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Rasmussen's syndrome: pathogenetic theories and therapeutic strategies

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Abstract

A syndrome of chronic partial epileptic seizures attended by progressive focal sensorimotor neurological deficit and cognitive decline, and with neuropathological features of a localized chronic encephalitis, was first defined by Rasmussen and his colleagues in 1958 [1]. Diagnosis of Rasmussen's syndrome (RS) is suggested by the typical clinical features of epilepsia partialis continua, episodes of complex partial status and intractability to standard anti-epileptic drugs. Support for the diagnosis is provided by interictal electroencephalographic evidence of multiple independent lateralized epileptiform abnormalities, and radiological evidence of focal brain atrophy. T2-weighted magnetic resonance imaging may demonstrate high intensity signals in the white matter, consistent with gliosis, and positron emission tomography and single photon emission computed tomography may demonstrate localized changes in glucose metabolism and cerebral perfusion. Ultimately, however, diagnosis is dependent on the neuropathological appearances at brain biopsy or hemispherectomy. These show some variability [2], ranging from an ongoing inflammatory process with microglial nodules, neuronophagia, perivascular lymphocytic cuffing and glial scarring to “non-specific” changes with very few or no microglial nodules, mild perivascular inflammation and various degrees of neuronal loss and glial scarring.

Most predominantly an affliction of children, RS frequently presents before the age of 5 years [3, 4]. Adults may also be affected, albeit very rarely [4–7]. The syndrome is uncommon; the largest series reported to date is of 48 cases [4] and only 11 of 510 patients operated on at one centre for intractable epilepsy between 1974 and 1992 had clinical and pathological findings consistent with the diagnosis [6]. However, these may be underestimates [8]. The finding of focal encephalitic changes in 5–10% of patients undergoing temporal lobectomy for intractable complex partial seizures [9] may represent a non-progressive variant of RS.

Prognosis is poor, for although the neurological deficit usually stabilizes ultimately, seizures may continue, necessitating surgical intervention. Functionally complete but anatomically subtotal hemispherectomy is the operation of choice [10, 11] early surgery in children to pre-empt intellectual decline has been advocated [12]. Although the syndrome is uncommon, it merits attention because of the significant handicap suffered by affected individuals.

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Correspondence to A. J. Larner.

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Larner, A.J., Anderson, M. Rasmussen's syndrome: pathogenetic theories and therapeutic strategies. J Neurol 242, 355–358 (1995). https://doi.org/10.1007/BF00868389

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Key words

  • Rasmussen's syndrome
  • Epilepsy
  • Chronic encephalitis
  • Viruses
  • Autoimmunity