Meningitis, encephalitis and

brain abscess
By
D Ogoina
 Introduction
• Meningitis – defined as inflammation of the
covering of the brain and spinal cord
(meninges)
• Leptomeningitis- inflammation of the pia,
arachnoid mata and underlying sub-arachnoid
space
• Most cases of meningitis present with
leptomeningitis
 Epidemiology
• World wide distribution, no specific geographical
variations in causative organisms.
• However, epidemic meningitis (due to Neisseria
meningitidis) is commoner in the meningitic belt
of sub Saharan Africa described by Lapeysonnie-
mainly affecting countries of West Africa- Guinea
Burkina Faso, Nigeria, Senegal etc
• A disease of all age groups and both sexes
The meningitic belt
Seroepidemiology of meningococcal meningitis
• Serogroups
– 12 serogroups (A, B, C, 29E, H, I, K, L,
W135, X, Y and Z) based on the
structure of the polysaccharide capsule.
– A, B, C, W135, X and Y responsible for
invasive disease
 Aetiology/Classification
• Acute (<4 weeks) or chronic (≥4weeks)
• Infectious or non- infectious
• Age group based classification
• Community acquired/Hospital
acquired/immunocompromised
• Septic (bacterial organisms in CSF) or Aseptic
meningitis (no organism in CSF)
• Pyogenic (bacterial), granulomatous, and aseptic
 Infectious meningitis
• Commonest cause of meningitis
• Most infectious agents may cause meningitis
depending on exposure and predisposing
factors
 Causes of infectious meningitis
Bacteria Viruses Fungus Parasites

Gram positive- Enteroviruses, Cryptococcus Naegleria fouleri

staphylococci, streptococci, Polivirus, neoformans (Amoebic
streptococcus pneumonia, Coxsackie A and B, meningitis)
listeria monocytogenes Echoviruses,
Mumps

Gram negative- Herpes simples Candida, Others rare

Haemophilus influenza type b, virus 1 and 2, Actinomyces,
Niesseria meningitidis, E coli, varicella zoster Aspergillosis,
proteus mirabilis, Klebsiella virus
spp, CMV

Chronic bacteria- Arboviruses, HIV, Histoplasmosis

Mycobacteria, Brucella spp,

Spirochaetes – T. pallidium, Lymphocytic Other fungi

Borrellia Borgdoferi, Choriomeningitis
Leptospira spp
 Non infectious meningitis
• Malignancy- carcinomatous meninigitis- due to
metastasis to the brain from any cancer, leukaemia,
lymphoma (rare)
• Sarcoidosis
• Connective tissue disease- SLE, Behcet’s disease,
wegener’s granulomatosis, Churg straus syndrome
• Chemical meningitis- due to contrast media injected
into the CNS
• Drugs – Ibuprofen, sulphonamide, immunoglobulin
• Rupture of Epidermoid cyst and Dermoid cyst
• Eosinophilic meningitis
 Broad classification
Community acquired Hospital acquired Immunocompromised
Streptococcus pneumonia Gram negative organisms Cryptococcus
Haemophilus influenza Staphylococci spp Mycobacteria
Type b
Niesseria meningitidis Aseptic meningitis
Tuberculosis HIV
Others Listeria monocytogenes
 Meningitis according to age group
• Neonates-
Streptococcus agalactiae type 111, Listeria monocytogenes,
Staphylococcus epidermidis, Staphylococcus aureus, Streptococcus
pneumoniae, Gram negative organisms (Esch.coli,Proteus
mirabilis, Klebsiella, Enterobacter,
Pseudomonas aeruginosa, Citrobacter diversus, Salmonella),
Hemophilus influenzae type b

• Childhood to early adulthood:

Neisseria meningitidis, Streptococcus pneumoniae,
Staphylococcus aureus, Hemophilus influenzae type b

• Mid adulthood
Neisseria meningitidis, Streptococcus pneumoniae,
Staphylococcus aureus.

• Old age.
Neisseria meningitidis, Streptococcus
pneumoniae,Staphylococcus aureus.
L. monocytogenes, Gram-negative bacilli.
 Causes of chronic meningitis
• Infectious – TB, brucellosis, syphilis, fungi,
recurrent viral infection- recurrent aseptic
meningitis (Mollaret’s meningitis) –due to
HSV-2
• Non infectious – carcinomatous meningitis,
connective tissue disease, sarcoidosis
 Risk /Predisposing factors for
meningitis
• Infections of contiguous structures – sinusitis, otitis
media, scalp infection, skull trauma, mastoiditis,
cochlear implants
• Neurosurgical procedures
• Overcrowding- risk factor for Niesseria meningitis
( common in military barracks, college campuses, Hajj
pilgrimage)
• Secondary Immunosuppression- HIV, Diabetes, chronic
renal disease, chronic alcoholism, hyposplenism
• Primary immunodeficiency- complement deficiency,
cystic fibrosis
 Pathogenesis
• Acquisition of pathogenic organisms
• Spread from contiguous structures,
haematogenous seeding in the CNS or retrograde
neuronal pathway
• Release of microbial products, migration of
inflammatory cells to site of infection, release of
cytokines- inflammation of leptomeninges
• Disruption of blood brain barrier- resultant
vasogenic, cytotoxic and interstitial oedema
• CNS dysfunction ± cellular death
Pathogenesis/Pathophysiology

INFECTION OF CONTIGOUS NASOPHARYNGEAL COLONIZATION CONTAMINATED BLOOD BORNE INFECTION

STRUCTURES NEUROSURGICAL EQUIPMENT

LOCAL INVASION
ACTIVATION OF CLOTTING SYSTEM
BACTEREMIA

ENDOTHELIAL CELL INJURY

MENINGEAL INVASION
INCREASED BBB PERMEABILITY
SUBARACHNOID SPACE INFLAMMATION CEREBRAL VASCULITIS

INCREASED CSF OUTFLOW RESISTANCE

HYDROCEPHALUS
CYTOTOXIC OEDEMA
VASOGENC OEDEMA
INTERSITITIAL OEDEMA
CEREBRAL INFARCTION
INCREASED INTRACRANIAL PRESSURE

DECREASED CEREBRAL BLOOD FLOW

 Clinical features
• Cardinal features- Headache, high grade fever,
nuchal rigidity, ± altered mental status and
photophobia
• Other features- vomiting, prodromal URTI
symptoms, seizures
 Clinical features acute bacterial meningitis in adults
• Clinical features of acute
bacterial meningitis usually
develop over 24–48 hours
• Triad of acute bacterial
meningitis:
• Fever
• Neck stiffness
• Altered mental status
• Classical triad present in
less than 50% of adults
with proven bacterial
meningitis
• Typical Symptoms
• Fever (75–95%)
• Headache (80–95%)
• Photophobia (30–50%)
• Vomiting (90% of children; 10% of
adults)
• Signs
• Neck stiff ness (50–90%)
• Confusion (75–85%)
• Kernig’s sign (5%)
• Brudzinski’s signs (5%)
• Focal neurological deficit (20–30%)
• Fits (15–30%)
• Rash (10–15%)
• Other signs- papilloedema, coma
Complications
• Septic shock
• Petechiae and features of DIC (in
meningoccocemia)
• Seizures, cerebral oedema
• Septic arthritis
• Pericardial effusion
• Peripheral gangrene (septic emboli)
• Carvenous sinus thrombosis
• Cardiac arrhythmias and ischaemia
• Brain abscesses; Subdural effusions
• Decreased hearing and deafness
• Focal paralysis (due to cerebral
vasculitis, cerebral thrombosis)
• Hydrocephalus
• Blindness & Cranial nerve palsies
• SIADH & Waterhouse Frederickson
syndrome (due to adrenal
haemorrhage from DIC)
• Epilepsy &Cognitive impairment
 Diagnosis
• Gold standard- lumbar puncture with CSF culture
• Others – serological – detection of antigen of
pathogens
• PCR- detection of pathogen nucleic acid
• Serum procalcitonin level has been used to
distinguish between bacterial and aspetic
meningitis- increase serum procalcitonin
observed in bacterial meningitis
 CSF Findings in Meningitis by Etiologic Agent

Opening Pressure WBC count

Agent Glucose (mg/dL) Protein (mg/dL) Microbiology
(mm H2 O) (cells/µL)
Specific pathogen
demonstrated in
Bacterial 100-5000; >80%
200-300 < 40 >100 60% of Gram
meningitis PMNs
stains and 80% of
cultures
10-300; Normal, reduced in Normal but may be Viral isolation,
Viral meningitis 90-200
lymphocytes LCM and mumps slightly elevated PCR assays
Tuberculous 100-500; Acid-fast bacillus
180-300 Reduced, < 40 Elevated, >100
meningitis lymphocytes stain, culture, PCR
India ink,
Cryptococcal 10-200;
180-300 Reduced 50-200 cryptococcal
meningitis lymphocytes
antigen, culture
10-300; Normal but may be Negative findings
Aseptic meningitis 90-200 Normal
lymphocytes slightly elevated on workup
Negative findings
Normal values 80-200 0-5; lymphocytes 50-75 15-40
on workup
LCM = lymphocytic choriomeningitis; PCR = polymerase chain reaction; PMN = polymorphonuclear leukocyte; WBC =
white blood cell.
 Recommended Empiric Antibiotics for Suspected Bacterial

Meningitis, According to Age or Predisposing Factors  

Age or Predisposing Feature Antibiotics
Ampicillin plus either cefotaxime or an
Age 0-4 wk
aminoglycoside
Age 1 mo-50 y Vancomycin plus cefotaxime or ceftriaxone*
Vancomycin plus ampicillin plus ceftriaxone
Age >50 y
or cefotaxime plus vancomycin*
Vancomycin plus ampicillin plus either
Impaired cellular immunity
cefepime or meropenem
Recurrent meningitis Vancomycin plus cefotaxime or ceftriaxone
Basilar skull fracture Vancomycin plus cefotaxime or ceftriaxone
Vancomycin plus ceftazidime, cefepime, or
Head trauma, neurosurgery, or CSF shunt
meropenem
CSF = cerebrospinal fluid.
*Add ampicillin if Listeria monocytogenes is a suspected pathogen.
 Prevention

• Vaccination

• Chemoprophylaxis

• Other public health measure

 Vaccination
• Vaccines
– Meningococcal vaccine
– Pneumococcal vaccine
– H influenzae type B (Hib) vaccine
• Indications for pneumococcal and H influenza type B vaccine
– >65 years
– Individuals with chronic cardiopulmonary illnesses
– Functional or structural asplenia-e.g. Splenectomy
• Indications for meningococcal vaccines
– Underlying immune deficiencies- complement deficiency, HIV
– Functional or structural asplenia
– Travel to hyperendemic areas and epidemic areas
– Laboratory workers routinely exposed to N meningitidis
– College students and military recruits who live in dormitories
– High risk group during epidemics- mass vaccination (1-29yrs)
 Chemoprophylaxis
• Aims is to eradicate nasopharyngeal colonisation and transmission
• Useful to protect close contacts of patients with meningococcal
meningitis
– Close contacts are defined as household members and anyone
directly exposed to oral secretions
– To be effective in preventing secondary cases, chemoprophylaxis
must be initiated as soon as possible (i.e. not later than 48 hours after
diagnosis)
– Only effective when systemic antibiotics are used. Topical
(pharyngeal) disinfection/antibiotics are not useful
• Drugs
– Rifampicin (600mg bid 2 days)
– Ciprofloxacin (500mg single dose)
– Ceftriaxone (250mg single dose)
• Patients treated with penicillin should also receive clearance-effective
antibiotics before discharge
Take Home Messages
 Prognosis
• Worse in children and elderly
• Pneumoccocal meningitis commonest cause
of morbidity and mortality
• Immunocompromised patients at risk of death
without early treatment
 Encephalitis
• Encephalitis is defined by the presence of an
inflammatory process of the brain in
association with clinical evidence of
neurologic dysfunction.
• Of the pathogens reported to cause
encephalitis, the majority are viruses.
 Some causes of encephalitis
• Viruses-
– Herpes simplex virus, Varicella-zoster virus, Cytomegalovirus,
Epstein-Barr virus, Human herpesvirus 6, Influenza virus, Measles
virus, HIV, Rabies, Poliomyelitis, mumps, etc
• Bacteria-
– Tropenema pallidium, Chlamydia spp, mycobacterium
tuberculosis, listeria monocytoogenes, mycoplasma pneumonia,
bartonella spp, Borrelia burgdorferi, Rickettsia rickettsii
• Parasites/Protozoa-
– P.falciparum, Toxoplasma gondi, Trypanoma brucei gambiense,
Naegleria fowleri
• Fungi-
– histoplasma capsilatum, Cryptococcus neoformans, Coccidioides
species
 Clinical Presentation
• Fever, headache, and altered level of consciousness.
• Mental status changes-
– Mental status changes early in the disease course are generally
more common in patients with encephalitis, this finding does
not reliably differentiate patients with encephalitis from those
with bacterial meningitis.
• Acute cognitive dysfunction, behavioral changes, focal
neurologic signs, and seizures.
• In most cases, there is some concomitant meningeal
inflammation, in addition to the encephalitic component
—a condition commonly referred to as
“meningoencephalitis.”
 Differential diagnosis
• Infectious encephalitis and postinfectious or
postimmunization encephalitis or encephalomyelitis;
– mediated by an immunologic response to an antecedent
antigenic stimulus provided by the infecting microorganism or
immunization or to other antigens revealed as part of the initial
infection or vaccination.
• Encephalopathy (e.g., secondary to metabolic
disturbances, hypoxia, ischemia, drugs, intoxications,
organ dysfunction, or systemic infections),-
– defined by a disruption of brain function in the absence of a
direct inflammatory process in the brain parenchyma.
• Noninfectious CNS diseases (e.g., vasculitis, collagen
vascular disorders, and paraneoplastic syndromes)
Approach to patient with encephalitis
• Attempt should be made to establish an etiologic
diagnosis.
• Although there are no definitive effective treatments in
many cases of encephalitis, identification of a specific
agent may be important for prognosis, potential
prophylaxis, counseling of patients and family
members, and public health interventions.
• Questions and comments
Brain Abscesses
 CNS ABSCESSES
• Focal pyogenic infections of the central nervous system
• Exert their effects mainly by:
– Direct involvement & destruction of the brain or spinal
cord
– Compression of parenchyma
– Elevation of intracranial pressure
– Interfering with blood &/or CSF flow
• Include: Brain abscess, subdural empyema,
intracranial epidural abscess, spinal epidural
abscess, spinal cord abscess
 BRAIN ABSCESS

• Accounts for ~ 1 in 10,000

hospital admissions in US
(1500-2500 cases/yr)
• Major improvements
realized in diagnosis &
management the last
century, & especially over
the past three decades,
with:
 PATHOPHYSIOLOGY
• Begins as localized cerebritis (1-2 wks)
• Evolves into a collection of pus surrounded by a
well-vascularized capsule (3-4 wks)

• Lesion evolution (based on experimental animal models):

– Days 1-3: “early cerebritis stage”
– Days 4-9: “late cerebritis stage”
– Days 10-14: “early capsule stage”
– > day14: “late capsule stage”
 PATHOGENESIS
• Direct spread from contiguous foci (40-50%)

• Hematogenous (25-35%)

• Penetrating trauma/surgery (10%)

• Cryptogenic (15-20%)
 DIRECT SPREAD
(from contiguous foci)
• Occurs by:
– Direct extension through infected bone
– Spread through emissary veins, diploic veins, local
lymphatics
• The contiguous foci include:
• Otitis media/mastoiditis
• Sinusitis
• Dental infection (<10%), typically with molar infections
• Meningitis rarely complicated by brain abscess (more
common in neonates with Citrobacter diversus meningitis, of whom 70%
develop brain abscess)
 HEMATOGENOUS SPREAD
(from remote foci)

• Sources:
– Empyema, lung abscess, bronchiectasis,
endocarditis, wound infections, pelvic
infections, intra-abdominal source, etc…
– may be facilitated by cyanotic HD, AVM.
• Results in brain abscess(es) at middle
cerebral artery distribution
• Often multiple
 PREDISPOSING CONDITION &
LOCATION OF BRAIN ABSCESS

Otitis/mastoiditis Temporal lobe,

Cerebellum
Frontal/ethmoid sinusitis Frontal lobe

Sphenoidal sinusitis Frontal lobe,

Sella turcica
Dental infection Frontal > temporal lobe.

Remote source Middle cerebral artery

distribution (often multiple)
 Microbiology of
Brain Abscess
• Dependent upon:
• Site of primary infection
• Patient’s underlying condition
• Geographic location
• Usually streptococci and anaerobes
• Staph aureus, common after trauma or
surgery
• 30-60 % are polymicrobial
Predisposing Conditions & Microbiology of
Brain Abscess
Predisposing Condition
Otitis media or mastoiditis
Sinusitis (frontoethmoid or sphenoid)
Dental sepsis
Penetrating trauma or postneurosurgical
Usual Microbial Isolates
Streptococci (anaerobic or aerobic),
Bacteroides and Prevotella spp.,
Enterobacteriaceae
Streptococci, Bacteroides spp.,
Enterobacteriaceae, Staph. aureus,
Haemophilus spp.
Fusobacterium, Prevotella and
Bacteroides spp., streptococci
S. aureus, streptococci,
Enterobacteriaceae, Clostridium spp.
PREDISPOSING CONDITION USUAL MICROBIAL ISOLATES

Lung abscess, empyema, bronchiectasis Fusobacterium, Actinomyces, Bacteroides

Prevotellaspp., streptococci, Nocardia
Bacterial endocarditis S. aureus, streptococci
Congenital heart disease Streptococci, Haemophilus spp.
Neutropenia Aerobic gram-negative bacilli, Aspergillus
Mucorales, Candidaspp.
Transplantation Aspergillus spp., Candida spp.,
Mucorales, Enterobacteriaceae, Nocardia
spp., Toxoplasma gondii
HIV infection Toxoplasma gondii, Nocardia spp.,
Mycobacterium spp., Listeria
monocytogenes, Cryptococcus
neoformans
 MICROBIOLOGY OF BRAIN ABSCESS
AGENT FREQUENCY (%)
Streptococci (S. intermedius, including S. anginosus) 60–70
Bacteroides and Prevotella spp. 20–40
Enterobacteriaceae 23–33
Staphylococcus aureus 10–15
Fungi 10–15
Streptococcus pneumoniae <1
Haemophilus influenzae <1
Protozoa, helminths † (vary geographically) <1

Yeasts, fungi (Aspergillus ,Candida, Cryptococci, Coccidiodoides, Cladosporium

trichoides, Pseudallescheria boydii)
Protozoa, helminths (Entamoeba histolytica, Schistosomes Paragonimus
Cysticerci)
 CLINICAL MANIFESTATIONS
• Non-specific symptoms
• Mainly due to the presence of a space-
occupying lesion
• Headache/Anorexia, Nausea/Vomiting, lethargy, focal
neurological signs , seizures
• Signs/symptoms influenced by
• Location
• Size
• Virulence of organism
• Presence of underlying condition
CLINICAL MANIFESTATIONS
OF BRAIN ABSCESS
Headache 70%
Fever 50
Altered mental status 50-60
Triad of above three <50
Focal neurologic findings 50
Nausea/vomiting 25-50
Seizures 25–35
Nuchal rigidity 25
Papilledema 25
 LOCATION & CLINICAL FEATURES
• FRONTAL LOBE: Headache, drowsiness,
inattention, hemiparesis, motor speech disorder,

• TEMPORAL LOBE: Ipsilateral Headache,

aphasia, visual field defect

• PARIETAL LOBE: Headache, visual field

defects, endocrine disturbances

• CEREBELLUM: Nystagmus, ataxia, vomiting,

dysmetria
 DIFFERENTIAL DIAGNOSIS
• Malignancy
– Abscess has hypo-dense center, with surrounding smooth, thin-
walled capsule, & areas of peripheral enhancement.
– Tumor has diffuse enhancement & irregular borders.
– SPECT (PET scan) may differentiate. CRP too?
• CVA
• Hemorrhage
• Aneurysm
• Subdural empyema/Epidural abscess
 DIAGNOSIS

• High index of suspicion

• Contrast CT or MRI
• Drainage/biopsy, if ring enhancing
lesion(s) are seen
 IMAGING STUDIES

• MRI
– more sensitive for early
cerebritis, satellite lesions,
necrosis, ring, edema,
especially posterior fossa &
brain stem
• CT scan
• 99m Tc brain scan
– very sensitive; useful
where CT or MRI not
available
• Skull x-ray : insensitive,
– if air seen, consider
possibility of brain abscess
 LABORATORY TESTS
BRAIN ABSCESS
•Aspirate: Gram/AFB/fungal stains & cultures, cytopathology (+/-PCR for TB)
•WBC Normal in 40% ( only moderate leukocytosis in ~ 50%
& only 10% have WBC >20,000)
•CRP almost invariably elevated
•ESR Usually moderately elevated
•Blood Culture Often negative BUT Should still be done

•Lumbar Puncture Contraindicated in patients with known/suspected

brain abscess
Risk of herniation 15-30%
If done, may have normal CSF findings, but:
Usually elevated CSF protein & cell count (lymphs)
Unremarkable glucose & CSF cultures rarely positive
 TREATMENT
• Combined medical & surgical
• Aspiration or excision
• empirical antibiotics
• Empirical antibiotics are selected based on:
• Likely pathogen (consider primary source, underlying
condition, & geography)
• Antibiotic characteristics: usual MICs, CNS
penetration, activity in abscess cavity
• Modify antibiotics based on stains
• Duration: usually 6-8 wks
• after surgical excision, a shorter course may suffice
Armstrong ID, Mosby inc 1999
 Before Rx

After completion of Rx
 POOR PROGNOSTIC MARKERS
•Delayed or missed diagnosis
•Inappropriate antibiotics.
•Multiple, deep, or multi-loculated abscesses
•Ventricular rupture (80%–100% mortality)
•Fungal , resistant pathogens.
•Neurological compromise at presentation
•Short duration ,
• Rapidly progressive neuroimpairment
•Immunosuppressed host
•Poor localization, especially in the posterior fossa (before CT)
 PARASITIC
BRAIN ABSCESS
• Toxoplasmosis
• Neurocysticercosis
• Ameobic
• Echinococcal
NOCARDIA BRAIN ABSCESS
• Usually in immunosuppresed (CMI)
• >50% no known predisposing factor
• All pts with pulmonary nocardiosis should
undergo brain imaging to r/o subclinical CNS
nocardiosis
• Rx: Sulfa (T/S in-vitro synergy), imipenem,
ceftriaxone, amikacin, minocin
– Duration of about <a year.
– Needle aspiration or surgical excision needed in most.
• Relapse common
 BRAIN ABSCESS IN AIDS
• Toxoplasmosis is the most common
• Seropositive
• d/dx lymphoma
• Often empiric Rx given & biopsy only non-
responders
• Other causes Listeria, Nocardia, TB,
fungi…
 BRAIN TB
• Rare cause of brain abscess
• Usually in immunocompromised
• Tuberculoma is a granuloma (not a true
abscess )
• Biopsy/drainage (send for PCR too )
 FUNGAL BRAIN ABSCESS
(Aspergillus, Mucor ...)

• IMMUNOCOMPROMISED
• Poor inflammatory response, less
enhancement on CT.
• May present w much more advanced
disease (seizure, stroke more common)
• High mortality
• Rx: aggressive surgery + antifungal
BRAIN ABSCESS SEQUELAE
• Seizure in 30-60%
• Neuro deficits 30-50%
• Mortality 4-20%
• Questions and
comments