Abstract
Rasmussen encephalitis (RE) is a rare pediatric neuroinflammatory disease of unknown etiology characterized by intractable seizures, and progressive atrophy usually confined to one cerebral hemisphere. Surgical removal or disconnection of the affected cerebral hemisphere is currently the only intervention that effectively stops the seizures. Histopathological evaluation of resected brain tissue has shown that activated brain resident macrophages (microglia) and infiltrating T cells are involved in the inflammatory reaction. Here, we report that T cells isolated from seven RE brain surgery specimens express the resident memory T cell (TRM) marker CD103. CD103 was expressed by >50% of CD8+ αβ T cells and γδ T cells irrespective of the length of time from seizure onset to surgery, which ranged from 0.3 to 8.4 years. Only ~10% of CD4+ αβ were CD103+, which was consistent with the observation that few CD4+ T cells are found in RE brain parenchyma. Clusters of T cells in brain parenchyma, which are a characteristic of RE histopathology, stained for CD103. Less than 10% of T cells isolated from brain specimens from eight surgical cases of focal cortical dysplasia (FCD), a condition that is also characterized by intractable seizures, were CD103+. In contrast to the RE cases, the percent of CD103+ T cells increased with the length of time from seizure onset to surgery. In sections of brain tissue from the FCD cases, T cells were predominantly found around blood vessels, and did not stain for CD103. The presence of significant numbers of TRM cells in RE brain irrespective of the length of time between clinical presentation and surgical intervention supports the conclusion that a cellular immune response to an as yet unidentified antigen(s) occurs at an early stage of the disease. Reactivated TRM cells may contribute to disease progression.
Highlights
Rasmussen encephalitis (RE) is a rare chronic neuroinflammatory disease that primarily affects young children [1, 2]
Inflammatory markers and T cells have been identified in sections of resected brain tissue from focal cortical dysplasia (FCD) surgeries [22], to our knowledge, T cells have not been previously isolated from fresh FCD surgical material
As is suspected, the disease is triggered by an inflammatory reaction in the brain, we conjectured that some of the T cells found in surgically resected RE tissue may be tissue-resident memory T cells
Summary
Rasmussen encephalitis (RE) is a rare chronic neuroinflammatory disease that primarily affects young children [1, 2]. In the acute stage of the disease, RE patients present with intractable partial (focal) seizures that may spread to the rest of the brain. Hyperintensity in T2/FLAIR magnetic resonance images usually in one cerebral hemisphere is indicative of inflammation and atrophy. The inflammation may spread through the affected cerebral hemisphere, but generally does not cross over to the contralateral hemisphere [3]. In the residual stage of the disease, there is significant unilateral brain atrophy and permanent neurological deficits that may affect motor and sensory systems. Surgical removal or disconnection of the affected cerebral hemisphere is the only intervention that stops the seizures, but inevitably leaves the patient with some functional deficits. A better understanding of the inflammatory processes that occur in RE may lead to the development of alternative non-surgical treatments
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