Epilepsia , 33(5): 8 17-820, 1992 Raven Press, Ltd., New York 0 International League Against Epilepsy
Neonatal Hyperekplexia: A Case Report A. Pascotto and G. Coppola Clinic of Child Neuropsychiatry , Department of Pediatrics, Naples University, Naples, Italy
Summary: We report the case of a baby with transient generalized stiffness noticeable from the first days of life, hyperreflexia, massive jerks in response to sudden tactile and acoustic stimuli, and long-lasting myoclonic jerks closely resembling epileptic seizures. The father and pa-
ternal grandfather both had hyperekplexia. At age 3 years, the child had normal psychomotor development and persistent abnormal startle response to unexpected sounds or touch. Key Words: Hyperekplexia-seizuresNeonates-Electroencephalography.
Startle disease or hyperekplexia, a rare hereditary neurologic disorder, was first described by Kirstein and Silfverskiold (1958), with subsequent reports of affected families and sporadic cases (Suhren et al., 1966; Andermann et al., 1980; Lingam et al., 1981; Kurczynski, 1983; Markand et al., 1984; Saenz-Lope et al., 1984; Dooley and Andermann, 1989; Brown et al., 1991). The disorder, manifested by an exaggerated startle response, generalized muscular rigidity in infancy and prominent nocturnal myoclonus, is characterized by two abnormal forms of response to unexpected auditory, visual, and somaesthetic stimuli: the sustained tonic spasm and the briefer pathologic startle reflex. Both are presumed to be the result of activity in a common reflex center in the lower brainstem (Brown et al., 1991). Giant cortical somatosensory evoked potentials (SEPs) have been noted in probands and relatives. Hyperekplexia is easily mistaken for commoner problems such as epilepsy, spastic quadriparesis, ataxia, and myoclonic syndromes. A major and a minor form have been distinguished (Andermann et al., 1980). Symptomatology is dependent on age of onset. The major form, with neonatal onset, can be very severe, with newborns having repeated myoclonic jerks and increased muscle tone with life-threatening apnea due to contraction of respiratory muscles. Two sudden infant deaths have been reported (Suhren et al., 1966; Kurczynski, 1983; Vigevano et al., 1989). We report a 30-day-old
baby with startle disease and a family history of h y perekplexia.
CASE REPORT A male infant was born at term after a normal pregnancy with a birthweight of 3,150 g and an Apgar score of 9-10-10. Focal and generalized jerks were noticed soon after birth when loud noises occurred or when the infant was touched (particularly on the face or forehead). The jerks were associated with stiffness, slightly more pronounced in the lower limbs. During sleep, muscle tone was normal. In the first months, massive jerks occurred only during quiet sleep in response to sudden tactile or sound stimulations. Familial history disclosed massive jerks after unexpected stimuli, e.g., touching the tip of the nose or tapping the shoulder, in both the father and paternal grandfather. At age 1 month, complete blood cell count, urinalysis, blood electrolytes, glucose, calcium, phosphorus, creatinine, uric acid, SGOT, SGPT, lactic dehydrogenase, alkaline phosphatase, bilirubin, total protein, albumin, cholesterol, and triglyceride levels were normal. Metabolic screening for urinary amino acids was negative. Echoencephalogram, nuclear magnetic resonance imaging, and sleep and waking EEGs were normal. Polygraph recordings of paroxysmal episodes showed generalized rhythmic myoclonias (10-12/s) after stimulation, and the EEG showed diffuse low-voltage myogenic fast activity with slowing of background biorhythms at the end of seizures, probably caused by alterations in cardiorespiratory rate (Fig. 1). Seizures occurred while the patient was asleep and lasted from 20 s to
Received April 1992; revision accepted May 1992. Address correspondence and reprint requests to Professor A. Pascotto at Clinic of Child Neuropsychiatry, Department of Pediatrics, Via Pansini 5 , 80131 Naples, Italy.
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NEONATAL HYPEREKPLEXIA
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FIG. 2. Sleep EEG showing two consecutive startle responses induced by tactile stimulus (arrow) accompanied by high voltage artifactual potentials, mainly localized to the parietooccipital regions.
several minutes. Seizures were partially reduced by treatment with oral clonazepam. The parents had discovered that longer seizures could be stopped promptly by flexing the infant’s head and legs toward the trunk. This method was always effective. Seizures continued to occur daily until the baby was aged 4 months. Stiffness gradually decreased, although some paratonus was still evident at 18 months. The infant began kinesitherapy at 4 months. Growth and development were normal, and by 1 year he was walking without support and saying a few words. At age 3 years, the child was completely normal; mild hypertonia of the lower limbs was noticeable when he became upset or irritated. DISCUSSION
Our case is a major form of startle syndrome with neonatal onset (Andermann et al., 1980). In our patient, both longer seizures and simple startle reactions were accompanied by a sharp electropositive EEG wave, bisynchronous over the parietooccipital regions. In stronger startle reactions, these tended to diffuse anteriorly with a latency of a few milliseconds. Spike-wave complexes, whose voltage depended on stimulus intensity, were probably artifacts rather than cortical potentials, interpretable as
evoked responses to the sensory stimulus (Gastaut and Villeneuve, 1967). This surface electropositive sharp wave evidently is not ocular in origin (Markand et al., 1984) because it is either absent in prefrontal areas or appears first in the parietooccipital areas (Fig. 2). Our case supports the familial occurrence of startle disease (Suhren et al., 1966; Andermann et al., 1980). Startle seizures may be misdiagnosed if one is not aware of this syndrome. Medication effects are variable (Kurczynski, 1983; Vigevano et al., 1989). The best treatment for longer seizures, a potential cause of sudden infant death, is forcible flexion of the baby’s head and legs toward the trunk (Vigevano et al., 1989). It is of interest that in our case this method was devised spontaneously by the baby’s parents. Long-term prognosis appears good for psychomotor development. REFERENCES Andermann F, Keene DL, Andermann E, Quesney LF. Startle disease or hyperekplexia: further delineation of the syndrome. Bruin 1980;103:985-7. Brown P, Rothwell JC, Thompson PD, Britton TC, Day BL, Marsden D. The hyperekplexias and their relationship to the normal startle reflex. Bruin 1991;114: 1903-28. Dooley MJ, Andermann F. Startle disease or hyperekplexia: adEpilepsia, Vol. 33, No. 5 , 1992
A . PASCOTTO AND G . COPPOLA
820
olescent onset and response to valproate. Pediatr Neurol 1 9 8 9 5 126-7. Gastaut H, Villeneuve A. The startle disease or hyperekplexia: pathological surprise reaction. J Neurol Sci 1967;5:523-42. Kirstein L, Silfverskiold B. A family with emotionally precipitated drop seizures. Acta Paediatr Scand 1958;33:471-6. Kurczynski TW. Hyperekplexia. Arch Neurol 1983;40:246-8. Lingam S, Wilson J, Hart EW. Hereditary stiff-baby syndrome. A m J D i s Child 1981;135:909-11. Markand ON, Garg BP, Weaver DD. Familial startle disease (hyperekplexia): electrophysiologic studies. Arch Neurol 1984;41:71-4. Shenz-Lope E, Herranz-Tanarro FJ, Masdeu JC, Chacon Pena JR. Hyperekplexia: a syndrome of pathological startle responses. Ann Neurol 1984;15:36-41. Suhren 0, Bruyn GW, Tuynman JA. Hyperekplexia: a hereditary startle syndrome. J Neurol Sci 1966;3:577-605. Vigevano F, Di Capua M, Dalka Bernardina B. Startle disease: an avoidable cause of sudden infant death. Lancet 1989;1:216.
tance d’une rCponse en sursaut anormale aux stimulations sonores ou tactiles inopinkes. (P. Genton, Murseille)
RESUMEN Los autores publican un caso de un nifio con rigidez generalizada transitoria que aparici6 en 10s primeros dias de la vida asociada a hiperrreflexia y mioclonias masivas como respuesta a estimulos tictiles y aclisticos repentinos. Tambien presentaron contracciones mioclonicas durante largos periodos de tiempo que semejaban ataques epilepticos. El padre y el abuelo paterno habian tenido ataques del “sobresalto”. A 10s 3 aiios de edad el niiio se habia desarrollado normalmente desde el punto de vista psicomotor y persistian las respuestas anormales de sobresalto tras estimulos tactiles y sonoros inesperados. (A. Portera-Sanchez, Madrid)
ZUSAMMENFASSUNG &SUME Les auteurs rapportent le cas d’un nourrisson prksentant une rigidite generaliske transitoire qui a pu &re remarquee des les premiers jours de vie. Une hyperrekplexia, des secousses massives provoquees par des stimulations tactiles ou acoustiques soudaines, et de longues secousses myocloniques ressemblant de pres a des crises Cpileptiques. Le pere et le grand-pere paternel presentaient tous les deux une hyperekplexia. A 3 ans, l’enfant prksentait un dkveloppement psychomoteur normal et la persis-
Epilepsia, Vol. 33, N o , 5 . 1992
Wir berichten uber ein Neugeborenes mit transienter generalisierter Steifheit vom ersten Lebenstag an. Hyperreflexie, ausfahrenden Bewegungen auf plotzliche taktile oder akustische Stimuli sowie langanhaltende Myoklonien, die epileptischen Anfallen ahnelten. Vater und GroRvater hatten ebenfalls eine Hyperekplexie gehabt. Mit 3 Jahren bot das Kind eine normale psychomotorische Entwicklung. Es hatte jedoch noch eine abnorme Startle-Antwort bei unerwartetem LBrm oder Beruhrung. (C. G. Lipinski, HeidelberglNeckargemund)
Neonatal Hyperekplexia: A Case Report A. Pascotto and G. Coppola Clinic of Child Neuropsychiatry , Department of Pediatrics, Naples University, Naples, Italy
Summary: We report the case of a baby with transient generalized stiffness noticeable from the first days of life, hyperreflexia, massive jerks in response to sudden tactile and acoustic stimuli, and long-lasting myoclonic jerks closely resembling epileptic seizures. The father and pa-
ternal grandfather both had hyperekplexia. At age 3 years, the child had normal psychomotor development and persistent abnormal startle response to unexpected sounds or touch. Key Words: Hyperekplexia-seizuresNeonates-Electroencephalography.
Startle disease or hyperekplexia, a rare hereditary neurologic disorder, was first described by Kirstein and Silfverskiold (1958), with subsequent reports of affected families and sporadic cases (Suhren et al., 1966; Andermann et al., 1980; Lingam et al., 1981; Kurczynski, 1983; Markand et al., 1984; Saenz-Lope et al., 1984; Dooley and Andermann, 1989; Brown et al., 1991). The disorder, manifested by an exaggerated startle response, generalized muscular rigidity in infancy and prominent nocturnal myoclonus, is characterized by two abnormal forms of response to unexpected auditory, visual, and somaesthetic stimuli: the sustained tonic spasm and the briefer pathologic startle reflex. Both are presumed to be the result of activity in a common reflex center in the lower brainstem (Brown et al., 1991). Giant cortical somatosensory evoked potentials (SEPs) have been noted in probands and relatives. Hyperekplexia is easily mistaken for commoner problems such as epilepsy, spastic quadriparesis, ataxia, and myoclonic syndromes. A major and a minor form have been distinguished (Andermann et al., 1980). Symptomatology is dependent on age of onset. The major form, with neonatal onset, can be very severe, with newborns having repeated myoclonic jerks and increased muscle tone with life-threatening apnea due to contraction of respiratory muscles. Two sudden infant deaths have been reported (Suhren et al., 1966; Kurczynski, 1983; Vigevano et al., 1989). We report a 30-day-old
baby with startle disease and a family history of h y perekplexia.
CASE REPORT A male infant was born at term after a normal pregnancy with a birthweight of 3,150 g and an Apgar score of 9-10-10. Focal and generalized jerks were noticed soon after birth when loud noises occurred or when the infant was touched (particularly on the face or forehead). The jerks were associated with stiffness, slightly more pronounced in the lower limbs. During sleep, muscle tone was normal. In the first months, massive jerks occurred only during quiet sleep in response to sudden tactile or sound stimulations. Familial history disclosed massive jerks after unexpected stimuli, e.g., touching the tip of the nose or tapping the shoulder, in both the father and paternal grandfather. At age 1 month, complete blood cell count, urinalysis, blood electrolytes, glucose, calcium, phosphorus, creatinine, uric acid, SGOT, SGPT, lactic dehydrogenase, alkaline phosphatase, bilirubin, total protein, albumin, cholesterol, and triglyceride levels were normal. Metabolic screening for urinary amino acids was negative. Echoencephalogram, nuclear magnetic resonance imaging, and sleep and waking EEGs were normal. Polygraph recordings of paroxysmal episodes showed generalized rhythmic myoclonias (10-12/s) after stimulation, and the EEG showed diffuse low-voltage myogenic fast activity with slowing of background biorhythms at the end of seizures, probably caused by alterations in cardiorespiratory rate (Fig. 1). Seizures occurred while the patient was asleep and lasted from 20 s to
Received April 1992; revision accepted May 1992. Address correspondence and reprint requests to Professor A. Pascotto at Clinic of Child Neuropsychiatry, Department of Pediatrics, Via Pansini 5 , 80131 Naples, Italy.
817
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4 dCIC
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NEONATAL HYPEREKPLEXIA
819
FIG. 2. Sleep EEG showing two consecutive startle responses induced by tactile stimulus (arrow) accompanied by high voltage artifactual potentials, mainly localized to the parietooccipital regions.
several minutes. Seizures were partially reduced by treatment with oral clonazepam. The parents had discovered that longer seizures could be stopped promptly by flexing the infant’s head and legs toward the trunk. This method was always effective. Seizures continued to occur daily until the baby was aged 4 months. Stiffness gradually decreased, although some paratonus was still evident at 18 months. The infant began kinesitherapy at 4 months. Growth and development were normal, and by 1 year he was walking without support and saying a few words. At age 3 years, the child was completely normal; mild hypertonia of the lower limbs was noticeable when he became upset or irritated. DISCUSSION
Our case is a major form of startle syndrome with neonatal onset (Andermann et al., 1980). In our patient, both longer seizures and simple startle reactions were accompanied by a sharp electropositive EEG wave, bisynchronous over the parietooccipital regions. In stronger startle reactions, these tended to diffuse anteriorly with a latency of a few milliseconds. Spike-wave complexes, whose voltage depended on stimulus intensity, were probably artifacts rather than cortical potentials, interpretable as
evoked responses to the sensory stimulus (Gastaut and Villeneuve, 1967). This surface electropositive sharp wave evidently is not ocular in origin (Markand et al., 1984) because it is either absent in prefrontal areas or appears first in the parietooccipital areas (Fig. 2). Our case supports the familial occurrence of startle disease (Suhren et al., 1966; Andermann et al., 1980). Startle seizures may be misdiagnosed if one is not aware of this syndrome. Medication effects are variable (Kurczynski, 1983; Vigevano et al., 1989). The best treatment for longer seizures, a potential cause of sudden infant death, is forcible flexion of the baby’s head and legs toward the trunk (Vigevano et al., 1989). It is of interest that in our case this method was devised spontaneously by the baby’s parents. Long-term prognosis appears good for psychomotor development. REFERENCES Andermann F, Keene DL, Andermann E, Quesney LF. Startle disease or hyperekplexia: further delineation of the syndrome. Bruin 1980;103:985-7. Brown P, Rothwell JC, Thompson PD, Britton TC, Day BL, Marsden D. The hyperekplexias and their relationship to the normal startle reflex. Bruin 1991;114: 1903-28. Dooley MJ, Andermann F. Startle disease or hyperekplexia: adEpilepsia, Vol. 33, No. 5 , 1992
A . PASCOTTO AND G . COPPOLA
820
olescent onset and response to valproate. Pediatr Neurol 1 9 8 9 5 126-7. Gastaut H, Villeneuve A. The startle disease or hyperekplexia: pathological surprise reaction. J Neurol Sci 1967;5:523-42. Kirstein L, Silfverskiold B. A family with emotionally precipitated drop seizures. Acta Paediatr Scand 1958;33:471-6. Kurczynski TW. Hyperekplexia. Arch Neurol 1983;40:246-8. Lingam S, Wilson J, Hart EW. Hereditary stiff-baby syndrome. A m J D i s Child 1981;135:909-11. Markand ON, Garg BP, Weaver DD. Familial startle disease (hyperekplexia): electrophysiologic studies. Arch Neurol 1984;41:71-4. Shenz-Lope E, Herranz-Tanarro FJ, Masdeu JC, Chacon Pena JR. Hyperekplexia: a syndrome of pathological startle responses. Ann Neurol 1984;15:36-41. Suhren 0, Bruyn GW, Tuynman JA. Hyperekplexia: a hereditary startle syndrome. J Neurol Sci 1966;3:577-605. Vigevano F, Di Capua M, Dalka Bernardina B. Startle disease: an avoidable cause of sudden infant death. Lancet 1989;1:216.
tance d’une rCponse en sursaut anormale aux stimulations sonores ou tactiles inopinkes. (P. Genton, Murseille)
RESUMEN Los autores publican un caso de un nifio con rigidez generalizada transitoria que aparici6 en 10s primeros dias de la vida asociada a hiperrreflexia y mioclonias masivas como respuesta a estimulos tictiles y aclisticos repentinos. Tambien presentaron contracciones mioclonicas durante largos periodos de tiempo que semejaban ataques epilepticos. El padre y el abuelo paterno habian tenido ataques del “sobresalto”. A 10s 3 aiios de edad el niiio se habia desarrollado normalmente desde el punto de vista psicomotor y persistian las respuestas anormales de sobresalto tras estimulos tactiles y sonoros inesperados. (A. Portera-Sanchez, Madrid)
ZUSAMMENFASSUNG &SUME Les auteurs rapportent le cas d’un nourrisson prksentant une rigidite generaliske transitoire qui a pu &re remarquee des les premiers jours de vie. Une hyperrekplexia, des secousses massives provoquees par des stimulations tactiles ou acoustiques soudaines, et de longues secousses myocloniques ressemblant de pres a des crises Cpileptiques. Le pere et le grand-pere paternel presentaient tous les deux une hyperekplexia. A 3 ans, l’enfant prksentait un dkveloppement psychomoteur normal et la persis-
Epilepsia, Vol. 33, N o , 5 . 1992
Wir berichten uber ein Neugeborenes mit transienter generalisierter Steifheit vom ersten Lebenstag an. Hyperreflexie, ausfahrenden Bewegungen auf plotzliche taktile oder akustische Stimuli sowie langanhaltende Myoklonien, die epileptischen Anfallen ahnelten. Vater und GroRvater hatten ebenfalls eine Hyperekplexie gehabt. Mit 3 Jahren bot das Kind eine normale psychomotorische Entwicklung. Es hatte jedoch noch eine abnorme Startle-Antwort bei unerwartetem LBrm oder Beruhrung. (C. G. Lipinski, HeidelberglNeckargemund)
