NEUROLOGY

FOR THE NON-NEUROLOGIST

SATURDAY, MAY 6, 2017

University Conference Center

500 University Drive
Hershey, PA 17033

A continuing education service of Penn State College of Medicine

 FAST FACTS
Neurology for the Non-Neurologist, May 6, 2017, D6056-17-Y
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DISCLOSURE
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limitation, FDA-approved uses and any off-label uses.

The following speakers and planning committee members disclose:

Elisabeth Lucassen, MD
Biogen Speakers Bureau
EMD Serono Speakers Bureau
Genzyme Consultant/Advisor
Norvartis Speakers Bureau
Thyagarajan Subramanian, MD
Acadia Pharmaceuticals Speakers Bureau, Consultant/Advisor
ADAMAS Research Grant
Allergan Research Grant
Merz Pharmaceuticals Research Grant
USWorldMed Consultant/pAdvisor

The following speakers and planning committee members have no conflicts of interest to disclose:
Aiesha Ahmed, MD*
Margaret Clanagan*
Sol De Jesus, MD
David Ermak, DO
Tiffany Fisher, MD
Divpreet Kaur, MD
Stephen Ross, MD, FAAN
Mark Stahl, MD, PhD

*planning committee member

**speaker and planning committee member

Penn State Continuing Education staff involved in the planning of this activity have no financial relationships with any commercial interests
relevant to this activity.

Speakers are required to inform the program audience when they are discussing off-label or investigational uses of devices or drugs.
AcuteIschemicStroke
ContinuityAcrossthe
SpectrumofCare

DavidErmak,DO
 ClinicalStrokeDiagnosticsand
Management

DavidErmak,DO
AssistantProfessor

Disclosures
None
 Objectives
Reviewthepathophysiologyofischemicstrokeandtheappropriateclinical
evaluation

Brieflyreviewacutestrokeinterventionwithfocusonintraarterial
managementstrategiesthroughreviewofrecentlypublishedstudies

Reviewcurrentrecommendationsforsecondarypreventionofischemic
stroke

Becomefamiliarnewerandlesscommonantithrombotics

Beonthelookoutforthetakeawayslides,thesearehighyield
informationataglance.

StrokeTypes
STROKE Primary 15%

hemorrhage

85%
Subarachnoid
Ischemic stroke Intraparenchymal

20% 25% 20% 30% 5%

Atherosclerotic Small Cardiogenic Cryptogenic Other, unusual

Large vessel Vessel Embolism stroke Causes
Disease Disease Prothrombotic states
Atrial fibrillation
Dissections
Valve disease
Arteritis
Ventricular thrombi
Migraine/vasospasm
Many others
Hypoperfusion Arteriogenic Drug abuse
emboli Many more

Adapted from:
Chest 1998;114(5):683S-698S
 Definitions
CorticalSigns
Gazepreference,aphasia,neglect,hemianopsia
SmallVessel
Smallpenetratingarteriesindeepsubcortical
locations
E.g.:lenticulostriate,thalamogeniculate
LargeVessel
Aorta,Subclavian,Brachiocephalic,CCA,ICA,
MCA,ACA,PCA,Basilar,Vertebral

MeanArterialPressure
CPP=MAP ICP
2 /3
AllCBFisforwardatalltimes(ICA,MCA,Verts,
Basilar,etc.)
2/3ofthecardiaccycleisspentindiastole
 MeanArterialPressure
ThefocusonMAPrangeshouldonlybeused
intheacutesetting;thegoalbeingtoperfuse
thebrainatriskofinfarctionduringanacute
stroke(i.e.savethepenumbra).
Thiscanbenormallyachievedbycerebral
autoregulation
InacutestrokethereisregionalchangesinICP
andoftenthelossofvascularautoregulation

CerebralAutoregulation
Cerebral Blood Flow

Chronic Hypotension
Normal
Chronic Hypertension

Mean Arterial Pressure

 Case1
75y/oMpresentstoEDviaEMS
Eatinglunchwithdaughterwhenhedroppedhisfork
fromhisrighthandandspeechbecamegarbled
Hearrives45minutesafterhislastknownwellwith
witnessedonsetofsymptoms
DoesntroutinelyseeaPCP,takesnoRxmedications
BloodGlucoseis105
NonContrastCTshowedhyperdense LMCA
NIHSS12
Whatisyournextstep?

AcuteStrokeTreatment
03hours
IVtPA IAintervention
34.5hours
IVtPA IAintervention
4.58hours
IAinterventionforAnteriorCirculation
Upto2448hours
IAInterventionforPosteriorCirculation
Thisisreallyforbasilarthrombosisthatwillotherwise
resultindeathorcatastrophicneurologicdisability
 TimeisBrain
Every15minuteaccelerationinstartoftPA
afteronsetwasassociatedwith:
4%greateroddsofwalkingindependentlyat
discharge,
3%greateroddsofbeingdischargedtohome
ratherthananinstitution
4%loweroddsofdeathbeforedischarge
4%loweroddsofexperiencingsymptomatic
hemorrhagictransformationofinfarct
JAMA, June 19, 2013Vol 309, No. 23 2

Case1(cont)
IVtPA wasgivenwithin30minutesofER
arrival.
Whatothertestingdoyouwant?
CTAngiogramoftheHEADandNECK
 BeyondIVtPA
Patientswithlargevesselocclusion(LVO)maybenefit
fromadvancedmechanicalinterventionwith
thrombectomy device
Criteria:
NIHSS6
Onsettogroin<6hours
LVOinintracranialcirculationinareachablelocation
Themostcriticalstepisidentifyingthepatientsearly
andarrangingforprompttransfer.
OptimaldiagnostictestingshouldincludeaCTAofthe
headandneckinadditiontothenonconCT

IntraarterialDevices

Solitaire Stent-retriever

Penumbra Suction Catheter

Merci retrieval device

 MRCLEANStudy
In patients with acute ischemic stroke due to a proximal intracranial
arterial occlusion, intraarterial treatment (with retrievable stents in 82%
of patients) within 6 hours improved functional outcome at 90 days.
Alteplase was given to 89% of patients before randomization.
MRS 0-2: 32.6% compared to 19.1% ---- OR 2.16

N Engl J Med 2015; 372:11-20

IntraarterialIntervention
ESCAPE
EndovasculartreatmentforSmallCoreandAnteriorcirculationProximalocclusionwith
EmphasisonminimizingCTtorecanalizationtimes
315patients,stoppedearlyduetobenefit
ARRforthrombectomy 3.1
MRS02:53%comparedto29%
EXTENDIA
EXtending thetimeforThrombolysisinEmergencyNeurologicalDeficitswithIntraArterial
therapy
70patients,stoppedearlyduetobenefit
Earlyneuroimprovement:80%comparedto37%
MRS02:71%comparedto40%
SWIFTPRIME
SolitaireWiththeIntentionForThrombectomy asPRIMary treatmentforacuteischemic
strokE
196patients,stoppedearlyduetobenefit NEngl JMed2015;372:10191030
ORformRS shiftpvalue0.0002 NEngl JMed2015;372:10091018
MRS02:60%comparedto35% NEngl JMed2015;372:22852295
 Case1(cont)
YourpatientwentforEndovascularTherapy
(ET).
AstentretrieverdevicewasusedtoremovetheL
MCAclot.
NIHSSimprovedto5postprocedure
Mildrightsidedweaknessandmildexpressiveaphasia
Whatarethestepsneededtodelineatethe
strokeetiology?

IschemicStrokeDiagnostics
Neuroimaging:CT/MRIbrain
VascularImaging:
BrainAngiogram
CT,MR,U/S
NeckAngiogram
CT,MR,U/S
CardiacEvaluation
Echocardiogram
TTEsufficientinmost,includebubblestudytoevaluateforPFOinthose<65;somemay
needTEEdependingonclinicalcontext
EKG,Telemetry,Holter,LoopRecorder
Labs
Mandatory
A1c,Lipids Seesupplementaryslidesforsuggestedevalua onfor
hypercoagulable statesandautoimmunedisease
Ancillary
hypercoagulablestudies,autoimmunestudies
Renal Failure MRI/CT
MRI/CT
Transcranial ADoppler

Pacemaker N
G
I
Carotid ultrasound

O
Lipids G
HBA1C R
A
M

Echo
EKG/Tele/Holter

Case1(cont)
CardiacTelemetryshowsAtrialFibrillation
withrateof80100
Echocardiogramshowedseverebiatrial
dilation,preservedEF,normalvalves
Angiogramwith<50%stenosisofbilateral
ICAs
Lipids:210/120/35/147
A1C:5.8%
 Cardioembolism
ManagementStrategies
IVtPA
Recanalizationrateabout25%foranoccludedMCA
IVFluids
BPSupport
MAP90120
<220/120acutely
Ultimatelynormotension followJNC8/SPRINT*
ACEi,ARB,diuretic,CCB,BB(indicatedhereduetopresenceofcardiac
disease)
Anticoagulation
HeparindripwithPTTgoal2xbaseline(usually5070),nobolus
+/ Statin,LDLgoal<100
* See supplementary slides

Cardioembolism
Physiology
Potentialcauses
AFib,cardiomyopathy,anteriorSTEMI+/ LVThrombus,valvular disease
Pathology
Foroneormorereasonsstasisofblooddevelopswithacardiacchamberorstructural
aspectsoftheheartcreateanidusforthrombusformation
ClinicalPresentation
Largesegmentalinfarction
Differentialweakness(e.g.,MCA=face/arm>>leg)
+/Corticalsigns
Borderzone infarction
Nondifferentialweakness
Maninbarrelweakness
Multifocalinfarcts
Scatteredembolicanresultinavarietyofmixedsymptoms
SubcorticalStroke/Lacunarsyndrome
~5%oflacunes areembolicinnature
 Cardioembolism
LongtermManagementforspecificcircumstances
AtrialFibrillation
CoumadinorNOAC
Ifnot,ASA+/ Plavix
Cardiomyopathy
Antiplateletvs.anticoagulant
Nomortalitybenefit,butfewerischemiceventsinanticoagulationgroup
AnteriorSTEMI+/ LVThrombus
Warfarinindicatedforatleast36months
Valvular disease
MVStenosis
Antiplatelet+/ warfarin
Bioprosthesis
Antiplatelet+/ warfarin
MechanicalProsthesis
Warfarin+/ antiplatelet
Seesupplementaryslidesforaddi onal
informationonNOACs

ProstheticValve
MechanicalValves
InitialTherapy
AVR:INRgoal23
MVR:INRgoal2.53.5
Ifhistoryofstroke/TIAbeforeinsertionofmechanicalMVR/AVRandlowrisk
ofbleedingaddlowdoseASA
SecondaryPrevention
IfstrokedespitetherapeuticINR+lowdoseASA,thenincreaseASAto325,
and/orincreasetargetINR
Bioprosthetic AVR/MVR:
Initial
antiplatelettherapyalone
SecondaryPrevention
IfStrokedespiteantiplatelettherapy,thenaddwarfarinwithtargetINR23
 Case2
66y/oMadmittedwith12hoursofsevereleft
hemiparesis,MRIshowsinternalcapsule
ischemicstroke
Angiographywasnormal
Echocardiogramwasnormal
uncontrolledDM(A1C9.7%)
uncontrolledHTN(170/90)
uncontrolledDyslipidemia(230/140/29/165)

SmallVesselDisease
Physiology
Riskfactors
HTN,dyslipidemia,diabetes,smoking,OSA,obesity
ClinicalPresentation
LacunarSyndromes
Subcorticallocations
Coronaradiata,internalcapsule,thalamus,basalganglia,brainstem
Nondifferentialweakness(face=arm=leg)
Absenceofcorticalsigns
Mayhaveastutteringcourse
e.g.,capsularwarningsyndrome

Examples of Lacunar Syndromes in

Supplementary slides
 SmallVesselDisease
ManagementStrategies
IVtPA
Effective
IVFluids
BPSupport
MAP90120
<220/120acutely
Ultimatelynormotension followJNC8/SPRINT*
ACEi,ARB,diuretic,CCB
AntiplateletloadingifnoIVtPA
Aspirin325mg 81mg
Clopidogrel300mg 75mg
Statin
GoalLDL<70
DiabetesTreatment
GoalA1C<7%
SmokingCessation
Cerebrovasc Dis. 2014;37(1):5-13. doi: 10.1159/000356796.
Epub 2013 Dec 17

* See supplementary slides

Case3
55y/oMadmittedwithrecurringepisodesof
leftsidedhemiparesisoverlast2weeks.
2ppdSmoker
BorderlineDiabetic(6.1%)
HTNonLisinopril10mg(144/89)
Lipids:170/105/33/124;notonstatin
Notonanyantithrombotics
 Case3
Whataretheurgent
actionstobetaken?
Whataretheshort
termplans?
Whatarethelong
termplans?

Case3
Urgent
AntiplateletLoading
Highintensitystatin(e.g.Atorvastatin40mg)
IVFluids&BPcontrol
Toohighrisksmorevasculardamage,
Toolowriskshypoperfusion
Consultforcarotidendarterectomy(CEA)
ShortTerm
CEAwithin2weeksand6wks ofDAPT(ASA/Clopidogrel)
LongTerm
OptimalRiskFactorModification
SingleAntiplateletagent
QuitSmoking
 LargeVesselDisease
ManagementStrategies
IVtPA
Recanalizationrateabout10%foranoccludedICA
Recanalizationrateabout25%foranoccludedMCA
IVFluids
BPSupport
MAP90120
<220/120acutely
ConsiderallowingforshorttermpermissiveHTN140160systolicforthefirstseveral
weeksifnoCEA
Ultimatelynormotension followJNC8/SPRINT*
ACEi,ARB,diuretic,CCB
Antiplateletloading:Aspirin,Clopidogrel
Statin
LDLgoal<70
SmokingCessation

* See supplementary slides

LargeVesselDisease
Physiology
RiskFactors
HTN,dyslipidemia,diabetes,smoking,OSA,obesity
Atherosclerosisresultingin
Arterytoarteryemboliorthrombosisofvessel
Hypoperfusion
ClinicalPresentation
Amaurosis Fugax
Largesegmentalinfarction
Differentialweakness(e.g.,MCA=face/arm>>leg)
+/Corticalsigns
Watershed/Borderzone infarction
Nondifferentialweakness
Maninbarrelweakness
LargeVesselDeepWatershedIschemia

LargeVesselEmbolicStroke
 LargeVesselDisease

Carotiddisease:earlyendarterectomy(<2wks)
Maybepossibletoreopenanacutelyoccludedartery
Benefitgreatestin>70%stenosis
Intracranialatheroscleroticdisease
Bestmedicaltherapy>>>>stenting
Dualantiplatelets,statin(goalLDL<70),diabetesmgmt (A1C
<7%),HTNcontrol(<140/80),diet,weightloss,tobaccocessation
Stentsmaybeappropriateforthosewhoareperfusion
dependent

AntithromboticReview
Antithrombotic
Antiplatelet
Classical:Aspirin,Clopidogrel,Aggrenox(ASAERDP)
Others:cilostazol,ticagrelor,prasugrel
Anticoagulant
Warfarin
NOACs
FactorXa inhibitors
Rivaroxaban,Apixiban,Edoxaban
DirectThrombinInhibitors
Dabigatran
 SummaryofClassical
Antiplatelets
ASA~20%RRR
Aggrenox~37%RRRandprovensuperiortoASA
PlavixsuperiortoASAincompositeendpointbut
notinstrokesubgroupalone
TIAsnotincluded
MostusefulinthosewithPAD
AggrenoxandPlavixaresimilarlyeffective
Combinationtherapyisnotrecommendeddueto
anincreasedriskofbleeding
See supplementary slides for brief breakdown of the trials leading to these conclusions

OtherAntithrombotics
Cilostazol (Pletal)
PDEinhibitor
MetaAnalysis from2013pooled4trialswhich
comparedASAtoCilostazol andfound
Nodifferenceinischemicstroke
FewerHemorrhagicStrokeswithCilostazol
FewerGIbleedswithCilostazol
Cilostazol betterthanASAincompositeendpointof
stroke,MI,vasculardeath
Nodifferenceinmortality
The American Journal of Cardiology, Volume 112, Issue 8, 15 October
2013, Pages 1230-1234.
 OtherAntithrombotics
Ticagrelor
P2Y12ADPreceptorantagonist
PLATOTrial(Ticagrelor vsClopidogrel)
Comparesthesedrugsinpatientspresentingwithacutecoronary
syndrome
Ticagrelor betterthanClopidogrelatreducingcompositeend
pointofMI,stroke,andvasculardeath
Nodifferenceinischemicstrokepreventioninsubgroupanalysis
FDAreviewsuggestsoriginaldataunderestimatedriskofstrokeand
thereisanonsignificanttrendtowardsincreasedriskofstrokeon
Ticagrelor.Thisseemstobedrivenbyriskofhemorrhagicstroke.

N Engl J Med 2009; 361:1045-1057; September 10, 2009 DOI:

10.1056/NEJMoa0904327

OtherAntithrombotics
Prasugrel (Effient)
Blackboxwarning:donotgivetopatientswith
historyofstrokeorTIAduetoincreasedriskof
bleeding
Ticlopidine (Ticlid)
Blackboxwarning:Neutropenia,agranulocytosis,
aplasticanemia,TTP
 Itsassimpleas.
A AppropriateAntithrombotic
B BloodPressure
C Cholesterol
D Diabetes/Diet
E Exercise
F ForgetSmoking(NoFumar)

THANKYOU
 SUPPLEMENTARYSLIDES

LacunarStrokeSyndromes
ClumsyHandDysarthria
AtaxicHemiparesis
PureMotor
PureSensory
Sensorimotor
 Hypercoagulable Labs
PT/INR
PTT
Homocysteine
ProteinC
ProteinS
Antithrombin III
ActivatedproteinCResistance
ResistancetoAPCimpliesFactorVLeidenispresent
GeneticTestingforFVLeidencouldbedoneinstead,butAPCresistanceismuchlessexpensive
andissimilarlysensitive
Anitphospholipid SyndromeLabs
LupusAnticoagulant
Beta2Glycoproteins
Anticardiolipin antibodies
ProthrombinGeneMutation
Considerinyoungpatientswithfamilyhistoryofthrombosis

CoagulationDisorders
Disorder Venous Arterial HereditaryorAcquired
ATIIIdeficiency + +/ Hereditary
ProteinCDeficiency + Hereditary
ProteinSDeficiency + Hereditary
ProthrombinGeneMutation + +/ Hereditary
FactorVLeiden + +/ Hereditary
Antiphospholipid AbSyndrome + + Acquired
IncreasedFactorVIIIactivity + +/ Hereditary
Hyperhomocysteinemia + + Mixed
Oralcontraceptives + +/ Acquired
Cancer + + Acquired
 Autoimmunelabs
ESR
CRP
RF
ANAwithreflexivepanel
SSA
SSB

Primary/SecondaryStrokePrevention
(carotidendarterectomy)

Symptomatic carotidarterystenosis
>70%:superiortomedicaltherapy.
5069%:selectivebenefit(men,stroke,hemisphericevents).
<50%:nobenefit(?selectcases).
Increasingbenefitwithadvancedage.
Surgicalmorbidity/mortality<5%(TIA)and<7%
(stroke).
Early endarterectomy within2weeks (Oxford).
 Primary/SecondaryStrokePrevention
(carotidendarterectomy)

Asymptomatic carotidarterystenosis
>60%stenosis (considerpossibleCEA;
however>80%probablymoreidealbefore
CEAconsideration).
Surgicalmorbidity/mortality<3%.

LandmarkStrokeStudies
NOACs
RELY
Dabigatran superiortowarfarinatreducingischemicstroke
IncreasedriskofGIbleeding
LowerriskofICH
ROCKETAF
Rivaroxaban noninferiortowarfarinatreducingischemicstroke
LowerriskofICH
ARISTOTLE
Apixaban noninferiortowarfarinatreducingischemicstroke
LowerriskofICH
ENGAGEAFTIMI
Edoxaban issuperiortowarfarinatreducingcompositeofstroke,systemicembolism,ordeath
Highdoseisnoninferiortowarfarinatreducingischemicstroke
Lowdoseisinferiortowarfarinatreducingischemicstroke
LowerriskofICHwithbothhighandlowdose
Manycaveatssurroundingrenalfunction,thebettertheCrCl thelesseffectivethedrug
 LandmarkStrokeStudies
Antiplatelets
AspirinMetaanalysis
Lowdoseaspirinjustaseffectiveashighdose
MATCH
Combinationofaspirinandplavix resultsinincreasedbleeding
risk
CAPRIE
Plavixsuperiortoaspirin,mostnotablyinPAD
ESPS2andESPIRIT
Aggrenoxsuperiortoaspirin
PROFESS
Clopidogrel andAggrenoxareequivalent

Aspirin
Summary:
~20RRRforstroke,MI,vasculardeath
Nodifferenceindose

Lancet 2009; 373:1849-60

 Aggrenox
EuropeanStrokePreventionStudy2(ESPS2)1
ComparedASAtoERDPtocombinationversusplacebo
ASAreducedstrokeby18%
ERDPreducedstrokeby16%
ASA+ERDP(Aggrenox)reducedstrokeby37%
ESPRIT2
ComparedASAtoASA+ERDP
ASA+ERDPaffordsa1%absoluteriskreductionperyearoveraspirinalone
DiscontinuationrateofASA+ERDPwashighcomparedtoASAalonedueto
sideeffectofheadache(alsodiarrhea)

1. J Neuro Sci 1996; 143:1-13

2. Lancet 2006; 367:1665-73

Aggrenox

Lancet 2006; 367:1665-73

 Plavix
CAPRIE
RCT:ASA325mgvs Plavix
75mg
Plavixgrouphadlowerevent
rateofMI,vasculardeathor
strokecomparedtoASA
5.32%vs 5.83%,p=0.043
Patientswhosawthemost
benefittoplavix werethose
withconcomitantPAD

Lancet 1996; 348: 1329-39

Plavix
PRoFESS
Nodifferencebetweenplavix andaggrenox inpreventing
recurrentstroke,MIorvasculardeath
 MATCHSafety:

NetBenefit/RiskofCombinedEndpoint/SeriousBleeding

LandmarkStrokeStudies
Statins
HeartProtectionStudy
Statinsreducevasculareventsinthosewith
knownvasculardisease
SPARCL
Statinsreducevasculareventsinthosewithout
knownvasculardisease;statinsincreaseriskof
hemorrhagicstroke
 LandmarkStrokeStudies
antiHTN
PROGRESS&HYVET,
Diuretics+/ ACEIreducesincidenceofstroke
HOPE
ACEIreducesstroke
LIFE
ARBreducesstroke
STOP2
CCBreducesstroke

JNC8
 JNC8

SPRINT
IntensiveBPcontrol
(<120/80)reduceddeath
andprimaryoutcomes
Primaryoutcome:
FirstoccurrenceofMI,ACS,
heartfailure,stroke,death
fromCVcause
Subgroup:nodifferencein
strokeratebetween2
groups
TheSPRINTResearchGroup.NEngl JMed2015;373:21032116.
 Polyneuropathy:
Suddenvs.Insidious

DivpreetKaur,MD
NOTES
InfectionsinNeurology

SolDeJesus,MD
 Infections in Neurology
SolDeJesusM.D.
AssistantProfessorDepartmentofNeurology
PennstateHersheyMedicalCenter
5/6/2017

Disclosures

None
 Objectives

Reviewclinicalpresentation,diagnosisanddifferential
diagnosisofbacterialmeningitis,viralmeningitisandHSV
encephalitis
Discussappropriatetreatmentandfollowupcareofthe
differentnervoussysteminfections
Casereview

General information and anatomy

Bacteria,virusesandothermicroorganismscanaffect
intracranialstructuresviahematogenous orneighboringspread
orviaaccessthroughanatomicdefect:
Meninges(duramater,arachnoid,andpiamater)
Cerebralinvolvement
Terms
Meningitis inflammationoftheprotectivecoveringofthebrainand
spine
Encephalitis inflammationofthebrain
Meningoencephalitis inflammationofboththemeningesandbrain
substance

http://www.thevisualmd.com/searchimg.php?idu=10917 https://www.studyblue.com/notes/note/n/scbrainmeninges/deck/15454233
Clinical approach CNS infection

RecognizepossibilityofaCNSinfection
Predisposingconditionssystemicinfection,headtrauma,
cancer,alcoholism/immunodeficient states,prior
neurosurgery
Initiatetreatment
Identifycause
Optimizemanagement

*Earlyrecognitionandtreatment=bestpossible
outcome

CNS infection recognition

Meningitis Encephalitis
Fever Fever

Headache(severe) Headache

Neckstiffness
Positivemeningealsigns
Brudzinski andKernig
Otherpossible:alteredmental
status(AMS),photophobia,
raisedintracranialpressure
Confusion/disorientation/A
MS
Focalneurologicdeficits
Seizures
Drowsiness/coma
Raisedintracranialpressure

Symptompresentationcanoverlap
 Clinical approach CNS infection

Historyandphysicalexaminationarekey!
Age,season,geographiclocation
Timecourseofsymptomandsymptompresentationcan
provideclues
Acute(<24h),subacute(<7d),chronic(<4wks)

Patientdisposition
Bacterialmeningitisandencephalitisrequireinpatientcareand
observation
Viralmeningitisifwellappearingmayconsideroutpatientwithclose
treatmentandfollowup.Ifuncleardiagnosisattimeofevaluation
admitforobservationandpossibleempirictherapy.

Diagnostic approach in CNS infection

AssessclinicalstatusandstabilizeA,B,Cs
Completeinfectiousworkuplookingforsource
Obtainbloodgramstainandculture

ObtainlumbarpunctureandcompleteCSFstudies,normal
valuesbelow:
Color:clear
Openingpressure:1020cmH2O
Cellcountanddifferential:05cells/mm(<2PMN)
Protein:<45mg/dl[2040]
Glucose:>60%ofserumglucose[5070]
Stainandculturesdependingonclinicalsuspicionif+adjust
therapyif suspectasepticmeningitis
 CSFstudiesprofile
*Note:thefollowingareguidesandnotmettoreplaceclinicaljudgementbasedonpatientspecificpresentation.CSFresults arevariable

BacterialMeningitis Aseptic(viral)Meningitis

Color:clearorcloudy Color:clear
Openingpressure:Normalor
Openingpressure:increased >25 cm
H2O Cellcountanddifferential:elevated 5
500 cells/mmLymphocytepredominant
Cellcountanddifferential:pleocytosis
>1010,000cells/mm(PMN>50% Protein:mildtomoderateincrease
neutrophilpredominant) Glucose:Normal canbemidlly
decreasedinHSV1&2,VZV,mumps
Protein:increased 100500mg/dl
StainandculturesCSFgram
Glucose:decreased <40mg/dlor<60% stain/cultures,bacterialantigens,CSF
ofserumglucose PCRHSV,VZV

Stainandcultures:CSFgramstain/ ViralculturesforHSVarealmostalways
negativeneedPCR
bacterialcultures,bacterialantigens

CSF studies profile

*Note: the following are guides and not met to replace clinical judgement based on patient specific presentation. CSF results are variable

Viralencephalitis
Color:clear

Openingpressure:Normalorelevated

Cellcountanddifferential:05cells/mm(<2
PMN)

Protein:normalormildlyelevated(lymphocyte
predominant)

Glucose:Normal

Stainandculturesdependingonclinical
suspicion
 Bacterial meningitis differential
Differentialforacutebacterialinclude:
nonbacterialinfections(viral,fungus,tuberculosis)
noninfectious(subarachnoid)
malignancy/paraneoplasticprocess
drugs
Mostcommoncausesofbacterialmeningitisbyage:
NeonateGroupBstrep,E.Coli,Listeriamonocytogenes
Children H.influenza,pneumococci(S.pneumoniae),meningococci
(Neisseria)
Adults<50yo pneumococci(S.pneumoniae),meningococci(N.
meningitides)
Adults>50yo sameasunder50plusListeriamonocytogenes,
staphylococci,gramnegativebacilli

Viral meningitis/encephalitis differential

Asepticmeningitis
Herpesvirus
HSV,VZV,EBV,CMV
Myxo/paramyxovirus
Influ/parainfluenza,measles/mumps
Enterovirus
Polio,Coxsackie,Echovirus
Togavirus
Equine(Eastern,Western),St.Louis,WestNile,California,Japanese
Tickborne
Lyme,Ricketssia
Others
HIV,adenovirus,rabies,
Diagnostic approach in CNS infection
Makinganappropriatediagnosiswillguidetreatment,
informregardingprognosisandhaspublichealth
implications.
Donotdelayantibioticorantiviraltreatmenttoobtaina
lumbarpuncture
Spaceoccupyingmasslesion,skininfectionoversightof
procedure,signsofcerebralherniationare
contraindicationstolumbarpuncture.
Roleofneuroimaging
ShouldbeperformedbeforeLPwhenthereisalterationof
consciousness,focalneurologicaldeficit,papilledema,seizure
andinimmunocompromisedpatients

ClinicalVignette
*Answerstobereviewedanddiscussedduringseminar
 Case 1
RFisa60yearoldgentlemanpresentstotheemergencydepartment
forsymptomsofheadache,fever(103F),chillsearpainanddrainage
asof2daysago.Familyexpressedconcernashewasnotactinglike
himselfandwascomplainingofneckstiffness.Onevaluationthere
wasnofocalneurologicdeficit,openingpressurewas200mmH2O
withacellcountof1500PMNpredominance,RBC2,glucosewas20
mg/dlandprotein90mg/dl.Serumglucosewasnormal,therewasa
slightleukocytosisandelevatedESR.Gramstainandculturesare
pending.

Whatarethesymptomsthatmakeyoususpectanacutebacterial
meningitis?
Whatshouldbeincludedwithinyourdifferentialforthepresentation?
InterpretCSFresults
Reviewofempirictreatmentoptions

Empiric antibiotherapy

Basedonageandpossiblecausativeorganisms
Vancomycin
Thirdgenerationcephalosporin(examples:Ceftriaxoneor
Cefotaxime)
Ampicillin H.influenza(newborns+adultsover50)
?dexamethasone
?Acyclovir
Onceorganismisisolated,tailorantibiotictherapies
 Role of steroid in bacterial meningitis

Highsuspicionofbacterialmeningitis
Dexamethasoneinitiatedpriortoorwithfirstdoseof
antibioticsandcontinuedfor4daysincasesofS.pneumoniae
mayimproveoutcome.
Shouldbediscontinuedifgramstainorculturesrevealother
pathogens

ComplicationsofMeningitis
*Candevelopatanytimeduringcourseofdisease

Acute(12days) SubacutetoChronic(during
Brainedema hospitalizationandpost
Increasedintracranial discharge)
hypertension Hydrocephalus
AMSincludecoma, Abscessformation
hypertensionwith Cognitiveimpairment
bradycardia,papilledema,CN
VIpalsy Focalneurologicdeficit(motor
Seizures paresis)
SIADH Cranialnerveinvolvement
Hearingloss
 Predictors of poor outcome

Seizure
Alteredmentalstatus
Hypotension

Case 2
SAisa30yearoldfemalepresentstotheemergencydepartment
witha3dayhistoryoffever(103.2F),nausea,lightsensitivity,
headacheandneckpain.Shestartedaantibioticscoursewith
amoxicillinforapossiblepharyngitisseveraldaysprior.On
examinationsheisuncomfortablebutalertandorientedwithout
evidenceoffocalneurologicdeficit.Bloodculturesandlumbar
punctureareperformed.Openingpressurewasnormal,CSFreveals
250cellswith86%neutrophilpredominance,CSFglucoseof47
mg/dlandProteinof49mg/dl.

IstheCSFindicativeofabacterialorviralmeningitis?
Whatisthenextstepinmanagement?
 Case 2 continued

SAcontinuestoimproveclinically
CSFgramstainandCSF/blood/urineculturesarenegativefor
bacteria,virusesorfungus
MRIwandwithoutcontrastisnormal
RepeatLPrevealed180cells,lymphocytepredominantwith
normalglucoseandprotein.

Hasyourdiagnosischanged?

Case 2 continued

Patientwasmanagedsupportivelyanddischargedhomeafter
thesecondLPwithoutanysequelae.
Patientpresentstoyouroffice2dayspostdischargeduetoa
occipitalthrobbingheadache,neckstiffness,headmovement
andsittingorstandingexacerbatethepain,sheremains
afebrilewithoutanynewneurologicdeficit.

Whatisyounextstep?
Whatisyourdifferentialdiagnosis?
 Case 3
HH80yearoldwomanpresentedtothehospitallethargic.Thedayof
thepresentationsheexperienceaseizureandcollapsed,thefamily
called911.Familytellsyouhehasbeenactingunlikeherselfandover
thelastweekhasbeenexperiencingvisualhallucinations.Examination
islimitedduetoconfusionsheisfoundtohavesomewordfinding
difficultyandisveryunstableonherfeet.Bloodpressurewas200/90,
shehadatemperatureof103,therewasnoevidenceofnuchalrigidity
orotherneurologicdeficit.

Whatisyournextstepinmanagementandclinicalsuspicion?
WhatwouldyouexpectontheCSFtestingbasedonclinical
presentation?
Whatarepotentialcomplicationsandlongtermprognosisinthese
patients?

Case 3 continued
CTheadwasnegative,lumbarpuncturewasobtainedand
revealedWBCcount1500cell/mm3(4%neutrophil,70%
lymphocyte,26%monocyte),RBC68cells,glucose87mg/dl,
protein40mg/dl.Blood,urineandCSFgramstainwas
negative.CulturesandCSFHSVispending.Antibioticsand
Acyclovirareempiricallyinitiated.
Day3ofheradmissionsheishypoventilating andisless
responsiverequiringintubation.

Whatisyournextstep?
 Predictors of poor outcome in HSV
encephalitis

Age
Durationofsymptomspriortoantiviraltherapy
Levelofconsciousness

Lyme disease
Controversyinthefield
Ticbornediseasewithmultisystemeffectsskin,heart,joints,
nervoussystem
Diagnosisrequires:
Possibleexposure
Clinicalsymptoms
Laboratoryconfirmation
Threestagesofdisease
Earlylocalized(erythemamigrains)+ viralsyndrome~1monthfrom
tickbite
Earlydisseminated~3wks3m
LateLymediseaseseveralmonths
 Clinical presentation

Peripheralnervoussystem Centralnervoussystem
Mononeuropathy Meningitis
multiplex (lymphocytic)
Radiculopathy
Myelitis
Cranialneuropathy(CN
VIIunilateralorbilateral) Encephalopathy
Plexopahty Encephalitis(rare)
Polyneuropathy
Entrapment
neuropathies

Serologic testing

LookforIgM+IgGantibodies
Canremainpositiveforseveralmonths
ELISAscreening,Westernblotconfirmatory(atleast2amongIgM
andatleast5amongIgG)
Borrelia cultureandPCRverylowsensitivity
 Treatment

Earlydiseasedoxycyclineoramoxicillinorallyfor23weeks
CNSinvolvementormeningitisrequiresCeftriaxoneor
PenicillinGfor2128days
Noevidencesupportingprolongedantibioticcoursefor
presumedchronicLyme

CNS infections clinical pearls and

pitfalls
AtypicalpresentationsofCNSinfectionsmayoccurintheelderlyoryoung
patients.
<50%ofpatientspresentwiththeclassictriadofacutebacterialmeningitis.
CSFproteinistheleastspecific
RBCscanincreaseproteinandWBCs.NotsufficienttodetermineSAHorHSV.
CorrectCSFprotein(subtract1mg/dlproteinforevery1000RBC/mm3).
Ifresultsareinconclusiveitmayhavebeenanearlysampleifsuspectmeningitis
orencephalitisconsiderempirictreatment.
IfCSFisnotclassicbutstillsuspectmeningitis/encephalitisthinkoflesscommon
causesTB,Fungal,adenoviruses,VZV,etc
Donotdelayinitiatingantibioticstoobtainimagingorlumbarpuncturewhen
meningitisisthelikelydiagnosis.
 MultipleSclerosis
anditsMimics

ElisabethLucassen,MD
 ElisabethLucassen,MD
CodirectorofthePennStateComprehensiveMS
Center
May6,2017

Disclosures
SpeakersbureauforBiogen,EMDSerono,Genzyme,
Novartis,Teva
Objectives
UnderstandthebasicdiagnosticworkupforMS
OverviewofcommonMSsyndromes:opticneuritis
andtransversemyelitis
MSmimicswhichonesnottomiss
AcutevschronictreatmentofMS
WhatshouldaPCPdoinfollowupforMSpatients?

Case
A27yo womanpresentswithopticneuritisintheright
eye.MRIoftheheadrevealsenhancementoftheright
opticnerveaswellas3otherperiventricularlesions.
LumbarpunctureshowsanincreasedIgG indexand
>5oligoclonal bands.Labwork testingforMSmimics
isunremarkable.Sherespondswellto3daysofIV
methylprednisolone(Solumedrol)1,000gadaywith
nearly100%returnofhervision.
Whatisthediagnosis?
Whatarehertreatmentoptions?
 Overview
MultipleSclerosis(MS)isachronicdemyelinating
diseaseofthecentralnervoussystem(CNS)inwhich
theprimarytargetofinjuryisthemyelinsynthesized
bytheoligodendrocyte.
MSisthoughttobeanimmunemediateddisease.
MSischaracterizedbyrelapsesorflareupsaswellas
progressionofdisability.

MostofMSpatients(8085%)presentwith
relapsingremitting disease.Relapses
occurasepisodesseparatedintimeand
space withintheCNS.About15%present
withprimaryprogressive disease.
BrainMRIinapatientwithMS.FLAIRimagingshowswhite
matterabnormalities.
MRIinapatientwithMS.ThisT1studyshowsblackholes,which
aresuggestiveofareasofscarring(sclerosis)andlossofaxons.

SomeMSabnormalitiesmaylooklikeneoplasms.Theabnormality
ontheleftscan(FLAIR)appearsasaringenhancinglesiononthe
rightscan(T1enhanced).
Gadolineum enhancingabnormalitiesonT1imagingisoftentaken
toindicateactiveMSdisease.

Evokedpotentialsareoftenabnormal:visual
evoked(VER),brainstemauditoryevoked
(BAER),andsomatosensoryevoked(SER)
takentogetherareabnormalin~90%.
 LaboratoryWorkupinMS
Cerebrospinalfluid(CSF)isabnormalin~90%ofMS
patients.IncreasedIgG indexandoligoclonal
bands arepresent.Itisnotclearastowhatantigens
theIgG isdirectedandwhethertheIgG playsarolein
diseasepathogenesisorisonlyamarkerofthedisease.

MSMimicsLaboratory
CBC
CMP
VitaminB12
Folicacid
ACE
Lyme
Syphilis
HSV
CMV
Toxoplasmosis
HTLV1
HIV
Rheumatologyscreen:ANA,ESR,ANCA,anticardiolipin antibodies
OpticNeuritis
Typicalsymptoms:acuteonsetofmonocularvisual
impairmentandperiorbitalpain,oftenaggravatedby
eyemovement
Arelativeafferentpupillarydefectintheaffectedeye
canusuallybedemonstratedviatheswinging
flashlighttest
Colordesaturationischaracteristicandcanbe
demonstratedclinically
Toconfirmdiagnosis(andruleoutalternative
diagnoses)wouldrefertoanophthalmologist

Acuteopticneuritis(retrobulbarneuritis)inMS,T1enhancedscans.The
leftofticnerveisenhancedjustbeforetheopticchiasm,seeninthe
axialscanontheleftandthecoronalscanontheright.
OpticNeuritis
OftentheinitialmanifestationofMS,butalsocanbe
seenwithSjogrens,SLE,sarcoidosis,Lyme,Bartonella,
syphilis,measles,mumps,herpes,medssuchas
quinineandsomeantibiotics
Exceptinverymildcases,treatmentwithashort
courseofhighdoseIVmethylprednisoloneshouldbe
offered
IfthepatienthasatleasttwolesionsonbrainMRI
(excludingtheopticnerve),thisishighlysuspicious
forMSandwouldwarrantconsiderationforstartinga
DMT.

TransverseMyelitis
MSpatientwithcervicalcordlesion(myelitis),T2scan.Bright
whitespinalfluidaroundthecordandtheareaofmyelitisinthe
cordareseenatC4.

TransverseMyelitis
Mostlikelyetiologiesofacutetosubacutemyelopathyare
infectiousorinflammatory
Whenaninflammatorymyelopathyisaccompaniedbyat
leasttwoT2hyperintensities,theprobabilityofsubsequent
MSdiagnosisis>90%,andaDMTwouldberecommended
Patientswithatypicalsyndromeoffulminantmyelitis,
accompaniedbynearcompleteinvolvementofthespinal
cordsegmentandabsenceofbrainMRIlesions,onlyhave
~10%probabilityofdevelopingMS
TypicaltreatmentisIVmethylprednisolone1000mgdailyx
5days;plasmapheresiscanbetriedifrefractorytoIV
corticosteroids
MSMimics:Lyme
NeurologiccomplicationsofLymearemultiple,varied,
andeasilyconfusedwithother
infectious/inflammatoryconditions
Diagnosisrequiresevidenceofpossibleexposureto
tickbites,clinicalfindingssuggestiveofneurologic
manifestationsofLyme,andpositivelabstudies
(serologies +/ CSFLymeantibodies)
Nervoussysteminvolvementgenerallyreflects
disseminateddisease
Acuteneurologicinvolvementoccursweekstoseveral
monthsafteratickbite

MSMimics:Lyme
Neurologicpresentationscaninclude:cranial
neuropathies,lymphocyticmeningitis,
radiculoneuritis,opticneuritis(rare),Guillan Barre
syndrome,encephalomyelitis,peripheral
neuropathy
Diagnosisofneuroborreliosis shouldbemadewith
cautioninseronegativepatients,thoughserum
antibodiescanbenegativeinthefirst46weeks
Serologictestingis2tiered:ELISAfollowedby
confirmatoryWesternblot
MSMimics:Lyme
CSFLymePCRhaslowsensitivity;proofinCSF
requiresdetectionofagreaterlevelofantibodiesin
theCSFcomparedtotheserum
Standardtreatmentincludesparenteralantibiotics,
specificallyceftriaxoneorpenicillin,for24weeks
CSFanalysisshouldbeperformedafterthe24week
treatmenttoassessforneedfortreatment
continuation;persistentpleocytosis suggeststheneed
forretreatment

MSMimics:Neurosarcoidosis
Amultisysteminflammatorydisorderofunknown
etiology;pathologyshowsnoncaseating granulomas
andmultinucleatedgiantcells
MorecommoninAfricanAmericans,morefrequently
seeninmidAtlanticstates
Pulmonaryinvolvementismostcommonsystemic
manifestation:neurologicinvolvementisonlyinseen
in5%ofpatientswithsarcoidosis(withorwithout
systemicinvolvement)
PositiveACEcansuggestsarcoidosis,butneedbiopsy
ofanaffectedorganfordefinitediagnosis
MSMimics:Neurosarcoidosis
Mostcommonpresentation:chronicmeningitiswithHA,
oftenaccompaniedbyencephalopathyorcranialnerve
palsy(II,VII,VIII)
Myelopathyisalsocommonlyseen,sometimeswith
involvementoftheconusmedullaris
Hypothalamusorpituitaryglandcanbeaffecteddiabetes
insipidusorotherhypothalamicendocrinologic
dysfunction
CSFshowsmoderatelymphocyticpleocytosis,mild/mod
proteinelevation
Treattypicallywithsteroids,methotrexatewhichisoften
managedbypulmonologist

MSMimics:Sjogren Syndrome
AvarietyofperipheralneuropathiesoccurinSSand
arethemosttypicalneurologicmanifestations
(sensoryneuronopathy,autonomicneuropathy,
mononeuritis multiplex,cranialneuropathies,
radiculoneuropathy)occursinabout1020%ofSS
CNSinvolvementmayoccurandsometimesmimics
MScanseemultiplelesionsinthebrain.Spinalcord
andopticnervescanbeaffectedaswell
Episodescanbestrokelikeormimicrelapsingcourse
30%(withCNSinvolvement)canhaveoligoclonal
bandsintheCSF
MSMimics:Sjogren Syndrome
Thecharacteristicantibodies,antiRO(SSA)andanti
LA(SSB),arepresentinapproximately60%of
patients,buttheirpresenceisnotspecificforSS
Pathologicconfirmationcanbeobtainedbybiopsyof
aminorsalivarygland
SSwithCNSinvolvementtypicallytreatedwith
steroids,immunosuppressionwithazathioprineor
cyclophosphamide

MSMimics:B12deficiency
Mosttypicalsyndrome:Subacutecombined
degenerationloss ofvibrationandpositionsense,
canleadtosevereweakness,spasticity,clonus,
fecal/urinaryincontinence
CNSsymptomscanincludememoryloss,irritability,
extrapyramidalsigns
Canseeopticnerveatrophy
Brainimagingcanshowdiffuseandsymmetricwhite
matterchanges
Lesionsinthespineinvolvetheposteriorcolumns
MSMimics:B12deficiency
ScreenviaB12andMMAlevels
Ifsyndromeofsubacutecombineddegeneration,
wouldalsorecommendcheckingcopperandfolate
Treatmentconsistsofreplenishmentmanypatients
needinjectionsifnotabsorbingproperly
Imagingfindingscanbereversibleoncepatientsare
treated

Otherhighyieldmimics

SmallVesselDisease Migraine
AcutetreatmentinMS
IVMethylprednisoloneruleoutinfection/metabolic
derangementsfirst,thencangive1g/dayx3daysfor
mild/moderaterelapsesor1g/dayx5daysforsevere
relapses.Cangivepo steroidtaperafterwardsif
indicated.
ACTHoptionforpatientswithhx poorresponseto
Methylprednisolone,hx ofunstableDM,orhx steroid
inducedpsychosis
PlasmaexchangeorIVIGcanbeusedwhenfailed
responsetooneoftheabove

FDAapprovedDiseasemodifying
TherapiesforRelapsingRemittingMS
Injectableoptions:
Interferonb1b(Betaseron;1993)
Interferonb1b(Extavia;2009)
Interferonb1a(Avonex;1996)
Interferonb1a(Rebif;1998)
Interferonba1(Plegridy;2014)
Glatiramer acetate(Copaxone;1996;40mgdosage;2014)
Daclizumab (Zinbryta;2016)

Oraloptions:
Fingolimod (Gilenya;2010)
Teriflunomide (Aubagio;2012)
Dimethylfumarate (Tecfidera,2013)

Intravenousinfusions:
Natalizumab (Tysabri;2006)
Alemtuzumab (Lemtrada;2014)
Mitoxantrone (Novantrone;2000)
OtherMSrelatedproblems
Fatigue
Pain
Spasticity
Urinaryandbowelissues
Sexualdysfunction
Cognitivedysfunction
Depressionandothermooddisorders

ThePCPsroleinMScare
Worktogetherwiththeneurologisttofindsolutions
teamworkisvital!
Pseudorelapses inMSarequitecommoni.e.UTIsare
commonandcanmakeMSsymptomsworse.Treatthe
infectionbeforethinkingabouttheneedforsteroids
Makesuretofaxanylabwork youchecktotheneurologist,
especiallyiftheyareonadrugthatrequiresmonitoring
(mostdo)
GoaheadandtreatotherMSrelatedproblems(i.e.
depression,urinarydysfunction)ifyouarecomfortable
doingso,otherwisewouldrecommendreferralto
subspecialists
 References
Feinstein,A.MultipleSclerosisanddepression.Mult
Scler 2o11;17(11):12761281.
MillerA,DeAngelis TM.Neuroimmunology.Oxford
UniversityPress,2012.
Pugliatti M.MultipleSclerosis:preventingprogression
anddisabilityinMSwhentotreat?NatRevNeurol.
2013Mar;9(3):129130.
http://www.nationalmssociety.org
http://www.utdol.com
 AdultEpilepsy

TiffanyFisher,MD
 EPILEPSYOVERVIEW
FirstTimeSeizureEvaluation,AntiepilepticDrugs
(Selection,SideEffects,Interaction),PennDOT,
Pregnancy
NeurologyfortheNonNeurologist
TiffanyL.Fisher,MD,PhD
May6,2017

DEFINITIONS

Anepilepticseizuresisatransientoccurrenceofsingsand/or
symptomsduetoabnormalexcessiveorsynchronousneuronal
activity
Disorderofthebraincharacterizedbyanenduringpredisposition
togenerateepilepticseizures(FisherRSetal,Epilepsia.2005;46:47072)

Twounprovokedseizuresmorethan24hoursapart(HauserWAetal,Epilepsia
1991;32:42945)
 PRACTICALDEFINITION

Twounprovokedseizuresmorethan24hoursapart(HauserWAetal,
Epilepsia. 1991;32:42945)

Oneunprovokedorreflexseizurewithaprobabilityoffurther
seizuressimilartothegeneralrecurrenceriskofatleast60%
aftertwounprovokedseizures,occurringoverthenext10
years
Diagnosisofanepilepsysyndrome,i.e.BECTs,JME,CAE,LGS,
Westsyndrome(FisherRSetal,Epilepsia. 2014;55:47582)

FIRSTTIMESEIZUREEVALUATION

Historyandphysical
Bloodtests:CBC,metabolicpanel,glucose,hepaticandrenal
function
Blood/Urinescreenfordrugs
MRIbrainscan
Routineelectroencephalogram(EEG)
Considerlumbarpunctureifmeningitis/encephalitissuspected
andpotentialforbrainherniationexcluded
 TREATMENTOFFIRSTTIMESEIZURE

Controversialgivenpreviousdiscussionwith1662%
recurrencewithin5yearsforanunprovokedseizure
Relapserateincreased
Abnormalimaging
Abnormalneurologicalexamination
AbnormalEEG
Familyhistory

FirstSeizureTrialGroup.Neurology.1993;43:47883
Camfield etal.Epilepsia.2002;43:6623.

2015AANGuideline
Recurrencerisk AEDs
Greatest:first2years ImmediateAEDreducesriskof
recurrenceinthefirst2yrs,butmay
Higherriskwith: notimproveQOLorlongterm
Priorbraininsult (>3yrs)prognosisofsustained
EEGwithepileptiform
seizureremission
abnormalities
Significantbrainimaging Adverseeffectsin7%to31%,
abnormality predominantlymildandreversible
Nocturnalseizure

Neurology 2015;84:1705-1713
 ANTIEPILEPTICDRUGSELECTION
1993 felbamate (FBM),gabapentin(GBP)
1857 bromides
1994 lamotrigine(LTG)
1912 phenobarbital(PB)
1997 topiramate (TPM),tiagabpine (TGB)
1937 phenytoin(PHT)
1999 levetiracetam (LEV)
1944 trimethadione
2000 oxcarbazepine(OXC),zonisamide (ZNS)
1954 primidone(PRM)
2004 pregabalin (PGB)
1958 adrenocorticotropichormone(ACTH)
2008 lacosamide (LCS),rufinamide (RUF)
1960 ethosuximide (ETX)
2009 vigabatrin (VGB)
1963 diazepam
2011 clobazam (CLB),ezogabine (EZG)
1974 carbamazepine(CBZ)
2012 peramapanel (PRM)
1975 clonazepam(CZP)
2013 eslicarbazepine (ESL)
1978 valproate(VPA)
2016 brivaracetam (BRV)

AEDSELECTION
BroadSpectrumAgents NarrowSpectrumAgents
Valproate PartialOnsetseizures AbsenceSeizures
Felbamate Phenytoin Ethosuximide
Lamotrigine Carbamazepine
Topiramate Oxcarbazepine
Zonisamide Gabapentin
Levetiracetam Pregabalin
Rufinamide* Tiagabine
Vigabatrin* Lacosamide*
Clobazam* Eslicarbazepine*
Parampanel* Ezogabine*

*NewAEDs(approvedsince2008)
 ANTIEPILEPTICDRUGSELECTION

GOAL CONSIDERATIONS
Noseizures Efficacy
Nosideeffects Effectiveness
Drugsafety
Tolerability
Comorbidconditions
Interactionwithotherdrugs
Easeofuse
Cost

AEDMECHANISMSOFACTION
Increaseinhibition
Opposeseizuregeneration/propagation
Quickenseizuretermination
Decreaseexcitation
Opposeseizuregeneration/propagation
Inhibition(IPSPs)aremostoften
evokedbyGABAorglycinergic
presynapticneurons
NeurotransmitterbindingopensCl
channels

Opposerapidneuronalfiring
Actionpotential/sodiumchanneleffects
Stabilizeneuronalmembranes
Releaseofneurotransmitters
Excitation(EPSPs)aremostoften
evokedbyglutaminergic (CNS)and
cholinergic(PNS)presynaptic
neurons
Neurotransmitterbindingopens
cation channelspermeabletoNa+,
Ca2+,K+
 AEDMECHANISMSOFACTION

Increaseinhibition
Opposeseizuregeneration/propagation
Quickenseizuretermination

Decreaseexcitation
Opposeseizuregeneration/propagation

Opposerapidneuronalfiring
Actionpotential/sodiumchanneleffects
Stabilizeneuronalmembranes
Releaseofneurotransmitters
 AEDMECHANISMSOFACTION

Increaseinhibition
Opposeseizuregeneration/propagation
Quickenseizuretermination

Decreaseexcitation
Opposeseizuregeneration/propagation

Opposerapidneuronalfiring
Actionpotential/sodiumchanneleffects
Stabilizeneuronalmembranes
Releaseofneurotransmitters
 MULTIPLEMECHANISMSOFACTION
VPA
InhibitsvoltagegatedNa+channels
PotentiatesGABAbyinhibitingGABAtransaminase
SuppressesNMDAmediatedexcitation
TPM
InhibitsvoltagegatedNa+channels
InhibitsglutamateatAMPA/kainitereceptors
bitsactivationofLtypevoltagedependentCa2+channels
Inhibitscarbonicanhydrase
ZNS
InhibitsvoltagegatedNa+channels
InhibitsactivationofTtypevoltagedependentCa2+channels
Inhibits(weak)carbonicanhydrase
FBM
InhibitsvoltagegatedNa+channels
SuppressesNMDAmediatedexcitation
PotentiatesGABAbycausingbarbituratelikeresponseatGABAAR

NEWAEDS

1857 bromides 1993 felbamate (FBM),gabapentin(GBP)

1912 phenobarbital(PB) 1994 lamotrigine(LTG)
1937 phenytoin(PHT) 1997 topiramate (TPM),tiagabpine (TGB)
1944 trimethadione 1999 levetiracetam (LEV)
1954 primidone(PRM) 2000 oxcarbazepine(OXC),zonisamide (ZNS)
1958 ACTH 2004 pregabalin (PGB)
1960 ethosuximide (ETX) 2008 lacosamide (LCS),rufinamide (RUF)
1963 diazepam 2009 vigabatrin (VGB)
1974 carbamazepine(CBZ) 2011 clobazam (CLB),ezogabine (EZO)
1975 clonazepam(CZP) 2012 peramapanel (PER)
1978 valproate(VPA) 2013 eslicarbazepine (ESL)
2016 brivaracetam (BRV)
 NEWAEDS

Lacosamide (Vimpat) Clobazam (Onfi)

InhibitsvoltagegatedNa+ channels 15benzodiazepinewithoutnitrogenin
Adjunctforpartialonsetepilepsy Bringat14siteofmolecule
Dizziness,ataxia,nausea,diplopia, Partialandgeneralizedonsetepilepsy
blurredvision,vertigo Halfsedatingas14benzodiazepines

Rufinamide (Banzel) Perampanel (Fycompa)

InhibitsvoltagegatedNa+ channels NoncompetitiveAMPAantagonist
AdjunctforLGS Adjunctforpartialseizuresandprimary
Contraindicatedinpatientswithfamilial GTCs
shortQTsyndrome Oncedailydosing(106hourhalflife)
Homicidalideation

NEWAEDS
Ezogabine (Potiga)
Formerlyknownasretigabine
ActivatesK+ channels
Adjunctforpartialseizures
Blueskinorretinalepitheliumdiscoloration(requireseyeexam);rare
urinaryretention
Eslicarbazepine (Aptiom)
ImmediatelyconvertstoSlicarbazepine
Partialonsetepilepsy
Supposedlybettersideeffectsandlessinteraction
Brivaracetam (Briviact)
Samemechanismaslevetiracetam butwith20foldgreateraffinity
Partialonsetepilepsy
Sleepiness,dizziness,nausea
 Perampanel

NatureReviewsNeurology

AEDMECHANISMOFACTION
Na+ Ca++ H-current Glutamate GABA Carbonic
AED Channel Channel enhance- Receptor Enhance- Anhydrase
Blockade Blockade ment Antagonism ment Inhibition
X (NMDA
PHT X
glycine)
CBZ, OXC X X (CBZ>OXC)
barb,
X (GABAA)
benzo
ESM X
VPA X X X
FBM X X X (NMDA) X
X (NMDA
GBP X X
glycine)
LTG X X X (kainate)
X
TPM X X X X
(AMPA,kainate)
TGB X (reuptake)
LEV X (kainate)
ZNS X X X
PGB X
X (slow
LCM
inact.)
RUF X
VGB X (metab.)
 AEDCOMMONSIDEEFFECTS

Drowsiness PHT ataxia

Dizziness CBZ,OXC,LTG,LCS dizziness,diplopia
Sedation VPA tremor,weightgain,
Cognitiveimpairment thrombocytopenia,sedation
Ataxia TPM cognitive/speecheffects
Paradoxicalhyperactivity LEV sedation,irritability
CBZ,GBP,PGB weightgain
TPM,ZNS,FBM weightloss/anorexia

Susceptibilityisindividualizedandtypicallydoserelated

IDIOSYNCRATICSIDEEFFECTS

Serious/Uncommon Common
CBZ heartblock CBZ neutropenia(monitorif
granulocytes>1000andstable)
PHT Lupus,lymphadenopathy
VPA thrombocytopenia(monitor
VPA thromobocytopenia, ifPLT>50000andstable)
pancreatitis CBZ,OXC,ESL hyponatremia
TPM kidneystones(1%),acute (monitorifNa>125)
glaucoma, EZO urinaryretention
hypohydrosis/hyperthermia Liverenzymeinducers elevated
LFTs(monitorif2xnormalbutnot
ZNS kidneystones(1%), risingrapidlyandnormalTbili)
hypohydrosis/hyperthermia
 ADEVERSEEFFECTS DRUGRASH
15.9%ofpatientsexperiencearash
2.8%averagerateofAEDrelatedrashwith2.1%causing
discontinuation

=rashratesignificantlygreaterthanaverageofallotherAEDs(p<0.003)
=rashratesignificantlylowerthanaverageofallotherAEDs(p<0.003)
=trendtowardssignificantly higherthanaveragerashrateofallotherAEDs(0.003<p<0.05)
=trendtowardssignificantlylowerthanaveragerashrateofallotherAEDs(0.003<p<0.05)
Arif Hetal,Neurology.2007;68:17019.

ADEVERSEEFFECTS DRUGRASH

StevensJohnsonSyndrome/Toxic
Rare EpidermalNecrolysis
Gabapentin Carbamazepine
Levetiracetam Lamotrigine
Pregabaline Phenobarbital
Depakote Phenytoin
Topiramate
ADEVERSEEFFECTS DRUGRASHINASIANPOPULATION
12/2007FDAalertforincreasedriskofSJS/TENinpatientswithHLA
B*1502allele(estimatedabsoluteriskofthosewithalleleis5%)
AlleleisalmostexclusivelyfoundinAsians
1015%ofpopulationisChinaThailand,Malaysia,Indonesia,Phillipines,
andTaiwan
24%inIndia
<1%inJapanandKorea
59/60AsianpatientwithSJS/TENhadallelevs4%ofCBZtolerant
patients
Asiansshouldbescreenedforallelepriortoinitiatingtreatment
withcarbamazepine

AEDINTERACTIONS

Inducers Inhibitors
Carbamazepine Valproate
Phenytoin
Primidone Felbamate
Phenobarbital Rufinamide

Oxcarbazepine
Topiramate
Felbamate
 AEDINTERACTIONS

Serumconcentrationsmaynotaccuratelyreflecttheunbound
proportionofdrugduetodisplacementfrombindingsitesby
otherhighlyproteinbounddrugs
Unboundserumconcentrationscanbehelpfulinpatients
takingthesedrugs
Phenytoin
Valproate
Carbamazepine
Tiagabine
Ezogabine

AEDSERUMCONCENTRATION

Useasaguidebutnottodictateclinicaldecisionmaking
UsefulforoptimizingAED,assessingcompliance,monitoring
duringpregnancyorOCPuse,teasingoutdrugdrug
interactions
Considerpharmacokineticfactors,i.e.nonlinearkinetics,first
orderkinetics,halflife
Individuallydefined

Patsalos etal,Epilepsia.2008:49:123976.
 MONITORINGAEDTHERAPY

Efficacy
Usepatientcalendarstocalculate
seizurefrequency
Levelsareasurrogateforefficacy:
useformonitoringcomplianceor
changesinpharmacokinetics
Toxicity/Tolerability
Routinelyinquireaboutcommon
sideeffects
Useopenendedinterviewing
Instructtocallimmediatelyif
lethargy,nausea,vomiting,ataxia,
orincreaseinseizures
Educatecaretakersespecially
whenpatientfeedbackislimited

THERAPEUTICENDPOINTS

RateofIntroduction

IntroduceAEDslowlyifpossible SLOW
RAPID tolerability safety
Increasedoseuntilseizures VPA CBZ LTG
controlledorsideeffectsobtained PHT PB
LEV TPM
GBP TGB
Individualresponseandside PGB
effectsvarygreatly ZNS
OXC
FBM
 AGGRESSIVEAEDTHERAPY

SelectAED

PushAED

No,nontoxic Sz No,toxic
Free?

Yes

ConsiderAED
Reduction

Naritoku,2003

PENNDOTREQUIREMENTS

Drivinglawsdifferbystate
PhysiciansarerequiredtoreportseizuresbylawinPA
Patientsmustremainseizurefreeforsixmonthsunless
otherwisespecified,i.e.provoked,nocturnal,etc
Twoseparateforms(firstformtostopdrivingandthen
anotherformtoresumedriving)
Alsoincludesspellswherepatientmaysufferlossof
consciousnessorawareness
 PREGNANCY
96%ofpregnanciesinmotherswithepilepsyproducenormal
children
Thereisanincreasedrateoffetalmalformationsassociatedwith
antiepilepticdrugexposureandmoresowithpolytherapy
Riskappearstobedoserelatedformostdrugs
GTCduringpregnancyismostdangerous(ultimatelycontrolismore
importantthantheAED)
Intracranialhemorrhage
Fetalbradycardia
LowerIQinchildren
Mostavailabledataonriskcomesfrompregnancyregistries

HardenCLetal,Neurology. 2009;73(2):13341

MAJORCONGENITALMALFORMATIONS

Safest
Lamotrigine(25.2%)
Levetiracetam (3%)
Carbamazepine(2.26.3%)
Phenytoin(2.96.7%)

Significantrisk
Valproate(12.5%)
Phenobarbital(6.4%)
Topiramate (4.7%)
HardenCLetal,Continuum. 2014;20:6079
EPILEPSYANDPREGNANYANDMANAGEMENT
GUIDELINES
AttemptAEDtherapywiththelowesteffectivedose
ConsiderswitchingAEDspriortopregnancy
Establishbaselinetherapeuticlevels
Folicacidsupplementationof0.45mgperday
Refertomaternalfetalmedicine(recommendlevelIIultrasound)
MonitorAEDlevelsatleastmonthlyandadjustdoseaccordingly
Benefitslikelyoutweighriskformostdrugs
Lamotrigineclearanceincreasesdramaticallyoverthecourseofpregnancy
Metabolismalsoincreasedforlevetiracetam,oxcarbazepine,phenobarbital,and
phenytoin
Carbamazepinelevelsmayberelativelystablebutdependonindividualpatient
Postpartumplanneededtoavoidtoxicity

DRUGRESISTANTEPILEPSY
Failure of adequate trials of two tolerated, appropriately
chosen, and used anti-epileptic drug schedules (monotherapy
or combination) to achieve sustained seizure freedom (ILAE 2010)

Drug resistant epilepsy (35%)

Polytherapy Surgery VNS/RNS Diet

Referral to a specialized epilepsy center

 SUPPLEMENTARYSLIDES

Slidesafterthispointprovideadditionalmaterialthatlikely
cannotbediscussedduringthelecture

ActionPotentialandIonConductance
Absoluterefractoryperiod

Relativerefractoryperiod
 Adjunctivetherapysideeffects

CBZ somnolence
GBP somnolence,dizziness
LCS dizziness
LEV somnolence
PGB somnolence,dizziness,weightgain
RUF dizziness,somnolence
VGB somnolence
ZNS somnolence,cognitiveeffects

AEDSelection
Monotherapy Adjunct
VPA + +
LTG + +
OXC + +
TPM + + Absence Myoclonic PGTC

LEV + ETX +

GBP + + VPA + ++ ++
TGB + LTG ++ +/ worse +
LCS + +
LEV ? + +
PGB +
ZNS + TPM ? ? +

EZO + ZNS ? ? ?
PER +
PHT, CBZandotherolderAEDs grandfathered
 BRV

Longtermadverseeffects

PHT gums,skinosteoporosis,neuropathy,cerebellaratrophy
VPA weightgain,alopecia,
CBZ ?Osteoporosis
PB learningproblems,osteoporosis,connectivetissueeffects
 AEDInteraction Warfarin

Antiplatelet/
AED Anticoagulant PotentialClinicalEffect
Phenytoin(PHT) 1.Warfarin 1.IncreasesINR*
2.Aspirin 2.IncreasesfreePHT
Carbamazepine (CBZ) Warfarin DecreasesINR

Phenobarbital(Pb) Warfarin DecreasesINR

Primidone (PRM)

Valproic acid(VPA) 1.Warfarin 1.SlightdecreaseinINR

2.Aspirin 2.IncreasesfreeVPA
*AEDsincreasemetabolismofwarfarin,butwarfarinis99%proteinbound,andPHT
andVPAincreasewarfarinsfreefraction.
INR=internationalnormalizedratio.

BoggsJ.In:Ettinger AB,Devinsky O,eds.Managing

EpilepsyandCoExistingDisorders.Boston:Butterworth
C-Slide 43 Heinemann;2002:3947.

AEDInteraction Contraception

DecreaseContraceptionEfficacy DecreaseLamotrigineEfficacy
Carbamazepine Candecreaselevelsbyupto50%
Clobazam
Eslicarbazepine Levelsmayincreasesignificantly
Felbamate duringtheplaceboweekofOCPs
Oxcarbazepine
Parampanel IUDiscontraceptivemethodofchoice
Phenobarbital forwomentakinglamotrigine
Phenytoin
Rufinamide
Topiramate
Gaffield MEetal.Contraception 2011;83:1629
 MajorCongenitalMalformations

1.62.1%riskingeneralpopulation
4.5%riskwithAEDmonotherapy
8.6%riskwithAEDpolytherapy
 Headaches

StephenRoss,MD,FAAN
 CurrentStandardofCareOutpatient
andInpatientHeadacheManagement
StephenRoss,MD
PennStateDepartmentofNeurology
May6,2017
http://www.themigraineproject.com/

Disclosure
of
PotentialConflictsofInterest

nothing

2
 Content

HeadacheDiagnosis
Primary
Secondary
Neuralgia
Q&A

InpatientvsOutpatient
Evaluationapproachisnodifferent

Keepinmind:cautionaboutseverepain,new
pain,changeinpaincharacteristics,pain
associatedwithotherconditions(e.g.fever,
newonsetseizure,immunocompromised
state)

4
39 yearoldfemalepresentswithaoneyear
historyofsevererightorbitalpainthatoccurs
forabout5minutes,10timesperdayevery
dayforacoupleofweeksthennothingfora
monthortwo.Thenattacksagain.Atthe
sametimeaspaingetsrightptosisand
lacrimation.

Examnormal
Testsnormal

What is this?

IHS Headache Classification

(International Headache Society)
http://www.ihs-
classification.org/_downloads/mixed/International
-Headache-Classification-III-ICHD-III-2013-
Beta.pdf

ICHD, 3rd Edition

Cephalalgia July 2013
33(9) 629-808

6
 PARTONE
(primary)
Migraine
Tensiontypeheadache
Trigeminalautonomiccephalalgias
Otherprimaryheadaches

PARTTWO
(secondary)
Trauma
Vascular
IntracranialNonvascular
Substance
Infection
Homeostasis
HEENT
Psychiatric

8
 PARTTHREE
(mixed)
Cranialneuralgiasandcentralcausesoffacialpain
Other

39 yearoldfemalepresentswithaoneyear
historyofsevererightorbitalpainthatoccurs
forabout5minutes,10timesperdayevery
dayforacoupleofweeksthennothingfora
monthortwo.Thenattacksagain.Atthe
sametimeaspaingetsrightptosisand
lacrimation.

Examnormal
Testsnormal
What is this?

10
39yearoldfemalepresentswithaoneyear
historyofheadachesthatoccurtwotimes
permonth,duration8hours,bilateral,
pressure,severe,worsewithroutine
activity,associatedwithnausea.Physical
examinationisnormal.
Whatisthis?

11

PARTONE

Migraine
Tensiontypeheadache
ClusterheadacheandTrigeminalautonomic
cephalalgias
Otherprimaryheadaches

12
 IHSMigraine

1.1Migrainewithoutaura
1.2Migrainewithaura
1.3Chronicmigraine
1.4Complicationsofmigraine
1.5Probablemigraine
1.6Episodicsyndromesthatmaybeassociatedwith
migraine

12,000 per 100,000

13

MIGRAINEwithoutAURA
IHSCRITERIA
Atleast5 episodes
Headachewithatleast Duration:4 72hours
two of: Duringheadacheat
1. Location:Unilateral leastone of:
2. Characteristic: 1. Nauseaand/or
Pulsating vomiting
3. Intensity:Moderate 2. Photophobiaand
Severe phonophobia
4. Exacerbators: Notbetteraccounted
Aggravatedby for
routineactivity

14
 TheMigraineProcess:Activationofthe
TrigeminalNucleusCaudalis(TNC)

15

Migrainewithaura

1Migrainewithtypicalaura
2Migrainewithbrainstemaura
3Hemiplegicmigraine
4Retinalmigraine

16
 TypicalAura
1ormoresymptoms(fullyreversible)
Visual
Sensory
Speech
2ormore
Atleastoneaurasymptomspreadsgraduallyover
5minutes,and/ortwoormoresymptomsoccurin
succession
Eachindividualaurasymptomlasts560minutes
Atleastoneaurasymptomisunilateral
Theauraisaccompanied,orfollowedwithin60
minutes,byheadache

17

www.perret-optic.ch www.migraine-aura.org

wisedoctors.com
www.kopzorgen.nl

18
 Migraine Treatment

Lifestyle modification
Attack treatment
Prevention treatment

19

Lifestyle modification
Substances Diet triggers
Hormones Skipping
Meals/diet
change

Stress Sleep too

Smell/visual/motion
much/little

20
 AttackMigraineTreatment
U1

NSAIDs* Triptan
Ergotamine Sumatriptan*
Nasal Sumatriptan/naproxen*
dihydroergotamine* Rizatriptan*
Otherergot Zolmitriptan*
formulations* Naratriptan*
Almotriptan*
Frovatriptan*
Eletriptan*

*FDAapproved

21

Migraineacutetreatmentalgorithm
I. Formularyrestrictions?
II. Priortrials?
III. Arethereanyvasoconstrictorcontraindications?
A. Yes:nonspecifictreatment
1. NSAIDs,Phenothiazine,Tramadol,Barb,Narc
B. No: Isthereanyreasontousenonoral?
1. Yes:SC(SumatriptanImitrex/Sumavel)NS(Suma,
Zolmi,DHE)PR(ergot)
2. No: Fastonsetorsevereonset?
a. Yes: Triptans (A,S,E,R,Z,Ergot(DHE)
b. No: NSAIDs,Triptans (Nara,Frova)

22
Migraineacutetreatmentconsiderations
I. TreatEarly
II. Wait(1)2hoursbeforeredosing
(46hoursnonspecific)
I. Max2/day,4/week
II. If1st dosedoesnothelpatall,2nd doseunlikelyto
I. Considercoadministerantiemetic
II. ConsidercoadministerNSAID
III. Considerrescuemedicine
IV. Whatisthe3rd lineoption?(office,ED,parenteral)

23

MigrainePrevention
FDA Published
Propranolol,Timolol,Valproic Amitriptyline/Nortriptyline
acid,Topiramate Gabapentin
Atenolol/Metoprolol/Nadolol
Verapamil
Ketoprofen/Naproxen
onabotulinumtoxinA
Fluoxetine
Every 3 months
Venlafaxine
Candesartan
Cefaly Lisinopril
20 minutes/day
Neurology. 2012 Apr
24;78(17):1337-45

24
 Migrainepreventivetreatment
algorithm
I. Formularyrestrictions?
II. Priortrials?
III. Arethereanycomorbidfeatures?
A. Yes: treataccordingly
1. Depression: SNRI,SSRI
2. Epilepsy: Topam,Gabap
3. Insomnia: TCA
4. Moodswings: VPA,AED
5. Hypertension: BB,CCB
6. Tremor: BB
B. No:
1. FDA: Topam,BB
2. EBM: TCA,AED

25

Migrainepreventivetreatmentconsiderations
I. Consideruseif
A. > 2daysperweek
B. Lossoffunctionduringattack
II. Startlow,titrateuntilresultorsideeffectsormax
A. Inderal:10tid or60LAqd to180
B. Elavil: 10or25qhs to150
C. Topamax:25qd to50bid
III. Ifnoteffective,considerbloodlevel
IV. Ifeffective,considertaperingaftermonths

26
 IHSMigraine

1.1Migrainewithoutaura
1.2Migrainewithaura
1.3Chronicmigraine
1.4Complicationsofmigraine
1.5Probablemigraine
1.6Episodicsyndromesthatmaybeassociatedwith
migraine

27

ChronicMigraine
Headache,> 15days/monthfor>3months
Inapatientwithhistoryofmigraine
> 8days/month>3months:migrainous
Notbetteraccountedfor

Treatment

28
 Chronicdailyheadache
1. >15days/month,>3months
2. Dosecondarycausesneedtoberuledout?e.g.
a. Temporalarteritis
b. MOH
c. Posttraumatic
3. Primary
a. ChronicMigraine
b. ChronicTensiontypeHeadache
c. ChronicClusterHeadache(related)
d. TrigeminalNeuralgia
e. Newdailypersistentheadache

29

IHSMigraine

1.1Migrainewithoutaura
1.2Migrainewithaura
1.3Chronicmigraine
1.4Complicationsofmigraine
1.5Probablemigraine
1.6Episodicsyndromesthatmaybeassociatedwith
migraine

30
 StatusMigrainosis
Headacheinapatientwithmigraine
>72hoursunremittinganddebilitating
Notbetteraccountedfor

31

StatusMigrainosis

NoFDAapproved Triptan
NoPracticeparameter Ergotamine

Parenteral
Rest/hydration
Ketorelac
Phenothiazine
Valproic acid
Narcotic
Steroid

32
 PARTONE

Migraine
Tensiontypeheadache
Trigeminalautonomiccephalalgias(ClusterHA)
Otherprimaryheadaches

33

CLUSTERHEADACHE
Men>Women
Severe,unilateral,periorbital/temple
Ipsilateralautonomicsymptom(Ptosis,Miosis,Nasal
congestion,Tearing) and/or
Senseofrestlessnessoragitation
Duration15180minutes
Freq qod to8/day
Episodic/chronic

34
 CLUSTERHEADACHE
Treatment
Verapamil
Triptans
(sumatriptansc*) Lithium
Ergotamines Antiepileptics(G,T,V)
Oxygen Occipitalnerve
block/stimulation
Melatonin10mg
Destructivesurgery
Steroids
Hypothalamic
stimulation
*FDAapproved
Neurology 2010;75;463-473
35

Shortlastingunilateralneuralgiformheadache
attackswithconjunctivalinjectionandtearing
(SUNCT)
A.Atleast20attacksfulfillingcriteriaBD
B.Moderateorsevereunilateralheadpain,withorbital,supraorbital,
temporaland/orothertrigeminaldistribution,lastingfor1600seconds(up
to10minutes)andoccurringassinglestabs,seriesofstabsorinasawtooth
pattern
C.Atleastoneofthefollowingcranialautonomic symptomsorsigns,
ipsilateraltothepain:sameasforClusterHeadache
D.Attackshaveafrequencyofatleastoneadayformorethanhalfofthe
timewhenthedisorderisactive
E.IpsilateralconjunctivalinjectionANDtearing
F.NotbetteraccountedforbyanotherICHD3diagnosis

36
 TAC
Clusterheadache
Paroxysmalhemicrania
Shortlastingunilateralneuralgiformha
Hemicraniacontinua

37

TACtreatment
Cluster:triptan,ergot,oxygen,verapamil
Paroxysmalhemicrania:indomethacin
Shortlastingunilateralneuralgiform
headaches:
treatsimilartotrigeminalneuralgia
(antiepilepticmeds)
Hemicrania continua:indomethacin

38
 PARTONE

Migraine
Tensiontypeheadache
ClusterheadacheandTrigeminalautonomic
cephalalgias
Otherprimaryheadaches

39

PRIMARYSTABBINGHEADACHE
Brief(<30seconds)
severe,sharp
unilateral,variable
PredominantlyinTrigeminal1territory
Notrigger
MorefrequentwithMigraine

Tx:Indomethacin
40
 HYPNICHEADACHE
Mostbetween6784yearsold
Dullpain(variable)
unilateralorholocephalic
noassociatedautonomicfeatures
< 1photophobia,phonophobia,nausea
occursaboutsametimeeverynight(few
hoursafterBed)
Duration> 15minutes
Freq13/night(atleast15timespermonth)
Tx:Indocin,Lithium,Caffeine,Topamax

41

PartOne:Other
PrimaryCoughHeadache
PrimaryExerciseHeadache
PrimaryHeadacheAssociatedwithSexualActivity
PrimaryThunderclapHeadache
ColdStimulusHeadache
ExternalPressureHeadache
PrimaryStabbingHeadache
NumularHeadache
HypnicHeadache
NewDailyPersistentHeadache

42
29yearoldmalepresentswith4month
historyofheadachesthatoccurfivetimes
permonth,duration8hours,unilateral,
pounding,severe,associatedwithnausea
andphotophobia.Newonsetthedayof
mildclosedheadinjuryandconcussion.
Physicalexaminationisnormal.
Whatisthis?

43

PARTTWO

Trauma
Vascular
IntracranialNonvascular
Substance
Infection
Homeostasis
HEENT
Psychiatric
44
 PartTwo:secondarycauses
1. Evaluation
2. Treatment

45

When to do testing for the patient with headache?

46
 REDFLAGSfor
SECONDARYHEADACHES
Age>50years Recentmalignancy,non
Worstoflife trivialheadtraumaor
Firstoflife seizures
Thunderclaponset Unexplainedfever
Markedchangeinpattern Bloodpressuregreater
Unusualassociated than180/115
features(blindness, Persistentorunexplained
diplopia,confusion, vomiting
weakness) Focalabnormalities
Lackofresponseto Meningealsigns
abortivemedications

47

DiagnosticEvaluation
ofHeadache
History,Physical
Imaging
LP
Bloodstudies
Other

Referral

48
 Secondaryheadaches
Treatment
Definitivetreatment
-blood pressure treatment
-antibiotic
-CPAP
Symptomatictreatment(basedonphenotype)
-migrainous
-TAC like
-neuralgiform
-musculoskeletal

49

PERSISTENTHEADACHEattributedto
mild
TRAUMATICHEADINJURY
A.AnyheadachefulfillingC&D
B.Traumaticinjurytotheheadhasoccurred
C.Headachedevelopedwithin7days
D.Headachepersistsfor>3monthsafter
headinjury
E.Notbetteraccounted

50
PERSISTENTHEADACHEattributedto
mild
TRAUMATICHEADINJURY

Evaluation:historyandphysical

Treatment:
Specificnone
Symptomatic dependsonphenotype

51

PARTTWO
Trauma
Vascular
IntracranialNonvascular
Substance
Infection
Homeostasis
HEENT
Psychiatric

52
Headacheattributedtoasubstanceor
itswithdrawal
8.3Headacheattributedtosubstancewithdrawal
8.3.2Opioidwithdrawalheadache

A.HeadachefulfillingcriterionC
B.Opioidintakedailyfor>3months,whichhasbeeninterrupted
C.Evidenceofcausationdemonstratedbybothofthefollowing:
1.headachehasdevelopedwithin24hoursafterlastopioidintake
2.headachehasresolvedwithin7daysaftertotalopioidwithdrawal
D.NotbetteraccountedforbyanotherICHD3diagnosis

53

PARTTHREE

Cranialneuralgiasandcentralcausesoffacialpain
Other

54
 45yearoldfemalepresentswithaoneyear
historyofheadachesthatoccuraboutten
timesperday,durationtwominutes,right
forehead,stabbing,severe.Physical
examinationisnormal.

55

Trigeminalneuralgia
A.AtleastthreeattacksofunilateralfacialpainfulfillingcriteriaB andC
B.Occurringinoneormoredivisionsofthetrigeminalnerve,with noradiationbeyondthetrigeminaldistribution
C.Painhasatleastthreeofthefollowingfourcharacteristics:
1.recurringinparoxysmalattackslastingfromafractionof asecondto2minutes
2.severeintensity
3.electricshocklike,shooting,stabbingorsharpinquality
4.precipitatedbyinnocuousstimuliaffectedsideofthe
face
D.Noclinicallyevidentneurologicaldeficit
E.Notbetteraccountedfor

.004-.015%
10/100,000

56
 TRIGEMINALNEURALGIA
Carbemazepine,Oxcarbazepine
Baclofen,Lamotrigine,Pimozide
Gabapentin,Phenytoin,Divalproexsodium,
Clonazepam

Denervationprocedures
Microvasculardecompression
GammaKnife

57

GeneralApproachtothePersonwithHeadache
https://www.youtube.com/watch?v=423JhqFygI4

1. Doesthehistory/physicalraiseconcernabout
anundiagnosedsecondarycontributor?
Evaluation
?Anyspecifictreatment
2. Whatistheprimaryheadachediagnosisor
principalheadachephenotype?
Symptomatictreatment
3. Reassess
58
 Websites
NationalHeadacheFoundation
www.headaches.org
AmericanHeadacheSociety
www.ahsnet.org
InternationalHeadacheSociety
www.Ihs.org
AmericanAcademyofNeurology
PracticeParameters
http://www.aan.com/practice/guideline/index.cfm?fuseacti
on=home.welcome&Topics=16&Submit=Search

59
 ParkinsonsDiseaseReview
forthePrimaryCarePhysician
andHospitalist

ThyagarajanSubramanian,MD

NOTES
NonParkinsonsTremors

MarkStahl,MD,PhD
NOTES