L.4 Dr.Roua Al yaseenCentral Nervous System Infections
Viral infections of the CNS are much more common than bacterial infections,which, in turn, are more common than f ungal and parasitic infections.
Meningitis : means primary involvement of the meninges.
Encephalitis : indicates brain parenchymal involvement.
Meningoencephalitis: involvement of both.
Brain abscess is the best example of a focal infection of the CNS.
Et iology1- In the neonatal period (0 –28 days): Groups B streptococci ,E.
coli,Klebsiella , Listeria monocytogenes
2- Infants & children (2 mo to 12 yr of age
N. meningitidis , then S. pneumoniae , and H. influenzae type b
3- Those with underlying immunologic or anatomic (splenic dysfunction,
cochlear defects or implants) disorders increase the risk of meningitis from less
common pathogens such as Pseudomonas aeruginosa, Staphylococcus aureus,
coagulase -negative staphylococci, Salmonella spp., and Listeria
The major risk factors for meningitis include:
1- Young age (neonats & young infants).
2- Recent colonization with pathogenic bacteria paranasal sinusitis, otitis media,
m astoiditis, orbital cellulitis, pen et rating cranial trauma, dermal sinus tracts, or
3- Close cont act (household, daycare centers ) with individuals having disease
transmission through respiratory tract secr et ions or dropl et s.
4- Poverty, and male gender.
5- infants and young children with occult bacteremia.
A A cute Bacterial Meningitis
6- Specific host defense defects likea) Complement system (C5 –C8) defect recurrent meningococcal infection.
b) Defects of the properdin system let hal meningococcal disease.
c) Splenic dysfunction (sickle cell anemia) or asplenia pneumococcal.
8- Those with meningomyelocele staphylococcal9- Those with CSF shunt coagulase -negative staphylococci.
Pathology & pathophys iology : Damage to the cerebral cortex occurs due to vascular occlusion ,hypoxia,
bacterial invasion , toxic encephalopathy , elevated ICP, ventriculitis, and
Vascular and parenchymal cerebral changes will occur result in vasculitis, ,thrombosis of small cortical veins, occlusion of major venous sinuses,
necrotizing arteritis producing subarachnoid hemorrhage.
Cerebral infarction, resulting from vascular occlu sion due to inflammation,vasospasm, and thrombosis.
Inflammation of spinal nerves and roots produces meningeal signs, andinflammation of the cranial nerves produces cranial neuropathies of optic,
oculomotor, facial, and auditory nerves
↑ CSF protein may be due to ↑ vascular permeability of blood brain barrierwith loss of albumin -rich fluid; whereas ↓ CSF glucose is due to ↓ glucose
transport by the cerebral tissue.
Increase Intracranial Pressure (ICP) by severalmechanisms include: -
1. Cerebral edema; it is due to cytotoxic, vasogenic or interstitial edema.
2. Hydrocephalus; it is mainly c ommunicating HC due to adhesion of the
3. SIADH (syndrome of inappropriate antidiur et ic hormone secr et ion).
4. Subdural effusionThe ons et is either sudden or insidious.
Sudden ons et : is less common manifestation & associated with rapidly
progressive manifestations of shock, purpura, DIC, and ↓ consciousness which
often progress to coma or death within 24 hr.
Insidious ons et : is more common & manifested as nonspecific findings e.g.fever, headache, anorexia, photophobia, poor feeding, myalgia , arthralgia ,
tachycardia, hypotension, & skin rash e.g. p et echiae , purpura
Signs of meningeal irritation include nuchal rigidity, back pain, Kernig signand Brudzinski sign. In children younger than 12 –18 mo, Kernig and
Brudzinski signs are not consistently present.
In infants, there is bulging fontanel & diastasis (widening) of sutures. Signs of Increased ICP include: headache, nausea, vomiting, cranial
nerve palsy (especially the abduc ent & oculomotor); severe cases causing
Cushing triad which include hypertension, bradycardia, & irregular respiration
(apnea or hyperventilation).
Other signs include: papilledema, decorticate or decerebrate posturing, stupor,coma, or signs of herniation.
Seizures (focal or generalized) due to cerebritis, infarction, or electrolytedisturbances occur in 20 –30% of patients with meningitis.
Alterations of mental status
Inv estigations:1-Lumbar puncture(LP) & cerebrospinal fluid(CSF) examination :
During LP, the patient is placed in the lateral position, but sick neonates should
be placed in upright position. The ideal interspace for LP is L3 -L4 or L4 -L5
which d et ermined by drawing horizontal line from one anterior superior iliac
spine to the other.
CSF should be sent for G -stain, cultu re, & biochemistry( protein, suga r ,WBC &differential).
Normal value of CSF analysis:age WBC(mm 3) Protein
20 -45 60% of blood
50 -80 clear
120 60% of blood
CSF findings in CNS infectionsPMN (polymorphonuclear neutrophiles),
-Turbid CSF is present when the CSF leukocyte count exceeds 200 –400/mm 3.-The Gram stain is positive in 70 –90% of patients with untreated bacterial
The analysis of CSF obtained from children already receiving antibiotics
(partially treated meningitis ), was negative on Gra m stain and culture.
Neutrophilic Pleocytosis, elevated protein level, and a reduced concentration of
CS F glucose usually not affected.
Bacterial antigen may be d et ected in the CSF by agglutination test.
-Bloody CSF indicated either traumatic LP or subarachenoid hemorrhage& thesedifferentiated by centrifuged the CSF, if traumatic it become clear, but if
hemorrhage it remain xanthochromic.
Note : In traumatic CSF, WBC count & protein are affected, but G -stain, culture& glucose level not influenced.
-CSF sent also for : Lactate & LDH which may be high in bacterial meningitis while
normal in aseptic meningitis.
WBC(mm 3) Protein(mg/dl)
100 -10,000 PMN
100 -500 Decrease
Rarely 1000,PMN early
LP should be performed whenever bacterial meningitis issuspected, but there are some CONTRAINDICATIONS for (immediate)
LP include: -
1. Evidence of ↑ ICP e.g. ↓ consciousness , cranial nerve palsies, Cushingtriad, papilledema; whereas bulging fontanel alone in infants is not a
2. Severe cardiopulmonary compromise e.g. shock that require prompt
3. Infection of skin that overlying the site of LP.
4. Thrombocytopenia is a relative contraindication for LP.
2. Blood culture When LP is delayed , Blood culture should be taken (which
is +ve in 80 - 90% of ca ses), then empirical antibiotic therapy can be
3. CT scan for evidence of a brain abscess or increased ICP should not delay
therapy. LP may be performed later on after ↑ ICP has been treated.
4. CRP, ESR, and procalcitonin have been used to differentiate bacterial
(usually elevated) from viral causes of meningitis.
Other investigations may include: CBP, blood urea, serum electrolytes, urinefor specific gravity (for SIADH), & tests of coagulation function if there is
evidence of DIC.
Treatment .It consists of supportive care & antibiotic therapy.
Supportive Care include: -
1. Repeated medical and neurologic assessments especially in the 1st 72
hr e.g. chart for vital signs, fluid input & urine output, pupillary
reflexes, level of consciousness… et c.
2. Patients should initially receive nothing by mouth. Shock should betreated with fluid resuscitation +/_ inotropic agents; whereas if there is
no hypotension, IV fluid should be restricted to half or two thirds of
maintenance until it can be established that ↑ ICP or SIADH is notpresent, then full maintenance can be given.
3. ↑ ICP can be treated by: head elevation, restriction of IV fluid,furosemide (1 mg/kg) or mannitol , and endotracheal intubation with
hyperventilation . Glycerol has also been used to ↓ cerebral edema by ↑
plasma osmolality & enhance cerebral circulation.
4. Seizures should be treated with IV diazepam (0. 3 mg/kg/dose) orlorazepam ; for maintenance Treatment of seizures, give phenytoin
which is b et ter than phenobarbital because it produces less CNS
Antibiotic Therapy: -Empirical antibiotic therapy can be initiated after taken CSF culture as :
Vancomycin vial + Cefotaxime vial or Ceftriaxone + IV
Corticosteroid for 2 days.
until the result of culture appear then change the treatment
-S. pneumonia is sensitive to Vancomycin .-H. influenza is sensitive to Cefotaxime or Ceftriaxone .
-N. meningitides is sensitive to Penicillin G .
Note: 3rd generation cephalosporins are also effective in N. meningitides& β -lactam - sensitive S. pneumonia infection.
L. monocytogenes (come in neonate ) is only sensitive to Ampicillin.
Duration of antibiotic Treatment in uncomplicated meningitis as follows: -N. meningitidis for 5-7 days .
H. influenza for 7-10 days .
S. pneumonia for 10 -14 days ;
whereas Gram -negative bacilli e.g. E. coli or P. aeruginosa either 3 wk or
at least 2 wk after CSF sterilization.
Corticosteroids use in meningitis: -IV Dexam et hasone use for 2 days to patients >6 wks. of age with
meningitis specifically due to H. influenzae type b had result in shorter
duration of fever, lower CSF protein and lactate levels, and reduction in
sensorineural hearing loss .
The maximum benefits of corticosteroids if given 1 –2 hr before antibioticsare initiated.
Acute Complications include: seizures, increased ICP, cranial nerve
palsies, stroke, cerebral or cerebellar herniation, thrombosis of Dural
venous sinuses, SIADH, & DIC.
Subdural effusions; it occur in the minority of patients butasymptomatic in the majority; it is mor e common in infants resulted in
bulging fontanel, diastasis of sutures, enlarging head circumference,
emesis, seizures, & fever; it may be treated by aspiration.
Thrombocytosis, eosinophilia, and anemia may develop duringtherapy of meningitis.
Pericarditis or arthritis may occur after Treatment of meningitis,especially due to N. meningitides .
Late complications(outcome) : 35% of patients have late sequelae,particularly after pneumococcal meningitis include:
1-Sensorineural hearing loss: occurs in 30% of patient s with pneumococcal
meningitis, It is due to labyrinthitis or direct auditory nerve inflammation.
3-mental r et ardation.
5-behavioral problems & learning disabilities.
Factor associated with poor prognosis include: -a. Seizures that persist after the 4th day of illness or seizures that are
difficult to control.
b. Coma or focal neurologic signs on presentation.
c. High concentration of bacteria or low leukocyte count in the CSF.
d. Infants < 6 mo
PreventionIt is either by vaccination or antibiotic prophylaxis.
S. pneum onia; pneumococcal vaccine is recommended for children < 2 yr
of age and those at high risk e.g. asplenia or immunodeficiency.
No antibiotic Prophylaxis is required.
H. influenza type b; Conjugated vaccines for Hib started at 2 mo of age.
Rifampin Prognosis should be given to all house -hold c ontacts (except
pregnant women) once for 4 days.
N. menin gitides; vaccine is recommended for high -risk children > 2 yr,
Rifampin for 2 days; ciprofloxacin or ceftriaxone (single dose) also can be
given. They should be given to all contacts (regardless of immunization
status) e.g. household, daycare center, nursery school contacts, and health
care workers who have dir ect exposure to oral secretions .
Follow up1- Daily assessment of:
Vital signs, body weight, urine output, OFC,& neurologic assessment. This
to d et ect the complications as early as possible & interfere rapidly such as:
blood pr.& HR ICP
body wt.& oliguria SIADH
OFC subdural effusion or hydrocephalus.
2- Long term follow up include monthly visit to chec k for OFC, mentality,
vision and hearing.
Viral meningoencephalitis is the most common cause of CNS infection.Et .
Enteroviruses are the most common cause of viral meningo -
encephalitis. It spread directly from person to person
Herpes simplex virus type 1 (HSV -1) is an important cause of
severe , sporadic encephalitis. Brain involvement usually is focal .
Herpes simplex virus type 2 (HSV -2) may cause severe encephalitis
with diffuse brain involvement in neonates .
Varicella -zoster virus (VZV) may cause CNS infection (especially
cerebellar ataxia) in associated with chickenpox.
CLINICAL MANIFESTATIONThe onset is generally acute, CNS signs and symptoms are preceded by a
nonspecific febrile illness of a few days' duration.
In the infant the presenting manifestations are irritability and lethargy .
In older children are headache(frontal or generalized) and hyperesthesia.;
adolescents frequently complain of retrobulbar pain. Fever, nausea and
vomiting, photophobia, and pain in the neck, back, and legs are common.
progressing to stupor with convulsions.
Focal neurologic signs may be present, especially in HSV -1 wh ich causesever encephalitis, progression to coma & death occurs in 70% of cases
without antiviral treatment.
Loss of bowel and bladder control may occur . Skin rash may occurs with
enteroviruses & measles infection.
CSF exam; see the table above.
Serology of blood may be useful in d etermining some viral CNS
infection e.g. arbovirus infection
EEG show diffuse slow wave activity.
CT & MRI show swelling of brain parenchyma.Note: HSV encephalitis is suggested by focal seizures & focal finding on
EEG, CT, or MRI especially if involve the temporal lobe.
TreatmentHSV encephalitis is treated with IV Acyclovir, for 2 -3 wk.
Otherwise, Treatment of viral meningoencephalitis is supportive .
Mild disease may require only symptomatic relief. More severe diseasemay require hospitalization and intensive care .
Headache and hyperesthesia are treated with rest, non –aspirin -
containing analges ics & reduction in room light, noise, and
Fever; ac eta minophen .
Vomiting; phenothiazine .
Poor oral intake; IV fluids ,Total parenteral nutrition may be
required in prolonged coma.
Complications Guillain -Barre syndrome, Transverse myelitis, Hemiplegia,and Cerebellar ataxia.
Most children recover compl et ely from viral infections of the CNS,
especially those due to enteroviruses, whereas others have high mortality
rate e.g. HSV, or have severe sequelae e.g. epileptic, visual, or auditory.
P re vention.Isolation of cases, vaccination is available for some viruses e.g. varicella,
& measles .