CNS

• Neisseria meningitidis


  • Oxidase Test
• Neisseria meningitidis
• Dura mater


  Tough outer membrane
• Arachnoid mater


  Lacy, weblike middle membrane
• Pia mater


  Firmly attached to brain & spinal cord and has rich blood supply
• Subarachnoid space


  Contains many of the blood vessels that feed the brain and spinal cord and is between arachnoid mater and pia mater
• Routes of CNS infection

  • Bloodstream
  • Direct extension (from middle ear, sinuses)
  • Trauma (bone fractures, medical procedures)
  • Through peripheral nerves (rabies, herpes zoster virus)
• Meningitis


  Inflammation of the meninges, including subarachnoid space, leading to a constellation of signs and symptoms and presence of inflammatory cells in CSF
• Meningoencephalitis


  Inflammation of the meninges and brain parenchyma
• Triad of meningitis symptoms

  • Fever
  • Nuchal rigidity
  • Headache
• Other meningitis symptoms


  • Altered mental status
  • Increased sleepiness
  • N/V
  • Photalgia
  • Seizures
  • Coma
• Time definitions of meningitis

  • Acute (<7 days)
  • Chronic (≥4 weeks)
• Causes of acute bacterial meningitis

  • Escherichia coli
  • GBS
  • Neisseria meningitidis
  • Streptococcus pneumoniae
  • Listeria monocytogenes
• Causes of acute viral meningitis

  • Enteroviruses
  • Poliovirus
  • Measles (SSPE)
  • Influenza
  • Lymphocytic choriomeningitis virus
• Causes of chronic bacterial meningitis

  • Mycobacterium tuberculosis
  • Borrelia burgdorferi (Lyme disease)
  • Treponema pallidum (Syphilis)
  • Leptospira interrogans
• Causes of chronic fungal meningitis

  • Cryptococcus neoformans
  • Coccidioides immitis
  • Histoplasma capsulatum
  • Blastomyces dermatitidis
  • Aspergillus fumigatus
  • Mucormycetes
• Most common causative agents of bacterial meningitis by age

  • Infants and children: GBS, E. coli, S. pneumoniae, N. meningitidis, H. Influenzae
  • Young adults: S. pneumoniae, N. meningitidis
  • Middle-aged and older adults: S. pneumoniae, N. meningitidis, L. monocytogenes
• Streptococcus pneumoniae


  Gram(+), nonmotile, encapsulated, alpha-hemolytic, lancet-shaped diplococci. Most cases occur in children 1 month to 4 years of age. Most common cause of acute bacterial meningitis in adults.
• Bacteria are passed from person to person by coughing, sneezing, kissing. Most are transferred to the meninges via the bloodstream.
• Streptococcus pneumoniae treatment


  • Penicillin if penicillin susceptible
  • Ampicillin
  • 3rd gen cephalosporin (ceftriaxone or cefotaxime)
• Haemophilus influenzae


  Formerly the most common cause of acute bacterial meningitis in children 5 months to 5 years of age. Requires X (hemin) and V (NAD) factors for growth.
• Neisseria meningitidis


  Gram(-) coffee bean-shaped, nonmotile, encapsulated diplococci. Associated with or found inside polymorphonuclears.

  
• Neisseria meningitidis serotypes


  • A, B, C, W135, Y
• Neisseria meningitidis culture characteristics

  Convex, glistening, elevated, mucoid colonies, 1-5 mm diameter, nonhemolytic, opaque or transparent. Modified Thayer-Martin agar is a selective/specific medium.

  
• Neisseria meningitidis growth requirements

  • Capnophilic - grow best at 5-10% CO2
  • Anaerobe or facultative anaerobe
  • Produce oxidase
  • Catalase(+)
• Neisseria meningitidis antigenic structure

  • Capsule
  • MW proteins
  • IgA1 protease
  • Meningococcal LPS endotoxin (lipooligosaccharide)
• Neisseria meningitidis clinical disease

  Humans are the only natural host. Majority produce asymptomatic colonization/carriage in the nasopharynx, especially in adolescents and young adults.
• Neisseria meningitidis clinical manifestations

  • Fulminant meningococcemia
  • Meningococcal meningitis
• Fulminant meningococcemia


  Widespread vascular injury characterized by endothelial necrosis, intraluminal thrombosis, and perivascular hemorrhage. Initially petechial rash becomes purpuric and often on limbs. Disseminated intravascular coagulation and Waterhouse-Friderichsen syndrome may occur.
• Meningococcal meningitis


  Most important complication. After bacteria enter the meninges, they multiply in the CSF. Neurologic damage due to direct bacterial toxicity, indirect inflammatory processes, and systemic effects.
• Neisseria meningitidis laboratory diagnosis

  • Clinical specimens: blood, CSF, nasopharyngeal swabs, puncture material from hemorrhagic skin lesions
  • Gram stain
  • Culture
  • Serology (latex agglutination, hemagglutination)
• Neisseria meningitidis treatment


  • Penicillin G (drug of choice)
  • Chloramphenicol or 3rd generation cephalosporin (cefotaxime or ceftriaxone) for penicillin allergy
• Neisseria meningitidis carrier state eradication

  • Rifampin 600 mg q12 x 2 days
  • Ciprofloxacin 500 mg single dose
  • Ceftriaxone 250 mg as a single IM or IV injection
• Neisseria meningitidis prevention


  • Meningococcal vaccine (serogroups A, C, Y, W-135) given in persons 9 months to 55 years old
  • Recommended for high risk groups: asplenia, C' deficiencies, travellers, closed populations, clinical lab workers
• Listeria monocytogenes


  Short, gram(+), non spore-forming, facultatively intracellular, facultatively anaerobic, beta-hemolytic rods. Catalase(+). Tumbling end to end motility at 22-28°C but not at 37°C.
• Listeria monocytogenes culture


  Grows on 5% sheep blood agar showing small zone of hemolysis. Catalase(+), oxidase(-).

  
• Listeria monocytogenes antigenic structure


  • Listeriolysin O (LLO)
  • PLC A and PLC B
  • ActA
• Listeria monocytogenes pathogenesis


  Infections follow ingestion of contaminated food. Induces its own internalization by cells that are not normally phagocytic.

  
• Listeria monocytogenes clinical disease in non-pregnant adults

  Meningitis presentation is more frequently subacute; nuchal rigidity and meningeal signs are less common. Meningoencephalitis and focal CNS infection are most common in immunocompromised patients.
• Listeria monocytogenes clinical disease in pregnant women (listeriosis)


  Nonspecific acute or subacute febrile illness, usually bacteremic. Involvement of the CNS is uncommon, but preterm delivery is a common complication.