Biochemistry 460

1. EPILEPSY
Case Study
Madison Brenamen

2. Consider the Following Patient
■ A mother brings her 8 year old daughter, Kali, into the clinic to see her
primary care physician for her yearly check-up.When the doctor asks
Kali’s mother if there is anything she is concerned about, she states that
she notices that Kali sometimes will stare off into space for extended
period of time, she sometimes will blink her eyes rapidly, and when this
occurs she seems to not be aware of her surroundings. Kali’s mom is
wondering whether this is just Kali not paying attention or if there is
something wrong with her.

3. Do you think there is
something wrong with
Kali? If so, what would
your diagnosis be?

4. What tests would you perform to figure
out what may be going on?
■ Review Kali’s medical history and her family medical history to see if there is a disease
that runs in the family
■ Blood sample to check for infections, genetic conditions, etc.
■ Electroencephalogram (EEG)
■ Computerized tomography scan (CT)
■ Magnetic resonance imaging (MRI)
■ Neuropsychological tests

5. Diagnosis– Epilepsy
■ Upon performing the tests the doctor felt
was necessary, Kali was diagnosed with
Epilepsy
■ Kali does have a family history of Epilepsy
and when the EEG was performed, when
Kali would go into one of her fits, it showed
changes in the normal pattern of Kali’s
brain waves.

6. Absence
seizures
■ Kali was experiencing
absence seizures, one of the
6 types of generalized
seizures
■ These types of seizures are
common in children
■ Some of the symptoms of
this type of seizure can be
seen to the left

7. Biochemistry Behind
Epilepsy
■ As a nerve transmits an electrical signal, sodium
and potassium move into and out of the cell,
depending on their concentration gradients.
■ When the signal reaches the end of the nerve,
neurotransmitters are released to continue the cell
to cell communication (excitatory) or stop the
communication (inhibitory).This can be seen in the
figure to the right.
■ When too many neurotransmitters are released and
there is over-activity of the excitatory
neurotransmitters or under-activity of the
inhibitory neurotransmitters, the electrical flow of
the brain is thrown off, causing a seizure.

8. Biochemistry Behind Epilepsy Cont.
■ The motor cortex and temporal lobes of the brain are more susceptible to be the
source of seizures
– Their nerve cells are very sensitive to abnormal situations which cause abnormal
electrical transmission (i.e. low oxygen levels, infections)
■ Seizures occur when neurotransmitters (i.e. dopamine) send the electrical signals
through the brain at a rate that is too fast

9. Treatments
■ Antiepileptic drugs
– Narrow–spectrum: for a specific
type of seizure.
■ Examples for treatment of
absence seizures:
– Clobazam (Onfi)
– Divalproex (Depakote)
– Broad-spectrum: used if patient
has more than one type of
seizure
■ Examples:
– Clonazepam (Klonopin)
– Lamotrigine (Lamictal)
■ Surgery
– Used when tests show that
seizures occur in an area of
brain that does not provide vital
function
■ Vagus Nerve Stimulation

10. How do
antiepileptic
drugs work?
■ Divided based on their
mechanism of action
– Sodium Channel
– CalciumChannel
– GABAERIGIC
– Glutamate
– CA Inhibitor
– Other
■ Some drugs work on a
combination of channels

11. Sodium Channel Blockers
■ Prevent sodium channels
from returning to their
active state and making
them stay in their inactive
state
■ Prevent axons from firing
repetitively
■ Examples:
– Carbamazepine
– Phenytoin
– Lacosamide

12. Calcium Channel Blockers
■ Prevent the depolarization that
cause the “spike-and-wave
discharges” associated with
absence seizures
■ Used for controlling absence
seizures

13. GABA
Enhancers
■ Gamma-aminobutyric acid (GABA)
■ A and B receptors
– Binding to GABA-A receptor
causes chloride to flow into the
cell through chloride channels,
making the cell more negative,
and thus having a lower resting
potential
– Binding to GABA-B causes a
potassium channel to be opened
■ Antiepileptic drugs act differently on
GABA depending on their sites of
action

14. GABA
Receptor
Antagonists
■ GABA is the most
important inhibitory
neurotransmitter
■ Inhibit the GABA receptors
■ Affect the amount of time
that chloride channels are
open
■ Examples
– Clobazam
– Lorazepam
– Diazepam
GABA
Reuptake
Inhibitors
■ Inhibit the 4 GABA-
transporting compounds
which carry GABA from
synaptic space to neurons
so that it can be
metabolized
■ This causes an increased
amount of GABA in
synaptic cleft
■ Examples:
– Tiagabine
– Nipecotic acid
GABA
Transaminase
Inhibitors
■ GABA is metabolized by
GABA-transaminase
■ By inhibiting the
enzymatic process, there is
an increase in the
concentration of GABA
outside of the cells
■ Example:
– Vigabatrin

15. Glutamate Blockers
■ Modify glutamate receptors which bind
glutamate (excitatory neurotransmitter) at
the binding sites AMPA and NDMA
– AMPA– channel opens in receptor
which allows sodium and little bit of
calcium to enter
– NDMA– channel opens which allows
sodium and a large quantity of calcium
to enter
■ Very limited use
– Cause psychosis and hallucinations
– Blocked NMDA receptors can cause
problems with learning and memory
■ Examples:
– Felbamate
– Topiramate

16. Carbonic
Anhydrase
Inhibitors
■ Inhibits carbonic anhydrase
which decreases pH and
increases [H+]
■ Potassium ions move to
outside of cell to balance the
acid-base situation causing
hyperpolarization
■ Example:
– Acetazolamide

17. Neuronal Potassium
Channel Openers
■ A new medication approved by the FDA in
2011– Ezogabine (Potiga)
– “The FDA approved ezogabine as
adjunctive therapy in partial-onset
seizures uncontrolled by current
medications”
■ Side effects
– Potassium channels are also present in
smooth muscle in the bladder and the
heart, so this medication could cause
problems with that muscle tissue

18. How does epilepsy affect you?
A.I have epilepsy
B.Someone in my immediate family has epilepsy
C.Someone in my extended family has epilepsy
D.Someone I know has epilepsy
E. No one I know has epilepsy

19. References
■ MayoClinic Staff Print. "Epilepsy." Overview - Epilepsy - Mayo Clinic. N.p., 06 Nov. 2015.
Web. 15 Dec. 2016.
■ Natelson, S., DJ Miletich,CF Seals, DJVisintine, and RF Albrecht. "Clinical Biochemistry
of Epilepsy. I. Nature of the Disease and a Review of the Chemical Findings in
Epilepsy." ClinicalChemistry. U.S. National Library of Medicine, 25 June 1979.Web. 15
Dec. 2016.
■ Nordqvist, Christian. "Epilepsy:Causes, Symptoms andTreatments." Medical News
Today. MediLexicon International, 31 Dec. 2015.Web. 15 Dec. 2016.
■ Ochoa, JuanG., MD, andWillise Riche, MD. "Antiepileptic Drugs." Antiepileptic Drugs:
Overview, Mechanism of Action, Sodium Channel Blockers. Medscape, 8 Mar. 2016.Web.
15 Dec. 2016.
■ Schachter, Steven, MD, Patricia Schafer, RN, MN, and Joseph Sirven, MD. "What
Happens DuringA Seizure?" Epilepsy Foundation. N.p., 01 Mar. 2014.Web. 15 Dec.
2016.