Prognostic Significance of Acute Epilepsia Partialis Continua Tallie Z. Baram, MD, PhD, Wendy G. Mitchell, MD, and O. Carter Snead, III, MD
We present 3 patients in whom epilepsia partialis continua was the presenting sign of an acute, rapidly evolving and catastrophic neurologic illness. Initial seizures were partial simple (i.e., eye deviation in one, finger twitching in one) which progressed to multifocal partial seizures. The course of the epilepsia partialis continua was 36-41 days. Prognosis was uniformly poor (i.e., death in 2, vegetative state in 1); therefore, epilepsia partialis continua in the context of an acute neurologic illness may herald a grim outcome. Baram TZ, Mitchell WG, Snead OC III. Prognostic significance of acute epilepsia partialis continua. Pediatr Neurol 1991:7:144-6.
Introduction Epilepsia partialis continua (EPC) denotes partial simple or partial complex seizures continuing for a prolonged period [1,2]. Described in both children and adults, EPC has diverse etiologies and outcomes [1]. The majority of reported pediatric EPC cases have been associated with chronic, progressive encephalitis of the Rasmussen type. Rasmussen encephalitis is characterized by EPC and progressive hemiparesis usually evolving over many months to years, eventually resulting in hemiplegia and loss of function of the involved hemisphere [3-7]. We present 3 patients in whom EPC was an early and major component of an acute, rapidly evolving illness, clinically and etiologically distinct from Rasmussen encephalitis. The course was rapid; maximal neurologic dysfunction was evident within days. Causative factors varied, but the outcome was uniformly poor. EPC may present in the context of acute, catastrophic neurologic disease, resulting in a dismal outcome.
From the Department of Neurology; University of Southern California; and Division of Neurology; Childrens Hospital of Los Angeles; Los Angeles, California.
144
PEDIATRIC NEUROLOGY
Vol. 7 No. 2
Case Reports Patient 1. A 7-year-old Salvadoran boy developed li~ver (40.5"C), pharyngitis, and gastroenteritis. A generalized seizure occurred on the first day, followed by very frequent partial seizures and stupor. Seizures originated in either arm oi- in the face, sometimes occurring simultaneously bilaterally. Electrnencephalography (EEG)disclosed nearly continuous partial onset of clectrographic seizures, correlating closely with observed motor activit>. Fpileptic activity originated in either hemisphere, sometimes with bilateral asynchromms independent discharges. Antiepileptic drugs (AEDs) that failed to aher the seizures included carbamazepine, phenytom, Iorazepam, and clorazcpate. Very high-dose phenobarbital eliminated clinical seizures only when an electrographic burst-suppressinn pattern was achieved. Over a peJiod ~1' several weeks, a continuously increasing dose of phenobarbital was re quired to maintain seizure control 18l. The course was progressively downhill; death occurred on the 391h day. Cerebmspinal fluid (CSF) obtained on the fourth day of illness harbored an cntcrovirus with tile growth properties of ('oxsackie A. Autopsy revealed diffuse neuronal hiss and gliosis. Patie,t 2. A 5-year-old Hispanic girl presented with fever, gastroenteritis, and interinittent eye deviation to the left. On the first 3 days of illness she was alert and coherent during episodes of persistent leftward eye deviation with irregular left jerk nystagmus. On the fourth day, one of these events progressed to a generalized tonic-oh/nit seizure, followed by altered sensorium. She continued to have ahnosl conslant partial seizures with an electrographic seizure discharge hx:alized to the right parietal-occipital region which correlated with the eye movements (Fig 1). Subsequently, bilateral but independent clinical and electrographic seizures developed. Acutely, the seizures were refractory to conventional doses of AEDs and abated only when very large doses of barbiturates (i.e., phenobarbital, pentobarbital) induced a burst-suppresskm pattern on EEG. During the second week of illness, high-dose carbamazepine transiently decreased the frequency aod amplitude of motor phenomena. CSF findings are listed in Table 1. Computed tomography (CT) and magnetic resonance imaging I MRII revealed a cerebellar infarct and bitemporal abnormal signal. Cerebral angiography (lid not reveal a vasculitis and a brain biopsy from the involved cerebellum demonstrated inflammation and nonspecific gliosis. Corticosteroids and acyclovir were administered with no change in mental status or seizures. EPC abated 36 days after onset: however, 6 months later, the child is able to open her eyes but has ml purposeful movements and little response to the environment. She has trequent tocal motor seizures, mainly of the left arm. Patient J. A 27-year-old man with hemophilia and transfusion-related AIDS presented with focal motor seizures involving the left hand which occurred 6 months after an episode of severe measles. (The measles virus was cultured from the CSF.) Four days later, continuous left thumb twitching developed. Electrographic discharges tit the right midparietal region coincided with the thumb movements, Clinical seizures progressed to involve the left ann and, eventually, the left side of the face. MRI revealed a small lesion inw~lving a single gyms m the right mid-parietal cortex (Fig 2). The seizures were refractory to high levels of AEDs; independent partial seizure activity of the right arm and face developed, as well as palatal and laryngeal involvement. The patient died 41 days after the onset of EPC. CSF results arc listed in Table I. Brain biopsy and autopsy revealed cortical and white matter gliosis and microglial nodules, without multinucleated giant cells. Cowdry A inclusions were found on the 2 brain specimens, but neither measles nor human immunodeficiency viral particles were lound. Progressive ineasles encephalitis was diagnosed on
Communications should be addressed to: Dr. Baram; Division of Neurology; Childrens Hospital of Los Angeles; RO. Box 54700; Los Angeles, CA 90054-0700. Received August 9, 1990; accepted November 14, 19911.
s4~ Fpl
- F:I
FS - C3
C$
-
P3
P3 - 01
Fp2 - F4 F4 - C4
C4 ° P4
P4 - 02
Fp$ - F7
F7 - T3
- ~ J~q--' . ~ , ~ , ~ . r ' ~
~i-'-~.~ j~ ~,,~:\H.
....% - - ~ J " ~ , - ~ . , - ~
~ / , ~ . ~ - ~ .\- ~ - v
~
T3 - T5 T5 - 01
Fp2 - F8 F8 - T4 T4 - T6
T6 - 02
EOG
Figure 1. EEG of Patient 2 revealing the correlation of electrographic discharges originating in the right occipital electrode (02), with rhythmic eye movements as evident on the electro-oculogram (EOG). EEG was performed using a 17-channel Nihon Koden apparatus. Electrode placement was according to the International 10-20 System; gold electrodes were applied with paste. Vertical calibration bar indicates 50 pV; horizontal bar denotes 1 sec.
the basis of the appropriate clinical course 6 months after detection of measles virus in the CSF of an immunocompromisedhost [9,10]. Discussion
EPC first described at the end of the nineteenth century, is considered to be a manifestation of focal cortical dysfunction, involving the motor strip [1,12]. The clinical entities associated with EPC have included infection (granuloma, abscess, encephalitis), autoimmune disease, infarction, trauma, metabolic encephalopathy, and others [1,3,11-14]. Although EPC is commonly associated with epileptic discharges limited to one cortical region, Thomas et al. emphasized that in a significant number of patients more than one focus is found and the patients may exhibit "concurrent though independent twitching" [1]. Thus, as in our patients, it may be difficult to distinguish EPC from multifocal epilepsy. The majority of patients in series of EPC have had an indolent course. The mean duration of EPC in the 32
patients reported by Thomas et al. was 25 months [1]. In pediatric patients, a well-delineated entity of slowly progressive unilateral hemispheric dysfunction associated with EPC was described by many authors [13-7]. In reviewing 48 patients with "chronic encephalitis" and epilepsy, Rasmussen and Andermann found about 50% with EPC [6]. The course was indolently progressive, with "insidious and gradual" neurologic deterioration. The patients we encountered had a distinctly different course: explosive onset of focal or generalized seizures progressed rapidly to EPC, followed by altered sensorium leading to coma and death or a vegetative state. Their ages of onset and course are also quite distinct from that of the hemiconvulsion-hemiparesis syndrome [15]. In the series reported by Thomas et al., 5 of 12 patients with EPC of less than 1 week's duration died [1]. Their ages were not recorded. Mikati et al. described a boy with an abrupt onset of EPC leading, over 1 month, to coma [16]. The patient recovered and his neurologic examination 1 year later was normal. The etiology of his EPC was not elucidated. EPC
Table 1. Abnormal CSF and brain findings of patients with EPC Patient
No./Age
CSF Chem-
CSF
CSF
(yrs)/Sex
istry (mg/dl)
Cells
Culture
I/7/M
Protein 32 Glucose 91
5 white 6 red
2/5/F
Protein 27 Glucose 83
15 white 1 red
3/27/M
Protein 33 Glucose 109
2 white 0 red
Enterovirus
Brain Pathology Biopsy/Autopsy
Meningitis, gliosis, neuronal loss Cerebellum-gliosis
Measles virus
Gliosis, microglial nodules
Baram et al: Prognosis of Acute EPC 145
References
Figure 2. MRI scan performed on Patient 3 demonstrating a small lesion in the right midparietal region (arrow). This MRI was obtained o n a 0.5 T Technicare instrument. T~-wei~hted image." TR 3,000 mseu, TE 96 msec.
has been described with progressive measles encephalitis in 4 immunocompromised children [9]. Their courses, as in Patient 3, were short (9 days to 2 months) and fatal. Our patients had in common a fulminant illness, probably resulting from viral cerebritis. CSF studies in all were abnormal and a putative causative organism was found in two. Thus, EPC may herald an acute encephalitis whose etiology should be aggressively sought and treated because otherwise the outcome may be poor.
146
PEDIATRIC NEUROLOGY
Vol. 7 No. 2
[1] Thomas JE, Reagan TJ, Klass DW. Epilepsia partialis continua. A review of 32 cases. Arch Neurnl 1977:34:266-75. [2] Gastau! H. Classification of status epilepticus. In: DelgadoEscueata AV, Wasterlain CG, Treiman DM, Porter RJ, eds. Slalus epb lepticus. New York: Raven Press, 1983:34:29-35. [3] Rasmussen T, OIszewski J, Lloyd-Smith D, Focal seizures due to chronic localized encephalitis. Neurology 1958:8:435 45. [4] Rasmussen T. McCann W, Clinical sludies of palienls with focal epilepsy due to "chronic encephalitis," Trans Am Neurol Assnc 1968;93:89 94. [5] Piatt Jlt Jr, Hwang PA, Armstrong DC. P.eckcl LE, Hofl'man HJ. Chronic focal encephalitis (Rasmussen syndrome): Six cases. Epilepsia 198g:29:268-79. [6] Rasmussen Y. Andermann F, Update on the syndrome o[ "chronic encephalitis" and epilepsy. ('leve Clin J Mcd 1989:56(suppl): $181-4. 17] Gupla PC, Rapin I. Houroupian DS, Roy S, L,lena JF, Tandnn PN. Smoldering encephalitis in children. Neuropediatrics 1984:15: 191-7. [8] Crawfnrd TO, Mitchell WG, Fishman LS, Snodgrass SR, Very high dose phenobarbital for ret?actory status epileplicus in children. Neurology 1988;26:1035-40. [9] Aicardi J, Goutieres F. Arsenio-Nunes ML, l,ebon P. Acute measles encephalitis in chiklren witll immunosuppression. Pediatrics 1977"59:232-9. [101 Baram TZ, Norman MG. Encephalopathy in a 14 year okl boy with leukemia in remissinn. Clinical Pathological Cont2:rence. Pediatr Neurosci 1987; 13:52-60. [111 Shapoval AN. Tick-borne encephalitis and epilepsy. Zh Nevropatol Psikhiatr 1981:81:835-41. [121 Komsuoglu SS, Liman O, Gurkan H, Epilepsia partialis conlinua following perlussis infecliolL ('lin Electroencephalogr 1985:16: 45 7. [13] Bansal SK, Sawhney IMS, Chopra JS. Epilepsia purtialis continua in Sjorgen syndrome. Epilepsia 1987;28:362-3. [14] Singh BM, Gupta DR. Strobos RJ. Nonketolic hyperglycemia and epilepsia partialis continua. Arch Neurol 1973:29:1~7-90. [15] Dreifuss FE. Focal and multifocal cortical seizures. In: Swaiman KF, ed. Pediatric neurology: Principles and practice. St. Louis: CV Mosby, 1989;393-411. [16] Mikati MA, [,ee WL, DeLong GR. Protracted epileptilorm encephalopathy: An unusual fl~rm of partial complex status epilepticus. Epilepsia 1985;26:563-7 I.
We present 3 patients in whom epilepsia partialis continua was the presenting sign of an acute, rapidly evolving and catastrophic neurologic illness. Initial seizures were partial simple (i.e., eye deviation in one, finger twitching in one) which progressed to multifocal partial seizures. The course of the epilepsia partialis continua was 36-41 days. Prognosis was uniformly poor (i.e., death in 2, vegetative state in 1); therefore, epilepsia partialis continua in the context of an acute neurologic illness may herald a grim outcome. Baram TZ, Mitchell WG, Snead OC III. Prognostic significance of acute epilepsia partialis continua. Pediatr Neurol 1991:7:144-6.
Introduction Epilepsia partialis continua (EPC) denotes partial simple or partial complex seizures continuing for a prolonged period [1,2]. Described in both children and adults, EPC has diverse etiologies and outcomes [1]. The majority of reported pediatric EPC cases have been associated with chronic, progressive encephalitis of the Rasmussen type. Rasmussen encephalitis is characterized by EPC and progressive hemiparesis usually evolving over many months to years, eventually resulting in hemiplegia and loss of function of the involved hemisphere [3-7]. We present 3 patients in whom EPC was an early and major component of an acute, rapidly evolving illness, clinically and etiologically distinct from Rasmussen encephalitis. The course was rapid; maximal neurologic dysfunction was evident within days. Causative factors varied, but the outcome was uniformly poor. EPC may present in the context of acute, catastrophic neurologic disease, resulting in a dismal outcome.
From the Department of Neurology; University of Southern California; and Division of Neurology; Childrens Hospital of Los Angeles; Los Angeles, California.
144
PEDIATRIC NEUROLOGY
Vol. 7 No. 2
Case Reports Patient 1. A 7-year-old Salvadoran boy developed li~ver (40.5"C), pharyngitis, and gastroenteritis. A generalized seizure occurred on the first day, followed by very frequent partial seizures and stupor. Seizures originated in either arm oi- in the face, sometimes occurring simultaneously bilaterally. Electrnencephalography (EEG)disclosed nearly continuous partial onset of clectrographic seizures, correlating closely with observed motor activit>. Fpileptic activity originated in either hemisphere, sometimes with bilateral asynchromms independent discharges. Antiepileptic drugs (AEDs) that failed to aher the seizures included carbamazepine, phenytom, Iorazepam, and clorazcpate. Very high-dose phenobarbital eliminated clinical seizures only when an electrographic burst-suppressinn pattern was achieved. Over a peJiod ~1' several weeks, a continuously increasing dose of phenobarbital was re quired to maintain seizure control 18l. The course was progressively downhill; death occurred on the 391h day. Cerebmspinal fluid (CSF) obtained on the fourth day of illness harbored an cntcrovirus with tile growth properties of ('oxsackie A. Autopsy revealed diffuse neuronal hiss and gliosis. Patie,t 2. A 5-year-old Hispanic girl presented with fever, gastroenteritis, and interinittent eye deviation to the left. On the first 3 days of illness she was alert and coherent during episodes of persistent leftward eye deviation with irregular left jerk nystagmus. On the fourth day, one of these events progressed to a generalized tonic-oh/nit seizure, followed by altered sensorium. She continued to have ahnosl conslant partial seizures with an electrographic seizure discharge hx:alized to the right parietal-occipital region which correlated with the eye movements (Fig 1). Subsequently, bilateral but independent clinical and electrographic seizures developed. Acutely, the seizures were refractory to conventional doses of AEDs and abated only when very large doses of barbiturates (i.e., phenobarbital, pentobarbital) induced a burst-suppresskm pattern on EEG. During the second week of illness, high-dose carbamazepine transiently decreased the frequency aod amplitude of motor phenomena. CSF findings are listed in Table 1. Computed tomography (CT) and magnetic resonance imaging I MRII revealed a cerebellar infarct and bitemporal abnormal signal. Cerebral angiography (lid not reveal a vasculitis and a brain biopsy from the involved cerebellum demonstrated inflammation and nonspecific gliosis. Corticosteroids and acyclovir were administered with no change in mental status or seizures. EPC abated 36 days after onset: however, 6 months later, the child is able to open her eyes but has ml purposeful movements and little response to the environment. She has trequent tocal motor seizures, mainly of the left arm. Patient J. A 27-year-old man with hemophilia and transfusion-related AIDS presented with focal motor seizures involving the left hand which occurred 6 months after an episode of severe measles. (The measles virus was cultured from the CSF.) Four days later, continuous left thumb twitching developed. Electrographic discharges tit the right midparietal region coincided with the thumb movements, Clinical seizures progressed to involve the left ann and, eventually, the left side of the face. MRI revealed a small lesion inw~lving a single gyms m the right mid-parietal cortex (Fig 2). The seizures were refractory to high levels of AEDs; independent partial seizure activity of the right arm and face developed, as well as palatal and laryngeal involvement. The patient died 41 days after the onset of EPC. CSF results arc listed in Table I. Brain biopsy and autopsy revealed cortical and white matter gliosis and microglial nodules, without multinucleated giant cells. Cowdry A inclusions were found on the 2 brain specimens, but neither measles nor human immunodeficiency viral particles were lound. Progressive ineasles encephalitis was diagnosed on
Communications should be addressed to: Dr. Baram; Division of Neurology; Childrens Hospital of Los Angeles; RO. Box 54700; Los Angeles, CA 90054-0700. Received August 9, 1990; accepted November 14, 19911.
s4~ Fpl
- F:I
FS - C3
C$
-
P3
P3 - 01
Fp2 - F4 F4 - C4
C4 ° P4
P4 - 02
Fp$ - F7
F7 - T3
- ~ J~q--' . ~ , ~ , ~ . r ' ~
~i-'-~.~ j~ ~,,~:\H.
....% - - ~ J " ~ , - ~ . , - ~
~ / , ~ . ~ - ~ .\- ~ - v
~
T3 - T5 T5 - 01
Fp2 - F8 F8 - T4 T4 - T6
T6 - 02
EOG
Figure 1. EEG of Patient 2 revealing the correlation of electrographic discharges originating in the right occipital electrode (02), with rhythmic eye movements as evident on the electro-oculogram (EOG). EEG was performed using a 17-channel Nihon Koden apparatus. Electrode placement was according to the International 10-20 System; gold electrodes were applied with paste. Vertical calibration bar indicates 50 pV; horizontal bar denotes 1 sec.
the basis of the appropriate clinical course 6 months after detection of measles virus in the CSF of an immunocompromisedhost [9,10]. Discussion
EPC first described at the end of the nineteenth century, is considered to be a manifestation of focal cortical dysfunction, involving the motor strip [1,12]. The clinical entities associated with EPC have included infection (granuloma, abscess, encephalitis), autoimmune disease, infarction, trauma, metabolic encephalopathy, and others [1,3,11-14]. Although EPC is commonly associated with epileptic discharges limited to one cortical region, Thomas et al. emphasized that in a significant number of patients more than one focus is found and the patients may exhibit "concurrent though independent twitching" [1]. Thus, as in our patients, it may be difficult to distinguish EPC from multifocal epilepsy. The majority of patients in series of EPC have had an indolent course. The mean duration of EPC in the 32
patients reported by Thomas et al. was 25 months [1]. In pediatric patients, a well-delineated entity of slowly progressive unilateral hemispheric dysfunction associated with EPC was described by many authors [13-7]. In reviewing 48 patients with "chronic encephalitis" and epilepsy, Rasmussen and Andermann found about 50% with EPC [6]. The course was indolently progressive, with "insidious and gradual" neurologic deterioration. The patients we encountered had a distinctly different course: explosive onset of focal or generalized seizures progressed rapidly to EPC, followed by altered sensorium leading to coma and death or a vegetative state. Their ages of onset and course are also quite distinct from that of the hemiconvulsion-hemiparesis syndrome [15]. In the series reported by Thomas et al., 5 of 12 patients with EPC of less than 1 week's duration died [1]. Their ages were not recorded. Mikati et al. described a boy with an abrupt onset of EPC leading, over 1 month, to coma [16]. The patient recovered and his neurologic examination 1 year later was normal. The etiology of his EPC was not elucidated. EPC
Table 1. Abnormal CSF and brain findings of patients with EPC Patient
No./Age
CSF Chem-
CSF
CSF
(yrs)/Sex
istry (mg/dl)
Cells
Culture
I/7/M
Protein 32 Glucose 91
5 white 6 red
2/5/F
Protein 27 Glucose 83
15 white 1 red
3/27/M
Protein 33 Glucose 109
2 white 0 red
Enterovirus
Brain Pathology Biopsy/Autopsy
Meningitis, gliosis, neuronal loss Cerebellum-gliosis
Measles virus
Gliosis, microglial nodules
Baram et al: Prognosis of Acute EPC 145
References
Figure 2. MRI scan performed on Patient 3 demonstrating a small lesion in the right midparietal region (arrow). This MRI was obtained o n a 0.5 T Technicare instrument. T~-wei~hted image." TR 3,000 mseu, TE 96 msec.
has been described with progressive measles encephalitis in 4 immunocompromised children [9]. Their courses, as in Patient 3, were short (9 days to 2 months) and fatal. Our patients had in common a fulminant illness, probably resulting from viral cerebritis. CSF studies in all were abnormal and a putative causative organism was found in two. Thus, EPC may herald an acute encephalitis whose etiology should be aggressively sought and treated because otherwise the outcome may be poor.
146
PEDIATRIC NEUROLOGY
Vol. 7 No. 2
[1] Thomas JE, Reagan TJ, Klass DW. Epilepsia partialis continua. A review of 32 cases. Arch Neurnl 1977:34:266-75. [2] Gastau! H. Classification of status epilepticus. In: DelgadoEscueata AV, Wasterlain CG, Treiman DM, Porter RJ, eds. Slalus epb lepticus. New York: Raven Press, 1983:34:29-35. [3] Rasmussen T, OIszewski J, Lloyd-Smith D, Focal seizures due to chronic localized encephalitis. Neurology 1958:8:435 45. [4] Rasmussen T. McCann W, Clinical sludies of palienls with focal epilepsy due to "chronic encephalitis," Trans Am Neurol Assnc 1968;93:89 94. [5] Piatt Jlt Jr, Hwang PA, Armstrong DC. P.eckcl LE, Hofl'man HJ. Chronic focal encephalitis (Rasmussen syndrome): Six cases. Epilepsia 198g:29:268-79. [6] Rasmussen Y. Andermann F, Update on the syndrome o[ "chronic encephalitis" and epilepsy. ('leve Clin J Mcd 1989:56(suppl): $181-4. 17] Gupla PC, Rapin I. Houroupian DS, Roy S, L,lena JF, Tandnn PN. Smoldering encephalitis in children. Neuropediatrics 1984:15: 191-7. [8] Crawfnrd TO, Mitchell WG, Fishman LS, Snodgrass SR, Very high dose phenobarbital for ret?actory status epileplicus in children. Neurology 1988;26:1035-40. [9] Aicardi J, Goutieres F. Arsenio-Nunes ML, l,ebon P. Acute measles encephalitis in chiklren witll immunosuppression. Pediatrics 1977"59:232-9. [101 Baram TZ, Norman MG. Encephalopathy in a 14 year okl boy with leukemia in remissinn. Clinical Pathological Cont2:rence. Pediatr Neurosci 1987; 13:52-60. [111 Shapoval AN. Tick-borne encephalitis and epilepsy. Zh Nevropatol Psikhiatr 1981:81:835-41. [121 Komsuoglu SS, Liman O, Gurkan H, Epilepsia partialis conlinua following perlussis infecliolL ('lin Electroencephalogr 1985:16: 45 7. [13] Bansal SK, Sawhney IMS, Chopra JS. Epilepsia purtialis continua in Sjorgen syndrome. Epilepsia 1987;28:362-3. [14] Singh BM, Gupta DR. Strobos RJ. Nonketolic hyperglycemia and epilepsia partialis continua. Arch Neurol 1973:29:1~7-90. [15] Dreifuss FE. Focal and multifocal cortical seizures. In: Swaiman KF, ed. Pediatric neurology: Principles and practice. St. Louis: CV Mosby, 1989;393-411. [16] Mikati MA, [,ee WL, DeLong GR. Protracted epileptilorm encephalopathy: An unusual fl~rm of partial complex status epilepticus. Epilepsia 1985;26:563-7 I.
