CNS infection

CNS INFECTIONS

depend on the location of the infection (the meninges or the parenchyma of the brain and spinal cord), the causative organism (virus, bacterium, fungus or parasite), and whether the infection is acute or chronic

Meningitis

Acute infection of the meninges presents with a characteristic combination of pyrexia, headache and meningism.
Meningism consists of headache, photophobia and
stiffness of the neck, often accompanied by other signs
of meningeal irritation, including Kernig’s sign (extension
at the knee with the hip joint flexed causes spasm
in the hamstring muscles) and Brudzinski’s sign (passive
flexion of the neck causes flexion of the hips and knees

Bacterial meningitis

Many bacteria can cause meningitis but geographical patterns vary, as does age-related sensitivity

Bacterial causes of meningitis

Less common
Common
Age of onset
Listeria monocytogenes
Gram-negative bacilli
(Escherichia coli,
Proteus)
Group B streptococci
Neonate
Mycobacterium
tuberculosis
Haemophilus
influenzae
Neisseria meningitidis
Streptococcus
pneumoniae
Pre-school
child
Listeria monocytogenes
Mycobacterium
tuberculosis
Staphylococcus aureus
(skull fracture)
Haemophilus
influenzae
Neisseria meningitidis
Streptococcus
pneumoniae
Older child
and adult


Clinical features
Headache, drowsiness, fever and neck stiffness are the
usual presenting features. In severe bacterial meningitis
the patient may be comatose and later there may be focal
neurological signs.
When accompanied by septicaemia, it may present very
rapidly, with abrupt onset of obtundation due to cerebral
oedema.

Complications of meningococcalsepticaemia

Meningitis
• Rash (morbilliform, petechial or purpuric)
• Shock
• Intravascular coagulation
• Renal failure
• Peripheral gangrene
• Arthritis (septic or reactive)
• Pericarditis (septic or reactive

In pneumococcal and Haemophilus infections there may be an associated otitis media.

Pneumococcal meningitis may be associated with pneumonia and occurs especially in older patients and alcoholics as well as those without functioning spleens
Listeria monocytogenes is an increasing cause of meningitis and brainstem encephalitis in
the immunosuppressed, people with diabetes, alcoholics and pregnant women


Investigations
Lumbar puncture is mandatory unless there are contraindications
If the patient is drowsy and has focal neurological signs or seizures, is immunosuppressed,
has undergone recent neurosurgery or has suffered
a head injury, it is wise to obtain a CT to exclude
a mass lesion (such as a cerebral abscess) before lumbar puncture because of the risk of coning.

This should not, however, delay treatment of a presumptive meningitis.

If lumbar puncture is deferred or omitted, it is essential to take blood cultures and to start empirical treatment

CSF Findings in Meningitis

Glucose
Protein
Predominant Cell Type
Condition
> 50 % of blood glucose
< 40 mg/dL
All lymphocytes
(0–5 cells/μL)
Normal CSF
< 50% of blood glucose (may be extremely low
Elevated
Leukocytes (usually PMNs), often greatly increased
Bacterial meningitis
Usually normal
Elevated
Lymphocytes (may be mixed; PMNs and lymphocytes during the first 24–48 h)
Viral meningitis
< 50% of blood glucose (may be extremely low
Elevated
PMNs and lymphocytes (usually mixed pleocytosis)
Tuberculous meningitis
< 50% of blood glucose (may be extremely low
Elevated
Usually lymphocytes
Fungal meningitis


Management
There is an untreated mortality rate of around 80%, so action must be swift.
If bacterial meningitis is suspected, the patient should be given parenteral benzylpenicillin
immediately (intravenous is preferable) and prompt hospital admission should be arranged. The only contraindication is a history of penicillin anaphylaxis.

Treatment of pyogenic meningitis ofunknown cause

1. Adults aged 18–50 yrs with or without a typical
meningococcal rash
• Cefotaxime 2 g IV 4 times daily or
• Ceftriaxone 2 g IV twice daily
2. Patients in whom penicillin-resistant pneumococcal
infection is suspected, or in areas with a significant
incidence of penicillin resistance in the community
As for (1) but add:
• Vancomycin 1 g IV twice daily or
• Rifampicin 600 mg IV twice daily

3. Adults aged > 50 yrs and those in whom Listeria

monocytogenes infection is suspected (brainstem signs,
immunosuppression, diabetic, alcoholic)
As for (1) but add:
• Ampicillin 2 g IV 6 times daily or
• Co-trimoxazole 50 mg/kg IV daily in two divided doses
4. Patients with a clear history of anaphylaxis to β-lactams
• Chloramphenicol 25 mg/kg IV 4 times daily plus
• Vancomycin 1 g IV twice daily


5. Adjunctive treatment
Dexamethasone 0.15 mg/kg 4 times daily for 2–4 days
Corticosteroids significantly reduce hearing loss and neurological sequelae, but do not reduce overall mortality

Chemotherapy of bacterial meningitiswhen the cause is known

Alternative
agents
Regimen of choice
Pathogen
Cefuroxime,
ampicillin
Chloramphenicol
Benzylpenicillin
2.4 g IV 6 times
daily for 5–7 days
N. meningitidis
Chloramphenicol
Cefotaxime 2 g IV
4 times daily or
ceftriaxone 2 g IV
twice daily for
10–14 days
Strep. pneumoniae
(sensitive to
β-lactams, MIC
< 1 mg/L)
Vancomycin plus
rifampicin*
Moxifloxacin
Gatifloxacin
As for sensitive
strains but add
vancomycin 1 g IV
twice daily or
rifampicin 600 mg
IV twice daily
Strep. pneumoniae
(resistant to
β-lactams)


Chemotherapy of bacterial meningitiswhen the cause is known
Alternative
agents
Regimen of choice
Pathogen
Chloramphenicol
Cefotaxime 2 g IV
4 times daily or
ceftriaxone 2 g IV
twice daily for
10–14 days
H. influenzae
Ampicillin 2 g IV
4-hourly plus
co-trimoxazole
50 mg/kg daily in
two divided doses
Ampicillin 2 g IV
6 times daily plus
gentamicin 5 mg/
kg IV daily
L. monocytogenes
Chloramphenicol
Cefotaxime 2 g IV
4 times daily or
ceftriaxone 2 g IV
twice daily for
10–14 days
Strep. suis


Adverse prognostic features include
hypotensive shock,
a rapidly developing rash,
a haemorrhagic diathesis,
multisystem failure
and age over 60 years.

Prevention of meningococcal infection

Close contacts of patients with meningococcal infection
should be given 2 days of oral rifampicin.
In adults, a single dose of ciprofloxacin is an alternative.
If not treated with ceftriaxone, the index case should
be given similar treatment to clear infection from the
nasopharynx before hospital discharge. Vaccines are
available for most meningococcal subgroups but not
group B, which is among the most common serogroup
isolated in many countries.

Tuberculous meningitis

Tuberculous meningitis most commonly occurs shortly after a primary infection in childhood or as part of miliary tuberculosis


Clinical features oftuberculous meningitis
Symptoms
• Headache
• Vomiting
• Low-grade fever
• Lassitude
• Depression
• Confusion
• Behaviour changes
Signs
• Meningism (may be absent)
• Oculomotor palsies
• Papilloedema
• Depression of conscious
level
• Focal hemisphere signs

Onset is much slower than in other bacterial meningitis over 2–8 weeks.

If untreated, it is fatal in a few weeks but complete recovery is usual if treatment is
started early.
When treatment is initiated later, the rate of death or serious neurological deficit may be as high as 30%.


The tubercle bacillus may be detected in a smear of the centrifuged deposit from the CSF but a negative result does not exclude the diagnosis.
The CSF should be cultured but, as this result will
not be known for up to 6 weeks, treatment must be
started without waiting for confirmation.
Brain imaging may show hydrocephalus, brisk meningeal enhancement on enhanced CT or MRI, and/or an intracranial tuberculoma.

Management

As soon as the diagnosis is made or strongly suspected,
chemotherapy should be started using one of the regimens that include pyrazinamide.
The use of corticosteroids in addition to anti-tuberculous
therapy has been controversial. Recent evidence suggests
that it improves mortality, especially if given early,
but not focal neurological damage.
Surgical ventricular drainage may be needed if obstructive hydrocephalus develops.

Viral meningitis

Viruses are the most common cause of meningitis, usually resulting in a benign and self-limiting illness requiring no specific therapy.
A number of viruses can cause meningitis, the most common being enteroviruses.

Clinical features

Viral meningitis occurs mainly in children or young adults, with acute onset of headache and irritability and the rapid development of meningism. The headache is usually the most severe feature. There may be a high pyrexia but focal neurological signs are rare.


The diagnosis is made by lumbar puncture.
Management
There is no specific treatment and the condition is usually benign and self-limiting.
The patient should be treated symptomatically in a quiet environment. Recovery usually occurs within days

Viral encephalitis

Clinical features
Viral encephalitis presents with acute onset of headache, fever, focal neurological signs (aphasia and/or hemiplegia, visual field defects) and seizures. Disturbance of consciousness ranging from drowsiness to deep coma supervenes early and may advance dramatically.
Meningism occurs in many patients.

Investigations

Imaging by CT scan may show low-density lesions in the temporal lobes but MRI is more sensitive in detecting early abnormalities.
Lumbar puncture should be performed once imaging has excluded a mass lesion. The CSF usually contains excess lymphocytes but polymorphonuclear
cells may predominate in the early stages. The CSF may be normal in up to 10% of cases.
Some viruses, including the West Nile virus, may cause a sustained neutrophilic CSF. The protein content may be elevated but the glucose is normal.
The EEG is usually abnormal in the early stages, especially in herpes simplex
encephalitis, with characteristic periodic slow-wave activity in the temporal lobes.
Virological investigations of the CSF, including PCR for viral DNA, may reveal the causative organism but treatment initiation should not
await this.


Management
Optimum treatment for herpes simplex encephalitis (aciclovir 10 mg/kg IV 3 times daily for 2–3 weeks) has
reduced mortality from 70% to around 10%. This should
be given early to all patients suspected of suffering from
viral encephalitis.
Some survivors will have residual epilepsy or cognitive
impairment.
Anticonvulsant treatment may be needed and raised intracranial pressure may indicate the need for dexamethasone.

Cerebral abscess

Bacteria may enter the cerebral substance through penetrating injury, by direct spread from paranasal sinuses or the middle ear, or secondary to septicaemia. The site of abscess formation and the likely causative organism are both related to the source of infection.
Initial infection leads to local suppuration followed by
loculation of pus within a surrounding wall of gliosis,
which in a chronic abscess may form a tough capsule.
Haematogenous spread may lead to multiple abscesses.

Clinical features

A cerebral abscess may present acutely with fever, headache, meningism and drowsiness, but more commonly presents over days or weeks as a cerebral mass lesion with little or no evidence of infection.
Seizures, raised intracranial pressure and focal hemisphere signs occur alone or in combination. Distinction from a cerebral tumour may be impossible on clinical grounds.

Investigations

Lumbar puncture is potentially hazardous in the presence of raised intracranial pressure and CT should always precede it.
CT reveals single or multiple lowdensity areas, which show ring enhancement with contrast and surrounding cerebral oedema.
There may be an elevated white blood cell count and ESR in patients with active local infection.


Management and prognosis
Antimicrobial therapy is indicated once the diagnosis is
made. The likely source of infection should guide the
choice of antibiotic.
Surgical drainage by burr-hole aspiration or excision
may be necessary, especially where the presence of
a capsule may lead to a persistent focus of infection.
Epilepsy frequently develops and is often resistant to
treatment.
Despite advances in therapy, the mortality rate
remains at 10–20% and this may partly relate to delay in
diagnosis and initiation of treatment.

Transmissible spongiformencephalopathies

include a number of veterinary and medical conditions that are characterised by the histopathological triad of cortical spongiform change, neuronal cell loss and gliosis. Associated with these changes, there is deposition
of amyloid made up of an altered form of a normally occurring protein, the prion protein.

Creutzfeldt–Jakob disease

Variant Creutzfeldt–Jakob disease
Gerstmann–Sträussler–Scheinker disease, fatal familial insomnia and kuru