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Seizures and CNS Infections

Seizures and CNS Infections. Alyssa Morris, R2 December 18 th , 2008 Thanks to: Dr Carol Holmen and Dr Wojtowicz Dr Dowling. Objectives. CNS Infections Meningitis Encephalitis Abscesses Brain Spinal epidural Seizures Classification Status Epilepticus. Case #1.

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Seizures and CNS Infections

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  1. Seizures and CNS Infections Alyssa Morris, R2 December 18th, 2008 Thanks to: Dr Carol Holmen and Dr Wojtowicz Dr Dowling

  2. Objectives CNS Infections • Meningitis • Encephalitis • Abscesses • Brain • Spinal epidural Seizures • Classification • Status Epilepticus

  3. Case #1 • 60M cough for four days with runny nose, fever for 12H, generalized H/A and neck stiffness • PMHx: none • 38.8, 100, 120/86, 16, 98%

  4. Meningitis • Inflammation involving the meninges and CSF • Can be infectious and noninfectious • Bacterial Meningitis • 5 cases /100,000 people in US • Men>women • Increases in late winter and early spring • Viral Meningitis • Incidence not really know because a lot not reported • Increase in summer months

  5. Etiology • What are the most common bacterial pathogens in adults? • Streptococcus pneumoniae • Neisseria meningitidis • Listeria monocytogenes • What are some non-infectious causes? • Drug-induced • Carcinomatous • Serum sickness • Vasculitis • SLE/sarcoid

  6. Etiology • Arboviruses • Herpes Viruses • HSV, CMV, EBV, Varicella-zoster • Enteroviruses • Coxsackie, echovirus, polio • Lymphocytic choriomeningitis virus • Retroviruses • Paramyxoviruses • Rabies virus

  7. Pathophysiology-Bacterial 1. nasopharyngeal colonization 2. penetration- variety of mechanisms 3. bacterial intravascular survival- evasion of the complement pathway and capsular properties 4. cross BBB to enter CSF Dural venous sinuses, cribiform plate, choroid plexus 5. Bacterial proliferation 6. convergence of leukocytes into the CSFand TNFalpha, IL 1,6

  8. Pathophysiology-Bacterial All of the inflammatory factors contribute to a cascade of events 1. increased permeability of BBB, cerebral vasculitis, edema 2. increased ICP 3. decreased cerebral blood flow 4. cerebral hypoxia 5. glucose transport into the CSF is decreased and an increased use by brain, bacteria and leukocytes 6. increased permeability leads to increased proteins

  9. Pathophysiology-Viral • Enter the human host thru skin, resp tract, GI tract, infected blood product or donor organs • Viral replication outside of CNS • spreads to CNS: • Hematogenous spread* • Retrograde transmission along neuronal axons • Direct invasion of subarachnoid space after infection of nasal mucosa Q: What would be some predisposing risk factors?

  10. Host Risk Factors • Age<5 • Age>60 • Male • Low SES • Crowding • Splenectomy • Sickle cell dz • African-American • Alcoholism w cirrhosis • diabetes • Immunologic defects • Recent colonization • Dural defects • Continuous infection (sinusitis) • Household contact • Thalassemia • IVDU • Bacterial endocarditis • VP shunt • malignancy

  11. Clinical Features • Appear ill and present soon after onset • Classic triad: fever, nuchal rigidity, ALOC • 33% don’t have this though! • Systemic infection • Non-specific rash, fever, myalgia, SIRS/sepsis • Meningeal irritation • Protective mechanism to prevent stretching of inflammed nerve roots • Kernig, Brudzinski, neck stiffness, Jolt apprehension, HA, CN palsy • Cerebral edema/incresed ICP • ALOC, HA, vomit, seizure, focal neuro deficits

  12. Clinical Features Does your patient have meningitis? Attia et al JAMA 1999;281:175 • Classic triad: fever, neck stiffness, ALOC • <2/3 have all 3 Sx • 99-100% of patients have at least 1 • Essentially eliminate Dx of meningitis if none present • Hx inadequate to dx meningitis • HA sensitivity 50%, N/V 30% • PE findings have variable sensitivities

  13. Kernig’s Sign • Flex hip to 90 degrees • Test positive if pain in back and legs or resist extension beyond 130 degrees

  14. Brudzinski’s Sign • Passive flexion of the nect • Sign + if flex legs at hips to lift legs

  15. Jolt Accentuation • Rotate head side to side at 2-3x/s • + if H/A worsens

  16. Clinical Features • Your patient had a +Kernig sign, do you think this means he has meningitis? • What if he didn’t have a positive test, would you cross meningitis off of your differential?

  17. Clinical Features How are accurate are meningeal signs? Thomas et al. Clin Inf Dis 202;35:46 • 297 patients w suspected meningitis, examine before LP • Nuchal rigidity (inability to passively flex neck) • Sens 30%, Spec 68%, +LR 0.94, -LR 1.02 • Kernig’s and Brudzinski’s sign • Sens 5%, Spec 95%, +LR 0.97, -LR 1.0 • JAMA article • Conclusions: • Kernig, Brudzinski only helpful if present (spec not sens)

  18. Diagnosis • You are still worried about meningitis and want to do an LP. Are you going to CT before doing it? • When do you scan first and when do you not scan first?

  19. CT and LP CT before LP in suspected meningitis. Hasburn et al. NEJM, 2001;345:1727 • 301 pts w suspected meningitis • 235 (78%) had CT before LP • 56 (24%) had abnormal results • 11 (5%) had mass effect • Features associated with abn CT: • Age>60 • Immune compromised • Hx CNS dz • Hx seizure in week before CT • Abn neuro exam

  20. CT and LP • 96 pts had no high risk features, 93 (NPV 97%) had normal CT *** what about 3 who had abnormal????? • 11 pts w mass effect, only 4 no LP as a result • No herniation in other 7 at 7 days but small numbers! • Absence of high risk features indentified those unlikely to have abn CT (LR 0.1, 0.03-0.31) and safe to proceed to immediate LP • 22% w/o CT • No adverse outcomes reported • May have missed lesion that could expedite tx • Small number of pts w mss effect and LP

  21. LP • You decide to LP your patient. • What are some contraindications to LP? • Intracranial lesion with mass effet • Local infection at puncture site • How can you perform LP to limit complications? • HA in up to 60% of pts • Believed due to CSF leak thru pucture in dura

  22. Prevention of PLPHA PROVEN • Needle size • Needle type • Re-inserting stylet • Bevel orientation UNPROVEN • Bed rest • Hydration • Paramedian approach • Volume of CSF removed *See Shawn’t talk on remergs.com for comprehensive review of the literature

  23. PLPHA and Needle Size • Numerous studies have clearly demonstrated that the smaller the needle, the lower the IR of PLPHA

  24. PLPHA and Needle Type • Non-Cutting (aka atraumatic, pencil-point, blunt) • Whitacre • Cutting • Quincke

  25. Re-Inserting Stylet • Theory is that w/d of needle w/o stylet would result in arachnoid fibers being w/d leading to a persistent dural leak because of a hole that is not as easily healed • In a large RCT of 600 pts incidence of PLPHA with reinsertion and w/o reinsertion was 5% and 16% respectively

  26. Bevel Orientation • Theory that needle insertion parallel to longitudinal fibers result in less leakage because bevel pushes fibers away rather than transecting them • Bevel up when pt in LLD, to the side when sitting up • Studies not on ED pts • Bevel orientation likely only significant if using cutting needle

  27. LP Technique Strauss et al. JAMA 2006; 296:2012. LP technique and analysis • Atraumatic vs standard needles no decrease in odds of post LP HA (show a trend) • ARR 12.3%, -1.72-26.2% • OR 0.46 (0.19-1.07) • Reinsertion of stylet decreased HA • ARR 11.3%, 6.5-16.2% • Bed rest does not reduce risk of post LP HA

  28. LP Analysis • The results are back: • WBC 900 • 90% PMN • Glucose 3 • Protein 300 • What is the dx?

  29. LP Analysis Strauss et al. JAMA 2006;296:2012. LP technique and analysis • Bacterial meningitis accurately diagnosed by: • CSF:blood glucose <0.4 (LR 18, 12-27) • CSF WBC >500/uL (LR 15, 10-22) • CSF lactate >3.5mmmol/l (LR 21, 14-32) • CSF WBC<500/ul (LR 0.3, 0.2-0.4 • MANY cases of bacterial meningitis w CSF WBC<100!

  30. Treatment • If you are getting a CT before the LP • Get BC ASAP • Start empiric Abx before getting CT • The earlier Abx started the better • Goal of 30 min from presentation • CSF sterilized approx 2h after Abx w neisseria, 4 hr with pneumococcus

  31. Steroids and Meningitis De Gans et al. NEJM 2002;347:1549. Dexamethasone in adults with bacterial meningitis • N=301 • Inclusion Criteria: >17y.o, suspected meningitis in combo with cloudy CSF, +gram stain or CSF WBC>1000 • Exclusion criteria: rxn to Beta lactam Abx or steroids, pregnant, VP shunt, treated w oral or parenteral Abx in previous 48hr, hx or active TB or fungal infxn, recent hx of head trauma, neurosx, PUD • Dex 10mg Q6H x4d vs placebo given 15 min before Abx • Primary outcome- reduction of risk of unfavorable outcomes measured by Glasgow Outcome Score at 8 wks

  32. Unfavorable outcome 15% vs 25% • RR 0.59, 0.37-0.94, p=0.03, favoring dex group • Death 7% vs 15% • RR 0.48,0.24-0.96, p=0.04, favoring dex group • Seizure 5% vs 12% (p=0.04), favoring dex group • Dex had no significant effect on neuro sequelae or hearing loss

  33. CHR Pathway • See hand out • Key points: • Blood cultures and other labs before starting tx if possible • Dex before Abx • Abx before imaging • If not doing imaging, LP before steroids and Abx • Tailor Abx tx based on C/S

  34. CASE

  35. Encephalitis • Inflammation of the brain itself • Caused by same viruses as viral meningitis • Much less common than viral meningitis • Virus enters and can spread to CNS same as viral meningitis • Particular viruses may preferentially attack parts of CNS • HSV to temporal lobes

  36. Encephalitis • Meningeal irritation • ALOC, personality change • Fever • H/A • Seizures and focal neuro deficits much more common

  37. WNV Encephalitis • Culex mosquito feeds on infected birds (jays, ravens, crows) and then transmists to humans • Peaks in aug-sept • Increase in incidence since 2003 • Incubation period of 3-15d • Spectrum of Dz from fever to encephalitis

  38. WNV • West Nile fever • Sudden fever, adenopathy, H/A, abdo pain, n/V, rash, photopphobia, conjunctivitis, anorexia, myalgia/arthralgia • Meningoencephalitis • 0.5% of those infected • More likely in elderly • Weakness, all have myoclonus and fever, flaccid paralysis resembling GBS • Need a 4th sample of CSF and must specify concerned about WNV

  39. CASE #3 • 45M IVDU brought in by EMS after witnessed GTC seizure • PMHx: IVDU, no known sz d/o, no EtOH abuse • Meds: none • 38.9, 14, 110/70, 90, 95%, BG 6.1, GCS 14 • Given he’s had a sz, you decide to CT him

  40. DDx Ring Enhancing Lesion on CT MAGIC DR M- metastases A- Abscess (bacterial, atypical organisms, fungal pathogens…) G- glioma and other primary neoplasms (lymphoma) I- infarction C- contusion D- demyelination (MS, acute disseminated encephalomyelitis) R- resolving hematomoa

  41. Pathophysiology • Focal collection in brain parenchyma • Direct spread usually causes single lesion • Otogenic: temporal lobe, cerebellum • Sinus/odontogenic: frontal lobe • Hematogenous spread gives multiple abscesses • Pulmonary most common source • Direct inoculation • Surgery • trauma

  42. Clinical Features • Subacute course • Most have H/A, localized to side of lesion • Severe, not relieve with OTC drugs • 50% have fever or focal neuro signs • 25% have seizures • Meningeal signs uncommon

  43. Dx • Start with non-enhanced CT • Appears as a focal area of low density within the subcortical white matter • Can then get enhanced • The walls enhance b/c of increased blood vessels, inside is necrotic and is lower density • MR is more sensitive • Not likely us ordering it • Blood cultures

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