Journal of Neuro-Ophthalmology, December 2007, Volume 27, Issue 4

The 59th Annual Meeting of the American Academy of Neurology

NEURO- OPHTHALMOLOGY AT LARGE The 59th Annual Meeting of the American Academy of Neurology, Boston, Massachusetts April 28- May 5, 2007 The 59th Annual Meeting of the American Academy of Neurology highlighted breakthrough research on the most critical issues facing neurologists. More than 1,500 poster and platform presentations covering the spectrum of neurology were presented. We have summarized material of interest to neuro- ophthalmologists. RETINOVASCULAR DISEASE The results of local intra- arterial thrombolysis for CRAO with tissue plasminogen activator ( tPA) in the ophthalmic artery were reported. All patients received " conventional therapy" with paracentesis and oxygen/ carbon dioxide rebreathing with or without tPA. In the 21 patients receiving tPA, the visual acuity outcome was better than without tPA. Comparing treated and untreated patients at 24 hours: one Snellen line improvement in 71% vs 10%, 3 lines in 33% vs 5%, and final visual acuity better than 20/ 200 in 43% vs 14%. Although the results are encour­aging, this study was not randomized and the average latency from onset of visual loss to treatment with tPA was 3 hours compared with 23 hours for those receiving " conventional therapy" ( Lee AW, Baltimore, MD, S07.001). TRANSIENT ISCHEMIC EVENTS Thirty eight patients with transient global amnesia ( TGA) underwent MRI scans with diffusion- weighted imaging ( DWI). Ten were studied on an MRI with a 1.5 Tesla ( T) magnet and 28 were studied on a 3.0 T magnet. Vascular risk factors were present in 17 patients and 14 episodes were triggered after emotional upsets. Among the 28 patients studied with 3.0 T, 29% showed unilateral or bilateral acute ischemic lesions of the hippocampus. None of the 10 patients studied with 1.5 T showed lesions. The authors appropriately concluded that high Tesla MRI may be helpful in detecting subtle ischemic changes in TGA ( Lee SY, Seoul, Korea, P02.094). A study focused on atypical clinical presentations of transient ischemic attacks ( TIAs) had an interesting tangential finding. Of 395 TIA patients, 110 ( 29%) had abnormalities on DWI MRI, demonstrating that in many patients with TIA symptoms, there is some tissue infarction ( Hakan A, Boston, MA, P01.097). The effect of hospital admission on stroke risk following TIA in 552 patients was presented. Cumulative stroke risk at 30 days was lower ( 1.9%) in the group admitted ( n = 381) than in the group not admitted ( 1.9%) ( P = 0.002). These data suggest that the early risk of stroke is lower after TIA in those hospitalized than in those discharged from the emergency room ( Poisson SN, Ann Arbor, MI, S24.001). Pontine infarction may be lacunar or territorial ( involving the entire territory of a penetrating artery). A study was designed to test the hypothesis that basilar artery abnormalities and certain vascular risk factors could determine which type of infarct had occurred. Among patients with lacunar infarcts ( n = 12), there was no basilar stenosis and 75% had diabetes mellirus ( DM). Among the patients ( n = 13) with territorial pontine infarcts, 67% had basilar stenosis and only 31% had DM. These findings support the hypothesis that lacunar pontine infarct is asso­ciated with DM and territorial pontine infarct is associated with basilar stenosis. ( Royter V Los Angeles, CA, POL 109). A case- control study was designed to determine if cardiovascular risk factors increase the risk of thrombo­embolic ( TE) events during intravenous immunoglobulin ( IVIg) infusions. Nineteen cases with TE events associated with IVIg infusions were compared with an age- matched control group without TE events. No single cardiovascular risk factor was associated with TE events, but the TE risk was elevated when 2 or more cardiovascular risk factors were present ( odds ratio = 1.39). This trend became statistically significant when 4 or more vascular risk factors ( odds ratio = 10.50, 95% CI: 1.91, 57.58) were present. This study suggests that clinicians who prescribe IVIg should carefully consider the risk of stroke and myocardial infarction in elderly patients with multiple cardiovascular risk factors ( Caress J, Winston- Salem, NC, P08.122). There is a growing use of transcranial Doppler ( TCD) to screen patients with stroke or migraine for intracardiac right- to- left shunt ( IRLS). A retrospective study compared the diagnostic utility and reliability of various provocative maneuvers for the detection of IRLS using TCD. Among J Neuro- Ophthalmol, Vol. 27, No. 4, 2007 321 J Neuro- Ophthalmol, Vol. 27, No. 4, 2007 Wang and Moster 316 patients who had undergone TCD and transesophageal echocardiography ( TEE), 125 ( 39%) had IRLS. Of these, 103 ( 82%) had a positive TCD study with cough and 107 ( 89%) with valsalva; 123 ( 99%) had a positive study with either cough or valsalva, and 69 ( 55%) had a positive study at rest. Only 63 patients ( 50%) had a positive study at rest, and after cough and valsalva. This study suggested that TCD could be useful to detect IRLS, especially with provocative maneuvers ( Selim M, Boston, MA, P08.117). STROKE PREVENTION The SPARCL ( Stroke Prevention by Aggressive Reduction in Cholesterol Levels) trial found that 80 mg/ day atorvastatin reduced the future risk of stroke and major cardiovascular events in patients with stroke or TIA within the prior 6 months. In a post- hoc analysis, the effects of 80 mg/ day atorvastatin in patients with a history of carotid stenosis participating in the SPARCL trial were determined. Among the 4731 subjects with carotid stenosis, random­ization to atorvastatin treatment was associated with a 34% reduction in stroke. Major cardiovascular events ( cardiac death, fatal and non- fatal myocardial infarction, stroke and resuscitated cardiac arrest) were reduced by 36% and revascularization procedures were reduced by 50%, includ­ing a 54% reduction in carotid revascularization ( Sillesen H, Paris, France, S34.005). Low cholesterol level is a known risk factor for intracerebral hemorrhage ( ICH), and statin use increased the risk of ICH in a recent randomized trial. A single center prospective cohort study sought to determine if statin use affected 180- day outcome and risk of ICH recurrence in those who had suffered ICH. Of 483 subjects, 100 were taking a statin at the time of ICH ( 21%). Statin users and statin non- users had a similar unadjusted 180- day mortality ( 45% vs 53%) and 180- day independence rate ( 27% vs 30%). In multivariate models adjusted for ICH volume and other factors, statin use was associated with an increased 180- day survival ( OR = 2.32, 95% CI 1.27- 4.22, P = 0.006) and 180- day independence rate ( OR = 1.95, 95% CI 1.00- 3.83, P = 0.05). The study concluded that there was a mild but not significant increase in risk of ICH recurrence in statin users ( FitzMaurice E, Brookline, MA, S48.006). A retrospective study evaluated the effect of aspirin use on outcome in ischemic stroke patients undergoing acute endovascular procedures. Among 77 patients the rate of recanalization was not different in patients on aspirin ( P = 0.3). There was not an increased risk of ICH among patients on aspirin ( P = 0.2). This study suggested that use of aspirin is not associated with increased risk of ICH in patients with acute ischemic stroke who undergo endovas­cular procedures ( Alexandras L, Newark, NJ, P06.107). A study evaluated the safety of aggressive blood pressure control with nicardipine infusion prior to IV tPA for acute ischemic stroke. Retrospective chart review of 258 patients that received IV tPA was divided into three groups: no medication, labetalol, and nicardipine ( with or without labetalol) before IV tPA. The results suggested that the use of nicardipine prior to IV tPA treatment is not associated with an increased rate of ICH. Aggressive management of blood pressure higher than 185/ 110 with a rapidly active agent such as nicardipine may increase the number of patients eligible for IV tPA ( Martin- Schild S, League City, TX, S44.008). TREATMENT OF STROKE A study of a single- center 10- year experience in thrombolysis for stroke patients 80 years or older was presented. Age 80 years was independently and inversely associated with functional independence at hospital discharge ( P = 0.030) but not with increased risk of ICH or in- hospital mortality. The authors suggested that very old stroke patients may have higher baseline stroke severity and poorer functional outcomes at discharge, but that these data should not be used to exclude older patients from thrombolysis based on age alone ( Flaster M, Phoenix, AZ, P06.124). A study was designed to compare the long- term results of treatment of symptomatic intracranial stenosis with primary angioplasty ( n = 25) or stent placement ( n = 22). The mean stenosis decreased from 72% (± 21%) to 29% (± 22%) in the angioplasty- treated group and from 71% (± 10%) to 21% (± 21%) in the stent- treated group. There was no difference in time to ipsilateral stroke, repeat procedure, or death. At 24 months, major ipsilateral stroke-free survival was 69% (± SE of 17%) for angioplasty and 84% (± SE of 9%) for stent. There was a suggestion of a higher adverse event rate ( repeat procedure, stroke or death) in patients treated with primary angioplasty at 24 months ( Qureshi A, Bloomfield, NJ, P07.126). CAROTID ARTERY STENTING A single- center prospective study of 127 patients was undertaken to determine the risk of carotid artery stenting ( CAS) in patients with pre- occlusive lesions (> 90% steno­sis) or the " string sign" of severe narrowing distal to the stenosis. The incidence of stroke and vascular death was 6.3%. This study suggested that severe ICA stenosis can be safely treated with protected CAS but the presence of a string sign may be an angiographic predictor of peri- procedural complications ( Mazighi, M, Paris, France, P07.127). CEREBRAL VENOUS THROMBOSIS In a group of 230 consecutive patients with cerebral venous thrombosis ( CVT), 9 patients had isolated CVT of 322 © 2007 Lippincott Williams & Wilkins AAN Meeting J Neuro- Ophthalmol, Vol. 27, No. 4, 2007 the posterior fossa. All patients had subacute presentation- 4 with cerebellar symptoms and 5 with symptoms of intracranial hypertension. Three cases were idiopathic, three associated with the puerperium, and one each with oral contraceptive use, anemia, and dehydration. CT was nonspecifically abnormal in 5 patients, showing cerebellar infarction with mass effect in 5 patients and hemorrhage in 2. MRI was abnormal in 8 of 9 patients who had the study, showing venous sinus thrombosis. One patient was diag­nosed by autopsy. Two ( 22%) patients died in the acute stage, one patient was discharged in a vegetative state; functional outcome was favorable in 6 ( 67%) patients. Initial diagnosis ( tumor, arterial stroke) was often incorrect ( Ruiz- Sandoval JL, Queretaro, Mexico, PO 1.098). A randomized study comparing the treatment of CVT with unfractionated heparin or low molecular weight hep­arin ( LMWH) was presented. Thirty five patients received unfractionated heparin in a dose of 800- 1000 U/ hour in infusion form, maintaining aPTT in range of 1.5- 2 times normal for a duration of 7- 10 days and 40 patients received LMWH 200 anti X- a units/ kg/ day in 2 divided doses for 7- 10 days. Oral anticoagulants were continued subse­quently for 3- 12 months, maintaining INR of 2- 3. In the unfractionated heparin group at 90 days, complete recovery was observed in 29 cases, partial recovery of 3 cases, and death in 3 cases. In the LMWH group, complete recovery was observed in 34 patients, partial recovery in 3 patients, and death in 3 cases. The authors concluded that anti­coagulation is safe in CVT, even with hemorrhagic infarcts, carrying a morbidity and mortality of less than 10%. LMWH was found to be more cost effective, having fewer side effects and no requirement for lab monitoring ( Modi M, Chandigarh, India, P01.099). DURAL FISTULA A retrospective analysis of 27 consecutive dural carotid- cavernous fistula ( DCCF) patients was performed to determine the efficacy of treatment by transvenous embolization. Orbital and neuro- ophthalmological symp­toms were the most common clinical presentation at diagnosis ( n = 25). Venous drainage of the fistula involved the ipsilateral superior ophthalmic vein in 24 patients, the contralateral cavernous sinus in 6, and a lep to - meningeal vein in 5 cases. Twenty patients received endovascular treatment either via a transvenous ( n - 16) or a transarterial approach ( n = 4). Complete occlusion of the fistula was obtained in 87% of patients treated by the transvenous approach and in 25% of patients treated by the transarterial approach. One cerebral hemorrhage occurred after trans­venous embolization of a DCCF with lep to- meningeal drainage. On follow- up, all patients treated by the trans­arterial route remained symptomatic whereas 71% of patients treated by the transvenous route were asymptom­atic. Although the numbers are small, this study suggests that transvenous embolization may be a safe and effective endovascular approach in patients with DCCF ( Theaudin M, Paris, France, P05.019). CEREBRAL ANEURYSM A study compared endovascular and surgical approaches for unruptured intracranial aneurysm from Nationwide Inpatient Survey ( NIS) data. In a two- year period, there were 19,648 admissions for unruptured intra­cranial aneurysms. Surgical and endovascular treatment was performed in 7,543 and 380 patient admissions, res­pectively. There was a trend for a larger proportion of patients aged 65 years or greater to be treated with endo­vascular treatment ( P - 0.06). The length of hospitalization was shorter in patients treated with endovascular treatment ( 6 ± 0.5 versus 7 ± 0.2, P = 0.009). There was a trend toward a higher rate of discharge home ( rather than to a long term medical care facility) for patients treated with endovascular treatment ( 85% vs 76%, P = 0.08). Endovascular treatment maybe associated with shorter length of hospitalization and higher rates of discharge to home ( Divani A, Newark, NJ, P05.036). LEBER HEREDITARY OPTIC NEUROPATHY A study sought to determine if an increase in mitochondrial DNA copy number is a compensatory strategy in Leber hereditary optic neuropathy ( LHON) in 35 patients, 57 unaffected carriers of LHON families with the 11778/ ND4 mutation, and spouses of patients and carriers, who served as controls. Patients had a significant increase in mtDNA content per cell compared to controls but not as much of an increase as in unaffected carriers. These results suggest that increasing mtDNA may be a strategy of protection and may be successful in unaffected mutation carriers ( Carelli V, Bologna, Italy, S07.002). NONARTERITIC ISCHEMIC OPTIC NEUROPATHY A retrospective review found that 23% of 727 consecutive patients with nonarteritic ischemic optic neuropathy ( NAION) were afflicted when they were below the age of 50 years. Similar risk factors to older patients were found, but there was a relatively high risk of involvement of the fellow eye at 41% after a mean duration of 12 months. Only 6% had ipsilateral recurrence. Hyper­tension was found in 35%, DM in 21%, smoking in 29%, hypercholesterolemia in 20%, and small cup/ disc ratio in 84%. Visual function was better in the younger group than the older group ( Bruce B, Atlanta, GA, POL 138). 323 J Neuro- Ophthalmol, Vol. 27, No. 4, 2007 Wang and Moster INFLIXIMAB AND OPTIC NEUROPATHY A 79- year- old woman presented with blurred vision and decreased color perception and had finger counting at 2 feet OD and 20/ 50 OS, impaired color perception, right inferior quadrantanopia, and extensor plantar responses. Brain MRI revealed multi- focal, cystic- appearing, periph­erally enhancing lesions involving both occipito- parietal and temporal lobes. The optic nerves showed increased T2 signal and mild enhancement bilaterally. CSF exam was normal except for slightly elevated myelin basic protein level ( 2.7 ng/ mL). She underwent stereotactic brain biopsy of an occipital lesion. The pathology showed a non­neoplastic active inflammatory destructive white matter process with demyelination. In- situ hybridization for JC virus DNA was negative. Infliximab was suggested as the cause ( Halker RB, Rochester, MN, P06.078). MULTIPLE SCLEROSIS The 15- year data from the Optic Neuritis Treatment Trial were reported. The most predictive feature for the subsequent development of clinically definite multiple sclerosis ( CDMS) remained the brain MRI. In contrast to the 10- year data, where patients were stratified into 0 vs 1 or more intracranial white matter lesions, the 15- year data showed increasing risk with an increase in the number of lesions. The patients without MRI lesions had a 23% CDMS conversion rate, those with one or two lesions had a 56% CDMS conversion rate, those with 3 to 6 lesions had a 71% CDMS conversion rate, and those with more than 6 lesions had a 74% CDMS conversion rate ( Eggenberger E, East Lansing, MI, LPS0.001). A study was done to evaluate the 2 different McDonald criteria for dissemination in space in patients with demyelinating " clinically isolated syndromes" ( CIS) to see which is better in predicting subsequent conversion to CDMS. The first criterion was MRI lesions alone and the second was MRI lesions and positive oligoclonal bands ( OCB) in the cerebrospinal fluid ( CSF). Fifty- eight patients with CIS were prospectively studied with follow- up at 5 years. The sensitivity of MRI lesions alone was 73.53%, specificity was 87.50%, and accuracy was 79.31%. The presence of at least two MRI lesions plus oligoclonal bands yielded a sensitivity of 94.29%, a specificity of 95.65, and an accuracy of 94.82%. The presence of OCB plus two MRI lesions is highly accurate in predicting CIS conversion to CDMS. MRI criteria alone have a high specificity but less sensitivity and accuracy than MRI plus OCB ( Alvarez- Cermeno JC, Madrid, Spain, S22.004). In a 20- year follow up study on 85 patients with CIS, MS developed in 55 ( 64%), in 88%> with an abnormal baseline MRI scan and in 19% with a normal baseline MRI scan. Among those who developed MS, 22 had developed the secondary progressive ( SP) form and 33 the relapsing-remitting ( RR) form at follow- up. T2 lesion volume at baseline and at 20 years correlated moderately with EDSS ( P < 0.003). The estimated rate of lesion growth was 2.24 cm3 per year in SPMS and 0.79 cm3 per year in RRMS. The difference of 1.45 cm3 per year was highly significant ( P < 0.001). The study suggested that lesion load contin­ues to increase for at least 20 years in relapse- onset MS and that the rate of lesion growth is higher in SPMS than in RRMS ( Fisniku LK, London, United Kingdom, S42.004). The outcome of patients with subclinical MRI " demyelinating lesions" was the subject of 2 reports. A group of 7 women and 3 men with MRI white matter lesions discovered during evaluation of headaches were followed for a mean of66.4 ± 41.6 months after the initial MRI. Using the McDonald criteria, 50% of the patients converted to MS over a mean follow- up period of 48.2 ± 30.3 months. Mean age at initial MRI tended to be older for converters ( 44.8 ± 15.6) than non- converters ( 26.0 ± 7.1) ( Siva A, Istanbul, Turkey, P04.069). A study reported the 5- year MRI and clinical follow-up in 30 patients with subclinical MRI demyelinating lesions found during investigation of headache ( 14), migraine ( 6), craniocerebral trauma ( 3), depression ( 3), endocrinopathies ( 2), epilepsy ( 1), and cognitive deterio­ration ( 1). The mean time for second brain MRI was 6 months. At that time, 80% had developed MRI evidence of dissemination of disease in time and space. Eleven patients developed a clinical episode of demyelination, consisting of optic neuritis in 5, brainstem dysfunction in 3, sensory symptoms in 2, and cognitive deterioration in 1. The mean time between the first brain MRI and CIS was 2.3 years ( 0.8- 5) ( Lebrun C, Nice, France, P04.082). These two studies demonstrate that coincidentally finding MS lesions on MRI carries risk of subsequent CDMS in a manner similar to having a CIS. Several analyses of the association of MS with other immune diseases were reported. A study of 31044 sub­jects came from the Sample Adult file of the 2002 National Health Interview Survey ( NHIS). The MS population ( N = 89) had an increased prevalence of asthma ( 26.5% vs 10.6%, P < 0.0001), chronic bronchitis ( 11.2% vs 4.4%, P = 0.004), inflammatory bowel disease ( 18.7% vs 5.5%, P < 0.0001), thyroid disease ( 13.1% vs 6.9%, P = 0.08), allergies to food/ odor ( 22.7% vs 6.9%, P < 0.0001), allergies to medication ( 20.6% vs 13.0%, P = 0.06), and skin problems ( 14.3% vs 8.7%, P = 0.07) compared to the general population. Subjects were at higher risk of having MS if they had asthma ( OR = 3.1, 95% CI 1.8- 5.3), chronic bronchitis ( OR = 2.7, 95% CI 1.4- 5.4), inflammatory bowel disease ( OR = 4.0, 95% CI 2.- 7.8), thyroid disease ( OR = 2.0,95% CI 0.9- 4.5), allergies to food/ odor ( OR = 4.0, 324 © 2007 Lippincott Williams & Wilkins AAN Meeting J Neuro- Ophthalmol, Vol. 27, No. 4, 2007 95% CI 2.1- 7.6), allergies to medication ( OR = 1.7, 1.0- 3.1), and skin disease ( OR = 1.8, 95% CI 1.0- 3.2). Age and sex- adjusted logistic regression showed that the presence of at least one of these immune- mediated conditions increased the odds of having MS by a factor of 2.8 ( 95% CI 1.8- 4.4, P < 0.0001). There was an exponential relationship between the number of simultaneously diagnosed im­mune- mediated conditions and the odds of having MS ( Finkelstein J, Baltimore, MD, P04.067). Prior small epidemiologic studies have suggested that psoriasis and rheumatoid arthritis ( RA) are associated with an increased risk of MS. A case- control study using data from the General Practice Research Database, containing the electronic medical records of about 5% of the UK population, identified 4423 cases with demyelinating condi­tions ( 73% MS, 21% optic neuritis, 3% transverse myelitis) and used 22,115 controls. Psoriasis was not associated with an increased risk of demyelination and there was an inverse association with RA ( Mines D, Collegeville, PA, P04.081). Three OCT studies produced results that support the use of RNFL thickness as an outcome measure in clinical trials of neuroprotective or neuro- reparative drugs in MS. One OCT study of MS patients found that RNFL thinning correlates with brain atrophy ( Gordon- Lipkin E, Baltimore, MD P02.044). Another OCT study found that RNFL thickness was strongly associated with brain volume and was inversely associated with disability ( Grazioli E, Buffalo NY, P02.050). A third study looking at inter- rater and cross- center reproducibility of OCT found that there is good reproducibility in both ( Cettomai D, Baltimore, MD, P02.051). Improvement in motor function has been reported in MS patients treated with fampridine ( 4- aminopyridine). A Phase 3 multi- center trial of oral fampridine found had a higher proportion of responders in the treated than in the placebo group ( 34.8% vs 8.3%; P < 0.001), with improvement in walking speed ( Goodman A, Rochester, NY, S32.003). A comparative study of intravenous mitoxantrone ( MTX) and cyclophosphamide ( CTX) in MS was reported. Seventy- five patients received MTX ( 31 RR, 44 secondary progressive) and 78 CTX ( 15 RR, 63 SP). There was no significant difference in time to first relapse but time to progression was slightly shorter in MTX than in CTX patients. Active MRI scans were reduced by 69% in MTX and 63% in CTX patients ( P = 0.10). Side effects led to discontinuation of therapy in a significantly higher proportion of CTX patients. CTX may represent a thera­peutic alternative to MTX for very active/ progressive MS ( Zipoli y Florence, Italy, P06.076). Combining intramuscular interferon beta la ( EVI IFN ( 3- la) with immunosuppressive agents might theoretically improve treatment efficacy A double- blind, placebo- controlled study compared the efficacy of EVI IFN ( 3- la plus azathioprine ( AZA) alone or with prednisone, with that of IM IFN ( 3- la monotherapy. There were no significant differences in dis­ability progression among the treatment groups at 2 and 5 years ( Havrdova E, Buffalo, NY, P06.089). A study compared the side effects of high doses of intravenous and oral methylprednisolone ( MP) in MS. Patients received 1 g/ day IV MP for 3 to 5 days ( 58 courses) or 1 g IV MP the first day and 1 g orally/ day for 2 days ( 59 courses). The frequency of side effects was similar in the 2 protocols and included metallic taste ( 74% vs 78%), headache ( 34.5% vs 45.8%), digestive manifestations ( 27.6% vs 34%), flushes ( 46.6% vs 40.7%), cutaneous eruption ( 8.6% vs 13.6%), insomnia ( 51.7% vs 42.4%), psychiatric manifestations ( 36.2% vs 47.5%), infections ( 5.4% vs 5.1%), and palpitations ( 19% vs 30.5%). One patient had a slight hypokalemia. Most symptoms dis­appeared rapidly after the last pulse of MP. This study suggests that the side effects of high doses of MP did not differ when the medication was given IV or orally ( Le Page E, Rennes, France, P06.100). BECOME is a randomized, prospective study com­paring the efficacy by MRI parameters of standard doses of Betaseron ( interferon [ IFN] ( 3- lb) ( Bayer HealthCare Pharmaceuticals, Wayne, NJ) and Copaxone [ glatiramer acetate ( GA)] ( Teva Pharmaceutical Industries Ltd., Petach Tikva, Israel) in patients with relapsing MS over 2 years. A total of 75 patients were randomized to receive either IFN ( 3- lb ( 36 patients) or GA ( 39 patients). Using 3.0 T MRI, no difference was observed in the development of new lesions between the two groups ( Lincoln JA, Valencia, Spain, S42.005). NEUROMYELITIS OPTICA A study of neuromyelitis optica ( NMO) IgG antibody ( Ab) in 130 patients with active RR MS found that none of the patients had measurable NMO antibody. The rationale for the study was that prior reports comparing NMO and MS patients may have been biased by including stable inactive MS patients and that NMO Ab might be related to disease activity as an epiphenomenon of active inflamma­tion. The patients in this study all had at least one relapse in the past year, were off immunomodulatory agents for at least 2 months, and were being enrolled in a rituximab trial. These results support the high degree of specificity of NMO Ab for NMO ( Smith C, San Francisco, CA, P01.039). A study reported the prevalence of NMO Ab in 20 patients from 2 medical centers who met the 1999 diagnostic criteria for NMO. Only 6 patients ( 30%) had the Ab. Time from symptom onset was much greater in those with the Ab ( 13.5 years) than in those without Ab ( 5.5 years). Extensive spinal cord involvement was seen in 50% 325 J Neuro- Ophthalmol, Vol. 27, No. 4, 2007 Wang and Moster of those with Ab and in no one without Ab. This small series raises the possibility that NMO positivity may relate to duration of disease and extent of spinal cord involvement ( Glisson CC, Philadelphia, PA, POL 145). There was a study of NMO Ab prevalence in patients with NMO, MS, and controls with or without other immune diseases. NMO Ab was found in 21/ 37 patients with NMO and in 6/ 6 patients with isolated longitudinally extensive transverse myelitis ( LETM), who are considered to be at high risk for NMO. By contrast, Ab was present in only 4/ 144 patients with MS and was absent in patients with systemic autoimmune diseases ( 0/ 45) and in healthy con­trols ( 0/ 29), corresponding to a sensitivity and specificity of 56.8% and 98.3% for NMO. These findings suggest that testing for NMO Ab enables a reliable distinction to be made between NMO and MS and between NMO and other autoimmune diseases affecting the CNS ( Jarius S, Oxford, United Kingdom, P04.060). A study was designed to test the pathogenicity of the anti- aquaporin- 4 antibodies in a rat model. Adult rats were immunized with peptides corresponding to the extracellular domains of the aquaporin- 4 water channel. When anti-aquaporin- 4 antibody titers reached or surpassed titers observed in patients with NMO, the rats were injected intraperitoneally with a pro- inflammatory lipopolysaccha-ride ( LPS) that transiently increased the permeability of the blood- brain- barrier to antibodies, including the anti-aquaporin- 4 antibodies. Immunized rats injected with LPS developed weakness and motor incoordination in all four extremities, limiting their ability to walk over a grid. Prior to injection of LPS, the rats had no motor dysfunction and unimmunized rats injected with LPS did not develop weakness. This study provides hope for a preliminary rat model of NMO by pro- inflammatory LPS injection in the setting of immunization against the aquaporin- 4 water channel ( Levy M, Baltimore, MD, P04.061). A retrospective analysis of rituximab treatment of 24 cases of NMO was presented. Two patients died of intercurrent infections 10 and 12 months after last rituximab infusion. The posttreatment relapse rate was significantly lower than the pretreatment relapse rate. EDSS scores of 91% of patients stabilized or improved. Infusion-related transient side effects occurred in 25% of patients and were not dose- limiting. Rituximab was associated with a reduced number of attacks and improved or stable disability but the occurrence of two deaths raises safety concerns ( Jacob A, Port Jefferson, NY, S32.002). A study of patients with NMO or LETM was designed to determine the overlap with Sjogren syndrome. Seventeen patients diagnosed with NMO, isolated LETM, or recurrent optic neuritis had extensive serological work­ups for autoimmunity. Lip biopsies were performed for diagnosis of Sjogren syndrome. Four out of 6 patients with clinical NMO had a strongly positive lip biopsy consistent with Sjogren syndrome. Three out of 4 patients with high NMO- IgG titers had a positive lip biopsy. Five out of 5 patients with LETM had a positive lip biopsy. No patients with recurrent optic neuritis had a positive lip biopsy. Only 2/ 10 patients with a positive lip biopsy had elevated SSA or SSB. The authors concluded that a high percentage of patients with NMO or LETM have features of Sjogren syndrome ( Javed A, Oak Park, IL, P04.058). Fundoscopic examinations, fundus photography, and Stratus OCT were performed on 10 NMO patients and 13 MS patients with a history of ON. In contrast to MS, NMO patients often had narrowed arterioles that extended far into the retinal periphery and appeared to have thickened vessel walls ( 0/ 26 MS eyes, 15/ 20 NMO eyes, P < 0.0001), suggesting vascular pathology in NMO. The average RNFL was thinner in NMO patients ( 67.9 microns in NMO compared to 90.4 microns in MS, P < 0.017). Rather than being concentrated in the maculopapular bundle, thinning of the RNFL in NMO appeared to be more diffuse, involving the arcuate bundles and nasal portion of the nerve fiber layer. Distinct vascular changes on fundoscopic examination and markedly reduced RNFL thickness on OCT may eventually assist in distinguishing NMO from MS ( Green A, San Francisco, CA, S52.004). IDIOPATHIC INTRACRANIAL HYPERTENSION ( IIH) A study of idiopathic intracranial hypertension ( IIH) in African Americans included 263 white patients and 203 African American patients. Obesity, hypertension, anemia, and sleep apnea were more common in the African American patients. Visual acuity initially and at follow- up was worse in this group. Humphrey visual fields were not different at presentation but were worse at follow- up in the African Americans. The relative risk of blindness for African Americans was 3.2 for one eye and 4.8 for blindness in both eyes. The opening pressure averaged 40 cm H20 in African Americans and 34 cm H20 in whites. This pressure differ­ence was proposed as one feature that might underlie the clinical differences. This study suggests that IIH in African Americans is a relatively aggressive disease ( Bruce B, Atlanta, GA, S07.003). HEMISPATIAL NEGLECT A study of hemispatial neglect in the first 2 months following cerebellar stroke in 28 patients was presented. Based on the hypothesis that cognitive deficits occur due to disruption of reciprocal cerebrocerebellar connections, the neglect would be expected to be on the same side as the lesion. However, among the 29% who had neglect, it was equally ipsilesional and contralesional. In 12 patients who 326 © 2007 Lippincott Williams & Wilkins AAN Meeting J Neuro- Ophthalmol, Vol. 27, No. 4, 2007 had SPECT perfusion scans, no correlation of perfusion defects with side of neglect was seen. The authors speculate that vestibular disruption may have a role in this condition ( Kim EJ, San Francisco, CA, PO 1.005). VISUAL RESTORATION THERAPY IN HOMONYMOUS HEMIANOPIA A report of the role of visual restoration therapy ( VRT) in visual field improvement in 118 patients with homonymous hemianopia was presented. Visual fields were measured with suprathreshold 43 X 32° high resolution campimetry pretreatment and monthly for 6 months. Among 118 patients, the mean absolute improvement in stimuli detection was 12.3%. Improvements of > 3% were found in 85 patients ( 72.0%). Improvement did not correlate with age, duration of lesion, or whether the hemianopia was complete or partial ( Romano JG, Miami, FL, S37.005). THIRD CRANIAL NERVE PALSY A review of publications related to evaluation of third nerve palsy with digital subtraction angiography ( DSA) and computerized tomographic angiography ( CTA) was pre­sented. The author's conclusion was that CTA should be performed except in patients with no pupillary dysfunction and complete external dysfunction. If CTA is negative, DSA is indicated only if there is pupil dysfunction and complete EOM and lid dysfunction in men younger than 50 years. Patients with normal pupils and partial external dysfunction do not need DSA except if there is superior division palsy or the patient is less than 50 years old ( Fletcher WA, Calgary, AB, Canada, POL 154). MYASTHENIA GRAVIS Studies of patients with muscle- specific tyrosine kinase ( MuSK) antibody- positive myasthenia gravis ( MMG) showed some differences in response to therapy as compared to those with acetylcholine receptor ( AChR) antibody- positive MG. A study reported that Anti- MUSK antibodies were found in 31 of 67 patients with generalized AChR antibody- negative MG. In these 31 patients, treatment responses ( expressed as number improved/ number treated) were: edrophonium 9/ 16, pyridostigmine 15/ 29, prednisone 15/ 20, azathioprine 7/ 13 ( 5 combined with prednisone), cyclosporine 8/ 8 ( 6 combined with prednisone), mycophe-nolate mofetil ( MMF) 17/ 19 ( 12 combined with predni­sone), rituximab added to MMF and prednisone 1/ 1, plasma exchange ( PLEX) 21/ 23, and IVIg 4/ 9. These results indicate a generally poor response to pyridostigmine, a good response to prednisone, immunosuppressive agents, and PLEX ( Sanders D, Durham, NC, P07.029). A study reported clinical and electrophysiological features and treatment outcomes of 46 patients with antibodies to MuSK retrospectively identified from eight university- based clinics in the United States. Of these 46 patients, 33 ( 72%) had predominantly bulbar manifes­tations. Repetitive nerve stimulation ( RNS) was abnormal in 83% and single fiber EMG was abnormal in 90%. Only 15% had a good response to pyridostigmine. By contrast, a good clinical response was seen to corticosteroids in 47%, to other immunusuppressive agents in 30%, to IVIg in 20%, and to PLEX in 52%. Thymectomy was considered beneficial in 4 of 16 ( 25%) patients at three years. Overall, treatment outcome was very favorable in 74% of cases; two patients achieved complete stable remission, seven achieved pharmacologic remission, and 25 had only mild symptoms. This survey confirms that MuSK- Ab positive MG has prominent bulbar involvement and that anticho­linesterase treatment is relatively ineffective. Immunother­apy helps, with the possible exception of IVIg ( Pasnoor M, Kansas City, KS, P07.030). A prospective study of 16 patients with refractory generalized MG treated with weekly methotrexate injec­tions ( 25- 50 mg) showed that 87% improved. Only 1 patient developed a side effect of elevated hepatic enzymes which reversed on discontinuation of the drug. This study suggests that methotrexate could be an alternative drug for treatment of refractory MG ( Abdou AM, Alexandria, Egypt, P07.035). NYSTAGMUS In 117 patients with downbeat nystagmus ( DBN), 62% had an identifiable cause, including cerebellar degen­eration ( 21%), stroke ( 9%), and cervico- medullary junction malformations ( 7%). Two novel causes reported were episodic ataxia type 2 and vestibular migraine ( Wagner JN, Munich, Germany, S07.005). A randomized, double- masked, placebo- controlled trial of memantine or gabapentin in 48 patients with con­genital nystagmus ( idiopathic or associated with afferent pathway disease) was reported. Outcome measures were visual acuity, nystagmus intensity, and foveation time, and subjective questionnaires about visual and social function. Memantine and gabapentin showed a significant benefit over placebo ( P = 0.004). Patients with afferent disease had little improvement in visual acuity but eye movement recordings did show some improvement. There was no significant difference between the effects of gabapentin and memantine. This well- designed small study demonstrates that gabapentin and memantine may benefit patients with 327 J Neuro- Ophthalmol, Vol. 27, No. 4, 2007 Wang and Moster congenital nystagmus ( Gottlob I, Leicestershire, UK, S07.006). Benign paroxysmal positional vertigo ( BPPV) is often cured by canal repositioning maneuvers. A study of the recurrence rate in BPPV patients with either posterior canal BPPV ( 352 patients) or horizontal canal BPPV ( 270 patients) was presented. With horizontal canal BPPV, the recurrence rate was 4.1% at 30 days, 19% at one year, 25% at two years, 27% at three years, and 32% at six years. With posterior BPPV, the rates were 3.4% at 30 days, 21.9% at one year, and 40.8% at six years. The study shows that even after successful treatment, BPPV recurs in a significant proportion of patients and increasingly over time ( Kang J, Seoul, Republic of Korea, P01.151). MOVEMENT DISORDERS In a study of visual function in Parkinson disease ( PD), the NEI- VF25- QOL score was reduced to 79 compared to 97 for controls. Low- contrast visual acuity and contrast sensitivity best distinguished between PD patients and controls ( Ko MW, Philadelphia, PA, POL 137). Two pathologic studies of progressive supranuclear palsy ( PSP) demonstrated the challenges in diagnosing the disease. The clinical presentations and antemortem diag­noses were reviewed in 19 pathologically- proven cases of PSP. Clinically, 11 had had findings typical of PSP, two had had findings typical of PD, two had had findings typical of Alzheimer, two had had findings typical of Alzheimer and Lewy body dementia. The correct clinical diagnosis of PSP was made in only four patients. This study suggests that the diagnosis of PSP is often missed antemortem in favor of other PD- like illnesses ( Evidente VG, Scottsdale, AZ, P02.021). PSP is considered to have 2 clinical phenotypes: classic PSP ( Richardson syndrome) and PSP- parkinsonism. Among 21 consecutive patients proven pathologically to have PSP, 24% had been clinically characterized as having PSP- parkinsonism and 67% as having Richardson syn­drome. Two patients had progressive aphasia, dressing apraxia, and an alien hand, which the presenters classified as a third clinical phenotype that they called " PSP- cortical dysfunction." The post- diagnosis lifespan of the patients with PSP- parkinsonism was significantly longer ( 11.6 years) than that of the patients with Richardson syndrome ( 6.4 years) or those with those with PSP- cortical dysfunc­tion ( 5 years). Men predominated only in the Richardson syndrome cases. The PSP- parkinsonism patients did not have supranuclear palsy or falling early in the disease course and could not be easily differentiated from PD. This study, like the study described above, points out the phenotypic variance of pathologic PSP ( Kanazawa N, Niigata, Japan, P02.023). HEADACHE The efficacy of prophylactic botulinum toxin A ( BTX- A) injections in preventing migraine headache attacks is controversial. Two studies tested BTX- A in the treatment of migraine. In a study to determine whether the presence of cutaneous allodynia ( CA) is correlated with better response, 70 patients with episodic migraine were enrolled in an 8 month randomized, double- blind, placebo- controlled, cross­over study. Patients were divided according to presence of CA ( 30 with and 40 without CA) and assessed by quantitative sensory testing ( QST). Both groups were injected at baseline and after 4 months with BTX- A ( total dose 80 U) and/ or placebo ( saline). Only the patients with CA reported significant reduction ( P < 0.01) of migraine frequency and number of headache days following BTX- A treatment. This study suggests that CA could be a predictive factor for responders to BTX- A prophylactic therapy in migraine ( Relja M, Zagreb, Croatia, S25.005). A study examined the efficacy, safety, and satisfac­tion with BTX- A treatment in 61 migraine patients previ­ously failing prophylaxis due to compliance issues. This was a randomized, double- blind, single- center, placebo-controlled study ( months 1- 3) with a subsequent cross- over to open- label BTX- A treatment ( months 4- 6) for placebo-treated patients. The number of headache days and headache frequency decreased from baseline at months 2, 5, and 6 in BTX- A- treated patients but at no time point for placebo- treated patients. This study suggests that BTX- A may be a useful treatment option for migraine patients demonstrating low compliance with other prophylactic regimens ( Schreiber CP, Springfield, MO, P08.004). A study compared efficacy and safety profiles of topiramate and amitriptyline for migraine prophylaxis. Eligible subjects aged 18 years or less with episodic migraine were randomized to treatment with 50 mg topiramate twice a day ( 169 patients) or 100 mg/ at bedtime amitriptyline ( 157 patients) for 26 weeks. Topiramate resulted in statistically significant improvements in all three Migraine- Specific Quality- of- Life Questionnaire ( MSQ) domains compared with amitriptyline. Improvements in the Quality of Life- Enjoyment and Satisfaction Questionnaire- Short Form ( Q- LES- Q- SF) and Migraine Disability Assess­ment ( MIDAS) were similar for both treatments. The most commonly reported adverse events were: topiramate-paresthesias ( 30%), fatigue ( 17%), somnolence ( 12%), hypesthesia ( 11.0%), nausea ( 10%); amitriptyline- dry mouth ( 36%), fatigue ( 24%), somnolence ( 18%), weight gain ( 14%), dizziness ( 11%). This study showed that topiramate was at least as effective as amitriptyline in reduc­ing mean monthly migraine episode rates and that ami­triptyline was more likely to cause weight gain ( Dodick D, Scottsdale, AZ, P08.001). 328 © 2007 Lippincott Williams & Wilkins AAN Meeting J Neuro- Ophthalmol, Vol. 27, No. 4, 2007 PARTIAL EPILEPSY LOOKING LIKE HEMIFACIAL SPASM A 58- year- old man had excessive blinking of the left eye and upper face that was continuous for months. He reported a similar bout of facial twitching 3 years prior to presentation that had spontaneously resolved after 3 months. On examination, the movements had a tonic and clonic component and substantially attenuated or disap­peared during volitional tasks such as grimacing, tongue protrusion, and mouth opening. Video EEG showed frequent right frontotemporal epileptiform discharges associated with the left facial twitching. He experienced nearly complete resolution with 1,400 mg/ day carbamaze-pine. This case report suggests that partial epilepsy can look like hemifacial spasm even if the abnormal movements disappear during voluntary motor tasks ( Espay AJ, Cincinnati, OH, P04.056). Tracy Wang, MD Mark L. Moster MD Albert Einstein Medical Center and Wills Eye Institute Thomas Jefferson University School of Medicine Philadelphia, Pennsylvania 329