Seizures and CNS Infections by qjFn2f17

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									      Seizures and CNS
             Infections
               Alyssa Morris, R2
           December 18th, 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

 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%
                 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
                      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
                      Etiology
 Arboviruses

 Herpes Viruses
   HSV, CMV, EBV, Varicella-zoster

 Enteroviruses
   Coxsackie, echovirus, polio

 Lymphocytic choriomeningitis virus

 Retroviruses

 Paramyxoviruses

 Rabies virus
    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
    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
        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?
                   Host Risk Factors
 Age<5                      Immunologic defects
 Age>60                     Recent colonization
 Male                       Dural defects
 Low SES                    Continuous infection (sinusitis)
 Crowding                   Household contact
 Splenectomy                Thalassemia
 Sickle cell dz             IVDU
 African-American           Bacterial endocarditis
 Alcoholism w cirrhosis     VP shunt
 diabetes                   malignancy
                  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
               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
PE FINDING             SENSITIVITY
Fever                  85%
Neck Stiffness         70%
ALOC                   67%
Focal Neuro deficits   23%
Rash                   22%
Kernig                 57%
Brudzinski             97%
Jolt accentuation      97%
                  Kernig’s Sign
 Flex hip to 90 degrees

 Test positive if pain in back and legs or resist extension
  beyond 130 degrees
               Brudzinski’s Sign

 Passive flexion of the nect

 Sign + if flex legs at hips to lift legs
             Jolt Accentuation

 Rotate head side to side at 2-3x/s

 + if H/A worsens
              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?
                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)
                    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?
                    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
                       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
                             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
            Prevention of PLPHA

PROVEN                                      UNPROVEN
 Needle size                                Bed rest
 Needle type                                Hydration
 Re-inserting stylet                        Paramedian approach
 Bevel orientation                          Volume of CSF removed




*See Shawn’t talk on remergs.com for comprehensive review of the literature
      PLPHA and Needle Size

 Numerous studies have clearly demonstrated that the
  smaller the needle, the lower the IR of PLPHA
      PLPHA and Needle Type

 Non-Cutting (aka atraumatic, pencil-point, blunt)
   Whitacre

 Cutting
   Quincke
            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
             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
                   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
                    LP Analysis

 The results are back:
   WBC 900
   90% PMN
   Glucose 3
   Protein 300

 What is the dx?
                   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!
                       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
      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
 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
                 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
CASE
                  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
  o HSV to temporal lobes
                  Encephalitis

 Meningeal irritation

 ALOC, personality change

 Fever

 H/A

 Seizures and focal neuro deficits much more common
            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
                             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
                     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
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
              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
SOURCE                             PATHOGENS

Paranasal sinuses                  Streptococcus (especially Streptococcus milleri), haemophilus, bacteroides,
                                   fusobacterium


Odontogenic sources                Streptococcus, bacteroides, prevotella, fusobacterium, haemophilus


Otogenic sources                   Enterobacteriaceae, streptococcus, pseudomonas, bacteroides


Lungs                              Streptococcus, fusobacterium, actinomyces

Urinary tract                      Pseudomonas, enterobacter

Penetrating head trauma            Staphylococcus aureus, enterobacter, clostridium

Neurosurgical procedure            Staphylococcus, streptococcus, pseudomonas, enterobacter

Endocarditis                       Viridans streptococcus, S. aureus

Congenital cardiac                 Streptococcus
malformations (especially right-
to-left shunts)
              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
                                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
                                 Tx
 Identify and tx source of infection
   Cefotaxime or ceftriaxone + flagyl
        otogenic and sinogenic abscesses and if no source
   Vanco if S aureus suspected

 Consult neurosx

        ?aspiration

 Steroids if significant mass effect
CASE
       Spinal Epidural Abscess
 Most common in the thoracolumbar area
   Larger area with more fatty tissue prone to infection

 Usually posterior, may be anterior if below L1
   Anterior dura adherent to vertebra above this level

 Begin as focal infection in disc or jxn b/t disc and vertebral
  body (discitis)

 Longitudinal extension common, often 3-5 segments

 More often from single organism
   Staph after neuro trauma
   Streptococci with contiguous spread
              Risk Factors
 Epidural catheter placement
 DM
 EtOH
 HIV
 Trauma
 Spine Sx
 Adjacent infection
 IVDU
            Clinical Features
 Classic Triad: fever, back pain, focal Sx
   Few have all three

 Non-specific malaise

 Focal signs of cord compression
   Can progress from focal severe back pain to
    paralysis
   Paralysis can quickly become irreversible
                          Dx
 MUST consider it
 Labs not that helpful
 Increased ESR, +/- WBC
 XR
   May show osteomyelitis
 BC
 CT guided aspiration
 MRI most sensitive and show anatomy very well
                      Tx

 Consult Spine
   Likely to need early surgical decompression
    +IV ABx
 Abx
   Cover staph, strep, GNB
   Clox/flagyl/cefotaxime until have C/S results
   Vanco if concern of MRSA
                    CASE

 56M brought in by EMS for witnessed seizure
  activity. Was post-ictal when EMS arrived.
 PMHx: none

 Meds: none

 37.7, 15, 70, 130/80, 98%, BS 6.2, GCS 15
                  Seizures

 Definition: clinical manifestation of excessive
  abn cortical neuron activity
 Complex and poorly understood

 To have ALOC
   Must involve both cortices or RAS in
    brainstem
 Q: How do you classify primary seizures?
                Classification
1. Partial
    Discharges begin in localized area of cortex
    Often secondary to a structural lesion
    A) Simple partial (no change in LOC)
    B) Complex partial (impaired LOC
    Can become secondarily generalized
    Features of simple: flocal clonic movt’s,
    paresthesias, sensory experiences, sense of déjà vu
   Features of complex: automatisms, lip smacking,
    repeated swallowing or phrases, maintain higher
    cortical fxn
                   Classification
2. Generalized
   Consciousness altered
   Simultaneous activation of entire cerebral cortex OR
   Focus that is often subcortical and midline leading to prompt
      loss of consciousness and bilateral involvement
     A) Tonic-clonic: convulsive
     B) Absence: sudden cessation of N conscious activity
     C) Myoclonic: single or repetitive jerking movements
     D) Tonic: muscle tome increased and stiffen
     E) Clonic: rhythmic jerking movements
     F) Atonic: loss of muscle tone (“drop attack”)
                 CASE cont…

 Back to the case…

 What would you like to know on history?

 What are you looking for on physical exam?
                        HX
 Need to first determine if really was a seizure b/c
  can be confused with
   Syncope, pseudoseizure, rigors, migraine,
    mov’t d/o, narcolepsy
 Aura
 Progression of motor activity
 Incontinence
 Localized vs generalized/ symmetric vs
  assymetric
 Duration
                       Hx
 Post-ictal

 If known sz d/o
   Med compliance
   Change in meds
   Usualy seizure pattern/triggers

 Other
   EtOH
   Drugs
   pregnancy
                     PE

 Look for focal neuro deficits

 Look for signs of systemic illness

 Search for injuries secondary to seizure

 ALWAYS check temp and chem strip
           First Time Seizure

 Back to the case…

 He tells you he has never had a seizure
 before.
 What would you be concerned about? (DDx)

 What would your work up consist of?
      Causes of Secondary Szs
D- Drugs
  Cocaine, lidocaine, BDZ, TCA, SSRI, propranolol, theophylline,
    EtOH w/d

I- Infection
  Meningitis, encephalitis, abscess

M- metabolic
  Hypoxia, hypo/hyperglycemia, hyperCa, hypo/hypernatremia,
    renal or hepatic failure

E- eclampsia/ encephalopathy (hypoxic)
S- structural
  ICH, tumor, AVM, trauma, degenerative dz
       DDx- Drugs causing Sz
“OTIS CAMPBELL”
 Organophosphates
 TCA
 INH, insulin
 Sympathomimetics
 Camphor, cocaine
 Amphetamines, anticholinergics
 Methylxantines (theophylline)
 PCP
 BDZ
 EtOH w/d
 Lithium/lidocaine
 Lead/lindane
                           Dx
 Krumholz et al. Neurology 2007;69:1996. Evaluating an
  apparent unprovoked first seizure in adults.

 An evidence-based review using strict review criteria

 EEG- 23% revealed epileptiform abnormalities, predictive
  of seizure recurrence
   Recommended routinely as level B evidence

 CT/MR- 10% significantly abn
   Recommend routinely as level B evidence

 Blood work: CBC, Blood glucose, lytes, cr, ca, mg found
  abn in 15%
                        Dx
 Other investigations prn
   B-HcG
   AED levels
   Tox screen
   CK

 When would you not CT a patient who seized?
     Febrile sz
     Typical seizure
                         Dx
 ACEP recommendations for CT: Scan if-
   New focal deficits
   1st seizure
   Change in pattern
   Persistent change in LOC
   Recent head trauma
   Coagulopathy
   Anticoagulated
   HIV, immunosuppressed
   Meningismus
   Alcoholism
                  Case cont…

 Back to the case…

 CT and labs N

 Your patient starts seizing again. How do you want to
  manage him?
                               Tx
 Back to basics:
   ABCs, chem strip
   IV, O2, sat monitor, suction available
   Gentle, firm restraint
   Place on side to reduce aspiration

 Known seizure Hx
   Check serum levels of AEDs
   Controversial as to if load (1/2 dose) on spec

 New Onset seizure
   Neuro consult- does not need to be as inpatient
   NO DRIVING until seen by neuro
                        Mx

 Who does neuro want to see?
   New onset seizure
   Focal neuro exam abnormality
   Persistent ALOC
   New intracranial lesion- with neurosx
   Change in seizure pattern
   Poorly controlled seizures
   Pregnant patient
                          Drugs
 In general
   1st line: BDZ
      Directly enhance GABA-mediated neuronal inhibition
      Terminate 75-90% seizures
   2nd line: Phenytoin
      Suppresses neuronal recruitment but does suppress
       electrical activity at the ictogenic focus
     Onset is 10-30 min
   2nd line: Phenobarbital
     Decreases ictal and physiologic cortical activity thru
       GABA enhancement
     Onset is 15-30 min
                     Drugs
 Fosphenytoin
   Pro-drug of phenytoin with similar activity
   Less local rxn
   Expensive!
 Valproate
   Increases GABA concentration
   Can be given rectally
 Propofol
   Acts at a location other than the BDZ binding site
    and modifies Cl channel
   Theoretically synergistic with BDZ and barbiturates
            Status Epilepticus
 Continuous seizure activity >30 min OR recurrent seizures
  with incomplete recovery between episodes

 Some recommend revising to activity lasting longer than 5
  minutes

 Most common cause is noncompliance with AEDs

 Pathophys:
   GABA receptors less sensitive to BDZ as seizures become
    prolonged in animals
   NMDA recpetors become more effective in animals with
    prolonged seizures
                          Tx

 ABCs
   Intubate early

 O2, IV, chem strip, monitors

 American Academy of Neurology
   1st line: Lorazepam 4mg IV slowly (2mg/min)
   Rpt
   If 1st line fails, unlikely to respond to another BDZ
    or phenobarbital
                  Benzos

 Lorazepam preferred over diazepam
   Alldredge et al NEJM 2001;345:631
   SE aborted in 59% vs 43%

 1st line drug

 Watch for resp depression
               Phenytoin

 Load after BDZ given

 18-20mg/kg (15mg/kg in elderly)

 Watch for injection site rxn, hypotension
 and dysrhythmias
             Drugs Used in SE
 Lorazepam 4mg IV at 2mg/min
 Midazolam 2.5-15mg IV, 0.2mg/kg IM, can also
    infuse
   Phenytoin 20mg/kg IV at 50mg/min
   Fosphenytoin 20mg.kg IV at 50mg/min
   Phenobarbital 20mg/kg IV at 60-100mg/min
   Propofol 1-2mg/kg then 2-15mg/kg/h
   Valproate 20mg PR or 20mg IV
   Pentobarbital 5mg/kg at 25mg/min then titrate to
    EEG
   Isoflurane

								
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