Lecture 1Bacterial meningitis

Dr. Abdelraouf A. Elmanama

Islamic University-Gaza

Medical Technology Department

Lecture outlines

• Introduction

• Simplified anatomy of the CNS

• Etiology (causes of bacterial meningitis)

• Pathophysiology

• Clinical manifestations

Objectives

• Define meningitis• Describe prevalence of meningitis• Explain pathophysiology• Identify clinical manifestations • Know the appropriate antibiotic

treatment per age group

DefinitionMeningitis: inflammation of theleptomeninges (the tissuessurrounding the brain and spinal

cord) • Bacterial meningitis

• Aseptic meningits: infectious or noninfectious

Viral, Rickettsiae, Mycoplasma Fungal, spirochetes: syphilis, LymeProtozoa: malaria

Malignancy Lupus erythematous

Lead or mercury poisoning

Anatomy

Meningies

CNS infections

• MeningitisInfection of the subarachnoid space with meningeal

involvement

• EncephalitisInflammation of brain

• MeningoencephalitisInflammation of brain with meningeal involvement

• Brain AbscessPathogens may be bacterial, TB, viral, fungal, or

parasitic

CSF

• About 85% of CSF produced by the

choroid plexus which also controls the

constituency of CSF

• CSF volume varies by age with a normal adult having a steady state volume of ~150cc

Meningitis Bacterial Pathogens

• Mechanical Barriers IntactS. pneumoniae (pneumococci)N. meningitidis (meningococci, Groups A,B,C,Y, &W135)H. influenzae (type B or Hib)Immunizations may also affect likely pathogenSpecial situations B. anthracis

• Traumatic alteration or other risk factorsS. aureusE. coli or P. aeruginosaMay depend on circumstances

Meningitis Bacterial Pathogens

• Neonatal

• Children < 1 month of age

• Pathogens acquired from birth canal

• E. coli

• Group B Streptococci (S. agalactiae)

Initial symptoms and signsSymptoms or Sign Relative frequency% Headache >90 Fever >90 Meningismus >85 Altered sensorium >80 Kernig’s or Brudzinski’s signs

>50

Focal findings 10-20 Papilledema <1

DESCRIPTION of symptomes• Severe headache .A person with meningitis may describe the headache as the worst one

they’ve ever had.

• High fever. The infection can cause a high fever (39°C or over) which does not get lower with a tepid bath or fever-reducing medicine.

• Stiff neck. Swelling in the meninges (membranes around the spinal cord and brain) causes a stiff neck that makes it extremely painful to move the neck or head.

• Nausea and vomiting. Vomiting is common with many illnesses. However, if vomiting happens with the other symptoms listed, it may be caused by meningitis.

• Numbness or loss of feeling. Sepsis (also known as blood poisoning) can reduce the amount of blood that gets to a person’s hands and feet, causing numbness, coldness, or loss of feeling.

• Light sensitivity. A person with meningitis may find it painful to look at bright lights, and will try to avoid them.

• Confusion. Swelling around the brain can make a person confused and seem "out of it.“

• Rash. Purple spots that do not turn white when you press on them are a sign of sepsis (also known as blood poisoning) .

• Seizures. Sometimes people with meningitis have seizures similar to the kind that people with epilepsy have

Rashes

Pathophysiology

Nasopharyngeal colonization

Local invasion

Bacteremia

Meningeal invasion

Bacterial replication in the subarachnoid space

Release of bacterial components (cell wall, LOS)

Cerebral microvascular endothelium Macrophages, neutrophils, other CNS Cells

Cytokines

Subarachnoid space inflammationCerebral vasculitis

Increased CSF outflow resistance

Hydrocephalus

Interstitial edema

Increased intracranial pressure

Decreased cerebral blood flow and loss of cerebrovascular autoregulation

Cytotoxic edema

Cerebral infarction

Increased BBB permeability

Vasogenic edema

Pathophysiology

• Meningitis:– Infection of meninges (dura, arachnoid, pia

mater).– Caused by:

• Bacteria, viruses, fungi, parasites, or toxins.• Bacterial ***25% mortality in adults• Viral meningitis• Fungal meningitis

• Bacterial Meningitis:– Infection of the pia mater and arachnoid, the

subarachnoid space, the ventricular system, and the CSF.

– Infectious agents:• Meningococcus (Neisseria meningitidis)

• pneumococcus (streptococcus pneumoniae)

– URI---blood borne---CNS entry– Inflammatory response by meninges, CSF, ventricles. – Neutrophils migrate producing exudate that plugs off

CSF flow around the brain and spinal cord.

Neisseria meningitidisNasopharynx

Streptococcus pneumoniaeNasopharynx or direct extension across

skull fracture

Listeria monocytogenesGI tract, placenta

Haemophilus influenzae Nasopharynx

Staphylococcus aureusBacteremia, skin, or foreign body

Staphylococcus epidermidisSkin or foreign body

Organism Site of entry

• Once in CSF, the absence of antibodies & complement components allows bacterial infection to flourish

• Cascade of events:– Cell wall and membrane products of organism disrupt capillary

endothelium of CNS (BBB)– Margination and transmigration of PMNs across endothelia in CSF

• Release of cytokines and chemokines into the CNS– Inflammation of subarachnoid space

• Mortality: 3 to 13%– Rate varies with organism– Higher with gram negative organism

• Neurologic Sequelae: 10 % of surviving patients

Long-term Neurological Complications

Adverse Outcomes at One Year of Age of 12 Infants With Bacterial Meningitis

Category of Disability Number

Development delay 10

Cerebral palsy 1

Microcephaly 3

Hemiparesis 3

Hearing loss 1

Blindness 2

Seizure disorder 3

Total number of disabilities exceeds the number of infants owing to the presence of multiple disabilities in most subjects

Pathogenesis

– Majority of cases are hematogenous in origin

– Organisms have virulence factors that allow bypassing of normal defenses• Proteases• Polysaccharidases

Pathology and Pathogenesis

– Sequential steps allow the pathogen into the CSF

• Nasopharyngeal colonization• Nasopharyngeal epithelial cell invasion• Bloodstream invasion• Bacteremia with intravascular survival• Crossing of the BBB and entry into the CSF• Survival and replication in the subarachnoid space

• Pathology– Hallmark

• Exudate in the subarachnoid space• Accumulation of exudate in the dependent areas of

the brain• Large numbers of PMN’s • Within 2-3 days inflammation in the walls of the

small and medium-sized blood vessels• Blockage of normal CSF pathways and blockage

of the normal absorption may lead to obstructive hydrocephalus