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

1. Basic concepts on CNS infections

2. Bacterial infections

3. Viral infections

4. Fungal infections

5. Parasitic infections

6. Infections common in immunocompromised hosts

Page 4: Basic Concepts on CNS Infections

Key Questions

1. How does it occur?

2. Why does it happen?

3. How does it show?

4. 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.