Non-invasive neuromodulation in the acute treatment of migraine: a systematic review and meta-analysis of randomized controlled trials.

OBJECTIVE: A systematic review and meta-analysis was performed to determine the efficacy of non-invasive neuromodulation modalities for the treatment of acute migraine. BACKGROUND: Although pharmacological treatments are the gold standard for the management of acute migraine, some patients may require non-pharmacological treatment options. Non-invasive neuromodulation may provide an alternative, and techniques include transcranial magnetic stimulation (TMS), non-invasive vagal nerve stimulation (nVNS), non-painful remote electrical stimulation (NRES), and external trigeminal nerve stimulation (e-TNS). METHODS: This systematic review and meta-analysis was performed following PRISMA guidelines. We searched PUBMED, EMBASE, ClinicalTrials.gov, Cochrane Center Register of Controlled Trials, and LILACS databases. We included randomized controlled clinical trials studying patients with migraine treated with any form of non-invasive neuromodulation. Primary outcome was pain freedom within 2 h post-treatment. Secondary outcomes were pain relief within 2-h post-treatment and sustained pain freedom and sustained pain relief 48 h post-treatment. RESULTS: Pooled analysis demonstrated a significant effect of non-invasive neuromodulation on pain-free rates within 2 h (RR, 1.66; 95% CI, 1.35 to 2.05; P < 0.00001) and pain relief rates within 2 h (RR, 1.52; 95% CI, 1.13 to 2.05; P = 0.005) post-treatment. Non-invasive neuromodulation had no significant effect on sustained pain freedom at 48 h (RR, 1.56; 95% CI, 0.68 to 3.59; P = 0.29) or sustained pain relief at 48 h (RR, 1.47; 95% CI, 0.57 to 3.77; P = 0.43) after administration. CONCLUSION: Neuromodulation has demonstrated some efficacy in acute migraine management and may be considered in the treatment paradigm of acute migraine in patients with contraindications to pharmacological therapies.

Incidence and Current Treatment Gaps in Pediatric Stroke and TIA: An Ontario-Wide Population-Based Study.

BACKGROUND: Reported incidence rates of pediatric stroke and transient ischemic attack (TIA) range widely. Treatment gaps are poorly characterized. We sought to evaluate in -Ontario, the incidence and characteristics of pediatric stroke and TIA including care gaps and the predictive value of International Classification of Diseases (ICD) codes. METHODS: A retrospective chart review was conducted at 147 Ontario pediatric and adult acute care hospitals. Pediatric stroke and TIA cases (age < 18 years) were identified using ICD-10 code searches in the 2010/11 Canadian Institute for Health Information's Discharge Abstract Database (CIHI-DAD) and National Ambulatory Care Reporting System (NACRS) databases in the Ontario Stroke Audit. RESULTS: Among 478 potential pediatric stroke and TIA cases identified in the CIHI-DAD and NACRS databases, 163 were confirmed as cases of stroke and TIA during the 1-year study period. The Ontario stroke and TIA incidence rate was 5.9 per 100,000 children (3.3 ischemic, 1.8 hemorrhagic and 0.8 TIA). Mean age was 6.4 years (16% neonate). Nearly half were not imaged within 24 h of arrival in emergency and only 56% were given antithrombotic treatment. At discharge, 83 out of 121 (69%) required health care services post-discharge. Overall positive predictive value (PPV) of ICD-10 stroke and TIA codes was 31% (range 5-74%) and yield ranged from 2.4 to 29% for acute stroke or TIA event; code I63 achieved maximal PPV and yield. CONCLUSION: Our population-based study yielded a higher incidence rate than prior North-American studies. Important care gaps exist including delayed diagnosis, lack of expert care, and departure from published treatment guidelines. Variability in ICD PPV and yield underlines the need for prospective data collection and for improving the pediatric stroke and TIA coding processes.

Utility of Neurovascular Imaging in Acute Neonatal Arterial Ischemic Stroke.

OBJECTIVE: To evaluate the prevalence of magnetic resonance angiography (MRA) findings and clinically characterize neonates with arterial ischemic stroke (AIS) who have abnormal or variable vasculature. STUDY DESIGN: This was a single-center, retrospective study of patients with neonatal stroke from 1991 to 2012. We reviewed charts and neuroimaging, including MRA, in neonates with AIS. Clinical data of patients with MRA findings were compared with the control group of neonates with AIS and a normal MRA. RESULTS: We identified 142 cases of neonatal AIS, of which 81 patients had magnetic resonance imaging and MRA. Among the neonates with arterial neuroimaging, 29 had arterial findings (for a prevalence rate of 20%-35%). The majority of the findings were stenotic or hypoplastic branches. Two patients had presumed carotid artery dissection. Low Apgar scores and the presence of sepsis were significantly (P <.05) more common in neonates with MRA findings. CONCLUSION: The prevalence of arterial abnormalities or variations in neonatal AIS has been underestimated because neurovascular imaging is often not performed. We recommend an MRA for neonates with AIS, particularly those who have low Apgar scores and/or sepsis, to rule out a vasculopathy that may warrant therapeutic intervention.

Neighborhood Disadvantage, Race and Ethnicity, and Postpartum Depression.

Importance: Postpartum depression (PPD) is a debilitating condition with higher rates among Black individuals. Increasingly, neighborhood disadvantage is being recognized as a contributor to poor health and may be associated with adverse postpartum mental health; however, associations between neighborhood disadvantage, race and ethnicity, and PPD have not been examined. Objective: To investigate the association between neighborhood disadvantage and PPD and evaluate the extent to which these associations may differ by race and ethnicity. Design, Setting, and Participants: This population-based cross-sectional study included 122 995 postpartum Kaiser Permanente Northern California members 15 years or older with a live birth between October 7, 2012, and May 31, 2017, and an address in the electronic health record. Analyses were conducted from June 1, 2022, through June 30, 2023. Exposures: Neighborhood disadvantage defined using quartiles of the Neighborhood Deprivation Index (NDI), a validated census-based socioeconomic status measure; self-reported race and ethnicity ascertained from Kaiser Permanente Northern California electronic health records. Main Outcomes and Measures: Multivariable Poisson regression was conducted to assess associations between neighborhood disadvantage, race and ethnicity, and a diagnosis of PPD. Results: Of 122 995 included postpartum individuals, 17 554 (14.3%) were younger than 25 years, 29 933 (24.3%) were Asian, 8125 (6.6%) were Black, 31 968 (26.0%) were Hispanic, 47 527 (38.6%) were White, 5442 (4.4%) were of other race and ethnicity, and 15 436 (12.6%) had PPD. Higher neighborhood disadvantage and race and ethnicity were associated with PPD after covariate adjustment. Compared with White individuals, Black individuals were more likely to have PPD (adjusted relative risk [ARR], 1.30; 95% CI, 1.24-1.37), whereas Asian (ARR, 0.48; 95% CI, 0.46-0.50), and Hispanic (ARR, 0.92; 95% CI, 0.89-0.96) individuals and those identified as having other race and ethnicity (ARR, 95% CI, 0.90; 0.85-0.98) were less likely to have PPD. Associations between NDI and PPD differed by race and ethnicity (likelihood ratio test for interaction, χ212 = 41.36; P < .001). Among Black individuals, the risk of PPD was the greatest overall and increased with neighborhood disadvantage in a dose-response manner (quartile [Q] 2 ARR, 1.39 [95% CI, 1.13-1.71]; Q3 ARR, 1.50 [95% CI, 1.23-1.83]; Q4 ARR, 1.60 [95% CI, 1.32-1.93]; Cochrane-Armitage test for trend, P < .001). Neighborhood disadvantage was associated with PPD among Asian (Q2 ARR, 1.17 [95% CI, 1.04-1.31]; Q3 ARR, 1.20 [95% CI, 1.06-1.35]) and White (Q3 ARR, 1.14 [95% CI, 1.07-1.21]; Q4 ARR, 1.17 [95% CI, 1.09-1.26]) individuals and those of other race and ethnicity (Q3 ARR, 1.34 [95% CI, 1.09-1.63]; Q4 ARR, 1.28 [95% CI, 1.03-1.58]), but the magnitude of risk was lower. Neighborhood disadvantage was not associated with PPD among Hispanic individuals (eg, Q2 ARR, 1.04 [95% CI, 0.94-1.14]; Q3 ARR, 1.00 [95% CI, 0.91-1.10]; Q4 ARR, 0.98 [95% CI, 0.90-1.08]). Conclusions and Relevance: In this cross-sectional study of postpartum individuals, residing in more disadvantaged neighborhoods was associated with PPD, except among Hispanic individuals. Neighborhood disadvantage may be associated with racial and ethnic differences in postpartum mental health. Geographic targeting of mental health interventions may decrease postpartum mental health inequities.

Obstructive sleep apnea syndrome and neuropsychological function in pediatric stroke.

OBJECTIVES: To assess the prevalence of obstructive sleep apnea syndrome (OSAS) in children with arterial ischemic stroke (AIS) and to evaluate its association with neuropsychological outcomes. METHODS: We conducted a cross-sectional study of sleep health and neuropsychological outcome in children with AIS. A consecutive cohort of children attending a stroke clinic were assessed using a standardized pediatric sleep questionnaire (PSQ) and standardized measures of pediatric stroke outcome and intellectual, executive and adaptive function. High risk for OSAS was defined as PSQ score ≥0.33. RESULTS: Overall, 102 children were included (55% males, median age: 9 years [interquartile-range [IQR]: 6-14]). The prevalence of OSAS in children with AIS was significantly higher compared to published normative prevalence rate (25.5% vs 5%, p < 0.001). Children with OSAS were more likely to have infarcts affecting both the anterior and posterior circulation (37.5% vs 9.5%, p = 0.021). In addition, children with OSAS had significantly higher median Pediatric Stroke Outcome Measure (PSOM) scores (2 [IQR: 0-2] vs 1 [IQR: 1-3.5], p = 0.01) and were more likely to be prescribed concomitant medications affecting sleep architecture (50% vs 22.4%, p = 0.007). OSAS was associated with significantly lower scores on intellectual, memory, cognitive, behavioral, attention, executive and adaptive function scales. The association between PSQ and intellectual ability and working memory remained statistically significant upon controlling for potential confounding factors including stroke related characteristics (neurologic impairment and arterial territory). CONCLUSIONS: The prevalence of OSAS in children with AIS compared to healthy controls is significantly elevated and is associated with poor neuropsychological outcomes. We highlight the importance of regular screening for OSAS - a modifiable risk factor - in children with AIS. The specific risk factors for OSAS and the potential benefits of therapeutic interventions in this patient population warrant further investigation.

Spectrum of cerebral arteriopathies in children with arterial ischemic stroke.

OBJECTIVE: To determine that children with arterial ischemic stroke (AIS) due to an identifiable arteriopathy are distinct from those without arteriopathy and that each arteriopathy subtype has unique and recognizable clinical features. METHODS: We report a large, observational, multicenter cohort of children with AIS, age 1 month to 18 years, enrolled in the International Pediatric Stroke Study from 2003 to 2014. Clinical and demographic differences were compared by use of the Fisher exact test, with linear step-up permutation min-p adjustment for multiple comparisons. Exploratory analyses were conducted to evaluate differences between cases of AIS with and without arteriopathy and between arteriopathy subtypes. RESULTS: Of 2,127 children with AIS, 725 (34%) had arteriopathy (median age 7.45 years). Arteriopathy subtypes included dissection (27%), moyamoya (24.5%), focal cerebral arteriopathy-inflammatory subtype (FCA-i; 15%), diffuse cerebral vasculitis (15%), and nonspecific arteriopathy (18.5%). Children with arteriopathic AIS were more likely to present between 6 and 9 years of age (odds ratio [OR] 1.93, p = 0.029) with headache (OR 1.55, p = 0.023), multiple infarctions (OR 2.05, p < 0.001), sickle cell anemia (OR 2.9, p = 0.007), and head/neck trauma (OR 1.93, p = 0.018). Antithrombotic use and stroke recurrence were higher in children with arteriopathy. Among arteriopathy subtypes, dissection was associated with male sex, older age, headache, and anticoagulant use; FCA-i was associated with hemiparesis and single infarcts; moyamoya was associated with seizures and recurrent strokes; and vasculitis was associated with bilateral infarctions. CONCLUSION: Specific clinical profiles are associated with cerebral arteriopathies in children with AIS. These observations may be helpful indicators in guiding early diagnosis and defining subgroups who may benefit most from future therapeutic trials.

Epidemiology and Outcomes of Arterial Ischemic Stroke in Children: The Canadian Pediatric Ischemic Stroke Registry.

BACKGROUND: Pediatric arterial ischemic stroke remains incompletely understood. Population-based epidemiological data inform clinical trial design but are scant in this condition. We aimed to determine age-specific epidemiological characteristics of arterial ischemic stroke in neonates (birth to 28 days) and older children (29 days to 18 years). METHODS: We conducted a 16-year, prospective, national population-based study, the Canadian Pediatric Ischemic Stroke Registry, across all 16 Canadian acute care children's hospitals. We prospectively enrolled children with arterial ischemic stroke from January 1992 to December 2001 and documented disease incidence, presentations, risk factors, and treatments. Study outcomes were assessed throughout 2008, including abnormal clinical outcomes (stroke-related death or neurological deficit) and recurrent arterial ischemic stroke or transient ischemic attack. RESULTS: Among 1129 children enrolled with arterial ischemic stroke, stroke incidence was 1.72/100,000/year, (neonates 10.2/100,000 live births). Detailed clinical and radiological information were available for 933 children (232 neonates and 701 older children, 55% male). The predominant clinical presentations were seizures in neonates (88%), focal deficits in older children (77%), and diffuse neurological signs (54%) in both. Among neonates, 44% had no discernible risk factors. In older children, arteriopathy (49% of patients with vascular imaging), cardiac disorders (28%), and prothrombotic disorders (35% of patients tested) predominated. Antithrombotic treatment increased during the study period (P < 0.001). Stroke-specific mortality was 5%. Outcomes included neurological deficits in 60% of neonates and 70% of older children. Among neonates, deficits emerged during follow-up in 39%. Overall, an initially decreased level of consciousness, a nonspecific systemic presentation, and the presence of stroke risk factors predicted abnormal outcomes. For neonates, predictors were decreased level of consciousness, nonspecific systemic presentation, and basal ganglia infarcts. For older children, predictors were initial seizures, nonspecific systemic presentation, risk factors, and lack of antithrombotic treatment. Recurrent arterial ischemic stroke or transient ischemic attack developed in 12% of older children and was predicted by arteriopathy, presentation without seizures, and lack of antithrombotic treatment. Emerging deficit was predicted by neonatal age at stroke and by cardiac disease. CONCLUSIONS: This national data set provides a population-based disease incidence rate and demonstrates the protective effect of antithrombotic treatment in older children, and frequent long-term emerging deficits in neonates and in children with cardiac disorders. Further clinical trials are required to develop effective age-appropriate treatments for children with acute arterial ischemic stroke.