Searched for: person:balcel01
Optical coherence tomography and disease subtype in multiple sclerosis
Pulicken, M; Gordon-Lipkin, E; Balcer, L J; Frohman, E; Cutter, G; Calabresi, P A
OBJECTIVE: To examine retinal nerve fiber layer (RNFL) thickness, macular volumes (MV), and visual acuity in multiple sclerosis (MS) eyes, with and without history of acute optic neuritis (ON). METHODS: RNFL thickness was measured in 326 MS and 94 control eyes using optical coherence tomography (OCT). MV and vision testing were done in a subset of the cohort. MS subtype was classified as relapsing-remitting (RRMS, n = 135), primary progressive (PPMS, n = 12), and secondary progressive (SPMS, n = 16). RESULTS: MS ON eyes had decreased RNFL thickness (84.2 microm) compared to controls (102.7 microm) (p < 0.0001). Unaffected fellow eyes of MS ON eyes (93.9 microm) (p < 0.01) and patients with MS with no history of ON (95.9 microm) (p < 0.05) also had decreased RNFL. RRMS (94.4 microm) (p < 0.001), PPMS (88.9 microm) (p < 0.01), and SPMS (81.8 microm) (p < 0.0001) (adjusted for age and duration of disease) had decreased RNFL compared to controls. There were significant differences in RNFL thickness within quadrants of peripapillary retina comparing relapsing to progressive MS subtypes. MV was decreased in MS ON eyes (6.2 mm(3)) (p < 0.0001) and SPMS subjects (6.2 mm(3)) (p < 0.05) compared to controls (6.8 mm(3)). CONCLUSION: Retinal nerve fiber layer (RNFL) is significantly decreased in multiple sclerosis (MS) optic neuritis (ON) eyes, unaffected fellow eyes of patients with MS ON, and MS eyes not affected by ON in our cohort. Macular volumes (MV) showed a significant decrease in MS ON eyes. Progressive MS cases showed more marked decreases in RNFL and MV than relapsing-remitting MS. OCT is a promising tool to detect subclinical changes in RNFL and MV in patients with MS and should be examined in longitudinal studies as a potential biomarker of retinal pathology in MS.
PMID: 18040015
ISSN: 0028-3878
CID: 222492
Retinal nerve fiber layer is associated with brain atrophy in multiple sclerosis
Gordon-Lipkin, E; Chodkowski, B; Reich, D S; Smith, S A; Pulicken, M; Balcer, L J; Frohman, E M; Cutter, G; Calabresi, P A
OBJECTIVE: Optical coherence tomography (OCT) noninvasively quantifies retinal nerve fiber layer (RNFL) thickness. Studies show RNFL thinning in multiple sclerosis (MS), and we assessed its association with brain atrophy. METHODS: RNFL thickness was measured in 40 patients with MS and 15 controls. Brain parenchymal fraction (BPF) and partial brain volumes were estimated from cranial MRI scans using SIENA-X. Multiple linear regression modeling assessed the association between OCT and MRI measures of atrophy. RESULTS: Minimum RNFL thickness and subject age together predict 21% (p = 0.005) of the variance in BPF in all patients with MS and 43% (p = 0.003) of the variance in BPF in the subgroup with relapsing remitting MS (RRMS; n = 20). The partial correlation coefficient between BPF and minimum RNFL thickness, controlling for age, is 0.46 (p = 0.003) in all patients with MS and 0.69 (p = 0.001) in patients with RRMS. These associations are driven by CSF volume but not by gray or white matter volume. There is no significant association of these variables among controls. CONCLUSIONS: In multiple sclerosis (MS), retinal nerve fiber layer thickness is associated with brain parenchymal fraction and CSF volume. These data suggest that quantification of axonal thickness in the retina by optical coherence tomography (OCT) provides concurrent information about MRI brain abnormality in MS. OCT should be examined in longitudinal studies to determine if it could be used as an outcome measure in clinical trials of neuroprotective drugs.
PMID: 17938370
ISSN: 0028-3878
CID: 222502
Seizure-free outcome in randomized add-on trials of the new antiepileptic drugs
Gazzola, Deana M; Balcer, Laura J; French, Jacqueline A
PURPOSE: The goal of this study is to (1) provide clinically useful, previously unpublished comparative analyses of seizure-freedom rates for newer antiepileptic drugs (AEDs), and (2) recommend a standard for data presentation and analysis. METHODS: Data were reviewed from placebo-controlled adjunctive trials in refractory patients of gabapentin (GPN), lamotrigine (LTG), topiramate (TOP), tiagabine (TGB), oxcarbazepine (OXC), levetiracetam (LEV), zonisamide (ZNS), and pregabalin (PGB). Seizure-freedom analyses in these publications, if included at all, consistently included both patients who completed the trial, and those who dropped out prior to completion (last observation carried forward, LOCF). This has the potential to increase reported seizure-free outcomes. Pharmaceutical companies were contacted for the provision of unpublished seizure-free data in the patients who completed the entire study. RESULTS: In most cases, LOCF analysis produced a higher rate of seizure freedom compared to complete analysis. A total of 0%-1.1% of the LOCF population was seizure-free in the GPN trials (complete data not available). For the remaining AEDs, seizure-freedom results in the LOCF versus complete populations were: 0.7% versus 0.8% (LTG trial); 12% versus 2.6% (OXC trial); 3.6%-6.4% versus 3.9%-7.1% (LEV trial); 3.7%-7.9% versus 1.3%-1.4% (PGB trial); and 6.0% versus 3.0% (ZNS trial, minus titration period). CONCLUSIONS: By employing LOCF, a clinically unrealistic picture of seizure-free rates may be reported. Access to complete data is informative, as it includes only those patients who were able to tolerate the drug at doses that produced seizure freedom. Ideally, data from both ITT and complete analyses should be made available
PMID: 17521343
ISSN: 0013-9580
CID: 74773
Natalizumab reduces visual loss in patients with relapsing multiple sclerosis
Balcer, L J; Galetta, S L; Calabresi, P A; Confavreux, C; Giovannoni, G; Havrdova, E; Hutchinson, M; Kappos, L; Lublin, F D; Miller, D H; O'Connor, P W; Phillips, J T; Polman, C H; Radue, E-W; Rudick, R A; Stuart, W H; Wajgt, A; Weinstock-Guttman, B; Wynn, D R; Lynn, F; Panzara, M A
OBJECTIVE: To examine the effects of natalizumab on low-contrast letter acuity as a prespecified tertiary endpoint in two randomized clinical trials and to evaluate the usefulness of low-contrast letter acuity testing as a candidate test of visual function in multiple sclerosis (MS). METHODS: AFFIRM and SENTINEL were randomized, double-blind, placebo-controlled, multicenter, phase 3 clinical trials of natalizumab in relapsing MS. Natalizumab was evaluated as monotherapy in AFFIRM and as add-on to interferon beta-1a in SENTINEL. Vision testing was performed at 100% contrast (visual acuity) and low-contrast (2.5% and 1.25%). RESULTS: The risk of clinically significant visual loss (predefined as a two-line worsening of acuity sustained over 12 weeks) at the lowest contrast level (1.25%) was reduced in the natalizumab treatment arms by 35% in AFFIRM (hazard ratio = 0.65; 95% CI: 0.47 to 0.90; p = 0.008) and by 28% in SENTINEL (hazard ratio = 0.72; 95% CI: 0.54 to 0.98; p = 0.038, Cox proportional hazards models). Mean changes in vision scores from baseline were also significantly different, reflecting worsening in non-natalizumab groups. CONCLUSIONS: Natalizumab reduces visual loss in patients with relapsing multiple sclerosis. Low-contrast acuity testing has the capacity to demonstrate treatment effects and is a strong candidate for assessment of visual outcomes in future multiple sclerosis trials.
PMID: 17438220
ISSN: 0028-3878
CID: 174779
Profiles of obesity, weight gain, and quality of life in idiopathic intracranial hypertension (pseudotumor cerebri)
Daniels, Anthony B; Liu, Grant T; Volpe, Nicholas J; Galetta, Steven L; Moster, Mark L; Newman, Nancy J; Biousse, Valerie; Lee, Andrew G; Wall, Michael; Kardon, Randy; Acierno, Marie D; Corbett, James J; Maguire, Maureen G; Balcer, Laura J
PURPOSE: Obesity and weight gain are known risk factors for idiopathic intracranial hypertension (IIH; or pseudotumor cerebri). The authors examined profiles of body mass index (BMI) and patterns of weight gain associated with IIH. They also examined vision-specific health-related quality of life (HRQOL) in newly diagnosed IIH patients and explored the relative contribution of obesity and weight gain to overall HRQOL in this disorder. DESIGN: Matched case-control study. METHODS: Female patients with newly diagnosed IIH (n = 34) and other neuro-ophthalmologic disorders (n = 41) were enrolled in a case-control study to assess patterns of self-reported weight gain. The HRQOL was examined using the 25-Item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) and the SF-36 Health Survey (Physical Components Summary and Mental Components Summary [MCS]). RESULTS: Higher BMIs were associated with greater risk of IIH (P = .003, logistic regression analysis adjusting for case-control matching), as were higher percentages of weight gain during the year before symptom onset (P = .004). Moderate weight gain (5% to 15%) was associated with a greater risk of IIH among both obese and nonobese patients. Obesity and weight gain influenced the relation between HRQOL and IIH only for subscale scores reflecting mental health (SF-36 MCS). The NEI-VFQ-25 and SF-36 subscale scores were lower in IIH compared with other neuro-ophthalmologic disorders and published norms. CONCLUSIONS: Higher levels of weight gain and BMI are associated with greater risk of IIH. Even nonobese patients (BMI <30) are at greater risk for IIH in the setting of moderate weight gain. Vision-specific and overall HRQOL are affected to a greater extent in IIH than in other neuro-ophthalmologic disorders.
PMID: 17386271
ISSN: 0002-9394
CID: 174679
Multiple sclerosis and the ophthalmologist
Mowry, Ellen M; Balcer, Laura J; Galetta, Steven L
Multiple sclerosis is a common demyelinating disorder of the central nervous system, and neuro-ophthalmologic manifestations occur in the majority of patients. This article provides a review of the pathogenesis, epidemiology, and classification of multiple sclerosis. Neuro-ophthalmologic abnormalities associated with multiple sclerosis, including acute demyelinating optic neuritis and internuclear ophthalmoplegia, are described in detail. Current and emerging technologies designed to assess visual function in multiple sclerosis are discussed. A summary presents the appropriate evaluation and management of patients with optic neuritis and other first demyelinating events (also referred to as clinically isolated syndromes).
PMID: 17394758
ISSN: 1527-7313
CID: 174678
Fear sensitivity and the psychological profile of patients with psychogenic nonepileptic seizures
Hixson, John D; Balcer, Laura J; Glosser, Guila; French, Jacqueline A
Psychogenic nonepileptic seizures (PNES) remain a poorly understood phenomenon for both patients and their physicians. Recent work has begun to focus on the possible psychological underpinnings of this diagnosis, but few studies have focused on specific emotional pathologies. This study sought to investigate the impact of a specific emotional measure: self-reported fear sensitivity. Three patient groups (patients with PNES, patients with epilepsy, and healthy volunteers) were administered the Modified Fear Survey Schedule, along with other neuropsychological batteries. As expected, the PNES and epilepsy cohorts demonstrated elevated levels of depression, anxiety, and comorbid psychiatric conditions. The PNES group independently exhibited a statistically significant higher level of fear sensitivity compared with both patients with epilepsy and healthy volunteers. This fear-specific trait was independent of other comorbid psychological factors or psychiatric conditions. These results suggest that patients with PNES exhibit disproportionately elevated fear sensitivity on self-report measures when compared with patients with epilepsy. This finding may reflect an elevated internal 'setpoint' for appraising the intensity of emotional settings
PMID: 16997635
ISSN: 1525-5050
CID: 74762
Validation and test characteristics of a 10-item neuro-ophthalmic supplement to the NEI-VFQ-25
Raphael, Brian A; Galetta, Kristin M; Jacobs, Dina A; Markowitz, Clyde E; Liu, Grant T; Nano-Schiavi, M Ligia; Galetta, Steven L; Maguire, Maureen G; Mangione, Carol M; Globe, Denise R; Balcer, Laura J
PURPOSE: To determine whether a 10-Item Neuro-Ophthalmic Supplement increases the capacity of the 25-Item National Eye Institute Visual Function Questionnaire (NEI-VFQ-25) to capture self-reported visual dysfunction in patients with neuro-ophthalmologic disorders. DESIGN: A cross-sectional survey to examine the characteristics of a 10-Item Neuro-Ophthalmic Supplement to the 25-Item NEI-VFQ-25 in a cohort of patients with neuro-ophthalmologic disorders. METHODS: The 10-Item Neuro-Ophthalmic Supplement was designed previously by our research group by survey and focus-group methods. In the present study, the NEI-VFQ-25 and 10-Item Supplement were administered concurrently to patients and disease-free control subjects. High-contrast visual acuities with patient usual distance correction were measured with the use of Early Treatment Diabetic Retinopathy Study (ETDRS) charts. RESULTS: Diagnoses for patients (n = 215) included optic neuritis, multiple sclerosis, idiopathic intracranial hypertension, ischemic optic neuropathy, stroke, ocular myasthenia gravis, ocular motor palsies, and thyroid eye disease. Scores for the 10-Item Supplement had a significant capacity to distinguish patients vs disease-free control subjects that was independent of the NEI-VFQ-25 composite score (odds ratio in favor of patient vs control status for 10-point worsening in Supplement scores: 2.7 [95% confidence interval [CI], 1.6, 4.6]; P < .001, logistic regression models that account for NEI-VFQ-25 composite score, age, and gender). Patients with visual dysfunction (binocular Snellen equivalents worse than 20/20) had significantly lower mean scores (9-21 points lower); these differences remained significant after accounting for age and gender (P >or= .001, linear regression). Supplement items and composite scores demonstrated appropriate degrees of internal consistency reliability. CONCLUSION: The 10-Item Neuro-Ophthalmic Supplement demonstrates a capacity to capture self-reported visual dysfunction beyond that of the NEI-VFQ-25 alone, which supports validity for this new scale. The use of the 10-Item Supplement in clinical trials and epidemiologic studies will examine its capacity to demonstrate treatment effects in longitudinal cohorts.
PMID: 17046704
ISSN: 0002-9394
CID: 174681
Predictors of future publication record and academic rank in a cohort of neurology residents
Dorsey, E Ray; Raphael, Brian A; Balcer, Laura J; Galetta, Steven L
We identified characteristics associated with future publication record and academic rank in a cohort of neurology residents from a single institution. Seventy-six percent of women and 94% of men currently hold academic positions (p = 0.10). Early publications may lay the foundation for future academic investigation as publishing before (p = 0.01) and during (p < 0.001) residency was associated with higher post-residency publication rates. Publication differences between women and men (1.5 vs 2.4 publications/year; p = 0.03) warrant further investigation.
PMID: 17060557
ISSN: 0028-3878
CID: 174680
Optical coherence tomography in multiple sclerosis
Frohman, Elliot; Costello, Fiona; Zivadinov, Robert; Stuve, Olaf; Conger, Amy; Winslow, Heather; Trip, Anand; Frohman, Teresa; Balcer, Laura
We do not have currently satisfactory clinical and anatomical correlates to gauge disability in multiple sclerosis. Structural biomarkers (such as MRI) are hindered because they cannot precisely segregate demyelination from axonal elements of tissue injury within the CNS. Axonal degeneration in multiple sclerosis is related to irreversible disability, which suggests that the confirmation of neuroprotective strategies needs highly quantifiable measures of axon loss that can be correlated with reliable measures of physiological function. The coupling of quantifiable measures of visual function with ocular imaging techniques, such as optical coherence tomography, enables us to begin to understand how structural changes in the visual system influence function in patients with multiple sclerosis. In this review, we consider the usefulness of optical imaging of the retina as a biomarker for neurodegeneration in multiple-sclerosis.
PMID: 16987732
ISSN: 1474-4422
CID: 174682