3. Terminology
• Encephalitis
– Acute, diffuse, inflammatory process affecting brain
parenchyma
– Most commonly viral
• Encephalopathy
– Clinical syndrome of altered mental status, manifesting as
reduced consciousness or altered behaviour
– Many causes, incl. viral encephalitis
Acute Encephalitis Syndrome :
- Defined as a person of any age, at any time of year with the
acute onset of fever and a change in mental
status(confusion, disorientation, coma, or inability to talk)
and/ or new onset of seizures ( excluding simple febrile sz.)
5. Causes of acute viral encephalitis
Sporadic causes
• Herpes viruses
– HSV-1, HSV-2, CMV, EBV, HHV6, HHV7 , VZV
• Enteroviruses
– Coxsackie, echoviruses, enteroviruses 70/71, poliovirus
• Paramyxoviruses
– Measles, mumps
• Others (rarer causes)
– Influenza viruses, Adenovirus, parvovirus, rubella virus, rabies , HIV
Geographically restricted causes
• Arboviruses — Japanese B, St Louis, West Nile, Eastern equine, Western
equine, Venezuelan equine, tick borne encephalitis viruses, Dengue virus,
Chikungunya v
• Bunyaviruses — La Crosse strain of California virus
• Reoviruses — Colorado tick fever virus
6. Herpes simplex encephalitis
• HSV encephalitis (HSE) most common cause of
viral encephalitis in industrialised nations
• 90% HSV-1
• HSV-2 more common in immuno-compromised,
neonates
7. HSV-1
• Primary infection occurs in oral mucosa
• Virus then travels along trigeminal nerve to ganglion
• 70% cases of HSV-1 encephalitis already have antibody
present suggesting reactivation of virus which is the
most common mechanism
• In children, HSV-1 encephalitis occurs during primary
infection
8. HSV-2
• Transmitted via genital mucosa
– Genital herpes in adults
• HSV-2 may cause
– Meningitis (esp. recurrent meningitis)
– Encephalitis (esp in neonates)
– Lumbosacral radiculitis
• Neonates can be infected during delivery:
neonatal herpes (disseminated infection often
with CNS involvement)
11. Encephalopathy vs encephalitis?
Encephalopathy Encephalitis
Clinical features
Fever Uncommon Common
Headache Uncommon Common
Depressed mental status Steady deterioration May fluctuate
Focal neurological signs Uncommon Common
Type of seizure Generalised Generalised or focal
Laboratory findings
Blood Leucocytosis uncommon Leucocytosis common
CSF Pleocytosis uncommon Pleocytosis common
EEG Diffuse slowing Diffuse slowing and focal
abnormalities
MRI Often normal Focal abnormalities
12. Pathogenesis of viral encephalitis
• Depends on the virus
– direct viral destruction of cells
– Para or post-infectious inflammatory or immune-
mediated response
• Most viruses primarily infect brain parenchyma
and neuronal cells
• Some cause a vasculitis
• Demyelination may follow infection
13. Viral encephalitis – clinical presentation
• Typical presentation
– Acute flu-like prodrome
– High fever, severe headache
– Altered consciousness (lethargy, drowsiness, confusion,
coma)
– Seizures
– Focal neurological signs
• More subtle presentations
– Low grade fever
– Speech disturbances (dysphasia, aphasia)
– Behavioural changes
– Subacute and chronic presentations can be caused by CMV,
VZV, HSV (immuno-compromised)
14. • A study on HSV-1 encephalitis*
– 91% febrile on admission
– 76% disorientated
– 59% speech disturbances
– 41% behavioural change
– 33% seizures
*Raschilas et al 2002 Clin Infect Dis
15.
16.
17.
18. Typical CSF findings in CNS infections
Viral Bacterial TB Fungal Normal
Opening
pressure
Normal/high High High High/v. high 10-20 cm
Colour Clear Cloudy Cloudy/yellow Clear/cloudy Clear
Cells/mm3
Sl. increase
5-1000
High/v. high
100-50,000
Sl. increase
25-500
Normal/high
0-1000 < 5
Differential Lymphocytes Neutrophils Lymphocytes Lymphocytes Lymphocytes
CSF/plasma glc
ratio
Normal Low Low/v. low
(<30%)
Normal/low
66%
Protein (g/l) Normal/high
0.5-1
High
>1
High/v. high
1-5
Normal/high
0.2-5 <0.45
Bloody tap: subtract 1 WBC for every 700 RBCs
subtract 0.1g/l protein for every 1000 RBCs
Terms combined to give eg meningo-enephalitis, encephalomyelitis
Most geographically restricted viruses are arthropod-borne
Mollaret’s meningitis is strictly a recurrent meningitis of unknown cause but feeling is that HSV-2 may cause most cases
HSV targets brain parenchyma in temporal lobes, sometimes with frontal or parietal involvement Mumps can cause acute viral encephalitis or a delayed immune-mediated encephalitis Measles causes a post-infectious encephalitis which may have a severe haemorrhagic component (acute haemorrhagic leukoencephalitis) Influenza A may give diffuse cerebral oedema VZV causes a vasculitis
Normal glucose ratio said to be 66% but probably not significant until values are below 50% Viral CNS infections: early LP may show mainly neutrophils (or no cells) Acute bacterial meningitis which has been partly treated with antibiotics may show mostly lymphocytes and cell count may not be very high TB meningitis may show polymorphs early on Listeria can look like TB but history shorter