Autosomal recessive limb girdle muscular dystrophy: Prospective study and characterisation of 280 cases by immunohistochemistry and immunoblotting

Abstracts / Journal of the Neurological Sciences 333 (2013) e422–e480

Conclusion: Achieving a status of MM or better by maximum PSL dose or reduced PSL dose combined with other agent may improve the present MG status and QOL.

doi:10.1016/j.jns.2013.07.1533

Abstract - WCN 2013 No: 563 Topic: 7 - Neuromuscular disorders Effect of food on pharmacokinetics of 3,4-Diaminopyridine in rats and healthy volunteers N. Ishidaa,b, E. Kobayashic, R. Matsushitab, K. Komaid. a Department of Pharmacy, National Hospital Organization Iou Hospital, Kanazawa, Japan; bGraduate School of Natural Science and Technology, Division of Pharmaceutical Sciences, Kanazawa University, Kanazawa, Japan; cDepartment of Pharmacy, National Hospital Organization Kanazawa Medical Center, Kanazawa, Japan; dDepartment of Neurology, National Hospital Organization Iou Hospital, Kanazawa, Japan Background: 3,4-Diaminopyridine (3,4-DAP) is commonly used to treat neuromuscular diseases such as Lambert–Eaton myasthenic syndrome and multiple sclerosis; however, the pharmacokinetics of 3,4-DAP is not well understood. Objective: We aimed to investigate the effect of food on the pharmacokinetics of 3,4-DAP in rats and humans. In addition, we aimed to study the effect of food on the intestinal absorption of 3,4-DAP in rats. Material and methods: We administered single 3,4-DAP doses of 10 mg/kg orally or 2 mg/kg intravenously to Wistar male rats (n = 4– 7) and 10 mg 3,4-DAP to healthy volunteers (n = 5) in the fasting state and after meals. The intestinal absorption rate of 3,4-DAP was estimated by using a in situ closed loop method in rats. Results: The areas under the serum concentration time curve for 3,4-DAP significantly decrease by food intake, and the corresponding bioavailability values were also significantly decrease from 25.1% ±4.0% to12.1% ± 0.8% (mean ± SD; P b 0.01) in rats. In the healthy volunteers, fasting might have reduced the time to reach the maximum serum concentration (Cmax) of 3,4-DAP and elevated Cmax. In situ close loop method, food reduced the intestinal absorption rate of 3,4-DAP by 5–10%. Conclusion: These studies showed that food intake lowered the absorption of 3,4-DAP. Therefore, the administration of 3,4-DAP without food might be a candidate of improvement of the effect. doi:10.1016/j.jns.2013.07.1534

Abstract - WCN 2013 No: 660 Topic: 7 - Neuromuscular disorders Clinical picture of anti-MuSK-antibody-positive juvenile myasthenia gravis in Japan R. Nakataa, M. Motomuraa, H. Shiraishia, T. Naritaa, T. Yoshimurab, A. Kawakamia, M. Tsujihatac. aDepartment of Clinical Neuroscience and Neurology, Graduate School of Biomedical Sciences, Nagasaki, Japan; b School of Health Science, Nagasaki University, Nagasaki, Japan; cNagasaki Kita Hospital, Nagasaki, Japan Objective: The present study aimed to determine the characteristics of anti-muscle-specific receptor tyrosine kinase (MuSK)-antibodypositive juvenile myasthenia gravis (JMG) (onset before age 15). Information on JMG is limited, and they are reported to be clinically and immunologically distinct from adult onset myasthenia gravis (MG). Patients and methods: Four patients were positive for anti-MuSKantibody among 28 patients collected nationwide from 2006 through

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2009 for antibody assay in our institute. We investigated the clinical characteristics and measured IgG subclasses in these patients. Results: All four patients presented generalized MG with relatively severe clinical course. There were no thymus abnormalities. IgG subclass was dominantly of IgG4 subclass. Conclusions: The clinical characteristics and clinical course of antiMuSK-antibody-positive JMG differ from general JMG or adult-onset MG. doi:10.1016/j.jns.2013.07.1535

Abstract - WCN 2013 No: 612 Topic: 7 - Neuromuscular disorders Baff (B cell activating factor) can be the clinical marker in myasthenia gravis W. Sakaia, S. Nakaneb, T. Naritac, M. Motomurac, H. Matsuoa. aDepartment of Neurology, Nagasaki Kawatana Medical Center, Higashisonogi, Japan; b Department of Clinical Research, Nagasaki Kawatana Medical Center, Nagasaki, Japan; cDepartment of Clinical Neuroscience and Neurology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan Background: Myasthenia gravis (MG) is an antibody mediated disease in which the target autoantigen is the acetylcholine receptor (AChR) at the postsynaptic membrane of the neuromuscular junction. B cell activating factor (BAFF) is the potent B cell survival factor and is necessary for peripheral B cell differentiation and maturation. Excess BAFF promotes the survival and growth of autoreactive B cells. The previous studies have shown that serum BAFF levels in patients with MG are higher than in control subjects. BAFF may play an important role in the pathogenesis of MG. Objective: To compare serum BAFF levels in patients with AChR antibody positive MG (AChR MG) and muscle specific kinase antibody positive MG (MuSK MG). Patients and methods: We retrospectively analyzed 14 ocular AChR MG, 31 generalized AChR MG and 25 MuSK MG. We compared the serum BAFF levels with the clinical characteristics among 3 groups. Results: The serum BAFF levels in generalized AChR MG (1559.6 ± 108.6 pg/mL) were significantly higher than in MuSK MG (568.1 ± 36.3 pg/mL) and ocular AChR MG (598.1 ± 65.9 pg/mL). There was a correlation between the serum BAFF levels and disease severity in AChR MG. The serum BAFF levels of the generalized AChR MG with thymic abnormalities (1536.4 ± 728.8 pg/mL) were statistically higher than the ocular AChR MG. Conclusion: The serum BAFF levels are increased in patients with generalized AChR MG compaired to MuSK MG and ocular AChR MG. doi:10.1016/j.jns.2013.07.1536

Abstract - WCN 2013 No: 643 Topic: 7 - Neuromuscular disorders Autosomal recessive limb girdle muscular dystrophy: Prospective study and characterisation of 280 cases by immunohistochemistry and immunoblotting A. Nalini. Department of Neurology, National Institute of Mental Health and Neurosciences, Bengaluru, India Background: ARLGMD is a common disorder in Southern India due to high consanguinity. Objective: To study pattern of ARLGMD in India. Materials and methods: Prospective study of 300 cases seen between February 2010 and October 2012. All suspected cases of ARLGMD

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Abstracts / Journal of the Neurological Sciences 333 (2013) e422–e480

attending the NMD clinic underwent phenotypic characterisation, muscle immunohistochemistry (IHC) and immunoblotting (IB). Results: 280 cases biopsied, 226 had IHC and 176 of these IB. 54 patients excluded. Consanguinity—45.2%. 200 confirmed to have specific ARLGMD by IHC and/or IB. Commonest form:LGMD 2B (82/246– 33.33%). Mean age of onset—21.17 ± 6.32 (8–41 years). Mean duration—7.24 ± 5.86 (1–36 years). Mean CK—7966.7 ± 6029.6 IU/L(131– 24037). All demonstrated dysferlin deficiency on IHC/IB. Second commonest-LGMD 2I (51/246–20.73%). Mean age of onset—12.64 ± 7.17 (1–29 years). Mean duration—8.54 ± 6.50 (1–27 years) Mean CK—4059.56 ± 3210.8 (211–14667 IU/L). α-DG deficiency by IHC-9, IB-51. Third commonest LGMD 2C-F (35/246–14.23%). All confirmed by IHC/IB. Mean age of onset—5.89 ± 3.45(1–20 years). Mean duration— 4.56 ± 2.85 (1–12 years). Mean CK—8688.31 ± 6113.86 IU/L (684– 23577). Fourth group-LGMD 2A (25/246–10.16%). Age of onset— 15.52 ± 11.18 (2–41 years). Mean duration—9.84 ± 9.33 (2–37 years). Mean CK—2742.58 ± 2144.96 IU/L (286–9018). All confirmed by IB. Fifth group-LGMD 2G (8/246–3.25%). Mean age of onset—12.38 ±11.35 (5 to 40 years). Mean duration—8.50 ± 6.87 (2–23 years). CK-718-9253 IU/L (mean ± SD; 2574.4 ± 2847.52). Proximo-distal form with muscle atrophy, calf hypertrophy, foot drop. The course was slow in majority. All confirmed on IB. Last group-LGMD 2J-2 cases. Confirmed on IHC. Conclusion: Our study confirms that LGMD 2B is the most common form of ARLGMD among our cohort. Further LGMD2I and 2G have a wider existence and may be among the common ARLGMDs in Indian population. doi:10.1016/j.jns.2013.07.1537

Abstract - WCN 2013 No: 763 Topic: 7 - Neuromuscular disorders The importance of follow-up thoracic imaging in myasthenia gravis patients H. Muraia, K. Utsugisawab, S. Suzukic, T. Imaid, Y. Naganeb, M. Masudae, S. Konnof, Y. Suzukig, S. Nakaneh, J.-I. Kiraa. aDepartment of Neurology, Kyushu University, Fukuoka, Japan; bHanamaki General Hospital, Hanamaki, Japan; cKeio University School of Medicine, Tokyo, Japan; d Sapporo Medical University School of Medicine, Sapporo, Japan; eTokyo Medical University, Tokyo, Japan; fToho University Medical Center Ohhashi Hospital, Tokyo, Japan; gNational Hospital Organization Sendai Medical Center, Sendai, Japan; hNational Hospital Organization Nagasaki Kawatana Medical Center, Kawatana, Japan Background: Approximately 20–30% of myasthenia gravis (MG) patients are accompanied by thymoma. In elderly patients, extra-thymic malignancies are also a matter of concern. Although most MG patients undergo thoracic imaging at the initial diagnosis, the follow-up protocol for thoracic imaging is not clear. Objective: To elucidate the follow-up status of thoracic imaging in MG. Patients and methods: From among 676 MG patients in 11 neurological centers, we evaluated 649 patients whose disease duration was over 1 year. The latest thoracic imaging (CT or MRI) after an interval of 1 year or more from the initial scan was evaluated in each case. The rate of abnormal findings and the details of findings in cases without thymoma (group N) and with thymoma (group T) were then investigated. Results: Thoracic imaging follow-up was performed in 337 (51.9%) of MG patients studied (48.8% in group N, 74.1% in group T). The average interval was 7.3 years in group N and 7.8 years in group T. Abnormal findings were detected in 9.0% in group N and 25.2% in group T. Abnormal findings included breast cancer, swelling of lymph nodes and respiratory system infection in group N, while recurrence or enlargement of thymoma accounted for 76.9% of the abnormal findings in group T.

Conclusion: It is important to keep following up thoracic imaging in MG patients since the rate of abnormal findings is high even 7 years after onset. doi:10.1016/j.jns.2013.07.1538

Abstract - WCN 2013 No: 719 Topic: 7 - Neuromuscular disorders The initial electrodiagnostic signs that distinguish acute inflammatory demyelinating polyneuropathy from acute motor axonal neuropathy C.S.J. Lima, N. Yukib, T. Umapathic. aYong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; bDepartment of Medicine, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore; cDepartment of Neurology, National Neuroscience Institute, Singapore, Singapore Background: Guillain–Barré syndrome (GBS) is divided into 2 neurophysiological subtypes, acute inflammatory demyelinating polyneuropathy (AIDP) and acute motor axonal neuropathy (AMAN). The early electrodiagnostic findings of AIDP overlap with AMAN, leading to the latter's under-diagnosis. Serial nerve conduction studies (NCSs) are more sensitive, but not always feasible. Objective: To derive diagnostic criteria that distinguish AMAN from AIDP at presentation, by delineating their nascent electrodiagnostic features. Patients and methods: We used at least 2 serial NCSs to categorise GBS patients into AIDP and AMAN. The initial NCS was scrutinized for features discriminating the 2 subtypes. Results: Using serial NCSs, 30 GBS patients were divided into 11 AIDP, 14 AMAN, and 5 unclassified cases. The initial NCS, done at median 7 and range 2-14 days, showed prolonged distal motor latency in 7 AIDP and 8 AMAN patients. Six AIDP patients had slowing in non-entrapment sites and 4 had temporal dispersion (TD). Only 1 AMAN patient had these. Slowing at entrapment site was less specific, occurring in 8 AIDP and 3 AMAN patients. Three AIDP patients had conduction block (CB), all with slowing across the block. Seven nerves in 5 AMAN patients had CB, 5 without slowing. Conclusion: The most specific initial signs of AIDP were slowing in nonentrapment sites and TD. CMAP reduction in at least 2 nerves without TD or slowing at non-entrapment sites and non-slowing CB predict AMAN. Using these features, 22 out of 30 patients were assigned to the right GBS subtypes; current criteria were correct in 14 patients. doi:10.1016/j.jns.2013.07.1539

Abstract - WCN 2013 No: 761 Topic: 7 - Neuromuscular disorders LGMD2I: Immunohistochemical and immunoblot technique assisted identification of 51 cases with both duchenne and becker phenotype S. Modia, A. Nalinia, N. Gayathrib, M.S. Bharathc, B. Sunithab, K. Polavarapua. a Department of Neurology, NIMHANS, Bengaluru, India; bDepartment of Neuropathology, NIMHANS, Bengaluru, India; cDepartment of Neurochemistry, NIMHANS, Bengaluru, India Background: LGMD 2I is caused by mutations in fukutin-related protein gene (FKRP). Objective: To describe the phenotype and findings of immunohistochemistry (IHC) and immunoblot (IB) in LGMD2I. Materials and methods: Prospective study of 300 cases of ARLGMD seen at Neuromuscular Disorders clinic between February 2010–