ENCEPHALITIS

-GUNASEELAN KUMAR

DEFINITION

Acute central nervous system (CNS) dysfunction with radiographic or laboratory evidence of brain inflammation CNS dysfunction includes
seizures
focal

neurologic findings alteration in mental status.

CAUSES
VIRUS

Arboviruses

examples: Japanese encephalitis; West Nile encephalitis virus; Eastern,Western and Venzuelan equine encephalitis virus; tick borne encephalitis virus Eg: HSV-1, HSV-2, varicellazoster virus, cytomegalovirus, Epstein-Barr virus

Herpes viruses

Adenoviruses Influenza A Enteroviruses, poliovirus Measles, mumps, and rubella viruses Rabies

CAUSE- VIRUS (JE)

Most important cause of arboviral encephalitis worldwide, with over 45,000 cases reported annually Transmitted by culex mosquito (breeds in rice fields) Mosquitoes become infected by feeding on domestic pigs and wild birds infected with Japanese encephalitis virus Infected mosquitoes transmit virus to humans and animals during the feeding process

CAUSES

Bacteria
H. influenza S. pneumoniae N. meningitidis M. tuberculosis Mycoplasma pneumoniae

Others

Rickettsia, Spirochete & Malaria

TYPES
Two forms Primary encephalitis Post or parainfectious encephalitis (secondary)

TYPESPRIMARY ENCEPHALITIS

Primary encephalitis
Results

from direct CNS invasion by the offending

agent the gray matter often is targeted.

TYPESPRIMARY ENCEPHALITIS

Organisms gain entry to the CNS directly Eg. arboviruses initially cause bloodstream infection, then enter the CNS via endothelial cell infection cell transport, or carriage in cells enteringthe CNS. An alternative mechanism Eg. herpes simplex virus (HSV), rabies, and possibly poliovirus is retrograde transport in neurons (less immune surveillance) Eg. amoeba Naegleria fowleri is entry through the olfactory mucosa.

TYPESPRIMARY ENCEPHALITIS

Variety of anatomic sites can be infected

HSV neurons in the temporal lobe Rabies pons, medulla, cerebellum, hippocampus Japanese encephalitis brainstem and basal ganglia

Neurologic signs and symptoms develop after infection result of direct

neuronal

injury, the host inflammatory response (include perivascular inflammation, gliosis, and brain

TYPESSECONDARY ENCEPHALITIS
Post/parainfectious (secondary)
not

caused by direct CNS infection neurologic effects are the consequence of the hosts immune response faulty immune system reaction in response to an infection elsewhere in the body) often affects the white matter

TYPESSECONDARY ENCEPHALITIS

occurs days to weeks after the onset of an infection pathogen is not detected in the CNS in postinfectious encephalitis hypothesized to be caused by an aberrant immune response against brain antigens such as myelin basic protein Subsequent demyelination causes focal or global CNS dysfunction Postinfectious encephalitis often is called acute disseminated encephalomyelitis (ADEM).

CLINICAL MANIFESTATION

Initial Signs
Fever

(usually high grade) Headache Malaise Anorexia Nausea and Vomiting Abdominal pain

CLINICAL MANIFESTATION

Developing Signs
Altered

LOC mild lethargy to deep coma confused, delirious, disoriented Mental aberrations : Hallucinations personality change behavioral disorders ; occasionally frank psychosis Focal or general seizures in >50% severe cases. Severe focused neurologic deficits

CLINICAL MANIFESTATION
Neurologic Signs Most Common

Aphasia Ataxia

Hemiparesis

with hyperactive tendon reflexes Involuntary movements Cranial nerve deficits (ocular palsies, facial weakness)

DIAGNOSIS

PATIENT HISTORY PHYSICAL EXAM LABORATORY AND RADIOLOGICAL INVESTIGATIONS

DIAGNOSISPATIENTS HISTORY

Recent travel and the geographical :

Africa Cerebral malaria Asia Japanese encephalitis High risk regions of Europe and USA Lyme disease

Recent animal bites Tick borne encephalitis orRabies

Occupation

Forest worker, exposed to mosquitoes Medical personnel, possible exposure to infectiousdiseases Farmers- pig farms (nipah virus), japanese encephalitis

DIAGNOSIS PHYSICAL EXAM

Focal neurological deficit HSV encephalitis Hallucination or aphasia HSV encephalitis Local paresthesia Rabies encephalitis Brain stem signs, Unilateral peripheral motor weakness or Cerebellar sign Meliodosis Eschar Scrub typhus ParotitisMumps Systemic sign eg. Rash Mycoplasma & Enterovirus Regional adenopathies herpangina, HFMD (enterovirus)

DIAGNOSISLABORATORY

FBC : usually within the reference range Electrolytes : usually within reference range

Syndrome of inappropriate secretion of antidiuretic hormone (SIADH)

Serum glucose: Use this level as a baseline for determining normal CSF glucose values RP / LFT :Assess organ function and the need to adjust the antibiotic dose Coagulation profile : if DIC is suspected Urinary electrolyte test: if SIADH is suspected

DIAGNOSISLABORATORY (NON-CNS)

Cultures of body fluid specimens

(e.g., from blood,stool, nasopharynx, or sputum) to identify various viral, bacterial, and fungal etiologies of encephalitis Lumbar puncture- CSF examination (Polymorphonuclear cells may predominate early in the illness but are replaced by mononuclear cells within hours)

Viral culture Viral PCR may identify the virus body fluids other than CSF Serology tests antibodies to an specific virus (IgM) JEV,Dengue, Mycoplasma (4 fold rising)

DIAGNOSISLAB (CNS)

CSF- virus-specific IgM in CSF specimens may be indicative of CNS disease caused by that pathogen Nucleic acid amplification tests (such as PCR) Herpes simplex PCR should be performed on all CSF specimens in patients with encephalitis . In patients with encephalitis who have a negative herpes simplex PCR result, consideration should be given to repeating the test 37 days later in those with a compatible clinical syndrome or temporallobe localization on neuroimaging Viral cultures of CSF specimens (not routinely recommended) Brain biopsy (rarely done;unknown etiology whose condition deteriorates despite aggressive treatment with acyclovir

DIAGNOSISIMAGING

Imaging- to rule out SOL and other causes of CNS disturbance MRI is the most sensitive to evaluate patient with encephalitis (CT/CECT only if MRI not available/cant be performed)

DIAGNOSISIMAGING

EEG-needed to assess seizure activity and may help localize the region of encephalitic involvement

TREATMENT
EMPERICAL THERAPHY Acyclovir should be initiated to all patient suspected encephalitis, pending results Other antimicrobial esp presumed bacterial meningitis should be started if clinically suggestive In case postinfectious encephalitis or encephalitis unknown cause- Intravenous Ig/corticosteroid should be started after consulting ID specialist

TREATMENT
SPECIFIC THERAPHY Herpes simplex - Acyclovir Varicella Zoster Acyclovir CMV- Ganciclovir Mycoplasma pneumonia-azithromycin, doxycycline, or a fluoroquinolone Mycobacterium TB- 4 drug anti TB with dexamethasone

TREATMENT
SUPPORTIVE TREATMENT Reduce intracranial pressure : restrict fluid, hyperventilation( if on ventilator), lower body temperature , Rest, nutrition, fluids (SIADH), antipyretic, Anticonvulsant Acute psychosis : haloperidol

PROGNOSIS

Depends the virulence of the virus and on variables associated with the patient's health status, such as extremes of age, immune status, and preexistingneurologic conditions Rabies, EEE, JE, and untreated HSE have high rates of mortality and severe morbidity, including mental retardation, hemiplegia, and seizures

Acute Disseminated Encephalomyelitis (ADEM)

Postinfectious encephalitis often features that permit classification as ADEM.

infection that occurred days to weeks before the onset of neurologic symptoms.

The infectionmay be memorable

measles, or minor, such as a respiratory tract infection

The diagnosis usually is considered because of the distinctive findings on MRI of the brain and spine Classically, white matter is affected more than gray matter, but basal ganglion and thalamic lesions often are described

Acute Disseminated Encephalomyelitis (ADEM)

Distinguishing ADEM important to optimize therapy

high doses of glucocorticoids to limit further, presumed immune-mediated, damage to the CNS Alternative are IVIG

Most patients who have ADEM make a clear and often complete recovery (however, the prognosis should be guarded)

CONCLUSION

Encephalitis is an uncommon and disturbing illness whose cause often remains enigmatic despite extensive diagnostic efforts. Clinicians should focus

treatable and common causes; empiric therapy for bacterial meningitis and herpes simplex encephalitis should be started while awaiting results

Many patients will not receive a specific diagnosis Duration of therapy should be decided in consultation with neurology and infectious disease specialists. Supportive care and early referral for rehabilitation maximize functional recovery.

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