24 UME_NeuroPsych_Neuropathology of CNS Infections_Final
Page 1: Introduction
VINUNIVERSITY PPPA
11111 Neuropathology of CNS Infections
Page 2: Objectives
Learning Objectives
Define and describe the main patterns of infection involving the CNS.
Focus on type of inflammatory response and location.
Identify common organisms responsible for each infection pattern.
Recognize gross and microscopic pathology of common CNS infections (bacterial, viral, fungal, and parasitic).
Page 3: Course Outline
Overview of CNS Infections
Basic concepts on CNS infections
Bacterial infections
Viral infections
Fungal infections
Parasitic infections
Infections common in immunocompromised hosts
Page 4: Basic Concepts on CNS Infections
Key Questions
How does it occur?
Why does it happen?
How does it show?
Useful terms
Page 5: Access of Infectious Organisms to the CNS
Mechanisms of Access
Hematogenous Spread: Via bloodstream—most common mechanism.
Local Extension: From paranasal sinuses and middle ear.
Retrograde Transport: From peripheral nervous system (certain viruses).
Direct Implantation: Due to open traumatic injury, surgery, or injections.
Page 6: Why Infections Occur in the CNS
Immunologic Privilege
Predisposing factors that impair defense mechanisms:
Immunosuppression: Seen in transplant patients.
Mechanical Devices/Surgical Interventions.
Anatomical Congenital Malformations.
Hyposplenism and Asplenia.
Page 7: Inflammatory Responses in CNS Infections
Types of Inflammatory Infiltrates
Neutrophils: Associated with acute inflammation (bacterial meningitis, cerebritis, abscess).
Mononuclear Cells: Lymphocytes and plasma cells, associated with chronic inflammation (aseptic viral meningitis, encephalitis).
Page 8: Inflammatory Infiltrates by Organism
Specific Organisms and Locations
Granulomatous Inflammation: Mycobacteria, spirochetes, fungi, and parasites.
Microglial Nodules: Seen in viral encephalitis.
Page 9: Microglia
Role of Microglia in CNS
Resident Scavenger Cells: Originating from monocyte/macrophage lineage, migrate to the brain during early development.
Macrophages are also recruited from the periphery at sites of injury.
Page 10: Locations of CNS Infections (1/2)
Types of Inflammation
Pachymeningitis: Infection spread into layers of dura mater.
Meningitis/Leptomeningitis: Inflammation of pia and arachnoid.
Encephalitis: Inflammation of the brain with mononuclear cells; usually viral.
Cerebritis: Inflammation with neutrophils; usually bacterial.
Page 11: Locations of CNS Infections (2/2)
Myelitis: Inflammation of the spinal cord.
Poliomyelitis: Inflammation of spinal gray matter.
Ganglionitis: Inflammation of dorsal root ganglia.
Radiculitis: Inflammation of intradural spinal nerve roots.
Meningoencephalitis and myeloradiculitis may involve multiple structures.
Page 12: Bacterial Infections
Overview
Focus on Bacterial Abscess and Acute Bacterial Meningitis.
Mycobacteria (tuberculosis) are a significant focus.
Page 13: Bacterial CNS Infections
Introduction
Compartmentalization by the meninges: inhibits the spread of infections.
Epidural space—e.g., epidural abscess.
Subdural space—e.g., subdural abscess.
Subarachnoid space—e.g., leptomeningitis/meningitis.
Parenchyma—e.g., abscess/diffuse cerebritis.
Page 14: Brain Abscess: Gross Pathology
Features
Discrete, Round Lesions: Characterized by central liquefactive necrosis/purulent material.
Surrounding Fibrotic Capsule: Forms due to the body's immune response.
Mass Effect: Can cause herniation due to increased intracranial pressure.
Page 15: Brain Abscess: Sources and Organisms
Infection Sources
Local: From sinusitis, otitis, mastoiditis.
Hematogenous: Secondary to septic emboli or congenital heart disease shunts.
Common Organisms
Staphylococcus aureus and Streptococci: Often found in polymicrobial infections.
Bacterial Endocarditis: Can lead to infectious emboli reaching the brain.
Page 16: Types of Bacterial Infections
Overview
Bacterial Abscess, Acute Bacterial Meningitis, Mycobacteria (tuberculosis).
Page 17: Acute Bacterial Meningitis
Common Agents
Worldwide: Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae cause approximately 80% of cases.
Age-related Differences:
Neonates (0-6 months): Group B Streptococcus, Escherichia coli, Listeria monocytogenes.
Children and Adults (6 months to 60 years): Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae.
Adults (>60 years) and Immunosuppressed Patients: Streptococcus pneumoniae, Listeria monocytogenes.
Page 18: Types of Bacterial Infections
Summary
Bacterial Abscess, Acute Bacterial Meningitis, Mycobacteria (tuberculosis).
Page 19: Mycobacterial Infection of the CNS
Tuberculous Meningitis
Most common form of mycobacterial CNS infection, almost always caused by Mycobacterium tuberculosis.
Other Forms Include:
Tuberculomas of the brain and spinal cord.
Tuberculous Vertebral Osteomyelitis: Often presents with cranial nerve involvement and hydrocephalus.
Page 20: Viral Infections
Types of Viral Infections
Lymphocytic (Aseptic) Meningitis and Viral Encephalitis.
Page 21: CNS Viral Infections: Manifestations
Inflammation Patterns
Aseptic Meningitis: Inflammation restricted to the meninges; enteroviruses (over 80% cases).
Polioencephalitis/Poliomyelitis: Encephalitis affecting grey matter (poliovirus, coxsackieviruses, arboviruses, rabies).
Page 22: Acute Viral Encephalitis
Common Causes
La Crosse, St. Louis, West Nile, Japanese, Eastern and Western Equine Encephalitis.
Herpesviruses: HSV 1, HSV 2, VZV, EBV, CMV, Rabies.
Page 23: Arboviral Encephalitis
Key Features
Arboviruses: RNA viruses transmitted by arthropod vectors; lead to epidemic encephalitis.
Humans are incidental hosts in the life cycle between vertebrate hosts and arthropods.
Page 24: Herpetic Encephalitis (HSV-1)
Pathological Characteristics
Classical Presentation: Bilateral, asymmetrical, hemorrhagic necrosis of temporal lobes.
Differential Diagnosis: Must exclude infarction and contusions.
Page 25: Herpetic Encephalitis (HSV-1)
Pathological Features
Intranuclear Viral Inclusions: Signs of viral replication and infection within cells.
Lymphocyte and Macrophage Infiltration: Part of the immune response to infection.
Page 26: Other Causes of Herpetic Encephalitis
CMV and VZV
Cytomegalovirus: Significant CNS pathology in congenital and immunosuppressed cases.
Varicella-Zoster Virus: Rarely causes encephalitis, can lead to granulomatous arteritis.
Page 27: Fungal Infections
Overview
Common Fungal Infections: Include Aspergillosis and Zygomycosis (Mucor).
Page 28: Fungal Infections: Risk Factors
Predisposing Conditions
Neutropenia, Hematologic Malignancies, HIV/AIDS, Immunosuppressive Drugs, Diabetes Mellitus, IV Drug Use.
Mechanical Breakdown of the blood-brain barrier increases susceptibility.
Page 29: Aspergillosis
Microscopic Findings
Infiltration of Blood Vessels: Characteristic of fungal infections.
Vascular Thrombosis and Hemorrhage: Damage to blood vessels due to fungal invasion.
Grocott Silver Stain: Used to identify thin filamentous fungal forms with branching.
Page 30: Aspergillosis Transmission
Pathways of Infection
Acquired by hematogenous spread from invasive pulmonary/sinus aspergillosis, common in severely immunocompromised patients.
Page 31: CNS Fungal Infections: Manifestations
Clinical Features
Leptomeningitis, Diffuse Encephalitis, Space-occupying Lesions (granulomas/abscesses).
Acute Cerebrovascular Events: Resulting from vascular invasion and thrombosis.
Page 32: Overview of Fungal Infections
Overview
Common Types: Aspergillosis and Zygomycosis (Mucor).
Page 33: Zygomycosis (Mucormycosis)
Classic Clinical Presentation
Diabetic Ketoacidosis, Rhinocerebral Disease.
Genera Involved
Rhizopus, Mucor, Absidia: Fungal agents responsible for disease.
Page 34: Parasitic Infections
Overview
Types of Infections: Include Amebic Encephalitis and Cysticercosis.
Page 35: Primary Amebic Encephalitis: Naegleria fowleri
Disease Characteristics
Fulminant Meningoencephalitis: Associated with cerebral swelling and hemorrhagic necrosis; primarily affects frontal lobes and olfactory bulbs.
Page 36: Parasitic Infections
Overview
Amebic Encephalitis and Cysticercosis.
Page 37: Cysticercosis
Key Features
Infection by Cysticerci: Larvae of the tapeworm Taenia solium, the most common helminthic CNS disease.
Page 38: Cysticercosis CNS Involvement
Types of Cysts
Parenchymal, Meningeal, Ventricular Cysts; spinal cysts are rare.
Page 39: CNS Infections in the Immunocompromised Host
Common Infections
Progressive Multifocal Encephalopathy, Cryptococcal Meningitis, Toxoplasmosis, Coccidioidomycosis, HIV Encephalopathy.
Page 40: Progressive Multifocal Leukoencephalopathy
Virus Features
Caused by JC Virus (polyoma virus). Nearly universal serologic evidence of exposure by adolescence. Tropism for Oligodendroglia: leads to demyelinating lesions.
Page 41: Progressive Multifocal Leukoencephalopathy: Microscopic Pathology
Characteristics
Lipid-laden Macrophages: Found within lesions.
Perivascular Inflammation: Important pathological feature.
Intranuclear Viral Inclusions: Indicative of JC virus infection.
Page 42: Cryptococcal Meningitis
Pathogen
Cryptococcus neoformans: Most common fungal CNS infection, can present fulminantly or indolently. Mortality rate is approximately 30%.
Pathological Features
Minimal inflammatory response with lymphocytes, plasma cells, eosinophils, and multinucleated giant cells.
Page 43: Toxoplasmosis
Overview
Toxoplasma gondii: Protozoan parasite; risk factors include exposure to cat feces and undercooked meat. Symptoms primarily affect neonates and immunosuppressed individuals.
Page 44: Toxoplasmosis Diagnostics
Diagnostic Methods
Imaging, History, Serology: Seroprevalence varies greatly regionally.
CSF PCR: 50-70% sensitive for diagnosing Toxoplasmic encephalitis; biopsy is gold standard but may not always be necessary.
Page 45: Toxoplasmosis: Pathology
Clinical Presentation
Commonly presents as multiple ring-enhancing lesions in the brain. Free microorganisms may be found at the periphery of necrotic lesions.
Page 46: Toxoplasmosis Patterns
Pathological Features
Recognizable via H&E and special stains; easier with immunohistochemical techniques.
Page 47: HIV Encephalitis
Overview
Previously prevalent in HIV patients before HAART therapy availability.
Affects subcortical white matter, basal ganglia, and brainstem.
Pathological Features
Widespread Low-Grade Inflammation: Characteristics include perivascular lymphocytes, microglial nodules, and multinucleated giant cells.
Page 48: Summary of Infections
Overview
The route of infection, risk factors, and pathological patterns in the CNS depend on the CNS infecting agent.
Bacterial infections primarily cause Acute Bacterial Meningitis, Cerebral Abscess, and Tuberculous Meningitis. Viral infections primarily cause Lymphocytic Meningitis and Acute Encephalitis.
Page 49: Summary of Infections in Immunocompromised Host
Key Infections
Fungal infections usually related to Aspergillus and Zygomycosis/Mucormycosis.
Parasitic infections mainly include Primary Amebic Encephalitis and Cysticercosis.
Most common CNS infections of the immunocompromised include Cryptococcal Meningitis, Toxoplasmosis, HIV Encephalopathy, and Progressive Multifocal Encephalopathy.