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P47 Thymectomy – role in the management of myasthenia gravis
Abstracts, UK Neuromuscular Translational Research Conference 2010 Posters / Neuromuscular Disorders 20S1 (2010) S5–S30
large scale multi-centre natural history trials of the non-dystrophic myotonias (NDM) and Andersen-Tawil syndrome (ATS). The aims of the trials are: to characterize the phenotypic spectrum associated with specific genetic defects; collate data on disease progression and evaluate investigations used in diagnosis. Our preliminary data suggest a number of key findings: the NDMs and ATS are associated with a wide phenotypic spectrum; they exhibit considerable genetic heterogeneity; the absence of mutations in a few individuals suggests that other new genes are also likely to underlie both disorders; and finally neurophysiological testing has an important role to play in diagnosis. The completion of these natural history trials will enhance our understanding of genotype-phenotype correlations, engender more accurate monitoring of the natural histories of NDM and ATS and allow us to assess endpoints for future treatment trials. P45 Poster Double-blind placebo controlled cross-over study to investigate the efficacy of mexiletine in patients with non-dystrophic myotonia in the UK D. Raja Rayan1 , E. Matthews1 , G. Barreto1 , S.V. Tan1 , L. Dewar1 , J. Burge1 , M.G. Hanna1 . 1 MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK Non-dystrophic myotonia (NDM) is characterised by muscle stiffness due to delayed relaxation of the muscle following voluntary contraction. At present there are no high quality randomised controlled trials investigating treatment for NDM. Mexiletine is a use-dependent sodium channel blocker. Anecdotal evidence and uncontrolled clinical trials have shown improvement in stiffness after administration. We are therefore looking at the efficacy of mexiletine in our NDM patients in a doubleblinded placebo controlled cross-over study in collaboration with the CINCH (Clinical Investigation of Neurological Channelopathies) study group. We aim to recruit a total of 15 patients in the UK with nondystrophic myotonia as part of 60 patients recruited internationally at 6 centres. All patients will be randomised to a 4 week course of either mexiletine or placebo. This is followed by a one week wash out period and then a 4 week course of whichever drug the patient has not yet received. Patients are examined at the beginning and end of each treatment period. The primary outcome measure is the patient’s assessment of their stiffness recorded daily via an interactive voice response diary. Secondary outcome measures include the patient’s assessment of weakness, pain and fatigue; quality of life measures with INQoL and SF-36 questionnaires; clinical myotonia assessment; quantitative assessment of grip myotonia and neurophysiology measuring CMAPs from long and short exercise tests and needle EMG. This study aims to evaluate the efficacy of mexiletine in reducing stiffness in non-dystrophic myotonia. P46 Poster Quantification of grip myotonia using a novel accelerometer device: a pilot study L. Dewar1,2 , E. Matthews1 , G. Bahlke2 , M.G. Hanna1 . 1 MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, London WC1N 3BG, UK; 2 National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK Background: Grip myotonia impedes voluntary hand-opening due to delayed muscle relaxation. Patients often describe this as muscle stiffness. Currently there are a limited number of objective measures to quantify myotonia which impedes the ability to choose reliable outcome measures for therapeutic trials. Methods: We developed an accelerometer device which was attached to the right forearm and index finger. Subjects (patients with genetically confirmed myotonic disorder and healthy
S17
controls)were instructed to grip a peg with their right hand and on command fully extend their fingers as rapidly as possible. Time taken was measured by the accelerometer. Five successive grips/hand-openings were recorded over three trials on the same day to determine the validity and intra-rater reliability of the measurements. Results: Intraclass coefficients of variation (ICC) to test for intrarater reliability of the device were high. Good agreement between measures was found using Bland & Altman’s method. A significant difference in hand-opening time was observed between the control and myotonia groups (P = 0.015, F = 9.07). Descriptive data trends illustrated different patterns of response in the subjects with different sub-groups of myotonic disorders. Conclusion: Further studies with larger cohorts and methodological refinements are required but early data indicate the accelerometer device we have devised would be a useful and reliable tool to quantify myotonia. This could be used clinically to assess response to therapy and additionally as an outcome measure in therapeutic trials. If reproducible patterns in the sub-groups of myotonic disorders are found in larger cohorts this could suggest a potential diagnostic use.
Myasthenia Gravis P47 Poster Thymectomy – role in the management of myasthenia gravis J.E. Spillane1,2 , N.P. Hirsch1,2 , D.M. Kullmann1,2 , C. Taylor1,2 , R. Howard1,2 . 1 MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, London WC1N 3BG, UK; 2 National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK Background: The role of thymectomy in the management of MG continues to be debated. In the absence of an adequate RCT, it is essential to review clinical experience. Aim: To perform a 10 year audit of cases of thymectomy for MG in a tertiary referral centre. Methods: Medical case notes of all patients who underwent thymectomy were retrospectively reviewed. Results: 79 patients were identified. 22 were male. Average age at thymectomy was 32.5. Indications for thymectomy included: persistence of generalised symptoms (62%), bulbar symptoms (6%), a combination of both (8%), ocular MG (9%) and thymoma (15%). Over 90% were AChR ab positive. 45% had an enlarged gland on mediastinal imaging. Average length of ICU post-operatively was 2.2 days. Immediate post thymectomy complications included pneuomonia (3.7%), pneumothorax (3.7%) and wound infection (2.5%). 7.5% suffered a hypertrophic scar. There were no longterm complications. Thymic histology revealed hyperplasia (47%), thymoma (22%), atrophic changes (10%) and a normal gland (21%). 77% of patients achieved an improvement in one point or more on the MGFA scale post thymectomy during follow up (6 mths–2 yrs). Conclusion: Thymectomy is commonly performed for MG and is associated with a sustained improvement in the majority of our patients. P48 Late recurrent thymoma: a case series
Poster
J.E. Spillane1,2 , N.P. Hirsch1,2 , D.M. Kullmann1,2 , C. Taylor1,2 , R. Howard1,2 . 1 MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, London WC1N 3BG, UK; 2 National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK. Background: In patients with MG, thymoma may recur many years after initial resection. Aim: To describe cases of late recurrent thymoma amongst myasthenic patients in a tertiary referral centre.
large scale multi-centre natural history trials of the non-dystrophic myotonias (NDM) and Andersen-Tawil syndrome (ATS). The aims of the trials are: to characterize the phenotypic spectrum associated with specific genetic defects; collate data on disease progression and evaluate investigations used in diagnosis. Our preliminary data suggest a number of key findings: the NDMs and ATS are associated with a wide phenotypic spectrum; they exhibit considerable genetic heterogeneity; the absence of mutations in a few individuals suggests that other new genes are also likely to underlie both disorders; and finally neurophysiological testing has an important role to play in diagnosis. The completion of these natural history trials will enhance our understanding of genotype-phenotype correlations, engender more accurate monitoring of the natural histories of NDM and ATS and allow us to assess endpoints for future treatment trials. P45 Poster Double-blind placebo controlled cross-over study to investigate the efficacy of mexiletine in patients with non-dystrophic myotonia in the UK D. Raja Rayan1 , E. Matthews1 , G. Barreto1 , S.V. Tan1 , L. Dewar1 , J. Burge1 , M.G. Hanna1 . 1 MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, Queen Square, London WC1N 3BG, UK Non-dystrophic myotonia (NDM) is characterised by muscle stiffness due to delayed relaxation of the muscle following voluntary contraction. At present there are no high quality randomised controlled trials investigating treatment for NDM. Mexiletine is a use-dependent sodium channel blocker. Anecdotal evidence and uncontrolled clinical trials have shown improvement in stiffness after administration. We are therefore looking at the efficacy of mexiletine in our NDM patients in a doubleblinded placebo controlled cross-over study in collaboration with the CINCH (Clinical Investigation of Neurological Channelopathies) study group. We aim to recruit a total of 15 patients in the UK with nondystrophic myotonia as part of 60 patients recruited internationally at 6 centres. All patients will be randomised to a 4 week course of either mexiletine or placebo. This is followed by a one week wash out period and then a 4 week course of whichever drug the patient has not yet received. Patients are examined at the beginning and end of each treatment period. The primary outcome measure is the patient’s assessment of their stiffness recorded daily via an interactive voice response diary. Secondary outcome measures include the patient’s assessment of weakness, pain and fatigue; quality of life measures with INQoL and SF-36 questionnaires; clinical myotonia assessment; quantitative assessment of grip myotonia and neurophysiology measuring CMAPs from long and short exercise tests and needle EMG. This study aims to evaluate the efficacy of mexiletine in reducing stiffness in non-dystrophic myotonia. P46 Poster Quantification of grip myotonia using a novel accelerometer device: a pilot study L. Dewar1,2 , E. Matthews1 , G. Bahlke2 , M.G. Hanna1 . 1 MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, London WC1N 3BG, UK; 2 National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK Background: Grip myotonia impedes voluntary hand-opening due to delayed muscle relaxation. Patients often describe this as muscle stiffness. Currently there are a limited number of objective measures to quantify myotonia which impedes the ability to choose reliable outcome measures for therapeutic trials. Methods: We developed an accelerometer device which was attached to the right forearm and index finger. Subjects (patients with genetically confirmed myotonic disorder and healthy
S17
controls)were instructed to grip a peg with their right hand and on command fully extend their fingers as rapidly as possible. Time taken was measured by the accelerometer. Five successive grips/hand-openings were recorded over three trials on the same day to determine the validity and intra-rater reliability of the measurements. Results: Intraclass coefficients of variation (ICC) to test for intrarater reliability of the device were high. Good agreement between measures was found using Bland & Altman’s method. A significant difference in hand-opening time was observed between the control and myotonia groups (P = 0.015, F = 9.07). Descriptive data trends illustrated different patterns of response in the subjects with different sub-groups of myotonic disorders. Conclusion: Further studies with larger cohorts and methodological refinements are required but early data indicate the accelerometer device we have devised would be a useful and reliable tool to quantify myotonia. This could be used clinically to assess response to therapy and additionally as an outcome measure in therapeutic trials. If reproducible patterns in the sub-groups of myotonic disorders are found in larger cohorts this could suggest a potential diagnostic use.
Myasthenia Gravis P47 Poster Thymectomy – role in the management of myasthenia gravis J.E. Spillane1,2 , N.P. Hirsch1,2 , D.M. Kullmann1,2 , C. Taylor1,2 , R. Howard1,2 . 1 MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, London WC1N 3BG, UK; 2 National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK Background: The role of thymectomy in the management of MG continues to be debated. In the absence of an adequate RCT, it is essential to review clinical experience. Aim: To perform a 10 year audit of cases of thymectomy for MG in a tertiary referral centre. Methods: Medical case notes of all patients who underwent thymectomy were retrospectively reviewed. Results: 79 patients were identified. 22 were male. Average age at thymectomy was 32.5. Indications for thymectomy included: persistence of generalised symptoms (62%), bulbar symptoms (6%), a combination of both (8%), ocular MG (9%) and thymoma (15%). Over 90% were AChR ab positive. 45% had an enlarged gland on mediastinal imaging. Average length of ICU post-operatively was 2.2 days. Immediate post thymectomy complications included pneuomonia (3.7%), pneumothorax (3.7%) and wound infection (2.5%). 7.5% suffered a hypertrophic scar. There were no longterm complications. Thymic histology revealed hyperplasia (47%), thymoma (22%), atrophic changes (10%) and a normal gland (21%). 77% of patients achieved an improvement in one point or more on the MGFA scale post thymectomy during follow up (6 mths–2 yrs). Conclusion: Thymectomy is commonly performed for MG and is associated with a sustained improvement in the majority of our patients. P48 Late recurrent thymoma: a case series
Poster
J.E. Spillane1,2 , N.P. Hirsch1,2 , D.M. Kullmann1,2 , C. Taylor1,2 , R. Howard1,2 . 1 MRC Centre for Neuromuscular Diseases, UCL Institute of Neurology, London WC1N 3BG, UK; 2 National Hospital for Neurology and Neurosurgery, Queen Square, London WC1N 3BG, UK. Background: In patients with MG, thymoma may recur many years after initial resection. Aim: To describe cases of late recurrent thymoma amongst myasthenic patients in a tertiary referral centre.