<p> ENCEPHALITIS</p><p>Introduction</p><p>This is an acute encephalopathy due to an infectious agent.</p><p>Pathophysiology</p><p>Causes:</p><p>1. Herpes Virus Infection.</p><p>This is the commonest cause and the most readily treatable viral pathogen.</p><p>● Simplex (type 1 or type 2)</p><p>● Less commonly Varicella</p><p>2. Rarely, other childhood viruses including:</p><p>● Mumps</p><p>● Measles, including SSPE.</p><p>● Ebstein Barr virus</p><p>● CMV</p><p>3. HIV:</p><p>This can result in a primary encephalitis.</p><p>It may also predispose to a range of “atypical” organisms, including the following:</p><p>● Toxoplasmosis</p><p>● Mycoplasma</p><p>● Cryptococcus</p><p>● Treponema pallidum, (neuro-syphilis)</p><p>4. Arboviruses:</p><p>Various arthropod borne viruses, the exact one depending on geographical location and often occurring in epidemics. Examples include:</p><p>● Murray Valley Encephalitis virus.</p><p>● Japanese encephalitis virus.</p><p>5. Cerebral Malaria</p><p>6. Rabies:</p><p>● Consider if the patient is from an endemic area, especially in association with cranial nerve lesions.</p><p>7. Slow viruses:</p><p>● Kuru, predominantly cerebellar symptoms</p><p>● Creutz-feldt Jakob, a progressive dementia</p><p>8. Rarely, post vaccination.</p><p>9. In children a post viral (varicella) cerebellitis.</p><p>Differential Diagnosis:</p><p>Other important differential diagnoses associated with fever include:</p><p>● Other bacterial cerebral infections, meningitis, abscess</p><p>● Post ictal states.</p><p>● Heat stroke.</p><p>● Thyroid storm.</p><p>Clinical Features</p><p>Herpes simplex encephalitis (HSE) is by far the commonest cause in Australia.</p><p>The hallmarks are:</p><p>1. Fever.</p><p>2. CNS dysfunction:</p><p>● Altered conscious state, including coma</p><p>● Confusion</p><p>● Altered behaviour ● Focal signs may be seen.</p><p>3. Seizures</p><p>4. Headache</p><p>5. There may be associated meningism signs, with neck stiffness.</p><p>Notes:</p><p>● There may be a general viral prodrome, several days long consisting of fever, headache, nausea and vomiting, lethargy, and myalgias.</p><p>● The clinical presentation and course can be markedly variable. </p><p>● Acuity and severity of presentation correlates with prognosis.</p><p>● 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.</p><p>Investigations</p><p>1. Blood tests:</p><p>● FBE</p><p>● CRP</p><p>● U&Es and glucose.</p><p>● Others as clinically indicated, eg HIV, Viral serology, antibodies levels are useful in identifying arbovirus and toxoplasmosis.</p><p>2. CT scan:</p><p>● To rule out other pathology, such as intracranial haemorrhage.</p><p>● 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).</p><p>● 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.</p><p>● Has the advantage of being quick and relatively easy to perform.</p><p>3. MRI: ● This may show changes of HSE before any that can be observed with CT scanning and is the best imaging technique. </p><p>● The MRI shows pathologic changes, which are usually bilateral, in the medial temporal and inferior frontal areas, in cases of HSE.</p><p>● 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.</p><p>● Even if normal this will still not reliably exclude encephalitis.</p><p>4. Lumbar puncture:</p><p>This is the best investigation for definitive diagnosis.</p><p>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.</p><p>CSF is sent for analysis:</p><p>● Elevated protein, is suggestive.</p><p>● M&C, to rule out bacterial infection.</p><p>● Cell counts, there is usually a lymphocytosis.</p><p>● 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. </p><p>This is the most definitive readily available test.</p><p>CSF samples are sent off to the Victorian Infectious Diseases Laboratories (VIDRL). Results can be obtained within 12-24 hours.</p><p>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 </p><p>Any queries regarding PCR testing may be directed to VIDRL on 9342-2600.</p><p>● 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. </p><p>5. EEG: ● In HSE, characteristic paroxysmal lateral epileptiform discharges often are observed on EEG even before neuroradiographic changes. </p><p>● These findings are sensitive but not very specific for HSE.</p><p>6. Ultimately a brain biopsy may be necessary, however the need for this is now diminished with the availability of PCR testing.</p><p>7. Cerebral malaria:</p><p>● This must be strongly considered in the differential diagnosis, if the patient is a returned traveller from an endemic region. </p><p>Management</p><p>1. Assess and treat any immediate ABC issues.</p><p>2. IV access and take blood tests.</p><p>3. IV acyclovir:</p><p>● 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.</p><p>● Give acyclovir 10 mg/kg IV, 8-hourly for at least 14 days 2</p><p>See latest Antibiotic Guidelines for full prescribing details.</p><p>4. Antibiotics:</p><p>● 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). </p><p>5. Other measures will be supportive.</p><p>6. No satisfactory treatment currently exists for the acute arboviral encephalitides</p><p>Prognosis 1</p><p>Untreated HSE has a mortality rate of 50-75%, virtually 100% of survivors will have long-term motor and mental disabilities. </p><p>Treated HSE correlates strongly with the severity of illness at the time of medical intervention, and morbidity is usually quoted at approximately 20%.</p><p>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.</p><p>References</p><p>1. eMedicine Website October 2003, Encephalitis & HSE in Emergency medicine sections.</p><p>2. Antibiotic Guidelines, 13th ed 2006</p>