o Inflammation of the brain parenchyma.
o Varying incidence in different western countries but approximately 0.7-12.6 per 100,000 for adults.
o Causes of encephalitis include: direct infection, para-infectious/post-infectious and non-infectious.
o Infectious causes include many viruses, bacteria, fungi and parasites.
• Viruses are the most common causative agents.
• Herpes simplex virus (HSV) encephalitis is most common.
• Age specific incidence is bimodal, peaks in the young and the elderly.
• Other common viral causes include
o Most viral encephalitis is acute. Sub-acute and chronic presentations are suggestive of atypical infections.
o Para and/or post-infectious encephalitis, refers to inflammation of the brain parenchyma some time after initial infection.
• An example of this is acute disseminated encephalomyelitis (ADEM) after measles infection.
o Non-infectious causes include antibody-mediated encephalitis, which can be due to a paraneoplastic syndrome.
• Voltage gated potassium channel (VGKC) limbic encephalitis.
• Anti NMDA receptor antibody panencephalitis.
o Fever
o Headache
o Nausea & Vomiting
o Confusion
o Seizures
• Status epilepticus can be caused by underlying encephalitis
o Changes in personality and behaviour
o Speech distrubance
o Focal neurological symptoms
o Loss of consciousness
o Autonomic dysfunction, myoclonus and cranial neuropathies
• Commonly seen in brainstem encephalitis
• Listeriosis, brucellosis, tuberculosis (TB)
o Tremors or movement disorders
• Thalamic or basal ganglia involvement
• Flavavirus and alphavirus infections.
o Acute flaccid paralysis
• Characteristic of polio, other enteroviruses and flavaviruses.
o Meningism can occur however the clinical presentation is dominated by other symptoms
o Travel history.
o Recent history of chickenpox (suggestive of varicella zoster virus encephalitis).
o HIV status or history suggestive of immunocompromise.
o History of drug and alcohol abuse.
o Previous history of seizures (suggestive of epilepsy).
o No recent history of fever (common in antibody-associated encephalitides).
Examination findings
o Assess the patient’s airways, breathing and circulation.
o When possible the mental state of the patient needs to be examined.
o Look for possible signs of prior seizures such as tongue biting or injury.
• Subtle motor seizures may also be present (mouth, digit, eyelid twitching)
o Evidence of meningism
o Full neurological examination
• Focal signs may or may not be present
• Flaccid paralysis
o Papilloedema (raised intracranial pressure).
o Rash
o Injection sites indicating drug abuse.
o Animal or insect bites (source of infection).
o Exclude possible movement disorders.
Bedside tests
o Glucose
• Exclude hypoglycaemia
Laboratory investigations
o Standard (for all patients)
• Throat and rectal swabs
• If recent or current respiratory tract infection
• Sputum (bacteria) or bronchial lavage.
• Nose swab.
• If there is a suspicion of mumps then parotid gland duct or buccal swabs should be taken for viral culture or PCR.
• Blood
• Acute and convalescent cultures.
o Para-infectious immune mediated encephalitis
• AntiDNAse B and Anti-streptolysin O titre
• Influenza A and B PCR/or antibody in serum
o Suspected autoimmune/inflammatory encephalitis
• Blood
• Full blood count
• Ethrocyte sedimentation rate
• C-reactive protein
• Anti-nuclear antibodies
• Extracted nuclear antibodies
• Double strand DNA antibodies
• Anti-neutrophil cytoplasmic antibody
• Complement 3 and 4
• Lupus anticoagulant
• Cardiolipin
• Thyroglobulin
• Thyroperoxidase antibodies
• Ferritin
• Fibrinogen
• Triglycerides
• VGKC and NMDA antibodies
• Serum Angiotensin Converting Enzyme
• Serum 25OH Vitamin D
• 24hr urinary calcium
o Metabolic
• Blood
• Liver function tests
• Bone profile
• Thyroid function tests
• Urea and Electrolytes
• Arterial blood gas analysis
• Plasma lactate, pyruvate, amino acids, very-long chain fatty acids
• Porphyrins
• Urine
• Organic acids
• Porphyrins
• Faecal
• Porphyrins
o Vascular Neoplastic
• Blood
• Lactate dehydrogenase test
• IgG/A/M
• Protein electrophoresis
• Urinary
• Bence-jones proteins
• Other
• Bone marrow trephine
o Paraneoplastic
• Blood
• Anti-neuronal and onconeuronal antibodies.
• Alpha-fetoprotein
• Beta human chorionic gonadotrophin
o Toxic
• Blood
• Blood film
• Alcohol levels
• Paracetamol, salicylate, tricyclic and heavy metal levels
• Urine
• Alcohol levels
• Paracetamol, salicylate, tricyclic and heavy metal levels
• Illicit drug screen
o Septic Encephalopathy
• Blood
• Serum microbiology cultures, serology and PCR
Radiological investigations
o All patients may have to have CT scan if a lumbar puncture is contraindicated due to suspicion of raised intracranial pressure.
• Sometimes only clinical signs are needed
o Para-infectious immune mediated encephalitis
• MRI brain and spine
o Autoimmune/inflammatory encephalitis
• Whole body CT
o Metabolic
• N/A
o Vascular neoplastic
• CT or MRI head with venogram and/or angiogram
• MRI brain and MR spectroscopy
• CT chest/abdomen/pelvis
o Paraneoplastic
• CT or PET chest, abdomen and pelvis
o Toxic
• N/A
o Septic Encephalopathy
• N/A
Special investigations
o All patients with suspected encephalitis should have a lumbar puncture (LP) immediately after hospital admission unless contraindicated.
• LP
• Opening pressure.
• Total and differential white and red cell count.
• Microscopy, culture and sensitivities for bacteria.
o Mycobacterium tuberculosis if indicated.
• Protein and glucose should be compared with plasma glucose.
• All patients should have a CSF PCR test for Herpes Simplex Virus (1and 2), Varicella zoster virus and enteroviruses.
o Further viral pathogens if clinically indicated.
• Decision for further antibody testing should be made with infectious diseases team input.
o Para-infectious immune mediated encephalitis
• AntiDNAse B and Anti-streptolysin O titre
• Influenza A and B PCR/or antibody
• Biopsy
• Brain and meningeal
o Autoimmune/inflammatory encephalitis
• Angiotensin Converting Enzymes
• Biopsy
• Brain, meninges, skin and lymph node, peripheral nerve/muscle
o Metabolic
• Lactate
• Ammonia
• Pyruvate
• Amino acids
• Very long-chain fatty acids
• Biopsy
• Skin, lymph node, peripheral nerve/muscle
o Vascular neoplastic
• Cytological analysis
• Biopsy
• Brain and meningeal
o Paraneoplastic
• Biopsy
• Non-CNS viscera
o Toxic
• N/A
o Septic Encephalopathy
• N/A
o Only initial management of acute viral encephalitis in immunocompetent patients will be considered.
o Other causes of encephalitis including cases in immunocompromised patients would need specialist input.
o Initial stabilisation of the patient’s airway, breathing and circulation.
o Critical care input should be considered if there is a continued decline in consciousness to protect the airways (provide ventilator support), maintain ICP and correct electrolyte imbalances.
o Intravenous acyclovir (10mg/kg three times daily) should be started if:
• Investigation finding suggests viral encephalitis.
• Within 6 hours of admission if results unavailable.
• CSF findings normal but there is high clinical suspicion of HSV or VZV.
o In proven HSV encephalitis IV acyclovir should be continued at the same dose for 14-21 days.
• LP performed to check for negative CSF findings.
• Treatment can be stopped if there are two negative HSV PCR CSF findings 24-48hours apart
• Treatment can also be stopped if HSV PCR in the CSF is negative once over 72 hours from neurological symptom onset, unaltered consciousness and CSF white cell count less than 5×106/L.
o In proven VZV encephalitis IV acyclovir (10-15mg/kg) three times daily for up to 14 days is recommended.
• A short course of corticosteroids (prednisolone 60-80mg for 3-5 days) can be added.
o In proven enterovirus meningoencephalitis only supportive management is recommended
• In severe disease pleconaril (<0.1mcg/ml) or IV immunoglobulin can be used.
o Patients should not be discharged:
• Without a definite or suspected diagnosis.
• Without follow-up arrangements.
• Multi-disciplinary team follow-up approach with input from neuropsychologist, occupational therapist, physiotherapist and speech and language therapist.
o Acute:
• Seizures
• Malignant raised intracranial pressure
• Aspiration
• Systemic infection
• Electrolyte disturbances
• Death
o Chronic:
• Anxiety
• Depression
• Personality and behaviour change
• Epilepsy
• Memory problems
• Speech and language problems
• Movement problems

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