Seizure DisorderSeizure Disorder

Jeffrey T. Reisert, DOJeffrey T. Reisert, DOUniversity of New EnglandUniversity of New England

Physician Assistant ProgramPhysician Assistant Program27 AUG 200927 AUG 2009

Contact InformationContact Information

Jeffrey T. Reisert, DOJeffrey T. Reisert, DO

Jeffrey.T.Reisert@Hitchcock.orgJeffrey.T.Reisert@Hitchcock.org

Tenney Mountain Internal MedicineTenney Mountain Internal Medicine

251 Mayhew Turnpike251 Mayhew Turnpike

Plymouth, NH 03264Plymouth, NH 03264

(603) 536-6355(603) 536-6355

(603) 536-6356 (fax)(603) 536-6356 (fax)

ObjectivesObjectives

Define different patterns of seizuresDefine different patterns of seizuresRecognize symptoms of seizureRecognize symptoms of seizureBe able to differentiate types of Be able to differentiate types of

common seizures/patterns in children common seizures/patterns in children and adultsand adults

Recognize treatments of acute Recognize treatments of acute seizure, status epilepticus, and seizure, status epilepticus, and prevention of seizuresprevention of seizures

Illustrative CaseIllustrative Case

You are covering the ED when a 40 You are covering the ED when a 40 year old male presents by year old male presents by ambulance, reportedly for “Loss of ambulance, reportedly for “Loss of consciousness”consciousness”

You interview a sleepy patient and You interview a sleepy patient and interview their friend.interview their friend.

The patient works as a carpenter for The patient works as a carpenter for a home construction firm. His history a home construction firm. His history is benign.is benign.

What questions do you have?What questions do you have?

Important factsImportant facts

The patient was at the job site and The patient was at the job site and stated he didn’t feel well. His co-stated he didn’t feel well. His co-worker informs you he collapsed worker informs you he collapsed after saying he didn’t feel well.after saying he didn’t feel well.

He was noted to have “eyes that He was noted to have “eyes that rolled back in his head” and rolled back in his head” and drewling.drewling.

Then he tensed up and began Then he tensed up and began shaking for “a long time.”shaking for “a long time.”

What is your differential What is your differential diagnosis?diagnosis?

SeizureSeizureCardiac eventCardiac eventAlcohol withdrawal?Alcohol withdrawal?

Definition of Seizure DisorderDefinition of Seizure Disorder

Harrison’s Principles of Internal Medicine Harrison’s Principles of Internal Medicine defines a seizure as a paroxysmal event due defines a seizure as a paroxysmal event due to abnormal CNS discharge with resultant to abnormal CNS discharge with resultant manifestations depending on area involved.manifestations depending on area involved.

5-10% of population in lifetime have a 5-10% of population in lifetime have a seizureseizure

More prevalent in early childhood and later More prevalent in early childhood and later in adulthoodin adulthood

Epilepsy defines a patient with recurrent Epilepsy defines a patient with recurrent seizures (not a single seizure).seizures (not a single seizure). About 0.3-0.5% of populationAbout 0.3-0.5% of population

Types of seizuresTypes of seizures

International League Against International League Against Epilepsy (ILAE)-1981Epilepsy (ILAE)-1981

International classification of International classification of epileptic seizuresepileptic seizures

Table 348.1Table 348.1

Two basic types of seizuresTwo basic types of seizures

PartialPartialDeranged area of cerebral cortex often Deranged area of cerebral cortex often

due to a structural anomaly-due to a structural anomaly-Consciousness is preservedConsciousness is preserved

Further divided in to simple partial and Further divided in to simple partial and complex partial-Consciousness is complex partial-Consciousness is impairedimpaired

Third where partial seizures secondarily Third where partial seizures secondarily generalizedgeneralized

Generalized-Next slideGeneralized-Next slide

GeneralizedGeneralized

Diffuse region of brain firing Diffuse region of brain firing simultaneouslysimultaneously

Often due a widespread problemOften due a widespread problemCellular disorder (i.e.: mental Cellular disorder (i.e.: mental

retardation)retardation)Biochemical disruption (i.e.: low sodium)Biochemical disruption (i.e.: low sodium)Structural issue (i.e.: brain tumor)Structural issue (i.e.: brain tumor)

Simple Partial SeizuresSimple Partial Seizures

May be motor, sensory, autonomic, May be motor, sensory, autonomic, psychic but without loss of psychic but without loss of consciousness (LOC)consciousness (LOC)

Example: May get a hand tremor on Example: May get a hand tremor on opposite side of abnormal brain opposite side of abnormal brain activityactivity

Often clonic with repetitive Often clonic with repetitive flexion/extensionflexion/extension

EEG: Abnormal impulses in focal area EEG: Abnormal impulses in focal area of brainof brain

Variations of simple partial Variations of simple partial seizuresseizures

Jacksonian MarchJacksonian MarchMotor activity begins distally, like Motor activity begins distally, like

fingers, and spreads to whole extremityfingers, and spreads to whole extremityEEG: spike wavesEEG: spike waves

Todd’s paralysisTodd’s paralysisLocal paresis lasting minutes to hoursLocal paresis lasting minutes to hours

Epilepsia partialis continuaEpilepsia partialis continuaContinues hours to daysContinues hours to days

Additional symptoms in simple Additional symptoms in simple partial seizurespartial seizures

Changes in somatic sensations Changes in somatic sensations (paresthesias)(paresthesias)

Change in vision (flashing lights, Change in vision (flashing lights, hallucinations)hallucinations)

Changes in equilibrium (falling, Changes in equilibrium (falling, vertigo)vertigo)

Autonomic changes (flushing, Autonomic changes (flushing, sweating)sweating)

Odd feelings (déjà vu)Odd feelings (déjà vu)

Complex Partial SeizuresComplex Partial Seizures Focal activity progresses to loss of contact with Focal activity progresses to loss of contact with

environment (ictal stage)environment (ictal stage) StareStare Amnesia – may forget what happenedAmnesia – may forget what happened

Often begins with an aura stereotypical for the Often begins with an aura stereotypical for the patient……Feel funny.patient……Feel funny.

Followed by ictal stageFollowed by ictal stage Involuntary behaviorsInvoluntary behaviors Chewing, pickingChewing, picking

Post ictal confusionPost ictal confusion Lasts seconds to hoursLasts seconds to hours EEG between spells (inter ictal) usually normal (or EEG between spells (inter ictal) usually normal (or

may show brief discharge of spikes (sharp waves)may show brief discharge of spikes (sharp waves)

Partial seizures with secondary Partial seizures with secondary generalizationgeneralization

Electrical discharge spread and both Electrical discharge spread and both hemispheres become involvedhemispheres become involved

Results in tonic-clonic seizureResults in tonic-clonic seizureCommon when partial seizures in Common when partial seizures in

frontal lobefrontal lobeLook like generalized seizuresLook like generalized seizures

Generalized seizuresGeneralized seizures

Arise in both cerebral hemispheres Arise in both cerebral hemispheres simultaneouslysimultaneously

Look like focal seizure that Look like focal seizure that secondarily generalized though not secondarily generalized though not associated with a specific focal onset associated with a specific focal onset eventevent

Includes absence seizures and tonic-Includes absence seizures and tonic-clonic seizuresclonic seizures

Absence Seizures (Petit mal)Absence Seizures (Petit mal)

Brief LOC without postural control.Brief LOC without postural control.Usually last a few secondsUsually last a few secondsNo post ictal confusionNo post ictal confusionMay have other subtle findingsMay have other subtle findings

Eye blinkingEye blinkingChewingChewingClonic movement of handsClonic movement of hands

Absence seizures cont.Absence seizures cont.

Onset typically in childhood, 4-8 y/o Onset typically in childhood, 4-8 y/o or early adolescenceor early adolescence

Makes up 15-20% of childhood Makes up 15-20% of childhood seizuresseizures

May occur all day May occur all day long…..Daydreaming appearancelong…..Daydreaming appearance

Absence seizures cont.Absence seizures cont.

EEGEEGGeneralized symmetrical dischargeGeneralized symmetrical dischargeSpike and waveSpike and waveStart stop with inter-ictal normal EEGStart stop with inter-ictal normal EEGWorsen with hyperventilation maneuverWorsen with hyperventilation maneuver

May be associated with T-C seizuresMay be associated with T-C seizures60-70% of cases remiss in childhood60-70% of cases remiss in childhood

Atypical absence seizuresAtypical absence seizures

Similar to absence but symptoms last Similar to absence but symptoms last longerlonger

More motor featuresMore motor featuresMay have a brain abnormality such May have a brain abnormality such

as mental retardation/developmental as mental retardation/developmental delaydelay

Harder to tx than ordinary absence Harder to tx than ordinary absence seizuresseizures

Generalized Tonic-Clonic Generalized Tonic-Clonic SeizuresSeizures

10% of patients with epilepsy10% of patients with epilepsyAre the most common type when Are the most common type when

seizures are due to metabolic seizures are due to metabolic derangementderangement

Episodes are of sudden onsetEpisodes are of sudden onsetMay have prodrome but less so than May have prodrome but less so than

aura in focal seizures that secondarily aura in focal seizures that secondarily generalizegeneralize

T-C Seizures-CharacteristicsT-C Seizures-Characteristics

Tonic phaseTonic phase Increased muscle toneIncreased muscle tone

Often a moan or cryOften a moan or cry Change in respirationChange in respiration

Secretions poolSecretions pool CyanosisCyanosis Jaw clenches, bite tongueJaw clenches, bite tongue

Sympathetic symptomsSympathetic symptoms Increased BP, HRIncreased BP, HR Pupil dilationPupil dilation

T-C Seizure Features cont.T-C Seizure Features cont. Clonic activityClonic activity

Muscles relax and contractMuscles relax and contract Usually lasts about a minuteUsually lasts about a minute

Post-ictal statePost-ictal state UnresponsiveUnresponsive FlaccidFlaccid Salivation or airway obstructionSalivation or airway obstruction Bowel or bladder incontinenceBowel or bladder incontinence

Seizures may last minutes to hours before Seizures may last minutes to hours before awakeningawakening

Post seizurePost seizure HeadacheHeadache FatigueFatigue Muscle achesMuscle aches

T-C Seizures-EEGT-C Seizures-EEG

Tonic phaseTonic phaseIncreased low voltage fast activityIncreased low voltage fast activityHigh amplitude polyspike dischargesHigh amplitude polyspike discharges

Clonic phaseClonic phaseSpike and wave activity developsSpike and wave activity develops

Post ictalPost ictalSlowing then recoverySlowing then recovery

T-C Seizures-VariationsT-C Seizures-Variations

Atonic seizuresAtonic seizures 1-2 seconds lose motor tone1-2 seconds lose motor tone Brief loss of consciousness (LOC)Brief loss of consciousness (LOC) No post-ictal confusionNo post-ictal confusion Risk after head injuryRisk after head injury Also associated with other epileptic syndromesAlso associated with other epileptic syndromes

Myoclonic seizuresMyoclonic seizures Brief contraction or jerkBrief contraction or jerk Like when you fall asleep and you twitchLike when you fall asleep and you twitch Seen in brain injuriesSeen in brain injuries

Other Generalized Seizure Other Generalized Seizure categoriescategories

Juvenile myoclonic epilepsyJuvenile myoclonic epilepsyLennox Gastaut syndromeLennox Gastaut syndromeMesial temporal lobe epilepsyMesial temporal lobe epilepsy

Juvenile Myoclonic epilepsyJuvenile Myoclonic epilepsy

AdolescenceAdolescenceBilateral jerk with maintained Bilateral jerk with maintained

consciousnessconsciousnessWorse with awakening, sleep deprivationWorse with awakening, sleep deprivationBenignBenign

Good response to medsGood response to medsMay spontaneously remitMay spontaneously remit

Associated with other epileptic Associated with other epileptic syndromessyndromes

Lennox Gastaut syndromeLennox Gastaut syndrome

Seen in childrenSeen in children Multiple seizure typesMultiple seizure types EEG slowing and spike wavesEEG slowing and spike waves Usually impaired cognitive functionUsually impaired cognitive function Associated with central nervous system Associated with central nervous system

(CNS) disease(CNS) disease Developmental delayDevelopmental delay TraumaTrauma InfectionInfection Neural injuriesNeural injuries

Often difficult to controlOften difficult to control

Mesial temporal lobe epilepsyMesial temporal lobe epilepsy

Difficult to controlDifficult to controlPartial epilepsy with characteristic Partial epilepsy with characteristic

featuresfeaturesMRI shows hippocampal sclerosisMRI shows hippocampal sclerosis

Seizures-EtiologySeizures-Etiology

Harrison’s: Shift in balance of Harrison’s: Shift in balance of excitation and inhibition in CNSexcitation and inhibition in CNS

MechanismsMechanismsChange in seizure threshold (i.e.: Fevers Change in seizure threshold (i.e.: Fevers

in children)in children)Genetic roleGenetic roleTraumatic brain injuryTraumatic brain injuryOther events (strokes, infection)Other events (strokes, infection)Precipitating factorsPrecipitating factors

Seizure causes cont.Seizure causes cont.

Precipitating factorsPrecipitating factorsStressStressSleep deprivationSleep deprivationMensesMensesMedicationsMedicationsEtc.Etc.

May take years to develop after May take years to develop after eventevent

What happens?What happens?

A burst of electrical activityA burst of electrical activity Influx of extracellular calciumInflux of extracellular calcium

Excitatory molecules such as NMDA (N-methyl-D-Excitatory molecules such as NMDA (N-methyl-D-aspartate) may further calcium influxaspartate) may further calcium influx

Influx of sodiumInflux of sodium Under influence of GABA (Gamma-aminobutyric acid) or Under influence of GABA (Gamma-aminobutyric acid) or

potassium channelspotassium channels Spike dischargeSpike discharge Inhibitory neurons overwhelmed by calcium and Inhibitory neurons overwhelmed by calcium and

potassiumpotassium Propagation of action potentialsPropagation of action potentials Channel problems may be source of genetic Channel problems may be source of genetic

epilepsyepilepsy

Seizures, age basisSeizures, age basis

Table 348-4Table 348-4NeonatesNeonates

Birth injury, hypoxemiaBirth injury, hypoxemiaCongenital abnormalitiesCongenital abnormalitiesDrugs (maternal)Drugs (maternal)

Early ChildhoodEarly ChildhoodFebrile seizuresFebrile seizures

Febrile SeizuresFebrile Seizures 3-5% of children3-5% of children Most occur from 3mo to 5ysMost occur from 3mo to 5ys

Most 18-24 moMost 18-24 mo Infection typesInfection types

Otitis mediaOtitis media Respiratory infectionRespiratory infection GastroenteritisGastroenteritis

PresentationPresentation Early on in febrile illness T-C activityEarly on in febrile illness T-C activity

Recurrence about 1/3 of ptsRecurrence about 1/3 of pts Can be a simple febrile seizure (one event) or Can be a simple febrile seizure (one event) or

complex febrile seizure (repeated activity)complex febrile seizure (repeated activity) Not epilepsyNot epilepsy

Age cont.Age cont.

ChildhoodChildhood Usually when epilepsy becomes apparentUsually when epilepsy becomes apparent

AdolescenceAdolescence Think traumaThink trauma The worse the trauma the worse the seizuresThe worse the trauma the worse the seizures

AdulthoodAdulthood Cerebrovascular disease (50% of new onset seizures in Cerebrovascular disease (50% of new onset seizures in

adults)adults) TraumaTrauma CNS tumorsCNS tumors Degenerative diseasesDegenerative diseases Medical (Hypo/hyperglycemia, renal failure, liver Medical (Hypo/hyperglycemia, renal failure, liver

disease, and drugsdisease, and drugs

Diagnosis seizure disorderDiagnosis seizure disorder

History is key (observer/bystander)History is key (observer/bystander) EEGEEG

ASAP to measure brain activityASAP to measure brain activityAwakeness/activityAwakeness/activity

Burst of action potentialsBurst of action potentials Baseline alpha wave (8-13 Hz) with eyes closedBaseline alpha wave (8-13 Hz) with eyes closed Faster beta activity (>13 Hz) increase with Faster beta activity (>13 Hz) increase with

activity/eye opening. Amount varies.activity/eye opening. Amount varies. Slower theta activity (4-7 Hz) and delta (<4 Hz)Slower theta activity (4-7 Hz) and delta (<4 Hz)

EEG Cont.EEG Cont.

Different situations are assessed (montages)Different situations are assessed (montages) Awake/asleepAwake/asleep Eyes open/closed or with photo stimulationEyes open/closed or with photo stimulation HyperventilationHyperventilation Sleep deprivationSleep deprivation

Key findingsKey findings Abnormal activity that starts/stops abruptly ORAbnormal activity that starts/stops abruptly OR Abnormal activity during T-C seizureAbnormal activity during T-C seizure Inter-ictal may see spikes or sharp waves in 40% Inter-ictal may see spikes or sharp waves in 40%

of cases (worse prognosis) – harder to treatof cases (worse prognosis) – harder to treat

Evaluation and WorkupEvaluation and Workup

EEGEEG ImagingImaging

Most getMost getMRI bestMRI best

Blood testsBlood testsUsually normal (not helpful)Usually normal (not helpful)May see elevated prolactin level in first May see elevated prolactin level in first

30 mins.30 mins.

Differential diagnosisDifferential diagnosis

Table 348-6Table 348-6 SyncopeSyncope

Tired, sweaty, tunnel visionTired, sweaty, tunnel vision May have 10 sec of convulsive activityMay have 10 sec of convulsive activity (Seizures may have aura, cyanosis, LOC, >30 sec. (Seizures may have aura, cyanosis, LOC, >30 sec.

activity, post-ictal disorientation, muscle soreness, or activity, post-ictal disorientation, muscle soreness, or sleepiness)sleepiness)

Psychogenic seizuresPsychogenic seizures Non-epileptiform behaviors that resemble seizuresNon-epileptiform behaviors that resemble seizures Seen with stress/conversion reactionSeen with stress/conversion reaction Head turning, shaking, twitching, no LOC, pelvic thrust Head turning, shaking, twitching, no LOC, pelvic thrust

that waxes and wanesthat waxes and wanes ? Video EEG? Video EEG

Overview of treatmentOverview of treatment Basic life supportBasic life support

Vital signs, CPRVital signs, CPR Treat cause if identifiedTreat cause if identified

Infection, tumor, drugsInfection, tumor, drugs Cerebrospinal fluid tap?Cerebrospinal fluid tap? Imaging (MRI preferred)Imaging (MRI preferred)

Meds if more than one episode or high riskMeds if more than one episode or high risk 31-71% risk of second seizure in one year31-71% risk of second seizure in one year

Assess for likelihood of recurrenceAssess for likelihood of recurrence Are meds needed long term?Are meds needed long term? 2 year trial on meds?2 year trial on meds?

SafetySafety WorkWork DrivingDriving

Seizure meds, overviewSeizure meds, overview

Right drug for certain type of seizureRight drug for certain type of seizureOne drug?One drug?Add slowlyAdd slowlyOlder meds first lineOlder meds first line

Phenytoin (DilantinPhenytoin (Dilantin®), valproic acid ®), valproic acid (Depakote®), carbamazepine (Depakote®), carbamazepine (Tegretol®)(Tegretol®)

Newer meds secondNewer meds second

Medications-Mechanism of Medications-Mechanism of ActionAction

Block activity of ion channels or neurotransmittersBlock activity of ion channels or neurotransmitters Inhibit Na+ dependent action potentialsInhibit Na+ dependent action potentials

Phenytoin, carbamazepine, lamotrigine (LamictalPhenytoin, carbamazepine, lamotrigine (Lamictal®), ®), topiramate (Topamax®), zonisamide (Zonegran®)topiramate (Topamax®), zonisamide (Zonegran®)

Inhibit Ca++ channelsInhibit Ca++ channels PhenytoinPhenytoin

Decrease glutamate releaseDecrease glutamate release LamotrigineLamotrigine

Increase GABA functionIncrease GABA function Benzodiazepines, phenobarbitalBenzodiazepines, phenobarbital

Increase GABA availabilityIncrease GABA availability Valproic acid, gabapentin (NeurontinValproic acid, gabapentin (Neurontin®), tiagabine (Gabitril®)®), tiagabine (Gabitril®)

Inhibit Ca++ channels in thalamus (absence seizures)Inhibit Ca++ channels in thalamus (absence seizures) Ethosuximide, valproic acidEthosuximide, valproic acid

Treatment by seizure typeTreatment by seizure type

Partial seizuresPartial seizures Carbamazepine (3-4 x per day, low WBC, bone Carbamazepine (3-4 x per day, low WBC, bone

marrow aplasia, hepatotox)marrow aplasia, hepatotox) Phenytoin (1-2 x per day, levels, tox, Phenytoin (1-2 x per day, levels, tox,

hirsuitism, coarse facial features, gingival hirsuitism, coarse facial features, gingival hyperplasia, affect on bone metabolism)hyperplasia, affect on bone metabolism)

Lamotrigine (Rash)Lamotrigine (Rash) Valproic acid (GI tox, bone marrow Valproic acid (GI tox, bone marrow

suppression, hepatotox)suppression, hepatotox) Generalized seizuresGeneralized seizures

Valproic acid, lamotrigine, carbamazepine, Valproic acid, lamotrigine, carbamazepine, phenytoinphenytoin

Medications-MonitoringMedications-Monitoring

Adverse drug reactionsAdverse drug reactionsEffectivenessEffectivenessLevelsLevelsLiver function testsLiver function testsBlood countsBlood countsDrugs in combo?Drugs in combo?

Stopping drugsStopping drugs

Consider ifConsider ifLow riskLow riskOne seizure then seizure freeOne seizure then seizure freeNormal exam (no developmental delay, Normal exam (no developmental delay,

head injury, etc.)head injury, etc.)Normal EEGNormal EEGDo slowlyDo slowly

Driving implications?Driving implications?

Status epilepticusStatus epilepticus

Continuous seizureContinuous seizure Some say if more than 15-30 minsSome say if more than 15-30 mins Others if > 15 secondsOthers if > 15 seconds May range from T-C seizure to more subtle May range from T-C seizure to more subtle

(finger or eye movement)(finger or eye movement) May need EEG to verifyMay need EEG to verify

Medical emergencyMedical emergency Cardiovascular implicationsCardiovascular implications HyperthermiaHyperthermia Metabolic derangementsMetabolic derangements CNS injuryCNS injury

Status epilepticus-CausesStatus epilepticus-Causes

Metabolic problemsMetabolic problemsDrug toxicityDrug toxicityCNS infection or tumorCNS infection or tumorHead injuryHead injuryRefractory epilepsyRefractory epilepsy

Status epilepticus-TreatmentStatus epilepticus-Treatment

Metabolic work upMetabolic work upBenzodiazepine (Lorazepam, Benzodiazepine (Lorazepam,

diazepam (Valiumdiazepam (Valium®), others®), othersPhenytoin – can burn armPhenytoin – can burn armPhenobarbitalPhenobarbitalAnesthesiaAnesthesia

Surgical treatment of Surgical treatment of seizuresseizures

Use is primarily in refractory epilepsyUse is primarily in refractory epilepsy ProceduresProcedures

Temporal lobectomyTemporal lobectomy Focal lesion removal (or more such as Focal lesion removal (or more such as

hemispherectomy)hemispherectomy) Corpus callosotomyCorpus callosotomy

RequiresRequires EEG, Video EEGEEG, Video EEG NeuroimagingNeuroimaging SPECT or PET scans (functional)SPECT or PET scans (functional) Electrical mappingElectrical mapping

Vagal nerve stimulatorVagal nerve stimulator

Place a bipolar electrode in L vagus Place a bipolar electrode in L vagus nervenerve

Generator delivers a pulseGenerator delivers a pulseMay take a while to workMay take a while to workMOA: May simply increase seizure MOA: May simply increase seizure

thresholdthreshold

Other issuesOther issues

Developmental delay/mental retardationDevelopmental delay/mental retardation ParentingParenting StigmaStigma 2-3x greater death rate2-3x greater death rate Work? Driving?Work? Driving? Menstrual cycles may increase riskMenstrual cycles may increase risk PregnancyPregnancy

Seizures may worsen or improve in half of ptsSeizures may worsen or improve in half of pts May alter drug levelsMay alter drug levels Tx may cause birth defectsTx may cause birth defects May affect contraceptionMay affect contraception

Case wrap upCase wrap up HistoryHistory

No prior eventNo prior event IncontinenceIncontinence Sudden onsetSudden onset ProdromeProdrome Tonic clonic activityTonic clonic activity

ExamExam Post ictal grogginessPost ictal grogginess Wet pantsWet pants

Work up?Work up? ImagingImaging EEGEEG Check glucose, chemistries, drug level?Check glucose, chemistries, drug level? Meds or observe?Meds or observe?

TreatmentTreatment Dilantin or similarDilantin or similar No driving/laddersNo driving/ladders

Questions?Questions?

ReferencesReferences

Harrison’sHarrison’sUp-To-DateUp-To-DateNetterNetter