- HELLO. I WOULD LIKE TO WELCOME
YOU ALL TO OUR SECOND CALL

OF THE NEW FISCAL YEAR IN THE
"INTRODUCTION TO EPILEPSY"

AUDIO CALL SERIES.

MY NAME IS SEAN GAMBLE.

I'M WITH THE EMPLOYEE
EDUCATION SERVICES HERE IN

ST. LOUIS, AND I'M THE PROJECT
MANAGER FOR THE SERIES.

EVERYBODY'S LINE
SHOULD BE MUTED.

IF THEY'RE NOT, PLEASE MUTE
THEM, AND WE WILL OPEN THEM UP

AT THE END OF THE
PRESENTATION WHEN WE ARE READY

FOR QUESTIONS.

PLEASE LIMIT YOUR QUESTIONS TO
ONE PER PERSON SO EVERYBODY

HAS A CHANCE.

PLEASE BE SURE TO COMPLETE
YOUR EVALUATION TO GET CREDIT

FOR THIS PROGRAM.

COMPLETE DIRECTIONS FOR YOUR
EVALUATION ARE IN THE BROCHURE

OR ON THE CATALOG.

DEADLINE DATE TO COMPLETE THE
EVALUATION IS FEBRUARY 17.

FOR THOSE OF YOU THAT ARE NOT
VA, RYAN RIEGER HAS POSTED

THE PAPER COPY OF
THE EVALUATION.

THE DIRECTIONS ARE ON THAT.

YOU CAN SEND THEM IN.

NOW LET ME WELCOME OUR SPEAKER
FOR TODAY, DR. ALLAN KRUMHOLZ.

GO AHEAD, DOCTOR.

- THANK YOU, SEAN.

HELLO, AND WELCOME.

TODAY WE'RE GONNA BE TALKING
ABOUT CARE OF THE MOST

CHALLENGING AND DIFFICULT
TYPES OF EPILEPSY PATIENTS,

THOSE WHO DON'T RESPOND TO
INITIAL THERAPY AND GO ON TO BE

DISABLED BY RECURRING
SEIZURES.

AS I'LL BE TALKING, I'LL BE
POINTING OR MENTIONING CERTAIN

SLIDES, AND HOPEFULLY THOSE
NUMBERS WILL COINCIDE WITH

THE NUMBERS THAT YOU HAVE.

WELL, WHAT CAN BE DONE FOR
THESE PATIENTS WHO HAVE

REFRACTORY OR INTRACTABLE
SEIZURES, SEIZURES THAT JUST

DON'T--THAT DON'T...

[RUSTLING]

...VICTIMS OF EPILEPSY, AND
THEIR FAMILIES ARE ALSO VICTIMS

OF EPILEPSY.

AS IT TURNS OUT, I HOPE TO
SHOW YOU THAT THERE'S A GOOD

DEAL THAT CAN BE DONE
FOR THESE INDIVIDUALS,

PARTICULARLY WORKING IN
COLLABORATION WITH THE NEW

NETWORK OF VA EPILEPSY
CENTERS OF EXCELLENCE.

WE THINK THAT THE VA AND
MEDICINE AND HEALTH CARE

IN GENERAL HAVE A LOT
TO POTENTIALLY OFFER

THESE PATIENTS.

NOW, IF YOU LOOK AT THE
SECOND SLIDE, YOU'LL SEE THAT

EPILEPSY IS REALLY A
VERY COMMON DISEASE.

IT IS THE MOST COMMON
SERIOUS DISEASE CARED FOR BY

NEUROLOGISTS, AND SO
NEUROLOGISTS ARE LIKELY TO SEE

MANY EPILEPSY PATIENTS
IN THEIR PRACTICE.

IN FACT, 3% OF THE US
POPULATION IS AFFECTED

BY EPILEPSY.

ONE MIGHT THINK THAT IN THE
VA WE MIGHT SEE LESS OF THESE

PATIENTS WITH EPILEPSY BECAUSE
INDIVIDUALS WITH EPILEPSY ARE

SCREENED FROM SERVICE, BUT
IN FACT, BECAUSE OF THE HIGH

INCIDENCE OF TRAUMATIC BRAIN
INJURY CAUSING SEIZURES

AND THE FACT THAT MANY
PATIENTS WITH SEIZURES DEVELOP

THEM IN LATER LIFE AFTER
CONDITIONS SUCH AS STROKES,

SEIZURES IN OUR VETERAN
POPULATION ARE A VERY COMMON

AND SERIOUS PROBLEM.

SO FORTUNATELY, SEIZURES
ARE ALSO A TREATABLE PROBLEM

AND HAVE LONG BEEN A
TREATABLE PROBLEM.

ONE OF THE REASONS THAT I
CHOSE TO GO INTO EPILEPSY CARE

AS A NEUROLOGIST IS EVEN WHEN
I STARTED IN NEUROLOGY, ALMOST

40 YEARS AGO, SEIZURES WERE
ONE OF THE FEW TREATABLE

DISORDERS IN NEUROLOGY.

A LOT HAS CHANGED SINCE THEN.

THERE ARE MANY VERY TREATABLE
DISORDERS IN NEUROLOGY,

BUT EPILEPSY AND SEIZURES
REMAIN AMONG THE MOST

SUCCESSFULLY TREATED IN A WAY
THAT I THINK DESERVE A LOT

OF ATTENTION BECAUSE THEY
ARE TREATABLE AND IN SOME

CASES CURABLE.

UNFORTUNATELY, ALTHOUGH
EPILEPSY AND SEIZURES ARE

TREATABLE, THEY OFTEN CAN'T
BE COMPLETELY ELIMINATED,

AND SEIZURES AND EPILEPSY
DEVELOP INTO A CHRONIC

DISORDER, AND IN FACT NOT
EVERYONE WITH EPILEPSY CAN OR

WILL HAVE THEIR SEIZURES
COMPLETELY CONTROLLED.

SO WHAT CAN WE EXPECT IN
TERMS OF TREATING PEOPLE

WITH EPILEPSY AND SEIZURES
WHEN WE FIRST SEE SOMEONE

WITH A SEIZURE DISORDER?

WELL, THERE IS GOOD NEWS,
AND THERE IS BAD NEWS.

THE GOOD NEWS IS THAT
MOST PEOPLE WITH EPILEPSY,

THE GREAT MAJORITY, PERHAPS
70%, CAN BE COMPLETELY

CONTROLLED IN TERMS OF
COMPLETELY CONTROLLING THEIR

SEIZURES WITH MEDICATION.

NOW, THAT'S THE GOOD NEWS.

ON THE OTHER HAND, 20% WILL
CONTINUE TO HAVE SOME SEIZURES

BUT WILL HAVE THEM RARELY
ENOUGH TO BE SOMEWHAT

FUNCTIONAL OR AT LEAST
LARGELY FUNCTIONAL.

UNFORTUNATELY, 10% OF PATIENTS
WITH EPILEPSY WILL HAVE

SEIZURES SO FREQUENTLY AND
HAVE SUCH SEVERE SEIZURES

THAT THEY WILL BE COMPLETELY
DISABLED, AND THAT GROUP,

THE 20% OR 30% THAT HAS
THE INTRACTABLE SEIZURES OR

PERSISTENT SEIZURES, IS THE
GROUP THAT WE'RE GOING TO

CONCENTRATE ON TODAY.

SO WHAT I'M GONNA DO TODAY IN
THE REMAINING TIME IS TRY TO

CHARACTERIZE FOR YOU OR TO
DEFINE WHAT IS INTRACTABLE OR

REFRACTORY EPILEPSY, THESE
PATIENTS WHO REALLY REQUIRE

A LOT MORE ATTENTION AND
EFFORT THAN THOSE PATIENTS WHO

HAVE COME UNDER QUICK CONTROL.

WE'LL DISCUSS THE CONSEQUENCES
AND SIGNIFICANCE OF THIS

REFRACTORY OR
INTRACTABLE EPILEPSY.

THEN WE'LL TALK ABOUT
TREATMENT OPTIONS THAT WE HAVE

AVAILABLE TODAY, MANY OF
WHICH HAVE--ARE NEW AND RATHER

EXCITING--AND THEN ALSO TALK
ABOUT SOME OF THE TREATMENT

OPTIONS THAT ARE ON THE
HORIZON AND WE SHOULD

ALSO CONSIDER.

SO WHAT IS INTRACTABLE
OR REFRACTORY EPILEPSY?

THE DEFINITION VARIES
IN DIFFERENT STUDIES,

BUT IN GENERAL, WHAT IT REQUIRES
IS THAT SEIZURES PERSIST,

AND THAT MEANS THAT THEY
PERSIST DESPITE TREATMENT.

THE INTERNATIONAL LEAGUE
AGAINST EPILEPSY HAS RECENTLY

PROPOSED THAT THERE BE A
CONCEPT OF DRUG-RESISTANT

EPILEPSY, MEANING THAT IF
SEIZURES PERSIST AFTER A TRIAL

OF 2 OR 3 ANTIEPILEPTIC
DRUGS PROPERLY SELECTED

FOR THE SEIZURE TYPE AND GIVEN
AT REASONABLE DOSAGES,

THAT THOSE SEIZURES ARE
DRUG RESISTANT, AND THOSE

ARE THE PATIENTS THAT REALLY
SHOULD BE REFERRED TO

SECONDARY OR TERTIARY EPILEPSY
CENTERS SUCH AS OUR EPILEPSY

CENTERS OF EXCELLENCE
IN THE VA SYSTEM.

OTHER CONSIDERATIONS ARE THAT
NOT ONLY THOSE SEIZURES SHOULD

BE RESISTANT TO INITIAL
THERAPY, BUT THERE SHOULD BE

A MINIMUM NUMBER OF
SEIZURES THAT PERSIST EVEN

AFTER TREATMENT.

SO IT MEANS THAT SEIZURES MAY
OCCUR EVERY 6 MONTHS OR 12

MONTHS, OR THERE MAY BE
LONGER INTERVALS BETWEEN

THE SEIZURES, BUT IN GENERAL,
MOST SEIZURE PATIENTS WHO ARE

CONSIDERED TO HAVE INTRACTABLE
EPILEPSY WILL HAVE SEIZURES

RECURRING GENERALLY ABOUT
ONCE A YEAR OR MORE.

THE DURATION OF THE SEIZURES
SHOULD ALSO BE A LONG

PERIOD OF TIME.

SO PEOPLE WHO HAVE CLUSTERS OF
SEIZURES AND THEN COME UNDER

COMPLETE CONTROL FOR MANY
YEARS WOULDN'T NECESSARILY BE

CONSIDERED HAVING
INTRACTABLE EPILEPSY.

BUT THIS CONDITION SHOULD
PERSIST FOR A PERIOD OF TIME

OF SEVERAL YEARS IN ORDER TO
BE CONSIDERED INTRACTABLE OR

REFRACTORY AND BE THE WORST
OR MOST SERIOUS KIND

OF SEIZURE DISORDER.

AND FINALLY, THE SEIZURES,
IF THEY MEET THESE CRITERIA,

WILL GENERALLY BE DISABLING
FOR THE INDIVIDUAL.

SO, FOR EXAMPLE, PEOPLE WHO
HAVE SEIZURES OF SUCH SEVERITY

AND FREQUENCY WOULD NOT
BE ABLE TO DRIVE.

THEY WOULD BE LIMITED IN
VARIOUS KINDS OF EMPLOYMENT

AND ACTUALLY WOULD BE CONSIDERED
AT RISK OF PROBLEMS

SUCH AS SUDDEN DEATH.

SO, TURNING TO THE SIXTH SLIDE,

HOW CAN WE PREDICT WHICH
PATIENTS ARE AT MORE RISK

FOR BEING INTRACTABLE OR NOT
BEING ABLE TO HAVE THEIR

SEIZURES CONTROLLED?

WHEN WE FIRST SEE A PATIENT,
ARE THERE CLUES THAT MIGHT

ALLOW US TO DETERMINE THAT
ONE PATIENT WOULD TEND TO BE

INTRACTABLE AND MAY NEED
MORE FREQUENT ATTENTION OR

AGGRESSIVE INTERVENTION
THAN OTHER PATIENTS?

WELL, THERE ARE SOME CLUES.

ONE IS THAT THE MORE SEIZURES
THAT AN INDIVIDUAL HAS WHEN

THEY PRESENT OR BEFORE THEY'RE
STARTED ON ANTIEPILEPTIC

THERAPY, THE GREATER THEIR
LIKELIHOOD OF NOT COMING

UNDER CONTROL.

SO THE PATIENT WHO HAS JUST
HAD ONE OR TWO OR 3 SEIZURES

IS LIKELY TO DO MUCH BETTER
WITH THE ANTIEPILEPTIC DRUG

TREATMENT THAN A PATIENT
WHO MAY HAVE EXPERIENCED

100 SEIZURES OR 200 SEIZURES
BEFORE THEY ARE FIRST TREATED

WITHIN AN ANTIEPILEPTIC DRUG.

ANOTHER FACTOR IS HOW
FREQUENT THEIR SEIZURES ARE.

SO THE PATIENT WHO EXPERIENCES
SEIZURES MAYBE ONCE A YEAR

OR ONCE EVERY OTHER YEAR WILL
BE MUCH MORE LIKELY TO BE ABLE

TO BE CONTROLLED WITH
MEDICATIONS OR COME INTO

CONTROL THAN THE PATIENT WHO
HAS SEIZURES EVERY DAY OR

A COUPLE OF TIMES A WEEK OR
EVEN A COUPLE OF TIMES A MONTH.

SO AGAIN, THE MORE
FREQUENT THE SEIZURES ARE

AND THE GREATER THE NUMBER OF
SEIZURES, THE LESS LIKELY WE

ARE GOING TO BE ABLE TO
GET THEM UNDER CONTROL.

ANOTHER FACTOR THAT INFLUENCES
HOW LIKELY PATIENTS WILL BE

ABLE TO BE CONTROLLED WITH
MEDICATION IS HOW LONG THEY'VE

HAD THE SEIZURES.

SO PATIENTS WHO HAVE HAD
SEIZURES JUST START FOR THE VERY

FIRST TIME ARE THE BEST
CANDIDATES

FOR HAVING THEIR SEIZURES COME

UNDER CONTROL, BUT PATIENTS
WHO HAVE HAD SEIZURES FOR MANY

YEARS OR EVEN DECADES,

THEY WILL BE HARDER TO CONTROL
WHEN WE FIRST SEE THEM.

THE TYPE OF SEIZURES ALSO
PREDICT HOW LIKELY SEIZURES

WILL BE ABLE TO BE CONTROLLED.

SO GENERALIZED EPILEPSY,
SO-CALLED "PETIT MAL" OR

ABSENCE EPILEPSY, OR EVEN
OTHER TYPES OF GENERALIZED

EPILEPSY, ARE INTERESTINGLY
EASIER TO COME UNDER CONTROL

THAN SOME OF THE FOCAL
SEIZURE DISORDERS.

SOME OF THESE FOCAL SEIZURE
DISORDERS MAY THEN SECONDARILY

SPREAD AND BECOME GENERALIZED,
BUT IF THEY BEGIN FOCALLY,

IN GENERAL THEY WILL BE HARDER
TO CONTROL THAN IF THEY ARE

GENERALIZED AT THE ONSET.

ALSO, WE KNOW THAT DISORDERS
SUCH AS STRUCTURAL BRAIN

LESIONS, STROKES, TUMORS,
BRAIN INJURIES SUCH AS

INJURIES FROM TRAUMA, ARE LESS
LIKELY TO COME UNDER CONTROL

WITH MEDICATIONS THAN
INDIVIDUALS WHO HAVE NO KNOWN

CAUSE FOR THEIR SEIZURES
OR WHOSE SEIZURES MAY HAVE

A GENETIC ORIGIN OR
A FAMILIAR ORIGIN.

SO FOR OUR VETERANS
POPULATION, THIS POSES MORE

OF A PROBLEM BECAUSE MANY OF
OUR VETERANS ARE INDIVIDUALS

WHO FIRST COME TO OUR
ATTENTION AFTER HEAD INJURY OR

A STROKE OR SOME OTHER
STRUCTURAL LESION THAT MAY

INITIATE THEIR
SEIZURES, AND SO,

BECAUSE OF THAT, THEY MAY BE
GROUPS THAT WOULD BE LESS

LIKELY TO COME UNDER CONTROL.

NOW, IF SEIZURES OCCUR AND
ARE UNCONTROLLED, WHAT ARE

THE CONSEQUENCES FOR
THE INDIVIDUAL?

WELL, IF YOU LOOK AT SLIDE
NUMBER 7, YOU'LL SEE THAT

UNCONTROLLED SEIZURES HAVE
A REALLY SERIOUS IMPACT

ON QUALITY OF LIFE.

THIS IS A GRAPH SHOWING
YOU AMONG SEIZURE PATIENTS

IN GENERAL, THOSE THAT ARE
SOCIALLY INDEPENDENT AND HAVE

A GOOD QUALITY OF LIFE VERSUS
THOSE THAT ARE NOT INDEPENDENT

OR TOTALLY DEPENDENT
ON OTHERS FOR SUPPORT.

AND WHAT ONE SEES, THAT
ANYWHERE FROM 60% TO 80%

OF INDIVIDUALS WILL BE
COMPLETELY INDEPENDENT,

COMPLETELY FINANCIALLY AND
SOCIALLY INDEPENDENT OR LIVING

INDEPENDENTLY, BUT MAY
NOT BE WORKING, AND STILL

FUNCTIONING WELL.

20% WILL BE TOTALLY DEPENDENT
ON OTHERS FOR SUPPORT.

AND WHAT'S IMPORTANT TO
REMEMBER IS THAT THE PEOPLE

WHO ARE MOST DEPENDENT,
THOSE TOTALLY DEPENDENT PEOPLE

AND THOSE PEOPLE THAT ARE NOT
WORKING, ARE THE INDIVIDUALS

WITH INTRACTABLE SEIZURES.

SO IF YOU CAN HAVE YOUR
SEIZURES WELL CONTROLLED,

YOU'RE MUCH MORE LIKELY TO BE
A VERY ACTIVE AND PRODUCTIVE

MEMBER OF SOCIETY, WHILE IF
YOU DON'T, YOU'RE GOING TO

HAVE A MUCH POORER QUALITY
OF LIFE AND SOCIAL

AND FINANCIAL DEPENDENCE.

IF YOU LOOK IN SLIDE NUMBER
8, YOU'LL ALSO SEE THAT

THE CONSEQUENCES TO SOCIETY
OF INTRACTABLE OR UNCONTROLLED

SEIZURES ARE VERY
SERIOUS AS WELL.

THE OVERALL COST OF EPILEPSY
OR SEIZURES IN THE UNITED

STATES WAS ESTIMATED IN 1995
TO BE ABOUT $13 BILLION.

THE GREAT MAJORITY OF THAT
COST, OVER 80%, IS DUE TO

PATIENTS WHO HAVE SEIZURES
WHO CANNOT BE CONTROLLED

OR PATIENTS WHO
HAVE INTRACTABLE SEIZURES.

SO NOT ONLY ARE THESE PATIENTS
A TERRIBLE BURDEN FOR SOCIETY

IN THAT THEY ARE UNABLE
TO WORK AND THEY HAVE TERRIBLE

PROBLEMS THEMSELVES AND
THEIR FAMILIES, BUT THEY ALSO

PRESENT TREMENDOUS COSTS TO
SOCIETY OF NOT HAVING THEIR

SEIZURES CONTROLLED.

THE MAJOR COST THAT THIS
ARISES FROM IS THAT THESE

PEOPLE CANNOT WORK, AND THIS
LOSS OF PRODUCTIVITY IS

THE MAJOR REASON FOR THIS
TREMENDOUS COST OF THESE

INTRACTABLE SEIZURES.

SO AS YOU CAN SEE, INTRACTABLE
SEIZURES ARE TERRIBLE PROBLEMS

FOR PATIENTS AND THEIR
FAMILIES, BUT ALSO THEY ARE

A GREAT BURDEN AND COST TO
SOCIETY, AND SO IT'S IN OUR

BEST INTEREST AND OUR
PATIENTS' BEST INTEREST TO GET

THESE UNDER CONTROL AND
TO ELIMINATE SEIZURES

WHENEVER POSSIBLE.

SO WHAT ARE OUR TREATMENT
OPTIONS FOR PEOPLE

WITH EPILEPSY AND SEIZURES?

WELL, THIS IS--IN THIS DECADE,
THESE ARE OUR TREATMENT

OPTIONS, OR THE ARROWS THAT WE
HAVE IN OUR QUIVER TO TRY TO

CONTROL EPILEPSY AND SEIZURES
IN PATIENTS WHO WE SEE

WITH THOSE DISORDERS.

FIRST, WE OF COURSE START WITH
ANTIEPILEPTIC MEDICATIONS.

THAT IS THE MAINSTAY OF ALL
TREATMENT FOR EPILEPSY, AND AS

I MENTIONED BEFORE, IN 70%
TO 80% OF CASES, THAT WILL BE

VERY SUCCESSFUL.

I'D ALSO LIKE TO DISCUSS WITH
YOU IN THE REMAINING TIME

OTHER OPTIONS, INCLUDING
EPILEPSY SURGERY,

NEW APPROACHES TO CONTROL
THE SEIZURES THAT I'LL CALL

"NEUROSTIMULATION," SOME
EXPERIMENTAL STUDIES BEING

DONE ON RADIATION THERAPY TO
CONTROL SEIZURES, AND FINALLY,

NEW APPROACHES TO
IMMUNAL THERAPIES FOR EPILEPSY

AND GENETIC APPROACHES
TO EPILEPSY.

AND FINALLY, FOR THOSE PEOPLE
THAT DESPITE OUR BEST EFFORTS

WE CANNOT GET UNDER CONTROL
DESPITE OUR CONTINUED BEST

EFFORTS, IT'S IMPORTANT NOT TO
GIVE UP WITH THESE INDIVIDUALS

BECAUSE THERE ARE
SOCIOLOGICAL, SOCIAL,

AND PSYCHOLOGICAL
INTERVENTIONS THAT CAN HELP

THESE INDIVIDUALS REACH THEIR
FULL POTENTIAL EVEN THOUGH IT

MAY STILL REMAIN
SOMEWHAT LIMITED.

SO IN SLIDE NUMBER 10 AND 11,
WILL TALK ABOUT THE APPROACH

TO ANTIEPILEPTIC MEDICATIONS
BECAUSE THAT'S REALLY THE

MAINSTAY OF OUR TREATMENT FOR
THE GREAT MAJORITY OF PEOPLE

WITH EPILEPSY.

SO WHAT ARE OUR GOALS IN
TREATING SEIZURES IN TERMS

OF MEDICATIONS?

WELL, THE GOAL IS RATHER
SIMPLY STATED AS NO SEIZURES

AND NO SIDE EFFECTS, AND
THIS IS ENDORSED BY BOTH

THE AMERICAN EPILEPSY SOCIETY
AND THE EPILEPSY FOUNDATION,

BUT AS PRACTITIONERS,
THAT SHOULD BE OUR GOAL.

SO THAT MEANS THAT IF WE'RE
SEEING PATIENTS IN THE CLINIC

WHO ARE COMING BACK WITH
RECURRENT SEIZURES, EVEN RARE

RECURRENT SEIZURES,
IT'S REALLY NOT OPTIMAL TO

SIMPLY SAY, "WELL, HERE,
LET ME REFILL YOUR

"PRESCRIPTION, AND WE'LL
SEE YOU AGAIN IN 6 MONTHS

OR A YEAR."

ONE SHOULD REALLY DO ONE'S
BEST TO CONTROL WHATEVER

SEIZURES THE PERSON IS HAVING
AND ALSO IF THAT PERSON IS

HAVING SIDE EFFECTS TO BE
SURE, FIRST OF ALL, TO INQUIRE

ABOUT SIDE EFFECTS AND THEN
TO TRY TO ADJUST MEDICINES OR

CHANGE MEDICINES TO ELIMINATE
OR REDUCE SIDE EFFECTS.

SO IN TERMS OF TRYING TO
ATTAIN THIS GOAL, THIS IS

THE APPROACH THAT I SUGGEST,
AS NOTED IN THIS SLIDE

NUMBER 11.

FIRST, IT'S IMPORTANT TO
DETERMINE THE TYPE OF SEIZURE

SOMEONE IS HAVING.

THERE ARE VARIOUS
CLASSIFICATIONS OF EPILEPSY

AND VARIOUS TYPES

OF SEIZURES, AND DIFFERENT
DRUGS WILL BENEFIT PATIENTS

WITH A CERTAIN TYPE OF
SEIZURES BUT MAY NOT BENEFIT

PATIENTS WITH OTHER
TYPES OF SEIZURES.

SO ONE FIRST HAS TO DETERMINE
THE TYPE OF SEIZURE DISORDER

A PATIENT HAS, WHETHER IT'S A
FOCAL SEIZURE OR A GENERALIZED

SEIZURE, AND THEN SELECT FROM
THE CLASS OF DRUGS THAT ARE

SPECIFIC FOR THAT TYPE OF
SEIZURE THE DRUG THAT IS BEST

FOR THE PATIENT.

NOW, IN GENERAL, ONE
SELECTS A CLASS OF DRUGS

FOR A CERTAIN TYPE
OF SEIZURE TYPE.

THE INDIVIDUAL DRUGS IN
THAT CLASS GENERALLY HAVE

ABOUT THE SAME EFFICACY.

DESPITE THE DRUG PROMOTIONS
THAT YOU SEE AND THE DRUG

ADVERTISEMENTS THAT YOU SEE,
MOST DRUGS WORK ABOUT THE SAME

FOR A SEIZURE TYPE AS OTHER
DRUGS AS LONG AS YOU PICK

THE RIGHT CLASS OF DRUGS
FOR THAT SEIZURE TYPE.

SO WHETHER CARBAMAZEPINE OR
PHENYTOIN OR KEPPRA

IS THE BEST DRUG

FOR A FOCAL SEIZURE TYPE
ISN'T REALLY THE MAIN QUESTION

BECAUSE ALL THOSE DRUGS WORK
ABOUT THE SAME FOR CERTAIN

CLASSES OF SEIZURES, SUCH
AS FOCAL SEIZURES.

WHAT'S IMPORTANT IS TO CHOOSE
THE MEDICATION WHICH HAS THE

BEST SIDE EFFECT PROFILE FOR
THAT INDIVIDUAL BECAUSE ALL

THESE DRUGS HAVE SIDE EFFECTS,
AND DEPENDING ON THE SPECIFIC

NEEDS AND CIRCUMSTANCES OF
THAT INDIVIDUAL, ONE WANTS TO

CHOOSE THE DRUG THAT WILL BEST
CONTROL THE PERSON'S SEIZURES

AND ALSO HAVE THE LEAST SIDE
EFFECTS FOR THAT INDIVIDUAL

BASED ON THAT INDIVIDUAL'S
PERSONAL NEEDS.

ONCE ONE FINDS A DRUG OR
CHOOSES A DRUG OR DECIDES

ON A DRUG THAT ONE WANTS TO
USE FOR THAT INDIVIDUAL,

THE NEXT STEP IS TO GRADUALLY
INCREASE THAT DRUG SLOWLY TO

REASONABLE OR MAXIMAL DOSAGES.

ONE CAN SOMETIMES USE DRUG
LEVELS TO DETERMINE THAT,

BUT OFTEN WE SIMPLY INCREASE
THE DRUG UNTIL WE SEE THAT

THERE ARE EITHER SIDE EFFECTS
OR THAT THE SEIZURES COME

UNDER CONTROL.

DRUG LEVELS ARE IN MANY WAYS
NOT AS USEFUL AS WE ONCE

THOUGHT THEY WERE, ALTHOUGH HE
STILL CERTAINLY CAN USE THEM

TO DETERMINE IF PATIENTS
ARE IN THE BALLPARK IN TERMS

OF, NUMBER ONE, TAKING THEIR
MEDICATIONS, AND NUMBER TWO,

BEING AT A REASONABLE LEVEL--
HAVING A REASONABLE LEVEL

IN THEIR SYSTEM.

ONCE WE'VE INITIATED THIS
FIRST DRUG AND GIVEN IT

AN ADEQUATE TRIAL AND MADE
SURE THAT WE'VE PUSHED IT UP

TO MAXIMAL OR REASONABLE
TOLERATED DOSAGES, AND ONCE

WE'RE SURE THAT THIS IS THE
BEST DRUG FOR THE SEIZURE

TYPE, IF THAT DOESN'T CONTROL
THE SEIZURES, THEN WE HAVE TO

MAKE A CHANGE.

SO WHAT CAN WE DO?

WELL, THERE ARE
SEVERAL OPTIONS.

ONE THING WE CAN DO IS
TO TRY ANOTHER DRUG.

THERE ARE MANY DRUGS IN EACH
CLASS THAT WE CONSIDER, AND IF

ONE DRUG DOESN'T WORK AND IT'S
UNSUCCESSFUL, THEN WE CAN

TRY ANOTHER DRUG, AND WE CAN
CHANGE THAT SEVERAL TIMES.

WE CAN GO FROM ONE
DRUG TO ANOTHER DRUG.

IF SEIZURES PERSIST DESPITE
CHANGING FROM ONE DRUG TO

ANOTHER DRUG, THEN WE CAN TRY
TO COMBINE TWO OR 3 DRUGS,

AND GENERALLY MOST PEOPLE
SUGGEST ONE DOESN'T WANT TO

COMBINE TWO OR 3 DRUGS OR
BASICALLY ADD MORE THAN TWO OR

3 DRUGS ONTO ANOTHER DRUG
IN ORDER TO TREAT PATIENTS

BECAUSE AS ONE ADDS MORE AND
MORE DRUGS, ONE GETS MORE

SIDE EFFECTS.

AND THERE REALLY ISN'T A GREAT
DEAL OF EVIDENCE THAT ADDING

3, 4, AND 5 DRUGS TO A PATIENT
WILL DO ANY BETTER THAN HAVING

THEM JUST ON TWO OR
PERHAPS 3 DRUGS AT MOST.

SO WHAT CAN WE EXPECT WHEN
WE START A PATIENT

ON SEIZURE MEDICATIONS?

WELL, IF YOU LOOK AT SLIDE
NUMBER 12, IT KIND OF GIVES

YOU AN OVERVIEW OF AT LEAST--
AN OVERVIEW OF ONE STUDY WHICH

I THINK IS PRETTY
REPRESENTATIVE OF OTHER

STUDIES OF WHAT ONE CAN
EXPECT WHEN ONE STARTS SEIZURE

MEDICATIONS OR ANTIEPILEPTIC
MEDICATIONS IN A PATIENT WHO

HAS A NEWLY DIAGNOSED
EPILEPSY.

AND AGAIN, THERE'S GOOD
NEWS AND THERE'S BAD NEWS.

THE GOOD NEWS IS THAT MOST
OF THESE PATIENTS--AGAIN,

AS I SAID, 70% OR MORE OF
THESE PATIENTS--WILL COME

UNDER COMPLETE CONTROL.

THE FIRST DRUG IS OFTEN VERY
EFFECTIVE, AND THE FIRST

ANTIEPILEPTIC DRUG, IF IT'S
SELECTED FOR THE RIGHT CLASS

OF SEIZURES, WILL CONTROL
SEIZURES IN ALMOST 50%

OF PATIENTS TO THE POINT THAT
THEY WILL BE SEIZURE FREE,

WHICH IS REALLY WHAT
WE'RE AIMING FOR.

WE'RE AIMING TO CONTROL
SEIZURES COMPLETELY, AND THAT

WOULD BE SEIZURE FREEDOM FOR
A LONG PERIOD OF TIME.

IF THE FIRST DRUG DOESN'T
WORK, WHAT'S THE CHANCE THAT

THE SECOND DRUG WILL
THEN CONTROL SEIZURES?

WELL, IT'S LESS.

IT'S CONSIDERABLY LESS,
BUT IT'S CERTAINLY NOT ZERO.

IT'S DOWN TO 15%.

ONCE YOU'VE TRIED TWO DRUGS,
GOING TO A THIRD DRUG OR MORE,

THOSE CHANCES OF GETTING
SEIZURES UNDER CONTROL

GO WAY DOWN.

SO WITH A THIRD DRUG,
IT MAY BE 5%.

ONCE YOU GO TO THE FOURTH,
FIFTH, AND SIXTH DRUG, ADDING

ALL THOSE DRUGS ON,
YOU PROBABLY DON'T GET MUCH

MORE THAN AN ADDITIONAL
MAYBE 10% OR 15% OF PATIENTS

UNDER CONTROL.

AND UNFORTUNATELY WHAT THIS
MEANS, THAT ONCE PATIENTS HAVE

FAILED THE FIRST TWO OR 3 DRUGS
THAT WE USE TO TREAT

THEM FOR EPILEPSY, THEY ARE
LIKELY TO BE REFRACTORY,

AND IT WILL BE VERY HARD IN MANY
CASES TO GET THOSE PATIENTS

UNDER CONTROL.

AND THAT'S WHEN WE NEED TO
CONSIDER OTHER TREATMENTS.

WE NEED TO CONSIDER,
FOR EXAMPLE, REFERRING THOSE

PATIENTS FOR TERTIARY CARE
TO SOME OF OUR SPECIALIZED

EPILEPSY CENTERS, WHERE
THEY CAN BE EVALUATED

FOR EXPERIMENTAL DRUG
TREATMENTS OR INVESTIGATIONAL

DRUG TREATMENTS OR SURGERY
OR OTHER TYPES OF TREATMENT.

STILL, SELECTING THOSE DRUGS
WHEN WE START AND WHAT DRUGS

WE USE SUBSEQUENTLY
ISN'T AN EASY TASK.

IF YOU LOOK AT SLIDE NUMBER
11, YOU'LL SEE THAT THE

CLASSIFICATION OF SEIZURES
IS QUITE VARIED AND THE DRUGS

THAT WE USE WILL BE DETERMINED
ON HOW WE CLASSIFY PATIENTS

WITH SEIZURES.

SO WHEN WE SEE A PATIENT WITH
SEIZURES, IT'S IMPORTANT TO

TRY TO DETERMINE EXACTLY WHAT
SEIZURE TYPE THEY'RE HAVING

IN DEALING WITH THEM BECAUSE
DIFFERENT SEIZURE TYPES

WILL RESPOND TO DIFFERENT
MEDICATIONS.

AND THE WAY WE DETERMINE WHAT
TYPE OF SEIZURE TYPE A PATIENT

HAS, WHICH I WON'T GO INTO
GREAT DETAIL HERE BUT WILL

SIMPLY GIVE YOU A BRIEF
OVERVIEW OF, IS THAT IT

DEPENDS ON THE CLINICAL
HISTORY FROM A RELIABLE

OBSERVER OR THE PATIENT
TELLING YOU WHAT TYPES

OF SEIZURES THEY EXPERIENCE,
WHETHER THEY EXPERIENCE

CONFUSIONAL EPISODES OR AURAS,
SUGGESTING THAT THEY MAY HAVE

MORE FOCAL SEIZURES, OR IF
THEY SIMPLY HAVE GENERALIZED

TONIC-CLONIC SEIZURES FROM THE
START, SUGGESTING POSSIBLY

A MORE GENERALIZED
SEIZURE DISORDER.

THE EEG AND IMAGING STUDIES
CAN HELP US DETERMINE WHETHER

THESE ARE MORE FOCAL OR
GENERALIZED SEIZURES.

AND ULTIMATELY IF WE'RE NOT
SURE OF WHAT TYPE OF SEIZURES

A PATIENT HAS, ONE VERY USEFUL
APPROACH IS TO REFER THOSE

PATIENTS FOR VIDEO EEG
MONITORING, WHERE WE CAN

ACTUALLY CAPTURE THE SEIZURES
IN A CONTROLLED UNIT SUCH AS

EXIST IN OUR EPILEPSY CENTERS
OF EXCELLENCE, WHERE YOU CAN

OBSERVE A SEIZURE, YOU CAN
CORRELATE IT WITH THE ABNORMAL

ELECTRICAL ACTIVITY GOING ON
IN THE BRAIN, AND DETERMINE

HOW BEST TO TREAT IT.

WHEN WE CLASSIFY SEIZURES, THIS
IS A NEWER CLASSIFICATION

OF SEIZURES.

GENERALLY THEY'RE SEPARATED
INTO GENERALIZED SEIZURES SUCH

AS ABSENCE OR MYOCLONIC
SEIZURES AND FOCAL SEIZURES,

FOCAL SEIZURES BEING WHAT WE
USED TO CLASSIFY AS COMPLEX

PARTIAL OR PSYCHOMOTOR
SEIZURES, IF THEY IMPAIR

CONSCIOUSNESS OR FOCAL MOTOR
SEIZURES IF YOU DON'T HAVE

IMPAIRED CONSCIOUSNESS.

AND AGAIN, THERE ARE
OTHER TYPES OF SEIZURES.

IF ONE DOESN'T KNOW THE
SEIZURE CLASSIFICATION,

ONE DOESN'T KNOW IT, ONE
HAS TO JUST MAKE THE BEST

ASSESSMENT ONE CAN OF THE BEST
SEIZURE TYPE, BUT IF YOU'RE

NOT SURE OF WHAT TYPE OF
SEIZURES YOUR PATIENTS IS HAVING

AND THEY ARE CONTINUING TO
EXPERIENCE SEIZURES, THEN WE

NEED TO TURN TO TRYING
TO BETTER DIAGNOSE

THE SEIZURE TYPE.

NOW, WE HAVE TOOLS TO DO THAT.

IF YOU LOOK AT SLIDE
NUMBER 14, THIS IS A PICTURE

OF A PATIENT WHO IS ULTIMATELY
FOUND TO HAVE PRIMARY

GENERALIZED EPILEPSY AND IS IN
OUR EPILEPSY MONITORING UNIT.

AND IN OUR UNIT, WHEN WE
WITHDREW MEDICATIONS, WE SAW

A SEIZURE AND DETERMINED THAT
IT WAS AN EPILEPTIC SEIZURE

WITH ABNORMAL ELECTRICAL
ACTIVITY IN THE BRAIN.

AND IT'S IMPORTANT TO NOTE
THAT ABOUT 20% OF PATIENTS,

OR MAYBE EVEN MORE, WHO ARE
SEEN IN EPILEPSY CENTERS

WITH SO CALLED INTRACTABLE
EPILEPSY TURN OUT NOT TO HAVE

EPILEPSY AT ALL, BUT TURN
OUT TO HAVE PSYCHOLOGICAL

DISORDERS KNOWN AS PSYCHOGENIC
OR NON-EPILEPTIC SEIZURES,

AND THOSE PATIENTS ARE
VERY IMPORTANT TO IDENTIFY

BECAUSE THEY HAVE A CONDITION
OTHER THAN EPILEPSY AND THEY

DO BEST NOT ON ANTIEPILEPTIC
MEDICATIONS, BUT WITH OTHER

TYPES OF SUPPORTIVE TREATMENT.

SO AGAIN, DETERMINING
EXACTLY WHAT TYPE OF SEIZURES

YOUR PATIENT HAS IS VERY
IMPORTANT IN TERMS

OF GUIDING THERAPY.

SO, FOR EXAMPLE, FOR THIS
WOMAN, IF YOU LOOK AT THE NEXT

SLIDE--THAT WOULD BE SLIDE
NUMBER 15--YOU'LL SEE THAT HER

EEG SHOWS THAT SHE HAS A
PRIMARY GENERALIZED SEIZURE

DISORDER WHEN YOU HAVE
SPIKE IN WAVE DISCHARGES

ON THAT EEG.

AND WHEN WE SAW THAT AND WE
CORRELATED IT WITH HER SEIZURE

TYPE, SHE BENEFITED MOST FROM
THE DRUGS LIKE LEVETIRACETAM

AND VALPROIC ACID, WHICH
BROUGHT HER SEIZURES UNDER

COMPLETE CONTROL, WHICH IS
ONE OF THE NICE THINGS

ABOUT PRIMARY GENERALIZED
EPILEPSY, IS IF YOU CAN

DIAGNOSE IT AND ESTABLISH IT,
THESE PATIENTS ARE OFTEN VERY

EASY TO TREAT AND
BRING UNDER CONTROL.

NOW, IN SLIDE NUMBER 15,
YOU WILL SEE ANOTHER PATIENT,

AND THIS PATIENT IS ALSO IN OUR
EPILEPSY MONITORING UNIT,

BUT HE HAS A DIFFERENT SEIZURE
DISORDER, AS YOU'LL SEE

IN SLIDE NUMBER 17, IS THAT
WHEN HE EXPERIENCES A SEIZURE,

HIS SEIZURE ACTUALLY
BEGINS VERY FOCALLY.

IN THIS CASE, YOU SEE THIS
RHYTHMIC KIND OF ACTIVITY

IN HIS RIGHT TEMPORAL LOBE.

AND THIS GENTLEMAN HAS FOCAL
EPILEPSY, TEMPORAL LOBE

EPILEPSY, AND HE NEEDED A
DIFFERENT KIND OF MEDICATION

TO TREAT HIM.

AND UNFORTUNATELY, ULTIMATELY
HIS SEIZURES DID NOT COME

UNDER CONTROL WITH MEDICATION,
BUT HE DID DO WELL FINALLY WHEN

HE WAS TREATED WITH EPILEPSY
SURGERY TO REMOVE THAT FOCUS,

AND HIS SEIZURES CAME
UNDER COMPLETE CONTROL.

NOW, ONCE WE DETERMINE WHAT
TYPE OF EPILEPSY A PATIENT HAS,

EITHER FROM THE CLINICAL
HISTORY, FROM EEG, OR FROM

EPILEPSY MONITORING, WHAT
ARE OUR CHOICES IN TERMS

OF EPILEPTIC DRUGS?

WELL, THERE WE ARE THE VICTIM
OF A VAST ARRAY OF RICHES.

IF YOU LOOK AT SLIDE NUMBER
18, THE SLIDE HAD TO BE

TRIMMED DOWN A BIT, BUT IT
REALLY OUTLINES ALL OF THE--

IS MOST OF THE NEW AND OLD
ANTIEPILEPTIC DRUGS WE HAVE

AVAILABLE TO TREAT EPILEPSY.

AND I DON'T KNOW ABOUT YOU,
BUT I FIND THIS SLIDE KIND

OF OVERWHELMING.

THERE ARE SO MANY DRUGS
OUT THERE TO TREAT PEOPLE

WITH EPILEPSY, AND IT'S JUST
HARD TO KNOW WHICH ONE TO USE

AND WHICH ONE TO START WITH.

CERTAINLY, CERTAIN OF THESE
DRUGS ARE BETTER FOR CERTAIN

KINDS OF EPILEPSY.

SO AGAIN, WHETHER YOU'RE
DEALING WITH--ONCE YOU KNOW

THE TYPE OF EPILEPSY YOU'RE
DEALING WITH, YOU THEN NEED TO

PICK A DRUG THAT'S BEST
FOR THAT CLASS OF SEIZURES.

BUT THERE ARE MANY DRUGS
FOR THE VARIOUS CLASSES

OF SEIZURES.

AND AGAIN, BEAR IN MIND THAT
ONCE YOU GET THE RIGHT DRUG

FOR THAT TYPE OF SEIZURE
DISORDER, THEY ALL HAVE

ABOUT THE SAME EFFICACY.

SO HOW DO YOU DECIDE
WHICH ONES TO USE?

WELL, IF YOU LOOK AT THE
ASTERISK DOWN BELOW,

THOSE ARE THE NEWER
DRUGS THAT ARE AVAILABLE.

ACTUALLY THE MOST RECENT ONE,
CLOBAZAM, WHICH IS ACTUALLY

THE TRADE NAME FOR THAT WILL
BE ONFI, IS ONE THAT'S JUST

COME OUT, AND JUST BECAUSE
THEY'RE NEW DOESN'T NECESSARILY

MEAN THEY'RE BETTER.

THERE'S SOME EVIDENCE THAT
THE NEWER DRUGS HAVE LESS SIDE

EFFECTS, BUT IN TERMS OF
EFFICACY, THEY'RE REALLY ALL

ABOUT THE SAME.

SO HOW DO YOU PICK WHICH
DRUG ONE SHOULD USE?

WELL, YOU COULD SAY, WELL,
YOU SHOULD PICK THEM

ON THE BASIS OF THE
SIDE EFFECT PROFILE.

AND MY PATIENTS WILL OFTEN
ASK ME, "WELL, DR. KRUMHOLZ,

WHICH OF THE SEIZURE MEDICINES
HAVE NO SIDE EFFECTS?"

AND THE ANSWER TO THAT
IS VERY EASY.

THEY ALL HAVE SIDE EFFECTS.

IT'S REALLY A QUESTION OF
PICKING THE ONE THAT HAS

THE BEST SIDE EFFECT
PROFILE FOR THE PATIENT.

IT'S IN A SENSE KIND OF
PICKING YOUR POISON OR PICKING

THE MEDICINE THAT IS LEAST
LIKELY TO HURT YOUR PATIENT

BECAUSE OF THE SIDE EFFECTS.

SO IF YOU LOOK AT SLIDE NUMBER
14, THIS IS SOME EXPERTS

IN EPILEPSY THAT WERE POLLED
BACK IN 2000 ABOUT WHAT TYPE

OF--WHICH SEIZURE MEDICINE
WOULD BE BEST FOR A FOCAL

SEIZURE DISORDER?

AND YOU SEE HERE THAT THEY
LIST VARIOUS MEDICATIONS BASED

ON WHAT THEY THOUGHT WAS BEST,
BUT YOU CAN SEE THAT THERE ARE

A WIDE VARIETY OF MEDICINES TO
CHOOSE, AND IF YOU LOOK AT

THE ONES THAT WERE CONSIDERED
FIRST LINE, IT'S OFTEN BASED

ON THE FACT THAT THEY MAY
HAVE HAD THE BEST SIDE

EFFECT PROFILE.

SO AGAIN, SIDE EFFECTS ARE
VERY IMPORTANT IN DETERMINING

WHICH DRUGS YOU PICK FOR
A PATIENT WITH EPILEPSY.

IN FACT,
IF YOU LOOK AT SLIDE NUMBER

20, YOU'LL SEE A LITTLE
CARTOON THAT TO ME TYPIFIES

HOW I OFTEN THINK MY PATIENTS
FEEL WHEN THEY GO TO THE

MEDICINE CABINET TO TAKE THEIR
ANTIEPILEPTIC MEDICATIONS

AND SEE THE BOTTLE THAT JUST
SAYS, "SIDE EFFECTS" ON IT.

ALL THESE DRUGS HAVE SIDE
EFFECTS, AND WHEN YOU'RE

TRYING TO DECIDE WHAT DRUG
TO TREAT THE PATIENT WITH,

YOU REALLY NEED TO CONSIDER
THOSE IN TRYING TO DETERMINE

WHICH ONE THEY SHOULD USE.

SO NOW,
GOING TO SLIDE NUMBER 21,

HOW DO YOU DO THAT?

HOW DO YOU DETERMINE WHICH
IS THE BEST DRUG TO CHOOSE?

WELL, I USE THE ANALOGY,
OR I COMPARE THIS TO TRYING TO

TAILOR AN OUTFIT OR TAILOR
CLOTHES TO AN INDIVIDUAL.

YOU TAILOR THE DRUG TO
BEST FIT THE INDIVIDUAL.

SO, FOR EXAMPLE, IF YOU ARE
TRYING TO PICK OUT A DRESS OR

SUIT, MOST OBJECTS OF
CLOTHING WILL DO THE JOB.

SO AN INDIVIDUAL'S
PERSONAL PROFILE OR PERSONAL

PREFERENCES REALLY GUIDES
THE CHOICE AS TO WHAT SUIT OR

SHIRT OR SLACKS ONE PICKS.

AND AGAIN, MOST ANTIEPILEPTIC
DRUGS WILL HAVE SIMILAR

EFFICACY FOR SEIZURE CONTROL
BASED ON THE TYPE OF EPILEPSY.

SO THE SIDE EFFECT PROFILES
FOR THAT INDIVIDUAL REALLY

SHOULD, IN MY OPINION,
GUIDE WHAT DRUGS YOU CHOOSE.

SO IN LOOKING AT SLIDE NUMBER
22, YOU SEE THAT THERE ARE

MANY DIFFERENT
STYLES OF CLOTHES.

IF YOU LOOK AT SLIDE 23,
YOU'LL SEE THAT NOT ALL STYLES

ARE SUITABLE FOR
EVERY INDIVIDUAL.

SO, FOR EXAMPLE, STRIPES
ARE LOVELY FOR SOME PEOPLE,

BUT PROBABLY NOT EVERYONE
SHOULD WEAR STRIPES.

SO HOW ABOUT ANTIEPILEPTIC
DRUGS AND SIDE EFFECTS?

WELL, LET'S LOOK AT
SOME SPECIFIC EXAMPLES.

IF YOU'RE GONNA PICK AN
ANTIEPILEPTIC DRUG THAT HAS

THE BEST COGNITIVE PROFILE--
LET'S SAY YOU'RE DEALING

WITH SOMEBODY WHO HAS MEMORY
PROBLEMS OR COGNITIVE

DIFFICULTIES DUE TO A TRAUMATIC
BRAIN INJURY AND YOU'RE GONNA

PICK THE BEST DRUG FOR THEM.

YOU'D WANT TO AVOID CERTAIN
DRUGS, PARTICULARLY TOPIRAMATE

OR BARBITURATES OR PRIMIDONE,
BUT OTHER DRUGS AS LISTED

THERE HAVE BETTER SIDE EFFECT
PROFILES, AND YOU MIGHT WANT

TO TRY THOSE FOR
THAT INDIVIDUAL.

ON THE OTHER HAND, IF YOU'RE
DEALING WITH SOMEBODY WHO IS

QUITE OBESE OR SOMEBODY WHO
IS QUITE HEAVY, WE KNOW THAT

VALPROIC ACID TENDS TO CAUSE
INDIVIDUALS TO GAIN WEIGHT,

SO ONE MIGHT WANT TO STAY
AWAY FROM THAT DRUG; WHILE

TOPIRAMATE OFTEN PROMOTES
WEIGHT LOSS, SO THAT MIGHT BE

A GOOD DRUG FOR
THAT INDIVIDUAL.

IF YOU LOOK AT SOMEBODY WHO
HAS PSYCHOLOGICAL PROBLEMS,

YOU MIGHT WANT TO STAY
AWAY FROM A DRUG LIKE

LEVETIRACETAM OR KEPPRA, A VERY
POPULAR DRUG TODAY, BECAUSE IT

CAN CONTRIBUTE OR MAKE
PSYCHOLOGICAL PROBLEMS WORSE

FOR SOME INDIVIDUALS.

FOR WOMEN, AS YOU'LL SEE IN
SLIDE 23, THERE ARE SPECIFIC

PROBLEMS, AND MOST OF THESE
RELATE TO CERTAIN DRUGS,

IN PARTICULAR, VALPROIC ACID.

SO FOR THE MOST PART,
PARTICULARLY FOR WOMEN

OF CHILDBEARING POTENTIAL,
WE TEND TO STAY AWAY FROM

VALPROIC ACID AS A TREATMENT
BECAUSE IT POSES RISKS BOTH

FOR THE MOTHER AND
FOR THE CHILD.

SO I HOPE THIS GIVES YOU AN IDEA
OF HOW I GO ABOUT AND I THINK

ONE SHOULD GO ABOUT SELECTING
THE BEST SEIZURE MEDICINE

FOR A PATIENT.

IT'S REALLY BASED ON WHICH
MEDICINE IS BEST--WHICH CLASS

OF MEDICINES IS BEST FOR
THAT TYPE OF SEIZURE AND THEN

PICKING THE ANTIEPILEPTIC DRUG
THAT HAS THE BEST SIDE EFFECT

PROFILE FOR THAT INDIVIDUAL,
AND THEN USING THOSE KINDS

OF GUIDELINES TO DECIDE WHAT
YOU MIGHT GO TO NEXT OR WHAT

DRUG YOU MIGHT ADD TO
ANOTHER DRUG WHEN TAILORING

YOUR THERAPY.

SO THAT'S KIND OF AN OVERVIEW
OF ANTIEPILEPTIC DRUG THERAPY,

BUT ALSO WE'RE GOING TO TALK
ABOUT OTHER APPROACHES TO

THERAPY WHEN SEIZURE MEDICINES
DON'T WORK, AND AS YOU KNOW,

SEIZURE MEDICINES WON'T WORK
IN 20% TO 30% OF YOUR PATIENTS

DESPITE OUR BEST EFFORTS.

WELL, IF YOU LOOK AT SLIDE
NUMBER 26 AND 27, WE'LL TALK

ABOUT SOME OF
THOSE ALTERNATIVES.

THE FIRST ONE I'D LIKE TO TALK
ABOUT IS EPILEPSY SURGERY,

WHICH IS A MAJOR FOCUS OF OUR
EPILEPSY CENTERS OF EXCELLENCE

AND THE NETWORK OF EPILEPSY
CENTERS OF EXCELLENCE,

WHERE WE NOW HAVE SEVERAL
SITES THROUGHOUT THE COUNTRY

ESTABLISHED TO PROVIDE
EPILEPSY SURGERY TO PATIENTS--

TO VETERANS WHO NEED IT.

SO WHO ARE CANDIDATES
FOR EPILEPSY SURGERY?

WELL, FIRST, IT'S A PATIENT
WHO HAS THEIR SEIZURES

UNCONTROLLED OR THE PERSON
WHO HAS INTRACTABLE EPILEPSY.

USUALLY THE SEIZURE DISORDER IS
PERSISTING FOR SEVERAL YEARS

AND THEY'VE BEEN REFRACTORY
TO REASONABLE MEDICAL THERAPY,

WHICH I'VE ALREADY
OUTLINED FOR YOU.

THE SEIZURES SHOULD BE
SUBSTANTIALLY IMPAIRING THEIR

QUALITY OF LIFE, AND THE
BENEFIT OF SURGERY SHOULD

OUTWEIGH THE RISKS, AND
WE'LL TALK ABOUT WHAT THOSE

BENEFITS ARE.

IT DOESN'T NECESSARILY
MEAN THAT ONE HAS TO HAVE 5

SEIZURES A MONTH OR
3 SEIZURES A MONTH OR ANY

SPECIFIC NUMBER OF SEIZURES,
BUT IF THOSE SEIZURES ARE

PERSISTING AND THEY ARE
UNCONTROLLED WITH MEDICATION

AND THEY ARE DISABLING THAT
PERSON OR SUBSTANTIALLY

IMPAIRING THAT PERSON'S
QUALITY OF LIFE, THAT PERSON

IS A CANDIDATE FOR SURGERY.

SO HOW DO WE EVALUATE
PATIENTS FOR SURGERY?

WELL, FIRST OF ALL, I THINK
ONE NEEDS TO BE SURE THEY

HAVE EPILEPSY.

SO WE OFTEN WILL MONITOR THEM
WITH VIDEO EEG MONITORING OR

WILL LOOK AT THEIR EEGs.

WE'LL LOOK AT OTHER STUDIES
SUCH AS MAGNETIC RESONANCE

IMAGING OR SPECT SCANNING TO
SEE IF THEY HAVE PERCEPTIBLE

FOCAL LESIONS.

AGAIN, MOST OF THESE PATIENTS
WELL NEED TO BE ADMITTED TO

AN EPILEPSY MONITORING UNIT,
WERE SEIZURES CAN BE CAPTURED.

SOMETIMES THESE VIDEO
EEG STUDIES ARE COMBINED

WITH OTHER THINGS SUCH AS SPECT
SCANNING TO TRY TO LOCALIZE

THE SEIZURE FOCUS, SPECT
SCANNING BEING SINGLE PHOTON

EMISSION COMPUTED TOMOGRAPHY,
THAT THIS IS DONE DURING

A SEIZURE TO TRY TO
IDENTIFY A FOCUS.

AND FINALLY, NEUROPSYCHOLOGICAL
TESTING IS DONE TO TRY TO

DETERMINE WHETHER PEOPLE HAVE
DAMAGE TO ONE OR ANOTHER PART

OF THE BRAIN OR WHETHER THEY
ARE CANDIDATES FOR SURGERY,

MEANING THAT YOU CAN SAFELY
REMOVE PART OF THEIR BRAIN.

AND WHAT WE'RE LOOKING FOR
IS A CONVERGENCE OF DATA.

SO IF THE MRI SHOWS AN
ABNORMALITY IN A CERTAIN PART

OF THE BRAIN, THE EEG SHOWS
THE ABNORMALITY IN THE SAME

PART OF THE BRAIN, OTHER
STUDIES ALL POINT TO THE SAME

PART OF THE BRAIN, IF WE
CAN FOCUS ON THAT PART

OF THE BRAIN, THEN WE CAN
DETERMINE WHETHER THAT PERSON

IS A CANDIDATE FOR SURGERY,
AND THAT AREA CAN BE REMOVED

AND HOPEFULLY CONTROL
THAT PATIENT'S SEIZURES.

SO LOOKING AT THE NEXT SLIDE,
WHICH IS 29, THIS IS

AN EXAMPLE IN THIS CASE OF AN
MRI SCAN, AND THE AREA THAT

IS CIRCLED IS AN AREA OF
HIPPOCAMPAL ATROPHY.

YOU CAN SEE THAT THERE'S
A LITTLE AREA THAT SHOWS

A LITTLE MORE DARK SPACE IN
THERE, WHICH SHOWS THAT THAT

AREA IS--ON THE RIGHT SIDE--AN
AREA WERE SEIZURES MAY BE

ORIGINATING FROM.

SLIDE 30 IS AN MRI, AGAIN
SHOWING YOU AN AREA OF HYPER

INTENSITY IN THE
TEMPORAL LOBE.

AGAIN, THIS WOULD INDICATE
THAT THIS IS THE AREA WHERE

THE SEIZURES MAY BE ARISING.

IN SLIDE 31, THE ARROW IS
POINTING TO SEVERAL AREAS.

IF YOU LOOK AT
THE [INDISTINCT]

THERE, YOU SEE THAT IT JUST
LOOKS LIKE THERE'S A LITTLE

LUMP OR BUMP THERE,
OR ACTUALLY A PRETTY BIG ONE

IF YOU LOOK AT IT, IMPINGING
ON THE WHITE MATTER,

AND THAT'S A HETEROTOPIA.

THAT'S AN AREA THAT IF YOU
REMOVED AND THAT WAS THE SITE

OF THE PATIENT'S SEIZURES, YOU
COULD GET CONTROL OF THAT

PERSON'S SEIZURES AND
HOPEFULLY CURE THEM.

NOW, ON SLIDE 32, YOU'LL SEE
SOME OF THE TYPES OF METHODS

THAT WE USE TO LOCALIZE
THE SEIZURE FOCUS.

I WON'T GO INTO DETAIL.

I'LL DISCUSS THEM A
LITTLE BIT WITH YOU.

BUT FOR EXAMPLE, IF YOU LOOK
AT SLIDE NUMBER 33, YOU'LL SEE

THIS IS A SUBDURAL GRID.

THIS IS A RAY OF ELECTRODES
EMBEDDED IN PLASTIC THAT

ACTUALLY IS PUT OVER THE
SURFACE OF THE BRAIN AFTER

SURGERY THAT THEN RECORDS
SEIZURE DISCHARGES ONCE

THE PATIENT WAKES UP AND IS
PUT BACK IN HER EPILEPSY

MONITORING UNIT.

AND IF WE CAN PINPOINT THAT
THE SEIZURES ARE COMING FROM

ONE OR TWO PLACES ON THAT GRID,

WE CAN SAFELY REMOVE THAT AREA.

WE CAN ALSO STIMULATE THOSE
ELECTRODES TO SEE IF THOSE

AREAS OF THE BRAIN, OR WHAT WE
CALL ELOQUENT CORTEX, ARE PARTS

OF THE BRAIN THAT WE SHOULD
STAY AWAY FROM IN ORDER NOT TO

PRODUCE DEFICITS IN SPEECH
OR LANGUAGE OR MEMORY.

SO WHAT KIND OF SURGERY CAN
WE DO ON THE BRAIN?

WELL, THE MOST SUCCESSFUL
TYPE OF SURGERY IS

TEMPORAL LOBECTOMY.

THE EVIDENCE IS VERY STRONG
THAT TEMPORAL LOBECTOMIES,

IF SEIZURES ARE ARISING FROM
THE TEMPORAL LOBE AND THAT

TEMPORAL LOBE CAN BE SAFELY
REMOVED, THAT 60% TO 80%

OF PATIENTS WILL HAVE
THEIR SEIZURES CONTROLLED.

OTHER TYPES OF RESECTIONS--
REMOVING PART OF THE FRONTAL

LOBE OR OCCIPITAL LOBE--CAN
ALSO BE QUITE SUCCESSFUL,

MAINLY IF THERE'S A LESION
IN THAT AREA, BUT WE HAVE

THAT OPTION.

OTHER TYPES OF OPERATIONS OR
SURGERY THAT'S LESS OFTEN USED

ARE CORPUS CALLOSOTOMIES,
WHERE WE ACTUALLY DIVIDE

THE BRAIN IN HALF TRYING
TO PREVENT THE SPREAD

OF SEIZURES; HEMISPHERECTOMIES,
WHERE WE REMOVE HALF OF

THE BRAIN--AGAIN,
IT'S RESERVED PRIMARILY

FOR CHILDREN WITH EPILEPSY
BUT IS ANOTHER APPROACH--AND

THEN WHAT WE CALL MULTIPLE
SUBPIAL RESECTIONS, WHERE THE

BRAIN IS BASICALLY JUST--WHERE
WE STRIATE THE BRAIN OR JUST

MAKE LITTLE INCISIONS IN THE
BRAIN TRYING TO PREVENT

THE SPREAD OF SEIZURES.

THIS IS IN SLIDE 33.

YOU'LL SEE A PICTURE OF WHAT
A STANDARD TEMPORAL LOBECTOMY

LOOKS LIKE.

IN SLIDE--I'M SORRY, IN SLIDE
35, WILL SHOW YOU A SLIDE

OF A STANDARD
TEMPORAL LOBECTOMY.

IN SLIDE 36, YOU'LL SEE
IT SHOWN IN A LESS

SANITIZED VIEW.

THIS IS THE TEMPORAL LOBE
ACTUALLY BEING REMOVED,

AND THE AMOUNT OF TEMPORAL
LOBE WE REMOVE IS--IT MAY BE

THE SIZE OF A LEMON OR A LIME.

IT'S NOT A LARGE AREA, BUT
IT ABSOLUTELY IS CRITICAL.

LOOKING AT SLIDE 37,
YOU'LL SEE EXACTLY HOW

CRITICAL IT IS.

THIS IS A STUDY THAT WAS DONE
IN CANADA, WHERE EPILEPSY

SURGERY OFTEN NEEDS TO
BE DELAYED BECAUSE

OF THE CANADIAN HEALTH CARE
SYSTEM, BECAUSE OF THE FACT

THAT THERE AREN'T THAT
MANY FACILITIES DOING THIS

AND SO PATIENTS OFTEN NEED
TO WAIT FOR THEIR SURGERY.

AND HERE WHAT THEY DID IS THEY
TOOK 80 PATIENTS WITH TEMPORAL

LOBE EPILEPSY AND TREATED
40 IMMEDIATELY WITH TEMPORAL

LOBECTOMY AND THE OTHER 40
WAITED A YEAR OR SO FOR THEIR

TEMPORAL LOBECTOMIES.

AND THE RESULTS
WERE REMARKABLE.

OF THE PATIENTS WHO HAD
IMMEDIATE SURGERY, 55% OR 60%

WERE COMPLETELY SEIZURE FREE
AND HAD DRAMATICALLY IMPROVED

QUALITY OF LIFE, WHILE ONLY
7% OR 8% OF THE ONES TREATED

MEDICALLY WERE SEIZURE FREE.

FORTUNATELY, THE ONES WHO WERE
TREATED MEDICALLY SUBSEQUENTLY

WENT ON TO HAVE SURGERY.

BUT WHAT THIS SHOWS IS THAT
IF YOU HAVE THE RIGHT PATIENTS

AND YOU PICK THE RIGHT KIND OF
SURGERY, THESE PATIENTS CAN DO

VERY, VERY WELL.

NOW, IN THE REMAINING FEW
MINUTES, WHAT I'D LIKE TO TALK

TO YOU A BIT MORE ABOUT IS SOME
OF THE OTHER ALTERNATIVES

FOR CONTROLLING SEIZURES IN
PATIENTS WHO HAVE FAILED

MEDICAL THERAPY AND MAY NOT BE
SURGICAL CANDIDATES, OR OTHER

ALTERNATIVES TO SURGERY.

IF YOU LOOK AT SLIDE NUMBER
38, YOU'LL SEE A PHOTO OF,

I GUESS, AN OLD MOVIE OF
NEUROSTIMULATION, AND

NEUROSTIMULATION IS NOW ACTUALLY
BEING APPLIED TO EPILEPSY--NOT

QUITE IN THIS WAY,
FORTUNATELY, BUT IN OTHER WAYS

THAT I'LL DESCRIBE TO YOU.

THE HISTORY OF NEUROSTIMULATION
GOES BACK FOR A LONG TIME.

IN THE 1970s, CEREBELLAR
STIMULATION WAS USED WITHOUT

MUCH EFFECT.

IN THE 1980s, PEOPLE
TRIED DEEP BRAIN

STIMULATION, WHICH
WASN'T VERY EFFECTIVE.

BUT IN THE 1990s, VAGUS NERVE
STIMULATION WAS USED

AND PROVED TO BE VERY
EFFECTIVE FOR SOME PATIENTS,

AND IT HAS NOW BEEN APPROVED.

THERE ARE OTHER TYPES OF
STIMULATION NOW BEING TRIED AS

WELL, WHICH WE'LL
TALK ABOUT BRIEFLY.

BUT I WANTED TO FOCUS MORE ON
VAGUS NERVE STIMULATION BECAUSE

THIS IS AN FDA-APPROVED
TREATMENT SINCE 1997.

AND WHAT'S DONE HERE IS
ESSENTIALLY A PACEMAKER IS PUT

INTO THE CHEST.

IT IS CONNECTED TO THE VAGUS
NERVE IN THE NECK, USUALLY

ON THE LEFT SIDE OF THE NECK,
AND THIS STIMULUS WILL THEN

STIMULATE THE VAGUS NERVE
EVERY 5 MINUTES FOR 30 SECONDS

DAY IN AND DAY OUT.

AND THIS DEVICE IS APPROVED
FOR INDIVIDUALS WITH EPILEPSY

AND IT DEFINITELY IS EFFECTIVE
FOR SOME INDIVIDUALS.

IT BENEFITS--MOST STUDIES SHOW
THAT IT WILL DECREASE SEIZURES

BY 50% OR MORE IN UP
TO 50% OF PATIENTS.

THE MAXIMUM BENEFIT IS
GENERALLY ACCRUED BY ABOUT ONE

YEAR AFTER THE
DEVICE IS INSERTED.

SO IT TAKES SOME TIME.

SEIZURES WILL
DECREASE IN SEVERITY.

THERE IS IMPROVED LEVEL OF
CONSCIOUSNESS AND ALERTNESS.

THERE ARE VERY
FEW SIDE EFFECTS.

THE RISKS ARE VERY LOW,
AND THE BATTERY REPLACEMENT IS

SUCH THAT THESE PATIENTS ONLY
NEED TO HAVE THESE REPLACED

EVERY 10 YEARS OR SO.

HOW DOES THIS WORK?

WELL, IN SLIDE NUMBER 42,
THERE'S A LITTLE

CARTOON OF THIS.

BEST WE CAN TELL IS IT JUST
DISRUPTS THESE [INDISTINCT]

INPUTS TO THE BRAIN
AND INCREASES INHIBITION

AND SECONDARY GENERALIZATION
OF SEIZURES CAN BE AVERTED.

THE MECHANISMS IN THE NEXT
SLIDE THAT YOU'LL SEE THAT ARE

PROPOSED--THAT IS SLIDE
NUMBER 43--ARE THAT IT

DESYNCHRONIZES THE EEG,
AND THERE SOME OTHER

MECHANISMS THAT ARE
OUTLINED THERE.

IT DOES WORK.

IT CAN BE VERY EFFECTIVE
FOR THE RIGHT PATIENTS.

IT CAN RESULT IN DECREASED
MEDICATIONS, AND IT CAN BE

VERY USEFUL.

IN THE REMAINING FEW MINUTES,
I'LL JUST POINT OUT SOME OTHER

POTENTIAL AREAS
OF INVESTIGATION.

DEEP BRAIN STIMULATION,
WHICH IS DESCRIBED IN SLIDE

NUMBER 45, IS WHERE ELECTRODES
ARE ACTUALLY PUT INTO THE

THALAMUS, AND THIS CAN BE VERY
USEFUL FOR SOME PATIENTS,

BUT IT'S AN EXPERIMENTAL
TREATMENT.

IT'S NOW UNDER FDA
CONSIDERATION, AND AT THIS

POINT, IT HASN'T
BEEN APPROVED.

IF YOU LOOK AT SLIDE
NUMBER 47, THERE'S ANOTHER TYPE

OF STIMULATION WHICH
IS KNOWN AS RESPONSIVE

NEUROSTIMULATION.

THIS IS VERY EXCITING,
BUT AGAIN, IT'S NOT

AN APPROVED THERAPY.

WHAT'S DONE HERE IS THAT--
YOU'LL SEE THIS IN THE NEXT

FEW SLIDES--THAT THESE SEIZURE
DISCHARGES ARE--THAT THIS

DEVICE WILL DETECT SEIZURES.

JUST SORT OF LIKE AN
AUTOMATIC IMPLANTABLE CARDIAC

DEFIBRILLATOR DETECTS CARDIAC
ABNORMALITIES, THIS DETECTS

SEIZURE ABNORMALITIES IN
THE BRAIN AND THEN PRODUCES

AN ELECTRIC SHOCK WHICH
HOPEFULLY STOPS THE SEIZE.

AS THE OTHER SLIDES IN YOUR
SET WILL POINT OUT, THESE CAN--

THESE ARE BEING
STUDIED NOW IN PATIENTS.

THE INITIAL TRIALS LOOK
PROMISING, BUT SO FAR,

THIS HAS NOT RECEIVED FDA
APPROVAL, AND WE'RE WAITING

TO SEE THAT.

IN THE REMAINING FEW SLIDES,
I'LL JUST MENTION THEM TO YOU,

AND YOU CAN LOOK AT THEM
YOURSELVES, BUT BASICALLY

THERE ARE OTHER
TYPES OF TREATMENT.

RADIOTHERAPY IS CURRENTLY
UNDER USE IN EUROPE

FOR TREATING SEIZURES.

SO RATHER THAN REMOVING,
FOR EXAMPLE, A TEMPORAL LOBE,

RADIATION THERAPY IS DELIVERED
TO THAT TEMPORAL LOBE,

AND IT SEEMS TO WORK ABOUT THE
SAME AS SURGERY, AND THERE'S

LESS--IT'S THOUGHT TO HAVE
CERTAIN BENEFITS TO IT, BUT IT

HASN'T BEEN WELL STUDIED IN
THE UNITED STATES, ALTHOUGH

THERE ARE SEVERAL
TRIALS GOING ON HERE.

FINALLY, I WILL JUST SAY THAT
THERE ARE STUDIES GOING

ON INTO THE INFLAMMATORY BASIS
OF EPILEPSY, THE IMMUNE BASIS

OF EPILEPSY, AND THERE IS
INTERESTING RESEARCH GOING

ON INTO THE GENETIC BASIS OF
EPILEPSY TRYING TO TAILOR

SPECIFIC ANTIEPILEPTIC DRUGS
TO SPECIFIC TYPES OF EPILEPSY

AND DETERMINING WHICH PATIENTS
MIGHT BE AT RISK FOR SIDE

EFFECTS FOR VARIOUS
ANTIEPILEPTIC DRUGS.

AND IF YOU SIMPLY LOOK THROUGH
THOSE SLIDES, THEY SHOULD BE

REASONABLY SELF-EXPLANATORY.

BUT AGAIN, I THINK MY
TIME IS RUNNING SHORT.

SO I'M GONNA STOP HERE.

IF YOU HAVE QUESTIONS OR WOULD
LIKE TO DISCUSS THIS, I'D BE

HAPPY TO ADDRESS THEM.

IF WE DON'T COVER WHAT IS OF
INTEREST TO YOU, I'D BE HAPPY

TO ANSWER YOUR CALLS OR
E-MAILS TO ADDRESS MORE

SPECIFIC POINTS.

BUT AGAIN, THANK YOU FOR YOUR
TIME AND ATTENTION, AND I HOPE

WE'VE BEEN ABLE TO ADDRESS
SOME OF THESE ISSUES FOR YOU

ABOUT THIS VERY COMMON
AND VERY SERIOUS AND VERY

IMPORTANT DISORDER.

SO THANK YOU.

SEAN, ARE YOU STILL HERE?

- YES, I'M HERE.

I'M GONNA TRY TO GET
THE LINES OPENED UP.

ALL RIGHT, THEY'RE
OPENING UP THE LINES.

DOES ANYBODY HAVE
ANY QUESTIONS?

THE LINES ARE OPEN IF
ANYBODY HAS ANY QUESTIONS.

- I DO.

THIS IS JENNIFER BERTRAM
FROM WISCONSIN, AND I HAVE

A DAUGHTER THAT HAS HAD
INTRACTABLE EPILEPSY AND HAS

GONE THROUGH ALL THE
TREATMENTS THAT YOU'VE TALKED

ABOUT TODAY, WITH SURGERY,
DIET, MEDICATION, AND WE HAVE

STUMBLED UPON SOMETHING,
SO I'M REALLY INTERESTED

IN HEARING WHAT KIND OF
STUDIES ARE BEING DONE

WITH ANTI-INFLAMMATORY
PROCESS AND THE AUTOIMMUNE,

BECAUSE WE'VE BEEN DOING
SOME NON-STEROIDALS

FOR ABOUT A YEAR, AND WE HAVE
FOUND A 50% REDUCTION

IN SEIZURES, WHICH HAS BEEN
THE BEST TREATMENT WE HAVE

FOUND IN YEARS.

- MAY I ASK WHAT TYPE OF
SEIZURES YOUR DAUGHTER HAS?

- SHE HAS GENERALIZED EPILEPSY
STARTING IN THE FRONTAL LOBE.

IT'S ACTUALLY BIFRONTAL,
AND THE RIGHT FRONTAL WAS

RESECTED IN 2003.

- YEAH,
I THINK YOU'RE QUITE RIGHT

IN FOLLOWING UP ON SOME
OF THESE AUTOIMMUNE TYPES

OF TREATMENT FOR EPILEPSY.

THERE IS GROWING EVIDENCE THAT
EPILEPSY IS IN PART AN IMMUNE

DISORDER IN THAT IT'S
ASSOCIATED WITH INFLAMMATION

AND PROBLEMS IN TERMS OF
INFLAMMATORY REACTIONS

IN THE BRAIN.

IN FACT, I THINK IT'S...ON
ONE OF THESE SLIDES, SLIDE 53,

IT JUST TALKS ABOUT
INFLAMMATORY IMMUNE MECHANISMS

AND EPILEPSY.

AND WE ALL KNOW THAT CERTAIN
INFLAMMATIONS IN THE BRAIN CAN

CAUSE SEIZURES, AND IN FACT,
IT'S WORTHWHILE NOTING THAT

THE MOST COMMON CAUSE OF
EPILEPSY WORLDWIDE IS

NUEROCYSTICERCOSIS, WHICH IS A
PARASITE THAT INFLAMES THE

BRAIN AND CAUSES SEIZURES.

SO WE DO KNOW THAT
INFLAMMATORY IMMUNE MECHANISMS

ARE DEFINITELY SOMEHOW RELATED
TO SEIZURES, AND CERTAIN TYPES

OF SEIZURES, LIKE THESE
INFECTIONS, ARE CLEARLY

ASSOCIATED WITH EPILEPSY.

THERE ALSO ARE AUTOIMMUNE
DISORDERS SUCH AS MULTIPLE

SCLEROSIS, SYSTEMIC LUPUS,
AND OTHER DISORDERS THAT WE

KNOW ARE INFLAMMATION AND WE
KNOW THAT IF WE GET THOSE--

OR IMMUNE DISORDERS--IF WE
GET THAT UNDERLYING IMMUNE

DISORDER UNDER CONTROL,
THAT WILL CONTROL THE EPILEPSY.

SO THERE'S A LOT OF EVIDENCE
THAT CONTROLLING IMMUNE

MECHANISMS IN EPILEPSY COULD
BE HELPFUL, AND THERE ARE SOME

VERY SPECIFIC DISORDERS
THAT HAVE BEEN IDENTIFIED

WITH VARIOUS TYPES OF ANTI-
RECEPTOR ANTIBODIES, A LIMBIC

ENCEPHALITIS THAT CAN
BE VERY CATASTROPHIC.

USUALLY, UNLIKE YOUR
DAUGHTER'S, THEY OCCUR

A LITTLE LATER IN LIFE,
OR NOT NECESSARILY LATER,

BUT THEY TEND TO BE
VERY SEVERE AND VERY

ACUTE IN NATURE.

AND THERE ARE VARIOUS CENTERS,
INCLUDING, I THINK, THE MAYO

CLINIC AND ONE AT THE
UNIVERSITY OF PENNSYLVANIA,

IN WHICH YOU CAN SEND OFF
ANTIBODIES LOOKING FOR VARIOUS

TYPES OF RECEPTOR DISORDERS
THAT MIGHT BE AMENABLE

TO IMMUNOTHERAPY.

BUT MANY OF US HAVE COME TO
THE CONCLUSION THAT IF YOU

CANNOT CONTROL SEIZURES BY
THE USUAL MEANS, AND IT SOUNDS

LIKE YOUR DAUGHTER'S BEEN
THROUGH EVERYTHING, INCLUDING

SURGERY, THAT CONSIDERING
SOME OF THESE IMMUNE THERAPIES

IS WORTHWHILE.

AND SO WHAT ARE
THOSE THERAPIES?

WELL, I GUESS YOUR DAUGHTER HAS
TRIED SOME ANTI-INFLAMMATORIES,

BUT CORTICOSTEROID THERAPY,
INTRAVENOUS IMMUNOGLOBULINS,

PLASMA EXCHANGE--AGAIN,
THESE HAVE ALL BEEN TRIED

FOR SOME OF THESE DISORDERS
WITH VARYING DEGREES

OF SUCCESS, AND PERSONALLY
I THINK IT'S WELL WORTH

CONSIDERING THEM.

THE PROBLEM IS THAT ONCE
ONE GETS TO THE REALLY MUCH

STRONGER TYPE OF
IMMUNOSUPPRESSIVE THERAPY,

LIKE CYCLOPHOSPHAMIDE OR
VARIOUS REALLY STRONG

ANTI-NEOPLASTIC AGENTS, THEIR
RISKS ALSO INCREASE A LOT.

SO I COMMEND YOU ON TRYING
THESE THINGS AND WORKING

WITH THE PEOPLE IN YOUR AREA
TO TRY TO GET THESE UNDER

CONTROL, CONSIDERING THOSE,
BECAUSE IT'S REALLY A HOT NEW

AND IMPORTANT AREA IN TAKING
CARE OF REFRACTORY EPILEPSY.

AND I WISH YOUR DAUGHTER
THE BEST.

- THANK YOU VERY MUCH.

ARE THERE SPECIFIC TYPES
THAT YOU COULD POST OR SHOW

FAMILIES OR PEOPLE THAT ARE
WATCHING THAT YOU COULD LOOK

AT SOME OF THESE THINGS,
SOME OF THE THINGS WE WERE

TALKING ABOUT?

- YEAH,
I'LL TRY TO DO THAT.

I CAN TRY TO POST A
REFERENCE ON THIS.

I THINK THEY'RE BASICALLY
UNDER THE CATEGORY

INFLAMMATORY EPILEPTIC
ENCEPHALOPATHIES.

AND IF YOU E-MAIL ME OR IF
YOU JUST GIVE ME YOUR CONTACT

INFORMATION, I CAN
FORWARD THAT TO YOU.

- OK. I WILL E-MAIL YOU.

THANK YOU SO MUCH
FOR YOUR INFORMATION.

- THANK YOU.