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Year : 2020  |  Volume : 1  |  Issue : 1  |  Page : 15-17

Autoimmune encephalitis, the great masquerader: A case report and review of successful outcome in a child

Institute of Child Health, Sir Ganga Ram Hospital, New Delhi, India

Date of Submission23-Nov-2020
Date of Decision07-Dec-2020
Date of Acceptance09-Dec-2020
Date of Web Publication31-Dec-2020

Correspondence Address:
Dr. Fadila
Shakranwan House, Bakergunj, Patna - 800 004, Bihar
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jopcs.jopcs_5_20

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Autoimmune encephalitis (AE) is an important and treatable cause of acute encephalitis. It may mimic other conditions of the central nervous system, including primary psychiatric disorders, particularly early in the disease course. Due to similarities in clinical, imaging, and laboratory findings between autoimmune and infectious encephalitis, as well as limited awareness and availability of specific antibody testing, AE remains an elusive, often underrecognized etiology. If left untreated, it may be fatal or leave significant morbidities, but with prompt recognition and sequential immunotherapy, the prognosis is encouraging despite a stormy disease course. We report a 4-year-old child with abnormal behavior and recurrent seizures who was referred as encephalitis and subsequently diagnosed as AE and managed at our hospital. He recovered well because of early identification and adequate management.

Keywords: Autoimmune, anti-N-methyl-D-aspartate receptor, encephalitis, encephalopathy

How to cite this article:
Fadila, Kumar P. Autoimmune encephalitis, the great masquerader: A case report and review of successful outcome in a child. J Prim Care Spec 2020;1:15-7

How to cite this URL:
Fadila, Kumar P. Autoimmune encephalitis, the great masquerader: A case report and review of successful outcome in a child. J Prim Care Spec [serial online] 2020 [cited 2021 Mar 4];1:15-7. Available from: http://www.jpcs.com/text.asp?2020/1/1/15/305886

  Case report Top

A 4-year-old child was brought with recurrent episodes of seizures. He had a history of an upper respiratory tract infection (URTI) 3 weeks back which was managed symptomatically by a local pediatrician. One week later, he had an episode of seizure. Oral levetiracetam at 20 mg/kg/day was started by the local doctor. Magnetic resonance imaging (MRI) of the brain was done which was reported normal. Now, for recurrent seizure episodes, since 1 day, he was referred to us as acute encephalitis. The seizure was described as behavioral arrest with vacant stare and copious drooling for 2–3 min, followed by unresponsiveness for 10–15 min. On admission, he was alert, restless, with eyes open but poor eye contact and decreased verbalization. The rest of the systemic examination was normal. Birth history was unremarkable; development was adequate for age. On inquiry, the mother recalled subtle changes in behavior including poor sleep and temper tantrums for the past 1 week which she thought was due to the antiepileptic drug. He was admitted to the pediatric intensive care unit at our hospital, loaded with intravenous (IV) sodium valproate at 30 mg/kg. Levetiracetam was titrated to 40 mg/kg/day. IV antibiotics, IV acyclovir was started based on presumed infectious etiology. Basic laboratories including blood counts, liver and renal functions, and sepsis screen were normal. MRI of the brain with contrast was normal. Cerebrospinal fluid (CSF) analysis showed 10 cells (100% lymphocytes), 60 mg/dl glucose, and 29 mg/dl protein. CSF analysis was negative for pan neurotropic virus, bacterial antigens. Autoimmune antibody panel was sent. Electroencephalogram (EEG) had right temporal epileptiform discharges. Fluorodeoxyglucose positron emission tomography/computed tomography (FDG-PET/CT) of the brain showed hypometabolism in the right parietal, bilateral occipital areas [Figure 1].
Figure 1: Hypometabolism right parietal, bilateral occipital areas

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The child had rapid deterioration with repetitive oro-lingual-brachial movements and repeated seizures requiring mechanical ventilation and inotropic support. In view of clinical history, two normal MRIs, mild pleocytosis in CSF, negative sepsis markers, PET/CT changes, autoimmune encephalitis (AE) was suspected, and pending autoimmune antibody results, IV methylprednisolone pulses (30 mg/kg/day for 5 days) was given. However, the clinical condition of the child continued to worsen with irritability, altered sensorium, and persistence of abnormal limb movements. Intravenous immunoglobulin (IVIg) (2 g/kg over 5 days) was given next. Mild improvement in irritability and consciousness was noted after this. CSF report for anti-N-methyl-D-aspartate receptor (anti-NMDAR) antibody came back positive. His sensorium was still altered with no purposeful limb movements. Six cycles of plasmapheresis was given, and oral steroids were continued. Over the next 2 weeks, there was significant clinical improvement in terms of reduced irritability, abnormal limb movements, restlessness, and no seizures. His sensorium improved; he was making eye contact and reaching for objects. He was discharged on oral steroids, with the diagnosis of anti-NMDAR encephalitis. There was no relapse during 1-year follow-up.

  Discussion Top

AE must be considered in any child with acute or subacute encephalitis.[1] There is a history of fever followed later by behavioral symptoms, recurrent seizures, and movement disorders. Females are affected more than males.[2] The mean age of onset is 8 years (range 2–11 years). Seizures are present in more than 80% of cases, ranging from focal to generalized, including status epilepticus and can occur in any stage of the illness. Oral dyskinesias and choreoathetosis are important diagnostic pointers.[3] Seizures and movement disorders in children could have a wide differential, ranging from infectious etiology to metabolic derangements, or a hereditary syndrome, all of which has starkly different management protocols, which makes it important that we diagnose correctly and manage appropriately. Our case too had orofacial dyskinesia and this was picked up due to strong clinical suspicion.

AE can occur following viral infections and vaccinations. There was a prodrome of URTI, likely viral, in our case also. Relapses of herpes simplex virus encephalitis can also be due to secondary autoimmune process.[4] An underlying malignancy is common in adult patients, but rare in the pediatric population.

The anti-NMDAR antibody is the most commonly recognized autoantibody. NMDARs modulate human memory, cognition, learning, as well as neural plasticity. Other receptors commonly implicated in pediatric AE are myelin oligodendrocyte glycoprotein, and glutamic acid decarboxylase 65 (GAD65), leucine-rich glioma-inactivated protein 1 (LG 1).

Autoantibody testing is crucial for diagnosis, but over 60% of cases are seronegative,[5] hence treatment must not rely on autoantibody positivity solely. In our case, this test came back positive, but in view of suspicion of AE on clinical grounds, we had started managing the patient on the lines of AE before the report was made available to us. Early recognition and treatment has been linked to better neurocognitive outcome in children with AE.

Important points suggestive of AE include features of CNS inflammation (CSF pleocytosis and/oligoclonal bands,) MRI abnormalities (T2/fluid-attenuated inversion recovery signal hyperintensities involving the temporal lobe, cortex, and striatum), and a response to immunotherapy. However, over 50% of cases may have normal MRI at diagnosis[2],[6] as it was in our case. FDG-PET/CT of the brain is useful and may show abnormal brain metabolism early in the disease,[7] as in our case. EEG may show a delta brush pattern and extreme spindles, particularly in anti-NMDAR encephalitis.[6] Exclusion of other causes, especially viral encephalitis is paramount. Some useful differentiating feature is acute onset with fever in viral etiologies, presence of skin lesions/exanthema, high prevalence of paresis, low incidence of cognitive deficits, abnormal MRI with contrast enhancement at presentation, CSF with positive viral markers, EEG showing periodic lateralized epileptiform discharges, and lack of response to immunotherapy in viral encephalitis.

Treatment includes first-line therapy (pulse steroids, followed by oral steroids, IVIg, plasma exchange, or both), followed by second-line therapy (rituximab and cyclophosphamide). Stepwise escalation is done when there is poor response. Our child received IV methylprednisolone, followed by IVIg and then plasmapheresis due to the inadequate response. Third-line agents such as bortezomib and tocilizumab are reserved for refractory cases.[8],[9]

Relapses when present are milder than the first attack and are treated with repeat dosing of first-line agents. Long-term immunosuppression with azathioprine, mycophenolate mofetil may be considered. Fortunately, our case did not experience any relapse.

  Conclusion Top

AE is a treatable illness with excellent prognosis. Despite recent reports indicating that it is a common cause of encephalitis in children, the awareness is severely limited, with most patients being misdiagnosed as infectious encephalitis probably due to similarity in their presentations. This results in unnecessary and often prolonged course of antibiotics to sick children with little improvement. Behavioral changes and stereotyped body movements also pose a diagnostic dilemma. In addition, more than half of cases of AE are seronegative, making a clinician's acumen the most important factor in the management of children with AE. Our patient fared well despite a very difficult and long intensive care stay because immunomodulatory therapy was started based on clinical suspicion and after ruling out the common infectious etiology. Later on, the positive antibody report corroborated our findings. Clinicians should be made aware of this etiology so that cases can be picked up more promptly. When managed timely, most patients respond to first-line immunotherapy with little or no relapses. Early treatment and lack of intensive care admission are predictors of good outcome.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient's parents have given their consent for images and other clinical information to be reported in the journal. The patient's parents understand that name and initials will not be published and due efforts will be made to conceal the identity, but anonymity cannot be guaranteed.

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Conflicts of interest

There are no conflicts of interest.

  References Top

Sartori S, Nosadini M, Cesaroni E, Falsaperla R, Capovilla G, Beccaria F, et al. Paediatric anti-N-methyl-D-aspartate receptor encephalitis: The first Italian multicenter case series. Eur J Paediatr Neurol 2015;19:453-63.  Back to cited text no. 1
Florance NR, Davis RL, Lam C, Szperka C, Zhou L, Ahmad S, et al. Anti-N-methyl-D-aspartate receptor (NMDAR) encephalitis in children and adolescents. Ann Neurol 2009;66:11-8.  Back to cited text no. 2
Sridhar M, Kesavelu D. Clinical profile and neuropsychiatric outcome in children with anti-NMDAR encephalitis. Indian Pediatr 2019;56:247-50  Back to cited text no. 3
Prüss H. Postviral autoimmune encephalitis: manifestations in children and adults. Curr Opin Neurol 2017;30:327-33.  Back to cited text no. 4
Hacohen Y, Wright S, Waters P, Agrawal S, Carr L, Cross H, et al. Paediatric autoimmune encephalopathies: Clinical features, laboratory investigations and outcomes in patients with or without antibodies to known central nervous system autoantigens. J Neurol Neurosurg Psychiatry 2013;84:748-55.  Back to cited text no. 5
Armangue T, Titulaer MJ, Málaga I, Bataller L, Gabilondo I, Graus F, et al. Pediatric anti-N-methyl-D-aspartate receptor encephalitis-clinical analysis and novel findings in a series of 20 patients. J Pediatr 2013;162:850-600.  Back to cited text no. 6
Probasco JC, Solnes L, Nalluri A, Cohen J, Jones KM, Zan E, et al. Abnormal brain metabolism on FDG-PET/CT is a common early finding in autoimmune encephalitis. Neurol Neuroimmunol Neuroinflamm 2017;4:e352.  Back to cited text no. 7
Behrendt V, Krogias C, Reinacher-Schick A, Gold R, Kleiter I. Bortezomib treatment for patients with anti N-methyl-D-aspartate receptor encephalitis. JAMA Neurol 2016;73:1251-3.  Back to cited text no. 8
Lee WJ, Lee ST, Moon J, Sunwoo JS, Byun JI, Lim JA, et al. Tocilizumab in autoimmune encephalitis refractory to rituximab: An institutional cohort study. Neurotherapeutics 2016;13:824-32.  Back to cited text no. 9


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