2015-03-22

1

Meningitis

dr hab. n. med. Sylwia Kołtan

DEFINITIONS

• meningitis – is an inflammation of the meninges (membranes surrounding the central nervous system: dura mater, arachnoid mater and pia mater) - is recognized on the basis of an increased number of leukocytes in the CSF

2015-03-22

2

DEFINITIONS

• bacterial meningitis - meningitis with the presence of bacteria in the CSF

• aseptic meningitis - inflammation of the meninges without the presence of bacteria in the CSF

• meningitis and encephalitis - inflammation of both meningitis and brain tissue; the presence or absence of normal brain function distinguishes meningitis from encephalitis

PREDISPOSING FACTORS

Host Environmental

age - the youngest children and the elderly

collectivization (nurseries, kindergartens)

congenital and acquired immunodeficiency

sick in the family environment

cranial trauma

maternal cervical-vaginal colonization by potentially

pathogenic bacteria (neonatal infection)

sinusitis, otitis media, mastoiditis, inflammation of the bones of the skull

being in a hospital environment

neurosurgical procedures, ventriculoperitonea shunt

meningomyelocele

2015-03-22

3

RISK FACTORS IN NEONATS • birth asphyxia

• unclean vaginal examination

• foul smelling liquor

• prolonged labor (>24 h)

• preterm and low birth weight neonates

• prolonged ruptures of membranes (>18 h)

• maternal pyrexia

Causes of neonatal infections

2015-03-22

4

ETIOLOGY of MENINGITIS

infectious agents

bacteria

viruses

rickettsiae

spirochetes

mycoplasma

fungi

protozoa

nematodes

tapeworms

noninfectious factors

cancer

autoimmune diseases

Injuries

poisoning

drugs

autoimmune diseases

unknown

ASEPTIC MENINGITIS - ETIOLOGY

EB Medicine

2015-03-22

5

Clinical Pediatric Emergency Medicine Published June 1, 2013. Volume 14, Issue 2. Pages 146-156. © 2013.

Medical_- Labs (Medical Laboratories Portal)

2015-03-22

6

Clinical Pediatric Emergency Medicine Published June 1, 2013. Volume 14, Issue 2. Pages 146-156. © 2013.

IMPORTANT!

Can not be ignored microorganism detected in cerebrospinal fluid as a cause of meningitis due to unusual age or unique population! We treat the disease, and then look for the factors that lead to unusual infections!!!

2015-03-22

7

Questions to students

1. Why etiology of meningitis in children is changing?

Questions to students

2. Why polysaccharide encapsulated bacteria were the most common cause of meningitis?

2015-03-22

8

VIRAL MENINGITIS

VIRAL MENINGITIS - PATHOGENESIS

2015-03-22

9

VIRAL MENINGITIS

1. aseptic meningitis caused by enteroviruses is most common in the summer month, is more common than bacterial meningitis, and generally has benign clinical course; exceptions: neonates and patients with agammaglobulinemia

2. aseptic meningitis or meningoencephalitis resulting from herpes simplex virus (HSV) can have serious neurologic sequelae, and empiric therapy with acyclovir is warrented if the clinical course and workup are suggestive of HSV

BACTERIAL MENINGITIS – five key points for primary care

1. The incidense of bacterial meningitis has declined significantly over the past 30 years thanks to routine vaccination of children and selected adults; primary care clinicians have an important role in patient education regarding the importance of vaccination

2015-03-22

10

The Lancet. Infectious diseases: volume 14, No. 9, p813–819, September 2014

BACTERIAL MENINGITIS – INCIDENCE

2015-03-22

11

BACTERIAL MENINGITIS – five key points for primary care

2. Bacterial meningitis should be treated with broad-spectrum antibiotics immediately to prevent rapid clinical deterioration and a poor outcome, with subsequent antibiotic adjustments based on CSF culture results.

3. Chemoprophylaxis for close contacts of patients with Haemophilus influenzae and meningococcal meningitis is an important strategy for prevention of bacterial meningitis.

4. Dexamethasone therapy before or with the initial dose of antibiotics is recommended in children and adults.

5. Patients with bacterial meningitis should be admitted to the intensive care unit for close monitoring.

BACTERIAL MENINGITIS – PATHOGENESIS

2015-03-22

12

BACTERIAL MENINGITIS - PATOPHYSIOLOGY

BACTERIAL MENINGITIS –CLINICAL MANIFESTATIONS

Neonates Infants Children>1 year of age

fever fever fever

hypothermia irritability headache

somnolence somnolence vomiting

irritability bulging fontanelle photophobia

jaundice meningeal signs confusion

breathing problems skin lesions somnolence

vomiting vomiting hyperaesthesia

diarrhea seizures meningeal signs

neurological symptoms (seizures, confusion,

focal signs)

disturbances of consciousness

seizures

bulging fontanelle skin lesions

2015-03-22

13

BACTERIAL MENINGITIS –CLINICAL MANIFESTATIONS

BACTERIAL MENINGITIS –CLINICAL MANIFESTATIONS

2015-03-22

14

BACTERIAL MENINGITIS –CLINICAL MANIFESTATIONS

BACTERIAL MENINGITIS – MENINGEAL SIGNS

Opisthotonic posturing

2015-03-22

15

BACTERIAL MENINGITIS – MENINGEAL

So, when we can suspect bacterial meningitis?

Clinical Pediatric Emergency Medicine Published June 1, 2013. Volume 14, Issue 2. Pages 146-156. © 2013.

WATERHOUSE-FRIDERICHSEN SYNDROME

2015-03-22

16

WATERHOUSE-FRIDERICHSEN SYNDROME

The bacterial infection leads to massive hemorrhage into one or (usually) both adrenal glands. It is characterized by overwhelming bacterial infection meningococcemia leading to massive blood invasion, organ failure, coma, low blood pressure and shock, disseminated intravascular coagulation (DIC) with widespread purpura, rapidly developing adrenocortical insufficiency and death.

It occurs mainly in children younger than 10 years of age.

Prevention: vaccination against meningococcus and pneumococcus

TUBERCULOUS MENINGITIS

• especially common in young children and people with untreated HIV infection

• it kills or disables roughly half of everyone affected

• childhood disease can be prevented by vaccination and by giving prophylactic isoniazid to children exposed to infectious adults

• diagnosis is difficult because clinical features are non-specific and laboratory tests are insensitive, and treatment delay is the strongest risk factor for death

• large doses of rifampicin and fluoroquinolones might improve outcome, and the beneficial effect of adjunctive corticosteroids on survival might be augmented by aspirin

2015-03-22

17

TUBERCULOUS MENINGITIS

Lancet Neurology,, 2013, 12 (10), 999-1010

TUBERCULOUS MENINGITIS

Lancet Neurology,, 2013, 12 (10), 999-1010

2015-03-22

18

TUBERCULOUS MENINGITIS

MENINGITIS: DIAGNOSIS

THE CURRENT CRITERION STANDARD IN ESTABLISHING THE DIAGNOSIS OF MENINGITIS IN CHILDREN IS OBTAINING CSF. IN CASES OF DOUBT, THE TEST SHOULD BE PERFORMED ALWAYS

Cerebrospinal fluid should be examined in the content:

protein

glucose

cell count and differential

Gram stain

culture

PCR to look for viral genomes or mycobacterial genomes

2015-03-22

19

LUMBAR PUNCTURE

Journal of Emergency Medicine, Vol. 46, No. 1, pp. 141–150, 2014

LUMBAR PUNCTURE

2015-03-22

20

Journal of Emergency Medicine, Vol. 46, No. 1, pp. 141–150, 2014

LUMBAR PUNCTURE

Journal of Emergency Medicine, Vol. 46, No. 1, pp. 141–150, 2014

LUMBAR PUNCTURE

2015-03-22

21

CEREBROSPINAL FLUID

Journal of Emergency Medicine, Vol. 46, No. 1, pp. 141–150, 2014

MENINGITIS DIAGNOSIS

Clinical Pediatric Emergency Medicine Published June 1, 2013. Volume 14, Issue 2. Pages 146-156. © 2013.

2015-03-22

22

MENINGITIS: OTHER TESTS

• bacteriological testing other materials (blood cultures, urine cultures, the study of middle ear effusion)

• virological analysis other materials

• markers of inflammation (CBC, ESR, CRP)

• tuberculin skin test in cases of suspected tuberculous meningitis

• neurological and ophthalmological examination

MENINGITIS – HELPFUL TESTS IN DETECTED EARLY AND LATE COMPLICATIONS

• level of electrolytes in the blood, urine and plasma osmolality (syndrome of inappropriate antidiuretic hormone hypersecretion – SIADH - detection and diabetes insipidus)

• coagulogram - with signs of bleeding diathesis

• ophthalmic and neurological examination

• audiometry (detection of sensorineural hearing loss)

• imaging (anterior fontanelle ultrasonography, CT, MRI) with suspected hydrocephalus, hygroma subdurale, cerebrovascular thrombosis, brain abscesses

2015-03-22

23

MENINGITIS –EARLY COMPLICATIONS

• septic shock

• seizures

• disseminated intravascular coagulation (DIC)

• acute hydrocphalus

• cerebral hemorrhages

• syndrome of inappropriate antidiuretic hormone secretion (SIADH)

• diabetes insipidus

• intracranial hypertension syndrome

• brain abscess

• subdural empyema

• encephalopathy

• cranial nerve palsies

• subdural hygroma

• prolonged fever

• infarction of the brain or spinal cord

MENINGITIS –LATE COMPLICATIONS

• for all causes of bacterial meningitis, median risk of major and minor sequelae is 20 %

• major sequelae:

death (neonates ~ 20%, older < 10%)

hydrocephalus

bilateral hearing loss

major visual impairment

seizure disorder

severe cognitive disability (intelligencequotient [IQ] <70)

severe motor impairment

The Internet Journal of Infectious Diseases, 9, 2 (Namani S and all)

2015-03-22

24

MENINGITIS –LATE COMPLICATIONS

• minor sequelae:

less severe learning difficulties

unilateral hearing problems

mild visual deficits

minor motor disability

MENINGITIS –LATE COMPLICATIONS

• in summary:

hearing loss - the most common major sequelae

motor deficits and seizure disorders - also common

twenty percent of the children - more than one sequela

risk of sequelae is about twice as high in children under 5

variability in risk of sequelae is wide when delineated by pathogen, confirming pneumococcal meningitis as the most devastating infection, with a median risk of 35% for major or minor sequelae; in contrast, risk is about 14.5% for major or minor sequelae following Hib meningitis, and 9.5% following meningococcal

2015-03-22

25

MENINGITIS - TREATMENT

Meningitis treatment begins immediately after the diagnostic LP, without waiting for the results of the meningeal fluid analysis!

Antibiotics used as the first should have a sufficiently broad spectrum of activity, including all species of bacteria that

cause BM in a particular age group!

After receiving the results of bacteriological tests modification of the treatment from empirical to targeted!

The choice of antibiotic should take into account the penetration of the blood brain barrier!

MENINGITIS - TREATMENT

There appears to be a relatively convincing

benefit in preserving hearing using corticosteroids (GC) in

Hib meningitis, especially if given with the initial doses

of antibiotics.

Use of GC in TB meningitis may also improve outcomes.

However, there is little evidence to suggest use in

meningitis caused by other pathogens.

Given the frequent difficulty of

predicting pathogenic etiology at commencing antibiotics

(especially in low-vaccination regions where Hib

may still be common), as well as a low risk of side

effects for a short duration of steroids, a number of

guidelines and physicians still recommend the use of

steroids alongside empirical antibiotic treatment in

suspected bacterial meningitis

2015-03-22

26

CASE RAPORT

1. The Boy J.Sz. born on 14.01.2001r.

2. Parents: mother 29 ys., father 23 ys, healthy

3. Urban environment, good social conditions

4. Boy born with I pregnancy, physiological delivery on time, birth weight 3780 g, 8/9 Apgar points

5. In the 5 days of life from the evening:

panic cry from the spasms, tension leg

periodically apathetic

anorexia

body temperature high (in the rectal 39o C)

according to the mother infrequent urination

2015-03-22

27

1. On admision:

general condition medium, gradually deteriorated to severe

listless, hyperaesthesia, high pitched cry

jaundice

opistotonus, upper limb spasticity

sunken fontanelle

tachycardia and tachypnea

hepatosplenomegaly

CASE RAPORT

CASE REPORT

Results of laboratory tests:

CSF analysis:

turbid CSF

protein 343 mg% ( )

Pandy reaction (+++); N. Appelt (+)

Leukocyte count: 60 928/3= 20 309 ( )

glucose 18 mg% ( )

2015-03-22

28

Results of laboratory tests :

1. CBC:

RBC 5,75 M/ul

Hg 20 g%

Ht 63,6%

WBC 13,82 K/ul

platelets 208 K/ul

WBC differential: band 3%, neutrophils 51%, lymphocytes 44%, monocytes 2%

CASE REPORT

Results of laboratory tests :

1. Blood acd base balance:

pH 7,35

pCO 2 33,9

BE (-5,1)

HCO 3 18,5

pO2 47,9

O2 SAT 81,4%

CASE REPORT

2015-03-22

29

Results of laboratory tests :

1. CRP 111,5 mg/l

2. total bilirubin 10,7 mg/dl, conjugated 0,63 mg/dl

3. glucose we krwi 127 mg%

4. electrolytes: Na 146,1 mmol/l; K 5,12 mmol/l; Cl 107,6 mmol/l Ca 8,8 mg% Mg 0,94

5. Coagulation test: wsk. protrombinowy 45,8%, APTT 49,4 s, PT 29,1s; INR 2,1

CASE REPORT

Results of laboratory tests :

1. Microbiology culture tests:

CSF culture: E. coli (S: cephalosporins 2 i 3 generation, aminoglikosides, trimetoprim sulphametoxazol)

blood culture: E. Coli

urine culture: E. Coli 5000/ml

CASE REPORT

2015-03-22

30

Treatment:

antibiotics: cefotaxime, ampicillin, netilmicin

anti-brain swelling medications: dexamethasone, mannitol

treatment of coagulopathy: FFP

immunoglobulins: pentaglobin

CASE REPORT