Several viruses were implicated as causes of these
epidemics.
A. Japanese Encephalitis (JE)
There were major clinical and epidemiological
differences between the current illness and JE(6). Occurrence within 2
days of heavy rain after a hot summer, shorter prodrome, reaching peak
illness within 2 days, presence of abdominal colic, presence of
diarrhea, absence of meningeal irritation in all cases, good response
within 4 hours to IV mannitol, easily controllable seizures with one
dose of diazepam and phenytoin, rapid progression to death within one
day if IV mannitol was not given, normal CSF except for increased
tension in all cases, Middle cerebral artery territory infarcts on
neuroimaging, absence of sequelae in survivors and absence of
extrapyramidal disorders in survivors clearly excluded JE(6).
B. Chandipura Encephalitis
The epidemics were reported as Chandipura
Encephalitis by some with evidence from virus isolation, identification
by electron microscopy, immunofluorescence, PCR(7,10). Young mice,
infected with Chandipura virus intra-peritoneally, developed CNS
lesions, with necrosis particularly affecting neurons and ependymal
cells(11) proving that CHPV causes encephalitis in mice. Lack of
pleocytosis and normal protein in most CSF samples in these
epidemics(5,6,7,9,10) excludes significant necrosis of ependyma in
humans suggesting the cause to be an an acute catastrophic event
(stroke) in the brain(6,12) rather than encephalitis. Similar sentiments
have been earlier expressed by other clinicians.
C. Measles encephalitis
Two outbreaks of coma in children in Warangal
district of Andhra Pradesh and Vadodara district of Gujarat were
attributed to measles virus by National Institute of Virology,
India(13). However if there is no inflammation in the CNS, but only
brain edema, the detection of virus in CSF must be viewed with some
respectful skepticism(14). Some experts believe that the isolation of
measles virus in these epidemics was a result of laboratory
contamination with measles vaccine virus(14).
D. Epidemic Brain Attack
This epidemic coma was reported as Epidemic Brain
Attack (EBA) of childhood by some based on clinical features, normal CSF
in all cases, infarcts on neuroimaging and response to
treatment(5,6,12,15). Brain Attack (Stroke) should be diagnosed when
there are "Rapidly developing clinical signs of focal (or global)
disturbance of cerebral function, with symptoms lasting 24 hours or
longer or leading to death, with no apparent cause other than of
vascular origin"(16). When it occurs in epidemics, it is called Epidemic
Brain Attack or Epidemic Stroke(6,12).
The clinical, laboratory and neuroimaging features of
most patients during these epidemics were consistent with ischemic
damage suggesting the diagnosis of EBA.
The possible explanation of EBA occurring in epidemic
form could be that a virus is the cause of vasculitis presenting this
way but it is unlikely to be encephalitis. The possibility of laboratory
contamination is also to be considered. Raised intracranial tension is a
common feature of Reye syndrome and Epidemic Brain Attack. If all major
cerebral arteries are involved, Epidemic Brain Attack can mimic Reye
syndrome. Presence of fever and focal signs differentiate EBA from Reye
syndrome.
Reasons for acute onset with sudden death in EBA is
severe brain edema due to ischemia of large areas of brain caused by
transient vasospasm of Middle Cerebral Artery(6), resulting in
herniation and compression of the brainstem.
Fever, alteration of sensorium without rash or
meningeal signs of irritation, normal CSF, epidemic within 2 days of
heavy rain after a hot summer and neuroimaging features of infarction
are main features suggesting diagnosis of EBA.
The exact etiology of the sequence of events in these
attacks is unclear. Whether this multi-region outbreak was caused by a
large batch of contaminated food being distributed to the different
regions by a transport chain or by an unusual organism, spread by an
environmental vector or immigrant strains distributed by people
returning from holiday requires further epidemiological studies.
Conclusion: The episodes of acute coma in
children being reported from various parts of India in recent years do
not appear to be viral encephalitis. EBA seems to be the most likely
pathological diagnosis the cause of which is largely unclear. Role of
Chandipura Virus as an evolving human pathogen requires further
confirmation(12).
Acknowledgements
The authors convey their grateful thanks to
Dr.C.S.Bhaskaran and Dr.V.Murali Mohan for their stimulating discussions
and critical review of the article. Lastly, the authors are indebted to
the commendable secretarial services of Prof. Kamala Devi Potharaju and
Mr. Rahul Potharaju.
Key Messages |
Selection as well as timing of an
investigation are crucial to make a diagnosis in mystery diseases.
Laboratory contamination or errors must be
considered whenever unexpected results are obtained.
Fever, alteration of sensorium without rash
or meningeal signs of irritation, normal CSF, epidemic within 2
days of heavy rain after a hot summer and neuroimaging features of
infarction should suggest the diagnosis of EBA.
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