Pathophysiology

Anatomy

The cranial cavity is lined by the meninges, protective layers that surround the brain and skull. There are three layers of meninges in the cranial cavity:

Dura mater – “tough mother”; this is the outermost meninx, bilaminar (dural sinuses located between bilayers). The falx cerebri is a strong, arched fold of dura mater that descends vertically in the longitudinal fissure between the cerebral hemispheres (the meninges cover the brain between the hemispheres)
Arachnoid mater - this is the middle meninx, and it contains CSF in the subarachnoid space. It is composed of “cobweb” like filaments and forms cisterns where the brain invaginates.
Pia mater – “soft mother”; this is the innermost meninx, and is a smooth, translucent layer. It adheres to the outer surface of the CNS (brain and spinal cord).

(Blumenfeld, 2010)

Neisseria meningitidis

N. meningitidis, or meningococcus, is an aerobic, gram-negative diplococcus, closely related to N. gonorrhoeae. The organism has an inner (cytoplasmic) and an outer membrane, separated by a cell wall. The outer membrane contains protein structures that enable the bacteria to interact with the host cells as well as perform other functions.

The outer membrane is surrounded by a polysaccharide capsule that is necessary for pathogenicity because it helps the bacteria to resist phagocytosis and complement-mediated lysis. The outer membrane proteins and the capsular polysaccharide make up the main surface antigens of the organism.

Meningococci are transmitted by droplet aerosol or secretions from the nasopharynx of colonized persons. The bacteria attach to and multiply on the mucosal cells of the nasopharynx. In less than 1% of colonized persons, the organism penetrates the mucosal cells and enters the bloodstream.

The bacteria spread by way of the blood to many organs. In about 50% of bacteremic persons, the organism crosses the blood-brain barrier into the cerebrospinal fluid and causes meningitis. A preceding upper respiratory tract infection (URTI) may be a contributing factor.

(Rouphael and Stephens, 2012)

Bacterial Meningitis

Bacterial meningitis is an inflammation of the meninges, in particular the arachnoid and the pia mater, associated with the invasion of bacteria into the subarachnoid space. Streptococcus pneumoniae and Neisseria meningitidis are the most common and most aggressive pathogens of meningitis (Thigpen et al, 2011). (see below)

Current thinking is that high-grade bacteremia precedes meningitis and that bacteria invade the central nervous system (CNS) from the blood stream.

Pain receptors are located within the meninges, thus one of the classic symptoms of meningitis is a headache, with a severe, generalised headache often seen in bacterial meningitis in adults (Tunkel, 2015).

Meningeal inflammation and irritation result in a protective reflex to prevent stretching of the inflamed and hyper-sensitive nerve roots, which can be detected clinically as nuchal rigidity, Kernig's and Brudzinski's signs.

This can also cause cranial nerve palsies, such as facial nerve palsies. Strabismus, blindness and hearing loss are also associated with cranial nerve palsies in meningitis (Siddiqui, 2012)

Usually the inflammatory process is not limited to the meninges, but also affects the brain parenchyma, resulting in cerebral oedema, and potentially raised intracranial pressure. This can result in patients presenting with signs of raised ICP such as altered mental status, alterations in respiratory patterns, hypertension, ipsilateral pupil dilation, bradycardia and seizures.

The bacteraemic nature of the infection results in a systemic inflammatory and immunological response, resulting in fever (commonly >40C), myalgias, increased WBC count, rigors.

A rash may begin as an erythematous or maculopapular rash, which is normally short lived, followed by petechiae and purpura. Many gram-negative organisms can cause disseminated intravascular coagulation, exhausting clotting factors, and leading to widespread petechial haemorrhaging (Figure 1, right, click to enlarge) (Javid, 2014)

This can evenutally progress to fulminant meningococcemia, where there is a hemorrhagic eruption, hypotension, and cardiac depression, as well as rapid enlargement of petechiae and purpuric lesions. (Figure 2, right, click to enlarge) (Javid, 2014)

Streptococcus pneumoniae

S. pneumoniae or streptococcus is a gram-positive diplococcus with a well-formed capsule. Despite its name, the organism causes many types of pneumococcal infections other than pneumonia. S. pneumoniae is the leading cause of bacterial meningitis in adults in the USA.

As with it's stablemate N. meningiditis, it resides asymptomatically in the nasopharynx of colonized persons. The respiratory tract, sinuses, and nasal cavity are the parts of host body that are usually infected. In a proportion of susceptible carriers, such as the young, elderly and immunocompromised, the bacterium may spread to other locations and cause disease, such as meningitis.

(Alonso de Valasco et al, 1995)

Figure 1. Scattered petechiae in a patient with acute meningococcemia. (Javid, 2014)

Figure 2. Child with severe meningococcal disease and purpura fulminans. (Javid, 2014)