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INTRODUCTION: Post stroke cognitive impairment (PSCI) is a common complication of ischemic stroke. PSCI can involve different depending on clinical and stroke related characteristics. The aim of this study is to determine the factors associated with impairments in specific cognitive domains. METHODS: The Vitamins to Prevent Stroke (VITATOPS) trial is a large, multinational randomised controlled trial. In this substudy, consecutive patients admitted for ischaemic stroke or transient ischaemic attack (TIA) at a tertiary hospital in Singapore were included. PSCI was defined as impairment of any of the six cognitive subgroups - visuoconstruction, attention, verbal memory, language, visual memory and visuomotor function - that were assessed annually for up to five years. Univariate and multivariate Cox proportional hazard models were used to determine factors associated with impairments in each of these cognitive domains. RESULTS: A total of 736 patients were included in this study, of which 173 (23.5 %) developed cognitive impairment. Out of the six cognitive domains, the greatest proportion of patients had an impairment in visuoconstruction (26.4 %) followed by attention (19.8 %), verbal memory (18.3 %), language (17.5 %), visual memory (17.3 %) and visuomotor function (14.8 %). Patients with posterior circulation cerebral infarction (POCI) as the index stroke subtype had higher rates of cognitive impairment. Further subgroup analyses show that Indian race and advanced age were predictive of language impairment, whilst fewer years of education and POCI were predictive of verbal memory impairment. POCI was predictive of visual memory impairment, and advanced age and POCI were predictive of visuomotor function impairment. CONCLUSION: We identified visuoconstruction and attention domains to be the most affected in our Asian cohort of PSCI. Advanced age, lower levels of education, posterior circulation strokes and concomitant comorbidities such as peripheral artery disease are independent predictors of PSCI.
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Cognição , Disfunção Cognitiva , Humanos , Masculino , Feminino , Idoso , Pessoa de Meia-Idade , Singapura/epidemiologia , Fatores de Risco , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/epidemiologia , Fatores de Tempo , Memória , Medição de Risco , Prognóstico , AVC Isquêmico/diagnóstico , AVC Isquêmico/epidemiologia , Testes Neuropsicológicos , Atenção , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/complicações , Ataque Isquêmico Transitório/diagnóstico , Ataque Isquêmico Transitório/complicações , Ataque Isquêmico Transitório/psicologiaRESUMO
There is great interest in crosstalk between the gastrointestinal and immune systems. Small intestinal bacterial overgrowth (SIBO) is a bowel disorder prevalent among patients with Parkinson's disease; SIBO treatment has been shown to modulate neurological inflammation, motor and cognitive outcomes there. However, to date, no link between Alzheimer's dementia and SIBO has been established. This pilot study sought to estimate the prevalence of SIBO in Alzheimer's dementia in the outpatient setting in Singapore General Hospital. It entailed performing a hydrogen breath test and objectively scoring gastrointestinal symptoms and their severity in 48 patients, comparing symptom scores and mean breath test values in those with mild to moderate Alzheimer's against age- and sex-matched controls that did not fulfill DSM-V criteria for probable Alzheimer's. Here, the prevalence of positive breath tests and symptoms of SIBO were no greater among Alzheimer's patients than in controls. This suggests that the gut microbiome changes and increased bowel inflammation seen in previous studies on Alzheimer's patients are likely effected through pathways other than SIBO, and are likely more complex than a mere increase in small bowel bacterial volume. Rather, future research could be directed along the lines of qualitative changes in small bowel microbiota, or pathologies in other parts of the gastrointestinal tract such as the colon or stomach, aspects which are not adequately captured by the hydrogen breath test. Keywords: Alzheimer's disease; dementia; gut-brain axis; small intestinal bacterial overgrowth; microbiome.
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Doença de Alzheimer , Microbioma Gastrointestinal , Testes Respiratórios , Humanos , Intestino Delgado , Projetos PilotoRESUMO
Reading disorder is a recognized feature in primary progressive aphasia (PPA). Surface dyslexia, characterized by regularization errors, is typically seen in the English-speaking semantic variant of PPA (svPPA). However, dyslexic characteristics of other languages, particularly logographical languages such as Chinese, remain sparse in the literature. This study aims to characterize and describe the dyslexic pattern in this group of patients by comparing an English-speaking svPPA group with a Chinese-speaking svPPA group. The authors hypothesized that Chinese-speaking individuals with svPPA would likely commit fewer surface dyslexic errors. By accessing the database of Singapore's National Neuroscience Institute and the National Alzheimer's Coordinating Center of the United States, the authors identified three Chinese-speaking and 18 English-speaking patients with svPPA, respectively, for comparison. The results suggest that, instead of surface dyslexia, svPPA in Chinese-speaking individuals is characterized by a profound deep dyslexic error. Based on current evidence suggesting the role of the temporal pole as a semantic convergence center, the authors conclude that this region also mediates and converges lexical-semantic significance in logographical languages.
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Afasia Primária Progressiva/complicações , Dislexia/etiologia , Semântica , Idoso , Afasia Primária Progressiva/diagnóstico por imagem , Povo Asiático , Bases de Dados Factuais/estatística & dados numéricos , Dislexia/diagnóstico por imagem , Feminino , Humanos , Idioma , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Tomografia por Emissão de Pósitrons , Leitura , Estudos Retrospectivos , Estatísticas não ParamétricasRESUMO
OBJECTIVE: Hyperfamiliarity is a phenomenon where new stimuli are perceived as familiar. Previous studies have demonstrated familiarity disorder in mild cognitive impairment (MCI), but mostly from the perspective of a neuropsychological approach, and the exact correlation of MCI aetiologies with the phenomenon remains uncertain. Based on current evidence suggesting a frontal-subcortical pathway contributing to familiarity processing, we hypothesize that individuals with a vascular aetiology of MCI will likely suffer more familiarity deficits. This study aims to examine the real-life hyperfamiliarity symptoms in amnestic versus vascular MCI. METHODS: Informants of 11 amnestic and 9 vascular cognitive impairment patients were interviewed about the frequency of hyperfamiliarity symptoms in the previous month. MRI brain images of vascular cognitive impairment patients were analysed as well. RESULTS: Patients with vascular cognitive impairment with no dementia (VCIND) showed a significantly higher frequency of hyperfamiliarity for people but not places or objects. Within VCIND patients, overall basal ganglia hyperintensities, particularly in the putamen, were found to significantly correlate to hyperfamiliarity. CONCLUSIONS: Patients with VCIND suffer more real-life hyperfamiliarity during people recognition compared to patients with amnestic mild cognitive impairment (aMCI), despite a comparative global decline in cognitive. This is likely due to impaired memory retrieval and matching processes resulting from subcortical ischaemic lesions.
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Transtornos Cognitivos/complicações , Demência Vascular/complicações , Transtornos da Memória/etiologia , Reconhecimento Psicológico/fisiologia , Idoso , Idoso de 80 Anos ou mais , Transtornos Cognitivos/diagnóstico por imagem , Demência Vascular/diagnóstico por imagem , Feminino , Humanos , Imageamento por Ressonância Magnética , Masculino , Transtornos da Memória/diagnóstico por imagem , Pessoa de Meia-Idade , Testes Neuropsicológicos , Estatísticas não Paramétricas , Inquéritos e QuestionáriosRESUMO
1. During the course of metabolic profiling of lead Compound 1, glutathione (GSH) conjugates were detected in rat bile, suggesting the formation of reactive intermediate precursor(s). This was confirmed by the identification of GSH and N-acetylcysteine (NAC) conjugates in microsomal incubations. 2. It was proposed that bioactivation of Compound 1 occurs via the formation of a di-iminoquinone reactive intermediate through the involvement of the C-2 and C-5 nitrogens of the pyrimidine core. 3. To further investigate this hypothesis, structural analogs with modifications at the C-5 nitrogen were studied for metabolic activation in human liver microsomes supplemented with GSH/NAC. 4. Compounds 1 and 2, which bear secondary nitrogens at the C-5 of the pyrimidine core, were observed to form significant amounts of GSH/NAC-conjugates in vitro, whereas compounds with tertiary nitrogens at C-5 (Compound 3 and 4) formed no such conjugates. 5. These observations provide evidence that electron/hydrogen abstraction is required for the bioactivation of the triaminopyrimidines, potentially via a di-iminoquinone intermediate. The lack of a hydrogen and/or steric hindrance rendered Compound 3 and 4 incapable of forming thiol conjugates. 6. This finding enabled advancement of compound 4, with a desirable potency, safety and PK profile, as a lead candidate for further development in the treatment of malaria.
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Antimaláricos/metabolismo , Acetilcisteína/metabolismo , Animais , Bile/metabolismo , Biotransformação , Glutationa/metabolismo , Humanos , Microssomos Hepáticos/metabolismo , Quinonas , Ratos , Compostos de Sulfidrila/metabolismoAssuntos
Vacinas contra COVID-19/efeitos adversos , COVID-19/complicações , COVID-19/prevenção & controle , SARS-CoV-2/imunologia , Trombose Venosa/etiologia , Vacina BNT162 , COVID-19/epidemiologia , COVID-19/virologia , Vacinas contra COVID-19/administração & dosagem , Vacinas contra COVID-19/imunologia , Gerenciamento Clínico , Suscetibilidade a Doenças , Humanos , Incidência , Vacinação/efeitos adversos , Trombose Venosa/diagnóstico , Trombose Venosa/epidemiologiaRESUMO
Number processing disorder is an acquired deficit in mathematical skills commonly observed in Alzheimer's disease (AD), usually as a consequence of neurological dysfunction. Common impairments include syntactic errors (800012 instead of 8012) and intrusion errors (8 thousand and 12 instead of eight thousand and twelve) in number transcoding tasks. This study aimed to understand the characterization of AD-related number processing disorder within an alphabetic language (English) and ideographical language (Chinese), and to investigate the differences between alphabetic and ideographic language processing. Chinese-speaking AD patients were hypothesized to make significantly more intrusion errors than English-speaking ones, due to the ideographical nature of both Chinese characters and Arabic numbers. A simplified number transcoding test derived from EC301 battery was administered to AD patients. Chinese-speaking AD patients made significantly more intrusion errors (p = 0.001) than English speakers. This demonstrates that number processing in an alphabetic language such as English does not function in the same manner as in Chinese. The impaired inhibition capability likely contributes to such observations due to its competitive lexical representation in brain for Chinese speakers.
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Doença de Alzheimer/complicações , Transtornos Cognitivos/etiologia , Idioma , Matemática , Resolução de Problemas/fisiologia , Idoso , Idoso de 80 Anos ou mais , Doença de Alzheimer/fisiopatologia , Povo Asiático , Distribuição de Qui-Quadrado , Feminino , Humanos , Masculino , Entrevista Psiquiátrica Padronizada , Testes NeuropsicológicosRESUMO
The Mur ligases play an essential role in the biosynthesis of bacterial peptidoglycan and hence are attractive antibacterial targets. A screen of the AstraZeneca compound library led to the identification of compound A, a pyrazolopyrimidine, as a potent inhibitor of Escherichia coli and Pseudomonas aeruginosa MurC. However, cellular activity against E. coli or P. aeruginosa was not observed. Compound A was active against efflux pump mutants of both strains. Experiments using an E. coli tolC mutant revealed accumulation of the MurC substrate and a decrease in the level of product upon treatment with compound A ,: indicating inhibition of MurC enzyme in these cells. Such a modulation was not observed in the E. coli wild-type cells. Further, overexpression of MurC in the E. coli tolC mutant led to an increase in the compound A MIC by ≥16-fold, establishing a correlation between MurC inhibition and cellular activity. In addition, estimation of the intracellular compound A level showed an accumulation of the compound over time in the tolC mutant strain. A significant compound A level was not detected in the wild-type E. coli strain even upon treatment with high concentrations of the compound. Therefore, the lack of MIC and absence of MurC inhibition in wild-type E. coli were possibly due to suboptimal compound concentration as a consequence of a high efflux level and/or poor permeativity of compound A.
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Proteínas de Escherichia coli/metabolismo , Escherichia coli/citologia , Escherichia coli/enzimologia , Peptídeo Sintases/metabolismo , Alanina/metabolismo , Proteínas da Membrana Bacteriana Externa/genética , Proteínas da Membrana Bacteriana Externa/metabolismo , Escherichia coli/genética , Proteínas de Escherichia coli/genética , Proteínas de Membrana Transportadoras/genética , Proteínas de Membrana Transportadoras/metabolismo , Mutação , Peptídeo Sintases/genética , Pseudomonas aeruginosa/genética , Pseudomonas aeruginosa/metabolismo , Uridina Difosfato Ácido N-Acetilmurâmico/metabolismoRESUMO
Reactive metabolites (RMs) have been implicated as causal factors in many drug-associated idiosyncratic toxicities. This study aims at identification and mitigation of an RM liability associated with aminoimidazole and amino(aza)benzimidazole structural motifs from an antimalarial project. Nineteen compounds with different structural modifications were studied in rat and human liver microsomes using glutathione (GSH) and N-acetyl cysteine (NAC) as trapping agents for RM. Metabolite profiling of aminoimidazole compounds in initial studies revealed the presence of dihydrodiol metabolites suggestive of reactive epoxide precursors, confirmed by the identification of a dihydrohydroxy GSH conjugate in GSH supplemented incubations. Substitution of methyl group at a potential site of metabolism blocked the epoxidation; however, formation of an imine-methide RM was suspected. Masking the site of metabolism via benzimidazole and 4/7-azabenzimidazole resulted in the possible formation of quinone-imine intermediates as a product of bioactivation. Further, substitutions with electron withdrawing groups and steric crowding did not address this liability. Mitigation of bioactivation was achieved with 5/6-azabenzimidazole and with CF3 substitution at the 6-position of the 7-azabenzimidazole ring. Moreover, compounds devoid of imidazole -NH2 do not undergo bioactivation. This study, therefore, establishes aminoimidazole and amino(aza)benzimidazoles as potential toxicophores and describes ways to mitigate this bioactivation liability by chemical modification.
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Benzimidazóis/metabolismo , Animais , Compostos Aza/química , Benzimidazóis/análise , Cromatografia Líquida de Alta Pressão , Iminas/química , Quinonas/química , Ratos , Espectrometria de Massas em TandemRESUMO
Scaffold hopping from the thiazolopyridine ureas led to thiazolopyridone ureas with potent antitubercular activity acting through inhibition of DNA GyrB ATPase activity. Structural diversity was introduced, by extension of substituents from the thiazolopyridone N-4 position, to access hydrophobic interactions in the ribose pocket of the ATP binding region of GyrB. Further optimization of hydrogen bond interactions with arginines in site-2 of GyrB active site pocket led to potent inhibition of the enzyme (IC50 2 nM) along with potent cellular activity (MIC=0.1 µM) against Mycobacterium tuberculosis (Mtb). Efficacy was demonstrated in an acute mouse model of tuberculosis on oral administration.
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Mycobacterium tuberculosis/efeitos dos fármacos , Piridonas/síntese química , Tiazóis/síntese química , Inibidores da Topoisomerase II/síntese química , Inibidores da Topoisomerase II/farmacologia , Ureia/síntese química , Ureia/farmacologia , Administração Oral , Animais , Antituberculosos/síntese química , Antituberculosos/química , Antituberculosos/farmacologia , Modelos Animais de Doenças , Concentração Inibidora 50 , Camundongos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Piridonas/química , Piridonas/farmacologia , Tiazóis/química , Tiazóis/farmacologia , Inibidores da Topoisomerase II/química , Ureia/químicaRESUMO
BACKGROUND: Enterococcus faecalis biofilm formation within root canals poses a challenging problem in endodontics, often leading to treatment failure. To combat this issue, nanotechnology offers a promising avenue for enhancing antimicrobial efficacy. This study explores the potential synergistic effects of combining nanoscale silica particles with conventional antibiotics, including doxycycline, metronidazole, and ciprofloxacin, against E. faecalis biofilms. The unique characteristics of silica nanoparticles, such as their increased reactivity and ability to be functionalized with other compounds, make them ideal candidates for augmenting antibiotic efficacy. This research investigates the antimicrobial properties of these silica-based combinations and their potential to eliminate or inhibit E. faecalis biofilms more effectively than conventional treatments. Methodology: The methods involved the preparation of nanostructured silica particles and their combination with doxycycline, Flagyl, and ciprofloxacin at subinhibitory concentrations. These combinations were then tested against E. faecalis biofilms using the agar well diffusion technique. RESULTS: Preliminary results suggested that the synergistic interactions between silica nanoparticles and antibiotics can significantly enhance antimicrobial efficacy. The combined treatment exhibited superior inhibitory effects on E. faecalis compared to antibiotics or silica nanoparticles alone (P < 0.05). Conclusions: This study sheds light on the potential of nanoscale silica-based combinations to address the challenges posed by E. faecalis biofilms in endodontics. Understanding the mechanisms of synergy between nanoparticles and antibiotics can pave the way for the development of more effective and targeted strategies for root canal disinfection, ultimately improving the success rates of endodontic treatments.
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INTRODUCTION: Migraine is a prevalent and disabling primary headache disorder worldwide, causing significant years lost due to disability (YLD) and impacting various aspects of everyday life. Despite its high prevalence and substantial burden, there is a lack of comprehensive data on clinical patterns and management trends, in places like Tamil Nadu, India. This study aims and also fill gaps by investigating and analyzing the clinical characteristics, treatment patterns, and illness burden among patients with episodic migraine (EM) and chronic migraine (CM) in the state of Tamil Nadu. STUDY: This cross-sectional retrospective study was conducted at the Department of Neurology, Madras Medical College, Chennai, over a three-month period starting from January 2024 to March 2024. The study included migraine patients aged 18 years and above who met the International Classification of Headache Disorders (ICHD)-3 criteria and took treatment at the department. Data were collected using patient interviews, medical records, and counseling sessions and using a pre-designed questionnaire. Patient demographics, clinical characteristics, symptom prevalence, prescription patterns, and illness burden were analyzed accordingly. The Migraine Disability Assessment (MIDAS) questionnaire was used to measure the burden of illness. RESULTS: The analysis involved 400 migraine patients, 92.5% of them having EM and 7.5% of them having CM. The mean age of patients was 37.5 years, with a predominance of females (73.5%). Patients with CM had having significantly higher average number of headache days per month when compared to those with EM. Tension-type headache (TTH) and medication-overuse headache (MOH) were more prevalent in those CM patients. Trigger factors include lack of sleep, bright light exposure, and stress. Comorbidities such as diabetes mellitus, obesity, and depression were significantly higher in CM patients. Acute treatment included NSAIDs and Triptans, while preventive therapy was more commonly used in CM patients. The mean MIDAS score was significantly higher in CM patients, which indicates greater disability. CONCLUSION: The study provides valuable insights into the clinical characteristics, treatment patterns, and burden of illness among migraine patients in Tamil Nadu, India. Significant differences were observed between EM and CM patients, which highlights the need for comprehensive management strategies. Preventive therapy, lifestyle modifications, and comprehensive assessment of disability are all important in addressing the variable needs of migraine patients and also reducing the burden of illness. Further research is necessary to explore additional factors influencing migraine outcomes in this population.
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INTRODUCTION: Misdiagnosis rate of Dementia with Lewy Bodies (DLB) remains high despite being second most common cause of neurodegenerative dementia. To date, understanding of clinical profile of pathologically confirmed prodromal DLB remains limited. The main objective of this study was to describe and compare it with pathologically confirmed Alzheimer's disease (AD). METHODS: We accessed the National Alzheimer's Coordinating Center database from 2005 to December 2022 data freeze and included 111 and 501 prodromal DLB and AD patients respectively. First visit data was analyzed. RESULTS: Clinician-determined memory impairment is common in prodromal DLB (>70%) but associated with higher risk for AD diagnosis (OR 0.355, p = 0.0003). DLB had a higher proportion of non-amnestic mild cognitive impairment (MCI) diagnoses but statistically insignificance in differentiating the two. Inattention (OR 2.273, p = 0.0015), and neuropsychiatric features, such as visual hallucinations (OR 11.98, p < 0.0001), depressed mood (OR1.709, p = 0.0292), apathy (1.824, p = 0.0345), and night/REM sleep behaviors, are associated with DLB diagnosis. Hallucinations are infrequent (7-11%). Motor symptoms, particularly gait disorders (OR 4.570, p < 0.001), falls (OR3.939, p = 0.0003), tremors (OR2.237, p = 0.0154), slowness (OR3.573, p < 0.0001), and parkinsonism signs (OR2.443, p < 0.0001), are common. 32% showed no parkinsonism during initial presentation. Neuropsychological examination revealed less impaired memory and language but impaired executive function in DLB. CONCLUSION: In clinical practice, it is important to note that memory symptoms although being higher risk associated with AD diagnosis, are prominent in prodromal DLB. Psychosis is infrequent, and non-amnestic MCI is not necessarily associated with higher risk of DLB diagnosis. A careful clinical approach is key to improve the diagnosis of prodromal DLB.
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Doença de Alzheimer , Disfunção Cognitiva , Doença por Corpos de Lewy , Transtornos Parkinsonianos , Humanos , Doença por Corpos de Lewy/diagnóstico , Doença por Corpos de Lewy/complicações , Doença de Alzheimer/complicações , Corpos de Lewy , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/complicações , Transtornos Parkinsonianos/diagnóstico , Alucinações , Sintomas ProdrômicosRESUMO
BACKGROUND AND PURPOSE: A third of stroke patients suffer from post-stroke cognitive decline, depressive symptoms, and anxiety symptoms. B-vitamin supplementation provides a possible safe and affordable treatment to mitigate post-stroke neuropsychiatric sequelae via reducing homocysteine levels. Our study aims to examine the effect of B-vitamin supplementation in the prevention of post-stroke cognitive decline, depressive symptoms, and anxiety symptoms. Our secondary aims were to investigate associations between baseline factors and the three outcomes. METHODS: Patients were recruited as part of a Singaporean substudy of a randomized controlled trial that examined the effect of B-vitamin supplementation on recurrent cardiovascular events. Cognitive decline, depressive symptoms, and anxiety symptoms were assessed with neuropsychological assessments and Hospital Anxiety and Depression Scale 6 monthly. Cox regression analyses were performed to determine treatment efficacy. Logistic regression used to examine factors associated with cognitive decline, depressive symptoms, and anxiety symptoms. RESULTS: A total of 707 were included in the analyses. Survival and hazards ratio analysis showed no treatment effect of B-vitamins on cognitive decline, depressive symptoms, and anxiety symptoms. Cognitive decline was only associated with age. Depressive symptoms were associated with large anterior cerebral infarcts and hyperlipidemia. CONCLUSIONS: Our study showed no benefit of supplementation with B-vitamins for post-stroke cognitive decline, depressive symptoms, or anxiety symptoms. Depressive symptoms were associated with larger anterior cerebral infarcts, which may be reflective of the disability associated with larger infarcts.
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Transtornos Cognitivos , Acidente Vascular Cerebral , Complexo Vitamínico B , Humanos , Complexo Vitamínico B/uso terapêutico , Complexo Vitamínico B/farmacologia , Transtornos Cognitivos/prevenção & controle , Acidente Vascular Cerebral/complicações , Cognição , Suplementos Nutricionais , Infarto CerebralRESUMO
Primary parotid tuberculosis is a well-known but extremely rare entity even in endemic countries. Most of the cases are diagnosed late in the course of illness when the parotid shows features of cold abscess leading to facial disfigurement. Early diagnosis is a clinical challenge due to lack of clinical suspicion as well as absence of clinical or radiological tests suggestive of the disease. Fine needle aspiration cytology features of early tuberculosis can easily be confused with a pleomorphic adenoma. When ultrasound examination of a parotid lesion is atypical, image guided core needle biopsy can be helpful in differentiating these kinds of rare diseases from more common parotid pathologies.
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Ectopic and supernumerary parathyroid glands in the neck is a real surgical challenge especially in multi-gland pathologies. We report a supernumerary ectopic gland at a rare site in the neck in a chronic kidney disease patient which required a re-exploration following a deceptively successful bilateral neck dissection.
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Importance: Early-onset dementia, presenting in individuals younger than 65 years, is a diagnosis with significant social and financial implications. The early-onset form of dementia with Lewy bodies (DLB) is poorly understood. Objective: To investigate clinical features that distinguish early-onset DLB (onset and diagnosis at age <65 years) from late-onset DLB (onset at age ≥65 years) and from early-onset Alzheimer disease (AD) dementia. Design, Setting, and Participants: This is a retrospective case-control study on patients with pathologically confirmed DLB or AD enrolled in the National Alzheimer's Coordinating Center database from January 2005 to July 2017. The National Alzheimer's Coordinating Center Uniform Data Set comprised deidentified data collected by Alzheimer disease centers in the United States. Of patients fulfilling criteria for all-cause dementia at enrollment (n = 1152), those who at post mortem received a pathological diagnosis of either AD (n = 848) or Lewy body disease (n = 218) were selected. Excluding 52 patients owing to missing data and 12 diagnosed with Parkinson disease dementia, remaining patients were classified by age of symptom onset into early-onset AD, early-onset DLB, and late-onset DLB subgroups. Data were analyzed from June to December 2018 and from November to December 2021. Exposures: Demographics, cognitive, behavioral, and motor features recorded at first clinic visit and neuropathological characteristics at autopsy were analyzed by disease subgroup. Main Outcomes and Measures: Concordance between initial etiologic diagnosis of dementia and final pathological diagnosis was assessed, as was time to death. Results: A total of 542 individuals were categorized as having early-onset AD (n = 363; mean [SD] age, 53.0 [5.8] years; 208 [57.3%] male), early-onset DLB (n = 32; mean [SD] age, 57.9 [3.2] years; 23 [71.9%] male), and late-onset DLB (n = 147; mean [SD] age, 73.5 [5.5] years; 103 [70.1%] male). Early-onset DLB was clinically misdiagnosed in 16 individuals (50%). Features that predicted a diagnosis of early-onset DLB over early-onset AD included visual hallucinations (15 [46.9%] vs 42 [11.6%]), slowness (23 [71.9%] vs 95 [26.2%]), apathy (23 [71.9%] vs 189 [52.1%]), and motor deterioration that preceded cognitive and behavioral symptoms (7 [21.9%] vs 6 [1.7%]). Late-onset DLB had more amnestic features, but this was accounted for by a higher proportion of neocortical neuritic plaques and diffuse plaques (frequent in 79 [53.7%] vs 8 [25%]) than seen in early-onset DLB. Conclusions and Relevance: This study found that early-onset DLB has clinical features that distinguish it from early-onset AD, whereas features of late-onset DLB are associated with a higher burden of AD copathology.
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Doença de Alzheimer , Demência , Doença por Corpos de Lewy , Doença de Parkinson , Idoso , Doença de Alzheimer/patologia , Estudos de Casos e Controles , Demência/complicações , Feminino , Humanos , Doença por Corpos de Lewy/complicações , Masculino , Pessoa de Meia-Idade , Doença de Parkinson/complicações , Estudos RetrospectivosRESUMO
A 45-year-old male was admitted with severe orthostatic headache secondary to spontaneous intracranial hypotension. He had the site of cerebrospinal fluid (CSF) leakage identified at the anterolateral aspect of the C7-T1 spinal level. He first underwent a conventional posterior-approach cervical epidural blood patch (EBP) which provided immediate relief to the patient's symptoms; however, his symptoms recurred two days later. To better target the anterolateral leakage site, we employed an anterior-approach EBP under computed tomography (CT) guidance. After this attempt, the patient experienced complete relief of his symptoms, and the headache eventually resolved.
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CONTEXT: Occupational hazards at the building construction workplace are enormous. Good compliance to the use of personal protective equipment (PPE) alongside other safety measures is critical in reducing the hazards. Occupational hearing loss is one such occupational hazard among construction workers. AIMS: This study was conducted for determining the awareness of the benefits of PPE and its usage among construction workers along with hearing assessment. SETTINGS AND DESIGN: A cross-sectional study was conducted among construction workers in a building project in Mangaluru city in Dakshina Kannada district in South India. METHODS AND MATERIAL: After obtaining informed written consent, 110 construction workers were recruited by simple random sampling method. Basic information, awareness, and use of PPE were collected using a semistructured questionnaire through personal interviews. Hearing assessment was done by pure tone audiometry. STATISTICAL ANALYSIS USED: Data collected was analyzed. Chi-square test and Fischer's exact probability test were used to test the association between variables. RESULTS: Majority (85.5%) of the construction workers are working for duration of 15 years or less. Difficulty in hearing was reported by 9.6% of them. Awareness regarding benefits of using personal protective devices like helmets, masks, and earplugs/muffs were 58.2%, 56.4%, and 14.5%, respectively. The utilization of at least one PPE among them was 58.1%. The presence of sensory neural hearing loss (SNHL) in both/either ears was detected among 14.5% of the workers. There was a statistically significant association of SNHL among workers and their duration of construction work. CONCLUSION: The current study highlights that awareness and usage of PPE was low and a proportion of them had a hearing impairment. Occupational health and safety training along with a periodic examination of construction workers need to be focused so as to detect and manage occupational health hazards early.