Rasmussen ’ s Encephalitis

Address for correspondence: Dr. Nibedita Mitra E-mail: nibeditamitra1@yahoo.co.in 1Dr. Nibedita Mitra, MBBS, DCH, DNB (Pediatrics), Head of the Department of Paediatrics. 2Dr. G. Kavitha, DCH, DNB(Paediatrics), Senior Divisional Medical Officer, 3Dr. M. Nithya,DNB (Paediatrics), Senior Resident, 4Dr. Atish Bakhne,DCH,DNB (Pediatrics), Senior Resident. All from the Department of Paediatrics, Southern Railways head Quarter Hospital, Perambur, Chennai600023. Abstract

Introduction R asmussen's encephali s is a rare neurological disease of childhood characterised by progressive unilateral hemisphere atrophy, focal intractable seizures and progressive neurological defi cit 1 .It is rarely fatal but its eff ects are devasta ng.Early diagnosis is important before the process destroys much of the hemisphere.

The Case
A seven year old boy presented with le hemiparesis, and recurrent episodes of focal seizures on the le side.He was delivered at term with a birth weight of 2.7 kilograms and had an uneven ul neonatal period.His ini al mile stones were appropriate for age.
At the age of seven months, he was hospitalised with fever and status epilep cus.He recovered without neurological defi cit and was treated as febrile seizures.Two months later, child had one episode of s ff ening of the le upper and lower limbs las ng for approximately fi ve minutes and he recovered without neurological defi cit.Two weeks later mother no ced that child was not using the le upper and lower limbs as much as the right.
From then on, he used to have frequent episodes of seizures, always restricted to le limbs, some mes involving the le half of face with turning of face to le side and brief loss of consciousness.The frequency of seizures had been increasing to fi ve to six episodes every month.His le  side motor weakness increased to le hemi paresis.He also had aphasia, mild cogni ve impairment with learning diffi culty.He was on three an convulsants but the seizures episodes con nued with same frequency.
In the EEG there were epilep form discharges over the right hemisphere with sharp and slow wave complex.MRI brain showed diff use cor cal atrophy with exvacuo dialata on of cor cal sulci and lateral ventricle involving the right cerebral hemisphere.Altered signal intensity noted with in the right Thalamus.The T2W image shows diff use increased signal intensity in the cor cal and sub cor cal white ma er.The le cerebral hemisphere, brain stem and cerebellum are all within normal limits.There is progressive right cerebral atrophy as compared to CT brain done at the age of two years.
Progressive cerebral hemi atrophy with clinical deteriora on and focal EEG features was the key to diagnosis of Rasmussen's Encephali s for this child.He was put on daily dose steroids at 2 mg/kg of prednisolone daily.A er two months of treatment with prednisolone, there was a marked improvement with reduc on in his seizure frequency but no improvement in cogni on and aphasia.He has been referred to Neurosurgeon for considering the feasibility of hemispherectomy.

Discussion
Rasmussen's encephali s was fi rst described by Rasmussen et al in 1958.It is associated with slowly progressive neurological deteriora on and seizure in children.Seizures are o en the fi rst problem to appear.Simple par al motor seizures involving one side of the body were the most common (77%), followed by secondarily generalised tonic-clonic seizures ( 42%), complex par al seizures ( 19% with automa sm and 31% with subsequent unilateral motor involvement).(Oguni et al 1991) 1 Rasmussen's encephali s is a chronic infl ammatory disease of unknown origin and is envisaged as sporadic.Though rarely fatal, but its eff ects are devasta ng.The seizures are typically relentless and hemi paresis and mental impairment o en follow.
The disease is characterised by three stages.An ini al prodromal phase is characterised by a rela vely low seizure frequency and only rarely some degree of hemi paresis.It had a median dura on of 7.1 months.In acute phase of the disease, pa ents have frequent focal seizures and development of hemi paresis.The median dura on of acute period was 8 months.The acute phase was followed by a residual stage with a permanent and stable hemi paresis.The seizure reduc on can be explained par ally by the loss of neurons due to the infl ammatory process.The neuronal loss, one of the corner stone of RE also explains the worsening and irreversibility of the neurological status. 2 Although the defi ni ve diagnosis is to confi rm chronic infl ammatory changes in brain specimen, recent progress in clinical research has allowed a clinical diagnosis with a rela vely higher accuracy.Progressive cerebral hemiatrophy with clinical deteriora on and focal EEG features are the key to diagnosis, avoiding brain biopsy.
Progressive lateralised cerebral hemi atrophy demonstrated by CT scan and MRI appears to be a characteris c fi nding of Rasmussens Syndrome.One puzzling aspect of Rasmussens syndrome is why chronic encephali s always aff ects only one hemi sphere, leaving the other intact. 3ree key factors have been considered in the ae o-pathogenesis of this disease.These include viruses, auto an bodies (GLUR3 an bodies) and cyto toxic T lymphocytes.Based on these concepts diff erent therapeu c strategies have been pursued such as an viral agents, plasmapheresis, immunoadsorp on, immunosuppresion or immunomodula on with intravenous immunoglobulin 4 .However due to lack of larger studies, to date there is no established therapeu c strategy of this devasta ng disease.
The most eff ec ve treatment of Rasmussen's Encephali s with regard to seizure freedom is hemi spherectomy 4 .This procedure however is usually performed only at a later stage of the disease when a pa ent has developed a fi xed hemiparesis with loss of fi ne fi nger movement.
Although AEDs have li le or no eff ect on par al seizures, they reduce the risk of generalised seizures.An epilep c therapy is recommended through the disease.
We are presen ng this case because of its rarity and need of awareness for early diagnosis and treatment, to prevent severe neurological defi cit.The period of most extensive brain damage is on an average the 8 months of the acute disease phase.Early ini a on of immunotherapy has been suggested to improve the outcome and alter the natural history of the disease.Early Immunological therapies with steroids, immunoglobulin (IG), plasmapheresis, and immunosuppressive therapy with tacrolimus may prevent the loss of neurons and progressive cerebral atrophy and thus improve the outcome and alter the natural history of the disease.Future therapeu c interven ons should therefore focus on this me period rather than on later burnt out stage during which the majority of brain atrophy has already taken place.
Rasmussen's encephali s should always be considered in the diff eren al diagnosis of hemiparesis with par al seizures localised to the same side of hemiparesis.An early neuroimaging should be mandatory so that early therapy may prevent further loss of neurons.

Fig:
Fig: MRI brain showing diff use cor cal atrophy with exvacuo dilata on of cor cal sulci lateral ventricle involving the right cerebral hemisphere.

Table 1 : European Consensus Diagnos c Criteria for RE (2005 ) (Bien et al., 2005b) Diagnosis criteria according to Bien et al: If all primary criteria are present, the diagnosis is very likely. If that is not the case, two out of three secondary criteria must be present. Diagnos c Primary criteria Secondary criteria
Neurological defi cits or cerebral hemiatrophy should increase to be considered as being "progressive", which implicates that at least two clinical examina ons or MRI studies are carried out (6 months or more).** The signal can be seen either in the grey or the white ma er.*** Numerous macrophages, B lymphocytes, plasmocytes or viral inclusion bodies exclude the diagnosis of RE