Chapter 17: Infectious Diseases Affecting the Nervous System

Nervous System Anatomy and Functions

  • Central Nervous System (CNS): Consists of the brain and the spinal cord.
  • Peripheral Nervous System (PNS): Contains the nerves that emanate from the CNS to the sense organs and the periphery of the body.
  • Three Important Functions:
    • Sensory: Fulfilled by sensory receptors at the ends of peripheral nerves; these generate nerve impulses transmitted to the CNS.
    • Integrative: Translates sensation into thought.
    • Motor: Receives signals from the CNS to muscles and glands.
  • Neurons: Cells making up the tissues of the brain and spinal cord; they receive and transmit signals to and from the CNS and PNS.
  • Anatomical Structures:
    • The brain is situated inside the skull.
    • The spinal cord lies within the spinal column, surrounded by vertebrae.
    • Meninges: Soft tissue encased within three layers:
      • Dura mater: The outermost layer.
      • Arachnoid mater: The middle layer.
      • Pia mater: The innermost layer.
    • Subarachnoid Space: The space between the arachnoid and pia mater, which is filled with cerebrospinal fluid (CSF).
  • Cerebrospinal Fluid (CSF):
    • Provides nutrition to the CNS.
    • Provides a liquid cushion for the brain and spinal cord.
    • Microorganisms can be found in the CSF during meningitis.
  • Peripheral Nervous System Components:
    • Ganglion: A swelling in the nerve where cell bodies of neurons aggregate.
    • Nerves: Bundles of axons that receive and transmit nerve signals.
    • Synapse: The point where axons and dendrites of adjacent neurons communicate.
    • Neurotransmitters: Released from one cell to act on the next cell in a synapse.

Defenses of the Nervous System

  • Structural Defenses:
    • Bony casings of the brain (skull) and spinal cord (vertebrae) protect from traumatic injury.
    • CSF provides a cushioning function.
  • Blood-Brain Barrier:
    • The vascular interface between blood vessels serving the brain and the brain itself.
    • Cells in blood vessel walls allow very few molecules to pass through.
    • Prohibits most microorganisms and most antibiotics from entering the nervous system.
  • Immunological Privilege:
    • The CNS is only able to mount a partial, or different, immune response when exposed to an immunologic challenge.
    • Vital CNS functions are protected from the potentially detrimental effects of normal inflammatory/immune responses.
    • Microglia and Brain Macrophages: These have phagocytic capabilities, though their activity is reduced compared to phagocytic cells in other parts of the body.

Normal Biota of the Nervous System

  • Current State of Knowledge: It is still believed that there is no normal biota in either the CNS or PNS.
  • Clinical Significance: Finding microorganisms of any type in these tissues represents a deviation from a healthy state.
  • Exceptions and Influences:
    • Herpesviruses can live in a dormant state in the nervous system but are not considered normal microbiota.
    • The gut microbiome influences the nervous system, including the development of the brain, the blood-brain barrier, and the construction of peripheral nerves.

Highlight Disease: Meningitis

  • Definition: Inflammation of the meninges.
  • Anatomical Syndrome: Many different microorganisms can cause infection of the meninges, all producing similar symptoms.
  • General Signs and Symptoms:
    • Severe headache.
    • Painful or stiff neck.
    • Fever.
    • Nausea and vomiting.
    • Photophobia: Sensitivity to light.
    • Skin rashes (present in specific types).
    • Increased number of white blood cells in the CSF.
  • Diagnosis and Treatment:
    • Procedures include lumbar puncture (spinal tap), Gram stain, and culture of CSF.
    • Treatment with broad-spectrum antibiotics is started immediately when suspected.
  • Serious Forms: Acute meningitis caused by bacteria is generally more serious. Entrance to the CNS is often facilitated by coinfection or previous infection with respiratory viruses.

Bacterial Causes of Meningitis

  • Neisseria meningitidis:
    • Characteristics: Gram-negative diplococci known as meningococcus.
    • Epidemiology: Associated with epidemic forms; accounts for 15 to 20%15 \text{ to } 20\% of all cases. High risk in young children (vaccination starts at age 11) and those in close quarters (dorms, barracks).
    • Pathogenesis: Enters via upper respiratory tract, moves to blood, and penetrates meninges. Releases endotoxin, stimulating WBCs and causing vascular collapse, hemorrhage, and petechiae on the trunk/appendages.
    • Virulence Factors: IgA protease and a capsule.
    • Symptoms: Sudden onset, fever higher than 40 ∘C40\,^{\circ}C (104 ∘F104\,^{\circ}F), sore throat, delirium, shock, coma, and death within a few hours.
    • Treatment: Mortality rate of treated disease is 15%15\%. Requires immediate high-dose intravenous Penicillin G. Rifampin or tetracycline is used for preventive therapy for close contacts.
  • Streptococcus pneumoniae:
    • Characteristics: Small, gram-positive flattened coccus in end-to-end pairs (pneumococcus).
    • Clinical Impact: Most frequent cause of community-acquired meningitis. 25%25\% of patients also have pneumococcal pneumonia.
    • Virulence Factors: Polysaccharide capsule, alpha-hemolysin, and hydrogen peroxide. Induces brain cell apoptosis.
    • Treatment: Often penicillin-resistant. Initial treatment is Vancomycin + Ceftriaxone.
    • Prevention: Prevnar (13-valent childhood vaccine) and Pneumovax 23 (23-valent adult vaccine).
  • Haemophilus influenzae:
    • Causes severe meningitis. Most U.S. cases are nonserotype B strains. Rare in the U.S. due to 1988 vaccine, but common globally in children under 5.
  • Listeria monocytogenes:
    • Characteristics: Gram-positive coccobacilli to long filaments. No capsules or endospores; has 1 to 4 flagella.
    • Pathogenesis: Resistant to cold, heat, salt, pH extremes, and bile. Grows inside host cells and moves directly between cells.
    • Symptoms: Mild in healthy adults. For the elderly, immunocompromised, and neonates, it causes septicemia (death rate around 30%30\%).
    • Pregnancy: Highly susceptible; causes intrauterine infections, premature abortion, and fetal death.
    • Transmission: Reservoir is soil and water. Secondary sources include contaminated dairy, poultry, and meat (found in 10 to 15%10 \text{ to } 15\% of ground beef and 25 to 30%25 \text{ to } 30\% of chicken/turkey).
    • Diagnosis: Cold enrichment (specimen held at 4 ∘C4\,^{\circ}C for up to 4 weeks).
    • Treatment: Ampicillin and Trimethoprim-sulfamethoxazole.

Fungal and Viral Meningitis

  • Cryptococcus neoformans:
    • Characteristics: Fungus with spherical/ovoid shape and a large capsule.
    • Pathogenesis: Chronic meningitis with gradual onset (faster in AIDS patients). Symptoms include headache, nausea, and neck stiffness.
    • Transmission: Ecological niche is bird populations (pigeons). Yeast cells scatter in air/dust from bird droppings. Highest rates in AIDS, cancer, and diabetes patients.
  • Coccidioides species:
    • Characteristics: Fungi causing "Valley Fever." Forms septate hyphae at 25 ∘C25\,^{\circ}C which fragment into thick-walled arthroconidia. Germinates into spherules at 37 ∘ to 40 ∘C37\,^{\circ} \text{ to } 40\,^{\circ}C.
    • Pathogenesis: Pulmonary infection that can disseminate. Coccidioidomycosis of the meninges is the most serious form.
    • Transmission: Southwestern U.S. (100,000100,000 cases yearly), Mexico, Central and South America. Associated with farming, archeology, and construction.
  • Viral Meningitis (Aseptic Meningitis):
    • Characteristics: No bacteria, protozoa, or fungi in CSF. Viruses cause 4/54/5 cases of meningitis.
    • Epidemiology: 90%90\% caused by enteroviruses. Also HSV-2 (genital infection concurrent).
    • Outcome: Milder than bacterial; usually resolves in 2 weeks. Mortality rate is less than 1%1\%.

Neonatal Meningitis

  • Transmission: Usually vertical (in utero or during birth canal passage).
  • Trends: Rates increase as more premature babies survive due to immature immune systems.
  • Causative Agents:
    • Streptococcus agalactiae (Group B Streptococcus): Colonizes 10 to 30%10 \text{ to } 30\% of female genital tracts. Treated with Penicillin G at labor onset.
    • Escherichia coli (K1 strain): Second most common cause. Most common in premature babies with 20 to 30%20 \text{ to } 30\% mortality. Survivors often have permanent brain damage. Treated with Ceftazidime or Cefepime.
    • Cronobacter sakazakii: Transmitted via contaminated powdered infant formula. Mortality rates reach 40%40\%.

Zika Virus Disease

  • Causative Agent: Zika virus (Flaviviridae family). Related to Dengue, West Nile, and Yellow Fever.
  • Signs and Symptoms:
    • Adults: Skin rash, conjunctivitis, muscle/joint pain. Triggers Guillain-Barré syndrome.
    • Congenital Zika Virus Syndrome: Microcephaly (small head), vision problems, seizures, irritability, and swallowing problems.
  • Transmission: Aedes mosquito bite; sexual intercourse; vertical in utero.
  • Prevention: No vaccine. Supportive measures include intensive physical therapy and mechanical ventilation for Guillain-Barré syndrome.

Poliomyelitis

  • Definition: Acute enteroviral infection of the spinal cord inducing neuromuscular paralysis; also called infantile paralysis.
  • Causative Agent: Poliovirus (Picornaviridae family). Nonenveloped RNA virus with a naked capsid resistant to acid, bile, and detergents.
  • Pathogenesis: Adsorbs to mucosal cells in oropharynx and intestine. Multiplies in lymphoid tissue and sheds in throat/feces. Infiltrates motor neurons (anterior horn of spinal cord).
  • Clinical Forms:
    • Paralytic Disease: Flaccid paralysis of legs, abdomen, back, diaphragm, and bladder.
    • Bulbar Poliomyelitis: Affects brain stem and medulla; loss of cardiorespiratory control requires mechanical respirators. Atrophy of unused muscles causes severe deformities.
  • Prevention:
    • Inactivated Poliovirus Vaccine (IPV): Salk vaccine (19541954).
    • Oral Poliovirus Vaccine (OPV): Sabin vaccine (1960s1960s). Contains attenuated virus; rare risk of reversion to virulence.

Meningoencephalitis

  • Naegleria fowleri:
    • Causative Agent: Amoeba found in warm, natural bodies of fresh water.
    • Pathogenesis: Forced into nasal passages; burrows into nasal mucosa and migrates to the brain. Causes Primary Amoebic Meningoencephalitis (PAM). Result is massive destruction of brain/spinal tissue, hemorrhage, coma, and death within a week.
    • Treatment: Usually futile. Early therapy with Amphotericin B, Sulfadiazine, or Tetracycline may help.
  • Acanthamoeba:
    • Pathogenesis: Causes Granulomatous Amoebic Meningoencephalitis (GAM). Course is lengthier than Naegleria.
    • Transmission: Invades broken skin, conjunctiva, lungs, and urogenital epithelia. Risk factor: contact lens wearers and traumatic eye injuries.

Encephalitis

  • Acute Encephalitis:
    • Almost always viral, specifically arboviruses (insect-borne) like West Nile virus.
    • Signs: Behavior changes, confusion, decreased consciousness, seizures, and meningitis symptoms.
    • Arboviral Encephalitis: Transmitted by mosquito bites. Inflammation causes swelling/damage to brain and nerves. No satisfactory treatment exists; management involves supportive care.
    • Herpes Simplex Virus (HSV-1 and HSV-2): Encephalitis in newborns from HSV-positive mothers. In older adults, HSV-1 encephalitis results from reactivation of dormant virus in the trigeminal ganglion.
    • JC Virus: Causes Progressive Multifocal Leukoencephalopathy (PML) in immune-dysfunctional patients (AIDS). Demyelination of cerebrum. Generally fatal.
  • Subacute Encephalitis: Symptoms appear slower and are less striking.
    • Toxoplasma gondii: Flagellated protozoan parasite.
      • Host Cycle: Sexual phase in cat intestine; oocysts released in feces. Intermediate hosts (rodents/birds) infected via oocysts. Healthy humans usually asymptomatic or have mild sore throat/fever.
      • Brain Effects: Infected rats lose fear of cats. Humans with prior infection may show thrill-seeking behaviors and slower reaction times.
      • Congenital Infection: Severe; associated with stillbirth, hydrocephalus, and blindness.
      • Prevention: Hygiene (cat feces handling) and cooking meat (−20 ∘C-20\,^{\circ}C freezing).
    • Subacute Sclerosing Panencephalitis (SSPE): "Slow virus infection" occurring 7 to 157 \text{ to } 15 years after initial measles infection. Always fatal.

Prions and Creutzfeldt-Jakob Disease

  • Causative Agent: Prions (proteinaceous infectious particles with no genetic material).
  • Mechanism: Misfolded PrP protein causes a catalytic chain reaction, converting normal PrP into abnormal forms, leading to plaques and spongiform damage ("holes" in brain).
  • Disease Types:
    • Human TSEs: Creutzfeldt-Jakob Disease (CJD), Gerstmann-Strussler-Scheinker disease, fatal familial insomnia.
    • Animal TSEs: Scrapie (sheep/goats), BSE ("Mad Cow").
  • Characteristics of CJD: Altered behavior, dementia, Premature senility, and uncontrollable muscle contractions. Death usually within a year.
  • Resistance: Prions are resistant to chemicals, radiation, heat, and prolonged autoclaving.
  • CJD Variants: vCJD (contracted from BSE meat) has a median death age of 2828, whereas other CJD forms have a median age of 6868.

Rabies

  • Definition: Slow, progressive zoonotic disease characterized by fatal encephalitis.
  • Pathogenesis: Saliva from infected animal bite enters puncture wound. Virus multiplies at trauma site (11 week) then advances toward the CNS. Finally replicates in salivary glands.
  • Symptoms: Incubation 22 weeks to years. Prodromal phase: fever, nausea, fatigue. Ended almost inevitably in death until recent advancements.
  • Reservoirs: Wild mammals (raccoons, bats, skunks). Bats are the primary source of human rabies in the U.S.
  • Treatment: Combination of Human Rabies Immune Globulin (HRIG) infused into the wound and systemic vaccination.

Tetanus and Botulism

  • Tetanus (Lockjaw):
    • Causative Agent: Clostridium tetani, a gram-positive, endospore-forming anaerobic bacillus found in soil and animal GI tracts.
    • Neurotoxin: Tetanospasmin blocks the inhibition of muscle contraction.
    • Symptoms: Clenching of the jaw (Risus sardonicus - "sardonic grin"), arching of back, flexion of arms, extension of legs. Death via respiratory arrest.
    • Treatment: Human Tetanus Immune Globulin (TIG) and Penicillin G.
  • Botulism:
    • Causative Agent: Clostridium botulinum, an anaerobic endospore-former.
    • Neurotoxin: Botulinum toxin prevents the release of acetylcholine at neuromuscular junctions, causing flaccid paralysis.
    • Forms:
      • Infant Botulism (66%66\%): "Floppy-baby syndrome" often from raw honey or dust.
      • Wound Botulism (14%14\%): Associated with intravenous drug use.
      • Foodborne Botulism (10%10\%): Pure intoxication from poorly preserved home-canned foods.
    • Symptoms: Double vision, dizziness, difficulty swallowing, descending paralysis, and respiratory arrest.
    • Treatment: Antitoxin from the CDC; respiratory and cardiac support.