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P163 – 2479: Intra familial phenotypical variations in hypokalemic periodic paralysis
EUROPEAN JOURNAL O F PAEDIATRIC NEUROLOGY
excluded. Her spells characterized by spontaneous inward shift of left eye together with ptosis during 30 to 40 seconds without any nystagmoid movement, pupillary defect and change in consciousness. She was diagnosed as ONM. Her blood investigations, including haematological, biochemical, endocrine function tests and paraneoplastic as well as detailed vasculitic workup, were normal. Cerebrospinal fluid analysis for immunological markers, immunoglobulin (Ig) G index and oligoclonal band was all negative. The voltage-gated potassium channel (VGKC) antibody could not be detected in serum. Therefore we could not find an underlying abnormality to account for ONM. Treatment with carbamazepine 10 mg/kg twice a day was started and the attacks were completely resolved. Conclusion: After conducting a search of the medical literature using the terms “ONM” and “child” we identify only 5 previously published reports of ONM in children. To the best of our knowledge this patient is the youngest patient reported with a diagnosis of ONM.
P161 - 2452 HIF1 alpha abnormal distribution in muscle fibers in the cases of nemaline myopathy T.I. Baranich, T.V. Vinogradova, V.S. Sukhorukov, N.V. Klejmenova, A.V. Brydun, V.V. Nevstrueva, V.V. Glinkina. Department of Histology, Embryology and Cytology, Russian National Research Medical University named after N.I. Pirogov, Moscow, Russia Objective: The comparative study of immunohistochemical distribution of hypoxia marker HIF1 alpha and mitochondrial markers in striated muscle fibers of patients suffering from nemaline myopathy (NM) was performed for evaluation of tissue hypoxia’s role in the pathogenesis of NM, characterized by rod-shaped structures, which originated from the Z-disks of the sarcomeres. Methods: Fluorescence immunohistochemistry was performed. Primary mouse mitochondria monoclonal antibody, biotin conjugate (clone MTCO2) and Alexa Fluor 488 goat anti-mouse IgG as secondary antibody were used for mitochondria visualization. Visual image of HIF1 alpha was achieved by using primary rabbit polyclonal antibodies to HIF1 alpha and Alexa Fluor 555 goat anti-rabbit IgG as secondary antibody. Paraffin embedded muscle tissue section slides obtained from 3 NM patients were stained. Evaluation of the products is carried out by The EVOS® FL Imaging System. Results: Mitochondria and abnormal mitochondrial accumulations were visualized in subsarcolemmal zones of some muscle fibers. In the same muscle fibers we observed increased expression of HIF1 alpha; its localization matched with location of detected mitochondrial clusters, resulted in fluorescent lights overlapping and color change of subsarcolemmal zones luminescence. Furthermore, the most intensive fluorescence and clearly delineated HIF1 alpha clusters were observed in the areas of rods accumulation, pointing pronounced tissue hypoxia in these regions. Conclusion: While the diffuse subsarcolemmal zones of tissue hypoxia and increased number of mitochondrial clusters are often found in other myopathies, location of HIF1 alpha clusters in the rods areas is very unusual. Due to their brightness, HIF1 alpha clusters can be used in the quantification of muscular disorders severity at low magnification of fluorescence microscopy. No evidence whether these changes are secondary to rods accumulation or vice versa was found in the literature. In this way immunomorphological characterisation of energy muscle tissue metabolism of patients suffering from NM is of the current interest.
19s (2015) S1 – S152
S139
P162 - 2473 Andersen-Tawil syndrome with myopathy: Case report G. Öz Tunçer, M.G. Kutluk, P. Albayrak, S. Teber, G. Deda. Department of Pediatric Neurology, University of Ankara Faculty of Medicine Introduction: Andersen-Tawil syndrome (ATS) is a rare autosomal dominant potassium channelopathy characterized by periodic paralysis, ventricular arrhythmias, and dysmorphic features. We present a 14-year-old boy with characteristic features of ATS, and childhood onset myopathy. Case report: Fourteen years old boy admitted to our clinic with progressive muscle weakness and also described periods of severe weakness attacks for the last two years. Birth and family history were normal except 37 weeks of prematurity. At the age of four he started to fall down while walking and he descibed tiredness. At the age of 6 cardiac arrhythmia was detected. Investigations for muscle weakness showed that serum creatine kinase level was 625 U/L. Electromyography showed myopathic changes. The muscle biopsy didn’t demonstrate any specific finding. On his examination there was orbital hypertelorism, micrognathia, low set ears, clinodactyly, short stature, proximal muscle weakness of both upper and lower extremities. Deep tendon reflexes were hypoactive, Gowers sign was positive. On his electrocardiogram ventricular extrasystoles and U waves were seen. With the findings of severe worsening of limb weakness and dysmorphic features with cardiac arrhythmia ATS was suspected. Genetic testing confirmed a heterozygous mutation (R218W) in KCNJ2. After acetazolamide treatment attacks of severe muscle weakness and Gowers sign disappeared. Conclusion: Although ATS is charactized with episodes of muscle weakness, fixed myophaty had been reported only in two patients previously. All these two patients and our patient had heterozygous mutation (R218W) in KCNJ2. Because of the life threatening cardiac arrhythmias ATS must also be kept in mind in patients with fixed myophaty.
P163 - 2479 Intra familial phenotypical variations in hypokalemic periodic paralysis M. Joshi, N. Singh, M. Iqbal, P. Harijan, R. Saleem, A. Khan, N. Hussain. Department of Paediatric Neurology, University Hospitals of Leicester, Leicester, UK Objective: To describe cases of intra familial phenotypical variations in hypokalaemia periodic paralysis. Methods: Retrospective case note review. Results: We report a family of two siblings diagnosed with Hypokalaemia Periodic Paralysis who presented at different ages with different symptoms. Case1: A 16 years old boy presented with episodic weakness developed in the early hours of the morning with difficulty to get out of bed lasting up to 2 hours which was associated with reduce physical exercise, consumption of large amount of carbohydrate and missing regular meal time. His ECG was normal and CK was 363. His EMG showed features of myopathy features. His potassium level were <3.5. His clinical examination including neurological examination was unremarkable. Case 2: The 14 years old boy presented with 4 episodes of muscle stiffness where he was unable to lift his arm above the shoulder following large KFC meal. There were no other health problems. Father, paternal grandmother, paternal uncle and these 2 brothers are diagnosed with Familial Hypokalaemia Periodic Paralysis. Molecular genetic study showed both brother inherited same family genetic mutation in CACNA 1S gene (p.Arg1239His heterozygous mutation). Thyroid peroxidise antibodies were negative. Conclusion: Familial hypokalemic periodic paralysis is an autosomal dominant genetic muscle disease characterized by periodic attacks of muscle weakness associated with a decrease in serum potassium. In our cases, the clinical manifestation and the severity of the condition was
S140
EUROPEAN JOURNAL O F PAEDIATRIC NEUROLOGY
variable even within the family members with similar genotype. It is very important to check serum potassium level in a child presenting with muscle stiffness/weakness symptoms as it can be treated quickly with potassium supplement. Daily attention to restriction of vigorous exercises, reserved intake of carbohydrate and avoidance of exposure to coldness is helpful.
P164 - 2586 Congenital myasthenic syndrome in Israel: Genetic and clinical characterization S. Aharoni, A. Mimouni-Bloch, M. Daana, S. Edvardson, T. Dor-Wolman, A. Halevy, R. Cohen, L. Sagie, A.G. Engel, Y. Nevo. Department of Neurology, Schneider Children’s Medical Center of Israel, Petach Tikva, Israel affiliated to Sackler Faculty of Medicine, Tel Aviv University Objective: Congenital myasthenic syndromes (CMS) are a rare heterogeneous group of inherited neuromuscular disorders associated with distinctive clinical, electrophysiological and genetic abnormalities. Mutations in various genes of the neuromuscular junction may cause presynaptic, synaptic or postsynaptic defects. In this study, the genetic and clinical characteristics of Israeli patients with CMS were evaluated. Methods: Twentysix patients with CMS from 16 independent families in whom genetic mutation was detected were diagnosed in two Israeli medical centers. Genetic evaluation was initially performed depending on patients’ clinical symptoms and known CMS genes were sequenced. Patients of Jewish Iranian or Iraqi ethnic origin were screened directly for a known 38 A-G mutation in RAPSYN. In two patients, whole exome sequencing was analyzed. All patients’ medical records were reviewed and their clinical data, electrophysiological studies and outcome were recorded. Results: The diagnosis of CMS was confirmed in 26 patients of 16 families. Among these patients, 8 patients of 4 families had recessive mutations in COLQ, eight patients of 5 families, mutations in CHRNE, and eight patients of 5 families, mutations in RAPSN. CHRND was diagnosed in 2 patients from one family. The mean age of onset of clinical symptoms was 6 months. Ptosis, ophthalmoplegia and feeding problems were the most common symptoms. Conclusions: RAPSYN and CHRNE are the most common causes of CMS in our cohort. The second most common cause is COLQ. Specific mutations in RAPSYN, CHRNE and COLQ are detected in unique ethnic populations in Israel.
P165 - 2601 Breath-holding spells may be associated with maturational delay in myelination of brain stem S. Vurucu, M.S. Paksu, A. Karaoglu, O. Oz, H. Yaman, M. Gulgun, C. Saglam, B. Unay, R. Akin. Department of Pediatric Neurology, Gulhane Military Medical Faculty, Ankara, Turkey Objective: The aim of this study was to evaluate possible contribution of maturational delay of brainstem in the etiology of breath holding spells in children, using brainstem auditory evoked potentials. Methods: The study group included children with breath-holding spells. The control group was consisted of healthy, age and sex matched children. Age, gender, type and frequency of spell, hemoglobin, and ferritin levels in study group and brainstem auditory evoked potentials results in both groups were recorded. Study group was statistically compared with control group for brainstem auditory evoked potentials. Results: Thirty-two patients (16 boys and 16 girls), aged 4 to 60 months, and 21 healthy children (11 boys and 10 girls), aged 8 to 60 months were included in the study. The mean ages of study and control groups were 26.3±14.6 and 28.9±13.9 months, respectively. The III-V and I-V interpeak latencies were significantly prolonged in the study group compared to control group (2.07±0.2 msn;
19s (2015) S1 – S152
1.92±0.13 msn and 4.00±0.27 msn; 3.83±0.19 msn, p=0.009, p=0.03 respectively). At the same time, III-V and I-V interpeak latencies of patients without anemia in the study group compared to control group were significantly prolonged (2.09±0.24 msn; 1.92±0.13 msn and 4.04±0.28 msn; 3.83±0.19 msn, p=0.007, p=0.01 respectively). But, there were no significant difference between patients with anemia in the study group and control group for III-V and I-V interpeak latencies (p=0.17, p=0.69, respectively). Conclusion: Our results suggest that maturational delay in brainstem may have a role in the etiology of breath-holding spells in children.
P166 - 2607 Relationship between oxidative stress and chronic daily headache in children S. Vurucu, A. Karaoglu, M.S. Paksu, O. Yesilyurt, O. Oz, B. Unay, R. Akin. Department of Pediatric Neurology, Gulhane Military Medical Faculty, Ankara, Turkey Objective: Although there are reports that oxidative injury may play a role in the pathophysiology of some neurologic disorders, such as migraine and epilepsy, by disrupting and destructing cell membranes through formation of free radical and reactive oxygen species, the pathophysiology of headache is not clearly established. The aim of this study was to investigate the relationship between oxidative stress and chronic daily headache in children. Methods: Thirty-eight children with chronic daily headache (16 boys and 22 girls), aged from 7 to 15 years, were enrolled in the study. The control group consisted of 39 healthy children (17 boys and 22 girls), aged from 7 to 14 years old. The mean age was 10.9±2.2 years in both groups. Erythrocyte superoxide dismutase, catalase, glutathione peroxidase activities, and malondialdehyde levels, of all children in both groups were measured. Results: Mean erythrocyte superoxide dismutase, catalase, glutathione peroxidase activities, and malondialdehyde levels, were significantly higher in the study group than in the control group (p <0.001). Conclusion: The findings of this study suggest that oxidative stress may play a causal or consequential role in children with chronic daily headache.
P167 - 2623 The wide spectrum of neuropsychiatric profile in DMD in relation to underlying dystrophin gene mutations N. Deconinck, V. Ricotti, W. Mandy, M. Scoto, S. Messina, M. Pane, S. Laforesta, S. Baijot, G. Vita, E. Mercuri, D.H. Skuse, F. Muntoni. NMRC, Department paediatric neurology, UZ Gent, Gent, Belgium Objective: Duchenne muscular dystrophy (DMD) is associated with neurodevelopmental disorders. The aim of the study was to fully characterize the neuropsychiatric profile and to explore underlying genotype/phenotype associations with brainexpressed dystrophin isoforms. Methods: 130 DMD boys (mean age = 9.5 years) in four European neuromuscular centres (i.e. London, Brussels, Rome and Messina) were included in the study and completed IQ assessment and a screening questionnaire. Of these, 87 underwent complete neurodevelopmental assessment with structured diagnostic interview and parent reported questionnaire. The results were correlated to the underlying dystrophin gene mutations and the deduced pattern of brain dystrophin isoform expression. Results: The overall mean score on the screening neurodevelopmental questionnaire was significantly abnormal compared to the general paediatric population (p<0.001), Intelligence was overall below the population mean, with intellectual disability observed in 26.2% (n=35) of boys. Autistic spectrum disorder was reported in 20.7% (n=18), hyperactivity in 24.1% (n=21), inattention in in 43.7% (n=38) internalising and externalising problems 31.0% (n=27) and 17.2% (n=15) respectively. Neuropsychiatric disorders clustered together, with
excluded. Her spells characterized by spontaneous inward shift of left eye together with ptosis during 30 to 40 seconds without any nystagmoid movement, pupillary defect and change in consciousness. She was diagnosed as ONM. Her blood investigations, including haematological, biochemical, endocrine function tests and paraneoplastic as well as detailed vasculitic workup, were normal. Cerebrospinal fluid analysis for immunological markers, immunoglobulin (Ig) G index and oligoclonal band was all negative. The voltage-gated potassium channel (VGKC) antibody could not be detected in serum. Therefore we could not find an underlying abnormality to account for ONM. Treatment with carbamazepine 10 mg/kg twice a day was started and the attacks were completely resolved. Conclusion: After conducting a search of the medical literature using the terms “ONM” and “child” we identify only 5 previously published reports of ONM in children. To the best of our knowledge this patient is the youngest patient reported with a diagnosis of ONM.
P161 - 2452 HIF1 alpha abnormal distribution in muscle fibers in the cases of nemaline myopathy T.I. Baranich, T.V. Vinogradova, V.S. Sukhorukov, N.V. Klejmenova, A.V. Brydun, V.V. Nevstrueva, V.V. Glinkina. Department of Histology, Embryology and Cytology, Russian National Research Medical University named after N.I. Pirogov, Moscow, Russia Objective: The comparative study of immunohistochemical distribution of hypoxia marker HIF1 alpha and mitochondrial markers in striated muscle fibers of patients suffering from nemaline myopathy (NM) was performed for evaluation of tissue hypoxia’s role in the pathogenesis of NM, characterized by rod-shaped structures, which originated from the Z-disks of the sarcomeres. Methods: Fluorescence immunohistochemistry was performed. Primary mouse mitochondria monoclonal antibody, biotin conjugate (clone MTCO2) and Alexa Fluor 488 goat anti-mouse IgG as secondary antibody were used for mitochondria visualization. Visual image of HIF1 alpha was achieved by using primary rabbit polyclonal antibodies to HIF1 alpha and Alexa Fluor 555 goat anti-rabbit IgG as secondary antibody. Paraffin embedded muscle tissue section slides obtained from 3 NM patients were stained. Evaluation of the products is carried out by The EVOS® FL Imaging System. Results: Mitochondria and abnormal mitochondrial accumulations were visualized in subsarcolemmal zones of some muscle fibers. In the same muscle fibers we observed increased expression of HIF1 alpha; its localization matched with location of detected mitochondrial clusters, resulted in fluorescent lights overlapping and color change of subsarcolemmal zones luminescence. Furthermore, the most intensive fluorescence and clearly delineated HIF1 alpha clusters were observed in the areas of rods accumulation, pointing pronounced tissue hypoxia in these regions. Conclusion: While the diffuse subsarcolemmal zones of tissue hypoxia and increased number of mitochondrial clusters are often found in other myopathies, location of HIF1 alpha clusters in the rods areas is very unusual. Due to their brightness, HIF1 alpha clusters can be used in the quantification of muscular disorders severity at low magnification of fluorescence microscopy. No evidence whether these changes are secondary to rods accumulation or vice versa was found in the literature. In this way immunomorphological characterisation of energy muscle tissue metabolism of patients suffering from NM is of the current interest.
19s (2015) S1 – S152
S139
P162 - 2473 Andersen-Tawil syndrome with myopathy: Case report G. Öz Tunçer, M.G. Kutluk, P. Albayrak, S. Teber, G. Deda. Department of Pediatric Neurology, University of Ankara Faculty of Medicine Introduction: Andersen-Tawil syndrome (ATS) is a rare autosomal dominant potassium channelopathy characterized by periodic paralysis, ventricular arrhythmias, and dysmorphic features. We present a 14-year-old boy with characteristic features of ATS, and childhood onset myopathy. Case report: Fourteen years old boy admitted to our clinic with progressive muscle weakness and also described periods of severe weakness attacks for the last two years. Birth and family history were normal except 37 weeks of prematurity. At the age of four he started to fall down while walking and he descibed tiredness. At the age of 6 cardiac arrhythmia was detected. Investigations for muscle weakness showed that serum creatine kinase level was 625 U/L. Electromyography showed myopathic changes. The muscle biopsy didn’t demonstrate any specific finding. On his examination there was orbital hypertelorism, micrognathia, low set ears, clinodactyly, short stature, proximal muscle weakness of both upper and lower extremities. Deep tendon reflexes were hypoactive, Gowers sign was positive. On his electrocardiogram ventricular extrasystoles and U waves were seen. With the findings of severe worsening of limb weakness and dysmorphic features with cardiac arrhythmia ATS was suspected. Genetic testing confirmed a heterozygous mutation (R218W) in KCNJ2. After acetazolamide treatment attacks of severe muscle weakness and Gowers sign disappeared. Conclusion: Although ATS is charactized with episodes of muscle weakness, fixed myophaty had been reported only in two patients previously. All these two patients and our patient had heterozygous mutation (R218W) in KCNJ2. Because of the life threatening cardiac arrhythmias ATS must also be kept in mind in patients with fixed myophaty.
P163 - 2479 Intra familial phenotypical variations in hypokalemic periodic paralysis M. Joshi, N. Singh, M. Iqbal, P. Harijan, R. Saleem, A. Khan, N. Hussain. Department of Paediatric Neurology, University Hospitals of Leicester, Leicester, UK Objective: To describe cases of intra familial phenotypical variations in hypokalaemia periodic paralysis. Methods: Retrospective case note review. Results: We report a family of two siblings diagnosed with Hypokalaemia Periodic Paralysis who presented at different ages with different symptoms. Case1: A 16 years old boy presented with episodic weakness developed in the early hours of the morning with difficulty to get out of bed lasting up to 2 hours which was associated with reduce physical exercise, consumption of large amount of carbohydrate and missing regular meal time. His ECG was normal and CK was 363. His EMG showed features of myopathy features. His potassium level were <3.5. His clinical examination including neurological examination was unremarkable. Case 2: The 14 years old boy presented with 4 episodes of muscle stiffness where he was unable to lift his arm above the shoulder following large KFC meal. There were no other health problems. Father, paternal grandmother, paternal uncle and these 2 brothers are diagnosed with Familial Hypokalaemia Periodic Paralysis. Molecular genetic study showed both brother inherited same family genetic mutation in CACNA 1S gene (p.Arg1239His heterozygous mutation). Thyroid peroxidise antibodies were negative. Conclusion: Familial hypokalemic periodic paralysis is an autosomal dominant genetic muscle disease characterized by periodic attacks of muscle weakness associated with a decrease in serum potassium. In our cases, the clinical manifestation and the severity of the condition was
S140
EUROPEAN JOURNAL O F PAEDIATRIC NEUROLOGY
variable even within the family members with similar genotype. It is very important to check serum potassium level in a child presenting with muscle stiffness/weakness symptoms as it can be treated quickly with potassium supplement. Daily attention to restriction of vigorous exercises, reserved intake of carbohydrate and avoidance of exposure to coldness is helpful.
P164 - 2586 Congenital myasthenic syndrome in Israel: Genetic and clinical characterization S. Aharoni, A. Mimouni-Bloch, M. Daana, S. Edvardson, T. Dor-Wolman, A. Halevy, R. Cohen, L. Sagie, A.G. Engel, Y. Nevo. Department of Neurology, Schneider Children’s Medical Center of Israel, Petach Tikva, Israel affiliated to Sackler Faculty of Medicine, Tel Aviv University Objective: Congenital myasthenic syndromes (CMS) are a rare heterogeneous group of inherited neuromuscular disorders associated with distinctive clinical, electrophysiological and genetic abnormalities. Mutations in various genes of the neuromuscular junction may cause presynaptic, synaptic or postsynaptic defects. In this study, the genetic and clinical characteristics of Israeli patients with CMS were evaluated. Methods: Twentysix patients with CMS from 16 independent families in whom genetic mutation was detected were diagnosed in two Israeli medical centers. Genetic evaluation was initially performed depending on patients’ clinical symptoms and known CMS genes were sequenced. Patients of Jewish Iranian or Iraqi ethnic origin were screened directly for a known 38 A-G mutation in RAPSYN. In two patients, whole exome sequencing was analyzed. All patients’ medical records were reviewed and their clinical data, electrophysiological studies and outcome were recorded. Results: The diagnosis of CMS was confirmed in 26 patients of 16 families. Among these patients, 8 patients of 4 families had recessive mutations in COLQ, eight patients of 5 families, mutations in CHRNE, and eight patients of 5 families, mutations in RAPSN. CHRND was diagnosed in 2 patients from one family. The mean age of onset of clinical symptoms was 6 months. Ptosis, ophthalmoplegia and feeding problems were the most common symptoms. Conclusions: RAPSYN and CHRNE are the most common causes of CMS in our cohort. The second most common cause is COLQ. Specific mutations in RAPSYN, CHRNE and COLQ are detected in unique ethnic populations in Israel.
P165 - 2601 Breath-holding spells may be associated with maturational delay in myelination of brain stem S. Vurucu, M.S. Paksu, A. Karaoglu, O. Oz, H. Yaman, M. Gulgun, C. Saglam, B. Unay, R. Akin. Department of Pediatric Neurology, Gulhane Military Medical Faculty, Ankara, Turkey Objective: The aim of this study was to evaluate possible contribution of maturational delay of brainstem in the etiology of breath holding spells in children, using brainstem auditory evoked potentials. Methods: The study group included children with breath-holding spells. The control group was consisted of healthy, age and sex matched children. Age, gender, type and frequency of spell, hemoglobin, and ferritin levels in study group and brainstem auditory evoked potentials results in both groups were recorded. Study group was statistically compared with control group for brainstem auditory evoked potentials. Results: Thirty-two patients (16 boys and 16 girls), aged 4 to 60 months, and 21 healthy children (11 boys and 10 girls), aged 8 to 60 months were included in the study. The mean ages of study and control groups were 26.3±14.6 and 28.9±13.9 months, respectively. The III-V and I-V interpeak latencies were significantly prolonged in the study group compared to control group (2.07±0.2 msn;
19s (2015) S1 – S152
1.92±0.13 msn and 4.00±0.27 msn; 3.83±0.19 msn, p=0.009, p=0.03 respectively). At the same time, III-V and I-V interpeak latencies of patients without anemia in the study group compared to control group were significantly prolonged (2.09±0.24 msn; 1.92±0.13 msn and 4.04±0.28 msn; 3.83±0.19 msn, p=0.007, p=0.01 respectively). But, there were no significant difference between patients with anemia in the study group and control group for III-V and I-V interpeak latencies (p=0.17, p=0.69, respectively). Conclusion: Our results suggest that maturational delay in brainstem may have a role in the etiology of breath-holding spells in children.
P166 - 2607 Relationship between oxidative stress and chronic daily headache in children S. Vurucu, A. Karaoglu, M.S. Paksu, O. Yesilyurt, O. Oz, B. Unay, R. Akin. Department of Pediatric Neurology, Gulhane Military Medical Faculty, Ankara, Turkey Objective: Although there are reports that oxidative injury may play a role in the pathophysiology of some neurologic disorders, such as migraine and epilepsy, by disrupting and destructing cell membranes through formation of free radical and reactive oxygen species, the pathophysiology of headache is not clearly established. The aim of this study was to investigate the relationship between oxidative stress and chronic daily headache in children. Methods: Thirty-eight children with chronic daily headache (16 boys and 22 girls), aged from 7 to 15 years, were enrolled in the study. The control group consisted of 39 healthy children (17 boys and 22 girls), aged from 7 to 14 years old. The mean age was 10.9±2.2 years in both groups. Erythrocyte superoxide dismutase, catalase, glutathione peroxidase activities, and malondialdehyde levels, of all children in both groups were measured. Results: Mean erythrocyte superoxide dismutase, catalase, glutathione peroxidase activities, and malondialdehyde levels, were significantly higher in the study group than in the control group (p <0.001). Conclusion: The findings of this study suggest that oxidative stress may play a causal or consequential role in children with chronic daily headache.
P167 - 2623 The wide spectrum of neuropsychiatric profile in DMD in relation to underlying dystrophin gene mutations N. Deconinck, V. Ricotti, W. Mandy, M. Scoto, S. Messina, M. Pane, S. Laforesta, S. Baijot, G. Vita, E. Mercuri, D.H. Skuse, F. Muntoni. NMRC, Department paediatric neurology, UZ Gent, Gent, Belgium Objective: Duchenne muscular dystrophy (DMD) is associated with neurodevelopmental disorders. The aim of the study was to fully characterize the neuropsychiatric profile and to explore underlying genotype/phenotype associations with brainexpressed dystrophin isoforms. Methods: 130 DMD boys (mean age = 9.5 years) in four European neuromuscular centres (i.e. London, Brussels, Rome and Messina) were included in the study and completed IQ assessment and a screening questionnaire. Of these, 87 underwent complete neurodevelopmental assessment with structured diagnostic interview and parent reported questionnaire. The results were correlated to the underlying dystrophin gene mutations and the deduced pattern of brain dystrophin isoform expression. Results: The overall mean score on the screening neurodevelopmental questionnaire was significantly abnormal compared to the general paediatric population (p<0.001), Intelligence was overall below the population mean, with intellectual disability observed in 26.2% (n=35) of boys. Autistic spectrum disorder was reported in 20.7% (n=18), hyperactivity in 24.1% (n=21), inattention in in 43.7% (n=38) internalising and externalising problems 31.0% (n=27) and 17.2% (n=15) respectively. Neuropsychiatric disorders clustered together, with