Encephalitis

• Encephalitis is a broad term that refers to inflammation of the brain parenchyma.
• There are many different aetiologies of encephalitis which characteristically presents with abnormal brain function. This is suggested by altered mental status, motor/sensory deficits, personality change, or even speech alteration.
• Encephalitis may be due to a wide variety of pathologies including viral, post-infective, bacterial, autoimmune, or paraneoplastic.
• The most important infective aetiology to exclude is herpes simplex virus (HSV) encephalitis that is usually fatal without treatment.
• Aetiology:

  • Infectious - secondary to direct infection by a microorganism or virus
  • Non-infectious - usually secondary to an immune-mediated mechanism related to cancer, autoimmunity, or following an infection
• Infectious:

  • HSV is a common cause of sporadic encephalitis that can be targeted with treatment
  • Other viral pathogens - arboviruses, varicella-zoster virus, EBV and HIV
  • Bacteria - mycoplasma, TB
  • Fungi
  • Parasites
  • May be concurrent inflammation of the meninges leading to meningoencephalitis
• Paraneoplastic encephalitis: abnormal immune response against different parts of the brain in the setting of cancer. Thought to be due to shared antigens expressed exclusively by the tumour and nervous system
• Post-infectious encephalitis: development of encephalopathy (and other neurological signs) following an infection or vaccination. Due to shared antigens between infection and central nervous tissue. Causes generation of autoreactive T cells that react to antigens in the central nervous system leading to inflammation.
• Autoimmune encephalitis: an increasingly recognised condition whereby autoantibodies develop against neuronal cell surface/synaptic proteins that lead to characteristic clinical syndromes depending on the autoantibody present.
• HSV encephalitis:

  • Can occur in all ages
  • May be due to HSV type 1 or 2
  • Causes clinical syndrome characterised by rapid onset of fever, headache, altered mental status, new-onset seizures and/or neurological deficits
  • Behavioural changes may be seen
  • Can cause infection by direct invasion via the trigeminal nerve or olfactory nerve following primary oropharyngeal infection
  • Or due to reactivation of virus
  • Damage classically located within the temporal lobes
• Post-infectious encephalitis is an uncommon immune-mediated disorder that is usually seen in children.
• Post-infectious encephalitis, also known as acute disseminated encephalomyelitis (ADEM), is a demyelinating condition affecting the central nervous system. Demyelination refers to the destruction/loss of myelin that surrounds nerve axons and helps increase the rate of electrical impulses. Usually 4-13 days following an infection or vaccination.
• The N-Methyl-D-aspartate (NMDA) receptor in the brain is a receptor of glutamate, the primary excitatory neurotransmitter in the human brain.
• In NMDA-encephalitis there is a classic set of symptoms:

  • Psychiatric manifestations
  • Memory deficits
  • Sleep Deficits
  • Seizures
  • Altered mental status
  • Autonomic instability
• The classic presentation of acute encephalitis is fever, headache, altered mental status and/or focal neurological deficits.
• Possible symptoms of encephalitis:

  • Fever
  • Headache
  • Seizures
  • Altered mental status
  • behavioural changes
  • Brainstem dysfunction - dysphagia, dysarthria and gaze palsies
  • Memory problems
  • Focal neurological deficits
• Neuroimaging, electroencephalography (EEG) and cerebrospinal fluid (CSF) analysis are important in the work-up of encephalitis.
• Imaging of the brain is useful to exclude an alternative diagnosis such as cerebrovascular event (i.e. stroke) or space-occupying lesion (e.g. tumour). A CT may be completed initially because it is relatively easy to access and produces a quick result. However, MRI can provide more detail and some features on MRI may be supportive of encephalitis.
• An electroencephalogram is a non-invasive method of assessing and recording the electrical activity of the brain. In a patient with altered mental status of unknown cause is important to exclude non-convulsive status epilepticus. This refers to ongoing seizure activity without obvious tonic-clonic activity. Certain electrical activity on an EEG may be suggestive of encephalitis.
• • CSF protein: a rise in the protein content is typical with encephalitis. May be normal.
  • CSF viral PCR: involves amplification of viral genetic material within the CSF. Can be used to confirm the diagnosis of HSV encephalitis or other viral pathogens that can be tested.
  • CSF microscopy, culture and sensitivity: provides a white cell count that may be elevated in encephalitis. Microscopy and culture are completed to exclude a bacterial pathogen.
  • CSF glucose: typically normal in viral encephalitis
  • CSF serology: antibody tests can be performed on the CSF.
• The principal treatment of HSV encephalitis is intravenous aciclovir.
• Immunosuppressive therapies (e.g. steroids) can be used to treat paraneoplastic, autoimmune, and post-infective causes but it is essential an infection is excluded before these are initiated.
• MRI findings in encephalitis = abnormality highly restricted to bilateral medial temporal lobes on T2 weighted FLAIR images
• EEG findings = slow wave or epileptic activity corresponding to temporal lobes
• A large amount of patients with NMDAR have an underlying neoplasm - most commonly ovarian teratoma

  Therefore after diagnosis, patients should undergo screening for presence of a neoplasm
• First line treatment for autoimmune encephalitis:

  • IV corticosteroids
  • IV immunoglobulins
  • Plasmapheresis (alone or combined)
• Glutamate is the most common excitatory neurotransmitter in the brain. It works via the NMDA receptor.