|Year : 2021 | Volume
| Issue : 1 | Page : 27-30
Acute leukoencephalopathy with restricted diffusion associated with Japanese encephalitis virus
Leema Pauline Cornelius, Asir Julin Paulraj, Neeraj Elango
Department of Pediatric Neurology, Institute of Child Health and Hospital for Children, Madras Medical College, Chennai, Tamil Nadu, India
|Date of Submission||17-Jun-2020|
|Date of Decision||25-Sep-2020|
|Date of Acceptance||13-Oct-2020|
|Date of Web Publication||08-Jan-2021|
Dr. Leema Pauline Cornelius
Department of Pediatric Neurology, Institute of Child Health and Hospital for Children, Egmore, Chennai, Tamil Nadu
Source of Support: None, Conflict of Interest: None
Acute leukoencephalopathy with restricted diffusion (ALERD) is a clinicoradiological syndrome characterized by acute encephalopathy, seizures, and diffuse areas of restricted diffusion in bilateral cerebral parenchyma on magnetic resonance imaging. ALERD can occur following infections and exposure to drugs and toxins. Early recognition by neuroimaging and the institution of immunotherapy may be useful in improving neurological outcomes. We report a case of diffuse infectious ALERD associated with Japanese B encephalitis viral infection.
Keywords: Acute encephalopathy, acute leukoencephalopathy with restricted diffusion, Japanese encephalitis virus
|How to cite this article:|
Cornelius LP, Paulraj AJ, Elango N. Acute leukoencephalopathy with restricted diffusion associated with Japanese encephalitis virus. J Pediatr Crit Care 2021;8:27-30
|How to cite this URL:|
Cornelius LP, Paulraj AJ, Elango N. Acute leukoencephalopathy with restricted diffusion associated with Japanese encephalitis virus. J Pediatr Crit Care [serial online] 2021 [cited 2021 Jan 26];8:27-30. Available from: http://www.jpcc.org.in/text.asp?2021/8/1/27/306489
| Introduction|| |
Acute leukoencephalopathy with restricted diffusion (ALERD) is one of the infection-associated encephalopathy syndromes seen in childhood. There are two distinct types of ALERD according to the distribution of brain lesions-Diffuse ALERD with diffuse areas of restricted diffusion on magnetic resonance imaging (MRI) and central sparing ALERD well known as Acute Encephalopathy with biphasic Seizures and late reduced Diffusion (AESD). Most cases were associated with viral infections such as influenza, human herpes virus-6, 7, adenovirus, mycoplasma, and bacteria such as Escherichia More Details coli. Although there are numerous reports of AESD in world literature,,, reports of diffuse ALERD are scarce. To the best of our knowledge, there had been no reports of ALERD associated with the Japanese encephalitis virus. We report a case of diffuse infectious ALERD associated with Japanese encephalitis viral infection.
| Case Report|| |
A previously healthy 1-year-old male child presented with 1 day fever followed by generalized status epilepticus. There was no history of cough, loose stools, vomiting, recent exanthem, vaccination, or prior seizures. Examination revealed an unconscious child with a Glascow Coma Scale of 9 throwing generalized seizures. The child was febrile, had tachycardia, and was not in shock. The child required two doses of lorazepam and Injection. Levetiracetam 60 mg/kg in the emergency room following which seizures stopped and shifted to intensive care. The child did not require ventilation. After 2 h had one more seizure and Injection. sodium valproate was loaded in the dose of 20 mg/kg. The child continued to be drowsy for the next two days. There was no petechiae, purpura, eschar, or organomegaly. There were no lateralizing signs. Other system examination was normal. A provisional diagnosis of the acute encephalitic syndrome was made and evaluated.
Blood investigations showed polymorphonuclear leukocytosis and elevated C-reactive protein. Blood sugar, urea, creatinine, lytes, liver enzymes, and chest X-ray were normal. The blood culture was sterile. Computed tomography (CT) of the brain was normal. The child continued to be drowsy. There were no further seizures. The electroencephalogram showed background slowing. The child was treated with a meningitic dose of antibiotics, intravenous acyclovir, antiedema measures, and anticonvulsants-intravenous levetiracetam 30 mg/kg/day and sodium valproate 20 mg/kg/day in divided doses. The child regained sensorium on the 3rd day, however, had left hemiparesis.
In view of fever, status epilepticus and altered sensorium with subsequent hemiparesis, the probable differentials considered were focal encephalitis probably herpes encephalitis, meningitis with complications such as subdural collection or infarct, acute disseminated encephalomyelitis, and further investigations carried out.
MRI of the brain showed restricted diffusion in subcortical white matter in both cerebral hemispheres predominantly on the right side including the corpus callosum [Figure 1]d, [Figure 1]e, [Figure 1]f. T2 and fluid-attenuated inversion recovery (FLAIR) sequences showed subtle hyperintensities in the right parietooccipital region and right thalamus [Figure 1]a, [Figure 1]b, [Figure 1]c. Contrast MRI was not done. Cerebrospinal fluid (CSF) was normal with no cells, normal biochemistry, and sterile culture. Japanese encephalitis virus-specific IgM enzyme-linked immunosorbent assay (ELISA) was positive in CSF and serum. CSF polymerase chain reaction for herpes simplex, enteroviruses were negative. A diagnosis of diffuse infectious ALERD was made and intravenous methylprednisolone 30 mg/kg/day was given for 5 days. There were no further seizures. At discharge after 2 weeks, the child had regained head control, was able to sit independently, stand with support, however, had mild hemiparesis. MRI of the brain repeated 2 months later showed complete resolution of restricted diffusion and mild cerebral atrophy [Figure 1]g, [Figure 1]h, [Figure 1]i.
|Figure 1: (a and b) Axial T2W and fluid-attenuated inversion recovery magnetic resonance images showing subtle hyperintensities in the right parietooccipital region and thalamus. (c) Postcontrast T1W images showing no abnormal leptomeningeal or parenchymal enhancement. (d-f) Diffusion-weighted imaging images showing restricted diffusion in white matter in both cerebral hemispheres predominantly on the right side including the corpus callosum. There is no sparing of the perisylvian region. (g-i) Follow-up DWI images a month later showing complete resolution|
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| Discussion|| |
ALERD is a clinicoradiological syndrome characterized by acute encephalopathy with restricted areas of diffusion in subcortical white matter on MRI. Infectious ALERD occurs following infections and toxic ALERD with exposure to toxins, drugs of abuse, and cranial irradiation. According to the distribution of brain lesions, there are two distinct groups-diffuse ALERD with diffuse areas of restricted diffusion on MRI and central sparing type which spares the central regions of the brain. Our child presented with diffuse ALERD due to Japanese encephalitis viral infection.
Patients with diffuse ALERD display a severe phenotype with rapid deterioration of consciousness, a systemic inflammatory response in which multiorgan dysfunction, shock, and disseminated intravascular coagulation occur. Inflammatory cytokines such as interleukin-6 and tumor necrosis factor in serum and CSF are elevated. Laboratory abnormalities including elevated liver enzymes, creatine kinase, hyperglycemia, and metabolic acidosis are prominent. CSF examination is usually normal (no pleocytosis or increase in proteins) which helps in ruling out infectious causes of acute febrile encephalopathy. Our patient presented with an acute onset of fever, status epilepticus, and prolonged altered sensorium. However, there were no further seizures and no evidence of multiorgan dysfunction. CSF examination was normal except JE specific IgM ELISA positivity in CSF.
CT of the brain is mostly normal. The changes in conventional sequences of MRI such as T1W, T2W, and FLAIR are usually subtle. Diffusion-weighted imaging (DWI) shows the characteristic “bright tree appearance,” which represents high-signal intensity in the widespread subcortical white matter, which has the appearance of tree branches with low apparent diffusion coefficient on ADC mapping. Hyperintensities can be seen in the caudate nucleus, but the rest of the basal ganglia, thalami, and corpus callosum are usually spared. The resolution of diffusion restriction is seen in 2–4 weeks. Mild-to-severe cerebral atrophy can occur. Initial CT brain was normal and MRI on the 3rd day of the illness picked up the characteristic bright tree appearance in our child.
It has been speculated that hypercytokinemia associated with diffuse ALERD may contribute to its pathogenesis. In addition to direct viral invasion, the Japanese encephalitis virus activates microglia that secrete cytokines such as interleukin-1 and tumor necrosis factor alpha which can cause toxic effects on the brain. Cases of ALERD were associated with viral infections such as influenza, human herpes virus-6, 7, adenovirus, mycoplasma, and bacteria such as E. coli.
To the best of our knowledge, this is the first case of ALERD associated with the Japanese encephalitis virus.
Central sparing ALERD (AESD) is characterized by a biphasic course-an initial prolonged febrile seizure followed by a cluster of partial seizures several days later. MRI of the brain may be normal during the first 2–3 days, but reveal high signal intensity on DWI in the subcortical white matter sparing the primary sensory motor area during recurrence of seizures. Another differential to be considered is acute necrotizing encephalitis in which imaging typically shows bilateral symmetrical thalamic involvement which may later develop necrosis and hemorrhages. In autoimmune encephalitis, MRI is either normal or shows the involvement of the limbic structures. Toxic ALERD due to cranial irradiation, drugs, and environmental toxins can be ruled out by careful history.
In addition to supportive care, pulse steroids and immunoglobulin G are used after ruling out neuro infections. N-methyl-D-aspartate receptor antagonist dextromethorphan and apoptosis inhibitor cyclosporine A have been tried in cases of AESD. Diffuse ALERD is associated with a mortality rate of 5%–10% and >two-thirds develop sequelae such as hyperactivity, language delay, cognitive impairment, dyskinesias, and hemiparesis. Our child had residual hemiparesis post 3 months follow-up.
| Conclusion|| |
ALERD is a novel cause of acute encephalopathy in children. Diagnosis can be easily missed unless diffusion-weighted images are acquired. Japanese encephalitis may rarely present ALERD early recognition by neuroimaging and the institution of immunotherapy is useful in improving neurological outcomes.
Declaration of patient consent
The authors certify that they have obtained all appropriate patient consent forms. In the form the patient (s) has/have given his/her/their consent for his/her/their images and other clinical information to be reported in the journal. The patients understand that their names and initial s will not be published and due efforts will be made to conceal their identity, but anonymity cannot be guaranteed.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
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