Meningitis.pptx approach to meningitis treatment

Meningitis

1. Meningitis Prepared by: Anter Aljilany MSc. Neurology MD candidate Faculty of Medicine-Cairo University Aug.2024

2. Agenda Introduction. Clinical presentation. CSF testing. Etiology. Indications for Imaging. Treatment. Complications. Prognosis. Prevention. Viral meningitis. Parasitic meningitis. Chronic meningitis. Mollaret Meningitis.

3. Introduction Infections must be considered in the differential diagnosis for any possible neurological presentation: Cerebral like headache, seizures, focal deficits, encephalopathy or cranial neuropathy. Myelopathy Radiculopathy and peripheral neuropathy. Neuromuscular junction disorder. Myopathy. Neurological infections can be caused by any category of microbes: viruses, bacteria, fungi, or parasites.

4. A 58-year-old man with no past medical history presented with 3 days of fever and 1 day of confusion . Two days earlier, he had been treated with IM penicillin for presumed pneumonia and discharged, although he remained febrile and fatigued. He had no headache, nausea, or vomiting. Examination revealed a temperature of 39°C , obtundation, nuchal rigidity, and a positive Brudzinski sign but no focal deficits. Blood cultures were collected. Brain CT without contrast was unremarkable. And he was admitted to isolation room in the ICU. What is the diagnosis and possible etiology? CASE SCENARIO

5. Answer: This case is typical for meningitis. Comment: Meningitis is an inflammation of the meninges which is either septic or aseptic. Infective causes include bacterial, viral, fungal or parasitic. While noninfective include sarcoidoisis , malignancy ( meningitidis carcinomatosis), autoimmune diseases, chemical meningitis (rupture dermoid) or drug induced.

6. Symptoms: F ever. H eadache. S tiff neck. C hange in mental status. Other symptoms include photophobia, nausea, vomiting, seizure, cranial neuropathies. The clinical presentation

7. Signs of meningismus include : Nuchal rigidity. Kernig sign. Brudzinski neck sign sign . Brudzinski leg sign. Lassegue sign. Amoss ( Hoyne ) sign (Tripod position). The clinical presentation

8. Amoss sign (Tripod sign)

9. A 58-year-old man with no past medical history presented with 3 days of fever and 1 day of confusion . Two days earlier, he had been treated with IM penicillin for presumed pneumonia and discharged, although he remained febrile and fatigued. He had no headache, nausea, or vomiting. Examination revealed a temperature of 39°C , obtundation, nuchal rigidity, and a positive Brudzinski sign but no focal deficits. Blood cultures were collected. Brain CT without contrast was unremarkable. And he was admitted to isolation room in the ICU. What is the next step in management of this patient? CASE SCENARIO

10. Answer: ( CSF examination and Biofire film array meningitis/encephalitis panel). Collects four tubes. Start empirical antibiotics immediately (LP should not delay antibiotic initiation) Our patient CSF examination showed: Turbid colour . Protein : 435 mg/dL. WBCs : 2350 (68% polymorphonuclear leukocytes). Glucose : 18 mg/dL with a serum glucose of 85 mg/dl.

11. CSF testing in diagnosis of meningitis CSF glucose: The ideal is to take blood sample 1 hour before lumbar puncture. Measure random blood glucose and CSF glucose ( Normal CSF glucose is more than 40% of blood glucose level. Hypoglycorrhachea : less than 40% of blood glucose level (or less than 40mg/dl). Its causes include bacterial, TB, Fungal, inflammatory ( e.g , sarcoidosis), malignancy and some viral infections ( e.g , West Nile, HIV, CMV, enteroviruses).

12. CSF glucose: Mechanisms of low CSF glucose in bacterial meningitis: Impaired glucose transporter system Leukocytes utilization of glucose Bacterial consumption of glucose. N.B Unreliable in diabetic patient (frequent swings of blood glucose).

13. CSF protein : Normal value less than 35 mg/dl Elevated in meningitis due to disruption of BBB. CSF protein mg/dl Type of meningitis ≥ 100 Bacterial ≤120 Viral ≥ 50 Granulomatous

14. CSF cellularity: Normal CSF cells is 0-5 cell/mm3 . Dominant cells CSF cells Type of meningitis PMNs 100-60,000 Bacterial Lymphocytes Less than 100 (rarely less than 1000) Viral Early PMNs, late Lymph. Less than 500 Granulomatous N.B CSF eosinophilia : parasitic or fungal infections, hypereosinophilic syndrome, granulomatosis with polyangiitis, Hodgkin disease, and glioblastoma invading the meninges

15. Etiology of bacterial meningitis Common organisms Patient group GBS, E.coli, L. monocytogens Neonate E. coli, S. agalactiae, and L. monocytogenes Infants S. Pneumoniae , N.meningitidis , H.influenza Adults and children L.monocytogenes , G- ve bacilli Age above 65yr, immunocompromised, Alcoholic Staphylococcus species Neurosurgery, Trauma Pseudomonas and G- ve bacilli Hospital acquired Listeria may also cause rhombencephalitis which is presented by cranial nerve palsies, ataxia and other cerebellar signs, and a decreased level of consciousness.

16. N. meningitidis N. meningitidis can lead to Waterhouse Friderichsen syndrome (septic shock, adrenal insufficiency, purpura, DIC and multiple organ failure which can be fatal within hours). Eculizumab (complement 5 inhibitor used in MG and NMO) is associated with a 1000-fold to 2000-fold increased incidence of meningococcal meningitis. Administration of the meningococcal vaccine is recommended before beginning eculizumab treatment.

17. Purpura in meningococcemia

18. CSF Gram stain, AFB and culture. CSF serology (antigen or antibodies IgM, IgG). Molecular diagnostics ( PCR or Metagenomic Next-Generation Sequencing). Microbiological diagnosis

19. PCR based assay: The BioFire FilmArray Meningitis/Encephalitis (ME) Panel is a multiplex PCR platform that evaluates for several common meningitis pathogens.

20. The BioFire FilmArray Meningitis/Encephalitis (ME) Panel

21. Indications of neuroimaging in patient with meningitis Papilledema. Signs of lateralization, fits or DCL. Known case of brain tumor or systemic cancer. Immune deficiency .

22. Axial postcontrast T1-weighted MRI demonstrating leptomeningeal and ependymal enhancement

23. Bacterial meningitis is a neurologic emergency and is universally fatal if untreated. Outcomes are worse with delayed treatment. Empiric antibiotics should be initiated as soon as the diagnosis of bacterial meningitis is considered, guided by age and past medical history. Treatment of bacterial meningitis

24. Empiric Antibiotic Therapy of Bacterial Meningitis Treatment Clinical context Vancomycin+ceftriaxone+dexamethasone Vancomycin 15-20 mg/kg IV every 8-12 hours (not to exceed 2 g per dose or a total daily dose of 60 mg/kg AND Ceftriaxone 2 g IV every 12 hours or cefotaxime 2 g IV every 4-6 hours AND Dexamethasone 10 mg IV every 6 hours for 4 days Adults Above treatment plus ampicillin 2 g IV every 4 hours (for Listeria) or, If penicillin allergy, trimethoprim-sulfamethoxazole 10-20 mg/kg/d (trimethoprim component) IV divided every 6-12 hours. Elderly (≥50) Alcoholic or immunosupression Ceftriaxone 50mg/kg IV every 12 hours or cefotaxime 100mg/kg IV every 8 hours AND Vancomycin 15 mg/kg IV every 6 hours PLUS Dexamethasone 0.15 mg/kg IV every 6 hours for 2 days Children and infants

25. Empiric Antibiotic Therapy of Bacterial Meningitis Treatment Clinical context Ampicillin plus aminoglycoside or ampicillin plus cefotaxime Neonate (Full term) Vancomycin plus ceftazidime (2gm Q8hr) plus ampicillin Hospital acquired meningitis, traumatic or neurosurgery

26. Antibiotic choice according to type of bacteria Drug of choice Bacteria type Vancomycin plus ceftriaxone or cefotaxime Streptococcus pneumoniae Ampicillin or penicillin G+/-aminoglycoside Listeria monocytogenes Ceftriaxone or cefotaxime Neisseria meningitidis Vancomycin/ linezolid Staphylococcus Ampicillin or penicillin G+/-aminoglycoside Group B Streptococcus Ceftiaxone or cefotaxime Haemophilus influenzae Ceftazidime or cefepime +/- aminoglycoside Pseudomonas aeroginosa N.B Ampicillin (L. monocytogens ) must be added to any patient with meningitis who is above age 50yrs, alcoholic or immunocompromised. Shift to meropenem 2gm/8hrs if there is no improvement within 2 days.

27. Role of dexamethasone Dexamethasone IV should be given 0-30 minutes before antibiotics , for 4 days. It decrease adhesion & inflammation by inhibiting IL-1 & TNF. Advantage: To reduce incidence of deafness due to S. pneumonia. To reduce neurological sequelae in children with H. influenza.

28. Duration of Antibiotic Therapy of Bacterial Meningitis 10-14days Streptococcus pneumoniae 7-10 days N. meningitidis H. influenza variable Staphylococcus species 21days Gram-negative bacilli L. monocytogens 14-21 days Group B Streptococcus

29. Complications of meningitis Long term complications Short term complications Hearing loss (the most common 10%) Subdural effusion and empyema (20-39%) Cognitive impairement Focal neurological deficit and seizure (Stroke, CSVT, cerebritis, abscess or subdural empyema, malignancy) (3-14%) Epilepsy Hydrocephalus 7% Blindness

30. Epidural abscess and empyema

31. Brain Abscess- Dual rim sign , ring enhancement, edema and diffusion restriction

32. Meningitis and hydrocephalus

33. Prognosis Mortality rate Bacteria type 3-7% H. Influenza N. Meningitis GBS 15% L.monocytogenes 20% S. pneumoniae

34. Bad Prognostic Signs Decreased level of consciousness on admission. Onset of seizures within 24 h of admission. Signs of increased ICP. Young age (infancy) and age 50 or more. Comorbidity including shock and/or the need for mechanical ventilation. Delay in the initiation of treatment. Decreased CSF glucose concentration < [2.2 mmol/L (40 mg/dL)]. Markedly increased CSF protein concentration > [3 g/L (300 mg/dL)].

35. Prevention of bacterial meningitis A-Vaccination 1-H. influenza type b (Hib vaccine). 2-N. meningitidis vaccine (Capsular groups A, B, C, W, Y). 3-S. pneumoniae vaccine(PCV 10, PCV 13).

36. Chemoprophylaxis

37. Acute viral meningitis Less severe symptoms than bacterial meningitis. CSF can differentiate between both types. The most common causes are enterovirus, HSV-2, and VZV, mumps, covid 19, west nile virus and other viruses. CSF PCR is diagnostic in most viruses.

38. Herpes simplex type 2( HSV2): HSV2 causes meningitis while HSV 1 causes encephalitis. Diagnosis: PCR HSV 2 can also cause chronic recurrent meningitis (Mollaret meningititis ), treated by acyclovir 10mg/kg/dose TIDx10-14 days then oral valacyclovir or vamciclovir .

39. Varicella zoster virus : Associated with chicken pox, herpes zoster, meningitis, and stroke (VZV vasculitis) with Left MCA preference. Treated by acyclovir . N.B: (Before taking Fingolimod ( Gilenya ), patients must do VZV IgM and IgG test. They must be IgM negative and IgG positive to take the drug. If VZV IgG is negative they must take 2 doses of VZV vaccine to prevent dissiminated VZV infection ).

40. West Nile virus: It is a mosquito-transmitted flavivirus. The most common cause of summer meningitis epidemics in the USA. It can cause flaccid paralysis (anterior horn cells) like poliomyelitis. Associated with parkinsonism. Lab test of choice: CSF anti-West Nile Virus IgM . Imaging characteristic : bilateral basal ganglia patches. Treatment: Supportive.

41. Parasitic meningoencephalitis Amebic meningoencephalitis: Free living amoebas, Naegleria fowleri and acanthamoeba Swimming in warm water is a risk factor. Rapidly fatal . Diagnosis : Suspected by CSF eosinophilia and confirmed by direct observation of motile trophozoite on CSF wet mount smear or PCR. Treatment : pentamidine, sulfadiazine, fluconazole, and clarithromycin.

42. Naegleria trophozoite in CSF of patient with amebic CNS infection. (CSF sediment cytospin stained with Wright giemsa )

43. Chronic meningitis More than 1 month duration. Etiology: Chronic bacteria (TB, syphilis, lyme disease). fungal infection. Chronic viral infection (HIV, HSV2, VZV). Carcinomatosis. Inflammatory or autoimmune diseases (sarcoid, IgG4 related diseases).

44. Mollaret meningitis Recurrent meningitis. HSV2 is the most common cause. Other causes include VZV, CNS epidermoid cyst .

45. References Coninuum , Neuroinfectious diseases (2021) Myoclinic Board Review Q and A Board Review https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8001510/ . https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4937456/ . https://www.sciencedirect.com/science/article/pii/S2950194624000190.