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Show NEURO- OPHTHALMOLOGY AT LARGE 61st Annual Meeting of the American Academy of Neurology Seattle, Washington April 25- May 2, 2009 The scientific sessions this year included 2021 platform presentations and posters. There were 11 educa-tional courses in neuro- ophthalmology and neuro- otology given by the following faculty: Robert Baloh, Laura Balcer, Valerie Biousse, James Corbett, Wayne Cornblath, Fiona Costello, Kathleen Digre, Eric Eggenberger, Scott Eggers, Terry Fife, Steven Galetta, Christopher Glisson, Timothy Hain, Janet Helminski, Aki Kawasaki, David Kumpe, R. John Leigh, Grant Liu, Mark Moster, Nancy Newman, David Newman- Toker, Victoria Pelak, Sharon Polensek, Valerie Purvin, John Pula, Janet Rucker, Jonathan Trobe, Ronald Tusa, Gregory Van Stavern, and David Zee. The topics most relevant to neuro- ophthalmologists are sum-marized here. NEURODEGENERATIVE DISEASES Adam Boxer and colleagues ( San Francisco, CA) used eye movement recordings to identify clinical differ-ences in patients with frontotemporal lobar degeneration ( FTLD) who had tau vs. TDP- 43 autopsy pathology. The investigators recorded saccades in 11 patients with FTLD-TDP- 43 and 10 patients with FTLD- tau. Horizontal and vertical saccade times were higher in the tau group than the TDP- 43 group ( P < 0.02). Using a receiver operating curve ( ROC) analysis, the authors demonstrated that slowed saccades accurately distinguished TDP- 43 from tau patients. Detailed examination of the brainstem ocular motor nuclei was conducted in 5 representative patients and revealed increased pathologic burden in the tau patients. The authors concluded that saccadic abnormalities are a useful predictor of pathologic subtypes of FTLD, possibly due to greater brainstem involvement in the tau subtype. ( S42.006) Shawn Smyth and colleagues ( Aurora, CO) con-ducted a retrospective study of computerized visual field ( CVF) defects in 9 patients with clinically diagnosed posterior cortical atrophy ( PCA). Eight patients were found to have homonymous hemianopia ( HH) or quadrantanopia and 1 had bilateral visual field constriction. All patients progressed to dementia ( 8 had probable Alzheimer disease and 1 had probable dementia with Lewy bodies). The authors concluded that the characteristic visual field defects seen in PCA patients probably reflect pathology to the primary and visual association cortices. ( P09.171) OPTIC NEURITIS AND MULTIPLE SCLEROSIS Noa Raz and colleagues ( Jerusalem, Israel) con-ducted psychophysical tests of visual function in patients with acute optic neuritis ( ON) to characterize the deficits with respect to parvocellular and magnocellular pathways. Ten patients and 10 control subjects were studied at presentation, after 1 month, and after 4 months with visual acuity, computerized visual fields, contrast sensitivity, color perception, static high- contrast object detection, motion detection, coherent moving noise perception, and object-from- motion ( OFM) perception. One month after the acute phase, the initial deficits of visual acuity, contrast sensitivity, color perception, visual fields, and static object detection had returned to normal or near- normal levels in 9 of 10 patients. However, the patients had persistently defective motion processing, with reduced OFM percep-tion, higher motion detection thresholds, and prolonged reaction times. The level of OFM impairment correlated with the conduction delay detected on visual evoked potentials. The authors suggested that abnormalities of the magnocellular pathway after ON may be responsible for the patients' persistent visual complaints, particularly regard-ing motion processing, despite normal standard visual testing. Low- contrast acuity, which is probably mediated by the parvocellular pathway, was not assessed. ( P04.077) Takafumi Hosokawa and colleagues ( Osaka, Japan) reported a retrospective analysis of Goldmann visual field defects after ON in 15 patients with neuromyelitis optica ( NMO) and 20 patients with multiple sclerosis ( MS). Anti-aquaporin 4 antibodies were positive in all patients with NMO and negative in all patients with MS. Altitudinal hemianopia was seen in 33% of patients with NMO and in none of the patients with MS ( P < 0.05). ( The patients with MS all showed central scotomas.) The authors suggested that an altitudinal field defect may distinguish NMO from MS and postulated an ischemic mechanism for the optic neuropathy in NMO. The study was limited by a small J Neuro- Ophthalmol, Vol. 29, No. 4, 2009 363 sample size, and the results are at variance with the Optic Neuritis Treatment Trial, which found that 15% of typical patients with ON had altitudinal defects. ( P04.093) Claire Riley and colleagues ( New York, NY) conducted a meta- analysis to evaluate the prognostic value of cerebrospinal fluid ( CSF) abnormalities in patients with a clinically isolated syndrome ( CIS) and > 2 MRI lesions to determine progression to clinically definite multiple sclerosis ( cdMS). Using unpublished data from the trials of glatiramer acetate and interferon beta for patients with CIS ( BENEFIT, IFNb- 1a ETOMS, and GA PreCISe), they examined the CSF results and clinical outcomes from patients receiving placebo. Abnormal CSF was defined as oligoclonal banding ( OCBs) and/ or an elevated IgG index, and patients without both sets of these data were excluded. The presence of a CSF abnormality did not predict the likelihood of progression to cdMS. In addition, this study demonstrated that most patients with CIS and MRI abnormalities also have CSF abnormalities, but that the presence of CSF abnormalities does not have significant additional prognostic value in predicting the risk of cdMS over 2 years. ( P02.119) Jonathan McNulty and colleagues ( Dublin, Ireland) conducted a diffusion tensor tractography study to evaluate the integrity of the medial longitudinal fasciculus ( MLF) in patients with internuclear ophthalmoplegia ( INO). They studied 12 patients with INO and 12 matched control subjects. Participants underwent conventional MRI and diffusion tensor imaging. Regions of interest approximat-ing the MLF were identified. Qualitative MLF abnormal-ities were detected in all 12 subjects and in no control subjects. One shortcoming was that this method is not specific and produces extraneous fiber tracts apart from the MLF. ( P04.082) Ari Green and colleagues ( San Francisco, CA) reported the correlation between N- acetylaspartate ( NAA) levels in normal- appearing gray matter ( NAGM) and a measurement of retinal nerve fiber layer ( RNFL) thick-ness performed 2 years later in a cohort of patients with MS and CIS. They studied 179 patients ( aged 32.9 6 9.5, 65% women) using proton spectroscopy imaging ( 1 H- magnetic resonance spectroscopy [ MRS]). NAGMNAAvalues corre-lated with average RNFL measures ( R = 0.22, P < 0.0001). This study demonstrates that reduced cerebral NAA levels are predictive of future axonal loss in the anterior visual pathway. ( P05.156) Esther Bisker and colleagues ( Philadelphia, PA) conducted a longitudinal study to assess the degree of RNFL thinning associated with the loss of low- contrast acuity and high- contrast acuity in patients with MS. In their study, 365 patients ( 725 eyes) underwent optical coherence tomography ( OCT)- 3 imaging at baseline and at 6- month intervals during a mean follow- up period of 1.5 years ( range 0.5- 3.7 years) at three academic centers. Visual function testing was performed using low- contrast ( 2.5 and 1.25% levels) and Early Treatment Diabetic Retinopathy Study ( ETDRS) acuity charts. Worsening of low- contrast acuity was noted in 33% of MS eyes. Of these eyes with visual loss, only one third had a known history of ON. Two-line ( 10- letter) losses of 2.5% low- contrast acuity were associated with a 1.6- mm decrement in RNFL thickness over time ( P = 0.009), and losses of 1.25% contrast acuity were associated with a 3.7- mm decrement ( P = 0.02). The authors concluded that visual loss may be present even in the absence of a history of ON and that reduced low-contrast acuity is associated with RNFL thinning over time. These findings suggest that gradual optic nerve axonal loss may be an important feature of MS. ( S57.004) Deanna Cettomai and colleagues ( Baltimore, MD) reported the concordance between RNFL thickness measured by OCT and the clinical findings of optic nerve pallor or afferent pupillary defect ( APD) on 212 consecutive patients. The mean RNFL was 96 6 15 m ( n = 366) in eyes without pallor and 78.7 6 20.6 m ( n = 58) in eyes with pallor. Mean RNFL was 84.7616.1 m ( n = 41) for eyes with an APD was detected and 95.4616.8 mm ( n = 383) for eyes without an APD. In patients for whom the ratio of the mean RNFL between the two eyes was < 90%, an APD was detected on clinical examination in 86% ( sensitivity = 0.28, specificity = 0.93). There was wide variability across physicians in the accuracy of detecting pallor or an APD. The authors suggested that OCT is a more sensitive measure of subclinical optic nerve damage than clinical examination alone and that OCT may be a useful adjunct in the management of patients with MS. ( P05.158) Salim Abboud and colleagues ( Hinckley, OH) reported their findings on the reproducibility of serial OCTwithout pharmacologic pupillary dilation ( PPD). They conducted 2 serial measurements at least 1 week apart of the peripapillary RNFL thickness and macular volume ( MV) in 10 consecutive healthy volunteers by Stratus OCT without PPD. All studies were conducted by a single operator. Across subjects, the coefficient of variation ( COV) for independent serial measures of RNFL was 2.86% and for MV was 1.90%. The authors concluded that serial measurements of RNFL and MV are sufficiently precise to use as outcome measures in longitudinal studies, even when implemented without PPD. ( P05.164) Sally Chang and colleagues ( Philadelphia, PA) evaluated the utility of measuring low- contrast acuity in addition to the standard Multiple Sclerosis Functional Composite ( MSFC) by assessing the strength of correla-tions of these assessments with RNFL thickness measure-ments. They studied 164 patients ( 326 eyes, aged 47 6 10 years), measuring low- contrast letter acuity ( 2.5% and 1.25% levels), high- contrast acuity ( ETDRS charts), and 364 q 2009 North American Neuro- Ophthalmology Society J Neuro- Ophthalmol, Vol. 29, No. 4, 2009 Prasad and Moster standard MSFC. Scores for MSFC with low- contrast acuity added ( MSFC- 4) had greater correlations with RNFL thickness compared with the standard MSFC ( P = 0.07 for MSFC, P = 0.005 for MSFC- 4 with 2.5% low- contrast, and P = 0.007 for MSFC- 4 with 1.25% contrast). The authors concluded that measurement of low- contrast acuity increases the capacity of the MSFC to capture the effects of axonal loss in the anterior visual pathway. ( P04.076) Gurdesh Bedi and colleagues ( Miami Beach, FL) conducted a retrospective study to evaluate the efficacy of rituximab on the relapse rate and disability in NMO. Among 19 patients treated with rituximab, relapses occurred in 5 patients. The authors concluded that rituximab leads to a significant reduction in relapses in patents with NMO. ( P04.099) NONARTERITIC ANTERIOR ISCHEMIC OPTIC NEUROPATHY Edward Atkins and colleagues ( Atlanta, GA) eval-uated the treatment of nonarteritic anterior ischemic optic neuropathy ( NAION) in the United Stated using a Web-based anonymous survey ( n = 1595) of US neuro-ophthalmologists ( US- NO = 350), Georgia ophthalmologists ( GA- O = 340), Georgia neurologists ( GA- N = 322), and Georgia optometrists ( GA- OD = 583). For acute treatment, 63% of GA- N and GA- O and 80% of US- NO use antiplatelet agents, 10% of physicians use oral steroids, 19% of GA- N use high- dose intravenous steroids, 22% of US- NO and 13% of GA- O use topical brimonidine, and 7% of US- NO use intravitreal bevacizumab. For secondary prevention of fellow eye involvement, > 74% physicians use antiplatelet agents, whereas 10%- 15% of ophthalmology-trained US- NO and GA- O also use brimonidine in this setting. More than 80% of physicians manage vascular risk factors aggressively; 15% of US- NO obtain carotid ultrasound compared with 51% of GA- O and 72% of GA-N, and 16% of US- NO obtain neuro- imaging compared with 25% of GA- O and 84% of GA- N. The authors conclude that, despite insufficient evidence, most physicians currently use antiplatelet agents for acute treatment and secondary preven-tion of NAION. Other popular treatments include intravitreal bevacizumab, topical brimonidine, and steroids. Neurolo-gists are less familiar with the management of NAION than ophthalmologists and neuro- ophthalmologists. ( P04.079) VISUAL LOSS Wolfgang Heide and colleagues ( Celle, Germany) investigated visual search patterns in patients with acute HH. They tested the hypothesis that visual search in HH is determined purely by the visual- sensory deficit by comparing 9 patients with HH due to acute occipital stroke with 9 healthy subjects with a simulated ‘‘ virtual'' HH ( VHH) and 9 control subjects with normal visual fields. They recorded eye movements while subjects searched for targets among distractors. All patients, even those with small lesions restricted to the visual cortex, showed longer search durations than VHH subjects. Their longer search duration correlated with a higher number of both fixations and ‘‘ re- fixations'' ( repeated scanning of fixated items). Scan- path strategies were similar in HH and VHH subjects. The authors concluded that pure visual input failure alone does not fully account for abnormal visual search in patients with isolated occipital lesions. They postulate that the longer search durations may result either from changes in visual attention due to disconnections of the visual cortex or from an early stage of compensatory eye movements. ( S57.005) Sashank Prasad ( Philadelphia, PA) received the S. Weir Mitchell award for excellence in basic science research from the American Academy of Neurology Alliance. He and his colleagues studied structural and functional changes of the visual pathway in patients with early- onset blindness. They studied 10 blind subjects and 10 sighted control subjects, collecting BOLD functional MRI ( fMRI) data ( during a language comprehension/ semantic decision task), a volumetric anatomical scan, a resting perfusion scan, and diffusion tensor imaging. They found that during sentence comprehension, blind subjects demonstrated sig-nificant occipital activation in addition to left hemispheric language areas ( BOLD D, blind 0.9% vs. sighted 0.0%; P < 0.05). Furthermore, they found a positive correlation across subjects between resting occipital perfusion and the amount of cross- modal task activation ( R = 0.5; P < 0.05). In addition, white matter atrophy and a reduction in anisotropy were correlated ( R = 0.7; P = 0.07). On the other hand, no structural measures predicted the amount of functional cross- modal activation ( P > 0.1). The authors concluded that significant structural and functional differences exist between early- blind and sighted subjects. In addition, lack of correlation between structural and functional measures may suggest that these forms of plasticity are independent in the brain's response to early blindness. A larger study is necessary to explore that possibility. IDIOPATHIC INTRACRANIAL HYPERTENSION In a retrospective review of 230 consecutive patients with idiopathic intracranial hypertension ( IIH) over 8 years, Sachin Kedar and colleagues ( Jackson, MS) studied the effect of patient factors on the level of opening pressure ( OP) in patients at presentation and the effect of OP on visual outcomes. They found an OP at presentation of 388 6 93 mm H2O that negatively correlated with age ( r = 0.2). Gender, race, initial body mass index ( BMI), weight 365 Neuro- Ophthalmology at Large J Neuro- Ophthalmol, Vol. 29, No. 4, 2009 change, presenting symptom, and time interval to pre-sentation were not associated with OP. Higher OP was associated with worse initial vision. Patients with visual acuity ( VA) $ 20/ 100 had an OP of 382 6 90 mm H2O and those with a VA < 20/ 100 had an OP of 515 6 77 mm H2O; patients with normal visual fields ( VFs) had an OP of 390 6 85 mm H2O and those with severely constricted VFs had an OP of 439 6 110 mm H2O. Patients with normal-appearing optic nerves had an OP of 358 6 94 mm H2O, whereas those with grade 4- 5 papilledema had an OP of 439 6 109 mm H2O. There was no significant association, however, between OP and visual outcome ( improvement or worsening of VA or VFs or appearance of ON during follow- up). The authors concluded that a higher presenting OP in patients with IIH is associated with worse initial VA, VF loss, and ON appearance, but that OP is not predictive of the clinical course. ( P04.080) J. Alexander Fraser and colleagues ( Atlanta, GA) conducted a case- control study to evaluate potential risk factors for IIH in 24 men and matched control subjects. They administered a telephone questionnaire ( including the Androgen Deficiency of Aging Men [ ADAM] question-naire for hypogonadism and the Berlin questionnaire for sleep apnea) and explored medical comorbidities, obesity patterns, endocrinologic problems, reproductive health, medications and drugs, and sleep apnea. After controlling for BMI, men with IIH were more likely than control subjects to have symptoms of androgen insufficiency The authors concluded that men with IIH have a higher prevalence of symptoms suggestive of androgen deficiency and sleep apnea and that these factors may be etiologically related. ( P04.071) Beau Bruce and colleagues ( Decatur, GA) conducted a retrospective cohort study of 411 consecutive adults with IIH and 38 matched control subjects from three centers. In this group they identified 20 patients ( 5%) older than 50 years at diagnosis and 18 ( 4%) with a normal BMI. Both groups were more likely to be white ( P = 0.04, 75% vs. 49%) than the rest of the IIH cohort. Older patients with IIH had a lower BMI but were still generally obese ( P = 0.025, 33 vs. 38). At presentation, they were less likely to report headache ( P < 0.001, 35% vs. 76%) and more likely to complain of visual changes ( P = 0.01, 45% vs. 21%). At last follow- up, they were more likely to have persistent optic disc edema ( P = 0.002), but they had similar, if not better, visual outcomes than younger patients did. Among patients with normal BMI, medication- induced IIH was more frequent ( P = 0.007, 28% vs. 7%). No patient with IIH who had a normal BMI had severe visual loss in either eye ( P = 0.09, 0% vs. 16%). The authors concluded that older patients and those with a normal BMI make up a small proportion of those with IIH but seem to have better visual outcomes than typical patients with IIH. ( P04.072) HEREDITARY DISEASES Margherita Milone and colleagues ( Rochester, MN) reported a patient with progressive external ophthalmople-gia and a mutation in OPA1 without associated visual loss or optic atrophy. The patient was a 48- year- old woman who had myopathy, neurosensory hearing loss, migraine, and gastrointestinal dysmotility in addition to ophthalmoplegia. There was no loss of visual acuity, optic atrophy, visual field defect, or dyschromatopsia, although neither optical coher-ence tomography nor visual evoked potentials were perfor-med. Electromyography revealed myopathy and muscle biopsy revealed cytochrome c oxidase ( COX)- negative fibers ( but not ragged- red fibers). Multiple mitochondrial DNA ( mtDNA) mutations were identified. The autosomal genes commonly associated with multiple mtDNA dele-tions ( POLG1, POLG2, ANT1, and PEO1) were sequenced, and no mutations were found. A heterozygous in- frame deletion ( p. R38 S43del) was identified in OPA1, which has been reported previously in two Danish patients with nonsyndromic autosomal dominant optic atrophy. The case broadens the spectrum of phenotypes associated with OPA1 mutations by demonstrating multiple systemic abnormal-ities in the absence of optic nerve dysfunction. ( P01.050) Gerald Pfeffer and colleagues ( Vancouver, BC) conducted a retrospective study of patients with chronic progressive external ophthalmoplegia ( CPEO) to compare the yield of levator palpebrae biopsy to skeletal muscle biopsy. In a chart review of 36 patients with CPEO who underwent biopsy and had mitochondrial DNA testing, they found that the diagnostic yield of a skeletal biopsy was 50% ( 13 of 26) and that of a levator palpebrae biopsy was 85% ( 11 of 13). Three of the subjects who initially had negative skeletal muscle biopsies subsequently had positive levator palpebrae biopsies. The authors suggested that patients with CPEO undergoing levator palpebrae resection should undergo a biopsy of that muscle because of its higher yield. ( S55.005) Valeria Barcella and colleagues ( Milan, Italy) reported abnormalities of the pregeniculate and postgeni-culate visual pathway in patients with LHON studied by MRI. They studied 5 patients with LHON and 10 healthy control subjects. They assessed the correlations between diffusion tensor ( DT) tractography and voxel- based mor-phometry ( VBM) data with OCT measures and fMRI acti-vation of the visual cortex. VBM analyses revealed optic nerve and chiasm atrophy, as well as a significant reduction of occipital gray matter, in all patients with LHON. There was reduced fractional anisotropy ( FA) in the left optic radiation, which correlated across subjects with OCT RNFL measurements. The patients demonstrated reduced activation in area VI bilaterally. The authors concluded that optic nerve damage in LHON may induce retrograde 366 q 2009 North American Neuro- Ophthalmology Society J Neuro- Ophthalmol, Vol. 29, No. 4, 2009 Prasad and Moster structural and functional changes of the visual pathways, although the study does not exclude the possibility that retrogeniculate alterations are also directly due to mito-chondrial dysfunction. ( S57.003) Matthew Kirkman and colleagues ( Newcastle upon Tyne, UK) assessed visual disability in the role of environ-mental risk factors in 402 LHON carriers ( with mitochon-drial DNA mutation G3460A [ n = 71], G11778A [ n = 270], and T14484C [ n = 61]), identified from 125 independent pedigrees. Of these, 196 were clinically affected, and 74.5% of the affected subjects were men. Subjects received a structured questionnaire focusing on alcohol and tobacco exposure ( before visual loss for affected individuals), and the Visual Function Index ( VF- 14) scale, which assesses impairment in activities of daily living, ranging from 0 ( worst) to 100 ( best). Affected patients with the T14484C mutation had higher VF- 14 scores compared with those with the G3460A and G11778A mutations ( P < 0.0001). Heavy cumulative tobacco consumption was significantly associated with visual loss in a binary logistic regression model ( odds ratio [ OR] 3.26, 95% confidence interval [ CI] 1.31- 8.07, P = 0.011). Maximum intensity of alcohol consumption, on the other hand, did not correlate with visual loss on multivariate analysis ( OR 2.75, 95% CI 0.76- 10.02, P = 0.125). The authors concluded that the VF- 14 provides a useful tool in assessing visual dysfunction in LHON and that smoking may contribute to reduced visual function. The role of alcohol consumption is not so clear. ( IN2- 1.004) Valerio Carelli and colleagues ( Bologna, Italy) reported a correlation in LHON between axonal mtDNA copy number and the pattern of neurodegeneration in optic nerve cross sections. Their conclusions were based on a post- mortem analysis of 2 LHON/ 11778 patients ( 4 eyes) and 6 control subjects ( 12 eyes). They found that the mtDNA content/ central regions of the optic nerve was significantly lower ( P < 0.05) than in the superior, nasal, and inferior regions. They concluded that the papillomac-ular bundle axons of the temporal quadrant are the most vulnerable in LHON and have the lowest amount of mtDNA. The mechanism by which reduced mtDNA copy number and ganglion cell death are linked remains to be elucidated. ( P04.073) Chiara La Morgia and colleagues ( Bologna, Italy) assessed the integrity of the retinohypothalamic tract ( RHT) that originates from the intrinsically photosensitive melanopsin- containing retinal ganglion cells ( ipRGCs) in mitochondrial optic neuropathies. They studied 5 patients with LHON, 4 patients with dominant optic atrophy, and 9 control subjects. They assessed optic neuropathy severity by OCT. A melatonin suppression test ( MST) was performed, collecting plasma samples hourly from 12: 30 pm to 3: 30 am and performing a nighttime suppression test using monochromatic ( 470 nm) blue light between 1: 30 and 3: 30 am. The suppression score was calculated by comparing the suppression night melatonin level to the baseline night level. A significant suppression of melatonin plasma levels by light was observed in control subjects ( 67 6 17%) and in patients ( LHON 65 6 25%; DOA 57 6 33%) without a difference between groups. From post-mortem eyes of 2 patients with LHON and 2 control subjects, immunohistochemical analysis of retinal sections through the optic nerve head revealed a relative preserva-tion of ipRGCs in patients with LHON compared with control subjects, despite the severe loss of total RGCs. The authors concluded that in LHON and DOA, there is preservation of circadian phototransduction. Their autopsy study in LHON suggests that this may relate to sparing of ipRGCs. ( IN5- 2.00) NEUROMUSCULAR DISEASE Mark Kupersmith ( New York, NY) conducted a retrospective analysis of patients with ocular myasthenia gravis ( OMG) to determine the effect of chronic low- dose corticosteroids in controlling diplopia and preventing pro-gression to generalized myasthenia gravis ( GMG). Patients who had OMG for longer than 4 years or who subsequently developed GMG were identified. Unless contraindicated, patients with diplopia generally received prednisone therapy. Diplopia was present at the last examination in 27% of the prednisone- treated group and 57% of the prednisone- untreated group. Although the study is limited by its retrospective design, the authors concluded that in patients with OMG, prednisone may reduce the incidence of GMG, delay its onset, and control diplopia. ( S55.002) Michael Hehir and colleagues ( Charlottesville, VA) retrospectively evaluated the outcomes of a large cohort of patients with GMG treated with mycophenolate mofetil ( MMF). Two recent randomized controlled trials ( RCTs) have failed to demonstrate benefit of MMFover prednisone alone as initial immunotherapy, but these studies were limited by short duration or sensitive outcome measures. The authors reviewed the clinical outcomes of seropositive patients with myasthenia gravis receiving MMF mono-therapy ( n = 35) or MMF + prednisone therapy ( n = 68) for longer than 3 months. Patients were assessed by MG-Manual Muscle Test ( MMT) score and MGFA Post- Intervention Status ( PIS). Median follow- up was 2.2 years; 60% were followed > 24 months. Patients treated with MMF monotherapy began to improve between 6 and 12 months; 80% of patients followed for > 24 months had an MMT < 4 and PIS of minimal manifestations or pharma-cologic remission. Patients treated with combination therapy had a prednisone dose reduction after 12 months; at > 24 months, 53% had been weaned completely from 367 Neuro- Ophthalmology at Large J Neuro- Ophthalmol, Vol. 29, No. 4, 2009 prednisone and 75% took < 7.5 mg prednisone/ day. Three patients discontinued MMF because of side effects. The authors concluded that MMF is an effective treatment as either monotherapy or adjunctive therapy to prednisone. The long follow- up demonstrated a corticosteroid- sparing effect of MMF during the second and third year of therapy that could not be demonstrated by studies of shorter duration. This study, however, did not include patients treated with prednisone alone, limiting a full evaluation of the benefit of MMF. ( S55.001) NEURO- OTOLOGY G. Michael Halmagyi and colleagues ( Sydney, Australia) reported the utility of the horizontal head impulse test ( HIT) to detect gentamicin- induced vestibu-lotoxicity. In the HIT, the patient's head is rapidly rotated by the examiner while the patient fixates on the examiner's nose. If there is a deficit in the vestibulo- ocular reflex, one sees a refixation saccade at the end of the rotation. The authors quantified vestibulotoxicity by measuring the gain of the horizontal vestibulo- ocular reflex ( VOR) at different accelerations ( 750 patients demonstrated an essentially symmetric deficit of HIT gain along a continuous spectrum from normal to complete bilateral vestibular loss). The deficits occurred even at the slowest head accelerations. Across subjects, HIT gain correlated better with caloric testing ( rho = 0.85, P = 0.0001) than with rotational testing ( rho = 0.55, P = 0.046). The cumulative amplitude of overt catch- up saccades was 5.6 times greater in patients than in control subjects. The authors concluded that the horizontal HIT is a sensitive measure of gentamicin- associated vestibulotoxicity. ( S57.001) Jorge Kattah and colleagues ( Peoria, IL) studied the localizing value of skew deviation in patients with acute vestibular syndrome ( AVS) in a cross- sectional study over 9 years. Their cohort consisted of consecutive patients with AVS who presented with vertigo, nausea/ vomiting, un-steady gait, and/ or head motion intolerance and had at least one stroke risk factor. They underwent structured exam-ination, including horizontal HIT and cover testing for ocular alignment, within 72 hours of symptom onset, and neuroimaging. CNS causes were confirmed by MRI or CT. A total of 101 patients with AVS were enrolled, of whom 25 had a peripheral vestibulopathy and 76 had a brainstem cause ( 72 ischemic strokes, 2 demyelinating lesions, 1 hemorrhage, and 1 anticonvulsant toxicity). Skew deviation ( mean 9.9 prism- diopters, range 3- 20 prism- diopters) was present in 15% of the total study population and correlated with brainstem involvement: it occurred in 4% ( 1 of 25) with a peripheral lesion, 4% ( 1 of 28) with pure cerebellar lesions, and 27% ( 3 of 48) with a brainstem lesion ( P = 0.004). Of note, the presence of skew deviation correctly predicted the presence of lateral pontine stroke in 2 of the 3 patients in whom positive results for a horizontal HIT had suggested a peripheral cause. The authors concluded that although skew deviation is an insensitive marker of central pathologic changes, when it is detected it is reasonably specific for brainstem involvement among patients with AVS. ( S57.002) David Newman- Toker and colleagues ( Baltimore, MD) evaluated the cost- effectiveness of diagnostic decision support ( DDS) relative to current clinical practice for identifying stroke among patients with dizziness in the emergency department ( ED). DDS systems are interactive computer programs that use a software algorithm and patient data to suggest diagnoses that assist the clinician. The authors evaluated DDS by combining literature and expert- derived estimates of probabilities and utilities with local hospital cost estimates to compare hypothetical diagnostic strategies. The base case was a 65- year- old patient in average health without disability presenting either with new persistent dizziness (> 24 hours, at risk for stroke) or new transient dizziness (< 24 hours, at risk for transient ischemic attack [ TIA]). The alternative diagnostic strategies were ‘‘ CT all,'' ‘‘ MRI all,'' and ‘‘ admit all.'' Outcome measures were cost, quality- adjusted life- years ( QALYs) and incremental cost- effectiveness ratios ($/ QALY). The authors found that for persistent dizziness, DDS operating at 92% sensitivity and specificity ($ 10,400/ QALY) or ‘‘ MRI all'' ($ 12,200/ QALY) could outperform current practice at acceptable cost. ‘‘ CT all'' would be less effective and ‘‘ admit all'' would not be cost- effective ($ 190,000/ QALY beyond ‘‘ MRI all''). For transient dizziness, DDS operating at 85% sensitivity and specificity ($ 81,400/ QALY) could outperform current practice at moderately acceptable cost. ‘‘ CTall'' and ‘‘ MRI all'' would provide less quality for the cost, and ‘‘ admit all'' would not be cost effective ($ 379,000/ QALY beyond current practice). The authors concluded that bedside DDS could reduce cerebrovascular misdiagnosis among acutely dizzy patients at acceptable societal cost. ( P04.083) Yoon- Hee Cha and colleagues ( Los Angeles, CA) evaluated the association between benign recurrent vertigo ( BRV) and migraine by studying 208 patients with BRV recruited through a university neurotology clinic with a standardized questionnaire- based interview. In their study, 180 of 208 patients ( 87%) met the International Classifi-cation of Headache Disorders 2004 criteria for migraine, 112 with aura ( 62%) and 68 without aura ( 38%); 28 ( 13%) did not meet criteria for migraine. Among patients with migraine, 70% experienced migraine symptoms ( headache, aura, photophobia, or auditory symptoms) with some or all of their vertigo attacks, meeting the criteria for definite migrainous vertigo. The remaining 30% of patients did not experience concurrent migraine symptoms and vertigo. The 368 q 2009 North American Neuro- Ophthalmology Society J Neuro- Ophthalmol, Vol. 29, No. 4, 2009 Prasad and Moster age of onset and duration of vertigo attacks did not differ significantly between patients with migraine ( 34 6 1.2 years) and patients without migraine ( 31 6 3.0 years). In patients with migraine, the age of onset of migraine head-ache preceded the onset of vertigo spells by an average of 14 years and aura preceded vertigo by 8 years. The duration of vertigo attacks was generally between 1 hour and 1 day. The authors concluded that the high association between BRV and migraine favors its recognition as a migraine equivalent syndrome. However, many patients with BRV and migraine never have migraine symptoms during the actual vertigo attack. The recognition of vertigo attacks as part of a migraine syndrome may be obscured by its later onset relative to the onset of headache and auras. ( S46.002) MISCELLANEOUS TOPICS Suzanne Lesage and colleagues ( Baltimore, MD) evaluated the correlation between retinal vascular abnor-malities and cognition in elderly individuals. They studied 803 participants within a prospective community popula-tion study ( Atherosclerosis Risk in Communities [ ARIC]). Cognitive assessments included word fluency ( WF), digit symbol substitution ( DSS), and delayed word recall ( DWR). Retinal photographs were evaluated for small microaneurysms or hemorrhages. WF scores declined to a greater degree in people with retinopathy than in those without retinopathy ( 1.64 [ 95% CI 3.3 to 0.02] and + 0.06 [ 95% CI 0.6 to 0.8], respectively), even after adjustment for diabetes, hypertension, smoking, and apolipoprotein E allele status. Individuals with retinopathy had increased odds ( 2.18 [ 95% CI 1.02- 4.64]) of having the greatest decline on DSS. There was no association between DWR performance and retinal vascular abnormalities. The authors concluded that microvascular retinopathy correlates with cognitive measures in elderly individuals, possibly by serving as a marker for cerebral vascular disease. ( P09.126) Thomas Buchanan and colleagues ( Salt Lake City, UT) conducted an 8- year retrospective chart review to assess the demographic features of individuals with the diagnosis of photophobia. They examined other underlying diagnoses, employment status, treatments, and outcomes. The population included 63 women and 61 men, with a mean age at presentation of 37 years ( range 6 months- 94 years) and mean age of 27.3 years at onset of photophobia. Photophobia was most often attributed to migraine ( 49.2%), followed by dry eye syndrome ( 35.5%), pro-gressive supranuclear palsy ( 8.1%), prior eye trauma ( 7.3%), prior head trauma ( 4.84%), and other ocular conditions, including blepharitis ( 12.9%). No cause was found in nearly 25% of the patients, among whom most were children. Among these patients, 24% reported that the symptom interfered with quality of life and 7.4% reported depression. Glasses with FL- 41 tint were prescribed for almost 50% of the patients, among whom a majority reported benefit. The authors concluded that photophobia affects a diverse population and is associated with a variety of diagnosable conditions, including headache, traumatic brain injury, and other neurologic and ocular diseases. Depression and reduced quality of life were very common among these patients. ( P04.078) Sashank Prasad, MD Division of Neuro- ophthalmology Hospital of the University of Pennsylvania Philadelphia, Pennsylvania Mark L. Moster, MD Division of Neuro- ophthalmology Albert Einstein Medical Center Wills Eye Institute Thomas Jefferson University School of Medicine Philadelphia, Pennsylvania markmoster@ gmail. com 369 Neuro- Ophthalmology at Large J Neuro- Ophthalmol, Vol. 29, No. 4, 2009 |
