Febrile encephalopathy

D KALPANA

Addl. Professor of Pediatric Neurology,

Medical College, Thiruvananthapuram

Definition of terms

Differential diagnosis

Points from history/epidemiology

Investigations

Supportive management

Specific management

Autoimmune encephalitis

ENCEPHALOPATHY

• Diffuse disturbance of brain function without inflammation

ENCEPHALITIS

• Dysfunction of brain associated with inflammation

FEBRILE ENCEPHALOPATHY

• a/c onset of fever (<1wk)+alteration of consciousness >12 hrs

Febrile

ENCEPHALOPATHY

Temp >380C

Seizures

Alteration of cerebral function

Focal neurological signs

inflammation

Cellular CSF

Imaging /EEG suggestive of inflammation

Clinically, a case of Acute Encephalitis Syndrome (AES) is defined as a person of any age, at any time of year with the acute onset of fever and at least one of:

a) change in mental status (including symptoms such as confusion, disorientation, coma, or inability to talk);

b) New onset of seizures (excluding simple febrile seizures.

( A simple febrile seizure is defined as a seizure that occurs in a child aged 6 months to less than 6 years old, whose only finding is fever and a single generalized convulsion lasting less than 15 minutes, and who recovers consciousness within 60 minutes of the seizure)

Bull World Health Organ 2008, 86(3):178-186.

INFECTIONS

DEMYELINATION - ADEM

AUTOIMMUNE ENCEPHALITIS

DRUGS/TOXINS

COLLAGEN VASCULAR DISORDERS

SEIZURES –NON CONVULSIVE STATUS

METABOLIC

ICSOL

Viral encephalitis

Herpes simplex type 1. type2

Varicella zoster

HHV6

Epstein Barr virus

Arboviruses – JE,West Nile,Dengue, Chikun

gunya,

Rhabdoviruses-rabies

Orthomyxo –H1N1

Paramyxo –measles

HIV

Bacterial

Meningitis

Brain abscess

Sepsis associated encephalopathy

Leptospirosis

Typhoid

M. tuberculosis

Rickettsial (scrub typhus)

Parasitic

Cerebral malaria

Toxoplasma

Features of infection

Evidence of CNS involvement

Features of raised intracranial tension

Signs and symptoms of meningeal irritation

• HSV is sporadic

• JE epidemicsepidemiology

• Rabiesh/o animal bites

• JE

• Dengue

• Chikun GunyaMosquito bites

• LeptospirosisWorking/playing

in dirty water

• TBMContact withTB

•Maculopaular

•Petechiae/purpura

•Vesicles

•Eschar

•Herpes labialis

Fever with rash

• H1N1Respiratory symptoms

• enteroviruses

• PolioDiarrhoea,vomiting

• Mumps

• EB virus

• HIVParotitis

• Dengue

• leptospirosisMyalgia,arthralgia

Abnormal

behaviour/psychosisHSV

Limbic encephalitis

NCSE

Meningeal signsMENINGITIS

ADEM

meningoencephalitis

Opisthotonic posture

Choreoathetosis

JE,autoimmune

Asymmetric signs and

symptoms

EncephalitisTBM

ADEM

AtaxiaADEM

VZV

Entero virus

Lower cranial nerve

palsiesTBM

VASCULITIS

Brainstem encephalitis

JE,west nile

PapilloedemaICSOL

Hydrocephalus –TBM

Hypertensive

encephalopathy

Visual lossOptic neuritis

Hypertensive

encephalopathy

lymphadenopathy

Hypotension

shock

organomegaly

• EB virus

• leptospira

• dengue

• Chikungunya

• leptospira

• EBVIRUS

• dengue

• Lepto

• HIV

• COLLAGEN

management

SHOCK SEPSIS

INTRCRANIAL INFECTION

• ENCEPHALITIS

• MENINGITIS

• TBM

SEIZURE

• STATUS EPILEPTICUS

• NON CONVULSIVE STATUS

RAISED ICT

• PAIPPEDEMA

• GCS<8

• ASYMMETIC PUPILS

• POSTURING

• ABSENT DOLL’S EYE

METABOLIC

• HYPOGLYCEMIA

• HYPERAMMONEMIA

• ACIDOSIS

• DKA

• DRUGS

CSF STUDY

EEG

IMAGING

CONTRAINDICATIONS

IMAGING BEFORE LP IN RAISED ICT

EMPIRICAL ANTIBIOTICS +ACYCLOVIR IF DELAY OF

SEVERAL HRS IS EXPECTED

NOTE THE OPENING PRESSURE

CELLS

GRAM STAIN,CULTURE

PROTEIN

SUGAR

VIROLOGICAL STUDIES –PCR,IgM

TBPCR

LACTATE

• PMN

• High protein, low sugar, gram stainBACTERIAL MENINGITIS

• Few lymphocytes

• Normal protein

• Normal sugar

ASEPTIC MENINGITIS

• lymphocytic

• Normal sugar, normal to slightly raised protein

VIRAL ENCEPHALITIS

• Opalescent, cob web

• Lymphocytic

• High protein. Low sugar

TUBERCULOUS MENINGITIS

Take at least 5 ml of CSF

Be sure that it is not mixed with blood

Sensitivity and specificity are relatively good

Can be negative very early in HSV and after

10 days of treatment

Never stop Acyclovir before repeating once

more after 72hrs – if clinical history, EEG and

imaging are suggestive

Serum/CSF Ig M antibodies useful in JE

Paired samples – 4 fold rise in titre

MRI is preferable to CT scan-

CTis advised in unstable patients, delirious

children who cannot be kept still for 30 min

JE

RABIES

Diffuse slowing suggests encephalopathic

process

PLEDS in HSE

Triphasic waves in metabolic encephalopathy

Non convulsive status epilepticus

Should be suspected in confusion, stupor,

unarousable coma

Subtle features like eye blinking, nystagmus,

perioral twitching, automatisms may be seen

May follow convulsive seizures

EEG is the only diagnostic clue

Response to diazepam can be demonstrated

in simultaneous EEG recording

Generalised/complex partial

Maintain Normothermia

Normoglycemia

Normal electrolyte balance

Normotension

Management of raised ICT

minimal stimulation

Head end elevation

Avoid hypotonic fluids

3% saline

Mannitol 20% solution

hyperventilation

Management of

seizures/status

epilepticus

Identify SIADH and

manage

Rapid correction of

hyponatremia may

lead to central

pontine

myelinolysis

Abnormal /psychotic behaviour – haloperidol+

phenergan

Choreoathetosis – dopa blockers

Dystonia - tetrabenezine, anticholinergics,

muscle relaxants

HSE –ACYCLOVIR I/V 10 mg/kg/dose 8 hrly

x 14 -21 days. (500 mg/m2)Neonates 20

mg/kg/dose

Oral acyclovir has very low bioavailability

Oral valacyclovir can be used

Very costly

Empirical acyclovir

Repeat LP after 72 hrs if initial PCR is

negative – and stop Acyclovir after that.

Other drugs effective - foscarnet

Varicella zoster – acyclovir

HHV 6 - foscarnet +gancyclovir

CMV – gancyclovir

H1N1- oseltamivir

Rickettsia – doxycycline

Mycoplasma – azithromycin

Leptospira – penicillin

Bacterial meningitis – ceftriaxone+ vancomycin

ADEM – steroids, IVIG

Autoimmune encephalitis - immunosuppressants

Even in best centres a definite diagnosis of

encephalitis is reached only in 42% of cases (Granerod et al)

ADEM in 21%

1% autoimmune encephalitis

37% no definite diagnoses

Undiagnosed viral infections

Autoimmune causes

Unidentified metabolic causes

Poorly understood CNS condition

Manifests lethargy –delirium

Pathogenesis bacterial invasion of brain

endotoxins

derangement of neurotransmitter and

amino acid and microvascular changes

Prognosis---serious

May be seen in patient with

1. mechnical ventilation

2.critical ill patient in micu (sedatives, neuromuscular blocking agents, dyselectrolytemia,hepatic failure may contribute)

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. cryptococcal meningitis

5.syphilis

6.tumours (primary CNS lymphoma )or drug related complications

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 severe falciparum malaria requires

ICU admission

Selective cytoadherence and sequestration of parasitized RBC’S in cerebral venules and

toxin release at schizont rupture are possible pathological mechanism

Systemic complications like hypoglycemia may contribute to development of coma

Diagnosis – PS for MP

Treatment – artesunate is better than quinine

often presents with fever

behavioural abnormalities

psychosis

movement disorders

seizures/status

May be paraneoplastic –teratoma ovary in young females

Often no tumour is identified

Antibodies to NMDA ,VGKC receptors

Treatment – IVIG, plasmapheresis

?

?

?

A variety of infective and non infective conditions

in children can present as acute febrile

encephalopathy

Stabilisation of patient and supportive

management helps a lot in reducing morbidity and

mortality

Identification of specific etiology helps in

institution of specific therapy

Awareness of Autoimmune encephalitis is

important – another treatable cause like ADEM

In a significant proportion of cases aetiology is yet

to be identified