No abstract

No abstract

Air pollution exposures are linked to neuroinflammation and neuropathology in young urbanites. Forty percent of exposed children and young adults exhibit frontal tau hyperphosphorylation and 51% have amyloid-β diffuse plaques compared to 0% in low pollution controls. In older adults, white matter hyperintensities (WMH) are associated with cognitive deficits while inflammatory markers correlate with greater atrophy than expected for age. We investigated patterns of WMH, magnetic resonance imaging (MRI) volume growth, blood inflammatory mediators, and cognition in matched children from two urban cohorts: one severely and one minimally exposed to air pollution. Baseline and one year follow-up measurements of cognitive abilities, brain MRI volumes, and blood were collected in 20 Mexico City (MC) children (10 with WMH+, and 10 without WMH-) and 10 matched controls (WMH-). MC WMH- children display the profile of classical pro-inflammatory defensive responses: high interleukin 12, production of powerful pro-inflammatory cytokines, and low concentrations of key cytokines and chemokines associated with neuroprotection. MC WMH+ children exhibit a response involved in resolution of inflammation, immunoregulation, and tissue remodeling. The MC WMH+ group responded to the air pollution-associated brain volumetric alterations with white and grey matter volume increases in temporal, parietal, and frontal regions and better cognitive performance compared to MC WMH-. We conclude that complex modulation of cytokines and chemokines influences children's central nervous system structural and volumetric responses and cognitive correlates resulting from environmental pollution exposures. Identification of biomarkers associating systemic inflammation to brain growth is critical for detecting children at higher risk for cognitive deficits and neurodegeneration, thereby warranting early implementation of neuroprotective measures.

The objective of this study is to describe the characteristics of patients with pachymeningitis (PM) in granulomatosis with polyangiitis (GPA) from Latin America, including three young patients. This is a retrospective case series. Patients were classified according to the ACR criteria, the 2012 Chapel Hill Consensus Conference Nomenclature and the EMA algorithm. Demographic, clinical, serological, and neuroimaging characteristics are described. Thirteen patients (nine females, four males) were identified. Mean age ± SD of PM diagnosis was 35.5 ± 20.4 years (median 48, range 8-71 years). Mean time ± SD between GPA first symptom and PM diagnosis was 59.8 ± 70.1 months (median 48, range 2-252 months). An important difference between children and adults was the median time elapsed between first GPA symptoms and PM diagnosis (range 2-4 months vs 5-252 months, respectively). Chronic headache was present in all, followed by intracranial hypertension (n = 5), single cranial nerve palsy and orbital mass (n = 4), seizures (n = 3), cavernous sinus syndrome and multiple cranial nerve palsies (n = 2), and meningism and cerebellar syndrome (n = 1 each). At time of PM diagnosis, mean BVAS/WG (Birmingham Vasculitis Activity Score for Wegener's granulomatosis) was 4 ± 2.4 and mean VDI of 2 ± 1.6, mostly due to ENT damage. Gadolinium-enhanced brain MRI showed dural thickening in 12 patients and leptomeningeal enhancement in one. All received a combination of glucocorticoids plus immunosuppressants, rituximab being used favourably in one refractory case. Improvement was observed in 12 patients. Chronic headache should lead to suspect PM. PM predominates in localised GPA. Children may present it earlier in the disease course than adults. Treatment is non-standardised and remains difficult.

Residency in cities with high air pollution is associated with neuroinflammation and neurodegeneration in healthy children, young adults, and dogs. Nonsteroidal anti-inflammatory drugs may offer neuroprotection. The authors measured the plasma concentrations of 3-nitrotyrosine and the cerebro-spinal-fluid concentrations of prostaglandin E2 metabolite and the oligomeric form of amyloid derived diffusible ligand; measured the mRNA expression of cyclooxygenase-2, interleukin 1beta, CD14, and Aquaporin-4 in target brain areas; and evaluated brain MRI, cognition, and neuropathology in 8 dogs treated with a preferential cyclooxygenase-2 inhibitor (Nimesulide) versus 7 untreated litter-matched Mexico City dogs. Nimesulide significantly decreased nitrotyrosine in plasma (p < .0001), frontal gray IL1beta (p = .03), and heart IL1beta (p = .02). No effect was seen in mRNA COX2, amyloid, and PGE2 in CSF or the MRI white matter lesions. All exposed dogs exhibited olfactory bulb and frontal accumulation of Abeta(42) in neurons and blood vessels and frontal vascular subcortical pathology. White matter hyperintense MRI frontal lesions were seen in 4/6 non-treated and 6/8 treated dogs. Nonsteroidal anti-inflammatory drugs may offer limited neuroprotection in the setting of severe air pollution exposures. The search for potentially beneficial drugs useful to ameliorate the brain effects of pollution represents an enormous clinical challenge.