1. CENTRAL NERVOUS SYSTEM INFECTIONS

3. CNS infection include:- -Meningitis -Meningoencephalitis -Encephalitis -Brain abscess -Subdural empyema -Epidural abscess - Septic venous sinus thrombophlebitis

4. MAJOR ROUTES OF CNS INVASION 1-Hematogenous spread -Respiratssory system – especially lung - abscess -Bacterial endocarditis -GIT and GUT infections -Superficial or deep abscesses

5. 2-Venous spread from pericranial sites of infection -Paranasal sinuses -Middle ear and mastoid -Craniofacial or dental infections

6. 3-Penetrating trauma 4-Entry through defects in skull or spinal column may be congenital or acquired in patients with recurrent meningitis 5-By lymphatic spread to the spinal canal

7. Acute Bacterial Meningitis Definition:- is an acute purulent infection of meninges ((arachnoid- mater and pia-mater)) and subarachnoid space. It associated with CNS inflammatory reaction. When the meninges, the subarachnoid space and the brain parenchyma are involved in the inflammatory reaction called meningoencephalites

9. Epidemiology The annual incidence is > 2.5 cases / 100000 population. Etiology - S. pneumoniae :is the most common cause, about (50%) of adults > 20 years. The predisposing conditions include; pneumococcal pneumonia, sinusitis or otitis media, alcoholism, diabetes, splenectomy and CSF rhinorrhea.

10. -N. meningitidis : for 25% of all cases, between ages of 2 and 20 years. petechial or purpuric rash provide a clue to the diagnosis and can causes septecemia and circulatery collapse. -Group B streptococcus or S. agalactiae 15% of all cases, in neonates and individuals > 50 years.

11. -Listeria monocytogenes accaunt about 10% of all cases,causes meningitis and rhombencephalitis(brainstem encephalitis) in neonates, pregnant women, individuals >60 years and immunocompromised individuals of all ages -H. influenzae accaunt for about 10% all case. It causes meningites in unvaccinated children and adult

12. -Staphylococcus aureus and coagulase negative staphylococci it occur following neurosurgical procedure particularly shunting procedures for hydrocephalus. -Enteric gram-negative bacilli it occur in chronic and debilitating disease such diabetes, cirrhosis, in those with chronic UTI and complicate neurosurgical procedures

13. Pathophysiology 1- the organism colonize in the nasopharyngeal epithelial cells. 2- the bacteria are transported across epithelial cells to the intravascular space.

14. 3- the blood born bacteria reach the ventricular choroid plexus, and directly infect choroid Plexus epithelial cells and gin access to the CSF. 4- The bacteria are able to multiply rapidly within CSF because of the absence of effective host immune defenses

16. Clinical features: Meningitis can present as : -Acute meningitis progress over few hours -Subacute meningitis progress over several days -chronic meningitis progress over four weeks

17. CLINICAL FEATURES The characterstic clinical triad of meningitis are fever, neck stiffness and altered mental state are found in 44% of patients. Although at least two of four finding of headache, fever, neck stiffness or altered mental state are in 97% of patients. Meningism cnnsist of headache, photophobia and neck stiffness, often accompanied by kernig, s sign and brudzinski, s sign.

18. The level of consciousness can vary from lethargy to coma, in two third of patients and absent in patient with viral meningitis. Nausea, vomiting. Focal or generalized seizure in 20 % of patient. Signs of raised intracranial pressure include a deteriorating or reduced level of consciousness, papilledema, dilated poorly reactive pupils, sixth nerve palsies, decerebrate posturing, and the cushing reflex (bradycardia, hypertension, and irregular respiration )

19. Signs of meningeal irritation 1-neck stiffness: resistance to passive forward flexion of the neck. 2-kernig sign: extension at the knee with the hip joint flexed causes spasm in the hamstring muscle. 3-brudzinski sign: passive flexion of the neck causes flexion of hips and knees.

20. Diagnosis of Bacterial meningitis Blood culture, polymerase chain reaction and throat swab should be immediately taken The diagnosis of bacterial meningitis made by lumbar puncture and examination of CSF

21. The need to do MRI or CT scan of brain prior to lumbar puncture if:- 1- The patient has papillodema 2- Focal neurological deficit 3- History of recent head trauma 4- Decreased level of consciousness 5- Seizures

23. Normal CSF Pressure 50-180mm H2O. Color clear Red cell count zero White cell count less than 5 cell/mm³ (of. lymphocyte type). Glucose 40 – 7o mg/dl. 2.22- 3.89mmol/L Protein 15 - 50 mg/dl. 0.15 – 0.5 g/L

24. CSF examination in bacterial meningitis show - Increased CSF pressure>200mm H20 - white blood cells increased between 1000-5000/mm³ with polymorph nuclear leukocytosis - Decreased Glucose <40mg/dl (<2.2mmol/L) and CSF/serum glucose<0.4 - increased protein>45mg/dl (>0.45g/L)

25. - Gram stain is positive in 60-90% of untreated patients. - Culture is positive in>80% of patients - Polymerase chain reaction can detect small number of viable and nonviable organisms in CSF.

26. Treatment of acute bacterial meningitis the goal is to begin empirical antibiotic therapy within 60min of patients arrival in the emergency room before result of CSF Gram's stain and culture. The empirical therapy include a combination of dexamethasone, third generation cephalosporin (e.g ceftriaxone or cefotaxim) and vancomycin plus acyclovir

27. Specific Antimicrobial Therapy 1-N. meningitidis: penicillin G 40000u/kg every 4hours. If resistance cefotaxime 2gm IV every 4 hours or ceftriaxone 2gm every 12 hours, for 7days 2-S. pneumoniae: cefotaxime 2 Gm IV every 4 hours or ceftriaxone 2 Gm IV every 12 hours, or Cefepime 2 Gm IV every 8 hours and Vancomycin 1Gm every 12 hours for 14 days.

28. 3-H. influenzae : cefotaxime, ceftriaxone are the drugs of choice due to the increused incidence of B. Lactamases 4- Listeria monocytogenes: Treated with Ampicillin 2gm IV every 4 hours. Gentamicin is often added 7.5 mg/kg per day every 8 hours. cotrimoxazol 50mg/kg/day IV in 2 divided doses in pencillin-allergic patients. for at least 3weeks

29. 5-Staphylococcus aureus or coagulase – negative staphylococci is treated with nafcillin 100-200mg/kg/day in 4 divided doses. Vancomycin 1gm IV every 12hours for patient allergic to penicillin 6-Gram- Negative Bacillary Meningitis cefotaxime, ceftriaxona and ceftazidime are the drugs of choice, but P.aeruginosa should be treated with ceftazidime,cefepime or meropenem 6 gm IV every 8 hours.

30. Prophylaxis for close contact with patient has N. meningitidis meningitis 1-Adult 600mg rifampicin every 12hours for 4 doses -Children 1month-12years 10mg/kg rifampicin every 12years for 4doses. -Neonate<1month 5mg/kg every 12hours for 4doses

31. 2-Alternatine to refampicin adult can be treated with one dose of ciprofloxacin ((750mg)) or one dose of azithromycin 500mg or one intramuscular dose of ceftriaxone 250mg.

32. The role of dexamethasone It exerts its benefit by inhibiting the synthesis of IL-1 and TNF at the level of mRNA, decreasing CSF outflow resistance,and stabilizing the blood- brain barrier. It is significantly decrease the hearing loss and must be given prior or within the first antiboitics dose

33. Prognosis The risk of death from bacterial meningitis increases with:- 1- decrease level of consciousness on admission. 2- onset of seizures within 24 h of admission. 3- signs of increased ICP. 4- young age (infancy) and age >50

34. 5- the presence of comorbid conditions including shock and /or the need for mechaqnical ventilation. 6- delay in the initiation of treatment. Mortality rate 3-7% for meningitis caused by H. influenzae, N. meningitids or group B streptococci. 15% for that due to L. monocytogenes 20% for S. pneumoniae

35. Common sequelae in 25% include: 1-decreased intellectual function 2-memory impairment 3-siezures 4-hearing loss 5-gait disturbances