Meningitis and Encephalitis in the Older Patient

1. Meningitis and Encephalitis in the Older Patient Debra Bynum, MD Division of Geriatric Medicine University of North Carolina Chapel Hill April 2007

2. Outline • Cases for thought… • Meningitis and Encephalitis: general features and causes • Diagnosis: review of CSF findings • Meningitis: specific causes • Encephalitis: specific causes • Zoom in on important arboviruses and tick-borne illnesses • Summary of diagnosis and treatment • Review of the cases

3. Cases • 1. Active 78-y/o man with prior hx of aortic valve replacement years ago, presents with fever, slight confusion, dehydration. Initial concern for SBE, but CSF :TNC of 20. His serum Na 128. All cultures negative. What would the DDX include? • 2. 85-y/o with severe dementia admitted with fever, ?stiff neck and worsening confusion and lethargy. CXR and U/A are negative. What would you do? • 3. Healthy community living 75-y/o presents with personality changes, confusion, agitation. She has no fever, no other evidence of infection. What to do? • 4. 80-year-old man presents with low grade fever and coma after several days of myalgias and viral-like illness. Exam is notable for some Parkinsonian type features… initial concern would be for ?

4. Meningitis • Inflammation of the meninges • Classic triad: • Fever • Headache • Severe, frontal, photophobia, n/v • Jolt accentuation • Meningismus/altered mental status • Meningeal signs • Kernig sign: one leg with hip flexed, pain in back with extension of knee • Brudzinski sign: flexion of legs and thighs when neck is flexed

5. Encephalitis • Inflammation of the cerebral cortex • Fever, HA, altered mental status • Key: early mental status changes • More commonly viruses • Obtundation/coma • Behavioral or speech problems, neurological signs, seizures • Meningoencephalitis • Difference from meningitis: less likely fever, more likely personality/behavioral changes

6. Causes of Meningitis • Bacterial • Viral • Fungal: cryptococcus • Mycobacteria: MTB • Parasitic/protozoa: Naegleria fowleri • Noninfectious • Medications • Paraneoplastic

7. Acute Bacterial Meningitis • Streptococcus pneumoniae • Neisseria meningitidis • Listeria monocytogenes • Haemophilus influenzae: nearly unheard of since vaccinations • Less common: Gram negatives (Klebsiella, E. coli) • History of procedure: Staphylococcus

8. Viral Meningitis • Aseptic meningitis • Spectrum with encephalitis, meningo-enchephalitis • Enteroviruses • HSV • VZV • Arboviruses (arthropod borne viruses) • West Nile, Eastern Equine, Western Equine, St. Louis, California, Japanese Encephalitis • HIV • Rabies virus • Adenovirus • CMV, EBV

9. Encephalitis • Viral • HSV • Arboviruses • VZV, CMV, EBV, HIV, rabies • Enteroviruses • Bacterial • Listeria monocytogenes • Tick-borne illnesses • RMSF: Rickettsia rickettsii • STARI: Borrelia lonestari • Lyme: Borrelia burgdorferi • Ehrlichiosis: Ehrlichia chaffoensis

10. Meningitis in the Elderly • Decreased total incidence; increased in elderly • Increased prevalence of Listeria (25%) • 30-50%: S. pneumoniae • Less likely Neisseria and Haemophilus • Less likely fever and meningeal signs; more likely neurological symptoms, seizure, coma • More often complicated by pneumonia • Older patients with neurological impairment: 50% mortality

11. Meningitis • Risk Factors • Age (bimodal peak) • Prior neurosurgery, alcoholism, malignancy, steroids, HIV, sinusitis, DM • Clinical suspicion • Triad: fever, nuchal rigidity, altered mental status: only seen in 40% elderly • Only 59% of elderly patients with acute bacterial meningitis had fever • Most have at least ONE symptom

12. The Diagnosis • LP if suspicion • Do not delay antibiotics if suspected! • CT prior to LP in patients with focal neurological deficits, seizures, HIV, or elderly • MRI: to identify areas of CNS involvement • Temporal involvement with HSV • Basilar meningitis with TB

13. The Lumbar Puncture: Risks • Headache: 10-25% • Typical: appears suddenly upon standing • Decrease CSF pressure with small leak • Decrease risk: small (<20 g) needle, leave patient prone after procedure • Blood patch • Infection (small) • Local bleeding: traumatic tap to epidural hematoma • Brain herniation

14. The LP • Opening Pressure • Important data • Only in lateral decubitus (not position usually done under radiology) • Xanthochromia • Yellow/orange color of centrifuged CSF • RBC lysis – oxyhemoglobin, bilirubin • Blood in subarachnoid space at least 2-4 hrs • More likely due to blood in CSF and less likely traumatic tap

15. CSF Findings

16. CSF: Some Catches • Protein least specific • TB: early neutrophilic predominance • Encephalitis, RMSF, tick-borne illnesses: inc CSF WBC • Listeria: misread as “contamination”/diphtheroids • Listeria: bacterial meningitis that can have significant encephalitis and abscess, and CSF with lymphocytes! • RBCs that do not clear: SAH or HSV

17. CSF: More Pearls • Correction factors for traumatic tap • “trauma” and RBCs increase protein and with an increase in RBCs come an increase in WBCs • True CSF protein = subtract 1 mg/dL protein for every 1000 RBC/mm3 • True WBC in CSF: actual WBC in CSF – (WBC in blood x RBC in CSF)/ RBC in blood

18. Meningitis: Specific Causes

19. Strep Pneumoniae Meningitis • Now most common cause (H flu rare) • 30-50% cases of bacterial meningitis in elderly • Otitis 30%, sinusitis 8%, pneumonia 18% • Elderly more often have pneumonia (bad) • Bad markers: older age, low platelets, dec CSF glucose, no otogenic focus • Vaccination: recommended in all over age 65 • Efficacy in elderly/immunocompromised NOT clear • Decrease bacteremia/meningitis

20. Listeria • Food-borne outbreaks • Herd animals • Common, likely cause of mild GI illnesses • Invasive disease with bacteremia and CNS involvement may follow other GI infection (piggy back…) • Increased risk with depressed cellular immunity: pregnant women, elderly, AIDS, lymphoma, steroid use, transplant patients

21. Listeria… • Small, anaerobic gm + baccillus • Look like diphtheroids, contaminants • Cerebritis, brain abscess • Confusion, altered LOC, seizure, movement • Mortality 22% in older patients with CNS dz • 20% of all cases of bacterial meningitis in patients over age 60 • Brain abscess: 10% CNS infections • Usually due to bacteremia • Concomitant meningitis in 25-40% (rare with other causes of brain abscess)

22. Listeria… Big Points • NOT uncommon in elderly • Meningitis, encephalitis, focal brain abscess • Add Ampicillin • Diphtheroids in CSF: listeria unless proven otherwise

23. TB Meningitis • Tuberculous meningitis (most common) • Intracranial tuberculomas • Spinal tuberculous arachnoiditis • Meningitis: inflammation from rupture of subependymal tubercle into subarachnoid space • Basilar meningitis, CN palsies, hydrocephalus • Subacute or chronic • Initial neutrophilic pattern on CSF • Very high CSF protein may be seen • AFB smears often neg; need HIGH volume sent to lab

24. Viral Meningitis • Aseptic meningitis • May be difficult to initially separate from partially treated bacterial meningitis (obligates empiric treatment for bacterial) • Differentiate from true aseptic (drug related such as NSAIDs, paraneoplastic)

25. Viral Meningitis • Finland study: etiology found in 66% patients with aseptic meningitis • Viral encephalitis: etiology only found in 36% cases • Viral prodrome, sore throat, myalgias, ill contacts, GI complaints; summer/fall season • Most common= enteroviruses (25%) • Echoviruses • Coxsackievirus

26. Viral Meningitis • Less common causes • Adenoviruses: URI sxs, year round • CMV, EBV, HIV, influenzae • Measles, mumps, rabies, rubella, varicella • ?future avian flu (usually not CNS sxs, more URI/pneumonia/ARDS and DIC)

27. Encephalitis: Specific Causes

28. Encephalitis Lethargica… • The Awakenings… • 1916: von Economo described CNS disorder with lethargy and Parkinsonian features following viral syndrome with pharyngitis • 1916-1927 epidemic; now sporadic cases • 1918: influenza pandemic, ?connection (?immune mediated process)

29. Encephalitis • More likely to be viral • Etiology only found in 35% cases • HSV-1: 10% cases (but accounts for over 50% cases in patients over 50) • HSV-2 • VZV (?up to 10% in some series) • Tick or insect borne diseases: 10%

30. Encephalitis • Acute Viral Encephalitis • Direct viral infection of neuronal cells • Perivascular inflammation • Destruction of gray matter • Post-Infectious Encephalomyelitis • Follows viral or bacterial infection • Demyelination of white matter • ?autoimmune component triggered by infectious agent

31. HSV Encephalitis • 2-4 cases/million people/year • Acute infection or more commonly reactivation of latent infection (trigeminal nerve ganglion) • Characteristic site of damage: temporal lobe • MRI findings of necrosis in temporal lobe • Necrosis = RBC s on CSF!

32. HSV Encephalitis • Dysphasia, bizarre behavior, seizures • Abnormal EEG • High mortality: 30% with treatment • Survivors: 10% long term disability • Fever +/- • Treatment: Acyclovir (60-75% mortality without treatment)

33. HSV Encephalitis: Big Points • Odd behavior, think encephalitis • If thinking encephalitis, add acyclovir • RBCs on CSF (with xanthochromia or lack of clearing between tube 1 and 4), think HSV • Temporal symptoms • Temporal necrosis or abnormalities on MRI

34. Arboviruses and Encephalitis • Arbovirus: Arthropod Borne Virus • RNA viruses transmitted by mosquitoes or ticks • 10 % cases of sporadic encephalitis (?higher in elderly, up to 50% cases during epidemics)

35. Arboviruses and Encephalitis • Alphavirus family: • Eastern Equine Encephalitis ** • Western Equine Encephalitis • Flavivirus family: • St Louis Encephalitis ** • Japanese Encephalitis • California Encephalitis • West Nile Virus **

36. West Nile Virus and Encephalitis in the Elderly

37. West Nile Virus • 1937: West Nile district Uganda (mild cases) • Middle east/ Israel (14% fatality) • 1996: outbreak in Romania (4% fatality) • 1999: NY outbreak (11% fatality) • Subsequent west spread to most states • 2002: 4156 reported cases in US, 284 deaths • 2003: 9858 cases, 262 deaths

38. West Nile Virus • Season: summer • Mosquito transmission (currently infects 43/ 174 different types of North American mosquitoes) • Other routes • Placenta • Lactation • Transfusion • Organ transplant

39. West Nile Virus • Disease of the elderly • Higher mortality in elderly • Other risk factors not clear (?maybe HTN and DM leading to better virus entry)

40. WNV: Predictors • Admission diagnoses: • 30%: aseptic meningitis • 15%: fever • 18%: viral infection • 14%: UTI • 10% pneumonia • 7% : encephalitis • 5%: probable WNV (year 2001) • Mortality rates highest with: • Initial diagnosis of encephalitis (35% of those who died), • No headache (50% had HA, 7% those that died had HA), and • Initial mental status changes

41. WNV • Presenting symptoms • HA, fever, mental status changes • CN findings, optic neuritis • Myoclonus • Flaccid Paralysis • With or without encephalitis • Asymmetric weakness/paralysis, no sensory loss • Anterior horn cells (polio like) • Absent DTRs

42. WNV • Movement Disorders • Parkinsonian • Tremors • Bradykinesia • Cogwheel rigidity • Postural instability • Masked facies • 80-100% will have rest or intention tremor • 30% will have myoclonus

43. WNV: Diagnosis • High index of suspicion • CSF: usually 200 TNC; 5-10% can have over 500 TNC, 5% with < 5 TNC • CSF with 50% neutrophils • Elevated CSF protein • CSF for ab studies: anti WNV ab, and negative SLE IgM (up to 40% cross reactivity in earlier studies)

44. WNV: Treatment • ?nucleoside analogues (ribavirin – no benefit in Israel) • Human Immunoglobulin : protective antibodies (patients from Israel with high titers of anti-WNV ab); if effective, only in early disease • ?vaccine development (effective in horses in 2001) • ?inactivated JEV vaccine?

45. Meningitis and Encephalitis: Others

46. Tick-Borne Diseases • RMSF ** • Lyme Disease ** • Ehrlichiosis ** • STARI ** • Tularemia • Babesiosis • Colorado Tick Fever

47. Rocky Mountain Spotted Fever • Rickettsia rickettsii • Gm negative intracellular bacteria • Endothelial cells: small vessel vasculitis • Southeast, summer • Dog Tick, Wood Tick • 2nd most common tick-borne illness • Fever/headache/nausea/rash 80% • Rash: blanching maculopapular, palms/soles, spreads centrally, later petechial and purpuric • Hyponatremia, thrombocytopenia, inc ALT • CSF: inc TNC, inc protein; neg gram stain

48. RMSF: Diagnosis • Clinical suspicion • Low threshold to empirically treat • Rash may be absent in 20% • RMSF serologies: initial may be negative; need convalescent titers several weeks later

49. RMSF: Treatment • Doxycycline 100 BID • Do not delay • ?newer quinolones: probably, but no studies and no recommendations • No indication for prophylactic treatment after uncomplicated tick bite • Prevention: frequent inspection

50. RMSF: Big Points • Empiric Treatment if even suspected • In North Carolina, any fever, HA, neuro syndrome will need treatment • First serology titers NOT reliable • Hyponatremia, low platelets, elevated LFTs, think RMSF… • Do not wait for the rash…