- I WOULD LIKE TO WELCOME
YOU ALL TO OUR FOURTH CALL

FOR THE FISCAL YEAR,
WITH THE INTRODUCTION TO

EPILEPSY AUDIO CALL SERIES.

MY NAME IS SEAN GAMBLE
AND I'M WITH THE EMPLOYEE

EDUCATION SERVICES IN ST. LOUIS,

AND I'M THE PROJECT MANAGER
FOR THIS SERIES.

OUR LINES ARE ON MUTED,
WILL BE OPENED UP

AT THE END OF THE
PRESENTATION WHEN WE ARE

READY FOR QUESTIONS.

PLEASE BE SURE TO COMPLETE
YOUR EVALUATION TO GET

CREDIT FOR THIS PROGRAM.

COMPLETE DIRECTIONS FOR
YOUR EVALUATION CAN BE

FOUND IN THE BROCHURE
OR IN THE CATALOG.

DEADLINE DATE TO COMPLETE
THE EVALUATION IS MAY 16th.

NOW LET ME INTRODUCE
OUR SPEAKER FOR TODAY.

IT IS DR. JAMES CHEN.

DR. CHEN, GO AHEAD.

- HI. GOOD MORNING.

IT'S IN LOS ANGELES.

SO THE TOPIC WE ARE GOING
TO TALK ABOUT TODAY IS POST

TRAUMATIC EPILEPSY AND
TREATMENT, AND IT'S REALLY

A VERY ANCIENT CONDITION.

IT STARTED IN THE
HIPPOCRATIC TIME,

BUT PROBABLY BASED ON
THIS CONDITION, SOME HEAD

INJURY, PEOPLE DEVELOPED
POST TRAUMATIC EPILEPSY.

AND BECAUSE OF THAT,
HE ACTUALLY HAD A VERY

INTERESTING OBSERVATION
AND REALLY HE SAW

THIS CONDITION FROM THE
CONCEPT AT THAT TIME, WHICH

REALLY THINK
IT'S [INDISTINCT]

BY THE DEMONS, AND IT WAS
CALLED SACRED DISORDER.

AND HE REALLY THINK
THAT EPILEPSY WAS

A BRAIN DISORDER,
AND THAT CONCEPT WAS CORRECT,

EVEN ABOUT 2,000 YEARS AGO.

BUT IT WAS NOT UNTIL, LIKE,
IN 19th CENTURY THAT THIS

CONCEPT HAS BEEN REALLY
ACCEPTED, THAT THE EPILEPSY

IS A BRAIN DISORDER.

SO THE CONDITION WE ARE
TALKING ABOUT TODAY,

THE POST TRAUMATIC
EPILEPSY, IS REALLY A VERY

ANCIENT CONDITION.

IT HAS BEEN AROUND IN HUMAN
HISTORY BECAUSE OF WAR,

OF BATTLES AND FIGHT AND
HEAD INJURIES, AND PEOPLE

WOULD DEVELOP EPILEPSY
AFTER THAT, SO IT'S A VERY

ANCIENT CONDITION, AND WAY
BEFORE THAT WE LINK TO

A LOT OF CURRENT KNOWLEDGE
TO EPILEPSY THAT WE ALREADY

HAVE BEEN LIVING
WITH THIS CONDITION.

AND SO WE CAN GO TO THE
FIRST SLIDE, WHICH, YOU CAN

SEE OUR MR. GAGE HERE.

THIS CASE IS A VERY WELL-
KNOWN PERSON IN THE FIELD

OF NEUROLOGY AND
PSYCHOLOGY, AND THE REASON

HE'S SO WELL-KNOWN IS
DUE TO AN ACCIDENT.

HE WAS A RAILROAD FOREMAN
AND AGENT FOR THE AGENCY

WHO WAS CONSTRUCTING
A RAILROAD IN VERMONT,

AND AN EXPLOSION HAPPENED.

AND A ROD, A COUPLE OF RODS
ACTUALLY WENT THROUGH HIS

NECK FROM THE LEFT,
THIS MASSIVE BONE AREA,

AND IT WENT THROUGH
AND THEN DESTROYED HIS

LEFT FRONTAL LOBE AREA,
ESSENTIALLY, ON THE MEDIAL

SIDE OF THE FRONTAL LOBE.

AND HE ACTUALLY WALKED AWAY
FROM THAT ACCIDENT

WITHOUT MUCH HARM,
EXCEPT FOR THE PAIN.

AND HE HAD A SORT OF CHANGE
OF PERSONALITY, SO THAT

PART IS VERY WELL-KNOWN.

IT'S A WELL-STUDIED CASE
FOR THE PERSONALITY CHANGE

AND THE LINKAGE TO THE
FRONTAL LOBE REGION.

A LESS WELL-KNOWN

CONDITION IS HE DEVELOPED
POST TRAUMATIC EPILEPSY,

AND A FEW YEARS LATER,
HE ACTUALLY DIED

IN STATUS EPILEPTICUS.

STATUS EPILEPTICUS,
FOR PEOPLE WHO ARE NOT

MEDICAL PROVIDERS--I WOULD
LIKE TO JUST PUT A FEW

WORDS HERE BECAUSE THIS
IS ONLY TIME I'M GOING TO

TOUCH ON THIS CONDITION.

IT'S A CONDITION THAT IS A
PERSISTENT EPILEPTIC STATE,

SO A PATIENT COULD
GO INTO A SEIZURE.

AND FOR MOST SEIZURES,
IT WILL SPONTANEOUSLY STOP.

THAT'S WITH MOST SEIZURES.

AND INSTEAD, IN
STATUS EPILEPTICUS, IT

BECOMES PERSISTENT.

AND THERE'S NO END IN
SIGHT, THE SEIZURE COULD

CONTINUE ON FOR DAYS OR
WEEKS OR EVEN FOR MONTHS,

AND THAT CONDITION IS
STATUS EPILEPTICUS.

AND IN STATUS, MORTALITY IS
VERY HIGH, AND PATIENT

COULD EASILY DIE
DURING STATUS.

SO ONE OF THE COMPLICATIONS
OF HAVING POST TRAUMATIC

EPILEPSY IS GO INTO STATUS
AND DIE YEARS AFTER

THE INJURY, IF THE
CONDITION ACTUALLY COULD

CONTINUE TO DETERIORATE
AND HAVE A MAJOR NEGATIVE

IMPACT ON THE SURVIVAL OF
THE PATIENTS WHO SUFFER

FROM THIS CONDITION.

AND THIS ALL HAPPENED
BEFORE ANY PHARMACOTHERAPY

WAS AVAILABLE.

HE DIED PROBABLY THE
YEAR AFTER BROMIDE WAS

INTRODUCED IN LONDON IN
1850s, AND BROMIDE WAS

THE FIRST PHARMACOTHERAPY
AGENT AVAILABLE

FOR SEIZURE DISORDERS.

AND COMPARED TO THAT TIME
POINT, NOWADAYS WE HAVE

MORE THAN 10 DIFFERENT
ANTICONVULSION AGENTS

REALLY COULD ATTACK

DIFFERENT MECHANISMS
IN THE BRAIN, PREVENT

THOSE SEIZURES.

WE HAVE MADE QUITE
A BIT OF PROGRESS

IN THE PHARMACOTHERAPY OF
THE POST TRAUMATIC EPILEPSY

AND SEIZURES IN GENERAL.

HOWEVER, IF WE COMPARE
TO THE TIME POINT

OF THE HIPPOCRATIC TIMES,
FROM THE UNDERSTANDING THE

POST TRAUMATIC EPILEPSY IS
A BRAIN DISORDER, THERE ARE

STILL MANY UNKNOWNS, AND WE
HAVEN'T REALLY GAINED MUCH

GROUND IF WE THINK ABOUT DO
WE KNOW HOW TO PREVENT

THE DEVELOPMENT OF POST
TRAUMATIC EPILEPSY?

SO WE BASICALLY DON'T HAVE
ANY WAY TO PREVENT IT.

AND THEN A LARGE PROPORTION
OF PATIENTS WHO SUFFER FROM

POST TRAUMATIC EPILEPSY
WILL BECOME INTRACTABLE,

MEANS THEY CANNOT
BE CONTROLLED BY

THE KNOWN MEDICATIONS.

AND FOR THOSE PATIENTS,
WE REALLY HAVE A FEW

THERAPIES THAT WE CAN
PROVIDE TO THOSE PATIENTS,

WHICH I WILL DISCUSS LATER.

BUT NONE OF THEM ARE
OPTIMAL, YOU KNOW, SO REALLY--

AND ALSO, LOOKING AT THE
IDEOLOGY OF HOW THE POST

TRAUMATIC EPILEPSY WOULD DEVELOP
AFTER A HEAD INJURY,

WHAT ARE THE PATIENT'S
MECHANISM OF ANY ONE

OF CHANGES OF THE NUMBER OF
CHANGES IN THE BRAIN THAT

OCCUR AFTER A HEAD INJURY.

WE HAVEN'T REALLY GAINED
MUCH GROUND FROM 2,000

YEARS AGO, FROM THAT
UNDERSTANDING THAT POST

TRAUMATIC EPILEPSY
IS A BRAIN DISORDER.

SO I WOULD LIKE TO--IN THE
FOLLOWING SLIDE, IT GOES

THROUGH SOME OF THE
CURRENT UNDERSTANDINGS,

AND THE PURPOSE OF THE
TALK IS REALLY TO DISCUSS

THE CONCEPTS.

AND I MADE THE SLIDE A
LITTLE BIT WORDY BECAUSE I

BELIEVE IF YOU SEE THE SLIDE

YOU WILL SIT RIGHT IN FRONT
OF THE COMPUTER, SO IN CASE

THERE WAS AN IMPORTANT
POINT THAT I DIDN'T REALLY

GO INTO DETAIL, THEN YOU
CAN GO BACK

AND LOOK AT THE SLIDE.

SO IT'S A LITTLE BIT
WORDY SLIDE.

SO THE NEXT SLIDE

IS THE INTRODUCTION OF
THIS CONDITION, PTE, POST

TRAUMATIC EPILEPSY.

IT'S REALLY A MAJOR,
LONG-TERM COMPLICATION

AFTER A HEAD INJURY, USUALLY
A TRAUMATIC BRAIN INJURY,

AND IT USUALLY DEVELOPS
WITHIN 5 YEARS

OF THE HEAD INJURY.

AND IT MAY NOT BE THERE IN
THE INITIAL PHASE

OF EVERY PATIENT.

PATIENT COULD HAVE A MAJOR
HEAD INJURY, PENETRATED

HEAD WOUND.

THEY'RE IN REHAB FOR
MONTHS, AND THEN FINALLY

WERE SENT HOME, AND THEN
THE SEIZURES STRIKE.

THE POST TRAUMATIC EPILEPSY
DEVELOPS AT THAT TIME,

AFTER THE PATIENT WAS
SENT BACK HOME, BACK TO

COMMUNITY, OR ACTUALLY ALREADY
BACK TO A NORMAL LIFE,

AND THEN THIS CONDITION
WILL HAPPEN.

AND WITH THE POST TRAUMATIC
EPILEPSY, A MAJOR PROPORTION

OF THE PATIENTS ACTUALLY
COULD BECOME INTRACTABLE.

SO THIS REALLY POTENTIALLY,
FOR SOME OF THE PATIENTS,

THERE'S REALLY NO PART
IN IT FOR THIS CONDITION

TO GO SOUTH.

AND IN MR. GAGE'S CASE,
HE ACTUALLY DIED FROM

THE STATUS EPILEPTICUS
AT THE END.

SO WE WOULD HAVE TO LOOK AT

WHAT WOULD BE THE RISK OF
DEVELOPING POST TRAUMATIC

EPILEPSY AFTER
A HEAD INJURY.

LET'S GO TO THE NEXT SLIDE.

ALTHOUGH THE RISK IS ABOUT
10% TO 25%, AND THIS IS

FROM THE VETERAN STUDIES FROM
KOREAN AND VIETNAM WARS,

WE CAN DIVIDE THE TYPE
OF HEAD INJURY

INTO 3 MAJOR CATEGORIES.

ONE IS SEVERE, ONE IS
MODERATE, AND ONE IS MILD,

AND THESE SEEM TO
HAVE DIFFERENT RISK.

FOR THE MODERATE OR SEVERE
CAUSE OF INJURY IS ABOUT 5%

PATIENTS, BUT IN THE KOREAN
AND VIETNAM WAR STUDY,

BECAUSE THEY HAVE
PENETRATING BRAIN INJURIES

THAT COME WITH THEIR
WOUNDS, ABOUT HALF, 50%

OF THEM WOULD DEVELOP
POST TRAUMATIC EPILEPSY.

ANOTHER MAJOR CONCERN IS
FOR THE RETURNING VETERANS

FROM AFGHANISTAN AND IRAQ,
AND A LOT OF THEM HAVE MILD

BRAIN INJURY,
EXPLOSION PLUS INJURY.

HOWEVER, THE RISK FOR
THIS GROUP OF PATIENTS

IS UNKNOWN.

WE REALLY DON'T HAVE
THE NUMBER AND WHAT

PERCENTAGES OF THEM
WOULD DEVELOP

POST TRAUMATIC EPILEPSY.

IT'S UNKNOWN.

AND ALSO, IT'S UNKNOWN
WHETHER THEY--FOR PEOPLE

WHO HAVE REPEATED MINIMUM
TBI, WOULD HAVE INCREASED

RISK OF PTE OR NOT.

AND THIS IS REALLY FOR THE
RECENTLY RETURNED VETS,

AND A LOT OF THEM REALLY
HAD DRAMATIC EXPOSURE

TO THOSE INJURIES.

SO THE NEXT SLIDE
WAS BASICALLY A SUMMARY

OF THE IMPORTANT ISSUES FOR
POST TRAUMATIC EPILEPSY.

THIS IS IN GENERAL FOR MOST
PATIENTS WITH EPILEPSY.

BUT ESPECIALLY FOR THIS GROUP
OF PATIENTS--VETERANS--

A LOT OF THEM ALSO HAD
A DIAGNOSIS OF PTSD.

AND THEIR PRESENTATION OF
POST TRAUMATIC EPILEPSY

COULD BE JUST ACCOMPLISHED
BY THE SEIZURE,

AND SO SOMETIMES THE
DIFFERENTIAL DIAGNOSIS

COULD BE AN ISSUE IN HOW
TO [INDISTINCT], TOO.

AND ON THE BASING MECHANISM,

AS FAR AS HOW THESE TWO ARE
RELATED IS ALSO STILL NOW

UNDER RESEARCH
AT THIS POINT.

AND THE REST OF THE
SUBJECT, WE WILL COVER

THE COMMON CONCERN FOR ANY
PATIENT WHO HAS EPILEPSY;

THAT THEY ARE ACCIDENT-PRONE,
THEY COULD GET DRUNK

OR THEY COULD [INDISTINCT]
OR THEY WOULD HAVE FRACTURES.

AND FROM THE SEIZURE ITSELF,
THEY COULD DEVELOP

MEDICAL COMPLICATION
LIKE ASPIRATION PNEUMONIA

DURING SEIZURES, OR
THEY COULD HAVE CARDIO

ARRHYTHMIA OR HYPOXIA.

AND IN THE YOUNGER AGE,
ESPECIALLY WITH EPILEPSY,

ESPECIALLY IN THE MIDDLE
AGE GROUP, THEY ALSO HAVE

A LITTLE BIT INCREASED
RISK OF A CONDITION

CALLED SUDEP.

SUDEP IS A WELL-RECOGNIZED

CONDITION, SUDDEN
UNEXPECTED DEATH

IN PATIENT WHO
HAS EPILEPSY.

AND IT'S A WELL-STUDIED
CONDITION,

HOWEVER, THE REASON BEHIND IT
IS STILL NOT FULLY UNDERSTOOD.

PEOPLE SPECULATE THAT IT'S
PROBABLY, IN THE MIDDLE

OF A SEIZURE, A PATIENT WHO
HAS A SEIZURE BEFORE WOULD

HAVE A HIGH CHANCE
OF DEVELOPING CARDIO

ARRHYTHMIA, AND FROM
THAT THEY MIGHT HAVE

A SUDDEN DEATH.

SO THAT ONE CONDITION HAS TO BE
CONCERNED ABOUT FOR PTE,

AND THE OTHER MAJOR CONCERN
IS SOME OF THE SEIZURE IS

NOT REAL CONTROLLED,
THEY WOULD ACTUALLY BECOME

MEDICALLY INTRACTABLE.

SO THE NEXT SLIDE.

AND BECAUSE OF ALL THIS
COMPLICATION, THEY REALLY

WILL HAVE A LOT OF SOCIAL
CONSEQUENCES FOR THE PATIENT

WHO SUFFERS FROM POST
TRAUMATIC EPILEPSY.

IT REALLY WOULD INTERFERE
WITH THEIR RE-INTEGRATION

INTO SOCIETY, ESPECIALLY
FOR THE RETURNING VETERANS.

AND THEN IT WOULD BE
DIFFICULT TO HAVE A JOB

IF YOU CANNOT DRIVE, AND SO
THE OPPORTUNITY TO CONTROL IT

REALLY IS VERY IMPORTANT,
AND THERE ARE ALSO OTHER

PHYSICAL, EMOTIONAL ISSUES
AND NEUROBEHAVIOR ISSUES

THAT HAVE TO BE CONSIDERED.

SO LET'S GO TO
THE NEXT SLIDE.

WE'LL SEE THE DEFINITION
OF POST TRAUMATIC EPILEPSY,

AND I WILL DISCUSS THIS
PRETTY MUCH IN THE LATER

ADDRESS PRETTY MUCH WHAT PEOPLE
SET AS A DEFINITION.

AND IN THE LATER PART OF
THE TALK, I WILL DISCUSS

HOW THIS MIGHT HAVE SOME
PROBLEM IN HOW TO DEAL

WITH THE CURRENT-DAY PATIENTS
AND WE WILL DISCUSS THAT,

BUT THAT WAS
THE DEFINITION.

THE TRADITIONAL DEFINITION IS
PATIENT NEED TO HAVE

TWO OR MORE UNPROVOKED SEIZURES
AFTER A HEAD INJURY,

AND THE "UNPROVOKED" MEANS
IT'S A SPONTANEOUS SEIZURE.

SO IF PATIENT HAS A SEIZURE,
AN EXTENSION OF A HEAD INJURY,

THAT'S CONSIDERED
A PROVOKED SEIZURE.

AND FOR ANY HEALTHY PERSON,
INCLUDING, LIKE, ME

OR ANYONE WHO HAS A NORMAL
AND HEALTHY BRAIN,

IF YOU PERTURB THE BRAIN ENOUGH,
THEY'RE GOING TO HAVE A SEIZURE.

SO THAT TYPE OF SEIZURE IS
CALLED PROVOKED SEIZURE;

IT DOESN'T COUNT.

THEY NEED TO HAVE TWO OR
MORE SPONTANEOUS SEIZURES

AFTER A HEAD INJURY.

AND WE WOULD LIKE TO SEE
THE SEIZURE HAPPEN

UP TO 7 DAYS AFTER
THE HEAD INJURY.

ANY SEIZURES THAT OCCUR
WITHIN 7 DAYS OF A HEAD

INJURY IS CONSIDERED
A PROVOKED SEIZURE.

AND WOULD BE EVEN BEST
TO BE AT LEAST ONE MONTH

BEYOND THE HEAD INJURY;
THAT WOULD BE CONSIDERED

MORE SPONTANEOUS SEIZURES.

SO LET'S GO TO
THE NEXT SLIDE.

MORE ON THE DEFINITION OF PTE.

HOWEVER, IN
THE PUBLISHED ARTICLES,

PEOPLE ALSO USE A LITTLE BIT
DIFFERENT DEFINITION--

BY ACCEPTING ONE SEIZURE
AFTER A HEAD INJURY,

AS LONG AS THAT SEIZURE'S
UNPROVOKED--

AS THE DEFINITION
OF POST TRAUMATIC EPILEPSY.

AND THERE'S A VERY GOOD REASON
TO USE THIS MEDICAL DEFINITION.

IN ONE STUDY, IT FOUND THAT
86% OF PATIENTS, IF THEY

HAVE ONE LATE, UNPROVOKED
POST TRAUMATIC SEIZURE,

THEY WILL DEVELOP ANOTHER
SEIZURE WITHIN TWO YEARS.

THERE'S A VERY HIGH
POTENTIAL OF PATIENTS

WHO ARE JUST GOING TO BE
DESTINED FOR A SECOND SEIZURE.

SO IT'S PROBABLY ACCEPTABLE
TO USE ONE SPONTANEOUS SEIZURE,

UNPROVOKED SEIZURE
AFTER A HEAD INJURY

AS A DEFINITION
FOR [INDISTINCT].

PATIENTS WHO FILL THE
CRITERIA, THEN YOU CAN

INITIATE THE PHARMACOTHERAPY.

SO, YEAH, THE ADVANTAGE
IS YOU CAN INITIATE

THE ANTICONVULSIONS
THERAPY EARLY.

AND SO ANY DEFINITION,
THIS WOULD DEFINITELY WORK

THERE, INCLUDING PATIENTS
WHO PROBABLY DON'T NEED

LONG-TERM PHARMACOTHERAPY

AND WOULD HAVE THE RISK

OF BEING PLACED ON
PHARMACOTHERAPY FOR A LONG TIME.

SO THIS ISSUE WE WILL DISCUSS
LATER, BUT THIS IS

THE DEFINITION.

AND THE NEXT SLIDE.

THIS ONE WILL SHOW YOU WHY

THE ONE WEEK IS REALLY
A GOOD CUTOFF.

THIS IS FROM A
SEVERAL-HUNDRED-PATIENT STUDY

THAT DEVELOPED SEIZURES
AND A HISTOGRAM

DIVIDED INTO 8 DIFFERENT WEEKS.

AND MOST OF THE SEIZURES
AFTER A HEAD INJURY

OCCURRED WITHIN
THE FIRST WEEK.

THERE'S STILL A LITTLE BIT
SEIZURE THAT CAN OCCUR

FROM WEEK 2 TO WEEK 8,
BUT IT SEEMS THAT MOST

OF THE PROVOKED SEIZURES
WOULD OCCUR WITHIN ONE WEEK.

SO ANY SEIZURE THAT'S AFTER
ONE WEEK PROBABLY CAN BE

COUNTED AS UNPROVOKED,
OR MOST LIKELY TO BE

UNPROVOKED, BUT
IT'S A GRAY ZONE.

ONCE IT GOES BEYOND 4 WEEKS,
MOST LIKELY THOSE

SEIZURES ARE PROVOKED,
AND I WILL DISCUSS THAT.

IN A NORMAL SENSE, POST
TRAUMATIC EPILEPSY WOULD

TAKE SOME PROCESS TO OCCUR
IN THE BRAIN, AND THAT

PROCESS USUALLY DOESN'T
HAPPEN, IT DOESN'T GET TO

A COMPLETION WITHIN
WEEKS OR DAYS.

IT'S A PROCESS
CALLED EPILEPTOGENESIS.

IT'S A PROCESS THAT THE
EPILEPSY WOULD DEVELOP

AND THEN BECOME
ESTABLISHED.

AND SO THAT PROCESS WILL
USUALLY TAKE MONTHS TO

YEARS TO HAPPEN, AND SO
ONE-MONTH CUTOFF IS A PRETTY

GOOD TRADE-OFF, AND IT'S
IN CLINICAL PRACTICE.

IF A PATIENT WHO HAS A
SEIZURE ONE MONTH BEYOND

HEAD INJURY WOULD BE
PRETTY SAFE TO BE COUNTED

AS UNPROVOKED SEIZURES.

AND IF THEY HAVE ONE
SEIZURE, UNPROVOKED SEIZURE

AFTER HEAD INJURY, PROBABLY
THOSE PATIENTS SHOULD BE

CLASSIFIED AS HAVING
POST TRAUMATIC EPILEPSY.

THE NEXT SLIDE,
WE'LL DISCUSS THE RISK,

AND THE RISK REALLY
CAN BE [INDISTINCT]

INTO 3 DIFFERENT
[INDISTINCT] PATIENTS.

ONE HAS A MILD TBI; THE
OTHER CATEGORY WAS MODERATE

AND THE OTHER ONE IS
SEVERE, AND THEY SEEM TO

HAVE DIFFERENT RISK.

THE MILD TBI PATIENT
WHO HAS LOST CONSCIOUSNESS

FOR LESS THAN 30 MINUTES,
AND THEY SHOULD NOT HAVE

ANY SKULL BONE FRACTURE.

FOR SOME OF THIS MILD TBI
GROUP, THEY SOMETIMES DON'T

HAVE REALLY LOSS
OF CONSCIOUSNESS.

THEY ONLY HAD A DAZE OR
STUNNED OR SOME ALTERNATION

OF CONSCIOUSNESS FOR
A GREAT DEAL OF TIME.

IN THE MODERATE GROUP IS
THE PATIENT WHO HAS LOSS

OF CONSCIOUSNESS
AND POST TRAUMATIC AMNESIA

FOR 30 MINUTES TO 24 HOURS,

AND THEY MIGHT HAVE
A SKULL FRACTURE.

AND THE SEVERE ONE IS REALLY--
THEY HAD INTRACRANIAL PATHOLOGY.

THAT'S A BRAIN CONTUSION,
HEMATOMA, OR THEY WERE

IN A COMA FOR MORE
THAN 24 HOURS.

AND THE NEXT SLIDE
WILL COMPARE THE RISK

OF DEVELOPING PTE AFTER TBI.

IN THE MILD TBI GROUP IS
ONLY ABOUT .7% FOR 5 YEARS,

AND MODERATE TBI ABOUT 1.2%.

BUT WHEN THERE IS SEVERE TBI,
THIS CAN GO AS HIGH AS 10%.

THIS IS FROM ONE STUDY,
BUT SINCE DIFFERENT STUDY

HAS A DIFFERENT RESULT,
LET'S GO TO THE NEXT SLIDE

AND YOU WILL COMPARE FROM
DIFFERENT GROUPS

AND FROM DIFFERENT STUDIES.

BUT OVERALL, IT SEEMS THAT

THE MAXIMUM RISK, OVERALL,

EVERYTHING, MAXIMUM RISK
IS UP TO...10% TO 20%.

BUT THIS IS AN OVERALL
GROUP, BUT WE KNOW THAT

FROM THE VETERANS FROM
KOREAN WAR AND VIETNAM WAR

STUDY, IF THERE'S A
PENETRATING HEAD INJURY,

THE RISK COULD BE
AS HIGH AS 50%.

AND THE RISKS ALSO
CONTINUE ON FOR MANY YEARS.

LET'S GO TO THE NEXT SLIDE.

THIS IS A VERY LARGE-SCALE
STUDY FROM DENMARK,

FROM 1977 TO 2002,

AND IT DIVIDES THE PATIENTS
INTO MILD BRAIN INJURY,

SEVERE BRAIN INJURY,
AND PATIENTS

WHO HAVE SKULL FRACTURES,
AND DEVELOPED THAT

FOR OVER 10 YEARS.

AND YOU LOOK AT
THE TOP LINE, 4 LINES,

IT'S A RISK OF DEVELOPING
POST TRAUMATIC EPILEPSY.

AND FOR THE SEVERE
HEAD INJURY GROUP, EVEN AFTER

10 YEARS, THE RISK NEVER REALLY
RETURNED TO BASELINE.

YOU CAN SEE THE DOTTED LINE
RIGHT ABOUT THE AXIS AT

THE BASELINE INCIDENCE, AND THAT
SEVERE HEAD INJURY PATIENTS,

EVEN 10 YEARS AFTER
THE HEAD INJURY, IS NEVER

REALLY RETURNED TO BASELINE
AND HOVER AROUND 5%, 10%.

THE MILD GROUP AND SKULL
FRACTURE GROUP IS A LITTLE

BIT BETTER, BUT STILL IS
NOT REALLY COMPLETELY BACK

TO BASELINE EVEN
AFTER 10 YEARS.

AND YOU CAN SEE THAT
THE RISK IS REALLY THE HIGHEST

WITHIN THE FIRST ONE
TO TWO YEARS

ON THIS SLIDE.

NOW LET'S GO TO
THE NEXT ONE.

SO WHAT ARE THE HIGH-RISK
FACTORS IN DEVELOPING POST

TRAUMATIC EPILEPSY?

THE COMMONLY KNOWN FACTORS

ARE THE DEPRESSED
SKULL FRACTURE,

IF THERE'S A BRAIN CONTUSION,
IF THERE'S

AN INTRACRANIAL HEMORRHAGE,
IF THERE'S A LONG COMA DURATION,

OR DURING THE HEAD INJURY,
THE LOW GLASGOW COMA SCALE,

WHICH IS A COMA SCALE THAT WOULD
GIVE A NUMBER TO A PATIENT

TO ASSESS HOW DEEP
THE COMA WAS AND OLDER AGE.

OLD AGE IS SOMETIMES SEEN
AS A HIGH-RISK FACTOR.

AND FOR A PATIENT WHO ONLY
HAS A MILD TBI, EVEN IF

THEY HAVE PROVOKED
SEIZURE IN THE ACUTE HEAD INJURY

KEY RANGE, IT DOESN'T
NECESSARILY INCREASE THE RISK

OF DEVELOPING POST
TRAUMATIC EPILEPSY LONG-TERM.

LET'S GO TO THE NEXT SLIDE.

BUT THERE ARE ALSO OTHER--
MANY RISK PARAMETERS THAT

ACTUALLY HASN'T REALLY BEEN
STUDIED, LIKE BASED

ON THE MRI FINDING IN THE
ACUTE HEAD INJURY STATE.

THE PET SCAN FINDING--
OR EVEN A NEWER METHOD

OF MRI, [INDISTINCT]
DIFFUSION,

CANCER IMAGING METHOD.

AND ALL THESE METHODS
WILL REALLY SEE THE FINE

STRUCTURAL DAMAGES
OR PHYSIOLOGICAL CHANGES

OF THE BRAIN AFTER TBI.

AND ALL THESE FINDINGS
HAVEN'T REALLY BEEN USED

TO STUDY WITH SO WE CAN
IDENTIFY SPECIFIC RISK

FACTORS FOR POST
TRAUMATIC EPILEPSY.

SO IT JUST...I'LL TRY
TO DISCUSS THAT,

EVEN RE-IDENTIFY SOME
KNOWN HIGH-RISK FACTORS.

THERE ARE ALSO PARAMETERS
THAT WE STILL DON'T KNOW

BECAUSE THERE'S REALLY NO STUDY
FOR THOSE PARAMETERS.

AND LET'S LOOK AT
THE DETAILS OF THE RISK

OF DEVELOPING PTE IN VETERANS
IN THE NEXT SLIDE.

I MENTIONED THAT IN
THE KOREAN WAR STUDY

OF ALMOST 35% TO 45%,
AND IN THE VIETNAM,

HEAD INJURY ABOUT 53%,

BUT THESE TWO STUDIES ARE
A BIT DIFFERENT.

ACTUALLY, DURING
THE KOREAN WAR ERA,

NO PROPHYLACTIC
TREATMENT WAS GIVEN.

PATIENTS WITH HEAD INJURY,
NO ANTICONVULSIVE WAS GIVEN.

IN THE VIETNAM WAR ERA,
PHENYTOIN ACTUALLY

WAS GIVEN TO ALL PATIENTS
WITH A PENETRATING TBI

AND THEN FOR 6 MONTHS.

HOWEVER, IT WAS NOT REALLY
FOLLOWED ON WHETHER

PATIENT WAS COMPLYING
WITH MEDICATION OR NOT.

HOWEVER, THIS PROPHYLACTIC
TREATMENT FOR 6 MONTHS

DOESN'T SEEM TO CHANGE
THE INCIDENCE

OF DEVELOPING POST
TRAUMATIC EPILEPSY.

AND ANOTHER THING, THE TYPE
OF INJURY ARE DIFFERENT

BETWEEN THOSE TWO WARS, SINCE
THEY HAD MORE BULLET WOUNDS IN

THE KOREAN WAR AND MORE SHRAPNEL
WOUNDS IN THE VIETNAM WAR.

AND SO THIS WILL RAISE ONE ISSUE
IN ALL THE CLINICAL TRIALS

OF THE POST TRAUMATIC
EPILEPSY STUDY.

IT IS VERY DIFFICULT
TO CONTROL THE TYPE

OF TRAUMATIC BRAIN INJURY.

EVEN IF YOU HAVE A DOUBLE-
BLINDED CONTROL STUDY,

IT'S VERY DIFFICULT TO
MATCH THE CONTROL GROUP

AND THE STUDY GROUP IN TERM
OF THE SIZE

OF THE HEAD INJURY,
THE LOCATION OF HEAD INJURY,

AND THE SEVERITY
OF HEAD INJURY.

THOSE THINGS ARE NOW REALLY
DIFFICULT TO CONTROL.

LET'S GO TO THE NEXT SLIDE.

ABOUT 50% OF PATIENTS
WHO WILL DEVELOP PTE,

ACTUALLY, THE FIRST SEIZURE
HAPPENED WITHIN ONE YEAR

OF THE HEAD INJURY.

BUT ABOUT 15% OF PATIENTS,
THIS COULD BE--

COULD HAPPEN AFTER 5 YEARS.

AND A RECENT STUDY FROM THE
VIETNAM WAR, A HEAD INJURY STUDY

THAT WAS JUST RECENTLY PUBLISHED
IN THE PAST TWO YEARS,

IT SHOWED THAT EVEN 35 YEARS
LATER AFTER A MAJOR HEAD INJURY,

PATIENTS STILL COULD DEVELOP
POST TRAUMATIC EPILEPSY,

WHICH MEANS THE RISK
OF DEVELOPING POST TRAUMATIC

EPILEPSY NEVER RETURNS
TO BASELINE,

EVEN 30, 40 YEARS LATER.

THE BRAIN SOMEHOW
REMEMBERED THAT INSULT,

AND THERE'S SOME UNKNOWN
MECHANISM THAT COULD BE COOKING

IN THE BRAIN
FOR 30 YEARS OR MORE,

AND AT THAT TIME GIVE
THE PATIENT

AN EPILEPTIC DISORDER.

SO LET'S GO TO THE NEXT SLIDE.

THIS IS FROM THE
KOREAN WAR STUDY.

IT LOOKS DAUNTING,
BUT ACTUALLY THIS IS

NOT A DIFFICULT TO
UNDERSTAND SLIDE.

THIS IS FROM OVER 100 VETERANS
FROM THE KOREAN WAR

WHO HAD DEVELOPED POST
TRAUMATIC EPILEPSY.

AND SO, FROM THE FIRST
SEIZURE, WE JUST COUNT

HOW MANY SEIZURES THEY
DEVELOP ON A TIME AXIS.

AND ALL THIS, OVER 100
PATIENTS ARE LINED UP

FROM THE FIRST SEIZURE AND HOW
SOON AFTER THE HEAD INJURY

THEY DEVELOPED THE POST
TRAUMATIC EPILEPSY.

AND SO THIS IS--ALL THE
DOTS ON THE SLIDE MEANS

THESE ARE DISCRETE
SEIZURES, CURRENT,

AND SO IT WOULD LINE UP.

AND SO,
IF YOU LOOK AT THE AXIS,

YOU CAN SEE THIS IS
THEN OVER 11 YEARS.

AND IF YOU LOOK AT THE "Y" AXIS,

ABOUT 50% OF
THE "Y" AXIS THERE,

AND THEN GO TO THE PATIENT
POPULATION STAT,

YOU CAN SEE THAT THAT
PRETTY MUCH MEANS 50%

OF PATIENTS WHO DEVELOPED
THEIR FIRST SEIZURE

WITHIN ONE YEAR.

AND WITHIN TWO YEARS,
ABOUT 80% OF PATIENTS

WILL HAVE DEVELOPED
THEIR FIRST SEIZURES.

BUT AFTER THAT, THE GROUP
OF PATIENTS WILL REALLY--

SOME OF THEM EVEN DID NOT
DEVELOP THEIR FIRST SEIZURE

UNTIL 8 YEARS OR 7 YEARS
AFTER THEIR HEAD INJURY.

SO THIS WILL GIVE YOU A
GOOD OVERVIEW OF HOW THIS

CONDITION--WHY, AT
THE TIME FRAME OF THIS,

POST TRAUMATIC EPILEPSY
COULD DEVELOP.

NOW LET'S TALK ABOUT THE
PROGNOSIS IN THE NEXT SLIDES

AND ABOUT SOME OF THE
PATIENTS THAT THE--

THE SECOND MESSAGE WAS DECIDED
THERE'S ONE BRIGHT SPOT

FOR THIS CONDITION, IS SOME
OF THE PATIENTS WILL GO

INTO SPONTANEOUS REMISSION,
AND THE RATE HAS BEEN LOW.

IT'S ABOUT 35% TO 40%
OF PATIENTS.

SO IT MEANS, WITH TREATMENT
OR WITHOUT TREATMENT,

AT SOME POINT, THE CONDITION
WOULD...DISAPPEAR

AND GO INTO SPONTANEOUS
REMISSION, AND THIS WOULD BE

THE BEST OUTCOME OUT OF
THIS POST TRAUMATIC EPILEPSY.

AND THIS IS USUALLY--
THE THING I TELL MY PATIENTS,

IF THEY HAVE POST TRAUMATIC
EPILEPSY IS REALLY THERE'S

A CHANCE THAT THIS COULD GO
INTO SPONTANEOUS REMISSION,

BUT YOU CAN'T CONTROL IT.

ALSO VERY IMPORTANT
IN HELPING THE PATIENT

TO GET TO THAT POINT.

HOWEVER, ON THE OTHER SIDE
OF THE COIN IS ACTUALLY

A LOGICAL SENSE OF PATIENTS--
IT IS 13% IN SOME INSTANCES.

SOME STUDIES ACTUALLY COULD BE
HIGHER, AND IF 30%, ABOUT 30%,

PATIENTS ACTUALLY COULD BECOME
REFRACTORY TO MEDICAL TREATMENT.

SO THE NEXT SLIDE WILL
CONTINUE THE PERCENTAGE

OF INTRACTABILITY
MEANS REFRACTORY

TO MEDICAL TREATMENT
IN DIFFERENT IDEOLOGY

OF EPILEPSY, AND HEAD
INJURY IS MAYBE SOMEWHERE

IN THE MIDDLE, THAT ABOUT
30% OF PATIENTS WHO BECOME

SEIZURE-FREE FOR MORE THAN
ONE YEAR, WHILE THE OTHER

PATIENTS MIGHT HAVE
SOME INTRACTABILITY

WITH OR WITHOUT TREATMENT.

AND LET'S GO TO THE NEXT SLIDE,
WHICH WE HAVE TOUCHED EARLIER.

IT'S REALLY THERE'S A MAJOR
SOCIOECONOMIC [INDISTINCT]

FOR THIS CONDITION.

AND SO THE WAY WE HOPEFULLY
COULD FIND A WAY

TO OPTIMIZE TREATMENT
CONDITIONS AND EVEN TO PREVENT

THE DEVELOPMENT OF
THIS CONDITION BECAUSE

WE KNOW FROM HEAD INJURY TO
DEVELOPMENT OF THIS CONDITION,

THERE'S A TIME BASE
AND IT COULD BE YEARS,

AND SO WHY NOT DO
SOME INTERVENTION?

AND THIS WAS ACTUALLY THE ACTIVE
STUDIES IN THE SEVENTIES

AND EIGHTIES AND
EVEN EARLY NINETIES.

AND LET'S GO TO
THE NEXT SLIDE.

THERE WERE SEVERAL
OBSERVATIONAL STUDIES

THAT USED DIFFERENT
ANTICONVULSION AGENTS,

INCLUDING--PT IS PHENOBARBITAL,
AND PST IS PHENYTOIN,

VT IS A VALPROIC ACID.

THOSE ARE THE COMMONLY
USED ANTICONVULSANTS

IN THE EIGHTIES
AND THE SEVENTIES.

AND PEOPLE FOUND THAT
AS ACTUALLY SOMEWHAT

ENCOURAGING, AS PEOPLE WHO
WERE TREATED TEND TO HAVE

A LITTLE BIT OF CHANCE
OF PROTECTIONS

FOR DEVELOPING POST
TRAUMATIC EPILEPSY.

BUT THESE OBSERVATIONAL STUDIES
ARE NOT CONTROLLED, SO THE...

IT IS DIFFICULT TO SAY FOR SURE
THAT OBSERVATION IS VALID.

SO PEOPLE FOLLOW UP
WITH SEVERAL RECOGNIZED

CLINICAL TRIALS.

HOWEVER, THE RESULTS FROM
THE RECOGNIZED CLINICAL

TRIALS WERE QUITE
DISAPPOINTING.

THE CONCLUSION BASICALLY WAS
THERE WAS NO BENEFICIAL EFFECT

BY USING ALL THIS
ANTICONVULSIVE AGENTS

IN PREVENTING THE DEVELOPMENT
OF ANTICONVULSIONS.

THE FOLLOW-UP HERE
IN ALL THESE STUDIES,

ABOUT 3 MONTHS TO 5 YEARS.

AND EVEN IN 3 STUDIES,
THERE WERE SOME

PARADOXICALLY STUDIED
PATIENTS WHO WILL RECEIVE

THE AGENT; ACTUALLY HAS
A LITTLE BIT OF HIGHER

INCIDENCE OF DEVELOPING
POST TRAUMATIC EPILEPSY.

THERE'S ONE BLIND STUDY
SHOWING THAT THERE MIGHT BE

SOME BENEFICIAL EFFECT OF
THE PHENYTOIN.

SO THE DATA IS
PRETTY MESSY IN THIS SENSE.

AND HERE, I REALLY NEED
TO POINT OUT ANOTHER POINT

OF THE DIFFICULTY WITH
THIS TYPE OF STUDY

AND INTERPRETING THE DATA.

THE POINT IS THE DRUG
THAT WAS USED WAS, LIKE,

PHENYTOIN, PHENOBARBITAL,
AND CARBAMAZEPINE.

AND ALL THESE DRUGS ARE
CALLED ANTIEPILEPTIC DRUGS,

BUT IN REALITY, THEY ARE
ANTICONVULSANT DRUGS.

MEANS THEY ARE DRUGS
THAT CAN REDUCE

THE HYPEREXCITABILITY OF
THE BRAIN.

AND THE HYPEREXCITABILITY
IS REALLY THE REASON BEHIND

THE BRAIN THAT COULD
GO INTO A SEIZURE; IT'S

BECOME HYPEREXCITABLE.

AND ALL THESE DRUGS ARE
REALLY SCREENED FOR THEIR

EFFECT ON ACTIVE SEIZURES
IN ANIMAL MODELS,

AND THAT'S HOW THIS
CHEMICAL COMPOUND WILL

IDENTIFY INITIALLY.

SO ALL THE ANTIEPILEPTIC
DRUGS ON THE MARKET

NOWADAYS ARE REALLY DRUGS
THAT ARE GOOD FOR ACTIVE

SEIZURES AND ARE DRUGS
REALLY GOOD TO REDUCE THE

HYPEREXCITABILITY, BUT NOT
DRUGS THAT REALLY COULD

PREVENT THE DEVELOPMENT
OF EPILEPSY, OF A PROCESS

CALLED EPILEPTOGENESIS.

SO...THERE'S ONE CAVEAT
THERE, IS THIS STUDY,

EVEN IN THE CLINICAL TRIALS,
RANDOMIZED CLINICAL TRIALS,

DIDN'T REALLY SHOW ANY RESULTS.

DOESN'T REALLY MEAN OTHER DRUGS
THAT COULD COME ALONG WOULD NOT

BE BENEFICIAL, AND THE REASON IS
WHAT I TOLD YOU EARLIER.

THE TBI STUDY IS VERY
DIFFICULT TO CONTROL BECAUSE

IT'S DIFFERENT SIZE AND LOCATION
AND SEVERITY OF THE TBI.

EVEN IN THE CONTROL STUDY,
IT IS DIFFICULT TO CONTROL.

AND SECONDLY, THE
MEDICATIONS USED COULD BE

REALLY THE WRONG TYPE
OF DRUGS THAT WERE USED.

BUT BASICALLY, THE RESULT IS
THERE'S NO BENEFICIAL EFFECT.

AND THE NEXT SLIDE IS
A META-ANALYSIS.

THERE'S DIFFERENT STUDIES THAT
HAVE HAD A DIFFERENT OUTCOME.

PEOPLE PULL THIS STUDY TOGETHER,

AND THIS IS RAW DATA
FROM THE META-ANALYSIS.

WE CAN JUMP TO THE NEXT SLIDE.

BASICALLY, IT'S
THE [INDISTINCT] REVIEW

USING THE META-ANALYSIS
AND BY QUOTING 10

RANDOMIZED [INDISTINCT]
CLINICAL SIDE.

THEY STUDY TOGETHER,
AND IN THE 10 TRIALS

WERE A TOTAL OF 2,036 PATIENTS.

THEY HOPEFULLY COULD
[INDISTINCT] SOME UNDERSTANDING

OF THIS CONDITION.

AND THE CONCLUSION WAS THAT
THE ANTICONVULSANT DRUG WAS

THE ONLY GOOD IN REDUCING
THE RISK OF THE EARLY

PROVOKED SEIZURES AFTER
THE TRAUMATIC BRAIN INJURY.

AND THERE'S REALLY
NO BENEFICIAL EFFECT

IN THE PREVENTION OF
THE DEVELOPMENT OF POST

TRAUMATIC EPILEPSY.

AND THEY ALSO FOUND THAT
THE TREATED GROUP ACTUALLY

SUFFERED AN EVEN
HIGHER INCIDENCE

OF THE ANTICONVULSANT
SIDE EFFECTS

ON THE NEUROBEHAVIOR SIDE,
MEMORY AND NEUROBEHAVIOR SIDE.

AND THERE'S ALSO SOME
CONCERNS THAT THE TREATED

GROUP ACTUALLY COULD
SOMEHOW HINDER THE BRAIN

RECOVERY AFTER
THE HEAD INJURY.

SO LET'S GO TO
THE NEXT SLIDE.

SO WHAT WOULD BE THE ROLE
OF ANTICONVULSANTS AFTER

A TRAUMATIC BRAIN INJURY?

WE THINK THAT...WITHIN THE
FIRST WEEK OR FIRST MONTH

AFTER HEAD INJURY,
THE ANTICONVULSIVES TEND

TO HAVE SOME PROPHYLACTIC ROLE

IN CONTROLLING THE EARLY
PROVOKED SEIZURES.

BUT IT'S NOT EFFECTIVE
IN PREVENTING THE POST

TRAUMATIC EPILEPSY, AND I
WANT TO BE SPECIFIC THAT

THESE ARE MOSTLY FOR
THOSE ANTICONVULSIVES

LIKE PHENYTOIN AND PHENOBARBITAL
AND VALPROIC ACID.

MANY OF THE NEWER
ANTICONVULSIVES HAVEN'T

BEEN EVALUATED
FOR THIS PURPOSE.

AND THE NEXT SLIDE WILL DISCUSS
SOME PHILOSOPHICAL DISCUSSIONS

ON WHETHER ANTICONVULSIVES NEED
TO BE USED OR NOT TO BE USED.

AND I WILL JUST DISCUSS THIS

IN MORE OF A PHILOSOPHICAL
AND CONCEPTUAL DISCUSSION.

IF THE PATIENTS WILL
RECEIVE ANTICONVULSIVE

PROPHYLACTIC TREATMENT,

THEY TEND TO
HAVE A HIGH INCIDENCE

OF THE SIDE EFFECTS,
SUCH AS COGNITIVE IMPAIRMENT

OR SOME OF THEM HAVE
MENTAL BEHAVIOR PROBLEMS;

ESPECIALLY, A PATIENT PUT ON
PHENOBARBITAL TENDS

TO HAVE MORE
NEUROBEHAVIOR PROBLEMS.

AND ALL THIS, AND ONE
CONCERN IS [INDISTINCT]

COULD BE EVEN MUCH WORSE
IN PATIENTS WHO HAVE

HEAD INJURY.

AND THE ANTICONVULSIVE
ACTUALLY COULD INTERFERE

WITH THE RECOVERY, TOO.

THERE WAS SOME
EVIDENCE OF THAT, TOO.

SO LET'S GO TO
THE NEXT SLIDE.

SO HOW ABOUT NOT USING IT?

IF WE DON'T... [INDISTINCT]

AND SO...FOR NOW, IT'S--
POTENTIALLY THIS DRUG

ACTUALLY COULD HAVE SOME
EFFECT, AND THAT WAS SHOWN

IN THE OBSERVATIONAL STUDY,
BUT BECAUSE IT CONTROLS

PROCESS ACTIVITY,
THE SIGNAL WAS COVERED

BY THE BACKGROUND NOISE BECAUSE
IT'S DIFFICULT TO CONTROL

AND IT'S VERY MESSY DATA.

AND SO ALL THOSE ISSUES
HAVE TO BE CONSIDERED.

BUT LET'S GO TO
THE NEXT SLIDE.

AND ANOTHER ISSUE IS
THE TIMING OF THE TREATMENTS.

WHEN THE ANTICONVULSIVE
TREATMENT WAS INITIATED

AT THE HEAD INJURY SEEMS
TO BE AN ISSUE,

AND I WANTED TO POINT OUT
THIS ONE OBSERVATIONAL STUDY,

ACTUALLY IN 1979.

ANY HEAD INJURY PATIENTS,
PENETRATED HEAD INJURY,

THEY WOULD RECEIVE ONE GRAM
OF PHENYTOIN I.V., TREATED

RIGHT AWAY, AND IN THIS
OBSERVATIONAL STUDY,

THERE'S A MAJOR
DIFFERENCE--LIKE, ONLY 10%

IN THE TREATED GROUP
DEVELOPED POST TRAUMATIC

EPILEPSY, AND 50% IN
THE UNTREATED GROUP.

THAT'S VERY SIMILAR TO
THE VIETNAM WAR STUDY.

SO ALL THESE THINGS WOULD
COMPLICATE THE ISSUES.

AND SO LET'S GO TO
THE NEXT SLIDE.

I'M GOING TO, BECAUSE OF
TIME ISSUE, I'M GOING TO

SKIP SOME OF THE SLIDES
ON THE EPILEPTOGENESIS.

SO THE FIRST SLIDE
ON EPILEPTOGENESIS,

I'M GOING TO SKIP.

THE [INDISTINCT] MODEL,
I'M GOING TO SKIP.

LET'S GO TO THE NEXT ONE.

ONSET OF EPILEPTOGENESIS,
AND EPILEPTOGENESIS IS

A PROCESS AFTER A BRAIN INJURY

THAT SOMEHOW, DURING
THE RECOVERY PROCESS,

THE PLAN WOULD PLAY
INTO THE HAND,

THE RECOVERY PROCESS WOULD PLAY
INTO THE HAND OF THE...

THE EPILEPSY DEVELOPMENT,

AND THIS PROCESS IS
CALLED EPILEPTOGENESIS.

AND WHEN DID THIS PROCESS START?

THAT'S AN ISSUE THAT
WE DON'T HAVE AN ANSWER,

BUT THERE WAS ACTUALLY
SOME EVIDENCE SHOWING

THAT THIS ACTUALLY
COULD HAPPEN VERY EARLY,

AND IF THAT'S THE CASE, THE
PROPHYLACTIC TREATMENT ACTUALLY

SHOULD BE STARTED AS EARLY AS
POSSIBLE AFTER THE HEAD INJURY.

SO ONE PIECE OF ANIMAL EVIDENCE
FROM GRABER AND PRINCE FROM '04

IS THEY DO AN UNDERCUT
POST TRAUMATIC MODEL.

AND BASICALLY THEY'VE USED
A KNIFE AND CUT A SMALL PIECE

OF THE CORTEX AND KEEP
THE VASCULAR SUPPLY.

AND THE CORTEX BECOMES AN ISLAND
AND BECOMES DETACHED

FROM THE ROUTE TO THE
BRAIN, AND THAT'S CALLED

UNDERCUT MODEL, AND IT'S
A BRAIN INJURY MODEL.

AND THEY FOUND THAT THERE'S
A PRETTY GOOD PERIOD OF 3 DAYS

IN THE RODENT MODEL
THAT IF THEY USE TTX,

WHICH IS A SODIUM
CHANNEL ANTAGONIST,

OR A BLOCKER THAT WILL BLOCK OFF
THE SODIUM CHANNEL FUNCTION,

THEY SEE SOME KIND
OF PROTECTIVE EFFECT

FOR DEVELOPING POST
TRAUMATIC EPILEPSY.

SO IT SEEMS THAT THERE WAS
SOME KIND OF WINDOW,

A VERY NARROW WINDOW
IN THE ANIMAL MODEL.

AND I CANNOT DIRECTLY
TRANSLATE THIS INTO HUMANS.

HOWEVER, IT'S SOMETHING
FOR PEOPLE TO THINK ABOUT,

THAT THE TIMING OF
TREATMENT, PROPHYLACTIC,

COULD BE ANOTHER FACTOR
THAT NOW WEREN'T CONTROLLED BY

ALL OF THOSE CLINICAL
TRIALS, INCLUDING

OBSERVATIONAL AND CONTROL
STUDIES, AND THAT MIGHT BE

WHY THE FINDINGS WERE
SO MESSY AND NOISY.

SO NOW GO TO THE NEXT SLIDE.

SO THIS AND ALL THOSE--
UNDERSTANDING WE PROBABLY

CAN HAVE A HYPOTHESIS,
THAT ACTUALLY THE HEAD INJURY

COULD START THE PROCESS
OF THIS EPILEPTOGENESIS

IN MOTION, BUT IT ALSO
REQUIRES MANY OTHER

ACCESSORY FACTORS, SUCH AS
THE GENETIC PROPENSITY,

WHICH I WILL DISCUSS
A LITTLE BIT LATER.

THE NEUROGENESIS, THE REPAIR

OF THE BRAIN TISSUE,
ET CETERA, WILL ALL

PARTICIPATE, AND AT SOME
POINT, THIS PROCESS COULD

GO IN THE WRONG DIRECTION
AND THE POST TRAUMATIC

EPILEPSY COULD DEVELOP.

AND THIS IS A PROCESS
THAT COULD BE, AT BEST,

A FEW MONTHS, A WEEK, OR EVEN
AS LONG AS 35 YEARS

AFTER THE HEAD INJURY.

ALSO--GO TO THE NEXT SLIDE.

SO, BASED ON THIS
HYPOTHESIS--I WOULD LIKE TO

PROPOSE THAT THE TIMING OF
INITIATING ANTIEPILEPTIC

TREATMENT IS CRUCIAL AND
SHOULD BE OPTIMALLY STARTED

RIGHT AFTER THE HEAD
INJURY, OR ADDED BEFORE

THE EXPECTED HEAD INJURY.

LIKE, SOMEONE WHO KNOWS
FOR SURE HE'S GOING TO HAVE

A HEAD INJURY PROBABLY
SHOULD PUT OUT SOME KIND

OF AGENT FOR PROPHYLAXIS
ALREADY,

BUT THIS IS REALLY,
REALLY JUST AN IDEA.

THERE'S NO DATA TO SUPPORT
THAT THIS WILL WORK,

BUT IT'S REALLY ALL BASED
ON THE FINDINGS THAT WE HAVE

AND PROBABLY SOMETHING
WE CAN SPECULATE.

AND ALSO, PATIENTS NEED
TO BE INITIATED

ON ANTI-EPILEPTOGENETIC
TREATMENT.

THIS IS DIFFERENT FROM
THE ANTIEPILEPTIC AGENT

WE HAD BEEN USING.

THIS IS SOMETHING, BY USING
IN THE FUTURE, IF AN AGENT

THAT COULD SPECIFICALLY
DEVELOP TO SLOW

OR REVERSE THE EPILEPTOGENESIS.

NOW, THIS IS AN AGENT
THAT NEEDS TO BE USED

AS EARLY AS POSSIBLE.

LET'S GO TO THE NEXT SLIDE.

TALKING ABOUT
GENETIC PROPENSITY.

THAT'S THE FINDING THAT'S
ALSO NOISY AND MESSY THERE

THAT, FROM THE VIETNAM
HEAD INJURY STUDY,

DIDN'T REALLY FIND
THAT IF A FAMILY MEMBER

HAS EPILEPSY
HAS REALLY ANY ROLE

IN INCREASING
THE RISK OF HAVING PTE.

BUT [INDISTINCT] SEEMS
TO SOMEHOW RELATE

TO THE INCREASED RISK OF PTE

IN A GROUP OF PATIENTS
[INDISTINCT] SUBJECT.

ANOTHER ISSUE HERE IS...

INCIDENCE OF PHENOMENON CALLED
GENOTYPE PHENOTYPE DISCORDANCE.

THE SIMPLE-MINDED
UNDERSTANDING IS LOOKING

AT THE GENOTYPE AS SOMEONE
WHO HAS A GENOTYPE.

THEY WOULD DEFINITELY DEVELOP
A CERTAIN GENOTYPE.

SO THE SIMPLE-MINDED
UNDERSTANDING IS IF YOU

HAVE A MUTATION OF
AN EPILEPTIC GENE,

THEN YOU'RE GOING
TO DEVELOP THAT EPILEPSY.

AND IN ANIMAL MODEL AND IN
HUMAN SUBJECT, WE FIND OUT

THERE'S ACTUALLY A BIG
DISCORDANCE BETWEEN

GENOTYPE AND PHENOTYPE.

THE PEOPLE WHO HAD THE
GENOTYPE DON'T NECESSARILY--

WOULD DEVELOP EPILEPSY,
AND SO IT'S REALLY

THE GENOTYPE THAT'S
GIVING YOU A PROPENSITY

TO DEVELOP EPILEPSY.

AND THE DEVELOPMENT
OF EPILEPSY

REQUIRES [INDISTINCT]

FROM OTHER FACTORS,
SO ALL THIS WILL COMPLICATE

[INDISTINCT] OF THIS
GENETIC PROPENSITY.

LET'S GO TO THE NEXT SLIDE.

SO THERE ARE MANY NEW AEDs,

AND I BELIEVE PEOPLE, IF YOU
ARE A PATIENT, YOU PROBABLY

HAVE QUESTIONS ON THOSE
NEWER AEDs THAT YOU--

WOULD THEY BE HELPFUL
IN PREVENTING

POST TRAUMATIC EPILEPSY
AND WHAT ARE THE EFFECTS?

UNFORTUNATELY, THERE IS
A LACK OF DATA IN THIS RESPECT,

SO I DO SUPPORT
THE COMMONLY USED AEDs,

AND THERE'S ACTUALLY A NEW ONE
RECENTLY APPROVED BY FDA.

[INDISTINCT]

...WAS ALSO FOUND
IN AN OBSERVATIONAL STUDY

IN [INDISTINCT],

AND IT'S EFFECTIVE
IN 68% OF PATIENTS.

[INDISTINCT]

...HASN'T BEEN APPROVED BY FDA,
SO I'M GOING TO SKIP THAT,

BUT POTENTIALLY
IT COULD BE GOOD FOR YOU

IF IT'S APPROVED BY FDA.

SO LET'S GO TO
THE NEXT SLIDE.

SO THERE ARE MANY ISSUES WITH
THAT [INDISTINCT] UNDERSTANDING.

THERE ARE ISSUES IN THE
DIAGNOSIS AND TREATMENT

OF THE POST TRAUMATIC
EPILEPSY,

AS WHO SHOULD GET SCREENED
AND HOW TO SCREEN THIS PATIENT

AND WHEN TO START TREATMENT.

AND FOR THOSE
INTRACTABLE PATIENTS,

WHAT WOULD BE THE CRITERIA
FOR SURGICAL EVALUATION,

AND WHAT WOULD BE THE OUTCOME
MEASURES OF ALL THESE THINGS?

SO LET'S GO TO
THE NEXT SLIDE.

SO WE CAME UP WITH SOME
PRELIMINARY GUIDELINES

FOR DETECTION AND THERAPY
OF POST TRAUMATIC EPILEPSY.

ONE IS THE EARLY TREATMENT.

A PATIENT WHO HAS A HEAD
INJURY, WE RECOMMEND

THAT THEY SHOULD PUT ON
ANTICONVULSANTS TO REDUCE

THOSE [INDISTINCT]
PROVOKED SEIZURES.

AND ALSO WITH THAT
UNDERSTANDING THAT EARLY

INTERVENTION MIGHT HAVE
SOME PROPHYLACTIC EFFECT,

EVEN IF IT REALLY HASN'T
BEEN FULLY ESTABLISHED.

THERE ARE ONLY A FEW LINES
OF EVIDENCE FROM ANIMAL STUDY

AND FROM THAT PHENYTOIN I.V.
STUDY, OBSERVATIONAL STUDY.

AND THEY SHOULD BE PUT ON
ANTICONVULSANTS FOR A WEEK,

AND IT'S A WEEK
AFTER THE TREATMENT.

WE DO NOT RECOMMEND LONG-TERM
ANTICONVULSANT TREATMENT,

AND ANTICONVULSANT TREATMENT
SHOULD BE INITIATED AS EARLY

AS POSSIBLE AFTER
THE ESTABLISHED DIAGNOSIS

OF POST TRAUMATIC EPILEPSY.

AND THIS IS THE ISSUE HERE:
BASED ON THE DEFINITION,

PATIENT NEEDS TO HAVE ONE
CLINICAL SEIZURE AFTER

THE HEAD INJURY TO MEET
THE CRITERIA

OF POST TRAUMATIC EPILEPSY.

BUT WE HAVE SEEN PATIENTS
WHO DON'T REALLY FIT

WITH THIS CRITERIA,
BUT WE SUSPECT THEY MIGHT

DEVELOP POST TRAUMATIC EPILEPSY
OR THEY ARE IN THE PROCESS

OF DEVELOPING THIS CONDITION.

LET'S GO TO THE NEXT SLIDE.

WE DO EEG SCREENING
IN SOME OF THE PATIENTS

WHO HAD THE MOST SEVERE
HEAD INJURIES,

AND WE'VE SEEN A NORMAL EEG.

AND PATIENTS HAVEN'T HAD
A CLINICAL SEIZURE,

SO WHAT ARE YOU TO DO WITH
THIS GROUP OF PATIENTS?

DO YOU TREAT THEM OR
YOU DON'T TREAT THEM?

IF YOU TREAT THEM,
WHAT WOULD BE THE CRITERIA

TO CONTINUE OR TERMINATE
THE ANTICONVULSIVE THERAPY?

AND SO ALL THOSE ISSUES
ARE STILL IN THE GRAY ZONE

AND IT HASN'T
REALLY BEEN ESTABLISHED

WHAT WOULD BE THE BEST WAY
TO DEAL WITH IT.

LET'S GO TO THE NEXT SLIDE,
THE PHARMACOTHERAPY.

IF A PATIENT NEEDED TO BE
ON ANTICONVULSIVE THERAPY,

WE WILL RECOMMEND
ESTABLISHED MONOTHERAPY,

AND THEN, IF ONE AGENT
DOESN'T WORK, YOU WILL

SWITCH MONOTHERAPY WITH THE
OTHER AGENT, AND IF MONOTHERAPY

DOESN'T WORK, THEN YOU WILL
CONSIDER DOING POLYTHERAPY,

WITH COMBINATION
OF MEDICATIONS,

AND HOPEFULLY TO REACH
SEIZURE CONTROL

WITH NO SIDE EFFECT.

AND LET'S GO TO
THE NEXT SLIDE.

THAT'S FOR THOSE PATIENTS
WHO ARE MEDICALLY REFRACTORY.

THEY SHOULD BE EVALUATED FOR
SURGICAL APPROACH, AND THEY

DEFINITELY NEED TO HAVE
AN INPATIENT--

EITHER EEG MONITORING
AND HAVE A PET SCAN

AND ALL THE OTHER STANDARD
SURGICAL WORK-UPS.

AND SOME OF THEM WILL REQUIRE
INTRACRANIAL ELECTROSTUDIES.

THEY WILL REQUIRE
INTRACRANIAL STUDIES

FOR THIS STUDY AND WILL
REQUIRE ONE OTHER STUDY,

WHICH I DON'T THINK I HAVE TIME
TO GO INTO THE DETAILS

OF THE PROCESS OF THE
SURGICAL WORK-UP.

AND THE KEY POINT HERE
IS PATIENTS WHO

ARE REFRACTORY,
SURGICAL APPROACH

OR [INDISTINCT]

PROBABLY WOULD BE
THE SECOND-BEST HOPE

TO CONTROL THE SEIZURES HERE,

SO THEY NEED TO BE
EVALUATED.

AND THIS PAST MONDAY,
WE JUST HAD A PATIENT

WHO ACTUALLY HAS POST
TRAUMATIC EPILEPSY.

HE DEVELOPED SEIZURE STILL
IN SERVICE, IN HIS 20s,

AND HE'S 58.

HE HAD INTRACTABLE
EPILEPSY, AND FINALLY,

WE HAVE A TEMPORAL
LOBECTOMY FOR HIM

THIS PAST MONDAY
IN OUR O.R. HERE.

AND WE ALSO MAPPED THE
SEIZURE AREAS BEFORE

AND AFTER THE RESECTION AND
SEE THE FOCUS ACTUALLY WAS

ABOUT 5 CENTIMETERS BACK
FROM THE RIGHT SIDE

OF THE TEMPORAL TIP.

AND SO IT'S A PRETTY LARGE
RESECTION FOR HIM, AND ALSO

THERE WAS SOME ACTIVITY
COMING FROM THE MEDIAL SIDE,

FROM HIS HIPPOCAMPUS,
SO WE ACTUALLY DID

A PRETTY LARGE
RESECTION FOR HIM.

SO A COMMONLY SEEN PHENOMENON

IN SURGICAL APPROACH IS
THERE'S A MAJOR DELAY.

IF SEIZURE HAS BECOME
INTRACTABLE IN HIS 20s,

IT TOOK HIM ANOTHER 30 YEARS
FOR HIM TO RECEIVE THE SURGERY.

WE HOPED THE SURGERY COULD
ERADICATE THE SEIZURES

FOR HIM; WE DON'T KNOW YET.

BUT ONE MAJOR POINT HERE
FOR SURGICAL APPROACH IS

PATIENTS WHO HAVE
INTRACTABLE EPILEPSY,

POST TRAUMATIC EPILEPSY.

THEY SHOULD BE READY
FOR SURGICAL APPROACH.

WHETHER THEY NEED SURGICAL
APPROACH OR NOT, THAT'S

A DIFFERENT ISSUE, A
VERY COMPLICATED ISSUE.

AND ANOTHER POINT I WANT
TO MAKE OR MENTION HERE IS

DIFFERENT EPILEPSY
CENTERS DO THINGS A LITTLE

DIFFERENTLY FROM EACH
OTHER, AND SO THAT'S

ANOTHER POINT THAT I WANT
PEOPLE TO BE AWARE OF.

AND THE NEXT SLIDE
WILL BE THE LAST ONE.

I DON'T THINK--I HAVE RUN OUT
OF TIME, AND BASICALLY

I JUST WANT TO HIT A
FEW KEY POINTS HERE.

IN THE RECENT SURVEY SENT
TO RETURNED VETERANS,

WE ARE ALSO SEEING SOME OF THEM
HAVE EPILEPTIC-LIKE EVENTS,

BUT AFTER
INPATIENT [INDISTINCT]

WHAT THEY HAVE ARE
NON-EPILEPTIC EVENTS,

NOT REAL EPILEPTIC EVENTS.

AND HOW TO DEAL WITH THIS
CONDITION SEEMS TO REQUIRE

SOME NEW STUDY ON HOW TO
WORK ON THESE PATIENTS

AND TREATMENTS; THEY ALL
REQUIRE NEW STUDY.

AND SO I THINK I WILL
FINISH MY TALK NOW.

- THEY'RE OPENING THE LINES UP.

IS THERE ANY QUESTION?

- YEAH, I HAVE A QUESTION.

THIS IS DR. [INDISTINCT]
FROM SIOUX FALLS VA.

HOW LONG AFTER THE POST
TRAUMATIC EPILEPTIC SEIZURE

DOES THE MEDICATION--
OR BE MEDICATED

FOR POST TRAUMATIC SEIZURE?

IS IT 2 YEARS, 3 YEARS,
OR FOREVER?

- OK, SO THERE'S NO CLEAR
GUIDELINE FOR THAT,

BUT REMEMBER, PATIENT HAS
ABOUT 30%, 40% CHANCE

OF GOING INTO
SPONTANEOUS REMISSION,

AND THERE'S 30% OF
GOING INTO [INDISTINCT],

SO THE BEST HOPE IS WE USE
PHARMACOLOGICAL DRUGS

TO CONTROL THE SEIZURES
IN PATIENTS TRYING TO FIND

A WAY TO GO INTO
SPONTANEOUS REMISSION.

SO I WOULD GO BY THE CRITERIA.

IF PATIENT IS SEIZURE-FREE
AND THE EEG ALSO NORMALIZES,

AND AFTER 2, 3 YEARS, I MIGHT
CONSIDER TAKING PATIENT

OFF MEDICATION AND SEE
HOW IT GOES.

AND AS I POINTED, ACTUALLY
IT COULD GO EITHER WAY.

SOME OF THE PATIENTS
ACTUALLY HAVE REMISSION

OF THE EPILEPSY, SO THEY CAN
CONTINUE TO BE OFF MEDICATION,

AND WE SEE THIS EVEN IN PATIENTS

WHO HAVE FAIRLY SEVERE
HEAD INJURY.

THEY STILL HAVE A CHANCE
TO GO INTO REMISSION,

AND SOME OF THEM, IF THEY HAVE
RECURRENCE, THEN YOU HAVE NO

CHOICE; YOU HAVE TO PUT
THEM BACK ON THERAPY.

- HOW LONG FOR THEM
TO STAY IN THERAPY?

I SAW ONE PATIENT WHO HAD
A SEIZURE 3, 4 YEARS AGO

AND HAD A TRAUMATIC
BRAIN INJURY.

OK, HE WAS ON THE [INDISTINCT]
AND IT WAS STOPPED

SEVERAL MONTHS LATER.

AND NOW, IN THE LAST TWO WEEKS,
HE HAD ANOTHER SEIZURE,

SO BASICALLY DOES HE NEED
THE [INDISTINCT] FOREVER, OR...

- IS HE OFF STEROIDS?
- YES, THEY'VE STOPPED.

- OK, IF PATIENT HAVE RECURRENCE
WHEN WE TRY TO GET PATIENTS OFF,

THAT USUALLY MEANS
IT'S HARDER TO--

I WOULD SHOOT FOR
THE SECOND GOAL

IF PATIENT IS SEIZURE-FREE
UNDER MEDICATION,

AND IT WOULD BE HARD FOR ME
TO TRY TO DO IT AGAIN.

I USUALLY WOULD NOT
TRY TO DO IT AGAIN.

I WOULD KEEP IT FOR A LONG,
LONG TIME, MIGHT BE AT LEAST

5, 10 YEARS BEFORE I THINK
ABOUT TAKING PATIENTS OFF

THE MEDICATION.

[INDISTINCT]

...AND YOU NEED TO BE
SUPPRESSED BY SOME MEDICATIONS.

BUT IF YOU CAN SUPPRESS IT AND
ACHIEVE A SEIZURE-FREE STATUS

FOR THE PATIENT WITH SOME
OF THE THERAPY,

THAT WOULD BE GOOD
FOR THE PATIENT, YEAH.

- YEAH,
I HAVE A QUESTION.

I MISSED THE INITIAL
PART OF THE TALK.

CAN YOU PLEASE [INDISTINCT]
ME A PREFERENCE?

WHAT IS THE BEST INITIAL
TREATMENT TODAY TO START

MONOTHERAPY FOR THE PATIENTS?

- OH, YES.

THERE'S REALLY NO
BEST TREATMENT.

JUST LIKE ANY EPILEPSY,
IT'S FOR THE PATIENT.

YOU HAVE TO LOOK
AT PATIENT'S MEDICAL

CONDITIONS AND THEN
YOU CHOOSE A DRUG BASED

ON THAT, AND IT DEPENDS
BECAUSE IF THEY'RE ALL

PARTIAL SEIZURES,
[INDISTINCT].

SO MOST OF THE DRUGS YOU
CAN USE, AND YOU THINK

ABOUT THE SIDE EFFECTS
AND THE EFFICACY.

SOMETIMES YOU MIGHT NEED TO
TRY A FEW DRUGS BEFORE YOU

FIND A DRUG THAT REALLY
WORKS FOR THE PATIENT

AND DECIDE IF PATIENT
CAN TOLERATE IT.

SO I CANNOT REALLY PROPOSE
ANY SPECIFIC DRUG AS

THE BEST DRUG, BUT
I USUALLY NOWADAYS,

I LIKE TO START WITH A DRUG THAT
IS PHARMACOKINETICALLY SIMPLE.

THAT MEANS A DRUG THAT DON'T
INTERACT WITH OTHER AGENTS,

WHICH WILL MAKE IT EASIER TO USE
AND ALSO EASIER ON THE SIDE

THAT WE DON'T HAVE TO
WORRY ABOUT MIGRAINES

OR HYPONATREMIA OR
LIVER FUNCTIONS.

SO [INDISTINCT],

I MIGHT START WITH A
DRUG LIKE LEVETIRACETAM,

LACOSEMIDE, AND EVEN,
LIKE--NEURONTIN

IS PHARMACOKINETICALLY SIMPLE,

BUT PROBABLY IN
GENERAL, IT'S NOT A VERY

GOOD SEIZURE MEDICATION,
BUT AS AN AGENT THERAPY,

IT PROBABLY WILL WORK.

AND LYRICA PROBABLY IS
SOMEWHERE IN THE CATEGORY,

TOO, BUT IN SOME PATIENTS,
ACTUALLY, THEY ALSO DO WELL.

SO ALL THESE THINGS NEED TO
BE CONSIDERED, BUT IF YOU

KNOW THIS PATIENT IS
SOMEONE WHO HAS A VERY

REFRACTORY CONDITION, HE IS
HAVING A SEIZURE ONCE EVERY

SEVERAL DAYS, THEN YOU
PROBABLY HAVE TO THINK

OF THE MOST EFFECTIVE
MEDICATION FOR THE PATIENT

AND YOU PROBABLY WANT
DEFINITELY TO INCLUDE SOME

SODIUM KIND OF DRUG,
LIKE IN THE PHENYTOIN

AND [INDISTINCT] CATEGORY

TO PREVENT A SECONDARY
[INDISTINCT]

AND YOU PROBABLY WANT TO
INCLUDE DRUGS THAT WILL

REALLY WORK ON
THE [INDISTINCT] SYSTEM.

THAT'S DEPAKOTE AND,
YOU KNOW, EVEN SOME OTHER

DRUGS THAT WORK ON
THE [INDISTINCT] SYSTEM.

AND, LIKE, A BROAD SPECTRUM DRUG

LIKE TOPAMAX, WHICH
HAS SOME [INDISTINCT].

AND [INDISTINCT]

...SOMETIMES IS
ALSO GOOD FOR THAT.

SO I THINK IT HAS
TO BE CASE BY CASE.

THERE'S NO STANDARD
RECOMMENDATION,

AND I WOULD BASE IT ON
PATIENT'S BACKGROUND,

MEDICAL...AND ESTABLISH
A PHARMACOKINETICALLY EASIER,

SIMPLE DRUG, BUT IF
PATIENT'S MEDICAL CONDITION

REQUIRE A DRUG THAT
ACTUALLY WE CONSIDER

IN GENERAL MORE EFFECTIVE,
THEN YOU PROBABLY

SHOULD START WITH THAT DRUG
[INDISTINCT].

- CAN YOU SAY
A COUPLE OF WORDS

ABOUT ENTAB, THE NEW
MEDICINE [INDISTINCT]?

- YEAH. OK.

ENTAB IS A RELATIVELY
NEW MEDICATION.

IT'S REALLY A DRUG THAT
WORKS ON A NEW MECHANISM

COMPARED TO OTHER
ANTICONVULSANTS.

IT'S FINE IN ACTIVATING
A SLOW, INACTIVATING GATE

OF A SODIUM CHANNEL.

IT'S A SODIUM CHANNEL DRUG,
BUT IT'S ON A DIFFERENT

SODIUM CHANNEL COMPARED
TO TEGRETOL, PHENYTOIN,

AND [INDISTINCT].

IT'S KIND OF SLOW IN ACTIVATING
THE SODIUM CHANNEL.

AND THIS SODIUM CHANNEL CAN
ALSO BE FOUND IN THE HEART,

SO I'M USUALLY CAREFUL WITH
PATIENTS WHO HAVE CARDIO

CONDITIONS LIKE CARDIO
ARRHYTHMIA OR HEART FAILURE.

EVEN IN THE CLINICAL TRIAL,
IT DOESN'T SEEM TO BE

A MAJOR ISSUE, BUT I USUALLY
WOULD BE CAREFUL THERE.

BUT OTHERWISE, I'VE FOUND ENTAB
TO BE FAIRLY EASY TO USE,

AND IT COMES WITH I.V. FORM,
SO WE USE IT EVEN

FOR INPATIENT A LOT, TOO, HERE.

AND IN MY EXPERIENCE, IT'S
REALLY ONE OF THE GOOD DRUGS

IF PATIENT DOESN'T HAVE
A CARDIO HISTORY.

I WOULD HAVE A [INDISTINCT]

AND THIS ONE, TOO, YEAH.

- THANK YOU.
- OK.

- IS THERE ANY OTHER QUESTION?

ALL RIGHT, DR. CHEN.

I WANT TO THANK YOU
FOR PRESENTING TODAY.

I WANT TO MAKE SURE
EVERYBODY FILLS OUT

THE SURVEY ONCE THEY'RE
COMPLETE, TO ENSURE THAT

THEY RECEIVE CREDIT
FOR THIS COURSE.

AND THANK YOU, GUYS.