Dr.Venkatesh Kumar M, Dr.Vinayan(Pediatric Neurology), Dr.C.Jayakumar, AIMS,Kochi.
Three years old girl, 1st child of non- consanguinous marriage with uneventful birth history and normal development with mild hyperactivity in premorbid state presented with complaints of paroxysmal events started at the age of 2.5 years .
At the age of 2.5 years ,the child had one episode of GTCS with fever lasting for a duration of 15 minutes which was managed as simple febrile seizure and advised clobazam prophylaxis. After few days,she started having paroxysmal events in the form of vacant stare with gaze preference towards left side lasting for 3-4 seconds followed resumption of activity occurring at a frequency of once every 10-15 days.
She was taken to local hospital where 4 hours VEEG was done which showed frequent left anterior temporal electrical activities. She was started on Levitreacetam .
MRI brain showed left frontal mild periventricular leukomalacia ,small periventricular signal changes and subtle FLAIR hypointensities in left hippocampus and uncus.
Change in seizure semiology was noticed from 2.9 years of age, She started having staring episodes to left along with right hand in abduction and falling to the left side followed oral and hand automatisms with impaired awareness. Events continued to recur every 10-15 days, 2-3 events in a day .So regular clobazam was added after which seizures changed semiology and started occurring in clusters.
Evaluation was done again outside ,Prolonged VEEG was done which showed the same findings.
Oxcarbazapine was added with not much response.
After a gap of 15 days, seizures happened in clusters for 5 days at a frequency of 2-3 per day daily.
MRI brain was repeated showing similar changes as described previously. She was admitted for serum NMDA receptor antibody and Serum NMO-MOG( Neuromyelitis Optica- Myelin Oligodendrocyte Glycoprotein) work up which turned out to be negative.
CSF autoimmune workup ,normal.Leviteracetam was tapered and stopped. Topiramate and valproate were tried, but with out much improvement.
H/O Seizures in paternal cousin sister and febrile seizures in mother( at 2 yrs of age).There were no neurocutaneuos markers and no facial dysmorphism .Auxology revealed normal growth parameters.CNSexamination was unremarkable.
Differential diagnosis considered at this point are:
1. Sturge Weber Syndrome
2. Rasmussen’s Encephalitis
3. Tuberous sclerosis
4. Mitochondrial myopathy with lactic acidosis and stroke like episodes(MELAS)
5. Hemimegalencephaly.
6. Cerebral vasculitis.
Investigations:
Hemogram: TC-10.83 ku/ml, N/L- 36.8%/54.4 %, Hb- 13.5 gm/dl, Plt-4 lakh.
LFt,RFT: normal.
S.Na+: 138 mEq/L, K+: 3.6 mEq/L, Ca2+: 9.05 mg/dl, Mg2+:2.3 mg/dl, CPK: 111 U/L.
CRP: 0.17 mg/L, Amylase: 42 U/L, Lipase: 25.7 U/L, TSH: 1.80 IU/ml.
25-OH Vitamin- D: 12.12 ng/ml (low)
Ammonia: 63 umol/L(high)
Prolonged 24 hour VEEG : showed left hemispheric and generalized epileptiform abnormalities along with non-specific disturbances of electrical functions over left hemisphere. Recorded one electroclinical event suggestive of focal seizure of left hemispheric onset.
Ophthalmology evaluation : Normal fundus.
VEP, BERA : Normal.
MRI Brain: showed mildly diffuse atrophy of left cerebral hemispheres with disproportionate atrophy of left caudate nucleus.
PET MRI : showed significant hypometabolism in left cerebral hemisphere (frontal,parieto-temporal cortex) with minimal to moderate hypometabolism in left caudate nucleus,thalamus and bilateral hippocampus.
Overall electro-clinico-radiological impression is more suggestive of Rasmussens encephalitis.
Hence Diagnosis of RASMUSSEN’S ENCEPHALITIS is made.
She was continued on multiple Anti-epileptics which was started from outside( Valproate,Oxcarbazapine,Topiramate and Clobazam ). Multidisciplinary treatment including immunotherapy,audiological evaulation was advised.
She was admitted with breakthrough seizures after 4 months, managed with Inj.Methyl Prednisolone along with other AED’s and discharged with Oral prednisolone with immunomodulation on followup in OP basis
6 months later,she was again admitted with breakthrough seizures with different semiology, immunotherapy with anti-seizure medications continued.
Hence option of hemispherectomy was also considered and on follow up.
DISCUSSION:
Rasmussen encephalitis, sometimes referred to as Rasmussen syndrome, is a rare disorder of the central nervous system characterized chronic progressive inflammation (encephalitis) of one cerebral hemisphere. As a result, the patient usually experiences frequent episodes of uncontrolled electrical disturbances in the brain that cause epileptic seizures (epilepsy) and progressive cerebral destruction. With time, further symptoms may include progressive weakness of one side of the body (hemiparesis), language problems (if on the left side of the brain) and intellectual disabilities.
The exact cause of this disorder is not known.
The two leading ideas are that the brain inflammation might be a reaction of a foreign antigen (infection) or an autoimmune disease limited to one side of the brain resulting in brain damage.
After the peak inflammatory response is reached, the progression of this disorder appears to slow or stop, and the patient is left with permanent neurological deficits.
Clinical features:
Typically, affected individuals develop focal seizures that may progress to near continuous seizures termed epilepsia partialiscontinua (EPC). EPC is characterized a rapid, rhythmic succession of contractions and relaxations of a muscle or muscle group (myoclonus), particularly of the arms, legs, and face, that may occur singularly or in a repetitive, continuous series. In Rasmussen this occurs consistently on one side of the body opposite the side of the inflammation.
Most affected children will exhibit progressive paralysis of one side of the body (hemiparesis) and if the seizures continue developmental disabilities. Developmental arrest and developmental regression were noted.Some affected children may exhibit degeneration (atrophy) of one side of the brain and/or progressive confusion, disorientation and deterioration of intellectual abilities (dementia).
Cause: The exact cause of Rasmussen encephalitis is not known. Rasmussen encephalitis is an autoimmune disorder thought to be T-cell mediated .
Treatment of Rasmussen encephalitis is mostly symptomatic and supportive. Various anti-seizure medications (anticonvulsants) may be used to treat seizures. Medical treatments targeted at possible autoimmune disease may be tried, including steroids, immunoglobulin and tacrolimus. Immunological therapies (tacrolimus, intravenous immunoglobulins, potentially others as well) may slow down the neurological and structural deterioration but usually does not improve the epilepsy or progressive brain atrophy. Its precise role in management of Rasmussen encephalitis remains to be determined.
Surgery usually in the form of a cerebral hemispherectomy is the only way to cure the seizures and halt neurodevelopmental regression. However, there are inevitable functional deficits including hemiparesis (weakness of one side) and hemifielddefect (impairment of vision to one side), and where the dominant side of the brain is affected, there may be an effect on language. The difficulty is often deciding on the necessary and best timing of surgery, dependent on the severity of epilepsy and degree of effect on learning and progression of the disease. The decision should be made jointly the family and specialist center that has experience treating patients with this condition.
Take home message: Extensive workup and optimal diagnosis in any case of multiple seizure episodes, considering Rasmussen’s encephalitis with multi-diagnostic approach can slow the progression of disease and improve the prognosis of condition.