Encephalitis & Intracranial Abscesses Assistant Prof./ Tamer Ata M.D., Ph.D. MEDICAL MICRIBIOLIOGY AND IMMUNOLOGY FACULTY OF MEDICINE AL-MAAREFA COLLEGES

Encephalitis Definition: is inflammation of the parenchyma of the brain, due direct viral invasion. Epidemiological pattern: Epidemic (eg, due to arbovirus, echovirus, coxsackie virus, or poliovirus) Sporadic (eg, due to herpes simplex, rabies, varicella- zoster, or mumps virus)

Encephalitis DNA viruses RNA viruses Herpes viruses HSV1&2 VZV CMV Causes: DNA viruses RNA viruses Herpes viruses HSV1&2 VZV CMV Polyoma viruses JC virus Picorna viruses (enteroviruses) *polioviruses *coxsackie viruses * ECHO viruses ArBo viruses Rhabdoviruses (rabies virus) Reteroviruses (HIV) Influenza viruses Measles virus

Encephalitis Mode of infection: Droplet and contact (measles , JC, Herpes, influenza), Ingestion (enteroviruses), Insect bites (arthropod-borne viruses), Animal bites (rabies). NB: viruses reach the CNS via the Bloodstream (most viruses ). Some viruses as herpes simplex virus (HSV), varicella-zoster virus (VZV), and rabies may also travel to the CNS along nerves. Clinically: fever, headache, confusion, coma, convulsions, paralysis, focal neurological deficit.

Herpes simplex virus the most common cause of viral encephalitis (20-30%) cause 70% mortality in untreated cases Mortality decreased with using acyclovir antiviral treatment HSV1 in immunocompromised person → viremia → CNS also can extend from nerves to CNS causing encephalitis (focal temporal lesion) HSV2 in females with genital herpes at labor → neonatal herpes→ neonatal encephalitis

HSV 1 1ry infection Latency Reactivation Recurrence Gengivostomatitis: vesicle in mouth cavity, sore throat Conjunctivitis Herpeticwhitlow Viremia in immune-compromised patients → encephalaitis & hepatitis Ascend along trigeminal nerve to enter trigeminal nerve ganglion Stress as -Common cold -Prolonged sun exposure -menses Keratitis Cold sore → vesicles with crust at angle of mouth and nose HSV2: genital herpes (vesicles at external genitalia) and latent in sacral root ganglion

Varicella-Zoster virus: Varicella (chicken pox = fever and pleomorphic skin rash which start in trunk) in immunocompromised children may complicated with viremia and encephalitis Latent in sacral root ganglion → with decreased cell mediated immunity (aging) → zoster (painful vesicles along intercostal nerve) Also aspirin (NSAID) therapy of chicken pox could cause Reye syndrome (fatty liver & brain swelling and encephalopathy)

CMV Influenza virus latent in monocyte/macrophage In HIV and transplantation immune-compromised patients → reach CNS → retinitis and encephalitis In pregnancy → congenital infection → fetal microcephaly and mental retardation Influenza virus in immunocompromised children may complicated with viremia and encephalitis Also aspirin (NSAID) therapy influenza in children could cause Reye syndrome

Ar.Bo. Viruses Family Virus Vector Flavi-viruses St Louis Encephalitis Birds → mosquito West Nile fever Toga-viruses Eastern Equine Encephalitis (EEE) WWE VEE Horses → mosquito Bunya-viruses La Cross Encephalitis Mosquito California Encephalitis

Rhabdo-viruses → Rabies virus Zoonotic in saliva of raped canine animals as dogs → bite → human Multiply in muscles and peripheral nerves → ascend along nerves to spinal cord (dorsal tract) → ascend to basal ganglia (2nd replication and damage to their nuclei) Flue like symptoms, insomnia, irritability, hydrophobia, hallucination, coma and death. Treatment: human rabies Ig &killed rabies vaccine (HDCV→ 5 doses SC)

Diagnosis of encephalitis 1. CSF analysis: similar with viral meningitis - ↑ RBCs in herpes viruses - PCR : detect viral nucleic acid in CSF - culture: isolate the virus on suitable cell line 2. Biopsy guided by CT: Multinucleated giant cell with intranuclear inclusions → HSV and VZV Foci of swollen cells with intranuclear olw’eye → CMV intracytoplasmic Negri bodies → rabies 3. Serological: detect specific IgM in patient’s serum

Multinucleated giant cell with intranuclear inclusions → HSV and VZV Foci of swollen cells with intranuclear olw’eye → CMV intracytoplasmic Negri bodies → rabies

Slow CNS infections JC virus → infect oligodendrocyte in HIV & transplant patients → demyelination → progressive multifocal leukoencephalopathy Reteroviruses → HIV: in late stage reach CNS through monocyte → progressive demyelination → progressive multifocal leukoencephalopathy → dementia, memory loss Measles → late complication in which a defective measles virus persist in CNS → chronic degeneration → subacute sclerosing pan-enecephalitis. Prions: infective protein which transmitted from cows, sheeps and goats to human through ingestion of infected brain →sub acute spongiform encephalopathy (CreutzFeldt-Jakob disease or made cow disease)

Guillain-Barre syndrome Acute inflammatory demyelinating poly-encephalopathy with ascending paralysis and muscle weakness Occur post infections with Cambylobacter (gastroenteritis) Influenza virus (resp. tract infection) Zika virus (systemic febrile illness)

Extradural or epidural abscess Intracranial abscess Rare serious life threatening infections Include: Brain abscess Subdural empyema Extradural or epidural abscess Collection of pus intra cerebral Collection of pus between dura mater and arachnoid matter Collection of pus between dura mater and the skull.

Epidemiology Source or rout of infections Direct extension from cranial infections (commonest 50%) as sinusitis, mastoiditis, otitis media, mental infection 2. hematogenous (25%) e.g. endocarditis, IV drug abuser, immunocompromised patients Trauma (10%) as penetrating wound or neurosurgery Unknown

Epidemiology Causative agent Bacterial (usually mixed aerobic and anaerobic) - the most common is Streptococci and bacteroides Fungal as Cryptococcus, candida, aspergillus in immunocompromised Protozoal as toxoplasma in immunocompromised Aerobic anaerobic Staph. spp. (common in trauma) Strept. Spp. (dental & otitis media) Enterobactericiaeia as E. coli (chronic ear infection ) Bacteroides Anaeronic strept.

Clinically: fever, headache, focal neurological deficit, ↑ ICT Investigation: CT or MRI Aspiration guided by CT: culture and sensitivity (aerobic and anaerobic) → proper specific antibiotic NB: lumbar puncture and CSF is contraindicated (WHY) Treatment: surgical drainage under umbrella of empirical antibiotic as ceftriaxone, metronidazole, vancomycin Shift antibiotic therapy according to results of antibiotic and senility results

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