DEFINITION

Encephalitis is a partial or complete inflammation of

the brain caused by various infectious agents: viruses
(90%), rickettsiae, bacteria, fungi, protozoa,
metazoars and / or toxins produced by them.

Histologically, it involves cellular infiltration and

neuronal destruction

It is manifested clinically through a group of

neuropsychiatric symptoms.
ETIOLOGY
 It can occur at any age (infectious, non-infectious cause).
 Most often - viral origin
 The same pathogen can cause encephalitis and / or meningitis and / or
myelitis (encephalomyelitis, nevraxitis).

 Other diseases: autoimmune vasculitis, sarcoidosis, etc.

 Encephalopathy - nevrax involvement - non-infectious origin

 chemicals (arsenic, bismuth, mercury)
 medicines
 various toxic substances (CO)
 endogenous toxins (uremia, diabetes, liver failure)
 hypertensive encephalopathy
ETIOLOGY AND ENTRANCE
Etiology:
 viruses (arboviruses, entero-, herpes-, echo-, polyo- HIV,
coxsackie-, measles, rubella, mumps virus, CMV, influenza,
rabies virus),
 non-viral causes: rickettsia, bacteria, fungus, protozoar,
metazoar, mycoplasma, prions, drug reaction, Q fever

Entrance of the infection:

 Skin: bite, sting, abrasion or traumatic wound
 Gastrointestinal
 Airway
 Transplacental: Rubella, Cytomegalovirus
PATHOGENESIS
 Primary - the primary localization of the infection

 Secunder – condition results from a faulty immune system reaction to an

infection elsewhere in the body or can be a complication of a current
infectious disease

 Infectious - as a direct effect of an acute infection, or as one of the sequelae

of a latent infection

 Postinfectiosus - some infectious diseases - measles, varicella, vaccine,

rubella - in the convalescent phase – the mechanism is based on allergic
reaction of the host (histologically – demyelination)

 Postvaccinal - its mechanism is similar, but occurs after active

immunization

 Slow viruses - a special group of encephalitis with a chronic progressive

course:
 - SSPE (caused by morbilli virus (hypermutated measles virus) -
Subacute sclerosing panencephalitis), Kuru, LEMP, Creutzfeld-Jacob
disease
By affected area:
 Polyioencephalitis - gray matter
 Leukoencephalitis - white matter
 Panenkephalitis - white and gray matter

Epidemiology
 It depends on the epidemiology of the pathogen,
 is influenced by the occurrence of the animal reservoir
in a given area
 seasonally dependent
 occurrence of the vector (e.g. mosquito).
CLINICAL MANIFESTATIONS
 The incubation time depends on the pathogen

 The onset is acute, fever, headache, confusion, restlessness, characterized by 3 groups of

symptoms:

 Infectious syndrome
 symptom group associated with increased intracranial pressure - sometimes associated with
neck stiffness, Kernig, Brudzinski signs

 Nervous system symptom group - this may manifest itself in the following:
 cortical involvement: localized or generalized convulsions, restlessness, hallucinations,
confusion, stupor, coma, sensory disturbances
 pyramidal involvement: spastic paresis, paraplegia, hyperreflexia, Babinski +
 extrapyramidal involvement: parkinson's tremor, muscle hypertension
 hypothalamus: central hyperthermia, diabetes insipidus
 cerebellum: ataxia, dysmetria, nystagmus
 temporal lobe: hallucinations, aphasia
 cerebrospinal fluid syndrome: mild modifications (elevated protein levels, 10-100 cells /
mm3, occasionally high CSF glucose), but may be completely normal.
Case description
 35 years old female patient
 Presents at the ED, acute onset of:
 Psychomotoric agitation
 Desorientation
 Memory problems
 Right unilateral clonic convulsion
Clinical examination
 Hard to examinate (agitated patient)
 Difficulty with word recall
 Temporo spatial disorientation
 Neck stiffness
 Assimetrical reflexes
 Right hemiparesis with central facial
paresis
 RR: 20/min, Puls: 100/min, TA:
120/80mmHg, abdomen nontender, no
hepato or splenomegaly
Suspected Diagnosis:
 Acute bacterial meningitis
 Acute encephalitis
 Subarachnoideal hemorrhage
 Cerebral tumour
 Epileptic seizure
 Acute stroke
PARACLINICAL
INVESTIGATIONS
 Cranial CT scan – diffuse cerebral
edema
 IRM scan – zones with hyperdensity
(T1) left temporal lobe
 Fundoscopic exam – normal
Lumbar puncture
 CSF:
 Clear aspect
 Pleocytosis: 450 lym/mm3, RBC: 300/mm3
 Glucose: 60mg/dl
 Protein: 500 mg/dl
 PCR-HS1 – DNA: positive
LABORATORY INVESTIGATIONS
 ESR: 30mm/h, CRP: 10mg/L, Fibr: 380 mg/dl
 CBC: HGB: 12,3 g/dl, leu:6540/mm3, RBC:
4,24x103, HTC: 38%, PLT: 260.000mmc
 AST: 50U/L, ALT: 75 U/L; GGT: 120 U/L, LDH: 120
U/L, BiT: 0,78mg/dl, INR: 1,2
 BUN: 46,3 mg/dl, creat: 0,67mg/dl
 Na: 141 mmol/L, K: 3,7mmol/L
 Fe: 65 mg/dl, Mg: 1,78mg/dl
 Glucose: 75 mg/dl
 Anti-HSV1 Ab IgG: pozitive
 Anti-HIV: negative
 EEG: periodical complexes in temporal region
FINAL DIAGNOSIS
 HERPES SIMPLEX 1 VIRUS
MENINGO-ENCEPHALITIS
Sustaining the diagnosis
 Clinical symptoms
 Infectious syndrome
 Imagistical findings – without intracranial
space occupying lesions/acute stroke
 CSF:
 Viral infection (Lym, RBC!)
 Poz PCR HSV-1
DDx
 Other viral encephalitis – arbovirus, other
herpesviruses: CMV, EBV, VZV; enteroviruses,
influenza virus, mumps virus, JC virus
 Cerebral abscess, subdural empyema
(bacterial, fungal, rikettsial, mycobacterial)
 Neurosiphylis
 Primary/secondary brain tumor
 Paraneoplastic encephalitis
 Acute stroke
 Non-infecetious: vasculitis, lupus
POS DG
 Young woman – stressed lifestyle
 Acute onset of symptoms
 After 48 h – neurologic manifestations
 Susp neuroinfection
 MRI brain – demielinization zone on the left
temporal lobe (no space ocupying lesion)
 Fundoscopic exam – neg
 Lumbal puncture – clear aspect, lym
pleocytosis, RBC-300/mmc, glu-norm, prot-
elevated, PCR-HSV-1:poz
TREATMENT
 Aciclovir – 10mg/kg i.v. 8 hours, 21 days
 Dexamethasone 3x8mg i.v.
 Manitol 20% 3x100mg/24h
 Vit B1, B6, B12
 Anticonvulsivant
OUTCOME
 3-4 days with hyperpirexia
 GCS: 10 pts – superficial coma
 72 hours after – afebrile
 Desorientation, retrograde amnesia,
memory loss
 No seizures
OUTCOME
 Repeated IRM brain – no edema,
temporal lesion in resorbtion
 Discharged after 21 days
 Neuropsychiatric recuperation

 After 3 months present at our clinic - full

recovery
Complications
 Neurological sequels
 Cognitive or motoric problems
 Seizures
 Memory problems
 Death
Question 1
Choose the right answer regarding the
characteristical signs and symptoms in a
herpetic meningoencephalitis
a) Hedeache
b) Psichyatric disorders
c) Fever is absent
d) Hemiparesis
e) Focal seizures
Question 2
Regading the positive diagnosis of herpetic
meningoencephalitis are true:
a) Hemocultures
b) CSF: lymphocytosis, RBC, elevated
protein
c) Specific antibody detection from the
serum
d) Brain MRI
e) HSV-1 detection from the CSF with
polymerase chain reaction
Case description
 76 years old male patient
 Presents at the ED, acute onset of:
 Fever 38C
 Confusion
 Movement disorders – difficulty of walking
 Fatigability
 Lethargy, somnolence
Personal medical history
 Chronic lymphocytic leukemia - in
remission
 Urban environment
 Works in the garden
 Multiple insects bites
Clinical examination
 High fever 39 C
 Neck stiffness
 Difficulty of walking, ataxia
 Muscular rigidity (Parkinson-like)
 Positive Romberg sign
 Pulmonary auscultation – normal breath
sounds with rhonchi
 SaO2: 94%, Puls: 87/min, TA:110/68mmHg
Suspected Diagnosis:
 Acute meningo-encephalitis
LABORATORY INVESTIGATIONS
 CBC: HGB: 15,8 g/dl, leu: 9870/mm3, RBC:
5,1x103, HTC: 45%, PLT: 260.000mmc
 AST: 120U/L, ALT: 140 U/L; GGT: 632 U/L, LDH:
160 U/L, BiT: 0,65mg/dl, INR: 1,1, IP: 80%
 BUN: 30 mg/dl, creat: 0,97mg/dl
 Na: 144 mmol/L, K: 4,5mmol/L
 Fe: 65 mg/dl, Mg: 1,78mg/dl
 Glucose: 90 mg/dl
 Prot tot: 6,5g/dl
PARACLINICAL
INVESTIGATIONS
 Hemocultures - neg
 Fundoscopic exam – normal
 Cranial CT scan – normal
 IRM scan – diffuse cerebral atrophy
Lumbar puncture
 CSF:
 Clear aspect
 Pandy: neg
 Pleocytosis: 160 lym/mm3
 Glucose: 60 mg/dl
 Protein: 107 mg/dl

 CSF examination
- usual culture medium: no bacterial growth
- cultivation of Sabouraud media: mycological negative
- gram stain smear / Ziehl neelson / negative
- Lowenstein-Jesen - Mycobacterium tuberculosis absent
Serology
 Serologic detection of enteroviruses:
negative
 Serologic detection for WN virus –
positive (IgM) (ELISA)
 Anti-WN IgM antibodies – positive in
CSF
FINAL DIAGNOSIS
 WEST NILE ENCEPHALITIS
 CHRONIC LYMPHOCYTIC LEUKEMIA -
IN REMISSION
WEST NILE ENCEPHALITIS
 arthropod-borne flavivirus that was first
isolated from the blood
 The main vector species – mosquitoes
(Culex pipiens, Culex tarsalis)
 Following the 1996 outbreak in
Bucharest – from 400 cases - 17 patient
died
 Risk factors: old age, neoplasm,
malignant hemopathies
WEST NILE ENCEPHALITIS
CLINICAL MANIFESTATIONS
 Incubation period: 2-14 days
 Asthenia
 Memory problems
 Headache
 Ataxia
 Movement disorders, loss of balance
 Tremor, parkonson like rigidity
 Fever, confusion, disorientation, altered
mental status, stupor, coma
 Neuroinvasive disease
Sustaining the diagnosis
 Clinical symptoms
 CSF:
 Lym(<500/mmc), might elevated prot
 Imagistical findings – no specifical
modification
 ELISA- anti WN IgM antibodies serum
 Anti-WN IgM antibodies – positive in
CSF
DDx
 Other viral encephalitis:
 VZV
 Denga virus – travelers in endemic region
 Herpes simplex
 Stroke
 Intracranial space occupying lesions
TREATMENT
 Monitorization of vital functions
 Hidro-electrolitic balance
 Corticosteroidal treatment
 No etiological treatment
 IgIV – in neuroinvasive infection – can
be an alternative

Potential treatments, including antiviral compounds,

immunomodulatory therapies and vaccines, are all areas of
active research in animals and humans
PROGNOSIS
 Elderly patients, immunosuppressed,
with neoplasms/ transplant recipients
 Altered mental status
 High mortality rate!
PROPHYLAXIS
 Insect bite protection
 Mosquito control methods
 Blood donor screening for West Nile
virus
 Vaccination - currently licensed for use
in horses, under way - studies in
humans
 Following the arbovirus circulation in the
area
Question 1
The clinical manifestations in West Nile
encephalitis are:
a) Hedeache
b) Parkinson-like rigidity
c) Fever
d) Ataxia
e) Focal seizures
Question 2
The risk factors for developing West Nile
encephalitis:
a) Young age
b) Lymphocytic leukemia
c) Cardiac transplant recipient
d) Old age
e) Outdoor swimming