Chapter 20: Infectious Diseases Manifesting in the Nervous System – Structure, Defenses, and Major Pathogens

20.1 The Nervous System, Its Defenses, and Normal Biota

Overview of the Nervous System

The nervous system is divided into two main components, each with distinct anatomical and functional roles. Understanding these divisions is essential for appreciating how infectious diseases can impact neural tissues.

• Central Nervous System (CNS): Composed of the brain and spinal cord, responsible for processing and integrating information.

• Peripheral Nervous System (PNS): Consists of nerves emanating from the CNS to sense organs and peripheral tissues.

Functions of the Nervous System

• Sensory: Sensory receptors at peripheral nerve endings generate impulses transmitted to the CNS.

• Integrative: The CNS translates impulses into sensations or thoughts and drives motor functions.

• Motor: Involves activation of muscles and glands.

Protective Structures and Fluids

• Bone: The brain is encased in the skull; the spinal cord is protected by the vertebral column.

• Meninges: Three protective membranes surrounding the CNS: dura mater, arachnoid mater, and pia mater.

• Cerebrospinal Fluid (CSF): Fills the subarachnoid space, provides nutrition, and acts as a cushion for the brain and spinal cord.

Defenses of the Nervous System

• Bony casings: Protect against traumatic injury.

• CSF: Serves as a shock absorber.

• Blood–Brain Barrier: Specialized endothelial cells restrict passage of most molecules and microbes into the CNS, making infections rare but also complicating drug delivery.

Specialized Immune Cells

• Microglial cells: CNS-resident phagocytes.

• Brain macrophages: Present but less active than peripheral phagocytes.

Nervous System	Defenses	Normal Biota
CNS & PNS	Bony structures, blood–brain barrier, microglial cells, macrophages	None

Normal Biota and the Gut–Brain Axis

• The CNS and PNS are considered sterile; detection of microbes indicates pathology.

• Emerging evidence suggests the gut microbiome may influence CNS function and autoimmunity (the gut–brain axis).

20.2 Infectious Diseases Manifesting in the Nervous System

Overview of Meningitis

Meningitis is inflammation of the meninges, most often caused by bacteria, but also by viruses and fungi. Rapid diagnosis and treatment are critical due to the risk of severe neurological damage or death.

• Symptoms: Fever, headache, stiff neck, nausea, vomiting, photophobia, seizures, altered mental status.

• Pathogenesis: Virulence factors enable pathogens to penetrate the blood–brain barrier.

Major Bacterial Causes of Meningitis

• Neisseria meningitidis: Gram-negative diplococcus, significant cause of epidemic meningitis. Virulence factors include capsule, endotoxin, and IgA protease. Diagnosed by Gram stain, culture, and oxidase test.

• Streptococcus pneumoniae: Gram-positive, encapsulated coccus, leading cause of community-acquired meningitis. Produces alpha-hemolysin and hydrogen peroxide. Two vaccines available.

• Haemophilus influenzae (type b): Gram-negative coccobacillus, historically a major cause, now rare due to vaccination.

• Listeria monocytogenes: Gram-positive rod, grows in cold, heat, salt, and bile; can cross placenta, causing fetal death. Associated with contaminated dairy, poultry, and meat.

Major Fungal Causes of Meningitis

• Cryptococcus neoformans: Encapsulated yeast, causes chronic meningitis, especially in immunocompromised patients. Transmitted via bird droppings.

• Coccidioides spp.: Dimorphic fungus ("Valley Fever"), endemic in the Americas. Forms spherules in tissue; inhalation of spores is the main route.

Viral Meningitis

• Accounts for the majority of meningitis cases ("aseptic meningitis").

• Most common in children; 90% caused by enteroviruses.

• Generally milder than bacterial or fungal forms; resolves in about two weeks.

Meningitis Disease Table

Causative Organism(s)	Most Common Modes of Transmission	Virulence Factors	Culture/Diagnosis	Prevention	Treatment	Distinctive Features	Epidemiological Features
Neisseria meningitidis	Droplet contact	Capsule, endotoxin, IgA protease	Gram stain/culture of CSF, blood, rapid antigen tests	Conjugated vaccine, prophylactic antibiotics	Penicillin G, ceftriaxone	Petechiae, rapid decline	Highest incidence in children/young adults
Streptococcus pneumoniae	Droplet contact	Capsule, alpha-hemolysin, hydrogen peroxide	Gram stain/culture of CSF	Two vaccines (Prevnar, Pneumovax)	Ceftriaxone, vancomycin	No petechiae, underlying susceptibility	Most common in adults
Haemophilus influenzae	Droplet contact	Capsule	Cultured on chocolate agar	Hib vaccine	Ceftriaxone	Severe, rapid onset	Rare in vaccinated populations
Listeria monocytogenes	Vehicle (food)	Intracellular growth	Cold enrichment, rapid methods	Cooking food, avoiding unpasteurized dairy	Ampicillin, gentamicin	Asymptomatic in healthy adults	High mortality in neonates, elderly
Cryptococcus neoformans	Vehicle (air, dust)	Capsule, melanin production	Negative staining, biochemical tests	N/A	Amphotericin B, flucytosine	Chronic, common in AIDS patients	90% of infections in HIV+ patients
Coccidioides spp.	Vehicle (air, dust, soil)	Granuloma (spherule) formation	Identification of spherules, Sabouraud's agar	Avoiding airborne exposure	Fluconazole, amphotericin B	Endemic regions only	200–300 cases/year in endemic areas
Viruses	Droplet contact	Lytic infection of host cells	Viral culture, antigen tests	N/A	Supportive care	Milder than bacterial/fungal	26,000–42,000 hospitalizations/year in US

Neonatal and Infant Meningitis

• Usually transmitted from mother to infant during birth or in utero.

• Most common causes: Streptococcus agalactiae (Group B strep), Escherichia coli (K1 strain), and Listeria monocytogenes.

• Premature infants are at higher risk; mortality rates have declined but morbidity remains significant.

Causative Organism(s)	Most Common Modes of Transmission	Virulence Factors	Culture/Diagnosis	Prevention	Treatment	Distinctive Features	Epidemiological Features
Streptococcus agalactiae	Vertical (during birth)	Capsule	Culture mother’s genital tract, CSF culture of infant	Chemoprophylaxis of mother	Penicillin G plus aminoglycosides	Most common; positive culture of mother confirms diagnosis	Colonizes 10–30% of women
Escherichia coli (K1)	Vertical (during birth)	Capsule	CSF Gram stain/culture	N/A	Cefotaxime or combination therapy	Suspected if infant is premature	20% mortality in premature infants
Listeria monocytogenes	Vertical	Intracellular growth	Cold enrichment, rapid methods	Cooking food, avoiding unpasteurized dairy	Ampicillin, gentamicin	Asymptomatic in healthy adults	High mortality in neonates

Meningoencephalitis

• Definition: Inflammation of both the brain and meninges.

• Causative agents: Amoebas such as Naegleria fowleri (primary amoebic meningoencephalitis) and Acanthamoeba (granulomatous amoebic meningoencephalitis).

Causative Organism(s)	Most Common Modes of Transmission	Virulence Factors	Culture/Diagnosis	Prevention	Treatment	Epidemiological Features
Naegleria fowleri	Vehicle (exposure to warm freshwater)	Invasiveness	CSF exam, brain imaging, biopsy	Avoid swimming in warm, untreated water	Pentamidine, sulfadiazine	Rare, almost always fatal
Acanthamoeba	Direct contact	Invasiveness	CSF exam, brain imaging, biopsy	N/A	Surgical excision, pentamidine	Immunocompromised patients