Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed

Effect of Eight Weeks of High Intensity Interval Training and Crocin Consumption on Serum Markers of Dox-induced Cardiotoxicity in Male Wistar Rats

Objective: Doxorubicin (Dox) is a very effective drug for the treatment of a wide range of cancers. However, in healthy tissues, especially cardiac tissue, it can lead to cytotoxicity. This study aims to determine the effect of 8 weeks of high intensity interval training (HIIT) and crocin consumption on serum markers of Dox-induced cardiotoxicity in male rats Methods: In this study, 32 male Wistar rats were randomly divided into four groups: healthy control, doxorubicin, doxorubicin + HIIT,  and doxorubicin + crocin + HIIT. The HIIT program was performed for 8 weeks, five days a week, with two 2-min intervals and 80% intensity in the first week and eight 2-minute intervals and 90% intensity of maximum speed in the final weeks. The last group received 10 mg/kg body weight of crocin by gavage for 8 weeks. Dox was injected subcutaneously seven times at a dose of 2 mg/kg. Forty-eight hours after the last training session and after anesthesia, blood samples were taken directly from the left ventricle; after separating serum from plasma, the levels of lactate dehydrogenase (LDH) and creatine kinase isoenzyme (CK-MB) were measured. Data were analyzed using independent t-test and one-way analysis of variance. The significance level was set at 0.05. Results: The Dox injection led to a significant increase in LDH and CK-MB levels in rats compared to the healthy control group (P=0.001). However, 8 weeks of HIIT significantly reduced the serum levels of LDH (P=0.001) and CK-MB (P=0.017) compared to the Dox group. In addition, 8 weeks of HIIT plus crocin consumption significantly reduced the LDH (P=0.001) and CK-MB (P=0.001) levels compared to the Dox group. There was no significant difference between the effects of HIIT alone and HIIT plus crocin consumption on the serum levels of LDH (P=0.087) and CK-MB (P=0.877) in rats received doxorubicin. Conclusion: It seems that HIIT alone and in combination with crocin consumption can reduce the changes in serum levels of LDH and CK-MB induced by doxorubicin

Evaluation of efficacy and tolerability of levetiracetam as an add-on therapy in intractable epilepsy of children

Objective: One-third of epilepsy of children is refractory and this study was conducted to evaluate efficacy and adverse events of levetiracetam as an add-on therapy in treatment of refractory epilepsy of children. Materials & Methods: In a quasi- experimental study, seizures frequency and side effects of 314 children aged 1-14 years with refractory epilepsy who were referred to Pediatric Neurology Clinic of Shahid Sadoughi Medical Sciences University, Yazd, Iran and treated with levetiracetam for six months, were evaluated. Results: 142 girls and 172 boys with mean age of 6.78±2.12 years were evaluated. At the end of six months of treatment with levetiracetam, 20% became seizure free, 28% had more than 50% decrease in seizure frequency, 38% did not have a notable change in seizure frequency and 14% experienced an increase in seizure frequency. Good response (stopping of all seizures or more than 50% reduction in seizure frequency) was seen in 51% of mixed type, 61% of myoclonic seizures, 64% of generalized tonic clonic seizures, 69 % of partial seizures, 100 % of tonic seizures and in 40 % of atonic seizures. Levetiracetam was significantly more effective in partial seizures, idiopathic epilepsies, children with normal developmental status and normal brain MRI. Twelve children discontinued the treatment due to severe drowsiness, restlessness and exacerbation of seizures. Transient and mild side effects were seen in 9%(N=28) including somnolence, anorexia, fatigue, headache, ataxia and diplopia. Conclusion: Levetiracetam could be considered as an efficient and safe adjunct therapy in treatment of refractory epilepsy in children. &nbsp

Global, regional, and national incidence of six major immune-mediated inflammatory diseases: findings from the global burden of disease study 2019Research in context

Summary: Background: The causes for immune-mediated inflammatory diseases (IMIDs) are diverse and the incidence trends of IMIDs from specific causes are rarely studied. The study aims to investigate the pattern and trend of IMIDs from 1990 to 2019. Methods: We collected detailed information on six major causes of IMIDs, including asthma, inflammatory bowel disease, multiple sclerosis, rheumatoid arthritis, psoriasis, and atopic dermatitis, between 1990 and 2019, derived from the Global Burden of Disease study in 2019. The average annual percent change (AAPC) in number of incidents and age standardized incidence rate (ASR) on IMIDs, by sex, age, region, and causes, were calculated to quantify the temporal trends. Findings: In 2019, rheumatoid arthritis, atopic dermatitis, asthma, multiple sclerosis, psoriasis, inflammatory bowel disease accounted 1.59%, 36.17%, 54.71%, 0.09%, 6.84%, 0.60% of overall new IMIDs cases, respectively. The ASR of IMIDs showed substantial regional and global variation with the highest in High SDI region, High-income North America, and United States of America. Throughout human lifespan, the age distribution of incident cases from six IMIDs was quite different. Globally, incident cases of IMIDs increased with an AAPC of 0.68 and the ASR decreased with an AAPC of −0.34 from 1990 to 2019. The incident cases increased across six IMIDs, the ASR of rheumatoid arthritis increased (0.21, 95% CI 0.18, 0.25), while the ASR of asthma (AAPC = −0.41), inflammatory bowel disease (AAPC = −0.72), multiple sclerosis (AAPC = −0.26), psoriasis (AAPC = −0.77), and atopic dermatitis (AAPC = −0.15) decreased. The ASR of overall and six individual IMID increased with SDI at regional and global level. Countries with higher ASR in 1990 experienced a more rapid decrease in ASR. Interpretation: The incidence patterns of IMIDs varied considerably across the world. Innovative prevention and integrative management strategy are urgently needed to mitigate the increasing ASR of rheumatoid arthritis and upsurging new cases of other five IMIDs, respectively. Funding: The Global Burden of Disease Study is funded by the Bill and Melinda Gates Foundation. The project funded by Scientific Research Fund of Sichuan Academy of Medical Sciences & Sichuan Provincial People's Hospital (2022QN38)