Revised Encephalitis

ENCEPHALITIS

DR.M.B.AMANULLAH. Department of Pediatrics

Yenepoya Medical College

DEFINITIONS• ENCEPHALITIS is defined as an Inflammatory process of the central

nervous system with dysfunction of brain.

• In most patients both brain and meninges are involved resulting in meningoencephalitis

• Mostly caused by viruses and sometimes by other microorganisms.

• ENCEPHALOPATHY implies cerebral dysfunction due to non infectious causes like toxins, poisons, endocrinal, autoimmune disorders etc. Here there is no inflammatory process. It mimics encephalitis.

ETIOLOGY• Acute Encephalitis may be

1) PRIMARY and 2) PARAINFECTIOUS

• PRIMARY: That is Direct invasion & replication of the virus

leading to tissue necrosis

eg: Encephalitis due to Herpes simplex, Arbo virus & rabies

•

• 2) PARAINFECTIOUS:

• post infectious inflammatory response characterised by immune

mediated central nervous system damage. There will be

Demyelination with preservation of neurons & their Axons.

• Eg: ADEM (ACUTE DISSEMINATED

ENCEPHALOMYELITIS) Eg – measles, EBV, .

• Distinction between primary & parainfectious is difficult.

ETIOLOGYENCEPHALITIS :

• VIRAL ; • R.N.A viruses – Mumps, measles,

rubella, enteroviruses • D.N.A. Viruses – Herpes simplex,

CMV.• Epstein Barr, Pox Group.• ARBO viruses – Japanese B, West

Nile. Russian spring summer.• Hiv,Rabies,Choriomeningitis

virus, Dengue,• slow viruse infections, Prions.

• NON- VIRAL• BACTERIAL : Pyogenic,

Tubercular.• FUNGI: Candida , Cryptococcus,

Mucormycosis. • SPIROCHETES : Syphilis ,

Borrelia• PARASITIC : Cysticercosis,

Malaria

ETIOLOGYENCEPHALOPATHY

• Hypoxic encephalopathy• Metabolic - Diabetic ketoacidosis, uremia, hepatic coma• Fluid & Electrolyte disturbances.• Toxic / heavy metal poisoning, insecticides , substance abuse ,

alcohol.• Malignancies• Mitochondrial disorders

PATHOLOGY

• Pathological changes are non specific except in Herpes Simplex

encephalitis and rabies, where specific inclusions are demonstrable.

• Gross examination of brain usually shows DIFFUSE EDEMA,

CONGESTION & HEAMORRAGHES.

• Microscopically,there may be PERIVASCULAR CUFFING with

lymphocytes & Neutrophils.

• Neurons show Necrosis & degeneration , associated with

neuronophagocytosis.

CLINICAL FEATURES

• Clinical features are variable.• Common signs & symptoms Include FEVER, SENSORIAL ALTERATIONS ranging from

irritability to deep Coma, SEIZURES & NEUROLOGIC DEFICITS.

CLINICAL FEATURES

• Usually the onset is SUDDEN.• Child will have high Fever, Headache,

Vomiting, Mental Confusion, Irritability, Apathy, Loss of Consciousness.

• Often associated With Seizures.

Clinical Features

• Increased Intracranial pressure results in HYPERVENTILATION, CARDIORESPIRATORY INSUFFICIENCY,

• DECEREBRATION, and AUTONOMIC DYSFUNCTION.

• Various PALSIES like Ocular Palsy, Cerebellar Syndromes & Speech disturbance Can occur

Clinical Features

• In Herpes Encephalitis Lateralization To One Side with involvement of Temporal or Frontal lobe may be Seen.

• In Japanese Encephalitis Extrapyramidal Symptoms are commonly be seen.

CUSHINGS TRIADCheyne Stokes breathingBRADYCARDIAINCREASED BP

FALSE LOCALISING SIGNS Pupillary abnormalities, ptosis, VI nerve palsy, ophthalmoplegia, paralysis of upward gaze,

TYPICAL FEATURES OF INCREASED ICT

PAPILLEDEMA

FEATUES OF BRAIN HERNIATION

Unchecked brain swelling may lead to herniation at tentorial hiatus,

compression of mid brain causing deteroriation in Conciousness

Herniation of cerebellum through the foramen Magnum causes

distortion & compression of medulla oblongata with severe

disturbance of vital centres leading to respiratory or cardiac arrest.

PROGNOSIS• The course of the Illness can be variable ,from a

mild illness with complete spontaneous recovery to very severe forms.

• There may be severe Neurological residua, which may totally incapacitate the child.

DIAGNOSIS• Arrive at a precise etiological diagnosis by aCareful history, systemic examination, account of recent

illnesses or exposure to toxins.LUMBAR PUNCTURE must be done if there is no

papilledema.EEG , Neuroimaging Studies -C.T or MRI. Serum electrolytes, Blood sugar , Urea, Blood

Ammonia, Metobolic Screening, Serum Lactate,Urinary ketones, urinary analysis should be done.

Diagnosis

• Toxicologic studies to should be undertaken in suspected cases.

• Other treatable causes such as Enteric encephalophathy, malaria, shigella, toxins, poisoning, diabetes mellitus & renal diseases

should be ruled out.

• CSF Shows Mild Pleocytosis (> 5 cells / cu.mm) – observed in 95% cases ( Initial polymorphonuclear & later lymphocytic ).

• Slightly Elevated protein , and normal sugar.• Presence of RBCs in CSF is characteristic of

Herpes simplex virus Encephalitis.

LUMBAR PUNCTURE

• Viral culture ,Serology & PCR may be performed on the CSF. CSF PCR is considerd as Primary diagnostic test for CNS infection caused by CMV,EBV.,VZV & Entero.

• High (> 1000 cells/ cumm) – Arbovirus , mumps etc• Atypical lymphocytes – EBV encephalitis• Neutrophil predominance – bacterial , leptospirosis

EEG• Typically shows shows DIFFUSE SLOW WAVE

ACTIVITY in Encephalitis indicating diffuse cerebral dysfunction but is not of diagnostic value .

• Periodic latralized epileptiform discharges ( PLEDS) is Characteristic in HSV & other focal encephalitis.

NEUROIMAGING STUDY

• CT and MRI brain can help to diffentiate Viral encephalitis from metabolic or toxic disorders & Acute Disseminated Encephalomyelitis.

• BRAIN BIOPSY is rarely done nowadays.

MRI Findings in Herpes Simplex Encephalitis

DIFFERENTIAL DIAGNOSIS

1. Brain abscess 2. Cerebral malaria 3. Tuberculosis 4. Enteric

encephalopathy5. Acute Intermittent

porphyria6. Subdural empyema7. Haemorrhagic stroke8. Neoplasms of CNS

8. Para or post infectious encephalomyelitis

9. Atypical bacterial / fungal / parasitic infections of CNS

10. Toxic-metabolic encephalopathy

11. Septicemia 12. Collagen vascular disease 13. Endocarditis

TREATMENT• The AIM of treatment is• 1) SAVE THE LIFE• 2) PREVENT NEUROLOGICAL RESIDUA,• 3)RELIVE SYMPTOMS

TREATMENT - GENERAL• Treat in ICU• Maintain Airway• Maintain breathing• Maintain Circulation – appropriate I.V. fluids• Seizures should be controlled .• Cerebral edema

– Mannitol 1-2 gm/ Kg infuse quickly– Glycerol orally– Diuretics– Steroids– Elective hyperventilation

TREATMENT• Should be managed in the ICU.• Air way Should be kept patent & assisted respiration

given if necessary• HYPERPYREXIA is managed with vigorous

hydrotherapy & antipyretics.• SHOCK is managed by infusion of appropriate fluid, • Dextran or vasopressors. Dopamine or dobutamine

are added to the infusion to maintain the B.P.

Treatment

• SEIZURES are controlled by intravenous Diazepam & phenytoin.

• Raised intracranial pressure is managed by I.V. Infusion of 20% Mannitol Solution given in 30 minutes and corticosteroids such as Dexamethasone.

HERPES SIMPLEX ENCEPHALITS• IS Caused by HERPES SIMPLEX TYPE I and 2

VIRUS . (Type 2 in Neonates)• Clinical picture includes Fever of sudden onset,

Mental confusion, Vomiting , Meningeal irritation,

• Headache and Papilledema.• Seizures & neurological deficits are common.

HERPES SIMPLEX ENCEPHALITS

• IMPORTANT DIAGNOSTIC CLUES ARE

• LOCALISING SIGNS

– (focal seizures,focal parlyses. Focal EEG changes.),

• PRESENCE OF RBC IN CSF

• FOCAL INVOLVEMENTOF TEMPEROL LOBE ON CT

or MRI

TREATMENT - SPECIFIC• Should be instituted immediately. • At present HSE is the only treatable viral encephalitis:-

– Drug : Acyclovir ( Inj. Zovirax 250 mg vials)– Dose : 10 mg / kg IV infusion 8 hrly for 2-3 wks.– Toxicity : Elevation of BUN and Creatinine ,Thrombocytopenia , G.I. ( nausea, vomiting , diarrhea), Neurotoxicity (lethargy or obtundation, disorientation , confusion

agitation , hallucination , tremors, seizures), Renal insufficiency (adjust dose )

• In Acyclovir resistant cases Foscarnet is the only drug available.

PROGNOSIS• Untreated HSVE has mortality of 70% .

• On treatment mortality is 30-40%

• Complete recovery occurs in 38.5% cases receiving early acyclovir.

JAPANESE ENCEPHALITIS• CAUSED BY SINGLE STRANDED RNA VIRUS

OF THE FAMILY FLAVIVIRDAE• JE is a mosquito borne viral disease of humans

as well as horses , pigs, and other domestic animals.

• the vectors are night biting mosquito ie.• CULEX TRITATENIORHYNCUS SUMMAROSUS and CULEX VISHNUI.

CLINICAL FEATURES• After an INCUBATION PERIOD (between 4 to 14

days) cases typically progress through the following 4 stages

• PRODROMAL ILLNESS (Lasting about 2- 3 days)• ACUTE STAGE (lasting 3-4 days)• SUB ACUTE STAGE ( lasting 7-10 days) CONVALESNCE (lasting 4-7 wk)

CLINICAL FEATURES• Onset may be characterized by abrupt onset of

Fever ,headache, respiratory symptoms, anorexia, • Abdominal pain ,vomitting and sensory changes. • Psychotic episodes.• Grand mal epilepsy may be seen in some children(10 -24 percent of children)Parkinsonian like nonintention tremor and cogwheel

rigidity can also seen in some children.

CLINICAL FEATURES

• the Characteristic feature of JE is RAPIDLY

CHANGING CENRTAL NERVOUS SYSTEM SIGNS

( eg: hyperreflexia followed by hyporeflexia or

plantar response that change ).

• SENSORIUM Of the patient may vary progressing

to coma.

Diagnosis• JE should be suspected in patients who are

exposed to night biting mosquitos in endemic areas• Acute phase serum collected early in the illness

should be tested for VIRUS SPECIFIC IgM ANTIBODIES

• Also a four fold or greater increase in IgG antibody titer in paired acute & convalesent sera.

• VIRUS Can also be identified by PCR.

TREATMENT• NO Specific for treatment JE.• INTENSIVE SUPPORTIVE CARE & CONTROL

OF SEIZURES.

PROGNOSIS• FATALITY RATES ARE HIGHEST IN CHILDRENIN THE AGE GROUP OF 5-9 YRS.• Sequele is directly related to the severity and age of

the patient. Most common in children younger than 10 yrs.

• Common sequeles are MENTAL DETERIORATION• SEVERE EMOTIONAL INSTABILITY, PERSONALITY

CHANGES, MOTOR ABNORMALITIES, SPEECH DISTURBANCES

PREVENTION OF ENCEPHALITIS.

There are 3 types of JE vaccines,-1) Mouse brain derived inactivated vaccine (not used nowdays).

2) cell culture derived inactivated vaccine is used in older children & adults. Administerd I.M as two 0.5 ml doses ,28days Apart.

3) A cell cuture derived live attenauated JE VACCINE (most

efficacious ) is now available .it is a single dose vaccine & can be used in children .

PREVENTION

• CNS viral infections by Measles, Mumps, polio & varicella can be prevented by appropriate vaccines

• Control of insect vectors & adequate personal protection.

• ------------------•

SUB ACUTE SCLEROSING PANENCEPHALITIS (SSPE)

• Is a chronic complication of Measles .• It has a delayed onset & out come is always fatal.• It appears to result from a peristent Infection with

an altered measles virus that is harbored intracellularly in the CNS for several years.

• After 7-10 yrs the virus apparently regains virulence & attacks the cells in the CNS that offerd the virus protection.

SSPE

• SSPE is characterised by behavioural & intellectual deterioration , followed by myoclonic epilepsy.

• The disease is progressive in nature finally leading to extrapyramidal symptoms in inte form of dystonia & Rigidity. Dementia,coma & death follows.

• There is no defenitive cure.

Questions on Encephalitis.

1) Discuss Etiology , Clinical manifestations & management of Viral Encephalitis .

2) C.S.F in Viral Encephalitis.3) Japanese Encephalitis Vaccines.4) Discuss the management & complications Herpes Encephalitis.5) Write a short note on Subacute Sclerosing

panencephalitis..

MCQs on Encephalitis

• 1) Early treatment with ACYCLOVIR on suspicion of Herpes Encephalitis is justified since it

• A) prevents transmission of infection from person to person

• B) prevents serious Sequales• C) controls Seizures.

MCQ

• 2) Rapidly changing CNS signs are characteristic of a) Dengue fever b) Herpes encephalitisc) Japanese Encephalitis.

3) All of the following are caused by ARBO viruses except , a) Rabies b) Western Equine Encephalitis

c) Japanese encephalitis d) eastern Equine encephalitis.

MCQ

• 4) one of the following drug is not used in the treatment of Herpes Encephalitis,

• 1) Acylovir• 2) Gancyclovir.• 3) Oseltamvir• 4) Foscarnet.

MCQ

• 5) SSPE (Subacute Sclerosing Pan encephalitis ) is a late complication of

1) German Measles.2) Herpes Encephalitis3) Measles4) Japanese Encephalitis

MCQ

• 6) LATRALIZATION to one side is frequently seen in

• 1) Japanese Encephalitis• 2) Rabies• 3) Herpes Encephalitis• 4) SSPE.

MCQ

• 7) CUSHING S TRIAD INCLUDES • 1) Increased B.P.• 2) Tachycardia• 3) Cheyne Stokes Breathing• 4) Bradycardia.

MCQ

• 8) Negri bodies is an inclusion body seen in• 1) Rabies • 2) Mumps Encephalitis• 3) SSPE• 4) Japenese encephalitis.

MCQ

• 9) Herpes simplex Virus type 2 can causeEncephalitis in 1) Adolascents 2) New borns 3) Old aged.

MCQ

• 10) Presence of RBCs in CSF & focal involvement of temporal lobe Can be important diagnostic tool in 1) SSPE

• 2) Herpes simplex encephalitis.• 3) Dengue fever.

Thank you