ABSTRACT
INTRODUCTION: Adults with Juvenile myoclonic epilepsy (JME) are at increased risk for psychiatric comorbidities, personality traits, and abnormality in executive function. But studies on adolescents and their impact on quality of life are scarce in the literature. MATERIALS AND METHODS: This cross-sectional study was performed between August 2019 and October 2022 to compare the prevalence of psychiatric comorbidities in adolescents with JME and age and gender-matched healthy controls. After completing DSM-5 Structured Clinical Interview (SCID-5) initially in all patients, we measured the severity of individual psychiatric problems like anxiety, depression, and somatic symptoms by using an appropriate psychometric scale. We also measured both groups' intelligence quotient (IQ), executive function, and quality of life. RESULTS: One hundred patients with JME (14.3 ± 2.5 years, 48 boys) and 100 controls were enrolled. Psychiatric disorders were observed in 46% of JME and 6% of controls (p < 0.01). Psychiatric comorbidities noted in the patients with JME were: somatic symptom and related disorders(n = 14), anxiety (n = 13), adjustment disorders (n = 12), depression (n = 11), oppositional defiant disorder (n = 6), conduct disorder (n = 5), anorexia nervosa (n = 3), narcissistic (n = 3), histrionic (n = 1), substance-related disorder (n = 1), borderline (n = 2) and antisocial personality disorder (n = 2). The prevalence of depressive disorders, anxiety disorders, adjustment disorders, somatic symptoms, related disorders, and any personality disorder was significantly more in the JME group (p < 0.01 for all). Female gender, higher Epilepsy Stigma Scale score, and lower Epilepsy Outcome Expectancy Scale were significantly associated with depressive disorders (p = 0.04, 0.03, 0.03 respectively). Similarly, for anxiety, only female gender and lower Epilepsy Outcome Expectancy Scale were significant associated factors (p = 0.03, 0.02 respectively). CONCLUSIONS: Psychiatric disorders like anxiety, depression, and personality disorders are more frequent in adolescents with JME than in controls.
Subject(s)
Medically Unexplained Symptoms , Myoclonic Epilepsy, Juvenile , Adult , Male , Humans , Female , Adolescent , Myoclonic Epilepsy, Juvenile/complications , Myoclonic Epilepsy, Juvenile/epidemiology , Myoclonic Epilepsy, Juvenile/psychology , Quality of Life , Prevalence , Cross-Sectional StudiesABSTRACT
Although several studies have shown that undernutrition is frequent in children with cerebral palsy (CP), studies determining predictors of undernutrition and its impact on health-related quality of life (HRQoL) are scarce. This study aimed to assess the prevalence, severity, and predictors of malnutrition in children with CP and its impact on quality of life. This prospective study was performed between August 2019 and December 2021 in children with a clinical diagnosis of CP aged 2-18 years. We also intended to determine the socio-demographic and clinical predictors of undernutrition in these children and its impact on HRQoL, measured by the cerebral palsy quality of life (CPQoL)-Primary Caregiver reported version. Out of 569 (5.4 ± 2.8 years of age, 74% boys) children with CP, 71%, 44%, and 72% children were underweight, wasted, and stunted respectively, whereas 22%, 11%, and 21% were severely underweight, wasted and stunted respectively. Lower socioeconomic status, higher Gross Motor Function Classification System, and Manual Ability Classification System level were found to be significantly associated with the severity of stunting and underweight (p < 0.05), but not with wasting. CPQoL score in children with CP aged > 4 years was lower in patients with severe wasting, stunting, and underweight, as compared to their rest of the counterparts when adjusted for socio-demographic and other clinical variables (p < 0.05). Conclusion: Chronic undernutrition is more common than severe acute malnutrition in children with CP. The severity of undernutrition is an important predictor of impaired HRQoL in children with CP. What is Known: ⢠Several studies have shown that undernutrition is frequent in children with cerebral palsy; however, studies determining predictors of undernutrition and its impact on health-related quality of life are scarce. What is New: ⢠Our study identifies that lower socioeconomic status, higher Gross Motor Function Classification System, and Manual Ability Classification System level are significantly associated with the severity of stunting and being underweight. ⢠Chronic undernutrition is more common than severe acute malnutrition in children with cerebral palsy. Its severity is an important predictor of impaired health-related quality of life in children with cerebral palsy.
Subject(s)
Cerebral Palsy , Malnutrition , Severe Acute Malnutrition , Male , Child , Humans , Infant , Female , Thinness/epidemiology , Nutritional Status , Quality of Life , Cerebral Palsy/complications , Cerebral Palsy/epidemiology , Prevalence , Prospective Studies , Malnutrition/diagnosis , Malnutrition/epidemiology , Malnutrition/etiology , Growth Disorders/epidemiology , Severe Acute Malnutrition/complicationsABSTRACT
BACKGROUND: Vinpocetine as a neuroprotective agent is effective in acute ischemic stroke in some randomized controlled trials (RCTs). Since the last systematic review has been published in 2008, which didn't find conclusive evidence favoring its use, two more RCTs have also been completed. METHODS: Relevant electronic databases were searched with a suitable combination of Medical Subject Headings terms to detect publications describing RCTs exploring the safety and efficacy of vinpocetine in patients with acute ischemic stroke. The risk of bias was determined by using the Cochrane Collaboration's tool for assessing the risk of bias in RCTs after full-text review and relevant data extraction. Higgins and Thompson's I2 method was used to assess heterogeneity in studies. The presence of publication bias was assessed by Egger's test. We used a random effect model when I2 was more than 50% and a fixed-effect model for other parameters. RESULTS: Four placebo-controlled RCTs enrolling a total of 601 and 236 patients in vinpocetine and placebo groups, respectively, were included. The number of patients with death or significant disability was lower in the vinpocetine group than that in the placebo group at both 1 and 3 months (relative risk 0.80, 95% confidence interval [CI] 0.65-0.99 and relative risk 0.67, CI 0.48-0.92, p = 0.04 and 0.02, respectively). The degree of disability in participants at 1 month and 3 months was also lower in vinpocetine group than that in the placebo group (standardized mean difference (SMD) 0.49, 95% CI 0.03-0.95 and SMD 1.22, CI 0.23-2.24, p = 0.001 and 0.04, respectively). Change in mini-mental state examination score compared with baseline at trial enrolment was also better in the vinpocetine group than in the placebo group (pooled weighted mean difference 0.92, 95% CI 0.02-1.82, p = 0.04). CONCLUSIONS: Vinpocetine has some promising efficacy in patients with ischemic stroke when used in the acute stage in reducing the disability, but presently there is not enough evidence to suggest that it also reduces case fatality. More double-blind, placebo-controlled RCTs of adequate sample size are needed before making recommendations for the routine administration of vinpocetine for all patients with acute ischemic stroke.
Subject(s)
Ischemic Stroke , Neuroprotective Agents , Stroke , Vinca Alkaloids , Humans , Ischemic Stroke/drug therapy , Neuroprotective Agents/adverse effects , Randomized Controlled Trials as Topic , Stroke/drug therapy , Vinca Alkaloids/adverse effectsABSTRACT
BACKGROUND: Schizophrenia, a chronic severe psychiatric illness of unknown aetiology, has been shown to be associated with HLA alleles but at varied degree in different population. The present study has focussed on analysing the frequency of HLA class I and class II alleles in persons with schizophrenia from South India. METHODS: Ninety seven individuals with schizophrenia and 103 age- and gender-matched controls were typed for HLA- A, B, C, DRB1 and DQB1 loci by next-generation sequencing in Illumina MiniSeq using MIA FORA NGS FLEX HLA typing kit. RESULTS: The results showed that HLA-A*01:01:01, B*37:01:01 and C*01:02:01 were positively associated with schizophrenia while HLA-B*35:03:01 and DRB1*04:03:01 were negatively associated. Gender-specific associations revealed that DRB1*10:01:01 and DQB1*05:01:01 were positively associated while DQB1*03:02:01 was negatively associated with female subjects with schizophrenia. A*24:02:01~B*37:01:01~C*06:02:01~DRB1*10:01:01~DQB1*05:01:01 is the predominant haplotype in schizophrenia population when compared to healthy controls. Amino acid association in susceptible and protective alleles has shown that the presence of peptide in the peptide-binding groves of mature HLA-A protein (K, M, V, R and V at 44th, 67th, 150th, 156th and 158th position), HLA-B protein (D and S at 77th and 99th position) and HLA-C protein (M at 99th position) confer susceptibility to the disease, only in the absence of E (Glutamic acid) at 74th position in mature HLA-DRB1 protein. Interaction of amino acids in protective alleles namely B*35:01:01 and DRB1*04:03:01 has revealed that aspartic acid at 114th (D) position in mature HLA-B protein and glutamic acid (E) at 74th position of mature HLA-DRB1 protein have a combined effect in protecting against the disease. CONCLUSION: The study has revealed the HLA association with schizophrenia in south Indian population. The amino acid interaction with the disease needs to be confirmed in a larger population.
Subject(s)
HLA-A Antigens/genetics , HLA-B Antigens/genetics , HLA-C Antigens/genetics , HLA-DQ beta-Chains/genetics , HLA-DRB1 Chains/genetics , Schizophrenia/genetics , Adult , Female , Gene Frequency , Genetic Predisposition to Disease , Genotype , Haplotypes , Histocompatibility Testing , Humans , India , Male , Middle Aged , Schizophrenia/immunology , Sex FactorsABSTRACT
Background & objectives: Duchenne muscular dystrophy (DMD) is an X-linked recessive disorder and is caused mainly by deletion, duplication and point mutations in the DMD gene. Diagnosis of DMD has been a challenge as the mutations in the. DMD: gene are heterogeneous and require more than one diagnostic strategy for the validation of the mutation. This study was planned to evaluate the targeted next-generation sequencing (NGS) as a single platform to detect all types of mutations in the DMD gene, thereby reducing the time and costs compared to conventional sequential testing and also provide precise genetic information for emerging gene therapies. Methods: The study included 20 unrelated families and 22 patients from an Indian population who were screened for DMD based on phenotypes such as scoliosis, toe walking and loss of ambulation. Peripheral blood DNA was isolated and subjected to multiplex ligation-dependent probe amplification (MLPA) and targeted NGS of the DMD gene to identify the nature of the mutation. Results: In the study patients, 77 per cent of large deletion mutations and 23 per cent single-nucleotide variations (SNVs) were identified. Novel mutations were also identified along with reported deletions, point mutations and partial deletions within the exon of the DMD gene. Interpretation & conclusions: Our findings showed the importance of NGS in the routine diagnostic practice in the identification of DMD mutations over sequential testing. It may be used as a single-point diagnostic strategy irrespective of the mutation type, thereby reducing the turnaround time and cost for multiple diagnostic tests such as MLPA and Sanger sequencing. Though MLPA is a sensitive technique and is the first line of a diagnostic test, the targeted NGS of the DMD gene may have an advantage of having a single diagnostic test. A study on a larger number of patients is needed to highlight NGS as a single, comprehensive platform for the diagnosis of DMD.
Subject(s)
Dystrophin/genetics , High-Throughput Nucleotide Sequencing/methods , Muscular Dystrophy, Duchenne/diagnosis , Muscular Dystrophy, Duchenne/genetics , Mutation , Polymorphism, Single Nucleotide , Adolescent , Child , Child, Preschool , DNA Mutational Analysis , Exons , Gene Deletion , Genome, Human , Humans , India/epidemiology , Male , Multiplex Polymerase Chain Reaction , Phenotype , Point Mutation , Sequence DeletionABSTRACT
Human mitochondrial DNA is transcribed by POLRMT with the help of two initiation factors, TFAM and TFB2M. The current model postulates that the role of TFAM is to recruit POLRMT and TFB2M to melt the promoter. However, we show that TFAM has 'post-recruitment' roles in promoter melting and RNA synthesis, which were revealed by studying the pre-initiation steps of promoter binding, bending and melting, and abortive RNA synthesis. Our 2-aminopurine mapping studies show that the LSP (Light Strand Promoter) is melted from -4 to +1 in the open complex with all three proteins and from -4 to +3 with addition of ATP. Our equilibrium binding studies show that POLRMT forms stable complexes with TFB2M or TFAM on LSP with low-nanomolar Kd values, but these two-component complexes lack the mechanism to efficiently melt the promoter. This indicates that POLRMT needs both TFB2M and TFAM to melt the promoter. Additionally, POLRMT+TFB2M makes 2-mer abortives on LSP, but longer RNAs are observed only with TFAM. These results are explained by TFAM playing a role in promoter melting and/or stabilization of the open complex on LSP. Based on our results, we propose a refined model of transcription initiation by the human mitochondrial transcription machinery.
Subject(s)
DNA-Binding Proteins/metabolism , Methyltransferases/metabolism , Mitochondria/genetics , Mitochondria/metabolism , Mitochondrial Proteins/metabolism , Promoter Regions, Genetic , Transcription Factors/metabolism , Transcription Initiation, Genetic , Binding Sites , DNA, Mitochondrial , Humans , Models, Biological , Multiprotein Complexes , Protein BindingABSTRACT
Single-subunit RNA polymerases (RNAPs) are present in phage T7 and in mitochondria of all eukaryotes. This RNAP class plays important roles in biotechnology and cellular energy production, but we know little about its fidelity and error rates. Herein, we report the error rates of three single-subunit RNAPs measured from the catalytic efficiencies of correct and all possible incorrect nucleotides. The average error rates of T7 RNAP (2 × 10-6), yeast mitochondrial Rpo41 (6 × 10-6), and human mitochondrial POLRMT (RNA polymerase mitochondrial) (2 × 10-5) indicate high accuracy/fidelity of RNA synthesis resembling those of replicative DNA polymerases. All three RNAPs exhibit a distinctly high propensity for GTP misincorporation opposite dT, predicting frequent AâG errors in RNA with rates of â¼10-4 The AâC, GâA, AâU, CâU, GâU, UâC, and UâG errors mostly due to pyrimidine-purine mismatches were relatively frequent (10-5-10-6), whereas CâG, UâA, GâC, and CâA errors from purine-purine and pyrimidine-pyrimidine mismatches were rare (10-7-10-10). POLRMT also shows a high CâA error rate on 8-oxo-dG templates (â¼10-4). Strikingly, POLRMT shows a high mutagenic bypass rate, which is exacerbated by TEFM (transcription elongation factor mitochondrial). The lifetime of POLRMT on terminally mismatched elongation substrate is increased in the presence of TEFM, which allows POLRMT to efficiently bypass the error and continue with transcription. This investigation of nucleotide selectivity on normal and oxidatively damaged DNA by three single-subunit RNAPs provides the basic information to understand the error rates in mitochondria and, in the case of T7 RNAP, to assess the quality of in vitro transcribed RNAs.
Subject(s)
DNA-Directed RNA Polymerases/metabolism , Mitochondrial Proteins/metabolism , Mutation , Saccharomyces cerevisiae Proteins/metabolism , Transcription Elongation, Genetic , Viral Proteins/metabolism , 8-Hydroxy-2'-Deoxyguanosine , Bacteriophage T7/enzymology , Base Pair Mismatch , DNA Damage , DNA-Directed RNA Polymerases/genetics , Deoxyguanosine/analogs & derivatives , Deoxyguanosine/metabolism , Fluorescence Polarization , Humans , Mitochondrial Proteins/genetics , Mutation Rate , Oxidation-Reduction , Recombinant Fusion Proteins/metabolism , Recombinant Proteins/metabolism , Saccharomyces cerevisiae/enzymology , Saccharomyces cerevisiae Proteins/genetics , Substrate Specificity , Transcription Factors/metabolism , Viral Proteins/geneticsABSTRACT
Primases use single-stranded (ss) DNAs as templates to synthesize short oligoribonucleotide primers that initiate lagging strand DNA synthesis or reprime DNA synthesis after replication fork collapse, but the origin of this activity in the mitochondria remains unclear. Herein, we show that the Saccharomyces cerevisiae mitochondrial RNA polymerase (Rpo41) and its transcription factor (Mtf1) is an efficient primase that initiates DNA synthesis on ssDNA coated with the yeast mitochondrial ssDNA-binding protein, Rim1. Both Rpo41 and Rpo41-Mtf1 can synthesize short and long RNAs on ssDNA template and prime DNA synthesis by the yeast mitochondrial DNA polymerase Mip1. However, the ssDNA-binding protein Rim1 severely inhibits the RNA synthesis activity of Rpo41, but not the Rpo41-Mtf1 complex, which continues to prime DNA synthesis efficiently in the presence of Rim1. We show that RNAs as short as 10-12 nt serve as primers for DNA synthesis. Characterization of the RNA-DNA products shows that Rpo41 and Rpo41-Mtf1 have slightly different priming specificity. However, both prefer to initiate with ATP from short priming sequences such as 3'-TCC, TTC, and TTT, and the consensus sequence is 3'-Pu(Py)2-3 Based on our studies, we propose that Rpo41-Mtf1 is an attractive candidate for serving as the primase to initiate lagging strand DNA synthesis during normal replication and/or to restart stalled replication from downstream ssDNA.
Subject(s)
DNA, Fungal/biosynthesis , DNA, Single-Stranded/metabolism , DNA-Directed RNA Polymerases/metabolism , Mitochondrial Proteins/metabolism , Multiprotein Complexes/metabolism , Saccharomyces cerevisiae Proteins/metabolism , Saccharomyces cerevisiae/metabolism , Transcription Factors/metabolism , DNA Polymerase I/genetics , DNA Polymerase I/metabolism , DNA, Fungal/genetics , DNA, Single-Stranded/genetics , DNA-Directed RNA Polymerases/genetics , Mitochondrial Proteins/genetics , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae Proteins/genetics , Transcription Factors/geneticsABSTRACT
Cancer research has made significant progress in recent years, and extracellular vesicles (EVs) based cancer investigation reveals several facts about cancer. Exosomes are a subpopulation of EVs. In the present decade, exosomes is mostly highlighted for cancer theranostic research. Tumor cell derived exosomes (TEXs) promote cancer but there are multiple sources of exosomes that can be used as cancer therapeutic agents (plant exosomes, stem cell-derived exosomes, modified or synthetic exosomes). Stem cells based regenerative medicine faces numerous challenges, such as promote tumor development, cellular reprogramming etc., and therefore addressing these complications becomes essential. Stem cell-derived exosomes serves as an answer to these problems and offers a better solution. Global research indicates that stem cell-derived exosomes also play a dual role in the cellular system by either inhibiting or promoting cancer. Modified exosomes which are genetically engineered exosomes or surface modified exosomes to increase the efficacy of the therapeutic properties can also be considered to target the above concerns. However, the difficulties associated with the exosomes include variations in exosomes heterogenity, isolation protocols, large scale production, etc., and these have to be managed effectively. In this review, we explore exosomes biogenesis, multiple stem cell-derived exosome sources, drug delivery, modified stem cells exosomes, clinical trial of stem cells exosomes, and the related challenges in this domain and future orientation. This article may encourage researchers to explore stem cell-derived exosomes and develop an effective and affordable cancer therapeutic solution.
Subject(s)
Exosomes , Extracellular Vesicles , Neoplasms , Humans , Exosomes/metabolism , Regenerative Medicine/methods , Neoplasms/drug therapy , Stem CellsABSTRACT
BACKGROUND: Prediction of pregnancies at risk of preterm birth (PTB) may allow targeted prevention strategies. OBJECTIVES: To assess quality of clinical practice guidelines (CPGs) and identify areas of agreement and contention in prediction and prevention of spontaneous PTB. SEARCH STRATEGY: We searched for CPGs regarding PTB prediction and prevention in asymptomatic singleton pregnancies without language restriction in January 2024. SELECTION CRITERIA: CPGs included were published between July 2017 and December 2023 and contained statements intended to direct clinical practice. DATA COLLECTION AND ANALYSIS: CPG quality was assessed using the AGREE-II tool. Recommendations were extracted and grouped under domains of prediction and prevention, in general populations and high-risk groups. MAIN RESULTS: We included 37 CPGs from 20 organizations; all were of moderate or high quality overall. There was consensus in prediction of PTB by identification of risk factors and cervical length screening in high-risk pregnancies and prevention of PTB by universal screening and treatment for asymptomatic bacteriuria, screening and treatment for BV in high-risk pregnancies, and use of preventative progesterone and cerclage. Areas of contention or limited consensus were the role of PTB clinics, universal cervical length measurement, biomarkers and cervical pessaries. CONCLUSIONS: This review identified strengths and limitations of current PTB CPGs, and areas for future research.
Subject(s)
Practice Guidelines as Topic , Premature Birth , Humans , Premature Birth/prevention & control , Pregnancy , Female , Risk Factors , Cervical Length Measurement , Quality Assurance, Health Care , Pregnancy, High-RiskABSTRACT
Mitochondrial transcription factor A (TFAM) employs DNA bending to package mitochondrial DNA (mtDNA) into nucleoids and recruit mitochondrial RNA polymerase (POLRMT) at specific promoter sites, light strand promoter (LSP) and heavy strand promoter (HSP). Herein, we characterize the conformational dynamics of TFAM on promoter and non-promoter sequences using single-molecule fluorescence resonance energy transfer (smFRET) and single-molecule protein-induced fluorescence enhancement (smPIFE) methods. The DNA-TFAM complexes dynamically transition between partially and fully bent DNA conformational states. The bending/unbending transition rates and bending stability are DNA sequence-dependent-LSP forms the most stable fully bent complex and the non-specific sequence the least, which correlates with the lifetimes and affinities of TFAM with these DNA sequences. By quantifying the dynamic nature of the DNA-TFAM complexes, our study provides insights into how TFAM acts as a multifunctional protein through the DNA bending states to achieve sequence specificity and fidelity in mitochondrial transcription while performing mtDNA packaging.
Subject(s)
DNA Packaging , DNA, Mitochondrial , DNA-Binding Proteins , Fluorescence Resonance Energy Transfer , Mitochondrial Proteins , Nucleic Acid Conformation , Promoter Regions, Genetic , Transcription Factors , DNA-Binding Proteins/metabolism , DNA-Binding Proteins/chemistry , DNA-Binding Proteins/genetics , Mitochondrial Proteins/metabolism , Mitochondrial Proteins/genetics , Mitochondrial Proteins/chemistry , Transcription Factors/metabolism , Transcription Factors/chemistry , Transcription Factors/genetics , DNA, Mitochondrial/genetics , DNA, Mitochondrial/metabolism , Humans , Transcription Initiation, Genetic , Mitochondria/metabolism , Mitochondria/genetics , Single Molecule Imaging , DNA-Directed RNA Polymerases/metabolism , DNA-Directed RNA Polymerases/chemistry , DNA-Directed RNA Polymerases/genetics , Base Sequence , Protein BindingABSTRACT
Tuberculosis (TB) is a leading cause of mortality attributed to an infectious agent. TB primarily targets the lungs, but in about 16% cases can affect other organs as well, giving rise to extrapulmonary TB (EPTB). However, an optimal regimen for EPTB treatment is not defined. Although the recommended treatment for most forms of EPTB is the same as pulmonary TB, the pharmacokinetics of EPTB therapy are not as well studied. To address this gap, we formulate a whole-body physiologically-based pharmacokinetic (PBPK) model for EPTB that for the first time includes the ability to simulate drug concentrations in the pleura and lymph node, the most commonly affected sites of EPTB. Using this model, we estimate the time-dependent concentrations, at potential EPTB infection sites, of the following four first-line anti-TB drugs: rifampicin, ethambutol, isoniazid, and pyrazinamide. We use reported plasma concentration kinetics data to estimate model parameters for each drug and validate our model using reported concentration data not used for model formulation or parameter estimation. Model predictions match the validation data, and reported pharmacokinetic parameters (maximum plasma concentration, time to reach maximum concentration) for the drugs. The model also predicts ethambutol, isoniazid, and pyrazinamide concentrations in the pleura that match reported experimental values from an independent study. For each drug, the predicted drug concentrations at EPTB sites are compared with their critical concentration. Simulations suggest that although rifampicin and isoniazid concentrations are greater than critical concentration values at most EPTB sites, the concentrations of ethambutol and pyrazinamide are lower than their critical concentrations at most EPTB sites.
Subject(s)
Isoniazid , Tuberculosis , Humans , Pyrazinamide , Ethambutol , Rifampin/pharmacokinetics , Tuberculosis/drug therapy , Antitubercular AgentsABSTRACT
INTRODUCTION: Older children and adults with spinal muscular atrophy (SMA) have been shown to have more anxiety, depression, and other behavioral problems in a few studies. But no similar studies have been performed in infants and young children with SMA. METHOD: Behavioral co-morbidities of young children with SMA were compared with healthy and children with chronic non-neurological illness control group. Infant Behavior Questionnaire-Revised (IBQ-R) and parent-report version of chid behavior checklist (CBCL) were used for infants and preschool-age children respectively. RESULTS: A total of 35 SMA children (age at symptom onset-5.9 ± 2.8 months, at enrolment-21.4 ± 7.1 months, 65% boys, 11, 19 and 5 were SMA 1, 2 and 3 respectively) and 24 siblings (38.6 ± 11.2 months, 71% boys) were enrolled. We also enrolled 15 children with nephrotic syndrome as age and gender matched control to SMA children in age-group 2-5 years (27.7 ± 9.1 months, 67% boys). In infants with SMA, the scale scores of IBQ-R were significantly higher for distress to limitation, fear, sadness, and falling reactivity/rate of recovery from distress (p = 0.005; 0.03; 0.001, and 0.04) and lower for soothability as compared to healthy control group (p = 0.04). Similarly, for the three dimensions of temperament computed from these 13 domains, the mean scale score for surgency/extraversion was lower and negative affectivity was higher (p = 0.04 and 0.03), in infants with SMA as compared to healthy controls. For preschool age group, the internalizing problem scores (p = 0.009 and 0.03) and stress problem scores (p = 0.002 and 0.04) were higher in the SMA group, as compared to both the healthy control group and diseased control group. While assessing the syndrome scale scores, the score was higher for emotionally reactive (p = 0.0002 and 0.01) and anxious domains (p < 0.0001 and p = 0.0002) compared to both healthy and diseased control groups. CONCLUSION: Infants and young children with SMA suffer from increased internalizing problems like anxiety, depression and probably their healthy siblings are also at increased levels of stress, depicted by increased somatic complaints.
Subject(s)
Muscular Atrophy, Spinal , Problem Behavior , Spinal Muscular Atrophies of Childhood , Male , Adult , Humans , Child , Infant , Child, Preschool , Adolescent , Female , Siblings , Cross-Sectional StudiesABSTRACT
PURPOSE: This systematic review explored how virtual reality (VR) has been used to rehabilitate aphasia. MATERIALS AND METHODS: Empirical studies were included where VR was used to target language, well-being, or quality of life in adults with acquired language impairment. Degenerative communication disabilities were excluded. Seven health databases were searched in October 2021. Risk of Bias was assessed using published checklists and completeness of intervention reporting evaluated. Narrative synthesis described forms of VR, rationales given, outcome measures, communication functions targeted, characteristics of interventions, and outcomes achieved within the framework of impairment, activity, and participation. RESULTS: Fourteen studies, involving 229 participants, met the criteria. The studies employed four forms of VR with various rationales given. Interventions used published and novel protocols. Primary outcomes targeted language impairment (12/14), activity (1/14), and well-being (1/14) and achieved positive outcomes in impairment and activity. All studies were exploratory. Risk of bias was high. Findings are discussed in the context of gains achieved by VR in other health contexts and the multi-user gaming literature. CONCLUSIONS: Uses of VR in aphasia rehabilitation described in the literature are limited. Most applications target the remediation of language impairments. Opportunities to address activity, participation, and wider aspects of well-being are rare.IMPLICATIONS FOR REHABILITATIONResearch documenting the use of virtual reality (VR) to rehabilitate aphasia is limited and exploratory, so does not yet offer clear guidance for clinicians.Many of the identified studies have used known published protocols (e.g., naming therapy or scripts therapy) delivered through the novel VR format and focus on language impairment outcomes.VR offers clinicians a unique opportunity to address communication activity and participation through the use of multi-user virtual worlds, but this has only been explored by only two research teams.
Subject(s)
Aphasia , Virtual Reality Exposure Therapy , Adult , Humans , Aphasia/rehabilitation , Quality of LifeABSTRACT
Objectives: This study aims to compare the cost-effectiveness of oral prednisolone and adrenocorticotropic hormone injection in West syndrome patients, the two most common hormonal therapies used for this condition. Materials and Methods: In this prospective and observational study, we documented sociodemographic, epilepsy, and development-related variables at baseline and up to 6 months after starting hormonal therapy, in all consecutive eligible patients of WS between August 2019 and June 2021, apart from the direct medical and non-medical costs and indirect health-care costs. We selected cost per quality-adjusted life-year (QALY) gained, per one patient with spasm freedom, one positive responder (>50% reduction in spasms), one relapse-free patient, and one patient with development gain. We determined whether incremental cost-effectiveness ratio for these parameters crossed the threshold value in base-case analysis and alternate scenario analysis. Results: Out of 52 patients screened, 38 and 13 patients enrolled in ACTH and prednisolone group. On D28, 76% and 71% achieved spasm cessation (P = 0.78) and the total cost of treatment was INR 19783 and 8956 (P = 0.01), in ACTH and prednisolone group respectively. For all pre-specified parameters, the cost/effectiveness ratios including cost/QALY gain were higher in ACTH group and the corresponding ICER values for all these parameters crossed the threshold cost value of INR 148,777 in base-case analysis and also in alternative scenario analysis. Conclusion: Treatment with oral prednisolone is more cost-effective as compared to ACTH injection for children with WS.
ABSTRACT
INTRODUCTION: Nutritional vitamin B12 deficiency has been shown to cause Infantile epileptic spasms syndrome (IESS) in infants in anecdotal studies. METHODS: In this retrospective cohort study, we intended to study the clinical presentation, neurophysiological, laboratory abnormalities, treatment, and neurodevelopmental outcome at 6-months in infants presenting with IESS secondary to nutritional vitamin B12 deficiency (NVBD) and to compare these variables from the rest of the infants with IESS without vitamin B12 deficiency. We included only spasm-free cases or those who showed at least a 50% reduction in spasm frequency on D7 after starting oral/parenteral vitamin B12. We used well-validated measurement tools like the Developmental Assessment Scale for Indian Infants (DASII), Child Feeding Index (CFI), Burden of amplitudes and epileptiform discharges (BASED) score, countable Hypsarrhythmia paroxysm index (cHPI), durational Hypsarrhythmia paroxysm index (dHPI), and Early childhood epilepsy severity scale (E-CHESS) score for documenting these variables. RESULTS: Data from 162 infants with IESS (21 caused by NVBD) were included in our study. The NVBD group had more patients residing in the rural region, with lower socioeconomic status, vegetarian mothers and poor complementary feeding index (p<0.001 for all). The NVBD group also had less number of patients requiring antiseizure medications (ASMs) and hormonal therapy(p<0.001), remained seizure free at six months (p=0.008), lower number of clusters per day (p=0.02) and the number of spasms per clusters at presentation (p=0.03), lower BASED score (p=0.03) and cHPI, dHPI at presentation (p<0.001). All of them remained spasm-free, with normal electroencephalogram at 6-months. Development quotient at baseline, at 6-months, and improvement in development quotient between these two-time points were more in the vitamin B12 deficiency group (p<0.001). All of them had clinical features of pre-ITS (infantile tremor syndrome) or ITS and it was found to be the only independent predictor of NVBD in infants with IESS. Mothers of all these infants had low serum vitamin B12 levels (<200 pg/ml). CONCLUSIONS: Nutritional vitamin B12 deficiency may cause IESS in infants. Hence, vitamin B12 deficiency needs to be ruled out in patients with IESS without any definite etiology.
Subject(s)
Spasms, Infantile , Vitamin B 12 Deficiency , Humans , Infant , Retrospective Studies , Spasms, Infantile/etiology , Spasms, Infantile/complications , Syndrome , Vitamin B 12/therapeutic use , Vitamin B 12 Deficiency/complications , Vitamin B 12 Deficiency/drug therapyABSTRACT
Objectives: Although several studies have shown sensory processing abnormalities in pediatric subjects with attention-deficit hyperactivity disorder (ADHD), there is significant heterogeneity among their results. Materials and Methods: This study was performed to compare the sensory processing abilities of children and adolescents with and without ADHD aged 6-15 years and to correlate the sensory processing problems in these patients, with the symptom profile and severity of ADHD. While child sensory profile-2 (SP-2) was used to assess, the sensory processing abilities of ADHD patients, revised Connor's parent rating scale revised, Malin's intelligence scale for Indian children, grade level assessment device, and child behavior checklist were used to assess ADHD symptom severity, intelligence, learning, and behavioral problems, respectively. Results: A total of 66 ADHD patients enrolled (60 boys), 22 (28%), 7 (9%), and 49 (63%) cases were the ADHD-hyperactive-impulsive (ADHD-HI), ADHD-inattentive, and ADHD-combined (ADHD-C) types, respectively, and 33 typically developing controls. The ADHD patients had a significantly low raw score on most of the factors, sections, and response patterns of SP-2 (P < 0.05), but only four and one ADHD patients had auditory and visual processing scores outside the normal clinical range. There was a trend toward higher scores in the children with ADHD-C and ADHD-HI subtypes. There was a moderate negative correlation between hyperactivity/impulsivity T-score and auditory processing scores in the SP (P < 0.05, r = -0.43). We observed a negative correlation, although weak, between visual processing scores and hyperactivity/impulsivity and a positive correlation between the severity of conduct disorder-related problems, oppositional defiant problems, anxiety problems, and auditory as well as tactile processing scores (P < 0.05). In the quadrant score summary, the scores for all four types, that is, sensory sensitivity, low registration, sensation avoiding, and sensation seeking, were significantly more in the ADHD group, as compared to healthy controls. Conclusion: Sensory processing abilities in ADHD children differ from that of typically developing children when objectively assessed, although most of the ADHD children had scores in the clinically normal range. The sensory processing profile also has an impact on the severity and comorbidity profile of ADHD patients.
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Introduction: There is no bedside clinical examination-based prediction score for Duchenne muscular dystrophy/Becker muscular dystrophy (DMD/BMD) in children with neuromuscular diseases (NMDs) presenting with proximal limb-girdle weakness. Methods: We compared the details of 200 cases of lower motor neuron type of weakness and had some proximal limb-girdle muscle weakness and divided them into 2 groups: with/without a confirmed diagnosis of DMD/BMD. We determined the predictive factors associated with a diagnosis of DMD/BMD using multivariate binary logistic regression. We assessed our proposed prognostic model using both discrimination and calibration and subsequently used the bootstrap method to successfully validate the model internally. Results: A total of 121 patients had DMD/BMD and the rest of the patients had other diagnoses. Male gender, presence of Gower's sign, valley sign, toe walking, calf pseudohypertrophy, and tongue hypertrophy were independent predictors for a confirmed diagnosis of DMD/BMD and included in the final CVT2MG score (Calf pseudohypertrophy, Valley sign, Toe walking, Tongue hypertrophy, Male gender, and Gower's sign). The final model showed good discrimination (AUC = 87.4% [95% CI: 80.5-92.3%, P < 0.001]) and calibration (P = 0.57). A score of 6 or above appeared to be the best cutoff for discriminating between the DMD/BMD group and the rest of the group with both sensitivity and specificity of 98%. The interrater reliability was almost perfect between two pediatric neurologists and strong between a pediatric neurologist and a pediatric neurology trainee resident (k = 0.91 and 0.87). Conclusion: The CVT2MG score has good sensitivity and specificity in predicting a confirmed diagnosis of DMD/BMD in subsequent tests.
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Objectives: Acute repetitive seizures (ARSs) are one of the few commonly encountered neurological emergencies in children. There is a need for an appropriate timeline-based treatment protocol, which will be shown to be safe and efficacious in a clinical study. Materials and Methods: This was a retrospective chart review to determine the efficacy of a pre-specified treatment protocol for the management of ARSs in children aged 1-18 years. The treatment protocol was specifically applied in children with a diagnosis of epilepsy and not critically ill, who met the criteria for ARSs, with the exemption of new onset of ARSs. The first tier of treatment protocol focused on intravenous lorazepam, optimization of dose of existing anti-seizure medications (ASMs), and control of triggers like acute febrile illness, while second-tier focused on adding one or two additional ASMs, commonly used in cases with seizure clusters or status epilepticus. Results: We included the first 100 consecutive patients (7.6 ± 3.2 years, 63% boys). Our treatment protocol was successful in 89 patients (58 and 31 required first-tier and second-tier treatment). The absence of pre-existing drug-resistant epilepsy and the presence of acute febrile illness as a triggering factor (P = 0.02 and 0.03) were associated with the success of the first tier of the treatment protocol. Excessive sedation (n = 29), incoordination (n = 14), transient gait instability (n = 11), and excessive irritability (n = 5) were the most common adverse effects observed during the initial 1 week. Conclusion: This pre-specified treatment protocol is safe and efficacious in controlling ARSs in cases with established epilepsy who are not critically sick. External validation from other parts of the world/centers and a more diverse epilepsy population are required before generalizing the protocol into clinical practice.
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INTRODUCTION: The clinical assessment scale for autoimmune encephalitis (CASE) is a recently developed and validated scale to rate the severity of autoimmune encephalitis (AE) in adults. But it is yet to be validated in pediatric AE cases. METHODS: In a prospective observational study, we determined the validity and prognostic utility of CASE in the pediatric population with a diagnosis of probable or definite AE. We also determined clinical, neuroimaging, or laboratory-based prognostic factors for favorable clinical outcomes at 3 months after presentation. We used weighted kappa statistics and the intra-class correlation coefficient of individual item scores and total scores for determining inter-observer and intra-observer reliability respectively. RESULTS: We enrolled a total of 54 patients (28 girls, probable [45%] or definite [55%] AE). Functional status score (FSS), CASE score, and other scores showed significant improvement at the time of discharge and 3-months, as compared to baseline (p < 0.0001). The intra-observer and interobserver reliability of the total scores was excellent (k = 0.94 and 0.95 respectively). CASE was also found to have good internal consistency (Cronbach-α = 0.83). The corrected item-total correlations of all items were >0.40. The correlation between the total CASE score and FSS score at admission, at discharge, and at 3 months was strong (r = 0.90, 0.92, and 0.94, p < 0.001). In multivariate analysis, only seropositivity or definite AE and CASE score at baseline was found to be significant predictive factors for functional status at 3 months (p = 0.03, 0.01). CONCLUSION: CASE score can be used for monitoring the severity of pediatric AE patients. It also has prognostic usefulness for predicting functional independence on follow-up.