Meningitis & Encephalitis

Dr. Faheem Nazir

1
2
 MENINGITIS

• Acute infections of the nervous system are

among the most important problems in
medicine

3
 Cont…

• Each may present with a nonspecific

prodrome of fever and headache

4
 Symptoms of meningitis

• Fever
• Headache
• Vomiting

5
 Signs of Meningitis

• Nuchal rigidity (“stiff neck”)

• Kernig’s sign
- Elicited with the patient in the supine position
- The thigh is flexed on the abdomen, with the
knee flexed; attempts to passively extend the
knee elicit pain when meningeal irritation is
present

6
 Cont…
• Brudzinski’s sign
- Elicited with the patient in the supine position
and is positive when passive flexion of the
neck results in spontaneous flexion of the hips
and knees

7
8
9
 Causes of meningitis
Infective

10
Cont…

11
Cont…

12
Bacterial causes of meningitis

13
Cont…

14
 ACUTE BACTERIAL MENINGITIS

• Acute purulent infection within the subarachnoid

space
• Associated with a CNS inflammatory reaction
that may result in decreased consciousness,
seizures, raised intracranial pressure (ICP), and
stroke

15
 Cont…
• The meninges, the subarachnoid space,
and the brain parenchyma are all
frequently involved in the inflammatory
reaction (meningoencephalitis)

16
 EPIDEMIOLOGY

• Annual incidence in the United States of >2.5

cases/100,000 population
• Organisms most often responsible
- Streptococcus pneumoniae (∼50%)
- Neisseria meningitidis (∼25%)
- Group b streptococci (∼15%)
- Listeria monocytogenes (∼10%)
- Haemophilus influenzae type b (<10%)

17
 ETIOLOGY

• S. pneumoniae is the most common cause of

meningitis in adults >20 years of age
• Predisposing conditions
- Pneumococcal pneumonia
- Coexisting acute or chronic pneumococcal sinusitis
or otitis media

18
 Cont..
- Alcoholism
- Diabetes
- Splenectomy
- Hypogammaglobulinemia
- Complement deficiency
- Head trauma with basilar skull fracture
and CSF Rhinorrhea

19
 ETIOLOGY

• N. meningitidis
- The presence of petechial or purpuric skin
lesions can provide an important clue to the
diagnosis of meningococcal infection

20
 Cont…
- Enteric gram-negative bacilli

- Predisposing condition:

- Chronic and debilitating diseases such

as diabetes, cirrhosis, or alcoholism and
in those with chronic urinary tract
infections
- Neurosurgical procedures, particularly
craniotomy and head trauma with csf
rhinorrhea or otorhhea 21
 ETIOLOGY

• Otitis, mastoiditis, and sinusitis are

predisposing and associated conditions for
meningitis due to
- Streptococci Sp.
- Gram-negative Anaerobes
- S. Aureus
- Haemophilus sp and Enterobacteriaceae

22
 Cont…
• Meningitis complicating endocarditis
- Viridans streptococci
- S. Aureus, s. Bovis
- HACEK group (Haemophilus sp
Actinobacillus actinomycetemcomitans,
Cardiobacterium hominis, Eikenella
corrodens, Kingella kingae), or
enterococci

23
 ETIOLOGY

• Group B streptococcus, or S. agalactiae

- Meningitis in neonates
- Individuals >50 years of age, particularly
those with underlying diseases
• Staphylococcus aureus and cngs
- Following invasive neurosurgical procedures

24
 Cont…
• L. monocytogenes
- meningitis in neonates (<1 month of
age)
- Pregnant women
- individuals >60 years
- Immunocompromised individuals of all
ages

25
 PATHOPHYSIOLOGY

• Bacteria that cause meningitis, initially colonize

the nasopharynx by attaching to
nasopharyngeal epithelial cells
•
• Bacteria are transported across epithelial cells
in membrane-bound vacuoles to the
intravascular space

26
 Cont…
• Once in the bloodstream, bacteria are able
to avoid phagocytosis by neutrophils and
classic complement-mediated bactericidal
activity due to polysac.capsule

• Bloodborne bacteria can reach the

intraventricular choroid plexus, directly
infect choroid plexus epithelial cells, and
gain access to the CSF

27
 Conti….

• Multiply rapidly d/t absence of effective host

defenses
• Inflammatory reaction induced by the invading
bacteria(crtical event)
• Cytokine response
• Increase in CSF protein concentration and
leukocytosis
28
 Cont…

• Lysis of bacteria release of cell wall

components into sas
• TNF-α and IL-1β increase
permeability of the blood brain
barriervasogenic edema and the
leakage of serum proteins into the
subarachnoid space

29
The pathophysiology of the neurologic complications of bacterial meningitis

30
 CLINICAL PRESENTATION

• The classic clinical triad of meningitis

- Fever
- Headache
- Nuchal rigidity(pathognomonic)
• A decreased level of consciousness occurs in
>75% of patients and can vary from lethargy to
coma
• Nausea, vomiting, and photophobia
31
 CLINICAL PRESENTATION

• Seizures(20–40%)
• Focal seizures
- Focal arterial ischemia or infarction,
- Cortical venous thrombosis with hemorrhage, or
- Focal edema

32
 Cont…
• Generalized seizure activity and status
epilepticus
- Hyponatremia
- Cerebral anoxia
- Toxic effects of drugs such as high-dose
penicillin

33
 CLINICAL PRESENTATION
• Raised ICP(90% hae csf pressure >180mmh2o
- Deteriorating or reduced level of consciousness
papilledema
- Dilated poorly reactive pupils
- Sixth nerve palsies
- Decerebrate posturing
- Cushing reflex (bradycardia, hypertension, and
irregular respirations)
- Cerebral herniation

34
 Investigation

• Blood cultures
• csf examination
• PCR techniques can be used on both blood and
CSF to identify bacterial DNA
• Neuroimaging – ct or mri

35
 Cont…
• MRI(preffered)
- Cerebral edema
- Ischemia
- Diffuse meningeal enhancement is often
seen after the administration of
gadolinium
• Petechial skin lesions, if present, should
be biopsied
36
Examination of the CSF

38
Treatment
Bacterial meningitis is a medical emergency.
The goal is to begin antibiotic therapy within 60 min of a patient’s arrival in
the emergency room.
 Empirical antimicrobial therapy is initiated in patients with suspected
bacterial meningitis before the results of CSF Gram’s stain and culture are
known
Combination of dexamethasone, a third- or fourth-generation cephalosporin
(e.g.,ceftriaxone, cefotaxime, or cefepime), and vancomycin, plus acyclovir, and
doxycycline( during tick season)

Metronidazole is added to the empirical regimen to cover gram-negative anaerobes in

patients with otitis, sinusitis, or mastoiditis.
Dexamethasone exerts its beneficial effect by inhibiting the synthesis of IL-1β and
TNF-α at the level of mRNA, decreasing CSF outflow resistance, and stabilizing the
blood-brain barrier.

The rationale for giving dexamethasone 20 min before antibiotic therapy is that
dexamethasone inhibits the production of TNF-α by macrophages and microglia
only if it is administered before these cells are activated by endotoxin.
Chemotherapy of bacterial meningitis when the cause is known

42
INCREASED INTRACRANIAL PRESSURE:

Emergency treatment of increased ICP includes

• Elevation of the patient’s head to 30–45°,

•Intubation and hyperventilation (Paco2 25–30 mmHg), and
• Mannitol.
•Should be managed in an intensive care unit;
•Accurate ICP measurements are best obtained with an ICP monitoring device
PROGNOSIS

Mortality rate is 3–7% for meningitis caused by H. influenzae, N. meningitidis,

or group B streptococci; 15%for that due to L. monocytogenes; and 20% for S.
pneumoniae
Risk of death from bacterial meningitis increases with:

(1) decreased level of consciousness on admission,

(2) onset of seizures within 24 hof admission,
(3) signs of increased ICP,
(4) young age (infancy) and age >50,
(5) the presence of comorbid
conditions including shock and/or the need for mechanical ventilation, and
(6) delay in the initiation of treatment.
Decreased CSF glucose concentration (<2.2 mmol/L [<40 mg/dL]) and
markedly increased CSF protein concentration (>3 g/L [> 300 mg/dL]) have
been predictive of increased mortality and poorer outcome.
Moderate or severe sequelae occur in 25% of survivors.

Common sequelae include :

•decreased intellectual function,

•memory impairment ,
•seizures,
•hearing loss
• dizziness,
•and gait disturbances
 ACUTE VIRAL MENINGITIS

• Most common cause of meningitis, usually

resulting in a benign and self-limiting illness
requiring no specific therapy

• It is much less serious than bacterial meningitis

unless there is associated encephalitis

46
 Cont…
• Viral meningitis occurs mainly in children
or young adults, with acute onset of
headache and irritability and the rapid
development of meningism

47
 Cont…
• The headache is almost invariably
present and most often frontal or
retroorbital along with photophobia.
• There may be a high pyrexia but focal
neurological signs are rare.

48
•Enteroviruses - most common cause of viral meningitis,
accounting for >85% of casesin which a specific etiology
can be identified.
•Most likely cause of viral meningitis in the summer and fall
months, especially in children
CSF reverse transcriptase PCR (RT-PCR) is the diagnostic
procedure of choice and is both sensitive (>95%) and
specific (>100%).
•HSV meningitis -second in importance to enteroviruses as
a cause of viral meningitis
•In adults, the majority of cases of uncomplicated meningitis
are due to HSV-2,
•Whereas HSV-1 is responsible for 90% of cases of HSV
encephalitis.
•Diagnosis of HSV meningitis is usually by HSV CSF PCR
 LABORATORY DIAGNOSIS

• CSF examination
- Lymphocytic pleocytosis (25–500 cells/μl)
- A normal or slightly elevated protein concentration
(0.2–0.8 g/L [20–80 mg/dl])
- A normal glucose concentration
- A normal or mildly elevated opening pressure (100–
350 mmh2o)

51
 LABORATORY DIAGNOSIS

• Polymerase chain reaction amplification of

viral nucleic acid
- PCR has become the diagnostic procedure of
choice and is substantially more sensitive than
viral cultures
• Viral culture
- CSF cultures
- Throat swabs, stool, blood, and urine culture
• Serologic studies
52
 Management

•There is no specific treatment and patient should

treated symptomatically
•Analgesics, antipyretics, and antiemetics.
•Fluid and electrolyte status should be monitored.
•Oral or intravenous acyclovir may be of benefit in patients
with meningitis caused by HSV-1 or 2 and in cases of severe
EBV or VZV infection

53
SUB ACUTE MENINGITIS

• Unrelenting headache
• Still neck
• Low-grade fever, and
• Lethargy
• Days to several weeks
Common causative organisms
• M. tuberculosis
• C. neoformans
• H. capsulatum
• C. immitis and
• T.pallidum
 Tuberculous meningitis

• Tuberculous meningitis is now uncommon in

developed countries in previously healthy
individuals

• It remains common in developing countries and

is seen more frequently as a secondary
infection in patients with the Acquired Immune
Deficiency Syndrome (AIDS)
56
 Pathophysiology

• Tuberculous meningitis is usually caused by the

acid-fast organism Mycobacterium tuberculosis
• The usual local source of infection is a
caseous focus in the meninges or brain
substance adjacent to the CSF pathway

57
Initial infection acquired by inhalation of
aerosolized droplet nuclei  millet seed–
sized (miliary) tubercles form in the
parenchyma of the brain during
hematogenous dissemination of tubercle
bacilli (in the course of primary infection in
lungs)  tubercles enlarge and are usually
caseating  Subependymal caseous foci
cause meningitis via discharge of bacilli and
tuberculous antigens into the SAS.
leads to intense inflammatory reaction
production of a thick exudate that fills the
basilar cisterns and surrounds the cranial
nerves and major blood vessels at the base
of the brain.
 Pathophysiology
• Rich described two stages in the pathogenesis
of tuberculous meningitis
• First a bacterial seeding of the meninges and
subpial regions of the brain with the formation
of tubercles

• Followed by the rupture of one or more of the

tubercles and the discharge of bacteria into the
subarachnoid space
60
Clinical features and staging of tuberculous meningitis

61
 Investigations(CSF)

• Increased opening pressure

• Usually clear but, when allowed to stand, a fine

clot (‘spider web’) may form

• Up to 10 and 500 white cells per cubic

millimeter, rarely more, predominantly
lymphocytes, but can contain neutrophils
62
 Cont…
• Rise in protein (between 1-5 g/L in most
cases, but much higher if the flow of
CSF is blocked around the spinal cord)

• Fall in glucose (20- 40 mg/ dL)

• Last tube of fluid collected at lp for afb
staining

63
 Investigations(CSF)

Detection of tubercle bacilli

• Direct
- Staining (eg Ziehl Neelsen method) of CSF
sediment (10–40% of cases)
- Culture (diagnostic in up to 50% of cases,
gold standard)-takes 4-8 weeks

64
 Cont…
• Indirect
- PCR /NAAT from the CSF (Xpert MTB/RIF assay)
• Rapidly permits the detection of small
amounts of tubercle bacilli
• Sensitivity close to 80 percent
• 10 percent false-positive rate
- IGRA in CSF
- CSF- ADA
• Non specific marker

65
 Other tests

• MT
• CXR P/A view-in more than hallf of cases e/o
old pulmonary lessions or a milliary pattern
• CT/MRI of brain
- Tuberculoma(ring enhancing lessions)
- Hydrocephalus
- Infarction
- Meningeal enhancement (abnormal enhancement
of basal cisterns or ependyma) by contrast MRI 66
 Treatment of CNS tubercular infection

• Combination of four drugs-isoniazid (INH),

rifampin (RMP), ethambutol (EMB), and / or
pyrazinamide (PZA) for the first 2 months

• When the antimicrobial sensitivity of the M.

tuberculosis isolate is known, ethambutol can
be discontinued
67
 Cont…
• If the clinical response is good,
pyrazinamide can be discontinued after 8
weeks and isoniazid and rifampin
continued alone for the next 6–12 months

• Antibiotics must be given for a prolonged

period, 9 to 12 months if first-line
treatment has been given

68
 Treatment of CNS tubercular infection

• Adjunctive dexamethasone significantly

enhanced the chances of survival among
persons > 14 years of age but did not reduce
the frequency of neurologic sequelae(25%)

69
 Cont…
• The dexamethasone schedule
(1)0.4 mg/kg per day given IV with
tapering by 0.1 mg/kg per week until
the fourth week, when 0.1 mg/kg per
day was administered; followed by

(2)4 mg/d given by mouth with tapering

by 1 mg per week until the fourth week,
when 1 mg/d was administered
70
Chronic meningitis

Diagnosed when a characteristic neurologic

syndrome exists for >4 weeks and is
associated with a persistent inflammatory
response in the cerebrospinal
fluid (CSF) (white blood cell count >5/μL)..
The causes are varied, and appropriate
treatment depends on identification of the
etiology.
Five categories of disease account for most
cases of chronic meningitis:
(1)meningeal infections,
(2) malignancy,
(3) autoimmune inflammatory disorders,
(4) chemical meningitis, and
(5) parameningeal infections
74
75
76
 Encephalitis is defined as an inflammation of the brain caused either by
infection, usually with a virus, or from a primary autoimmune process.

The most commonly identified viruses causing sporadic cases of acute encephalitis
in immunocompetent adults are herpesviruses (herpes simplex virus [HSV],
varicellazoster virus [VZV], Epstein-Barr virus [EBV]).

Epidemics of encephalitis are caused by arboviruses including Alphaviruses (e.g.,

eastern equine encephalitis [EEE] virus), Flaviviruses (e.g., West Nile virus [WNV],
St. Louis encephalitis virus, Japanese encephalitis virus, Powassan virus), and
Bunyaviruses (e.g., California encephalitis virus serogroup, La Crosse virus).

Japanese encephalitis – most common cause of acute viral encephalitis in India

78
79
80
81
82
83
84
 CSF PCR has become the primary diagnostic test for CNS infections caused by CMV, EBV,
HHV-6, and enteroviruses.

The sensitivity (~96%) and specificity (~99%) of HSV CSF PCR are equivalent to or
exceed those of brain biopsy.

Serologic Studies and Antigen Detection

• For many arboviruses including WNV, serologic studies remain important diagnostic
tools.
• Serum antibody determination is less useful for viruses with high seroprevalence rates
in the general population such as HSV, VZV, CMV, and EBV
CT/MRI/EEG IN HS ENCEPHALITIS:

Focal findings in a patient with encephalitis should always raise the possibility of HSV
encephalitis. Examples of focal findings include:
(1)Areas of increased signal intensity in the frontotemporal, cingulate, or insular regions of
the brain on T2-weighted, fluid-attenuated inversion recovery (FLAIR), or diffusion-weighted
MRI
(2) focal areas of low absorption, mass effect, and contrast enhancement on CT; or
(3) periodic focal temporal lobe spikes on a background of slow or low-amplitude
(“flattened”) activity on EEG
88
89
90
91
92
93
94
95