1. Acute Viral Encephalitis and Brain Abscess

2. Acute Viral Encephalitis Approximately 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.

3. 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.

4. N

5. N 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.

7. N 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)

8. 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.

9. N 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.

10. Pathogenesis of Rabies: N

11. 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.

12. 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.

13. 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.

14. N 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.

15. Diagnosis of Viral Encephalitis: CSF abnormalities are similar to those found in viral meningitis. Hematological analysis: Leukocytes count in CSF: 10-500 cell/mm 3. Differential count: Neutrophils: predominate in first 24 hours, then decreased. Lymphocytes increases. Red blood cells per mm 3 : 10-500 cells (HSV infection). RBCs are not present in other CNS infections.

16. 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.

17. 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.

18. N 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.

19. N 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.

20. N 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.