Psych Neuro Exam 3: Cavanaugh Seizure Disorders

Epilepsy seizure: Due to sudden abnormal ___ discharges in the brain

electrical

Non-epileptic seizure: no unusual electrical activity in brain; most often caused by __ stress or ___ condition

mental, physical

3 classifications of seizures:

1. ____

2. ____

3. ___ onset

focal, generalized, unknown

____= seizure starts from 1 side of brain

focal

Focal seizures are further classified by level of awareness (____ or ___ ___)

aware, impaired awareness

Focal seizures are further classified by features of seizures (____ or ___-___)

motor, non-motor

A focal seizure that spreads to involve both sides of brain called a "___ to ___ seizure"

focal, bilateral

____= seizure starts from both sides of brain

generalized

Generalized seizures are not classified based on level of awareness, because the patient is presumed to have ___ ___

impaired awareness

Generalized seizures are further classified by features of seizures (____ or ___-___)

motor, non-moter

Unknown Onset Seizures are further classified by features of seizures (____ or ___-___ or ____)

motor, non-motor, unclassified

Focal Seizure with Awareness

-no loss of ____

-previously called simple partial seizure

consciousness

Focal Seizure with Impaired Awareness

-starts local and ___ to areas the cause loss of consciousness

-previously called complex partial seizure

spreads

Generalized tonic-clonic seizure

-Tonic phase: body ____, possible cry, ____, incontinence

stiffens, cyanosis

Generalized tonic-clonic seizure

-Clonic phase: ___ movements, possible salivary ___, cyanosis, eyes blinking

jerking, frothing

Generalized tonic-clonic seizure

-Postictal: ___, very ___, limbs and body are limp

confused, tired

Seizures = too much ___ (↑ glutamate) or too little ___ (↓ GABA)

excitation, inhibition

Excitatory synapse

1. Action potential arrives → voltage-gated Na⁺ channels open → ___ travels to axon terminal

depolarization

Excitatory synapse

2. Depolarization → opens voltage-gated ___ channels → Ca²⁺ influx into presynaptic neuron

Ca²⁺

Excitatory synapse

3. Ca²⁺ → activates synaptic vesicle 2A protein (___) on synaptic vesicles → allowing them to fuse with the presynaptic membrane and release ____

SV2A, glutamate

Excitatory synapse

4. Glutamate binds ____ and ____/___

NMDAr, AMPAr/KAr

NMDAr, AMPAr, and KAr are all ionotropic ion channel receptors (channel opens immediately and ___ and ____ flow into neuron)

Na+, Ca2+

Excitatory synapse

5. Glutamate binds NMDAr and AMPAr/KAr → ions (Na+, Ca2+) flow into neuron → ____

depolarization

Inhibitory synapse

1. Glutamate → converted to ___ (via ____) and packaged into vesicles

GABA, GAD

Inhibitory synapse

2. AP arrives → depolarization → voltage-gated __ channels open → Ca²⁺ influx

Ca²⁺

Inhibitory synapse

3. Ca²⁺ triggers vesicles to ___ and ___ released into synaptic cleft

fuse, GABA

Inhibitory synapse

4. GABA binds GABA receptors (ionotropic ion channel receptors) → ___ influx into postsynaptic neuron

Cl-

Inhibitory synapse

5. Cl- influx→ Hyperpolarization (inside becomes more ___) → ___ likelihood of action potential

negative, decreased

Inhibitory synapse

6. GABA transporter (GAT1) → ___ of GABA → terminates signal

reuptake

Excitatory: Na⁺ ± Ca²⁺ influx → depolarization → _____ chance of AP (fires)

Inhibitory: Cl⁻ influx → hyperpolarization → ____ chance of AP (no firing)

increased, decreased

Drug Target: Decrease excitation by blocking voltage gated ___ channel

-phenytoin

-carbamazepine

-valproic acid

-felbumate

-rufinamide

-lamotrigine

-lacosamide

-topiramate

-zonisamide

-oxcarbazepine

Na+

α₂δ subunit = part of voltage-gated ___ channel (acts like a “hinge”)

Ca²⁺

Drug Target: Decrease excitation by blocking voltage gated ___ channel

-gabapentin

-pregabalin

Ca²⁺

Drug Target: Drug Target: Decrease excitation by blocking ___ (therefore blocking ability of vesicles to fuse to the membrane)

-levetiracetam

SV2A

Drug Target: Drug Target: Decrease excitation by blocking ____

-felbamate

-valproic acid

NMDAr

Drug Target: Decrease excitation by blocking ____/___

-topiramate

-perampanel

AMPAr, KAr

Drug Target: Increase inhibition by blocking ____ to prevent breakdown of GABA

-vigabatrin

GABA-T

Drug Target: Increase inhibition by blocking ____ to prevent reuptake of GABA

-tiagabine

GAT1

Drug Target: Increase inhibition by blocking postsynaptic T-type ____ channels to prevent depolarization of postsynaptic neuron

-ethosuxamide

calcium

Drug Target: Increase inhibition agonizing ____

-benzodiazepines

-barbiturates

-felbamate

-topiramate

-zonisamide

GABA

Drug Target: Increase inhibition by decreasing GABA ___

-valproic acid

turnover

Carbanic anhydrase (CA) inhibitors

-___ (used as add-on for various seizure types)

-_____ + ____ (as part of their broader mechanism)

acetazolamide, topiramate, zonisamide

Carbanic anhydrase (CA) inhibitors

-reduce neuronal ___

-cause an accumulation of ___

excitability, CO2

Carbanic anhydrase (CA) inhibitors

-by causing an accumulation of CO2, these drugs lower intracellular ___, inhibit neuronal ___, and enhance __-mediated inhibition

pH, firing, GABA

Tuberous Sclerosis Complex (TSC)

-rare genetic disorder causing ____ ____ to grow in organs like the brain, kidneys, heart, and skin, often leading to epilepsy, autism, and developmental delays

noncancerous tumors

What drug is used for patients 2 years and older with Tuberous Sclerosis Complex (TSC)?

everolimus

everolimus

-inhibits the mechanistic ___ ___ ___ (mTOR) pathway, which is overactive due to genetic mutations

target of rapamycin

everolimus

-by inhibiting the mTOR pathway, the drug reduced ___-mediated excitatory activity, decreases ___, and inhibits cell ___

glutamate, neuroinflammation, growth

Lennon-Gastaut Syndrome (LGS) and Dravet Syndrome (DS) are treatment-___ forms of childhood epilepsy

resistant

Lennon-Gastaut Syndrome (LGS)

-severe form of epilepsy that occurs during infancy or early childhood

-___, ____, and ___ ___ seizures

atonic, tonic, atypical absence

Dravet Syndrome (DS)

-severe form of epilepsy

-hallmark first symptom = fever-related (____) seizures usually between 4-12 months

febrile

Dravet Syndrome (DS)

-patients will develop other types of seizure with increased ___ of disease

severity

What drugs do we use for Lennon-Gastaut Syndrome (LGS) and Dravet Syndrome (DS)?

fenfluramine, cannabidiol

Fenfluramine Mechanisms:

1. Sigma-1 ____ → inhibits ___ influx in glutamate neurons

agonist, Ca2+

Fenfluramine Mechanisms:

2. ____-like effects → blocks & reverses ___ → increased serotonin release

amphetamine, SERT

Fenfluramine Mechanisms:

3. 5-HT1A ____ → removes autoreceptor brake → increased serotonin release

antagonist

Fenfluramine Mechanisms:

4. 5-HT2A, 2C, 1D ____ → activates ___ neurons and increases dendritic spines in GABA neurons → increased inhibition

agonist, GABA

Cannabidiol Mechanisms:

1. Antagonizes ____ receptors → reduces calcium release from ______ stores and potentially modulates neuroinflammation

GPR55, intracellular

Cannabidiol Mechanisms:

2. Desensitizes ___ channels → reduces ____ calcium influx, further calming neuronal activity.

TRPV1, extracellular

Cannabidiol Mechanisms:

3. Inhibits adenosine reuptake (____ pumps) → increases extracellular adenosine, which reduces excitability and neurotransmitter vesicle release

ENT1

3 antiepileptic drugs that induce their own metabolism?

phenobarbital, phenytoin, carbamazepine

Phenytoin

-rapid IV administration poses a significant risk of ___ toxicity

cardiac

Stevens-Johnson Syndrome (___) and Toxic Epidermal Necrolysis (___) are life-threatening, drug-induced immune reactions causing severe skin detachment, blistering, and mucous membrane erosion

SJS, TEN

Higher risk for SJS/TEN in people of Southeast ___ descent with the HLA-B*___ allele

Asian, 1502

Teratogenicity→ risk of ___ defects and neural ___ defects with anti-seizure medications

heart, tube

Valproate → especially associated with ___ ____ (spine and spinal cord don’t form properly during early fetal development)

spina bifida