Eric Eggenberger

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.

Tracking retinal nerve fiber layer loss after optic neuritis: a prospective study using optical coherence tomography.

Introduction Optic neuritis causes retinal nerve fiber layer damage, which can be quantified with optical coherence tomography. Optical coherence tomography may be used to track nerve fiber layer changes and to establish a time-dependent relationship between retinal nerve fiber layer thickness and visual function after optic neuritis. Methods This prospective case series included 78 patients with optic neuritis, who underwent optical coherence tomography and visual testing over a mean period of 28 months. The main outcome measures included comparing inter-eye differences in retinal nerve fiber layer thickness between clinically affected and non-affected eyes over time; establishing when RNFL thinning stabilized after optic neuritis; and correlating retinal nerve fiber layer thickness and visual function. Results The earliest significant inter-eye differences manifested 2-months after optic neuritis, in the temporal retinal nerve fiber layer. Inter-eye comparisons revealed significant retinal nerve fiber layer thinning in clinically affected eyes, which persisted for greater than 24 months. Retinal nerve fiber thinning manifested within 6 months and then stabilized from 7 to 12 months after optic neuritis. Regression analyses demonstrated a threshold of nerve fiber layer thickness (75μm), which predicted visual recovery after optic neuritis. Conclusions Retinal nerve fiber layer changes may be tracked and correlated with visual function within 12 months of an optic neuritis event.

An ice test for the diagnosis of myasthenia gravis

OBJECTIVE To determine whether ice application to a ptotic eyelid can differentiate myasthenic from nonmyasthenic ptosis. DESIGN Prospective, multicenter, nonrandomized, comparative trial. PARTICIPANTS Twenty patients with myasthenia gravis (MG) and ptosis were evaluated in the neuro-ophthalmology service. CONTROL SUBJECTS: Twenty patients with nonmyasthenic ptosis evaluated in the same locale. METHODS Palpebral fissures were measured before and immediately after a 2-minute application of ice to the ptotic eyelid. MAIN OUTCOME MEASURES The difference in palpebral fissures in millimeters before and after ice application. Two or more millimeters of improvement after ice application was considered a positive ice test result. RESULTS A positive ice test result was noted in 16 of the 20 (80%) patients with MG and in none of the 20 patients without MG (P < 0.001). Of the 4 patients with MG and complete ptosis, 3 had a negative ice test result. CONCLUSIONS The ice test is a simple, short, specific, and relatively sensitive test for the diagnosis of myasthenic ptosis. The sensitivity of the ice test in patients with complete ptosis decreases considerably.

Sleep apnea and intracranial hypertension in men

PURPOSE To investigate sleep apnea as an associated finding in idiopathic intracranial hypertension (IIH) in men. DESIGN Multicenter, retrospective, noncomparative interventional case series. METHODS Retrospective review of all men with the diagnosis of IIH seen within the last 5 years at three tertiary care academic ophthalmologic institutions. Cases with sleep apnea (SA) and IIH were identified and reviewed. RESULTS Thirty-two cases of IIH in men were reviewed. Six cases with SA met the modified Dandy criteria for the diagnosis of IIH. Of these six patients, one received acetazolamide alone, four received acetazolamide and continuous positive airway pressure (CPAP), and one was treated with CPAP alone. All patients had preserved central acuity (20/20 or better in both eyes), enlarged blind spots, and optic disc edema in both eyes. Five patients had normal visual fields after treatment, and one patient had residual visual field loss. Three patients had normal optic nerve examinations, with resolution of the optic disc edema at last follow-up. After resolution of the optic disc edema, these three patients were maintained on CPAP but discontinued acetazolamide. Two patients had persistent but improved papilledema and are under continued treatment with acetazolamide and CPAP. One patient had optic disc pallor in both eyes and is stable. CONCLUSIONS SA was a common finding in men meeting the modified Dandy criteria for IIH in adults. Treatment of sleep apnea with nocturnal oxygenation may improve the signs and symptoms of IIH in affected men.

Minocycline treatment and pseudotumor Cerebri syndrome

PURPOSE To demonstrate the association between minocycline treatment and development of the pseudotumor cerebri syndrome. METHODS A retrospective study was conducted of 12 patients from five neuro-ophthalmic referral centers who developed pseudotumor cerebri syndrome after being treated with standard doses of minocycline for refractory acne vulgaris. The main outcome measures included resolution of headaches, transient visual obscurations, diplopia, papilledema, and visual fields static thresholds after withdrawal of minocycline and treatment for increased intracranial pressure. RESULTS Nine (75%) of the 12 patients developed symptoms of the pseudotumor cerebri syndrome syndrome within 8 weeks of starting minocycline therapy; six were not obese. Two patients developed symptoms only after a year had elapsed because of commencement of treatment with minocycline. One patient was asymptomatic, and pseudotumor cerebri syndrome was diagnosed by finding papilledema on routine examination 1 year after minocycline was started. None of the patients developed recurrences for at least 1 year after the discontinuation of minocycline and treatment for increased intracranial pressure, but three (25%) of the 12 patients had substantial residual visual field loss. CONCLUSION Minocycline is a cause or precipitating factor in pseudotumor cerebri syndrome. Although most patients have prominent symptoms and are diagnosed promptly, others are asymptomatic and may have optic disk edema for a long period of time before diagnosis. Withdrawal of minocycline and treatment for increased intracranial pressure lead to resolution of the pseudotumor cerebri syndrome, but visual field loss may persist.

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 …

Progressive visual loss from giant cell arteritis despite high-dose intravenous methylprednisolone

BACKGROUND Giant cell arteritis (GCA) often presents with devastating visual loss in the elderly, yet the ideal treatment is unknown. The disease most often has been treated with oral prednisone, although recently the use of the high-dose intravenous methylprednisolone (IVMP) has been reported to enhance visual recovery. METHODS The authors reviewed patient charts from two university-based neuroophthalmology services and reviewed all previously reported cases of GCA treated with IVMP. RESULTS Four patients with GCA exhibited severe, progressive visual loss after at least 48 hours of high-dose IVMP. A fifth patient had further visual loss in one eye and improvement in the other eye after 24 hours of IVMP. In previous reports of IVMP treatment in GCA, four patients lost vision and 14 patients recovered vision. The authors review the details of these reports. CONCLUSIONS The results of IVMP treatment of patients with visual loss from GCA are similar to the results of treatment with oral corticosteroids, with IVMP treatment being more costly and having a small risk of sudden death. The optimal dosage and route of corticosteroid treatment for GCA with visual loss remain elusive and warrant a treatment trial.

Pituitary apoplexy: Evaluation, management, and prognosis

Purpose of review To review the current standard of care in the diagnosis and treatment of pituitary apoplexy and to determine any updated clinical management strategies. Recent findings Pituitary apoplexy is a rare but life-threatening medical emergency. Presenting signs and symptoms often include severe headache, visual loss, ophthalmoplegia, altered consciousness, and impaired pituitary function. Common predisposing factors include closed head trauma, blood pressure alterations, history of pituitary irradiation, cardiac surgery, anticoagulation, treatment with dopamine agonists, pituitary stimulation testing, and pregnancy. MRI imaging is the most sensitive sequence for the detection of acute and old intracranial hemorrhage. Patients often require emergent intravenous fluids, blood transfusions, and high-dose corticosteroids. Patients who remain clinically and neurologically unstable require urgent transsphenoidal surgical decompression as definitive treatment. Summary In patients with pituitary apoplexy, improvement in visual field defects, visual acuity, and diplopia is typically observed after emergent application of therapy, often including medical and surgical treatment. Some patients may require long-term hormonal therapy after surgery.

Isolated Third, Fourth and Sixth Cranial Nerve Palsies From Presumed Microvascular Versus Other Causes: A Prospective Study

PURPOSE To estimate the proportion of patients presenting with isolated third, fourth, or sixth cranial nerve palsy of presumed microvascular origin versus other causes. DESIGN Prospective, multicenter, observational case series. PARTICIPANTS A total of 109 patients aged 50 years or older with acute isolated ocular motor nerve palsy. TESTING Magnetic resonance imaging (MRI) of the brain. MAIN OUTCOME MEASURES Causes of acute isolated ocular motor nerve palsy (presumed microvascular or other) as determined with early MRI and clinical assessment. RESULTS Among 109 patients enrolled in the study, 22 had cranial nerve III palsy, 25 had cranial nerve IV palsy, and 62 had cranial nerve VI palsy. A cause other than presumed microvascular ischemia was identified in 18 patients (16.5%; 95% confidence interval, 10.7-24.6). The presence of 1 or more vasculopathic risk factors (diabetes, hypertension, hypercholesterolemia, coronary artery disease, myocardial infarction, stroke, and smoking) was significantly associated with a presumed microvascular cause (P = 0.003, Fisher exact test). Vasculopathic risk factors were also present in 61% of patients (11/18) with other causes. In the group of patients who had vasculopathic risk factors only, with no other significant medical condition, 10% of patients (8/80) were found to have other causes, including midbrain infarction, neoplasms, inflammation, pituitary apoplexy, and giant cell arteritis (GCA). By excluding patients with third cranial nerve palsies and those with GCA, the incidence of other causes for isolated fourth and sixth cranial nerve palsies was 4.7% (3/64). CONCLUSIONS In our series of patients with acute isolated ocular motor nerve palsies, a substantial proportion of patients had other causes, including neoplasm, GCA, and brain stem infarction. Brain MRI and laboratory workup have a role in the initial evaluation of older patients with isolated acute ocular motor nerve palsies regardless of whether vascular risk factors are present.

Diagnosis and management of giant cell arteritis: a review

Purpose of review This article aims to provide a review of giant cell arteritis (GCA) clinical features, differential diagnosis, treatment options, and recent literature. Recent findings GCA, first described by Horton et al., is a systemic immune-mediated vasculitis affecting medium-sized and large-sized arteries. Characteristic findings include headache, jaw claudication, visual loss, and constitutional symptoms (malaise, fever, weight loss, loss of appetite). Localized GCA symptoms are the end-result of vascular insufficiency and tissue ischemia. Temporal artery biopsy (TAB) remains the gold standard for diagnosis. Additional diagnostic tests include blood tests (erythrocyte sedimentation rate, ESR; C-reactive protein, CRP; platelets) and imaging modalities (ultrasound of the arteries; fluorescein angiography, FA; MRI; and positron emission tomography, PET). The mainstay of management includes high-dose corticosteroids, and additional cytotoxic drugs, antitumor necrosis factor monoclonal antibody, and antiplatelet aggregation therapy may be used. The goal of treatment is to prevent ischemic damage and halt progression of visual loss in the affected eye and prevent involvement of the fellow eye. Summary Further research is warranted concerning the immunogenetics of GCA. Further treatment trials are also needed to develop more specific and sensitive diagnostic tests and new corticosteroid-sparing treatment modalities.