Authors :
Presenting Author: Julian Larkin, MRCPI – BEAUMONT HOSPITAL
Tudor Munteanu, MRCPI – Epilepsy Fellow, Beaumont Hospital; Cliodhna Murray, MRCPath – Neuropathologist, Beaumont Hospital; Amre Shahwan, MB, FRCPI (Paeds) – Consultant Epileptologist/Neurophysiologist, Children's Health Ireland at Temple Street; Kathleen Gorman, MD MB BCh BAO FRCPI (Paeds) – Consultant Paediatric Neurologist, Children's Health Ireland at Temple Street; Kieron Sweeney, MB, FRCS – Consultant Neurosurgeon, Beaumont Hospital; Alan Beausang, MB, FRCPath, FFPath, FRCPI – Consultant Neuropathologist, Beaumont Hospital; Peter Widdess-Walsh, MB, FRCPI, FAES – Consultant Neurologist, Beaumont Hospital
Rationale:
Rasmussen’s encephalitis (RE) is a rare cause of chronic focal epilepsy which is characterized by T-cell mediated inflammation and microglial activation. It presents with progressive, refractory focal seizures affecting one brain hemisphere and has an intractable course. Hemispherectomy has been the typical definitive approach for RE yet represents a disabling intervention for patients whose disease has emerged beyond the first years of life. Various immune-modifying therapies have been trialled with a view to slowing or halting the progression of disease. Here we present two cases of RE: comparing the neuropathology and immunology findings at different stages (childhood, adolescence, and adulthood).
Methods:
We performed a retrospective analysis of case records for two patients with Rasmussen’s encephalitis. Clinical data, as well as neuroimaging, pathology, and immunology records, were collected. We compared the findings from tissue collected from both biopsy and surgery, examining the differences between the two patients as well as before and after immunotherapy/different stages of the disease course.
Results:
The first case was diagnosed at three years of age with an evolving right-sided hemiplegia and focal unaware seizures with left eye deviation. Seizures evolved to right sided Epilepsy Partialis Continua (EPC) with partial response to immunotherapy. MRI showed progressive left hemiatrophy. Brain biopsy was suggestive of a highly active encephalitis with perivascular and parenchymal lymphocytic inflammation, microglial activation, and gliosis. A modified left hemispherotomy and disconnection surgery has resulted in seizure freedom.
The second case had onset of disease at fifteen years and was treated with immunotherapy. Initial histopathology, from a right frontal lobe biopsy, was characterized by chronic encephalitis with T-cell rich perivascular and parenchymal inflammation. There was evidence of microglial nodules and widespread microglial activation, as well as subpial and parenchymal gliosis. Given intact neurological and motor function they did not undergo surgery at this point. They then underwent right frontal and right anterior temporal resection for epilepsy control approximately eight years after initial diagnosis. Examination of resected tissue revealed minimal or mild parenchymal and perivascular T-cell infiltrate with mild microglial activation, along with hippocampal sclerosis and cortical gliosis consistent with their history of chronic epilepsy. Following the early immune therapy and later focused surgical resection, they now are seizure free with minimal deficit or disability.
Conclusions: Childhood onset RE is known to behave more aggressively than disease of onset in adolescence or adulthood. The two cases presented here illustrate the spectrum of neuropathology across these age groups.
We suggest that there is a graded level of severity of the T-cell infiltrate, microglial activation, and other markers of inflammation from early childhood to adolescence to adulthood, with the latter sample potentially representing a quiescent or "burnt out" phase of the disease.Funding: N/A