Dr. Abhijeet Deshmukh

• Causes• Typical presentation• Investigations• Treatment• Prognosis

Terminology• Encephalitis

– Acute, diffuse, inflammatory process affecting brain parenchyma– Most commonly viral

• Encephalopathy– Clinical syndrome of altered mental status, manifesting as reduced consciousness or altered

behaviour– Many causes, incl. viral encephalitis Acute Encephalitis Syndrome :- Defined as a person of any age, at any time of year with the acute onset of fever and a change in

mental status(confusion, disorientation, coma, or inability to talk) and/ or new onset of seizures ( excluding simple febrile sz.)

• Meningitis: meningeal inflammation• Myelitis: spinal cord inflammation• Radiculitis: nerve root inflammation

Causes of acute viral encephalitisSporadic causes• Herpes viruses

– HSV-1, HSV-2, CMV, EBV, HHV6, HHV7 , VZV• Enteroviruses

– Coxsackie, echoviruses, enteroviruses 70/71, poliovirus• Paramyxoviruses

– Measles, mumps• Others (rarer causes)

– Influenza viruses, Adenovirus, parvovirus, rubella virus, rabies , HIV

Geographically restricted causes• Arboviruses — Japanese B, St Louis, West Nile, Eastern equine, Western equine,

Venezuelan equine, tick borne encephalitis viruses, Dengue virus, Chikungunya v• Bunyaviruses — La Crosse strain of California virus• Reoviruses — Colorado tick fever virus

Herpes simplex encephalitis

• HSV encephalitis (HSE) most common cause of viral encephalitis in industrialised nations

• 90% HSV-1

• HSV-2 more common in immuno-compromised, neonates

HSV-1• Primary infection occurs in oral mucosa• Virus then travels along trigeminal nerve to ganglion

• 70% cases of HSV-1 encephalitis already have antibody present suggesting reactivation of virus which is the most common mechanism

• In children, HSV-1 encephalitis occurs during primary infection

HSV-2• Transmitted via genital mucosa

– Genital herpes in adults• HSV-2 may cause

– Meningitis (esp. recurrent meningitis)– Encephalitis (esp in neonates)– Lumbosacral radiculitis

• Neonates can be infected during delivery: neonatal herpes (disseminated infection often with CNS involvement)

Causes of encephalopathy• Hypoxic/ischaemic• Metabolic (liver and renal failure, diabetes)• Toxic (drugs)• Vascular (vasculitis, SLE, SAH, SDH, stroke, Behcet’s)• Epileptic (non-convulsive status)• Nutritional deficiency• Systemic infections (malaria)• Traumatic brain injury• Malignant hypertension• Mitochondrial cytopathy (Reye’s and MELAS syndromes)• Hashimoto’s encephalopathy• Paraneoplastic limbic encephalitis

Non-viral causes of infectious encephalopathy

Bacterial Mycobacterium tuberculosis

Mycoplasma pneumoniae

Listeria monocytogenes

Borrelia burgdorferi

Leptospirosis

Brucellosis

Legionella

Tropheryma whippeli (Whipple’s disease)

Nocardia actinomyces

Treponema pallidum

Salmonella typhi

All causes of Pyogenic meningitis

Rickettsial Rickettsia rickettsia (Rocky Mountain spotted fever)

Rickettsia typhi (endemic typhus)

Rickettsia prowazeki (epidemic typhus)

Coxiella burnetti (Q fever)

Fungal Cryptococcus

Aspergillosis

Candidiasis

Coccidiomycosis

Histoplasmosis

North American blastomycosis

Parasitic Human African trypanosomiasis (sleeping sickness)

Cerebral malaria

Toxoplasma gondii

Echinococcus granulosus Schistosomiasis

Encephalopathy vs encephalitis?

Encephalopathy Encephalitis

Clinical features

Fever Uncommon Common

Headache Uncommon Common

Depressed mental status Steady deterioration May fluctuate

Focal neurological signs Uncommon Common

Type of seizure Generalised Generalised or focal

Laboratory findings

Blood Leucocytosis uncommon Leucocytosis common

CSF Pleocytosis uncommon Pleocytosis common

EEG Diffuse slowing Diffuse slowing and focal abnormalities

MRI Often normal Focal abnormalities

Pathogenesis of viral encephalitis

• Depends on the virus– direct viral destruction of cells – Para or post-infectious inflammatory or immune-

mediated response • Most viruses primarily infect brain parenchyma

and neuronal cells• Some cause a vasculitis• Demyelination may follow infection

Viral encephalitis – clinical presentation• Typical presentation

– Acute flu-like prodrome– High fever, severe headache– Altered consciousness (lethargy, drowsiness, confusion,

coma)– Seizures– Focal neurological signs

• More subtle presentations– Low grade fever– Speech disturbances (dysphasia, aphasia)– Behavioural changes– Subacute and chronic presentations can be caused by CMV,

VZV, HSV (immuno-compromised)

• A study on HSV-1 encephalitis*– 91% febrile on admission– 76% disorientated– 59% speech disturbances– 41% behavioural change– 33% seizures

*Raschilas et al 2002 Clin Infect Dis

Typical CSF findings in CNS infectionsViral Bacterial TB Fungal Normal

Opening pressure

Normal/high High High High/v. high 10-20 cm

Colour Clear Cloudy Cloudy/yellow Clear/cloudy Clear

Cells/mm3 Sl. increase5-1000

High/v. high100-50,000

Sl. increase25-500

Normal/high0-1000 < 5

Differential Lymphocytes Neutrophils Lymphocytes Lymphocytes Lymphocytes

CSF/plasma glc ratio

Normal Low Low/v. low (<30%)

Normal/low66%

Protein (g/l) Normal/high0.5-1

High>1

High/v. high1-5

Normal/high0.2-5 <0.45

Bloody tap: subtract 1 WBC for every 700 RBCs subtract 0.1g/l protein for every 1000 RBCs

MICROBIOLOGICAL INVESTIGATIONS AVAILABLE IN AES

MRI brain (T2W image): right temporal lobe high signal in a patient with herpes encephalitis

Axial DWI: restricted diffusion in the left medial temporal lobe consistent with herpes encephalitis.

Preventive strategies

(i) Surveillance for cases of AES;(ii) Vector control; (iii) Reduction in man-vector contact; (iv) Vaccination.

Prognosis in HSE

• Mortality > 70% if untreated (20% with Rx)• Poor prognostic factors

– GCS < 7– Delay in starting aciclovir (esp > 2 days)

• 2/3 rds pts have neuropsychiatric sequelae– 69% memory impairment– 45% personality/behaviour change– 41% dysphasia– 25% epilepsy