ENCEPHALITIS

INFLAMMATION OF BRAIN
 Presented By
1.FAISAL AHMED
ROLL NO-1047
2.SAIMA SABRINA
ROLL NO-1033
3.FERDOUSI RAHMAN
ROLL NO-1030
Department of Biochemistry & Molecular Biology
Jahangirnagar University
 AT A GLANCE
1. Introduction
2. Forms
3. Causes and Spread
4. Pathophysiology
5. Sign and Symptoms
6. Different types of Encephalitis
7. Molecular biology and immunology of flaviviruses
8. Molecular mechanism
9. Route of Transmission
10. Neuroprotective Mechanisms of Lithium in Encephalitis
11. Diagnosis
12. Treatment
13. Prevention
 INTRODUCTION
 Although the term "encephalitis" literally means "
inflammation of the brain," it usually refers to brain
inflammation resulting from a viral infection.
 The severe and potentially life-threatening form of
this disease is rare that only occurs in approximately
0.5 per 100,000 individuals - most commonly in
children, the elderly, and people with weakened i
mmune systems
(i.e., those with HIV/AIDS or cancer).
 Experts suspect that the actual incidence of encephalitis
is probably much higher — but because most people
have such mild signs or symptoms, many cases go
unrecognized.
 FORMS

Encephalitis occurs in two forms — 1.primary form

2.secondary form
 Primary encephalitis involves
direct viral infection of brain and spinal cord.
 In secondary encephalitis, a viral infection first
occurs
elsewhere in body and then travels to brain.
Visiting the doctor and receiving timely treatment is
important because the course of the disease is
unpredictable.
 CAUSES AND SPREAD

 
                                                                                        
                           

                       

                                  
                                  
                             
FIG: Culex mosquitoes lay their eggs in water, and the eggs hatch into larvae as shown here.
The larvae mature into adult Culex mosquitoes that carry the viruses that cause Japanese
encephalitis, St. Louis encephalitis, and West Nile encephalitis
 PATHOPHYSIOLOGY
•The virus replicates outside the CNS and gains
entry either by hematogenous spread or by
traveling along neural and olfactory (HSV)
pathways.
• Once across the blood-brain barrier, the virus
enters neural cells, affecting gray matter
disproportionately to white matter.
• Focal pathology is the result of neuron cell
membrane receptors, found only in specific
portions of the brain and accounts for regional
tropism found with some viruses. For example,
HSV.
•Presence of Negri bodies in the hippocampus
and cerebellum are pathognomonic of rabies,
as are HSV Cowdry type A inclusions with
hemorrhagic necrosis in the temporal and
orbitofrontal lobes.
•In contrast to viruses that invade gray matter
directly, acute disseminated encephalitis and
post infectious encephalomyelitis (PIE),
secondary to measles (most common), Epstein-
Barr virus (EBV), and CMV, are immune-
mediated processes, which result in multifocal
demyelination of perivenous white matter.
 SIGN AND SYMPTOMS
 More commonly - fever
-headache
-photophobia
-poor appetite
-loss of energy
-weakness
-nausea and vomiting
-seizures
 Less commonly -stiffness of the neck
-stiffness of the limbs
-slowness in movement and clumsiness
depending on which specific part of the brain is involved.
 The symptoms of encephalitis are caused by the brain's defense
mechanisms activating to get rid of the infection.
 DIFFERENT TYPES OF
ENCEPHALITIS
 Limbic system Encephalitis
 Amebic Infections
 Eastern Equine Encephalitis
 Encephalitis Lethargica
 Japanese Encephalitis
 Meningoencephalitis
 LaCrosse Encephalitis
 Rasmussen's Encephalitis
 St. Louis Encephalitis
 Subacute Sclerosing Panencephalitis
 Tickborne Encephalitis
 Western Equine Encephalitis
LIMBIC SYSTEM
ENCEPHALITIS
• Herpes Simplex Virus (HSV)
encephalitis has its own
neuroanatomy. It tends to attack a
part of the brain known as the
"limbic system", a set of
interconnected brain structures
responsible for the integration of
emotion, memory, and complex beh
avior
. This disease is important to
recognize because there is an
effective drug treatment, acyclovir.
• It is the most frequently fatal of
all encephalitis.
 Meningoencephalitis In AD
Patients
 Antibodies targeting amyloid beta peptide
proteins which have been used during research
on Alzheimer's disease cause
meningoencephalitis (ME).
 AN1792 , a potential immunotherapeutic
agent for use in Alzheimer's disease (AD),
approximately 6% of the treated AD patients
(18/300) developed meningoencephalitis (ME).

Fig: Brain Damage In Early

Alzheimer's Disease.
 Molecular biology and
immunology of flaviviruses
 Flaviviruses enter cells by
receptor-mediated endocytosis
and the acidic pH in the endosome
triggers an irreversible
conformational change in the
viral fusion protein (E) (a class II
viral fusion protein) that drives
the fusion of the viral membrane
with the endosomal membrane,
resulting in the release of the
viral genome into the cytoplasm.
Amino acid positions on the E
protein of flaviviruses indicating
the binding sites of neutralizing
antibodies.
 Molecular mechanism of
encephalitis
 Japanese encephalitis virus (JEV), a mosquito-borne flavivirus that
causes severe human disease, has been shown to block the
interferon (IFN)-induced Janus kinase signal transducer and
activation of transcription (Jak-Stat) signaling cascade by
preventing Tyk2 tyrosine phosphorylation and Stat activation.
 It has been demonstrated that expression of the JEV nonstructural protein
NS5 readily blocked IFN-stimulated Jak-Stat signaling events such as
Stat1 nuclear translocation and tyrosine phosphorylation of Tyk2 and Statl.
 The role of JEV NS5 as an IFN antagonist was further demonstrated
by its ability to block the induction of interferon-stimulated genes and
the antiviral effect of IFN-α against the IFN-sensitive
encephalomyocarditis virus, which appears to
replicate and kill cells that express NS5 even with alpha IFN
treatment.
 Furthermore, the molecular mechanism responsible for IFN antagonism by
NS5 probably involves protein tyrosine phosphatases (PTPs), as the
IFN-blocking events in both JEV-infected and NS5-expressing cells were
reversed by sodium orthovanadate, a broad-spectrum inhibitor of PTPs.
It has been suggested that JEV NS5 is an IFN antagonist and that it
may play a role in blocking EIFN-stimulated Jak-Stat signaling via activation
of PTPs during JV infection.
 Infected Cell Protein (ICP)47 Enhances
Herpes Simplex Virus Neurovirulence by
Blocking the CD8+ T Cell Response
The herpes simplex virus (HSV) infected cell protein (ICP)47
blocks CD8+ T cell recognition of infected cells by inhibiting
the transporter associated with antigen presentation (TAP).
 ICP47 could reduce the effectiveness of the CD8+ T cell

response.
 ICP47 might inhibit the direct interaction of CD8+ cells with

infected neurons by contributing to the failure of infected

neurons to express MHC class I protein.
 HSV ICP47 can inhibit a CD8+ T cell response that prevents

lethal encephalitis following from corneal infection.

ROUTE OF TRANSMISSION
 Neuroprotective Mechanisms
of Lithium in Encephalitis

Fig: Lithium activates the Wnt and

phosphatidylinositol 3-kinase Akt signaling pathways
to promote cell survival in the absence of soluble
survival factors.
 DIAGNOSIS
Doctors use several tests to diagnose encephalitis,
including:
 imaging tests, such as computed tomography (CT) scans or
 magnetic resonance imaging (MRI), to check the brain for
swelling, bleeding, or other abnormalities
 electroencephalogram (EEG), which records the electrical
signals in the brain, to check for abnormal brain waves
 blood tests to confirm the presence of bacteria or viruses in
the blood, and whether a person is producing antibodies in
response to a germ.
 spinal tap
 brain biopsy
 TREATMENT
Treatment is usually symptomatic. Reliably tested
specific antiviral agents are available only for a few viral
agents (e.g. acyclovir for herpes simplex virus) and are
used with limited success for most infection except
herpes simplex encephalitis. In patients who are very sick,
supportive treatment, such as mechanical ventilation,
is equally important.
 Prehospital Care
 Emergency Department Care
 Consultations
 Medication :Drug category-
Antiviral. Ex-Acyclovir
Corticosteroids. Ex-Dexamethasone
 PREVENTION
 The best way to prevent encephalitis is to
avoid getting infected with the viruses or other germs
that can cause it.
 Staying as healthy as possible by eating a balanced diet
and getting plenty of rest can help keep your immune
system in shape.
 Immunizations are also an important way to protect people
from diseases like chickenpox and measles.
 In areas where viruses are transmitted by insect bites,
protect yourself by wearing long sleeves and pants and
applying an insect repellent.
 Try to avoid
unnecessary outdoor activities at dawn and dusk when
mosquitoes are most likely to bite.