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

Background Disorders 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. Methods We 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. Findings Globally, 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. Interpretation As 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. Funding Bill & Melinda Gates Foundation

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

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

Abstract Number ‐ 204: Robotics in Neuro‐Endovascular Field: Back to the Future

Introduction For more than three decades, robotic assisted surgery has been proposed, studied and put into action clinically. Likewise, it was cleared by the Food and Drug Administration for percutaneous coronary intervention in 2012 (K120834) and peripheral vascular intervention including carotid intervention in 2018 (K173288), but has not yet received clearance for intracranial neurovascular intervention in the USA. Recently, several pilot clinical studies assessed robotically performed neurointerventions. Methods We performed comprehensive electronic search till July 2022 on PubMed/Medline to retrieve all relevant studies and data were extracted for baseline characteristics, design, procedure type, safety and feasibility outcomes for qualitative synthesis. Results Our results yielded nine single center studies in UK, USA and China performed since 2015. The performed procedures included diagnostic cerebral angiography (36 patients), caroti aartery stenting (37 patients), unspecified robotic assisted intracranial intervention (18 patients) and stent‐assisted coil embolization of a basilar artery aneurysm (one case). The used robotic systems included Corpath GRX (5 studies), Magellan (2 studies), RobEnt (one study) and VIR‐2 (one study). The robotic assisted neurointervention was successful clinically without complications across all studies and for all procedures. The learning curve sounded promising but there were limitations in the design of systems for completing all steps robotically. Conclusions Robotics assisted procedures appear to be feasible and safe in neuro‐intevention field. Advantages include high accuracy, stability, safety, simplicity, versatility, monitoring, endothelial protection, and potential for remote access for procedures such as mechanical thrombectomy for acute ischemic stroke. However, there are many challenges including cost, manual steps, lack of manual resistance feeling, irrationality in the spatial arrangement of the robotic system and operating table. Additionally, most of the included studies were retrospective with small sample size and short term follow up and more well‐designed comparative prospective studies are needed to confirm these results

Abstract Number ‐ 156: Transradial versus Transfemoral Access for Mechanical Thrombectomy: A Meta‐Analysis of Nine Studies (2,161 Patients)

Introduction Previous studies have compared the transradial access (TRA) with the transfemoral access (TFA) in patients undergoing mechanical thrombectomy (MT) for acute ischemic stroke (AIS). We conducted this meta‐analysis to provide comprehensive evidence regarding the comparison of procedural and clinical outcomes of the TRA versus the TFA in AIS patients undergoing MT. Methods We performed a comprehensive literature search of four electronic databases (PubMed, Scopus, Web of Science, Cochrane CENTRAL) from inception until 1 May 2022. All duplicates were removed, and all references of the included studies were screened manually for any eligible studies. The full‐text articles of eligible abstracts were retrieved and screened for continued eligibility. Relevant data were extracted and then analyzed. For outcomes that constitute continuous data, the mean difference (MD) between the two groups and its standard deviation (SD) were pooled. For outcomes that constitute dichotomous data, the frequency of events and the total number of patients in each group were pooled as odds ratio (OR) between the two groups. Results Nine studies were included in this meta‐analysis, all of which were observational studies. The population of the studies was homogenous comprising a total of 2,161 patients who underwent MT, including 446 in the TRA group and 1,715 in the TFA group. There were no significant differences across the two groups in terms of successful recanalization (Thrombolysis in cerebral Infarction [TICI] score of 2b‐3: OR 0.83, 95% CI [0.55 to 1.25], P = 0.36) (Figure 1, A), complete recanalization (TICI 3: OR 1.16, 95% CI [0.50 to 2.68], P = 0.73), favorable functional outcome (90‐day modified Rankin scale [mRS] score of 0–2 (OR 0.86, 95% CI [0.53 to 1.41], P = 0.56), first‐pass reperfusion (OR 0.88, 95% CI [0.64 to 1.19], P = 0.41), number of passes (MD 0.12, 95% CI [‐0.18 to 0.42], P = 0.43) (Figure 1, B), access‐to‐reperfusion time (MD ‐3.92 minutes, 95% CI [‐9.49 to 1.65], P = 0.17), the amount of contrast used (MD 5.03 mL, 95% CI [‐20.27 to 30.33], P = 0.70), or symptomatic intracranial hemorrhage (OR 0.86, 95% CI [0.47 to 1.57], P = 0.62). However, access‐site complications were significantly less frequent in the TRA group as compared to the TFA group (OR 0.18, 95% CI [0.06 to 0.51], P = 0.001) (Finger 1, C). Conclusions In patients undergoing MT for AIS, the collective evidence suggests that the TRA seems to result in lower rates of access‐site complications than the TFA without any significant compromise in other clinical or procedural metrics. Large prospective studies are warranted

Abstract Number ‐ 153: Mobile stroke units in acute ischemic stroke: A comprehensive meta‐analysis of nineteen controlled trials

Introduction In certain circumstances, mobile stroke units (MSU) with on‐site treatment teams and a computed tomography scanner may offer faster therapy with tissue plasminogen activator (tPA) for stroke patients who need immediate treatment. We conducted a systematic review and meta‐analysis to compare clinical outcomes in MSU patients to those in conventional care. Methods We searched key electronic databases from inception till September 2021. The primary outcomes were mortality at 7 days and 90 days. The secondary outcomes included modified Rankin scale (mRS) at 90 days, alarm to intravenous thrombolysis (IVT) or intra‐arterial recanalization, and time from symptom onset or last known well (LKW) to thrombolysis. Results We included nineteen controlled trials and cohort studies to conduct our final analysis. Our comparison revealed that 90‐day mortality rate significantly declined in MSU group as compared to conventional care group (OR = 0.81, 95%CI [0.69,0.95]), while there was no significant difference at 7 days (OR = 0.88, 95%CI [0.68,1.15]). As regard achieving functional independence at 90 days (mRS = 0–2), MSU showed better results (OR = 1.24, 95%CI [1.03,1.49]). MSU was associated with shorter time from symptoms onset or LKW to thrombolysis (MD = ‐36.79, 95%CI [‐47.48, ‐26.10]) and alarm to IV thrombolysis or intra‐arterial recanalization (MD = ‐29.69, 95%CI [‐34.46, ‐24.92]). Conclusions Stroke patients treated in MSU had a lower incidence of the 90‐day mortality. They also had better functional independence at 90 days and time from symptom onset or LKW to thrombolysis than those treated with conventional care

Higher Procedural Volumes are Associated with Faster Treatment Times, Better Functional Outcomes, and Lower Mortality in Patients Undergoing Endovascular Treatment for Acute Ischemic Stroke

Objective We aimed to characterize the association of hospital procedural volumes with outcomes among acute ischemic stroke (AIS) patients undergoing endovascular therapy (EVT). Methods This was a retrospective, observational cohort study using data prospectively collected from January 1, 2016, to December 31, 2019, in the Get With The Guidelines-Stroke registry. Participants were derived from a cohort of 60,727 AIS patients treated with EVT within 24 hours at 626 hospitals. The primary cohort excluded patients with pretreatment NIHSS6 hours, and inter-hospital transfers. There were two secondary cohorts: (1) EVT metrics cohort: excluded patients with missing data on time from door-to-arterial-puncture; (2) Intravenous thrombolysis (IVT) metrics cohort: only included patients receiving IVT ≤4.5 hours of onset.ResultsThe primary cohort (mean±SD age, 70.7 ±14.8 years; 51.2% female; median [IQR] baseline NIHSS 18.0 [13-22]; IVT use, 70.2%) comprised 21,209 patients across 595 hospitals. The EVT metrics cohort and IVT metrics cohort comprised 47,262 and 16,889 patients across 408 and 601 hospitals, respectively. Higher procedural volumes were significantly associated with higher odds (expressed as adjusted odds ratio [95% confidence interval] for every 10-case-increase in volume) of discharge to home (1.03[1.02-1.04]), functional independence at discharge (1.02[1.01-1.04]), and lower rates of in-hospital mortality (0.96[0.95-0.98]). All secondary measures were also associated with procedural volumes. Interpretation Among AIS patients primarily presenting to EVT capable hospitals (excluding those transferred from one facility to another and those suffering in-hospital strokes), EVT at hospitals with higher procedural volumes was associated with faster treatment times, better discharge outcomes, and lower rates of in-hospital mortality

Abstract Number ‐ 52: Stem Cell Therapy for Ischemic Stroke: A Meta‐Analysis of 18 Studies including 724 Patients

Introduction The published clinical data assessing stem cell therapy for ischemic stroke (IS) are inconclusive. We conducted this comprehensive meta‐analysis to evaluate the efficacy and safety of stem cell therapy in the treatment of IS. Methods We searched electronic databases/search engines for studies comparing stem cell therapy to control in the treatment of IS from inception to June 2022. References were screened manually for eligibility. The relevant baseline data along with outcomes measured by modified Rankin scale (mRS), National Institutes of Health Stroke Scale (NIHSS), Barthel index (BI) and death were extracted and analyzed. Results We included 18 studies (12 randomized controlled trials (RCTs) and six non‐RCTs) comprising a total of 724 patients including 365 in the stem cells and 359 in the control group. Pooled results considering the last follow‐up point across 12 studies showed that stem cells significantly decreased mRS scores in relation to control (MD = ‐0.265, 95% CI [‐0.403 to ‐0.1269], P‐value = 0.00017). There was no publication bias (P = 0.4). The univariate meta‐regression demonstrated that route of administration, stem cell type, stroke type, and study design did not significantly contribute to the heterogeneity of the stem cells effect estimate (P >0.05). Additional analyses showed no significant differences in mRS scores between stem cells and control after seven days to three months (n = seven studies; MD = ‐0.039, 95% CI [‐0.22 to 0.15], P‐value = 0.681) and six to twelve months (n = ten studies; MD = ‐0.13, 95% CI [‐0.37 to 0.089], P‐value = 0.234). However, stem cells significantly decreased mRS scores in relation to control after two to four years (n = four studies; MD = ‐0.28, 95% CI [‐0.49 to ‐0.068], P‐value = 0.0096). Similarly, pooled results considering the last follow‐up point across nine studies showed that stem cells marginally decreased NIHSS scores in relation to control (MD = ‐1.185, 95% CI [‐2.37 to 0.00], P‐value = 0.05) with no publication bias (P = 0.5). Moreover, pooled results from 11 studies showed that stem cells significantly increased BI in relation to control (MD = 5.36, 95% CI [2.51 to 8.21], P‐value = 0.0002) with no publication bias (P = 0.675). Pooled results from 17 studies showed that stem cells treatment was significantly associated with lower risk of death in relation to control group (RR = 0.565, 95% CI [0.345 to 0.927], P‐value = 0.024). Conclusions Stem cell therapy for the treatment of IS seems to be associated with improved functional outcomes and reduced mortality. Notably, the demonstration of the functional outcome benefit appears to be more evident on longer follow‐up times (>2 years). Additional prospective studies are needed and should consider longer follow‐up periods

Neurological Events Reported after COVID-19 Vaccines: An Analysis of Vaccine Adverse Event Reporting System

Objective To identify the rates of neurological events following administration of mRNA (Pfizer, Moderna) or adenovirus vector (Janssen) vaccines in the U.S. Methods We used publicly available data from the U.S. Vaccine Adverse Event Reporting System (VAERS) collected between January 1, 2021 and June 14, 2021. All free text symptoms that were reported within 42 days of vaccine administration were manually reviewed and grouped into 36 individual neurological diagnostic categories. Post-vaccination neurological event rates were compared between vaccine types and to age-matched baseline incidence rates in the U.S. and rates of neurological events following COVID. Results Of 306,907,697 COVID vaccine doses administered during the study timeframe, 314,610 (0.1%) people reported any adverse event and 105,214 (0.03%) reported neurological adverse events in a median of 1 day (IQR0-3) from inoculation. Guillain-Barre Syndrome (GBS), and cerebral venous thrombosis (CVT) occurred in fewer than 1 per 1,000,000 doses. Significantly more neurological adverse events were reported following Janssen (Ad26.COV2.S) vaccination compared to either Pfizer-BioNtech (BNT162b2) or Moderna (mRNA-1,273; 0.15% vs 0.03% vs 0.03% of doses, respectively, p = 1.5-fold higher than background rates. However, the rate of neurological events after acute SARS-CoV-2 infection was up to 617-fold higher than after COVID vaccination. Interpretation Reports of serious neurological events following COVID vaccination are rare. GBS, CVT and seizure may occur at higher than background rates following Janssen vaccination. Despite this, rates of neurological complications following acute SARS-CoV-2 infection are up to 617-fold higher than after COVID vaccination. ANN NEUROL 202

Timing of headache after COVID-19 vaccines and its association with cerebrovascular events: An analysis of 41,700 VAERS reports

Background Delayed-onset of headache seems a specific feature of cerebrovascular events after COVID-19 vaccines