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1.  Individual and Center-Level Factors Affecting Mortality Among Extremely Low Birth Weight Infants 
Pediatrics  2013;132(1):e175-e184.
OBJECTIVE:
To examine factors affecting center differences in mortality for extremely low birth weight (ELBW) infants.
METHODS:
We analyzed data for 5418 ELBW infants born at 16 Neonatal Research Network centers during 2006–2009. The primary outcomes of early mortality (≤12 hours after birth) and in-hospital mortality were assessed by using multilevel hierarchical models. Models were developed to investigate associations of center rates of selected interventions with mortality while adjusting for patient-level risk factors. These analyses were performed for all gestational ages (GAs) and separately for GAs <25 weeks and ≥25 weeks.
RESULTS:
Early and in-hospital mortality rates among centers were 5% to 36% and 11% to 53% for all GAs, 13% to 73% and 28% to 90% for GAs <25 weeks, and 1% to 11% and 7% to 26% for GAs ≥25 weeks, respectively. Center intervention rates significantly predicted both early and in-hospital mortality for infants <25 weeks. For infants ≥25 weeks, intervention rates did not predict mortality. The variance in mortality among centers was significant for all GAs and outcomes. Center use of interventions and patient risk factors explained some but not all of the center variation in mortality rates.
CONCLUSIONS:
Center intervention rates explain a portion of the center variation in mortality, especially for infants born at <25 weeks’ GA. This finding suggests that deaths may be prevented by standardizing care for very early GA infants. However, differences in patient characteristics and center intervention rates do not account for all of the observed variability in mortality; and for infants with GA ≥25 weeks these differences account for only a small part of the variation in mortality.
doi:10.1542/peds.2012-3707
PMCID: PMC3691533  PMID: 23753096
mortality rates; outcome; NICU; preterm infants; extremely preterm infants
2.  Ten-Year Review of Major Birth Defects in VLBW Infants 
Pediatrics  2013;132(1):49-61.
OBJECTIVE:
Birth defects (BDs) are an important cause of infant mortality and disproportionately occur among low birth weight infants. We determined the prevalence of BDs in a cohort of very low birth weight (VLBW) infants cared for at the Eunice Kennedy Shriver National Institute of Child Health and Human Development Neonatal Research Network (NRN) centers over a 10-year period and examined the relationship between anomalies, neonatal outcomes, and surgical care.
METHODS:
Infant and maternal data were collected prospectively for infants weighing 401 to 1500 g at NRN sites between January 1, 1998, and December 31, 2007. Poisson regression models were used to compare risk of outcomes for infants with versus without BDs while adjusting for gestational age and other characteristics.
RESULTS:
A BD was present in 1776 (4.8%) of the 37 262 infants in our VLBW cohort. Yearly prevalence of BDs increased from 4.0% of infants born in 1998 to 5.6% in 2007, P < .001. Mean gestational age overall was 28 weeks, and mean birth weight was 1007 g. Infants with BDs were more mature but more likely to be small for gestational age compared with infants without BDs. Chromosomal and cardiovascular anomalies were most frequent with each occurring in 20% of affected infants. Mortality was higher among infants with BDs (49% vs 18%; adjusted relative risk: 3.66 [95% confidence interval: 3.41–3.92]; P < .001) and varied by diagnosis. Among those surviving >3 days, more infants with BDs underwent major surgery (48% vs 13%, P < .001).
CONCLUSIONS:
Prevalence of BDs increased during the 10 years studied. BDs remain an important cause of neonatal morbidity and mortality among VLBW infants.
doi:10.1542/peds.2012-3111
PMCID: PMC3691532  PMID: 23733791
birth defects; prematurity; Neonatal Research Network; low birth weight
3.  Obstructive sleep apnea in idiopathic intracranial hypertension: comparison with matched population data 
Journal of neurology  2013;260(7):1748-1751.
Patients with idiopathic intracranial hypertension (IIH) frequently have coexisting obstructive sleep apnea (OSA). We aimed to determine if the prevalence and severity of OSA is greater in patients with IIH than would be expected given their other risk factors for OSA. We included 24 patients (20 women, 4 men) with newly-diagnosed IIH who had undergone overnight polysomnography. We calculated the expected apnea-hypopnea index (AHI) for each patient, based on their age, sex, race, body mass index (BMI), and menopausal status, using a model derived from 1741 randomly-sampled members of the general population who had undergone overnight polysomnography. We compared the AHI values obtained from polysomnography with those predicted by the model using a paired t-test. Our study had 80% power to detect a 10 unit change in mean AHI at α=0.05. Eight patients (33.3%; 6 women, 2 men) had OSA by polysomnography. AHIs from polysomnography were not significantly different from those predicted by the model (mean difference 3.5, 95% CI: −3.0–9.9, p=0.28). We conclude that the prevalence and severity of OSA in IIH patients is no greater than would be expected for their age, sex, race, BMI, and menopausal status. It remains unclear if the presence or treatment of OSA influences the clinical course of IIH.
doi:10.1007/s00415-013-6858-6
PMCID: PMC3707935  PMID: 23412355
Idiopathic intracranial hypertension; Papilledema; Obstructive sleep apnea; Intracranial pressure
4.  Diagnostic accuracy and use of non-mydriatic ocular fundus photography by emergency department physicians: Phase II of the FOTO-ED study 
Annals of emergency medicine  2013;62(1):28-33.e1.
Objective
During the first phase of the FOTO-ED Study, 13% (44/350;95%CI:9–17%) of patients had an ocular fundus finding, such as papilledema, relevant to their emergency department (ED) management found by non-mydriatic ocular fundus photography reviewed by neuro-opthalmologists. All of these findings were missed by ED physicians (EPs), who only examined 14% of enrolled patients by direct ophthalmoscopy. In the present study, we evaluated the sensitivity of non-mydriatic ocular fundus photography, an alternative to direct ophthalmoscopy, for relevant findings when photographs were made available for use by EPs during routine clinical care.
Methods
354 patients presenting to our ED with headache, focal neurologic deficit, visual change, or diastolic blood pressure ≥120 mmHg had non-mydriatic fundus photography obtained (Kowa nonmyd-alpha-D). Photographs were placed on the electronic medical record for EPs review. Identification of relevant findings on photographs by EPs was compared to a reference standard of neuro-ophthalmologist review.
Results
EPs reviewed photographs of 239 patients (68%). 35 patients (10%;95%CI:7–13%) had relevant findings identified by neuro-ophthalmologist review (6 disc edema, 6 grade III/IV hypertensive retinopathy, 7 isolated hemorrhages, 15 optic disc pallor, and 1 retinal vascular occlusion). EPs identified 16/35 relevant findings (sensitivity:46%;95%CI:29–63%), and also identified 289/319 normal findings (specificity:96%; 95%CI:87–94%). EPs reported that photographs were helpful for 125 patients (35%).
Conclusions
EPs used non-mydriatic fundus photographs more frequently than they perform direct ophthalmoscopy, and their detection of relevant abnormalities improved. Ocular fundus photography often assisted ED care even when normal. Non-mydriatic ocular fundus photography offers a promising alternative to direct ophthalmoscopy.
doi:10.1016/j.annemergmed.2013.01.010
PMCID: PMC3722897  PMID: 23433654
5.  Outcomes of Small for Gestational Age Infants < 27 Weeks’ Gestation 
The Journal of pediatrics  2013;163(1):55-60.e1-3.
Objective
To determine whether small for gestational age (SGA) infants <27 weeks gestation is associated with mortality, morbidity, growth and neurodevelopmental impairment at 18–22 months’ corrected age (CA).
Study design
This was a retrospective cohort study from National Institute of Child Health and Human Development Neonatal Research Network’s Generic Database and Follow-up Studies. Infants born at <27 weeks’ gestation from January 2006 to July 2008 were included. SGA was defined as birth weight <10th percentile for gestational age by the Olsen growth curves. Infants with birth weight ≥10th percentile for gestational age were classified as non-SGA. Maternal and infant characteristics, neonatal outcomes and neurodevelopmental data were compared between the groups. Neurodevelopmental impairment was defined as any of the following: cognitive score <70 on BSID III, moderate or severe cerebral palsy, bilateral hearing loss (+/− amplification) or blindness (vision <20/200). Logistic regression analysis evaluated the association between SGA status and death or neurodevelopmental impairment.
Results
There were 385 SGA and 2586 non-SGA infants. Compared with the non-SGA group, mothers of SGA infants were more likely to have higher level of education, prenatal care, cesarean delivery, pregnancy-induced hypertension and antenatal corticosteroid exposure. SGA infants were more likely to have postnatal growth failure, a higher mortality and to have received prolonged mechanical ventilation and postnatal steroids. SGA status was associated with higher odds of death or neurodevelopmental impairment [OR 3.91 (95% CI: 2.91–5.25), P<0.001].
Conclusion
SGA status among infants <27 weeks’ gestation was associated with an increased risk for postnatal steroid use, mortality, growth failure and neurodevelopmental impairment at 18–22 months’ CA.
doi:10.1016/j.jpeds.2012.12.097
PMCID: PMC3947828  PMID: 23415614
extremely preterm infants; neurodevelopmental follow-up
6.  Late-Onset Sepsis in Very Low Birth Weight Infants from Singleton and Multiple Gestation Births 
The Journal of pediatrics  2013;162(6):1120-1124.e1.
Objectives
To describe and compare incidence of late-onset sepsis (LOS) and demographic and clinical characteristics associated with LOS in very low birth weight (VLBW) infants from singleton and multiple births and to examine the heritability in susceptibility to LOS among VLBW twins by comparing same-sex with unlike-sex twin pairs.
Study design
We studied infants with birth weight 401–1500 grams cared for at clinical centers of the NICHD Neonatal Research Network 2002–2008. Only the first episode of LOS was examined. Stepwise logistic regression models were fitted separately for singleton and multiple pregnancies to examine the maternal and neonatal factors associated with LOS. LOS due to only gram-negative bacteria among singleton and multiple pregnancies was also examined in separate models. The heritability of LOS was estimated by examining concordance of LOS between twins from same-sex and unlike-sex pairs.
Results
LOS occurred in 25.0% (3797/15,178) of singleton and 22.6% (1196/5294) of multiple VLBW infants. Coagulase-negative staphylococci were the most common infecting organisms, accounting for 53.2% of all LOS episodes in singletons and 49.2% in multiples. E. coli and Klebsiella species were the most commonly isolated gram-negative organisms, and Candida albicans was the most commonly isolated fungus. Concordance of LOS was not significantly different between same-sex and unlike-sex twin pairs.
Conclusions
LOS remains a common problem in VLBW infants. The incidence of LOS is similar for singleton and multiple infants. Similar concordance of LOS in same-sex and unlike-sex twin pairs provided no evidence that susceptibility to LOS among VLBW infants is genetically determined.
doi:10.1016/j.jpeds.2012.11.089
PMCID: PMC3633723  PMID: 23324523
Heredity; preterm infants; twins
7.  Use of Antihypotensive Therapies in Extremely Preterm Infants 
Pediatrics  2013;131(6):e1865-e1873.
OBJECTIVE:
To investigate the relationships among blood pressure (BP) values, antihypotensive therapies, and in-hospital outcomes to identify a BP threshold below which antihypotensive therapies may be beneficial.
METHODS:
Prospective observational study of infants 230/7 to 266/7 weeks’ gestational age. Hourly BP values and antihypotensive therapy use in the first 24 hours were recorded. Low BP was investigated by using 15 definitions. Outcomes were examined by using regression analysis controlling for gestational age, the number of low BP values, and illness severity.
RESULTS:
Of 367 infants enrolled, 203 (55%) received at least 1 antihypotensive therapy. Treated infants were more likely to have low BP by any definition (P < .001), but for the 15 definitions of low BP investigated, therapy was not prescribed to 3% to 49% of infants with low BP and, paradoxically, was administered to 28% to 41% of infants without low BP. Treated infants were more likely than untreated infants to develop severe retinopathy of prematurity (15% vs 8%, P = .03) or severe intraventricular hemorrhage (22% vs 11%, P < .01) and less likely to survive (67% vs 78%, P = .02). However, with regression analysis, there were no significant differences between groups in survival or in-hospital morbidity rates.
CONCLUSIONS:
Factors other than BP contributed to the decision to use antihypotensive therapies. Infant outcomes were not improved with antihypotensive therapy for any of the 15 definitions of low BP investigated.
doi:10.1542/peds.2012-2779
PMCID: PMC3666108  PMID: 23650301
extremely preterm infant; antihypotensive therapy; blood pressure; hypotension
8.  Rod-cone dystrophy in spinocerebellar ataxia type 1 
Archives of ophthalmology  2011;129(7):956-958.
doi:10.1001/archophthalmol.2011.172
PMCID: PMC4012413  PMID: 21746990
Spinocerebellar Ataxia Type-1; Retinopathy; Electroretinography
9.  “Optic neuritis” that is neither 
Neurology: Clinical Practice  2013;3(2):168-170.
A 28-year-old African American woman developed periocular pain worsening with eye movement and decreased vision in her left eye. A diagnosis of left optic neuropathy was made based on the findings of decreased vision in the left eye, a left relative afferent pupillary defect, and mild optic disc hyperemia in the left eye (figure 1), with normal retinae and maculae bilaterally. Automated perimetry showed a small central scotoma in the left eye. The pain with eye movements suggested an inflammatory mechanism (i.e., optic neuritis). Her neurologic examination was normal. MRI of the brain showed 2 small T2 hyperintense lesions in the right inferior frontal lobe and left periatrial white matter. The lesions did not enhance. Angiotensin converting enzyme level was slightly elevated. A chest CT was negative for pulmonary sarcoidosis. She did not receive steroids, and her visual function improved spontaneously over a few weeks. She had no neurologic symptoms and the diagnosis of clinically isolated syndrome was made. The patient declined treatment with an immunomodulatory agent.
doi:10.1212/CPJ.0b013e31828d9f50
PMCID: PMC3721238  PMID: 23914325
10.  Non-mydriatic ocular fundus photography and telemedicine: past, present, and future 
Neuro-ophthalmology (Aeolus Press)  2013;37(2):10.3109/01658107.2013.773451.
Non-mydriatic ocular fundus photography is a promising alternative to direct ophthalmoscopy, particularly when combined with telemedicine. This review discusses these technologies from a longitudinal perspective: past, present, and future. The focus is directed to the role that non-mydriatic fundus photography and telemedicine have played in medical research and patient care, with emphasis on the major advances to date. Also discussed are the challenges to their widespread application and their substantial promise for revitalizing the importance of the ocular fundus examination in patient care, providing improved access to ophthalmic consultative services, and facilitating clinical and epidemiologic research.
doi:10.3109/01658107.2013.773451
PMCID: PMC3826661  PMID: 24244059
Fundus photography; telemedicine; review; ophthalmology; neurology
11.  Idiopathic Intracranial Hypertension: Relation Between Obesity and Visual Outcomes 
Background
Increased body mass index (BMI) has been associated with increased risk of idiopathic intracranial hypertension (IIH), but the relationship of BMI to visual outcomes in IIH is unclear.
Methods
A retrospective chart review of all adult cases of IIH satisfying the modified Dandy criteria seen at our institution between 1989 and 2010 was performed. Demographics, diagnostic evaluations, baseline visit and last follow-up examination data, treatment and visual outcome data were collected in a standardized fashion. Groups were compared and logistic regression was used to evaluate the relationship of BMI to severe visual loss, evaluating for interaction and controlling for potential confounders.
Results
Among 414 consecutive IIH patients, 158 had BMI≥40 (WHO Obese Class III), and 172 had BMI 30–39.9. Patients with BMI≥40 were more likely to have severe papilledema at first neuro-ophthalmology encounter than those with a lower BMI (p=0.02). There was a trend toward more severe visual loss in one or both eyes at last follow up among those patients with BMI≥40 (18 vs. 11%, p=0.067). Logistic regression modelling found that ten unit (kg/m2) increases in BMI increased the odds of severe visual loss by 1.4 times (95%CI: 1.03–1.91, p=0.03), after controlling for sex, race, diagnosed hypertension, and diagnosed sleep apnea.
Conclusion
Our finding of a trend for severe papilledema and visual loss associated with increasing BMI suggests that very obese IIH patients should be closely monitored for progression of visual field loss.
doi:10.1097/WNO.0b013e31823f852d
PMCID: PMC3323689  PMID: 22217456
Idiopathic Intracranial Hypertension; Body Mass Index; Obesity; Visual Outcomes; Severe Vision Loss; Risk Factors
12.  MRI findings of elevated intracranial pressure in cerebral venous thrombosis versus idiopathic intracranial hypertension with transverse sinus stenosis 
Purpose
To determine whether MRI signs suggesting elevated intracranial pressure (ICP) are preferentially found in patients with idiopathic intracranial hypertension (IIH) than in those with cerebral venous thrombosis (CVT).
Methods
Among 240 patients who underwent standardized contrast-enhanced brain MRI/MRV at our institution between 9/2009 and 9/2011, 60 with abnormal imaging findings on MRV were included: 27 patients with definite IIH, 2 patients with presumed IIH, and 31 with definite CVT. Medical records were reviewed, and imaging studies were prospectively evaluated by the same neuroradiologist to assess for presence or absence of transverse sinus stenosis (TSS), site of CVT if present, posterior globe flattening, optic nerve sheath dilation/tortuosity, and the size/appearance of the sella turcica.
Results
29 IIH patients (28 women, 19 black, median-age 28, median-body mass index, 34) had bilateral TSS. 31 CVT patients (19 women, 13 black, median-age 46, median-BMI 29) had thrombosis of the sagittal (3), sigmoid (3), cavernous (1), unilateral transverse (7), or multiple (16) sinuses or cortical veins (1). Empty/partially-empty sellae were more common in IIH (3/29 and 24/29) than in CVT patients (1/31 and 19/31) (p<0.001). Flattening of the globes and dilation/tortuosity of the optic nerve sheaths were more common in IIH (20/29 and 18/29) than in CVT patients (13/31 and 5/31) (p<0.04).
Conclusion
Although abnormal imaging findings suggestive of raised ICP are more common in IIH, they are not specific for IIH and are found in patients with raised ICP from other causes such as CVT.
doi:10.3109/01658107.2012.738759
PMCID: PMC3765015  PMID: 24019557
idiopathic intracranial hypertension; cerebral venous thrombosis; venous hypertension; MRI; MRV; empty sella
13.  Nonmydriatic ocular fundus photography among headache patients in an emergency department 
Neurology  2013;80(5):432-437.
Objectives:
Determine the frequency of and the predictive factors for abnormal ocular fundus findings among emergency department (ED) headache patients.
Methods:
Cross-sectional study of prospectively enrolled adult patients presenting to our ED with a chief complaint of headache. Ocular fundus photographs were obtained using a nonmydriatic fundus camera that does not require pupillary dilation. Demographic and neuroimaging information was collected. Photographs were reviewed independently by 2 neuroophthalmologists for findings relevant to acute care. The results were analyzed using univariate statistics and logistic regression modeling.
Results:
We included 497 patients (median age: 40 years, 73% women), among whom 42 (8.5%, 95% confidence interval: 6%–11%) had ocular fundus abnormalities. Of these 42 patients, 12 had disc edema, 9 had optic nerve pallor, 6 had grade III/IV hypertensive retinopathy, and 15 had isolated retinal hemorrhages. Body mass index ≥35 kg/m2 (odds ratio [OR]: 2.3, p = 0.02), younger age (OR: 0.7 per 10-year increase, p = 0.02), and higher mean arterial blood pressure (OR: 1.3 per 10-mm Hg increase, p = 0.003) were predictive of abnormal retinal photography. Patients with an abnormal fundus had a higher percentage of hospital admission (21% vs 10%, p = 0.04). Among the 34 patients with abnormal ocular fundi who had brain imaging, 14 (41%) had normal imaging.
Conclusions:
Ocular fundus abnormalities were found in 8.5% of patients with headache presenting to our ED. Predictors of abnormal funduscopic findings included higher body mass index, younger age, and higher blood pressure. Our study confirms the importance of funduscopic examination in patients with headache, particularly in the ED, and reaffirms the utility of nonmydriatic fundus photography in this setting.
doi:10.1212/WNL.0b013e31827f0f20
PMCID: PMC3590046  PMID: 23284060
14.  Clinical course of idiopathic intracranial hypertension with transverse sinus stenosis 
Neurology  2013;80(3):289-295.
Objective:
Transverse sinus stenosis (TSS) is common in idiopathic intracranial hypertension (IIH), but its effect on the course and outcome of IIH is unknown. We evaluated differences in TSS characteristics between patients with IIH with “good” vs “poor” clinical courses.
Methods:
All patients with IIH seen in our institution after September 2009 who underwent a high-quality standardized brain magnetic resonance venogram (MRV) were included. Patients were categorized as having a good or poor clinical course based on medical record review. The location and percent of each TSS were determined for each patient, and were correlated to the clinical outcome.
Results:
We included 51 patients. Forty-six patients had bilateral TSS. The median average percent stenosis was 56%. Seventy-one percent of patients had stenoses >50%. Thirty-five of the 51 patients (69%) had no final visual field loss. Eight patients (16%) had a clinical course classified as poor. There was no difference in the average percent stenosis between those with good clinical courses vs those with poor courses (62% vs 56%, p = 0.44). There was no difference in the percent stenosis based on the visual field grade (p = 0.38). CSF opening pressure was not associated with either location or degree of TSS.
Conclusion:
TSS is common, if not universal, among patients with IIH, and is almost always bilateral. There is no correlation between the degree of TSS and the clinical course, including visual field loss, among patients with IIH, suggesting that clinical features, not the degree of TSS, should be used to determine management in IIH.
doi:10.1212/WNL.0b013e31827debd6
PMCID: PMC3589184  PMID: 23269597
15.  Outcome of Extremely Low Birth Weight Infants with Congenital Heart Defects in the Eunice Kennedy Shriver NICHD Neonatal Research Network 
Pediatric cardiology  2012;33(8):1415-1426.
Little is known about the outcomes of extremely low birth weight (ELBW) preterm infants with congenital heart defects (CHDs). The aim of this study was to assess the mortality, morbidity, and early childhood outcomes of ELBW infants with isolated CHD compared with infants with no congenital defects. Participants were 401–1,000 g infants cared for at National Institute of Child Health and Human Development Neonatal Research Network centers between January 1, 1998 and December 31, 2005. Neonatal morbidities and 18–22 months’ corrected age outcomes were assessed. Neurodevelopmental impairment (NDI) was defined as moderate to severe cerebral palsy, Bayley II mental or psychomotor developmental index < 70, bilateral blindness, or hearing impairment requiring aids. Poisson regression models were used to estimate relative risks for outcomes while adjusting for gestational age, small for gestational-age status, and other variables. Of 14,457 ELBW infants, 110 (0.8 %) had isolated CHD, and 13,887 (96 %) had no major birth defect. The most common CHD were septal defects, tetralogy of Fallot, pulmonary valve stenosis, and coarctation of the aorta. Infants with CHD experienced increased mortality (48 % compared with 35 % for infants with no birth defect) and poorer growth. Surprisingly, the adjusted risks of other short-term neonatal morbidities associated with prematurity were not significantly different. Fifty-seven (52 %) infants with CHD survived to 18–22 months’ corrected age, and 49 (86 %) infants completed follow-up. A higher proportion of surviving infants with CHD were impaired compared with those without birth defects (57 vs. 38 %, p = 0.004). Risk of death or NDI was greater for ELBW infants with CHD, although 20% of infants survived without NDI.
doi:10.1007/s00246-012-0375-8
PMCID: PMC3687358  PMID: 22644414
heart defects; congenital; follow-up studies
16.  The use of retinal photography in non-ophthalmic settings and its potential for neurology 
The neurologist  2012;18(6):350-355.
Background
Ocular fundus examination is an important element of the neurological examination. However, direct ophthalmoscopy is difficult to perform without pupillary dilation and requires extensive practice to accurately recognize optic nerve and retinal abnormalities. Recent studies have suggested that digital retinal photography can replace direct ophthalmoscopy in many settings.
Review Summary
Ocular fundus imaging is routinely used to document and monitor disease progression in ophthalmology. Advances in optical technology have made it easier to obtain high-quality retinal imaging, even without pupillary dilation. Retinal photography has a high sensitivity, specificity, and inter-/intra-examination agreement compared to in-person ophthalmologist examination, suggesting that photographs can be used in lieu of ophthalmoscopy in many clinical situations. Non-mydriatic retinal photography has recently gained relevance as a helpful tool for diagnosing neuro-ophthalmologic disorders in the emergency department. Additionally, several population-based studies have used retinal imaging to relate ophthalmic abnormalities to the risk of hypertension, renal dysfunction, cardiovascular mortality, subclinical and clinical stroke, and cognitive impairment. The possibility of telemedical consultation offered by digital retinal photography has already increased access to timely and accurate subspecialty care, particularly for underserved areas.
Conclusion
Retinal photography (even without pupillary dilation) has become increasingly available to medical fields outside of ophthalmology, allowing for faster and more accurate diagnosis of various ocular, neurologic and systemic disorders. The potential for telemedicine may provide the additional benefits of improving access to appropriate urgent consultation in both clinical and research settings.
doi:10.1097/NRL.0b013e318272f7d7
PMCID: PMC3521530  PMID: 23114666
direct ophthalmoscopy; retinal photography; fundus camera; telemedicine
17.  Exacerbation of Susac Syndrome Retinopathy by Interferon Beta-1a 
Archives of ophthalmology  2012;130(6):10.1001/archophthalmol.2011.1841.
doi:10.1001/archophthalmol.2011.1841
PMCID: PMC3809003  PMID: 22801853
18.  Choroidal Infarction in Fulminant Idiopathic Intracranial Hypertension 
doi:10.1097/WNO.0b013e3181c25581
PMCID: PMC3721341  PMID: 20404747
Choroid; Infarction; Papilledema; Intracranial Hypertension
19.  Treatment of Nonarteritic Anterior Ischemic Optic Neuropathy 
Survey of ophthalmology  2010;55(1):47-63.
Nonarteritic anterior ischemic optic neuropathy (NAION) is the most common clinical presentation of acute ischemic damage to the optic nerve. Most treatments proposed for NAION are empirical and include a wide range of agents presumed to act on thrombosis, on the blood vessels, or on the disc edema itself. Others are presumed to have a neuroprotective effect. Although there have been multiple therapies attempted, most have not been adequately studied, and animal models of NAION have only recently emerged. The Ischemic Optic Neuropathy Decompression Trial (IONDT), the only class I large multicenter prospective treatment trial for NAION, found no benefit from surgical intervention. One recent large, nonrandomized controlled study suggested that oral steroids might be helpful for acute NAION. Others recently proposed interventions are intravitreal injections of steroids or anti-vascular endothelial growth factor (anti-VEGF) agents. There are no class I studies showing benefit from either medical or surgical treatments. Most of the literature on the treatment of NAION consists of retrospective or prospective case series and anecdotal case reports. Similarly, therapies aimed at secondary prevention of fellow eye involvement in NAION remain of unproven benefit.
doi:10.1016/j.survophthal.2009.06.008
PMCID: PMC3721361  PMID: 20006051
nonarteritic anterior ischemic optic neuropathy; treatment; pathogenesis; Ischemic Optic Neuropathy Decompression Trial (IONDT)
20.  Feasibility Study of Early Blood Pressure Management in Extremely Preterm Infants 
The Journal of Pediatrics  2012;161(1):65-69.e1.
Objective
To assess the feasibility of a randomized placebo controlled trial (RCT) of blood pressure (BP) management for extremely preterm infants.
Study design
This was a prospective pilot RCT of infants 230/7 – 266/7 weeks gestation who had protocol-defined low BP in the first 24 postnatal hours. Enrolled infants were administered a study infusion (dopamine or placebo) and a study syringe medication (hydrocortisone or placebo).
Results
Of the 366 infants screened, 119 (33%) had low BP, 58 (16%) met all entry criteria, and 10 (3%) were enrolled. 161 (44%) infants were ineligible because they received early indomethacin. Only 17% of eligible infants were enrolled. Problems with consent included insufficient time, parent unavailability, and physician unwillingness to enroll critically ill infants. Two infants were withdrawn from the study due to the potential risk of intestinal perforation with simultaneous administration of hydrocortisone and indomethacin.
Conclusions
This pilot RCT was not feasible due to low eligibility and consent rates. An RCT of BP management for extremely preterm infants may require a waiver of consent for research in emergency care. The frequent use of early indomethacin and the associated risk of intestinal perforation when used with hydrocortisone may limit future investigations to only inotropic medications.
doi:10.1016/j.jpeds.2012.01.014
PMCID: PMC3357442  PMID: 22336574
Extremely preterm infant; hypotension; hydrocortisone; dopamine; informed consent
22.  Outcomes of Extremely Low Birth Weight Infants with Bronchopulmonary Dysplasia: Impact of the Physiologic Definition 
Early human development  2012;88(7):509-515.
Aims
We compared neurodevelopmental outcomes of extremely low birth weight (ELBW) infants with and without bronchopulmonary dysplasia (BPD), using the physiologic definition.
Study Design
ELBW (birth weights <1000 grams) infants admitted to the Neonatal Research Network centers and hospitalized at 36 weeks postmenstrual age (n=1,189) were classified using the physiologic definition of BPD. Infants underwent Bayley III assessment at 18-22 months corrected age. Multivariable logistic regression was used to determine the association between physiologic BPD and cognitive impairment (score < 70).
Results
BPD by the physiologic definition was diagnosed in 603 (52%) infants, 537 of whom were mechanically ventilated or on FiO2 > 30% and 66 who failed the room air challenge. Infants on room air (n=505) and those who passed the room air challenge (n=51) were classified as “no BPD” (n=556). At follow up, infants with BPD had significantly lower mean weight and head circumference. Moderate to severe cerebral palsy (7 vs. 2.1%) and spastic diplegia (7.8 vs. 4.1%) and quadriplegia (3.9 vs. 0.9%) phenotypes as well as cognitive (12.8 vs. 4.6%) and language scores < 70 (24.2 vs. 12.3%) were significantly more frequent in those with BPD compared to those without BPD. BPD was independently associated (adjusted OR 2.4; 95% CI 1.40-4.13) with cognitive impairment.
Conclusions
Rates of adverse neurodevelopmental outcomes in early childhood were significantly higher in those with BPD. BPD by the physiologic definition was independently associated with cognitive impairment using Bayley Scales III. These findings have implications for targeted post-discharge surveillance and early intervention.
doi:10.1016/j.earlhumdev.2011.12.013
PMCID: PMC3686277  PMID: 22236557
Outcome; preterm; bronchopulmonary dysplasia; physiologic definition
23.  Underdiagnosis of posterior communicating artery aneurysm in non-invasive brain vascular studies 
Introduction
Expert interpretation of modern noninvasive neuroimaging such as CTA or MRA should detect nearly all aneurysms responsible for an isolated third nerve palsy. Whether a catheter angiogram should still be obtained in cases with negative CTA or MRA remains debated, and mostly relies on whether the noninvasive study was correctly performed and interpreted. The aim of our study was to review the diagnostic strategies used to evaluate patients with isolated aneurysmal third nerve palsy at a large academic center.
Methods
Retrospective review of all cases with posterior communicating artery (PCom A) aneurysmal third nerve palsies seen at our institution since 2001.
Results
We identified 417 cases with third nerve palsy, aneurysm, or subarachnoid hemorrhage, among which 17 presented with an acute isolated painful third nerve palsy related to an ipsilateral PCom A aneurysm (mean age 52; range 33–83 years). Patients were classified into 3 groups based on the results of the noninvasive imaging obtained at initial presentation. Group I included 4 cases with subarachnoid hemorrhage on initial non-contrast head CT initially obtained in an emergency department for evaluation of their isolated third nerve palsy. Group II included 5 cases with isolated third nerve palsy and normal non-contrast head CT at presentation, immediately correctly diagnosed with a PCom A aneurysm at the referring institution. Group III included the 8 remaining cases who all had aneurysms that were missed on noninvasive studies at outside institutions. Review of these outside studies at our institution showed a PCom A aneurysm, confirming misinterpretation of these tests by the outside radiologists, rather than inadequate technique. Absence of specific training in neuroradiology and inaccurate clinical information provided to the interpreting radiologist were associated with test misinterpretation at the outside institutions. The average size of PCom A aneurysms causing an isolated third nerve palsy across all 3 groups was 7.3 mm, and was similar in each group.
Conclusion
Our study suggests that aside from an accurate history, the training and experience of the interpreting radiologist is probably the most important factor in determining the reliability of a noninvasive scan in patients with isolated third nerve palsies.
doi:10.1097/WNO.0b013e3181f8d985
PMCID: PMC3682504  PMID: 21150642
24.  An Update on Idiopathic Intracranial Hypertension 
Reviews in neurological diseases  2010;7(0):e56-e68.
Idiopathic intracranial hypertension (IIH) is a condition of unknown etiology often encountered in neurologic practice. It produces non-localizing symptoms and signs of raised intracranial pressure and, when left untreated, can result in severe irreversible visual loss. It most commonly occurs in obese women of childbearing age, but it can also occur in children, men, non-obese adults, and older adults. While it is frequently associated with obesity, it can be associated with other conditions, such as obstructive sleep apnea and transverse cerebral venous sinus stenoses. Recent identification of subgroups at high risk for irreversible visual loss, including black patients, men, and patients with fulminant forms of IIH, help guide the optimal management and follow-up. Ongoing studies of venous anatomy and physiology in IIH patients, as well as a recently begun randomized clinical treatment trial, should provide more insights into this common yet poorly understood syndrome of isolated intracranial hypertension.
PMCID: PMC3674489  PMID: 20944524
Idiopathic Intracranial Hypertension; Venous Sinus Stenosis; Ventriculoperitoneal Shunting; Lumboperitoneal Shunting; Optic Nerve Sheath Fenestration; Venous Sinus Stenting
25.  Deafness and blindness as a presentation of colorectal meningeal carcinomatosis 
We present a unique case of a patient with deafness and blindness secondary to carcinomatous meningitis from colorectal adenocarcinoma with accompanying radiologic and pathologic images and a brief review of the relevant literature.
PMCID: PMC3674494  PMID: 20966893
meningeal carcinomatosis; severe visual loss; severe hearing loss

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