Meningitis, pediatrics meningitis ,,,,,,

Meningitis

1. Meningitis BY: Berhane G/her (MD,ped.y3R) Lecture slides for C1 medical students of Adigrat university 2015 1/18/2017 meningitis 1

2. Objectives of the lecture At the end of this lecture,you are expected to: Elaborate the different causes of meningitis Describe clinical manifestations of bacterial meningitis beyond neonatal age Interprete findings of CSF analysis Outline management of bacterial meningitis Describe complications of meningitis Outline the prognosis and prevention 1/18/2017 meningitis 2

3. Outline of presentation Basic anatomy Introduction Bacterial meningitis Predisposing factors Mode of transmission Pathogenesis Pathology 1/18/2017 meningitis 3 8 .Clinical manifestations 9 .Diagnosis 10.Differential diagnosis 11. Treatment 14.Complications 15.Prognosis 16.Prevention 17. References

4. 1.Basic anatomy M eninges are connective tissue layers covering the brain and spinal cord which also form the blood-brain barrier. Dura Arachnoid Pia maters 1/18/2017 meningitis 4

5. 2. introduction Definition Meningitis - Infection of Arachnoid Mater and CSF Subarachnoid Space Cerebral ventricles Encephalitis - indicates brain parenchymal involvement. Meningoencephalitis These are examples of diffuse infection of the CNS. 1/18/2017 meningitis 5

6. Cont… Epidemiology 1.2 million cases worldwide. 135,000 deaths per year worldwide. One of the top 10 most common infections. Can affect all age groups but some are at higher risk. (young age) Male = Female 1/18/2017 meningitis 6

7. Cont… Etiology varies with different age groups and other predisposing factors. Bacterial Infections Viral Infections Fungal Infections (Cryptococcus neoformans) Inflammatory diseases (SLE) Chemicals (pb, Hg) Protozoans Rickettsial Malignancies In general, viral causes > bacterial > fungal & parasitic. 1/18/2017 meningitis 7

8. 3. Bacterial meningitis Etiology Causative organisms vary with patient age, while three bacteria accounting for over three-quarters of all cases: Neisseria meningitidis (meningococcus) Haemophilus influenzae (if very young and unvaccinated) Streptococcus pneumoniae ( pneumococcus) 1/18/2017 meningitis 8

9. Cont… I mmunocompromised Listeria monocytogenes Gram negative bacteria Hospital-acquired infections Klebsiella Escherichia coli Pseudomonas Staphylococcus aureus 1/18/2017 meningitis 9

10. Cont… The most common organisms Neonates and infants under the age of 2months Escherichia coli Pseudomonas Group B Streptococcus Staphylococcus aureus 1/18/2017 meningitis 10

11. Cont… Children over 2 months Haemophilus influenzae type b Neisseria meningitidis Streptococcus pneumoniae Children over 12 years Neisseria meningitidis Streptococcus pneumoniae 1/18/2017 meningitis 11

12. 4.Predisposing Factors Inadequate immunity esp. young age – A major risk factor Recent colonization of Nasopharynx Close contact, crowding, poverty Complement deficiency ( C5-C8 – recurrent meningococcal infection) Splenic dysfunction(Asplenia, Sickle cell anemia) - pneumococcal, H. influenza B, rarely Meningococcal T- lymphocyte defect (congenital, acquired) CSF leak (congenital, acquired) - Meningomyocele (S. aures, Gram –ves) - Basal skull fracture ( pneumococcal) 1/18/2017 meningitis 12

13. Cont… Lack of immunizations Contagious focus – rarely become a source Otitis media Mastoditis Orbital cellulitis Cranial / vertebral osteomyelitis etc 1/18/2017 meningitis 13

14. Cont… STREPTOCOCCUS PNEUMONIAE Children with anatomic or functional asplenia I nfection with HIV - 20- to 100-fold higher risk Otitis media S inusitis Pneumonia CSF otorrhea or rhinorrhea , The presence of a cochlear implant, and chronic graft versus host disease following bone marrow transplantation. 1/18/2017 meningitis 14

15. Cont… NEISSERIA MENINGITIDIS Five serogroups of meningococcus: A, B, C, Y, and W-135 May be sporadic or may occur in epidemics. Epidemic disease, especially in developing countries, is usually caused by serogroup A. Most infections - contact in a daycare facility, a colonized adult family member, or an ill patient with meningococcal disease. Children younger than 5 yr have the highest rates of meningococcal infection. A 2nd peak in incidence occurs in persons between 15 and 24 yr of age. 1/18/2017 meningitis 15

16. Pathogenesis of Meningococcal Infections (Better prognosis) 1/18/2017 meningitis 16

17. Cont… HAEMOPHILUS INFLUENZAE TYPE B Invasive infections occurs primarily in infants 2 mo–2 yr of age peak incidence is at 6–9 mo of age, and 50% of cases occurs in the 1st yr of life. Incompletely vaccinated children, and Blunted immunologic responses to vaccine (children with HIV infection) 1/18/2017 meningitis 17

18. 5.Mode of transmission Person to person contact via respiratory secretions or droplets Maternal flora – during the first months of life 1/18/2017 meningitis 18

19. 6.PATHOGENESIS Most commonly results from hematogenous dissemination of microorganisms from a distant site of infection. Bacteremia usually precedes meningitis or occurs concomitantly. Bacterial colonization of the nasopharynx with a potentially pathogenic microorganism is the usual source of the bacteremia. Uncommonly - meningitis occurs by direct extension from nearby focus 1/18/2017 meningitis 19

20. Cont… Attachment of pathogenes to mucosal epithelial cell through their pilli Penetrate the mucosa and enter into the circulation Bacterial survival in blood stream enhanced by capsules (interfer opsonic phagocytosis) Opsonic phagocytosis may be impaired In young infant – lack of preformed IgM or Ig G In immunodeficient and with complement defect 1/18/2017 meningitis 20

21. Cont… Bacteria enter CSF through choroid plexus of the lateral ventricle and meninges Complement and antibody concentration in the CSF is inadequate: Rapid multiplication 1/18/2017 meningitis 21

22. bacterial colonization of nasopharynx attach to mucosal epith. cell receptors by pili breach mucosa& enter circulation to CSF through choroid plexus of ventricles extracerebral CSF & subarachinoid space bacterial proliferation inflammation-cytokines large capsules interfere phagocytosis 1/18/2017 meningitis 22

23. Cont… Bacterial toxins and Inflammatory mediators are released. Bacterial toxins Lipopolysaccharide, LPS Teichoic acid Peptidoglycan Inflammatory mediators Tumor necrosis factor, TNF Interleukin-1, IL-1 Prostaglandin E2, PGE2 1/18/2017 meningitis 23

24. Cont… Bacterial toxins and inflammatory mediators cause suppurative inflammation. Inflammatory infiltration Increased Vascular permeability Tissue edema Blood-brain barrier alteration Thrombosis 1/18/2017 meningitis 24

25. 7.PATHOLOGY Meningeal exudates in different part of the brain Ventriculitis (purulent material within the ventricles) Infiltrates extending to the subintimal region of the small arteries and veins = Vasculitis = Thrombosis of small cortical veins 1/18/2017 meningitis 25

26. Cont… Cerebral infarction - microscopic / entire hemisphere Inflammation of spinal nerves and roots Inflammation of the cranial nerves Increased ICP cytotoxic cerebral edema vasogenic cerebral edema interstitial cerebral edema The SIADH secretion may produce excessive water retention and potentially increase the risk of elevated ICP 1/18/2017 meningitis 26

27. Cont… Hydrocephalus is a common complication of meningitis. Communicating hydrocephalus , most often Obstructive hydrocephalus Raised CSF protein level – due to increased vascular permeability of the blood-brain barrier and the loss of albumin-rich fluid from the capillaries and veins - subdural effusion Hypoglycorrhachia (reduced CSF glucose levels) - is due to decreased glucose transport by the cerebral tissue. 1/18/2017 meningitis 27

28. Cont… Inflammatory process may result in cerebral edema and damage of the cerebral cortex. Conscious disturbance Convulsion Motor disturbance Sensory disturbance and later psychomotor retardation 1/18/2017 meningitis 28

29. 8.Clinical manifestation More often, meningitis is preceded by several days of systemic infection manifestations less common, sudden onset with rapidly progressive manifestations of shock, purpura, DIC, and progressing to coma or death within 24 hr. 1/18/2017 meningitis 29 Meningococcemia with meningitis

30. Cont… The signs and symptoms of meningitis are related to: Nonspecific findings of systemic infection and Manifestations of meningeal irritation. 1/18/2017 meningitis 30

31. Nonspecific findings 1/18/2017 meningitis 31

32. Nonspecific findings 1/18/2017 meningitis 32

33. Cont… Meningeal irritation sign is found because the spinal nerve root is irritated. Neck stiffness Positive Kernig ’ s sign Positive Brudzinski ’ s sign in those younger than 12–18 mo, Kernig and Brudzinski signs are not consistently present. 1/18/2017 meningitis 33

34. Cont… Kernig ’ s sign Vladimir Kernig was a Russian physician Kernig sign is present if the patient, in the supine position with the hip and knee flexed at 90º, cannot extend the knee more than 135º and/or there is flexion of the opposite knee. 1/18/2017 meningitis 34

35. Cont… Brudzinski’s signs Jozef Brudzinski was a Polish physician Symphyseal sign Cheek phenomenon Contralateral reflex Neck sign- With the patient lying on the back: if the neck is forcibly bended forward, there occurs a reflexive flexion of the knees. 1/18/2017 meningitis 35

36. Cont… Increased intracranial pressure Headache, Projectile vomiting Hypertension ,Bradycardia Bulging fontanel Cranial sutures diastasis Coma ,Decerebrate rigidity Cerebral hernia Cranial nerve palsy Oculomotor nerve Abducen nerve - usually the first nerve to be compressed focal neurologic signs occur in 10-20%- ↑to 30% in pneumococcal meningitis 1/18/2017 meningitis 36

37. Cont… Seizures Seizures occur in about 20%-30% of children with bacterial meningitis. Seizures is often found in haemophilus influenzae and pneumococcal infection. Seizures is correlative with the inflammation of brain parenchyma, cerebral infarction and electrolyte disturbances. 1/18/2017 meningitis 37

38. Cont… - In some children, particularly young infants under the age of 3 months, symptom and signs of meningeal inflammation may be minimal. Fever is generally present, but its absence or hypothermia in a infant with meningeal inflammation is common. Only irritability, restlessness, dullness, vomiting, poor feeding, cyanosis, dyspnea, jaundice, seizures, shock and coma may be noted. Bulging fontanel may be found, but there is not meningeal irritation sign. 1/18/2017 meningitis 38

39. 9.DIAGNOSIS Confirmed by CSF analysis – lumbar puncture Contraindications for an immediate LP include: Evidence of increased ICP (other than a bulging fontanel) Severe cardiopulmonary compromise requiring prompt resuscitative measures for shock or in patients in whom positioning for the LP would further compromise cardiopulmonary function; and Infection of the skin overlying the site of the LP. Thrombocytopenia is a relative contraindication for LP. 1/18/2017 meningitis 39

40. Cont… Neonate Infants and older children PRESSURE (mm H 2 O) 50–80 50–80 LEUKOCYTES (mm 3 ) < 30 <5 WBC differential <60% neutrophils ≥75% lymphocytes 0% neutrophil PROTEIN (mg/dL) <90 20–45 GLUCOSE (mg/dL) 70-80 >50 (or 75% serum glucose) 1/18/2017 meningitis 40 Normal values of CSF

41. Cont… CSF – Findings in meningitis Usually in bacterial meningitis the WBC is >1000/mm3 ( 75-95% neutrophils) Cell count in CSF might be less than 100 Neutropenia Gram negatives Early disease The CSF become turbid when the leukocyte count exceeds 200- 400/mm3. 1/18/2017 meningitis 41

42. Cont… CSF – Findings in meningitis Pleocytosis may be absent in severe overwhelming sepsis and meningitis Gram stain is positive in 70-80% of cases Blood culture is positive in 80 – 90% of cases In failed/traumatic LP – repeat after 6 – 8 hrs at a higher interspace . In traumatic CSF: Gram stain, culture, and glucose level may not be influenced . Latex agglutination – partially treated meningitis 1/18/2017 meningitis 42

43. Further CSF Finding Comparison 1/18/2017 meningitis 43 Pathogen WBC’s % Neut Glucose Protein + Gram present Pyogenic >500 >80 Low >100 ~70 Listeria Monoctyogenes >100 ~50 Normal >50 ~30 Partial Treated Pyogenic >100 ~50 Normal >70 ~60 Aseptic, Often Viral 10 – 1, 000 Early: >50 Late: <20 Normal <200 N/A TB 50-500 <30 Low >100 Rare Fungal 50-500 <30 Low Varies High in Crypto Banmberger, David, Diagnosis, Initial Management, and Prevention of Meningitis Am Fam Physician.  2010 Dec 15;82(12): 1491-1498.

44. Cont… ↑ opening pressure - elevated protein- 100-500mg/dl, reduced glucose Other lab findings ↑ total WBC count Anemia, low platelet count - DIC 1/18/2017 meningitis 44

45. 10.Differential Diagnosis Aseptic meningitis refers to patients who have clinical signs and laboratory evidence for meningeal inflammation with negative routine bacterial cultures Infectious or non infectious Enteroviruses Herpes Simplex virus (HSV) HIV Lymphocytic Choriomeningitis virus (LCM) Mumps Other 1/18/2017 meningitis 45

46. Cont… Viral meningoencephalitis - less ill classic CSF profile: - normal/mild inc. opening pressure - mononuclear cells, <1000/mm3 - protein usu. 50-200mg/dl - glucose- normal. Partially treated bacterial meningitis - cells 5-10000/mm3, glucose normal/decreased, culture negative. 1/18/2017 meningitis 46

47. Cont… Enteroviral Meningitis Enteroviruses are thought to be the most common cause of viral meningitis Are a diverse group of RNA viruses including Coxsackie A & B, Echoviruses, and polioviruses. Account for >50% of cases and approximately 90% of cases in which a specific etiologic agent is identified. Majority of cases are in children or adolescents, but patients of any age can be affected. Transmitted primarily by fecal-oral route, but can also be spread by contact with infected respiratory secretions. 1/18/2017 meningitis 47

48. Cont… Tuberculous meningitis Usually occurs early, 2 – 6 months after the infection Suspected in : Fever persisting for 14 days and above Fever persisting for more than 7 days and there is a family member with tuberculosis A chest x ray suggests tuberculosis The patient remains unconscious Children with known or suspected HIV infection (cryptococcal meningitis also – Indian ink) CSF continue to have <500 cells/ml,mostly lymphocytes, elevated proteins (0.8-4g/l) and low glucose (<40mg/dl) 1/18/2017 meningitis 48

49. 11.Treatment Immediate treatment of associated multiple organ system failure , shock, and acute respiratory distress syndrome is also indicated. Drugs administered IV throughout the course of treatment Dose should be antimeningeal Reinstall the antibiotic based on culture and drug sensitivity Until the culture result arrives – emperical Rx If there are signs of increased ICP or focal neurologic findings, antibiotics should be given without performing an LP 1/18/2017 meningitis 49

50. Cont… Initial Antibiotic Therapy Crystalline penicillin= loading dose of 250,000 IU/kg IV stat followed by 500,000IU/Kg/24hrs IV divided in 8 doses PLUS Chloramphenicol = 50mg/Kg IV stat followed by 100mg/Kg/day IV Q 6 hourly L.monocytogenes – ampicillin (200 mg/kg/24 hr) given every 6 hr. Immunocompromised and gram-negative meningitis ceftazidime or an aminoglycoside 1/18/2017 meningitis 50

51. Cont… Duration Of Antibiotic Therapy Depends on the etiology but in general course of treatment ranges between 10 – 14 days S.pneumoniae- penicillin (400,000 U/kg/24 hr) 10-14 days N.meningitidis- penicillin (400,000 U/kg/24 hr) 5-7 days HIB-chloramphenicol 7-10 days Gram negatives - 3 wk or for at least 2 wk after CSF sterilization 1/18/2017 meningitis 51

52. Cont… Supportive care Control fever Maintain a clear airway Turn the child every 2 hours Fluid management Half to 2/3 rd of the maintainance Management of increased ICP Hyperventilation Mannitol/lasix Seizure should be treated with IV diazepam or phenytoin (if not controled) Strict follow up – esp. during the first 72 hours 1/18/2017 meningitis 52

53. Cont… Corticosteroids Rapid killing of bacteria releases toxic cell products. → cytokine mediated infl. Response, edema & neutrophilic response. - This will lead to additional neurologic injury with worsening of CNS Sx: - Dexamethasone- 0.15mg/kg/dose q6hr-2days (benefit max if given 1-2 hr before antibiotics) - Decreases permanent auditory nerve damage. - H. influenzae +/- pneumococcus 1/18/2017 meningitis 53

54. 12 . C omplications Acute -Seizure ↑ ICP CN palsies, cerebral & cerebellar herniation; Subdural effusion- in 10-30%, (asymptomatic in 85-90% of cases, esp in infants) symptoms- bulging fontanel,enlarging HC, emesis, Sz, fever, cranial transillumination aspiration indicated in ↑ ICP/decreased LOC 1/18/2017 meningitis 54

55. Cont… SIADH (Cerebral hyponatremia) Restriction of fluid supplement of serum sodium Diuretic Pericarditis, arthritis- due to bacterial dissemination, or immune complex deposition. DIC 1/18/2017 meningitis 55

56. Cont… Chronic complications Mental retardation Spasticity and/or paresis Seizures 1/18/2017 meningitis 56

57. 13.Prognosis MR- <10%- highest in pneumococcal severe neurodevelopmental abn.-in 10-20% Poor prognosis in: . < 6mo of age . >1mill.CFU bact./ml . Seizure for >4 days into Rx . Coma/ focal neurologic sign at admission . Absence of pleocytosis . Pneumococcal meningitis 1/18/2017 meningitis 57

58. 14.Prevention Vaccination and chemoprophylaxis N.meningitidis- Rifampin 10mg/kg/dose q12 hr for 2 days –for all close contacts of patients with meningococcal meningitis, Quadrivalent vaccine - A,C,Y,W135 for high risk children >2yr HIB- Rifampin 20mg/kg/day,once, 4 days for all household contacts Conjugate vaccine (Pentavalent)- from 2mo of age 1/18/2017 meningitis 58

59. Cont… S.pneumoniae PCV 10 – from 2mo of age No chemoprophylaxis 1/18/2017 meningitis 59

60. 15.References Nelson text book of pediatrics,19 th ed. Nelson essentials of pediatrics, 5 th ed. Current Pediatric diagnosis and treatment,18 th ed. Rudolph’s pediatrics, 21 st ed 1/18/2017 meningitis 60