Historical note and nomenclature
Startle epilepsy has been described in the 1989 International Classification of Epilepsies and Epileptic Syndromes as a symptomatic variety of epilepsy in which seizures occur with a specific mode of precipitation (Anonymous 1989). The most recent proposed classification (Engel 2001) includes startle epilepsy as an epilepsy syndrome sui generis under the heading reflex epilepsy. Modern descriptions of startle epilepsy date from the 1950s, but older literature suggests that some confusion may have existed between startle epilepsy and nonepileptic disorders such as hyperekplexia and Tourette syndrome, and confusion with nonepileptic paroxysmal movement disorders may persist.
Clinical manifestations
Startle epilepsy is characterized by seizures induced by sudden and unexpected stimuli, usually a sudden sound (Alajouanine and Gastaut 1955). Most patients with startle epilepsy are sensitive to only one sensory modality, but the unexpected nature of the stimulus rather than the sensory modality is the distinguishing feature. The seizures are frequent, usually lasting less than 30 seconds and consisting of a startle response followed by a brief but characteristic tonic phase, which is usually asymmetric. Many subjects fall, and clonic jerks may occur. Injury is common when the seizures occur in patients who are standing or able to fall while seated, or while they are in bathtubs or similar risky locations. Repetition of the stimulus will induce transient habituation. Such patients usually have long-standing static cerebral lesions and intellectual handicap. Many are hemiparetic; in these, the weak side is primarily and preferentially involved in the seizure. Spontaneous seizures occur, reportedly in all cases, but may be infrequent. Startle epilepsy is typically intractable and seizures may be frequent.
Etiology
Patients with startle epilepsy usually have other evidence of localized or diffuse static encephalopathy, such as hemiparesis or developmental delay of different etiologies. The insult typically occurs within the first 2 years of life and is often pre- or perinatal. Brain imaging may show localized lesions (mesial hypodensity) or diffuse lesions (Aguglia et al 1984; Guerrini et al 1990). The lateralized lesions usually involve sensorimotor and premotor cortex and white matter, but normal scans have been reported without neurologic deficit (Manford et al 1996). Such patients have precentral or perisylvian dysplastic lesions on MRI. Schizencephaly has also been found. Startle epilepsy often occurs with Down syndrome. Startle myoclonus, though not clearly startle epilepsy, has been reported in association with GM2 gangliosidosis (Nalini and Christopher 2004), and startle epilepsy has been reported with aspartylglucosaminuria (Labate et al 2004).
Pathogenesis and pathophysiology
The pathophysiology of startle epilepsy is conjectural. The seizures resemble supplementary motor seizures, and the localized lesions and seizure onset often involve that area or its surroundings. The epileptogenic lesion may be in the dorsolateral frontal lobe or in the perirolandic area (for a recent example with video illustration, see Nolan et al 2005). The startle reaction may trigger nearby epileptogenic tissue, but this does not explain patients with diffuse lesions and EEG abnormalities in whom diffuse deficiencies in cortical inhibition have been suggested (Andermann and Andermann 1986; Guerrini et al 1990; Serles et al 1999).
Differential diagnosis
Startle epilepsy should not be confused with startle disease (hyperekplexia) and other startle disorders and should be distinguishable on clinical, EEG, and radiologic grounds especially since the seizures of startle epilepsy can usually be easily induced for study during routine EEG recording (Andermann and Andermann 1986). Occasionally, startle epilepsy may be more difficult to distinguish from hyperekplexia (Cokar et al 2001). Startle stimuli can cause nonepileptic falls in Coffin-Lowry syndrome. Touch-evoked or tap seizures in children (Deonna 1998; Zafeiriou et al 2003) may have a startle component, but are not Startle Epilepsy as currently defined. In these, generalized epileptiform EEG activity and myoclonic seizures are evoked without clinical, radiologic, or EEG evidence of lateralized lesions. Infants and children with touch-evoked seizures usually are developmentally normal, with normal EEG background activity. Touch-evoked seizures are rare, and though usually relatively benign and often not requiring long-term treatment, they also have been reported with diffuse degenerative encephalopathies (Deonna 1998). Seizures induced by sudden dousing with hot water may also have a startle component at some time in their course but are not to be confused with startle epilepsy (Satishchandra et al 1998; Bebek et al 2001). Other reflex seizures, produced by cutaneous or proprioceptive stimulation, should also be distinguished from startle epilepsy (Vignal et al 1998; Kanemoto et al 2001).
Diagnostic workup
Startle epilepsy typically begins in neurodevelopmentally handicapped children. Associated disorders include infantile hemiplegia of typically static etiologies such as cortical dysplastic lesions, Down syndrome, anoxic encephalopathy, or remote infection and, rarely, progressive disorders such as inborn errors of metabolism. The EEG epileptiform abnormalities can be lateralized or regional in those with large unilateral lesions and hemiparesis: widespread lesions are associated with diffuse epileptiform activity. Scalp EEG ictal recording shows an initial vertex discharge followed by diffuse relative flattening or low voltage rhythm at about 10 Hz. Ictal depth electrode recordings have shown an initial high amplitude evoked response over motor areas corresponding to the vertex scalp activity, followed by ictal EEG discharge, which begins in lesioned motor or premotor cortex and spreads to mesial frontal, parietal, and contralateral frontal regions (Bancaud et al 1967; 1975; Vignal et al 1998). Subdural recordings in a patient with a small lesion next to the right supplementary sensorimotor area showed seizure onset in the right dorsolateral premotor cortex and the right supplementary sensorimotor area (Serles et al 1999).
Prognosis and complications
Startle epilepsy usually occurs in patients with severe preexisting encephalopathies, and usually only incomplete or temporary seizure control can be achieved. These patients, with intractable epilepsy, identifiable brain lesions, and neurologic and developmental abnormalities, have significantly increased mortality compared to the general population. Milder cases may occur in subjects with histories of more subtle neurologic handicap.
Management
Medical management with drugs appropriate for focal seizures is indicated and in milder cases can effectively control these reflex seizures (Cokar et al 2001). Improvement has been reported in startle epilepsy with carbamazepine when lateralized neurologic signs, focal lesions and localized or regional EEG abnormalities are present, and both clonazepam and clobazam (not available in the United States) have been useful adjuncts (Aguglia et al 1984; Saenz-Lope et al 1984; Labate et al 2004) although few patients have been studied in detail. Lamotrigine is reportedly useful (Faught 1999). Psychological interventions may also help (McCusker and Hicks 1999) Complete or lasting seizure control, however, is not usually possible. Surgery has been reported to control startle epilepsy associated with infantile hemiplegia (Oguni et al 1998; Caraballo et al 2004; Martinez-Manas et al 2004) and, in view of the nature of the seizures and their intractability, should perhaps be considered earlier and for more patients.
References
Aguglia U, Tinuper P, Gastaut H. Startle-induced epileptic seizures. Epilepsia 1984;25:712-20.
Alajouanine T, Gastaut H. La syncinésie-sursaut et l'épilepsie-sursaut à déclenchement sensoriel ou sensitif inopiné. Rev Neurol 1955;93:29-41.
Andermann F, Andermann E. Excessive startle syndromes: startle disease, jumping, and startle epilepsy. Adv Neurol 1986;43:321-38.
Anonymous. Proposal for revised classification of epilepsies and epileptic syndromes. Commission on Classification and Terminology of the International League Against Epilepsy. Epilepsia 1989;30(4):389-99.
Bancaud J, Talairach J, Bonis A. Physiopathogénie des épilepsies-sursaut (à propos d'une épilepsie de l'aire motrice supplementaire). Rev Neurol 1967;117:441-53.
Bancaud J, Talairach J, Lamarche M, Bonis A, Trottier S. Hypothèses neurophysiopathologiques sur l'épilepsie-sursaut chez l'homme. Rev Neurol 1975;131:559-71.
Bebek N, Gurses C, Gokyigit A, Baykan B, Ozkara C. Dervent A. Hot water epilepsy: clinical and electrophysiologic findings based on 21 cases. Epilepsia 2001;42(9):1180-4.
Caraballo R, Semprino M, Cersosimo R, Sologuestua A, Arroyo HA, Fejerman N. Hemiparetic cerebral palsy and startle epilepsy (in Spanish). Rev Neurol 2004;38:123-7.
Cokar O, Gelisse P, Livet MO, Bureau M, Habib M, Genton P. Startle response: epileptic or non-epileptic? The case for "flash" SMA reflex seizures. Epileptic Disord. 2001;3(1):7-12.
Deonna T. Reflex seizures with somatosensory precipitation. Clinical and electroencephalographic patterns and differential diagnosis, with emphasis on reflex myoclonic epilepsy of infancy. In: Zifkin BG, Andermann F, Beaumanoir A, Rowan AJ, editors. Reflex epilepsies and reflex seizures. Advances in neurology. Vol 75. Philadelphia: Lippincott-Raven; 1998:193-206.
Engel J Jr. A proposed diagnostic scheme for people with epileptic seizures and with epilepsy: report of the ILAE Task Force on Classification and Terminology. Epilepsia 2001;42(6):796-803.
Faught E. Lamotrigine for startle-induced seizures. Seizure 1999;8:361-3.
Guerrini R, Genton P, Bureau M, Dravet C, Roger J. Reflex seizures are frequent in patients with Down syndrome and epilepsy. Epilepsia 1990;31:406-17.
Kanemoto K, Watanabe Y, Tsuji T, Fukami M, Kawasaki J. Rub epilepsy: a somatosensory evoked reflex epilepsy induced by prolonged cutaneous stimulation. J Neurol Neurosurg Psychiatry 2001;70(4):541-3.
Labate A, Barone R, Gambardella A, et al. Startle epilepsy complicating aspartylglucosaminuria. Brain Dev 2004;26:130-3.
Manford MR, Fish DR, Shorvon SD. Startle-provoked epileptic seizures: features in 19 patients. J Neurol Neurosurg Psychiatry 1996;61:151-6.
Martinez-Manas R, Daniel RT, Debatisse D, et al. Intractable reflex audiogenic epilepsy successfully treated by peri-insular hemispherotomy. Seizure 2004;13:486-90.
McCusker CG, Hicks EM. Psychological management of intractable seizures in an adolescent with learning disability. Seizure 1999;8:358-60.
Nalini A, Christopher R. Cerebral glycolipidoses: clinical characteristics of 41 pediatric patients. J Child Neurol 2004;19:447-52.
Nolan MA, Otsubo H, Iida K, Minassian BA. Startle-induced seizures associated with infantile hemiplegia: implication of the supplementary motor area. Epileptic Disord 2005;7:49-52.
Oguni H, Hayashi K, Usui N, Osawa M, Shimizu H. Startle epilepsy with infantile hemiplegia: report of two cases improved by surgery. Epilepsia 1998;39:93-8.
Saenz-Lope E, Herranz-Tanarro FJ, Masdeu JC, Chacon Pena JR. Hyperekplexia: a syndrome of pathological startle responses. Ann Neurol 1984;15:36-41.
Satishchandra P, Ullal GR, Shankar SK. Hot water epilepsy. In: Zifkin BG, Andermann F, Beaumanoir A, Rowan AJ, editors. Reflex epilepsies and reflex seizures. Advances in neurology. Vol 75. Philadelphia: Lippincott-Raven; 1998:283-93.
Serles W, Leutmezer F, Pataraia E, et al. A case of startle epilepsy and SSMA seizures documented with subdural recordings. Epilepsia 1999;40(7):1031-5.
Vignal JP, Biraben A, Chauvel PY, Reutens DC. Reflex partial seizures of sensorimotor cortex (including cortical reflex myoclonus and startle epilepsy). In: Zifkin BG, Andermann F, Beaumanoir A, Rowan JA, editors. Reflex epilepsies and reflex seizures. Advances in neurology. Vol 75. Philadelphia: Lippincott-Raven Press; 1998:207-26.
Zafeiriou D, Vargiami E, Kontopoulos E. Reflex myoclonic epilepsy in infancy: a benign age-dependent idiopathic startle epilepsy. Epileptic Disord 2003;5(2):121-2.