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The spectrum of neuromyelitis optica
Abstracts / Journal of the Neurological Sciences 333 (2013) e358–e421
nuclear hormone receptor that specifically regulates TH17 cells by acting as a control switch for TH17 differentiation and function. We have discovered proprietary novel lead chemical scaffolds of the INV17 portfolio of small molecule RORγt inverse agonists. Objective: To establish the in vivo proof of concept of the lead clinical compound candidate INV-17 in the chronic mouse EAE model. Method: INV-17 was administered p.o. for 28 days as a prophylactic treatment in MOG35–55-induced C57BL/6 mice to assess the therapeutic benefit of preventing disease in a chronic-progressive EAE model. Result: Disease was successfully prevented in INV-17-treated mice with cumulative EAE scores (Scale: 0–5) of 3.3 ± 3.3 (p = 0.008) which is in striking contrast to 27.9 ± 6.2 of vehicle-treated animals with 100% disease incidence. Worse clinical score AUC of 26.50 ± 6.28 for the vehicle group was significantly different from 3.00 ± 3.00 (p = 0.0097) for the INV-17 group. INV-17 was well tolerated and INV-17-treated mice were unremarkable with optimal body conditions. Conclusion: The superior safety and efficacy data following chronic oral INV-17 dosing provide compelling evidence of the effectiveness of RORγt inverse agonism and support advancing INV-17 into Preclinical/ IND-enabling development stage. These findings highlight the potential promise of INV-17 as a safe & efficacious novel MS treatment. doi:10.1016/j.jns.2013.07.1327
Abstract — WCN 2013 No: 2881 Topic: 6 — MS & Demyelinating Diseases The prevalence of autoantibodies in ms patients in Riga East Clinical University Hospital, Latvia G. Karelisa,b, L. Vainsteineb, I. Mihailovaa,c. aRiga Stradins University, Riga, Latvia; bRiga East Clinical University Hospital, Riga, Latvia; c Paul Stradins Clinical University Hospital, Riga, Latvia Introduction: Multiple sclerosis (MS), lupus erythematosus (LE), antiphospholipid syndrome (AFS) are chronic, immune-mediated, relapsing–remitting disorders. Neurological symptoms and MRI can have the same picture, but pathogenesis and treatment are different. Objectives: To analyse antinuclear antibodies (ANA), antiphospholipid antibodies (APA) and lupus anticoagulant (LA) in MS patients with specific symptoms and MRI findings and determination of specificity, sensitivity in MS differential diagnosis. Methods: 31 MS patients from Riga East Clinical University Hospital were included in the study. The patients were in remission and did not get any disease modifying therapy before. The diagnosis was established in a classic way — with MRI by McDonald's criteria. Clinical symptoms, MRI, AFA IgG, IgM, LA, and ANA were analysed. Results: Of 31 patients 17 (55%) were female with mean age of 34.4 ± 9.8 and male 14 (45%), were mean age of 36.1 ± 8.8. All patients had changes in MRI according to McDonald's criteria. Spinal cord changes were detected in 90% of patients and optic neuritis in 59%. Spinal cord and optic nerve injury was noted more in females 55%. Positive autoantibody was detected in 1 female, who didn't have any clinical differences from other patients. Conclusions: 1. ANA, AFA positivity is not frequent in MS patients with classic MS symptoms and MRI findings. 2. Autoantibody tests in MS patients are to be considered when the symptoms of the disease are atypical. 3. MS patients with positive autoantibody tests, should be further reevaluated by repeating the autoantibody tests and observing the clinical symptoms, in order to review of the diagnosis on time. doi:10.1016/j.jns.2013.07.1328
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Abstract — WCN 2013 No: 2838 Topic: 6 — MS & Demyelinating Diseases The spectrum of neuromyelitis optica R. Kanesalingama, Y.K. Chiaa, G.B. Eowa, P.E.S. Easawb, M.H. Rafiac. a Penang Hospital, Georgetown, Kuala Lumpur, Malaysia; b Penang Medical College, Georgetown, Kuala Lumpur, Malaysia; c Kuala Lumpur General Hospital, Kuala Lumpur, Malaysia Background: Neuromyelits optica (NMO) is an idiopathic inflammatory demyelinating disease of the central nervous system with a predilection for the optic nerves and spinal cord with positive antiaquaporin 4 antibody. Objective: To review the clinical features of our patients who tested positive for anti-aquaporin 4 antibody. Methods: Patients referred to our clinic with positive anti-aquaporin 4 antibody were reviewed. Results: We reviewed 4 patients who had a history of transverse myelitis. 2 had a history of optic neuritis and both had recurrent myelitis and optic neuritis and were treated as mixed connective tissue disease and multiple sclerosis respectively. The remainder 2 had first onset transverse myelitis as their sole clinical finding. None were diagnosed as neuromyelits optica initially. All patients had longitudinally extensive transverse myelitis (LETM) on MRI. All 4 tested positive for anti-aquaporin 4 antibody. All patients had their diagnoses revised. 2 had definite NMO while the rest were classified as NMO Spectrum Disorder (NMOSD) as they did not meet the criteria for definitive NMO. Conclusions: All patients with longitudinally extensive transverse myelitis should be tested for anti-aquaporin 4 antibody. doi:10.1016/j.jns.2013.07.1329
Abstract — WCN 2013 No: 2822 Topic: 6 — MS & Demyelinating Diseases The effects of multiple sclerosis on women's sexuality: A controlled study H. Gumusa, Z. Akpınarb, H. Yılmazc. aKonya Education and Research Hospital, Konya, Turkey; bNecmettin Erbakan University, Konya, Turkey; c Physical Medicine and Rehabilitation, Konya Education and Research Hospital, Konya, Turkey MS is considered to have negative effects on women's sexual function. Sexual function of MS women seems to be associated with functional status and depression levels. Therefore, women with MS should also be evaluated with the suspicion of sexual dysfunction during the diagnostic and follow-up procedure. Mean age rates were 34.18 ± 8.23 in the study group and 35.32 ± 8.12 in controls (p N 0.05). While mean duration of complaints, and EDDS, BDI and total FSFI scores were 7.66 ± 5.47 years, 1.52 ± 1.43, 18.20 ± 10.56 and 20.31 ± 8.91 in patients respectively, the scores of BDI and total FSFI were 7.61 ± 5.43 and 30.55 ± 4.29 in controls, respectively. Compared to controls, BDI was higher, and total and subscores of FSFI were lower in women with MS (p b 0.001). In MS patients, a negative correlation was present between EDDS, and BDI (p b 0.001, r: −748), total FSFI (p b 0.001, r: −822), and among FSFI subscores, desire (p b 0.001, r: −779), orgasm (p b 0.001, r: −781), satisfaction (p b 0.001, r: −762), pain (p b 0.001, r: −711), lubrication (p b 0.001, r: −819) and arousal (p b 0.001, r: −812). Fifty-one premenopausal women with MS were included into the study group, and 57 healthy premenopausal women constituted controls. Functional status of MS patients was evaluated with Expanded Disability Status Scale (EDSS); depression levels with Beck Depression Inventory (BDI); and, sexual functions with Female Sexual Function Inventory (FSFI). While
nuclear hormone receptor that specifically regulates TH17 cells by acting as a control switch for TH17 differentiation and function. We have discovered proprietary novel lead chemical scaffolds of the INV17 portfolio of small molecule RORγt inverse agonists. Objective: To establish the in vivo proof of concept of the lead clinical compound candidate INV-17 in the chronic mouse EAE model. Method: INV-17 was administered p.o. for 28 days as a prophylactic treatment in MOG35–55-induced C57BL/6 mice to assess the therapeutic benefit of preventing disease in a chronic-progressive EAE model. Result: Disease was successfully prevented in INV-17-treated mice with cumulative EAE scores (Scale: 0–5) of 3.3 ± 3.3 (p = 0.008) which is in striking contrast to 27.9 ± 6.2 of vehicle-treated animals with 100% disease incidence. Worse clinical score AUC of 26.50 ± 6.28 for the vehicle group was significantly different from 3.00 ± 3.00 (p = 0.0097) for the INV-17 group. INV-17 was well tolerated and INV-17-treated mice were unremarkable with optimal body conditions. Conclusion: The superior safety and efficacy data following chronic oral INV-17 dosing provide compelling evidence of the effectiveness of RORγt inverse agonism and support advancing INV-17 into Preclinical/ IND-enabling development stage. These findings highlight the potential promise of INV-17 as a safe & efficacious novel MS treatment. doi:10.1016/j.jns.2013.07.1327
Abstract — WCN 2013 No: 2881 Topic: 6 — MS & Demyelinating Diseases The prevalence of autoantibodies in ms patients in Riga East Clinical University Hospital, Latvia G. Karelisa,b, L. Vainsteineb, I. Mihailovaa,c. aRiga Stradins University, Riga, Latvia; bRiga East Clinical University Hospital, Riga, Latvia; c Paul Stradins Clinical University Hospital, Riga, Latvia Introduction: Multiple sclerosis (MS), lupus erythematosus (LE), antiphospholipid syndrome (AFS) are chronic, immune-mediated, relapsing–remitting disorders. Neurological symptoms and MRI can have the same picture, but pathogenesis and treatment are different. Objectives: To analyse antinuclear antibodies (ANA), antiphospholipid antibodies (APA) and lupus anticoagulant (LA) in MS patients with specific symptoms and MRI findings and determination of specificity, sensitivity in MS differential diagnosis. Methods: 31 MS patients from Riga East Clinical University Hospital were included in the study. The patients were in remission and did not get any disease modifying therapy before. The diagnosis was established in a classic way — with MRI by McDonald's criteria. Clinical symptoms, MRI, AFA IgG, IgM, LA, and ANA were analysed. Results: Of 31 patients 17 (55%) were female with mean age of 34.4 ± 9.8 and male 14 (45%), were mean age of 36.1 ± 8.8. All patients had changes in MRI according to McDonald's criteria. Spinal cord changes were detected in 90% of patients and optic neuritis in 59%. Spinal cord and optic nerve injury was noted more in females 55%. Positive autoantibody was detected in 1 female, who didn't have any clinical differences from other patients. Conclusions: 1. ANA, AFA positivity is not frequent in MS patients with classic MS symptoms and MRI findings. 2. Autoantibody tests in MS patients are to be considered when the symptoms of the disease are atypical. 3. MS patients with positive autoantibody tests, should be further reevaluated by repeating the autoantibody tests and observing the clinical symptoms, in order to review of the diagnosis on time. doi:10.1016/j.jns.2013.07.1328
e363
Abstract — WCN 2013 No: 2838 Topic: 6 — MS & Demyelinating Diseases The spectrum of neuromyelitis optica R. Kanesalingama, Y.K. Chiaa, G.B. Eowa, P.E.S. Easawb, M.H. Rafiac. a Penang Hospital, Georgetown, Kuala Lumpur, Malaysia; b Penang Medical College, Georgetown, Kuala Lumpur, Malaysia; c Kuala Lumpur General Hospital, Kuala Lumpur, Malaysia Background: Neuromyelits optica (NMO) is an idiopathic inflammatory demyelinating disease of the central nervous system with a predilection for the optic nerves and spinal cord with positive antiaquaporin 4 antibody. Objective: To review the clinical features of our patients who tested positive for anti-aquaporin 4 antibody. Methods: Patients referred to our clinic with positive anti-aquaporin 4 antibody were reviewed. Results: We reviewed 4 patients who had a history of transverse myelitis. 2 had a history of optic neuritis and both had recurrent myelitis and optic neuritis and were treated as mixed connective tissue disease and multiple sclerosis respectively. The remainder 2 had first onset transverse myelitis as their sole clinical finding. None were diagnosed as neuromyelits optica initially. All patients had longitudinally extensive transverse myelitis (LETM) on MRI. All 4 tested positive for anti-aquaporin 4 antibody. All patients had their diagnoses revised. 2 had definite NMO while the rest were classified as NMO Spectrum Disorder (NMOSD) as they did not meet the criteria for definitive NMO. Conclusions: All patients with longitudinally extensive transverse myelitis should be tested for anti-aquaporin 4 antibody. doi:10.1016/j.jns.2013.07.1329
Abstract — WCN 2013 No: 2822 Topic: 6 — MS & Demyelinating Diseases The effects of multiple sclerosis on women's sexuality: A controlled study H. Gumusa, Z. Akpınarb, H. Yılmazc. aKonya Education and Research Hospital, Konya, Turkey; bNecmettin Erbakan University, Konya, Turkey; c Physical Medicine and Rehabilitation, Konya Education and Research Hospital, Konya, Turkey MS is considered to have negative effects on women's sexual function. Sexual function of MS women seems to be associated with functional status and depression levels. Therefore, women with MS should also be evaluated with the suspicion of sexual dysfunction during the diagnostic and follow-up procedure. Mean age rates were 34.18 ± 8.23 in the study group and 35.32 ± 8.12 in controls (p N 0.05). While mean duration of complaints, and EDDS, BDI and total FSFI scores were 7.66 ± 5.47 years, 1.52 ± 1.43, 18.20 ± 10.56 and 20.31 ± 8.91 in patients respectively, the scores of BDI and total FSFI were 7.61 ± 5.43 and 30.55 ± 4.29 in controls, respectively. Compared to controls, BDI was higher, and total and subscores of FSFI were lower in women with MS (p b 0.001). In MS patients, a negative correlation was present between EDDS, and BDI (p b 0.001, r: −748), total FSFI (p b 0.001, r: −822), and among FSFI subscores, desire (p b 0.001, r: −779), orgasm (p b 0.001, r: −781), satisfaction (p b 0.001, r: −762), pain (p b 0.001, r: −711), lubrication (p b 0.001, r: −819) and arousal (p b 0.001, r: −812). Fifty-one premenopausal women with MS were included into the study group, and 57 healthy premenopausal women constituted controls. Functional status of MS patients was evaluated with Expanded Disability Status Scale (EDSS); depression levels with Beck Depression Inventory (BDI); and, sexual functions with Female Sexual Function Inventory (FSFI). While