Figure 2: MRI Image A showing bilateral thalamic and putamen involvement with restricted diffusion (blue arrows) Image Bshows flair image showing bilateral thalamus hyperintensity.Image C is the T2 heme axial sequence showing haemorrhagic transformation (red arrow).
DISCUSSIONS
Acute necrotizing encephalopathy of childhood is a rare form of encephalopathy, its aetiology is yet unknown. It is often associated with viral infections such as influenza A and B, parainfluenza, and human herpes virus-6 (HSV-6).[4] There are few cases being reported in adult population especially in western countries although most of the cases affect children and adolescents, in which majority of them are seen to be of Asian origin.[2, 5]
The main pathogenesis of the disease remains unknown though several hypotheses have been made such as the autoimmune response inducing cytokine storm that later leads to neurovascular damage.[6] Another hypothesis is related to specific geographical location as described in some previous literature which has shown that Eastern Asian countries have genetic predisposition for region specific pathogens causing ANE.[7] This is in contrast with our patient who had no travel history to any of Eastern Asian countries.
ANE presents like any other forms of encephalopathy with non-specific prodromal symptoms including fever, cough, and gastrointestinal disturbances. As the disease progresses, in few days life threatening symptoms occur including seizures, ataxia and coma.[6] Reports from Eastern Asian countries showed the affected ages are usually between 6 to18 months old which accounts 50% of cases.[2] The onset of neurological dysfunction usually occurs from 12 to 72 hours after the onset in which 40% of the cases present with seizures.[2] A review done more recently by Yuan et al., showed that 94% of the cases have early seizure activity most frequently being persistent tonic-clonic in nature.[8] In our case, the patient presented with altered level of consciousness for the past 3 days, aphasia and excessive drowsiness. The symptoms were preceded by headache, but no seizures were reported.
The diagnosis of ANE significantly depends on the radiological hallmark with symmetrical lesions involving thalami, tegmentum of upper thalami and other regions of the brain such as the white matter, basal ganglia, brain stem and cerebellum.[9] The laboratory findings are not specific for the diagnosis as they are mainly supportive, most cases present with elevated white blood cell counts, C-reactive protein (CRP) and erythrocyte sedimentation rate (ESR).[10] Serum transaminase, lactate dehydrogenase (LDH), and creatinine kinase (CK) are frequently observed to be elevated as there is direct relation to increased fibrin degradation products.[8] Occurrence of electrolyte imbalance is uncommon. Cerebral spinal fluid (CSF) analysis though it accounts to be non-specific in most cases, has been observed to have raised protein concentration.[2,8]
Most of the reported causes of acute necrotizing encephalopathy are viral infections such as influenza, HSV-6, parainfluenza, and other related viral infections such as dengue virus hence it is important also to do the serology to understand the causative agent which may be of benefit in the treatment and outcome. In our case from the history and clinical presentation of the patient, meningitis was the main provisional diagnosis, then later ANE was added into our diagnosis list. Viral infections cause cytokine activation which leads to the trigger of coagulation cascade.[1] It is seen that chronic viral infections are associated with thrombotic complications while acute infections may cause both thrombosis and haemorrhagic complications[12], such as in our case, there was evidence of haemorrhagic transformation in the thalamic region.
The working diagnosis changed when MRI brain was done as the patient’s condition was not improving, and this is when acute necrotizing encephalopathy as an incidental finding was noted. The laboratory findings were not alarming for any central nervous system infection except for elevated transaminase level which is usually noted in acute necrotizing encephalopathy, lumbar puncture was contraindicated due to presence of cerebral oedema.
Currently there is no consensus on the treatment for acute necrotizing encephalopathy. Treatment is mainly based on a symptomatic approach which includes use of empirical antiviral treatment.[11] Depending on the patient’s clinical condition, intensive care admission may be required such as in cases with active convulsions or other life-threatening conditions such as septic shock. Most of the literatures recommend the use of intravenous glucocorticoids and immunoglobulins as it has been seen to improve the patient’s clinical condition remarkably.[6, 10] In our patient a combination of intravenous immunoglobulin, antiviral medications together with antibiotics were empirically prescribed medications during his hospital stay. Although immunoglobulin injection was not initiated early, its efficacy in this case cannot be predicted.
The outcome of ANE of childhood is generally poor. The mortality rate has been reported to be 30%. The survivors may be subjected to serious neurological complications such as muscle spasticity and speech disorders, but less than 10% of cases have recovered without any neurological sequelae.[8] Abnormal laboratory investigation with significant elevated levels of serum aminotransferase and CSF protein makes the prognosis of the disease to be worse.[10] With the aid of physiotherapy our patient could walk on his own in contrast with his initial presentation of being bed-bound with limited neuro-motor activities on his both upper and lower limbs.
CONCLUSION
It is unknown whether similar cases of ANE have been taking place in our setting and may obviously go unnoticed. This leads to delay in establishing early diagnoses and later to poor patient outcome. Our emphasis is to always maintain a high level of suspicion in similar clinical presentations to ensure ANE does not go unrecognized.