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Abstract
Background: Children with Down syndrome frequently develop infantile spasms (IS); however, variable seizure outcome has been reported and not much is known about the clinical-electrophysiological factors affecting these outcomes. Therefore, we evaluated the clinical, neuroimaging and electrophysiological data in our DS with IS patient cohort, with a relatively long follow-up duration, to address some of these issues. Methods: Disease characteristics, diagnostic tests and treatment outcomes from 15 children (F: M=7:8) with IS and DS (follow-up duration: 10-197 months) were analyzed. Results: The median age at onset of spasms was 7 (2-16) months. EEG showed hypsarrhythmia in 10 infants, and patterns of diffusely disorganised background with multifocal independent spike-wave activity in the remaining five. Brain MRI (n=8) revealed no abnormality in 3, microcephaly in 2, delayed myelination in one, and minimal volume changes in 2. PET scans (n=5) showed diffuse glucose hypometabolism in 3, focal hypo- or hypermetabolism in 1 and 2 patients, respectively, and increased or decreased basal-ganglia metabolism in one each. Spasms disappeared in 8 patients (53.3%; six off medication), with girls (5/7; 71%) responding slightly better than boys (3/8; 37.5%). Seven of the 8 responders had shown hypsarrhythmia. Cessation of spasms was achieved by ACTH alone (n=1) or in combination with vigabatrin or zonisamide (n=1, each), and monotherapy with zonisamide (n=2), topiramate (n=1), prednisone (n=1), and ketogenic diet (n=1). Two patients showed evolution into complex partial seizure or Lennox-Gastaut syndrome. One child had dystonic cerebral palsy associated with perinatal asphyxia. Conclusions: Spasms developed relatively later in patients with IS and DS, compared to cryptogenic IS patients, and showed modest response to treatment. Girls appear to have a better treatment response, with presence of hypsarrhythmia may signal a better treatment outcome.
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Copyright (c) 2017 Ajay Kumar
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References
1. Mikati MA, Lepejian GA, Holmes GL. Medical treatment of patients with infantile spasms. Clinical neuropharmacology. 2002;25:61-70.
2. Pellock JM, Hrachovy R, Shinnar S, Baram TZ, Bettis D, Dlugos DJ, Gaillard WD, Gibson PA, Holmes GL, Nordl DR, et al. Infantile spasms: a U.S. consensus report. Epilepsia. 2010;51:2175-89. doi:10.1111/j.1528-1167.2010.02657.x.
3. Osborne JP, Lux AL, Edwards SW, Hancock E, Johnson AL, Kennedy CR, Newton RW, Verity CM, O'Callaghan FJK. The underlying etiology of infantile spasms (West syndrome): information from the United Kingdom Infantile Spasms Study (UKISS) on contemporary causes and their classification. Epilepsia. 2010;51:2168-74. doi:10.1111/j.1528-1167.2010.02695.x.
4. Sanmaneechai O, Sogawa Y, Silver W, Ballaban-Gil K, Moshé SL, Shinnar S. Treatment outcomes of West syndrome in infants with Down syndrome. Pediatric neurology. 2013;48:42-7. doi:10.1016/j.pediatrneurol.2012.09.006.
5. Eisermann MM, DeLaRaillère A, Dellatolas G, Tozzi E, Nabbout R, Dulac O, Chiron C. Infantile spasms in Down syndrome—effects of delayed anticonvulsive treatment. Epilepsy Research. 2003;55:21-7. doi:10.1016/S0920-1211(03)00088-3.
6. Escofet C, Póo P, Valbuena O, Gassió R, Sanmartí FX, Campistol J. Infantile spasms in children with Down's syndrome. Revista de neurologia. 1995;23:315-7.
7. Goldberg-Stern H, Strawsburg RH, Patterson B, Hickey F, Bare M, Gadoth N, Degrauw TJ. Seizure frequency and characteristics in children with Down syndrome. Brain and Development. 2001;23:375-8. doi:10.1016/S0387-7604(01)00239-X.
8. Lujić L, Bosnjak VM, Delin S, Duranović V, Krakar G. Infantile spasms in children with Down syndrome. Collegium antropologicum. 2011;35 Suppl 1:213-8.
9. Stafstrom CE, Konkol RJ. Infantile spasms in children with Down syndrome. Developmental medicine and child neurology. 1994;36:576-85.
10. Nascimento A, Ortez C. Infantile Spasms and Down Syndrome. International Medical Review on Down Syndrome. 2009;13:22-4. doi:10.1016/S2171-9748(09)70019-4.
11. O'Callaghan FJK, Lux AL, Darke K, Edwards SW, Hancock E, Johnson AL, Kennedy CR, Newton RW, Verity CM, Osborne JP. The effect of lead time to treatment and of age of onset on developmental outcome at 4 years in infantile spasms: evidence from the United Kingdom Infantile Spasms Study. Epilepsia. 2011;52:1359-64. doi:10.1111/j.1528-1167.2011.03127.x.
12. Caraballo R, Cersósimo R, Arroyo H, Fejerman N. Symptomatic West's syndrome: specific etiological link to unexpected response to treatment. Revista de neurologia. 1998;26:372-5.
13. Tatsuno M, Hayashi M, Iwamoto H, Suzuki Y, Kuroki Y. Epilepsy in childhood Down syndrome. Brain & development. 1984;6:37-44. doi:10.1016/S0387-7604(84)80008-X.
14. Romano C, Tiné A, Fazio G, Rizzo R, Colognola RM, Sorge G, Bergonzi P, Pavone L. Seizures in patients with trisomy 21. American journal of medical genetics Supplement. 1990;7:298-300.
15. Karvelas G, Lortie A, Scantlebury MH, Duy PT, Cossette P, Carmant L. A retrospective study on aetiology based outcome of infantile spasms. Seizure. 2009;18:197-201. doi:10.1016/j.seizure.2008.09.006.
16. Nabbout R, Melki I, Gerbaka B, Dulac O, Akatcherian C. Infantile spasms in Down syndrome: Good response to a short course of vigabatrin. Epilepsia. 2001;42:1580-3. doi:10.1046/j.1528-1157.2001.13501.x.
17. Nascimento A, Ortez-Gonzalez C. Down Syndrome and Epilepsy. In: Subrata D, editor. Genetics and Etiology of Down Syndrome: In Tech; 2011.
18. Caraballo RH, Fejerman N, Bernardina BD, Ruggieri V, Cersósimo R, Medina C, Pociecha J. Epileptic spasms in clusters without hypsarrhythmia in infancy. Epileptic disorders : international epilepsy journal with videotape. 2003;5:109-13.
19. Kossoff EH. Infantile spasms. The neurologist. 2010;16:69-75. doi:10.1097/NRL.0b013e3181d1416c.
20. Riikonen RS. Favourable prognostic factors with infantile spasms. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society. 2010;14:13-8. doi:10.1016/j.ejpn.2009.03.004.
21. Partikian A, Mitchell WG. Neurodevelopmental and epilepsy outcomes in a North American cohort of patients with infantile spasms. Journal of child neurology. 2010;25:423-8. doi:10.1177/0883073809341664.
22. Lux AL. Latest American and European updates on infantile spasms. Current neurology and neuroscience reports. 2013;13:334. doi:10.1007/s11910-012-0334-z.
23. Silva ML, Cieuta C, Guerrini R, Plouin P, Livet MO, Dulac O. Early clinical and EEG features of infantile spasms in Down syndrome. Epilepsia. 1996;37:977-82.
24. Chiron C, Raynaud C, Mazière B, Zilbovicius M, Laflamme L, Masure MC, Dulac O, Bourguignon M, Syrota A. Changes in regional cerebral blood flow during brain maturation in children and adolescents. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 1992;33:696-703.
25. Chugani HT, Phelps ME. Maturational changes in cerebral function in infants determined by 18FDG positron emission tomography. Science (New York, NY). 1986;231:840-3. doi:10.1126/science.3945811.
26. Chugani HT, Shewmon DA, Sankar R, Chen BC, Phelps ME. Infantile spasms: II. Lenticular nuclei and brain stem activation on positron emission tomography. Annals of neurology. 1992;31:212-9. doi:10.1002/ana.410310212.
27. Eisermann MM, Ville D, Soufflet C, Plouin P, Chiron C, Dulac O, Kaminska A. Cryptogenic late-onset epileptic spasms: an overlooked syndrome of early childhood? Epilepsia. 2006;47:1035-42. doi:10.1111/j.1528-1167.2006.00518.x.
28. Ronzano N, Valvo G, Ferrari AR, Guerrini R, Sicca F. Late-onset epileptic spasms: clinical evidence and outcome in 34 patients. Journal of child neurology. 2015;30:153-9. doi:10.1177/0883073814532547.
29. Curatolo P, Seri S, Verdecchia M, Bombardieri R. Infantile spasms in tuberous sclerosis complex. Brain & development. 2001;23:502-7.
30. Vignoli A, Zambrelli E, Chiesa V, Savini M, La Briola F, Gardella E, Canevini MP. Epilepsy in adult patients with Down syndrome: a clinical-video EEG study. Epileptic disorders : international epilepsy journal with videotape. 2011;13:125-32. doi:10.1684/epd.2011.0426.
31. Bahado-Singh RO, Wyse L, Dorr MA, Copel JA, O'Connor T, Hobbins JC. Fetuses with Down syndrome have disproportionately shortened frontal lobe dimensions on ultrasonographic examination. American journal of obstetrics and gynecology. 1992;167:1009-14.
32. Powell D, Caban-Holt A, Jicha G, Robertson W, Davis R, Gold BT, Schmitt FA, Head E. Frontal white matter integrity in adults with Down syndrome with and without dementia. Neurobiology of aging. 2014;35:1562-9. doi:10.1016/j.neurobiolaging.2014.01.137.
33. Bednarek N, Motte J, Soufflet C, Plouin P, Dulac O. Evidence of Late-Onset Infantile Spasms. Epilepsia. 1998;39:55-60. doi:10.1111/j.1528-1157.1998.tb01274.x.
34. Nordli DR, Korff CM, Goldstein J, Koh S, Laux L, Kelley KR. Cryptogenic late-onset epileptic spasms or late infantile epileptogenic encephalopathy? Epilepsia. 2007;48:206-8. doi:10.1111/j.1528-1167.2007.00978_2.x.
References
1. Mikati MA, Lepejian GA, Holmes GL. Medical treatment of patients with infantile spasms. Clinical neuropharmacology. 2002;25:61-70.
2. Pellock JM, Hrachovy R, Shinnar S, Baram TZ, Bettis D, Dlugos DJ, Gaillard WD, Gibson PA, Holmes GL, Nordl DR, et al. Infantile spasms: a U.S. consensus report. Epilepsia. 2010;51:2175-89. doi:10.1111/j.1528-1167.2010.02657.x.
3. Osborne JP, Lux AL, Edwards SW, Hancock E, Johnson AL, Kennedy CR, Newton RW, Verity CM, O'Callaghan FJK. The underlying etiology of infantile spasms (West syndrome): information from the United Kingdom Infantile Spasms Study (UKISS) on contemporary causes and their classification. Epilepsia. 2010;51:2168-74. doi:10.1111/j.1528-1167.2010.02695.x.
4. Sanmaneechai O, Sogawa Y, Silver W, Ballaban-Gil K, Moshé SL, Shinnar S. Treatment outcomes of West syndrome in infants with Down syndrome. Pediatric neurology. 2013;48:42-7. doi:10.1016/j.pediatrneurol.2012.09.006.
5. Eisermann MM, DeLaRaillère A, Dellatolas G, Tozzi E, Nabbout R, Dulac O, Chiron C. Infantile spasms in Down syndrome—effects of delayed anticonvulsive treatment. Epilepsy Research. 2003;55:21-7. doi:10.1016/S0920-1211(03)00088-3.
6. Escofet C, Póo P, Valbuena O, Gassió R, Sanmartí FX, Campistol J. Infantile spasms in children with Down's syndrome. Revista de neurologia. 1995;23:315-7.
7. Goldberg-Stern H, Strawsburg RH, Patterson B, Hickey F, Bare M, Gadoth N, Degrauw TJ. Seizure frequency and characteristics in children with Down syndrome. Brain and Development. 2001;23:375-8. doi:10.1016/S0387-7604(01)00239-X.
8. Lujić L, Bosnjak VM, Delin S, Duranović V, Krakar G. Infantile spasms in children with Down syndrome. Collegium antropologicum. 2011;35 Suppl 1:213-8.
9. Stafstrom CE, Konkol RJ. Infantile spasms in children with Down syndrome. Developmental medicine and child neurology. 1994;36:576-85.
10. Nascimento A, Ortez C. Infantile Spasms and Down Syndrome. International Medical Review on Down Syndrome. 2009;13:22-4. doi:10.1016/S2171-9748(09)70019-4.
11. O'Callaghan FJK, Lux AL, Darke K, Edwards SW, Hancock E, Johnson AL, Kennedy CR, Newton RW, Verity CM, Osborne JP. The effect of lead time to treatment and of age of onset on developmental outcome at 4 years in infantile spasms: evidence from the United Kingdom Infantile Spasms Study. Epilepsia. 2011;52:1359-64. doi:10.1111/j.1528-1167.2011.03127.x.
12. Caraballo R, Cersósimo R, Arroyo H, Fejerman N. Symptomatic West's syndrome: specific etiological link to unexpected response to treatment. Revista de neurologia. 1998;26:372-5.
13. Tatsuno M, Hayashi M, Iwamoto H, Suzuki Y, Kuroki Y. Epilepsy in childhood Down syndrome. Brain & development. 1984;6:37-44. doi:10.1016/S0387-7604(84)80008-X.
14. Romano C, Tiné A, Fazio G, Rizzo R, Colognola RM, Sorge G, Bergonzi P, Pavone L. Seizures in patients with trisomy 21. American journal of medical genetics Supplement. 1990;7:298-300.
15. Karvelas G, Lortie A, Scantlebury MH, Duy PT, Cossette P, Carmant L. A retrospective study on aetiology based outcome of infantile spasms. Seizure. 2009;18:197-201. doi:10.1016/j.seizure.2008.09.006.
16. Nabbout R, Melki I, Gerbaka B, Dulac O, Akatcherian C. Infantile spasms in Down syndrome: Good response to a short course of vigabatrin. Epilepsia. 2001;42:1580-3. doi:10.1046/j.1528-1157.2001.13501.x.
17. Nascimento A, Ortez-Gonzalez C. Down Syndrome and Epilepsy. In: Subrata D, editor. Genetics and Etiology of Down Syndrome: In Tech; 2011.
18. Caraballo RH, Fejerman N, Bernardina BD, Ruggieri V, Cersósimo R, Medina C, Pociecha J. Epileptic spasms in clusters without hypsarrhythmia in infancy. Epileptic disorders : international epilepsy journal with videotape. 2003;5:109-13.
19. Kossoff EH. Infantile spasms. The neurologist. 2010;16:69-75. doi:10.1097/NRL.0b013e3181d1416c.
20. Riikonen RS. Favourable prognostic factors with infantile spasms. European journal of paediatric neurology : EJPN : official journal of the European Paediatric Neurology Society. 2010;14:13-8. doi:10.1016/j.ejpn.2009.03.004.
21. Partikian A, Mitchell WG. Neurodevelopmental and epilepsy outcomes in a North American cohort of patients with infantile spasms. Journal of child neurology. 2010;25:423-8. doi:10.1177/0883073809341664.
22. Lux AL. Latest American and European updates on infantile spasms. Current neurology and neuroscience reports. 2013;13:334. doi:10.1007/s11910-012-0334-z.
23. Silva ML, Cieuta C, Guerrini R, Plouin P, Livet MO, Dulac O. Early clinical and EEG features of infantile spasms in Down syndrome. Epilepsia. 1996;37:977-82.
24. Chiron C, Raynaud C, Mazière B, Zilbovicius M, Laflamme L, Masure MC, Dulac O, Bourguignon M, Syrota A. Changes in regional cerebral blood flow during brain maturation in children and adolescents. Journal of nuclear medicine : official publication, Society of Nuclear Medicine. 1992;33:696-703.
25. Chugani HT, Phelps ME. Maturational changes in cerebral function in infants determined by 18FDG positron emission tomography. Science (New York, NY). 1986;231:840-3. doi:10.1126/science.3945811.
26. Chugani HT, Shewmon DA, Sankar R, Chen BC, Phelps ME. Infantile spasms: II. Lenticular nuclei and brain stem activation on positron emission tomography. Annals of neurology. 1992;31:212-9. doi:10.1002/ana.410310212.
27. Eisermann MM, Ville D, Soufflet C, Plouin P, Chiron C, Dulac O, Kaminska A. Cryptogenic late-onset epileptic spasms: an overlooked syndrome of early childhood? Epilepsia. 2006;47:1035-42. doi:10.1111/j.1528-1167.2006.00518.x.
28. Ronzano N, Valvo G, Ferrari AR, Guerrini R, Sicca F. Late-onset epileptic spasms: clinical evidence and outcome in 34 patients. Journal of child neurology. 2015;30:153-9. doi:10.1177/0883073814532547.
29. Curatolo P, Seri S, Verdecchia M, Bombardieri R. Infantile spasms in tuberous sclerosis complex. Brain & development. 2001;23:502-7.
30. Vignoli A, Zambrelli E, Chiesa V, Savini M, La Briola F, Gardella E, Canevini MP. Epilepsy in adult patients with Down syndrome: a clinical-video EEG study. Epileptic disorders : international epilepsy journal with videotape. 2011;13:125-32. doi:10.1684/epd.2011.0426.
31. Bahado-Singh RO, Wyse L, Dorr MA, Copel JA, O'Connor T, Hobbins JC. Fetuses with Down syndrome have disproportionately shortened frontal lobe dimensions on ultrasonographic examination. American journal of obstetrics and gynecology. 1992;167:1009-14.
32. Powell D, Caban-Holt A, Jicha G, Robertson W, Davis R, Gold BT, Schmitt FA, Head E. Frontal white matter integrity in adults with Down syndrome with and without dementia. Neurobiology of aging. 2014;35:1562-9. doi:10.1016/j.neurobiolaging.2014.01.137.
33. Bednarek N, Motte J, Soufflet C, Plouin P, Dulac O. Evidence of Late-Onset Infantile Spasms. Epilepsia. 1998;39:55-60. doi:10.1111/j.1528-1157.1998.tb01274.x.
34. Nordli DR, Korff CM, Goldstein J, Koh S, Laux L, Kelley KR. Cryptogenic late-onset epileptic spasms or late infantile epileptogenic encephalopathy? Epilepsia. 2007;48:206-8. doi:10.1111/j.1528-1167.2007.00978_2.x.