Infectious Diseases Manifesting in the Nervous System: Microbiology Study Notes

Chapter 20: Infectious Diseases Manifesting in the Nervous System

20.1 The Nervous System, Its Defenses, and Normal Biota

The nervous system is a complex network responsible for sensory input, integration, and motor output. Its unique anatomical and physiological features provide both protection and vulnerability to infectious diseases.

• Central Nervous System (CNS): Consists of the brain and spinal cord. Protected by the skull and vertebral column.

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

Functions of the Nervous System

• Sensory: Sensory receptors detect stimuli and transmit impulses to the CNS.

• Integrative: CNS processes impulses, resulting in sensation, thought, and motor function.

• Motor: Motor impulses control muscles and glands.

Structural Protection

• Meninges: Three protective layers surrounding the brain and spinal cord: Dura mater, Arachnoid mater, and Pia mater.

• Cerebrospinal Fluid (CSF): Fills the subarachnoid space, provides nutrition, and cushions the CNS.

Blood-Brain Barrier

• Specialized endothelial cells restrict passage of most molecules and microbes into the CNS.

• Allows freer passage of ions and metabolites elsewhere in the body.

• Limits drug and antibiotic access to the CNS.

Immune Defenses in the CNS

• Microglial cells: CNS-resident phagocytes.

• Brain macrophages: Provide additional immune surveillance.

• Phagocytic activity is lower than in other tissues.

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

Emerging Microbiome Results

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

• Recent research suggests the gut-brain axis: gut microbiota may influence CNS autoimmunity and brain chemistry.

20.2 Infectious Diseases Manifesting in the Nervous System

Numerous microorganisms can infect the nervous system, leading to conditions such as meningitis, encephalitis, and meningoencephalitis. Understanding causative agents, transmission, and prevention is crucial for clinical management.

Meningitis

• Definition: Inflammation of the meninges, most often caused by bacteria, viruses, or fungi.

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

• Diagnosis: Rapid and accurate diagnosis is essential to prevent mortality.

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

Major Bacterial Causes of Meningitis

• Neisseria meningitidis: Gram-negative diplococcus, epidemic meningitis, virulence via capsule, endotoxins, enzymes.

• Streptococcus pneumoniae: Gram-positive, end-to-end pairs, polysaccharide capsule, alpha-hemolysin, hydrogen peroxide, two vaccines available.

• Haemophilus influenzae: Gram-negative coccobacillus, "Hib" (serotype B), severe disease, vaccine has reduced incidence.

• Listeria monocytogenes: Gram-positive, variable morphology, intracellular growth, resistant to environmental extremes, associated with contaminated food.

Fungal Causes of Meningitis

• Cryptococcus neoformans: Encapsulated yeast, chronic meningitis, rapid onset in immunocompromised, transmitted via bird droppings.

• Coccidioides spp.: "Valley Fever," dimorphic fungus, endemic in southwestern U.S., true systemic infection.

Viral Meningitis

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

• Other causes: HSV-2, HHV-6, HHV-7, HHV-3, HIV.

• Generally milder than bacterial/fungal forms; resolves in ~2 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	Conjugate vaccine, prophylactic antibiotics	Ceftriaxone, penicillin	Petechiae, rapid decline	14% of bacterial cases; 1,000 cases/year in U.S.
Streptococcus pneumoniae	Droplet contact	Capsule, alpha-hemolysin, hydrogen peroxide	Gram stain/culture of CSF	Two vaccines	Ceftriaxone, vancomycin	Most common, no petechiae	Highest rates in children & elderly
Haemophilus influenzae	Droplet contact	Capsule	Culture on chocolate agar	Hib vaccine	Ceftriaxone, rifampin	Serious, acute, less common since vaccine	Virtually eliminated in U.S.
Listeria monocytogenes	Vehicle (food)	Intracellular growth	Cold enrichment, rapid methods	Cooking food, avoiding unpasteurized dairy	Ampicillin + gentamicin	Asymptomatic in healthy adults, septicemia in neonates	Mortality as high as 33% in symptomatic cases
Cryptococcus neoformans	Vehicle (air, dust)	Capsule, melanin production	Negative staining, biochemical tests	N/A	Amphotericin B, flucytosine	Acute or chronic, common in AIDS patients	90% of infections in HIV+ patients
Coccidioides spp.	Vehicle (air, dust, soil)	Granuloma (spherule) formation	Identification of spherules, cultivation	Avoiding airborne exposure	Fluconazole, amphotericin B	Almost exclusively in endemic regions	200-300 cases/year in U.S.
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 U.S.

Neonatal and Infant Meningitis

• Transmitted from mother in utero or during birth.

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

• Premature infants at higher risk; mortality and morbidity rates vary.

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 and treatment of mother	Penicillin G + aminoglycosides	Most common, positive culture of mother	1.8 cases per 1,000 live births
Escherichia coli (K1)	Vertical (during birth)	N/A	CSF Gram stain/culture	N/A	Ceftriaxone or cefotaxime	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	Mortality as high as 33% in symptomatic cases	Rare but deadly
Cronobacter sakazakii	Vehicle (baby formula)	Ability to survive dry conditions	Culture on rapid chromogenic agar	Safe preparation of formula	Supportive care	Rare, outbreaks in neonatal units	Few cases, but high mortality

Meningoencephalitis

• Definition: Inflammation of both the brain and meninges.

• Causative agents: Amoebas such as Naegleria fowleri and Acanthamoeba.

Causative Organism(s)	Most Common Modes of Transmission	Virulence Factors	Culture/Diagnosis	Prevention	Treatment	Epidemiological Features
Naegleria fowleri	Vehicle (freshwater exposure)	Invasiveness	CSF exam, brain imaging	Avoid untreated water entering nasal passages	Pentamidine, sulfadiazine	7 cases/year in U.S., mostly southern states
Acanthamoeba	Direct contact	Invasiveness	CSF exam, biopsy	N/A	Surgical excision, pentamidine	Immunocompromised patients

Additional info:

• Further sections in the chapter (not shown in these slides) would cover viral encephalitis, prion diseases, and other nervous system infections such as rabies, polio, tetanus, botulism, and African sleeping sickness, each with their causative agents, transmission, prevention, and treatment.