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.