CNS Infection: Initial Management

YOU DON’T DIAGNOSE WHAT YOU DON’T THINK OF

The classic triad of

> Fever

> Headache

> Meningism

with bonus points for

• Photophobia
• Nausea / Vomiting
• Altered mental state

Clinical features alone cannot confirm the diagnosis of meningitis.

A lumber puncture (LP) is essential to confirm the diagnosis of meningitis and establish the cause.

In one study, 95% of bacterial meningitis patients had at least two symptoms of headache, neck stiffness, fever and altered consciousness. The latter three features were present together in only 44% of cases. Neurological deficits are found in around one-third of patients REF

A rash in suspected meningitis makes N meningitidis more likely. However, 37% of meningococcal meningitis patients have no rash REF. Varicella and enterovirus can also be associated with a rash.

Risk factors for Listeria meningitis include overt or relative immune compromise, the latter including chronic illness, diabetes, alcohol dependency, malignancy or old age. Listeria meningitis is rarely seen in immunocompetent adults under 50 years of age.

Travel history, symptoms of otitis media / sinusitis, contact with another person with meningitis, sepsis or tuberculosis are other useful diagnostic clues.

Clinical Exam

> Can range from normal level of consciousness to coma

> Meningism

• Head jolt accentuation test (lateral head rotation worsens headache, most sensitive)
• Other signs less useful (e.g. Brudzinski sign)

> Papilloedema (indicates raised ICP) – Often hard to meaningfully appreciate in photophobic pts with altered mental state

> Tense fontanelle in babies

> Rash

> Non-blanching, purpuric

CREDIT

> Neisseria meningitidis is droplet spread.

> Droplet precautions must be used until this is excluded (i.e. long after the LP is done)

> This means standard precautions PLUS a surgical mask
More on DROPLET PRECAUTIONS

If you really think it could be meningitis, TAKE BLOOD CULTURES, then start treatment:

> Dexamethasone 10 mg IV adults (0.15 mg/kg Q6 hourly)

> Ceftriaxone 2 g IV (moxifloxacin 400 mg IV if severe ADR to penicillins)

Add:

> Aciclovir 10 mg/kg IV if encephalitis suspected

Encephalitis: Fever with any acute change in mental status, from a subtle change to coma

> Benzylpenicillin 2.4 g q4h if

> 50 years old

Pregnant

Immunocompromised

Alcoholic

> Vancomycin 25 mg/kg load then 15 mg/kg BD if:

You can’t do an LP

Recent hospitalisation

Known to be colonised with MRSA

Permanent central lines

Indigenous Australian

Recently had a beta lactam antibiotic

> Malaria Treatment

If a possibility

Artesunate 2.4 mg/kg

WHY?

Ideally we would get an LP before giving antibiotics to increase the chance of identifying the organism

But giving antibiotics as fast as possible (ideally within 30 min of presentation) increases the chances of a good neurological outcome.

In the real world, getting an LP done (usually requiring a CT first) AND actually administering the medications is impossible in < 30 minutes

Therefore give the treatment first, then get the CT & LP as soon as you can.

WHY THE ADD ONS?

Listeria is intrinsically resistant to cephalosporins, hence needing benzylpenicillin

Some Streptococcus pneumoniae is resistant to penicillins and cephalosporins, hence vancomycin

If MRSA possible, vancomycin also covers this.

Steroids reduce neurological complications after bacterial meningitis in high-income countries – Cochrane Review 2015

Cerebral malaria is devastating if missed. Obviously regional variation in frequency. Think about it in endemic areas and in returned travellers.

WHEN WOULDN’T YOU DO THIS?

If meningitis / encephalitis is less likely

For example:

A elderly patient on the ward post abdominal surgery with fever and altered mental state

> More likely to have another diagnosis; needs full fever & delirium workup, not stat treatment for meningitis

A trauma patient with a stiff neck and focal neurological signs in one arm

> More likely to have a neck injury and radiculopathy from trauma

A middle-aged patient with sudden onset severe headache, neck stiffness

> aSAH high possibility, although meningoencephalitis not excluded; worth doing CT +/- LP ASAP prior to meningitis treatment

Before an LP you usually need a non-con CTB
This is for 2 reasons:

1. To aid diagnosis
2. To prevent tonsillar herniation through the foramen magnum and “coning”

WHAT IS CONING?

Tonsillar herniation is characterized by the descent of the cerebellar tonsils through the foramen magnum, which compresses the medulla against the clivus/odontoid process.
It is described as “coning” as the brain tissue is squeezed down through the foramen like being squeezed into a cone. Clinically, progressive compression of the medulla causes Cushing’s reflex, eventually resulting in death.
CREDIT

WHEN DON’T YOU NEED A CTB?

If your patient has NONE of the following:

• Abnormal level of consciousness
• Age > 60 years
• Immunocompromise
• History of central nervous system disease
• History of seizure within one week before presentation
• Inability to answer two consecutive questions correctly or to follow two consecutive commands
• Gaze palsy
• Abnormal visual fields
• Facial palsy
• Arm drift or leg drift
• Abnormal language (e.g. aphasia)

WHAT FINDINGS ON CT MEAN DON’T LP?

• Mass lesion on CT scan
• Possible hydrocephalus on CT scan

LP’s are essential
Opening pressure is actually helpful in this scenario and should be measured. In a supine position, the opening pressure will equal the patient’s intracranial pressure (ICP). This can be converted from cm CSF to mm mercury using the following formula:
ICP in mmHg = 0.7 x opening pressure (in cm of CSF)
Some patients may require ultrasound-guided lumbar puncture (good videos of this are here and here).
Tests
For all
Basics: protein, cell count with differential, glucose, gram stain & culture.
PLUS

• Streptococcus pneumoniae antigen
• Herpes simplex virus (HSV) PCR
• Enterovirus PCR
• Varicella-zoster virus PCR

If immunocompromised and above is negative but CNS infection still likely, consider:

• Cryptococcal antigen
• Syphilis testing – Syphilis Total Antibody with Reflex, Serum and VDSF / VDRL
• Fungal and mycobacterial testing – TB, nocardia, histoplasma, blastomyces, coccidioides,
• D/W lab about amoeba if recent freshwater swimming
• Consider Lyme CSF IgG
• Toxoplasma gondii PCR
• JC virus PCR

Autoimmune encephalitis panel if suspicion for paraneoplastic or anti-NMDA receptor encephalitis.
If possible, hold additional fluid (> 5 ml) for further tests!

The usual indications like too unconscious to protect airway and hypoxic respiratory failure are rare
Also consider intubation if:
> Altered mental state and won’t stay still for CT or LP
> Hypoxic or hypercapnoeic which may cause 2ry brain injury combined with EICP

If intubating:

Do a neuroprotective intubation
Think about defending the cerebral perfusion pressure as a priority, i.e. keeping MAP > 80 mmHg if ICP unknown.

In more severe meningitis or encephalitis, ICP may be raised.
If you can get an opening pressure from the LP, the ICP can be calculated:
ICP in mmHg = 0.7 x opening pressure (in cm of CSF)
You can then target a CPP of 60-70 as with other brain injuries (e.g. TBI)
CPP = MAP – ICP
Prior to knowing the ICP, a MAP of > 80 mmHg is reasonable, although there is not evidence to support this approach.
In extreme cases, where there is clinical and radiological evidence of EICP, ICP monitors may be employed to more closely monitor the ICP allow titration of therapy.

BRAIN ABSCESS

There is no single best method for treating a brain abscess.

Treatment usually involves:

• Surgical treatment: needle drainage or excision
• Management of the primary source
• Long-term use of antibiotics: often IV x 6–8 weeks and possibly followed by oral route x 4–8 weeks.

Antibiotics alone are more likely to work if:

Medical therapy alone is more successful if:

• Treatment is begun in cerebritis stage (before complete encapsulation)
• Lesions are small (<3 cm)
• Duration of symptoms ≤ 2 wks
• Patients show definite clinical improvement within the first week of antibiotics

Location of the abscess clearly affects how keen neurosurgeons will be to operate too.
So identify with CT then MRI, start empirical antibiotics and discuss with Neurosurgery.

Anticonvulsants usually used prophylactically, mandatory if seizures occur.

SUBDURAL EMPYEMA

More here
Treatment:

• Surgical drainage
• Antibiotics
• Anticonvulsants usually empirically, mandatory of seizures occur

Empirical Antibiotics

• Ceftriaxone 2 g IV q12h AND
• Metronidazole 500 mg IV q8h AND
• Vancomycin if MRSA possible
• Ceftazidime if pseudomonas aeruginosa suspected

If post neurosurgery / trauma:

• Ceftazidime 2 g q8h or Cefepime 2g q8h AND
• Vancomycin

Spinal epidural abscess (SEA) is not covered by the above.

See fundamentals for more.

If a presentation includes fever, malaise and back pain, always think of SEA, especially if:

> Immunocompromised (e.g. by alcoholism, diabetes, IVDU, AIDS, chronic renal failure, malignancy)

> Old

> Following epidural anesthesia, spinal surgery, or trauma

Investigations often only show leukocytosis

An MRI with contrast is needed to diagnose

Treatment involves:

1. Urgent surgical decompression
2. Empirical Rx: Ceftriaxone 2 g q12h and vancomycin
3. Flucloxacillin 2 g q4-6h if proven MSSA
4. If post surgery use cefepime 2 g q8h or ceftazidime and vancomycin