1. Medical Grand Round
Dr. Lucy Strens
Consultant Neurologist
UHCW
Nov 24th
2009

2. Viral encephalitis
• Causes
• Typical presentation
• Investigations
• Treatment
• Prognosis

3. Terminology
• Encephalopathy
– Clinical syndrome of reduced consciousness
– Many causes, incl. viral encephalitis
• Encephalitis
– Acute, diffuse, inflammatory process affecting brain
parenchyma
– Most commonly viral
• Meningitis: meningeal inflammation
• Myelitis: spinal cord inflammation
• Radiculitis: nerve root inflammation

4. Causes of encephalopathy
• Hypoxic/ischaemic
• Metabolic (liver and renal failure, diabetes)
• Toxic (alcohol, drugs)
• Vascular (vasculitis, SLE, SAH, SDH, stroke, Behcet’s)
• Epileptic (non-convulsive status)
• Nutritional deficiency
• Systemic infections (malaria)
• Traumatic brain injury
• Malignant hypertension
• Mitochondrial cytopathy (Reye’s and MELAS syndromes)
• Hashimoto’s encephalopathy
• Paraneoplastic limbic encephalitis
• Neuroleptic malignant syndrome…….. (and more!)

5. Causes of acute viral encephalitis
Sporadic causes (not geographically restricted)
• Herpes viruses
– HSV-1, HSV-2, VZV, CMV, EBV, HHV6, HHV7
• Enteroviruses
– Coxsackie, echoviruses, enteroviruses 70/71, parechovirus, poliovirus
• Paramyxoviruses
– Measles, mumps
• Others (rarer causes)
– Influenza viruses, Adenovirus, parvovirus, lymphocytic choriomeningitis
virus, rubella virus, rabies
Geographically restricted causes
• Arboviruses — Japanese B, St Louis, West Nile, Eastern equine, Western
equine, Venezuelan equine, tick borne encephalitis viruses
• Bunyaviruses — La Crosse strain of California virus
• Reoviruses — Colorado tick fever virus

6. Non-viral causes of
infectious
encephalopathy
Bacterial Mycobacterium tuberculosis
Mycoplasma pneumoniae
Listeria monocytogenes
Borrelia burgdorferi
Leptospirosis
Brucellosis
Legionella
Tropheryma whippeli
(Whipple’s disease)
Nocardia actinomyces
Treponema pallidum
Salmonella typhi
All causes of pyogenic
meningitis
Rickettsial Rickettsia rickettsia (Rocky Mountain
spotted fever)
Rickettsia typhi (endemic typhus)
Rickettsia prowazeki (epidemic typhus)
Coxiella burnetti (Q fever)
Ehrlichiosis (Ehrlichia chaffeensis—
human monocytic ehrlichiosis)
Fungal Cryptococcus
Aspergillosis
Candidiasis
Coccidiomycosis
Histoplasmosis
North American blastomycosis
Parasitic Human African trypanosomiasis
(sleeping sickness)
Cerebral malaria
Toxoplasma gondii
Echinococcus granulosus
Schistosomiasis

7. 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

8. Herpes simplex encephalitis
• HSV encephalitis (HSE) most common cause of
viral encephalitis in industrialised nations
• Annual incidence 1 in 250,000-500,000
• 90% HSV-1
• HSV-2 more common in immuno-compromised,
neonates

9. HSV-1
• Primary infection occurs in oral mucosa
– 30% people get clinically apparent cold sores
– 90% healthy people have been infected with HSV-1
• Virus then travels along trigeminal nerve to ganglion in
most (if not all) those infected
• 70% cases of HSV-1 encephalitis already have antibody
present suggesting reactivation of virus most common
mechanism
• Why HSV-1 reactivates not known
• In children, HSV-1 encephalitis occurs during primary
infection

10. HSV-2
• Transmitted via genital mucosa
– Genital herpes in adults
– USA, 20% of adults sero-positive for HSV-2
• 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. Case example
• 57 yr old female
• 4 days N&V, severe headache, loss of appetite
• Confused, ‘unable to find right word’
• O/E
– Temp 39o
C, dysphasic, no focal neuro signs (upgoing
plantars)
– WCC 11.7, CRP 4

12. Case 2
• CSF
– WCC 36 (80% lymphocytes), RCC 2
– Normal glucose, protein 0.91g/l
– HSV-1 PCR positive

14. Viral encephalitis – clinical presentation
• Typical presentation
– Acute flu-like prodrome
– High fever, severe headache, N&V
– Altered consciousness (lethargic, drowsy, confused, coma)
– (Seizures)
– (Focal neurological signs)
• Recent study of 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. Clinical presentation
• More subtle presentations now recognised
– Low grade fever
– Speech disturbances (dysphasia, aphasia)
– Behavioural changes
• Subacute and chronic presentations can be
caused by CMV, VZV, HSV (immuno-
compromised)
• Any adult with seizure + fever or seizure from
which they do not recover must be investigated
for possible CNS infection

16. 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

17. Clues in history
• Recent rashes
• Vaccination history
• Travel history
• Recent animal/insect bites, contact with sick
animals
• Immunosuppression (HIV, transplant)
• Drugs, alcohol

18. Clues on examination
• Skin rashes, bites, injection sites
• Examine chest, abdo, ears, genitals, urine for
infection
• Meningism, subtle motor seizures, focal neuro
signs
• NB ‘cold sores’ not diagnostic!

19. Investigations
• General
– Haematological and biochemical blood screen
– Serology, blood cultures, HIV
– Drug screen, urine analysis
– CXR
• Neurological
– CT head, MRI brain
– LP (if not contraindicated on cranial imaging)
– EEG
– ((brain biopsy))

20. MRI brain (T2W image): right
temporal lobe high signal in a
patient with herpes
encephalitis

21. Axial DWI: restricted diffusion in the left medial temporal
lobe consistent with herpes encephalitis.

22. CSF examination
• Opening pressure
• Send samples for
– Cell count and differential
– Protein, glucose (plasma glucose)
– Gram stain and culture
– Viral PCRs (HSV 1*, HSV2, VZV, EBV, CMV,
enteroviruses)
– Other tests as appropriate (discuss with micro!)
*HSV-1 CSF PCR still positive in 80% pts after one week of treatment
(may be negative in first few days)
PCR tests for HSV have overall sensitivity and specificity >95%

23. 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

24. Management of viral encephalitis
• O2, fluids, NG feed?, ITU?
• Aciclovir
– Start as soon as suspect viral encephalitis
– iv aciclovir 10mg/kg tds
– 14-21 day course in confirmed HSE
– Monitor renal function
– Only stop if definite other diagnosis made
• Antibiotics too if delay in getting CSF/imaging
• Management of complications (brain swelling,
seizures)

25. Prognosis in HSE
• Mortality > 70% if untreated (20% with Rx)
• Poor prognostic factors
– Age > 60 yrs
– GCS < 7
– Delay in starting aciclovir (esp > 2 days)
• 2/3 rds pts have neuropsychiatric sequelae
– 69% memory impairment
– 45% personality/behaviour change
– 41% dysphasia
– 25% epilepsy
www.encephalitis.info