🦠Microbiology Unit 26 – Nervous System Infections

Key Pathogens and Diseases

• Viruses are the most common cause of nervous system infections and include herpes simplex virus (HSV), varicella-zoster virus (VZV), and enteroviruses
  • HSV-1 and HSV-2 can cause encephalitis, meningitis, and myelitis
  • VZV is responsible for chickenpox and shingles, which can lead to postherpetic neuralgia
• Bacteria such as Neisseria meningitidis, Streptococcus pneumoniae, and Haemophilus influenzae are major causes of bacterial meningitis
  • Listeria monocytogenes can cause meningitis in immunocompromised individuals and pregnant women
• Fungi like Cryptococcus neoformans and Candida albicans can cause meningitis, especially in immunocompromised patients (HIV/AIDS)
• Parasites such as Toxoplasma gondii and Naegleria fowleri can cause encephalitis and meningoencephalitis, respectively
• Prion diseases, including Creutzfeldt-Jakob disease (CJD), are rare but fatal neurodegenerative disorders caused by misfolded proteins

Anatomy and Physiology of the Nervous System

• The nervous system is divided into the central nervous system (CNS) consisting of the brain and spinal cord, and the peripheral nervous system (PNS) consisting of nerves and ganglia
• The blood-brain barrier (BBB) is a selective barrier formed by tight junctions between endothelial cells that protect the CNS from pathogens and toxins
  • Disruption of the BBB can lead to increased susceptibility to infections
• Cerebrospinal fluid (CSF) is a clear, colorless fluid that surrounds the brain and spinal cord, providing mechanical and immunological protection
  • CSF analysis is crucial for diagnosing nervous system infections
• Neurons are the primary functional units of the nervous system, responsible for transmitting electrical and chemical signals
• Glial cells, including astrocytes, oligodendrocytes, and microglia, provide support, insulation, and immune defense for neurons

Pathogenesis and Transmission

• Pathogens can enter the CNS through various routes, including hematogenous spread (bloodstream), direct invasion (trauma or surgery), and retrograde axonal transport (along nerves)
• Viruses often target specific cell types in the CNS, such as neurons (HSV, poliovirus) or glial cells (JC virus)
  • Viral replication within these cells leads to cell damage and inflammation
• Bacterial pathogens typically cause meningitis by colonizing the nasopharynx and entering the bloodstream, eventually crossing the BBB
  • Bacterial cell wall components and toxins contribute to inflammation and tissue damage
• Fungal pathogens often disseminate from the lungs or gastrointestinal tract to the CNS in immunocompromised individuals
• Parasites can enter the CNS through the bloodstream (Toxoplasma gondii) or directly through the nasal cavity (Naegleria fowleri)

Immune Response and Host Defense

• The innate immune response is the first line of defense against CNS infections, involving physical barriers (BBB), antimicrobial peptides, and immune cells (microglia, macrophages)
  • Toll-like receptors (TLRs) on immune cells recognize pathogen-associated molecular patterns (PAMPs) and initiate inflammatory responses
• The adaptive immune response is mediated by T lymphocytes and B lymphocytes, which provide specific, long-lasting protection
  • CD4+ T cells secrete cytokines to activate other immune cells, while CD8+ T cells directly kill infected cells
  • B cells produce antibodies that neutralize pathogens and mark them for phagocytosis
• Cytokines, such as interferons (IFNs), interleukins (ILs), and tumor necrosis factor (TNF), regulate the immune response and can contribute to inflammation
• Excessive inflammation in the CNS can lead to tissue damage, neuronal death, and long-term sequelae

Diagnostic Techniques

• CSF analysis is the gold standard for diagnosing nervous system infections, including cell count, glucose and protein levels, and microbiological tests
  • Elevated white blood cell count (pleocytosis) and low glucose levels are indicative of bacterial meningitis
  • Viral meningitis typically shows a mild pleocytosis with normal glucose levels
• Gram staining and culture of CSF can identify bacterial pathogens, while PCR is used for viral and some bacterial pathogens
• Neuroimaging techniques, such as CT and MRI, can reveal inflammation, abscesses, and structural abnormalities
  • Contrast-enhanced MRI is particularly useful for detecting focal lesions and assessing BBB integrity
• Serological tests, such as ELISA and Western blot, can detect pathogen-specific antibodies in serum and CSF
• Brain biopsy may be necessary in cases of suspected herpes simplex encephalitis or CNS tumors

Treatment Strategies

• Prompt initiation of appropriate antimicrobial therapy is crucial for improving patient outcomes and reducing morbidity and mortality
• Empiric antibiotic therapy for bacterial meningitis typically includes a third-generation cephalosporin (ceftriaxone) and vancomycin until the pathogen is identified
  • Listeria monocytogenes requires the addition of ampicillin or gentamicin
• Antiviral drugs, such as acyclovir for HSV and VZV, are used to treat viral encephalitis and meningitis
  • Foscarnet or cidofovir may be used for resistant herpes viruses
• Antifungal agents, like amphotericin B and flucytosine, are used for cryptococcal meningitis, often in combination
• Antiparasitic drugs, such as pyrimethamine and sulfadiazine, are used to treat toxoplasmosis
• Adjunctive therapies, including corticosteroids (dexamethasone), can help reduce inflammation and improve outcomes in some cases

Prevention and Control Measures

• Vaccination is the most effective way to prevent many nervous system infections, such as H. influenzae type b (Hib), S. pneumoniae, N. meningitidis, and VZV
  • Herd immunity is crucial for protecting individuals who cannot be vaccinated
• Practicing good hygiene, such as handwashing and covering coughs and sneezes, can reduce the spread of respiratory pathogens
• Safe food handling and preparation can prevent foodborne infections like listeriosis
• Prophylactic antibiotics may be given to close contacts of patients with bacterial meningitis to prevent secondary cases
• Infection control measures in healthcare settings, such as isolation precautions and proper disinfection, can prevent nosocomial transmission

Clinical Case Studies

• A 25-year-old male presents with fever, headache, neck stiffness, and photophobia. CSF analysis shows pleocytosis with low glucose levels. Gram stain reveals gram-negative diplococci, consistent with N. meningitidis meningitis.
• A 60-year-old female with a history of breast cancer and recent chemotherapy develops fever, altered mental status, and focal neurological deficits. MRI shows multiple ring-enhancing lesions, and CSF analysis reveals a mild pleocytosis with low glucose. Cryptococcal antigen test is positive, indicating cryptococcal meningitis.
• A 3-month-old infant presents with fever, irritability, and poor feeding. CSF analysis shows a high white blood cell count with predominant lymphocytes and normal glucose levels. PCR is positive for enterovirus, confirming viral meningitis.
• A 45-year-old HIV-positive male with a CD4 count of 50 cells/μL presents with headache, fever, and seizures. MRI reveals multiple focal lesions with surrounding edema. Serology and CSF PCR are positive for Toxoplasma gondii, leading to a diagnosis of cerebral toxoplasmosis.