The Janus-faced nature of Rasmussen’s Encephalitis

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Rasmussen encephalitis (RE) is an inflammatory unilateral progressive medically refractory epilepsy associated with hemiparesis, cognitive dysfunction, and hemispheric atrophy. Here, we present 2 cases from our institution that demonstrate the dual nature of RE in 2 similarly aged children. Overall, 2 types of RE have been described: type 1 has a short prodromal phase and more explosive onset and type 2 has a longer prodromal of partial seizures followed by hemiparesis and atrophy. Younger patients are more likely to fit into the type 1 presentation and have been described as more likely to have dual pathology. Perhaps the patients with a more acute onset are more likely to have a dual pathology as is found in our 2 cases. We review the typical findings in RE and discuss current treatment options, highlighting new experimental treatments.

Section snippets

Patient 1

J.J., a 4-year-old boy, presented following a history of seizures for 2 years. He had been in good health when he had a minor fall without any loss of consciousness. Later that evening, he had 3 seizures that were all characterized by left-sided facial twitching, drooling, and aphasia. Evaluation with computed tomography (CT) and magnetic resonance imaging (MRI) showed no remarkable findings, and electroencephalogram (EEG) demonstrated a normal background with right temporoparietal

Discussion

The pathologic description of the eponymous RE, as described first by Rasmussen, Olszewski, and Lloyd-Smith in 1958, still captures the essence of the intractable form of epilepsy that is seen today:

Occasional specimens of scarred, atrophic brain removed for the relief of focal cerebral seizures at the Montreal Neurological Institute have shown striking perivascular collections of round cells, particularly in less severely damaged areas of these specimens. In the past this perivascular cuffing

Pathogenesis

The etiology and pathogenesis of RE remains unknown. The pathologic findings of lymphocytic perivascular cuffing and activation of microglial nodules have suggested an underlying infectious or autoimmune etiology. Studies to identify infectious etiologies have yielded conflicting or inconclusive results.4 An autoimmune etiology was suggested when an attempt to generate antibodies to glutamate receptor subtypes induced RE following immunization with GluR3 proteins in rabbits.6 Further studies

Radiology

As illustrated earlier, neuroimaging in RE is an integral piece of diagnostic data.4 No formal recommendations exist to guide monitoring with MRI, but loose guidelines suggest repeat MRIs every 6-12 months. Although RE does not typically involve abnormal parenchymal contrast enhancement, an initial contrast-enhanced study should be performed to rule out alternative etiologies along with consideration of noncontrast CT scan of the head to rule out the presence of calcifications. Furthermore, the

Electroencephalogram

Although EEG is critical in the diagnosis of epilepsy, there have been no pathognomonic findings in the diagnosis of RE. There are limited studies evaluating the EEG and its changes over time in RE. An initial case report demonstrated early unilateral persistent delta slowing, which the authors suggested may herald RE in the absence of evident pathology on MRI. A systematic comparison of 19 children with RE with 17 patients with focal cortical dysplasia failed to demonstrate any specific early

Pathology

Patient 1’s microscopic pathology demonstrated scant perivascular lymphocytic cuffing, Chaslin subpial gliosis, and few microglial cluster formations but no neuronal loss, gliosis, or atrophy (Fig. 3A and B). In significant contrast, patient 2’s microscopic pathology demonstrated severe lymphocytic inflammation, microglial infiltrates, focal severe neuronal loss, and mild Chaslin subpial gliosis in the frontal lobe and hippocampus. In addition, there was a population of large dysmorphic neurons

Surgery

Currently, the only known definitive treatment of seizures in RE is surgical excision with complete functional hemispherectomy or hemispherotomy being the most successful. Seizure freedom rates are frequently >70%.20 Unfortunately, this leaves patients with the expected contralateral hemiplegia, hemianopia, and recoverable ambulatory function. The timing of surgery can be difficult, particularly in patients who have not developed significant motor deficits. Early surgery has been advocated

Conclusion

Our cases highlight the various faces of RE from subacute to rapid progressive, occult to dual pathology, wide-spread dysfunction to localized spreading injury. RE should be on the differential with any patient presenting with medically refractory focal seizures who develops hemiparesis or language deficits. Serial imaging is important as demonstrating progressive injury is essential when considering RE. Unfortunately, surgery remains the only option to prevent progressive decline and seizures.

Acknowledgments

We would like to thank Dr Bette Kleinschmidt-DeMasters for assisting with the pathology section and photomicrographs. We would like to thank our patients and their families for allowing us to care for and learn from them.

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