Nonepileptic paroxysmal disorders in infancy
- Thien T Nguyen, MD, PhD
Thien T Nguyen, MD, PhD
- Assistant Professor of Neurology
- Johns Hopkins University School of Medicine
- Peter W Kaplan, MB, FRCP
Peter W Kaplan, MB, FRCP
- Professor of Neurology
- Johns Hopkins University School of Medicine
- Angus Wilfong, MD
Angus Wilfong, MD
- Chief of Neurology
- Barrow Neurologic Institute at Phoenix Children's Hospital
Epilepsy is a condition characterized by an underlying susceptibility for recurrent seizures. The term seizure refers to a transient occurrence of signs and/or symptoms due to abnormal excessive neuronal activity of the brain.
Paroxysmal events are frequent in infancy. In one population-based cohort, they occurred in 9 percent of those in the first year of life . While seizures and epilepsy are commonly considered in the differential, these make up a small fraction (<10 percent) of these events.
Neonates and infants exhibit nonepileptic paroxysmal episodes that differ from those encountered in older children and adults (table 1). These may be difficult to differentiate from epileptic events because of the overlapping clinical symptoms as well as the difficulty in interpreting neonatal and infant electroencephalograms (EEG). It is important for clinicians to be aware of and recognize the transient nonepileptic events that resemble seizures in order to avoid unnecessary treatment and to institute the correct treatment when required.
This topic reviews nonepileptic paroxysmal events in the neonate and infant. The differential diagnosis of epilepsy in other age groups is reviewed separately. (See "Nonepileptic paroxysmal disorders in children" and "Nonepileptic paroxysmal disorders in adolescents and adults".)
NEONATES (BIRTH TO ONE MONTH OF AGE)
Normal neonates commonly exhibit a variety of paroxysmal movements including nonconjugate eye movements, sucking movements without associated eye abnormalities, and sleep-related myoclonus. These normal behaviors as well as the pathologic conditions discussed below can be difficult to distinguish from epileptic seizures, which can also have somewhat subtle manifestations. Electroencephalography (EEG), particularly video EEG monitoring, can be invaluable in distinguishing among these entities. In one study of neonates, 90 percent of abnormal movements suspicious for seizures were found to be nonepileptic on EEG recording . (See "Clinical features, evaluation, and diagnosis of neonatal seizures".)To continue reading this article, you must log in with your personal, hospital, or group practice subscription. For more information on subscription options, click below on the option that best describes you:
- Visser AM, Jaddoe VW, Arends LR, et al. Paroxysmal disorders in infancy and their risk factors in a population-based cohort: the Generation R Study. Dev Med Child Neurol 2010; 52:1014.
- Scher MS, Painter MJ. Controversies concerning neonatal seizures. Pediatr Clin North Am 1989; 36:281.
- Volpe, JJ. Neurology of the Newborn, 4th ed, WB Saunders Co, Philadelphia 2001.
- Kaplan, PW, Fisher, RS. Imitators of Epilepsy, 2nd ed, Demos Medical Publishing, New York 2005.
- Watanabe K, Hara K, Hakamada S, et al. Seizures with apnea in children. Pediatrics 1982; 70:87.
- Thach BT. Sleep apnea in infancy and childhood. Med Clin North Am 1985; 69:1289.
- O'Regan ME, Brown JK. Abnormalities in cardiac and respiratory function observed during seizures in childhood. Dev Med Child Neurol 2005; 47:4.
- Fenichel GM, Olson BJ, Fitzpatrick JE. Heart rate changes in convulsive and nonconvulsive neonatal apnea. Ann Neurol 1980; 7:577.
- Parker S, Zuckerman B, Bauchner H, et al. Jitteriness in full-term neonates: prevalence and correlates. Pediatrics 1990; 85:17.
- Armentrout DC, Caple J. The jittery newborn. J Pediatr Health Care 2001; 15:147.
- Shuper A, Zalzberg J, Weitz R, Mimouni M. Jitteriness beyond the neonatal period: a benign pattern of movement in infancy. J Child Neurol 1991; 6:243.
- Di Capua M, Fusco L, Ricci S, Vigevano F. Benign neonatal sleep myoclonus: clinical features and video-polygraphic recordings. Mov Disord 1993; 8:191.
- Walters AS. Clinical identification of the simple sleep-related movement disorders. Chest 2007; 131:1260.
- Paro-Panjan D, Neubauer D. Benign neonatal sleep myoclonus: experience from the study of 38 infants. Eur J Paediatr Neurol 2008; 12:14.
- Egger J, Grossmann G, Auchterlonie IA. Benign sleep myoclonus in infancy mistaken for epilepsy. BMJ 2003; 326:975.
- American Academy of Sleep Medicine. The International Classification of Sleep Disorders, 3rd ed, Chicago, IL 2014.
- Andrew M, Owen MJ. Hyperekplexia: abnormal startle response due to glycine receptor mutations. Br J Psychiatry 1997; 170:106.
- Bakker MJ, van Dijk JG, van den Maagdenberg AM, Tijssen MA. Startle syndromes. Lancet Neurol 2006; 5:513.
- Zhou L, Chillag KL, Nigro MA. Hyperekplexia: a treatable neurogenetic disease. Brain Dev 2002; 24:669.
- Giacoia GP, Ryan SG. Hyperekplexia associated with apnea and sudden infant death syndrome. Arch Pediatr Adolesc Med 1994; 148:540.
- Praveen V, Patole SK, Whitehall JS. Hyperekplexia in neonates. Postgrad Med J 2001; 77:570.
- Lion-Francois L, Mignot C, Vicart S, et al. Severe neonatal episodic laryngospasm due to de novo SCN4A mutations: a new treatable disorder. Neurology 2010; 75:641.
- Kotagal P, Costa M, Wyllie E, Wolgamuth B. Paroxysmal nonepileptic events in children and adolescents. Pediatrics 2002; 110:e46.
- Watemberg N, Tziperman B, Dabby R, et al. Adding video recording increases the diagnostic yield of routine electroencephalograms in children with frequent paroxysmal events. Epilepsia 2005; 46:716.
- Bye AM, Kok DJ, Ferenschild FT, Vles JS. Paroxysmal non-epileptic events in children: a retrospective study over a period of 10 years. J Paediatr Child Health 2000; 36:244.
- Lombroso CT, Lerman P. Breathholding spells (cyanotic and pallid infantile syncope). Pediatrics 1967; 39:563.
- DiMario FJ Jr. Breath-holding spells in childhood. Am J Dis Child 1992; 146:125.
- DiMario FJ Jr, Burleson JA. Autonomic nervous system function in severe breath-holding spells. Pediatr Neurol 1993; 9:268.
- Breningstall GN. Breath-holding spells. Pediatr Neurol 1996; 14:91.
- DiMario FJ Jr. Prospective study of children with cyanotic and pallid breath-holding spells. Pediatrics 2001; 107:265.
- Breukels MA, Plötz FB, van Nieuwenhuizen O, van Diemen-Steenvoorde JA. Breath holding spells in a 3-day-old neonate: an unusual early presentation in a family with a history of breath holding spells. Neuropediatrics 2002; 33:41.
- Kolkiran A, Tutar E, Atalay S, et al. Autonomic nervous system functions in children with breath-holding spells and effects of iron deficiency. Acta Paediatr 2005; 94:1227.
- Hüdaoglu O, Dirik E, Yiş U, Kurul S. Parental attitude of mothers, iron deficiency anemia, and breath-holding spells. Pediatr Neurol 2006; 35:18.
- Orii KE, Kato Z, Osamu F, et al. Changes of autonomic nervous system function in patients with breath-holding spells treated with iron. J Child Neurol 2002; 17:337.
- Hellström Schmidt S, Tedgård U, Pronk CJ. Breath-holding spells occur disproportionately more often in children with transient erythroblastopenia. Acta Paediatr 2016; 105:1088.
- DiMario FJ Jr, Sarfarazi M. Family pedigree analysis of children with severe breath-holding spells. J Pediatr 1997; 130:647.
- Moorjani BI, Rothner AD, Kotagal P. Breath-holding spells and prolonged seizures. Ann Neurol 1995; 38:512.
- Kuhle S, Tiefenthaler M, Seidl R, Hauser E. Prolonged generalized epileptic seizures triggered by breath-holding spells. Pediatr Neurol 2000; 23:271.
- Allan WC, Gospe SM Jr. Seizures, syncope, or breath-holding presenting to the pediatric neurologist--when is the etiology a life-threatening arrhythmia? Semin Pediatr Neurol 2005; 12:2.
- Boon R. Does iron have a place in the management of breath holding spells? Arch Dis Child 2002; 87:77.
- Goraya JS, Virdi VS. Persistence of breath-holding spells into late childhood. J Child Neurol 2001; 16:697.
- Haverkamp F, Noeker M. Traditional view empirically revisited: normal intellectual functioning in breath holding spells. Eur J Pediatr 1998; 157:354.
- Mocan H, Yildiran A, Orhan F, Erduran E. Breath holding spells in 91 children and response to treatment with iron. Arch Dis Child 1999; 81:261.
- Zehetner AA, Orr N, Buckmaster A, et al. Iron supplementation for breath-holding attacks in children. Cochrane Database Syst Rev 2010; :CD008132.
- Horrocks IA, Nechay A, Stephenson JB, Zuberi SM. Anoxic-epileptic seizures: observational study of epileptic seizures induced by syncopes. Arch Dis Child 2005; 90:1283.
- Donma MM. Clinical efficacy of piracetam in treatment of breath-holding spells. Pediatr Neurol 1998; 18:41.
- Sawires H, Botrous O. Double-blind, placebo-controlled trial on the effect of piracetam on breath-holding spells. Eur J Pediatr 2012; 171:1063.
- Kelly AM, Porter CJ, McGoon MD, et al. Breath-holding spells associated with significant bradycardia: successful treatment with permanent pacemaker implantation. Pediatrics 2001; 108:698.
- DiMario FJ Jr. Breath-holding spells and pacemaker implantation. Pediatrics 2001; 108:765.
- Caraballo RH, Capovilla G, Vigevano F, et al. The spectrum of benign myoclonus of early infancy: Clinical and neurophysiologic features in 102 patients. Epilepsia 2009; 50:1176.
- Maydell BV, Berenson F, Rothner AD, et al. Benign myoclonus of early infancy: an imitator of West's syndrome. J Child Neurol 2001; 16:109.
- Lombroso CT, Fejerman N. Benign myoclonus of early infancy. Ann Neurol 1977; 1:138.
- Donat JF, Wright FS. Clinical imitators of infantile spasms. J Child Neurol 1992; 7:395.
- Holmes GL, Russman BS. Shuddering attacks. Evaluation using electroencephalographic frequency modulation radiotelemetry and videotape monitoring. Am J Dis Child 1986; 140:72.
- Kanazawa O. Shuddering attacks-report of four children. Pediatr Neurol 2000; 23:421.
- Frankel EA, Shalaby TM, Orenstein SR. Sandifer syndrome posturing: relation to abdominal wall contractions, gastroesophageal reflux, and fundoplication. Dig Dis Sci 2006; 51:635.
- Vanasse M, Bedard P, Andermann F. Shuddering attacks in children: an early clinical manifestation of essential tremor. Neurology 1976; 26:1027.
- Lehwald N, Krausch M, Franke C, et al. Sandifer syndrome--a multidisciplinary diagnostic and therapeutic challenge. Eur J Pediatr Surg 2007; 17:203.
- Kabakuş N, Kurt A. Sandifer Syndrome: a continuing problem of misdiagnosis. Pediatr Int 2006; 48:622.
- Sheikh S, Stephen TC, Sisson B. Prevalence of gastroesophageal reflux in infants with recurrent brief apneic episodes. Can Respir J 1999; 6:401.
- Cohen HA, Nussinovitch M, Ashkenasi A, et al. Benign paroxysmal torticollis in infancy. Pediatr Neurol 1993; 9:488.
- Drigo P, Carli G, Laverda AM. Benign paroxysmal torticollis of infancy. Brain Dev 2000; 22:169.
- Rosman NP, Douglass LM, Sharif UM, Paolini J. The neurology of benign paroxysmal torticollis of infancy: report of 10 new cases and review of the literature. J Child Neurol 2009; 24:155.
- Giffin NJ, Benton S, Goadsby PJ. Benign paroxysmal torticollis of infancy: four new cases and linkage to CACNA1A mutation. Dev Med Child Neurol 2002; 44:490.
- Bleasel A, Kotagal P. Paroxysmal nonepileptic disorders in children and adolescents. Semin Neurol 1995; 15:203.
- Posner JB. Autoantibodies in childhood opsoclonus-myoclonus syndrome. J Pediatr 1997; 130:855.
- Manni R, Terzaghi M. Rhythmic movements during sleep: a physiological and pathological profile. Neurol Sci 2005; 26 Suppl 3:s181.
- Derry CP, Duncan JS, Berkovic SF. Paroxysmal motor disorders of sleep: the clinical spectrum and differentiation from epilepsy. Epilepsia 2006; 47:1775.
- NEONATES (BIRTH TO ONE MONTH OF AGE)
- Benign neonatal sleep myoclonus
- INFANTS (ONE MONTH TO ONE YEAR OF AGE)
- Breath-holding spells
- - Cyanotic breath-holding spells
- - Pallid breath-holding spells
- - Diagnosis
- - Prognosis and treatment
- Benign myoclonus of infancy
- Shuddering attacks
- Sandifer syndrome
- - Benign paroxysmal torticollis in infancy
- Abnormal eye movements
- Sleep-related rhythmic movement disorder