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BRIEF COMMUNICATIONS: T. Granata, L. Fusco, G. Gobbi, E. Freri, F. Ragona, G. Broggi, R. Mantegazza, L. Giordano, F. Villani, G. Capovilla, F. Vigevano, B. Dalla Bernardina, R. Spreafico, and C. Antozzi Experience with immunomodulatory treatments in Rasmussen’s encephalitis Neurology 2003; 61: 1807-1810 [Abstract] [Full text] [PDF]

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Tiziana Granata, Carlo Antozzi   (19 June 2004)

Experience with immunomodulatory treatments in Rasmussen’s encephalitis

Roy T Daniel, Jean-Guy Villemure, Chef de service, Department of Neurosurgery, CHUV, Rue de Bugnon 46, Lausanne 1011, Switzerland   (19 June 2004)

Reply to Daniel 19 June 2004
Tiziana Granata, National Neurological Institute C.Besta via Celoria 11, 20133 Milano, Italy, Carlo Antozzi Send Correspondence to journal: Re: Reply to Daniel granata{at}istituto-besta.it Tiziana Granata, et al.	The aim of our work was to review the efficacy of different immunomodulatory approaches in a series of Italian patients with proven Rasmussen’s encephalitis (RE), and to draw helpful conclusions for the management of this rare disease. It was not our intention to demonstrate that immunomodulation might substitute surgery. On the contrary, as stated in the discussion, we agree that surgical exclusion of the affected hemisphere is the only option that halts seizures and blocks neurologic deterioration. We do believe that “as soon as the diagnosis is secure, surgery should be the preferred treatment”. Nevertheless, surgery must be individualized, taking into account age at onset, progression rate, lateralization, neurological and neuropsychological impairment on the basis of which its correct timing must be decided. [6] We agree that early surgery is mandatory in children to stop seizures and prevent the onset of an epileptic encephalopathy, but not necessarily in adolescent-adult onset RE in which lateralization (together with the degree of motor impairment) plays a major role in deciding the timing of surgery. In this category, particularly in patients with involvement of the dominant hemisphere and slow disease course [7], immunomodulation can be tried to improve the patient conditions, evaluate the residual neurological deficit, and choose the most appropriate timing for hemispherectomy. [8] As far as bilateral RE (which is a rare exception), only case reports are available and no further conclusions can be drawn, including the possibility that immunomodulation could precipitate bilaterality. Patients with suspected RE, in which progressive deterioration has not yet occurred, remain candidates for immunotherapy provided that a detailed differential diagnosis is accomplished. We agree that establishing a firm diagnosis is mandatory, but do not think that immunomodulation might be detrimental in this category of patients in which only a “wait and see” approach can be alternatively proposed. It is likely that our proposal of immunomodulation as a way to “delay” surgery as mentioned in the discussion was misleading, and the term delay not appropriate to express our opinion that immunomodulation can be helpful in a proportion of RE patients in which hemispherectomy cannot be proposed early in the course, not yet indicated, or leading to unacceptable deficits. In the remaining conditions, which represent the majority of patients, hemispherectomy remains the standard of choice. References 6. Villemure JG. Functional hemispherectomy and peri-insular hemispherotomy in Rasmussen’s encephalitis. Proceedings of 2nd international symposium on Rasmussen's syndrome, Montreal 2002. 7. Hart YM, Andermann F, Fish DR, et al. Chronic encephalitis and epilepsy in adult and adolescence: a variant of Rasmussen’s syndrome? Neurology 48:418-424, 1997 8. Hart IK, Nicholas RS. Characterization and immunomodulatory management of adult-onset Rasmussen’s syndrome. Proceedings of 2nd international symposium on Rasmussen's syndrome, Montreal 2002.
Experience with immunomodulatory treatments in Rasmussen’s encephalitis 19 June 2004
Roy T Daniel, CHUV, Lausanne Department of Neurosurgery, CHUV, Rue de Bugnon 46, Lausanne 1011, Switzerland, Jean-Guy Villemure, Chef de service, Department of Neurosurgery, CHUV, Rue de Bugnon 46, Lausanne 1011, Switzerland Send Correspondence to journal: Re: Experience with immunomodulatory treatments in Rasmussen’s encephalitis roymercy{at}hotmail.com Roy T Daniel, et al.	Despite immunomodulation, 13 of 15 patients in the article by Granata et al [1] underwent surgery (after a mean interval of 5.2 years), because response was absent or short lived. The authors proposed immunomodulation to delay surgery in five clinical situations with the assumption (as we understand) that hemispheric damage would be better compensated with a chronic process (natural history of the disease during immunomodulation) when compared to an acute event like surgery. We present here our comments regarding these situations. Regarding dominant hemisphere RE with slow progression, deficits that are likely to occur after surgery also appear with immunomodulation over varying periods of time. Surgery seems to be the only option to halt the disease progression in RE. Delaying surgery could adversely affect the development of the normal hemisphere during the period of maximal brain plasticity. In cases that present with severe compromise of neurological status as a result of refractory status epilepticus,hemispherotomy should be considered on a semi-emergent basis. Some rare cases of bilateral RE reported in literature have had prior immunomodulation. [2,3] In our series, there was one patient who had severe involvement of the left hemisphere and developed mild anatomical MRI changes in the normal hemisphere after immunoglobulin therapy. Surgery provided a functional outcome. This raises the question whether immunomodulation could precipitate bilaterality in RE. In established bilateral RE, immunomodulation may be offered as palliation with an unproven efficacy. When RE diagnosis is uncertain, the use of any form of treatment is questionable and the emphasis should be placed on establishing a firm diagnosis. Surgery could be delayed due to incurring unacceptable deficits. However, the utility of immunomodulation in the long term for this group also remains unproven. The treatment should be individualized to the patient, based on the evaluation of the risks and benefits of surgery/immunomodulation. The response rate of 50% with immunomodulation (though limited in time), has to be weighed against the risks inherent in using this treatment [4,5] Our experience with disconnective hemispherectomy for 24 patients of RE showed excellent outcome in 95%, consistent with data from other surgical series. We believe that early surgery should be performed in the majority of patients, thus preventing the onset of an epileptic encephalopathy. References 1. Experience with immunomodulatory treatments in Rasmussen’s encephalitis. Granata T et al. Neurology 2003 ; 61 : 1807-1810. 2.Chinchilla D, Dulac O, Robain O et al. Reappraisal of Rasmussen’s syndrome with special emphasis on treatment with high doses of steroids. Journalof Neurology, Neurosurgery and Psychiatry 57: 1325-1333, 1994. 3.De Toledo JC, Smith DB.Partially successful treatment of Rasmussen’s encephalitis with zidovudine: symptomatic improvement followed by involvement of the contralateral hemisphere. Epilepsia 35: 352-355, 1994 4.Dulac O, Villanueva. High dose steroid treatment. Proceedings of 2nd international symposium on Rasmussen’s syndrome, Montreal 2002. 5.Oguni H, Muto A, Imai K, Maeda Y, Funatsuka M, Osawa M. The natural history of the disorder before and after immunological treatment. Proceedings of 2nd international symposium on Rasmussen’s syndrome, Montreal 2002.