Pathophysiology Causes



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ENCEPHALITIS




Introduction



This is an acute encephalopathy due to an infectious agent.

Pathophysiology

Causes:

1. Herpes Virus Infection.


This is the commonest cause and the most readily treatable viral pathogen.
● Simplex (type 1 or type 2)
Less commonly Varicella
2. Rarely, other childhood viruses including:
● Mumps
● Measles, including SSPE.
● Ebstein Barr virus
● CMV

3. HIV:
This can result in a primary encephalitis.


It may also predispose to a range of “atypical” organisms, including the following:
● Toxoplasmosis
Mycoplasma
● Cryptococcus
● Treponema pallidum, (neuro-syphilis)

4. Arboviruses:


Various arthropod borne viruses, the exact one depending on geographical location and often occurring in epidemics.
Examples include:
● Murray Valley Encephalitis virus.
● Japanese encephalitis virus.
5. Cerebral Malaria
6. Rabies:
● Consider if the patient is from an endemic area, especially in association with cranial nerve lesions.
7. Slow viruses:
● Kuru, predominantly cerebellar symptoms
Creutz-feldt Jakob, a progressive dementia
8. Rarely, post vaccination.
9. In children a post viral (varicella) cerebellitis.
Differential Diagnosis:
Other important differential diagnoses associated with fever include:
● Other bacterial cerebral infections, meningitis, abscess
● Post ictal states.
● Heat stroke.
● Thyroid storm.

Clinical Features




Herpes simplex encephalitis (HSE) is by far the commonest cause in Australia.

The hallmarks are:


1. Fever.
2. CNS dysfunction:
Altered conscious state, including coma
● Confusion
Altered behaviour
● Focal signs may be seen.
3. Seizures
4. Headache
5. There may be associated meningism signs, with neck stiffness.
Notes:
● There may be a general viral prodrome, several days long consisting of fever, headache, nausea and vomiting, lethargy, and myalgias.
● The clinical presentation and course can be markedly variable.
● Acuity and severity of presentation correlates with prognosis.
● The diagnosis of HSE should be considered in any patient with a progressively deteriorating level of consciousness, fever, abnormal CSF findings, and focal neurologic abnormalities in the absence of any other causes.

Investigations

1. Blood tests:


● FBE
● CRP
● U&Es and glucose.
● Others as clinically indicated, eg HIV, Viral serology, antibodies levels are useful in identifying arbovirus and toxoplasmosis.
2. CT scan:
● To rule out other pathology, such as intracranial haemorrhage.
● It is best to do this before LP, to help rule out raised ICP, (noting however that these investigations should never significantly delay empirical treatment).
● CT may show temporal or frontal lobe changes in HSE but is much less sensitive than MRI. Approximately one third of patients with HSE have normal CT findings on presentation.
● Has the advantage of being quick and relatively easy to perform.
3. MRI:
● This may show changes of HSE before any that can be observed with CT scanning and is the best imaging technique.
● The MRI shows pathologic changes, which are usually bilateral, in the medial temporal and inferior frontal areas, in cases of HSE.
● Although a better imaging modality than CT, the requirement for a patient to remain still for a prolonged period will be problematic however in a confused patient.
● Even if normal this will still not reliably exclude encephalitis.
4. Lumbar puncture:
This is the best investigation for definitive diagnosis.
It should not be done in the first instance however if there is a suspicion of raised intracranial pressure. CT scan cannot definitively rule this out, (but is helpful if positive), and signs of raised intracranial pressure may need to be judged on a clinical basis.
CSF is sent for analysis:
Elevated protein, is suggestive.
● M&C, to rule out bacterial infection.
● Cell counts, there is usually a lymphocytosis.
PCR studies, CSF polymerase chain reaction (PCR): A PCR for DNA HSV is 100% specific and 75-98% sensitive within the first 25-45 hours.
This is the most definitive readily available test.
CSF samples are sent off to the Victorian Infectious Diseases Laboratories (VIDRL). Results can be obtained within 12-24 hours.
HSV 1&2, Varicella and CMV are usually tested for. Other viruses can be tested for on request such as measles, HIV, influenza and adeno virus
Any queries regarding PCR testing may be directed to VIDRL on 9342-2600.
● LP however will be problematic in a confused patient. It may be possible in some cases with sedation, but if not empirical treatment should never be delayed.
5. EEG:
● In HSE, characteristic paroxysmal lateral epileptiform discharges often are observed on EEG even before neuroradiographic changes.
● These findings are sensitive but not very specific for HSE.
6. Ultimately a brain biopsy may be necessary, however the need for this is now diminished with the availability of PCR testing.
7. Cerebral malaria:
This must be strongly considered in the differential diagnosis, if the patient is a returned traveller from an endemic region.
Management
1. Assess and treat any immediate ABC issues.
2. IV access and take blood tests.
3. IV acyclovir:
IV acyclovir should be commenced in a timely manner if the diagnosis of herpes encephalitis is thought to be a possibility. Note that this should not be significantly delayed for investigations.
● Give acyclovir 10 mg/kg IV, 8-hourly for at least 14 days 2
See latest Antibiotic Guidelines for full prescribing details.
4. Antibiotics:
● In the first instance it will usually not be possible to rule out a bacterial meningitis and so antibiotics should also be given to cover this possibility, (see also bacterial meningitis guidelines).
5. Other measures will be supportive.
6. No satisfactory treatment currently exists for the acute arboviral encephalitides

Prognosis 1
Untreated HSE has a mortality rate of 50-75%, virtually 100% of survivors will have long-term motor and mental disabilities.
Treated HSE correlates strongly with the severity of illness at the time of medical intervention, and morbidity is usually quoted at approximately 20%.
Mortality and morbidity are also related to host factors, such as pre-existing CNS injury and the virulence of infecting organism.
Poor outcomes are more likely in infants younger than 1 year and adults older than 55 years.

References

1. eMedicine Website October 2003, Encephalitis & HSE in Emergency medicine sections.


2. Antibiotic Guidelines, 13th ed 2006


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