David I. Kaufman

A Randomized, Controlled Trial of Corticosteroids in the Treatment of Acute Optic Neuritis

Background and Methods. The use of corticosteroids to treat optic neuritis is controversial. At 15 clinical centers, we randomly assigned 457 patients with acute optic neuritis to receive oral prednisone (1 mg per kilogram of body weight per day) for 14 days; intravenous methylprednisolone (1 g per day) for 3 days, followed by oral prednisone (1 mg per kilogram per day) for 11 days; or oral placebo for 14 days. Visual function was assessed over a six-month follow-up period. Results. Visual function recovered faster in the group receiving intravenous methylprednisolone than in the placebo group; this was particularly true for the reversal of visual-field defects (P = 0.0001). Although the differences between the groups decreased with time, at six months the group that received intravenous methylprednisolone still had slightly better visual fields (P = 0.054), contrast sensitivity (P = 0.026), and color vision (P = 0.033) but not better visual acuity (P = 0.66). The outcome in the oral-prednisone group did ...

The Effect of Corticosteroids for Acute Optic Neuritis on the Subsequent Development of Multiple Sclerosis

BACKGROUND Optic neuritis is often the first clinical manifestation of multiple sclerosis, but little is known about the effect of corticosteroid treatment for optic neuritis on the subsequent risk of multiple sclerosis. METHODS We conducted a multicenter study in which 389 patients with acute optic neuritis (and without known multiple sclerosis) were randomly assigned to receive intravenous methylprednisolone (250 mg every six hours) for 3 days followed by oral prednisone (1 mg per kilogram of body weight) for 11 days, oral prednisone (1 mg per kilogram) alone for 14 days, or placebo for 14 days. Neurologic status was assessed over a period of two to four years. The patients in the first group were hospitalized for three days; the others were treated as outpatients. RESULTS Definite multiple sclerosis developed within the first two years in 7.5 percent of the intravenous-methyl-prednisolone group (134 patients), 14.7 percent of the oral-prednisone group (129 patients), and 16.7 percent of the placebo group (126 patients). The adjusted rate ratio for the development of definite multiple sclerosis within two years in the intravenous-methylprednisolone group was 0.34 (95 percent confidence interval, 0.16 to 0.74) as compared with the placebo group and 0.38 (95 percent confidence interval, 0.17 to 0.83) as compared with the oral-prednisone group. The beneficial effect of the intravenous-steroid regimen appeared to lessen after the first two years of follow-up. Signal abnormalities on magnetic resonance imaging (MRI) of the brain were a strong indication of risk for the development of definite multiple sclerosis (adjusted rate ratio in patients with three or more lesions, 5.53; 95 percent confidence interval, 2.41 to 12.66). The beneficial effect of treatment was most apparent in patients with abnormal MRI scans at entry. CONCLUSIONS In patients with acute optic neuritis, treatment with a three-day course of high-dose intravenous methylprednisolone (followed by a short course of prednisone) reduces the rate of development of multiple sclerosis over a two-year period.

Multiple sclerosis risk after optic neuritis: Final optic neuritis treatment trial follow-up

OBJECTIVE To assess the risk of developing multiple sclerosis (MS) after optic neuritis and the factors predictive of high and low risk. DESIGN Subjects in the Optic Neuritis Treatment Trial, who were enrolled between July 1, 1988, and June 30, 1991, were followed up prospectively for 15 years, with the final examination in 2006. SETTING Neurologic and ophthalmologic examinations at 13 clinical sites. PARTICIPANTS Three hundred eighty-nine subjects with acute optic neuritis. MAIN OUTCOME MEASURES Development of MS and neurologic disability assessment. RESULTS The cumulative probability of developing MS by 15 years after onset of optic neuritis was 50% (95% confidence interval, 44%-56%) and strongly related to presence of lesions on a baseline non-contrast-enhanced magnetic resonance imaging (MRI) of the brain. Twenty-five percent of patients with no lesions on baseline brain MRI developed MS during follow-up compared with 72% of patients with 1 or more lesions. After 10 years, the risk of developing MS was very low for patients without baseline lesions but remained substantial for those with lesions. Among patients without lesions on MRI, baseline factors associated with a substantially lower risk for MS included male sex, optic disc swelling, and certain atypical features of optic neuritis. CONCLUSIONS The presence of brain MRI abnormalities at the time of an optic neuritis attack is a strong predictor of the 15-year risk of MS. In the absence of MRI-detected lesions, male sex, optic disc swelling, and atypical clinical features of optic neuritis are associated with a low likelihood of developing MS. This natural history information is important when considering prophylactic treatment for MS at the time of a first acute onset of optic neuritis.

CHANGING INCIDENCE OF CANDIDA BLOODSTREAM INFECTIONS AMONG NICU PATIENTS IN THE UNITED STATES: 1995-2004

OBJECTIVES. Recent reports suggest that candidemia caused by fluconazole-resistant strains is increasing in certain adult populations. We evaluated the annual incidence of neonatal candidemia and the frequency of disease caused by different species of Candida among neonates in the United States. PATIENTS. The study included neonates admitted to 128 NICUs participating in the National Nosocomial Infections Surveillance system from January 1, 1995, to December 31, 2004 (study period). METHODS. Reports of bloodstream infection (BSI) with Candida spp.; Candida BSIs, patient admissions, patient-days, and central venous catheter days were pooled by birth weight category. The number of Candida BSIs per 100 patients (attack rate) and per 1000 patient-days (incidence density) was determined. Both overall and species-specific rates were calculated; data were pooled over time to determine the differences by birth weight category and by year to determine trends over time. RESULTS. From the 130523 patients admitted to NICUs during the study period, there were 1997 Candida spp. BSIs reported. Overall, 1472 occurred in the <1000-g birth weight group. Candida albicans BSIs were most common, followed by Candida parapsilosis, Candida tropicalis, Candida lusitaniae, Candida glabrata, and only 3 Candida krusei. Among neonates <1000 g, incidence per 1000 patient-days decreased from 3.51 during 1995–1999 to 2.68 during 2000–2004 but remained stable among heavier neonates. No increase in infections by species that tend to demonstrate resistance to fluconazole (C glabrata or C krusei) was observed. CONCLUSIONS. Although Candida BSI is a serous problem among neonates <1000 g, incidence has declined over the past decade, and disease with species commonly resistant to azoles was extremely rare.

The fellow eye in NAION: Report from the Ischemic Optic neuropathy decompression Trial Follow-up study

PURPOSE To examine the prevalence and incidence of second eye nonarteritic anterior ischemic optic neuropathy (NAION) and associated patient characteristics in patients enrolled in the Ischemic Optic Neuropathy Decompression Trial (IONDT) Follow-up Study. DESIGN Randomized clinical trial with observational cohort. METHODS Patients randomized to optic nerve sheath decompression surgery or careful follow-up had a diagnosis of acute unilateral NAION, visual acuity between 20/64 and light perception, and were aged 50 years or older. Eligible patients who declined randomization or whose visual acuity was better than 20/64 were not randomized but followed as part of an observational cohort. Follow-up examinations took place at 3, 6, 12, 18, and 24 months and annually thereafter. RESULTS Four hundred eighteen patients were enrolled; 258 randomized and 160 observed. Previous NAION or other optic neuropathy was present in the fellow eye of 21.1% (88/418) of patients at baseline. Four patients developed optic neuropathy in the fellow eye at follow up that could not be conclusively diagnosed as NAION. New NAION in the fellow eye occurred in 14.7% (48/326) of patients at risk during a median follow up of 5.1 years. Randomized patients experienced a higher incidence (35/201; 17.4%) than nonrandomized patients (13/125; 10.4%). A history of diabetes and baseline visual acuity of 20/200 or worse in the study eye, but not age, sex, aspirin use, or smoking were significantly associated with new NAION in the fellow eye. Final fellow eye visual acuity was significantly worse in those patients with new fellow eye NAION whose baseline study eye visual acuity was 20/200 or worse. CONCLUSIONS Follow-up data from the IONDT cohort provide evidence that the incidence of fellow eye NAION is lower than expected: new NAION was diagnosed in 14.7% of IONDT patients over approximately 5 years. Increased incidence is associated with poor baseline visual acuity in the study eye and diabetes, but not age, sex, smoking history, or aspirin use.

Visual Distortion Provoked by a Stimulus in Migraine Associated With Hyperneuronal Activity

Background.—Migraineurs with visual aura are highly susceptible to illusions and visual distortion and are particularly sensitive to a pattern of regularly spaced parallel lines or stripes.

Practice parameter: The role of corticosteroids in the management of acute monosymptomatic optic neuritis Report of the Quality Standards Subcommittee of the American Academy of Neurology

Optic neuritis (ON) is an inflammatory disorder of the optic nerve. Most cases are idiopathic or associated with MS. ON can be associated with a variety of systemic or ocular disorders and is the most common acute optic neuropathy in adults younger than 46 years. Among high-risk populations for MS, the incidence of ON is about 3 per 100,000 population per year, whereas in other areas the incidence is about 1 per 100,000 population per year.1-13 Acute ON often presents as an isolated clinical event without contributory systemic abnormalities (monosymptomatic ON). Clinical features include periocular pain, abnormal visual acuity and fields, reduced color vision, a relative afferent pupillary defect, and abnormal visual evoked potentials. The fundus may appear normal or demonstrate edema of the optic nerve head (papillitis).12-18 MRI white matter abnormalities identical to those seen in MS are found in 50 to 70% of monosymptomatic ON cases.19-22 The visual deficit of ON may worsen over 1 to 2 weeks and usually begins improving over the next month. Lack of improvement in visual function by 30 days is unusual.23 However, most patients have some residual visual function deficit, even if visual acuity improves to 20/20.1-18 Differential diagnosis includes compressive, ischemic, hereditary, toxic, or other inflammatory optic neuropathies (e.g., sarcoid). These conditions usually do not exhibit the same clinical pattern (table 1) or rate of recovery as monosymptomatic ON.1-13 View this table: Table 1. Features of acute demyelinating monosymptomatic optic neuritis Treatment of monosymptomatic ON has included oral, retrobulbar, and IV steroids, immunoglobulin, and acupuncture.23-77 Monosymptomatic acute ON is not rare and because the usefulness of oral prednisone in this disorder has recently been questioned,23,78-82 this practice parameter was developed to provide …

The predictive value of CSF oligoclonal banding for MS 5 years after optic neuritis

The predictive value of CSF oligoclonal banding for the development of clinically definite MS (CDMS) within 5 years after optic neuritis was assessed in 76 patients enrolled in the Optic Neuritis Treatment Trial. The presence of oligoclonal bands was associated with the development of CDMS(p = 0.02). However, the results suggest that CSF analysis is only useful in the risk assessment of optic neuritis patients when brain MRI is normal and is not of predictive value when brain MRI lesions are present at the time of optic neuritis.

Breast cancer metastatic to the Eye is a common entity

Breast cancer metastatic to the eye is a common entity occurring in up to 30% of women with metastatic disease. The prevalence of this lesion is not appreciated because of the dominant clinical picture of metastases occurring in other organs. The diagnosis should be suspected in any women with a history of breast cancer and any visual symptoms, particularly metamorphopsia and scotomata. A thorough ophthalmologic evaluation, aided by ultrasonography, computed tomography, or magnetic resonance scanning, usually confirms the diagnosis. Early treatment with radiation therapy can alleviate symptoms and control local disease. The recognition and treatment of this disorder is important in maximizing the quality of life in patients with metastatic breast cancer, especially because newer treatment regimens prolong survival and thereby increase the chances for ocular metastasis.

Effect of the Glycine Antagonist Gavestinel on Cerebral Infarcts in Acute Stroke Patients, a Randomized Placebo-Controlled Trial: The GAIN MRI Substudy

Background and Purpose: Gavestinel, GV150526, is a selective antagonist at the glycine site of the N-methyl-D-aspartate receptor. The safety and efficacy of GV150526 were studied in two phase III randomized placebo-controlled clinical trials of acute ischemic stroke patients within 6 h from onset [The Glycine Antagonist in Neuroprotection (GAIN) International and GAIN Americas Trials]. A planned MRI substudy within these trials investigated the effect of gavestinel on infarct volume. Methods: Patients enrolled in the GAIN trials at designated MRI substudy sites were eligible if they had a pretreatment acute cortical lesion on diffusion-weighted MRI of at least 1.5 cm diameter or 5 cm3. Final lesion assessment was performed on T2-weighted MRI at month 3. Blinded image analysis was performed centrally. The primary hypothesis was that gavestinel would attenuate lesion growth from baseline relative to placebo. Results: A total of 106 patients were eligible, 75 (34 gavestinel, 41 placebo) of whom had month 3 scans (primary analysis population). No effects of gavestinel on infarct volume were observed in the primary or other analyses. However, significant associations of lesion volume to clinical severity and outcomes were observed. Ischemic lesion volume decrease was predictive of substantial clinical improvement. Conclusion: Consistent with the clinical outcomes in the GAIN trials, no effects of gavestinel on ischemic infarction was observed. Concordance of results of the clinical outcome trials with those of this infarct volume substudy as well the associations of infarct volume to clinical outcomes further support the potential role of infarct volume as a marker of outcome in dose finding and proof of principle acute stroke trials.