INFECTIONS OF THE CENTRAL NERVOUS SYSTEM

Meningitis Encephalitis Brain abscess

MENINGITIS

A medical emergency!

Clinical features that suggest the diagnosis of acute meningitis

Headache Irritable Neck stiffness Photophobia Fever Vomiting Varying levels of consciousness Rash

Groups in which clinical features are not so specific

Neonates (first few weeks of life) Elderly Immunosuppressed

BACTERIAL

Incidence:

Primary meningitis: spread via the bloodstream

Secondary meningitis:Ears, sinuses, trauma,

Surgery

Main pathogens:Neisseria meningitidis

Strept. Pneumoniae

Haemophilus influenzae

N meningitidis (meningococcus) and meningococcal meningitis

The most common cause of acute bacterial meningitis

Most cases in children and young adults Gram negative diplococcus 3 main serological types A, B. C Person to person transmission Reservoir nasopharynx (2-25% carriage) Respiratory droplet spread Incubation period 1-3 days

Higher carriage rates in:

Children Overcrowding Schools, universities, other

institutions military

Most cases are sporadic Close family contacts of cases at risk Outbreaks may occur in eg, schools Group B serotype traditionally most

frequent cause Group C serotype has become

increasingly common Epidemics occur in eg, Africa, South

America

Nasopharyngeal carriage

Bloodstream infection

Meningitis

CLINICAL FEATURES

May be sore throat Progression from headache, drowsiness, signs

of meningitis Haemorrhagic skin rash (non-blanching) Sepsis complicated by intravascular coagulation,

shock, acute renal failure Bleeding into organs may occur eg, adrenal

gland causing Waterhouse Friderichsen syndrome

Gangrene of peripheral limbs

TREATMENT OF ACUTE BACTERIAL MENINGITIS KEYPOINTS:

Once the diagnosis is clinically suspected don’t delay treatment

If the causative agent is not clear eg, no rash, give ceftriaxone or cefotaxime

This provides cover of the 3 main causes until a microbiological diagnosis is made

If meningococcal meningitis confirmed then a change to high doses of benzylpenicillin can be considered

Chloramphenicol can be an alternative if allergy to beta lactams

MICROBIOLOGICAL DIAGNOSIS

If possible collect Cerebrospinal fluid (may not be, if raised intracranial pressure)

Blood culture, both before antibiotic therapy

Sample from petechial skin lesion may yield meningococcus

CSF subjected to cell count, gram stain of deposit, and culture on chocolate agar in CO2 atmosphere

CSF Abnormalities in Meningitis

Condition Appearance Cells/cu mm Gram Protein Glucose

Normal Clear, colourless

0-5 lymphocytes

Bacterial Cloudy, turbid

100-2000 polymorphs

Orgs High Low

‘Aseptic’ (viral)

Clear, slightly cloudy

10-500 lymphocytes

Normal Normal

TB Clear, slightly cloudy

10-500 lymphocytes

High Low

Cryptococcal Clear 10-200 lymphocytes

Normal, slightly elevated

Normal, slightly reduced

Additional lab investigations

Latex agglutination test on CSF to detect meningo polysaccharide antigen

PCR to amplify bacterial DNA in blood (EDTA sample) or CSF which may be positive even after start of antibiotics

Save serum sample for antibody tests with a subsequent “convalescent” sample

Set up antibiotic sensitivities to penicillin, cephalosporins, ampicillin, chloramphenicol and others

Some features of meningococcal isolate

Gram: gram negative cocci some within neutrophils (intracellular)

Grows within 24-48 hours best on chocolate agar in CO2

Will agglutinate with group specific antisera eg, B, C

Caution needed in lab as making suspensions can be a hazard to the lab worker (may acquire pathogen)

MENINGOCOCCAL MENINGITIS

Notifiable to public health authorities Close contacts in home, school/university,

nursery should be given antibiotic prophylaxis Rifampicin X 2 days (ciprofloxacin is used but

not licensed) Hospital contacts only need prophylaxis if

contact with secretions, eg, mouth to mouth resuscitation

Vaccine against group C now widely in use and for overseas travellers group A vaccine may be indicated

Pneumococcal meningitis

Strep pneumoniae is the cause, a capsulate gram positive coccus

Highest incidence in those at extremes of age, infants <3yrs and elderly

Alcoholism, debilitation, malnutrition, hyposplenism

May spread from middle ear or sinus infection

Or following trauma causing basal skull #

Pneumococcal meningitis: clinical features

Acute onset with rapid development of loss of consciousness

Skin rash not a feature May be a history of ear infection,

splenectomy Bacteraemia a feature Higher mortality than other causes High incidence of complications in

survivors

Microbiological investigations

CSF and blood cultures should be taken Gram stain of CSF deposit shows gram

positive cocci in short chains Culture on blood and choc agar in CO2

gives alpha haemolytic (green) colonies with “draughtsmen”

Direct sensitivities for penicillin, cefotaxime, ceftriaxone, ampicillin

Treatment

High doses of penicillin eg, 1.2g (2mill units) 2 hourly

Note some strains have reduced susceptibility to penicillin, and some are resistant!

Need to review to find a potential underlying risk factor

Polyvalent vaccine for risk groups eg, before splenectomy

Haemophilus influenzae meningitis

Gram negative coccobacillus, capsulated strains (type b used predominate)

Peak incidence 2 years old, range 3 months to 5 years

Incidence has declined greatly since the successful introduction of Hib vaccine

More insidious onset, no rash, lower mortality Diagnostic approach as for other causes Treament with cefotaxime or ceftriaxone

Other bacterial causes of meningitis in adults and children

Post trauma or surgeryStaph aureus, streps, anaerobes, coliforms, Pseudomonas

ImmunocompromisedListeria monocytogenes

OthersM tuberculosis, Leptospira, Borrelia burgdorferi

Tuberculous meningitis Higher incidence in immigrant populations who come

from countries with a higher incidence of TB Insidious onset High frequency of complications, cranial nerve palsies Delayed diagnosis makes complications more likely CSF shows predominantly lymphocytic response but

polymorphs also present High protein, low/absent sugar Treat: probably with 3 agents eg, isoniazid, rifampicin,

pyrazinamide Note occasional reports of MDR TB

CSF Abnormalities in Meningitis

Condition Appearance Cells/cu mm Gram Protein Glucose

Normal Clear, colourless

0-5 lymphocytes

Bacterial Cloudy, turbid

100-2000 polymorphs

Orgs High Low

‘Aseptic’ (viral)

Clear, slightly cloudy

10-500 lymphocytes

Normal Normal

TB Clear, slightly cloudy

10-500 lymphocytes

High Low

Cryptococcal Clear 10-200 lymphocytes

Normal, slightly elevated

Normal, slightly reduced

NEONATAL MENINGITIS Group B streptococcus (S agalactiae) and Esch coli are

the principal causes Travel via the bloodstream but direct infection may occur Premature rupture of membranes, pre-term delivery

(“VLBW”) are risk factors May complicate maternal infection High morbidity and mortality Clinical features can be non-specific Early onset Group B infection more common than late

onset disease Other causes: Listeria, Staph, Salmonella, other GNB Treat: Cephalosporin, or penicillin + aminoglycoside

BACTERIAL VIRAL

FUNGAL,OTHER

VIRAL MENINGITIS

Primarily affects children and young adults Milder signs and symptoms May start as respiratory or intestinal

infection then viraemia CSF shows raised lymphocyte count (50-

200/cu mm); protein and sugar usually normal

Full recovery expected

Causes of viral meningitis

Enteroviruses: Echo, coxsackie A ,B, polio Paramyxovirus: mumps Herpes simplex, VZV Adenoviruses Other: arboviruses, lymphocytic

choriomeningitis, HIV

Diagnosis: viral meningitis

Examination of CSF Storage at -700C of CSF for subsequent

virus isolation Additionally throat swab, stool, paired sera

CSF Abnormalities in Meningitis

Condition Appearance Cells/cu mm Gram Protein Glucose

Normal Clear, colourless

0-5 lymphocytes

Bacterial Cloudy, turbid

100-2000 polymorphs

Orgs High Low

‘Aseptic’ (viral)

Clear, slightly cloudy

10-500 lymphocytes

Normal Normal

TB Clear, slightly cloudy

10-500 lymphocytes

High Low

Cryptococcal Clear 10-200 lymphocytes

Normal, slightly elevated

Normal, slightly reduced

Fungal meningitis

Cryptococcus neoformans is main cause HIV and immunosuppressed pts at risk Insidious onset of headache, fever, neck

stiffness Diagnosis made on CSF examination Shows raised lymphocyte count, protein,

low sugar, capsulate yeasts, antigen Treat with amphotericin B +flucytosine

CSF Abnormalities in Meningitis

Condition Appearance Cells/cu mm Gram Protein Glucose

Normal Clear, colourless

0-5 lymphocytes

Bacterial Cloudy, turbid

100-2000 polymorphs

Orgs High Low

‘Aseptic’ (viral)

Clear, slightly cloudy

10-500 lymphocytes

Normal Normal

TB Clear, slightly cloudy

10-500 lymphocytes

High Low

Cryptococcal Clear 10-200 lymphocytes

Normal, slightly elevated

Normal, slightly reduced

ENCEPHALITIS

Affects children and adults mostly A variety of symptoms and signs Drowsiness, confusion, coma, fits, nerve

palsies, paresis May have sequelae eg, memory loss,

motor impairment, death EEG, brain scan, CSF exam, brain biopsy

may establish diagnosis

Causes of encephalitis

• Sporadic: Herpes simplex, mumps, VZV, EBV rabies

• Epidemic: Togaviruses: equine, louping ill, Japanese B,

enteroviruses

• Post-infectious: Measles, rubella, post-vaccination

• Degenerative: Measles (SSPE), vCJD, JC virus (PML)

Herpes simplex encephalitis

Most common cause of sporadic encephalitis in previously healthy

May be evidence of herpes infecion of skin, mucosae

Causes severe haemorrhagic encephalitis affecting temporal lobe,

Focal signs and epilepsy features High mortality so treatment urgently

needed with aciclovir

Other causes

VZV Mumps Rabies Mycoplasma pneumoniae Rickettsiae Toxoplasma

Subacute sclerosing panencephalitis (SSPE)

A rare complication of measles infection Usually affects children Intellectual impairment, involuntary

movements High titres of measles antibody Brain biopsy shows measles virus Fatal outcome

Prion diseases

Degenerative disorders Long incubation periods Slow progressive spongiform

encephalopathy Fatal outcome

• Kuru: occurred in New Guinea, diue to cannibalism, eating human brain

• Sporadic Creutzfeldt-Jacob disease (CJD): rare degenerative disease in over 50’s

• Recipients of growth hormone at increased risk, use of surgical instruments contamined with prion protein

• Prions are (Prp) proteins in abnormal configuration resistant to destruction

• Mutations of genes encoding these proteins can be inherited

New variant CJD

In 1980’s emergence of bovine spongiform encephalopathy (BSE)

Could be experimentally transmitted from brains of sheep with scrapie

Similarities between BSE and nvCJD Occurs in young people rapidly fatal Possibly acquired from eating infected beef/ beef

products Diagnosis on brain biopsy (? Tonsillar tissue) No treatment

Brain abscess

Can arise from direct inoculation of infection following trauma, surgery; from spread of infection of ear or sinuses; or haematogenous spread from eg, lungs, heart (endocarditis)

May be non-specific signs, neurological symptoms

Needs urgent investigation by CT/MRI scan Surgical treatment +antibiotics

Causes of brain abscess

Ear: mixed anaerobes, coliforms Sinus: pneumococci, streptococci Trauma/surgery: Staph aureus Chest: strep, staph, pneumococci

Diagnosis and treatment

Examination of pus aspirated from abscess

CSF Blood cultures Surgical drainage a priority Antibiotics chosen with good penetration

of CNS

Guillain-Barre syndrome

Infectious polyneuritis Paraesthesiae, progressive weakness of

limbs, respiratory failure High CSF protein Post infectious Various infections implicated including

Campylobacter, EBV, Mycoplasma Recovery likely to occur with supportive

care

Congenital CNS infections

Intrauterine infections: toxoplasma, rubella, cytomegalovirus, syphilis

During birth: herpes simplex, hepatitis B HIV