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Introduction: There has been considerable interest in the interplay between testosterone and cognition. Dihydrotestosterone (DHT), which has been correlated with cognitive function, is significantly reduced with the use of 5 alpha reductase inhibitors (5ARI) for prostatic enlargement. Our objective was to assess whether the use of 5ARIs was associated with an increased risk of incident dementia., Methods: We used a matched cohort design and linked administrative data from the province of Ontario, Canada. A total of 99 covariates were measured, and a propensity score was used for matching; 81,162 men who used a 5ARIs were matched to an equal number of men who did not., Results: New initiation of 5ARI medication was associated with an increased risk of dementia during the first (HR 2.18, 95% CI 2.01-2.35) and second (HR 1.52, 95% CI 1.39-1.67) year, however this risk was nonsignificant among the men with the longest exposure to 5ARIs (HR 1.06, 95% CI 0.98-1.14). There was no difference in the results between types of 5ARIs., Conclusion: As the strength of the association decreased with increased exposure, the higher risk seen in the initial two years likely represents the presentation and treatment of urinary symptoms which coexist with mild cognitive impairment and eventually progresses to a diagnosis of dementia., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Purpose: Blood-brain barrier breakdown (BBBB) occurs in relapsing remitting multiple sclerosis (RRMS). Relative recirculation (rR), a BBBB surrogate, may show inflammation undetectable by gadolinium. We compared normal appearing white matter (NAWM) rR in patients with and without disability measured with Symbol Digit Modalities Test and the Expanded Disability Status Scale (EDSS)., Methods: Thirty-nine RRMS patients were prospectively recruited and classified as impaired or non-impaired based on the SDMT and EDSS threshold ≥3. Significant demographic, MRI structural and regional rR characteristics were advanced into multivariate analysis to assess the association with impairment of cognition and EDSS. Bonferroni corrected p < 0.025 was applied to demographic and rR group comparisons; p < 0.05 was used in the final multivariate logistic regression., Results: rR was higher in NAWM (p = 0.012), NAGM (p = 0.004), and basal ganglia (p = 0.007) in cognitively impaired versus non-impaired patients. The difference between NAWM and T2HL rR was significant in cognitively non-impaired patients and approximated that of T2HL in impairment (0.084 vs. 0.075, p = 0.008; 0.118 vs. 0.101, p = 0.091, respectively). After adjusting for confounders, rR elevation for NAWM (OR 1.777; 95% CI 1.068-2.956; p = 0.026), NAGM (OR 2.138; 1.100-4.157; p = 0.025), and basal ganglia (OR 2.192; 1.120-4.289; p = 0.022) remained significantly predictive of cognitive impairment. NAWM area under the curve (AUC) for cognitive impairment was 0.783. No significant group differences or associations were seen for rR and EDSS impairment. No NAGM and cortical lesion rR difference was present within any of the impaired or non-impaired groups., Conclusion: rR elevation in NAWM, NAGM, and basal ganglia appears sensitive to cognitive impairment but not EDSS.

Competing Interests: POTENTIAL CONFLICT OF INTEREST: The authors have indicated they have no potential conflicts of interest to disclose.

Driving errors that predict on-road outcomes for persons with multiple sclerosis (PwMS) are not well studied. The objective of this study was to determine whether adjustment-to-stimuli and gap acceptance errors significantly predict passing/failing a standardized on-road assessment of PwMS. Thirty-seven participants completed visual ability and visual attention assessments, and participated in an on-road assessment, where seven types of driving errors and pass/fail outcomes were determined. Adjustment-to-stimuli (No.) and gap acceptance errors (commit/did not commit) significantly predicted passing/failing the on-road assessment, with an area under the curve of 91.6% ( p < .0001). With no gap acceptance errors committed, five adjustment-to-stimuli errors optimally determined pass/fail outcomes in PwMS. Furthermore, with no adjustment to stimuli errors committed, committing any gap acceptance errors also optimally determined pass/fail outcomes in PwMS. Further research may focus on visual, cognitive, and/or motor impairments underlying adjustment-to-stimuli and gap acceptance errors for eventual development of rehabilitation strategies for PwMS.

Objective: To determine the effect of an acute (1 week) and chronic (3 weeks) exposure to E-cigarette (E-cig) emissions on mucociliary clearance (MCC) in murine lungs., Methods: C57BL/6 male mice (age 10.5 ± 2.4 weeks) were exposed for 20 min/day to E-cigarette aerosol generated by a Joyetech 510-T ® E-cig containing either 0% nicotine (N)/propylene glycol (PG) for 1 week (n = 6), or 3 weeks (n = 9), or 2.4% N/PG for one week (n = 6), or 3 weeks (n = 9), followed by measurement of MCC. Control mice (n = 15) were not exposed to PG alone, or N/PG. MCC was assessed by gamma camera following aspiration of 99m technetium aerosol and was expressed as the amount of radioactivity removed from both lungs over 6 hours (MCC6hrs). Venous blood was assayed for cotinine levels in control mice and in mice exposed for 3-weeks to PG alone and N/PG., Results: MCC6hrs in control mice and in mice acutely exposed to PG alone and N/PG was similar, averaging (±1 standard deviation) 8.6 ± 5.2%, 7.5 ± 2.8% and 11.2 ± 5.9%, respectively. In contrast, chronic exposure to PG alone stimulated MCC6hrs (17.2 ± 8.0)% and this stimulation was significantly blunted following chronic exposure to N/PG (8.7 ± 4.6)% (p < .05). Serum cotinine levels were <0.5 ng/ml in control mice and in mice exposed to PG alone, whereas, N/PG exposed mice averaged 14.6 ± 12.0 ng/ml., Conclusions: In this murine model, a chronic, daily, 20 min-exposure to N/PG, but not an acute exposure, slowed MCC, compared to exposure to PG alone and led to systemic absorption of nicotine.

Objectives: One of the most frequently disabling symptoms in Multiple Sclerosis (MS) is cognitive impairment which is often insidious in onset and therefore difficult to recognize in the early stages, for both persons with MS and clinicians. A biomarker that would help identify those at risk of cognitive impairment, or with only mild impairment, would be a useful tool for clinicians. Using MRI, already an integral tool in the diagnosis and monitoring of disease activity in MS, would be ideal. Thus, this study aimed to determine if simple measures on routine MRI could serve as potential biomarkers for cognitive impairment in MS., Patients and Methods: We retrospectively identified 51 persons with MS who had a cognitive assessment and MRI within six months of the MRI. Simple linear measurements of the hippocampi, bifrontral and third ventricular width, bicaudate width and the anterior, mid and posterior corpus callosum were made. Pearson's correlations examined the relationship between these MRI measures and cognitive tests, and MRI measures were compared in persons with MS who were either normal or cognitively impaired on objective cognitive tests using Analysis of Covariance (ANCOVA)., Results: Bicaudate span and third ventricular width were both negatively correlated, while corpus callosal measures were positive correlated with cognitive test performance. After controlling for potential confounders, bicaudate span was significant different on measures of immediate recall. Both anterior and posterior corpus collosal measure were significantly different on measures of verbal fluency, immediate recall and higher executive function; while the anterior corpus callosum was also significantly different on processing speed. The middle corpus collosal measure was significantly different on immediate recall and higher executive function., Conclusion: This study presents data demonstrating that simple to apply MRI measures of atrophy may serve as biomarkers for cognitive impairment in persons with MS. Further prospective studies are needed to validate these findings., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Introduction: Since premature males are more likely to be diagnosed with bronchopulmonary dysplasia we hypothesized that differences in respiratory outcomes after initial hospital discharge and during the first 3 years of life would exist between females and males diagnosed with BPD., Methods: Subjects with the diagnosis of BPD were recruited from the Johns Hopkins Bronchopulmonary Dysplasia Clinic between 2008 and 2014. Clinical features were assessed through chart review (n = 482). Respiratory morbidities were assessed by caregiver questionnaires at clinic visits (n = 429), including emergency department visits, hospital admissions, systemic steroid use, and antibiotic use for respiratory reasons since the last BPD clinic visit or after initial hospital discharge if assessed at the first visit., Results: Male infants weighed significantly more at birth, had higher birth weight percentiles and were more likely to be non-white compared to female infants. The frequency of ever acute care use was 36.9% for emergency department visits, 27.4% for hospital admissions, 36.9% for systemic steroid use, and 40.5% for antibiotic use for a respiratory illness. No differences in respiratory morbidities were found between males and females. Females however, tended to be weaned from supplemental oxygen over 3 months later than males., Conclusions: Compared to females with BPD, males were more likely to weigh more, have higher birth weight percentiles and be non-white. After initial hospital discharge, there were no difference in respiratory morbidities between males and females with BPD. Female infants however were more likely to be weaned from supplemental oxygen at a later age than male infants. Pediatr Pulmonol. 2017;52:217-224. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Objective: Depression is more common among persons with multiple sclerosis (MS) than the general population. Depression in MS is associated with reduced quality of life, transition to unemployment, and cognitive impairment. Two proposed screening measures for depression in MS populations are the Hospital Anxiety and Depression Scale (HADS) and the Beck Depression Inventory-Fast Screen (BDI-FS). Our objective was to compared the associations of the BDI-FS and the HADS-D scores with history of depressive symptoms, fatigue, and functional outcomes to determine the differential clinical utility of these screening measures among persons with MS., Method: We reviewed charts of 133 persons with MS for demographic information; scores on the HADS, BDI-FS, a fatigue measure, and a processing speed measure; and employment status., Results: Structural equation modeling results indicated the HADS-D predicted employment status, disability status, and processing speed more effectively than did the BDI-FS, whereas both measures predicted fatigue., Conclusions: This study suggests the HADS-D is more effective than the BDI-FS in predicting functional outcomes known to be associated with depression among persons with MS. (PsycINFO Database Record, ((c) 2017 APA, all rights reserved).)

Although used across North America, many on-road studies do not explicitly document the content and metrics of on-road courses and accompanying assessments. This article discusses the development of the University of Western Ontario's on-road course, and elucidates the validity of its accompanying on-road assessment. We identified main components for developing an on-road course and used measurement theory to establish face, content, and initial construct validity. Five adult volunteer drivers and 30 drivers with multiple sclerosis participated in the study. The road course had face and content validity, representing 100% of roadway components determined through a content validity matrix and index. The known-groups method showed that debilitated drivers (vs. not debilitated), made more driving errors ( W = 463.50, p = .03), and failed the on-road course, indicating preliminary construct validity of the on-road assessment. This research guides and empirically supports a process for developing a road course and its assessment.

Background: Cognitive fatigue (CF) is a common complaint in persons with MS (PwMS). Fampridine-SR improves ambulation, fatigue and endurance, due to enhancing action potential formation by blocking potassium channels in demyelinated axons. Thus, through this same mechanism, it is hypothesized that Fampridine-SR could improve CF., Objective: To determine if Fampridine-SR objectively improves CF in PwMS., Methods: Sixty PwMS of any type with CF, defined as 3 or less correct responses when comparing the last third to the first third on the Paced Auditory Serial Addition Test (PASAT), were recruited from a tertiary care MS clinic in London (ON) Canada. Subjects also had to be between 18 and 64 years of age, inclusive, not had a relapse in the last 60 days or corticosteroids in the last 30 days, EDSS 0.0-7.0, and no other diagnosis that could cause cognitive impairment. A randomized double blind crossover design was used: subjects were randomized to either placebo or Fampridine-SR for 4 weeks, then after at least a one week washout, received the opposite treatment. Subjects were assessed before and after each treatment block. The primary outcome was the PASAT CF score after treatment with Fampridine-SR compared to placebo. T-tests and chi-square were used to compare demographics between the two groups (placebo-Fampridine-SR vs. Fampridine SR-placebo). Treatment effects were assessed using factorial ANOVA, with treatment (Fampridine-SR vs. placebo) and time (before and after treatment) as within-subject variables., Results: Of the 60 subjects randomized, 48 completed the study; three were removed due to an adverse event while in the treatment arm (one due to relapse while on placebo, one due to urinary retention and one due to dizziness and headache while on Fampridine-SR). The subjects had a mean age of 46.5±10.0 years, education of 13.6±1.9 years, and were diagnosed with MS 10.6±9.6 years ago. The majority were female (46, 76.7%), had relapsing remitting MS (41, 68.3%) with median EDSS of 3.5 (range 1.0-7.0). There were no significant demographic differences between the two groups. The treatment x time interaction within the factorial ANOVA on PASAT CF scores was statistically significant, F(1, 45)=8.28, p=0.006, suggesting there is a difference between the treatments (placebo vs. Fampridine-SR), over the course of the study. An evaluation of the mean scores suggests, however, that subjects saw a greater improvement when they were given the placebo, than when they were given the active medication. Similarly, individuals showed a greater increase in their information processing speed (as measured by the PASAT) over the course of treatment when they were given the placebo, as compared with the active medication F(1,45)=4.17, p=0.047., Conclusion: Although this small pilot study does not suggest that Fampridine-SR results in a statistically significant improvement of CF in MS patients, as compared to placebo, individuals demonstrated an improvement in both information processing speed and CF, suggesting further studies are warranted., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Definition of the Disease: Ataxia telangiectasia (A-T) is an autosomal recessive disorder primarily characterized by cerebellar degeneration, telangiectasia, immunodeficiency, cancer susceptibility and radiation sensitivity. A-T is often referred to as a genome instability or DNA damage response syndrome., Epidemiology: The world-wide prevalence of A-T is estimated to be between 1 in 40,000 and 1 in 100,000 live births., Clinical Description: A-T is a complex disorder with substantial variability in the severity of features between affected individuals, and at different ages. Neurological symptoms most often first appear in early childhood when children begin to sit or walk. They have immunological abnormalities including immunoglobulin and antibody deficiencies and lymphopenia. People with A-T have an increased predisposition for cancers, particularly of lymphoid origin. Pulmonary disease and problems with feeding, swallowing and nutrition are common, and there also may be dermatological and endocrine manifestations., Etiology: A-T is caused by mutations in the ATM (Ataxia Telangiectasia, Mutated) gene which encodes a protein of the same name. The primary role of the ATM protein is coordination of cellular signaling pathways in response to DNA double strand breaks, oxidative stress and other genotoxic stress., Diagnosis: The diagnosis of A-T is usually suspected by the combination of neurologic clinical features (ataxia, abnormal control of eye movement, and postural instability) with one or more of the following which may vary in their appearance: telangiectasia, frequent sinopulmonary infections and specific laboratory abnormalities (e.g. IgA deficiency, lymphopenia especially affecting T lymphocytes and increased alpha-fetoprotein levels). Because certain neurological features may arise later, a diagnosis of A-T should be carefully considered for any ataxic child with an otherwise elusive diagnosis. A diagnosis of A-T can be confirmed by the finding of an absence or deficiency of the ATM protein or its kinase activity in cultured cell lines, and/or identification of the pathological mutations in the ATM gene., Differential Diagnosis: There are several other neurologic and rare disorders that physicians must consider when diagnosing A-T and that can be confused with A-T. Differentiation of these various disorders is often possible with clinical features and selected laboratory tests, including gene sequencing., Antenatal Diagnosis: Antenatal diagnosis can be performed if the pathological ATM mutations in that family have been identified in an affected child. In the absence of identifying mutations, antenatal diagnosis can be made by haplotype analysis if an unambiguous diagnosis of the affected child has been made through clinical and laboratory findings and/or ATM protein analysis., Genetic Counseling: Genetic counseling can help family members of a patient with A-T understand when genetic testing for A-T is feasible, and how the test results should be interpreted., Management and Prognosis: Treatment of the neurologic problems associated with A-T is symptomatic and supportive, as there are no treatments known to slow or stop the neurodegeneration. However, other manifestations of A-T, e.g. immunodeficiency, pulmonary disease, failure to thrive and diabetes can be treated effectively.

Background: Cognitive impairment affects 40%-68% of relapsing-remitting multiple sclerosis (RRMS) patients. Gray matter (GM) demyelination is complicit in cognitive impairment, yet cortical lesions are challenging to image clinically. We wanted to determine whether cortical cerebral blood flow (CBF), cerebral blood volume (CBV), and mean transit time (MTT) differences exist between cognitively impaired (CI) and unimpaired (NI) RRMS., Methods: Prospective study of healthy controls (n = 19), CI (n = 20), and NI (n = 19) undergoing magnetic resonance imaging (MRI) and cognitive testing <1 week apart. White matter (WM) T2 hyperintense lesions and T1 black holes were traced. General linear regression assessed the relationship between lobar WM volume and cortical and WM CBF, CBV, and MTT. Relationship between global and lobar cortical CBF, CBV, and MTT and cognitive impairment was tested using a generalized linear model. Adjusted Bonferroni p < 0.005 was considered significant., Results: No significant differences for age, gender, disease duration, and any fractional brain or lesion volume were demonstrated for RRMS subgroups. Expanded Disability Status Scale (EDSS) and Hospital Anxiety and Depression Scale-Depression (HADS-D) were higher in CI. Lobar cortical CBF and CBV were associated with cognitive impairment (p < 0.0001) after controlling for confounders. Cortical CBV accounted for 7.2% of cognitive impairment increasing to 8.7% with cortical CBF (p = 0.06), while WM and cortical CBF accounted for 8.2% of variance (p = 0.04)., Conclusion: Significant cortical CBF and CBV reduction was present in CI compared to NI in the absence of structural differences., Competing Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s), 2016.)

Background: In the United States, approximately 12,000 preterm infants are diagnosed with bronchopulmonary dysplasia (BPD) and many of these infants require supplemental oxygen after initial hospital discharge. In children with BPD we sought to identify factors associated with supplemental oxygen use after initial hospital discharge, factors associated with duration of supplemental oxygen use, and methods used to wean off supplemental oxygen in the home environment., Methods: All subjects (n = 420) with the diagnosis of BPD were recruited from a single center Bronchopulmonary Dysplasia Clinic between 2008 and 2013. Subject information was obtained from patient history records, patient demographics, and caregiver questionnaires., Results: Younger gestational age and having a Nissen fundoplication were associated with home supplemental oxygen use in subjects with BPD. Of the 154 subjects who received supplemental oxygen at home, 38% received flows ≤1/8 LPM, 30% received flows >1/8 LPM and ≤1/4 LPM, 21% received flows >1/4 LPM and ≤1/2 LPM, and 11% received flows >1/2 LPM. Among subjects receiving ≤1/8 LPM of oxygen, the median age of weaning off oxygen was 10.1 months, but increased depending on level of oxygen flow at initial outpatient visit. Of the 137 subjects weaned off of oxygen during the study period, weaning was not supervised by a physician in 32.1% of subjects., Conclusion: Home supplemental oxygen use is common in infants diagnosed with BPD. In this study, the median age of weaning off supplemental oxygen was 10.1 months after initial hospital discharge. Unsupervised weaning of supplemental oxygen occurred in 32.1% of subjects with BPD. Pediatr Pulmonol. 2016;51:1206-1211. © 2016 Wiley Periodicals, Inc., (© 2016 Wiley Periodicals, Inc.)

Background: Pulmonary hypertension (PH) is a significant cause of morbidity in preterm infants, but no screening guidelines exist. We sought to identify risk factors and clinical outcomes associated with PH in preterm infants to develop a PH risk score., Methods: Retrospective analysis of two separate populations of preterm infants (NICU cohort n = 230; Clinic registry n = 580)., Results: 8.3% of the NICU cohort had PH after 4 weeks of age, while 14.8% of the clinic registry had PH after 2 months of age. Lower birth weights and longer initial hospitalizations were associated with PH in both populations (p<0.001 for all tests). Using adjusted logistic regression, patent ductus arteriosus (PDA) requiring ligation was associated with PH in both the NICU cohort (OR: 3.19; p = 0.024) and the clinic registry (OR: 2.67; p<0.001). Risk factors (birth weight ≤780 grams, home supplemental oxygen use, and PDA ligation) identified in the clinic registry (training dataset) were validated in the NICU cohort with 0-1 factors present were associated with ≤1.5% probability of having PH, any 2 factors with a 25% probability, and all 3 factors with a 40% probability., Conclusions: Lower birth weight, PDA ligation, and respiratory support were associated with PH in both populations. A PH risk score based on clinical indicators from the training dataset predicted PH in the validation set. This risk score could help focus resources to preterm infants at higher risk for PH. Further work is needed to determine whether earlier or more aggressive management of ductal lesions could alter PH outcomes., Competing Interests: The authors have declared that no competing interests exist.

Purpose: Detection of cortical abnormalities in relapsing-remitting multiple sclerosis (RRMS) remains elusive. Structural magnetic resonance imaging (MRI) measures of cortical integrity are limited, although functional techniques such as pseudo-continuous arterial spin labeling (pCASL) show promise as a surrogate marker of disease severity. We sought to determine the utility of pCASL to assess cortical cerebral blood flow (CBF) in RRMS patients with (RRMS-I) and without (RRMS-NI) cognitive impairment., Methods: A total of 19 age-matched healthy controls and 39 RRMS patients were prospectively recruited. Cognition was assessed using the Minimal Assessment of Cognitive Function in Multiple Sclerosis (MACFIMS) battery. Cortical CBF was compared between groups using a mass univariate voxel-based morphometric analysis accounting for demographic and structural variable covariates., Results: Cognitive impairment was present in 51.3% of patients. Significant CBF reduction was present in the RRMS-I compared to other groups in left frontal and right superior frontal cortex. Compared to healthy controls, RRMS-I displayed reduced CBF in the frontal, limbic, parietal and temporal cortex, and putamen/thalamus. RRMS-I demonstrated reduced left superior frontal lobe cortical CBF compared to RRMS-NI. No significant cortical CBF differences were present between healthy controls and RRMS-NI., Conclusion: Significant cortical CBF reduction occurs in RRMS-I compared to healthy controls and RRMS-NI in anatomically significant regions after controlling for structural and demographic differences., Competing Interests: The authors declare no conflict of interest., (© The Author(s), 2016.)

Introduction: Although disorders of mood and cognition are frequently observed in multiple sclerosis, their relationship remains unclear. We aimed to investigate whether this mood-cognition relationship is mediated by inefficient processing speed, a deficit typically associated with mood symptomatology in the psychiatric literature and a common deficit observed in multiple sclerosis patients., Method: In this study, comprehensive cognitive data and self-reported mood data were retrospectively analyzed from 349 patients with relapsing remitting multiple sclerosis. We performed a bootstrapping analysis to examine whether processing speed provided an indirect means by which depressive symptoms influenced cognitive functioning, specifically memory and executive function., Results: We observed that processing speed mediated the relationship between depressive symptoms and measures of memory and executive function. Interestingly, exploratory analyses revealed that this mediational role of processing speed was specific to MS patients who were younger, had a lower disability level, and had fewer years since MS diagnosis., Conclusions: Together, these findings have implications for mood and cognitive intervention with multiple sclerosis patients.

Rationale: Dopaminergic therapy improves some cognitive functions and worsens others in patients with Parkinson's disease (PD). These paradoxical effects are explained by the dopamine overdose hypothesis, which proposes that effects of dopaminergic therapy on a cognitive function is determined by the baseline dopamine levels in brain regions mediating that function., Objectives: We directly tested this prevalent hypothesis, evaluating the effects of levodopa on stimulus-reward learning in healthy young adults, who presumably have optimal baseline dopamine levels and dopamine regulation., Methods: Twenty-six healthy, young adults completed a probabilistic reversal learning task in a randomized, double-blind, placebo-controlled, crossover design. Participants completed one session on levodopa 100 mg/carbidopa 25 mg and another session on placebo., Results: We found that levodopa impaired reversal learning relative to placebo. Further analyses revealed that levodopa impaired learning from both punishment and reward., Conclusions: Exogenous dopamine impairs stimulus-reward learning, independent of PD pathology and prior to sensitization through repeated exposure, in healthy adults with normal cognition and baseline dopamine function. Our findings support the dopamine overdose hypothesis and caution clinicians about detrimental effects of levodopa in all clinical populations (e.g., early PD, restless leg syndrome) regardless of baseline cognitive and dopaminergic system function.

Objective: To evaluate the potential link between systemic inflammation and impaired lung function in people with ataxia-telangiectasia (A-T), we hypothesized that serum levels of interleukin (IL)-6, a proinflammatory cytokine, would correlate inversely with lung function in subjects with A-T., Study Design: Consecutive subjects with A-T were recruited from the Johns Hopkins Outpatient A-T Clinical Center. Serum levels of IL-6 and 8 were measured by enzyme-linked immunosorbent assay. Spirometry was performed in subjects ≥ 6 years of age on the same day that serum was obtained for measurements of cytokines., Results: Approximately 80% of subjects had elevated serum IL-6 levels (> 1.0 pg/mL). No association was found between elevated IL-6 and age. Elevated IL-8 levels were found in 23.6% of subjects, and all subjects with elevated IL-8 levels had elevated IL-6 levels. Subjects with elevated IL-6 levels (mean: 6.14 ± 7.47 pg/mL) had significantly lower mean percent forced vital capacity (FVC%, 50.5% ± 17.8%) compared with subjects with normal serum IL-6 levels (FVC% of 66.2 ± 16.1, P = .018). Greater IL-6 levels were associated with lower FVC% even after adjustment for receiving gamma globulin therapy (P = .024) and supplemental nutrition (P = .055)., Conclusions: An association was found between elevated serum IL-6 levels and lower lung function in subjects with A-T. In addition, subjects with both elevated IL-6 and IL-8 had the lowest mean lung function. These findings indicate that markers for systemic inflammation may be useful in identifying individuals with A-T at increased risk for lower lung function and may help in assessing response to therapy., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Cognitive impairment, anxiety, and depressive symptoms are common in multiple sclerosis (MS) and are known to interact in non-MS populations. This retrospective chart review examined this relationship in a relapsing-remitting MS population. A significant difference on measures of processing speed/working memory and visual-spatial memory was found in MS patients with anxiety compared with nonanxious MS patients, while a significant difference was found on measures of processing speed, visual-spatial memory and executive function in MS patients with depressive symptoms compared with those without. Further research is needed to determine the causal relationship between anxiety and depressive symptoms and cognitive impairment.

Background: Pathological laughing and crying (PLC) is common in multiple sclerosis (MS), defined as emotional expression that is exaggerated/incongruent with underlying mood. In other neurological disorders, PLC is associated with cognitive impairment (CI). Few studies have examined this relationship in MS., Objective: To determine the association between PLC and CI in an MS population., Methods: Retrospective chart review study of 153 MS subjects assessed in an outpatient clinic for CI. Data was collected on the minimal assessment of cognitive function in MS (MACFIMS), the Center for neurological study-lability scale (CNS-LS), a screening measure for PLC symptoms and the hospital anxiety and depression scale (HADS). Analyses of covariance compared performance on the MACFIMS between PLC (CNS-LS score ≥ 17, HADS-D ≤ 7) and non-PLC groups., Results: MS subjects positive for PLC on the CNS-LS but without depression had lower scores on the controlled oral word association test, a measure of verbal fluency, and the California verbal learning test - 2 immediate recall score, a verbal memory measure., Conclusions: This study demonstrates a connection between CI, specifically verbal fluency and verbal learning, and PLC in MS subjects. Further studies are warranted to explore the causative relationship between CI and PLC., (Copyright © 2015. Published by Elsevier B.V.)

Tobacco smoke and nicotine exposure during prenatal and postnatal life can impair lung development, alter the immune response to viral infections, and increase the prevalence of wheezing during childhood. The following review examines recent discoveries in the fields of lung development and tobacco and nicotine exposure, emphasizing studies published within the last 5 years. In utero tobacco and nicotine exposure remains common, occurring in approximately 10% of pregnancies within the United States. Exposed neonates are at increased risk for diminished lung function, altered central and peripheral respiratory chemoreception, and increased asthma symptoms throughout childhood. Recently, genomic and epigenetic risk factors, such as alterations in DNA methylation, have been identified that may influence the risk for long-term disease. This review examines the impact of prenatal tobacco and nicotine exposure on lung development with a particular focus on nicotinic acetylcholine receptors. In addition, this review examines the role of prenatal and postnatal tobacco smoke and nicotine exposure and its association with augmenting infection risk, skewing the immune response toward a T-helper type 2 bias and increasing risk for developing an allergic phenotype and asthmalike symptoms during childhood. Finally, this review outlines the respiratory morbidities associated with childhood secondhand smoke and nicotine exposure and examines genetic and epigenetic modifiers that may influence respiratory health in infants and children exposed to in utero or postnatal tobacco smoke., (Copyright © 2016 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Despite acute respiratory and chronic respiratory and gastro-intestinal complications, most infants and children with a history of oesophageal atresia / trachea-oesophageal fistula [OA/TOF] can expect to live a fairly normal life. Close multidisciplinary medical and surgical follow-up can identify important co-morbidities whose treatment can improve symptoms and optimize pulmonary and nutritional outcomes. This article will discuss the aetiology, classification, diagnosis and treatment of congenital TOF, with an emphasis on post-surgical respiratory management, recognition of early and late onset complications, and long-term clinical outcomes., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Rationale: Multiple sclerosis (MS) commonly affects cognitive function, most frequently presenting as impaired processing speed (PS). There are currently no approved treatments for PS in this population, but previous studies suggest amphetamines may be beneficial., Objective: The objective of this study is to determine if mixed amphetamine salts, extended release (MAS-XR) has the potential to improve impaired PS in MS patients in a randomized controlled pre- and post-dose testing study., Methods: Fifty-two MS patients demonstrating PS impairment on either the Symbol Digit Modalities Test (SDMT) or Paced Auditory Serial Addition Test (PASAT) were randomized to a single dose of 5 mg MAS-XR (n = 18), 10 mg MAS-XR (n = 20), or placebo (n = 14). Subjects were evaluated a second time, after taking the blinded medication. ANOVA was used to compare the change on the SDMT and PASAT in each of the treatment groups compared to the placebo. Cohen's d was used to calculate effect size., Results: At baseline, the mean SDMT score was 43.3 ± 7.2 and the mean PASAT was 34.8 ± 13.4, with 47 (90.4 %) and 25 (48.1 %) categorized as impaired on the SDMT and PASAT, respectively. The change in SDMT scores from baseline to post-treatment demonstrated significant improvement for the MAS-XR 10-mg dose compared to placebo, increasing by 5.2 ± 4.5 vs. 0.6 ± 4.4 points (p = 0.043), with a medium effect size of 0.47. Change on the PASAT was not significantly different in either treatment group., Conclusions: This study supports MAS-XR 10 mg as a potential treatment for MS patients with demonstrated PS impairment, warranting a larger longitudinal study.

Autonomic dysfunction is a prevalent and significant cause of disability among patients with multiple sclerosis. Autonomic dysfunction in multiple sclerosis is usually explained by lesions within central nervous system regions responsible for autonomic regulation, but novel evidence suggests that other factors may be involved as well. Additionally, the interactions between the autonomic nervous system and the immune system have generated increased interest about the role of autonomic dysfunction in the pathogenesis of multiple sclerosis. In this paper we analyze systematically the most relevant signs and symptoms of autonomic dysfunction in MS, considering separately their potential causes and implications., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background: Psychiatric side effects are known to occur with low dose corticosteroids. Standard of care for Multiple Sclerosis (MS) relapses is high dose corticosteroids (HDC), at least 1g/day for 3-5 days, and yet the relationship between this treatment and mood is not known. We sought to determine the frequency and potential predictors of (hypo)manic and depressive symptoms with HDC treatment for MS relapses., Methods: Consecutive MS subjects requiring HDC treatment were identified. The Mood Disorders Questionnaire (MDQ) and the Beck Depression Inventory-Fast Screen (BDIFS) were administered for (hypo)manic and depressive symptoms, respectively, prior to HDC, 3 days and one month post-HDC., Results: Eighty eight subjects completed the study. At relapse diagnosis, the mean BDIFS score was 4.2 (SD 3.1); the mean number of (hypo)manic symptoms endorsed on the MDQ was 4.3 (SD 3.5). Three days after completing HDC, 22.5% had an increase on the BDIFS and 38.2% endorsed more symptoms on the MDQ. A history of depression (p=0.006) and low reported quality of life (p=0.029) predicted an increase on the MDQ; the odds of an increase in (hypo)manic symptoms was 5.6 times higher with a history of any psychiatric disease/substance abuse (p=0.005). No predictors for worsening on the BDIFS were found., Limitations: Self-reported measures were used, anxiety was not evaluated and 17 subjects were lost to follow up., Conclusion: Depressive and hypo(manic) symptoms are commonly associated with HDC for MS relapses. It is important for clinicians and MS patients to be aware of this risk., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Multiple sclerosis is a neurologic inflammatory disease that can manifest with psychiatric symptoms. Although depression is the most common psychiatric diagnosis in patients with multiple sclerosis, how depression develops is not fully understood. We present the case of an individual who displayed episodic mood changes preceding an exacerbation of multiple sclerosis symptoms. The clinical and research implications of this association are discussed.

Methods: Timed-pregnant C57BL/6J mice were exposed to 2.4% nicotine in propylene glycol (PG) or 0% nicotine /PG once a day from gestational day 15 until delivery. After delivery, offspring and mothers were exposed to E-cigarette vapors for an additional 14 days from postnatal day 2 through 16. Following their last exposure serum cotinine levels were measured in female juvenile mice. Male mice underwent behavioral testing at 14 weeks of age to assess sensorimotor, affective, and cognitive functional domains., Results: Adult male mice exposed to 2.4% nicotine/PG E-cigarette vapors had significantly more head dips in the zero maze test and higher levels of rearing activity in the open field test compared to 0% nicotine/PG exposed mice and untreated controls. In the water maze test after reversal training, the 2.4% nicotine/PG mice spent more than 25% of time in the new location whereas the other groups did not., Conclusion: Adult male mice exhibited increased levels of activity in the zero maze and open field tests when exposed to E-cigarette vapor containing nicotine during late prenatal and early postnatal life. These findings indicate that nicotine exposure from E-cigarettes may cause persistent behavioral changes when exposure occurs during a period of rapid brain growth.

Tumefactive multiple sclerosis (MS) is an aggressive form of MS that can be difficult to treat with standard therapies. In severe MS relapses, plasma exchange (PLEX) has shown some benefit, but reports of its use in patients with tumefactive MS are limited. This article describes the successful use of PLEX in a patient with tumefactive MS. A 46-year-old right-handed woman with a recent diagnosis of MS presented with drowsiness, dysarthria, horizontal nystagmus, and quadriparesis. Her brain magnetic resonance images demonstrated multiple tumefactive demyelinating lesions in the medulla, bilateral periventricular white matter, and corona radiata white matter. She was initially treated with a 10-day course of intravenous methylprednisolone without benefit; therefore, PLEX was initiated. After the second exchange, the patient started to improve and was discharged initially to rehabilitation and then home. She was started on disease-modifying therapy with natalizumab and did not experience further relapses but had slow clinical decline during the next year, which led to discontinuation of natalizumab treatment. PLEX may be used as second-line treatment in corticosteroid-resistant MS relapses, but there are limited reports of its use in patients with tumefactive MS. This patient presented with aggressive disease with multiple tumefactive lesions and did not respond to standard treatment with corticosteroids. PLEX was successful in improving her symptoms, allowing her to return home, although the disease progressed during the next year.

While advances in medicine, technology and healthcare services offer promises of longevity and improved quality of life (QoL), there is also increasing reliance on a patient׳s skills and motivation to optimize all the benefits available. Patient engagement in their own healthcare has been described as the 'blockbuster drug of the century'. In multiple sclerosis (MS), patient engagement is vital if outcomes for the patient, society and healthcare systems are to be optimized. The MS in the 21st Century Steering Group devised a set of themes that require action with regard to patient engagement in MS, namely: 1) setting and facilitating engagement by education and confidence-building; 2) increasing the importance placed on QoL and patient concerns through patient-reported outcomes (PROs); 3) providing credible sources of accurate information; 4) encouraging treatment adherence through engagement; and 5) empowering through a sense of responsibility. Group members independently researched and contributed examples of patient engagement strategies from several countries and examined interventions that have worked well in areas of patient engagement in MS, and other chronic illnesses. The group presents their perspective on these programs, discusses the barriers to achieving patient engagement, and suggests practical strategies for overcoming these barriers. With an understanding of the issues that influence patient engagement in MS, we can start to investigate ways to enhance engagement and subsequent health outcomes. Engaging patients involves a broad, multidisciplinary approach., (Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.)

Background: A definitive diagnosis of multiple sclerosis (MS), as distinct from a clinically isolated syndrome, requires one of two conditions: a second clinical attack or particular magnetic resonance imaging (MRI) findings as defined by the McDonald criteria. MRI is also important after a diagnosis is made as a means of monitoring subclinical disease activity. While a standardized protocol for diagnostic and follow-up MRI has been developed by the Consortium of Multiple Sclerosis Centres, acceptance and implementation in Canada have been suboptimal., Methods: To improve diagnosis, monitoring, and management of a clinically isolated syndrome and MS, a Canadian expert panel created consensus recommendations about the appropriate application of the 2010 McDonald criteria in routine practice, strategies to improve adherence to the standardized Consortium of Multiple Sclerosis Centres MRI protocol, and methods for ensuring effective communication among health care practitioners, in particular referring physicians, neurologists, and radiologists., Results: This article presents eight consensus statements developed by the expert panel, along with the rationale underlying the recommendations and commentaries on how to prioritize resource use within the Canadian healthcare system., Conclusions: The expert panel calls on neurologists and radiologists in Canada to incorporate the McDonald criteria, the Consortium of Multiple Sclerosis Centres MRI protocol, and other guidance given in this consensus presentation into their practices. By improving communication and general awareness of best practices for MRI use in MS diagnosis and monitoring, we can improve patient care across Canada by providing timely diagnosis, informed management decisions, and better continuity of care.

Background: Following the initial reports of Chronic Cerebrospinal Venous Insufficiency (CCSVI) and the purported curative potential of venoplasty, (coined the 'liberation' procedure) Canadians living with multiple sclerosis (MS) began to travel abroad to receive the unregulated procedure, often placing them at odds with their health providers. The purpose of this study was to determine the factors influencing older MS patients' decision to undergo the procedure in order to develop more specific and targeted health information., Methods: We performed secondary analysis of data collected as part of the 'Canadian Survey of Health Lifestyle and Aging with MS' from people over the age of 55 years with MS symptoms for 20 or more years. The survey consisted of self-reported information on impairments, disability, participation, demographics, personal and environmental factors. In order to compare respondents who underwent the procedure to those who did not and to develop a predictive model, we created a comparison group using a case-control algorithm, controlling for age, gender and education, and matching procedure cases to controls 1:3. We used multivariate stepwise least likelihood regression of 'a priori' variables to determine predictive factors., Results: The prevalence of the 'liberation' procedure in our sample was 12.8% (95/743), substantially lower than reported in previous studies of complementary/alternative treatments in MS. The predictive model contained five factors; living alone (Odds ratio 0.24, 95%CI 0.09-0.63), diagnosis of anxiety (Odds ratio 0.29, 95%CI 0.10 - 0.84), rating of neurologist's helpfulness (Odds ratio 0.56, 95%CI 0.44 -0 .71), Body Mass Index (Odds ratio 0.93, 95%CI, 0.89 - 0.98) and perceived physical impact of MS (Odds ratio 1.02, 95%CI 1.01 - 1.04)., Conclusions: Predictive factors differed from previous studies of complementary/alternative treatment use likely due to both the invasiveness of the procedure and the advanced age of our study cohort. Our findings suggest that health professionals should target information on the risks and benefits of unregulated procedures to those patients who feel dissatisfied with their neurologist and they should include family members in discussions since they may be providing the logistical support to travel abroad and undergo the 'liberation' procedure. Our findings may be applicable to others with chronic disabling conditions who contemplate the user-pay unregulated invasive procedures available to them.

Objective: To standardize a method to measure cognitive fatigue in patients with multiple sclerosis (MS)., Background: Many patients with MS complain of cognitive fatigue, defined as a decline in cognitive performance during a task requiring sustained activity. Until now there has not been a standardized way to detect cognitive fatigue or determine its severity., Methods: We administered the Paced Auditory Serial Addition Test (PASAT) to 130 normal controls and 100 randomly selected patients with MS, and compared the number of correct responses between the first third and last third of the test., Results: The controls averaged 2 more correct responses in the last third of the PASAT than in the first third. The patients with MS averaged 2 to 3 fewer correct responses in the last third than the first third., Conclusions: Our study showed that comparing responses between the first and last thirds of the PASAT is a reliable method to measure cognitive fatigue in patients with MS. We also present normative data to be used to determine whether patients with MS have cognitive fatigue.

Background: Tobacco smoke exposure (TSE) may increase respiratory morbidities in young children with bronchopulmonary dysplasia (BPD). Rapid respiratory rates, close proximity to a smoking caregiver, and increased dermal absorption of tobacco smoke components can contribute to systemic exposure. In this study, hair nicotine levels were used as a biomarker of chronic TSE in young children with BPD to determine if hair nicotine levels correlate with caregiver self-report of TSE and respiratory morbidities., Methods: From 2012 to 2014, hair nicotine levels were measured from consecutive children seen in a BPD outpatient clinic and compared with caregiver questionnaires on household smoking. The relationship between respiratory morbidities and self-reported TSE or hair nicotine level was assessed., Results: The mean hair nicotine level from 117 children was 3.1 ± 13.2 ng/mg. Hair nicotine levels were significantly higher in children from smoking households by caregiver self-report compared with caregivers who reported no smoking (8.2 ± 19.7 ng/mg vs 1.8 ± 10.7; P < .001). In households that reported smoking, hair nicotine levels were higher in children with a primary caregiver who smoked compared with a primary caregiver who did not smoke. Among children with BPD who required respiratory support (n = 50), a significant association was found between higher log hair nicotine levels and increased hospitalizations and limitation of activity., Conclusions: Chronic TSE is common in children with BPD, with hair nicotine levels being more likely to detect TSE than caregiver self-report. Hair nicotine levels were also a better predictor of hospitalization and activity limitation in children with BPD who required respiratory support at outpatient presentation., (Copyright © 2015 by the American Academy of Pediatrics.)

Neonates and infants have a higher morbidity and mortality associated with lower respiratory tract illnesses compared with older children. To identify age-related and longitudinal differences in the cellular immune response to acute lung injury (ALI), neonatal and juvenile mice were given Escherichia coli LPS using a novel, minimally invasive aspiration technique. Neonatal and juvenile mice received between 3.75 and 7.5 mg/kg LPS by intrapharyngeal aspiration. Airway and lung cells were isolated and characterized by flow cytometry, cytokine/chemokine mRNA expression from lung homogenates was quantified, and lung morphometry and injury scores were performed. LPS-treated neonatal mice underwent adoptive transfer with adult T regulatory cells (Tregs). After LPS aspiration, lung monocytes isolated from neonatal mice had a predominant M2 phenotype, whereas lung monocytes from juvenile mice displayed a mixed M1/M2 phenotype. At 72 hours after LPS exposure, neonatal lungs were slower to resolve inflammation and expressed lower mRNA levels of CCL2, CCL5, CXCL10, and IL-10. Juvenile, but not neonatal, mice demonstrated a significant increase in airway Tregs after LPS exposure. Adoptive transfer of adult Tregs into LPS-challenged neonatal mice resulted in reduced lung inflammation and improved weight gain. These findings underscore several vulnerabilities in the neonatal immune response to LPS-induced ALI. Most striking was the deficiency in airway Tregs after LPS aspiration. Adoptive transfer of adult Tregs mitigated LPS-induced ALI in neonatal mice, highlighting the importance of age-related differences in Tregs and their response to ALI during early postnatal development.

Background and Objective: The definition of cardiovascular autonomic dysfunction in patients with multiple sclerosis is controversial. Thus, its true prevalence is unknown. We performed a systematic review and meta-analysis to compare the proportion of patients with multiple sclerosis that would be diagnosed with cardiovascular dysautonomia using a definition of at least one abnormal cardiac autonomic test vs. at least two abnormal studies., Methods: We searched PubMed, Embase, and Scopus from 1980 to December 2013 for publications reporting abnormal autonomic tests in patients with multiple sclerosis. We performed random-effects meta-analyses for calculating the proportion of patients diagnosed with autonomic dysfunction with both definitions., Results: We included 16 studies comprising 611 patients with multiple sclerosis, assessing ≥3 cardiovascular autonomic tests. The proportion of patients with autonomic dysfunction was two-fold higher (p=0.006) when using the definition of only one abnormal autonomic test (42.1%) compared to that using at least two abnormal results (18.8%)., Conclusions: We found a wide variation in the proportion of patients with multiple sclerosis diagnosed with cardiovascular dysautonomia by using the two definitions. Consensus is needed to define autonomic dysfunction in patients with multiple sclerosis. In the meantime, we encourage investigators to report results using both thresholds., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Background/objective: Electronic cigarette (E-cigarettes) emissions present a potentially new hazard to neonates through inhalation, dermal and oral contact. Exposure to nicotine containing E-cigarettes may cause significant systemic absorption in neonates due to the potential for multi-route exposure. Systemic absorption of nicotine and constituents of E-cigarette emissions may adversely impact weight and lung development in the neonate. To address these questions we exposed neonatal mice to E-cigarette emissions and measured systemic cotinine levels and alveolar lung growth., Methods/main Results: Neonatal mice were exposed to E-cigarettes for the first 10 days of life. E-cigarette cartridges contained either 1.8% nicotine in propylene glycol (PG) or PG vehicle alone. Daily weights, plasma and urine cotinine levels and lung growth using the alveolar mean linear intercept (MLI) method were measured at 10 days of life and compared to room air controls. Mice exposed to 1.8% nicotine/PG had a 13.3% decrease in total body weight compared to room air controls. Plasma cotinine levels were found to be elevated in neonatal mice exposed to 1.8% nicotine/PG E-cigarettes (mean 62.34± 3.3 ng/ml). After adjusting for sex and weight, the nicotine exposed mice were found to have modestly impaired lung growth by MLI compared to room air control mice (p<.054 trial 1; p<.006 trial 2). These studies indicate that exposure to E-cigarette emissions during the neonatal period can adversely impact weight gain. In addition exposure to nicotine containing E-cigarettes can cause detectable levels of systemic cotinine, diminished alveolar cell proliferation and a modest impairment in postnatal lung growth.

Electronic cigarette (e-cigarette) use has gained recent widespread popularity and acceptance in the general population. What effect e-cigarettes may have on pediatric health remains unknown. Although many jurisdictions have laws that prevent the sale of e-cigarettes to minors and the use of e-cigarettes in public places, infants, children, and adolescents are increasingly exposed to them. In this pediatric-focused review, we discuss the history of these devices, user demographics, known health effects, and current legislative efforts to protect minors from exposure.

Objective: To describe the characteristics of small for gestational age (SGA) and non-SGA infants with bronchopulmonary dysplasia (BPD) and to ascertain whether respiratory outcomes and health-care utilization patterns in these two populations differ., Study Design: Three hundred and twenty-five infants with BPD born at <32 weeks gestation were recruited in the outpatient setting. Sociodemographic data and indicators of respiratory morbidity were collected via questionnaire and retrospective chart review., Result: SGA infants were on average 1 month older than non-SGA infants at discharge from the neonatal intensive care unit and were more likely to have a weight less than 10th percentile at first clinic visit. History of SGA was associated with increased risk of emergency department visits as well as with caregiver perception of poor weight gain., Conclusion: SGA status in infants with BPD is associated with increased health-care utilization, including length of initial hospitalization and emergency department visits., Competing Interests: The authors declare no conflict of interest.

Increased blood pressure is a known adverse effect associated with corticosteroids but little is published regarding the risk with the high doses used in multiple sclerosis (MS). A 53-year-old female with known relapsing remitting MS presented with a new brainstem relapse. Standard of care treatment for an acute MS relapse, 1250 mg of oral prednisone for 5 days, was initiated. She developed an occipital headache and dizziness and felt generally unwell. These symptoms persisted after treatment was complete. On presentation to medical attention, her blood pressure was 199/110 mmHg, although she had no history of hypertension. MRI changes were consistent with posterior reversible encephalopathy syndrome (PRES), demonstrating abnormal T2 signal in both thalami, the posterior occipital and posterior parietal white matter with mild sulcal effacement. As her pressure normalized with medication, her symptoms resolved and the MRI changes improved. No secondary cause of hypertension was found. This is the first reported case of PRES secondary to high dose corticosteroid use for an MS relapse without a history of hypertension and with no other secondary cause of hypertension identified. This rare complication should be considered in MS patients presenting with a headache or other neurological symptoms during treatment for a relapse.

Cognitive impairment is a common and debilitating feature of multiple sclerosis (MS) that has only recent gained considerable attention. Clinical neuropsychological studies have made apparent the multifaceted nature of cognitive troubles often encountered in MS and continue to broaden our understanding of its complexity. Radiographic studies have started to decipher the neuroanatomic substrate of MS-related cognitive impairment and have shed light onto its pathogenesis. Where radiographic studies have been limited by inadequate resolution or non-specificity, pathological studies have come to the fore. This review aims to provide an overview of the nature of cognitive impairment typically seen in MS and to explore the literature on imaging and pathological studies relevant to its evolution. In particular, the relative contributions of gray (i.e., cerebral cortex, hippocampus, thalamus and basal ganglia) and white matter to MS-related cognitive impairment will be discussed and the importance of interconnectivity between structures highlighted. The pressing need for longitudinal studies combining standardized neuropsychometric, paraclinical and radiographic outcomes obtained during life with post-mortem tissue analysis after death is presented., (© 2014 International Society of Neuropathology.)

The impact of caring for children with deglutition disorders is poorly understood and tools to measure the unique concerns of these caregivers are lacking. The aims of this investigation were to develop and validate The Feeding/Swallowing Impact Survey (FS-IS) as an instrument designed to measure and improve understanding of caregiver issues. Demographic, economic, and dysphagic data were provided by the primary caregivers of 164 children (median age: 14 months, male: 78, female: 86) presenting for initial outpatient feeding/swallowing evaluations. Caregivers completed the PEDS-QL™ Family Impact Module (PEDS-QL™ FIM) and the FS-IS. A principal component analysis was conducted on the FS-IS to identify appropriate subscales. Concurrent validity was assessed by examining correlations between the FS-IS and PEDS-QL™ FIM. Caring for children with feeding/swallowing problems adversely impacted the Health-Related Quality of Life (HRQoL) of their caregivers. The FS-IS had a strong 3-factor solution to indicate 3 subscales: Daily Activities, Worry, and Feeding Difficulties. All three subscales and total score of the FS-IS correlated with PEDS-QL™ FIM. The FS-IS was validated as an instrument that may help clinicians detect specific factors that influence caregiver HRQoL, identify caregivers who might benefit from additional support, and ultimately improve the care of their children with feeding/swallowing disorders.

Objective: People with multiple sclerosis (MS) are living longer so strategies to enhance long-term health are garnering more interest. We aimed to create a profile of ageing with MS in Canada by recruiting 1250 (5% of the Canadian population above 55 years with MS) participants and focusing data collection on health and lifestyle factors, disability, participation and quality of life to determine factors associated with healthy ageing., Design: National multicentre postal survey., Setting: Recruitment from Canadian MS clinics, MS Society of Canada chapters and newspaper advertisements., Participants: People aged 55 years or older with MS symptoms more than 20 years., Outcome Measures: Validated outcome measures and custom-designed questions examining MS disease characteristics, living situation, disability, comorbid conditions, fatigue, health behaviours, mental health, social support, impact of MS and others., Results: Of the 921 surveys, 743 were returned (80.7% response rate). Participants (mean age 64.6±6.2 years) reported living with MS symptoms for an average of 32.9±9.5 years and 28.6% were either wheelchair users or bedridden. There was only 5.4% missing data and 709 respondents provided optional qualitative information. According to data derived from the 2012 Canadian Community Health Survey of Canadians above 55 years of age, older people with MS from this survey sample are about eight times less likely to be employed full-time. Older people with MS were less likely to engage in regular physical activity (26.7%) compared with typical older Canadians (45.2%). However, they were more likely to abstain from alcohol and smoking., Conclusions: Despite barriers to participation, we were able to recruit and gather detailed responses (with good data quality) from a large proportion of older Canadians with MS. The data suggest that this sample of older people with MS is less likely to be employed, are less active and more disabled than other older Canadians., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.)

Objectives: Infants with bronchopulmonary dysplasia (BPD) often undergo gastrostomy tube (GT) placement and/or Nissen fundoplication (Nissen) to improve weight gain and to attenuate chronic respiratory symptoms related to feeding difficulties. After initial hospitalization little is known how these children do with regard to respiratory symptoms when compared to children with BPD who did not receive GTs. This study was done to determine if differences in respiratory outcomes were associated with the presence of a GT or Nissen/GT in children with BPD during the first 2 years of life., Methods: Children (n = 398) were recruited from the Johns Hopkins BPD Outpatient Clinic. Medical charts were reviewed and acute care usage and respiratory symptoms were assessed by caregiver questionnaires., Results: Ninety-two children with BPD had GTs, with the majority placed by 6 months of age. Of children with GTs, 64.7% also had Nissen fundoplication. Children with Nissen/GTs were more likely to have birth weights <10th percentile and to be discharged on supplemental oxygen. After initial hospitalization, children with GTs and Nissen/GTs weaned off supplemental oxygen at significantly older ages than children without GTs. Children with Nissen/GTs also had more hospitalizations than children without GTs. Caregivers of children with GTs and Nissen/GTs reported similar respiratory symptoms as caregivers of children without GTs., Conclusion: Weaning off supplemental oxygen occurred later in children with GTs and Nissen/GTs compared to children without GTs. Although children with Nissen/GTs had more re-hospitalizations, there were no differences in reported respiratory symptoms between any of the groups by caregiver questionnaire., (© 2013 Wiley Periodicals, Inc.)

Objectives: Preterm infants and children with bronchopulmonary dysplasia (BPD) often experience significant respiratory morbidities during the first two years of life. Second hand smoke (SHS) has been demonstrated to lead to respiratory morbidities in the general population. The objectives of this study were to assess the prevalence/impact of SHS on preterm infants and children with BPD., Methods: Subjects (n = 352) were recruited from the Johns Hopkins BPD outpatient clinic between January 2008 and August 2012. Second hand smoke exposure and respiratory morbidities were assessed through questionnaires and chart review., Results: Twenty-eight percent of preterm infants with BPD were exposed to SHS in the home setting, despite having significant lung disease. SHS was associated with multiple measures of socio-economic status, including lower household income (P < 0.001), lower caregiver education level (P = 0.013), and having public versus private insurance (P = 0.002). We found no difference in acute care use or chronic symptoms with SHS exposure. We observed trends that preterm infants who were exposed to SHS were more likely to be prescribed inhaled corticosteroids (P = 0.054) and were weaned off of supplemental oxygen over 2 months later (P = 0.13) than infants not exposed to SHS., Conclusion: SHS exposure in preterm infants with BPD is common, even in those receiving supplemental oxygen and respiratory medications. Although there were no associations between respiratory outcomes and self-reported SHS exposure, trends toward increased use of inhaled steroids and a longer duration of supplemental oxygen use were noted. Further work is needed to determine more accurate means of assessing SHS risk in this vulnerable population., (© 2013 Wiley Periodicals, Inc.)

Objectives: Studies of multiple sclerosis (MS) incidence and prevalence from Africa, Asia, Australia and New Zealand are relatively scarce. We systematically reviewed MS incidence and prevalence in these regions including a standardized evaluation of study quality., Methods: We searched MEDLINE and EMBASE databases for studies of MS prevalence or incidence in Africa, Asia, Australia and New Zealand published in English or French between January 1, 1985 and January 31, 2011. Study quality was assessed using a standardized tool. All steps of the review were performed in duplicate., Results: Of 3925 citations identified, 28 studies met inclusion criteria and 21 of these were from Asia. Quality scores ranged from 1/8 to 8/8; the lowest scores were observed in studies from Asia (median 4/8, IQR 3,6). Prevalence was lowest in South African Blacks (0.22/100,000) and highest amongst Australian-born individuals in Australia (125/100,000). Prevalence increased over time in many countries. MS prevalence increased with increasing latitude only in some regions, and prevalence varied significantly with ethnicity. Eight studies reported incidence, which ranged from 0.67/100,000/year in Taiwan to 3.67/100,00/year in Australia., Conclusions: This comprehensive study provides an update of MS epidemiology in Africa, Asia, Australia, and New Zealand. Incidence and prevalence were lowest in Africa and Asia and highest in Australia, but many Asian studies were of poor quality. Use of consistent case ascertainment methods, standardized data collection tools, and similar outcomes would all improve study quality and comparability. The underlying basis of observed ethnic differences is an important area for future study., (© 2013 Elsevier B.V. All rights reserved.)

Background: Pulmonary disease contributes to significant morbidity and mortality in people with ataxia telangiectasia (A-T). To determine the association between age and lung function in children and young adults with A-T and to identify factors associated with decreased lung function, pulmonary function tests were performed in 100 consecutive people with A-T., Methods: Children and adults ranging from 6 to 29 years of age and with the diagnosis of A-T were recruited, and underwent pulmonary function tests., Results: The mean forced vital capacity % predicted (FVC %) in the population was 56.6 ± 20.0. Males and females between 6 and 10 years of age had similar pulmonary function. Older females were found to have significantly lower FVCs % than both older males (P < 0.02) and younger females (P < 0.001). The use of supplemental gamma globulin was associated with significantly lower FVC %. A modest correlation was found between higher radiation-induced chromosomal breakage and lower FVC % in males. No significant change in FVC % was found in a subset of subjects (n = 25) who underwent pulmonary function testing on two or more occasions over an average of 2 years., Conclusion: In children and young adults with A-T, older females and people who required supplemental gamma globulin had significantly lower lung function by cross-sectional analysis. Stable lung function is possible over a 2-year period. Recognition of groups who are at higher risk for lower pulmonary function may help direct care and improve clinical outcomes in people with A-T., (© 2013 Wiley Periodicals, Inc.)