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 VIRUSES
2. TOGAVIRUSES-
--ALPHA VIRUSES- EQUINE ENCEPHALITIS
--FLAVI VIRUSES-JE , . , DENGUE, OTHER
-- RUBI VIRUSE – RUBELLA VIRUS
3. PARAMYXOVIRUSES- MUMS , MEASLES ,
4.RHABDOVIRUSES-- RABIES VIRUS,
CHANDIPURA VIRUS
5. 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 encephalitis

2. Post infectious viral encephalitis
3. 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
diagnostics
IMAGING 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 neuropathies
2. 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/birds
Pigs-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