LETTERS TO THE EDITOR
|Year : 2022 | Volume
| Issue : 4 | Page : 763-767
A rare cause of acute febrile encephalopathy in a four year old boy–A case report with review of literature
Kiruthiga Sugumar1, Vaishnavi Srinivasan1, Aakash Chandran Chidambaram1, Dhandapany Gunasekaran1, Venkatesh Chandrasekaran1, Narayanan Parameswaran1, Bheemanathi H Srinivas2
1 Department of Pediatrics, Jawaharlal Institute of Postgraduate Medical Education and Research JIPMER, Puducherry, India
2 Department of Pathology, Jawaharlal Institute of Postgraduate Medical Education and Research JIPMER, Puducherry, India
|Date of Submission||09-Jan-2022|
|Date of Decision||22-Feb-2022|
|Date of Acceptance||20-Mar-2022|
|Date of Web Publication||12-May-2022|
Professor, Department of Pediatrics, Jawaharlal Institute of Postgraduate Medical Education and Research (JIPMER) Puducherry - 605 006
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Sugumar K, Srinivasan V, Chidambaram AC, Gunasekaran D, Chandrasekaran V, Parameswaran N, Srinivas BH. A rare cause of acute febrile encephalopathy in a four year old boy–A case report with review of literature. Ann Indian Acad Neurol 2022;25:763-7
|How to cite this URL:|
Sugumar K, Srinivasan V, Chidambaram AC, Gunasekaran D, Chandrasekaran V, Parameswaran N, Srinivas BH. A rare cause of acute febrile encephalopathy in a four year old boy–A case report with review of literature. Ann Indian Acad Neurol [serial online] 2022 [cited 2022 Oct 6];25:763-7. Available from: https://www.annalsofian.org/text.asp?2022/25/4/763/345146
A 4-year-old developmentally normal boy was brought with complaints of fever and vomiting of one day, with an onset of slurring of speech and facial asymmetry two hours before admission. There was no headache, altered sensorium, seizures, or weakness of limbs. There was no antecedent upper respiratory symptom or history of recent vaccination. There were no similar episodes in the past or significant family history. He had one episode of left focal seizure at admission and progressive deterioration of sensorium after that. Examination revealed normal vital signs with left upper motor neuron type of facial palsy, left hemiparesis, and signs of meningeal irritation. Fundus examination did not reveal any papilledema. A provisional diagnosis of acute meningoencephalitis was made and was started on empirical antibiotics, antiviral, antiedema, and antiepileptic medications. The complete blood count and blood biochemistry, including transaminases, were within normal limits. The cerebrospinal fluid (CSF) was acellular with mildly elevated protein (79 mg/dL) glucose (63 mg/dL, blood glucose- 96 mg/dL). A contrast-enhanced computed tomography (CECT) of the brain showed a right frontal hypodense lesion with no ring enhancement, suggestive of focal central nervous system (CNS) infection and possibly early cerebritis of brain abscess.
During the hospital stay, his sensorium worsened further, warranting mechanical ventilation. Magnetic Resonance Imaging (MRI) of the brain revealed a hyper-intense lesion in the right frontal and left parietal region, with foci of punctate hemorrhages [Figure 1], which was suggestive of acute hemorrhagic leukoencephalitis (AHLE). Since the possibility of infection was deemed less likely, he was pulsed with methylprednisolone for five days, followed by intravenous immunoglobulin (IVIG) (2 g/kg), as there was no improvement. After that, his condition remained static in terms of general well-being. The brain biopsy depicted acute hemorrhage and inflammatory infiltrates, confirming AHLE [Figure 2]. A detailed etiological workup for AHLE, including viral, bacterial, tubercular, and fungal organisms, was tested negative in appropriate CSF, blood, and nasopharyngeal specimens [Table 1]. Both CSF and serum tested negative for myelin oligodendrocyte glycoprotein (MOG) antibodies. Antinuclear antibodies were also tested negative. Hence, he was diagnosed with idiopathic AHLE.
|Figure 1: (a) Plain MRI T2 axial and (b) T2 FLAIR image showing hyperintensity in the right frontoparietal area with surrounding edema causing mass effect and midline shift with sub-falcine herniation; (c) and (d) Diffusion-weighted image showing high signal intensities in the right frontoparietal area with low ADC values suggestive of diffusion restriction; (e) susceptibility-weighted image (SWI) shows the area of blooming foci (blue arrow) suggestive of microhemorrhages; (f) Post-contrast T1 axial image showing moderate and heterogenous enhancement in the hyperintense area seen in T2 and FLAIR images|
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|Figure 2: (a) Sections from the brain biopsy show multifocal dense perivascular inflammatory infiltrate in white matter (H&EX40): (b) high power reveals predominantly lymphocytes around blood vessels (H&EX200): (c) areas of hemorrhage (arrowhead) in between inflammatory foci (H&EX100): (d) Luxol fast blue stain show perivascular loss of myelin (line arrow) indicates demyelination (LFBX100)|
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Later in the course, he had severe neurological sequelae in the form of aphasia, dyskinetic movements, spastic quadriparesis, contractures, and autonomic instability. The child was managed with a multi-disciplinary approach with physiotherapy, nutritional rehabilitation, and occupational therapy. He was discharged on tube feeds after 75 days of hospital stay. On follow-up, his neurological status did not show any worsening, and there was a subtle improvement in non-verbal communication and spasticity. However, the lost milestones showed no trend towards improvement. The follow-up neuroimaging done six months after the second imaging depicted ill-defined FLAIR (fluid-attenuated inversion recovery) hyperintensity areas in bilateral cerebral hemispheres with associated volume loss in the right cerebral hemisphere—features suggestive of gliotic sequelae to the previous insult. In addition, multiple blooming foci were noted in susceptibility-weighted imaging (SWI) in the right frontoparietal region, suggestive of hemosiderin deposits due to the previous hemorrhage.
In children, acute febrile encephalopathy (AFE) encompasses both infectious and noninfectious causes of fever with altered sensorium with or without seizures. CNS infections, notably viral encephalitis, are the most common cause of acute febrile encephalopathy among children in India. An etiology for AFE is not known in 40% of cases. AHLE is a fulminant presentation of AFE, characterized by demyelination, focal neurological deficits, rapid progression, irreversible sequelae, or death.
AHLE represents the severe form of acute disseminated encephalomyelitis (ADEM). AHLE, also called hyperacute ADEM, is more common in adults, whereas ADEM is more common in children. The first pediatric AHLE was reported in 1945 by Shallard and Latham. The characteristic features are acute onset, rapid neurological deterioration, multifocal brain lesions with necrosis, and hemorrhage. The pathogenesis of AHLE is believed to be autoimmune in nature following infectious triggers. However, half of the cases do not have a predisposing infection or vaccination, as with our index case. Infectious agents include HSV, EBV, Influenza A, JE, measles, mumps viruses, as well as mycoplasma and Plasmodium species. Rosman et al. reviewed nine cases of pediatric AHLE in 1997, where all of them had preceding infections before the onset of neurological symptoms.
The clinical presentation includes seizure, hemiparesis, cranial nerve palsies, aphasia, headache, and vomiting, of which the predominant symptoms were aphasia and hemiparesis in the reported pediatric patients. Diagnosis is usually made by clinical, radiological, and histopathological means. The common mimics of AHLE include acute meningoencephalitis/pyogenic meningitis, brain abscess, intracerebral hemorrhage, CNS vasculitis, and MOG encephalitis. Kabakus et al. reported a 3-year-old boy with acute hemorrhagic leukoencephalitis, manifesting as intracerebral hemorrhage, associated with herpes simplex virus type 1. In our case, the initial differentials were neuro-infection, MOG encephalitis, and CNS vasculitis, but CSF findings, negative autoimmune serology, and MRI evidence were pointers against the same, respectively.
Radiological diagnosis of AHLE by MRI brain is the gold standard and is characterized by large tumefactive lesions involving the white matter and sparing the cortex, associated punctate hemorrhages and extensive mass effect and surrounding edema, possibly involving of ganglia and thalami. Detection of cerebral microhemorrhages by gradient recalled echo (GRE) or the more sensitive susceptibility-weighted images (SWI) is an important finding. Similar findings were observed in our case. The presence of punctate hemorrhages and sparing of subcortical U-fibres helps in differentiating it from ADEM. The histopathology is depicted by edema, congestion, punctate hemorrhages macroscopically, and hemorrhages around the necrotic venules resembling ring and ball, white matter ischemic changes adjacent necrotic postcapillary venules and hemorrhage more prominent than demyelination, as observed in our case.
Treatment includes early diagnosis, aggressive supportive measures, such as managing cerebral edema, and immunomodulatory therapy like corticosteroids, IVIg, and plasmapheresis. The cases that were not treated with immunosuppression succumbed within days of onset neurological symptoms, whereas the first survivor of pediatric AHLE was following pulsed steroids. Panchal et al. reported an 8-year-old boy with AHLE who responded dramatically to IVIg following plasmapheresis. Our case was pulsed with a course of steroids and IVIg, and repeat neuroimaging revealed a mild improvement in the lesion. A brief review of the pediatric AHLE cases, with their neuroimaging and outcome, is summarized in [Table 2].
AHLE is rare in children, and hence any case of acute febrile encephalopathy, worsening within a matter of days, should prompt the treating pediatrician to evaluate for AHLE by MRI brain, which can pick up subtle findings, for the early start of treatment. Biopsy of the lesion is essential for confirmation of diagnosis due to the possibility of masqueraders with a similar picture.
KS, VS, and ACC managed the patient, reviewed the literature, and drafted the manuscript. VC, NP, and DG managed the patient, reviewed the manuscript, and critically revised the manuscript. BHS interpreted the histopathological image of the biopsy. All authors contributed to reviewing the literature, drafting the manuscript, and approving the final version of the manuscript. DG shall act as the guarantor of the paper.
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Conflicts of interest
There are no conflicts of interest.
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[Figure 1], [Figure 2]
[Table 1], [Table 2]