neuro: seizures/inflammatory

what is the nervous system?

highly specialized system responsible for control and integration of the body's activities

what can the nervous system be divided into?

Central Nervous System (CNS) & Peripheral Nervous System (PNS)

what does the CNS consists of?

brain and spinal cord

what does the PNS consist of?

cranial and spinal nerves & autonomic nervous system

what do ascending tracks do in the CNS?

carry sensory information from the periphery, muscles, and organs to the higher levels of the CNS

what do descending tracts do in the CNS?

carry impulses from the brain and result in voluntary muscle movement

what are the two types of cells?

neurons & neuroglia

what is the primary functional unit of the nervous system?

neuron

do neurons divide?

no but some new neurons may generate from stem cells after a brain injury

what are neuroglia cells?

• more numerous & are supportive to neuron

• can replicate

what do neuroglia provide?

support, nourishment, & protection to neurons

what are oligodendrocytes?

type of neuroglia that produces the myelin sheath for nerve fibers in the CNS and help make up the "white matter" of the brain

what are schwann cells?

type of neuroglia that myelinates the nerve fibers in the periphery

what are astrocytes?

• provide structural support to neurons and form the blood-brain barrier

• found in the "gray matter" of the brain

what happens when neurons are destroyed?

the tissue is replaced by the proliferation of neuroglial cells

what does a neuron consist of?

cell body, dendrites, axon

what is the cell body?

metabolic center of the neuron

what are dendrites?

short extensions from the body that receive and conduct nerve impulses

what are axons?

• extend varying distances from the cell body and carry nerve impulses

• they can be myelinated or unmyelinated

what is myelin sheath?

a white lipid substance that insulates and helps conduct the impulses

what does the initiation of a nerve impulse involve?

generation of an action potential

what happens after the action potential is initiated?

a series of action potentials travel along the axon

what happens when an action potential reaches the end of the nerve fiber?

it is transmitted across the junction (gap) between nerve cells by neurotransmitters

what is a synapse?

the point at which the nerve impulse jumps from one neuron to another

what is a neurotransmitter?

a chemical agent involved in the transmission of an impulse across this junction

what are examples of neurotransmitters?

acetylcholine, epinephrine, norepinephrine, serotonin, and dopamine

what is a seizure?

• brief episode of abnormal electrical activity in nerve cells of the brain cortex

• can involve motor, sensory or cognitive manifestations

what is a convulsion?

abnormal motor activity

what is seizure disorder (epilepsy)?

chronic, recurrent pattern of seizures

seizures: etiology

• primary (idiopathic)

• secondary: chemical imbalances & brain injuries

what chemical imbalances can cause seizures?

• drugs

• low blood sugar, sodium, or calcium

• low oxygen

• kidney or liver failure

what brain injuries can cause seizures?

traumatic, stroke

secondary etiology by age: children

• birth trauma

• infection (e.g., meningitis)

• congenital abnormalities

• high fevers

secondary etiology by age: middle years

• head injuries

• infections (e.g., meningitis)

• alcohol

• stimulant drugs

• medication side effects

secondary etiology by age: elderly

• brain tumors

• strokes

seizure disorder or epilepsy defined

a syndrome involving recurrent, paroxysmal seizures activity

what must a seizure have no evidence of?

reversible metabolic cause

seizures: pathogenesis

• group of abnormal neurons that spontaneously fire

• often this area is found to have scar tissue (gliosis)

• can recruit other neurons to spread

• spread can be local or global

what is emitted excessively during a seizure?

paroxysmal electrical discharges

seizure threshold

level at which seizure may be induced

what are common causes of seizures in children?

high fever, meningitis, genetics

seizure disorder: clinical manifestations

• depend on location of seizure focus

• may include some combination of sensations and perceptions, muscle movements, altered consciousness

how are seizures classified?

partial or generalized

generalized seizure

• involve both sides of the brain

• in most cases, consciousness is lost

partial seizure

• caused by focal irritations

• unilateral manifestations

• may stay focal or become generalized

• may or may not lose consciousness

parts of generalized seizures

• tonic-clonic

• absence

parts of partial seizure:

• simple partial

• complex partial

• partial that evolves into generalized

generalized seizure: tonic clonic

grand mal seizure

what is tonic clonic generalized seizure characterized by?

• loss of consciousness

• falling to ground

• stiffening of body (tonic) x 10-20 seconds

• jerking of extremities (clonic) x 30-40 seconds

symptoms of tonic clonic seizures

• salivation, tongue biting, incontinence

• NO memory afterwards

tonic phase

• prolonged skeletal muscle contraction

• "cry"

clonic phase

• alternating skeletal muscle contraction & relaxation

• arms & legs jerk

generalized seizure: absence

• petit mal

• occurs only in children

• outgrown by adolescence

what are absence seizures characterized by?

• brief staring spells

• extremely brief loss of consciousness

• may occur up to 100x/day

simple partial seizure

• no loss of consciousness

• less than 1 minute

• may involve simple motor, sensory, or other phenomena

where does a complex partial seizure usually begin?

temporal lobe

what are complex partial seizures characterized by?

• some alteration in consciousness

• lasts 45-90 seconds

• beginning = motionless and fixed gaze

• followed by “automatism” = repetitive, purposeless movements

• followed by brief period of confusion

what are the phases of a seizure?

• prodromal

• aural

• ictal

• post-ictal

prodromal phase

signs or activity that precede a seizure

aural phase

sensory warning

ictal phase

actual seizure

post-ictal phase

recovery period after a seizure

what is aura/prodrome?

• subjective sense of an impending seizure

• simple partial seizure

• important clue as to seizure focus

what are characteristics of the aura/prodome phase?

• jerking, HA, lethargy, mood alterations, palpitations

• odors (e.g., smells flowers), taste, sound

what is a complication of seizures?

status epilepticus

what is status epilepticus?

• a seizure that continues longer than usual

• continuing series of seizures without recovery period (lasts 30 minutes or more)

what type of seizure disorders are prone to status epilepticus?

• biggest concern with Tonic-clonic

• life-threatening situation

• respiratory arrest, hypoxia, brain damage, death

A patient had an aura before a recent tonic clonic seizure. Which statement best defines an aura?

subjective sense of an impending seizure

A 3-year-old is brought to the emergency department after having new onset seizure activity. What finding would indicate a cause of the seizure?

temp of 101.2

what are therapy goals for AED?

1. raise seizure threshold and reduce seizures

2. enable patient to live a normal or near normal live

AED drug considerations

• usually for long-term treatment

• must balance desire for seizure control with adverse effects

how do AED's work?

they suppress the seizure focus and spread of seizure activity

what are the four basic mechanisms of AED's?

1. suppression of sodium influx

2. suppression of calcium influx

3. blocking receptors for glutamate

4. potentiation of gamma-aminobutyric acid (GABA)

normal physiology of sodium & calcium

• play an important roles in the action potential of neurons

• to allow these ions into cells, the channels must be activated

what do Na blockers do?

• reversibly bind to sodium channels in the inactivated state (suppress influx)

• prolongs channel inactivation

examples of Na blockers

• phenytonin

• carbamazepine

• valproic acid

MOA: block glutamate receptors

• blocks action of glutamate at receptors -felbamate/topiramate

what is glutamate?

major excitatory neurotransmitter

what is GABA?

inhibitory neurotransmitter

MOA: GABA potentiation

• binds to GABA receptors

• promotes GABA release

• suppresses seizure activity

• ex: gabapentin

how do we decide what AED to use?

• selective for specific seizure disorders

• in order to effectively treat, you must have an accurate seizure diagnosis

• process of trial and error

what does phenytoin treat?

tonic-clonic and partial seizures but NOT absence

most common AEDs

• phenytoin

• levetiracetam

AEDs: newer agents

• glutamate suppressors (felbamate, topiramate)

• GABA potentiators (gabapentin, pregabalin)

traditional vs newer AEDs: efficacy

well established vs equally good

traditional vs newer AEDs: clinical experience

extensive vs less extensive

traditional vs newer AEDs: tolerability

less well tolerated vs better tolerated

traditional vs newer AEDs: drug interactions

extensive vs limited

traditional vs newer AEDs: safety in pregnancy

less safe vs safer

traditional vs newer AEDs: cost

less vs more expensive

major issues with AEDs

• monitoring plasma levels

• drug adherence: breakthrough seizures

• withdrawal: do not stop abruptly

• suicide risk

AEDs: general adverse effects

CNS depression:

• drowsiness, fatigue, sedation, confusion, cognitive changes

• children may have paradoxical hyperactivity, sleep disorders, & irritability

• GI disturbances

• motor disturbances (abnormal movements)

what is the most widely used AED?

phenytoin (dosing is highly individualized)

phenytoin MOA

inhibits hyperactive sodium channels

phenytoin indication

all forms of epilepsy except absence

what is phenytoin therapeutic range?

narrow

phenytoin adverse effcts

• hirsutism

• acne

• gingival hyperplasia

• hypertrophy of subcutaneous facial tissue

other problems with phenytoin

• teratogenic

• cardiovascular dysrhythmias (IV injection slowly & dilute in solution)

• many drug interactions (CYP inducer & subtrate)

alcohol is a CYP inhibitor. phenytoin is a substrate of the CYP system. if a patient drinks alcohol while taking phenytoin, what will happen?

the patient is at risk for phenytoin toxicity

phenytoin is an inducer of the CYP system. oral contraceptives are a substrate. if the 2 drugs are taken together, what could happen?

the patient is at risk for an unplanned pregnancy