CNS infections

Ahmad Rizal, dr., SpS (K), Ph.D

Bagian Saraf FKUP / RSHS
Bandung
 Terminology
• Primarily affects its coverings  meningitis
• Affects the brain parenchyma  encephalitis
• Affects the spinal cord  myelitis
• A patient may have more than one affected area,
and if all are affected, the patient has
"meningoencephalomyelitis“

• Localized pockets of infection:

– Within the brain or spinal cord  abscess
– Outside them there  epidural abscess or subdural
empyema
 Clinical syndromes
• Acute presentations: <2 days duration
– bacterial process (pyogenic)
– aggressive viral encephalitis
• Subacute presentations : broader spectrum of
diagnostic possibilities
– Tuberculous
– Fungal
– Parasitic
– Viral
– Non infectious: encephalopathy, ADEM, other
 Change in scenario
• Increase in immuno-compromised patients
– AIDS
– prolonged survival of cancer patients
– organ transplantation
• Increase in international travel
– rapid transmission to susceptible populations
– new diseases
• Widespread antibiotic use
– resistant organisms
 Signs and symptoms

• Headache
• Fever
• Neck stiffness (and other meningeal signs)
• Obtundation
 Diagnosis
• Suspicious clinical symptoms and signs
• CT of head to rule out abscess or other
space-occupying lesion, if it can be done
quickly
• Lumbar puncture
• Blood cultures
 Acute bacterial meningitis
• The big three: N.meningitides, S.pneumoniae,
H.influenzae
– Other: Listeria, pseudomonas, E.coli….

• Headache, fever, neck stiffness, obtundation

• focal signs, seizures, rash, shock..
• often fulminant

• CSF: high wbc (500- 20000 polymorphs), high protein,

low glucose
– But: partial treatment
• CT/MRI: may be normal
Meningococcal septicaemia
 Meningococcaemia

Meningococcal septicaemia
Picture: With the friendly permission of Dr. Noack (photographer) and Prof.Dittman,
in whose book the picture appears (German title:"Meningokokkenerkrankungen”)
 Bacterial meningitis: diagnosis
High index of suspicion
Prompt CSF examination
urgent smear for Gram stain
urgent latex agglutination testing for
bacterial antigens (meningococcus,
pneumococcus, H.infl)  not a routine
procedure in Bandung
Repeat CSF examination after 24 – 48 h
 Bacterial meningitis: antibiotics
• Ceftriaxone iv 4g; then 2g daily
– cefotaxime
– benzylpenecillin
– chloramphenicol

• Resistant pneumococcus
– add vancomycin 2g bd iv +/- rifampicin
• Listeria
– ampicillin
• Pseudomonas
– gentamicin
Bacterial meningitis: steroids
– Significantly reduce mortality and neurological
sequelae in adults with bacterial meningitis
– Should be used ROUTINELY in adults with
suspected bacterial meningitis
– Best effect to pneumococcal infection
– Give with/before 1st dose of antibiotics
– 10mg dexa 6 hourly for 4 days
– NOT in patients already started on antibiotics
(de Gaans, NEJM 2002; 347: 1549 – 56)
– Caution: may reduce penetration through BBB
• especially vancomycin
 Bacterial meningitis: steroids
• Don’t give in
– Late stage disease – may be harmful
– septic shock
– post neurosurgical meningitis
– immunosuppressed/i.compromised patients
• Stop if
– No pathogen identified on CSF smear and suspect
fungal/other infection
– No bacterial growth/other organism after 24- 48 hours
 Bacterial meningitis: treatment
• Other anti-inflammatory drugs?
– against CSF cytokines
– matrix metalloproteases
– reactive oxygen species
 Bacterial meningitis
Delay initiating treatment
Delay recognising complications

high mortality
more complication
 Late deterioration
• Subdural effusion
• Empyema
• Hydrocephalus
• Vasculitis:
– stroke
– diffuse brain injury
– oedema
• systemic
Cerebral infarction

T2 DWI
Subdural empyema
Vasculitis and stroke
Vasculitis, stroke, hydrocephalus
 Acute or subacute onset global
cerebral dysfunction

• Three diagnostic categories

– Infective encephalitis (typically viral)

– Encephalopathy (typically metabolic or toxic)

– ADEM
• Encephalopathy • Encephalitis
– Fever and headache
common
– Mental status –steady – Mental status –often
decline fluctuates
– Seizures –generalised – Seizures – focal and
generalised
– Focal signs common

– Blood – wbc
– Blood - wbc N
– CSF- wbc
– CSF – wbc N
– EEG – slow plus focal
– EEG – diffuse slowing
– MRI –often abnormal
– MRI – often normal
 Encephalitis?
• The physician addresses three
important questions:

– How likely is the diagnosis of encephalitis?

– What could be the cause of encephalitis?

– Which is the best treatment plan for the

patient with encephalitis?
 Causes of viral encephalitis
• Herpes simplex virus (HSV-1, HSV-2)
- treatable

• Other herpes viruses: VZV, CMV,EBV, human herpes virus 6 (HHV6)

• Adenoviruses

• Influenza A

• Enteroviruses, poliovirus

• Measles, mumps and rubella viruses

• Rabies

• Arboviruses— Japanese B encephalitis, West Nile encephalitis virus

• Bunyaviruses—La Crosse strain of California virus

• Reoviruses— Colorado tick fever virus

• Arenaviruses— lymphocytic choriomeningitis virus

 HSE
• Most commonly identified cause of viral
encephalitis in the US (10-20% of cases)
• Estimated annual incidence: 1 in 250,000
to 500,000 persons
• Cases distributed throughout the year
• Biphasic age distribution, with peaks at 5-
30 and >50 years of age
• HSV-1 virus causes more than 95% of
cases
 HSE
• Without treatment, mortality >70%
• Major morbidity in survivors
• Milder forms of the illness exist but are
rarely correctly identified
 HSE
• Clinical hallmark of HSV encephalitis:
acute onset of fever and focal neurological
symptoms
• Differentiation of HSV encephalitis from
other processes is difficult.
• CSF , CT, MRI, PCR
• High index of suspicion
– Even if CSF/imaging normal
 HSE
• Most common presentations include:
– fever in up to 90%
– severe headache
– focal or generalized convulsions
– alterations in behavior and consciousness
– disorientation, dysphasia, and hemiparesis
more rare
– motor paralysis present in < 50%
 HSV treatment
• Vidarabine: 1st effective antiviral therapy
• Acyclovir: proved more potent
– reduced mortality to 19-28%, compared with
50-54% with vidarabine (Whitley et al, NEJM
1992)
– dosed 10 mg/kg given 8h for 10-14 days
– toxicity rare: phlebitis, rash, ↑ transaminases,
GI disturbance, neurotoxicity
 Chronic meningitis
Signs and symptoms
• Headache
• Fever
• Meningismus
• Confusion
• Hydrocephalus

In general, symptoms develop slowly

Meningismus may be mild
There may be subtle mental status changes
 Diagnosis

• Difficult diagnosis because signs and symptoms

are often non-specific. It can be suspected in
any patient with a chronic encephalopathy, or a
patient with new onset of hydrocephalus
• MRI or CT of head may show hydrocephalus or
contrast enhancement of the basal meninges
• Lumbar puncture
 Causes
• Infectious:
– Bacterial
– Fungal
– Parasitic

• Non-infectious
 Causes
Infectious:
• M. tuberculosis
• Cryptococcus neoformans
• HIV
• Treponema pallidum
• Nocardia sp.
• Aspergillus sp.
• Taenia solium (cysticercosis)
• Toxoplasma gondii

Non-infectious:
• Neoplasm (esp. breast, lung)
• Neurosarcoidosis
• Behcet's disease
• CNS vasculitis
• Mollaret's meningitis
TBM
 TBM
• High mortality
– mainly due to complications
• hydrocephalus
• infarction
• ventriculitis
• Rapid diagnosis difficult
• High index of clinical suspicion
– Chronicity
– Basal meningitis
– Systemic illness
– High risk groups
 Clinical features
• Fever, headache, meningismus and mental status
changes
• Vomiting and other signs of increased intracranial
pressure may occur
• Cranial nerve palsies occurs in approximately 25% of
cases
• HIV infection is a risk factor for tuberculous meningitis
• Other mycobacteria (M. avium, M. africanus) can
produce human disease, and M. avium is an
opportunistic pathogen in AIDS patients
• Other involvement:
– Spinal cord  usually in the thoracic cord region
– Tuberculous spondylitis  psoas abscess, epidural abscess
 Cerebrospinal fluid
• lymphocytic pleocytosis
• elevated protein
• reduced glucose
• Staining: positive in 5 to 25%
• Culture: positive in approximately 60% of cases
• CSF PCR may be useful

• With treatment, the CSF returns to normal

slowly. Glucose is the first to normalize, but it
takes at least three weeks, and usually more
 Imaging
• Contrast-enhanced CT or MRI scans show
a basilar meningitis, with contrast
enhancement of the meninges in the
suprasellar area, prepontine cistern, or
interpeduncular fossa
• Obstructive or communicating
hydrocephalus may occur
TBM
TBM
tuberculomas
stroke
tuberculous abcess
 TBM - diagnosis

Gold standard is microscopy: ZN staining

TB culture
 TBM diagnosis: other
• CSF adenosine deaminase
– unreliable: false positives
– undefined in HIV

• PCR
– good after treatment has begun
TB
 TBM: treatment
• Quadruple therapy initially
– Isoniazid
– Rifampicin
– Pyrazinamide
– Ethambutol/streptomycin
• Steroids:
– Coma
– Dexamethasone 16mg/day 2-4 weeks
 Immunocompromised patients
• Multiple organisms in single or multiple
organs
• Unusual organisms
• Decreased sensitivity diagnostic tests
• Atypical presentations
– no fever in meningitis
• Clinical picture complicated
– multi-organ failure
 AIDS/HIV
• Meningitis
– Cryptococcus neoformans

• Encephalitis
– CMV

• Brain abcess
– Toxoplasma
Aspergillus
Nocardia
 Lumbar Puncture
Basically, LP should be undertaken on all patients with
suspected CNS infection

Contraindications:

• signs of raised intracranial pressure—

– altered pupillary responses,
– Absent Doll’s eye reflex
– decerebrate or decorticate posturing
– abnormal respiratory pattern
– Papilloedema
– hypertension
– bradycardia
 Lumbar Puncture
Contraindications (cont.):

• recent (within 30 minutes) or prolonged (over 30

minutes) convulsive seizures
• focal or tonic seizures
• other focal neurological signs
– hemi/monoparesis
– extensor plantar responses
– ocular palsies
 Lumbar Puncture
Contraindications (cont.):

• Glasgow Coma Score < 13 or deteriorating level of

consciousness
• Strong suspicion of meningococcal infection (typical
purpuric rash in an ill child)
• State of shock
• Local superficial infection
• Coagulation disorder
 Typical CSF formulas
Bacterial Viral Fungal Tuberculous
opening
normal or high normal normal or high usually high
pressure
WBC count
1,000-10,000 < 300 20-500 50-500
(cells/mm3)
PMN (%) >80 <20 <50 ~20
RBC count
slight increase normal normal normal
(cells/mm3)
protein very high
normal high high
(mg/dl) (100-500)
Glucose < 40 normal usually < 40 < 40
60-90 % AFB stain + in
Gram stain negative negative
positive 40-80%
culture (%
70-85 25 25-50 50-80
positive)