Seizures and Seizures and CNS CNS

InfectionsInfectionsAlyssa Morris, R2Alyssa Morris, R2

December 18December 18thth, 2008, 2008

Thanks to: Dr Carol Holmen and Thanks to: Dr Carol Holmen and

Dr WojtowiczDr Wojtowicz

Dr DowlingDr Dowling

ObjectivesObjectives

CNS InfectionsCNS Infections MeningitisMeningitis EncephalitisEncephalitis Abscesses Abscesses

Brain Brain Spinal epidural Spinal epidural

SeizuresSeizures ClassificationClassification Status EpilepticusStatus Epilepticus

Case #1Case #1

60M cough for four days with runny nose, 60M cough for four days with runny nose, fever for 12H, generalized H/A and neck fever for 12H, generalized H/A and neck stiffnessstiffness

PMHx: nonePMHx: none

38.8, 100, 120/86, 16, 98%38.8, 100, 120/86, 16, 98%

MeningitisMeningitis

Inflammation involving the meninges and Inflammation involving the meninges and CSFCSF• Can be infectious and noninfectious Can be infectious and noninfectious

Bacterial MeningitisBacterial Meningitis• 5 cases /100,000 people in US5 cases /100,000 people in US• Men>womenMen>women• Increases in late winter and early springIncreases in late winter and early spring

Viral MeningitisViral Meningitis• Incidence not really know because a lot not Incidence not really know because a lot not

reportedreported• Increase in summer monthsIncrease in summer months

Etiology Etiology What are the most common bacterial What are the most common bacterial

pathogens in adults?pathogens in adults? Streptococcus pneumoniaeStreptococcus pneumoniae Neisseria meningitidis Neisseria meningitidis Listeria monocytogenesListeria monocytogenes

What are some non-infectious causes?What are some non-infectious causes? Drug-inducedDrug-induced Carcinomatous Carcinomatous Serum sicknessSerum sickness Vasculitis Vasculitis SLE/sarcoidSLE/sarcoid

EtiologyEtiology ArbovirusesArboviruses

Herpes VirusesHerpes Viruses HSV, CMV, EBV, Varicella-zosterHSV, CMV, EBV, Varicella-zoster

EnterovirusesEnteroviruses Coxsackie, echovirus, polioCoxsackie, echovirus, polio

Lymphocytic choriomeningitis virusLymphocytic choriomeningitis virus

RetrovirusesRetroviruses

ParamyxovirusesParamyxoviruses

Rabies virusRabies virus

Pathophysiology-Pathophysiology-BacterialBacterial

1. nasopharyngeal colonization1. nasopharyngeal colonization

2. penetration- variety of mechanisms2. penetration- variety of mechanisms

3. bacterial intravascular survival- evasion of the 3. bacterial intravascular survival- evasion of the complement pathway and capsular propertiescomplement pathway and capsular properties

4. cross BBB to enter CSF4. cross BBB to enter CSFDural venous sinuses, cribiform plate, choroid Dural venous sinuses, cribiform plate, choroid

plexusplexus

5. Bacterial proliferation5. Bacterial proliferation

6. convergence of leukocytes into the CSFand 6. convergence of leukocytes into the CSFand TNFalpha, IL 1,6TNFalpha, IL 1,6

Pathophysiology-Pathophysiology-BacterialBacterial

All of the inflammatory factors contribute to a All of the inflammatory factors contribute to a cascade of eventscascade of events

1. increased permeability of BBB, cerebral vasculitis, 1. increased permeability of BBB, cerebral vasculitis, edemaedema

2. increased ICP2. increased ICP

3. decreased cerebral blood flow3. decreased cerebral blood flow

4. cerebral hypoxia4. cerebral hypoxia

5. glucose transport into the CSF is decreased and an 5. glucose transport into the CSF is decreased and an increased use by brain, bacteria and leukocytesincreased use by brain, bacteria and leukocytes

6. increased permeability leads to increased proteins6. increased permeability leads to increased proteins

Pathophysiology-ViralPathophysiology-Viral

Enter the human host thru skin, resp tract, GI Enter the human host thru skin, resp tract, GI tract, infected blood product or donor organstract, infected blood product or donor organs

Viral replication outside of CNSViral replication outside of CNS

spreads to CNS:spreads to CNS: Hematogenous spread*Hematogenous spread* Retrograde transmission along neuronal axonsRetrograde transmission along neuronal axons Direct invasion of subarachnoid space after Direct invasion of subarachnoid space after

infection of nasal mucosainfection of nasal mucosa

Q: What would be some predisposing risk factors?

Host Risk FactorsHost Risk Factors Age<5Age<5 Age>60Age>60 MaleMale Low SESLow SES CrowdingCrowding SplenectomySplenectomy Sickle cell dzSickle cell dz African-AmericanAfrican-American Alcoholism w cirrhosisAlcoholism w cirrhosis diabetesdiabetes

Immunologic defectsImmunologic defects Recent colonizationRecent colonization Dural defectsDural defects Continuous infection Continuous infection

(sinusitis)(sinusitis) Household contactHousehold contact ThalassemiaThalassemia IVDUIVDU Bacterial endocarditisBacterial endocarditis VP shuntVP shunt malignancymalignancy

Clinical FeaturesClinical Features Appear ill and present soon after onsetAppear ill and present soon after onset

Classic triad: fever, nuchal rigidity, ALOCClassic triad: fever, nuchal rigidity, ALOC 33% don’t have this though!33% don’t have this though!

Systemic infectionSystemic infection Non-specific rash, fever, myalgia, SIRS/sepsisNon-specific rash, fever, myalgia, SIRS/sepsis

Meningeal irritationMeningeal irritation Protective mechanism to prevent stretching of Protective mechanism to prevent stretching of

inflammed nerve rootsinflammed nerve roots Kernig, Brudzinski, neck stiffness, Jolt Kernig, Brudzinski, neck stiffness, Jolt

apprehension, HA, CN palsyapprehension, HA, CN palsy

Cerebral edema/incresed ICPCerebral edema/incresed ICP ALOC, HA, vomit, seizure, focal neuro deficitsALOC, HA, vomit, seizure, focal neuro deficits

Clinical FeaturesClinical Features

Does your patient have meningitis? Attia et al Does your patient have meningitis? Attia et al JAMAJAMA 1999;281:175 1999;281:175 Classic triad: fever, neck stiffness, ALOCClassic triad: fever, neck stiffness, ALOC <2/3 have all 3 Sx<2/3 have all 3 Sx 99-100% of patients have at least 1 99-100% of patients have at least 1 Essentially eliminate Dx of meningitis if none Essentially eliminate Dx of meningitis if none

presentpresent Hx inadequate to dx meningitisHx inadequate to dx meningitis

HA sensitivity 50%, N/V 30%HA sensitivity 50%, N/V 30% PE findings have variable sensitivitiesPE 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 SignKernig’s Sign

Flex hip to 90 degreesFlex hip to 90 degrees

Test positive if pain in back and legs or Test positive if pain in back and legs or resist extension beyond 130 degreesresist extension beyond 130 degrees

Brudzinski’s SignBrudzinski’s Sign

Passive flexion of the nectPassive flexion of the nect

Sign + if flex legs at hips to lift legsSign + if flex legs at hips to lift legs

Jolt AccentuationJolt Accentuation

Rotate head side to side at 2-3x/sRotate head side to side at 2-3x/s

+ if H/A worsens+ if H/A worsens

Clinical FeaturesClinical Features

Your patient had a +Kernig sign, do you Your patient had a +Kernig sign, do you think this means he has meningitis?think this means he has meningitis?

What if he didn’t have a positive test, would What if he didn’t have a positive test, would you cross meningitis off of your differential?you cross meningitis off of your differential?

Clinical FeaturesClinical Features

How are accurate are meningeal signs? Thomas How are accurate are meningeal signs? Thomas et al. et al. Clin Inf DisClin Inf Dis 202;35:46 202;35:46 297 patients w suspected meningitis, examine 297 patients w suspected meningitis, examine

before LPbefore LP Nuchal rigidity (inability to passively flex neck)Nuchal rigidity (inability to passively flex neck)

Sens 30%, Spec 68%, +LR 0.94, -LR 1.02Sens 30%, Spec 68%, +LR 0.94, -LR 1.02 Kernig’s and Brudzinski’s signKernig’s and Brudzinski’s sign

Sens 5%, Spec 95%, +LR 0.97, -LR 1.0Sens 5%, Spec 95%, +LR 0.97, -LR 1.0

JAMA articleJAMA article

Conclusions:Conclusions: Kernig, Brudzinski only helpful if present (spec Kernig, Brudzinski only helpful if present (spec

not sens)not sens)

DiagnosisDiagnosis

You are still worried about meningitis and You are still worried about meningitis and want to do an LP. Are you going to CT before want to do an LP. Are you going to CT before doing it? doing it?

When do you scan first and when do you not When do you scan first and when do you not scan first?scan first?

CT and LPCT and LP

CT before LP in suspected meningitis. CT before LP in suspected meningitis. Hasburn et al. Hasburn et al. NEJMNEJM, 2001;345:1727, 2001;345:1727 301 pts w suspected meningitis301 pts w suspected meningitis 235 (78%) had CT before LP235 (78%) had CT before LP 56 (24%) had abnormal results 56 (24%) had abnormal results

11 (5%) had mass effect11 (5%) had mass effect

Features associated with abn CT:Features associated with abn CT: Age>60Age>60 Immune compromisedImmune compromised Hx CNS dzHx CNS dz Hx seizure in week before CTHx seizure in week before CT Abn neuro examAbn neuro exam

CT and LPCT and LP

96 pts had no high risk features, 93 (NPV 97%) had 96 pts had no high risk features, 93 (NPV 97%) had normal CT *** what about 3 who had abnormal?????normal CT *** what about 3 who had abnormal?????

11 pts w mass effect, only 4 no LP as a result11 pts w mass effect, only 4 no LP as a result No herniation in other 7 at 7 days but small numbers!No herniation in other 7 at 7 days but small numbers!

Absence of high risk features indentified those Absence of high risk features indentified those unlikely to have abn CT (LR 0.1, 0.03-0.31) and safe unlikely to have abn CT (LR 0.1, 0.03-0.31) and safe to proceed to immediate LPto proceed to immediate LP

22% w/o CT22% w/o CT No adverse outcomes reportedNo adverse outcomes reported May have missed lesion that could expedite txMay have missed lesion that could expedite tx

Small number of pts w mss effect and LPSmall number of pts w mss effect and LP

LPLP

You decide to LP your patient. You decide to LP your patient.

What are some contraindications to LP?What are some contraindications to LP?• Intracranial lesion with mass effetIntracranial lesion with mass effet• Local infection at puncture siteLocal infection at puncture site

How can you perform LP to limit How can you perform LP to limit complications?complications? HA in up to 60% of ptsHA in up to 60% of pts Believed due to CSF leak thru pucture in duraBelieved due to CSF leak thru pucture in dura

Prevention of PLPHAPrevention of PLPHA

PROVENPROVEN Needle sizeNeedle size Needle typeNeedle type Re-inserting styletRe-inserting stylet Bevel orientationBevel orientation

UNPROVENUNPROVEN Bed restBed rest HydrationHydration Paramedian approachParamedian approach Volume of CSF Volume of CSF

removedremoved

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

PLPHA and Needle SizePLPHA and Needle Size

Numerous studies have clearly Numerous studies have clearly demonstrated that the smaller the needle, demonstrated that the smaller the needle, the lower the IR of PLPHAthe lower the IR of PLPHA

PLPHA and Needle PLPHA and Needle TypeType

Non-Cutting (aka atraumatic, pencil-point, Non-Cutting (aka atraumatic, pencil-point, blunt)blunt) WhitacreWhitacre

Cutting Cutting QuinckeQuincke

Re-Inserting StyletRe-Inserting Stylet

Theory is that w/d of needle w/o stylet Theory is that w/d of needle w/o stylet would result in arachnoid fibers being w/d would result in arachnoid fibers being w/d leading to a persistent dural leak because leading to a persistent dural leak because of a hole that is not as easily healedof a hole that is not as easily healed

In a large RCT of 600 pts incidence of PLPHA In a large RCT of 600 pts incidence of PLPHA with reinsertion and w/o reinsertion was 5% with reinsertion and w/o reinsertion was 5% and 16% respectivelyand 16% respectively

Bevel OrientationBevel Orientation

Theory that needle insertion parallel to Theory that needle insertion parallel to longitudinal fibers result in less leakage longitudinal fibers result in less leakage because bevel pushes fibers away rather because bevel pushes fibers away rather than transecting themthan transecting them

Bevel up when pt in LLD, to the side when Bevel up when pt in LLD, to the side when sitting upsitting up

Studies not on ED ptsStudies not on ED pts

Bevel orientation likely only significant if Bevel orientation likely only significant if using cutting needleusing cutting needle

LP TechniqueLP Technique

Strauss et al. Strauss et al. JAMAJAMA 2006; 296:2012. LP 2006; 296:2012. LP technique and analysistechnique and analysis• Atraumatic vs standard needles no decrease Atraumatic vs standard needles no decrease

in odds of post LP HA (show a trend)in odds of post LP HA (show a trend)• ARR 12.3%, -1.72-26.2%ARR 12.3%, -1.72-26.2%• OR 0.46 (0.19-1.07)OR 0.46 (0.19-1.07)

• Reinsertion of stylet decreased HAReinsertion of stylet decreased HA• ARR 11.3%, 6.5-16.2%ARR 11.3%, 6.5-16.2%

• Bed rest does not reduce risk of post LP HABed rest does not reduce risk of post LP HA

LP AnalysisLP Analysis

The results are back:The results are back: WBC 900WBC 900 90% PMN90% PMN Glucose 3Glucose 3 Protein 300Protein 300

What is the dx?What is the dx?

LP AnalysisLP Analysis

Strauss et al. JAMA 2006;296:2012. LP Strauss et al. JAMA 2006;296:2012. LP technique and analysistechnique and analysis

Bacterial meningitis accurately diagnosed Bacterial meningitis accurately diagnosed by:by: CSF:blood glucose <0.4 (LR 18, 12-27)CSF:blood glucose <0.4 (LR 18, 12-27) CSF WBC >500/uL (LR 15, 10-22)CSF WBC >500/uL (LR 15, 10-22) CSF lactate >3.5mmmol/l (LR 21, 14-32)CSF lactate >3.5mmmol/l (LR 21, 14-32)

CSF WBC<500/ul (LR 0.3, 0.2-0.4CSF WBC<500/ul (LR 0.3, 0.2-0.4 MANY cases of bacterial meningitis w CSF MANY cases of bacterial meningitis w CSF

WBC<100!WBC<100!

TreatmentTreatment

If you are getting a CT before the LPIf you are getting a CT before the LP Get BC ASAPGet BC ASAP Start empiric Abx before getting CTStart empiric Abx before getting CT The earlier Abx started the betterThe earlier Abx started the better

Goal of 30 min from presentationGoal of 30 min from presentation

CSF sterilized approx 2h after Abx w CSF sterilized approx 2h after Abx w neisseria, 4 hr with pneumococcus neisseria, 4 hr with pneumococcus

Steroids and Steroids and MeningitisMeningitis

De Gans et al. De Gans et al. NEJMNEJM 2002;347:1549. Dexamethasone 2002;347:1549. Dexamethasone in adults with bacterial meningitisin adults with bacterial meningitis N=301N=301 Inclusion Criteria: >17y.o, suspected meningitis in Inclusion Criteria: >17y.o, suspected meningitis in

combo with cloudy CSF, +gram stain or CSF combo with cloudy CSF, +gram stain or CSF WBC>1000WBC>1000

Exclusion criteria: rxn to Beta lactam Abx or steroids, Exclusion criteria: rxn to Beta lactam Abx or steroids, pregnant, VP shunt, treated w oral or parenteral Abx pregnant, VP shunt, treated w oral or parenteral Abx in previous 48hr, hx or active TB or fungal infxn, in previous 48hr, hx or active TB or fungal infxn, recent hx of head trauma, neurosx, PUDrecent hx of head trauma, neurosx, PUD

Dex 10mg Q6H x4d vs placebo given 15 min before Dex 10mg Q6H x4d vs placebo given 15 min before AbxAbx

Primary outcome- reduction of risk of unfavorable Primary outcome- reduction of risk of unfavorable outcomes measured by Glasgow Outcome Score at 8 outcomes measured by Glasgow Outcome Score at 8 wkswks

Unfavorable outcome 15% vs 25%Unfavorable outcome 15% vs 25% RR 0.59, 0.37-0.94, p=0.03, favoring dex RR 0.59, 0.37-0.94, p=0.03, favoring dex

groupgroup

Death 7% vs 15%Death 7% vs 15% RR 0.48,0.24-0.96, p=0.04, favoring dex groupRR 0.48,0.24-0.96, p=0.04, favoring dex group

Seizure 5% vs 12% (p=0.04), favoring dex Seizure 5% vs 12% (p=0.04), favoring dex groupgroup

Dex had no significant effect on neuro Dex had no significant effect on neuro sequelae or hearing losssequelae or hearing loss

CHR PathwayCHR Pathway

See hand out See hand out

Key points:Key points: Blood cultures and other labs before starting Blood cultures and other labs before starting

tx if possibletx if possible Dex before AbxDex before Abx Abx before imagingAbx before imaging If not doing imaging, LP before steroids and If not doing imaging, LP before steroids and

AbxAbx Tailor Abx tx based on C/STailor Abx tx based on C/S

CASECASE

EncephalitisEncephalitis

Inflammation of the brain itselfInflammation of the brain itself

Caused by same viruses as viral meningitisCaused by same viruses as viral meningitis

Much less common than viral meningitisMuch less common than viral meningitis

Virus enters and can spread to CNS same as Virus enters and can spread to CNS same as viral meningitisviral meningitis

Particular viruses may preferentially attack Particular viruses may preferentially attack parts of CNSparts of CNSo HSV to temporal lobesHSV to temporal lobes

EncephalitisEncephalitis

Meningeal irritationMeningeal irritation

ALOC, personality changeALOC, personality change

FeverFever

H/AH/A

Seizures and focal neuro deficits much more Seizures and focal neuro deficits much more common common

WNV EncephalitisWNV Encephalitis

Culex mosquito feeds on infected birds Culex mosquito feeds on infected birds (jays, ravens, crows) and then transmists to (jays, ravens, crows) and then transmists to humanshumans

Peaks in aug-septPeaks in aug-sept

Increase in incidence since 2003Increase in incidence since 2003

Incubation period of 3-15dIncubation period of 3-15d

Spectrum of Dz from fever to encephalitisSpectrum of Dz from fever to encephalitis

WNVWNV

West Nile feverWest Nile fever Sudden fever, adenopathy, H/A, abdo pain, Sudden fever, adenopathy, H/A, abdo pain,

n/V, rash, photopphobia, conjunctivitis, n/V, rash, photopphobia, conjunctivitis, anorexia, myalgia/arthralgiaanorexia, myalgia/arthralgia

Meningoencephalitis Meningoencephalitis 0.5% of those infected0.5% of those infected More likely in elderly More likely in elderly Weakness, all have myoclonus and fever, Weakness, all have myoclonus and fever,

flaccid paralysis resembling GBSflaccid paralysis resembling GBS Need a 4Need a 4thth sample of CSF and must specify sample of CSF and must specify

concerned about WNVconcerned about WNV

CASE #3CASE #3

45M IVDU brought in by EMS after 45M IVDU brought in by EMS after witnessed GTC seizurewitnessed GTC seizure

PMHx: IVDU, no known sz d/o, no EtOH PMHx: IVDU, no known sz d/o, no EtOH abuseabuse

Meds: noneMeds: none

38.9, 14, 110/70, 90, 95%, BG 6.1, GCS 14 38.9, 14, 110/70, 90, 95%, BG 6.1, GCS 14

Given he’s had a sz, you decide to CT himGiven he’s had a sz, you decide to CT him

DDx Ring Enhancing DDx Ring Enhancing Lesion on CTLesion on CT

MAGIC DRMAGIC DR

M- metastasesM- metastases

A- Abscess (bacterial, atypical organisms, fungal A- Abscess (bacterial, atypical organisms, fungal pathogens…)pathogens…)

G- glioma and other primary neoplasms (lymphoma)G- glioma and other primary neoplasms (lymphoma)

I- infarctionI- infarction

C- contusionC- contusion

D- demyelination (MS, acute disseminated D- demyelination (MS, acute disseminated encephalomyelitis)encephalomyelitis)

R- resolving hematomoaR- resolving hematomoa

PathophysiologyPathophysiology Focal collection in brain parenchymaFocal collection in brain parenchyma

Direct spread usually causes single lesionDirect spread usually causes single lesion Otogenic: temporal lobe, cerebellumOtogenic: temporal lobe, cerebellum Sinus/odontogenic: frontal lobeSinus/odontogenic: frontal lobe

Hematogenous spread gives multiple Hematogenous spread gives multiple abscessesabscesses Pulmonary most common sourcePulmonary most common source

Direct inoculation Direct inoculation Surgery Surgery traumatrauma

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 malformations (especially right-to-left shunts)

Streptococcus

Clinical FeaturesClinical Features

Subacute courseSubacute course

Most have H/A, localized to side of lesionMost have H/A, localized to side of lesion Severe, not relieve with OTC drugsSevere, not relieve with OTC drugs

50% have fever or focal neuro signs50% have fever or focal neuro signs

25% have seizures25% have seizures

Meningeal signs uncommonMeningeal signs uncommon

DxDx Start with non-enhanced CTStart with non-enhanced CT

Appears as a focal area of low density within Appears as a focal area of low density within the subcortical white matterthe subcortical white matter

Can then get enhancedCan then get enhanced The walls enhance b/c of increased blood The walls enhance b/c of increased blood

vessels, inside is necrotic and is lower densityvessels, inside is necrotic and is lower density

MR is more sensitiveMR is more sensitive Not likely us ordering itNot likely us ordering it

Blood culturesBlood cultures

TxTx Identify and tx source of infectionIdentify and tx source of infection

Cefotaxime or ceftriaxone + flagyl Cefotaxime or ceftriaxone + flagyl otogenic and sinogenic abscesses and if no otogenic and sinogenic abscesses and if no

sourcesource Vanco if S aureus suspectedVanco if S aureus suspected

Consult neurosx Consult neurosx

?aspiration?aspiration

Steroids if significant mass effectSteroids if significant mass effect

CASECASE

Spinal Epidural Spinal Epidural AbscessAbscess

Most common in the thoracolumbar areaMost common in the thoracolumbar area Larger area with more fatty tissue prone to Larger area with more fatty tissue prone to

infectioninfection

Usually posterior, may be anterior if below L1Usually posterior, may be anterior if below L1 Anterior dura adherent to vertebra above this levelAnterior dura adherent to vertebra above this level

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

Longitudinal extension common, often 3-5 Longitudinal extension common, often 3-5 segmentssegments

More often from single organismMore often from single organism Staph after neuro traumaStaph after neuro trauma Streptococci with contiguous spreadStreptococci with contiguous spread

Risk FactorsRisk Factors

Epidural catheter placementEpidural catheter placement DMDM EtOHEtOH HIVHIV TraumaTrauma Spine SxSpine Sx Adjacent infectionAdjacent infection IVDUIVDU

Clinical FeaturesClinical Features

Classic Triad: fever, back pain, focal Classic Triad: fever, back pain, focal SxSx Few have all threeFew have all three

Non-specific malaiseNon-specific malaise

Focal signs of cord compressionFocal signs of cord compression Can progress from focal severe Can progress from focal severe

back pain to paralysisback pain to paralysis Paralysis can quickly become Paralysis can quickly become

irreversibleirreversible

DxDx

MUST consider itMUST consider it Labs not that helpfulLabs not that helpful Increased ESR, +/- WBCIncreased ESR, +/- WBC XRXR

May show osteomyelitis May show osteomyelitis BCBC CT guided aspirationCT guided aspiration MRIMRI most sensitive and show anatomy very most sensitive and show anatomy very

wellwell

TxTx

Consult SpineConsult Spine Likely to need early surgical Likely to need early surgical

decompression +IV ABxdecompression +IV ABx

AbxAbx Cover staph, strep, GNBCover staph, strep, GNB Clox/flagyl/cefotaxime until have Clox/flagyl/cefotaxime until have

C/S resultsC/S results Vanco if concern of MRSAVanco if concern of MRSA

CASECASE

56M brought in by EMS for 56M brought in by EMS for witnessed seizure activity. Was witnessed seizure activity. Was post-ictal when EMS arrived. post-ictal when EMS arrived.

PMHx: nonePMHx: none

Meds: noneMeds: none

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

SeizuresSeizures

Definition: clinical manifestation of Definition: clinical manifestation of excessive abn cortical neuron excessive abn cortical neuron activityactivity

Complex and poorly understoodComplex and poorly understood

To have ALOCTo have ALOC Must involve both cortices or RAS Must involve both cortices or RAS

in brainstemin brainstem

Q: How do you classify primary Q: How do you classify primary seizures? seizures?

ClassificationClassification

11. Partial. Partial Discharges begin in localized area of Discharges begin in localized area of

cortexcortex Often secondary to a structural lesionOften secondary to a structural lesion A) Simple partial (no change in LOC)A) Simple partial (no change in LOC) B) Complex partial (impaired LOCB) Complex partial (impaired LOC Can become secondarily generalized Can become secondarily generalized Features of simple: flocal clonic movt’s, Features of simple: flocal clonic movt’s,

paresthesias, sensory experiences, paresthesias, sensory experiences, sense of déjà vusense of déjà vu

Features of complex: automatisms, lip Features of complex: automatisms, lip smacking, repeated swallowing or smacking, repeated swallowing or phrases, maintain higher cortical fxn phrases, maintain higher cortical fxn

Classification Classification

2. Generalized2. Generalized Consciousness alteredConsciousness altered Simultaneous activation of entire cerebral cortex ORSimultaneous activation of entire cerebral cortex OR Focus that is often subcortical and midline leading to Focus that is often subcortical and midline leading to

prompt loss of consciousness and bilateral prompt loss of consciousness and bilateral involvementinvolvement

A) Tonic-clonic: convulsiveA) Tonic-clonic: convulsive B) Absence: sudden cessation of N conscious activity B) Absence: sudden cessation of N conscious activity C) Myoclonic: single or repetitive jerking movementsC) Myoclonic: single or repetitive jerking movements D) Tonic: muscle tome increased and stiffenD) Tonic: muscle tome increased and stiffen E) Clonic: rhythmic jerking movementsE) Clonic: rhythmic jerking movements F) Atonic: loss of muscle tone (“drop attack”)F) Atonic: loss of muscle tone (“drop attack”)

CASE cont…CASE cont…

Back to the case…Back to the case…

What would you like to know on history? What would you like to know on history?

What are you looking for on physical exam?What are you looking for on physical exam?

HXHX

Need to first determine if really was a Need to first determine if really was a seizure b/c can be confused withseizure b/c can be confused with Syncope, pseudoseizure, rigors, Syncope, pseudoseizure, rigors,

migraine, mov’t d/o, narcolepsymigraine, mov’t d/o, narcolepsyAuraAuraProgression of motor activityProgression of motor activityIncontinenceIncontinenceLocalized vs generalized/ symmetric Localized vs generalized/ symmetric

vs assymetricvs assymetricDurationDuration

HxHx

Post-ictalPost-ictal

If known sz d/oIf known sz d/o Med complianceMed compliance Change in medsChange in meds Usualy seizure pattern/triggersUsualy seizure pattern/triggers

OtherOther EtOHEtOH DrugsDrugs pregnancypregnancy

PEPE

Look for focal neuro deficitsLook for focal neuro deficits

Look for signs of systemic illnessLook for signs of systemic illness

Search for injuries secondary to Search for injuries secondary to seizureseizure

ALWAYS check temp and chem ALWAYS check temp and chem stripstrip

First Time SeizureFirst Time Seizure

Back to the case…Back to the case…

He tells you he has never had a He tells you he has never had a seizure before.seizure before.

What would you be concerned What would you be concerned about? (DDx)about? (DDx)

What would your work up consist What would your work up consist of? of?

Causes of Secondary Causes of Secondary SzsSzs

D- DrugsD- DrugsCocaine, lidocaine, BDZ, TCA, SSRI, propranolol, Cocaine, lidocaine, BDZ, TCA, SSRI, propranolol,

theophylline, EtOH w/dtheophylline, EtOH w/d

I- InfectionI- InfectionMeningitis, encephalitis, abscessMeningitis, encephalitis, abscess

M- metabolicM- metabolicHypoxia, hypo/hyperglycemia, hyperCa, Hypoxia, hypo/hyperglycemia, hyperCa,

hypo/hypernatremia, renal or hepatic failurehypo/hypernatremia, renal or hepatic failure

E- eclampsia/ encephalopathy (hypoxic)E- eclampsia/ encephalopathy (hypoxic)

S- structural S- structural ICH, tumor, AVM, trauma, degenerative dzICH, tumor, AVM, trauma, degenerative dz

DDx- Drugs causing SzDDx- Drugs causing Sz

““OTIS CAMPBELL”OTIS CAMPBELL” OrganophosphatesOrganophosphates TCATCA INH, insulinINH, insulin SympathomimeticsSympathomimetics Camphor, cocaineCamphor, cocaine Amphetamines, anticholinergicsAmphetamines, anticholinergics Methylxantines (theophylline)Methylxantines (theophylline) PCPPCP BDZBDZ EtOH w/dEtOH w/d Lithium/lidocaineLithium/lidocaine Lead/lindaneLead/lindane

DxDx

Krumholz et al. Krumholz et al. NeurologyNeurology 2007;69:1996. 2007;69:1996. Evaluating an apparent unprovoked first seizure Evaluating an apparent unprovoked first seizure in adults.in adults.

An evidence-based review using strict review An evidence-based review using strict review criteriacriteria

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

CT/MR- 10% significantly abnCT/MR- 10% significantly abn Recommend routinely as level B evidenceRecommend routinely as level B evidence

Blood work: CBC, Blood glucose, lytes, cr, ca, Blood work: CBC, Blood glucose, lytes, cr, ca, mg found abn in 15%mg found abn in 15%

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Other investigations prnOther investigations prn B-HcGB-HcG AED levelsAED levels Tox screenTox screen CK CK

When would you not CT a patient who When would you not CT a patient who seized?seized?

Febrile szFebrile sz Typical seizureTypical seizure

DxDx ACEP recommendations for CT: Scan if- ACEP recommendations for CT: Scan if-

New focal deficitsNew focal deficits 11stst seizure seizure Change in patternChange in pattern Persistent change in LOCPersistent change in LOC Recent head traumaRecent head trauma CoagulopathyCoagulopathy AnticoagulatedAnticoagulated HIV, immunosuppressedHIV, immunosuppressed MeningismusMeningismus AlcoholismAlcoholism

Case cont…Case cont…

Back to the case…Back to the case…

CT and labs NCT and labs N

Your patient starts seizing again. How do Your patient starts seizing again. How do you want to manage him?you want to manage him?

TxTx Back to basics:Back to basics:

ABCs, chem stripABCs, chem strip IV, O2, sat monitor, suction availableIV, O2, sat monitor, suction available Gentle, firm restraintGentle, firm restraint Place on side to reduce aspiration Place on side to reduce aspiration

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

New Onset seizureNew Onset seizure Neuro consult- does not need to be as Neuro consult- does not need to be as

inpatientinpatient NO DRIVING until seen by neuroNO DRIVING until seen by neuro

MxMx

Who does neuro want to see?Who does neuro want to see? New onset seizure New onset seizure Focal neuro exam abnormalityFocal neuro exam abnormality Persistent ALOCPersistent ALOC New intracranial lesion- with New intracranial lesion- with

neurosxneurosx Change in seizure pattern Change in seizure pattern Poorly controlled seizuresPoorly controlled seizures Pregnant patient Pregnant patient

DrugsDrugs In general In general

11stst line: BDZ line: BDZ Directly enhance GABA-mediated neuronal Directly enhance GABA-mediated neuronal

inhibitioninhibition Terminate 75-90% seizuresTerminate 75-90% seizures

22ndnd line: Phenytoin line: Phenytoin Suppresses neuronal recruitment but does Suppresses neuronal recruitment but does

suppress electrical activity at the ictogenic suppress electrical activity at the ictogenic focusfocus

Onset is 10-30 minOnset is 10-30 min 22ndnd line: Phenobarbital line: Phenobarbital

Decreases ictal and physiologic cortical Decreases ictal and physiologic cortical activity thru GABA enhancementactivity thru GABA enhancement

Onset is 15-30 minOnset is 15-30 min

DrugsDrugs

FosphenytoinFosphenytoin Pro-drug of phenytoin with similar activityPro-drug of phenytoin with similar activity Less local rxnLess local rxn Expensive!Expensive!

ValproateValproate Increases GABA concentration Increases GABA concentration Can be given rectallyCan be given rectally

PropofolPropofol Acts at a location other than the BDZ Acts at a location other than the BDZ

binding site and modifies Cl channelbinding site and modifies Cl channel Theoretically synergistic with BDZ and Theoretically synergistic with BDZ and

barbituratesbarbiturates

Status EpilepticusStatus Epilepticus

Continuous seizure activity >30 min OR Continuous seizure activity >30 min OR recurrent seizures with incomplete recovery recurrent seizures with incomplete recovery between episodesbetween episodes

Some recommend revising to activity Some recommend revising to activity lasting longer than 5 minuteslasting longer than 5 minutes

Most common cause is noncompliance with Most common cause is noncompliance with AEDsAEDs

Pathophys:Pathophys: GABA receptors less sensitive to BDZ as GABA receptors less sensitive to BDZ as

seizures become prolonged in animalsseizures become prolonged in animals NMDA recpetors become more effective in NMDA recpetors become more effective in

animals with prolonged seizuresanimals with prolonged seizures

TxTx

ABCsABCs Intubate earlyIntubate early

O2, IV, chem strip, monitorsO2, IV, chem strip, monitors

American Academy of NeurologyAmerican Academy of Neurology 11stst line: Lorazepam 4mg IV slowly line: Lorazepam 4mg IV slowly

(2mg/min)(2mg/min) Rpt Rpt If 1If 1stst line fails, unlikely to respond to line fails, unlikely to respond to

another BDZ or phenobarbital another BDZ or phenobarbital

BenzosBenzos

Lorazepam preferred over Lorazepam preferred over diazepamdiazepam Alldredge et al NEJM Alldredge et al NEJM

2001;345:6312001;345:631 SE aborted in 59% vs 43%SE aborted in 59% vs 43%

11stst line drug line drug

Watch for resp depression Watch for resp depression

PhenytoinPhenytoin

Load after BDZ givenLoad after BDZ given

18-20mg/kg (15mg/kg in elderly)18-20mg/kg (15mg/kg in elderly)

Watch for injection site rxn, Watch for injection site rxn, hypotension and dysrhythmiashypotension and dysrhythmias

Drugs Used in SEDrugs Used in SE

Lorazepam 4mg IV at 2mg/minLorazepam 4mg IV at 2mg/minMidazolam 2.5-15mg IV, 0.2mg/kg IM, Midazolam 2.5-15mg IV, 0.2mg/kg IM,

can also infuse can also infuse Phenytoin 20mg/kg IV at 50mg/minPhenytoin 20mg/kg IV at 50mg/minFosphenytoin 20mg.kg IV at 50mg/minFosphenytoin 20mg.kg IV at 50mg/minPhenobarbital 20mg/kg IV at 60-Phenobarbital 20mg/kg IV at 60-

100mg/min100mg/minPropofol 1-2mg/kg then 2-15mg/kg/hPropofol 1-2mg/kg then 2-15mg/kg/hValproate 20mg PR or 20mg IVValproate 20mg PR or 20mg IVPentobarbital 5mg/kg at 25mg/min Pentobarbital 5mg/kg at 25mg/min

then titrate to EEGthen titrate to EEG IsofluraneIsoflurane