1. Bacterial and Non-Bacterial CNS Infections EMERGENCY NEUROLOGY LECTURE SERIES JULY 7, 2010 Dr. Abdullah Al-Salti R3

2. CNS INFECTIONS Overview Life-threatening problems with high associated mortality and morbidity. Life-threatening problems with high associated mortality and morbidity. Presentation may be acute, subacute, or chronic. Presentation may be acute, subacute, or chronic. Clinical findings determined by anatomic site(s) of involvement, infecting pathogen, and host response. Clinical findings determined by anatomic site(s) of involvement, infecting pathogen, and host response. Vulnerability of CNS to the effects of inflammation & edema mandates prompt diagnosis with appropriate therapy if consequences to be minimized. Vulnerability of CNS to the effects of inflammation & edema mandates prompt diagnosis with appropriate therapy if consequences to be minimized.

3. CNS INFECTIONS OUT LINE CNS INFECTIONS OUT LINE 1. Bacterial meningitis 2. Aseptic Meningitis 3. Viral Meningitis 4. Viral encephalitis

4. CNS Infections Meningitis Meningitis Bacterial, viral, fungal, chemical, carcinomatousBacterial, viral, fungal, chemical, carcinomatous Encephalitis Encephalitis Bacterial, viralBacterial, viral Meningoencephalitis Meningoencephalitis Abscess Abscess Parenchymal, subdural, epiduralParenchymal, subdural, epidural

5. INFECTIONS 4 routes which infectious agents can enter the CNS a) hematogenous spread i) most common - usually via arterial route - can enter retrogradely (veins) b) direct implantation i) most often is traumatic ii) iatrogenic (rare) via lumbar puncture iii) congenital (meningomyelocele) c) local extension (secondary to established infections) i) most often from mastoid, frontal sinuses, infected tooth, etc. d) PNS into CNS i) viruses - rabies - herpes zoster

6. BACTERIAL MENINGITIS Meningitis refers to an inflammatory process of leptomeninges and CSF. Meningoencephalitis refers to inflammation to meninges and brain parenchyma. Meningitis classified: a) acute pyogenic i) usually bacterial meningitis b) aseptic i) usually acute viral meningitis c) chronic i) usually TB, spirochetes, cryptococcus. Incidence of 3 cases/100,000 population/yr (~25,000 total cases).

7. COMMON BACTERIAL PATHOGENS BASED ON PREDISPOSING FACTOR IN PATIENTS WITH MENINGITIS Predisposing Factor Age 0-4 wk 0-4 wk 4-12 wk 4-12 wk 3 mo to 18 yr 3 mo to 18 yr 18-50 yr 18-50 yr >50 yr >50 yr Common Bacterial Pathogens Streptococcus agalactiae, Escherichia coli, Listeria monocytogenes, Klebsiella Listeria monocytogenes, Klebsiella pneumoniae, Enterococcus spp., Salmonella spp. pneumoniae, Enterococcus spp., Salmonella spp. S. agalactiae, E. coli, L. monocytogenes, Haemophilus influenzae, Streptococcus Haemophilus influenzae, Streptococcus pneumoniae, Neisseria meningitidis pneumoniae, Neisseria meningitidis H. influenzae, N. meningitidis, S. pneumoniae S. pneumoniae, N. meningitidis S. pneumoniae, N. meningitidis, L. monocytogenes, aerobic gram-negative bacilli monocytogenes, aerobic gram-negative bacilli

8. Clinical Features Signs and symptoms: rapid onset of fever rapid onset of fever headache headache photophobia photophobia nuchal rigidity nuchal rigidity lethargy, malaise lethargy, malaise altered mentation altered mentation seizure seizure vomiting. vomiting. van de Beek D, de Gans J, Tunkel AR, et al. Community-acquired bacterial meningitis in adults. N Engl J Med 2006;354(1):44 – 53.

9. Clinical Features Study of 493 adult patients with bacterial meningitis, the presence of the ‘‘ classic triad ’’ of fever, neck stiffness, and altered mental status was present in two-thirds of patients. Study of 493 adult patients with bacterial meningitis, the presence of the ‘‘ classic triad ’’ of fever, neck stiffness, and altered mental status was present in two-thirds of patients. fever WAS the most common element, in 95%. fever WAS the most common element, in 95%. (N Engl J Med 1993;328(1):21 – 8. ) Older patients with S. pneumoniae meningitis are more likely to have the classic triad. Older patients with S. pneumoniae meningitis are more likely to have the classic triad. Weisfelt M, van de Beek D, Spanjaard L, et al. Community-acquired bacterial meningitis in older people. J Am Geriatr Soc 2006;54(10):1500 – 7. Other studies have shown the classic triad to be less common, with estimates ranging from 21% to 51%. Other studies have shown the classic triad to be less common, with estimates ranging from 21% to 51%. All cases studied had at least one of the three signs; the absence of the all components of the classic triad excludes the diagnosis in immunocompetent individuals. All cases studied had at least one of the three signs; the absence of the all components of the classic triad excludes the diagnosis in immunocompetent individuals.

10. Physical examination A careful neurological examination is important to evaluate for : A careful neurological examination is important to evaluate for : focal deficitsfocal deficits increased intracranial pressure (ICP).increased intracranial pressure (ICP). Examination should include assessment for meningeal irritation Examination should include assessment for meningeal irritation Brudzinski ’ s sign Brudzinski ’ s sign Kernig ’ s sign Kernig ’ s sign findings include purpura or petechia of the skin, which may occur with meningococcemia. findings include purpura or petechia of the skin, which may occur with meningococcemia.

11. Bacterial meningitis Investigations

12. LP Single most impt diagnostic test. Single most impt diagnostic test. Mandatory, esp if bacterial meningitis suspected. Mandatory, esp if bacterial meningitis suspected. Tube #1 – glucose and protein Tube #1 – glucose and protein Tube #2 – cell count and differential Tube #2 – cell count and differential Tube #3 – gram stain and rountine culture, cyrptococcal antigen, AFB stain and culture Tube #3 – gram stain and rountine culture, cyrptococcal antigen, AFB stain and culture Tube #4 – VDRL, or viral studies (PCR) Tube #4 – VDRL, or viral studies (PCR)

13. CSF Characteristics BacterialViralFungalTB Opening Pressure Elevated Slight elevated Normal or High Usually high GlcLowNormalLowLow Pro Very high NormalHighHigh RbcsFewNoneNoneNone Wbcs (c/mm3) >200<200<5020-30 DiffPMNsMonoMonoMono

14. CT Before LP in Patients with Suspected Meningitis 301 pts with suspected meningitis; 235 (78%) had CT prior to LP 301 pts with suspected meningitis; 235 (78%) had CT prior to LP CT abnormal in 56/235 (24%); 11 pts (5%) had evidence of mass effect CT abnormal in 56/235 (24%); 11 pts (5%) had evidence of mass effect Features associated with abnl. CT were: Features associated with abnl. CT were: age >60,age >60, immunocompromise,immunocompromise, H/O CNS dz,H/O CNS dz, H/O seizure w/in 7d, &H/O seizure w/in 7d, & selected neuro abnlsselected neuro abnls Hasbun, NEJM 2001;345:1727 Hasbun, NEJM 2001;345:1727

15. CT head Before LP (Cont.) Neuro abnls included altered MS, inability to answer 2 consecutive questions or follow 2 consecutive commands, gaze palsy, abnl visual fields, facial palsy, arm or leg drift, & abnl language Neuro abnls included altered MS, inability to answer 2 consecutive questions or follow 2 consecutive commands, gaze palsy, abnl visual fields, facial palsy, arm or leg drift, & abnl language 96/235 pts (41%) who underwent CT had none of features present at baseline 96/235 pts (41%) who underwent CT had none of features present at baseline CT normal in 93 of these 96 pts (NPV 97%). CT normal in 93 of these 96 pts (NPV 97%). Of the 3 remaining patients, only 1 had mild mass effect on CT, and all 3 underwent lumbar puncture with no evidence of brain herniation Of the 3 remaining patients, only 1 had mild mass effect on CT, and all 3 underwent lumbar puncture with no evidence of brain herniation Hasbun, NEJM 2001;345:1727 Hasbun, NEJM 2001;345:1727

16. Consideration for lumbar puncture without neuroimaging David Somand, MDa,WilliamMeurer, MD Department of Emergency Medicine, University of Michigan, Taubman Center B1354 SPC #5303, 1500 East Medical Center Drive, Ann Arbor, MI 48109-5303, USA Department of Neurology, University of Michigan, Taubman Center 1914 SPC #5316, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-5316, USA Age less than 60 Age less than 60 Immunocompetent Immunocompetent No history of CNS disease No history of CNS disease No recent seizure (less than 1 week) No recent seizure (less than 1 week) Normal sensorium and cognition Normal sensorium and cognition No papilledema No papilledema No focal neurologic defecits No focal neurologic defecits

17. Acute bacterail meninigits MRI Not generally useful in acute diagnosis (Pt cooperation; logistics). Not generally useful in acute diagnosis (Pt cooperation; logistics). Very helpful in investigating potential complications developing later in clinical course such as venous sinus thrombosis or subdural empyema. Very helpful in investigating potential complications developing later in clinical course such as venous sinus thrombosis or subdural empyema.

18. Laboratory Testing Helpful in Distinguishing Bacterial from Viral Meningitis. CSF lactate. Elevated CSF lactate concentrations may be useful in differentiating bacterial from nonbacterial meningitis in patients who have not received prior antimicrobial therapy. Elevated CSF lactate concentrations may be useful in differentiating bacterial from nonbacterial meningitis in patients who have not received prior antimicrobial therapy. study of 78 patients with acute meningitis in which CSF lactate concentrations of >4.2mmol/L were considered to be a positive discriminative factor for bacterial meningitis. study of 78 patients with acute meningitis in which CSF lactate concentrations of >4.2mmol/L were considered to be a positive discriminative factor for bacterial meningitis. Sens Spec PPV NPV 96%, 100%, 100%, 97%. Furthermore, other factors (e.g., cerebralhypoxia/ischemia, anaerobic glycolysis,vascular compromise,and metabolism of CSF leukocytes) also may elevateCSF lactate concentrations. Furthermore, other factors (e.g., cerebralhypoxia/ischemia, anaerobic glycolysis,vascular compromise,and metabolism of CSF leukocytes) also may elevateCSF lactate concentrations. Therefore, measurement of CSF lactate concentrations is not recommended for patients with suspected community- acquired bacterial meningitis. Therefore, measurement of CSF lactate concentrations is not recommended for patients with suspected community- acquired bacterial meningitis. Practice Guidelines for the Management of Bacterial Meningitis Allan R. Tunkel,1 Barry J. Hartman,2 Sheldon L. Kaplan,3 Bruce A. Kaufman,4 Karen L. Roos,5 W. Michael Scheld,6and Richard J. Whitley7

19. Laboratory Testing Helpful in Distinguishing Bacterial from Viral Meningitis. C-reactive protein (CRP). Serum CRP concentrations were capable of distinguishing Gram stain – negative bacterial meningitis, with a sensitivity of 96%, a specificity of 93%, and a negative predictive value of 99%. Serum CRP concentrations were capable of distinguishing Gram stain – negative bacterial meningitis, with a sensitivity of 96%, a specificity of 93%, and a negative predictive value of 99%. Measurement of serum CRP concentration may be helpful in considering withholding antimicrobial therapy, on the basis of the data showing that a normal CRP has a high negative predictive value in the diagnosis of bacterial meningitis. Provided the CSF Gram stain result is negative. Measurement of serum CRP concentration may be helpful in considering withholding antimicrobial therapy, on the basis of the data showing that a normal CRP has a high negative predictive value in the diagnosis of bacterial meningitis. Provided the CSF Gram stain result is negative. Practice Guidelines for the Management of Bacterial Meningitis Allan R. Tunkel,1 Barry J. Hartman,2 Sheldon L. Kaplan,3 Bruce A. Kaufman,4 Karen L. Roos,5 W. Michael Scheld,6and Richard J. Whitley7

20. Laboratory Testing Helpful in Distinguishing Bacterial from Viral Meningitis. procalcitonin concentration. Elevated serum concentrations of the polypeptide procalcitonin, which are observed in patients with severe bacterial infection, were shown to be useful in differentiating between bacterial and viral meningitis. Elevated serum concentrations of the polypeptide procalcitonin, which are observed in patients with severe bacterial infection, were shown to be useful in differentiating between bacterial and viral meningitis. In a study of 59 consecutive children hospitalized for meningitis, the sensitivity of measurements of the serum procalcitonin concentration (using a cutoff of 15.0 mg/L) for the diagnosis of bacterial meningitis was 94%, and the specificity was 100%. In a study of 59 consecutive children hospitalized for meningitis, the sensitivity of measurements of the serum procalcitonin concentration (using a cutoff of 15.0 mg/L) for the diagnosis of bacterial meningitis was 94%, and the specificity was 100%. In adults, serum concentrations 10.2 ng/mL had a sensitivity and specificity of up to 100% for the diagnosis of bacterial meningitis. In adults, serum concentrations 10.2 ng/mL had a sensitivity and specificity of up to 100% for the diagnosis of bacterial meningitis. At present, because measurement of serum procalcitonin concentrations is not readily available in clinical laboratories, recommendations on its use cannot be made at this time. At present, because measurement of serum procalcitonin concentrations is not readily available in clinical laboratories, recommendations on its use cannot be made at this time. Practice Guidelines for the Management of Bacterial Meningitis Allan R. Tunkel,1 Barry J. Hartman,2 Sheldon L. Kaplan,3 Bruce A. Kaufman,4 Karen L. Roos,5 W. Michael Scheld,6and Richard J. Whitley7

21. Laboratory Testing Helpful in Distinguishing Bacterial from Viral Meningitis. PCR. In patients who present with acute meningitis, an important diagnostic consideration is whether the patient has enteroviral meningitis. In patients who present with acute meningitis, an important diagnostic consideration is whether the patient has enteroviral meningitis. Enteroviral RT-PCR has been tested in clinical settings by numerous investigators and has been found to be more sensitive than viral culture for the detection of enterovirus, with a sensitivity and specificity of 86% – 100% and 92% – 100%, respectively. Enteroviral RT-PCR has been tested in clinical settings by numerous investigators and has been found to be more sensitive than viral culture for the detection of enterovirus, with a sensitivity and specificity of 86% – 100% and 92% – 100%, respectively. lead to shortened patient hospitalization, decreased use of antimicrobial therapy for treatment of bacterial meningitis, and reduced need for ancillary diagnostic tests. lead to shortened patient hospitalization, decreased use of antimicrobial therapy for treatment of bacterial meningitis, and reduced need for ancillary diagnostic tests. Practice Guidelines for the Management of Bacterial Meningitis Allan R. Tunkel,1 Barry J. Hartman,2 Sheldon L. Kaplan,3 Bruce A. Kaufman,4 Karen L. Roos,5 W. Michael Scheld,6and Richard J. Whitley7

22. BACTERIAL MENINGITIS Managements

23. APPROACH TO THE PATIENT WITH SUSPECTED MENINGITIS Decision-Making Within the First 30 Minutes  Clinical Assessment  Mode of presentation  Acute (< 24 hrs)  Subacute (< 7 days)  Chronic (> 4 wks)  Historical/physical exam clues  Clinical status of the patient (ABCD)  Integrity of host defenses

24. Management algorithm for adults with suspected bacterial meningitis. Management algorithm for adults with suspected bacterial meningitis. Practice Guidelines for the Management of Bacterial Meningitis

25. Overall Goals in Management Overall Goals in Management 1.To promptly recognize the patient with an acute CNS infection syndrome 2. To rapidly initiate appropriate empiric therapy 3. To rapidly and specifically identify the etiologic agent, adjusting therapies as indicated 4.To optimize management of complicating features features

26. BACTERIAL MENINGITIS Antimicrobial Rx Therapy is generally IV, high dose, & bolus. Therapy is generally IV, high dose, & bolus. Dosing intervals should be appropriate for drug being administered. Dosing intervals should be appropriate for drug being administered. Utilize “ cidal ” therapy whenever possible. Utilize “ cidal ” therapy whenever possible. Initiate therapy promptly (ie, within 30 mins) Initiate therapy promptly (ie, within 30 mins)

27. THE THERAPY OF MENINGITIS CNS Penetration Good Diffusion Good Diffusion Penicillins Penicillins 3 rd & 4th Gen Cephs 3 rd & 4th Gen Cephs Chloramphenicol Chloramphenicol Rifampin Rifampin TSX TSX Poor Diffusion Poor Diffusion Early Gen Cephs Clindamycin AMGs Tetracyclines Macrolides

28. EMPIRIC THERAPY OF MENINGITIS IN THE ADULT Clinical SettingLikely Pathogens Therapy Community-acquiredS. pneumoniae Ceftriaxone N. meningitidis 2 gm q12h [Listeria] + [H. influenzae] Vancomycin 1-2 gm 12h +/- +/- Ampicillin 2 gm q4h Ampicillin 2 gm q4h Closed head traumaS. pneumoniae Pen G 3-4 mu q4h Streptococci + Vancomycin 1-2 gm q12h

29. EMPIRIC THERAPY OF MENINGITIS IN THE ADULT Clinical Setting Likely Pathogens Therapy High risk patientsS. aureus Vancomycin 2-3 gm/d Compromised hostsGram negative + Compromised hostsGram negative + Neurosurgical bacilli Ceftazidime 2 gm q8h or Neurosurgical bacilli Ceftazidime 2 gm q8h or Open head injuryListeria Cefepime 2 gm q8h Open head injuryListeria Cefepime 2 gm q8h Nosocomial [Ceftriaxone 2 gm q12h] Nosocomial [Ceftriaxone 2 gm q12h] Elderly [Cefotaxime 2 gm q4h] Elderly [Cefotaxime 2 gm q4h] +/- +/- Ampicillin 2 gm q4h Ampicillin 2 gm q4h

30. SPECIFIC THERAPY FOR KNOWN PATHOGENS Pathogen Recommended Therapy S. pneumoniae*Pen G 18-24 mu/d N. meningitidisor StreptococciAmpicillin 12 gm/d [Chloro 75-100 mg/kg/d] [Ceftriaxone 2-4 gm/d] H. influenzaeCefotaxime 12 gm/d [Ceftriaxone 2-4 gm/d] Group B strepPen G 18-24 mu/d or Ampicillin 12 gm/d [plus aminoglycoside]

31. SPECIFIC THERAPY FOR KNOWN PATHOGENS (continued) S. aureusNafcillin 12 gm/d [Vancomycin 2-3 gm/d] ListeriaAmpicillin 12 gm/d or Pen G 18-24 mu/d [plus aminoglycoside] Gram negativeCefotaxime 12 gm/d bacilli[Ceftriaxone 2-4 gm/d] bacilli[Ceftriaxone 2-4 gm/d] PseudomonasCeftazidime 6-8 gm/d or Cefepime 6 gm/d [plus aminoglycoside]

32. BACTERIAL MENINGITIS Duration of ATB Rx Pathogen Duration of Rx (d) Pathogen Duration of Rx (d) H. influenzae 7 H. influenzae 7 N. meningitidis 7 N. meningitidis 7 S. pneumoniae 10-14 S. pneumoniae 10-14 L. monocytogenes 14-21 L. monocytogenes 14-21 Group B strep 14-21 Group B strep 14-21 GNRs 21 GNRs 21 NEJ1997;336:708 NEJ1997;336:708

33. CORTICOSTEROIDS AND MENINGITIS Role of steroids still somewhat uncertain. Role of steroids still somewhat uncertain. Recent European study in adults suggested that Rx with dexa associated with ↓ in risk of unfavorable outcome (25% → 15%, RR 0.59) & in mortality (15% → 7%, RR for death 0.48). Recent European study in adults suggested that Rx with dexa associated with ↓ in risk of unfavorable outcome (25% → 15%, RR 0.59) & in mortality (15% → 7%, RR for death 0.48). Benefit primarily pts w/S. pneumo. Benefit primarily pts w/S. pneumo. Dose of dex was 10mg IV q6h X 4d; per protocol, dex given concurrent with or 15-20 mins before 1 st dose of ATBs. Dose of dex was 10mg IV q6h X 4d; per protocol, dex given concurrent with or 15-20 mins before 1 st dose of ATBs.

34. CORTICOSTEROIDS AND MENINGITIS (Cont) Only pts with cloudy CSF, + CSF GmS, or CSF WBC count >1000 were enrolled Only pts with cloudy CSF, + CSF GmS, or CSF WBC count >1000 were enrolled Accompanying editorial raised concerns about use of steroids in pts with DRSP who are being Rx ’ ed with vanc b/o ↓ in CNS conc of vanc with concurrent steroid use. Accompanying editorial raised concerns about use of steroids in pts with DRSP who are being Rx ’ ed with vanc b/o ↓ in CNS conc of vanc with concurrent steroid use. Practically speaking, almost all pts with presumed bacterial meningitis are candidates for at least 1 dose of dexa NEJM 2002;347:1549 Practically speaking, almost all pts with presumed bacterial meningitis are candidates for at least 1 dose of dexa NEJM 2002;347:1549

35. Acute bacterial meningitis Antibiotic prophylaxis Is recommended for high-risk exposures to patients with Neisseria or Hib meningitis.(potentially share secretions). Regimens include : single-dose ciprofloxacin or ceftriaxone. rifampin 600 mg every 12 hours for five doses. There is no indication for prophylaxis for exposure to pneumococcal meningitis. Quinolone resistance has been reported to Neisseria, and this class of antibiotics is no longer recommended for prophylaxis in parts of the United States. David Somand, MDa,WilliamMeurer, MD Department of Emergency Medicine, University of Michigan, Taubman Center B1354 SPC #5303, 1500 East Medical Center Drive, Ann Arbor, MI 48109-5303, USA Department of Neurology, University of Michigan, Taubman Center 1914 SPC #5316, 1500 E. Medical Center Drive, Ann Arbor, MI 48109-5316, USA

36. PREDICTORS OF ADVERSE CLINICAL OUTCOMES IN PTS WITH COMMUNITY-ACQUIRED BACTERIAL MENINGITIS Retrospecitve study; 269 pts (84% culture +). Retrospecitve study; 269 pts (84% culture +). Adverse clinical outcome in 36% of pts(Death 27%, neuro deficit 9%). Adverse clinical outcome in 36% of pts(Death 27%, neuro deficit 9%). ↓ BP, altered MS, and seizures on presentation all independently associated with adverse clinical outcome. ↓ BP, altered MS, and seizures on presentation all independently associated with adverse clinical outcome. Adverse outcomes in 5% of low risk pts (0 features), 37% of intermediate risk pts (1 feature), and 63% of high risk pts (2-3 features). Adverse outcomes in 5% of low risk pts (0 features), 37% of intermediate risk pts (1 feature), and 63% of high risk pts (2-3 features). Delay in administration of appropriate ATB Rx also associated with adverse clinical outcome. Delay in administration of appropriate ATB Rx also associated with adverse clinical outcome. Aronin et al, AIM1998;129:862 Aronin et al, AIM1998;129:862

37. Aseptic Meningitis

38. All non-bacterial causes of meningitis All non-bacterial causes of meningitis Typically less ill appearing than bacterial meningitis Typically less ill appearing than bacterial meningitis Most common cause is viral Most common cause is viral HSVHSV Consider especially in infants presenting with seizure Consider especially in infants presenting with seizure Usually HSV type II Usually HSV type II Treat with acyclovir Treat with acyclovir Enterovirus (coxsackie, echovirus)Enterovirus (coxsackie, echovirus) Typically occurs during late summer and fall Typically occurs during late summer and fall Spread via respiratory secretions and fecal-oral Spread via respiratory secretions and fecal-oral Affects all ages Affects all ages Generally self-limited illness Generally self-limited illness

39. Aseptic Meningitis Other Viral Other Viral HIVHIV Lymphocytic choriomeningitis virusLymphocytic choriomeningitis virus ArbovirusArbovirus MumpsMumps CMVCMV EBVEBV VZVVZV AdenovirusAdenovirus MeaslesMeasles RubellaRubella RotavirusRotavirus Influenza and parainfluenzaInfluenza and parainfluenza

40. Aseptic Meningitis Other infectious Other infectious Borrelia burgdorferiBorrelia burgdorferi Mycobacterium tuberculosisMycobacterium tuberculosis Treponema pallidumTreponema pallidum Mycoplasma pneumoniaeMycoplasma pneumoniae Rickettsia, erlichia, brucellaRickettsia, erlichia, brucella ChlamydiaChlamydia

41. Aseptic Meningitis Fungal Fungal CryptococcusCryptococcus CoccidiodesCoccidiodes HistoplasmosisHistoplasmosis Parasitic Parasitic AngiostrongylusAngiostrongylus ToxoplasmosisToxoplasmosis

42. Aseptic Meningitis Medication Medication NSAID ’ sNSAID ’ s BactrimBactrim PyridiumPyridium Malignancy Malignancy Lymphoma and leukemiaLymphoma and leukemia Metastatic carcinomaMetastatic carcinoma Autoimmune Autoimmune SarcoidSarcoid Behcet ’ sBehcet ’ s SLESLE

43. Viral Meningitis Very common Very common clinical course is less fulminant compared to bacterial clinical course is less fulminant compared to bacterial Often caused by enteroviruses Often caused by enteroviruses Polioviruses Polioviruses Coxsackieviruses Coxsackieviruses Echoviruses Echoviruses Treatment is supportive Treatment is supportive

44. VIRAL ENCEPHALITIS

45. Introduction Encephalitis is an acute inflammatory process affecting the brain Encephalitis is an acute inflammatory process affecting the brain Viral infection is the most common and important cause, with over 100 viruses implicated worldwide Viral infection is the most common and important cause, with over 100 viruses implicated worldwide Symptoms Symptoms FeverFever HeadacheHeadache Behavioral changesBehavioral changes Altered level of consciousnessAltered level of consciousness Focal neurologic deficitsFocal neurologic deficits SeizuresSeizures Incidence of 3.5-7.4 per 100,000 persons per year Incidence of 3.5-7.4 per 100,000 persons per year

46. VIRAL ENCEPHALITIS Enteroviruses Polioviruses Polioviruses Coxsackieviruses Coxsackieviruses Echoviruses EchovirusesTogaviruses Eastern equine Eastern equine Western equine Western equine Venezuelan equine Venezuelan equine St. Louis St. Louis Powasson Powasson California California West Nile West NileHerpesviruses Herpes simplex Herpes simplex Varicella-zoster Varicella-zoster Epstein Barr Epstein Barr Cytomegalovirus CytomegalovirusMyxo/paramyxoviruses Influenza/parainfluenzae Influenza/parainfluenzae Mumps Mumps Measles MeaslesMiscellaneous Adenoviruses Adenoviruses LCM LCM Rabies Rabies HIV HIV

47. Patient History Detailed history critical to determine the likely cause of encephalitis. Detailed history critical to determine the likely cause of encephalitis. Prodromal illness, recent vaccination, development of few days → Acute Disseminated Encephalomyelitis (ADEM). Prodromal illness, recent vaccination, development of few days → Acute Disseminated Encephalomyelitis (ADEM). Biphasic onset: systemic illness then CNS disease → Enterovirus encephalitis. Biphasic onset: systemic illness then CNS disease → Enterovirus encephalitis. Abrupt onset, rapid progression over few days → HSE. Abrupt onset, rapid progression over few days → HSE. Recent travel and the geographical context: Recent travel and the geographical context: Africa → Cerebral malariaAfrica → Cerebral malaria Asia → Japanese encephalitisAsia → Japanese encephalitis High risk regions of Europe and USA → Lyme diseaseHigh risk regions of Europe and USA → Lyme disease Recent animal bites → Tick borne encephalitis or Rabies. Recent animal bites → Tick borne encephalitis or Rabies. Occupation Occupation Forest worker, exposed to tick bitesForest worker, exposed to tick bites Medical personnel, possible exposure to infectious diseases.Medical personnel, possible exposure to infectious diseases.

48. History cont. Season Season Japanese encephalitis is more common during the rainy season.Japanese encephalitis is more common during the rainy season. Arbovirus infections are more frequent during summer and fall.Arbovirus infections are more frequent during summer and fall. Predisposing factors: Predisposing factors: Immunosuppression caused by disease and/or drug treatment.Immunosuppression caused by disease and/or drug treatment. Organ transplant → Opportunistic infectionsOrgan transplant → Opportunistic infections HIV → CNS infectionsHIV → CNS infections HSV-2 encephalitis and Cytomegalovirus infection (CMV)HSV-2 encephalitis and Cytomegalovirus infection (CMV) Drug ingestion and/or abuse Drug ingestion and/or abuse Trauma Trauma

49. Initial Signs Headache Headache Malaise Malaise Anorexia Anorexia Nausea and Vomiting Nausea and Vomiting Abdominal pain Abdominal pain

50. Developing Signs Altered LOC – mild lethargy to deep coma. Altered LOC – mild lethargy to deep coma. AMS – confused, delirious, disoriented. AMS – confused, delirious, disoriented. Mental aberrations: Mental aberrations: hallucinationshallucinations agitationagitation personality changepersonality change behavioral disordersbehavioral disorders occasionally frank psychosisoccasionally frank psychosis Focal or general seizures in >50% severe cases. Focal or general seizures in >50% severe cases. Severe focused neurologic deficits. Severe focused neurologic deficits.

51. Neurologic Signs Virtually every possible focal neurological disturbance has been reported. Virtually every possible focal neurological disturbance has been reported. Most Common Most Common AphasiaAphasia AtaxiaAtaxia Hemiparesis.Hemiparesis. Involuntary movementsInvoluntary movements Cranial nerve deficits (ocular palsies, facial weakness)Cranial nerve deficits (ocular palsies, facial weakness)

52. Other Causes of Encephalopathy Anoxic/Ischemic conditions Anoxic/Ischemic conditions Metabolic disorders Metabolic disorders Nutritional deficiency Nutritional deficiency Toxic (Accidental & Intentional) Toxic (Accidental & Intentional) Systemic infections Systemic infections Critical illness Critical illness Malignant hypertension Malignant hypertension Mitochondrial cytopathy (Reye ’ s and MELAS syndromes) Mitochondrial cytopathy (Reye ’ s and MELAS syndromes) Hashimoto ’ s encephalopathy Hashimoto ’ s encephalopathy Traumatic brain injury Traumatic brain injury Epileptic (non-convulsive status) Epileptic (non-convulsive status) CJD (Mad Cow) CJD (Mad Cow)

53. Differential Diagnosis Distinguish Etiology Distinguish Etiology (1) Bacterial infection and other infectious conditions(1) Bacterial infection and other infectious conditions (2) Parameningeal infections or partially treated bacterial meningitis(2) Parameningeal infections or partially treated bacterial meningitis (3) Nonviral infectious meningitides where cultures may be negative (e.g., fungal, tuberculous, parasitic, or syphilitic disease)(3) Nonviral infectious meningitides where cultures may be negative (e.g., fungal, tuberculous, parasitic, or syphilitic disease) (4) Meningitis secondary to noninfectious inflammatory diseases(4) Meningitis secondary to noninfectious inflammatory diseases

54. VIRAL ENCEPHALITIS DIAGNOSIS. DIAGNOSIS.LP: CSF usually colorless CSF usually colorless - slightly  pressure - initially a neutrophilic pleocytosis, which rapidly converts to lymphocytes - proteins are  - glucose is normal PCR for HSE and other viral infection is diagnostic. PCR for HSE and other viral infection is diagnostic.

55. VIRAL ENCEPHALITIS DIAGNOSIS.MRI: May show temporal or orbitofrontal cortex enhancement or edema in HSE. May show temporal or orbitofrontal cortex enhancement or edema in HSE. In most other acute viral encephalities, neuroimaging finding are nonspecific. In most other acute viral encephalities, neuroimaging finding are nonspecific. Can exclude subdural bleeds, tumor, and sinus thrombosis. Can exclude subdural bleeds, tumor, and sinus thrombosis.EEG: Non specificNon specific Diffuse slowing.Diffuse slowing. Focal abnormalities in the temporal region. HSVFocal abnormalities in the temporal region. HSV Brain biopsy : Reserved for patients who are worsening, have an undiagnosed lesion after scan, or a poor response to acyclovir. Reserved for patients who are worsening, have an undiagnosed lesion after scan, or a poor response to acyclovir.

56. Treatment. Only HSV disease has specific therapy available. Acyclovir is capable of improving patient outcome. dose : 10 mg/kg intravenously every 8 hours. Duration 14-21 days. ganciclovir can be used in CMV infections. pleconaril has shown promise in enteroviral. Outcomes Outcomes are variable depending on etiology. EEE and St. Louis encephalitis generally have high mortality rates and Severe neurologic sequelae among survivors. WNV is associated with significant morbidity and morality. Mortality of HSV encephalitis before acyclovir was 60% to 70%, and with treatment approximately 30%. Cognitive disability,seizures, and motor deficits are common sequelae seen among survivors

57. Bacterial and Non-Bacterial CNS Infections EMERGENCY NEUROLOGY LECTURE SERIES JULY 7, 2010 Dr. Abdullah Al-Salti R3