Michael C. Brodsky

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 ...

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.

Magnetic resonance imaging in pseudotumor cerebri

OBJECTIVE To determine whether magnetic resonance (MR) imaging can be used to predict the presence of elevated intracranial pressure. DESIGN Retrospective case series. PARTICIPANTS Twenty patients with pseudotumor cerebri and 20 control subjects. INTERVENTION Magnetic resonance imaging. MAIN OUTCOME MEASURES The presence or absence of the following six neuroimaging signs was measured: (1) flattening of the posterior sclera; (2) enhancement of the prelaminar optic nerve; (3) distension of the perioptic subarachnoid space; (4) intraocular protrusion of the prelaminar optic nerve; (5) vertical tortuosity of the orbital optic nerve; and (6) empty sella. RESULTS The MR imaging disclosed flattening of the posterior sclera in 80% of patients with pseudotumor cerebri, empty sella in 70%, distension of the perioptic subarachnoid space in 45%, enhancement of the prelaminar optic nerve in 50%, vertical tortuosity of the orbital optic nerve in 40%, and intraocular protrusion of the prelaminar optic nerve in 30%. Each neuroimaging sign was detected in 5% of control subjects, except for enhancement of the prelaminar optic nerve, which was not detected in control subjects. Based on these MR imaging signs, the examiner was able to predict the presence of elevated intracranial pressure in 90% of cases with pseudotumor cerebri and the absence of elevated intracranial pressure in all control subjects. CONCLUSIONS Elevated intracranial pressure produces a constellation of MR imaging signs that can assist in establishing the diagnosis of pseudotumor cerebri.

Heterozygous mutations of the kinesin KIF21A in congenital fibrosis of the extraocular muscles type 1 (CFEOM1).

Congenital fibrosis of the extraocular muscles type 1 (CFEOM1; OMIM #135700) is an autosomal dominant strabismus disorder associated with defects of the oculomotor nerve. We show that individuals with CFEOM1 harbor heterozygous missense mutations in a kinesin motor protein encoded by KIF21A. We identified six different mutations in 44 of 45 probands. The primary mutational hotspots are in the stalk domain, highlighting an important new role for KIF21A and its stalk in the formation of the oculomotor axis.

Congenital optic disk anomalies.

Over the past decade, a wealth of information has accumulated pertaining to the diagnosis and management of patients with congenital optic disk anomalies. As new examples of each entity have been detailed, the diagnostic criteria for each anomaly have become more clearly defined. The advent of sophisticated noninvasive neuroimaging techniques has further refined our ability to accurately detect and categorize the associated CNS anomalies that complicate many of these conditions. In light of recent findings, this review will critically examine many of the well-entrenched concepts pertaining to the diagnosis, evaluation, and treatment of patients with congenital optic disk anomalies. In so doing, it will attempt to dispel some longstanding misconceptions that pervade the literature and obscure our understanding of the pathogenesis, neuroradiological associations, and systemic implications of each anomaly.

Cyclosporine Eyedrops for the Treatment of Severe Vernal Keratoconjunctivitis

Twelve children with severe chronic vernal keratoconjunctivitis participated in a pilot study aimed at evaluating the effect of 2% cyclosporine eyedrops on the clinical course and symptoms of this disease. Eleven of the 12 children showed improvement after the first week of treatment. Nine patients demonstrated persistent improvement at the completion of the treatment schedule after six weeks. However, although seven of the children were symptom-free while being treated, only three were free of disease two months after cessation of the cyclosporine eyedrops. The other nine showed rapid recurrence of their symptoms.

Mutations in FRMD7, a newly identified member of the FERM family, cause X-linked idiopathic congenital nystagmus

Idiopathic congenital nystagmus is characterized by involuntary, periodic, predominantly horizontal oscillations of both eyes. We identified 22 mutations in FRMD7 in 26 families with X-linked idiopathic congenital nystagmus. Screening of 42 singleton cases of idiopathic congenital nystagmus (28 male, 14 females) yielded three mutations (7%). We found restricted expression of FRMD7 in human embryonic brain and developing neural retina, suggesting a specific role in the control of eye movement and gaze stability.

Mutations in FRMD7, a newly identified member of the FERM family, cause X-linked idiopathic congenital nystagmus.

Idiopathic congenital nystagmus is characterized by involuntary, periodic, predominantly horizontal oscillations of both eyes. We identified 22 mutations in FRMD7 in 26 families with X-linked idiopathic congenital nystagmus. Screening of 42 singleton cases of idiopathic congenital nystagmus (28 male, 14 females) yielded three mutations (7%). We found restricted expression of FRMD7 in human embryonic brain and developing neural retina, suggesting a specific role in the control of eye movement and gaze stability.

Idiopathic intracranial hypertension in children and adolescents.

PURPOSE To investigate sex distribution, frequency of obesity, and other associated conditions among children and adolescents with idiopathic intracranial hypertension. METHODS We conducted a retrospective chart review of patients aged 18 years or younger diagnosed with idiopathic intracranial hypertension between 1988 and 1995 at two medical centers. Meta-analyses were performed using our data pooled with published information. RESULTS Of 374 patients, 175 (46.8%) were male and 199 (53.2%) were female. Obesity was noted in 50 (29.6%) of the 169 patients for whom relevant data are available, and other associated conditions were noted in 185 (53.2%) of the 348 patients. CONCLUSIONS Idiopathic intracranial hypertension among children and adolescents affects boys and girls equally; concurrent obesity occurs less frequently than in adults; and other associated conditions or secondary causes are common.

Congenital Optic Disc Anomalies

Ophthalmologists and neurologists are frequently called upon to evaluate infants and children with decreased vision resulting from congenital anomalies of the optic disc. A comprehensive evaluation necessitates an understanding of the ophthalmoscopic features, associated neuro-ophthalmologic findings, pathogenesis, and appropriate ancillary studies for each anomaly. Over the past decade, new ocular and systemic associations have emerged, and theories of pathogenesis for many optic disc anomalies have been revised. Our increasing ability to subclassify different forms of excavated optic disc anomalies that were previously lumped together as colobomatous defects has further refined our ability to predict the likelihood of associated central nervous system (CNS) anomalies based solely on the appearance of the optic disc. Added to this has been the widespread clinical application of magnetic resonance (MR) imaging, which has refined our ability to identify subtle associated CNS anomalies and to predict the likelihood of associated neurodevelopmental and endocrinological problems. Based largely upon information that has emerged over the past decade, this chapter will examine the optic disc anomalies, summarize our current understanding of their pathogenesis and treatment, and detail associated neuroimaging findings that predicate the general medical management of affected children.