CENTRAL NERVOUS SYSTEM INFECTIONS

IN CHILDHOOD PERIOD
Case
8 months old, boy

Complaint: fever, crying, vomitting

History:
Fever for 2 days
Feeding time decreased
Then started to vomit (6-8times/day- projectile)
Today always prone to sleep
High fever up to 39,5 C
CNS infections:

• common infections during childhood

• High mortality and morbidity
• Prognosis depends on early diagnosis and treatment
• Despite safe, effective vaccines and potent, well-tolerated
antimicrobial drugs, CNS infections remain important causes
of neurologic disabilities.
CNS infections:
• Meningitis
• Encephalitis
• Meningoencephalitis
• Brain abcess
• Subdural ampiyema
• Slow viral infections
• Unusual infections of CNS (Neurosyphilis,
Neurocysticercosis, Toxo..)
Meningitis:
inflamation of meninges
It can be infectious or non-infectious (drugs,
malignancy, chemicals,…)
CNS infections:
• Meningitis
• Acute
• Acute bacterial
• Aseptic
• TBC meningitis
• Fungal meningitis
• Chronic
Acute bacterial meningitis

Etiology
The causative agent vary with age

Neonatal period:
Group B streptococci, E. coli, Listeria, Klebsiella
Infants-young children:
H.Influenza, N. Meningitis, S. Pnemonia
Older children:
N. Meningitis, S. Pnemonia
Acute bacterial meningitis

Pathogenesis:
Bacterial organism reach the meninges
-direct hematogenous invasion
-passage through the plexus choroideus
-rupture of superficial cortical absesses
-Nearing infections such as otitis,
sinusitis…
-Additionally, fractures of the skull or
congenital defects of the spine or skull
Acute bacterial meningitis
Clinical presentation
The symptoms and signs of bacterial meningitis in children;

•fever, •seizures
•headache, •Acute encephalopathy
(ranging from lethargy to
•vomiting,
stupor and coma)
•photophobia,
•focal neurological signs
•nuchal rigidity,
•meningeal signs (Kernig
and Brudzinski signs)
Acute bacterial meningitis

- Neck stiffness is the pathognomonic finding of

meningeal irritation.
Nuchal rigidity is present when the neck resists passive
flexion.
Acute bacterial meningitis
- Kernig's and Brudzinski's signs are classical signs of meningeal
irritation.
-Kernig's sign is elicited with the patient in the supine position.
Positive Kernig’s sign is inability to extend the leg with the hip
flexed.
Attempts to passively extend the leg elicit pain when
meningeal irritation is present.

Netter
images
Acute bacterial meningitis

Brudzinski's sign is positive when passive flexion of the neck

(with the patient in the supine position) results in
spontaneous flexion of the hips and knees.
Acute bacterial meningitis

•The presence of a diffuse erythematous maculopapular rash

resembling a viral exanthem may be an early manifestation of
meningococcemia.
•The skin lesions of meningococcemia may became rapidly
petechial. Petechiae are found on the trunk and lower
extremities, in the mucous membranes and conjunctiva and
occasionally on the palms and soles.
Acute bacterial meningitis

Waterhouse-Friderichsen syndrome:

Ten to 20% of children with meningococcal infection will

develop the Waterhouse-Friderichsen syndrome.

WFS which is characterized by sudden onset of a febrile

illness, large petechial hemorrhages in the skin and
mucous membranes, septic shock, disseminated
intravascular coagulation, acute adrenal insufficiency.
Acute bacterial meningitis

•Seizures occur in 40% of children with bacterial meningitis

typically during the first few days of the illness.

•Seizures may be focal or generalized. The majority of seizures

have a focal onset.
Acute bacterial meningitis

•Increased intracranial pressure is an expected

complication of bacterial meningitis, and is the major
cause of lethargy and coma in meningitis.

•The risk of cerebral herniation from acute bacterial

meningitis is approximately 6-8%.
Acute bacterial meningitis

Focal or diffuse cerebral edema is the most likely

etiology; however, hydrocephalus and dural sinus or
cortical vein thrombosis may also cause herniation.
Lumbar puncture may result in herniation in patients
with increased ICP.

!!!!!! When the possibility of increased intracranial

pressure exists, lumbar puncture should be delayed
until the increased intracranial pressure can be
treated.
Acute bacterial meningitis

The symptoms and signs of bacterial meningitis in infants;

-fever
-bulging anterior fontanel
-poor feeding
-lethargy
-irritability
-hypotonia
-seizures
Acute bacterial meningitis

The diagnosis of meningitis is based on clinical suspicion

and established by the CSF examination.
When to perform LP?

Bulging fontanelle
Stiff neck, meningeal signs
Acute encephalopathy associated with fever
Seizure with fever (in selected patients, particularly
younger than 6 months)
Acute bacterial meningitis

Contrendications for LP:

-Signs of increased ICP and progressive coma
-Skin infection over the LP site
-Cardiopulmonary instability
-Severe thrombocytopenia
Acute bacterial meningitis
Cerebrospinal fluid examination:
Examination of the (CSF) is crucial in the diagnosis of CNS infections.
The classic CSF abnormalities in bacterial meningitis are;
1. increased opening pressure;
2 . pleocytosis of polymorphonuclear leukocytes; (10- 10.000
WBC/mm³)
3. decreased glucose concentration (<40 mg/dl and/or CSF/serum
glucose ratio of <0.31);
4. increased protein concentration.
*with high wbc; cloudiness of CSF
 T Y P ICA L CS F F IN D IN G S IN M E N IN G IT IS
T u b ercu lo u s
CS F P aram eter B acterial M en in g itis V iral M en in g itis Fu n g al M en in g itis M en in g itis

O p en in g p ressu re >1 8 0 O ften n o rm al V ariab le >1 8 0

(m m H 2 O )

W B C (cells/m m 3 ) 1 ,0 0 0 -1 0 ,0 0 0 <3 0 0 2 0 -5 0 0 5 0 -5 0 0
M ed ian : 1 1 9 5 M ed ian : 1 0 0 V ariab le,d ep en d en t M ed ian : 2 0 0
R an g e: <1 0 0 -2 0 ,0 0 0 R an g e: 1 0 0 -1 ,0 0 0 u p o n fu n g u s R an g e: <5 0 -4 ,0 0 0

N eu tro p h ils (% ) >8 0 <2 0 U su ally <5 0 20

P ro tein (m g /d L) 1 0 0 -5 0 0 O ften n o rm al E levated 1 5 0 -2 0 0

G lu co se (m g /d L) <4 0 >4 0 U su ally <4 0 <4 0

G ram stain (% 6 0 -9 0 N eg ative N eg ative 3 7 -8 7 (A F S sm ear)

p o sitive)

Cu ltu re (% p o sitive) 7 0 -8 5 50 2 5 -5 0 5 2 -8 3
Acute bacterial meningitis

Microbiologic and serologic tests of CSF;

Gram stain and culture
Polymerase chain reaction (PCR) or antigen detection
Blood culture often identifies the causative organism. Gram stain
has a sensitivity of 60% to 90% and a specificity nearing 100%.
Acute bacterial meningitis
Neuroimaging do not take place in the diagnosis of
menengitis.
Meningeal/ependymal enhancement and widened
cisterns/sulci due to purulent exudate are suggestive
findings.

Neuroimaging is basically used to rule out other conditions

and to evaluate complications;
•hydrocephalus,
•diffuse cerebral edema,
•cerebritis/abscess,
•subdural effusion/empyema,
•infarct.
Acute bacterial meningitis

Recommendation for CT or MRI in infants and children with

meningitis
1- Newborn
2-Prolonged alteration of consciousness
3-Seizures 72 hours after start of treatment
4-Continued excessive irritability
5- Focal neurologic findings
6-Persistently abnormal CSF
7-Relapse or recurrence
Acute bacterial meningitis

Treatment:
Antibiotics:
Intravenous antibiotics should be started as soon as the diagnosis
of septic meningitis is suspected.
Empiric therapy is selected based on the most likely causal agent,
and whether antibiotic resistance is a likely factor.
Empirical antibiotic for children older than 3 months:
Ceftriaxone (100 mg/kg/day)
Acute bacterial meningitis

Dexamethasone (For children older than 2 months) migth be used

in selected patients
Acute bacterial meningitis

Supportive care:
-Patients must be monitored carefully (to identify CNS,
cardiovascular and metabolic complications) and neurological
examination should be repeated regularly.
-Fluid and electrolyte imbalance should be monitored
(with attention to the possibility of hyponatremia due to
inappropriate ADH secretion).
Acute bacterial meningitis

Outcome of bacterial meningitis depends on several factors,

including
-the child's age,
-the causative pathogen,
-the time of initiation and effectiveness of the treatment,
-the presence of immunedeficiency
Aseptic meningitis

Although the etiologic agent cannot be identified in most

cases, the viruses are usually the responsible pathogens.
Enteroviruses, mumps, arboviruses, herpes viruses are
common.
Infectious
1.Viruses: enteroviruses; polio, coxsackie, ECHO
Herpes group of viruses: HSV type 1 ve 2, VZV (Varicella Zoster
Virus), CMV (Cytomegalovirus), EBV (Epstein Barr Virus), HHV-6 (Human
Herpes Virus-6)
Respiratory viruses: Adenovirus, rhino virüs, Influenza A ve B,
mumps, HIV

Non- infectious
1.postinfectious/after vaccination: measeles, varicella, influenza
2. drugs: NSAD (non-steroidal anti-inflammatory drugs),
Trimetoprim-sulfametaksazol, intratechal metotreksate,..
3.systemic disorders: SLE, CNS vasculitis, Behçet disease,...
4.neoplasms
Aseptic meningitis

Clinical features:
Headache,
Irritability,
Lethargy,
Meningeal signs,
Fever,
Vomiting,
Photophobia,
Pain in the neck
Exanthemas may observed (Echoviruses)
Aseptic meningitis

CSF analysis yield:

Color: clear
Cell: There are mild to moderate lymphositosis
Protein: Usually normal
Glucose: Normal
Aseptic meningitis

Treatment:
Antiviral theraphy (acyslovir)- HSV
Until a bacterial cause is excluded by culture of blood and CSF,
antibiotics should be started.
Supportive care
Chronic meningitis

- Chronic meningitis is usually defined as inflammatory cells or

malignant cells in the meninges (meningitis) that persist
longer than one month.

-Chronic meningitis must be distinguished from recurrent

meningitis in which there are repeated episodes of meningitis
(The patient is asymptomatic with normal CSF between
episodes)
 Chronic meningitis
Etiological agents
Infectious
Bacteria:
Non-infectious
Mycobacterium tuberculosis Meningeal carcinomatosis

Treponema pallidum Leukemia in the meninges

Borrelia burgdorferi CNS sarcoidosis
Fungi
Cryptococcus neoformans

Coccidioides immitis

Histoplasma capsulatum

Virus
Human immunodeficiency virus
Parasite
Taenia solium ova (Cysticercosis)
Tuberculous meningitis

Tuberculosis meningitis is most common in children

between 6 months and 4 years.
About 15% of active tuberculosis is extrapulmonary and 6%
of that is meningeal.
Most cases to TB meningitis occur in developing countries.
 Tuberculous meningitis
Features suggestive of TB meningitis;
· Progressive subacute meningitis symptoms present for 1-3
weeks (fever, headache, irritability, vomiting, focal neurologic signs-
motor deficits or cranial nerve palsy-, lethargy, neck stiffness,
meningeal signs, coma, deterioration of vital signs)
· Hyponatremia, Positive tuberculin skin test 50%
· CSF with pleocytosis, elevated protein and decreased glucose
· Family members or friends with recent active TB
· Neuroimaging demonstrating enhancement of basal meninges
80% and a lesion consistent with tuberculoma 10-20%
Tuberculous meningitis

The cerebrospinal fluid (CSF) is always abnormal.

The opening pressure is often elevated in the majority and
occasionally is markedly elevated.
The CSF contains 30 to over 1,000 WBC/mm3.
Usually there is a mixture of lymphocytes and neutrophils
with lymphocytes predominating.
Tuberculous meningitis

The definitive diagnosis is made from CSF by isolation of M.

tuberculosis, identification of M. tuberculosis nucleic acid or
proteins, and/or detection of a specific humoral immune
response to M tuberculosis.
The concentrated CSF can be placed on solid media, such as
Lowenstein-Jensen, or liquid culture systems, such as the
BACTEC .

The most promising diagnostic test is PCR assay for detection

of fragments of M. tuberculosis DNA.
Tuberculous meningitis

Treatment:

Antituberculous drugs

Steroid

Supportive care

Treatment of complications (hydrocephalus, inappropriate

ADH secretion, ..)
Tuberculous meningitis

Prognosis:
The stage on hospitalization is the most important
predictor of outcome.
Neurological morbidities include hemiparesis, paraparesis,
quadriparesis, aphasia, mental retardation, dementia,
blindness, deafness, cranial nerve palsies, epilepsy, and
hypothalamic and pituitary dysfunction.
Fungal meningitis

Immunosuppressed individuals have a markedly increased

incidence of CNS fungal infections and are predisposed to a
wide variety of opportunistic fungi.

CSF examination is critical to establishing the diagnosis of

fungal meningitis.

The fluid is usually clear and colorless unless the pleocytosis is

markedly elevated or protein very elevated.
Fungal meningitis

The most common causes are Cryptococcus

neoformans , Coccidioides immitis , Histoplasma
Capsulatum, Candida and Blastomyces dermatitidis .
Fungal meningitis

The CSF white cell count is normally elevated with counts

ranging from 20 to 1,000 cells/mm 3 .
Lymphocytes normally predominate but some neutrophils are
frequently present.
CSF protein levels are elevated and range from 50-1,000 mg/dl.
The Gram stain of CSF is usually negative.
Fungal Cultures and special stainings are important in the
diagnosis
Brain edema
Brain abses, increased capillary permeability, disruption of blood brain barrier  vasogenic
edema
Secondary to infection and cell membrain pathology-- > cytotoxic edema

Classical clinical triad: headache- vomitting- papilledema

Clinical findings differ according to age.
During newborn and infancy period classical findings are not expected (open fontanelle)

Cushing triad (brain stem): hypertension- bradicardia- irregular breathing

Treatment:
* vasogenic edema: corticosteroids
*cytotosic edema : osmotic agents
Treatment of increased intracranial pressure;

1. step:
*Correction of iatrognic causes (sedation and prevention of hypertermia, hypoxia,
aspiration, hypercarbia)
*CSF drainage if indicated
*transient hyperventilation (PaCO2 35-38mmHg)

2. step
* transient hyperventilation (PaCO2 30-35mmHg )
*Mannitol
*%3 salin infusion

3.step
*Barbiturates
*Hypotermia
*Decompressive craniotonia
 !!!!!
 CNS infections are neurologic emergencies. Delay in treatment increases mortality and
morbidity.

 In case of suspicioun of menengitis, LP should be performed as soon as possible and ampiric

antibiotic treatment should be initiated intravenously. Treatment should be rearranged
according to culture results.

 For newborn period CNS infections should be kept in mind in cases with findings like decrease
in sucking and tendency to sleep,...

 Complaints of fever, vomitting, headache for a subacute period followed by changes in

conscious or coma may be a sign of tuberculosis menengitis. Tuberculosis within family or
within indiviuals in contact must be evaluated. High opening pressure in LP, high protein
levels, too low glucose is suggestive of tubrculos menengitis. In those cases anti-tuberculosis
treatment should be initiated and CSF PCR, cranial MRI, PPD, chest X-ray should be
performed.

 Lateralizing findings in neurological examination, high fever, involvement of cranial nerves, or

seizures in the foolow up of patients with menengitis or encephalitis can be indicative for
absses formation. Emergent neuroimaging should be performed.