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Although visual symptoms are common following concussion, quantitative measures of visual function are missing from concussion evaluation protocols on the athletic sideline. For the past half century, rapid automatized naming (RAN) tasks have demonstrated promise as quantitative neuro-visual assessment tools in the setting of head trauma and other disorders but have been previously limited in accessibility and scalability. The Mobile Interactive Cognitive Kit (MICK) App is a digital RAN test that can be downloaded on most mobile devices and can therefore provide a quantitative measure of visual function anywhere, including the athletic sideline. This investigation examined the feasibility of MICK App administration in a cohort of Division 1 college football players. Participants (n = 82) from a National Collegiate Athletic Association (NCAA) Division 1 football team underwent baseline testing on the MICK app. Total completion times of RAN tests on the MICK app were recorded; magnitudes of best time scores and between-trial learning effects were determined by paired t-test. Consistent with most timed performance measures, there were significant learning effects between the two baseline trials for both RAN tasks on the MICK app: Mobile Universal Lexicon Evaluation System (MULES) (p 0.001, paired t-test, mean improvement 13.3 s) and the Staggered Uneven Number (SUN) (p 0.001, mean improvement 3.3 s). This study demonstrated that the MICK App can be feasibly administered in the setting of pre-season baseline testing in a Division I environment. These data provide a foundation for post-injury sideline testing that will include comparison to baseline in the setting of concussion.

Uvular necrosis is a rare postoperative complication that can manifest from endotracheal tube intubation or laryngeal mask airway placement resulting in compression and restriction of blood flow to the uvula. This report describes three patients who underwent outpatient shoulder surgery under general anesthesia and were subsequently diagnosed with uvular necrosis. Their symptoms included persistent sore throat, dysphagia, odynophagia, and foreign body sensation, with swelling and white exudate on the uvular tip. All three patients were treated conservatively and had complete symptom resolution. While symptoms from uvular necrosis typically self-resolve within two weeks, it is important to recognize the condition and risk factors because patients may benefit from reassurance and conservative treatment.

Applying oncoplastic techniques to breast conservation therapy is believed to improve cosmetic and oncologic outcomes, compared with standard breast conservation therapy alone. This study aimed to perform a comprehensive review of the literature comparing outcomes of oncoplastic breast conservation therapy (BCT + R) with that of standard breast conservation therapy alone (BCT). A secondary objective was to compare these results to outcomes after oncoplastic breast conservation therapy performed at our institution (BCT + r).A literature search was performed in PubMed using key words, "oncoplastic," "partial breast reconstruction," and "breast conservation therapy." Case reports, case series, and studies with fewer than 10 patients and studies that did not report re-excision rates were excluded. A retrospective chart review was performed from 2011 to 2017 of all cases of oncoplastic breast conservation therapy performed at our institution by a single 2-surgeon team consisting of 1 breast surgeon and 1 plastic surgeon. Outcomes were assessed by comparing re-excision rates between the 3 comparison groups (BCT, BCT + R, BCT + r).The BCT group was made of 5965 patients (22 articles), and the BCT + R group comprised 2564 patients (41 articles). Re-excision rates in the BCT + R group were lower (4.0%) than the BCT group (17.2%, P = 0.0001). One hundred seventy-two patients comprised the BCT + r group and underwent oncoplastic breast conservation therapy during the study period at our institution. The re-excision rate in the BCT + r group was 1.7% and was significantly lower than the BCT group (P = 0.0001) and lower but not significantly different from the BCT + R group (P = 0.2113).Oncoplastic breast conservation therapy leads to lower re-excision rates compared with standard breast conservation therapy. Oncoplastic breast conservation therapy may improve oncologic outcomes compared with standard breast conservation therapy by allowing for more extensive resection without compromising aesthetic results.

In the original publication of the article, under the heading, Study limitations in the Discussion section, the second paragraph, fifth sentence was published incorrectly as “Patients with an L-Dex increase of ≥ 5.5 undergo…sleeve for 4 weeks”.

This prospective controlled observational cohort study assessed the performance of a novel panel of serum microRNA (miRNA) biomarkers on indicators of concussion, subconcussive impacts, and neurocognitive function in collegiate football players over the playing season. Male collegiate student football athletes participating in a Division I Football Bowl Subdivision of the National Collegiate Athletic Association (NCAA) were enrolled. There were a total of 53 participants included in the study, 30 non-athlete control subjects and 23 male collegiate student football athletes. Neurocognitive assessments and blood samples were taken within the week before the athletic season began and within the week after the last game of the season and measured for a panel of pre-selected miRNA biomarkers. All the athletes had elevated levels of circulating miRNAs at the beginning of the season compared with control subjects (p

Medical photography has become an important component of the evaluation and management of patients across many specialties. It is increasingly utilized in contemporary practice with modern smartphones and enhanced digital media. Photography can enhance and improve treatment plans and communication between providers and patients. Additionally, photography supplements education, research, and marketing in both print and social media. Ethical and medicolegal standards for medical photography, specifically for patients with breast disease, have not been formally developed to guide medical providers. To provide guidelines for breast care physicians using medical photography, the Ethics Committee of the American Society of Breast Surgeons presents an updated review of the literature and recommendations for ethical and practical use of photography in patient care. An extensive PubMed review of articles in English was performed to identify studies and articles published prior to 2018 investigating the use of medical photography in patient care and the ethics of medical photography. After review of the literature, members of the Ethics Committee convened a panel discussion to identify best practices for the use of medical photography in the breast care setting. Results of the literature and panel discussion were then incorporated to provide the content of this article. The Ethics Committee of the American Society of Breast Surgeons acknowledges that photography of the breast has become an invaluable tool in the delivery of state-of-the-art care to our patients with breast disease, and we encourage the use of this important medium. Physicians must be well informed regarding the concerns associated with medical photography of the breast to optimize its safe and ethical use in clinical practice.

Mild traumatic brain injury (mTBI/concussion) as experienced through sports, combat, and automobile-related injuries has emerged as a major public health issue. Unfortunately, only limited science ...

To summarize current technique, indications, and pitfalls of electrophysiologic testing used in ophthalmology.Visual evoked potentials (VEPs) may be useful as an objective measurement of refractive error in complicated patients. VEP P100 latency was found superior to color vision and visual field in early stages of hydroxychloroquine maculopathy. VEP results can be predictive of visual recovery in traumatic optic neuropathy. Multifocal electroretinogram (ERG) or VEP can provide an objective assessment of visual field defects not yet present on automated perimetry in patients with glaucomatous and nonglaucomatous optic neuropathies. In patients with intraocular lymphoma, reduced amplitudes of all ERG components can be recorded, with the b-wave amplitude being most significantly affected.Various visual electrophysiologic tests are useful to the ophthalmologist, each with different indications. The flash ERG is most useful in diffuse retinal disorders, whereas the multifocal ERG is superior in localized retinal disease. VEPs can be valuable in diagnosing optic neuropathies, nonorganic visual loss, and assessing visual function in infants or children.

Background The risk of optic disc haemorrhages on visual outcome in idiopathic intracranial hypertension (IIH) is unknown. We report the type and frequency of optic disc haemorrhages and other funduscopic abnormalities at baseline in the study eye of the 133 subjects enrolled in the Idiopathic Intracranial Hypertension Treatment Trial completing 6 months of follow-up. Methods We reviewed optic disc photographs to tabulate the frequency and type of optic disc haemorrhages, other funduscopic abnormalities and papilloedema grades of the study eye at baseline and analyse if their presence is associated with a poor visual outcome. Results 27.2% of subjects had nerve fibre layer haemorrhages in at least one eye. Five of seven, 71% of subjects that met criteria for treatment failure, had nerve fibre layer haemorrhages in at least one eye (Fisher9s exact test: p=0.02). There was a good correlation between presence of nerve fibre layer haemorrhages and Frisen grade (Spearman9s correlation, p=0.002; r=0.271). Subjects with nerve fibre layer haemorrhages had a higher cerebrospinal fluid pressure (40.0 mm water, p=0.04). There was poor correlation between nerve fibre layer haemorrhages at baseline and the perimetric mean deviation change at 6 months. Cotton wool spots were present in 4% of subjects, exudates in 3% and pseudodrusen in 4%. Conclusions Nerve fibre layer haemorrhages are common in patients with IIH with mild visual loss and correlate with the severity of the papilloedema. They occur more frequently in treatment failure subjects and therefore may be associated with poor visual outcomes. Trial registration number NCT01003639, Post-results.

To identify cutpoints for visual measures at baseline and 1 month predictive of abnormal 6-month vision that could be used as eligibility criteria in a clinical trial to test potential neuroprotection or myelin repair agents in patients with optic neuritis. To determine whether moderate-to-severe dysfunction in one or more visual measures at baseline or 1 month correlates with having major vision loss at 6 months.We used the Optic Neuritis Treatment Trial database to evaluate various cutpoints for baseline and 1-month vision levels that predicted abnormal 6-month vision. For selected cutpoints, we computed a 95% CI for positive predictive value and the required sample size if the cutpoint was to be used for clinical trial eligibility. We evaluated whether the degree of visual loss at baseline, 1 month, or change in visual function from baseline to 1 month correlated with 6-month visual acuity, contrast sensitivity, or threshold visual field.The best cutpoints for baseline and 1 month were visual acuityor= 20/50, contrast sensitivity1.0 log units, and visual field mean deviationor= -15 dB. The same levels of visual dysfunction at 1 month, but not at baseline, correlated with having 6-month moderate-to-severe loss for each of these measures (p = 0.01). A trial could require as few as 100 subjects for an outcome variable of one or more abnormal measures. Cutpoints at 1 month were highly predictive of abnormal 6-month vision, but the proportion of patients who would be eligible for a trial would be small.Provided data can be used either for the clinician to counsel patients on expected visual outcome or for designing studies to test therapies that might reduce the amount of permanent optic nerve damage due to optic neuritis in high-risk patients.

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.

Background— Inducible NO synthase (NOS)–derived peroxynitrite (ONOO − ) during ischemia/reperfusion contributes to ischemic brain injury. However, inducible NOS (iNOS) regulation in ischemic stroke remains unknown. Tetrahydrobiopterin (BH 4 ) is an essential cofactor for NOS activity. The present study tested the hypothesis that inhibition of endogenous BH 4 rate-limiting enzyme GTP cyclohydrolase I (GTPCH I), and thus BH 4 synthesis, reduces cerebral infarction via inhibiting iNOS and ONOO − in transient focal ischemia. Methods— Focal ischemia (2 hours) was created in adult male Sprague-Dawley rats (250 to 300 g) by middle cerebral artery occlusion (MCAO). Rats were treated 12 hours before MCAO with vehicle or diamino-6-hydroxypyrimidine (DAHP; 0.5 g/kg IP), a selective GTPCH I inhibitor. Brains were harvested 24 hours after reperfusion for assays of infarct volume, blood–brain barrier (BBB) permeability, GTPCH I activity, BH 4 levels, GTPCH I and NOS mRNA, protein expression, and superoxide anion (O 2 · − ) and ONOO − levels. Results— Endogenous GTPCH I activity, BH 4 levels, iNOS activity, and (O 2 · − and ONOO − levels were all augmented after ischemia/reperfusion. DAHP treatment significantly reduced GTPCH I activity, resulting in decreased BH 4 levels, iNOS activity, and ONOO − levels. Consequently, DAHP treatment significantly reduced the infarct size compared with the nontreated group (22.3±5.6 versus 38.3±7.4%; n=6; P P Conclusion— These results demonstrate that blockade of endogenous brain BH 4 synthesis attenuates cerebral infarction via inhibiting iNOS and ONOO − , which may provide a mechanistic basis of novel therapeutic strategies for ischemic stroke.

Background Participants enrolled in the Optic Neuritis Treatment Trial have been observed for more than a decade to assess the relationship between optic neuritis and the development of clinically definite multiple sclerosis. Objective To assess neurologic disability 10 to 12 years after an initial episode of optic neuritis. Design Longitudinal follow-up of a clinical trial. Setting Fourteen Optic Neuritis Treatment Trial clinical centers performed standardized neurologic examinations, including an assessment of neurologic disability. Participants One hundred twenty-seven patients who had developed clinically definite multiple sclerosis. Main outcome measures Functional Systems Scale and Expanded Disability Status Scale. Results The disability of most patients was mild, with 65% of patients having an Expanded Disability Status Scale score lower than 3.0. The degree of disability appeared to be unrelated to whether the baseline magnetic resonance imaging scan was lesion-free or showed lesions (P =.51). Among patients with baseline lesions, the degree of disability was unrelated to the number of lesions that were present on the scan (P =.14). Two patients died owing to severe multiple sclerosis, one of whom had no lesions revealed on the baseline scan. Conclusion Most patients who develop clinically definite multiple sclerosis following an initial episode of optic neuritis will have a relatively benign course for at least 10 years.

A retrospective chart review was performed for identification of patients with isolated internuclear ophthalmoplegia (INO) postcardiac catheterization from two neuro-ophthalmology units. Of the 110 patients with a diagnosis of INO who were evaluated during the observation period, five patients (4.5%) demonstrated relatively isolated INO occurring in the perioperative period of a cardiac endovascular procedure. These five patients underwent diagnostic catheterization alone (three patients), balloon angioplasty (one patient), or stent placement (one patient). All patients improved, with resolution of diplopia in primary position after a mean period of 82 days. The occurrence of INO in the postcardiac catheterization setting is not uncommon, and it appears to be related to dorsal pontine ischemia. The pontomesencephalic medial longitudinal fasciculus is supplied by small-caliber perforating end-arteries from the basilar trunk, which increases selective vulnerability of this area. Cardiac catheterization may precipitate microemboli involving these vessels, leading to internuclear ophthalmoplegia.

Each year brings new scientific knowledge that builds on itself in a geometric fashion. Ocular motility basic and clinical neurosciences continue to advance with this accelerating pace. The years 1997 through 1998 brought new knowledge to the motility world. This review focuses on the clinical advances within this realm, presented in supranuclear to myopathic organization. Part II of this review will appear in the September 2000 (20:3) issue.

Cabergoline is a potent, D2-selective new dopamine agonist with a half-life of 65 hours. We report two cases and review the literature on cabergoline in prolactinomas. Cabergoline appears to be more effective and better tolerated than bromocriptine, compliance may be improved, and costs are comparable. In cases of bromocriptine failure, unusually high starting doses of cabergoline may be necessary. Cabergoline may eventually replace bromocriptine as the drug of choice in prolactinomas.

In acute monosymptomatic optic neuritis, treatment with oral prednisone alone should be avoided. Therapy with intravenous methylprednisolone (1 g/day for 3 days) followed by 11 days of oral prednisone (1 mg/kg with a short taper) should be considered instead. This is particularly true if a patient considers accelerated visual recovery to be particularly urgent or if magnetic resonance imaging (MRI) demonstrates three or more signal abnormalities consistent with demyelination. In patients without a diagnosis of clinically definite multiple sclerosis (CDMS), an MRI should be considered to assess the prognosis for developing multiple sclerosis (MS) and to eliminate other causes of optic neuropathy. Foregoing an MRI or steroid treatment is an acceptable option. Chest x-ray, blood tests, and lumbar puncture are not necessary in evaluating patients with typical clinical features of optic neuritis. These tests may be appropriate, however, for patients who are about to undergo corticosteroid therapy, which could complicate or mask an unrecognized condition.

The transient pattern electroretinogram (PERG) was recorded from 16 patients with acute optic neuritis and from 13 patients with acute non-arteritic anterior ischemic optic neuropathy (AION). All patients were tested within 35 days from the the onset of visual symptoms and all had significant central visual field abnormalities in their affected eyes as quantified by automated perimetry. Analysis of the PERGs showed that the amplitude of the N95 peak was abnormally reduced for each eye affected with AION while it remained normal in optic neuritis. No significant alteration in P50 amplitude was observed in either condition. The loss of N95 amplitude in AION was highly correlated with the average depth of visual field loss (in decibels) within a radius of 10 degrees of fixation. These results suggest that PERG could be used early in the course of optic neuropathy to distinguish optic neuritis from AION in those cases for which the diagnosis is still uncertain after the clinical examination.

The peak latency of the pattern-reversal visual evoked potential is a sensitive measure of conduction delay in the optic nerve caused by demyelination. Despite its clinical utility, the pattern-reversal visual evoked potential has not previously been used in multicenter clinical trials, presumably because of difficulty in standardizing conditions between centers. To establish whether the pattern-reversal visual evoked potential could be adequately standardized for use as a measure in multicenter therapeutic trials for optic neuropathy or multiple sclerosis, stimulus and recording variables were equated at four centers and pattern-reversal visual evoked potentials were recorded from 64 normal subjects and 15 patients with resolved optic neuritis. Results showed equivalent latency and amplitude data from all centers, suggesting that stimulus and recording variables can be satisfactorily standardized for multicenter clinical trials. N70 and P100 peak latencies and N70-P100 interocular amplitude difference were sensitive measures of resolved optic neuritis.

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-methylprednisolone group (134 patients), 14.7 percent of the oral-prednisone group (129 patients), and 16.7 percent of the placebo grou...

The pattern electroretinogram (PERG) is a small electrical response of the retina to a reversing checkerboard pattern, usually less than 6 μV in amplitude. Unfortunately, the PERG can be obscured by artifacts such as blinks, eye movements, poor fixation, and amplifier saturation. Amplitude criterion artifact rejection systems found on commercial signal averagers eliminate large amplitude artifacts but are insensitive to small amplitude artifacts associated with amplifier saturation. Such saturation often occurs for several recording sweeps after large amplitude signals such as eye blinks are rejected. The presence of post-saturation artifacts complicates clinical PERG analysis. In this paper we describe procedures to remove these small amplitude artifacts from the PERG. These include computer selection of inputs for averaging and use of tracings with small input numbers to approximate PERG amplitudes. These procedures greatly reduce the variability of PERG amplitudes in the normal population, making PERG amplitude a more reliable clinical measure.

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 ...

We have reviewed the charts of 45 neuro-ophthamological patients diagnosed with 79 monocular visual field or visual acuity losses secondary to non-organic etiology. Our aim was to determine the percentage of patients that have improvement in vision. As part of the protocol, all patients had magnetic resonance images, pattern visual evoked potentials, and flash electroretinography in addition to complete neuro-ophthalmological examinations. A single physician performed both the initial and follow-up examinations of all patients. Thirty-three percent of these patients had visual field defects only, 62% had both visual field defects and visual acuity defects, and 5% had only visual acuity defects. After organic disease was ruled out, all were given a timetable for recovery and clear reassurance regarding their prognoses for visual recovery. Seventy-eight percent of these patients showed improvement or were normal, while 22% showed no improvement. Younger patients without obvious psychiatric disorder had better prognoses than older patients.

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.

The authors present the first case report of an aseptic meningitis associated with a uniquely documented retinal ischemia due to trimethoprim-sulfamethoxazole.A 20-year-old woman suffered an aseptic meningitis with retinal ischemia OU, due to ingestion of Bactrim. This case highlights the potential for neuro-ophthalmic side effects of the preparation. Review of the literature and their experience suggest that prompt recognition of the syndrome and withdrawal of the drug is necessary to prevent serious neurologic complications and visual loss.

To assess the risk of developing multiple sclerosis (MS) after optic neuritis and the factors predictive of high and low risk.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.Neurologic and ophthalmologic examinations at 13 clinical sites.Three hundred eighty-nine subjects with acute optic neuritis.Development of MS and neurologic disability assessment.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.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.

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.

Background The objective of this report is to describe the methods used to develop and validate a computerized system to analyze Humphrey visual fields obtained from patients with non-arteritic anterior ischemic optic neuropathy (NAION) and enrolled in the Ischemic Optic Neuropathy Decompression Trial (IONDT). The IONDT was a multicenter study that included randomized and non-randomized patients with newly diagnosed NAION in the study eye. At baseline, randomized eyes had visual acuity of 20/64 or worse and non-randomized eyes had visual acuity of better than 20/64 or were associated with patients refusing randomization. Visual fields were measured before treatment using the Humphrey Field Analyzer with the 24-2 program, foveal threshold, and size III stimulus. Methods We used visual fields from 189 non-IONDT eyes with NAION to develop the computerized classification system. Six neuro-ophthalmologists ("expert panel") described definitions for visual field patterns defects using 19 visual fields representing a range of pattern defect types. The expert panel then used 120 visual fields, classified using these definitions, to refine the rules, generating revised definitions for 13 visual field pattern defects and 3 levels of severity. These definitions were incorporated into a rule-based computerized classification system run on Excel® software. The computerized classification system was used to categorize visual field defects for an additional 95 NAION visual fields, and the expert panel was asked to independently classify the new fields and subsequently whether they agreed with the computer classification. To account for test variability over time, we derived an adjustment factor from the pooled short term fluctuation. We examined change in defects with and without adjustment in visual fields of study participants who demonstrated a visual acuity decrease within 30 days of NAION onset (progressive NAION). Results Despite an agreed upon set of rules, there was not good agreement among the expert panel when their independent visual classifications were compared. A majority did concur with the computer classification for 91 of 95 visual fields. Remaining classification discrepancies could not be resolved without modifying existing definitions. Without using the adjustment factor, visual fields of 63.6% (14/22) patients with progressive NAION and no central defect, and all (7/7) patients with a paracentral defect, worsened within 30 days of NAION onset. After applying the adjustment factor, the visual fields of the same patients with no initial central defect and 5/7 of the patients with a paracentral defect were seen to worsen. Conclusion The IONDT developed a rule-based computerized system that consistently defines pattern and severity of visual fields of NAION patients for use in a research setting.

Statins have recently been shown to exert neuronal protection in ischemic stroke. Reactive oxygen species, specifically superoxide formed during the early phase of reperfusion, augment neuronal injury. NADPH oxidase is a key enzyme for superoxide production. The present study tested the hypothesis that atorvastatin protects against cerebral infarction via inhibition of NADPH oxidase-derived superoxide in transient focal ischemia. Transient focal ischemia was created in halothane-anesthetized adult male Sprague-Dawley rats (250–300 g) by middle cerebral artery occlusion (MCAO). Atorvastatin (Lipitor, 10 mg/kg sc) was administered three times before MCAO. Infarct volume was measured by triphenyltetrazolium chloride staining. NADPH oxidase enzymatic activity and superoxide levels were quantified in the ischemic core and penumbral regions by lucigenin (5 μM)-enhanced chemiluminescence. Expression of NADPH oxidase membrane subunit gp91phox and membrane-translocated subunit p47phox and small GTPase Rac-1 was analyzed by Western blot. NADPH oxidase activity and superoxide levels increased after reperfusion and peaked within 2 h of reperfusion in the penumbra, but not in the ischemic core, in MCAO rats. Atorvastatin pretreatment prevented these increases, blunted expression of membrane subunit gp91phox, and prevented translocation of cytoplasmic subunit p47phox to the membrane in the penumbra 2 h after reperfusion. Consequently, cerebral infarct volume was significantly reduced in atorvastatin-treated compared with nontreated MCAO rats 24 h after reperfusion. These results indicate that atorvastatin protects against cerebral infarction via inhibition of NADPH oxidase-derived superoxide in transient focal ischemia.

Publisher Summary The eye, optic nerve, and chiasm are an accessible, easily quantifiable, sensory system within the brain. The retina is a highly specialized part of the brain's gray matter, while the optic nerve is a simplified central nervous system (CNS) white matter tract. Visual loss and recovery because of the optic nerve pathophysiology can be quantified by a number of modalities including visual acuity, color vision testing, pupillography, perimetry, fundoscopy, imaging, electrophysiology, and psychophysical techniques. The study of optic neuropathies has become an important tool for understanding the neurobiology, prognosis, and treatment strategies for many central nervous system diseases—for example, optic neuritis may well be a forme fruste of multiple sclerosis while anterior ischemic optic neuropathy (AION) is related to small vessel cerebral vascular disease. Advancing the understanding of optic neuropathies may well gain insight into therapeutic issues surrounding brain diseases such as multiple sclerosis and stroke.

Gene transfer of glial cell line-derived neurotrophic factor (GDNF) in rodent models of Parkinson's disease (PD) has been shown to protect against neurodegeneration either prior to or immediately after neurotoxin-induced lesions; however, the nigrostriatal pathway was largely intact when gene delivery was completed in these models, which may not accurately reflect the clinical situation encountered with Parkinson's patients. In this study, replication-incompetent adenoviral vectors encoding the rat GDNF gene were administered into the striatum 4 weeks following 6-hydroxydopamine (6-OHDA) injection in the unilateral striatum, more closely resembling fully developed PD. Apomorphine-induced rotational behavior testing was performed every week following 6-OHDA injection. At the 10th week after gene transfer, the striatal dopamine concentrations were measured by HPLC with an electrochemical detector and the number of tyrosine hydroxylase (TH)-positive dopamine neurons in the substantia nigra (SN) was determined by immunohistochemistry. Injection of 6-OHDA into the striatum produced stable increases in rotation, which reached a plateau between 4 and 5 weeks post-injection. The number of TH-positive neuron in the SN and dopamine levels in the striatum was significantly lower in the 6-OHDA group compared to the normal group. Gene transfer of GDNF, but not beta-galactosidase, significantly increased the number of TH-positive neurons and dopamine levels, with a subsequent behavioral recovery between 5 and 10 weeks following GDNF transduction. These findings demonstrate that adenovirus-mediated gene transfer of GDNF is efficacious even in the late stages of 6-OHDA-induced PD rats. They also provide further evidence on the effectiveness of GDNF-based gene therapy for experimental Parkinson's disease.

The optic nerve is a 50 mm by 4.5 mm white matter tract of the central nervous system (CNS). Its physiology and response to therapy can be precisely quantified by a number of common, easily available, neuro-ophthalmological techniques. Detection of an early, subtle, optic neuropathy is relatively easy compared with many of the difficult-to-document sensory or even motor complaints in early multiple sclerosis (MS).

PURPOSE To assess visual function more than 10 years after an episode of optic neuritis in patients enrolled in the Optic Neuritis Treatment Trial. DESIGN Longitudinal follow-up of a randomized clinical trial. METHODS Vision testing included measures of visual acuity, contrast sensitivity, and visual field. Quality of life was assessed with the National Eye Institute Visual Function Questionnaire. RESULTS Examinations were completed on 319 patients. In most patients, visual function test results in the eyes that experienced optic neuritis at study entry ("affected eyes") were normal or only slightly abnormal after 9.9 to 13.7 years. Visual acuity in the affected eyes was >or=20/20 in 74%, 20/25 to 20/40 in 18%

Background.—Migraineurs with visual aura are highly susceptible to illusions and visual distortion and areparticularly sensitive to a pattern of regularly spaced parallel lines or stripes.Purpose.—To determine whether the high degree of susceptibility to illusions and visual distortion in mi-graineurs with aura is associated with hyperneurological activity of the occipital cortex.Methods.—In order to investigate any relationships among neuronal activity, spatial frequency of square-wave gratings, and self-described visual distortion, we investigated the neuronal and psychophysical responses tosquare-wave gratings in migraineurs with visual aura and in nonheadache controls.Results.—Square-wave gratings provoked various types of visual distortion and illusions and induced a hyper-neuronal response in the visual cortex of migraineurs with visual aura, a response that strongly depended upon thestimulus spatial frequency.Conclusion.—The hyperneuronal activity of the occipital cortex is consistent with general cortical hyperexcit-ability in migraine.Key words: migraine, visual distortion, visual activation, functional MRIAbbreviations: SF spatial frequency, NHCs nonheadache controls, MWA migraine with aura, cpd cycles perdegree, BOLD blood oxygenation level dependent

To assess the ability of baseline MRI characteristics to predict the early development of clinically definite MS (CDMS) and combined CDMS/MRI outcomes in 190 patients with a positive MRI at the time of their first demyelinating event.Based on individual and sets of baseline MRI characteristics, the authors evaluated the percentage of patients meeting outcomes of CDMS and various combined CDMS/MRI outcomes by 18 months. They also optimized a cutpoint for dichotomizing each baseline MRI characteristic and evaluated these variables using logistic regression to determine which MRI characteristics best predicted CDMS by 18 months.The presence of two or more gadolinium-enhancing lesions better predicted the development of CDMS and combined CDMS/MRI outcomes by 18 months than any other individual MRI characteristic or set of MRI characteristics. Among patients with two or more gadolinium-enhancing lesions, 52% developed CDMS compared with 24% of patients with fewer than two lesions. For those meeting the criteria of Barkhof et al., 32% of patients developed CDMS compared with 16% of those not meeting these criteria. Irrespective of individual or sets of criteria, however, the majority of patients developed either CDMS or demonstrated disease activity on brain MRI by 18 months.For patients with positive MRI at the time of their initial neurologic event, both gadolinium-enhancing lesions and the Barkhof criteria are predictors for development of CDMS over a short interval. However, these results, based on a combined CDMS/MRI outcome, suggest that the majority of these patients are already in the earliest stages of MS, regardless of whether any further MRI criteria are met.

We evaluated 190 patients in the placebo group of the CHAMPS trial in order to assess factors associated with short-term clinical and brain magnetic resonance imaging (MRI) outcomes in patients with a first clinical demyelinating event involving the optic nerve, spinal cord, or brainstem/cerebellum, and subclinical demyelination on brain MRI. The two study outcomes were 1) development of clinically definite multiple sclerosis (CDMS) and 2) development of CDMS or two or more new or enlarging brain MRI T2 lesions. The presence of gadolinium (Gd)- enhancing lesions on the baseline scan was the only MRI characteristic associated with a higher risk of both the clinical and combined outcomes (p=0.003 and

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.

Objectives To determine the prognosis of internuclear ophthalmoplegia (INO) caused by infarction. Design Multicenter, retrospective observational case series. Participants Thirty three patients with ischemic-related INO. Methods Chart review of clinical details. Main outcome measure Resolution of diplopia in primary position. Results Of the group, 78.8% demonstrated resolution of diplopia in primary position with an average time to resolution of 2.25 months. The presence of associated neurologic symptoms (vertigo, ataxia, dysarthria, facial palsy, pyramidal tract signs) correlated with a worse prognosis for resolution of diplopia. When performed magnetic resonance imaging (MRI) demonstrated the causative infarct in only 52% of cases; the presence of an MRI-demonstrable lesion was not significantly associated with prognosis for resolution. Conclusions Similar to ischemic ocular motor palsies, most ischemic-based INO become asymptomatic in primary position over 2 to 3 months. The presence of associated features correlated with persistent diplopia. MRI has limited yield in demonstrating the causative infarct.

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 …

Purpose: To define a practice pathway for the evaluation of sixth-nerve palsies (SNPs) and to determine its cost—effectiveness and validity in a retrospective chart review. Methods: A Medline search of the English-language literature from 1966 to 1995 was performed to define the available clinical evidence and develop the practice pathway. The authors retrospectively reviewed 407 charts with the diagnosis of SNP seen at three centers. Information obtained included: etiologic diagnosis if known; development of new neurologic or ophthalmologic findings; and results and costs of neuroimaging studies, if performed. Results: Of the 407 patients, 98 underwent computed tomogra phy scans and 212 underwent magnetic resonance imaging of the head. Eighty cases were non-isolated, 317 were isolated SNP, and ten could not be classified from chart information. Of the 317 cases of isolated SNP, 49 were classified as traumatic; 5, congenital; 158, vasculopathic; 63, nonvasculopathic; and 42, progressive or unre solved. Following the recommendations of the practice pathway, the 158 patients clas sified as having vasculopathic SNP would not have undergone neuroimaging studies, realizing a savings of $100,000 in this study population of 407 patients. Conclusion: The recommendations of the practice pathway are supported by review of the literature and the retrospective review of these cases. However, a prospective study with a matched control group is needed to demonstrate regional and specialty-specific van ations in care and to strengthen the clinical certainty of the pathway recommendations. Key words: practice pathway; diagnostic evaluation; sixth cranial nerve palsies; oph thalmology. (Med Decis Making 1999;19:42-48)

Leber's Hereditary Optic Neuropathy is a mitochondrial genetic disorder that causes acute to subacute bilateral central loss of vision. It typically presents in young men in their second or third decade of life and onset later in life is rare. We describe a case of a 58-year-old man with late onset of LHON and discuss the importance of suspecting the diagnosis in appropriate cases.

This issue of Ophthalmology Clinics of North America was developed to help the reader understand how the neuro-visual system can be used by a careful clinician to assist with the diagnosis and treatment strategies for a wide spectrum of brain and systemic diseases. A meticulous clinician can diagnosis a number of diseases such as multiple sclerosis, myasthenia gravis, and degenerative diseases at the bedside by understanding how these abnormalities affect vision. We are indebted to the senior contributing authors and their associates for sharing their knowledge and expertise, rendering our task as editors a pleasure. Steven Galetta and his unit at the University of Pennsylvania review how multiple sclerosis can not only be diagnosed, but accurate treatment strategy and prognosis can be documented through a precise bedside examination and MRI scanning. David Weinberg’s team at the University of Vermont review some of the basic background information available on myasthenia gravis and provide excellent illustrations on how to make this diagnosis through ocular motility examinations. They also review bedside diagnostic techniques such as the brest testQ to avoid the need for Tensilon in most patients being evaluated for myasthenia. There is also a nice discussion on treatment strategy for not only symptoms but for the immunology of this muscle disease as well. Victoria Pelak reviews neuro-degenerative diseases and their

• Objective. —Changes in the brain on magnetic resonance images are common in patients with optic neuritis even when there is no other clinical evidence of multiple sclerosis. The current study was designed to determine systematically the prevalence of brain abnormalities on magnetic resonance images in the patients entered into the Optic Neuritis Treatment Trial. Design. —Prospective multicenter clinical trial. Setting. —Referral centers. Patients and Methods. —Brain magnetic resonance images from 418 patients with acute optic neuritis (77% women; mean age, 32.0 years) were evaluated at a central reading center with the use of a standardized classification system (ranging from 0 for normal to IV for most extensive changes). Results. —Of the scans, 40.9% were classified as grade 0, 10.8% as grade I, 9.1% as grade II, 6.7% as grade III, and 32.5% as grade IV. For patients with isolated (monosymptomatic) optic neuritis, 26.7% had two or more lesions. Conclusions. —We found a lower prevalence of brain magnetic resonance imaging abnormalities in isolated optic neuritis than previous studies have reported. This likely is due to our study having a higher degree of standardization of patient inclusion criteria, which limited patient selection bias.