Chronic Progressive Epilepsia Partialis Continua of Chi Idhood: Rasmussen Syndrome
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THEREis evidence that localised inflammation of the brain can result in focal seizures, often difficult to control, and focal signs such as hemianopia and hemiplegia. This is a syndrome which can be difficult to recognise. Chronic localised encephalitis yith focal epileptic seizures was described by RASMUSSEN et al. in 1958', and GASTAUTand colleagues defined the syndrome of hemiplegia, hemiconvulsions and epilepsy resistant t o anticonvulsant therapy (HHE syndrome) in 19602.
Rasmussen syndrotne In the original paper, RASMUSSENand his colleagues described three children: two had had minor systemic inflammatory episodes at the start of their illnesses, and the other had had measles four years before the onset of seizures. The illness caused seizures and slowly progressive hemiparesis, without any febrile reaction or coma, and its course at least suggested
encephalitis due to a viral infection. I t was considered futile to operate during the active phase of the disease, except from a diagnostic point of view. In 1978 RASMUSSEN3 reviewed 27 patients with a similar syndrome. All had been operated on for medically refractory focal epilepsy. Histological examination of the surgical specimens showed many large and small vessels with perivascular cuffs of lymphocytes, and glial nodules scattered throughout the grey and white matter. Degenerative changes first appeared as laminar necrosis, with prominent inflammatory cells; these progressed to the stage of spongy degeneration. None of the patients had the signs and symptoms usually associated with encephalitis, but they did show clinical and radiological evidence of a slowly progressive destructive process in the brain. The clinical signs were hemiparesis, homonymous hemianopia and mental retardation; the radiological evidence was of cerebral atrophy, usually progressive. The disease appeared to be lethal only in the first year or two, and eventually ceased to progress: Cortical excision carried out early in the course of the disease did not seem to aggravate the inflammatory process, but did not prevent further deterioration. However, when the illness had become stable, cortical excision produced a reasonably satisfactory reduction in the incidence of seizures. Examination of the CSF is often not helpful: the fluid can be completely normal, or the protein, white blood-cell count and colloidal gold curve can be abnormal on one occasion and completely normal on another. The EEG
findings are non-specific, but bilateral slow-wave activity in the presence of focal seizures is suggestive. Obviously, the finding of progressive hemiplegia and increasing slow-wave abnormalities in the EEG can suggest the possibility of a brain tumour. Again it was thought that the findings suggested an infectious agent, possibly a virus, and also that the chronic nature of the illness might be due to depression of antibody- and lymphocyte-mediated immunity. The seizures usually started at an early age, which could be due to the increased vulnerability of the immature brain to viral infections. These 27 patients were identified because of the severity of their symptoms; it is possible that a less extensive invasion of the brain may lead to focal epilepsy, and even mental retardation, for which there is no obvious cause. By the end of 1987 the series had increased to 48 p a t i e n d . Their initial seizures were often generalised and about half had episodes of epilepsia partialis continua. Epileptic status occurred in a few of these patients, and dysplasia as well as mental retardation can occur. Medical treatment, even with steroids, had little effect o n the seizures, but further experience of surgical treatment, including hemispherectomy, has confirmed its effectiveness. HHE syndrome H H E syndrome, well delineated by GASTAUTet al.', is characterised by the onset of convulsions, usually between the ages of six months and two years, followed by an ipsilateral motor deficit during the course of an acute febrile illness. Initially the paralysis is flaccid, but gradually becomes spastic. At a later date intractable epilepsy develops, which is usually of a psychomotor type. The syndrome must be distinguished from other forms of infantile hemiplegia associated with epilepsy, due to such causes as obstetrical trauma and antenatal pathology. If a cause can be found (usually for under half of the cases), it is often an infection of some kind, with vascular complications. Therefore, occasionally there may be an overlap between this syndrome and Rasmussen syndrome, although focal encephalitis was not reported in this original study'.
Evidence of infection in Rasmussen syndrome GUPTA and colleagues5 reported five children with a smouldering illness, with intractable seizures and progressive neurological deterioration, lasting from several months to 10 years; two of the children died. On brain biopsy or at autopsy, all five showed evidence of a persistent inflammatory reaction in a localised area of the brain, suggestive of infection with an unidentified viral agent. None of the children had the usual systemic signs of encephalitis, and none had an inflammatory response in the CSF. The author stressed that it would be necessary to plan sophisticated virological and immunological studies of patients with Rasmussen-like syndromes if an infectious agent is to be identified. FRIEDMAN et a1.6, in support of a viral origin for H H E syndrome, described an immunologically normal three-year-old girl with intractable focal motor seizures and left hemiparesis. The EEG showed focal abnormalities, mainly in the right mid-temporal area, but the CSF was normal. Viral studies by antibody tests and CSF culture were negative, but findings on histological examination of the cortical resection suggested a viral encephalitis. Viral crystals resembling those of enteroviruses were found in brain cells by electron-microscopy. It is claimed that this was the first direct proof of virus in brain material taken from a patient with HHE syndrome. Eleven years later PIATT et al.' recorded the histories of six patients with Rasmussen syndrome. All were treated by selective cortical excision and were found to have inflammatory changes in the excised specimens. These changes were regarded as a reflection of the underlying cause of the epilepsy, rather than a consequence of the seizures themselves. No definite evidence of a virus infection could be established. Surgical treatment did not result in satisfactory seizure control. It has been suggested that individuals with this condition can be divided into two groups, those who continue t o deteriorate and those who seem t o have stabilised, and the latter appear to respond to surgical treatment by localised cortical excision or
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hemi~pherectorny~. The poor response in this series could be due to the operations being performed early in the course of the illness. Claims have been made for the success of hemispherectomy for Rasmussen syndrome in terms of seizure remission, stabilisation of the neurological condition and an improvement in the level of function', but the indications for hemispherectomy d o not appear to be clear-cut. There is no evidence that treatment with steroids, suggested by the inflammatory changes, is of benefit.
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Rasmussen syndrome and cytomegalovirus infection Ten patients with Rasmussen syndrome and 46 age-matched controls with other neurological diseases were studied by POWERer aL9. In situ hybridisation with a biotinylated cytomegalovirus DNA probe was carried out on biopsy specimens. All of the patients with Rasmussen syndrome had a typical clinical picture, and histological examination of the specimens showed signs of an inflammatory process. Cytomegalovirus genomic material was demonstrated in neurons, astrocytes, oligodendrocytes and endothelial cells in seven of the 10 patients and in two of the controls. These results suggested that a cytomegalovirus infection was the cause of Rasmussen syndrome. These results were criticised by GILDEN and LIPTON" on the grounds of insufficient information, the absence of cytomegalovirus antigens in the six cases examined and the unexplained similar findings in two of the controls. In raises the addition, ROOT-BERNSTEIN" question of combined infections with cytomegalovirus and other organisms. FARRELLet al." investigated three patients with Rasmussen syndrome: resected brain tissue showed microglial nodules, neuronophagia, variable lymphocytic inflammatory cell infiltration and neuronal loss with gliosis. It was not possible to demonstrate cytomegalovirus antigen with standard immunohistological techniques and mouse monoclonal antiCMV, nor could CMV nucleic acid be found. Therefore there are still doubts about the role of cytomegalovirus infection in this condition.
Rasniussen syndrome and Epstein-Barr virus infection A four-year-old boy and a 22-year-old woman were investigated by WALTER and RENELLAI3. Both had histories of focal epilepsy, and examination of excised cortical material showed evidence of 'encephalitis. In situ hybridisation with biotin-labelled viral DNA probes, followed by detection with avidin-alkaline phosphatase complexes, showed Epstein-Barr virus genome in intranuclear central cores within the encephalitic infiltrations in both cases. The Epstein-Barr virus therefore may play a part in the pathogenesis of Rasmussen syndrome, possibly in association with diminished immunological resistance. Impaired immunity and Rasmussen syndrome It is possible that a number of viruses may be involved in causing this syndrome, and also that a viral infection could trigger an auto-immune mechanism of cortical and white matter destruction12. This could explain the negative viral studies and the demonstration of immune complexes in affected brain-tissue. ANDREWSet al. l4 studied a girl of nearly four years of age with typical symptoms and signs. Tests showed elevated serum antinuclear antioligoclonal bands and body titres, c s ~ elevated Igc: albumin ratio, lgc index and igc synthesis rate. Examination of a hemispherectomy specimen revealed widespread cerebral vasculitis with immunofluorescence staining for lgc, IgM, IgA, c3 and c l q , and ultrastructural evidence of vascular injury, in addition to severe cortical atrophy with marked neuronal loss. These findings suggest a possible vasculitis related to immune mechanisms. In addition, there is no doubt that chronic progressive encephalitis occurs in children with conditions such as x-linked hypogammaglobulinaemia. LYON et al. l 5 describe relentlessly progressive encephalitis in six boys with congenital hypogammaglobulinaemia. The pathological picture was that of a viral encephalitis, but all the virological investigations on brain biopsies and CSF were negative.
Therapeutic possibilities I f there is a possibility that Rasmussen syndrome is caused by bacterial-and especially viral-infections, the use of antibiotics and antiviral drugs such as acyclovir and ganciclovir, cytomegalovirus vaccination and BCG therapy may be effective in prevention or cure”. Further evidence of cytomegalovirus infection as a cause of this form of encephalitis is needed. Investigations such as whether CMV-specific gene sequences can be amplified with the polymerase-chain reaction and whether the virus can be cultured from cerebral tissues of affected children may help. There is evidence that ganciclovir has some effect on the cytomegalovirus, although a limiting factor is the neuropenia that can occur16. Studies on children with Rasmussen syndrome have amassed enough evidence now to justify intensive investigation of all possible infective agents, especially those of viral origin. In addition, appropriate drugs, such as antiviral agents, should be given a trial. NEIL GORDON Hitntly wood, 3 Styal Road, Wilmslow, Cheshire SKP 4AE. References 1 . Rasmusscn, T., Olszewski, J., Lloyd-Smith, D. (1958) ‘Focal seizures due to chronic localised encephalitis.’ Neurology, 8, 435-445. 2 . Gastaut, H., Pokier, F., Payan, H., Salamon, G., Toga, M., Vigouroux, M. (1960) ‘H.H.E. syndrome: hemiconvulsions, hemiplegia, epilepsy.’ Epilepsia, 1, 418-447. 3. Rasrnussen, T. (1978) ‘Further observations on
the syndrome of chronic encephalitis and epilepsy.’ Applied Neurophysiology, 41, 1-12. 4. Rasmussen, T., Andermann, F. (1989) ‘Update on the syndrome of “chronic encephalitis” and epilepsy.’ Cleveland Clinic Journal of Medicine, 56, S 18 I - I 84. 5. Gupta, P. C., Rapin, I., Houroupian, D. S., Roy, S., Llena, J. F., Tandon, P. M. (1984) ‘Smoldering encephalitis in children.’ Neiiropediatrics, 1 5, I 9 I - I 97. 6. Friedman, H., Ch’ien, L . , Parham, D: (1977) ‘Virus in brain of child with hemiplegia, hemiconvulsions, and epilepsy.’ Lancet, 2, 666. (Letter.) 7. Piatt. J . H.. Hwang. P. A,. Armstrone. D. C.. Becker, L..E., Horfman, H. J. (1988)’Chronic focal encephalitis (Rasmussen’s syndrome): six cases.’ Epilepsia, 29, 268-279. 8. Dalos, N., Vining, E. P. G., Carson, B., Freeman, J. M. (1986) ‘Rasmussen’s encephalitis: clinical recognition and surgical management.’ Epilepsia, 27, 594. 9. Power, C., Poland, S. D., Blume, W. T., Girvin, J. P., Rice, G. P. A. (1990) ‘Cytomegalovirus and Rasmussen’s encephalitis.’ Lancef, 336, 1282-1284. 10. Gilden, D. H., Lipton, H. (1991) ‘Cytomegalovirus and Rasmussen’s encephalitis.’ Lancet, 337, 239. (Letter.) 1 I . Root-Bernstein. R. S . 11991) ‘Cvtomeealovirus and Rasmussen’s encephaiitis.; Lancet, 337, 239-240. (Letter.) 12. Farrell, M. A., Cheng, L., Cornford, M. E., Grodv. W. W.. Vinters. H. V. 11991) ‘Cvtomegaidvirus and Rasm’ussen’s encephalik’ Lancet. 337, 1551-1 552. (Letter.) 13. Walter, G. F., Renella, R. R. (1989) ‘EpsteinBarr virus in brain and Rasmussen’s encephalitis.’ Lancet. 1, 279-280. (Letter.) 14. Andrews, J . M., Thompson, J. A., Pysher, T. J., Walker, M. L., Hamrnond, M. E. (1990) ‘Chronic encephalitis, epilepsy, and cerebrovascular immune complex deposits.’ Annals of Neurology, 28, 88-90. (Lerrer.) IS. Lyon, G., Griscella, C., Fernandez-Alvarez, E., Prats-Vines, J., Lebon, P. (1980) ‘Chronic progressive encephalitis in children with X-linked hypogammaglobulinernia.’ Neuropadiafrie, 11, 57-7 I . 16. Fletcher, C. V., Balfour, H. H. (1989) ‘Evaluation of ganciclovir for cytomegalovirus disease.’ NCP Annals of Pharrnacotherapy, 23. 5-12.
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. 6
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THEREis evidence that localised inflammation of the brain can result in focal seizures, often difficult to control, and focal signs such as hemianopia and hemiplegia. This is a syndrome which can be difficult to recognise. Chronic localised encephalitis yith focal epileptic seizures was described by RASMUSSEN et al. in 1958', and GASTAUTand colleagues defined the syndrome of hemiplegia, hemiconvulsions and epilepsy resistant t o anticonvulsant therapy (HHE syndrome) in 19602.
Rasmussen syndrotne In the original paper, RASMUSSENand his colleagues described three children: two had had minor systemic inflammatory episodes at the start of their illnesses, and the other had had measles four years before the onset of seizures. The illness caused seizures and slowly progressive hemiparesis, without any febrile reaction or coma, and its course at least suggested
encephalitis due to a viral infection. I t was considered futile to operate during the active phase of the disease, except from a diagnostic point of view. In 1978 RASMUSSEN3 reviewed 27 patients with a similar syndrome. All had been operated on for medically refractory focal epilepsy. Histological examination of the surgical specimens showed many large and small vessels with perivascular cuffs of lymphocytes, and glial nodules scattered throughout the grey and white matter. Degenerative changes first appeared as laminar necrosis, with prominent inflammatory cells; these progressed to the stage of spongy degeneration. None of the patients had the signs and symptoms usually associated with encephalitis, but they did show clinical and radiological evidence of a slowly progressive destructive process in the brain. The clinical signs were hemiparesis, homonymous hemianopia and mental retardation; the radiological evidence was of cerebral atrophy, usually progressive. The disease appeared to be lethal only in the first year or two, and eventually ceased to progress: Cortical excision carried out early in the course of the disease did not seem to aggravate the inflammatory process, but did not prevent further deterioration. However, when the illness had become stable, cortical excision produced a reasonably satisfactory reduction in the incidence of seizures. Examination of the CSF is often not helpful: the fluid can be completely normal, or the protein, white blood-cell count and colloidal gold curve can be abnormal on one occasion and completely normal on another. The EEG
findings are non-specific, but bilateral slow-wave activity in the presence of focal seizures is suggestive. Obviously, the finding of progressive hemiplegia and increasing slow-wave abnormalities in the EEG can suggest the possibility of a brain tumour. Again it was thought that the findings suggested an infectious agent, possibly a virus, and also that the chronic nature of the illness might be due to depression of antibody- and lymphocyte-mediated immunity. The seizures usually started at an early age, which could be due to the increased vulnerability of the immature brain to viral infections. These 27 patients were identified because of the severity of their symptoms; it is possible that a less extensive invasion of the brain may lead to focal epilepsy, and even mental retardation, for which there is no obvious cause. By the end of 1987 the series had increased to 48 p a t i e n d . Their initial seizures were often generalised and about half had episodes of epilepsia partialis continua. Epileptic status occurred in a few of these patients, and dysplasia as well as mental retardation can occur. Medical treatment, even with steroids, had little effect o n the seizures, but further experience of surgical treatment, including hemispherectomy, has confirmed its effectiveness. HHE syndrome H H E syndrome, well delineated by GASTAUTet al.', is characterised by the onset of convulsions, usually between the ages of six months and two years, followed by an ipsilateral motor deficit during the course of an acute febrile illness. Initially the paralysis is flaccid, but gradually becomes spastic. At a later date intractable epilepsy develops, which is usually of a psychomotor type. The syndrome must be distinguished from other forms of infantile hemiplegia associated with epilepsy, due to such causes as obstetrical trauma and antenatal pathology. If a cause can be found (usually for under half of the cases), it is often an infection of some kind, with vascular complications. Therefore, occasionally there may be an overlap between this syndrome and Rasmussen syndrome, although focal encephalitis was not reported in this original study'.
Evidence of infection in Rasmussen syndrome GUPTA and colleagues5 reported five children with a smouldering illness, with intractable seizures and progressive neurological deterioration, lasting from several months to 10 years; two of the children died. On brain biopsy or at autopsy, all five showed evidence of a persistent inflammatory reaction in a localised area of the brain, suggestive of infection with an unidentified viral agent. None of the children had the usual systemic signs of encephalitis, and none had an inflammatory response in the CSF. The author stressed that it would be necessary to plan sophisticated virological and immunological studies of patients with Rasmussen-like syndromes if an infectious agent is to be identified. FRIEDMAN et a1.6, in support of a viral origin for H H E syndrome, described an immunologically normal three-year-old girl with intractable focal motor seizures and left hemiparesis. The EEG showed focal abnormalities, mainly in the right mid-temporal area, but the CSF was normal. Viral studies by antibody tests and CSF culture were negative, but findings on histological examination of the cortical resection suggested a viral encephalitis. Viral crystals resembling those of enteroviruses were found in brain cells by electron-microscopy. It is claimed that this was the first direct proof of virus in brain material taken from a patient with HHE syndrome. Eleven years later PIATT et al.' recorded the histories of six patients with Rasmussen syndrome. All were treated by selective cortical excision and were found to have inflammatory changes in the excised specimens. These changes were regarded as a reflection of the underlying cause of the epilepsy, rather than a consequence of the seizures themselves. No definite evidence of a virus infection could be established. Surgical treatment did not result in satisfactory seizure control. It has been suggested that individuals with this condition can be divided into two groups, those who continue t o deteriorate and those who seem t o have stabilised, and the latter appear to respond to surgical treatment by localised cortical excision or
.
2 2
183
hemi~pherectorny~. The poor response in this series could be due to the operations being performed early in the course of the illness. Claims have been made for the success of hemispherectomy for Rasmussen syndrome in terms of seizure remission, stabilisation of the neurological condition and an improvement in the level of function', but the indications for hemispherectomy d o not appear to be clear-cut. There is no evidence that treatment with steroids, suggested by the inflammatory changes, is of benefit.
.-0C d
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Rasmussen syndrome and cytomegalovirus infection Ten patients with Rasmussen syndrome and 46 age-matched controls with other neurological diseases were studied by POWERer aL9. In situ hybridisation with a biotinylated cytomegalovirus DNA probe was carried out on biopsy specimens. All of the patients with Rasmussen syndrome had a typical clinical picture, and histological examination of the specimens showed signs of an inflammatory process. Cytomegalovirus genomic material was demonstrated in neurons, astrocytes, oligodendrocytes and endothelial cells in seven of the 10 patients and in two of the controls. These results suggested that a cytomegalovirus infection was the cause of Rasmussen syndrome. These results were criticised by GILDEN and LIPTON" on the grounds of insufficient information, the absence of cytomegalovirus antigens in the six cases examined and the unexplained similar findings in two of the controls. In raises the addition, ROOT-BERNSTEIN" question of combined infections with cytomegalovirus and other organisms. FARRELLet al." investigated three patients with Rasmussen syndrome: resected brain tissue showed microglial nodules, neuronophagia, variable lymphocytic inflammatory cell infiltration and neuronal loss with gliosis. It was not possible to demonstrate cytomegalovirus antigen with standard immunohistological techniques and mouse monoclonal antiCMV, nor could CMV nucleic acid be found. Therefore there are still doubts about the role of cytomegalovirus infection in this condition.
Rasniussen syndrome and Epstein-Barr virus infection A four-year-old boy and a 22-year-old woman were investigated by WALTER and RENELLAI3. Both had histories of focal epilepsy, and examination of excised cortical material showed evidence of 'encephalitis. In situ hybridisation with biotin-labelled viral DNA probes, followed by detection with avidin-alkaline phosphatase complexes, showed Epstein-Barr virus genome in intranuclear central cores within the encephalitic infiltrations in both cases. The Epstein-Barr virus therefore may play a part in the pathogenesis of Rasmussen syndrome, possibly in association with diminished immunological resistance. Impaired immunity and Rasmussen syndrome It is possible that a number of viruses may be involved in causing this syndrome, and also that a viral infection could trigger an auto-immune mechanism of cortical and white matter destruction12. This could explain the negative viral studies and the demonstration of immune complexes in affected brain-tissue. ANDREWSet al. l4 studied a girl of nearly four years of age with typical symptoms and signs. Tests showed elevated serum antinuclear antioligoclonal bands and body titres, c s ~ elevated Igc: albumin ratio, lgc index and igc synthesis rate. Examination of a hemispherectomy specimen revealed widespread cerebral vasculitis with immunofluorescence staining for lgc, IgM, IgA, c3 and c l q , and ultrastructural evidence of vascular injury, in addition to severe cortical atrophy with marked neuronal loss. These findings suggest a possible vasculitis related to immune mechanisms. In addition, there is no doubt that chronic progressive encephalitis occurs in children with conditions such as x-linked hypogammaglobulinaemia. LYON et al. l 5 describe relentlessly progressive encephalitis in six boys with congenital hypogammaglobulinaemia. The pathological picture was that of a viral encephalitis, but all the virological investigations on brain biopsies and CSF were negative.
Therapeutic possibilities I f there is a possibility that Rasmussen syndrome is caused by bacterial-and especially viral-infections, the use of antibiotics and antiviral drugs such as acyclovir and ganciclovir, cytomegalovirus vaccination and BCG therapy may be effective in prevention or cure”. Further evidence of cytomegalovirus infection as a cause of this form of encephalitis is needed. Investigations such as whether CMV-specific gene sequences can be amplified with the polymerase-chain reaction and whether the virus can be cultured from cerebral tissues of affected children may help. There is evidence that ganciclovir has some effect on the cytomegalovirus, although a limiting factor is the neuropenia that can occur16. Studies on children with Rasmussen syndrome have amassed enough evidence now to justify intensive investigation of all possible infective agents, especially those of viral origin. In addition, appropriate drugs, such as antiviral agents, should be given a trial. NEIL GORDON Hitntly wood, 3 Styal Road, Wilmslow, Cheshire SKP 4AE. References 1 . Rasmusscn, T., Olszewski, J., Lloyd-Smith, D. (1958) ‘Focal seizures due to chronic localised encephalitis.’ Neurology, 8, 435-445. 2 . Gastaut, H., Pokier, F., Payan, H., Salamon, G., Toga, M., Vigouroux, M. (1960) ‘H.H.E. syndrome: hemiconvulsions, hemiplegia, epilepsy.’ Epilepsia, 1, 418-447. 3. Rasrnussen, T. (1978) ‘Further observations on
the syndrome of chronic encephalitis and epilepsy.’ Applied Neurophysiology, 41, 1-12. 4. Rasmussen, T., Andermann, F. (1989) ‘Update on the syndrome of “chronic encephalitis” and epilepsy.’ Cleveland Clinic Journal of Medicine, 56, S 18 I - I 84. 5. Gupta, P. C., Rapin, I., Houroupian, D. S., Roy, S., Llena, J. F., Tandon, P. M. (1984) ‘Smoldering encephalitis in children.’ Neiiropediatrics, 1 5, I 9 I - I 97. 6. Friedman, H., Ch’ien, L . , Parham, D: (1977) ‘Virus in brain of child with hemiplegia, hemiconvulsions, and epilepsy.’ Lancet, 2, 666. (Letter.) 7. Piatt. J . H.. Hwang. P. A,. Armstrone. D. C.. Becker, L..E., Horfman, H. J. (1988)’Chronic focal encephalitis (Rasmussen’s syndrome): six cases.’ Epilepsia, 29, 268-279. 8. Dalos, N., Vining, E. P. G., Carson, B., Freeman, J. M. (1986) ‘Rasmussen’s encephalitis: clinical recognition and surgical management.’ Epilepsia, 27, 594. 9. Power, C., Poland, S. D., Blume, W. T., Girvin, J. P., Rice, G. P. A. (1990) ‘Cytomegalovirus and Rasmussen’s encephalitis.’ Lancef, 336, 1282-1284. 10. Gilden, D. H., Lipton, H. (1991) ‘Cytomegalovirus and Rasmussen’s encephalitis.’ Lancet, 337, 239. (Letter.) 1 I . Root-Bernstein. R. S . 11991) ‘Cvtomeealovirus and Rasmussen’s encephaiitis.; Lancet, 337, 239-240. (Letter.) 12. Farrell, M. A., Cheng, L., Cornford, M. E., Grodv. W. W.. Vinters. H. V. 11991) ‘Cvtomegaidvirus and Rasm’ussen’s encephalik’ Lancet. 337, 1551-1 552. (Letter.) 13. Walter, G. F., Renella, R. R. (1989) ‘EpsteinBarr virus in brain and Rasmussen’s encephalitis.’ Lancet. 1, 279-280. (Letter.) 14. Andrews, J . M., Thompson, J. A., Pysher, T. J., Walker, M. L., Hamrnond, M. E. (1990) ‘Chronic encephalitis, epilepsy, and cerebrovascular immune complex deposits.’ Annals of Neurology, 28, 88-90. (Lerrer.) IS. Lyon, G., Griscella, C., Fernandez-Alvarez, E., Prats-Vines, J., Lebon, P. (1980) ‘Chronic progressive encephalitis in children with X-linked hypogammaglobulinernia.’ Neuropadiafrie, 11, 57-7 I . 16. Fletcher, C. V., Balfour, H. H. (1989) ‘Evaluation of ganciclovir for cytomegalovirus disease.’ NCP Annals of Pharrnacotherapy, 23. 5-12.
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