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Natalizumab reduces multiple sclerosis severity: Analysis of patients from the AFFIRM and SENTINEL studies using the multiple sclerosis severity scale [Meeting Abstract]

Herbert, J; Kappos, L; Calabresi, P; Confavreux, C; Galetta, S; Giovannoni, G; Havrdova, E; Hutchinson, M; Lublin, F; Miller, D; O'Connor, PW; Phillips, J; Polman, C; Radue, EW; Rudick, R; Stuart, W; Wajgt, A; Weinstock-Guttman, B; Wynn, D; Bacon, J; Kister, I; Pace, A; Panzara, M
ISI:000257197201204
ISSN: 0028-3878
CID: 111998

Neuro-ophthalmologic manifestations of paraneoplastic syndromes

Ko, Melissa W; Dalmau, Josep; Galetta, Steven L
Paraneoplastic syndromes with neuro-ophthalmologic manifestations may involve the central nervous system, cranial nerves, neuromuscular junction, optic nerve, uvea, or retina. Most of these disorders are related to immunologic mechanisms presumably triggered by the neoplastic expression of neuronal proteins. Accurate recognition is essential to appropriate management.
PMID: 18347462
ISSN: 1070-8022
CID: 174733

Is neuromyelitis optica eyeing a distinct path from multiple sclerosis? [Comment]

Glisson, Christopher C; Galetta, Steven L
PMID: 18195231
ISSN: 0003-9950
CID: 174734

Clinical reasoning: a 59-year-old woman with acute paraplegia [Case Report]

Prasad, S; Price, R S; Kranick, S M; Woo, J H; Hurst, R W; Galetta, S
PMID: 18071136
ISSN: 0028-3878
CID: 684062

Relation of vision to global and regional brain MRI in multiple sclerosis

Wu, G F; Schwartz, E D; Lei, T; Souza, A; Mishra, S; Jacobs, D A; Markowitz, C E; Galetta, S L; Nano-Schiavi, M L; Desiderio, L M; Cutter, G R; Calabresi, P A; Udupa, J K; Balcer, L J
OBJECTIVE: To examine the relation between low-contrast letter acuity, an emerging visual outcome for multiple sclerosis (MS) clinical trials, and brain MRI abnormalities in an MS cohort. METHODS: T2 lesion volume and brain parenchymal fraction were determined for whole brain and within visual pathway regions of interest. Magnetization transfer ratio histograms were examined. Vision testing was performed binocularly using low-contrast letter acuity (2.5%, 1.25% contrast) and high-contrast visual acuity (VA). Linear regression, accounting for age and disease duration, was used to assess the relation between vision and MRI measures. RESULTS: Patients (n = 45) were aged 44 +/- 11 years, with disease duration of 5 years (range <1 to 21), Expanded Disability Status Scale score of 2.0 (0 to 6.0), and binocular Snellen acuity of 20/16 (20/12.5 to 20/25). The average T2 lesion volume was 18.5 mm(3). Patients with lower (worse) low-contrast letter acuity and high-contrast VA scores had greater T2 lesion volumes in whole brain (2.5% contrast: p = 0.004; 1.25%: p = 0.002; VA: p = 0.04), Area 17 white matter (2.5%: p < 0.001; 1.25%: p = 0.02; VA: p = 0.01), and optic radiations (2.5%: p = 0.001; 1.25%: p = 0.02; VA: p = 0.007). Within whole brain, a 3-mm(3) increase in lesion volume corresponded, on average, to a 1-line worsening of low-contrast acuity, whereas 1-line worsening of high-contrast acuity corresponded to a 5.5-mm(3) increase. CONCLUSIONS: Low-contrast letter acuity scores correlate well with brain MRI lesion burden in multiple sclerosis (MS), supporting validity for this vision test as a candidate for clinical trials. Disease in the postgeniculate white matter is a likely contributor to visual dysfunction in MS that may be independent of acute optic neuritis history.
PMID: 17881718
ISSN: 0028-3878
CID: 174776

The incidence and significance of anti-natalizumab antibodies: results from AFFIRM and SENTINEL

Calabresi, P A; Giovannoni, G; Confavreux, C; Galetta, S L; Havrdova, E; Hutchinson, M; Kappos, L; Miller, D H; O'Connor, P W; Phillips, J T; Polman, C H; Radue, E-W; Rudick, R A; Stuart, W H; Lublin, F D; Wajgt, A; Weinstock-Guttman, B; Wynn, D R; Lynn, F; Panzara, M A
OBJECTIVE: To determine the incidence and clinical effects of antibodies that develop during treatment with natalizumab. METHODS: In two randomized, double-blind, placebo-controlled studies (natalizumab safety and efficacy in relapsing remitting multiple sclerosis [MS, AFFIRM] and safety and efficacy of natalizumab in combination with interferon beta-1a [INF beta]1a] in patients with relapsing remitting MS [SENTINEL]) of patients with relapsing multiple sclerosis, blood samples were obtained at baseline and every 12 weeks to determine the presence of antibodies against natalizumab. Antibodies to natalizumab were measured using an ELISA. Patients were categorized as "transiently positive" if they had detectable antibodies (>or=0.5 microg/mL) at a single time point or "persistently positive" if they had antibodies at two or more time points >or=6 weeks apart. RESULTS: In the AFFIRM study, antibodies were detected in 57 of 625 (9%) of natalizumab-treated patients: Twenty (3%) were transiently positive and 37 (6%) were persistently positive. Persistently positive patients showed a loss of clinical efficacy as measured by disability progression (p
PMID: 17761550
ISSN: 0028-3878
CID: 174777

Health-related quality of life in multiple sclerosis: effects of natalizumab

Rudick, Richard A; Miller, Deborah; Hass, Steve; Hutchinson, Michael; Calabresi, Peter A; Confavreux, Christian; Galetta, Steven L; Giovannoni, Gavin; Havrdova, Eva; Kappos, Ludwig; Lublin, Fred D; Miller, David H; O'Connor, Paul W; Phillips, J Theodore; Polman, Chris H; Radue, Ernst-Wilhelm; Stuart, William H; Wajgt, Andrzej; Weinstock-Guttman, Bianca; Wynn, Daniel R; Lynn, Frances; Panzara, Michael A
OBJECTIVE: To report the relationship between disease activity and health-related quality of life (HRQoL) in relapsing multiple sclerosis, and the impact of natalizumab. METHODS: HRQoL data were available from 2,113 multiple sclerosis patients in natalizumab clinical studies. In the Natalizumab Safety and Efficacy in Relapsing Remitting Multiple Sclerosis (AFFIRM) study, patients received natalizumab 300 mg (n = 627) or placebo (n = 315); in the Safety and Efficacy of Natalizumab in Combination with Interferon Beta-1a in Patients with Relapsing Remitting Multiple Sclerosis (SENTINEL) study, patients received interferon beta-1a (IFN-beta-1a) plus natalizumab 300 mg (n = 589), or IFN-beta-1a plus placebo (n = 582). The Short Form-36 (SF-36) and a subject global assessment visual analog scale were administered at baseline and weeks 24, 52, and 104. Prespecified analyses included changes from baseline to week 104 in SF-36 and visual analog scale scores. Odds ratios for clinically meaningful improvement or worsening on the SF-36 Physical Component Summary (PCS) and Mental Component Summary were calculated. RESULTS: Mean baseline SF-36 scores were significantly less than the general US population and correlated with Expanded Disability Status Scale scores, sustained disability progression, relapse number, and increased volume of brain magnetic resonance imaging lesions. Natalizumab significantly improved SF-36 PCS and Mental Component Summary scores at week 104 in AFFIRM. PCS changes were significantly improved by week 24 and at all subsequent time points. Natalizumab-treated patients in both studies were more likely to experience clinically important improvement and less likely to experience clinically important deterioration on the SF-36 PCS. The visual analog scale also showed significantly improved HRQoL with natalizumab. INTERPRETATION: HRQoL was impaired in relapsing multiple sclerosis patients, correlated with severity of disease as measured by neurological ratings or magnetic resonance imaging, and improved significantly with natalizumab.
PMID: 17696126
ISSN: 0364-5134
CID: 174735

Papilledema as a manifestation of a spinal subdural abscess [Case Report]

Ko, Melissa W; Osborne, Benjamin; Jung, Sungmi; Jacobs, Dina A; Marcotte, Paul; Galetta, Steven L
Papilledema is an uncommon presentation of spinal cord processes. Spinal subdural abscess (SSA) is a rare site of post-operative infection. We report a patient who developed papilledema as the primary manifestation of a post-operative lumbar subdural abscess. A spinal abscess should be considered in the post-operative spinal surgery patient who develops papilledema in the setting of persistent back pain. The increased intracranial pressure associated with lumbar spinal cord abscess most likely results from a markedly elevated cerebrospinal fluid (CSF) protein or the disruption of CSF flow in the spinal cul-de-sac.
PMID: 17570401
ISSN: 0022-510x
CID: 174736

Neuromyelitis optica is a variant of multiple sclerosis [Historical Article]

Galetta, Steven L; Bennett, Jeffrey
PMID: 17562943
ISSN: 0003-9942
CID: 174737

Visual rehabilitation: now you see it; now you don't [Comment]

Glisson, Christopher C; Galetta, Steven L
PMID: 17536043
ISSN: 0028-3878
CID: 174738