meningitis in adults management and prognosis

Bacterial meningitis is an acute purulent infection within the subarachnoid
space. The meninges, the subarachnoid space, and the brain parenchyma are
all frequently involved in the inflammatory reaction (meningoencephalitis).
PREDISPOSING FACTORS:
 Systemic(especially respiratory ) or parameningeal infections
 DM, alcoholism, cancer, or other immunodeficiency states.
 Anatomical meningeal defect, prior neurosurgery, or head trauma.

ETIOLOGY
 S. pneumoniae (pneumococcal meningitis) is the most common cause account for
50% of all cases of bacterial meningitis mainly in adults >20 years of age.
 N. meningitidis (meningococcal meningitis) accounts for 25% of all cases of
meningitis mostly in children and young adults between the ages of 2 and 20.
 Group B streptococcus, or S. agalactiae: accounts for 15% of meningitis
predominantly in neonates.
 L. monocytogenes accounts for 10% predominantly in neonates (<1 month of age),
pregnant women, individuals >60 years, and immunocompromised individuals of all
ages.
 H. influenzae type b accounts for 10% of bacterial meningitis mainly in children.
 Staphylococcus aureus are important causes of meningitis that occurs following
invasive neurosurgical procedures, particularly shunting procedures, or as a
complication of of intrathecal chemotherapy.

PATHOGENESIS
 Bacteria typically gain access to the CNS by colonizing the nasopharynx,leading to tissue
invasion and hematogenous spread to the SAS.
 Bacteria can also spread to the meninges directly, through anatomic defect in the skull or
from parameningeal sites such as paranasal sinuses or middle ear.
 The low level of antibodies and complement and the few WBCs in the CSF are inadequate
to contain the infection.
 The resulting inflammatory response resulting in release of cytokines that promote BBB
permeability ,vasogenic edema, changes in cerebral blood flow and perhaps direct neuronal
toxicity

CLINICAL PRESENTATION
 Presentation is usually acute and patient may have symptoms of
meningitis for 1-7 days .
 The classic clinical triad of meningitis is fever, headache, and nuchal
rigidity.
 A decreased level of consciousness occurs in >75% of patients and can
vary from lethargy to coma.
 Nausea, vomiting, and photophobia are also common complaints.
 Seizures occur as part of the initial presentation of bacterial meningitis or
during the course of the illness in 20–40% of patients.

 Signs of meningeal irritation are seen in approximately 80% of
cases,
(often absent in the very young and very old, or with profound
impairment of consciousness).
These include:
• neck stiffness on passive flexion,
• thigh flexion upon flexion of the neck brudzinski sign ,
• resistance to passive extension of the knee with the hip flexed
kernig sign.
 A petechial rash is seen in 50-60% of patients with
N.meningitidis meningitis

Blood Studies
 complete blood count (CBC) with differential will
demonstrate polymorphonuclear leukocytosis.
 Serum electrolytes, to determine dehydration or syndrome of
inappropriate secretion of antidiuretic hormone (SIADH)
 Serum glucose (which is compared with the CSF glucose)
 Blood urea nitrogen (BUN) or creatinine and liver profile, to
assess organ function and adjust antibiotic dosing

 Cultures and Bacterial Antigen Testing
The utility of cultures is most evident when LP is delayed until head imaging
can rule out the risk of brain herniation, in which cases antimicrobial
therapy is rightfully initiated before CSF samples can be obtained.
These cultures include the following:
 Blood - 50% positive in meningitis caused by H influenzae, S
pneumoniae, or N meningitidis
 Nasopharynx
 Respiratory secretions
 Urine
 Skin lesions

DIAGNOSIS
The diagnosis of bacterial meningitis is made by examination of the CSF .
The need to obtain neuroimaging studies (CT or MRI) prior to LP requires clinical
judgment.
In an immunocompetent patient with no history of head trauma, a normal level of
consciousness, and no papilledema or focal neurologic deficits,
it is safe to perform LP without prior neuroimaging studies.

The classic CSF abnormalities in bacterial meningitis are:
(1) polymorphonuclear (PMN) leukocytosis (>100 cells/L ).
(2) decreased glucose concentration (<40 mg/dL) and/or CSF/serum glucose
ratio of <0.4
(3) increased protein concentration (>45 mg/dL) .
(4) increased opening pressure (>180 mmH2O ).
CSF bacterial cultures are positive in >80% of patients, and CSF Gram's
stain demonstrates organisms in >60%.

 broad-based bacterial PCR can detect small numbers of viable
and nonviable organisms in CSF and is expected to be useful for
making a diagnosis of bacterial meningitis in:
 patients who have been pretreated with oral or parenteral
antibiotics
 in whom Gram's stain and CSF culture are negative.
 When the broad-range PCR is positive, a PCR that uses specific
bacterial primers to detect the nucleic acid of S. pneumoniae, N.
meningitidis, Escherichia coli, L. monocytogenes, H. influenzae,
and S. agalactiae can be obtained based on the clinical
suspicion of the meningeal pathogen.

 The latex agglutination (LA) test for the detection of bacterial antigens of
S. pneumoniae, N. meningitidis, H. influenzae type b, group B
streptococcus, and E. coli strains in the CSF has been useful for making a
diagnosis of bacterial meningitis but is being replaced by the CSF bacterial
PCR assay.
 The CSF LA test has a specificity of 95–100% for S. pneumoniae and N.
meningitidis, so a positive test is virtually diagnostic of bacterial meningitis
caused by these organisms.
However, the sensitivity of the CSF LA test is only 70–100% for detection of
S. pneumoniae and 33–70% for detection of N. meningitidis antigens, so a
negative test does not exclude infection by these organisms.

DIFFERNTIAL DIAGNOSIS
 Viral meningoencephalitis, and particularly herpes simplex virus (HSV) encephalitis,
can mimic the clinical presentation of bacterial meningitis. The findings on CSF
studies, neuroimaging, and electroencephalogram (EEG) distinguish HSV encephalitis
from bacterial meningitis.
 Focal CNS infections , including subdural and epidural empyema and brain abscess,
should also be considered, especially when focal neurologic findings are present. MRI
should be performed in all patients with suspected meningitis who have focal features.
 subacutely evolving meningitis may be considered in the differential diagnosis of
acute meningitis. The principal causes include Mycobacterium tuberculosis ,and
Brucelosis.
 A number of noninfectious CNS disorders can mimic bacterial meningitis.
Subarachnoid hemorrhage SAH is generally the major consideration. Other
possibilities include chemical meningitis due to rupture of tumor contents into the
CSF (e.g., from a cystic glioma or craniopharyngioma epidermoid or dermoid cyst);

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. Antimicrobial therapy is
initiated in patients with suspected bacterial meningitis before the results of CSF
Gram's stain and culture and after obtaining blood sample for culture.
 The initial choice of antibiotics is empirical , based upon the age of the patient and
the predisposing factors .therapy is adjusted as indicated when the gram stain or
culture and sensitivity result become available
 Lumber puncture can be repeated to assess the response to therapy.CSF should be
sterile after 24 hours, and decrease in pleocytosis should occur within 3 days ,while
sugar may remain low for many days .
 Dexamethasone ,given immediately before the onset of antibiotics treatment and
continued for 4 days, can reduce mortality in patient with meningitis

Antibiotics Used in Empirical Therapy of
Bacterial Meningitis
Indication Antibiotic alternative agent
Less than 3 months Ampicillin + cefotaxime
or ceftriaxone
chloramphenicol +
gentamicin
3months -50 years Cefotaxime , ceftriaxone
or cefepime +
vancomycin
chloramphenicol +
vancomycin
Or
clindamycin
or
meropenem
Adults >55 and adults of any age with
alcoholism or other debilitating illnesses
Ampicillin + cefotaxime,
ceftriaxone or cefepime +
vancomycin
meropenem, TMP-SMX,
or doxycycline.
Hospital-acquired meningitis,
posttraumatic or postneurosurgery
meningitis, neutropenic patients, or
patients with impaired cell-mediated
immunity
Ampicillin + ceftazidime
+ vancomycin
meropenem +
vancomycin

Child (>1 month) Adult
Ampicillin 200 (mg/kg)/d, q4h 12 g/d, q4h
Cefepime 150 (mg/kg)/d, q8h 6 g/d, q8h
Cefotaxime 200 (mg/kg)/d, q6h 12 g/d, q4h
Ceftriaxone 100 (mg/kg)/d, q12h 4 g/d, q12h
Ceftazidime 150 (mg/kg)/d, q8h 6 g/d, q8h
Gentamicin 7.5 (mg/kg)/d, q8hb 7.5 (mg/kg)/d, q8h
Meropenem 120 (mg/kg)/d, q8h 3 g/d, q8h
Metronidazole 30 (mg/kg)/d, q6h 1500–2000 mg/d, q6h
Nafcillin 100–200 (mg/kg)/d, q6h 9–12 g/d, q4h
Penicillin G 400,000 (U/kg)/d, q4h 20–24 million U/d, q4h
Vancomycin 60 (mg/kg)/d, q6h 2 g/d, q12hb

PROGNOSIS
Mortality is 20% and the risk of death from bacterial meningitis increases
with :
(1) Decreased level of consciousness on admission.
(2) Onset of seizures within 24 h of 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.
(6) Delay in the initiation of treatment.
Common sequelae include: decreased intellectual function, memory impairment,
headache, hydrocephalus, SIADH, seizures, hearing loss and dizziness, and gait
disturbances.

Prevention
Vaccinations are available against pneumococci, meningococci, and
hemophilus influenzae type b (Hib) and are recommended in high‐
risk children.
All contacts with patients (individuals who have had contact with
oropharyngeal secretions, either through kissing or by sharing toys,
beverages, or cigarettes).
meningococcal meningitis should be given prophylactic rifampicin at a
dosage of 10 mg/kg in children and 600 mg/day in adults for 2 days.
In case of any contraindication for the use of rifampicin, asingle
intramuscular injection of ceftriaxone may be given.

ETIOLOGY
COMMON LESS COMMON
Enteroviruses
echoviruses,coxsackiviruses,
and human enteroviruses
VZV
HSV-2 EBV
Arboviruses

CLINICAL
MANIFESTATIONS
Headache : usually frontal or retro- orbital and is often associated with
photophobia and pain on moving the eye .
Nuchal rigidity :present in most cases ,but may be mild and present
only near the limit of neck anteflexion.
Constitutional symptoms : fever, malaise, myalgia ,nausea and
vomiting, abdominal pain and/or diarrhea.
Patient may have mild lethargy or drowsiness.
Sings of meningeal irritations: neck stiffness, Kernigs sign and
Brubzinskis sign

LABORATORY DIAGNOSIS
CSF Examination
is the most important laboratory test in the diagnosis of viral meningitis . the
typical profile is;
 WBC: (25 – 500 cells/mL) predominantly lymphocytes.
 Protein: normal or slightly elevated (20 – 80 mg/dl).
 Glucose : normal.
 Opening pressure : normal or slightly elevated (100 – 350 mm H2O).
Polymerase Chain Reaction
Amplification of viral – specific DNA or RNA from CSF using PCR amplification
has become the single most important method for diagnosing CNS viral infections .
Viral Culture
The sensitivity of CSF cultures for the diagnosis of viral meningitis and encephalitis, in
contrast to it utility in bacterial infection ,is generally poor.

Serological Studies
Serum antibodies determination remain a crucial diagnostic test for viruses
with low seroprevalence rates in the general population.
Neuroimaging Study
MRI and CT scan are not necessary for patients with uncomplicated viral
meningitis ,but should be performed in patients with altered consciousness,
seizures, focal neurological sings or symptoms ,or atypical CSF profiles.

TREATMENT
 Treatment of all patients is primarily symptomatic and includes use of
analgesics, antipyretics, antiemetics with fluid and electrolytes monitoring .
 Hospitalization is required for those patients who are immunocompromised;
have significant alteration of consciousness, seizures, or the presence of
focal signs and symptoms suggesting parenchymal brain involvement ; and
those who have atypical CSF profile
 Oral or intravenous acyclovir may be of benefit in patients with meningitis
caused by HSV, severe EBV or VZV infection. Seriously ill patients should
receive intravenous acyclovir (15 – 30 mg/kg per day in three divided
doses) which can be followed by an oral drug such as acyclovir (800 mg
five times daily),famciclovir (500 mg tid), or valacyclovir (1000 mg tid) for
a total course of 7 – 14 days. Patients who are less ill can be treated with
oral drug alone .

PREVENTION
Vaccination is an effective method of preventing the development of meningitis and
other neurological complications associated with poliovirus, mumps, and measles .
PROGNOSIS
In adult the prognosis for full recovery from viral meningitis is excellent. Rare
patients complain of persistent headache, mild mental impairment, incoordination,
or generalized asthenia for weeks to months .

In contrast to viral meningitis, where the infectious process and
associated inflammatory response are limited largely to the
meninges, in encephalitis the brain parenchyma is also
involved. Many patients with encephalitis also have evidence
of associated meningitis (meningoencephalitis).

ETIOLOGY
COMMON LESS COMMON
Herpesviruses
HSV-1
VZV
EBV
Rabies
Estern equine virus
Western equine virus
Arthropod-born viruses CMV
Enteroviruses
Mumps

CLINICAL MANIFESTATIONS
In addition to the acute febrile illness with evidence of meningeal involvement
characteristic of meningitis, the patient with encephalitis commonly has :
 depressed level of consciousness, ranging from mild lethargy to coma.
 evidence of focal neurologic signs and symptoms (aphasia, ataxia, weakness,
involuntary movements, and cranial nerves deficits).
 Patients may also have confusion, hallucinations, agitation, behavioral disorders,
and, at times, a frank psychosis.
 Focal or generalized seizures may occur.

Laboratory
Diagnosis
 CSF Examination
CSF examination should be performed in all patients with suspected viral
encephalitis unless contraindicated by the presence of severely increased ICP. The
characteristic CSF profile is indistinguishable from that of viral meningitis.
 CSF PCR
 CSF Culture
 Serologic Studies and Antigen Detection
 MRI, CT, EEG
Patients with suspected encephalitis almost invariably undergo neuroimaging
studies and often EEG. These tests help identify or exclude alternative diagnoses
and assist in the differentiation between a focal, as opposed to a diffuse, encephalitic
process. Focal findings in a patient with encephalitis should always raise the
possibility of HSV encephalitis which usually affect the frontotemporal surface of
the brain.
 Brain Biopsy

Treatment
 many patients will require care in an intensive care unit with monitoring of
the vital functions, careful monitoring of ICP, fluid restriction, and
suppression of fever.
 Seizures should be treated with standard anticonvulsant regimens, and
prophylactic therapy should be considered.
 As with all seriously ill, immobilized patients, encephalitis patients are at
risk for aspiration pneumonia, bed sores, DVT, and infections of indwelling
lines and catheters.
 Acyclovir is of benefit in the treatment of HSV and should be started
empirically in patients with suspected viral encephalitis, especially if focal
features are present . Adults should receive a dose of 10 mg/kg of acyclovir
intravenously every 8 h for a minimum of 14 days.

ACYCLOVIR
Prior to intravenous administration, acyclovir should be diluted to a concentration 7
mg/mL. (A 70-kg person would receive a dose of 700 mg, which would be diluted in a
volume of 100 mL.) Each dose should be infused slowly over 1 h rather than by rapid or
bolus infusion, to minimize the risk of renal dysfunction. Care should be taken to avoid
extravasation or intramuscular or subcutaneous administration. The alkaline pH of
acyclovir can cause local inflammation and phlebitis
Complications of therapy include elevations in blood urea nitrogen and creatinine levels ,
thrombocytopenia , gastrointestinal toxicity (nausea, vomiting, diarrhea) , and
neurotoxicity (lethargy , disorientation, confusion, agitation, hallucinations, tremors,
seizures) .

PROGNOSIS
The incidence and severity of sequelae were directly related to the age of the
patient and the level of consciousness at the time of initiation of therapy.
Patients with severe neurologic impairment (Glasgow coma score 6) at
initiation of therapy either died or survived with severe sequelae.
Young patients (<30 years) with good neurologic function at initiation of
therapy did substantially better (100% survival, 62% with no or mild
sequelae) compared with their older counterparts (>30 years; 64% survival,
57% no or mild sequelae).

pathopysiology
Tuberculous meningitis in adults does not develop acutely from hematogenous
spread of tubercle bacilli to the meninges. Rather,( miliary) tubercles form
in the parenchyma of the brain during hematogenous dissemination of
tubercle bacilli in the course of primary infection.
These tubercles enlarge and are usually caseating. Subependymal caseous foci
cause meningitis via discharge of bacilli and tuberculous antigens into the
SAS, producing an intense inflammatory reaction that leads to the
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.

Clinical Manifestations
 Patients with subacute meningitis typically have headache, stiff neck, low-
grade fever, night sweats and lethargy for days to several weeks before
presentation.
 The meningitis is often concentrated around the base of the brain, causing
cranial nerve palsies.
 Elevated intracranial pressure and hydrocephalus are common.
 It can also cause inflammation of the blood vessels as they leave the
meninges to enter the brain, causing strokes.

Laboratory Diagnosis
The classic CSF abnormalities in tuberculous meningitis are as follows:
(1) elevated opening pressure.
(2) lymphocytic pleocytosis (10–500 cells/L).
(3) elevated protein concentration in the range of 1–5 g/L (10–500 mg/dL).
(4) decreased glucose concentration in the range of 1.1–2.2 mmol/L (20–40
mg/dL).
The combination of unrelenting headache, stiff neck, fatigue,
night sweats, and fever with a CSF lymphocytic pleocytosis
and a mildly decreased glucose concentration is highly
suspicious for tuberculous meningitis.

 Positive smears are typically reported in only 10–40% of cases of
tuberculous meningitis in adults.
 Cultures of CSF take 4–8 weeks to identify the organism and are positive
in ~50% of adults. Culture remains the "gold standard" to make the
diagnosis of tuberculous meningitis.
 PCR for the detection of M. tuberculosis DNA has a sensitivity of 70–80%
but is limited at the present time by a high rate of false-positive results.

Treatment
Empirical therapy of tuberculous meningitis is often initiated on the basis of a high index of suspicion without
adequate laboratory support.
 first 2 months of intensive treatment require quadruple therapy with the combination of :
isoniazid (300 mg/d),
rifampin (10 mg/kg per day),
pyrazinamide (30 mg/kg per day in divided doses),
with the addition of one of the following:
ethambutol (15–20mg/kg/day),
streptomycin (15 mg/kg/day; maximum 1 g),
ethionamide (15–20 mg/kg/day).
 Isoniazid which has excellent CSF penetration – should be given together
with rifampicin for the continuation phase of treatment from months 3 to 9.
 Pyridoxine therapy (100 mg/day) should be given with isoniazid therapy to prevent the development of
peripheral neuropathy.
 Adjunctive corticosteroids, significantly reduce mortality across all severity grades. For this reason,
steroids should be administered in all cases from day 1 of treatment, in a tapering dose for the first 1–2
months.

Definition
A brain abscess is a focal, suppurative infection within the brain parenchyma,
typically surrounded by a vascularized capsule. The term cerebritis is often
employed to describe a nonencapsulated brain abscess.
Etiology
A brain abscess may develop
(1) by direct spread from a contiguous cranial site of infection, such as paranasal
sinusitis, otitis media, mastoiditis, or dental infection.
(2) following head trauma or a neurosurgical procedure.
(3) as a result of hematogenous spread from a remote site of infection.
The most important pathogens are:
Streptococcus spp. (40%), Enterobacteriaceae. (25%), anaerobes (30%), and
staphylococci (10%).

Clinical Presentation
The most common symptoms in patients with a brain abscess are :
 headache, often characterized as a constant, dull, aching sensation, either
hemicranial or generalized, and it becomes progressively more severe and
refractory to therapy.
 Fever is present in only 50% of patients at the time of diagnosis, and its
absence should not exclude the diagnosis.
 focal or generalized seizures.
 Focal neurologic deficits including hemiparesis, aphasia, or visual field
defects .
 Signs of raised ICP—papilledema, nausea and vomiting.
 Meningismus is not present unless the abscess has ruptured into the
ventricle or the infection has spread to the subarachnoid space.

Diagnosis
 Diagnosis is made by neuroimaging studies. MRI is better than CT for
demonstrating abscesses in the early (cerebritis) stages and is superior to CT for
identifying abscesses in the posterior fossa.
 Microbiologic diagnosis of the etiologic agent is most accurately determined by
Gram's stain and culture of abscess material obtained by stereotactic needle
aspiration.
 LP should not be performed in patients with known or suspected focal
intracranial infections.
 Additional laboratory studies may provide clues to the diagnosis of brain
abscess in patients with a CNS mass lesion. About 50% of patients have a
peripheral leukocytosis, 60% an elevated ESR, and 80% an elevated C-reactive
protein. Blood cultures are positive in ~10% of cases

Differential Diagnosis
Conditions that can cause headache, fever, focal neurologic signs, and
seizure activity include:
brain abscess, subdural empyema, bacterial meningitis, viral
meningoencephalitis, superior sagittal sinus thrombosis, and acute
disseminated encephalomyelitis.
When fever is absent: primary and metastatic brain tumors become the major
differential diagnosis. Less commonly, cerebral infarction or hematoma can
have an MRI or CT appearance resembling brain abscess.

Treatment
Optimal therapy of brain abscesses involves a combination of high-dose
parenteral antibiotics and neurosurgical drainage.
 Empirical therapy of brain abscess typically includes a third-generation
cephalosporin (e.g., cefotaxime or ceftriaxone) and metronidazole.
 In patients with head trauma or neurosurgical procedures, treatment
should include ceftazidime as the third-generation cephalosporin to enhance
coverage of Pseudomonas spp. and vancomycin for coverage of
staphylococci.
 Intravenous dexamethasone therapy (10 mg every 6 h) is usually reserved
for patients with substantial periabscess edema and associated mass effect
and increased ICP.

 Aspiration and drainage of the abscess under stereotactic guidance are
beneficial for both diagnosis and therapy, but complete excision of a
bacterial abscess via craniotomy or craniectomy is generally reserved for
multiloculated abscesses or those in which stereotactic aspiration is
unsuccessful.
 Serial MRI or CT scans should be obtained on a monthly or twice-
monthly basis to document resolution of the abscess

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