Nervous System Infections: Microbiology and Clinical Principles

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Nervous System Overview: Structure & Defenses

Central and Peripheral Nervous System

The nervous system is divided into two main parts: the Central Nervous System (CNS) and the Peripheral Nervous System (PNS). The CNS integrates information and sends action plans, while the PNS transmits sensory input and motor output.

CNS: Composed of the brain and spinal cord; responsible for processing and integrating information.
PNS: Composed of nerves; responsible for transmitting signals to and from the CNS.

Diagram of central and peripheral nervous system

Neurons: Types and Structure

Neurons are specialized cells that transmit signals throughout the nervous system. They are classified based on their function:

Sensory (Afferent) Neurons: Carry sensory information from the environment to the CNS.
Motor (Efferent) Neurons: Transmit commands from the CNS to muscles and glands.
Interneurons: Facilitate communication between sensory and motor neurons, primarily within the CNS.

Types of neurons: sensory, motor, interneuron

Neurons have distinct structural components:

Cell Body: Contains the nucleus and organelles.
Dendrites: Receive incoming signals.
Axon: Conducts electrical impulses away from the cell body.
Axon Terminal: Releases neurotransmitters to communicate with other neurons or effectors.

Parts of a neuron Myelinated neuron and direction of signal

Neurotransmitters

Neurotransmitters are chemical messengers released by neurons in response to stimuli. Examples include serotonin, dopamine, and epinephrine. They play a critical role in transmitting signals across synapses.

The Nervous System and the Microbiome

Microbiota and the Gut-Brain Axis

The nervous system itself contains no resident microbiota; any microbial presence is abnormal and potentially pathogenic. However, the gut-brain axis describes the bidirectional communication between the gastrointestinal tract's microbiota and the nervous system, influencing mood, cognition, and neurodegenerative diseases.

Gut-brain axis: Involves endocrine, nervous, and immune systems.
Alterations in gut microbiota can impact neurological health (e.g., anxiety, depression, Alzheimer's, Parkinson's).

Gut-brain axis: normal vs. stress/disease

Vulnerability of Nervous System Tissue

The brain, spinal cord, and nerves are highly susceptible to damage and have limited regenerative capacity. Loss of function due to injury or infection is often permanent, highlighting the importance of protective mechanisms.

Spinal cord injury and affected regions

Nervous System Defenses

Meninges

The meninges are three protective tissue layers (dura mater, arachnoid mater, pia mater) that surround the brain and spinal cord. They provide physical protection, supply nutrients, and remove waste.

Cranial and spinal meninges

Cerebrospinal Fluid (CSF)

Cerebrospinal fluid is produced within the brain and acts as a cushion for the CNS, protecting it from physical trauma and helping to maintain homeostasis.

CNS and cerebrospinal fluid location

Blood–Brain Barrier (BBB)

The blood–brain barrier is formed by specialized capillaries that tightly regulate the passage of substances from the blood into the CNS. Only small or lipophilic molecules can cross easily, providing a critical defense against pathogens.

Limits access of pathogens and toxins to sensitive neural tissue.
Some microbes have evolved mechanisms to bypass or disrupt the BBB.

Blood-brain barrier vs. regular capillary

Nervous System Infections

Types and Causes

Nervous system infections are rare due to robust defenses but can be severe. They are more likely after injury or in immunocompromised individuals. Major types include:

Meningitis: Inflammation of the meninges.
Encephalitis: Inflammation of the brain.
Meningoencephalitis: Inflammation of both the brain and meninges.

Normal brain vs. meningitis-affected brain

Etiological Agents

Viruses: Most common cause of meningitis and encephalitis; usually less severe than bacterial forms.
Bacteria: Cause more severe disease; require specialized virulence factors to cross the BBB.
Fungi and Parasites: Less common but possible causes.

Peripheral Nervous System Infections

Some viruses can establish latency in peripheral neurons, causing recurrent flare-ups. Certain bacterial toxins can also disrupt PNS function, leading to neurological symptoms.

Viral Nervous System Infections

General Features

Viruses, due to their small size, can more easily cross the BBB and infect nervous tissue. Common viral infections include poliomyelitis, rabies, and arboviral encephalitis.

Virus crossing the blood-brain barrier

Poliomyelitis (Polio)

Etiological agent: Poliovirus (Picornaviridae family), a small, non-enveloped RNA virus.
Transmission: Fecal-oral route.
Mechanism: Virus survives stomach acid, infects intestinal cells, replicates in muscle, and ascends motor neurons to the CNS, causing neuron lysis and inflammation.
Symptoms: Most cases are mild (flulike), but severe cases involve muscle weakness, paralysis (asymmetric or symmetric), and post-polio syndrome.
Prevention: Salk (IPV, inactivated) and Sabin (OPV, live attenuated) vaccines.

Poliovirus structure Child with polio-induced paralysis Oral polio vaccine administration

Rabies

Etiological agent: Rabies virus (Rhabdoviridae family), enveloped, single-stranded RNA virus.
Transmission: Zoonotic; typically via animal bite.
Mechanism: Virus replicates in muscle, travels via PNS to CNS, then spreads to other tissues. Does not lyse cells but disrupts neuron function and induces apoptosis.
Symptoms: Incubation (2–12 months), followed by fever, paraesthesia, neurological symptoms (hydrophobia, delirium), and almost always fatal after onset of neurological symptoms.
Diagnosis: Negri bodies in brain tissue.
Prevention: Postexposure prophylaxis, animal vaccination.

Rabies virus structure Negri bodies in brain tissue

Arboviral Encephalitis and Meningitis

Etiological agents: Arboviruses (e.g., West Nile virus, La Crosse virus), enveloped, single-stranded RNA viruses.
Transmission: Arthropod vectors (mosquitoes); humans are dead-end hosts.
Symptoms: Flulike symptoms, fever, headache; severe cases can cause neuroinvasive disease and death.
Prevention: Insect repellent, mosquito control.

West Nile virus structure Mosquito bite as arbovirus transmission

Bacterial Nervous System Infections - CNS

General Features

Bacterial meningitis is less common but more severe than viral forms, with high rates of mortality and long-term disability. Rapid diagnosis and treatment are critical.

Bacterial meningitis cross-section

Bacterial vs. Viral Meningitis: Diagnosis

CSF Culture: Bacterial meningitis shows growth; viral does not.
CSF Glucose: Bacterial meningitis often lowers CSF glucose; viral does not affect glucose levels.

Haemophilus Meningitis

Etiological agent: Haemophilus influenzae (type b most serious), Gram-negative.
Transmission: Normal microbiota; infection occurs when bacteria invade blood and CSF.
Symptoms: Sudden fever, headache, stiff neck, confusion.
Prevention: Hib vaccine; cases have dramatically decreased post-vaccine.

Haemophilus influenzae antigens Hib vaccine

Meningococcal Meningitis

Etiological agent: Neisseria meningitidis, Gram-negative aerobe with capsule (major virulence factor).
Transmission: Carried by 10% of population; outbreaks after capsular switching.
Symptoms: Rapid onset, petechial rash, can progress to severe lesions.
Prevention: Multiple vaccines (conjugate, polysaccharide, serogroup B).

Meningococcal meningitis progression Meningococcal vaccine impact

Pneumococcal Meningitis

Etiological agent: Streptococcus pneumoniae, Gram-positive diplococcus.
Mechanism: Produces pneumolysin exotoxin, causing severe inflammation and immune-mediated damage.
Prevention: PCV7 vaccine; most cases in nonimmunized children and elderly.

Streptococcus pneumoniae Pneumococcal meningitis brain scan

Listeria Meningitis (Listeriosis)

Etiological agent: Listeria monocytogenes, Gram-positive rod, grows at various pH and temperatures.
Transmission: Foodborne (tainted cheese, deli meats, produce).
Symptoms: Mild in healthy adults; severe in pregnant women, neonates, elderly, and immunocompromised.
Mechanism: Intracellular pathogen; escapes phagosome, uses actin tails to move cell-to-cell.
Prevention: Avoid high-risk foods; high mortality in vulnerable populations.

Listeria monocytogenes Foodborne transmission of Listeria Listeria risk groups Listeria actin-based motility Listeria infection in pregnancy Listeria prevention

Key Nervous System Vocabulary

Meninges: Three layers of tissue encasing the CNS.
Cerebrospinal fluid (CSF): Fluid cushioning and nourishing the CNS.
Concussion: Temporary CNS dysfunction due to physical force.
Coma: Prolonged unconsciousness resistant to waking.
Meningitis: Inflammation of the meninges.
Encephalitis: Inflammation of the brain.
Meningoencephalitis: Inflammation of both brain and meninges.
Lumbar puncture: Diagnostic removal of CSF via needle in lower back.
Immunocompromised: Individual with weakened immune system.
Cytolytic: Agent causing cell lysis.
Zoonosis: Disease transmitted from animals to humans.
Systemic infection: Infection affecting the whole body.
Paraesthesia: Prickling or "pins-and-needles" sensation.
Flaccid paralysis: Paralysis with inability to contract muscles.
Symmetric paralysis: Paralysis affecting both sides equally.
Asymmetric paralysis: Paralysis affecting one side more than the other.
Spastic paralysis: Inability to relax muscles.
Toxemia: Presence of toxins in the blood.
Serotype: Group of microbes sharing common surface antigens.