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Photosensitive complex partial seizures aggravated by phenytoin
Photosensitive Complex Partial Seizures Aggravated by Phenytoin Avinoam Shuper, MD and Eileen P.G. Vining, MD
A 10-year-old girl is described with pure photosensitive complex partial seizures which consisted of a frightening visual phenomenon of seeing "shadow people," then staring blankly with lip smacking and sometimes becoming limp. The seizures were triggered by bright sunlight. With the institution of phenytoin therapy, her seizure frequency increased dramatically without any clinical evidence of toxicity and her phenytoin blood levels were within the therapeutic range. Discontinuation of phenytoin led to a return to baseline seizure frequency. The mechanism by which antiepileptic drugs may aggravate seizures is still not understood; therefore, awareness of this phenomenon is crucial for early diagnosis and appropriate treatment. S h u p e r A , V i n i n g E P G . P h o t o s e n s i t i v e c o m p l e x partial s e i z u r e s a g g r a v a t e d b y p h e n y t o i n , P e d i a t r N e u r o l 1991;7: 471-2.
Introduction T h e e x a c e r b a t i o n o f s e i z u r e s in a p a t i e n t w h o is r e c e i v ing a n t i e p i l e p t i c d r u g ( A E D ) t h e r a p y m a y b e d u e to t h e following: (1) A d e c r e a s i n g b l o o d level o f a p r e v i o u s l y e f f e c t i v e a n t i e p i l e p t i c drug; (2) A d e g e n e r a t i v e - p r o g r e s s i v e n e u r o l o g i c p r o c e s s in w h i c h there is true d e t e r i o r a t i o n in the patient; or, (3) A s p o n t a n e o u s i n c r e a s e in the n u m b e r o f seizures, u n r e l a t e d to the A E D o r a n a d v e r s e e f f e c t c a u s e d specifically b y the A E D [1,2]. C a r e f u l m o n i t o r i n g o f seizure f r e q u e n c y a n d A E D b l o o d l e v e l s is c r u c i a l f o r a p p r o p r i a t e m a n a g e m e n t o f t h e epileptic patient. A w a r e n e s s o f the p o t e n t i a l s e i z u r e - w o r s e n i n g effects o f a n A E D is a p r e r e q u i s i t e f o r e a r l y r e c o g n i t i o n o f such a phenomenon.
From the Department of Neurology, Division of Pediatric Neurology; Johns Hopkins Hospital; Baltimore, Maryland.
W e r e p o r t a girl w i t h a p u r e p h o t o s e n s i t i v e c o m p l e x partial seizure disorder. H e r s e i z u r e s c l e a r l y b e c a m e w o r s e w h e n s h e was treated w i t h p h e n y t o i n , d e m o n s t r a t i n g t h e u n p r e d i c t a b l e s e i z u r e - w o r s e n i n g effect o f a n A E D .
Case Report This 10-year-old girl presented to our clinic at the age of 21/2 years with the recurrence of simple febrile seizures. No AED therapy was initiated. She returned at the age of 4 years when nonfebrile seizures developed. She was born at 37 weeks gestation after a normal pregnancy and uneventful delivery, weighing 2,100 gin. The perinatal period was unremarkable. In early infancy she had recurrent otitis media which subsequently led to left-sided hearing loss. She appeared to have mild developmental delay, was clumsy, and ultimately had a mild learning disability. At 6 years of age, a developmental evaluation revealed an IQ of 70. The pattern of her seizures was constant: she would experience a frightening visual phenomenon, consisting of seeing "shadow people," then her head and eyes turned to the right. She would stare blankly, exhibit lip smacking, and occasionally became limp or wobbly but rarely fell to the ground. The episode would last 2-5 min after which she would be sleepy and usually required a short nap; upon awakening she often had a headache. Her seizures had an obvious photosensitive nature. They always occurred in bright sunlight, routinely between 10:30 a.m. to 12:30 p.m., generally out of doors during the morning recess at school, or where there was bright sunlight. No other photic stimulation appeared to induce these seizures. The seizure frequency was constant, about 4 times a year for longer than 3 years. She was a pleasant interactive girl whose general physical and neurologic examinations were normal with the exception of left-sided heating loss. Cranial magnetic resonance imaging revealed a cavum septum pellucidum but no significant structural abnormality of the brain. Electroencephalography (EEG), performed at the age of 5 years, was moderately abnormal because of excessive diffuse and symmetric slow activity, with sporadic, bilaterally synchronous high-voltage sharp transients in the occipital leads. This activity was enhanced by intermittent photic stimulation, which at low flashing rates gave rise to an impressive occipital driving response. Subsequent EEGs continued to demonstrate some generalized slowing and a very good occipital driving response, but no longer disclosed evidence of sharp transients. The seizures were infrequent and the parents were appropriately reluctant to initiate an AED. Sunglasses failed to prevent recurrence of the episodes. At 7 years of age, after 3 seizures occurred over a short period of time, treatment with carbamazepine was begun. The initiation of this drug resulted in the appearance of a diffuse allergic rash which necessitated discontinuation. Phenytoin (125 rag/day) was administered with blood levels between 13-18 gg/ml. After initiation of phenytoin, seizures increased to about 1 seizure per month and approximately 5 months later to 4-7 per month, almost a 10-fold increase in number compared to the pretreatment period. The seizures continued to have the same photosensitive character. Clonazepam was added but was rapidly discontinued due to severe behavioral problems. Because it had not controlled the seizures, phenytoin was gradually withdrawn over 3 weeks. Seizures stopped immediately. The child has been without any AEDs for the past 14 months and has returned to her pre-phenytoin baseline. During this period she had 2 fully developed seizures and several short "auras" of seeing shadows.
Communications should be addressed to: Dr. Shuper; Neuropediatric Unit; Beilinson Medical Center; Petah Tiqva 49100, Israel. Received February 15, 1991; accepted July 25, 1991.
Shuper and Vining: Photosensitive Seizures
471
Discussion Photosensitive epileptic seizures (PES) may be classified into 2 major groups; pure PES and PES occurring in patients who have other types of seizures. PES occurs in 1:4,000 of those 5-24 years of age and in about 3% of all persons with epilepsy. They are more common in females (M/F = 1: 1.7). The onset of pure PES usually occurs between the ages of 8-19 years [3-6]. Multiple environmental stimuli can cause PES, such as sunlight passing through regularly spaced objects or reflected on water or snow, stroboscopic illumination, flickering of the television, and videogames [3-51. Bright sunlight per se is a rare cause of PES; only 1 patient has been described in the literature, a 9-year-old girl who had "passing out" episodes in the mornings as she left her house for school I7]. These episodes occurred only on sunny days. Environmentally induced PESs are most often generalized tonic-clonic seizures. Absence, myoclonic, or partial seizures are observed with much smaller frequency. Generalized tonic-clonic, absence, and myoclonic seizures may also be induced by photic stimulation in the laboratory. Complex partial seizures are only sporadically reported to be caused by environmental photic stimuli 13-7 I. There is no universally accepted approach to the management of PES. Some authors believe that no medication is consistently effective for all types of PES, suggesting that the pharmacologic agents should be chosen according to the seizure type, with no consideration of the photosensitivity [3]. This approach was utilized in our patient. Other studies, however, claim that sodium valproate is the most effective drug for PES 14,51. In the Papio papio baboon, an animal model for the study of PES and its therapy, barbiturates and benzodiazepines were most effective in controlling the PES, while phenytoin was relatively ineffective 18]. ~henytoin, however, was not reported to aggravate the potential for PES. The clinical features of our patient are unusual. She presented at an early age with pure photosensitive complex partial seizures, triggered by bright morning sunlight. Her seizures could not be artificially provoked in the laboratory with a variety of types and frequencies of lights. Phenytoin monotherapy was associated with a markedly increased number of seizures of the same type, while blood levels were in the therapeutic range and without clinical signs of drug toxicity. Thus, this effect appears to be related to the drug itself, rather than to an intoxication. Seizure exacerbation may result from cerebral intoxication, caused by either polypharmacy or monotherapy overdose. Patients who were treated with combinations of AEDs had an increased seizure frequency and seizure control improved as the dosages were decreased. In addition, reduction of treatment in monotherapy trials has led to reduced frequency of seizures and can be seen as evidence that drug therapy was previously making patients worse
472
PEDIATRIC NEUROLOGY
Vol. 7 No. 6
[ 1,9-11[. In patients treated with monotherapy of phenytoin or carbamazepine, "paradoxical intoxication" has been described, a situation in which seizure frequency increases as the blood level of the AED rises to the supratherapeutic range 112,131. Seizure control may also deteriorate in some instances where there appears to be an actual precipitation of the seizures by the newly introduced AED. Many of the commonly used AEDs share the capacity to exacerbate seizures. Children with mixed seizure disorders, particularly those with generalized slow spike-and-wave discharges on EEG, became worse on carbamazepine 12,141. Some investigators also suggested that carbamazepine may exacerbate epileptiform discharges on EEG [14]. Benzodiazepines have been reported to produce status epilepticus when injected intravenously in children with the LennoxGastaut syndrome 1151. Phenytoin and carbamazepine were reported to aggravate absence seizures [21. Although the underlying mechanism for photosensitive epilepsy is unknown, it is important to remember that the AED sometimes may be epileptogenic.
References
[11 Tayhw DC. McKinaly I. When not to treat epilepsy with drugs. Dev Med Child Neurol 1984:26:822-33. 121 Lerman P. Seizures induced or aggravated by anticonvulsants. Epilepsia 1986; 27:706- I 0. 131 Newmark ME, Penry JK. Photosensitivity and epilepsy: A review. New York: Raven Press. 1979. 14] Holmes GL. Diagnosis and management of seizures in children. In: Markowitz M . e d . Major problems in clinical pediatrics. Philadelphia: WB Saunders, 1987;30:166-7. [5] Jeavons PM, Bishop A, Harding GFA. Thc prognosis of photosensitivity. Epilepsia 1986;27:569-75. [61 Aicardi J. Stimulus-sensitive epilepsies, In: Epilepsy m children: International review of child neurnlogy series. New York: Raven Press, 1986, 17] Livingston S. Comprehensive management of epilepsy in infancy, childhood and adolescence. Springfield: C.C. Thomas, 1972:102-8. 18] Meldrum BS. Photosensitive epilepsy in Papio papio as a model fi~r drug studies. In: Cobb WA, Van Duijn H, eds. Contemporary clinical neurophysiology. Amsterdam: Elsevier Scientific Publishing, 1978:317-22. 19] Theodore WH, Porter RJ. Removal of sedative-hypnotic antiepileptic drugs from the regimens of patients with intractable epilepsy, Ann Neurol 1983; 13: 320-4. [101 Schmidt D. Reduction of two drug therapy in intractable epilepsy. Epilepsia 1983:24:368-76. 111] Aicardi J. Clinical approach to the management of intractable epilepsy. Dev Med Child Neurol 1988;311:429-40. [121 Levy L L Fenichel GM. Diphenylhydamoin activated seizures. Neurology 1965; 15:716-22. [13] Troupin AS, Ojemann LM. Paradoxical intoxication A cumplication of anticonvulsant administration. Epilepsia 1975:16:753-8. 114] Snead OC, Hosey LC. Exacerbation of seizures in children by carbamazepine. N Engl J Med 1985:313:916-21, 115] Tassinari CA, Dravet C, Rojer J, Cano JT, Gastaut H. Tonic status epilepticus precipitated by intravenous benzodiazepine in five patients with Lennox-Gastaut syndrome. Epilepsia 1972; 13:421-35.
A 10-year-old girl is described with pure photosensitive complex partial seizures which consisted of a frightening visual phenomenon of seeing "shadow people," then staring blankly with lip smacking and sometimes becoming limp. The seizures were triggered by bright sunlight. With the institution of phenytoin therapy, her seizure frequency increased dramatically without any clinical evidence of toxicity and her phenytoin blood levels were within the therapeutic range. Discontinuation of phenytoin led to a return to baseline seizure frequency. The mechanism by which antiepileptic drugs may aggravate seizures is still not understood; therefore, awareness of this phenomenon is crucial for early diagnosis and appropriate treatment. S h u p e r A , V i n i n g E P G . P h o t o s e n s i t i v e c o m p l e x partial s e i z u r e s a g g r a v a t e d b y p h e n y t o i n , P e d i a t r N e u r o l 1991;7: 471-2.
Introduction T h e e x a c e r b a t i o n o f s e i z u r e s in a p a t i e n t w h o is r e c e i v ing a n t i e p i l e p t i c d r u g ( A E D ) t h e r a p y m a y b e d u e to t h e following: (1) A d e c r e a s i n g b l o o d level o f a p r e v i o u s l y e f f e c t i v e a n t i e p i l e p t i c drug; (2) A d e g e n e r a t i v e - p r o g r e s s i v e n e u r o l o g i c p r o c e s s in w h i c h there is true d e t e r i o r a t i o n in the patient; or, (3) A s p o n t a n e o u s i n c r e a s e in the n u m b e r o f seizures, u n r e l a t e d to the A E D o r a n a d v e r s e e f f e c t c a u s e d specifically b y the A E D [1,2]. C a r e f u l m o n i t o r i n g o f seizure f r e q u e n c y a n d A E D b l o o d l e v e l s is c r u c i a l f o r a p p r o p r i a t e m a n a g e m e n t o f t h e epileptic patient. A w a r e n e s s o f the p o t e n t i a l s e i z u r e - w o r s e n i n g effects o f a n A E D is a p r e r e q u i s i t e f o r e a r l y r e c o g n i t i o n o f such a phenomenon.
From the Department of Neurology, Division of Pediatric Neurology; Johns Hopkins Hospital; Baltimore, Maryland.
W e r e p o r t a girl w i t h a p u r e p h o t o s e n s i t i v e c o m p l e x partial seizure disorder. H e r s e i z u r e s c l e a r l y b e c a m e w o r s e w h e n s h e was treated w i t h p h e n y t o i n , d e m o n s t r a t i n g t h e u n p r e d i c t a b l e s e i z u r e - w o r s e n i n g effect o f a n A E D .
Case Report This 10-year-old girl presented to our clinic at the age of 21/2 years with the recurrence of simple febrile seizures. No AED therapy was initiated. She returned at the age of 4 years when nonfebrile seizures developed. She was born at 37 weeks gestation after a normal pregnancy and uneventful delivery, weighing 2,100 gin. The perinatal period was unremarkable. In early infancy she had recurrent otitis media which subsequently led to left-sided hearing loss. She appeared to have mild developmental delay, was clumsy, and ultimately had a mild learning disability. At 6 years of age, a developmental evaluation revealed an IQ of 70. The pattern of her seizures was constant: she would experience a frightening visual phenomenon, consisting of seeing "shadow people," then her head and eyes turned to the right. She would stare blankly, exhibit lip smacking, and occasionally became limp or wobbly but rarely fell to the ground. The episode would last 2-5 min after which she would be sleepy and usually required a short nap; upon awakening she often had a headache. Her seizures had an obvious photosensitive nature. They always occurred in bright sunlight, routinely between 10:30 a.m. to 12:30 p.m., generally out of doors during the morning recess at school, or where there was bright sunlight. No other photic stimulation appeared to induce these seizures. The seizure frequency was constant, about 4 times a year for longer than 3 years. She was a pleasant interactive girl whose general physical and neurologic examinations were normal with the exception of left-sided heating loss. Cranial magnetic resonance imaging revealed a cavum septum pellucidum but no significant structural abnormality of the brain. Electroencephalography (EEG), performed at the age of 5 years, was moderately abnormal because of excessive diffuse and symmetric slow activity, with sporadic, bilaterally synchronous high-voltage sharp transients in the occipital leads. This activity was enhanced by intermittent photic stimulation, which at low flashing rates gave rise to an impressive occipital driving response. Subsequent EEGs continued to demonstrate some generalized slowing and a very good occipital driving response, but no longer disclosed evidence of sharp transients. The seizures were infrequent and the parents were appropriately reluctant to initiate an AED. Sunglasses failed to prevent recurrence of the episodes. At 7 years of age, after 3 seizures occurred over a short period of time, treatment with carbamazepine was begun. The initiation of this drug resulted in the appearance of a diffuse allergic rash which necessitated discontinuation. Phenytoin (125 rag/day) was administered with blood levels between 13-18 gg/ml. After initiation of phenytoin, seizures increased to about 1 seizure per month and approximately 5 months later to 4-7 per month, almost a 10-fold increase in number compared to the pretreatment period. The seizures continued to have the same photosensitive character. Clonazepam was added but was rapidly discontinued due to severe behavioral problems. Because it had not controlled the seizures, phenytoin was gradually withdrawn over 3 weeks. Seizures stopped immediately. The child has been without any AEDs for the past 14 months and has returned to her pre-phenytoin baseline. During this period she had 2 fully developed seizures and several short "auras" of seeing shadows.
Communications should be addressed to: Dr. Shuper; Neuropediatric Unit; Beilinson Medical Center; Petah Tiqva 49100, Israel. Received February 15, 1991; accepted July 25, 1991.
Shuper and Vining: Photosensitive Seizures
471
Discussion Photosensitive epileptic seizures (PES) may be classified into 2 major groups; pure PES and PES occurring in patients who have other types of seizures. PES occurs in 1:4,000 of those 5-24 years of age and in about 3% of all persons with epilepsy. They are more common in females (M/F = 1: 1.7). The onset of pure PES usually occurs between the ages of 8-19 years [3-6]. Multiple environmental stimuli can cause PES, such as sunlight passing through regularly spaced objects or reflected on water or snow, stroboscopic illumination, flickering of the television, and videogames [3-51. Bright sunlight per se is a rare cause of PES; only 1 patient has been described in the literature, a 9-year-old girl who had "passing out" episodes in the mornings as she left her house for school I7]. These episodes occurred only on sunny days. Environmentally induced PESs are most often generalized tonic-clonic seizures. Absence, myoclonic, or partial seizures are observed with much smaller frequency. Generalized tonic-clonic, absence, and myoclonic seizures may also be induced by photic stimulation in the laboratory. Complex partial seizures are only sporadically reported to be caused by environmental photic stimuli 13-7 I. There is no universally accepted approach to the management of PES. Some authors believe that no medication is consistently effective for all types of PES, suggesting that the pharmacologic agents should be chosen according to the seizure type, with no consideration of the photosensitivity [3]. This approach was utilized in our patient. Other studies, however, claim that sodium valproate is the most effective drug for PES 14,51. In the Papio papio baboon, an animal model for the study of PES and its therapy, barbiturates and benzodiazepines were most effective in controlling the PES, while phenytoin was relatively ineffective 18]. ~henytoin, however, was not reported to aggravate the potential for PES. The clinical features of our patient are unusual. She presented at an early age with pure photosensitive complex partial seizures, triggered by bright morning sunlight. Her seizures could not be artificially provoked in the laboratory with a variety of types and frequencies of lights. Phenytoin monotherapy was associated with a markedly increased number of seizures of the same type, while blood levels were in the therapeutic range and without clinical signs of drug toxicity. Thus, this effect appears to be related to the drug itself, rather than to an intoxication. Seizure exacerbation may result from cerebral intoxication, caused by either polypharmacy or monotherapy overdose. Patients who were treated with combinations of AEDs had an increased seizure frequency and seizure control improved as the dosages were decreased. In addition, reduction of treatment in monotherapy trials has led to reduced frequency of seizures and can be seen as evidence that drug therapy was previously making patients worse
472
PEDIATRIC NEUROLOGY
Vol. 7 No. 6
[ 1,9-11[. In patients treated with monotherapy of phenytoin or carbamazepine, "paradoxical intoxication" has been described, a situation in which seizure frequency increases as the blood level of the AED rises to the supratherapeutic range 112,131. Seizure control may also deteriorate in some instances where there appears to be an actual precipitation of the seizures by the newly introduced AED. Many of the commonly used AEDs share the capacity to exacerbate seizures. Children with mixed seizure disorders, particularly those with generalized slow spike-and-wave discharges on EEG, became worse on carbamazepine 12,141. Some investigators also suggested that carbamazepine may exacerbate epileptiform discharges on EEG [14]. Benzodiazepines have been reported to produce status epilepticus when injected intravenously in children with the LennoxGastaut syndrome 1151. Phenytoin and carbamazepine were reported to aggravate absence seizures [21. Although the underlying mechanism for photosensitive epilepsy is unknown, it is important to remember that the AED sometimes may be epileptogenic.
References
[11 Tayhw DC. McKinaly I. When not to treat epilepsy with drugs. Dev Med Child Neurol 1984:26:822-33. 121 Lerman P. Seizures induced or aggravated by anticonvulsants. Epilepsia 1986; 27:706- I 0. 131 Newmark ME, Penry JK. Photosensitivity and epilepsy: A review. New York: Raven Press. 1979. 14] Holmes GL. Diagnosis and management of seizures in children. In: Markowitz M . e d . Major problems in clinical pediatrics. Philadelphia: WB Saunders, 1987;30:166-7. [5] Jeavons PM, Bishop A, Harding GFA. Thc prognosis of photosensitivity. Epilepsia 1986;27:569-75. [61 Aicardi J. Stimulus-sensitive epilepsies, In: Epilepsy m children: International review of child neurnlogy series. New York: Raven Press, 1986, 17] Livingston S. Comprehensive management of epilepsy in infancy, childhood and adolescence. Springfield: C.C. Thomas, 1972:102-8. 18] Meldrum BS. Photosensitive epilepsy in Papio papio as a model fi~r drug studies. In: Cobb WA, Van Duijn H, eds. Contemporary clinical neurophysiology. Amsterdam: Elsevier Scientific Publishing, 1978:317-22. 19] Theodore WH, Porter RJ. Removal of sedative-hypnotic antiepileptic drugs from the regimens of patients with intractable epilepsy, Ann Neurol 1983; 13: 320-4. [101 Schmidt D. Reduction of two drug therapy in intractable epilepsy. Epilepsia 1983:24:368-76. 111] Aicardi J. Clinical approach to the management of intractable epilepsy. Dev Med Child Neurol 1988;311:429-40. [121 Levy L L Fenichel GM. Diphenylhydamoin activated seizures. Neurology 1965; 15:716-22. [13] Troupin AS, Ojemann LM. Paradoxical intoxication A cumplication of anticonvulsant administration. Epilepsia 1975:16:753-8. 114] Snead OC, Hosey LC. Exacerbation of seizures in children by carbamazepine. N Engl J Med 1985:313:916-21, 115] Tassinari CA, Dravet C, Rojer J, Cano JT, Gastaut H. Tonic status epilepticus precipitated by intravenous benzodiazepine in five patients with Lennox-Gastaut syndrome. Epilepsia 1972; 13:421-35.