ABSTRACT
BACKGROUND: Few treatment options exist for patients with severe central nervous system (CNS) tuberculosis (TB) worsening due to inflammatory lesions, despite optimal antitubercular therapy (ATT) and steroids. Data regarding the efficacy and safety of infliximab in these patients are sparse. METHODS: We performed a matched retrospective cohort study based on Medical Research Council (MRC) grading system and modified Rankin Scale (mRS) scores comparing 2 groups of adults with CNS TB. Cohort A received at least 1 dose of infliximab after optimal ATT and steroids between March 2019 and July 2022. Cohort B received only ATT and steroids. Disability-free survival (mRS score ≤2) at 6 months was the primary outcome. RESULTS: Baseline MRC grades and mRS scores were similar between the cohorts. Median duration before initiation of infliximab therapy from start of ATT and steroids was 6 (IQR: 3.7-13) months and for neurological deficits was 4 (IQR: 2-6.2) months. Indications for infliximab were symptomatic tuberculomas (20/30; 66.7%), spinal cord involvement with paraparesis (8/30; 26.7%), and optochiasmatic arachnoiditis (3/30; 10%), worsening despite adequate ATT and steroids. Severe disability (5/30 [16.7%] and 21/60 [35%]) and all-cause mortality (2/30 [6.7%] and 13/60 [21.7%]) at 6 months were lower in cohort A versus cohort B, respectively. In the combined study population, only exposure to infliximab was positively associated (aRR: 6.2; 95% CI: 2.18-17.83; P = .001) with disability-free survival at 6 months. There were no clear infliximab-related side effects noted. CONCLUSIONS: Infliximab may be an effective and safe adjunctive strategy among severely disabled patients with CNS TB not improving despite optimal ATT and steroids. Adequately powered phase 3 clinical trials are required to confirm these early findings.
Subject(s)
Disabled Persons , Infliximab , Tuberculosis, Central Nervous System , Adult , Humans , Antitubercular Agents/adverse effects , Antitubercular Agents/pharmacology , Infliximab/adverse effects , Infliximab/pharmacology , Retrospective Studies , Steroids , Treatment Outcome , Tuberculosis, Central Nervous System/drug therapyABSTRACT
Idiopathic intussusception is the most common form of intussusception in infants and young children. In older children and adults, intussusception being rare, the lead point is usually an underlying bowel pathology (Meckel's diverticulum, hemangioma, carcinoids, polyps, submucous lipomas, etc.) and these are called pathological lead points (PLP's). The management of an obese child with recurrent abdominal pain for over 2 years, diagnosed with ileo-ileal intussusception due to submucosal lipoma is reported here.
ABSTRACT
One of the concerns limiting the use of clozapine in schizophrenia treatment is the risk of rare but potentially fatal myocarditis. Our previous genome-wide association study and human leucocyte antigen analyses identified putative loci associated with clozapine-induced myocarditis. However, the contribution of DNA variation in cytochrome P450 genes, copy number variants and rare deleterious variants have not been investigated. We explored these unexplored classes of DNA variation using whole-genome sequencing data from 25 cases with clozapine-induced myocarditis and 25 demographically-matched clozapine-tolerant control subjects. We identified 15 genes based on rare variant gene-burden analysis (MLLT6, CADPS, TACC2, L3MBTL4, NPY, SLC25A21, PARVB, GPR179, ACAD9, NOL8, C5orf33, FAM127A, AFDN, SLC6A11, PXDN) nominally associated (p < 0.05) with clozapine-induced myocarditis. Of these genes, 13 were expressed in human myocardial tissue. Although independent replication of these findings is required, our study provides preliminary insights into the potential role of rare genetic variants in susceptibility to clozapine-induced myocarditis.
Subject(s)
Antipsychotic Agents , Clozapine , Myocarditis , Schizophrenia , Antipsychotic Agents/adverse effects , Clozapine/adverse effects , Genome-Wide Association Study , Humans , Myocarditis/chemically induced , Myocarditis/drug therapy , Myocarditis/genetics , Schizophrenia/drug therapy , Schizophrenia/geneticsABSTRACT
OBJECTIVE: To compare the findings of ultrasonography of the upper airway with flexible fiberoptic laryngoscopy and determine the efficacy of transcutaneous laryngeal ultrasonography for decannulation. DESIGN: Prospective cross-sectional study. SETTING: Tertiary care referral center in South India. PARTICIPANTS: Twenty-four patients with acquired brain injury (N=24). MAIN OUTCOME MEASURES: Participants underwent an airway assessment by ultrasonography followed by assessment of airway by flexible laryngoscopy done within the next 72 hours. RESULTS: Vocal cord assessment by ultrasonography revealed a sensitivity of 81.2% and specificity of 87.5%. A statistically significant association between vocal cord mobility as assessed by ultrasonography and decannulation was observed (sensitivity of 81.25%, specificity of 87.5%, P=.002). Although aspiration was not assessed by ultrasonography, a statistically significant association was observed between vocal cord mobility on ultrasonography and aspiration as assessed by laryngoscopy (sensitivity of 81.25%, specificity of 87.5%, P=.011). CONCLUSION: Laryngeal ultrasonography is an emerging diagnostic modality with a potential role for assessing vocal cord mobility and airway prior to decannulation in centers that lack the expertise and the infrastructure to perform a flexible laryngoscopy.
Subject(s)
Brain Injuries , Tracheostomy , Humans , Pilot Projects , Prospective Studies , Cross-Sectional Studies , Ultrasonography , Brain Injuries/diagnostic imagingABSTRACT
OBJECTIVE: Schizophrenia, a complex psychiatric disorder, is often associated with cognitive, neurological and neuroimaging abnormalities. The processes underlying these abnormalities, and whether a subset of people with schizophrenia have a neuroprogressive or neurodegenerative component to schizophrenia, remain largely unknown. Examining fluid biomarkers of diverse types of neuronal damage could increase our understanding of these processes, as well as potentially provide clinically useful biomarkers, for example with assisting with differentiation from progressive neurodegenerative disorders such as Alzheimer and frontotemporal dementias. METHODS: This study measured plasma neurofilament light chain protein (NfL) using ultrasensitive Simoa technology, to investigate the degree of neuronal injury in a well-characterised cohort of people with treatment-resistant schizophrenia on clozapine (n = 82), compared to first-degree relatives (an at-risk group, n = 37), people with schizophrenia not treated with clozapine (n = 13), and age- and sex-matched controls (n = 59). RESULTS: We found no differences in NfL levels between treatment-resistant schizophrenia (mean NfL, M = 6.3 pg/mL, 95% confidence interval: [5.5, 7.2]), first-degree relatives (siblings, M = 6.7 pg/mL, 95% confidence interval: [5.2, 8.2]; parents, M after adjusting for age = 6.7 pg/mL, 95% confidence interval: [4.7, 8.8]), controls (M = 5.8 pg/mL, 95% confidence interval: [5.3, 6.3]) and not treated with clozapine (M = 4.9 pg/mL, 95% confidence interval: [4.0, 5.8]). Exploratory, hypothesis-generating analyses found weak correlations in treatment-resistant schizophrenia, between NfL and clozapine levels (Spearman's r = 0.258, 95% confidence interval: [0.034, 0.457]), dyslipidaemia (r = 0.280, 95% confidence interval: [0.064, 0.470]) and a negative correlation with weight (r = -0.305, 95% confidence interval: [-0.504, -0.076]). CONCLUSION: Treatment-resistant schizophrenia does not appear to be associated with neuronal, particularly axonal degeneration. Further studies are warranted to investigate the utility of NfL to differentiate treatment-resistant schizophrenia from neurodegenerative disorders such as behavioural variant frontotemporal dementia, and to explore NfL in other stages of schizophrenia such as the prodome and first episode.
Subject(s)
Alzheimer Disease , Clozapine , Frontotemporal Dementia , Neurodegenerative Diseases , Schizophrenia , Alzheimer Disease/metabolism , Biomarkers , Child , Clozapine/therapeutic use , Frontotemporal Dementia/metabolism , Humans , Intermediate Filaments , Neurofilament Proteins , Schizophrenia/metabolism , Schizophrenia, Treatment-ResistantSubject(s)
Hair Removal , Laser Therapy , Hair , Hair Removal/adverse effects , Humans , Laser Therapy/adverse effects , Lasers , Lip , Pain/etiology , Pain/prevention & control , Pain Management , Silicone GelsSubject(s)
Alopecia/diagnosis , Dermoscopy/methods , Hair/diagnostic imaging , Alopecia/therapy , Humans , Treatment OutcomeSubject(s)
Problem Behavior , Schizophrenia , Clonidine/adverse effects , Humans , Schizophrenia/drug therapySubject(s)
Electroconvulsive Therapy , Metaphor , Humans , Informed Consent , Inpatients , Mental HealthSubject(s)
Clopenthixol/adverse effects , Lithium/adverse effects , Neurotoxicity Syndromes/etiology , Schizophrenia/therapy , Antipsychotic Agents/administration & dosage , Antipsychotic Agents/adverse effects , Brain/drug effects , Clopenthixol/administration & dosage , Drug Therapy, Combination , Electroconvulsive Therapy , Electroencephalography , Humans , Lithium/administration & dosage , Male , Middle Aged , Neurotoxicity Syndromes/diagnosisABSTRACT
Background and Hypothesis: Around 30% of people with schizophrenia are refractory to antipsychotic treatment (treatment-resistant schizophrenia; TRS). While abnormal structural neuroimaging findings, in particular volume and thickness reductions, are often observed in schizophrenia, it is anticipated that biomarkers of neuronal injury like neurofilament light chain protein (NfL) can improve our understanding of the pathological basis underlying schizophrenia. The current study aimed to determine whether people with TRS demonstrate different associations between plasma NfL levels and regional cortical thickness reductions compared with controls. Study Design: Measurements of plasma NfL and cortical thickness were obtained from 39 individuals with TRS, and 43 healthy controls. T1-weighted magnetic resonance imaging sequences were obtained and processed via FreeSurfer. General linear mixed models adjusting for age and weight were estimated to determine whether the interaction between diagnostic group and plasma NfL level predicted lower cortical thickness across frontotemporal structures and the insula. Study Results: Significant (false discovery rate corrected) cortical thinning of the left (p = 0.001, η2p = 0.104) and right (p < 0.001, η2p = 0.167) insula was associated with higher levels of plasma NfL in TRS, but not in healthy controls. Conclusions: The association between regional thickness reduction of the insula bilaterally and plasma NfL may reflect a neurodegenerative process during the course of TRS. The findings of the present study suggest that some level of cortical degeneration localised to the bilateral insula may exist in people with TRS, which is not observed in the normal population.
ABSTRACT
BACKGROUND: Brain structural alterations and cognitive dysfunction are independent predictors for poor clinical outcome in schizophrenia, and the associations between these domains remains unclear. We employed a novel, multiblock partial least squares correlation (MB-PLS-C) technique and investigated multivariate cortico-cognitive patterns in patients with treatment-resistant schizophrenia (TRS) and matched healthy controls (HC). METHOD: Forty-one TRS patients (age 38.5 ± 9.1, 30 males (M)), and 45 HC (age 40.2 ± 10.6, 29 M) underwent 3T structural MRI. Volumes of 68 brain regions and seven variables from CANTAB covering memory and executive domains were included. Univariate group differences were assessed, followed by the MB-PLS-C analyses to identify group-specific multivariate patterns of cortico-cognitive coupling. Supplementary three-group analyses, which included 23 non-affected first-degree relatives (NAR), were also conducted. RESULTS: Univariate tests demonstrated that TRS patients showed impairments in all seven cognitive tasks and volume reductions in 12 cortical regions following Bonferroni correction. The MB-PLS-C analyses revealed two significant latent variables (LVs) explaining > 90% of the sum-of-squares variance. LV1 explained 78.86% of the sum-of-squares variance, describing a shared, widespread structure-cognitive pattern relevant to both TRS patients and HCs. In contrast, LV2 (13.47% of sum-of-squares variance explained) appeared specific to TRS and comprised a differential cortico-cognitive pattern including frontal and temporal lobes as well as paired associates learning (PAL) and intra-extra dimensional set shifting (IED). Three-group analyses also identified two significant LVs, with NARs more closely resembling healthy controls than TRS patients. CONCLUSIONS: MB-PLS-C analyses identified multivariate brain structural-cognitive patterns in the latent space that may provide a TRS signature.
Subject(s)
Cognition Disorders , Schizophrenia , Cognition , Cognition Disorders/psychology , Humans , Male , Neuropsychological Tests , Schizophrenia, Treatment-ResistantABSTRACT
Obsessive-compulsive (OC) symptoms are clinically important phenomena in people with schizophrenia. Schizophrenia and obsessive-compulsive disorder (OCD) are considered as neurodevelopmental disorders with dysfunctional frontal subcortical circuitry. In this cross-sectional study, the authors tested the hypothesis that people with schizophrenia with OC symptoms form a subtype with a distinct neurological substrate. Using the Neurological Evaluation Scale (NES), the authors assessed 65 people with ICD-10 criteria for schizophrenia, 21 of whom had OC symptoms, and who were drug-naive or had not received any antipsychotic or anti-obsessive drugs for the previous 3 months. People with schizophrenia and OC symptoms were better educated than those without OC symptoms and differed significantly in proportion to premorbid OC symptoms, but did not differ on measures of psychopathology. Total NES scores and subgroup scores did not differ significantly between people with schizophrenia with or without OC symptoms, but the groups did differ in motor coordination test scores for the left side. Total NES scores correlated significantly with Positive and Negative Symptom Scales negative symptoms scores in those with OC symptoms but not in those without OC symptoms; this correlation was not observed with Yale-Brown Obsessive-Compulsive Scale scores. These findings, if replicated, suggest that OC symptoms in people with schizophrenia are due to differences in frontocerebellar neurological circuitry from those without OC symptoms, with possible neuro-developmental origins.
Subject(s)
Obsessive-Compulsive Disorder/diagnosis , Obsessive-Compulsive Disorder/psychology , Psychiatric Status Rating Scales , Schizophrenia/diagnosis , Schizophrenic Psychology , Severity of Illness Index , Adult , Cross-Sectional Studies , Female , Humans , Male , Obsessive-Compulsive Disorder/complications , Schizophrenia/complications , Young AdultABSTRACT
Resistance to pharmacological agents is commonly encountered in the treatment of acute episodes of mania. In contemporary practice guidelines, electroconvulsive therapy (ECT), once a widely used standalone intervention for mania, is no longer considered a first-line treatment. Stigma, logistics, and ethical factors constrain ECT administration in this condition and lead to its underutilization. However, the past three decades have produced promising research regarding the use of ECT in mania. Randomized controlled trials, albeit in limited numbers, the adoption of ultrabrief ECT, examination of the safety and efficacy of combining ECT with pharmacological agents, including lithium, and use of ECT as a maintenance strategy have enhanced our understanding of how and when to utilize this intervention in mania. In this comprehensive review, the authors summarize the evidence regarding the efficacy and safety of ECT in mania, including related syndromes, such as delirious mania and mixed affective states. The impact of technical parameters, particularly the choice of treatment frequency, electrode placements, and pulse width, are discussed in the light of recent evidence.
Subject(s)
Electroconvulsive Therapy , Mania/therapy , Electroconvulsive Therapy/methods , Humans , Treatment OutcomeABSTRACT
In small infants and babies who receive split or living-related adult left lateral segmental liver grafts, further reduction (hyper-reduction) of the graft may be necessary to optimize the size of the graft for the child. We report our experience with hyper-reduction of adult left lateral segment grafts in nine children. A retrospective review of the medical records of children who received hyper-reduced grafts at the Children's Hospital at Westmead, Australia was performed. Of 215 liver transplants performed on 186 children between 1986 and May 2009, 147 were reduced grafts. Nine grafts were further reduced (hyper-reduced) after an on-table assessment of graft size relative to the available abdominal space was made. Mean graft size reduction was by 30%. The pledgetted technique of resection was used in four patients. All required delayed closure of the abdomen, and in three patients, fascial closure was not possible and a Surgisis patch (Cook Surgical International, West Lafayette, IN, USA) was placed to augment the abdominal capacity. Two children had hepatic artery thrombosis. One was successfully thrombectomized. In the other, technical problems with the donor liver contributed to death 10 days post-transplant. Two bile leaks, one from the cut surface and the other at the anastomotic site, were oversewn at the time of abdominal closure. On follow-up (median 33 months), two developed biliary strictures requiring dilatation. Hyper-reduction of segmental grafts can be safely performed when needed. In view of its versatility, it may be preferable to hyper-reduce a graft rather than use a monosegment graft. Comparable long-term results are possible. The pledgetted technique of resection is easy, quick, and safe. The fact that it can be performed after revascularization with minimal blood loss adds great flexibility to this technically challenging procedure.