26.2 Bacterial Diseases of the Nervous System

Bacterial Meningitis

Bacterial meningitis is a life-threatening infection of the meninges, the membranes surrounding the brain and spinal cord. Three pathogens cause the majority of cases, and each one has a distinct morphology, virulence strategy, and at-risk population. Understanding the differences between them is a common exam target.

Characteristics of Bacterial Meningitis Pathogens

Neisseria meningitidis

N. meningitidis is a gram-negative diplococcus, with cells shaped like two kidney beans facing each other. Its polysaccharide capsule is a major virulence factor because it helps the bacterium evade phagocytosis and complement-mediated killing.

• Transmitted through respiratory droplets from close contact (dorm living, military barracks) or sharing items like utensils
• Symptoms appear suddenly: high fever, severe headache, and stiff neck
• A petechial rash (small, non-blanching purple spots) can develop when the bacterium enters the bloodstream and releases endotoxin, causing septicemia
• Demonstrates neurotropism, meaning it preferentially targets and infects the meninges

Streptococcus pneumoniae

S. pneumoniae appears as gram-positive, lancet-shaped diplococci (often in pairs). Like N. meningitidis, it relies on a polysaccharide capsule to resist phagocytosis.

• Normally colonizes the nasopharynx without causing disease, but can invade the meninges when host defenses are weakened
• Symptoms include high fever, severe headache, and nuchal rigidity (the inability to flex the neck forward, a classic meningitis sign)
• Elderly and immunocompromised individuals face the highest risk for invasive pneumococcal disease

Haemophilus influenzae

H. influenzae is a gram-negative coccobacillus that can appear as short rods or coccoid forms. Encapsulated strains, specifically type b (Hib), are the most virulent because the capsule has antiphagocytic properties.

• Transmitted through respiratory droplets; colonizes the nasopharynx
• In infants and young children, symptoms include fever, lethargy, and stiff neck
• Untreated infections can lead to hearing loss and lasting neurological damage
• The Hib vaccine has dramatically reduced the incidence of invasive disease (meningitis, epiglottitis) since its introduction

Clostridial Neurotoxins

Clostridium botulinum and Clostridium tetani produce two of the most potent toxins known to science. Both are anaerobic, gram-positive, spore-forming bacilli, but their toxins act on opposite sides of the neuromuscular equation. Botulinum toxin blocks excitatory signals, causing flaccid (floppy) paralysis. Tetanus toxin blocks inhibitory signals, causing spastic (rigid) paralysis. Keeping this distinction straight is the key to understanding both diseases.

Mechanisms of Clostridium Neurotoxins

Clostridium botulinum

C. botulinum is found in soil and marine sediments. It produces botulinum neurotoxin (BoNT), which acts at the neuromuscular junction.

How BoNT causes paralysis:

1. The toxin is absorbed (from food, a wound, or the infant gut) and travels through the bloodstream to peripheral nerve endings.
2. BoNT enters the nerve terminal and cleaves SNARE proteins, which are required for synaptic vesicles to fuse with the membrane.
3. Without functional SNARE proteins, acetylcholine cannot be released into the synapse.
4. The result is descending flaccid paralysis: muscles go limp starting from the head (drooping eyelids, difficulty swallowing) and progressing downward. Respiratory failure can follow if the diaphragm is affected.

There are distinct forms of botulism to know:

• Foodborne botulism results from eating preformed toxin in improperly canned or preserved foods (home-canned vegetables, fermented fish)
• Infant botulism occurs when an infant ingests C. botulinum spores (e.g., from honey), which germinate and produce toxin in the immature gut, where normal flora haven't yet established competitive exclusion

Clostridium tetani

C. tetani is found in soil and animal feces. It produces tetanospasmin, the toxin responsible for tetanus.

How tetanospasmin causes spastic paralysis:

1. Spores enter the body through a contaminated wound, especially deep puncture wounds where anaerobic conditions favor germination.
2. Vegetative cells produce tetanospasmin, which binds to peripheral nerve terminals.
3. The toxin travels retrograde (backward along the nerve) up to the spinal cord.
4. In the spinal cord, tetanospasmin blocks the release of inhibitory neurotransmitters (GABA and glycine) from interneurons.
5. Without inhibitory signaling, motor neurons fire continuously, causing uncontrolled muscle contractions and painful spasms.

Classic symptoms of tetanus:

• Trismus (lockjaw): spasm of the jaw muscles, often the first sign
• Opisthotonus: severe arching of the back due to spasm of the paraspinal muscles
• Progression to respiratory failure if the muscles of breathing go into spasm

Hansen's Disease (Leprosy)

Hansen's disease is a chronic infection caused by Mycobacterium leprae. It primarily damages peripheral nerves and skin, and the clinical form a patient develops depends almost entirely on the strength of their cell-mediated immune response.

Progression of Hansen's Disease

The pathogen

M. leprae is an acid-fast, obligate intracellular bacillus with a unique tropism for two cell types: macrophages and Schwann cells (the cells that form myelin sheaths around peripheral nerves). It grows extremely slowly, with an incubation period of 2 to 10 years before symptoms appear. Transmission occurs through respiratory droplets during prolonged close contact with untreated individuals.

Tuberculoid leprosy (paucibacillary)

This form develops when the patient mounts a strong cell-mediated immune response that contains the infection.

• Few, well-defined hypopigmented skin lesions
• Loss of sensation in affected areas due to nerve damage
• Muscle weakness and atrophy, particularly in the hands and feet
• Bacterial load is low ("paucibacillary" = few bacilli)

Lepromatous leprosy (multibacillary)

This form develops when the patient has a weak cell-mediated immune response, allowing bacteria to replicate unchecked.

• Numerous, poorly defined skin lesions appearing as nodules or plaques
• Leonine facies: nodular lesions on the face give a lion-like appearance
• Systemic involvement can affect the eyes (blindness), bones (resorption), and testes (infertility)
• Bacterial load is high ("multibacillary" = many bacilli)

Diagnosis and treatment

Diagnosis relies on skin biopsy with acid-fast staining to identify bacilli. Treatment requires long-term multi-drug therapy (MDT) combining dapsone, rifampicin, and clofazimine. Multiple drugs are used simultaneously to prevent the emergence of drug-resistant strains.

Neuropathogenesis of Bacterial Infections

Three concepts describe how bacteria cause nervous system disease. These terms come up repeatedly across the pathogens in this unit:

• Neuroinvasion: the process by which bacteria cross the blood-brain barrier (BBB) to enter the central nervous system. The BBB normally restricts pathogen entry, so bacteria that cause meningitis have evolved specific mechanisms to breach it (e.g., capsules that resist immune clearance in the bloodstream, adhesins that bind to endothelial cells).
• Neurotropism: the tendency of certain pathogens to preferentially infect neural tissue. N. meningitidis targeting the meninges and M. leprae targeting Schwann cells are both examples of neurotropism.
• Neurotoxicity: the ability of bacterial toxins to directly damage nervous system components. Botulinum toxin and tetanospasmin are the clearest examples, each destroying normal neurotransmission through different mechanisms.

These three factors often work together. A bacterium may first invade the CNS (neuroinvasion), target specific neural cells (neurotropism), and then produce toxins that disrupt function (neurotoxicity).