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| CASE REPORT |
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| Year : 2019 | Volume
: 56
| Issue : 3 | Page : 272-275 |
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Reversible splenial lesion in primary dengue fever
Ebenezer Daniel1, Ajay Kumar Mishra1, Pavithra Mannam2, I Ramya1
1 Department of Medicine, Christian Medical College, Vellore, India
2 Department of Radiology, Christian Medical College, Vellore, India
| Date of Submission | 15-Apr-2018 |
| Date of Acceptance | 15-May-2019 |
| Date of Web Publication | 09-Jul-2020 |
Correspondence Address:
Dr Ebenezer Daniel
Department of Medicine, Unit 5, Christian Medical College, Vellore–632 004, Tamil Nadu
India
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/0972-9062.289400
Keywords: Corpus callosum; dengue; encephalitis; splenial lesion
How to cite this article:
Daniel E, Mishra AK, Mannam P, Ramya I. Reversible splenial lesion in primary dengue fever. J Vector Borne Dis 2019;56:272-5 |
Dengue fever can present with acute neurological complications. These have been included in the clinical classification of severe dengue by the WHO[1]. Dengue encephalitis can commonly present with altered sensorium, headache, dizziness, seizures, and behavioural problems. Lesions in the corpus callosum have been previously reported in dengue. We describe two patients with primary dengue fever who presented with transient lesions in the splenium of the corpus callosum.
Case 1
A 25-yr-old gentleman, software engineer by profession, presented to the Christian Medical College, Vellore, Tamil Nadu, India with high-grade fever for five days, holocranial headache, projectile vomiting and irrelevant speech for two days. He was a non-vegetarian and an occasional ethanol consumer. He was noted to have bradycardia. There was an erythematous blanching maculopapular rash in the lower limbs. On abdominal examination, there was hepatosplenomegaly. There were no signs of meningeal irritation, papilledema or focal neurological deficits.
Laboratory parameters showed haemoconcentration, leucopenia, thrombocytopenia and mild transaminitis [Table 1]. There was mild hyponatremia. There were no other electrolyte abnormalities, hypoglycemia or hyperglycemia. He was noted to have methylcobalamine deficiency with pernicious antibody positive. Magnetic resonance imaging (MRI) of the brain revealed a boomerang-shaped T2 hyperintense and T1 hypointense lesion involving splenium of the corpus callosum. It showed diffusion restriction and no post-contrast enhancement [Figure 1]a, [Figure 1]b, [Figure 1]c. The apparent diffusion coefficient (ADC) levels were markedly low, varying between 0.2 to 0.3 × 10-3. The rest of the brain parenchyma was unremarkable. The non-structural protein-1 antigen along with IgM antibody for dengue was positive. | Figure 1: Magnetic resonance imaging of the brain of case 1: (a) DWI; and (b) T2 flair, showing hyperintensity (arrows) at the splenium of the corpus callosum (Boomerang sign) with; (c) diffusion restriction (broken arrow) in ADC; and (d, e, f) Near complete resolution of the lesion after 14 days.
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He was adequately hydrated following which the hyponatremia and haemoconcentration resolved. Fever defervesced following which the delirium resolved. The thrombocytopenia recovered after 10 days. A repeat MRI done on the Day 14 at discharge showed near-complete resolution of the splenial lesion [Figure 1]d, [Figure 1]e, [Figure 1]f.
Case 2
A 20-yr-old gentleman, a dental student presented with fever for two days, nausea and headache. There was one episode of repetitive speech at presentation. On examination, his vital parameters were normal. He was noted to have hepatomegaly and an erythematous rash in the abdomen. There was no papilledema or focal neurological deficits.
His laboratory values showed leucopenia. In view of the irrelevant repetition of speech an MRI of the brain was done which showed a lesion in the splenium of the corpus callosum which was hyperintense in T2 and hypointense in T1 with diffusion restriction (Dot sign) [Figure 2]. | Figure 2: Magnetic resonance imaging of the brain of case 2: (a) T2 flair; and (b) DWI showing hyperintensity (arrow) at the centre of the splenium of the corpus callosum (Dot sign); and (c) Near complete resolution of the lesion after 14 days.
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He was observed and as his fever defervesed, he developed thrombocytopenia. There were no bleeding manifestations. He was also noted to have methylcobalamine deficiency. He was adequately hydrated following which his platelet counts and white cell counts recovered. A repeat MRI after 14 days showed complete resolution of the lesion.
The corpus callosum constitutes the largest fibre pathway of the brain with around 190 million fibres. The axons radiate on both sides towards the cerebral cortex serving as commissural fibres. The splenium of the corpus callosum is separately supplied by the vertebrobasilar system. Transient splenial signal changes in the corpus callosum have been described in the post-ictal phase, antiepileptic drug toxicity, hypoglycaemia, posterior reversible encephalopathy syndrome, viral encephalitis, haemolytic uraemia syndrome and AIDS dementia complex. The pathogenesis is poorly understood but has been hypothesized to be due to inflammatory infiltrates, reversible demyelination, intramyelinic oedema causing separation of the myelin layers[2]. Besides this the fibres of the corpus callosum have been observed to have myelin sheaths with increased susceptibility to cytotoxic oedema as they have higher water content.
Dengue virus which belongs to the Flaviviridae family[3] has now been deemed as neurotropic. This does not come as a surprise since the other members of the flaviviridiae group like the Japanese encephalitis virus, West Nile virus and Zika virus are neurotropic. There is evidence of dengue causing encephalitis as evidenced by inflammatory infiltrates, cerebral oedema, brain necrosis, perivenous demyelination and focal haemorrhage in case reports previously described. The thalamus and globus pallidus have been the most common areas involved in dengue encephalitis. However, the concrete evidence for neurotropism is from the studies which have isolated RNA of the dengue virus and non-specific protein antigen-1 from the cerebrospinal fluid and brain parenchyma[4].
Observing the two patients we had managed and review of the available literature, we propose that the lesion commences at the centre of the splenium. This we base on the observation that the dot sign has been observed in patients who present early in the illness while the boomerang sign appears later.A close analysis of our first patient’s repeat MRI shows that there is minimal hyperintensity in T2 at the centre of the splenium leading us to hypothesize that the lesion resolves from outside inward.
There have been case reports of dengue with reversible splenial lesions [Table 2]. They have been associated with delirium, transient neurological deficits, and ophthalmoplegia. All the symptoms and signs described in these patients resolved completely with no reports of persisting deficits. | Table 2: Reported cases of dengue fever with reversible splenial lesions
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There are a few conditions that have been found to predispose the formation of transient lesions in the corpus callosum. Methylcobalamine deficiency, folate deficiency, hypoglycaemia, hyponatremia, and hypernatremia have been previously described. Our patient was noted to have methylocobalamine deficiency and hyponatremia. Methylcobalamine is essential for the normal neurodevelopment, myelination of the central nervous system and its maintenance. The biochemical basis postulated is the accumulation of S-adenosylhomocysteine leading to inhibition of transmethylation reactions[10]-
The causal effect of hyponatremia in the reversible splenial lesions is even more poorly understood. In the largest observational study of the relationship between hyponatremia and reversible splenial lesions, 25 of the 30 patients had hyponatremia at presentation[10]. Hence, iatrogenic factors like excessive hydration could be not be attributed as the cause. Earlier observational studies on transient splenial lesions caused by antiepileptic drugs lead to the hypothesis that there is variation in the arginine vasopressin levels[11]. This could explain hyponatremia by inappropriate ADH secretion and the cerebral oedema due to perturbation in the fluid balance seen in both the patients[12].
This lesion in the corpus callosum have been found to be reversible. The hypothesis again is due to the reversibility of the cerebral oedema or the clearance of the virus. The lesions with an identified etiology have been documented to resolve within 3 to 21 days[5]. However, it may be noted that the resolution of the lesion was radiological documentation and the lesion could have cleared earlier. There are a few reports of the persistence of lesion and they have been attributed to a coexisting contributing factor.
Reversible splenial lesion syndrome is a transient phenomenon seen in severe dengue with encephalitis. There is usually a complete resolution of the lesion. The lesion is possibly contributed by methylcobalamine deficiency. Further studies are required to elucidate the pathogenesis of this phenomenon.
Ethical statement
Written consent was obtained from the patients. Patients were admitted in November 2017 under Medicine Unit-V, Christian Medical College, Vellore, Tamil Nadu.
Conflict of interest
There are no conflicts of interest to disclose.
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[Figure 1], [Figure 2]
[Table 1], [Table 2]
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