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PP01.12 – 2602: Differential diagnosis of progressive myoclonic epilepsia: Five patients with Lafora disease
S32
EUROPEAN JOURNAL O F PAEDIATRIC NEUROLOGY
intractable epilepsy in a patient with NXF2 duplication. Case report: Joana, age 3, previously healthy, family history positive for epilepsy. At the age of 2 she had her first seizure, characterized by loss of awareness and subsequent hypotonia associated with an upper respiratory infection. Her condition then evolved to frequent, monomorphic seizures that proved to be refractory to medical treatment. The MRI (3Tz) showed slight asymmetry of the mesial regions, with no mesial atrophy or focal dysplasia, and the video-EEG monitoring displayed right temporal lobe activity. She started ketogenic diet with partial response. At the age of 3 she was admitted to the intensive care unit (ICU) due to pneumonia that evolved rapidly to septic shock resulting in death in 48 hours. The metabolic work-up was normal, as was the karyotype and study of sister chromatids exchange. The comparative genomic hybridization (GCH) array showed an interstitial duplication of chromosome X, region Xq22.1 including the NXF2 gene. Conclusions: Although rarely described, NFX2 gene could play a role in brain development, and thus play a role in developmental delay and epilepsy. More studies are needed to confirm this association.
PP01.12 - 2602 Differential diagnosis of progressive myoclonic epilepsia: Five patients with Lafora disease H.G. Poyrazoglu, S. Kumanda¸s, M. Canpolat, H. Per, H. Gümü¸s, A. Arslan, F. Özkınay. Firat University Faculty of Medicine Department of Pediatric Neurology, , Istanbul, Turkey Objective: Lafora disease (LD) is a rare, fatal, autosomal recessive hereditary disease characterized by epilepsy, myoclonus and progressive neurological deterioration. Diagnosis is made by polyglucosan inclusion bodies (Lafora bodies) shown in skin biopsy. Responsible mutations involves either the EPM2A or NHLRC1 (EPM2B) gene. Methods: We report genetic mutations and clinical courses of Lafora disease in 5 adolescents with homozygote NHLRC1 mutation and homozygous EPM2A mutation. Results: A total 5 patients (3 female, 2 male) were presented with progressive myoclonic epilepsy. In all cases there were no problems at birth, childhood, and their psychomotor development were normal and attended regular school. In general seizures began around at 13–14 years old. Over the time they demostrated ataxia, and significant deterioration occurred in mental functions, myoclonus of the extremities started, and 3 of all patients were unable to walk unassisted and one of them died at 15 years old. Axillary skin biopsies were performed to all and Lafora bodies in cytoplasm were demostrated. All patients parents are seconddegree relatives. Routine blood test, cerebrospinal fluid analaysis were normal. In three patients cranial magnetic resonance imaging (MRI) were normal, but 2 patients had mild serebral and serebellar atrophy. There were multifocal, from time-to-time generalized spike-wave activity were observed in their electroencephalography (EEG). Genetic analaysis for Lafora was studied and 2 patients (sublings) had same mutation) homozygous (c.336 C>A) p.Y112X mutation in EPM2A gene, homozygous (c.199 G>T) p. E67X mutation (2 patient had same mutation) in NHLRC1 gene, homozygous L 180V (CTG>GTC) mutation in EPM2A gene were detected. Conclusion: LD is characterized by progressive myoclonic epilepsy and neurodegenerative symptoms. Therefore early recognation is diffucult. If patient show progressive myoclonic seizures with progressive mental deterotation, as well as ataxi we should consider LD
19s (2015) S1 – S152
PP01.13 - 2471 Sturge-Weber syndrome is associated with complex malformations of cortical development – A case report T. Scholl, S. Samueli, A. Mühlebner-Fahrngruber, A. Dressler, K. Abraham, G. Gröppel, J. Hainfellner, T. Czech, D. Prayer, F. Laccone, M. Feucht. Division of Neonatology, Intensive Care Medicine and Neuropediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria We present an 11 months old girl with Sturge Weber syndrom (SWS) and infantile spasms, refractory to treatment; The child was delivered in the 36th week of gestation. On prenatal ultrasound the obstetrician noticed an enlargement of the right ventricle. Postnatal, the MRI showed at first indications for an early SWS; hypertrophy of the right hemisphere with reduced gyration, T1 hyperintense and Tw2 hypointense signal alterations in the right periventricular white matter; proliferation of superficial vessels after administration of contrast agent and on SWI sequences, and a dysplastic corpus callosum. From day 1 onwards the child presented with a severe muscular hypotonia and daily series of complex partial and focal seizures occurred. The EEG was concordant with continuous epileptic discharges over the right hemisphere. The establishment of several AEDs did not yield any seizure control. Extensive diagnostics were carried out and in the light of these results the suspicious diagnosis of a type III SWS with an isolated leptomeningeal-brain angiom, was raised. In the combination of the diagnostics and the patients poor general condition, the indication for epilepsy surgery was met. At the age of 7 months a functional hemispherotomy was performed. Since the surgery the patient is seizure-free and there is a significant improvement of motor skills, despite the expected left-sided hemiparesis. Neurohistopathological assessment of the resected tissue showed severe meningoangiomatosis associated with classical 4-layered polymicrogyria, although no mosaic mutation in the GNAQ gene was found. Detailed immunohistological analysis presented small immature neurons in a 4-layered cortical organization as well as various sizes of malformed bloodvessels within the meninges. In addition, a hyperactivation of the (PI3K)-AKT3-mTOR pathway (pS6, pAkt Ser 473) could be detected. Our case highlights the importance of thorough clinical assessment and the effect of epilepsy surgery also in highly complex malformations of cortical development.
PP02: Fetal Neurology PP02.1 - 2612 The clinical value of neuromediators (brain derivated neurotrophic factor, galanin, neuropeptid Y) in neonatal encephalopathy M. Tanrıverdi, N. Kultursay, H. Tekgul, E. Sozmen, O. Altın ˘ Koroglu, G. Serdaroglu, M. Yalaz. Department of Pediatrics, Ege Children’s Hospital, Ege University Medical School, Izmir, Turkey Objective: To investigate the diagnostic and prognostic value of neuromediators (brain derivated neurotrophic factor-BDNF, galanin and neuropeptide Y-NPY) in pretem and term neonates with neonatal encephalopathy. Methods: Fifty three neonates (preterm: 26, term: 27) who had lumbar puncture for the diagnostic investigation of neonatal encephalopathy in Ege University Children’s Hospital NICU were enrolled to the study. Study group were divided in to 4 groups according to their gestational ages and based on whether they had seizures or not: Group 1: preterm neonates with seizures (n=13), Group 2: preterm neonates without seizures (n=13), Group 3: term neonates with seizures (n=13), Group 4: term neonates without seizures (n=14). Control group consisted of 32 healthy newborns (preterm: 13, term: 19) who
EUROPEAN JOURNAL O F PAEDIATRIC NEUROLOGY
intractable epilepsy in a patient with NXF2 duplication. Case report: Joana, age 3, previously healthy, family history positive for epilepsy. At the age of 2 she had her first seizure, characterized by loss of awareness and subsequent hypotonia associated with an upper respiratory infection. Her condition then evolved to frequent, monomorphic seizures that proved to be refractory to medical treatment. The MRI (3Tz) showed slight asymmetry of the mesial regions, with no mesial atrophy or focal dysplasia, and the video-EEG monitoring displayed right temporal lobe activity. She started ketogenic diet with partial response. At the age of 3 she was admitted to the intensive care unit (ICU) due to pneumonia that evolved rapidly to septic shock resulting in death in 48 hours. The metabolic work-up was normal, as was the karyotype and study of sister chromatids exchange. The comparative genomic hybridization (GCH) array showed an interstitial duplication of chromosome X, region Xq22.1 including the NXF2 gene. Conclusions: Although rarely described, NFX2 gene could play a role in brain development, and thus play a role in developmental delay and epilepsy. More studies are needed to confirm this association.
PP01.12 - 2602 Differential diagnosis of progressive myoclonic epilepsia: Five patients with Lafora disease H.G. Poyrazoglu, S. Kumanda¸s, M. Canpolat, H. Per, H. Gümü¸s, A. Arslan, F. Özkınay. Firat University Faculty of Medicine Department of Pediatric Neurology, , Istanbul, Turkey Objective: Lafora disease (LD) is a rare, fatal, autosomal recessive hereditary disease characterized by epilepsy, myoclonus and progressive neurological deterioration. Diagnosis is made by polyglucosan inclusion bodies (Lafora bodies) shown in skin biopsy. Responsible mutations involves either the EPM2A or NHLRC1 (EPM2B) gene. Methods: We report genetic mutations and clinical courses of Lafora disease in 5 adolescents with homozygote NHLRC1 mutation and homozygous EPM2A mutation. Results: A total 5 patients (3 female, 2 male) were presented with progressive myoclonic epilepsy. In all cases there were no problems at birth, childhood, and their psychomotor development were normal and attended regular school. In general seizures began around at 13–14 years old. Over the time they demostrated ataxia, and significant deterioration occurred in mental functions, myoclonus of the extremities started, and 3 of all patients were unable to walk unassisted and one of them died at 15 years old. Axillary skin biopsies were performed to all and Lafora bodies in cytoplasm were demostrated. All patients parents are seconddegree relatives. Routine blood test, cerebrospinal fluid analaysis were normal. In three patients cranial magnetic resonance imaging (MRI) were normal, but 2 patients had mild serebral and serebellar atrophy. There were multifocal, from time-to-time generalized spike-wave activity were observed in their electroencephalography (EEG). Genetic analaysis for Lafora was studied and 2 patients (sublings) had same mutation) homozygous (c.336 C>A) p.Y112X mutation in EPM2A gene, homozygous (c.199 G>T) p. E67X mutation (2 patient had same mutation) in NHLRC1 gene, homozygous L 180V (CTG>GTC) mutation in EPM2A gene were detected. Conclusion: LD is characterized by progressive myoclonic epilepsy and neurodegenerative symptoms. Therefore early recognation is diffucult. If patient show progressive myoclonic seizures with progressive mental deterotation, as well as ataxi we should consider LD
19s (2015) S1 – S152
PP01.13 - 2471 Sturge-Weber syndrome is associated with complex malformations of cortical development – A case report T. Scholl, S. Samueli, A. Mühlebner-Fahrngruber, A. Dressler, K. Abraham, G. Gröppel, J. Hainfellner, T. Czech, D. Prayer, F. Laccone, M. Feucht. Division of Neonatology, Intensive Care Medicine and Neuropediatrics, Department of Pediatrics and Adolescent Medicine, Medical University of Vienna, Vienna, Austria We present an 11 months old girl with Sturge Weber syndrom (SWS) and infantile spasms, refractory to treatment; The child was delivered in the 36th week of gestation. On prenatal ultrasound the obstetrician noticed an enlargement of the right ventricle. Postnatal, the MRI showed at first indications for an early SWS; hypertrophy of the right hemisphere with reduced gyration, T1 hyperintense and Tw2 hypointense signal alterations in the right periventricular white matter; proliferation of superficial vessels after administration of contrast agent and on SWI sequences, and a dysplastic corpus callosum. From day 1 onwards the child presented with a severe muscular hypotonia and daily series of complex partial and focal seizures occurred. The EEG was concordant with continuous epileptic discharges over the right hemisphere. The establishment of several AEDs did not yield any seizure control. Extensive diagnostics were carried out and in the light of these results the suspicious diagnosis of a type III SWS with an isolated leptomeningeal-brain angiom, was raised. In the combination of the diagnostics and the patients poor general condition, the indication for epilepsy surgery was met. At the age of 7 months a functional hemispherotomy was performed. Since the surgery the patient is seizure-free and there is a significant improvement of motor skills, despite the expected left-sided hemiparesis. Neurohistopathological assessment of the resected tissue showed severe meningoangiomatosis associated with classical 4-layered polymicrogyria, although no mosaic mutation in the GNAQ gene was found. Detailed immunohistological analysis presented small immature neurons in a 4-layered cortical organization as well as various sizes of malformed bloodvessels within the meninges. In addition, a hyperactivation of the (PI3K)-AKT3-mTOR pathway (pS6, pAkt Ser 473) could be detected. Our case highlights the importance of thorough clinical assessment and the effect of epilepsy surgery also in highly complex malformations of cortical development.
PP02: Fetal Neurology PP02.1 - 2612 The clinical value of neuromediators (brain derivated neurotrophic factor, galanin, neuropeptid Y) in neonatal encephalopathy M. Tanrıverdi, N. Kultursay, H. Tekgul, E. Sozmen, O. Altın ˘ Koroglu, G. Serdaroglu, M. Yalaz. Department of Pediatrics, Ege Children’s Hospital, Ege University Medical School, Izmir, Turkey Objective: To investigate the diagnostic and prognostic value of neuromediators (brain derivated neurotrophic factor-BDNF, galanin and neuropeptide Y-NPY) in pretem and term neonates with neonatal encephalopathy. Methods: Fifty three neonates (preterm: 26, term: 27) who had lumbar puncture for the diagnostic investigation of neonatal encephalopathy in Ege University Children’s Hospital NICU were enrolled to the study. Study group were divided in to 4 groups according to their gestational ages and based on whether they had seizures or not: Group 1: preterm neonates with seizures (n=13), Group 2: preterm neonates without seizures (n=13), Group 3: term neonates with seizures (n=13), Group 4: term neonates without seizures (n=14). Control group consisted of 32 healthy newborns (preterm: 13, term: 19) who