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|Year : 2021 | Volume
| Issue : 4 | Page : 1010-1013
Uncommon Presentation of Rasmussen's Encephalitis
Arvind Vyas, Jaypalsing Ramdhan Ghunawat, Amit Kumar Bagaria, Dinesh Khandelwal
Department of Neurology, SMS Medical College, Jaipur, Rajasthan, India
|Date of Submission||02-May-2020|
|Date of Decision||08-Jul-2020|
|Date of Acceptance||08-Jul-2021|
|Date of Web Publication||2-Sep-2021|
Jaypalsing Ramdhan Ghunawat
Centre of Neurology, Asian Hospital, Aurangabad, Maharashtra
Source of Support: None, Conflict of Interest: None
Rasmussen's encephalopathy (RE) is an uncommon neurological disease of inflammatory origin which is characterized by intractable focal epilepsy, progressive limb weakness, and cognitive deterioration. RE presenting as movement disorder like hemidystonia or hemichorea is a rare occurrence. The duration of prodromal stage of RE is usually in weeks or months. Prolonged prodromal stage like in years is rarely reported. Magnetic resonance imaging (MRI) is a good biomarker in RE and it also suggests the sequential progression of disease. Here we report two cases of RE, one presenting with hemidystonia and other case with unusually prolonged prodromal stage duration of 7 years. In spite of severe hemi-atrophy of brain in second case response to immunomodulators was dramatic.
Keywords: Cerebellar diaschisis, hemi-dystonia, Rasmussen's encephalopathy, tacrolimusKey Message: Rasmussen's encephalopathy may be suspected in any patient with refractory focal epilepsy and hemi-dystonia. MRI brain is considered as biomarker. Prodromal stage may be variable ranging from month to years. It should be treated aggressively even after long duration of disease. Tacrolimus is an effective long-term immunosuppressive agent.
|How to cite this article:|
Vyas A, Ghunawat JR, Bagaria AK, Khandelwal D. Uncommon Presentation of Rasmussen's Encephalitis. Neurol India 2021;69:1010-3
Rasmussen's encephalopathy (RE), an uncommon neurological disease, is usually seen in children. It was first described by Rasmussen et al. in 1958. RE causes chronic inflammation resulting in unilateral brain atrophy. T-cell-mediated cytotoxicity against the neurons is implicated in the pathogenesis. The clinical presentation of RE is not that of acute encephalitis; however, the pathology shows viral etiology. A study from India revealed predominant CD3+ and CD68+ T cell inflammation and one case of additional CD20+ infiltrates. It is characterized by refractory focal epilepsy, progressive unilateral brain atrophy and limb weakness. Characteristic MRI brain findings are helpful in diagnosis of RE. It also excludes other causes and aids in monitoring the disease progress. Early immunotherapy has an important role in altering the natural history of the disease. Here we report two uncommon presentations of this rare disease.
| » Case -1|| |
An 8-year male child was admitted to the neurology department with the complaints of right-sided hemi-dystonia causing difficulty in writing and toe walking. These symptoms gradually progressed over the next 4 months as child had difficulty in eating food with right hand. He sustained trivial falls on uneven surface due to right foot dystonia. In last month he developed right facio-brachial dystonic attacks which were multiple episodes in a day. Later he developed right focal seizures involving face, right upper and lower limbs. Perinatal and developmental history was normal without any family history. Examination findings of higher mental function including cranial nerve examination were normal. He had dystonic movement of right upper limb with flexion at wrist, extension at metacarpophalangeal joints and plantar flexion at ankle. These movements were aggravated while walking. There was hypertonia in the right upper and lower limbs and power was 4/5 with positive Babinski on right side. Deep tendon reflexes, coordination and sensory examination were normal. Patient was on oxcarbamazepine and valproate in maximum doses with no improvement.
Routine blood counts, metabolic parameter, cerebrospinal fluid investigations were within normal limits. EEG showed theta slowing in left hemisphere. MRI brain showed atrophy in the left caudate, putamen, and dilatation of frontal horn of lateral ventricle, straightening and thinning of internal capsule and loss of normal boomerang in left frontal horn and incomplete sunset sign with high signals in the peri-insular area [Figure 1] and [Figure 2]. There was no evidence of lactate peak on magnetic resonance spectroscopy (MRS).
|Figure 1: Axial FLAIR images showing atrophy in the left caudate, putamen, and dilatation of frontal horn of lateral ventricle with high signals in the corona radiata|
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|Figure 2: T2-weighted images showing atrophy in the left caudate, putamen, and dilatation of frontal horn of lateral ventricle with high signals in the corona radiate|
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CSF study for viral markers were negative. CSF and serum antibodies to voltage-gated potassium channel complexes (VGKCs), Caspr2, NCMDA, AMPA1, AMPA2, GABARB1/B2 were tested negative. Computed tomography (CT) scan of the chest and abdomen was normal. Serum lactate were normal. Diagnosis of RE was established as per European consensus criteria part A.
Patient was managed with IV methylprednisolone (MPS) (1 gm/day) and IVIG (2 gm/kg) over five days. Seizures were controlled and dystonia also decreased. Patient was discharged on oxcarbamazepine, sodium valproate, and oral tacrolimus (0.1 mg/kg/d). On follow-up at 1 month, patient had significant improvement in dystonia and gait. On latest follow-up of this child in July 2020, he presented with clinical relapse of left hemidystonia with intermittent left focal seizures involving face after 6 months of clinical remission and was managed with IVIG and dose of tacrolimus was increased to 0.2 mg/kg/day divided two times a day (maximum 0.3 mg/kg/d). MRI brain showed disease progression with FLAIR and T2 hyperintensities in left caudate, putamen, and parietal lobe with volume loss and ventricular dilatation. He responded to the present treatment; however, parents were counseled about prognosis the treatment options including surgery.
| » Case -2|| |
A 21-year-old female developmentally normal till 11 years of age admitted with 10-year history of seizures. Seizure semiology was left complex partial seizures 4–5 episodes in March 2009. She was put on phenytoin 100 mg three times a day for one year and was seizure free for next 4 years. NCCT done in year 2009 was normal. In year 2016 she had left complex partial seizure; multiple episodes followed by progressive left hemiparesis and behavioral changes in form of easy irritability and cognitive decline. In year 2018 she had multiple refractory left focal seizures not controlled with four antiepileptics (valproate, levetiracetam, carbamazepine, phenytoin) in maximum dose. Examination findings revealed disorientation to time, place, person. There was hypertonia in left upper and lower limb with brisk deep tendon reflexes and extensor plantar response. Routine blood counts, metabolic parameter, cerebrospinal fluid investigations were within normal limits. EEG was normal.
MRI brain [Figure 3] and [Figure 4] was suggestive of atrophy in right hemisphere, widened cortical sulci, dilated sylvian fissure and ventricles on right with cortical hyperintensities on axial fluid attenuated inversion recovery (FLAIR) images. Axial T1 weighted image showed contralateral cerebellar diaschisis.
|Figure 3: Image showing atrophy of right hemisphere, widening of cortical sulci and sylvian fissure; dilated ventricles on right side and cortical hyperintensities|
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|Figure 4: Axial T1-weighted image shows contralateral cerebellar diaschisis|
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She was diagnosed as RE on basis of European consensus criteria part B. She was treated with combination of IV MPS and IVIG. At discharge, she was put on oral tacrolimus and was continued on two antiepileptics (sodium valproate and levetiracetam). On follow-up at 3 months after discharge, patient showed significant clinical improvement as she could walk with one-person support and no further seizures. At one year follow up, she could do all daily household activities and also started money handling with no further episode of seizure during follow up.
On recent follow-up of this patient in June 2020, she had no clinical worsening of left-sided weakness and also without any left focal seizures. She was doing all activities as well as money handling independently. Examination revealed the left-sided power of 4+/5 and mini-mental status examination of 28/30.
| » Discussion|| |
Rasmussen encephalitis is rare disease and incidence is 2·4 cases per 10 million people per year. RE can manifest from infancy to adulthood with average age of disease onset around 6 years. 58 years is the oldest reported age and adult-onset disease account for around 10% of the total cases.
Diagnosis of RE is based on characteristic clinico-radiological features. Brain biopsy, due to its invasive nature, is not required in majority of cases. Three clinical stages are proposed. Both of our patients presented in active clinical stage (stage 2). In the first case, the prodromal stage was of few weeks and second case had unusual long duration of 10 years.
Bien et al. also proposed a five-stage MRI model of RE. Maximum brunt of the disease with tissue loss occurs during the first 12 months after the onset of symptomatic disease. Our first patient presented in stage 2 and second patient in stage 4.
Rasmussen encephalitis presenting as hemidystonia is very rare., These patients present with dystonia, athetosis of unilateral limbs, correlating to atrophy of caudate and lentiform nucleus. [Table 1] shows a comparison of cases of movement disorders in RE. Our first case presented as left hemidystonia and then progressing to refractory focal seizures. MRI brain showed caudate and putaminal atrophy with straightening of internal capsule and specific signs such as near-total sunset sign, loss of boomerang sign, candle flame appearance, loss of genu sign; which are described previously. Second case showed hemispheric atrophy with cortical hyperintensity and contralateral cerebellar diaschisis. In contrast to previous literature our second patient had unusually prolonged prodromal stage of 7 years.
Focal seizures in RE are not necessarily associated with synchronized, rhythmic spike activity. Our first case had right-sided theta slowing and second case had normal EEG. CSF examination in most of the cases is normal. Our both cases had normal CSF examination. In both of our cases biopsy was not done as diagnosis was made on basis of European consensus criteria.
Hart et al. reported nineteen patients who were treated with IVIG or high dose steroids. Nine of these were treated with IVIG, including two being treated concomitantly with steroids. Plasma exchange is effective in some patients however, there is no lasting benefit. Our both cases responded well to IVIG and injection methylprednisolone. Tacrolimus is found to decrease the unihemispheric destructive process.
RE is an example of refractory epilepsy and almost all cases require surgery. Surgical treatment has resulted in complete disappearance of seizures and better outcome of patients with RE. Endoscopic hemispherotomy, a newer approach was used in three patients with RE in a study from India with class 1 Engels outcome.
Our both patients responded with immunotherapy and had significant clinical improvement in on follow-up, though first case had recent relapse, second case is well managed medically without further seizure or weakness, even after long duration of disease. We did not proceed for surgery in second case as it is well managed with immunotherapy; however, first case has hemidystonia with relapse and need further follow-up for treatment decision of surgery.
| » Conclusion|| |
RE is not a disease of childhood only and may affect adults also. Adult presentation could be due to prolonged prodrome in adolescence. EPC is not the only presentation; if the brunt of the disease is on basal ganglia predominantly then patient can present as hemi dystonia or hemichorea. MRI is considered as biomarker and brain biopsy is not necessary in most of the cases. We should recognize the likelihood of this disease in patients presenting with refractory partial seizures and hemi-dystonia. Patient should be treated aggressively with immunotherapy including IVIG, steroids and tacrolimus in early stage and even after long disease duration as in our second case.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2], [Figure 3], [Figure 4]