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Dr. Abhijeet Deshmukh
• Causes
• Typical presentation
• Investigations
• Treatment
• Prognosis
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.)
• Meningitis: meningeal inflammation
• Myelitis: spinal cord inflammation
• Radiculitis: nerve root inflammation
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
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
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
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)
Causes of encephalopathy
• Hypoxic/ischaemic
• Metabolic (liver and renal failure, diabetes)
• Toxic (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
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)
Fungal Cryptococcus
Aspergillosis
Candidiasis
Coccidiomycosis
Histoplasmosis
North American blastomycosis
Parasitic Human African trypanosomiasis (sleeping
sickness)
Cerebral malaria
Toxoplasma gondii
Echinococcus granulosus Schistosomiasis
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
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
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)
• 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
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
MICROBIOLOGICAL INVESTIGATIONS AVAILABLE IN AES
MRI brain (T2W image): right
temporal lobe high signal in a
patient with herpes
encephalitis
Axial DWI: restricted diffusion in the left medial temporal
lobe consistent with herpes encephalitis.
Preventive strategies
(i) Surveillance for cases of AES;
(ii) Vector control;
(iii) Reduction in man-vector contact;
(iv) Vaccination.
Prognosis in HSE
• Mortality > 70% if untreated (20% with Rx)
• Poor prognostic factors
– 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
Encephalitis

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Encephalitis

  • 2. • Causes • Typical presentation • Investigations • Treatment • Prognosis
  • 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.)
  • 4. • Meningitis: meningeal inflammation • Myelitis: spinal cord inflammation • Radiculitis: nerve root inflammation
  • 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)
  • 9. Causes of encephalopathy • Hypoxic/ischaemic • Metabolic (liver and renal failure, diabetes) • Toxic (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
  • 10. 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) Fungal Cryptococcus Aspergillosis Candidiasis Coccidiomycosis Histoplasmosis North American blastomycosis Parasitic Human African trypanosomiasis (sleeping sickness) Cerebral malaria Toxoplasma gondii Echinococcus granulosus Schistosomiasis
  • 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
  • 20.
  • 21. MRI brain (T2W image): right temporal lobe high signal in a patient with herpes encephalitis
  • 22. Axial DWI: restricted diffusion in the left medial temporal lobe consistent with herpes encephalitis.
  • 23.
  • 24. Preventive strategies (i) Surveillance for cases of AES; (ii) Vector control; (iii) Reduction in man-vector contact; (iv) Vaccination.
  • 25. Prognosis in HSE • Mortality > 70% if untreated (20% with Rx) • Poor prognostic factors – 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

Editor's Notes

  1. Terms combined to give eg meningo-enephalitis, encephalomyelitis
  2. Most geographically restricted viruses are arthropod-borne
  3. Mollaret’s meningitis is strictly a recurrent meningitis of unknown cause but feeling is that HSV-2 may cause most cases
  4. 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
  5. 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