We conclude that 2009 influenza A (H1N1) can cause significant acute and residual neurologic sequelae. Clinicians should consider Influenza within a comprehensive differential diagnosis in children with unexplained mental status changes during periods of pandemic influenza.

In rats, whisker trimming during development leads to persistent alterations in the function of cortical barrel circuits and to behavioral deficits later in life. Here we examined how whisker trimming begun either at birth (P0) or on postnatal day 12 (P12), around the onset of whisking behavior, affects receptive fields of layer IV barrel neurons. All whiskers on the left face were trimmed for 40-45 days and then allowed to regrow fully. Extracellular single-unit recordings and controlled deflections of principal and adjacent whiskers (PW and AW, respectively), individually or in paired combinations, were used to assess excitatory and suppressive effects of neighboring whiskers on barrel neurons. Results indicate that whisker trimming both from P0 and P12 leads to enlarged excitatory and weakened inhibitory receptive fields in layer IV neurons. PW- and AW-evoked responses are larger in magnitude in trimmed than in control animals; AW-evoked responses are disproportionately affected, decreasing the spatial focus of barrel neurons. Deprivation after P12 accounts for approximately 50% of the total effect observed in P0 trimmed animals. Suppressive interactions, evoked by two whiskers deflected in succession, are weaker in trimmed than in control animals. Suppressive caudal/rostral and ventral/dorsal gradients, however, seem unaffected by sensory deprivation. Thus the developmental period during which experience persistently modifies maturing barrel circuitry extends up to and likely beyond the onset of whisking behavior. Sensory deprivation during this time affects development of both excitatory and inhibitory receptive fields of barrel neurons and likely impairs cortical integration of sensory information from multiple whiskers.

Increased vascular stiffness correlates with a higher risk of cardiovascular complications in aging adults. Elastin (ELN) insufficiency, as observed in patients with Williams-Beuren syndrome or with familial supravalvular aortic stenosis, also increases vascular stiffness and leads to arterial narrowing. We used Eln mice to test the hypothesis that pathologically increased vascular stiffness with concomitant arterial narrowing leads to decreased blood flow to end organs such as the brain. We also hypothesized that drugs that remodel arteries and increase lumen diameter would improve flow. To test these hypotheses, we compared carotid blood flow using ultrasound and cerebral blood flow using MRI-based arterial spin labeling in wild-type (WT) and Eln mice. We then studied how minoxidil, an ATP-sensitive K channel opener and vasodilator, affects vessel mechanics, blood flow, and gene expression. Both carotid and cerebral blood flows were lower in Eln mice than in WT mice. Treatment of Eln mice with minoxidil lowered blood pressure and reduced functional arterial stiffness to WT levels. Minoxidil also improved arterial diameter and restored carotid and cerebral blood flows in Eln mice. The beneficial effects persisted for weeks after drug removal. RNA-Seq analysis revealed differential expression of 127 extracellular matrix-related genes among the treatment groups. These results indicate that ELN insufficiency impairs end-organ perfusion, which may contribute to the increased cardiovascular risk. Minoxidil, despite lowering blood pressure, improves end-organ perfusion. Changes in matrix gene expression and persistence of treatment effects after drug withdrawal suggest arterial remodeling. Such remodeling may benefit patients with genetic or age-dependent ELN insufficiency. NEW & NOTEWORTHY Our work with a model of chronic vascular stiffness, the elastin ( Eln) mouse, shows reduced brain perfusion as measured by carotid ultrasound and MRI arterial spin labeling. Vessel caliber, functional stiffness, and blood flow improved with minoxidil. The ATP-sensitive K channel opener increased Eln gene expression and altered 126 other matrix-associated genes.

AIM Dysautonomia after brain injury is a diagnosis based on fever, tachypnea, hypertension, tachycardia, diaphoresis, and/or dystonia. It occurs in 8 to 33% of brain-injured adults and is associated with poor outcome. We hypothesized that brain-injured children with dysautonomia have worse outcomes and prolonged rehabilitation, and sought to determine the prevalence of dysautonomia in children and to characterize its clinical features. METHOD We developed a database of children (n=249, 154 males, 95 females; mean (SD) age 11y 10mo [5y 7mo]) with traumatic brain injury, cardiac arrest, stroke, infection of the central nervous system, or brain neoplasm admitted to The Children’s Institute of Pittsburgh for rehabilitation between 2002 and 2009. Dysautonomia diagnosis, injury type, clinical signs, length of stay, and Functional Independence Measure for Children (WeeFIM) testing were extracted from medical records, and analysed for differences between groups with and without dysautonomia. RESULTS Dysautonomia occurred in 13% of children with brain injury (95% confidence interval 9.3–18.0%), occurring in 10% after traumatic brain injury and 31% after cardiac arrest. The combination of hypertension, diaphoresis, and dystonia best predicted a diagnosis of dysautonomia (area under the curve=0.92). Children with dysautonomia had longer stays, worse WeeFIM scores, and improved less on the score’s motor component (all p≤0.001). INTERPRETATION Dysautonomia is common in children with brain injury and is associated with prolonged rehabilitation. Prospective study and standardized diagnostic approaches are needed to maximize outcomes.