Clinical basics of meningitis

1. MENINGITIS
PRESENTER: DAUDI CHIRANZI
FACILITATOR: DR. C. ODUOR

2. DEFINITION
• Meningitis is a disease caused by the inflammation of the protective
membranes covering the brain and spinal cord known as the meninges.
• The inflammation is usually caused by an inflammatory process of the
leptomeninges and CSF within the subarachnoid space, usually caused
by an infection.
• The condition is classified as a medical emergency. Because of the
inflammation's proximity to the brain and spinal cord parenchyma
• Two presentations:
1. Meningitis- inflammation limited to the subarachnoid space.
2. Meningoencephalitis- inflammation involving both meninges and
brain parenchyma.

3. Anatomy of the meninges.

4. Etiology
Infections
• Bacterial infections, e.g. Escherichia coli and group B streptococci
(infants), Neisseria meningitides (young adults), Streptococcus
pneumoniae or Listeria monocytogenes (older adults), Mycobacterium
tuberculosis and Treponema pallidum (chronic forms)
• Rickettsia, e.g. Rickettsia rickettsii (Rocky mountain spotted fever)
• Viral infection, e.g. HSV-1, HSV-2, CMV (encephalitis), measles,
influenza (meningitis)
• Fungal infection,e.g. Cryptococcus neoformans, Candida albicans
• Parasitic (protozoal), e.g. Plasmodium falciparum, Naegleria fowleri,
Toxoplasma gondii

5. Etiology…
Physical injuries
Drugs, especially NSAIDs
Autoimmune reactions in the
• Severity/treatment of illnesses differs depending on the cause. Thus, it
is important to know the specific cause of meningitis.

6. Classification of meningitis
• Infectious meningitis
1. Acute pyogenic meningitis- Usually bacterial
2. Acute aseptic meningitis- Usually acute or subacute viral, ricketsial
3. Chronic meningitis- Usually tuberculous, spirochetal, or cryptococcal
• Non-infectious meningitis
1. Drug induced
2. Autoimmune
3. Metastasis

7. Epidemiology
• Together with sepsis, meningitis is estimated to cause more deaths in
children under 5 years of age than malaria.
• Neisseria meningitidis is the one with the potential to cause large
epidemics.
• Incidence rates of N. meningitidis meningitis are generally highest in
children less than five years of age and in adolescents. The worldwide
distribution of serogroups of N. meningitidis includes serogroups B and C
in the Americas, Europe, and Australia (most common), while serogroup A
causes the majority of disease in Africa and Asia.
• Even when the disease is diagnosed early and adequate treatment is started,
5% to 10% of patients die, typically within 24 to 48 hours after the onset of
symptoms.
• Bacterial meningitis may result in brain damage, hearing loss or a learning
disability in 10% to 20% of survivors.

8. Epidemiology…

9. Pathogenesis
a) Acute pyogenic meningitis
• Different bacteria involved:
Escherichia coli and group B streptococci- Neonates.
• This also includes Haemophilus influenza type b strain that includes
a pentose polysaccharide capsule which is a critical virulence factor
(allows resistance to phagocytosis and complement-mediated lysis).
Streptococcus pneumonia and Listeria monocytogenes- Older adults
• Once in the blood-stream, progression of pneumococcal meningitis
usually occurs in conjunction with a high-grade septicemia. Invasion of
the subarachnoid space may relate to the ability of pneumococci and
pneumococcal cell wall to bind to and have cytotoxic effects on vascular
endothelial cells.

10. Pathogenesis…
Neisseria meningitidis- Adolescents and young adults.
• Especially serogroup A (most common) and serogroup C
(associated with outbreaks).
• Includes initial meningococcal colonization that result in an
asymptomatic carrier state. Followed by the development of
invasive disease.
• Incubation period primarily(3-4 days), secondarily within 1-4 days
of the index case.
• Once the organism is blood-borne, more than 90% of
meningococcal disease is manifested as meningitis or
meningococcemia.
NB- All these acute etiologies include a primary reservoir site in the human
nasopharynx.

11. Pathophysiology
• Bacterial meningitis begins with the exposure of cells (e.g. endothelial
cells, leukocytes, microglia, astrocytes, and meningeal macrophages)
to bacterial products released during replication and death; inciting the
synthesis of cytokines and proinflammatory mediators.
• This process is likely initiated by the ligation of the bacterial
components (e.g. peptidoglycan and lipopolysaccharide) to pattern-
recognition receptors (e.g. Toll-like receptors (TLRs)).
• TNF-α and IL-1 are most prominent among the cytokines that mediate
this inflammatory cascade. TNF-α is a glycoprotein derived from
activated monocyte-macrophages, lymphocytes, astrocytes, and
microglial cells.
• IL-1 (a.k.a. endogenous pyrogen) is also produced primarily by
activated mononuclear phagocytes and is responsible for the induction
of fever during bacterial infections. Both IL-1 and TNF-α have been
detected in the CSF of individuals with bacterial meningitis.

12. Pathophysiology…
• Secondary mediators, such as IL-6, IL-8, nitric oxide, prostaglandins (eg,
prostaglandin E2 [PGE2]), and platelet activation factor (PAF)) amplify this
inflammatory event, either synergistically or independently.
• IL-6 induces acute-phase reactants in response to bacterial infection. The
chemokine IL-8 mediates neutrophil chemoattractant responses induced by
TNF-α and IL-1. Nitric oxide (a ROS) can induce cytotoxicity when produced
in high amounts. PGE2 (a product of COX), participate in the induction of
increased blood-brain barrier permeability.
• The net result of the above processes is
vascular endothelial injury
increased blood-brain barrier permeability, leading to the entry of many
blood components into the subarachnoid space (vasogenic edema and
increased CSF protein)
neutrophilic pleocytosis.

13. Clinical features of acute pyogenic meningitis
• Systemic- Fever
• CNS- Headache
- Altered mental status, e.g. confusion, psychotic, phonophobic, irritability,
delirium, sleepiness and coma.
- Bulging fontanelle (if euvolemic)
• Peripherally- Neck and back stiffness
- Photophobia
• GIT- Nausea and vomiting
-Loss of appetite
• CVS- Tachycardia
• Respiratory system- Tachypnoea

14. Complications…
• Waterhouse-Friderichsen syndrome- Resulting from meningitis-associated
septicemia with hemorrhagic infarction of the adrenal glands (most often with
meningococcal and pneumococcal meningitis)
• Hypotension or shock
• Hypoxemia
• Cardiac arrhythmias and ischemia
• Stroke
• Subdural effusion and hydrocephalus
• For immunosuppressed individuals- purulent meningitis may be caused by
several other infectious agents, such as Klebsiella or anaerobic organisms, and
may have an atypical clinical course.
NB- The classic triad for diagnosis of meningitis includes fever, headache and
neck stiffnes (at least two of these signs)

15. b) Acute aseptic meningitis
• Etiologies
Viral
Bacteria- Rickettsia rickettsii
Autoimmune cause
• Aseptic meningitis is a clinical term that applies to a situation where there
is an absence of organisms by bacterial culture in a patient with
manifestations of meningitis, including meningeal irritation, fever, and
alterations of consciousness of relatively acute onset.
• Viral etiologies include
Enteroviruses (80% cases%) including coxsackie virus,echovirus
Influenza
Herpes simplex virus type2 ( especially in infants)
Varicella zoster
HIV
Mumps
Measles

16. Viral acute aseptic meningitis
• Incubation period : 3 to 6 days.
• Duration of the illness : approximately 7 to 10 days.
• Milder and occurs more often than bacterial meningitis.
• Affects children and adults under age 30. Most infections occur in
children under age 5.
• Most viral meningitis is due to enteroviruses, that also can cause
intestinal illness.

17. Clinical features
• Same as acute pyogenic meningitis in addition to myalgia/muscle tenderness.
• The clinical course is less fulminant compared to acute pyogenic meningitis.
• General physical findings in viral meningitis are common, including:
Exanthemas- Widely spread out rash (diffuse rash)
Symptoms of pericarditis- Chest pain, fatigue/fever, shortness of breath
Symptoms of myocarditis- Chest pain, abnormal heart rhythm, murmur,
palpitations
Symptoms of conjunctivitis- Redness, itching and tearing of the eyes,
congestion and running nose.
• However, most cases of viral meningitis are benign and self-limited.

18. Clinical features…

19. c)Chronic meningitis
• Mainly caused by Mycobacterium tuberculosis complex and Cryptococcus
neoformans (fungi may also involve Coccidioides immitis, Histoplasma
capsulatum, Candida albicans, Mucormycosis and Aspergillus species)
• Associated with the immunosuppressed individuals.
• Mycobacterium tuberculosis complex-
A group of closely related species (M. tuberculosis, M. bovis, M.
bovis BCG, M. africanum, M. microti, and M. canetti), also called
tubercle bacilli. M. tuberculosis is the major cause.
Patients with active pulmonary TB (PTB) are the major source of the
tubercle bacilli. Spread of infection is primarily by inhalation of
aerosolized infectious droplet nuclei from PTB patients and lungs are
the main portal of entry.
Tuberculous meningitis usually results from the rupture of a
subependymal tuberculous focus into the CSF provoking a severe
local inflammatory and immunologic response in the subarachnoid
space. This causes most of the symptoms and ultimate morbidity of
tuberculous meningitis.

20. Chronic meningitis…
• Most of the fungi (especially Cryptococcus neoformans) are aerosolized and
inhaled and initiate a primary pulmonary infection which is usually self-
limited (a self-limited pneumonia may occur). Haematogenous dissemination
may follow the initial infection, with subsequent seeding in the CNS in the
setting of immunosuppression.
• Factors influencing dissemination include the polysaccharide capsule and
secreted enzymes including lacase, phospholipase B and urease (disrupts the
BBB).
• Cr.neoformans grows extensively in the subarachnoid space and perivascular
spaces, which become cystically distended to the point that brain sections
look like Swiss cheese.
• Cryptococcal meningitis has an insidious onset and may go on from weeks to
years. It can cause hydrocephalus, dementia, and focal neurological deficits.

21. chronic meningitis: Candida albicans…
• Occur as a manifestation of disseminated candidiasis, which most often
occurs in premature neonates in the presence of ventricular drainage
devices and as isolated chronic meningitis. Candida can also enter the
CNS at the time of craniotomy or through a ventricular shunt.
• Also involves people who have weakened immune systems, e.g.
HIV/AIDS, organ transplant, medication such as corticosteroids or TNF-α
inhibitors; pregnant women; extreme of age.
• Genes for adherence capacity, phenotypic switching (transition between
blastospores and hyphal forms), hydrolytic enzymes and secreted aspartyl
proteinases enable C. albicans to cross human brain microvascular
endothelial cells (BMEC) to cause CNS infection.

22. Clinical features of chronic meningitis
• Same as typical meningitis signs and symptoms (meningismus)
• Examination may include lymphadenopathy, papilledema, cranial nerve
palsies (e.g. strabismus).
• Evidence of immune-incompetence, e.g. HIV/AIDS patient, neonate,
older adults>60years of age, post-organ transplant, patient on
immunosuppression drugs, pregnant women,e.t.c

23. Risk factors for meningitis
• Extremes of age (<5 years or >60 years)
• Diabetes mellitus, CKD, adrenal insufficience, hypoparathyroidism or cystic
fibrosis.
• Immunosuppression, e.g. post-organ transplant patients.
• HIV infection.
• Crowding- associated with outbreaks.
• Splenectomy and sickle cell disease.
• Alcoholism and cirrhosis
• Recent exposure to others with meningitis
• Contiguous infections, e.g. sinusitis
• Dural defect, e.g. traumatic, surgical, congenital
• Malignancies, e.g. leukemias (Listeria monocytogenes)
• Bacterial endocarditis

24. Physical examination
• General examination
General condition- Altered mental status can range from irritability
to somnolence, delirium, and coma.
Exanthemas- Diffused rash
Lymphadenopathy (especially chronic type)
• Systemic examination
CNS- Cranial nerves exam
-Nuchal rigidity
-Kernig sign
-Brudzinski sign
-Glasgow coma scale (GCS)
Respiratory system
Abdominal exam
CVS
the absence of the
meningeal signs should not
defer the performance of
the LP.

25. Physical exam…

26. Differential diagnosis
• Noninfectious meningitis, including medication-induced meningeal
inflammation
• Meningeal carcinomatosis
• Central nervous system (CNS) vasculitis
• Stroke
• Encephalitis
• All causes of altered mental status and coma
• Leptospirosis
• Subdural empyema
• Brain neoplasm
• Delirium tremens
• Brain abscess

27. Diagnosis of meningitis
Specimen includes: CSF, blood, sputum, skin scrapings and
urine

28. Diagnosis…
• For lumbar puncture and CSF analysis, includes checking the following
parameters:

29. Diagnosis…
• Blood studies that may be useful include the following:
Complete blood count (CBC) with differential
Serum electrolytes
Serum glucose (which is compared with the CSF glucose)
Blood urea nitrogen (BUN) or creatinine and liver profile
HIV testing.
• In addition, the following tests may be ordered:
Blood, nasopharynx, respiratory secretion, urine or skin lesion (Gram
staining and culture)
Indian ink stain, latex agglutination test (Ag assay)(blood, CSF)-
Cryptococcus neoformans
Serology
Direct microscopy- yeast,
Germ-tube test
Syphilis testing- Venereal Disease Research Laboratory (VDRL) test
PCR
• Neuroimaging (CT of the head or MRI of the brain)

30. Diagnosis…
• Bacterial meningitis must be the first and foremost consideration in the differential
diagnosis of patients with headache, neck stiffness, fever, and altered mental
status. Acute bacterial meningitis is a medical emergency, and delays in instituting
effective antimicrobial therapy result in increased morbidity and mortality.
• Whenever the diagnosis of meningitis is strongly considered, a lumbar puncture
should be promptly performed. Examination of the cerebrospinal fluid (CSF) is
the cornerstone of the diagnosis. The diagnosis of bacterial meningitis is made by
culture of the CSF sample. The fluid should be sent for cell count (and differential
count), chemistry (i.e. CSF glucose and protein), and microbiology (i.e. Gram
stain and cultures).
• A concern regarding LP is that the lowering of CSF pressure from withdrawal of
CSF could precipitate herniation of the brain. Herniation can sometimes occur in
acute bacterial meningitis and other CNS infections as the consequence of severe
cerebral edema or acute hydrocephalus. Clinically, this is manifested by an altered
state of consciousness, abnormalities in pupil reflexes, and decerebrate or
decorticate posturing. The incidence of herniation after LP, even in patients with
papilledema, is approximately 1%.
• CT scan of the head may be performed before LP to determine the risk of
herniation. However, the decision to obtain a brain CT scan before LP should not
delay the institution of antibiotic therapy; such delay can increase mortality.