MENINGITIS

Definition
An inflammation of the meninges, especially the arachnoid mater and the pia mater, often
secondary to infection. Edema and inflammatory infiltrates lead to fever, focal neurological
deficits, decreased level of consciousness, and seizure.
 Infectious causes can be bacterial, viral, fungal, or parasitic
 While the etiology is usually infectious, ultimately it is the inflammatory changes in the
CNS that cause morbidity and mortality

Etiology
Lancet 2003; 361: 2139–48.

Curr Opin Infect Dis 2007; 20(3):272-277.

Causative organisms vary by age group:

Neonates (<3 Children Adults Elderly (>65)

mo)

Group B Streptococcus Streptococcus Streptococcus

Streptococcus pneumoniae (pneumococcus) pneumoniae pneumoniae
       
Escherichia coli Neisseria Neisseria meningitidis Neisseria
  meningitidis (meningococcus)   meningitidis
Listeria   (these two organisms  
monocytogenes Haemophilus influenzae type B (less cause 80% of cases) Listeria
common now with the advent of the monocytogenes
HiB vaccination)

If no organism can be isolated with routine culture and sensitivity assays of cerebrospinal fluid
(CSF), the condition is called aseptic meningitis, and the etiology is likely viral
(e.g. Enterovirus, HIV  and  HSV). Less common etiologies for aseptic meningitis include
tuberculous meningitis (Mycobacterium tuberculosis), Lyme disease (Borrelia spp.), parasitic
infections (e.g. Taenia solium, Toxoplasma gondii), and malignancy.

Pathogenesis
Ther Adv Neurol Disord. 2009; 2(6):401-412.
see figure.
 

Clinical features and pathophysiology

JAMA. 1999 Jul 14;282(2):175-81.

N Engl J Med 2004; 351:1849-1859.

Pediatrics. 2010 Nov;126(5):952-60.

Symptom Sign Mechanism

Chills, rigors Fever (T>38°) Endogenous cytokines (released during the immune

response to the invading pathogens) affect the
thermoregulatory neurons of the hypothalamus,
changing the central regulation of body temperature.
 
Invading viruses or bacteria produce exogenous
substances (pyrogens) that can also re-set
the hypothalamic thermal set point.

Nuchal Brudzinski sign and Kernig Flexion of the spine leads to stretching of the
rigidity (neck sign meninges.
stiffness)  
In meningitis, traction on the inflamed meninges is
painful, resulting in limited range of motion through
the spine (especially in the cervical spine).

Altered mental Decreased Glasgow Coma ↑ ICP → brain herniation → damage to the reticular

status Scale (GCS) formation (structure in the brainstem that governs
consciousness)

Focal Examples: cranial nerve Cytotoxic edema and ↑ ICP lead to neuronal
neurological palsies, hemiparesis, damage.
deficits, e.g. hypertonia, nystagmus  
vision loss Signs or symptoms depend on the affected area
(cerebrum, cerebellum, brainstem, etc.)

Seizures   Inflammation in the brain alters membrane

permeability, lowering the seizure threshold. Exact
seizure pathophysiology is unknown.

Headache Jolt accentuation of headache: Bacterial exotoxins, cytokines, and ↑ ICP stimulate
headache worse when patient nociceptors in the meninges (cerebral tissue itself
vigorously shakes head lacks nerve endings that generate pain sensation).

Photophobia   Due to meningeal irritation. Mechanisms unclear;

 pathways are thought to involve the trigeminal
nerve.

Nausea and   ↑ ICP stimulates the area postrema  (vomiting

vomiting centre), causing nausea and vomiting.

  Petechial rash Meningococcemia (due to N. meningitidis)

In the pediatric population, all of the above signs and symptoms are applicable. Additional signs
and symptoms in children include:
 Bulging fontanelles
o Bones of the skull do not join fully (form sutures) until age 2
o ↑ ICP → meninges protrude through gaps in skull bones
 Jaundice
o Impaired bilirubin excretion
o Exact mechanism unclear, associated with sepsis
 Reduced feeds, irritability, lethargy, and toxic appearance
o Fever, shock and cerebral edema can lead to such manifestations in children

Treatment
Clin Infect Dis. (2004) 39 (9):1267-1284.
The goal of treatment is to maintain cerebral perfusion pressure by preserving the mean arterial
pressure (e.g. fluid resuscitation) and normalizing intracranial pressure (e.g. elevating the head,
hyperventilation, controlling seizure activity; hyperventilation causes hypocapnia-mediated
cerebral vasoconstriction).
Cerebral perfusion pressure = Mean arterial pressure – ICP
The mainstay of treatment for bacterial meningitis is antibiotics; choice of antibiotic depends on
the organism isolated from blood and CNS cultures. Any delay in treatment results in increased
morbidity and mortality, so antibiotics are often started empirically based on the age of the
patient (see table in Etiology above) and any risk factors they may have (e.g. if they are
immunocompromised or have recently had neurosurgery). The antibiotic regimen is then
adjusted once the causative organism is known. Corticosteroids can be used adjunctively to
reduce inflammation in the brain if the pathogen is Streptococcus pneumoniae.
In viral meningitis, the treatment is supportive. In patients with suspected Herpes Simplex
Virus (HSV) infection, empiric antiviral therapy is started to prevent complications of HSV
encephalitis.
Distinguishing between viral and bacterial meningitis is done using blood and CSF cultures, as
well as lumbar puncture opening pressure (which reflects ICP) and CSF analysis.
   Bacterial Viral Mechanism
meningitis meningitis

Opening pressure Elevated Normal or Increased inflammation in bacterial meningitis

(N: 8-20 cm H2O) (20-30 cm H2O) mildly results a higher ICP and thus a high opening
increased pressure.

CSF glucose Decreased Normal In bacterial meningitis, glucose transport from the
(N: 2.8-4.4 (<2.2  mmol/L) blood into the CSF is impaired; inflammation of
mmol/L; the meninges leads to decreased glucose receptor
blood:CSF glucose expression. There is also increased anaerobic
ratio is normally glycolysis by leukocytes and brain cells.
0.3-0.9)

CSF protein Very high Mildly Bacterial meningitis leads to a more permeable
(N: 0.15-0.45 g/L) >1.5 g/L increased blood brain barrier (due to increased
0.5-2 g/L inflammation). Protein leaks into the subarachnoid
space from the blood, resulting in markedly
increased CSF protein levels.

Surgical management is indicated where there is extremely increased intracranial pressure,

infection of an adjacent bony structure (e.g. mastoiditis), skull fracture, or abscess formation.