CNS INFECTIONS

Classification of CNS Infections Diffuse Meningitis encephalitis Focal Brain abscess Epidural abscess Subdural empyema Herpes simplex encephalitis

Etiology of CNS Infection Syndrome Usual Causes Meningitis Bacterial Bacterial meningitis TB meningitis Viral Fungal Encephalitis Mainly viral Brain abscess Mainly bacterial, TB Others Protozoal, rickettsia, nematodes, cestodes

Meningeal Anatomy

Routes of Entry into the CNS Hematogenous spread Contiguous (bacterial) Sinus, ear, face Direct inoculation (bacterial) trauma Iatrogenic Surgery VP shunting Lumbar puncture Via nerves Herpes, Varicella, Rabies

Pathogenesis: Bacterial meningitis Bloodstream CNS seeding *Virulence factor: Bacterial capsule (H. influenzae, N. meningitides, S. pneumoniae, E. coli)

Pathogenesis: Tuberculous meningitis Pulmonary infection bacteremia CNS seeding in the meninges (Rich focus) Rupture of Rich focus

Pathogenesis: Viral Infection pathways Respiratory passages: mumps, measles, varicella Oro-intestinal route: poliovirus, enterovirus Oral/genital mucosa route: herpes Inoculation: rabies Maternal-fetal transfer: rubella, CMV, HIV

Viral Invasion Enters the body multiplies locally and in secondary sites Massive viremia Reticuloendothelial system Blood Brain Barrier CNS invasion cerebral capillaries choroid plexus

Viral Invasion via Peripheral nerves Inoculation (HSV, VZV, rabies) Local infection Centripetal movement (retrograde axoplasmic transport system) CNS invasion cerebral capillaries choroid plexus

Pathogenesis: Fungal infection May arise without obvious predisposing cause But usually due to opportunistic/ inadequate defenses AIDS Organ transplantation Diabetes Leukemia, lymphoma, malignancy Prolonged steroid therapy

Cardinal Manifestations of CNS Infections Fever Headache Alteration of Sensorium Focal neurologic signs Seizure Meningeal signs

Identifying the Organism Age of the patient Clinical setting Community-acquired Post-surgical nosocomial Immune status of the patient Evidence of systemic and local cranial disease

CNS Infection Syndromes according to length of symptoms DAYS Acute Meningitis Bacterial meningitis Viral meningitis DAYS TO WEEKS Subacute meningitis Tuberculous meningitis Cryptococcal meningitis Acute encephalitis Mumps Measles Rabies

CNS Infection Syndromes according to length of symptoms WEEKS TO MONTHS Space-Occupying Lesions Brain/ Spinal Abscess Subdural empyema Cysticercosis Toxin-Mediated Tetanus Botulism Post-Infectious Guillain-Barre Syndrome Acute Demyelinating Encephalomyelitis (ADEM)

CNS Infection Syndromes according to length of symptoms MONTHS TO YEARS Chronic meningitis Neurosyphilis Chronic Encephalitis Subacute Sclerosing Panencephalitis (SSPE) HIV Encephalitis Prion Disease Creutzfeldt-Jacob disease Kuru PML

Bacteria which invade the CNS

Viruses which invade the CNS HIV-1 & HIV-2 (human Immunodeficiency viruses) HSV-1 (Herpes simplex virus) HSV-2 (Herpes zoster virus) EBV (Epstein-Barr virus) CMV (Cytomegalovirus) Poliovirus rabies

Fungi which invade the CNS Cryptococcosis Candidiasis Aspergillosis Mucormycosis Coccidioidomycosis Histoplasmosis

Bacterial meningitis Suppurative meningitis

Bacterial meningitis Suppurative meningitis

Bacterial meningitis

Bacterial meningitis Suppurative Meningitis Gram stain: PMNs and intracellular bacteria

Meningococcemia

Neisseria meningitidis

Early TB Meningitis

Late TB Meningitis

Cryptococcal Meningitis

Cryptococcus: India Ink Stain

Brain Abscess DAY STAGE 1-3 Early cerebritis 4-9 Late cerebritis 10-13 Early Capsule Formation 14 onwards Late Capsule Formation

Diagnostics in CNS Infection CSF analysis Lumbar puncture Cisternal puncture Ventricular tap Q/Q, GS/CS,AFB, CALAS Neuroimaging CT scan MRI

CSF Profiles Profile Common Causes Purulent (acute) ↑PMNs, ↓glucose Bacterial Lymphocytic (subacute) ↑Lymph ↓glucose TB, fungal, CA Syphilis Lymphocytic Normal glucose viral

Bacterial meningitis – therapy according to Gram stain Probable organism Provisional antibiotics G(+) diplococci S pneumoniae Cefotaxime or ceftriaxone G(+) cocci S aureus or epidermidis Streptococci oxacillin G(-) intracellular diplococci N meningitidis Pen G or ampicillin G(-) bacilli E coli & other G(-)

Recommended Treatment for Fungal Meningitis Organism Treatment Cryptococcus neoformans Amphotericin B Flucytosine Candida Aspergillus Mucorales Coccidioides imitis

Recommended Treatment for Viral Meningitis Virus Treatment HSV-1 (Herpes simplex virus) Acyclovir HSV-2 (Herpes zoster virus) Rabies Human rabies immune globulin Human diploid cell line vaccine

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