP) is a chronic T-cell mediated inflammatory disease of unknown etiology. Hence, no gold standard treatment modalities are available. Due to therapeutic challenges offered by conventional therapy, there is a need for effective alternate treatment with minimal side effects. The development of lasers has brought light to the treatment of obstinate OLP. Three cases of male patients in the age group 30–40 years complaining of a burning sensation in the mouth have been mentioned. Clinical and histopathological investigations showed typical findings of OLP. The treatment was started with conventional therapy of corticosteroids. The symptoms were assessed on the visual analog scale (VAS) and showed marked reduction but without complete alleviation. Hence, ablation of the lesion using a 980 nm soft-tissue diode laser was planned. The outcome of the treatment was successful, VAS 0 and no recurrence occurred in 11 months follow-up. The results of a 980 nm diode laser for the treatment of OLP are satisfactory and should be considered as a treatment alternative to conventional remedies

Patient Knowledge, Attitude and Perceptions towards Botulinum Toxin Treatment for Movement Disorders in India

Objective@#There is limited literature on the knowledge, attitude, and perceptions (KAP) of botulinum toxin (BoNT) treatment among patients and caregivers. The objective of this study was to assess the KAP in patients undergoing BoNT treatment for movement disorders. @*Methods@#One hundred patients with movement disorders from National Institute of Mental Health and Neurosciences Hospital in Bengaluru, South India, were recruited. The patients underwent demographic, clinical, and Patient Knowledge Questionnaire on Botulinum Toxin Use in Movement Disorders (PKQ-BMD)-based evaluations. @*Results@#The mean age of patients at the time of presentation was 47.97 ± 14.19 years (range, 12–79). Of all the patients, 26 (28%) patients were anxious, and 86% of these patients were reassured after appropriate counseling. There were 83 (89%) patients who found BoNT to be a costlier option. Education and previous Internet searches influenced positive performance in the “knowledge” domain and overall PKQ-BMD scores. The “number of injections” was also positively correlated with KAP performance. @*Conclusion@#This study showed that knowledge and perceptions about BoNT treatment need to be further improved. Wider availability of the Internet has provided a positive impact on patients’ and carers’ KAP. Internet-based information, higher educational qualifications of the patients, and a higher number of BoNT injection sessions are the most important predictors of satisfactory KAP related to BoNT injection treatment in patients with movement disorders.

Patient Knowledge, Attitude and Perceptions towards Botulinum Toxin Treatment for Movement Disorders in India

Objective@#There is limited literature on the knowledge, attitude, and perceptions (KAP) of botulinum toxin (BoNT) treatment among patients and caregivers. The objective of this study was to assess the KAP in patients undergoing BoNT treatment for movement disorders. @*Methods@#One hundred patients with movement disorders from National Institute of Mental Health and Neurosciences Hospital in Bengaluru, South India, were recruited. The patients underwent demographic, clinical, and Patient Knowledge Questionnaire on Botulinum Toxin Use in Movement Disorders (PKQ-BMD)-based evaluations. @*Results@#The mean age of patients at the time of presentation was 47.97 ± 14.19 years (range, 12–79). Of all the patients, 26 (28%) patients were anxious, and 86% of these patients were reassured after appropriate counseling. There were 83 (89%) patients who found BoNT to be a costlier option. Education and previous Internet searches influenced positive performance in the “knowledge” domain and overall PKQ-BMD scores. The “number of injections” was also positively correlated with KAP performance. @*Conclusion@#This study showed that knowledge and perceptions about BoNT treatment need to be further improved. Wider availability of the Internet has provided a positive impact on patients’ and carers’ KAP. Internet-based information, higher educational qualifications of the patients, and a higher number of BoNT injection sessions are the most important predictors of satisfactory KAP related to BoNT injection treatment in patients with movement disorders.

Intrauterine upper limb thrombosis: an unusual presentation

Intrauterine thrombosis with extremity ischemia presenting at birth in a newborn is a rare event. A 29 year old mother, 2nd gravida with one first trimester spontaneous abortion delivered a 33week gestation male preterm baby. On Examination, the entire left upper limb was ischemic and edematous with an absent flow on Doppler USG. Low molecular weight heparin (LMWH) was started after which gradually the limb turned pink with good volume pulsations. Thrombophilia mutation studies revealed the heterozygous state for the MTHFR (C677T) mutation only in the mother. Prompt diagnosis and early treatment has a favourable outcome in cases of intra-uterine thrombo-embolism.

A cross sectional study to find incidence of clinically detectable congenital malformations and factors affecting it in tertiary care hospital

Background: Congenital malformations are emerging as an important perinatal problem, contributing sizably to the perinatal mortality with considerable repercussions on the mothers and the families. Patients with multiple congenital anomalies present a relatively infrequent but tremendously difficult challenge to the pediatrician. Authors objective was to study the incidence of clinically detectable congenital malformations among consecutive births in hospital deliveries examined during hospital stay.Methods: A prospective cross sectional study was conducted in Department of Pediatrics at Dr R N Cooper Municipal General Hospital, Mumbai from June 2016 to June 2017. All live births from June 2016 to June 2017 were considered in the studyResults: The total number of deliveries in our hospital were 3120(100%) and the total number of babies with congenital anomaly were 43(1.4%), So the incidence of congenital anomalies amongst study population was 1.4%. The involvement of various systems was seen in our study. The involvement of CNS (9.3%), Eye (7%), ENT (28%), GIT (20.9%), Urinary Tract (2.3%), Musculoskeletal System (35%), Gentialia (7%), CVS (7%).Conclusions: Congenital malformation, one of the important causes of infant mortality and morbidity can be reduced by proper preconception care and level two anomaly scan. Congenital anomalies must be identified, as early diagnosis and surgical correction of malformed babies offer the best chance for survival.

Situs Inversus With Atrial Septal Defect And Pulmonary Stenosis Presenting As Cortical Blindness

Cortical blindness is a rare form of blindness characterized by the normal anterior visual afferent system. Cerebrovascular diseases, tumor involving bilateral occipital lobe, cardiac surgery or cerebral angiography are common causes for cortical blindness. Some cases may be associated with denial of blindness when it is called Anton syndrome. We came across a 9-year-old male child presenting to us for evaluation of blindness which turned out to be cortical blindness after the examination. EEG and VEP were consistent with cortical blindness with MRI showing parieto-occipital lobe signal intensity alterations. Evaluation for the cause of cortical blindness led to the diagnosis of situs inversus in the patient with an atrial septal defect. The patient had an episode of dehydration due to gastroenteritis which resulted in vascular compromise thereby leading to hypoxic damage to the brain and cortical blindness. Presentation of cortical blindness in a patient of situs inversus is unique and hence being reported

Evaluation Of Immunomodulatory Activity Of Diosgenin In Rats

Background: Theimmune system is intrinsic to health. Modulation of the immune responses to alleviate the diseases by using herbal plants has been of interest for many years. Diosgenin, a naturally occurring steroid saponin mainly present in the seeds of fenugreek (Trigonella foenum graecum)and in the root tubers of wild yams (Dioscorea vil-losa). Activation of specific and nonspecific immunity results in stimulation of immune response. Diosgenin has the positive effects on both specific and nonspecific immunity.Aim: To study the immunomodulatory activity of Diosgen-in in rats. Method: The suspension of Diosgenin wasgiven orally at the dosage level of 50, 100 and 150 mg/kg for 21 days in a rat. The immunomodulatory activity on specific and non-specific immunity was studied by haemagglutina-tion antibody (HA) titer, delayed type hypersensitivity (DTH) response and carbon clearance test. Immunosuppres-sion in a rat was induced by using Cyclophosphamide (100 mg/kg, p.o.). Sheep red blood cells (SRBCs) were used as antigen (0.1ml 20% SRBCs) in haemagglutinating antibody titer and delayed type hypersensitivity response methods. Result: Diosgenin exhibited significant increase in the production of antibody titer in response to SRBC antigen. A significant increase in both primary and secondary HA titer was observed in immunosuppressed group treated with Diosgenin when compared with negative control. A significant increase in the DTH response was observed in immu-nosuppressed animals treated with Diosgenin, pre-sensitized with SRBCs antigen. Diosgenin exhibited significant in-crease in phagocytic index against control group, indicating the stimulation of the reticuloendothelial system. Con-clusion: The study indicates that Diosgenin triggers stimulatory effect on specific and nonspecific immune response. The immunostimulant effect of Diosgenin could be attributed due to its saponin glycoside.

Protective Effect Of Diosgenin Against Carbon Tetrachloride And Cisplatin Induced Hepatotoxicity In Rats

Background: Activation of hepatic stellate cells (HSC) plays central role in the development of liver fibrosis. In HSC activation, the transforming growth factor-β1 (TGF-β1) is considered to be the main stimuli factor. Diosgenin are the steroidal saponin and found in Trigonella foenum graecum Linn (Fenugreek) and some other species of Dioscorea. Diosgenin attenuates HSC activation by inhibiting transforming growth factor-β. Aim: In present study an attempt was made to explore the effect of diosgenin on liver fibrosis. Methods: Liver fibrosis was induced in rats by carbon tetrachloride (CCl4) 1 ml/kg intraperitoneally twice a week for 28 days and cisplatin 3mg/kg intraperitoneally at 0, 1, 3 week for 4 weeks. The extent of liver fibrosis was assessed by measuring the weight of liver and levels of total bili-rubin (TBL), hydroxyproline (HP) and serum enzymes due to deposition of extracellular matrix (ECM). Results: The administration of diosgenin reduced the liver weight of CCl4 and cisplatin treated animals and reduced the TBL, HP level and serum enzymes significantly and inhibited liver fibrosis induced by CCl4and cisplatin. Conclusion: The result obtained in the present investigation, Diosgenin treatment exerted significant hepatoprotective effect in animals by inhibiting ECM deposition and HSCs activation.

Montelukast and cetrizine may ameliorate progression of rheumatoid arthritis.

Rheumatoid arthritis is an autoimmune disorder. It is a chronic progressive disease resulting in inflammation of joints and painful deformity and immobility of various joints. Being an autoimmune disease, there’s lacuna in proper management of the disease. Current options like steroids and DMARD’S (disease modifying anti-rheumatic drugs) are the cornerstone in therapy of the disease, but have their own limitation. New drugs and better methods for management of rheumatoid arthritis are still evolving. The present review highlights the possible involvement of Montelukast, an antagonist of leukotriene receptors and Cetrizine, an antihistaminic drug in amelioration of the progression of the disease.

Using risk factors for detection and prognostication of uveal melanoma.

The early detection of malignancy, particularly uveal melanoma, is crucial in protecting visual acuity, salvaging the eye, and preventing metastasis. Risk factors for early detection of uveal melanoma have been clearly delineated in the literature and allow identification of melanoma when it is tiny and simulates a nevus. These factors include thickness >2 mm, presence of subretinal fluid (SRF), symptoms, the orange pigment, margin near optic disc, acoustic hollowness, surrounding halo, and absence of drusen. The importance of early detection is realized when one considers melanoma thickness, as each millimeter increase in melanoma thickness imparts 5% increased risk for metastatic disease. Newer imaging modalities like enhanced depth imaging optical coherence tomography and fundus autoflouroscence facilitate in detection of SRF and orange pigment. Additional molecular biomarkers and cytological features have been identified which can predict the clinical behavior of a small melanocytic lesion. Features that suggest a poor prognosis include higher blood levels of tyrosinase m‑RNA, vascular endothelial growth factor, insulin‑like growth factor; monosomy 3 and gains in chromosome 8. Management of uveal melanoma includes enucleation (for large), local eye wall resection, brachytherapy, charged particle irradiation, and thermotherapy (for small to medium tumors). Although the role of a good clinical evaluation cannot be underestimated, it is advisable to evaluate the various radiological, molecular, and cytological features, to enhance the accuracy of early diagnosis and improved prognosis.

Oseltamivir-resistant influenza A(H1N1) pdm09 virus: first reported case from India.

Background: Recent studies on antiviral susceptibiliy from South-East Asia, Europe and the United States have shown sporadic neuraminidase inhibitor (NAI) resistance in A(H1N1)pdm09 viruses. We undertook a study to evaluate NAI resistance in these viruses isolated in India. Methods: Pandemic influenza viruses, isolated from 2009 to 2013, along with clincal samples were genetically analysed for known resistance markers in the neuraminidase (NA) gene. Clinical samples (n=1524) were tested for H275Y (N1 numbering; H274Y in N2 numbering) mutation by real time reverse transcriptase PCR (rRT-PCR). One hundred and ten randomly selected resistant and sensitive viruses were analysed by phenotypic assay. Results: All but one of the 2013 A(H1N1)pdm09 isolates were sensitive to oseltamivir. Genetic analysis of this isolate as well as the original clinical material showed that the presence of H275Y mutation was responsible for reduced susceptibility to oseltamivir in the patient. This was confirmed by phenotypic assay. Conclusion: The emergence of a pandemic influenza strain resistant to oseltamivir emphasizes the need for monitoring antiviral resistance as part of the National Influenza Programme in India.