ACUTE FEBRILE ENCEPHALOPATHY- Common condition leading to

hospital admission in adults and children in

india.

- CNS infections are commonest cause of

non traumatic coma in elderly and children.

ENCEPHALOPATHY

A diffuse disease of brain that alters its structure or function .

Encephalopathy caused by variety of infective , metabolic , toxic , ishemic / hypoxic , nutritional causes .

encephalopathy may result from pathogenic mechanisms affecting nervous system directly or systemic complication like hypoglycemia , hypovolemia , hyperpyrexia ,hypoxia ,anemia ,hepatic / renal failure and bleeding may contribute to its pathogenesis.

Encephalitis, an inflammation of the brain parenchyma, presents as diffuse and/or focal neuropsychological dysfunction. From an epidemiologic and pathophysiologic perspective, encephalitis is distinct from meningitis, though on clinical evaluation the two often coexist (meningoencephalitis) with signs and symptoms of meningeal inflammation, such as photophobia, headache, or a stiff neck.

Cerebritis describes the stage preceding abscess formation and implies a highly destructive bacterial infection of brain tissue, whereas acute encephalitis tends most commonly to be a viral infection with parenchymal damage ranging from mild to profound.

FEBRILE ENCEPHALOPATHY CHALENGES IN MANAGEMENT Physicion /intensivist is faced with

the challenge of emergency management , identification of cause and its treatment not only to ensure survival but also to prevent long term sequelae , neurological or otherwise .

few of such clinical situation which present as febrile encephalopathy are

CLASSIFICATION

INFECTIVE NONINFECTIVE -VIRAL INFECTIONS - HYPERTHERMIC

- PARASITIC INFECTIONS - BACTERIAL INFECTIONS - FUNGAL INFECTIONS

VIRAL ENCEPHALITIS

CAUSATIVE VIRUSES:- DNA VIRUSES :- HERPES VIRUS - HERPES SIMPLEX -VARICELLA-

ZOSTER -CMV -EBV PAPOVA VIRUS -JC VIRUSES

RNA VIRUSES :-1. PICORNA VIRUS-ENTERO- POLIO

VIRUSES2. TOGAVIRUSES-

--ALPHA VIRUSES- EQUINE ENCEPHALITIS

--FLAVI VIRUSES-JE , . , DENGUE, OTHER -- RUBI VIRUSE – RUBELLA VIRUS3. PARAMYXOVIRUSES- MUMS , MEASLES , 4.RHABDOVIRUSES-- RABIES VIRUS,

CHANDIPURA VIRUS5. RETRO VIRUSES -- HIV

VIRAL ENCEPHALITIS

viral encephalitis can be due to direct effects of an acute infection or as one the sequelae of a latent infection

pathogenesis:- virus enter the body through respiratory tract alimentory tract skin conjuctiva genitalia vertical transmission ( along peripheral nerve axons e. g.HSV ,

RABIES)

In general viral encephalitis can be caused by three different mechanisms :-

1. acute virus encephalitis2. Post infectious viral encephalitis3. Slow virus infections

CLINICAL FEATURES Prodromal phase :-few days –several

days Meningial signs Altered conciousness Change in mental status Seizurs Focal neurological distrubances -aphasia -ataxia -hemiparesis -involuntory movements -cranial nerve palsy sensory distrubances

- involvement of hypothalamic pituitary axis

- temp. dysregulation - diabetes insipidus - SIADH - BRAINSTEM ENCEPHALITIS - SYSTEMIC INVOLVEMENT

LABORATORY DIAGNOSIS OBJECTIVES :- 1. to differentiate encephalitis from

other conditions mimicking encephalitis 2.to search treatable cause 3. for prognostic and epidemiological

purposes BASIC INVESTIGATIONS :- PS, CBC ,

BLOOD SUGER, LFT , KFT , CP, URINE EXAMINATION

1. CSF:- - pressure is high

-proteins increased -glucose normal Pleocytosis (10-2000 cells /mm) -early stage-PMN -generally – lymphocytic pleocytosis -severly immunocompramised-

absent pleocytosis -atypical lymphocytes-EBV,CMV,HSV -PMN pleocytosis- echo virus 9 -entero

viruses CSF : -ELIZA -CULTURE

PCR:- -CSF,BLOOD -diagnostic –

HBV,HSV,CMV,VZV and ENTEROVIRUSES

-results are not affected by < 1 week of antiviral therapy

SEROLOGICAL STUDIES :- -serum antibody detection by paired

serum sample examination -antibody titers at least 4 times initial

test are diagnosticsIMAGING TECHNIQUES -MRI (preferred)

-C.T.SCAN -SPECT -PET Helps to differentiate between focal and

diffuse lesion EEG:- -diffuse encephalitis-diffuse slow

activity - focal lesion-e.g.HSV spike and slow wave activity and

periodic lateralised epileptiform discharges arising

from temporal and frontal lobe

BRAIN BIOPSY RABIES- GOLD STANDARD -HSV D/D:- Non infective causes:- -vascular disease - tumors - toxic encephalopathy -reye’s syndrom -SLE Infective cause - non viralencephalitis

meningitis ,brain abscess

Herpes simplex encephalitis Double stranded DNA virus Types: 1. HSV-1 2. HSV- 2 Most common cause of sporadic cases of

viral encephalitis >95% - HSV-1 Affect all ages , both sexes, all over world Pathogenesis: - enter CNS via peripheral nerves -children and young adults -

primary infection

adults - reactivation - reinfection Pathology: - sever necrotising encephalitis

-brain swollen , congested , hemorrhagic damage with necrosis and liquefaction of temporal and frontal lobe

- eosinophilic intranuclear inclusion bodies(cowdry type A)

CLINICAL FEATURES:- - insidious onset - prodromal phase – 4 to 10 days - signs of of encephalitis - signs of frontal and temporal lobe

dysfunction DIGNOSIS: -MRI - normal -diffuse cerebal edema -focal abnormalities 1. mass efects 2. infarctive changes -CSF PCR – dignostic - EEG – spike and slow wave activity –

temporal lobe - serological test – not useful for early dignosis - brain biopsy

Treatment:-

General treatment of viral encephalitis

Acyclovir – 10 mg /kg , 8 hourly iv slowly x 14d.

Complications :- -Renal dysfunction -trombocytopenia -g.i.toxicity -nurotoxicity Prevention:-vaccines are under trial

VARICELLA ZOSTER ENCEPHALITIS VZV DNA Virus Neurological complications –rare -90% encephalitis – 50% cerebellar ataxia Cerebellar syndrom – few days to 2 weeks after rash Complete recovery Diagnosis - imaging - CSF not specific - EEG Mortality – 1o % Sequel - 25 % Encephalitis - rare complications of zoaster -seen in older persons with cranial

nerve involving TREATMENT: - ACYCLOVIR - SPECIFIC VZ IMMUNOGLOBULIN

CYTOMEGALOVIRUS ENCEPHALITIS Double strand DNA virus Common opportunistic pathogen in

immunocompramised Most common pathogen to infect foetus via

transplacental spread Cytomegalic incusion disease - < 5 % of infected

fetus -low birth weight - joundice - hepatosplenomegaly - thrombocytopenia -choroidoretinitis -encephalitis

Pathology - periventricular calcification - ventricular dilatation Dignosis -PCR – CMV –DNA inCSF TREATMENT GANCICLOVIR -induction phase 5 mg / kg BD - maintainance phase 5 mg /kg

BD FOSCARNATE - Induction phase -60 mg /kg

TDS -maintenance – 60 to 12o mg/ kg

OD CIDOFOVIR - 5 mg / kg once weekly for two

weeks

EBV ENCEPHALITIS

Ds- DNA Neurological complication -0.5 % Encephalitis- cerebellum Treatment - symptomatic

RABIES ENCEPHALITIS Bullet shaped rhabdo virus – RNA Virus

Transmited by bite of infected animal

Virus reaches CNS via peripheral nerves

Pathology - neuronal destruction

- negri bodies

Incubation period – 3 weeks to 3 months

Clinical features – prodromal phase – 1 – 4 days

- encephalitis phase

- brain stem encephalitis

-dumb rabies – ascending GBS

Diagnosis

- isolation of virus

- infected secretion

- brain biopsy

-autopsy

- serological studies

- detection of viral antigen in infected tissue

- PCR

Treatment - post exposure prophylaxis - wound cleaning -passive immunization –

human rabies immunoglobulins - active immunization –

anti rabies vaccine ( HDCV) Once clinical disease is developed

tratment is supporative Prevention - pre exposure prophylaxis - HDCV – 0,7,28

MEASLES ENCEPHALITIS Encephalitis in measles can occur in three forms:- 1. post infectious measles encephalitis (95%) 2. subacute measles encephalitis 3. subacute sclerosing pan encephalitis

1. post – infectious mesles encephalitis Immunocompetent M=F Incidence – 1 :1000 Pathogenesis – abnormal immune response to to

myline basic protein Pathology - periventricular demylination and gliosis Signs develop within 8 days of onset measles - fever - other forms of encephalitis

TREATMENT Symptomatic Mortality - 15% Sequale - > 50 %

ARBOVIRAL ENCEPHALITIS -SEASONAL DISEASE -INFECTION FROM ORTHOPOD PATHOLOGY -focal necrosis of neurons - inflamatory glial nodules -perivascular lymphoid cuffing CLINICAL FEATURES 1.fever, abdo.pain,respiratory

symptoms 2 .vertigo, sore throat 3. headache, meningeal signs ,

photophobia,vomiting.

Infection to human present from no symptoms to febrile headache to aseptic meningitis and finally full-blown encephalitis

Acute encephalitis lasts from a few days to 2-3 wks

Acute illness requires management of comatoes patient having elevated ICP , inappropriate secreation of antidiuretic hormones, resp.failure and convulsions

No specific therapy for these viral encephalitis

DENGUE VIRUS ENCEPHALOPATHY - No satishfactory treatment exists for the relatively

common arboviral encephalitis , which vary in epidemiology , mortality and morbidity , if not clinical presentation

- dengue virus encephalopathy is a rare but recognised cause of acute febrile encephalopathy in india and occurs in febrile stage.

- caused by a.aegypti -macrophage /monocyte infection is central to the

pathogenesis of dengue fever and origine of DHF / DSS

Neurological manifastations 1. Mono neuropathies2. Polynuropathies 3. Guillain barre’s syndrom 1-4 % patient of dengue admission s/o clouding of

conciousness.

variety of pathological processes interact to cause coma in some of these patients :- such as

1. hypotension 2. cerebral edema 3. micro vascular or frank hemmorrhage 4. hypernitremia 5. fulminant hepatic failure DIAGNOSIS Isolation of dengue virus from CSF or

brain tissue TREATMENT Symptomatic and supportive

JAPANESE ENCEPHALITIS

Caused by group B arbovirus 1871-first found in japan 1935-virus isolated from japan 1955 – virus isolated in india at

vellore(TN)NATURAL CYCLE OF TRANSMISSION OF

VIRUS-animal/birds -----mosquito------animal/birdsPigs-amplifier host Humans –incidental dead host

Post monsoon Japanese Encephalitis (JE) epidemics have been reported from Uttar Pradesh, Assam and other parts of the country. JE is the single largest cause of viral encephalitis in world today. The incidence has been reported to be high among pediatric age group with high mortality (30%).

.

Diagnosis may be established by serological tests and JE virus-specific IgM antibody or RT-PCR in the cerebrospinal fluid (CSF). Since there is no specific anti-viral therapy for JE as of today

Diagnosis may be established by serological tests and JE virus-specific IgM antibody or RT-PCR in the cerebrospinal fluid (CSF). Since there is no specific anti-viral therapy for JE as of today

. Brain CT and MRI scans reveal low density areas and abnormal signal intensities in the thalamus, basal ganglia which correlate with clinical findings of tremor, rigidity and abnormal movements that are common in the acute phase of illness.

TREATMENT:- SYMPTOMATIC mortality-20% to 40%

HIV ENCEPHALOPATHY

MANIFESTATION MAY BE HIV VIRUS ITSELF OR ITS NEUROLOGICAL COMPLICATION D/T OPPORTUNISTIC INFECTION LIKE

1. CNS tuberculosis 2. cytomegalo virus encephalitis 3. toxoplasmosis 4. creptococcal meningitis 5.syphilis 6.tumours (primary CNS lymppphoma )or

drug related complications

Clinical features -apathy , inability to conentrate -lack of drive -poor memory - depression -Altered sleep rhythm -Decrease work performance -motor symptoms - premitive reflexes -patrient pregressive to vegitative

DIAGNOSIS -demonstration of decline in

cognative function - MMSE -IMAGING- cerebral atrophy - CSF - increse proteins ,

cells TREATMENT - HAART therapy

MALARIA ENCEPHALOPATHY CEREBRAL MALARIA The potentially fatal complication of

falciparum malaria ( most important cause of unarousable coma in febrile patients in endemic area )

SUSCEPTIBILITY - childrens - pregnant women - non – immune adults 20 % all sever falciparum malaria

requires ICU admission

Pathology Selective cytoadherence and

sequestration of parasitized RBC’S in cerebral venules and toxin release schizont rupture are possible pathological mechanism

Systemic complications may contribute to development of coma

dignosis HRP kit ( beb side test ) direct microscopy for parasite imagination CT – correlate well with level of

consiousness and severity of disease

TREATMENT:- - recent trial has suggested that absolute reduction of mortality with use of

artesunate compared to quinine in patients of severe falciparum malaria - ICU care - correction of hypoglycemia - acidosis and anemia MORTALIT:- - 15 -20 % with neurological sequelae like - cortical blihdness , - ataxia - aphasia %

Sepsis associated encephalopathy Poorly understood CNS condition Manifests lethargy –delirium Pathogenesis bacterial invasion of brain-----------------------

endotoxine------------blood brain transport--------------derangement of neurotransmetter and amino acid and microvascular changes

Prognosis---serious May be seen in patient with 1. mechnical ventilation 2.critical ill patient in micu ( may be measures that

these patient receive as sedative , resuscition fluid , environmental stimuli may contribute)

Leptospirosis encephalopathy Meningoencephalitis and asepticmeningitis are

commonmanifestation of leptospirosis -can occure in unicteric patients hence high index of

suspicion is required for dignosis

Manifastation -hepatic / renal failure Intra pulmonary hemorrhage with coma may

contriiibute to coma CSF xanthocromia , persistent polymorphonuclear

leukocytosis and increase ICT have negative prognostic value