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P16.3 Neuromyotonia as a main sign of a possible new type of hereditary axonal neuropathy
S96 Conclusion: In a population with high rate of consanguinity clinical categorization enables distinction between MG and CMS in the majority of children with myasthenia. P16.3 Neuromyotonia as a main sign of a possible new type of hereditary axonal neuropathy V. Milic-Raˇ sic´ 1 *, S. Todorovic1 , J. Nikodinovic2 , J. Mladenovic2 , ´ P. DeJonghe3 , A. Jordanova3 , J. Baets4 , M. Zimo4 , M. Keckarevic5 , V. Brankovic2 . 1 School of Medicine, University of Belgrade, Serbia, 2 Clinic for Child Neurology and Psychiatry, School of Medicine, University of Belgrade, Serbia, 3 University of Antwerp, Belgium, 4 Genetics in Neurogenetics group, VIB Department of Molecular Genetics, University of Antwerp, Belgium, 5 Biological Faculty, University of Belgrade, Serbia Background: Charcot-Marie-Tooth disease (CMT) is a heterogeneous group of hereditary motor and sensory neuropathies. Prevalence of CMT in Belgrade population was 9.0/1,000,000, compatible with other European studies (Mladenovic, 2010). The most frequent type was CMT1 followed by CMT2. Aim: Clinical and genetic analysis of CMT2. Method: The diagnosis of CMT2 was established at Clinic of Neurology and Psychiatry for Children and Youth, Belgrade, using ENMC Workshop criteria (1998). Neurological disability score (NDS) was used for disability assessment (Dyck et al,1993). Conventional techniques was applied for EMNG studies (De Lisa et al.,1987) on Premier (Medelec) apparatus. Molecular genetics studies were done in the Center for Human Molecular Genetics, Belgrade and VIB Department of Molecular Genetics, Antwerpen. Results: 35 CMT2 patients (18 male, 17 female) had higher NDS score than CMT1A (Wilcoxon rank sum: p < 0.01). Weakness NDS subscore in CMT2 was statistically significantly higher than in CMT1A (Wilcoxon rank sum test: p < 0.001). Neuromyotonia (NM) was found in 9 CMT2 patients (8 female, 1 male) and we noticed very unique group of CMT patients plus NM. All of them presented with autosomal recessive trait of inheritance, very severe phenotype, axonal EMG pattern and unknown genetic defect. 17p11.2 duplication/deletion and mutation in MPZ, Cx32, MFN2 gene were excluded. Neuromyotonia wasn‘t found in any CMT1A patients. Conclusion: CMT2 is less frequent than CMT1 and more severe than the most frequent CMT1A subtype. We define clinically and neurophysiologicaly group of CMT2 patients, presenting as a possible new CMT type. Genetical analyses are in progress now. P16.4 Response to daily salbutamol in spinal muscular atrophy type III G. McCullagh1 *, M. Main1 , F. Muntoni1 , A.Y. Manzur1 , M.-C. Scoto1 , S. Robb1 . 1 Dubowitz Neuromuscular Centre, Great Ormond Street Hospital London, United Kingdom Background: Salbutamol, a beta-2 agonist, has improved muscle strength in open pilot studies of SMA and enhances SMN protein levels in-vitro. As in other centres, we offer a trial of salbutamol to children with SMA II and III aged over 3 years. Aim: To review responsiveness and tolerability to salbutamol in 18 SMA III children (16 ambulant). Methods: Physiotherapy assessments were recorded at baseline (1 and 6 months pre salbutamol), after 3, 6 and 12m of therapy and 6 monthly thereafter, with BP and 12 lead ECG pre, after 3m and yearly thereafter. Dose was 1 mg TDS, increasing after 1 week to 2 mg TDS. Children over 8y were offered slow release salbutamol 4 mg bd. Results: Age at salbutamol treatment was 4.8 18.4 y (median 9.75 y), therapy duration 1 month to 8y (median 11m). Reported benefits included increased stamina, prolonged
Poster sessions walking distance and reduced falls. Analysis of objective response measures, myometry, timed tests and functional assessments including 6 minute walk test, Hammersmith DMD Motor Ability and North Star Ambulatory assessment scales is ongoing. The non ambulant Hammersmith SMA scale showed, as expected, a ceiling effect at baseline in 44%. Salbutamol was well tolerated. Three discontinued treatment due to side effects, one rash, one tremor, one behavioural concerns (all derived motor benefit, two requested re-starting salbutamol at lower dose). Conclusions: Oral salbutamol is well tolerated and appears to improve motor ability in SMA III. Appropriate functional outcome measures for this patient group including 6 min walk test should be used in the future. P16.5 Diagnostic accuracy of stimulation single fibre EMG findings in children with DOK7 congenital myasthenic syndrome J.C. McHugh1 , S.A. Robb2 *, A.Y. Manzur2 , D. Beeson3 , F. Muntoni2 , M.C. Pitt1 . 1 Department of Clinical Neurophysiology, Institute of Child Health and Great Ormond Street Hospital, London, United Kingdom, 2 Dubowitz Neuromuscular Centre Institute of child Health and Great Ormond Street Hospital, United Kingdom, 3 Neurosciences Group, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom Background: DOK7 mutations account for a high proportion of congenital myasthenic syndromes (CMS) in childhood, but misdiagnosis is common. Early diagnosis is important as ephedrine or salbutamol treatment may improve muscle strength and reduce morbidity. Aim: To review the diagnostic accuracy of stimulation single fibre EMG (StimSFEMG) of orbicularis oculi in children with DOK7 CMS and identify any specific features which facilitate diagnosis. Methods: Data from StimSFEMG of orbicularis oculi are presented from 11 children (4 female; age range 4 months to 12 years) with a genetically confirmed DOK7 CMS diagnosis. StimSFEMG data were recorded using concentric needle electrodes at a stimulus frequency of 10Hz, using a Keypoint electromyograph. Referral diagnosis was myopathy, myasthenia, or vocal cord paralysis. The number of fibres recorded by StimSFEMG in each child was 10−77 (median 33). Results: All 11 children had abnormal jitter measurement as per automated analysis by the single fibre program: increased average mean consecutive difference (MCD) (normal 26ms) in 11/11 patients; more than 10% of individual fibres with MCD > 34 in 10/11 cases; block being present in 3/11. However, areas of normal muscle were frequently encountered, and extensive testing of the same muscle was required to ascertain abnormality in many cases. Conclusions: StimSFEMG is a very useful aid in the diagnostic evaluation of children with suspected DOK7 CMS, abnormality was present in 100% of our series by conventional quantitative analysis. However, the patchy nature of abnormality on StimSFEMG is emphasised, and extensive study of muscle is indicated where DOK7 mutations are considered. P16.6 Juvenile myasthenia gravis: characteristics of children in Kwazulu-Natal, South Africa V. Govender1 *, L. Mubaiwa1 , R. Govender1 . 1 Division of Paediatric Neurology, University of Kwazulu-Natal, South Africa Background: Juvenile Myasthenia gravis is a relatively rare condition. There is a paucity of data in the clinical profile and outcome of children with juvenile myasthenia from resource poor settings. The high incidence of HIV and tuberculosis makes the management challenging.
Poster sessions walking distance and reduced falls. Analysis of objective response measures, myometry, timed tests and functional assessments including 6 minute walk test, Hammersmith DMD Motor Ability and North Star Ambulatory assessment scales is ongoing. The non ambulant Hammersmith SMA scale showed, as expected, a ceiling effect at baseline in 44%. Salbutamol was well tolerated. Three discontinued treatment due to side effects, one rash, one tremor, one behavioural concerns (all derived motor benefit, two requested re-starting salbutamol at lower dose). Conclusions: Oral salbutamol is well tolerated and appears to improve motor ability in SMA III. Appropriate functional outcome measures for this patient group including 6 min walk test should be used in the future. P16.5 Diagnostic accuracy of stimulation single fibre EMG findings in children with DOK7 congenital myasthenic syndrome J.C. McHugh1 , S.A. Robb2 *, A.Y. Manzur2 , D. Beeson3 , F. Muntoni2 , M.C. Pitt1 . 1 Department of Clinical Neurophysiology, Institute of Child Health and Great Ormond Street Hospital, London, United Kingdom, 2 Dubowitz Neuromuscular Centre Institute of child Health and Great Ormond Street Hospital, United Kingdom, 3 Neurosciences Group, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Oxford, United Kingdom Background: DOK7 mutations account for a high proportion of congenital myasthenic syndromes (CMS) in childhood, but misdiagnosis is common. Early diagnosis is important as ephedrine or salbutamol treatment may improve muscle strength and reduce morbidity. Aim: To review the diagnostic accuracy of stimulation single fibre EMG (StimSFEMG) of orbicularis oculi in children with DOK7 CMS and identify any specific features which facilitate diagnosis. Methods: Data from StimSFEMG of orbicularis oculi are presented from 11 children (4 female; age range 4 months to 12 years) with a genetically confirmed DOK7 CMS diagnosis. StimSFEMG data were recorded using concentric needle electrodes at a stimulus frequency of 10Hz, using a Keypoint electromyograph. Referral diagnosis was myopathy, myasthenia, or vocal cord paralysis. The number of fibres recorded by StimSFEMG in each child was 10−77 (median 33). Results: All 11 children had abnormal jitter measurement as per automated analysis by the single fibre program: increased average mean consecutive difference (MCD) (normal 26ms) in 11/11 patients; more than 10% of individual fibres with MCD > 34 in 10/11 cases; block being present in 3/11. However, areas of normal muscle were frequently encountered, and extensive testing of the same muscle was required to ascertain abnormality in many cases. Conclusions: StimSFEMG is a very useful aid in the diagnostic evaluation of children with suspected DOK7 CMS, abnormality was present in 100% of our series by conventional quantitative analysis. However, the patchy nature of abnormality on StimSFEMG is emphasised, and extensive study of muscle is indicated where DOK7 mutations are considered. P16.6 Juvenile myasthenia gravis: characteristics of children in Kwazulu-Natal, South Africa V. Govender1 *, L. Mubaiwa1 , R. Govender1 . 1 Division of Paediatric Neurology, University of Kwazulu-Natal, South Africa Background: Juvenile Myasthenia gravis is a relatively rare condition. There is a paucity of data in the clinical profile and outcome of children with juvenile myasthenia from resource poor settings. The high incidence of HIV and tuberculosis makes the management challenging.