ENCEPHALITIS

Dr Muhammad Abdelmoneim ICU

Registrar

Definition

Encephalitis, an inflammation of the brain parenchyma which presents as diffuse and/or focal neuropsychological dysfunction

Meningitis vs Encephalitis

Normal brain function is the distinctionSeizures and postictal state can occur in meningitis Some times it is difficult to differentiate

Cerebritis describes the stage preceding abscess formation and implies a highly destructive bacterial infection of brain tissue

Definitions

Etiology

Infectious :

• Viral (HSV-VZV-CMV-EBV-Arboviruses-Ticoviruses)• Parasitic ( Toxoplasmosis)• Bacterial rare ( Mycoplasm)

Non-infectious : • Post infection (demylinating process)• Autoimmune

Epidemiology

•Determining the true incidence of encephalitis is impossible

•HSE, the most common cause of sporadic encephalitis in Western countries, is relatively rare; the overall incidence is 0.2 per 100,000, with neonatal HSV infection occurring in 2-3 per 10,000 live births

•The arbovirus group is the most common cause of episodic encephalitis, with a reported incidence similar to that of HSV

•These statistics may be misleading in that most people bitten by arbovirus-infected insects do not develop clinically apparent illness and, of those who do, less than 10% develop overt encephalitis

Pathophysiology

Infectious :

Many viruses are transmitted by humans, though most cases of HSE are thought to be reactivation of HSV lying dormant in the trigeminal ganglia

Mosquitoes or ticks inoculate arbovirus, and rabies virus is transferred via an infected animal bite or exposure to animal secretions

With some viruses, such as varicella-zoster virus (VZV) and cytomegalovirus (CMV), an immune-compromised state is usually necessary to develop clinically apparent encephalitis

In general, the virus replicates outside the CNS and gains entry to the CNS either by hematogenous spread or by travel along neural pathways (eg, rabies virus, HSV, VZV)

•Non-infectious:

The etiology of slow virus infections, such as those implicated in the measles-related subacute sclerosing panencephalitis (SSPE) and progressive multifocal leukoencephalopathy (PML), is poorly understood

Pathophysiology

•Once across the blood-brain barrier, the virus enters neural cells, with resultant disruption in cell functioning, perivascular congestion, hemorrhage, and a diffuse inflammatory response that disproportionately affects gray matter over white matter

•Regional tropism associated with certain viruses is due to neuron cell membrane receptors found only in specific portions of the brain, with more intense focal pathology in these areas

A classic example is the HSV predilection for the inferior and medial temporal lobes

Pathophysiology

In contrast to viruses that invade gray matter directly, acute disseminated encephalitis and postinfectious encephalomyelitis (PIE), most commonly due to measles infection and associated with Epstein-Barr virus (EBV) and CMV infections, are immune-mediated processes that result in multifocal demyelination of perivenous white matter

Pathophysiology

Presentation

Variable

The acuity and severity of the presentation correlate with the prognosisA history of mosquito or tick bites or exposure to mouse/rat droppings should be soughtanimal bite(s)

A prodrome of several days and consists of fever, headache, nausea and vomiting, lethargy, and myalgias

Presentation

The classic presentation is encephalopathy with diffuse or focal neurologic symptoms, including

•Behavioral and personality changes, with decreased level of consciousness

•Neck pain, stiffness

•Photophobis

•Lethargy

•Generalized or focal seizures (60% of children with CE)

•Acute confusion or amnestic states

•Flaccid paralysis (10% of patients with WNE)

Presentation

•(VZV), (EBV), (CMV), measles virus, or mumps virus includes a prodrome of rash, lymphadenopathy, hepatosplenomegaly, and parotid enlargement

•Dysuria and pyuria are reported with St Louis encephalitis

•Extreme lethargy has been noted with West Nile encephalitis (WNE)

Presentation

Physical Examination

•Typically

•Altered mental status

•Personality changes are very common

•Focal findings, such as hemiparesis, focal seizures, and autonomic dysfunction

•Movement disorders (St Louis encephalitis, eastern equine encephalitis [EEE], western equine encephalitis [WEE])

• Ataxia • Cranial nerve defects

Meningismus (less common and less pronounced than in meningitis)Unilateral sensorimotor dysfunction (postinfectious encephalomyelitis [PIE])Dysphagia, particularly in rabies

HSV in neonates (aged 1-45 d) may include the following:

Herpetic skin lesions over the presenting surface from birth or with breaks in the skin, such as those resulting from fetal scalp monitorsKeratoconjunctivitisOropharyngeal involvement, particularly buccal mucosa and tongueEncephalitis symptoms, such as seizures, irritability, change in level of attentiveness, bulging fontanellesAdditional signs of disseminated, severe HSV include jaundice, hepatomegaly, and shock

Complications

• Seizures • Syndrome of inappropriate secretion of antidiuretic hormone (SIADH) • Increased intracranial pressure (ICP) •Coma

Work-up

Most cases are viral in origin

•So in addition to standard test, studies may be performed to identify the infectious agent causing the encephalitis

•It is important, when possible, to distinguish acute arboviral encephalitides from potentially treatable acute viral encephalitides (HSE and VZE) as a high suspicion for these disorders and prompt treatment can reduce the severity of neurological sequelae and can be lifesaving

LP should be performed on all patients suspected of having a viral encephalitis

•Gram staining to rule out bacterial meningitis

•PCR for HSV DNA 100% specific and 75-98% sensitive within the first 25-45 hours. Types 1 and 2 cross-react, but no cross-reactivity with other herpes viruses occurs

•Virul culture when viruses other than HSV are suspected( Mumps, Measles, Influenza, Parainfluenza) or in case PCR is not available

•Serologic tests for toxoplasmosis can be helpful in light of an abnormal computed tomography (CT) scan, particularly in the case of single lesions

Work-up

CT, MRI, EEG

Performance of a head CT scan with and without contrast agent should be performed in virtually all patients with encephalitis

This should be done prior to LP if there are focal complaints or findings, signs to search for evidence of elevated intracranial pressure (ICP), obstructive hydrocephalus, or mass effect due to focal brain infection

Work-up

(a) CT in the early stages of herpes encephalitis showing reduced attenuation in the right temporal lobe. (b) MR image showing bilateral changes involving the temporal lobes and right cingulate gyrus.

•MRI is more sensitive than CT scanning in demonstrating brain abnormalities earlier in the disease course

•In HSE, MRI may show several foci of increased T2 signal intensity in medial temporal lobes and inferior frontal gray matter. Head CT commonly shows areas of edema or petechial hemorrhage in the same areas

•Invovement of the thalamus and basal ganglia may be observed in the setting of encephalitis due to respiratory virul infection, Creutzfeld-Jacob disease, arbovirus and TB

•In toxoplasmosis, contrast-enhanced head CT typically reveals several nodular or ring-enhancing lesions. Because lesions may be missed without contrast, MRI should be performed in patients for whom use of contrast material is contraindicated

Work-up

bilateral frontal cortex and subcortical white matter This is a typical pattern for viral encephalitis

HSV tends to attack the "limbic system" responsible for the integration of emotion, memory, and complex behaviorThere is a region of very bright signal on MR in the medial temporal lobe at left (patient's right). This corresponds to an area of active viral leptomeningeal and brain tissue infection. ( Image was taken 5 days after infection)

Work-up

•In HSE, electroencephalography (EEG) often documents characteristic paroxysmal lateral epileptiform discharges (PLEDs), even before neuroradiography changes. Eventually, PLEDs are positive in 80% of cases; however, the presence of PLEDs is not pathognomonic for HSE

Work-up

•Brain Biopsy

•Although most histologic features are nonspecific, brain biopsy is the criterion standard because of its 96% sensitivity and 100% specificity.

Treatment

•Emergency Department CareWith the important exceptions of HSE and varicella-zoster encephalitis, the viral encephalitides are not treatable beyond supportive care.

Treatments for T gondii and cytomegalovirus (CMV) encephalitis are available but generally not initiated in the ED

•The goal of treatment for acutely ill patients is administration of the first dose or doses of acyclovir, with or without antibiotics or steroids, as quickly as possible.

The standard for acute bacterial meningitis is the initiation of treatment within 30 minutes of arrival

Collect laboratory samples and blood cultures before the start of IV therapy.

Even in uncomplicated cases of encephalitis, most authorities recommend a neuroimaging study (eg, MRI or, if that is not available,CT scan before LP

Management of hydrocephalus and increased intracranial pressure

•Empiric adult emergency treatment for herpes simplex virus (HSV) meningoencephalitis and varicella-zoster virus (VZV) encephalitis consists of acyclovir 10 mg/kg (infused over 1 h) q8h for 14-21 days

•In HIV-positive patients, consider foscarnet, given the increased incidence of acyclovir-resistant HSV and herpes zoster virus (HZV)