Meningeal syndrom

Meningeal syndrom (signs and symptoms)

Intracranial hypertension signs
headache, nausea, vomitus

Radicular irritation resulting in muscle spasms (meningeal signs)
stiff neck
spine sign
Lassegue sign

+

Other signs of CNS disorders
focal neurologic signs
convulsions
irritability or lethargy and stupor
delirium

Differencial diagnosis of meningeal syndrom

inflammation

meningitis bacterialis x focal inflammation
(cerebritis or brain abscess)

Haemophilus influenzae type b (5m.-5yrs.)
At birth the levels of maternal Ab are adequate for protection of the infant. Once the level falls at about 3 months, incidence of meningitis increases, from 2-3 yrs. the own immunity developes)
Neisseria meningitidis(up to 4 yrs. and adolescents)
Streptococcus pneumoniae
Streptococcus pyogenes group A
Streptoccocus group B so called Str. agalactiae (neonates)
Staphylococcus aureus (posttraumatic meningitis, I.E. )
Staphyloccous epidermidis (shunt meningitis, I.E.)
Gramnegative rods -neonates, neurosurgical procedures,
Almost every bacteria has been able to cause meningitis
in imunocompromised patients

Nocardia asteroides more often local lesions

aseptic meningitis or meningoencephalitis

- viral

TBE (arboviruses)

*enteroviruses

(Coxackie viruses. Echo, polio, EV 71)

*respiratory viruses- influenza, parainfluenzae
*other respiratory agents Mycoplasma pneumoniae and Chlamydiae

herpesviridae
HVH 1,2 (focal necrotizing encephalitis)

EBV, CMV, VZV

bacterial

leptospirosis neurolues

Lyme disease -neuroboreliosis

Amoebic encephalitis

Naegleria fowleri

Acanthamoeba

Balamuthia mandrillaris

Fungal inflammation of CNS

Candida (long term therapy with widebroad AB, neonates, diabetes mellitus etc)

(exceptionally immunocompetent) Cryptococcus neoformans (indicative disease for AIDS)

Aspergillus

TBC meningitis

beware of growing incidence of tbc

Non- infectious causes of meningeal syndrome

traumatic

spontaneous hemorrhage !!!!!! ( aneurysm , arteriovenous malformation)

tumor

encephalopathy

* toxic disorders (usually fever is present) in non CNS infections (pneumonia, Shigella , typhus abdominalis , brucellosis etc.)

* hepatic encephalopathy syndrome -Reye syndrome

* metabolic disorders - uremia, hepatic encephalopathy, inborn errors of metabolismus, water intoxication, hyponatremie, or hypernatremia, hypoxia

How to differentiate the causes of meningeal syndrome ???

Check historic epidemiologic details of importance in CNS inflammation

*exposure to illnesses in other humans
*exposure to vectors such as ticks or mosquitoes
*exposure to animals, especially sick ones (rabies, antropozoonozes)
*recent travel (especially to high risk areas for TBE, rabies, poliomyelitis, epidemic areas for meningococcal infections etc.)
*exposure to enviromental toxins

History of illness itself

acute x subacute x slow x biphasic beggining and outcome of illness

fever

otologic history (chronic otitis media)

trauma -craniocerebral injury - postraumatic meningitis

hydrocephalus-shunt or neurosurgery procedures or invasive examination (lumbar punture) in history

Underlaying diseases

especially those leading to severe imunologic disorders (AIDS, cancer on chemotherapy or radiation, diabetes, long-term corticosteroid therapy etc.)

Laboratory examinations in the case of suspected inflammation of CNS

Examination of CSF

Lumbar puncture

technique:

1) Restrain patient in recumbent or upright position
2) Scrub hands, wear surgical gloves and mask
3) Locate L3-4 interspace at the level of the iliac crest
4) Clean back thoroughly with alcohol, then with iodine solution, wipe it dry with sterile towels
5) Insert spinal needle in the L3-4 interspace, directed toward the umbilicus
6) Remove the stylet when the dura ‘pop’ is felt or do it periodically
7) If blood returns, the procedure may be repeated in the L2-3 interspace

Contraindication:

Increased intracranial pressure or a mass lesion of the CNS
Instability of patient
Suspected abscess in lumbar area
CT scan should be obtained first
Fundoscopic examination is need prior LP to obtain clear view of the optic disc

Subdural tap

-in subdural effusion occuring sometimes in or after therapy in infants. Effusion can be detected by ultrasonography or CT scans. Subdural fluid aspiration (when indicated) is done through open fontanell. Whole procedure must be performed under strict aseptic conditions. The goal of this procedure is diagnostic (examination of CSF sterile effusion x empyema) and therapeutic ( fluid removing)

Ventricular tap

- usually performed by neurosurgeons

Suboccipital puncture

-if indicated must be performed by very well skilled personal only because of high risk of complications

Processing CSF from bacterial meningitis patients

Culture for bacteria (and fungi)

Protein and glucose testing (compare with simultaneous blood glucose level)

Total white and red blood cell count (Fuchs-Rosenthal staining for cellular differentiation)

Sediment for staining ( Gram stain for bacteria differentiation, acid fast stain, India ink , dark field examination for spirochetes or leptospiral infection)

Supernatant for antigen detection (usually by Latex aglutination, PCR)

Processing CSF from aseptic meningitis patients

Protein and glucose testing

Total white and red blood cell count

Isolation, PCR, electronoptic examination for bacteria and viruses

Antibody detection in CSF (herpetic infections, Lyme borreliosis), or antibody detectin in blood (leptospirosis, Lyme disease)

Differencial diagnosis according the CSF examination

	bacterial meningitis	aseptic meningitis	tbc meningitis
color	white,milk like	clear straw, water like	yellowish
clarity	opaque	transparent	opalescent, but also clear
viskosity	high	normal	variable
protein	İ İ İ	normal or	İ İ İ
glucose	ß ß	normal	ß ß
lymphocytes	0 -	-	-
polymorphonuclears			0 -
culture for bacteria	positive	negative	negative
other methods	Latex agglutinatin	viral isolation, PCR	PCR, acid fast stain

Cytological and biochemical limits in CSF

AGE	lymphocytes	PMN	protein (g/l)	glucose (mmol/l) 60-80% of blood glucose	Cl- (mmol/l)
neonates	up to 100/3 cells (up to 60% PMN)		up to 1g/l	according to blood glucose	not significant
up to 1 yr.	Up to 15/3	0/3	0.2 -0.4 g/l	2.2 - 3.2	not significant
Up to 10 yrs.	up to 10/3	0/3	0.2 -0.4	2.2 -4.2	less than 116 in tbc meningitis

Adults

up to 9/3

0/3

0.2 -0.4

2.2 -4.2

under the low limit- not always in tbc meningitis

Bacterial infections

Blood cultures

Avoiding or minimizing unnecessary contamination- how to do it??

Strict aseptic technique - use two different desinficiens ( alcohol and iodisol etc) for skin and also for hemoculture bottles. caps.

Automatic noninvasive microbial detection systems - Bactec, Bactec Alert- these systems used advanced colorimetric of fluorescent carbon oxid ( CO2) detection technology to determine the presence of microorganismus in specially designed bottles.. These blood culture systems continuously and simultaneously monitor, agitate and incubate blood culture vials.

These hemoculture bottles can be used for aerobic and anaerobic culture (for the latter special anaerobic containers are needed)

Prior iniciating antibiotic therapy hemoculture collection must be obtained !!

Pathogenesis of bacterial meningitis

Primary meningitis -bacteria colonise the nasopharynx, then passes into blood where multiplies, causing bacteraemia, a preliminary stage in invasive manifestations such as meningitis, septicemia, arthritis, pneumonia, pericarditis

Hematogenous spread

x

Secundary meningitis (There exist a site of inflammation which the infection is spreading from)

Contagious spread

* otogenic ( otitis media, mastoiditis, sinusitis frontalis, ethmoiditis)

* postraumatic (skull fracture, craniocerebral injury)

* meningitis in infective endocarditis as a product of long distance embolising so called mycotic abscesses-primary mass lesion of infection is on cardiac valves (hematogenous spread)

Pathogenesis of intracranial hypertension - lifethreating complication of meningitis

interstitial edema cytotoxic edema

Intracranial hypertension

vasogenic edema hyperproduction of CSF

low absorption of CSF

hyperviskosity

Lost of the brain blood flow autoregulation

ICP higher than MAP results in severe impairment of brain perfusion even in a brain death

Pathogenesis of cytotoxic brain edema in Hib meningitis

--------------------------------------------------------------

leptomeningitis

cortical trombophlebitis

compromised cortex blood perfusion ENCEPHALOPATHY

cortical hypoxemia

anaerobic glycolysis

ATP synthesis hypoglycorrachia lactate

ionts gradients failure

brain edema

effect of excitating aminoacids (glutamate, aspartate) on ionts gradients

intake of Na, Cl into brain cells following by calcium intake into these cells cell death

Management of meningitis

1) Initial evaluation

Lumbar puncture

Blood culture

Complete blood and platelet count

Electrolyte analysis

Blood urea (dehydration/renal function)

Creatinin

Glucose (comparision to CSF glucose)

Blood gases

Coagulation factors (Quick, APTT)

Liver enzymes

Urinalysis

Chest X-ray

Paranasal cavities X-ray

Skull X-ray if trauma in history is present

Supportive care

Monitor blood pressure

Monitor fluid balance,

neurologic and cardiac signs

Ultrasound of head if a subdural effusion is suspected in infants or CT scan in older children or in adults if any suspicion on a mass effects of brain is present

Treatment of bacterial meningitis

Causative therapy = antibiotics

empiric therapy

for children the 3^rd generation cephalosporins (ceftriaxon, cefotaxim, ceftazidime)

for adults chloramphenicol

Dosage:

CTR 100mg/kg/den once a day or in two daily doses

CTX 200mg/kg/day in three daily doses

CTZ 150 mg/kg/day in two daily doses

CMP[chloramphenicol] 100-200 mg/kg/day - maximum daily dose is 12g (three times a day)

2) special regimens

Meningococcal infections in the case of sensitive strain Penicilin G is possible for therapy - dosage

200 000 j./kg/day in four daily doses every six hour.

In case of infection by sensitive pneumococcal strain PEN G 400 000j/kg/day x beware penicilin resistant strains !!!! even multiresistant strains ( the 3^rd generation cephalosporins resistance ) -vancomycin, or combination with newer chinolones

Haemophilus influenzae type b -beta lactamase producer -3^rd generation cefalosporins

Hib- non betalactamase producer might be used ampicillin 400mg/kg/day in four daily doses is possible

Staphyloccocus aureus oxacilin, vancomycin

Staph. epid. Vancomycin

Gramnegative bacilli the 3^rd generation cephalosporins usually in combination with aminoglycosides

Fungal meningitis -Amphotericin B (liposolubile forms)

PRSP

MIC less than 0.125 mg/l-senzitive

MIC 0.125-1.0 mg/l -intermediate

MIC equal or more than 2 mg/l-resistant

Risk factors of patients for systemic infection with PRSP

Patients older than 10 yrs.

Immunosuppresion

Rapidly fatal underlying disease

Previous antibiotics

Pneumococcus serotypes 14 and 23

Therapy of PSRP

the 3^rd generation cephalosporin

Therapy of cephalosporin-resistant strains od Str.pn.

vancomycin 60 mg/kg in 4 div.dos.

rifampicin

for invasive disease carbapenems, cefpirom, clindamycin (good penetration across BBB morover doesn´t affected by dexamethason therapy)

Combinations:

with newer chinolones (clinafloxacin, sparfloxacin)

Supportive therapy

* corticosteroids - dexamethason ( 0.8mg/kg/day in two daily doses -two day regimen -european styl of dexamethason administration and american style is 0.6mg/kg/day in four daily doses -four day regimen) (hearing impairment)

* manitol 1,5 - 2,0 g/kg/day in 4-6 doses

* IVIG

* Anticonvulsant for seizures

Supportive intensive care including

* cardiovascular support ( inotropic drugs to keep systemic pressure and renal function)

* endotracheal intubation for mechanical ventilator support to correct hypoventilation, hypoxemia (power method against brain oedema, ARDS)

Outpatient follow up

auditory testing (audiometric examination, evocating potentials)

head circumference

neurologic examination

ultrasound if necessary

CT scan if necessary

Prophylaxis and prevention of bacterial meningitis

Vaccination

Pneumo 23

(polyvalent pneumococcal vaccine, includes 23 serotypes responsible for at least 85% pneumococcal infections))

Recommendations for persons over 2 yrs. of age, at risk of serious pneumococcal infections:

people 65 yrs of age or older
patients with chronic illness ( e.g.: cardiovascular d., pulmonary d., dibates, cirrhosis, alkoholic patients and
patients with CSF leak)
immunocompromised patients (asplenia, sickle cell anemy, lymphoma, chronic renal failure, prior organ transplantation)
patients with asymptomatic or symptomatic HIV infection
special groups (persons living in special enviroments or special settings, e.g., old persons hospitalized or livind in institutions)

Haemophilus type b conjugate vaccine

vaccines are consist of PRP (polyribosyl-ribitol-phosphate) coupled to a carrier protein

tetanus protein

OMP (meningococcus B)

diphteric protein

CRM modified diphteria protein

Indications:

in children from 2 months upwards for the prevention of invasive Hib infections, such meningitis, epiglottitis, arthritis, septicaemia and cellulitis

conjugated vaccine does not confer protection against infections due to other types of H.inf. or against tetanus, diphteria or meningococcal infections.

Complication of bacterial meningitis

Early complications:

deafness

cerebral edema

seizures

cranial nerve palses

shock

disseminated intravascular trombosis

myocarditis, pericarditis

subdural effusion

brain abscess

Late sequelae

hydrocephalus

cranial nerve palses (including deafness and blindness)

paralysis

mental retardation (including speech delay)

seizures

Sequelae following neonatal meningitis

hydrocephalus

psychomotoric delay (including speech delay)

paresis

blindness

deafness

epilepsy

Bacterial meningitis in neonates

1) Etiology

E.coli (type K1)

Streptoccocus agalactiae group B

other gramnegative bacilli (Pseudomonas, Proteus, Klebsiella, Salmonella, Citrobacter etc.)

Listeria monocytogenes

2) Pathogenesis

The source of infection is mother (genital, urinary and intestinal tracts)

3) Risk factor

Prolonged delivery or every event allowing bacterias from intestine, urinary or genital tract to get in the sterile intrauterine cavity.

Infection or colonisation of mother during delivery

Congenital malformations like encephalocele, meningocele etc.

4) Incidence

- vary from area to area and from state to state 0.14 %....5.0 % depends on socioeconomic conditions, medical care level etc.

5) Clinical features

are not specific

* hypothermia, hyperthermia

* cardiovascular instability

* cyanosis

* seizures, abnormal neonate reflexes (asymetric Moro, absence of sucking reflex etc.)

* full, pulsating fontanell

* hyperbilirubinemia

* rush

* infection in other sites, for example pneumonia

Differencial diagnosis intracranial haemorrhage, neonatal sepsis, congenital disorders

Management of neonatal meningitis

Lumbar puncture

Blood culture

remain the main methods for detecting a causative agent

Monitoring of blood pressure, neurologic and cardiac signs, fluid balance, blood gases

Seizures and haemorhages are often encountered

Cardiovascular supportive care and mechanical ventilation is very often needed

Neonates must be admitted at NICUs !!

Causative therapy of neonatal meningitis

ampicilin + aminoglycoside

ampicilin + cefotaxime

Recommanded doses mg/kg/day : a number of daily doses

AB	age 0-7 days	age 8-28 days
amikacin **	15-20 : 2	20-30 : 3
ampicilin	100-125 : 2	150-200: 3 or 4
cefotaxim	100: 2	150-200: 3 or 4
ceftazidim	60: 2	90: 3
CMP **	25: 1	50: 2
gentamicin **	5: 2	7,5: 3
meticilin	100-150: 2 or 3	150-200: 3 or 4
ticarcilin	150-225: 2 or 3	225-300: 3 or 4
tobramicin **	4: 2	6: 3
vancomycin **	20: 2	30: 3