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Trihexyphenidyl and isoprinosine in the treatment of subacute sclerosing panencephalitis
ELSEVIER
Trihexyphenidyl and Isoprinosine in the Treatment of Subacute Sclerosing Panencephalitis M a g d a L a h o r g u e N u n e s , M D , P h D , Jaderson Costa Da Costa, M D , P h D , and Luis F e r n a n d o Garcias Da Silva, M D
Six cases of subacute sclerosing panencephalitis (1 stage I, 3 stage II, 2 stage III) were diagnosed at our institution in the last 10 years. Five patients were treated with isoprinosine and the antiepileptic drug valproic acid. Three patients presented with myoclonic seizures refractory to valproic acid and the usual antiepileptic therapy. They received trihexyphenidyl with good results. We suggest the use of trihexyphenidyl in combination with isoprinosine in patients with subacute sclerosing panencephalitis with myocionic seizures refractory to valproic acid. Nunes ML, da Costa JC, da Silva LFG. Trihexyphenidyl and isoprinosine in the treatment of subacute sclerosing panencephalitis. Pediatr Neurol 1995; 13:153-156.
Introduction Subacute sclerosing panencephalitis (SSPE) is a chronic progressive neurodegenerative disease related to persistence of measles paramixovirus in the central nervous system (CNS). It may follow natural measles infection or, less commonly, vaccination with live measles virus vaccine. Although it has been virtually eliminated in the United States, it is endemic in countries where measles was not eradicated. It affects children of different ages and young adults, who usually had measles at an early age, in a frequency of one per million. Epidemiologic studies disclosed that SSPE is 2-4 times more common in males. The patients usually pass through four stages: mental deterioration, motor dysfunctions progressing to convulsions, coma, and death within 1-5 years [1-3]. Sometimes the clinical course can be confused with psychiatric diseases (e.g., schizophrenia) [4,5]. Occasional remissions and improvements have been reported [2,6,7]. From the Divisionof Neurology;Sio Lucas Hospital and PUCRS School of Medicine;Porto Alegre, Brazil.
© 1995 by ElsevierScienceInc. • 0887-8994/95/$9.50 SSDI 0887-8994(95)00145-6
Pathological changes are widespread in the cerebrum, in both white and gray matter. A grayish leptomeningeal exudate is generally present at all stages and some degree of atrophy is usually evident. The key histologic feature is the presence of intranuclear inclusion bodies in neurons and oligodendroglia. Electron microscopy reveals an abnormality (i.e., complete absence of budding from CNS cells and mature virions) [8]. There are many hypotheses to explain the persistence of the virus in the pathogenesis of SSPE: immunologic immaturity of the host, persistence of maternal antibody, high infective dose [8], multiple viral mutations [9], and failure to synthesize M protein [10]. The diagnosis is based on at least three of the following criteria: (a) clinical manifestations [11,12], (b) abnormal EEG [13,14], (c) hyperglobulinorrachia, elevated serum or cranial spinal fluid measles antibody [2,6], (d) histologic features [8]. Treatment still evokes great controversy. Isoprinosine (Inosiplex), an agent with both antiviral and immune enhancing properties, has been widely used to slow the progression of SSPE [2,3,6,7,15,16]. Intravenous or intrathecal a-interferon, alone or in combination with isoprinosine, has also been used with varying results [ 11,1719]. However, the seizures are often difficult to control and resistant to antiepileptic therapy. The purpose of our study was to evaluate the evolution of SSPE in patients treated with isoprinosine and trihexyphenidyl (THP), and to report preliminary results of THP treatment for refractory seizures.
Case Reports Patient 1. This 22-year-oldwhite womanwas admittedto our hospital in 1990. One year beforeadmission she experiencedvisual and auditory hallucinations followed by gait disturbance and frequent fails, and
Communicationsshouldbe addressedto: Dr. Nunes; Divisionof Neurology;Silo Lucas Hospital; Av. Ipiranga 6690, #322; Porto Alegre-RS, Brazil 90610-000. ReceivedNovember29, 1994; acceptedMay 31, 1995.
Nunes et al: Trihexypbenidyland isoprinosinein SSPE 153
- - -°' - - ~ N ,
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Figure I. CT scan of Patient 1 (November, 1989) disclosed a parietooccipital calcification.
3 months later, partial seizures. By that time, she had become pregnant and presented with behavioral disturbances. By the end of the pregnancy, she experienced visual problems that progressed to complete visual loss in 15 days. Neurologic examination on hospital admission disclosed ataxia, myoclonic seizures, and bilateral pyramidal signs. Computed tomography (CT) revealed a calcification (Fig 1). A metabolic and infectious screening was normal. Visual evoked potential studies disclosed prolongation of the latencies. Cerebrospinal fluid (CSF) protein was 48 mg/dl. EEG disclosed periodic slow wave complexes (PSWC) (Fig 2). Measles antibody was present in CSF (1:10) and serum (1:80). It was not known if the patient had had measles in infancy. Treatment was initiated with isoprinosine (100 mg/kg/day) and valproic acid (VA) (1,200 mg/ day). Seizures persisted and amantadine (200 mg/day) therapy was begun, One week later amantadine was discontinued and THP (15 mg/day) was introduced with progressive improvement of seizures and total control within about 2 weeks. The patient was discharged 1 month later on a regimen of isoprinosine, VA, and THP. She has been followed for 4 years. The patient decided to discontinue medication about 1 year ago and seizures have not recurred. On the last follow-up in March, 1994, she could walk, talk, follow simple commands, and had sphincter control. Neurologic examination disclosed hypereflexia, papillar atrophia, language perseveration, and inappropriate behavior (continuous laughing). She had some demential symptoms and was unable to take
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PEDIATRIC NEUROLOGY
care of her personal hygiene or perform domestic duties. EEG disclosed basal rhythm of 8-9 Hz and no epileptogenic activity (Fig 3). CT disclosed extensive atrophy (Fig 4). Patient 2. This 10-year-old white boy was admitted with a history of normal development until 8 years of age when he experienced myoclonic and generalized tonic-clonic seizures that did not respond to phenobarbital therapy. He developed neuropsychomotor delay followed by progressive aphasia and spastic tetraparesia. He had had two previous admissions without diagnosis. Past medical history was positive for measles at age 3 years. One day before admission to our hospital he experienced fever and excessive somnolence. Neurologic examination disclosed coma Glasgow 9, bilateral pyramidal signs, frequent myoclonic seizures, and occasional generalized tonic-clonic seizures. CT scan revealed mild atrophy and white matter hypodensity. CSF was normal with 37 mg/dl protein. EEG disclosed PSWC (Fig 5). Measles antibody was 1:20 in CSF and 1:60 in serum. VA therapy was initiated at a dose of 30 mg/kg/day which was increased to 60 mg/kg/day. THP therapy (6 mg/day) was added without significant clinical improvement. Isoprinosine was considered but not used. The patient was discharged at the parents' request still having occasional seizures and was lost to follow-up. Patient 3. This 5-year-old white boy was admitted to Sho Lucas Hos-
,-..--..e-~_
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Figure 2. EEG (on admission) of Patient 1 disclosed periodic slow wave complexes.
154
Figure 3. Most recent EEG (March, 1994) of Patient 1 disclosed posterior alpha and anterior theta rhythms (patient awake); artifacts caused by voluntary movements were demonstrated.
Vol. 13 No. 2
Figure 4.
CT scan (April, 1994) of Patient I disclosed diffuse atrophy.
F7
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Fp2 - F4
F 4 - cA
pl
02
Fpe - FB
Figure 5.
EEG of Patient 2 disclosed periodic slow wave complexes.
pital in July, 1993 because of seizures. One and a half years before admission he experienced gait disturbance, irritability, progressive speech disorder (stutter), and frequent falls. Neurologic deterioration was progressive. Antenatal course and delivery were normal, the parents were not consanguineous, and there was no family history of epilepsy. He had had an exanthema suggestive of measles at 4 months of age. At first examination he had a delay on neuropsychologic development, aphasia, spastic tetraparesis, myoclonic seizures, extension spasms, and visual deficit. EEG disclosed PSWC (Fig 6), CSF protein was 36 mg/dl, measles antibody 1:1,280 and CSF 1:20. CT scan disclosed mild atrophy. Visual evoked potential studies revealed bilateral lentification on optic pathways. Other examinations (i.e., TORCH, anti-HIV, screening for inborn errors of metabolism) were normal. Isoprinosine (100 mg/kg/ day) and VA (30 mg/kg/day) therapy was initiated. The VA dosage was increased to 50 mg/kg/day without control of the seizures and THP was added (6 mg/day). He remained seizure free for 3 months and had partial recovery of gait and speech. Treatment was interrupted by the parents, seizures returned, and he again lost speech and gait. Treatment was reestablished and partial improvement occurred but the parents again discontinued medication and his general condition worsened without recovery.
Discussion The incidence of SSPE has been declining in the developed countries as a response to rubeola immunization programs. The response to treatment of SSPE has not been
clearly established and is debatable [20]. Isoprinosine, a virustatic agent, is believed to exert an inhibitory action on the process of viral replication in host cells and seems to reduce the morbidity and mortality of patients [6,15]. a-Interferon has been used intravenously and/or intrathecally but a large multicenter study is needed to verify its effectiveness [11,17,19]. A treatment protocol using a combination of oral isoprinosine and intraventficular a-interferon 2b is in use in Saudi Arabia and the degree of immunologic competency appears to be one factor in treatment success or failure [21]. The efficacy of anticholinergic drugs as adjunctive treatment of patients with refractory partial epilepsy was studied by Jabbari [22] based on previous experimental trials in animals demonstrating that anticholinergic drugs protect animals against electroshock seizures. We followed 6 patients with SSPE [7,16]; one was diagnosed with stage I SSPE, three with stage II, and two with stage III. Five patients were treated with isoprinosine. Of the 3 patients treated with isoprinosine and VA, one had no improvement, one had initial improvement but was lost to follow-up, and one, now 10 years old, is seizure free with normal neuropsychomotor development and attends a regular school. THP was associated in 3 patients with myoclonic seizures refractory to VA and usual antiepileptic therapy. Patient 1 had complete control of the seizures and remission of the symptoms with sequelae. Patient 2, the only one in whom isoprinosine was not used, experienced no improvement and <50% reduction of seizures. Patient 3 achieved complete control of the seizures and symptoms for 3 months. His clinical course worsened on discontinuation of medication. Our patient experience indicates that (1) favorable prognosis is related to early diagnosis; (2) treatment begun in the early stages of the disease is more effective; and (3) THP in combination with isoprinosine reduces seizures in some patients. We therefore suggest the use of THP in combination with isoprinosine in patients with SSPE and myoclonic seizures refractory to the usual antiepileptic therapy.
References
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~
.
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Figure 6.
EEG of Patient 3 disclosed periodic slow wave complexes.
[1] Modlin JF, Halsey NA, Eddins DL, et al. Epidemiology Of subacute sclerosing panencephalitis. Pediatrics 1971 ;94:231-6. [2] Graves MC. SSPE. Neurol Clin 1984;2:267-79. [3l Dhib-Jalbut S, Johnson KP. Measles virus diseases. In: McKendall RR, Stroop WG, eds. Handbook of neurovirology. New York: Marcel Dekker, 1994:539-54. [4] Sallb EA. SSPE presenting at age 21 as a schizophrenia-like state with bizarre dysmorphic features. Br J Psychiatry 1988;152:709-71. [5] Duncalf CM, Kent JNG, Harbord M, et al. SSPE presenting as schizophreniform psychosis. Br J Psychiatry 1989;155:557-9. [6] Dyken PR, Swift A, Durant MA. Long-term follow up of patients with SSPE treated with Inosiplex. Ann Neurol 1981;11:359-64. 17l Nunes ML. Panecefalite esclerosante subaguda: Aspectos clfnicos, epidemiol6gicos, teral~uticos e progn6stico. J Liga Brasileira Epilepsia 1992;5:23-30.
Nunes et al: Trihexyphenidyl and isoprinosine in SSPE
155
[8] Anderson JR. Viral encephalitis and its pathology. Curr Top Pathol 1988;76:23-60. [9] Cattaneo R, Schimid A, Billeter MA, et al. Multiple viral mutations rather than host factors cause defective measles virus gene expression in a SSPE cell line. J Virol 1988;62:1388-97. [10] Dhib-Jalbut S, McFarland HF, Mingioli ES, et al. Humoral and cellular immune responses to matrix protein of measles virus in subacute sclerosing panencephalitis. J Virol 1988;62:2483-9. [11] Gascon GG, Yamani S, Crowell J, et al. Combined oral isoprinosine-intraventricular alpha interferon therapy for SSPE. Brain Dev 1993; 15:346-55. [12] Gascon GG. Guidelines for the SSPE Consortium Members. Rhode Island: Department of Pediatric Neurology, Brown University, 1995, 1-9. [13] Brimani DJ. Etude electrencephalographique de 40 malade atteints de panencephalite sclerosant subaiguE. Rev EEG Neurophysiol Clin 1986;16:433-43. [14] Lombroso CT. Remarks on the EEG and movement disorder in SSPE. Neurology 1968;18:69-75.
156
PEDIATRIC NEUROLOGY
Vol. 13 No. 2
[15] Jones CE, Dyken PR, Huttenlocher PR, et al. Inosiplex therapy in SSPE, a multicentre, non randomized study in 98 patients. Lancet 1982;8:1034-7. [16] da Costa JC, da Silva LFG, Nunes ML. Panencefalite esclerosante subaguda associada a gestac~.o: Tratamento com trihexafenidil e isoprinosine. J Liga Brasileira Epilepsia 1991 ;4:17-21. [17] Hatanaka T, Sugimoto T, Kobayashi Y. Electroencephalographic changes during interferon therapy in a case of subacute sclerosing panencephalitis. Eur Neurol 1989;29:6-9. [18] Maimone D. Intrathecal interferon in SSPE. Acta Neurol Scand 1988;78:161-6. [19] Yalaz K, Anlar B, Oktem F. Intraventricular interferon and oral Inosiplex in the treatment of SSPE. Neurology 1992;42:488-91. [20] Gellin B, Katz SL. Measles: State of the art and future directions. J Infect Dis 1994;170(suppl):S3-14. [21] Sultan TB, Parhar RS, Kirtkant S, et al. Immunologic status of Saudi patients with SSPE. Pediatr Neurol 1992;8:348. [22] Jabbari B. Trihexiphenidil and partial epilepsy. Epilepsia 1989:30:725.
Trihexyphenidyl and Isoprinosine in the Treatment of Subacute Sclerosing Panencephalitis M a g d a L a h o r g u e N u n e s , M D , P h D , Jaderson Costa Da Costa, M D , P h D , and Luis F e r n a n d o Garcias Da Silva, M D
Six cases of subacute sclerosing panencephalitis (1 stage I, 3 stage II, 2 stage III) were diagnosed at our institution in the last 10 years. Five patients were treated with isoprinosine and the antiepileptic drug valproic acid. Three patients presented with myoclonic seizures refractory to valproic acid and the usual antiepileptic therapy. They received trihexyphenidyl with good results. We suggest the use of trihexyphenidyl in combination with isoprinosine in patients with subacute sclerosing panencephalitis with myocionic seizures refractory to valproic acid. Nunes ML, da Costa JC, da Silva LFG. Trihexyphenidyl and isoprinosine in the treatment of subacute sclerosing panencephalitis. Pediatr Neurol 1995; 13:153-156.
Introduction Subacute sclerosing panencephalitis (SSPE) is a chronic progressive neurodegenerative disease related to persistence of measles paramixovirus in the central nervous system (CNS). It may follow natural measles infection or, less commonly, vaccination with live measles virus vaccine. Although it has been virtually eliminated in the United States, it is endemic in countries where measles was not eradicated. It affects children of different ages and young adults, who usually had measles at an early age, in a frequency of one per million. Epidemiologic studies disclosed that SSPE is 2-4 times more common in males. The patients usually pass through four stages: mental deterioration, motor dysfunctions progressing to convulsions, coma, and death within 1-5 years [1-3]. Sometimes the clinical course can be confused with psychiatric diseases (e.g., schizophrenia) [4,5]. Occasional remissions and improvements have been reported [2,6,7]. From the Divisionof Neurology;Sio Lucas Hospital and PUCRS School of Medicine;Porto Alegre, Brazil.
© 1995 by ElsevierScienceInc. • 0887-8994/95/$9.50 SSDI 0887-8994(95)00145-6
Pathological changes are widespread in the cerebrum, in both white and gray matter. A grayish leptomeningeal exudate is generally present at all stages and some degree of atrophy is usually evident. The key histologic feature is the presence of intranuclear inclusion bodies in neurons and oligodendroglia. Electron microscopy reveals an abnormality (i.e., complete absence of budding from CNS cells and mature virions) [8]. There are many hypotheses to explain the persistence of the virus in the pathogenesis of SSPE: immunologic immaturity of the host, persistence of maternal antibody, high infective dose [8], multiple viral mutations [9], and failure to synthesize M protein [10]. The diagnosis is based on at least three of the following criteria: (a) clinical manifestations [11,12], (b) abnormal EEG [13,14], (c) hyperglobulinorrachia, elevated serum or cranial spinal fluid measles antibody [2,6], (d) histologic features [8]. Treatment still evokes great controversy. Isoprinosine (Inosiplex), an agent with both antiviral and immune enhancing properties, has been widely used to slow the progression of SSPE [2,3,6,7,15,16]. Intravenous or intrathecal a-interferon, alone or in combination with isoprinosine, has also been used with varying results [ 11,1719]. However, the seizures are often difficult to control and resistant to antiepileptic therapy. The purpose of our study was to evaluate the evolution of SSPE in patients treated with isoprinosine and trihexyphenidyl (THP), and to report preliminary results of THP treatment for refractory seizures.
Case Reports Patient 1. This 22-year-oldwhite womanwas admittedto our hospital in 1990. One year beforeadmission she experiencedvisual and auditory hallucinations followed by gait disturbance and frequent fails, and
Communicationsshouldbe addressedto: Dr. Nunes; Divisionof Neurology;Silo Lucas Hospital; Av. Ipiranga 6690, #322; Porto Alegre-RS, Brazil 90610-000. ReceivedNovember29, 1994; acceptedMay 31, 1995.
Nunes et al: Trihexypbenidyland isoprinosinein SSPE 153
- - -°' - - ~ N ,
...., ~ . , 4 ~ ~
Figure I. CT scan of Patient 1 (November, 1989) disclosed a parietooccipital calcification.
3 months later, partial seizures. By that time, she had become pregnant and presented with behavioral disturbances. By the end of the pregnancy, she experienced visual problems that progressed to complete visual loss in 15 days. Neurologic examination on hospital admission disclosed ataxia, myoclonic seizures, and bilateral pyramidal signs. Computed tomography (CT) revealed a calcification (Fig 1). A metabolic and infectious screening was normal. Visual evoked potential studies disclosed prolongation of the latencies. Cerebrospinal fluid (CSF) protein was 48 mg/dl. EEG disclosed periodic slow wave complexes (PSWC) (Fig 2). Measles antibody was present in CSF (1:10) and serum (1:80). It was not known if the patient had had measles in infancy. Treatment was initiated with isoprinosine (100 mg/kg/day) and valproic acid (VA) (1,200 mg/ day). Seizures persisted and amantadine (200 mg/day) therapy was begun, One week later amantadine was discontinued and THP (15 mg/day) was introduced with progressive improvement of seizures and total control within about 2 weeks. The patient was discharged 1 month later on a regimen of isoprinosine, VA, and THP. She has been followed for 4 years. The patient decided to discontinue medication about 1 year ago and seizures have not recurred. On the last follow-up in March, 1994, she could walk, talk, follow simple commands, and had sphincter control. Neurologic examination disclosed hypereflexia, papillar atrophia, language perseveration, and inappropriate behavior (continuous laughing). She had some demential symptoms and was unable to take
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PEDIATRIC NEUROLOGY
care of her personal hygiene or perform domestic duties. EEG disclosed basal rhythm of 8-9 Hz and no epileptogenic activity (Fig 3). CT disclosed extensive atrophy (Fig 4). Patient 2. This 10-year-old white boy was admitted with a history of normal development until 8 years of age when he experienced myoclonic and generalized tonic-clonic seizures that did not respond to phenobarbital therapy. He developed neuropsychomotor delay followed by progressive aphasia and spastic tetraparesia. He had had two previous admissions without diagnosis. Past medical history was positive for measles at age 3 years. One day before admission to our hospital he experienced fever and excessive somnolence. Neurologic examination disclosed coma Glasgow 9, bilateral pyramidal signs, frequent myoclonic seizures, and occasional generalized tonic-clonic seizures. CT scan revealed mild atrophy and white matter hypodensity. CSF was normal with 37 mg/dl protein. EEG disclosed PSWC (Fig 5). Measles antibody was 1:20 in CSF and 1:60 in serum. VA therapy was initiated at a dose of 30 mg/kg/day which was increased to 60 mg/kg/day. THP therapy (6 mg/day) was added without significant clinical improvement. Isoprinosine was considered but not used. The patient was discharged at the parents' request still having occasional seizures and was lost to follow-up. Patient 3. This 5-year-old white boy was admitted to Sho Lucas Hos-
,-..--..e-~_
_ _
~
Figure 2. EEG (on admission) of Patient 1 disclosed periodic slow wave complexes.
154
Figure 3. Most recent EEG (March, 1994) of Patient 1 disclosed posterior alpha and anterior theta rhythms (patient awake); artifacts caused by voluntary movements were demonstrated.
Vol. 13 No. 2
Figure 4.
CT scan (April, 1994) of Patient I disclosed diffuse atrophy.
F7
TS
Fp2 - F4
F 4 - cA
pl
02
Fpe - FB
Figure 5.
EEG of Patient 2 disclosed periodic slow wave complexes.
pital in July, 1993 because of seizures. One and a half years before admission he experienced gait disturbance, irritability, progressive speech disorder (stutter), and frequent falls. Neurologic deterioration was progressive. Antenatal course and delivery were normal, the parents were not consanguineous, and there was no family history of epilepsy. He had had an exanthema suggestive of measles at 4 months of age. At first examination he had a delay on neuropsychologic development, aphasia, spastic tetraparesis, myoclonic seizures, extension spasms, and visual deficit. EEG disclosed PSWC (Fig 6), CSF protein was 36 mg/dl, measles antibody 1:1,280 and CSF 1:20. CT scan disclosed mild atrophy. Visual evoked potential studies revealed bilateral lentification on optic pathways. Other examinations (i.e., TORCH, anti-HIV, screening for inborn errors of metabolism) were normal. Isoprinosine (100 mg/kg/ day) and VA (30 mg/kg/day) therapy was initiated. The VA dosage was increased to 50 mg/kg/day without control of the seizures and THP was added (6 mg/day). He remained seizure free for 3 months and had partial recovery of gait and speech. Treatment was interrupted by the parents, seizures returned, and he again lost speech and gait. Treatment was reestablished and partial improvement occurred but the parents again discontinued medication and his general condition worsened without recovery.
Discussion The incidence of SSPE has been declining in the developed countries as a response to rubeola immunization programs. The response to treatment of SSPE has not been
clearly established and is debatable [20]. Isoprinosine, a virustatic agent, is believed to exert an inhibitory action on the process of viral replication in host cells and seems to reduce the morbidity and mortality of patients [6,15]. a-Interferon has been used intravenously and/or intrathecally but a large multicenter study is needed to verify its effectiveness [11,17,19]. A treatment protocol using a combination of oral isoprinosine and intraventficular a-interferon 2b is in use in Saudi Arabia and the degree of immunologic competency appears to be one factor in treatment success or failure [21]. The efficacy of anticholinergic drugs as adjunctive treatment of patients with refractory partial epilepsy was studied by Jabbari [22] based on previous experimental trials in animals demonstrating that anticholinergic drugs protect animals against electroshock seizures. We followed 6 patients with SSPE [7,16]; one was diagnosed with stage I SSPE, three with stage II, and two with stage III. Five patients were treated with isoprinosine. Of the 3 patients treated with isoprinosine and VA, one had no improvement, one had initial improvement but was lost to follow-up, and one, now 10 years old, is seizure free with normal neuropsychomotor development and attends a regular school. THP was associated in 3 patients with myoclonic seizures refractory to VA and usual antiepileptic therapy. Patient 1 had complete control of the seizures and remission of the symptoms with sequelae. Patient 2, the only one in whom isoprinosine was not used, experienced no improvement and <50% reduction of seizures. Patient 3 achieved complete control of the seizures and symptoms for 3 months. His clinical course worsened on discontinuation of medication. Our patient experience indicates that (1) favorable prognosis is related to early diagnosis; (2) treatment begun in the early stages of the disease is more effective; and (3) THP in combination with isoprinosine reduces seizures in some patients. We therefore suggest the use of THP in combination with isoprinosine in patients with SSPE and myoclonic seizures refractory to the usual antiepileptic therapy.
References
.
~
.
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Figure 6.
EEG of Patient 3 disclosed periodic slow wave complexes.
[1] Modlin JF, Halsey NA, Eddins DL, et al. Epidemiology Of subacute sclerosing panencephalitis. Pediatrics 1971 ;94:231-6. [2] Graves MC. SSPE. Neurol Clin 1984;2:267-79. [3l Dhib-Jalbut S, Johnson KP. Measles virus diseases. In: McKendall RR, Stroop WG, eds. Handbook of neurovirology. New York: Marcel Dekker, 1994:539-54. [4] Sallb EA. SSPE presenting at age 21 as a schizophrenia-like state with bizarre dysmorphic features. Br J Psychiatry 1988;152:709-71. [5] Duncalf CM, Kent JNG, Harbord M, et al. SSPE presenting as schizophreniform psychosis. Br J Psychiatry 1989;155:557-9. [6] Dyken PR, Swift A, Durant MA. Long-term follow up of patients with SSPE treated with Inosiplex. Ann Neurol 1981;11:359-64. 17l Nunes ML. Panecefalite esclerosante subaguda: Aspectos clfnicos, epidemiol6gicos, teral~uticos e progn6stico. J Liga Brasileira Epilepsia 1992;5:23-30.
Nunes et al: Trihexyphenidyl and isoprinosine in SSPE
155
[8] Anderson JR. Viral encephalitis and its pathology. Curr Top Pathol 1988;76:23-60. [9] Cattaneo R, Schimid A, Billeter MA, et al. Multiple viral mutations rather than host factors cause defective measles virus gene expression in a SSPE cell line. J Virol 1988;62:1388-97. [10] Dhib-Jalbut S, McFarland HF, Mingioli ES, et al. Humoral and cellular immune responses to matrix protein of measles virus in subacute sclerosing panencephalitis. J Virol 1988;62:2483-9. [11] Gascon GG, Yamani S, Crowell J, et al. Combined oral isoprinosine-intraventricular alpha interferon therapy for SSPE. Brain Dev 1993; 15:346-55. [12] Gascon GG. Guidelines for the SSPE Consortium Members. Rhode Island: Department of Pediatric Neurology, Brown University, 1995, 1-9. [13] Brimani DJ. Etude electrencephalographique de 40 malade atteints de panencephalite sclerosant subaiguE. Rev EEG Neurophysiol Clin 1986;16:433-43. [14] Lombroso CT. Remarks on the EEG and movement disorder in SSPE. Neurology 1968;18:69-75.
156
PEDIATRIC NEUROLOGY
Vol. 13 No. 2
[15] Jones CE, Dyken PR, Huttenlocher PR, et al. Inosiplex therapy in SSPE, a multicentre, non randomized study in 98 patients. Lancet 1982;8:1034-7. [16] da Costa JC, da Silva LFG, Nunes ML. Panencefalite esclerosante subaguda associada a gestac~.o: Tratamento com trihexafenidil e isoprinosine. J Liga Brasileira Epilepsia 1991 ;4:17-21. [17] Hatanaka T, Sugimoto T, Kobayashi Y. Electroencephalographic changes during interferon therapy in a case of subacute sclerosing panencephalitis. Eur Neurol 1989;29:6-9. [18] Maimone D. Intrathecal interferon in SSPE. Acta Neurol Scand 1988;78:161-6. [19] Yalaz K, Anlar B, Oktem F. Intraventricular interferon and oral Inosiplex in the treatment of SSPE. Neurology 1992;42:488-91. [20] Gellin B, Katz SL. Measles: State of the art and future directions. J Infect Dis 1994;170(suppl):S3-14. [21] Sultan TB, Parhar RS, Kirtkant S, et al. Immunologic status of Saudi patients with SSPE. Pediatr Neurol 1992;8:348. [22] Jabbari B. Trihexiphenidil and partial epilepsy. Epilepsia 1989:30:725.