Is Rasmussen's Syndrome a Treatable, Chronic Viral Encephalitis?

ABSTRACT & COMMENTARY

Source: McLachlan RS, et al. Treatment of Rasmussen's syndrome with ganciclovir. Neurology 1996;47:925-928.

Rasmussen's syndrome consists of a progressively more disabling form of encephalitis that includes Rolandic area partial complex, unilateral motor status epilepticus which progresses slowly but steadily into hemiplegia and cognitive deterioration. Recent studies by Rogers et al suggest that the presence of autoantibodies to glutamate receptor GluR3 contributes to the devastation caused by the disease (Science 1994;265:648-651), a concept strengthened by the fact that plasmapheresis temporarily provides "dramatic" improvements in neurological function (Andrews, et al. Neurology 1996;46:242-246). Other studies have identified cytomegalovirus (CMV) and Herpes simplex virus 1 in brain tissues of many tested cases. In this respect, Jay et al (Neurology 1995;45:108-117) found CMV genome in the brains of 71% of patients with Rasmussen's syndrome compared with 4% of controls.

Table

Treatment of non-AIDS patients with Rasmussen's syndrome

Age Duration
and Sex of Illness Symptoms Antibodies Outcome
7F 3 Months Focal Siezures: Serum:HSV, "Cure"
face, arm, leg; CMV, 18 Months
generalized: mycoplasm; duration.
20-60/d. CSF: negative.
6F 34 Months Limbic-motor Brain tissue Seizures
Partial left CMV+. almost
seizures- stopped,
dementia; left hemiparesis,
hemiparesis. dementia
remain fixed.
24F 4 Years Right focal Brain tissue Illness halted,
motor seizures, CMV+. not improved.
dysphasia, finally
generalized.
2M 8 Months Left hemiclonic Brain tissue No benefit.
and generalized CMV+.
seizures.

Against this background, McLachlan et al treated four non-AIDS patients with Rasmussen's syndrome, giving the antiviral drug ganciclovir. (See Table.) One improved greatly, two improved their rate of seizures but did not reverse other disabilities, and one child continued to progress after therapy.

In their discussion, the authors cite from the literature the case of an 18-year-old woman with Rasmussen's and persistent CMV genome identified in brain. After four years of disease, zidovudine temporarily halted the progression of her disease, but she relapsed 21 months later. Another person with a poorly defined history of 22 months of CMV encephalitis, not typically characteristic of Rasmussen's, immediately halted seizures, but additional information is not provided.

COMMENTARY

Rasmussen's encephalitis is an uncommon but frightful disease that affects either sex predominantly as children. Characteristically, the illness progresses inexorably, eventually producing over a matter of 3-4 years almost continuous focal motor seizures, progressive ipsilateral weakness, and dementia. Until very recently, the only treatment that would stop the major symptoms consisted of ipsilateral cerebral hemispherectomy. Accordingly, current methods of curbing presumed chronic autoimmune damage may deserve use in many circumstances. For the moment, however, it would also seem appropriate to employ ganciclovir as a first order of effort to halt the process. Two suggestive points arise from McLachlan et al's study: 1) in their first case, they could not identify CMV in the brain, nor was the brain biopsy characteristic for Rasmussen's, yet she recovered; 2) the fact that other Herpesviruses, including simplex and zoster have been identified in Rasmussen brains. Since one cannot know which, if any, virus is causative, the evidence suggests that the antiviral agent ganciclovir deserves to be given a therapeutic trial on first evidence of the illness and before PCR results are known.