Meningitis

1. M E N I N G I T I S
P R E S E N T E D B Y
N U R U L H I D A Y U B I N T I I B R A H I M
N I K N O R L I Y A N A

2. OUTLINE
1. Introduction to meningitis
2. Risk factor
3. Anatomy and prognosis
4. Aetiology
5. History and physical examination
6. Clinical features
7. Complications
8. Differential diagnosis
9. Investigations
10. Management

3. INTRODUCTION
 Meningitis is a disease caused by the inflammation of the meninges.
 The inflammation is usually caused by an infection of the fluid surrounding the
brain and spinal cord.
 It can be life-threatening because of the inflammation’s proximity to the brain
and spinal cord; therefore the condition is classified as a medical emergency.
 If not treated, meningitis can lead to brain swelling and cause permanent
disability, coma, and even death.
 Broadly classified as :
I. Acute meningitis
II. Chronic meningitis
WHAT IS MENINGITIS?

4. TERMS
Set of symptoms similar to those of meningitis but not caused by meningitis.
 Meningism is caused by non-meningitic irritation of the meninges, usually associated
with acute febrile illness, especially in children and adolescents.
 It therefore requires differentiating from other CNS problems with similar symptoms,
including meningitis and some types of intracranial hemorrhage.
 The severity of clinical features varies with the causative organism.
M E N I N G I S M

5. RISK FACTORS
Risk factors that place people at higher risk for bacterial meningitis include
the following:
 Adults older than 60 years of age
 Children younger than 5 years of age
 People with alcoholism
 People with sickle cell anemia
 People with cancer, especially those receiving chemotherapy
 People who have received transplants and are taking drugs that suppress
the immune system
 People with diabetes
 Those recently exposed to meningitis at home
 People living in close quarters (military barracks, dormitories)
 IV drug users
 People with shunts in place for hydrocephalus

6. ANATOMY OF MENINGES
The meninges is the system of the membranes which envelops
the CNS. It has 3 layers:
1. Dura mater
2. Arachnoid mater
3. Pia mater
Subarachnoid space – is the space which is filled with CSF

7. ANATOMY OF MENINGES

8. ANATOMY OF MENINGES

9. ANATOMY OF MENINGES

10. TRANSMISSION
H O W D O E S M E N I N G I T I S S P R E A D ?
An infectious agent can gain access to the CNS and cause meningeal disease via any of
the 3 following major pathways:
Direct contiguous spread (e.g. sinusitis, otitis media, congenital malformations, trauma,
or direct inoculation during intracranial manipulation)
1 . I N V A S I O N O F T H E B L O O D S T R E A M
Invasion of the bloodstream (i.e., bacteremia, viremia, fungemia, or parasitemia) and
subsequent hematogenous seeding of the CNS
2 . R E T R O G R A D E N E U R O N A L PAT H W AY
A retrograde neuronal (eg, olfactory and peripheral nerves) pathway (eg, Naegleria
fowleri or Gnathostoma spinigerum)
3 . D I R E C T C O N T I G U O U S S P R E A D

11. TRANSMISSION
H O W D O E S M E N I N G I T I S S P R E A D ?
3 . D I R E C T C O N T I G U O U S S P R E A D
 Local extension from contiguous extracerebral infection (eg, otitis media,
mastoiditis, or sinusitis) is a common cause.
 Possible pathways for the migration of pathogens from the middle ear to the
meninges include the following:
1. The bloodstream
2. Preformed tissue planes (eg, posterior fossa)
3. Temporal bone fractures
4. The oval or round window membranes of the labyrinths

12. PATHOGENESIS

13. PATHOGENESIS

14. PROGNOSIS
Patients with meningitis who present with an impaired level of
consciousness are at increased risk for neurologic sequelae or death.
A seizure during an episode of meningitis also is a risk factor for mortality
or neurologic sequelae, particularly if the seizure is prolonged or difficult
to control.
In bacterial meningitis, several risk factors are associated with death and
with neurologic disability. A risk score has been derived and validated in
adults with bacterial meningitis. This score includes the following
variables, which are associated with an adverse clinical outcome:
1. Older age
2. Increased heart rate
3. Lower Glasgow Coma Scale score
4. Cranial nerve palsies
5. CSF leukocyte count lower than 1000/μL
6. Gram-positive cocci on CSF Gram stain

15. PROGNOSIS
 Advanced bacterial meningitis can lead to brain damage,
coma, and death.
 In 50% of patients, several complications may develop in the
days to weeks following infection.
 Long-term sequelae are seen in as many as 30% of survivors
and vary with etiologic agent, patient age, presenting
features, and hospital course. Patients usually have subtle CNS
changes.

16. AETIOLOGY
B A C T E R I A L
V I R A L
F U N G A L
P H Y S I C A L I N J U R Y
D R U G S R E A C T I O N
Severity/ treatment of illness differ depending on the cause. Thus, it is
important to know the specific cause of meningitis.

17. AETIOLOGY
B A C T E R I A L M E N I N G I T I S V I R A L M E N I N G I T I S
 The most serious form of meningitis is
bacterial.
 Even with treatment, bacterial meningitis
can be fatal some of the time.
 If bacterial meningitis progresses rapidly,
in 24 hours or less, death may occur in
more than half of those who develop it,
even with proper medical treatment.
 Determining how many people get viral
meningitis is difficult because it often
remains undiagnosed and is easily
confused with the flu.
 The prognosis for viral meningitis is much
better than that for bacterial meningitis,
with most people recovering completely
with simple treatment of the symptoms.

18. AETIOLOGY
F U N G A L M E N I N G I T I S A S E P T I C M E N I N G I T I S
 Fungal meningitis is a serious form of
meningitis that is normally limited to
people with impaired immune systems.
 Aseptic meningitis is a term referring to
the broad category of meningitis that is
not caused by bacteria.
 Approximately 50% of aseptic meningitis
is due to viral infections.
 Other less common causes include drug
reactions or allergies, and inflammatory
diseases like lupus.
 It occurs in individuals of all ages but is
more common in children

19. BACTERIAL CAUSES
 Listeria monocytogenes ( >50 years old)
 Group A β-hemolytic streptococcus
 Group B β-hemolytic streptococcus
 Mycoplasma pneumoniae
 Gram –ve rods
C O M M O N O R G A N I S M S :
1. Streptococcus pneumoniae (α-hemolytic streptococcus)
2. Neisseria meningitidis
3. Haemophilus influenzae
O T H E R O R G A N I S M S :
V I R A L C A U S E S
 Enteroviruses
 Herpes simplex virus

20. ORGANISMS
R I S K O R P R E D I S P O S I N G F A C T O R S B A C T E R I A L P A T H O G E N
Age 3 months – 18 years
 Neisseria meningitidis
 Streptococcus penumoniae
 Haemophilus influenza
Age 18 – 50 years
 Streptococcus penumoniae
 Neisseria meningitidis
 Haemophilus influenza
Age > 50 years
 Streptococcus penumoniae
 Neisseria meningitidis
 Listeria monocytogenes
 Aerobic gram-negative bacilli
Immunocompromised state
 Streptococcus penumoniae
 Neisseria meningitidis
 Listeria monocytogenes
 Aerobic gram-negative bacilli
Intracranial manipulation, including neurosurgery
 Staphylococcus aureus
 Coagulase negative staphylococci
 Aerobic gram-negative bacilli, including
Pseudomonas aeruginosa
Basilar skull fracture
 Streptococcus penumoniae
 Haemophilus influenza
 Group A streptococci

21. NEISSERIA MENINGITIDIS
 Also known as meningococcal meningitis
 Gram negative aerobic cocci, capsule
 10% of healthy people are healthy nasopharyngeal
carriers
 Begin as throat infection, rash
 Vaccination is recommended

22. NEISSERIA MENINGITIDIS
STREPTOCOCCUS PNEUMONIAE
 Gram positive diplococci
 70% of people are healthy nasopharyngeal carriers
 Most common in children (1 month to 4 years)
 Mortality: 30% in children, 80% in elderly
 Prevented by vaccination

23. NEISSERIA MENINGITIDIS
HISTORY TAKING
 ~25% of those who develop meningitis have symptoms that develop
over 24 hours. The remainder generally become ill over one to seven
days.
 ~25% of patients have concomitant sinusitis or otitis that could
predispose to S pneumoniae meningitis.
 Occasionally, if someone has been on antibiotics for another infection,
the symptoms can take longer to develop or may be less intense.
 If someone is developing fungal meningitis (most commonly someone
who is HIV positive), the symptoms may take weeks to develop.
D U R AT I O N

24. NEISSERIA MENINGITIDIS
HISTORY TAKING
 In contrast, patients with subacute bacterial meningitis and most
patients with viral meningitis present with neurologic symptoms
developing over 1 – 7 days.
 Chronic symptoms lasting longer than 1 week suggest the presence of
meningitis caused by certain viruses or by tuberculosis, syphilis, fungi
(especially cryptococci), or carcinomatosis.
D U R AT I O N

25. NEISSERIA MENINGITIDIS
HISTORY TAKING

26. NEISSERIA MENINGITIDIS
HISTORY TAKING
S Y M P T O M S I G N M E C H A N I S M
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 rigidity (neck stiffness) Brudzinski sign and Kernig sign Flexion of the spine leads to stretching of
the meninges.
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 status Decreased Glasgow Coma Scale (GCS) ↑ ICP → brain herniation → damage to
the reticular formation (structure in the
brainstem that governs consciousness)

27. NEISSERIA MENINGITIDIS
HISTORY TAKING
S Y M P T O M S I G N M E C H A N I S M
Focal neurological deficits, e.g. vision loss Examples: cranial nerve palsies,
hemiparesis, hypertonia, nystagmus
Cytotoxic edema and ↑ ICP lead to
neuronal damage.
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: headache
worse when patient vigorously shakes head
Bacterial exotoxins, cytokines, and ↑ ICP
stimulate nociceptors in the meninges
(cerebral tissue itself lacks nerve endings
that generate pain sensation).
Photophobia Due to meningeal irritation. Mechanisms
unclear; pathways are thought to involve
the trigeminal nerve.
Nausea and vomiting ↑ ICP stimulates the area
postrema (vomiting centre), causing nausea
and vomiting.
Petechial rash Meningococcemia (due to N. meningitidis)

28. NEISSERIA MENINGITIDIS
HISTORY TAKING
O T H E R I M P O R TA N T H I S T O R Y
 Contact with TB patient (TB meningitis)
 Infection of middle ear, sinuses, lung or tooth and gum (brain abscess)
 Contact with infected bodily secretions (meningitis, herpes encephalitis)
 Sexual contact with a person infected with HIV (HIV encephalopathy)
 Penetrating head trauma (brain abscess)
 Neurosurgical complications (meningitis, brain abscess)
 A chronic illness, such as cancer
 A weakened immune system, such those with alcoholism, diabetes, HIV or people
who have had organ transplant.
 A history of recent antibiotic use should be elicited. 40% of patients who present
with acute or subacute bacterial meningitis have previously been treated with oral
antibiotics (presumably because of misdiagnosis at the time of initial presentation).

29. NEISSERIA MENINGITIDIS
PHYSICAL EXAMINATION
G E N E R A L E X A M I N AT I O N
 Non-toxic looking might suggestive of viral origin.
 Sick, toxic looking might suggest bacterial origin.
 Glasgow-coma scale
 Kernig’s sign
 Brudzinki’s sign
 Look for other source of infections:
 Cutaneous petachie/purpura rash  meningococcus
 Middle ear, sinus infection
 Pneumonia  pneumococcus
 Papilledema (increase ICP)
 Cranial nerves examination (III, IV, V, VI, and VII)
S P E C I F I C E X A M I N AT I O N

30. NEISSERIA MENINGITIDIS
PHYSICAL EXAMINATION
K E R N I G ’ S S I G N ( M E N I N G E A L S T R E T C H T E S T )

31. NEISSERIA MENINGITIDIS
PHYSICAL EXAMINATION
B R U D Z I N S K I ’ S S I G N ( M E N I N G E A L S T R E T C H T E S T )

32. NEISSERIA MENINGITIDIS
CLINICAL FEATURES
C H R O N I C M E N I N G I T I S
 Lymphadenopathy
 Papilledema and tuberculomas during funduscopy
 Meningismus
 Cranial nerve palsies
 Occurs most common shortly after primary infection in childhood or as part of
military TB.
 The presentation of chronic tuberculous meningitis may be acute, but the classic
presentation is subacute and spans weeks. Patients generally have a prodrome
consisting of fever of varying degrees, malaise, and intermittent headaches.
T U B E R C U L O U S M E N I N G I T I S

33. NEISSERIA MENINGITIDIS
CLINICAL FEATURES
Cranial nerve palsies (III, IV, V, VI, and VII) often develop, suggesting basilar
meningeal involvement.
Clinical staging of tuberculous meningitis is based on neurologic status, as
follows:
 Stage 1 - No change in mental function, with no deficits and no
hydrocephalus
 Stage 2 - Confusion and evidence of neurologic deficit
 Stage 3 - Stupor and lethargy
T U B E R C U L O U S M E N I N G I T I S
C L I N I C A L S TA G I N G O F T U B E R C U L O U S M E N I N G I T I S

34. NEISSERIA MENINGITIDIS
CLINICAL FEATURES

35. NEISSERIA MENINGITIDIS
COMPLICATIONS
1 . H E A R I N G L O S S
2 . C E R E B R A L O E D E M A A N D I N C R E A S E D I C P
4 . B R A I N A B S C E S S
4 . S T R O K E
Infections / inflammation from subarachnoid space  via cochlear aqueduct  inner ear
 Inflammatory response – damages cochlear (hair cells)
Cerebral edema may be vasogenic, from increased vascular permeability, cytotoxic from cerebral hypoxia, interstitial, from
increased CSF volume, or a combination of all. Increased intracranial pressure, in turn, causes decreased cerebral perfusion,
hypoxia/ischemia, and neuronal necrosis.
3 . D I S S E M I N AT E D I N T R A V A S C U L A R C O A G U L O PAT H Y ( D I C )
Bacterial products can damage the brain and blood vessels directly. Bacterial toxins cause neuronal apoptosis, and cell wall
lipopolysaccharide (endotoxin), released from bacteria, activates clotting causing disseminated intravascular coagulation (DIC).

36. NEISSERIA MENINGITIDIS
DIFFERENTIAL DIAGNOSIS
1 . S u b a r a c h n o i d h e m o r r h a g e
2 . T B m e n i n g i t i s
3 . S p a c e - o c c u p y i n g l e s i o n
4 . M e n i n g o e n c a p h a l i t i s
5 . E p i l e p s y

37. NEISSERIA MENINGITIDIS
INVESTIGATIONS
B L O O D T E S T S
1. Full blood count ( white cell count)
2. C-reactive protein
3. Blood culture and sensitivity
L U M B A R P U N C T U R E A N D C S F A N A LY S I S
For definitive diagnosis of meningitis, CSF needs to be collected for analysis.
C O N T R A I N D I C AT I O N S
 Infected skin over needle entry site
 Suspicion of increase ICP
 Coagulopathy
 Significant cardiorespiratory compromise
 Immunocompromised

38. NEISSERIA MENINGITIDIS
INVESTIGATIONS
L U M B A R P U N C T U R E A N D C S F A N A LY S I S
T E S T B A C T E R I A L V I R A L F U N G A L T U B E R C U L A R
Opening pressure Elevated Normal Variable Variable
WBC count >1,000 / mm3 <100/mm3 Variable Variable
Cell differential Neutrophils Lymphocytes Lymphocytes Lymphocytes
Protein Mild to marked
elevation
Normal or mildly
elevated
Elevated Very high
CSF-to-serum
glucose ratio
Markedly decreased normal Low Low
I M A G I N G
If a patient has the following:
Focal neurologic findings (excluding cranial nerve palsies), new-onset seizures, severely immunocompromised
state, papilledema or presents with coma, perform a head computed tomography scan prior to doing a lumbar
puncture to rule out the presence of intracranial mass lesions because of the potential risk for herniation

39. NEISSERIA MENINGITIDIS
MANAGEMENT
S U P P O R T I V E T R E AT M E N T
Airway, breathing and circulation
 Mechanical ventilation – level of consciousness is very low / evidence of respiratory failure
 Intravenous fluid therapy – if hypotension or shock are present
Monitor vital signs and neurologic status regularly
Maintain adequate hydration and nutrition – tube feeding may be necessary
D E F I N I T I V E T R E AT M E N T ( P H A R M A C O T H E R PA P Y )
1. Antibiotic therapy
2. Anti-inflammatory therapy
3. Agents to decrease intracranial pressure (ICP)
4. Anti-convulsants

40. NEISSERIA MENINGITIDIS
MANAGEMENT
A N T I B I O T I C S ( A C U T E M E N I N G I T I S )
I N F E C T I O N
S U G G E S T E D T R E A T M E N T
C O M M E N T S
P R E F E R R E D A L T E R N A T I V E
Common organisms:
 Streptococcus
pneumoniae
 Neisseria meningitidis
 Haemophilus influenzae
Ceftriaxone 2gm IV q12h
OR
Cefotaxime 2 – 4gm IV q8h
Dexamethasone 10mg IV q6h
is recommended to be
administered 15 to 20 minutes
before or at the time of first
dose of antibiotics, for up to 4
days or until there is no
evidence of pneumococcal
meningitis.
Antibiotic treatment must be
started immediately,
regardless of any
investigations undertaken. If
no organism isolated and
patient is responding,
continue antibiotics for 14
days.

41. NEISSERIA MENINGITIDIS
MANAGEMENT
A N T I B I O T I C S ( A C U T E M E N I N G I T I S )
I S O L A T E D C A U S A T I V E
O R G A N I S M
S U G G E S T E D T R E A T M E N T
C O M M E N T S
P R E F E R R E D A L T E R N A T I V E
HAEMOPHILUS INFUENZAE
(GRAM –VE BACILLI)
Ceftriaxone 2gm IV q12h
STREPTOCOCCUS PNEUMONIAE
(GRAM +VE COCCI)
Benzylpenicillin 4MU IV q4-
6h for 10-14 days.
For penicillin resistant strains
Vancomycin 1gm IV q12h
NEISSERIA MENINGITIDIS
(GRAM –VE COCCI)
Prophylaxis for household and
close contact of meningococcal
meningitis
Ceftriaxone 2gm IV q12h
Ciprofloxacin 500mg PO as
single dose;
Close contacts are defined as
those individuals who have
had contact with
oropharyngeal secretions
either through kissing or by
sharing toys, beverages, or
cigarettes.

42. NEISSERIA MENINGITIDIS
MANAGEMENT
A N T I B I O T I C S ( C H R O N I C M E N I N G I T I S )
I N F E C T I O N
S U G G E S T E D T R E A T M E N T
C O M M E N T S
P R E F E R R E D A L T E R N A T I V E
TUBERCULOUS MENINGITIS
Mycobacterium tuberculosis
Intensive 2 months S/EHRZ
and 10 months HR
Pyridoxine 10- 50mg PO q24h
needs to be prescribed
together with Isoniazid.
(Streptomycin should replace
Ethambutol in TB meningitis
as it crosses BBB better than
Ethambutol.)
Treatment is continued for 12
months.
CPG on management of
Tuberculosis, 3rd edition,
2012; 16, 22, 40-42, 56)
WHO Treatment of
Tuberculosis Guidelines, 4th
ed. 2009

43. NEISSERIA MENINGITIDIS
MANAGEMENT
A N T I - I N F L A M M AT O R Y T H E R A P Y
Dexamethasone 10 mg IV 6 hourly x 4 days
Mannitol 1 – 1.5 g/kg IV given over 15 minutes
I C P L O W E R I N G A G E N T
A N T I C O N V U L S A N T S
Diazepam, Lorazepam
Administered if patient has seizure
Action:
Mannitol is a hyperosmolar agent that makes the intravascular space hyperosmolar to the brain and permits movement of water
from brain tissue into the intravascular compartment

44. NEISSERIA MENINGITIDIS
PREVENTION AND PROPHYLAXIS
P R E C A U T I O N
Completion of recommended schedule of vaccination is an effective way of protecting individuals from certain
types of bacterial meningitis (E.g. meningococcus, pneumococcus and Hib)
F O L L O W U P
 Repeat cerebrospinal fluid exam in patients in whom there is doubt about the success of therapy or the
accuracy of the initial diagnosis
 Patients who respond promptly to therapy may no longer need repeat cerebrospinal fluid exams
 Monitor for hydrocephalus and treat the condition appropriately - hydrocephalus usually manifests within the
first few weeks of infection and is treated with ventriculoperitoneal shunting
 Monitor for neurologic sequelae and provide appropriate supportive therapy
 Sequelae include hearing impairment, cranial nerve palsies and motor deficits
 Supportive therapy should be individually tailored
Use of mask, gloves, and gowns prevents spread of disease as meningitis is a droplet infection
V A C C I N AT I O N

45. THANK YOU