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A multicenter study on Leigh syndrome: disease course and predictors of survival.

ABSTRACT: BACKGROUND: Leigh syndrome is a progressive neurodegenerative disorder, associated with primary or secondary dysfunction of the mitochondrial oxidative phosphorylation. Despite the fact that Leigh syndrome is the most common phenotype of mitochondrial disorders in children, longitudinal natural history data is missing. This study was undertaken to assess the phenotypic and genotypic spectrum of patients with Leigh syndrome, characterise the clinical course and identify predictors of survival in a large cohort of patients. METHODS: This is a retrospective study of patients with Leigh syndrome that have been followed at eight centers specialising in mitochondrial diseases in Europe; Gothenburg, Rotterdam, Helsinki, Copenhagen, Stockholm, Brussels, Bergen and Oulu. RESULTS: A total of 130 patients were included (78 males; 52 females), of whom 77 patients had identified pathogenic mutations. The median age of disease onset was 7 months, with 80.8% of patients presenting by the age of 2 years. The most common clinical features were abnormal motor findings, followed by abnormal ocular findings. Epileptic seizures were reported in 40% of patients. Approximately 44% of patients experienced acute exacerbations requiring hospitalisation during the previous year, mainly due to infections. The presence of pathological signs at birth and a history of epileptic seizures were associated with higher occurrence of acute exacerbations and/or relapses. Increased lactate in the cerebrospinal fluid was significantly correlated to a more severe disease course, characterised by early onset before 6 months of age, acute exacerbations and/or relapses, as well as brainstem involvement. 39% of patients had died by the age of 21 years, at a median age of 2.4 years. Disease onset before 6 months of age, failure to thrive, brainstem lesions on neuroimaging and intensive care treatment were significantly associated with poorer survival. CONCLUSIONS: This is a multicenter study performed in a large cohort of patients with Leigh syndrome. Our data help define the natural history of Leigh syndrome and identify novel predictors of disease severity and long-term prognosis.

SUBMITTER: Sofou K

PROVIDER: S-EPMC4021638 | biostudies-literature | 2014

REPOSITORIES: biostudies-literature

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A multicenter study on Leigh syndrome: disease course and predictors of survival.

Sofou Kalliopi K De Coo Irenaeus F M IF Isohanni Pirjo P Ostergaard Elsebet E Naess Karin K De Meirleir Linda L Tzoulis Charalampos C Uusimaa Johanna J De Angst Isabell B IB Lönnqvist Tuula T Pihko Helena H Mankinen Katariina K Bindoff Laurence A LA Tulinius Már M Darin Niklas N

Orphanet journal of rare diseases 20140415

<h4>Background</h4>Leigh syndrome is a progressive neurodegenerative disorder, associated with primary or secondary dysfunction of the mitochondrial oxidative phosphorylation. Despite the fact that Leigh syndrome is the most common phenotype of mitochondrial disorders in children, longitudinal natural history data is missing. This study was undertaken to assess the phenotypic and genotypic spectrum of patients with Leigh syndrome, characterise the clinical course and identify predictors of survi ...[more]

PMID: 24731534

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Project description:ObjectiveThis observational cohort study aims to quantify disease burden over time, establish disease progression rates, and identify factors that may determine the disease course of Leigh syndrome.MethodsSeventy-two Leigh syndrome children who completed the Newcastle Paediatric Mitochondrial Disease Scale (NPMDS) at baseline at 3.7 years (interquartile range [IQR] = 2.0-7.6) and follow-up assessments at 7.5 years (IQR = 3.7-11.0) in clinics were enrolled. Eighty-two percent of this cohort had a confirmed genetic diagnosis, with pathogenic variants in the MT-ATP6 and SURF1 genes being the most common cause. The total NPMDS scores denoted mild (0-14), moderate (15-25), and severe (>25) disease burden. Detailed clinical, neuroradiological, and molecular genetic findings were also analyzed.ResultsThe median total NPMDS scores rose significantly (Z = -6.9, p < 0.001), and the percentage of children with severe disease burden doubled (22% → 42%) over 2.6 years of follow-up. Poor function (especially mobility, self-care, communication, feeding, and education) and extrapyramidal features contributed significantly to the disease burden (τb ≈ 0.45-0.68, p < 0.001). These children also deteriorated to wheelchair dependence (31% → 57%), exclusive enteral feeding (22% → 46%), and one-to-one assistance for self-care (25% → 43%) during the study period. Twelve children (17%) died after their last NPMDS scores were recorded. These children had higher follow-up NPMDS scores (disease burden; p < 0.001) and steeper increase in NPMDS score per annum (disease progression; p < 0.001). Other predictors of poor outcomes include SURF1 gene variants (p < 0.001) and bilateral caudate changes on neuroimaging (p < 0.01).InterpretationThis study has objectively defined the disease burden and progression of Leigh syndrome. Our analysis has also uncovered potential influences on the trajectory of this neurodegenerative condition. ANN NEUROL 2022;91:117-130.

Project description:BackgroundSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) can induce conjunctivitis signs and symptoms. However, limited information is available on their impact on COVID-19 disease phenotype. Quantification of ocular signs/symptoms can provide a rapid, non-invasive proxy for predicting clinical phenotype. Moreover, the existence and entity of conjunctival viral shedding is still debated. This has relevant implications to manage disease spread. The purpose of this study was to investigate conjunctivitis signs and symptoms and their correlation with clinical parameters, conjunctival viral shedding in patients with COVID-19.MethodsFifty-three patients hospitalized between February 25th and September 16th, 2020 at the San Raffaele Hospital, in Milan, Lombardy, Italy with a confirmed diagnosis of SARS-CoV-2 were evaluated. Presence of interstitial pneumonia was confirmed with computed tomography scan imaging. Ocular signs and symptoms, anosmia/ageusia, clinical/laboratory parameters, and reverse transcriptase-polymerase chain reaction (RT-PCR) from nasopharyngeal and conjunctival swabs for COVID-19 virus were analyzed.ResultsForty-six out of 53 patients showed a positive nasopharyngeal swab for SARS-CoV-2 infection at the time of conjunctival evaluation. All the conjunctival swabs were negative. Conjunctivitis symptoms were present in 37% of patients. Physician-assessed ocular signs were detected in 28% of patients. Patients with ocular symptoms or signs tended to be older: 76.8 years (62.4-83.3) vs 57.2 years (48.1-74.0), p = 0.062 and had a longer hospitalization: 38 days (18-49) vs. 14 days (11-21), p = 0.005. Plasma levels of Interleukin-6 were higher in patients with signs or symptoms in comparison with those without them: 43.5 pg/ml (19.7-49.4) vs. 8 pg/ml (3.6-20.7), p = 0.02. Red cell distribution width was also significantly higher: 15 (14.3-16.7) vs 13.2 (12.4-14.4), p = 0.001.ConclusionsWe found that over a third of the patients had ocular signs or symptoms. These had higher prevalence in patients with a more severe infection. No viral shedding was detected in the conjunctiva. Our results suggest that prompt detection of conjunctivitis signs/symptoms can serve as a helpful proxy to predict COVID-19 clinical phenotype.

Project description:BackgroundAlthough substantial progress has been made in combating the crisis of multi-drug resistance tuberculosis (MDR-TB), it remained the major public health threat globally.ObjectiveTo assess patients' survival and its predictors among patients receiving multi-drug resistance tuberculosis treatment at MDR-TB treatment centers of southern and southwestern Ethiopia.MethodsA multicenter retrospective observational study was conducted from April 14 to May 14, 2019, among patients receiving MDR-TB treatment at three MDR-TB treatment centers, Butajira, Arbaminch and Shenengibe Hospitals, located in south and southwestern Ethiopia. A total of 200 records were reviewed using a check list adopted from the national MDR-TB treatment charts and other relevant documents. Data were entered into Epi-Data version 4.2.0 for cleaning and exported to STATA-13 for analysis. Descriptive analysis was carried out and results were presented by text, tables, and charts. Kaplan-Meier (log-rank test) and Cox regression were used to compare baseline survival experience and to determine predictors of patients' survival (death), respectively. The adjusted hazard ratio (AHR) was used to measure the strength of association and a p-value of <0.05 was considered to declare statistical significance.ResultsOf 200 patients, 108 (54%) of them were males. The mean (+ standard deviation) age of the study population was 32.9±9.5years. During follow-up, 22 (11%) deaths were reported. The overall incidence density of death was 11.99, 95% CI [7.89-18.21] per 100,000person-years. The median (interquartile range (IQR)) survival time was 375(249-457) days. Comorbidity (AHR = 23.68, 95% CI [4.85-115.46]), alcohol consumption (AHR = 4.53, 95% CI [1.21-16.97]), and history of poor adherence (AHR = 12.27, 95% CI [2.83-53.21]) were independently associated with patients' survival (death).ConclusionIn this study, the incidence density of mortality was very high. Alcohol consumption, poor adherence, and the presence of comorbidity were independently associated with death. Hence, alcohol users, patients with comorbidity and poor adherence should be given due attention during therapy.

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A multicenter study on Leigh syndrome: disease course and predictors of survival.

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A multicenter study on Leigh syndrome: disease course and predictors of survival.

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