Discussion:-
There have been few attempts to study scrub typhus in Nepal. In 1981, a
high probability of scrub typhus was identified in Nepal by detecting
high antibody titers (10%) in healthy adults. IgM antibodies to O.
tsutsugamushi were positive in samples from various regions, including
30 districts in Nepal. Positive cases have been found in different
ecological regions of Nepal 9.
Humans are infected by the bite of the larvae of the leptothrombidium
mite. From the bite site, bacteria are distributed throughout the body
via blood and lymph. It induces endothelial injury, leukocyte
perivascular infiltration, increased vascular permeability, and an
vasculitic response with severe microvascular thrombosis leading to
organ damage 1,10. Classically, scrub typhus presents
with fever, headache, cough, myalgia, arthralgia, lymphadenopathy, and
maculopapular rash that begins from the trunk and spreads to the limbs11–13. The ’eschar’, which are thought to be the
hallmark of the disease, are the bites of these chiggers that creates
wound similar to ’cigarette burns’ 1,10.
”Characteristic” symptoms of scrub typhus have been occasionally
reported, with the characteristic crust occurring in only 20% of
patients and lymphadenopathy in 24%. Nevertheless, the eschar occurs
more frequently in adults, and conversely, and conversely organanomegaly
can occur in children. However, the absence of these signs should not
rule out scrub typhus infection, as these features are present in only 1
in 4-5 patients with confirmed CNS scrub typhus. Given its potential
impact on long-term morbidity, clinicians should be alert to the
possibility of acute convulsive activity in children with central
nervous system scrub typhus 14. The microbe has an
increased propensity of infecting organs that are highly vascularized,
like the liver, brain, heart, and lungs 11. Hence,
beginning from 2nd week, the infection, if untreated, progresses to
complications like acute diffuse encephalomyelitis, encephalopathy,
meningitis, cranial nerve palsies, congestive heart failure, vasculitis,
myocarditis, pneumonia, acute respiratory distress syndrome, acute renal
failure, gastrointestinal bleeding, alterations in liver functions and
pancreatitis 11–13,15. Among the complications,
myocarditis and encephalitis are the most life-threatening ones16. Doxycycline is the drug of choice and azithromycin
is the drug of choice for children and pregnant women17.
Despite the growing number of clinical studies addressing the
neurological complications of tsutsugamushi disease, there are
surprisingly few studies to clarify the underlying mechanisms of
neuroinvasion and neuroinflammation 8. Spread of
bacteria from the periphery to the central nervous system occurs by
hematogenous spread 18,19.
Although the exact mechanism of entry into the central nervous system is
unknown, there is evidence that direct entry may occur through damage to
the microvascular endothelium or disruption of the blood-brain barrier
through transcellular translocation of bacteria, which can occur
independently or by way of macrophages that have engulfed the bacterium.
After entering the central nervous system, it activates specific
transcription factors, such as the nuclear factor kappa B, which causes
inflammation [14]. Orientia tsutsugamushi has an endothelial cell
tropism and invades dendritic cells, monocytes and tissue macrophages.
Endothelial invasion causes vascular injury with intestinal perivascular
mononuclear infiltration leading to complications 20.
Several neurological syndromes have been reported in association with
scrub typhus. Literature review reveals case reports of acute transverse
myelitis, myoclonus, parkinsonism, and acute disseminated
encephalomyelitis 21–23. Solitary or multiple cranial
neuropathy is a well-known neurological manifestation of scrub typhus
infection 2. Cranial nerve disorders such as facial
paralysis, sensorineural hearing loss, trigeminal neuralgia, and
diplopia due to abduction paralysis were observed24–27. Few authors suggest that scrub typhus should
be considered as a differential diagnosis in all patients with aseptic
meningitis with renal or hepatic impairment living in endemic areas28. They found that the CSF profile mimics tuberculous
meningitis or viral meningitis. CSF had predominantly lymphocytic
pleocytosis, elevated protein with low or normal glucose.
As per the definition, acute encephalitis syndrome presents with the
fever in association with seizure, altered mental status and the focal
neurological signs like ataxia, aphasia, cranial nerve palsy or
hemiparesis 12. Our patient presented with the
symptoms of fever, headache, vomiting, and altered mental status
associated with the signs of bilateral lateral rectus palsy, dysphagia,
regurgitation of food, dysarthria, and left-sided UMN type facial palsy
that is suggestive of acute encephalitis syndrome with cranial nerve
palsy.
The Neuroimaging findings for meningoencephalitis due to scrub typhus
are quite limited. There have been reports of radio imaging findings of
lesions on a white matter involving the subcortical, periventricular
deep white matter, corpus callosum, cerebellar peduncles, brain stem,
and basal ganglia, as well as grey matter lesion and microhemorrhages29. Kar et. al(2014) have reported the presence of
diffuse cerebral edema along with T2-weighted and FLAIR hyperintensities
in the putamen and thalamus, suggesting brain parenchymal involvement12. The diagnosis of encephalitis in our case was
further supported by the multiple mildly increased T2DM/FLAIR signal in
the midbrain, pons, and left middle cerebellar peduncle.