- Email: [email protected]
6.
Abstracts / Journal of Clinical Neuroscience 21 (2014) 2033–2058
6. A video-oculographic study of acute vestibular neuritis Hayley Roberts a,b, Sean McGuigan a,b, Bernard Infeld a,b, Ron Sultana a, Richard Gerraty a,b a b
Epworth HealthCare, Richmond, VIC, Australia Monash University, Clayton, VIC, Australia
The clinical signs of vestibular neuritis (VN) are spontaneous nystagmus and a positive horizontal head impulse test (hHIT). Both of these signs can be subtle and difficult to determine, especially for non-experts. Also, a normal hHIT may be due to covert saccades. Spontaneous nystagmus resolves, but many patients never recover normal vestibulo-ocular reflex (VOR) gain. Some patients with apparent acute VN have a normal examination within 24 hours. We aimed to quantify with a video oculographic device the VOR gain and catch up saccades early in acute VN, and repeat measurements daily during their hospital admission. We enrolled adults with acute VN presenting to the emergency department within 24 hours of symptom onset. We recorded the eye movement response to rapid head impulses using the ICS Impulse video-oculographic device (GN Otometrics, Taastrup, Denmark) on each day of their hospital admission. There were nine patients with acute VN. They had marked variation in initial VOR gains. Four patients had VOR gains in the normal range, despite having signs and symptoms of VN. Most patients’ VOR gains increased during their admission, but five remained in the abnormal range. Patients with lower VOR gains were less likely to improve into the normal range. We also observed a reduction in the VOR gain on the unaffected side in those patients. No patient with initially abnormal VOR gain recovered normal VOR gain and resolution of physical signs. Early video head impulse testing in the emergency department and each day of admission is feasible and well tolerated in acute VN. Quantitation of VOR gain acutely could have implications for the diagnosis of VN or pseudoneuritis, and could help select patients for corticosteroid treatment or further investigation. http://dx.doi.org/10.1016/j.jocn.2014.06.020
2035
We examined a cohort of patients with aquaporin-4 antibody seronegative neuromyelitis optica spectrum disorder (NMOSD) for serum antibodies against the autoantigen myelin oligodendrocyte glycoprotein (MOG). We performed a flow cytometry cell-based assay using live human embryonic kidney 293 cells lentivirus-transduced to express full-length surface MOG. We tested the serum of 23 adult patients with aquaporin-4 antibody seronegative NMOSD, including bilateral and recurrent optic neuritis (BON; n = 11), longitudinally extensive transverse myelitis (LETM; n = 10), and sequential BON and LETM (n = 2), as well as patients with multiple sclerosis (MS; n = 76), and controls (n = 52), for the presence of MOG antibodies (MOG-Abs). MOG-Abs were detected in 9/23 patients with aquaporin-4 antibody seronegative NMOSD compared to 1/76 MS patients and 0/52 controls (p < 0.001). MOG-Abs were detected in 8/11 BON, 0/10 LETM, and 1/2 sequential BON and LETM patients. MOG-Ab positive patients were significantly more likely to relapse, have a rapid response to steroid therapy, and relapse on steroid cessation than MOG-Ab negative patients (p < 0.05). Serial samples showed an association of MOG-Abs with relapse. While 8/9 MOG-Ab positive patients had a favourable visual outcome, one experienced sustained visual impairment, three had retinal nerve fiber layer atrophy on follow-up, and one had residual spinal disability. Antibodies to MOG have a strong association with bilateral and recurrent optic neuritis, and may be a clinical biomarker. MOG-Abs associated BON is a relapsing disorder which is frequently steroid responsive and often steroid dependent. Failure of early recognition and institution of immunotherapy may be associated with sustained impairment. http://dx.doi.org/10.1016/j.jocn.2014.06.021
8. Comparison of switch to fingolimod or interferon beta/glatiramer acetate as second line therapy in active multiple sclerosis Anna He a, Timothy Spelman b, Vilija Jokubaitis b, Helmut Butzkueven a,b, Tomas Kalincik a,b, MSBase Study Group c a
Royal Melbourne Hospital, Melbourne, VIC, Australia University of Melbourne, Melbourne, VIC, Australia c The MSBase Foundation, Melbourne, VIC, Australia b
7. Antibodies targeting myelin oligodendrocyte glycoprotein in bilateral and recurrent optic neuritis Sudarshini Ramanathan a,b, Stephen Reddel c,d, Andrew Henderson b, John Parratt e, Michael Barnett d,f, Prudence Gatt g, Vera Merheb a, Mahtab Ghadiri f, Con Yiannikas c, Steve Vucic b, Graeme Stewart g, Andrew Bleasel b, David Booth g, Victor Fung b, Russell Dale a, Fabienne Brilot a a Neuroimmunology group, Institute for Neuroscience and Muscle Research, The Kids Research Institute at the Children’s Hospital at Westmead, Sydney Medical School, University of Sydney, Westmead, NSW, Australia b Department of Neurology, Westmead Hospital, Westmead, NSW, Australia c Department of Neurology, Concord Repatriation General Hospital, Concord, NSW, Australia d Brain and Mind Research Institute, University of Sydney, Camperdown, NSW, Australia e Department of Neurology, Royal North Shore Hospital, St Leonards, NSW, Australia f Department of Neurology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia g Institute for Immunology and Allergy Research, Westmead Millennium Institute for Medical Research, University of Sydney, Westmead, NSW, Australia
Autoantibodies such as those targeting aquaporin-4 are important biomarkers in central nervous system demyelination.
This study aimed to compare the effectiveness of fingolimod with interferon beta or glatiramer acetate (IFN/GA) as second line agents in reducing relapse rates, accumulation of disability and increasing treatment persistence in active multiple sclerosis. Data was extracted from MSBase, an international multiple sclerosis patient registry. Patients were identified who had failed first line therapy with IFN/GA and had switched to either fingolimod or another IFN/ GA preparation. Propensity score matching was used to match patients in each treatment arm by baseline clinical and demographic characteristics. Paired Cox proportional hazards models was used to evaluate differences in time to first relapse and time to treatment discontinuation between the two groups. Paired t-tests were used to estimate differences in relapse frequency and change in disability. There were 692 patients switching to IFN/GA and 206 switching to fingolimod who were eligible for inclusion. The matching procedure identified 477 and 149 closely matched patients in the respective groups who were used for outcomes analyses. Follow-up was censored at 18 months post-switch (median 11 months). Patients switching to fingolimod had a lower hazard of relapse (hazard ratio 0.50, 95% confidence interval [CI] 0.39–0.64) and lower annualised relapse rates (0.31 versus 0.59, p = 0.01) compared to IFN/GA. There was no difference in disability scores between groups. The fingolimod group also had a lower hazard of treatment discontinuation (hazard ratio 0.39, 95%CI 0.28–0.53) compared to IFN/GA. Following an on-treatment relapse with IFN/GA, switching to fingolimod is
6. A video-oculographic study of acute vestibular neuritis Hayley Roberts a,b, Sean McGuigan a,b, Bernard Infeld a,b, Ron Sultana a, Richard Gerraty a,b a b
Epworth HealthCare, Richmond, VIC, Australia Monash University, Clayton, VIC, Australia
The clinical signs of vestibular neuritis (VN) are spontaneous nystagmus and a positive horizontal head impulse test (hHIT). Both of these signs can be subtle and difficult to determine, especially for non-experts. Also, a normal hHIT may be due to covert saccades. Spontaneous nystagmus resolves, but many patients never recover normal vestibulo-ocular reflex (VOR) gain. Some patients with apparent acute VN have a normal examination within 24 hours. We aimed to quantify with a video oculographic device the VOR gain and catch up saccades early in acute VN, and repeat measurements daily during their hospital admission. We enrolled adults with acute VN presenting to the emergency department within 24 hours of symptom onset. We recorded the eye movement response to rapid head impulses using the ICS Impulse video-oculographic device (GN Otometrics, Taastrup, Denmark) on each day of their hospital admission. There were nine patients with acute VN. They had marked variation in initial VOR gains. Four patients had VOR gains in the normal range, despite having signs and symptoms of VN. Most patients’ VOR gains increased during their admission, but five remained in the abnormal range. Patients with lower VOR gains were less likely to improve into the normal range. We also observed a reduction in the VOR gain on the unaffected side in those patients. No patient with initially abnormal VOR gain recovered normal VOR gain and resolution of physical signs. Early video head impulse testing in the emergency department and each day of admission is feasible and well tolerated in acute VN. Quantitation of VOR gain acutely could have implications for the diagnosis of VN or pseudoneuritis, and could help select patients for corticosteroid treatment or further investigation. http://dx.doi.org/10.1016/j.jocn.2014.06.020
2035
We examined a cohort of patients with aquaporin-4 antibody seronegative neuromyelitis optica spectrum disorder (NMOSD) for serum antibodies against the autoantigen myelin oligodendrocyte glycoprotein (MOG). We performed a flow cytometry cell-based assay using live human embryonic kidney 293 cells lentivirus-transduced to express full-length surface MOG. We tested the serum of 23 adult patients with aquaporin-4 antibody seronegative NMOSD, including bilateral and recurrent optic neuritis (BON; n = 11), longitudinally extensive transverse myelitis (LETM; n = 10), and sequential BON and LETM (n = 2), as well as patients with multiple sclerosis (MS; n = 76), and controls (n = 52), for the presence of MOG antibodies (MOG-Abs). MOG-Abs were detected in 9/23 patients with aquaporin-4 antibody seronegative NMOSD compared to 1/76 MS patients and 0/52 controls (p < 0.001). MOG-Abs were detected in 8/11 BON, 0/10 LETM, and 1/2 sequential BON and LETM patients. MOG-Ab positive patients were significantly more likely to relapse, have a rapid response to steroid therapy, and relapse on steroid cessation than MOG-Ab negative patients (p < 0.05). Serial samples showed an association of MOG-Abs with relapse. While 8/9 MOG-Ab positive patients had a favourable visual outcome, one experienced sustained visual impairment, three had retinal nerve fiber layer atrophy on follow-up, and one had residual spinal disability. Antibodies to MOG have a strong association with bilateral and recurrent optic neuritis, and may be a clinical biomarker. MOG-Abs associated BON is a relapsing disorder which is frequently steroid responsive and often steroid dependent. Failure of early recognition and institution of immunotherapy may be associated with sustained impairment. http://dx.doi.org/10.1016/j.jocn.2014.06.021
8. Comparison of switch to fingolimod or interferon beta/glatiramer acetate as second line therapy in active multiple sclerosis Anna He a, Timothy Spelman b, Vilija Jokubaitis b, Helmut Butzkueven a,b, Tomas Kalincik a,b, MSBase Study Group c a
Royal Melbourne Hospital, Melbourne, VIC, Australia University of Melbourne, Melbourne, VIC, Australia c The MSBase Foundation, Melbourne, VIC, Australia b
7. Antibodies targeting myelin oligodendrocyte glycoprotein in bilateral and recurrent optic neuritis Sudarshini Ramanathan a,b, Stephen Reddel c,d, Andrew Henderson b, John Parratt e, Michael Barnett d,f, Prudence Gatt g, Vera Merheb a, Mahtab Ghadiri f, Con Yiannikas c, Steve Vucic b, Graeme Stewart g, Andrew Bleasel b, David Booth g, Victor Fung b, Russell Dale a, Fabienne Brilot a a Neuroimmunology group, Institute for Neuroscience and Muscle Research, The Kids Research Institute at the Children’s Hospital at Westmead, Sydney Medical School, University of Sydney, Westmead, NSW, Australia b Department of Neurology, Westmead Hospital, Westmead, NSW, Australia c Department of Neurology, Concord Repatriation General Hospital, Concord, NSW, Australia d Brain and Mind Research Institute, University of Sydney, Camperdown, NSW, Australia e Department of Neurology, Royal North Shore Hospital, St Leonards, NSW, Australia f Department of Neurology, Royal Prince Alfred Hospital, Camperdown, NSW, Australia g Institute for Immunology and Allergy Research, Westmead Millennium Institute for Medical Research, University of Sydney, Westmead, NSW, Australia
Autoantibodies such as those targeting aquaporin-4 are important biomarkers in central nervous system demyelination.
This study aimed to compare the effectiveness of fingolimod with interferon beta or glatiramer acetate (IFN/GA) as second line agents in reducing relapse rates, accumulation of disability and increasing treatment persistence in active multiple sclerosis. Data was extracted from MSBase, an international multiple sclerosis patient registry. Patients were identified who had failed first line therapy with IFN/GA and had switched to either fingolimod or another IFN/ GA preparation. Propensity score matching was used to match patients in each treatment arm by baseline clinical and demographic characteristics. Paired Cox proportional hazards models was used to evaluate differences in time to first relapse and time to treatment discontinuation between the two groups. Paired t-tests were used to estimate differences in relapse frequency and change in disability. There were 692 patients switching to IFN/GA and 206 switching to fingolimod who were eligible for inclusion. The matching procedure identified 477 and 149 closely matched patients in the respective groups who were used for outcomes analyses. Follow-up was censored at 18 months post-switch (median 11 months). Patients switching to fingolimod had a lower hazard of relapse (hazard ratio 0.50, 95% confidence interval [CI] 0.39–0.64) and lower annualised relapse rates (0.31 versus 0.59, p = 0.01) compared to IFN/GA. There was no difference in disability scores between groups. The fingolimod group also had a lower hazard of treatment discontinuation (hazard ratio 0.39, 95%CI 0.28–0.53) compared to IFN/GA. Following an on-treatment relapse with IFN/GA, switching to fingolimod is