MENINGITIS
CHIKE AND FRANCES
ML 416
MENINGES
The brain and spinal cord are covered by
connective tissue layers collectively called the
meninges which form the blood-brain barrier.
1-the pia mater (closest to the CNS)
2-the arachnoid mater
3-the dura mater (farthest from the CNS).
The meninges contain cerebrospinal fluid
(CSF).
MENINGITIS
Meningitis is an inflammation (swelling) of
the protective membranes covering the brain
and spinal cord known as the meninges. This
inflammation is usually caused by an
infection of the fluid surrounding the brain
and spinal cord.
if severe, may become encephalitis, an
inflammation of the brain
4 weeks
CAUSES OF MENINGITIS
• Bacterial Infections
• Viral Infections
• Fungal Infections(Cryptococcus
neoformans,Coccidiodes immitus)
• Inflammatory diseases (SLE)
• Cancer
• Trauma to head or spine.
Bacterial MENINGITIS
BACTERIAL meningitis is an acute purulent infection within
the subarachnoid space.
It is associated with a CNS inflammatory reaction that may
result in decreased consciousness, seizures, raised
intracranial pressure (ICP) and stroke
Newborns: Group B Streptococcus, Streptococcus
pneumoniae, Listeria monocytogenes, Escherichia coli
Babies and children: Streptococcus pneumoniae, Neisseria
meningitidis, Haemophilus influenzae type b (Hib), group B
Streptococcus
Teens and young adults: Neisseria meningitidis,
Streptococcus pneumoniae
Older adults: Streptococcus pneumoniae, Neisseria
meningitidis, Haemophilus influenzae type b (Hib), group B
Streptococcus, Listeria monocytogenes
CLINICAL PRESENTATION OF BM
Meningitis can present as either an acute fulminant
illness that progresses rapidly in a few hours or as a
subacute infection that progressively worsens over
several days.
The classic clinical triad of meningitis is fever,
headache, and nuchal rigidity,
A decreased level of consciousness occurs in
Variation from lethargy to coma.
Nausea, vomiting, and photophobia
Seizures
Focalseizures are usually due to focal arterial ischemia
or infarction, cortical venous thrombosis with
hemorrhage, or focal edema.
COMPLICATION
Raised ICP is the major cause of obtundation and
coma in this disease.
Signs of increased ICP include
a deteriorating or reduced level of consciousness,
papilledema,
dilated poorly reactive pupils, sixth nerve palsies,
decerebrate posturing
the Cushing reflex (bradycardia, hypertension, and
irregular respirations).
The most disastrous complication of increased ICP is
cerebral herniation
CT SCAN OF CEREBRAL HERNIATION
Suspected bacterial meningitis is a medical
emergency; thus, immediate steps must be
taken to establish the specific diagnosis, and
empirical antimicrobial treatment must be
started rapidly. The mortality of untreated
bacterial meningitis approaches 100% and,
even with optimum treatment, mortality and
morbidity might happen.
DIAGNOSIS
blood cultures should be immediately
obtained via lumber puncture.
Nt.
empirical antimicrobial adjunctive
dexamethasone therapy initiated without delay
CT scan or MRI
fundoscopy
The classic CSF abnormalities in bacterial meningitis
(1) polymorphonuclear (PMN) leukocytosis (>100
cells/μL in 90%),
(2) decreased glucose concentration(<2.2 mmol/L
[<40 mg/dL] and/or CSF/ serum glucose ratio of
<0.4 in ∼60%),
(3) increased protein concentration (>0.45 g/L [>45
mg/dL] in 90%),
CSF bacterial cultures are positive in >80% of
patients,
MENINGOCOCCAL DISEASE
Meningococcal disease describes infections caused
by the bacterium Neisseria meningitidis (also
termed meningococcus).
it is the best known as a cause of meningitis
(Meningococcal meningitis)
It carries a high mortality rate if untreated but is a
vaccine-preventable disease.
widespread blood infection can result in septicemia
(Meningococcemia)
PATHOGENESIS
Infection of upper respiratory tract
Invasion of blood stream (bacteraemia)
Seeding & inflammation of meninges
CLINICAL PRESENTATION OF MD
DIFFERENTIAL DIAGNOSIS
Acute Disseminated Encephalomyelitis
Aseptic Meningitis
Haemophilus Meningitis
Herpes Simplex Encephalitis
Intracranial Epidural Abscess
Leptomeningeal Carcinomatosis Imaging
Lyme Disease
Neonatal Meningitis
Staphylococcal Meningitis
Subdural Empyema
Tuberculous Meningitis
Viral Meningitis
KERNIG’S SIGN
One of the physically
demonstrable
symptoms of
meningitis is Kernig's
sign. Severe stiffness
of the hamstrings
causes an inability to
straighten the leg
when the hip is flexed
to 90 degrees.
BRUDZINSKI'S SIGN.
Another physically
demonstrable
symptoms of meningitis
is Brudzinski's sign.
Severe neck stiffness
causes a patient's hips
and knees to flex when
the neck is flexed.
One sign of meningococcal
septicaemia is - rash -This rash
is caused by blood leaking
under the skin. It starts
anywhere on the body. It can
spread quickly to look like
fresh bruises.
This rash is more difficult to
see on darker skin. Look on the
paler areas of the skin and
under the eyelids.
This that does not fade under
pressure ( ‘Glass test’)
PURPURA FULMINANS
THERAPY FOR
MENINGOCOCCAL MENINGITIS
This infection is best treated with penicillin
Although there are scattered case reports of N.
meningitidis resistant to penicillin, such strains
are still very rare
A third-generation cephalosporin is an effective
alternative to penicillin for meningococcal
meningitis
A five day duration of therapy is adequate
However, when penicillin is used, there may still
be pharyngeal colonization with the infecting
strain. As a result, the index patient may need to
take rifampin, a fluoroquinolone, or a
cephalosporin
FUNGAL MENINGITIS
Fungal meningitis is caused by fungi like
Cryptococcus and Histoplasma and is usually
acquired by inhaling fungal spores from the
environment. People with certain medical
conditions like diabetes, cancer, or HIV are at
higher risk of fungal meningitis
CRYPTOCOCCOSIS
C. neoformans is the leading infectious cause
of meningitis in patients with AIDS. It is the
initial AIDS defining illness in ~2% of patients
and generally occurs in patients with CD4+ T
cell counts <100/μL. Cryptococcal meningitis
is particularly common in patients with AIDS
in Africa, occurring in ~5% of patients.
CLINICAL PICTURE
Most patients present with a picture of subacute
meningoencephalitis
with fever, nausea, vomiting, altered mental status,
headache, and meningeal signs.
The incidence of seizures and focal neurologic deficits is
low.
The CSF profile may be normal or may show only modest
elevations in WBC or protein levels and decreases in
glucose.
In addition to meningitis, patients may develop
cryptococcomas
cranial nerve involvement.
Approximately one-third of patients also have pulmonary
disease.
skin lesions
cryptococcoma
Uncommon manifestations of cryptococcal infection
include skin lesions that resemble molluscum
contagiosum,
lymphadenopathy, palatal and glossal ulcers,
arthritis,gastroenteritis, myocarditis, and
prostatitis.
The prostate gland may serve as a reservoir for
smoldering cryptococcal infection.
DIFFERENTIAL DIAGNOSIS
Acanthamoeba
Basal Cell Carcinoma
Histoplasmosis
Lipomas
Molluscum Contagiosum
Pneumocystis jiroveci Pneumonia
Syphilis
Toxoplasmosis
Tuberculosis
DIAGNOSIS
The identification of organisms in spinal fluid
with India ink examination or by the
detection of cryptococcal antigen.
A biopsy may be needed to make a diagnosis
of CNS cryptococcoma.
TREATMENT
Treatment is with IV amphotericin B, at a dose
of 0.7 mg/kg daily, or liposomal amphotericin
4-6 mg/kg daily, with flucytosine, 25 mg/kg for
at least 2 weeks, and, if possible, until the CSF
culture turns negative.
This is followed by fluconazole, 400 mg/d PO
for 8 weeks, and then fluconazole,200 mg/d
until the CD4+ T cell count has increased to
>200 cells/μL for 6 months in response to cART.
Repeated lumbar puncture may be required to
manage increased intracranial pressure.
VIRAL MENINGITIS
Meningitis caused by viruses, like enteroviruses,
arboviruses and herpes simplex viruses, is serious
but often is less severe than bacterial meningitis,
and people with normal immune systems usually get
better on their own. There are vaccines to prevent
some kinds of viral meningitis.
Reservoirs:
-Humans for Enteroviruses, Adenovirus, Measles,
Herpes Simplex, and Varicella
-Natural reservoir for arbovirus birds, rodents etc.
NON–INFECTIOUS MENINGITIS
causes include:
Cancers
Systemic lupus erythematosus (lupus)
Certain drugs
Head injury
Brain surgery
This type of meningitis is not spread from person to person.
Like other types it is characterized by sudden onset of fever,
headache, and stiff neck. It is often accompanied by other symptoms,
such as:
Nausea
Vomiting
Photophobia (sensitivity to light)
Altered mental status (confusion)
NEUROTUBERCULOSIS
Intracranial
Tuberculous meningitis
Spinal
Spinal meningitis
TUBERCULOUS MENINGITIS
It is the most devastating form of extra-pulmonary
tuberculosis with 30% mortality and disabling
neurological sequelae in > 25% survivors
It is caused by the human strain of Myobacterium
tuberculosis.
However in immunocompromised patients, atypical
mycobacteria are an important cause of infection
Commonest form of neurotuberculosis (70 to 80%)
It is also the commonest form of chronic meningitis
CLINICAL PRESENTATION
Clinical features include ill health for 2-8 weeks
prior to development of meningeal irritation.
Non specific symptoms include malaise, anorexia,
fatigue, low grade fever, myalgia and headache.
Prodromal symptoms in infants and children include
irritability, drowsiness, poor feeling, and abdominal
pain
Meningeal irritation - neck stiffness, Kernig’s sign,
Bickelle’s sign and Brudzinski’s sign.
Cranial nerve palsies (20-30%), fundus -
papilloedema or rarely choroid tubercles, seizures,
focal neurological deficits secondary to infarction.
Visual loss may be due to optic nerve involvement,
optochiasmatic arachnoiditis, third ventricular
compression of optic chiasma, ethambutol toxicity
and occipital lobe infarction.
Increasing lethargy, confusion, stupor, deep coma,
decerebrate or decorticate rigidity.
Clinical Features Children (%) Adults
(%)
Symptoms
Headache 20-50 50-60
Nausea/vomiting 50-75 8-40
Apathy/behavioural changes 30-70 30-70
Seizures 10-20 0-15
Signs
Fever 50-10060-100
Meningismus 70-10060-70
Cranial nerve palsy 15-30 15-40
Coma 30-45 20-30
STAGING OF TBM
TBM is classified into 3 stages according to the British
Medical Research Council (MRC) criteria
Stage I: Prodromal phase with no definite neurologic
symptoms.
Stage II: Signs of meningeal irritation with slight or no
clouding of sensorium and minor (cranial nerve
palsy) or no neurological deficit.
Stage III: Severe clouding of sensorium, convulsions, focal
neurological deficit and involuntary movements
DIFFERENTIAL DIAGNOSIS OF TBM
Fungal meningitis (cryptococcosis, histoplasmosis,
blastomycosis, coccidioidal mycosis)
Viral meningoencephalitis (herpes simplex, mumps)
Partially treated bacterial meningitis
Neurosyphills
Focal parameningeal infection
CNS toxoplasmosis
Neoplastic meningitis (lymphoma, carcinoma)
Neurosarcoidosis
DIAGNOSTIC CRITERIA FOR TBM
Class Definition
Definite Acid-fast bacilli seen in the cerebrospinal fluid.
Probable Patients with one or more of the following:
i. Suspected active pulmonary TB on chest radiography.
ii. AFB found in any specimen other than the CSF.
iii. Clinical evidence of extrapulmonary tuberculosis.
Possible Patients with at least four of the following:
i. History of tuberculosis.
ii. Predominance of lymphoytes in the cerebrospinal fluid.
iii. A duration of illness of more than six days.
iv. A ratio of CSF glucose to plasma glucose of less than 0.5.
v. Altered consciousness
vi. Turbid cerebrospinal fluid.
vii. Focal neurologic signs.
PRINCIPLES OF TREATMENT OF
TBM
Treatment should be started early in suspected
TBM.
Multiple antimicrobial drugs are required.
Drugs must adequately cross the blood-CSF barrier
to achieve therapeutic concentrations in CSF.
Drugs should be taken on a regular basis for a
sufficient period to eradicate the CNS infection.
Intrathecal therapy is not required.
LIST OF ANTITUBERCULAR DRUGS
First-Line Drugs Second-Line Drugs
INH Cycloserine
Rifampicin Ethionamide
Rifapentine Levofloxacin*
Rifabutin* Moxifloxacin*
Ethambutol Gatifloxacin*
Pyrazinamide p-aminosalicylic acid**
Streptomycin**
Amikacin/Kanamycin*
Capreomycin
* Not approved by U.S. FDA
** Included in second-line drugs due to toxicity, limited
efficacy or difficulty in administration
ASEPTIC MENINGITIS
refers to patients who have clinical signs and
laboratory evidence for meningeal inflammation
with negative routine bacterial cultures
lymphoma, leukemia, and metastatic carcinomas
and adenocarcinomas can occasionally present with
an aseptic meningitis syndrome
It can also be drug induced and has correlation
with SLE, in whom DIAM appears to occur more
commonly
ASEPTIC VIRAL MENINGITIS
Enteroviruses
Herpes Simplex virus (HSV)
Herpes Simplex Meningitis
Increasinglyrecognized as a cause of aseptic meningitis,
with improving diagnostic techniques and a continued
increase in the transmission of HSV-2
HIV
Lymphocytic Choriomeningitis virus (LCM)
Mumps
Other less common causes include West Nile, St Louis
Encephalitis, and California Encephalitis (although
most commonly assoc. with encephalitis). May also
accompany primary VZV, outbreaks of herpes zoster,
EBV, CMV, and adenoviruses.
ASEPTIC BACTERIAL INFECTIONS
Parameningeal bacterial infections (epidural,
subdural abcess)
Partially treated bacterial meningitis or
patients who develop meningitis while
already on antibiotics
Leptospira species
Lyme disease (Borrelia burgdorferi)
M. Tuberculosis (look for signs of disease
elsewhere in the body as a clinical clue)
Bacterial endocarditis
SIGNS OF ASEPTIC MENINGITIS
Kernig’s sign
Brudzinski's sign
Jolt Accentuation of HEADACHE Sign
Patient rotates head in horizontal plane two
to three times per second, and the test is
considered positive if this worsens the
headache pain.
MOLLARET'S MENINGITIS
Mollaret's meningitis is a recurrent or chronic
inflammation of the meninges. Since
Mollaret's meningitis is a recurrent, benign
(non-cancerous), it is now referred to as
benign recurrent lymphocytic meningitis
it is associated with pleocytosis in the
cerebrospinal fluid“
recent work has associated this problem with
herpes simplex viruses, which cause cold
sores and genital herpes
CLINICAL PRESENTATION
chronic, recurrent episodes of headache
stiff neck,
meningismus,
fever;
Many people have side effects between bouts
that vary from chronic daily headaches to
after-effects from meningitis such as hearing
loss
INVESTIGATIONS
blood tests (electrolytes, liver and kidney
function, inflammatory markers and a complete
blood count)
X-ray examination of the chest.
analysis of the cerebrospinal fluid through
lumbar puncture (LP).
However, if the patient is at risk for a cerebral
mass lesion or elevated intracranial pressure
(recent head injury, a known immune system
problem, localizing neurological signs, or
evidence on examination of a raised ICP), a
lumbar puncture may be contraindicated because
of the possibility of fatal brain herniation.
CSF RESULTS
In cerebrospinal fluid (CSF) pleocytosis with
large "endothelial" cells, neutrophil
granulocytes, and lymphocytes; and attacks
separated by symptom-free periods of weeks
to months; and spontaneous remission of
symptoms and signs
TREATMENT
Acyclovir is the treatment of choice for
Mollaret's meningitis
The IHMF recommends that patients with
benign recurrent lymphocytic meningitis
receive intravenous acyclovir in the amount of
10 mg/kg every 8 hours, for 14–21 days. More
recently, the second-generation antiherpetic
drugs valacyclovir and famciclovir have been
used to successfully treat patients with
Mollaret's.
THERAPY FOR STREPTOCOCCUS PNEUMONIAE
The conventional approach to the treatment
of pneumococcal meningitis was the
administration of penicillin alone for two
weeks at a dose of four million units
intravenously every four hours
Good results have also been obtained with
third generation cephalosporins
However, the problem of treating
pneumococcal meningitis has recently been
compounded by the widespread and
increasingly common reports of
pneumococcal strains resistant to penicillin
Cefotaxime or ceftriaxone can be used if the MIC
for these drugs is less than 0.5 µg/mL
It is recommended that vancomycin (2 g/day)
should be given with cefotaxime or ceftriaxone in
the initial treatment of pneumococcal meningitis if
there has been beta-lactam resistance noted locally
Vancomycin should be continued if there is high
level penicillin resistance and an MIC >0.5 µg/mL to
third generation cephalosporins
If corticosteroids are given, rifampin should be
added as a third agent since it increases the
efficacy of the other two drugs
The usual duration of therapy is two weeks
THERAPY FOR HAEMOPHILUS INFLUENZAE
A third generation cephalosporin is the drug of
choice for H. influenzae meningitis
Patients with H. influenzae meningitis should be
treated for five to seven days
For adults, a dose of 2 g every six hours of
cefotaxime and 2 g every 12 hours of ceftriaxone is
more than adequate therapy
Pharyngeal colonization persists after curative
therapy and may require a short course of rifampin
if there are other children in the household at risk
for invasive Haemophilus infection
The recommended dose is 20 mg/kg per day (to a
maximum of 600 mg/day) for four days
VACCINE FOR MENINGITIS
There are vaccines against Hib and against some
strains of N. meningitidis and many types of
Streptococcus pneumoniae.
The vaccine against haemophilus influenze (Hib)
has reduced Hib meningitis cases by 95 percent
since 1985.
There are vaccines to prevent meningitis due to S.
pneumoniae. The pneumococcal polysaccharide
vaccine is recommended for all persons over 65
years of age and younger persons at least 2 years
old with certain chronic medical problems.
HSV MENINGITIS TREATMENT
Most cases are self limited and will require
only symptomatic treatment
There have been anecdotal cases that
suggest clinical improvement with acyclovir
treatment. Antiviral therapy is
recommended in patients with primary HSV
infection or with severe neurological
symptoms. (inpatient-IV acyclovir 10mg/kg
Q8°, outpatient with high dose oral
acyclovir/valacyclovir/or famciclovir)
Patients with frequent recurrences might
benefit from acyclovir prophylaxis
HIV MENINGITIS TREATMENT
The meningitis associated with primary
infection resolves in most patients without
treatment, and patients are typically
assumed to have a benign viral meningitis.
This occasionally leads to missing the
diagnosis of HIV.
DIAM TREATMENT
Treatment is simply to stop the offending
agent and await resolution of the symptoms.
Unfortunately, since this is a diagnosis of
exclusion because of the seriousness of a
missed bacterial meningitis, it is not an easy
diagnosis to make until a bacterial infection
can be ruled out
The end
