Global Prevalence and Incidence of Amyotrophic Lateral Sclerosis: A Systematic Review.

BACKGROUND AND OBJECTIVES: Amyotrophic lateral sclerosis (ALS) is a rare neurodegenerative disorder affecting upper and lower motor neurons. Due to its rarity and rapidly progressive nature, studying the epidemiology of ALS is challenging, and a comprehensive picture of the global burden of this disease is lacking. The objective of this systematic review was to describe the global incidence and prevalence of ALS. METHODS: We searched MEDLINE, Embase, Global Health, PsycInfo, Cochrane Library, and CINAHL to identify articles published between January 1, 2010, and May 6, 2021. Studies that were population based and reported estimates of prevalence, incidence, and/or mortality of ALS were eligible for inclusion. This study focuses on the incidence and prevalence. Quality assessment was performed using a tool developed to evaluate methodology relevant to prevalence and incidence studies. This review was registered with PROSPERO, CRD42021250559. RESULTS: This search generated 6,238 articles, of which 140 were selected for data extraction and quality assessment. Of these, 85 articles reported on the incidence and 61 on the prevalence of ALS. Incidence ranged from 0.26 per 100,000 person-years in Ecuador to 23.46 per 100,000 person-years in Japan. Point prevalence ranged from 1.57 per 100,000 in Iran to 11.80 per 100,000 in the United States. Many articles identified cases with ALS from multiple data sources. DISCUSSION: There is variation in reported incidence and prevalence estimates of ALS across the world. While registries are an important and powerful tool to quantify disease burden, such resources are not available everywhere. This results in gaps in reporting of the global epidemiology of ALS, as highlighted by the degree of variation (and quality) in estimates of incidence and prevalence reported in this review.

Current Referral Practices for Diagnosis and Intervention for Children with Cerebral Palsy: A National Environmental Scan.

OBJECTIVES: To describe current physician referral practices with respect to age at referral to medical specialists for initial diagnosis of cerebral palsy (CP) and rehabilitation specialists for intervention and to identify factors associated with delayed referral. STUDY DESIGN: National environmental scan of 455 children diagnosed with CP who were born in Canada between 2008 and 2011, selected from 4 sites within the Canadian CP Registry (Edmonton, Calgary, Toronto, and Montreal). Two sources of information were used-children's medical charts and the population-based registry, which provided corresponding data for each child. Primary outcomes extracted from the charts were age at referral for diagnostic assessment, age at diagnosis, age at referral for rehabilitation services, and age at initial rehabilitation intervention. Twelve variables were explored as potential predictors. Descriptive statistics, bivariate analyses, and multiple linear regressions were conducted. RESULTS: Median age (in months) at referral for diagnostic assessment was 8 (mean: 12.7 ± 14.3), diagnosis 16 (mean: 18.9 ± 12.8), referral for rehabilitation services 10 (mean: 13.4 ± 13.5), and rehabilitation initiation 12 (mean: 15.9 ± 12.9). Lower maternal education, mild severity of motor dysfunction, type of CP, early discharge after birth, and region of residence explained between 20% and 32% of the variance in age at referral for assessment, diagnosis, referral for rehabilitation, and rehabilitation initiation. CONCLUSIONS: Findings suggest wide variability exists in the age at which young children with CP are referred to specialists for diagnosis and intervention. User-friendly tools are therefore needed to enhance early detection and referral strategies by primary care practitioners, to ensure early interventions to optimize developmental outcomes and enhance opportunities for neural repair at a younger age.

The Placenta in Neonatal Encephalopathy: A Case-Control Study.

OBJECTIVE: We assessed whether specific histologic placental lesions were associated with risk for neonatal encephalopathy, a strong predictor of death or cerebral palsy. STUDY DESIGN: Case-control study of singletons with gestational ages ≥35 weeks. Data were abstracted from a prospectively collected database of consecutive births at a hospital in which placental samples from specified sites are collected and stored for all inborn infants. Placentas of infants with neonatal encephalopathy were compared with randomly selected control infants (ratio of 1:3). Placental histologic slides were read by a single experienced perinatal pathologist unaware of case status, using internationally recommended definitions and terminology. Findings were grouped into inflammatory, maternal, or fetal vascular malperfusion (FVM) and other lesions. RESULTS: Placental samples were available for 73 of 87 (84%) cases and 253 of 261 (97%) controls. Delivery complications and gross placental abnormalities were more common in cases, of whom 4 died. Inflammation and maternal vascular malperfusion did not differ, and findings consistent with global FVM were more frequent in case (20%) than control (7%) placentas (P = .001). There was a trend toward more segmental FVM and high-grade FVM (fetal thrombotic vasculopathy) among cases. Some type of FVM was observed in 24% of placentas with neonatal encephalopathy. In infants with both neonatal encephalopathy and placental FVM, more often than in infants with neonatal encephalopathy without FVM, electronic fetal monitoring tracings were considered possibly or definitely abnormal (P = .028). CONCLUSIONS: Vascular malperfusion of subacute or chronic origin on the fetal side of the placenta was associated with increased risk of neonatal encephalopathy.

Cerebral Palsy after Neonatal Encephalopathy: How Much Is Preventable?

OBJECTIVES: To determine the expected proportion of term cerebral palsy (CP) after neonatal encephalopathy (NE) that could theoretically be prevented by hypothermia and elucidate the perinatal factors associated with CP after NE in those who do not meet currently used clinical criteria required to qualify for hypothermia ("cooling criteria"). STUDY DESIGN: Using the Canadian CP Registry, we categorized children born at ≥ 36 weeks with birth weight ≥ 1800 g with CP after moderate or severe NE according to the presence or absence of cooling criteria. Maternal, perinatal, postnatal, and placental factors were compared between the 2 groups. A number needed to treat of 8 (95% CI 6-17) to prevent one case of CP was used for calculations. RESULTS: Among the 543 term-born children with CP, 155 (29%) had moderate or severe NE. Sixty-four of 155 (41%) met cooling criteria and 91 of 155 (59%) did not. Shoulder dystocia was more common in those who did not meet cooling criteria (OR 8.8; 95% CI 1.1-71.4). Low birth weights (20% of all singletons), small placentas (42%), and chorioamnionitis (13%) were common in both groups. CONCLUSIONS: The majority of children with CP after NE did not meet cooling criteria. An estimated 5.1% (95% CI 2.4%-6.9%) of term CP after NE may be theoretically prevented with hypothermia. Considering shoulder dystocia as an additional criterion may help recognize more neonates who could potentially benefit from cooling. In all cases, a better understanding of the antenatal processes underlying NE is essential in reducing the burden of CP.