Acute Viral Encephalitis and Brain

Abscess

Acute Viral EncephalitisApproximately 20,000 cases of encephalitis occur in USA each year mostly by viruses.

CNS infectious diseases occur in two forms:o Neuronal transmission (limited to the CNS).o Hematogenous dissemination with multi-organ

involvement.

Causes of acute viral encephalitis:• Herpes simplex 1.• Rabies Virus infection.• Arboviruses.• Enterovirus infection.

Herpes simplex virus-1 (HSV-1)• Common etiology of sporadic viral encephalitis. • Associated with 70% mortality rate if untreated.• Classification:o Family: Herpesviridae.o Subfamily: - Alphaherpesvirinae; rapid

growth cycle with cell death.• General properties:– Icosahedral enveloped – Double stranded DNA virus.– Latency in nerve ganglia.

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Pathogenesis of HSV-1: • Primary infection of upper respiratory tract

epithelial cells; mild pharyngitis, or gingivostomatitis.

• Virus transported up peripheral nerve to sensory neuron in trigeminal ganglion and establish latent infection their.

• Fibers emerging from the trigeminal ganglion innervate the dura of the middle and anterior cranial fossa, and meningeal arteries.

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• Spread from the meninges and meningeal arteries to the contiguous cortex (temporal and frontal lobe).

• Destruction of neurons causes mononuclear infiltration from the perivascular sheaths (Virchow-Robin spaces).

• None-effective immune response; lymphocytic infiltration; severe destruction of brain tissue.

• Result: Focal cerebral cortical encephalitis. • Symptoms: fever, headache and altered mental

status (disorientation, behavioral disturbance, hallucination e.g. smell hallucination)

Rabies Virus infection: Zoonosis:

• Classification:– Family: Rhabdoviridae.– Genera: Lyssavirus. – Species: Rabies.

• General properties: • Helical enveloped Ss RNA virus.• Surface glycoproteins are antigenic for

production of neutralizing antibodies. • Neurotropism: Entry into the neuron by receptor

mediated endocytosis.

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Pathogenesis of Rabies:

-Bite of an infected animal, or exposure of mucous membrane or non-intact skin to animal saliva.

-Incubation period (1 to 3 months) .

-Local replication, neuromuscular junction, infection of peripheral nerves.

-The virus ascend within the peripheral nerves to the spinal cord to brainstem, cerebellum, and other brain parenchymal tissue (diffuse encephalitis).

-From brain tissue, the virus descend along autonomic nerves to skin, cornea, and salivary glands.

Pathogenesis of Rabies:N

Arboviruses: (Arthropod-born Viruses)• Transmitted by insects; mosquitoes, or ticks.

A-Togaviridae and Bunyaviridae: in USA.

B-Flaviviridae Family:–General properties of flaviviruses: Icosahedral

enveloped single stranded RNA viruses.– Examples:• West Nile virus: Encephalitis in America,

Africa, Middle East, and Europe.• Japanese encephalitis virus: Asia, India,

Australia.

• Ticknborne encephalitis virus: Russia, Europe.

Pathogenesis of Flaviviridae: • Mosquito bite; skin inoculation; infection of

endothelial cells of small blood capillaries and skin dendritic cells.

• Invade the blood (primary viremia).

• Infection of reticuloendothelial system (macrophages of the liver and spleen and endothelial cells).

• Secondary viremia; the virus cross the BBB through the choroid plexus to infect the brain tissues.

• Subcortical white matter encephalitis.

Enterovirus infection:

• Classification: Picornaviridae.

• Etiology: Coxsackievirus A and B, Poliovirus, and Echovirus.

• General properties: Icosahedral non-enveloped single-stranded RNA virus.

• Pathogenesis:

– Viral replication in oropharynx and intestinal mucosa.

– Intestinal lymphoid tissue infection; viremia.

– Meninges infection; aseptic meningitis.

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• Coxsackievirus A and B encephalitis is established from meningitis.

• Poliovirus is transferred by retrograde axonal transport to infect the neurons of the gray matter of both the brain and spinal cord; then destroy them by lysis.

• Result: Acute encephalomyelitis and paralytic poliomyelitis.

Diagnosis of Viral Encephalitis:CSF abnormalities are similar to those found in viral

meningitis.

Hematological analysis:• Leukocytes count in CSF: 10-500 cell/mm3.• Differential count: Neutrophils: predominate

in first 24 hours, then decreased. Lymphocytes increases.

• Red blood cells per mm3: 10-500 cells (HSV infection). RBCs are not present in other CNS infections.

Biochemistry analysis: • Glucose concentration mg/dL: 40-80 (normal).• Protein concentration: mg/dL: 50-100

(Slightly elevated) normal protein: 20-50mg/dl.

Molecular detection of virus genes by PCR.

Brain Abscess:Brain abscess is a focal infection (pus collection) of the brain parenchyma, caused by bacteria, fungi, or parasites.

Types of brain abscess:

-Acute brain abscess.

-Chronic brain abscess.

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Microorganisms that cause brain abscess reach the brain by:• Direct extension from a contiguous focus of

infection: (otitis media, sinusitis or mastoiditis; veins that bridge the surrounding bony structures and cerebral cortex can become infected (septic thrombophlebitis).

• Hematogenous dissemination: acute bacterial endocarditis, septicemia,…

• Direct penetration: Skull fractures or surgical procedures.

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Acute brain abscess:

-Causative agents: Staphylococci , group A and D Streptococci and mixed anaerobic and aerobic bacteria.

-The mixture of aerobic and anaerobic bacteria is similar to the combination of bacteria found in the mouth, external ear canal or a parameningeal infection such as otitis media, sinusitis and mastoiditis.

Treatment:

Drainage and broad-spectrum antibiotics: Vancomycin, metronidazole, and ceftriaxone. Quinolones or macrolides work effectively at acidic pH.

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Chronic Brain Abscess:

(located in either meninges or brain tissues).

The most common causative agents are:

-Bacteria: Mycobacterium tuberculosis.

-Fungi: Cryptococcus neoformans, or other fungi.

Other causes of brain Abscess:

-Parasites:

A -Taenia solium (Cysticercosis).

B - Toxoplasma species.

C -Entamoeba histolytica: extraintestinal amoebiasis: rare.