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|NI FEATURE: FACING ADVERSITY…TOMORROW IS ANOTHER DAY! - LETTER TO EDITOR
|Year : 2017 | Volume
| Issue : 4 | Page : 867-868
Acute necrotizing encephalitis associated with cardiovascular manifestations
Jithangi Wanigasinghe1, Tharanga Jayathunge2, Pyara D Ratnayake2
1 Department of Paediatrics, University of Colombo, Colombo, Sri Lanka
2 Neurology Unit, Lady Ridgeway Hospital, Colombo, Sri Lanka
|Date of Web Publication||5-Jul-2017|
Faculty of Medicine, University of Colombo, Colombo
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Wanigasinghe J, Jayathunge T, Ratnayake PD. Acute necrotizing encephalitis associated with cardiovascular manifestations. Neurol India 2017;65:867-8
Acute necrotizing encephalitis (ANE) is a rare condition in children, characterized by initial viral-like symptoms, characteristic imaging findings, followed by rapid deterioration with coma and even death. Mortality is reported in up to 40% patients, whereas recovery without neurological deficit is limited to approximately 30% of the cases.
The involvement of different tissues in patients from the same family concomitantly in ANE is reported; however, changes in endocardium or myocardium have not been described previously. We would like to report the case of two Sri Lankan children from the same family who developed ANE concomitantly and exhibited changes in cardiac muscle as endocardial fibrosis and left ventricular hypertrophy.
A 5-year old previously well child suffered from mild fever, vomiting, and coryza, followed by rapid deterioration with irritability, listlessness progressing to failure to wake up, and refractory status epilepticus. She had persistently low Glasgow Coma Scale scores. There was no clinical abnormality in the cardiovascular system. Peripheral blood parameters were normal with mild excess of lymphocytes; C-reactive protein (CRP) was normal, and there was moderate elevation of liver transaminases. Other liver functions and renal functions were normal. Serum was negative for Herpes simplex virus (HSV), Japanese encephalitis, or Dengue viral antibodies; cerebrospinal fluid (CSF) analysis was not performed due to the comatose state of the patient. Computed tomography (CT) scan of the brain revealed hypodensities involving white matter of the external capsules and pons in a fairly symmetrical distribution [Figure 1] without contrast enhancement. There was no cerebral edema, midline shift, or venous sinus thrombosis. Despite aggressive treatment, she died on the 4th day of the admission.
|Figure 1: Computed tomographic scan of the elder sibling performed on day 4 of the illness showing the hypointensity of both external capsules and pons (white arrow)|
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Postmortem macroscopy revealed patchy hemorrhages over the brain cortex, white matter, and brainstem. Histology showed cerebral hemorrhages with areas of scattered lymphocytes and meninges with lymphoid aggregates, which was compatible with the diagnosis of hemorrhagic meningoencephalitis.
Heart macroscopy showed areas of fibrosis in the endocardium and myocardium. Histology revealed subendocardial collagenous fibrosis extending into the deep myocardium. The pericardium and coronary arteries were normal. Special staining facilities were not available.
Her 20-month old healthy brother, with similar mild fever and coryzal symptoms was hospitalized earlier; he had no abnormality in any of the systems; in particular, there was no clinical evidence of cardiomegaly or abnormal heart rate. Within 24 hours, his illness also progressed, and he rapidly developed short duration seizures and deterioration of Glasgow coma scale. He was managed for ANE with intravenous high dose methyl-prednisolone, intravenous immunoglobulins, and rituximab while covering for infections. His peripheral blood counts, renal, and liver functions were normal. Investigations for an infective etiology (viral and bacterial) were negative. CSF analysis showed no cellular response; however, the CSF protein was120 mg/dl. His CT scan images showed a clinical picture identical to that of his sister, revealing a hypointensity in the external capsule and brainstem [Figure 2]. Magnetic resonance imaging (MRI) images obtained six weeks later did not show any significant abnormality.
|Figure 2: Computed tomographic scan of the second sibling showing similar hypointense changes in bilateral external capsules and bilateral thalami (white arrow)|
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His level of consciousness and acute development regression gradually improved over the next 12–14 days. Due to the sister's postmortem finding of endocardial fibrosis, an echocardiogram was done on day 15, which showed mild concentric left ventricular hypertrophy persisting with mild improvement in subsequent studies. No peripheral cause for this was evident.
He improved with intense rehabilitation to near premorbid state but again presented 4 months later with a similar symptomatology of status epilepticus and encephalopathy following initial mild febrile symptoms. Serological and CSF studies showed no etiology. MRI confirmed the clinical diagnosis of recurrence of ANE; typical changes were seen in the bilateral thalami, external capsules, and the brainstem [Figure 3]. Unlike the first episode, his recovery was poor with fluctuations in blood pressure requiring ionotropic support despite aggressive therapy. He suffered from severe neurological dysfunction with little response to rehabilitation. Echocardiography during the acute state showed ventricular hypertrophy; however, a repeat evaluation 6 months later showed reversal to normal wall thickness.
|Figure 3: T2 images of second sibling during recurrence showing patchy changes in bilateral thalami, external capsules, and brainstem (white arrows)|
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ANE is a rare disease with very high case fatality and neurologic disability. Early treatment with steroids is reported to result in better prognosis. The exact pathological basis is still not well understood. Environmental factors (preceding infection) and several host factors (immunological responsiveness) have been implicated in the pathogenesis. The implicated list of viruses is long. Massive surge of cytokine levels, referred to as a cytokine storm, particularly of interleukin -6 (IL-6), tumor necrosis factor alpha (TNF-α) in the serum, and CSF  are the implicated host factors. They are responsible for different systemic manifestations such as acute liver derangement, shock, disseminated intravascular coagulation, and alteration of vessel wall permeability in the brain causing hemorrhage and edema. Endocardial fibrosis or ventricular wall hypertrophy has not been documented previously. Improvement in echogenic characteristics of the heart in the surviving child is a pointer towards a reversible destructive change related to the surge of cytokines. A genetic basis to this recurrent and familial form of ANE was reported by Neilson et al., in their family of 16 affected individuals. A mutation affecting RANBP2 has been recognized in approximately 75% cases of ANE. RANBP2 mutation is linked to the pathogenesis because of its potential role in cellular trafficking in mitochondria as well as in other immunological processes such as viral entry, antigenic presentation, cytokine signaling, immune responses, as well as blood–brain barrier maintenance. Our two siblings also may have carried this mutation in which recurrence of the disease is reported.
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[Figure 1], [Figure 2], [Figure 3]