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PP08.2 – 2626: Long term outcome of acute transverse myelitis in childhood: A single centre experience from North India
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EUROPEAN JOURNAL O F PAEDIATRIC NEUROLOGY
generation sequencing”. The mutation could also be detected in the patient’s mother. A therapy with CBZ reduced both the boy’s seizure frequency and the frequency of his paroxysmal tachycardia significantly. Discussion: SCN9A mutations have also been described for Dravet syndrome and familial febrile seizures, whereas our patient showed a familial absence-like generalized epilepsy in combination with paroxysmal tachycardia. Our patient, his mother and also his aunt were successfully treated with CBZ, which could suggest that the patient’s c.684C>G; p.I228M mutation causes a “gain of function” of the Nav1.7 sodium channel. The additional cardiac symptoms could also be an effect of the SCN9A mutation.
PP08: Inflammatory Disease of the CNS 1 PP08.1 - 2529 Cyclophosphamide in treatment resistant tumour negative pediatric NMDAR encephalitis N. Sankhyan, P. Singhi, R. Suthar, A.G. Saini, J. Sahu. Pediatric Neurology, PGIMER, Chandigarh, India Objective: Report 2 children with treatment resistant NMDAR encephalitis. Case reports and results: Case 1: A 4.5 year-oldgirl presented with an 8 week history of acute onset agitation, insomnia, abnormal involuntary movements, and mutism. On examination, she had no visual fixation or auditory perception, no communication or understanding, had continuous dyskinetic movements. A diagnosis of anti NMDAR-encephalitis was concluded after the IgG antibodies to NR1 subunit of NMDA receptors was positive in both CSF and serum. She was given methylprednisolone and 4 weeks later IVIG, with no response. Cyclophosphamide pulse therapy (3 doses monthly cycles) was initiated 8 months into the illness with the child still in vegetative state. There was remarkable improvement with cyclophosphamide therapy. At the last follow up, 21 months after onset she has started attending regular school. Case 2: A 8-year-old boy presented with acute onset seizures, impaired speech, lack of sleep, and abnormal behaviour. On examination he was delirious,mute and had abnormal movements. CSF and serum IgG antibodies to NR1 subunit of NMDA receptor were positive. He was treated with pulse methylprednisolone and IVIG. Two weeks later, the child was given Rituximab (4 doses every 4 weeks) with no improvement. Cyclophosphamide pulse therapy (3, monthly cycles) was initiated after 6 months of his disease onset. At last follow up, 12 months after disease onset he continues to be normal and attends regular school. Conclusion: Use of cyclophosphamide resulted in near complete recovery in two children with tumor negative NMDAR encephalitis resistant to steroids, IVIG and Rituximab (case 2). This despite the fact that the illness was severe and the symptoms had persisted for more than 6 months. This suggests that cyclophosphamide is an effective immunomodulator in children with Anti NMDAR encephalitis. Its use should be considered in children with incomplete or no response to first line agents.
PP08.2 - 2626 Long term outcome of acute transverse myelitis in childhood: A single centre experience from North India N. Sankhyan, R. Suthar, J. Sahu, N.K. Khandelwal, S. Singhi, P. Singhi. Assistant Professor, Pediatric Neurology, PGIMER, Chandigarh, India Objective: To study the clinical profile of children with acute transverse myelitis and its long term outcome. Methods: Retrospective analysis of children <12 years of age diagnosed with ATM over a period of 6 years from a single tertiary care in-
19s (2015) S1 – S152
stitute in north India. Results: During the study period 61856 children (<12 years) were admitted in the pediatric emergency. Thirty six children (21 boys, median age-7.5 years) were diagnosed with ATM. Weakness was symmetrical at onset in 27 (75%), with lower limb power ≤1/5 on MRC scale in 27 (75%), a sensory level was present in 25 (69.4%) and bladder dysfunction in 31 (86.1%) children. Quadriparesis was present in 14 (38.9%) children, respiratory weakness in 11 (30.6%) and 6 (16.8%) required mechanical ventilation. Acute complete cord syndrome was seen in 29 (80.6%) and acute partial cord syndrome in 7 (19.4%). MRI showed longitudinal extensive myelitis (LETM) in 27 (75%) children. Two children had serum anti-aquaporin antibody positive. On a median follow up of 35 months (range IQR 11–57 months); 16 (44.4%) children remained dependent for their daily needs and 15 (41.7%) were non ambulatory or required assistance to walk. Severe weakness at onset with power ≤1 on MRC scale, spinal shock, respiratory muscle weakness, mechanical ventilation, greater mean time to diagnosis and treatment was associated with a bad outcome. ATM was a monophasic illness in all, except in 3 children; all with neuromyelitis optica spectrum disorder. None of the children had progression to multiple sclerosis. Conclusion: In this study we have described largest cohort of children with ATM from India. The disease was severe and involved long segments (≥3) of cord in majority. Nearly half the children remain dependent on follow up. Genetic and ethnic difference might be responsible for higher prevalence of NMO and lack of progression to MS in our cohort.
PP08.3 - 2856 Luciferase assay to detect neutralizing antibodies in adolescent Bulgarian multiple sclerosis patients treated with interferon beta S. Ivanova, I. Milanov, R. Skrobanska, V. Dimitrova, V. Bojinova. MHATNP Objective: To determine whether NABs presence influences clinical efficacy and safety of IFNβ. Methods: A group of 11 adolescents MS partients treated with IFN β over 18 months was assessed. Binding antibodies (BABs) were detectd by ELISA and the possitive sera were tested by luciferase gene receptor assay for neutralizing antibodies. Cut – offs for BABs positivity of >50 BTU and for NABs positivity of <1 LU/ml were set. Results: This adolescent MS cohort had as mean age 16.7 at the time of the assessment. Disease duration is 3.9 y. (1.5–12). and 63.6% are females. Expanded Disability Status Scale (EDSS) at the time of assessment is between 1.5 and 6.0. Ten of eleven are BAB positive and six of ten are NAB positive. Two of NAB (+) and two of NAB (−) were treated with IVIG 10% as co-treatment because of suboptimal effect of interferion beta. Four of six are continuing IFN β treatment even though they are NAB (+) because they have no other opportunities or do not meet criteria for switching therapy. Conclusion: Luciferase assay is easier to run than golden standard cytopathic effect assay. It has a lower cost if running after detecting of binding antibodies by ELISA. NABs detection is helpful for timely treatment discontinuation owing to loss of medication efficacy. Evidence-based decisions are urgently needed to define “responders” and “non-responders” – a key issue in pediatric and adolescent MS patients owing to concerns regarding rapid escalation to more-powerful therapies with greater potential toxicities. Proper treatment is necessary in order not to acumulate diability in this period of very active disease
EUROPEAN JOURNAL O F PAEDIATRIC NEUROLOGY
generation sequencing”. The mutation could also be detected in the patient’s mother. A therapy with CBZ reduced both the boy’s seizure frequency and the frequency of his paroxysmal tachycardia significantly. Discussion: SCN9A mutations have also been described for Dravet syndrome and familial febrile seizures, whereas our patient showed a familial absence-like generalized epilepsy in combination with paroxysmal tachycardia. Our patient, his mother and also his aunt were successfully treated with CBZ, which could suggest that the patient’s c.684C>G; p.I228M mutation causes a “gain of function” of the Nav1.7 sodium channel. The additional cardiac symptoms could also be an effect of the SCN9A mutation.
PP08: Inflammatory Disease of the CNS 1 PP08.1 - 2529 Cyclophosphamide in treatment resistant tumour negative pediatric NMDAR encephalitis N. Sankhyan, P. Singhi, R. Suthar, A.G. Saini, J. Sahu. Pediatric Neurology, PGIMER, Chandigarh, India Objective: Report 2 children with treatment resistant NMDAR encephalitis. Case reports and results: Case 1: A 4.5 year-oldgirl presented with an 8 week history of acute onset agitation, insomnia, abnormal involuntary movements, and mutism. On examination, she had no visual fixation or auditory perception, no communication or understanding, had continuous dyskinetic movements. A diagnosis of anti NMDAR-encephalitis was concluded after the IgG antibodies to NR1 subunit of NMDA receptors was positive in both CSF and serum. She was given methylprednisolone and 4 weeks later IVIG, with no response. Cyclophosphamide pulse therapy (3 doses monthly cycles) was initiated 8 months into the illness with the child still in vegetative state. There was remarkable improvement with cyclophosphamide therapy. At the last follow up, 21 months after onset she has started attending regular school. Case 2: A 8-year-old boy presented with acute onset seizures, impaired speech, lack of sleep, and abnormal behaviour. On examination he was delirious,mute and had abnormal movements. CSF and serum IgG antibodies to NR1 subunit of NMDA receptor were positive. He was treated with pulse methylprednisolone and IVIG. Two weeks later, the child was given Rituximab (4 doses every 4 weeks) with no improvement. Cyclophosphamide pulse therapy (3, monthly cycles) was initiated after 6 months of his disease onset. At last follow up, 12 months after disease onset he continues to be normal and attends regular school. Conclusion: Use of cyclophosphamide resulted in near complete recovery in two children with tumor negative NMDAR encephalitis resistant to steroids, IVIG and Rituximab (case 2). This despite the fact that the illness was severe and the symptoms had persisted for more than 6 months. This suggests that cyclophosphamide is an effective immunomodulator in children with Anti NMDAR encephalitis. Its use should be considered in children with incomplete or no response to first line agents.
PP08.2 - 2626 Long term outcome of acute transverse myelitis in childhood: A single centre experience from North India N. Sankhyan, R. Suthar, J. Sahu, N.K. Khandelwal, S. Singhi, P. Singhi. Assistant Professor, Pediatric Neurology, PGIMER, Chandigarh, India Objective: To study the clinical profile of children with acute transverse myelitis and its long term outcome. Methods: Retrospective analysis of children <12 years of age diagnosed with ATM over a period of 6 years from a single tertiary care in-
19s (2015) S1 – S152
stitute in north India. Results: During the study period 61856 children (<12 years) were admitted in the pediatric emergency. Thirty six children (21 boys, median age-7.5 years) were diagnosed with ATM. Weakness was symmetrical at onset in 27 (75%), with lower limb power ≤1/5 on MRC scale in 27 (75%), a sensory level was present in 25 (69.4%) and bladder dysfunction in 31 (86.1%) children. Quadriparesis was present in 14 (38.9%) children, respiratory weakness in 11 (30.6%) and 6 (16.8%) required mechanical ventilation. Acute complete cord syndrome was seen in 29 (80.6%) and acute partial cord syndrome in 7 (19.4%). MRI showed longitudinal extensive myelitis (LETM) in 27 (75%) children. Two children had serum anti-aquaporin antibody positive. On a median follow up of 35 months (range IQR 11–57 months); 16 (44.4%) children remained dependent for their daily needs and 15 (41.7%) were non ambulatory or required assistance to walk. Severe weakness at onset with power ≤1 on MRC scale, spinal shock, respiratory muscle weakness, mechanical ventilation, greater mean time to diagnosis and treatment was associated with a bad outcome. ATM was a monophasic illness in all, except in 3 children; all with neuromyelitis optica spectrum disorder. None of the children had progression to multiple sclerosis. Conclusion: In this study we have described largest cohort of children with ATM from India. The disease was severe and involved long segments (≥3) of cord in majority. Nearly half the children remain dependent on follow up. Genetic and ethnic difference might be responsible for higher prevalence of NMO and lack of progression to MS in our cohort.
PP08.3 - 2856 Luciferase assay to detect neutralizing antibodies in adolescent Bulgarian multiple sclerosis patients treated with interferon beta S. Ivanova, I. Milanov, R. Skrobanska, V. Dimitrova, V. Bojinova. MHATNP Objective: To determine whether NABs presence influences clinical efficacy and safety of IFNβ. Methods: A group of 11 adolescents MS partients treated with IFN β over 18 months was assessed. Binding antibodies (BABs) were detectd by ELISA and the possitive sera were tested by luciferase gene receptor assay for neutralizing antibodies. Cut – offs for BABs positivity of >50 BTU and for NABs positivity of <1 LU/ml were set. Results: This adolescent MS cohort had as mean age 16.7 at the time of the assessment. Disease duration is 3.9 y. (1.5–12). and 63.6% are females. Expanded Disability Status Scale (EDSS) at the time of assessment is between 1.5 and 6.0. Ten of eleven are BAB positive and six of ten are NAB positive. Two of NAB (+) and two of NAB (−) were treated with IVIG 10% as co-treatment because of suboptimal effect of interferion beta. Four of six are continuing IFN β treatment even though they are NAB (+) because they have no other opportunities or do not meet criteria for switching therapy. Conclusion: Luciferase assay is easier to run than golden standard cytopathic effect assay. It has a lower cost if running after detecting of binding antibodies by ELISA. NABs detection is helpful for timely treatment discontinuation owing to loss of medication efficacy. Evidence-based decisions are urgently needed to define “responders” and “non-responders” – a key issue in pediatric and adolescent MS patients owing to concerns regarding rapid escalation to more-powerful therapies with greater potential toxicities. Proper treatment is necessary in order not to acumulate diability in this period of very active disease