NEURO 11-22-12

NEUROPHYSIOLOGY & TRANSIENT DISORDERS

CLINICAL APPLICATIONS: SEIZURES & EPILEPSIES
NERVOUS SYSTEM
- MAJOR FUNCTIONS: transmission, storage, &
processing of information
- Accomplished by the generation, conduction, &
integration of electrical activity & by the synthesis &
release of chemical agents
- Electrical activity in neurons & muscle cells is manifested
as electrical potentials --- membrane potentials
MEMBRANE POTENTIALS
- Difference in electrical potential between the inside &
outside of a cell
- All neurons (including their cell bodies, dendrites, &
axons), astrocytes, & muscle cells have a membrane
Effector cells
potential
- All membrane potentials result from the flow of ions
through channels in the membrane
- Ions involved include potassium (K+), sodium (Na+),
calcium (Ca2+), & chloride (Cl-)
CELL MEMBRANES
- Separate ions into different concentrations in the exterior
& interior of the cell
- Concentration of Na, Ca & Cl is higher extracellularity
- K+ & impermeable anions (A-) is higher intracellularity
- Maintenance of concentration gradients:
a. Lipid bilayer relatively impermeable to Na, K, Cl,
& Ca2+ ions
b. By active transport of these ions across the
membrane by ATP-dependent ion pumps
ION CHANNELS
- Transmembrane proteins that provide aqueous pores
which allow the movement of ions according to the
transmembrane concentration gradient
- Where ions move passively across cell membrane --permeability
- Open & close in response to specific stimuli
o Changes in membrane potential (VOLTAGEGATED)
o Binding of NT to a post-synaptic receptor
(LIGAND-GATED)
o Chemical changes in cytoplasm (CHEMICAL
GATED)
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Activation of a sensory receptor cell

MEMBRANE POTENTIALS
- Include the following
1. Resting potentials
2. Action potentials
3. Local potentials
a. Synaptic potentials
b. Generator (or receptor) potentials
c. Electronic potentials
RESTING MEMBRANE POTENTIAL
- Is the membrane potential when the cell is at rest & not
processing incoming information
- Potential depends primarily on the trans-membrane
concentration of K because the membrane at rest is
highly permeable to this ion
- Steady state depends on the activity of the ATPdependent Na-K pump, which pumps K into & Na out
of the cell
to maintain RMP of -70mV Na-K pump must be
functional
- Maintenance of the trans-membrane ion concentration
critical for survival & excitability of the cell thus
depends on energy metabolism
COMPARISON OF LOCAL POTENTIAL & ACTION
POTENTIAL
FEATURE
LOCAL
ACTION
POTENTIALS
POTENTIALS
RESPONSE TO Graded (proportional All-or-none
STIMULI
to intensity)
AMPLITUDE
Decremental
Nondecremental
PROPAGATION Remain localized
Propagate at a
distance
ION
Na+, K+, Cl-, Ca2+ Na+, K+,
CHANNELS
sometimes
INVOLVED
Ca2+
FUNCTION
Sensory transduction Conduction of
(receptor potential) electrical signals
NT effect (synaptic
at a distance
potential)
along axons
Passive propagation
of other
potentials
(electrotonic
potentials)

LOCAL POTENTIAL
- Stimuli that produce local changes in membrane potential,
that determine the ability of the membrane to reach the
threshold to trigger an action potential
- Localized and graded signals whose size varies in
proportion to the size of the stimulus
- Local potentials can be summated and integrated by single
cells ---- integral part of the processing of information
by the nervous system
- Receptor or generator potentials, synaptic potentials, and
electrotonic potentials
- GENERATOR OR RECEPTOR POTENTIALS
occur in receptor cells (touch R in skin, light R in
eye)
- SYNAPTIC POTENTIALSoccur at synapses, elicited
by binding of a NT to a R
- ELECTROTONIC POTENTIALSfrom any
localized change in membrane potential --- elicits a
current flow to surrounding areas of membrane --produces a small change in membrane potential of
adjacent areas
- result from transient changes in permeability of ion
channels, which may either increase or decrease the
ability of the cell membrane to reach the threshold to
trigger an AP
- If RMP is depolarized from 80 to 70 mV during the
local potential, the local potential has an amplitude of
10 mV
- Potential change is one of decreasing negativity (or of
depolarization), but it could also be one of increasing
negativity (or of hyperpolarization)
- Stimuli that increase permeability (open the channel) to
sodium or calcium produce local potentials that make
the membrane potential positive with respect to the
resting potential --- DEPOLARIZATION (cell more
excitable)
- Stimuli that increase permeability to K+ or Cl produce
local potentials that make the membrane potential
negative with respect to the resting potential --HYPERPOLARIZATION (cell less excitable)
SUMMATION
- Summated potentials may reach threshold and produce an
AP when single potentials individually are subthreshold
- When a stimulus is applied to a localized area of the
membrane, the change in membrane potential has both
a temporal and spatial distribution
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SUMMATION OF LOCAL POTENTIALS IN A

NEURON
SPATIAL SUMMATION occurs when an increasing
number of nerve terminals release more neurotransmitter to
produce larger excitatory postsynaptic potentials (EPSPs).
TEMPORAL SUMMATION occurs when a single terminal
discharges repetitively more rapidly to produce larger EPSPs.
ACTION POTENTIALS
- electrical signals or nerve impulses by which information
is conducted from one area to another within a single
cell
- All-or-none change in membrane potential in the body or
axon of a neuron or within a muscle fiber
- Amplitude does not depend on the intensity of the
stimulus
- Generated in neuronal cell bodies or axons and conducted
by axons, & conduction velocity depends on the
diameter of axon & presence of myelin sheath
ACCOMMODATION
- If a current or voltage is applied to a membrane for more
than a few milliseconds, the ion channels revert to their
resting state, changing ionic conductance of the
membrane in a direction to restore the resting potential
to baseline value
- EXCITABILITY - the ability of a neuron or muscle cell
to generate an action potential which depends on the
ability of the membraneto reach a threshold to open the
voltage-gated Na+ channel
- the threshold is approximately 10 mV positive from the
resting potential
- Once the local potential reaches threshold, an AP is
generated

the more intense the stimulus, the larger the

local potential and the higher the frequency of
discharge of APs
APs are conducted along axons
PROPAGATION - another important characteristic of
AP
o permits NS to transmit information from one
area to another
o velocity depends on the distribution of ion
channels, diameter of axon, and presence or
not of a myelin sheath
SALTATORY CONDUCTION - an AP at one node of
Ranvier produces sufficient longitudinal current flow to
depolarize adjacent nodes to threshold, thereby
propagating the AP along the nerve in a skipping
manner
Sodium is the channel active in the nodes of Ranvier
On reaching the pre-synaptic axon terminal, the AP elicits
a membrane depolarization that results in opening of
voltage-gated Ca++ channels
Influx of Ca++ into the pre-synaptic terminal triggers the
release of NT which transmit information from one cell
to another by converting the electrical signal (action
potential) into a chemical signal (neurotransmitter
release) and then back into an electrical signal (synaptic
potential)
Synaptic potentials produce electrotonic potentials, which
can then initiate another action potential
NT binds to a receptor molecule in the postsynaptic cell
membrane --- triggering synaptic potential
o according to type of NT and R --- may or
the excitability of the postsynaptic neuron by
eliciting depolarization or hyperpolarization of
its membrane
o

SYNAPTIC TRANSMISSION
- A SYNAPSE is a specialized contact zone where one
neuron communicates with another neuron
- NEUROEFFECTOR JUNCTION - contact zone
between an axon terminal and a muscle fiber or other
nonneural target
- 2 TYPES OF SYNAPSES: chemical & electrical
- CHEMICAL SYNAPSES are the more common form of
communication in the NS. Makes use of
neurotransmitters
- ELECTRICAL makes use of ions
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POST SYNAPTIC POTENTIALS

RECEPTOR
IONIC
MECHANISM
NICOTINIC
Na or Ca
IONOTROPIC
conductance
GLUTAMATE
GABAA GLYCINE Cl conductance
G PROTEIN K conductance
COUPLED R
K conductance

EFFECT
Fast excitation
Fast inhibition
Slow excitation
Fast inhibition

2 TYPES OF POST-SYNAPTIC EFFECT

1. CLASSIC NEUROTRANSMISSION
- fast excitation (excitatory postsynaptic potential) or
inhibition (inhibitory postsynaptic potential) potentials allow
rapid, point-to-point transfer of excitatory or inhibitory
information between cells mediated through ion channel R
(ligand-gated)
- Ion channels that open in response to the chemical
transmitter, allowing the rapid influx of cations
(Na+,Ca2+) or Cl, are called ligand-gated receptors
2. NEUROMODULATION
- a change in the ability of the postsynaptic cell to
respond to other neurotransmitters
- activation of these G protein-coupled receptors does
not elicit fast excitatory or inhibitory postsynaptic responses but
rather elicits a change in neuronal excitability
- K+ channels are the main target for neuromodulatory
signals
COMPARISON OF CLASSIC NEUROTRANSMISSION &
NEUROMODULATION
FEATURE
CLASSIC
NEURO
NEURO
MODULATION
TRANSMISSION
FUNCTION
Rapid synaptic
Regulation of
excitation or
neuronal
inhibition
excitability & NT
release
RECEPTOR
Ion channel R
G-protein coupled
MECHANISMS
(ligand-gated)
R
IONIC
Opening of Na or
Opening or closing
MECHANISMS
Ca channels (fast
of voltage-gated K
EPSP) or Cl
or Ca channels
channels (fast
IPSP)

CLINICAL CORRELATIONS
- Transient alterations in function are the result of
reversible disturbances in neuronal excitability, the
ability to propagate action potentials, or communication
by chemical synapses
- reflect abnormalities in resting, local, or action potentials
that are due to the failure of ion pumps to maintain
electrochemical gradients, to impaired function of ion channels,
or to alterations in the ionic composition of the ECF
TRANSIENT DISORDERS
NEURONAL
FOCAL
EXCITABILITY
DISORDERS
INCREASED () Focal seizure
Tonic spasm
Muscle cramp
Paresthesia
Paroxysmal pain
DECREASED () TIA
Migraine aura
Transient
mononeuropathy

GENERALIZED
DISORDER
Generalized seizure
Tetany

Syncope
Concussion
Cataplexy
Periodic paralysis

DEFINITION OF TERMS
SEIZURE transient & reversible alteration of behavior caused
by a paroxysmal, abnormal & excessive neuronal discharge
(symptom or sign)
EPILEPSY 2 or more seizures not directly provoked by
intracranial infection, drug withdrawal, acute metabolic changes
or fever (diagnosis)
CONVULSION intense paroxysm of involuntary repetitive
muscular contractions (motor component of seizure)
INCIDENCE OF EPILEPSY
- PREVALENCE: 5-10 per 1000
- 44 cases per 100,000 persons each year (US data)
- 10% will experience a seizure by age 80
- Bimodal distribution (1st yr of life & over 60 y/o)
- 2/3 of all epileptic seizures begin in childhood
- 75% unclear etiology - idiopathic
CLASSIFICATION OF SEIZURES
- SEVERAL WAYS TO CLASSIFY SEIZURES:
According to
o PRESUMED ETIOLOGY idiopathic
(primary), or symptomatic (secondary)
o Site of origin
o CLINICAL FORM generalized or focal
o FREQUENCY isolated, cyclic, or repetitive
o Special electrophysiologic correlates
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- DISTINCTION IS MADE BETWEEN

o Classification of seizures (clinical
manifestations of epilepsy; grandma, petit mal
etc) &
o Classification of epilepsies or epileptic
syndromes which are disease constellations
INTERNATIONAL CLASSIFICATION OF EPILEPTIC
SEIZURES
1. PARTIAL/FOCAL: occur within discrete regions of the
brain can localize the lesion
a. SIMPLE PARTIAL: motor, somatosensory or
special sensory, autonomic, psychic-cognitive
b. COMPLEX PARTIAL: with impaired
consciousness
2. GENERALIZED: arise from both cerebral hemispheres
simultaneously; bilaterally symmetrical & without local
onset
a. Absence
b. Myoclonic
c. Clonic
d. Tonic
e. Atonic
f. Tonic-Clonic
3. SPECIAL EPILEPTIC SYNDROMES
a. Myoclonus & myoclonic seizures
b. Reflex epilepsy
c. Acquired aphasia with convulsive disorder
d. Febrile & other seizures of infancy &
childhood
e. Hysterical seizures
INTERNATIONAL CLASSIFICATION OF EPILEPSY &
EPILEPSY SYNDROMES
1. LOCALIZATION-RELATED
a. Idiopathic
b. Symptomatic
2. GENERALIZED EPILEPSIES & SYNDROMES
a. Idiopathic, with age related inset or Primry
Generalized (BNFC, absence, JME, etc.)
b. Symptomatic or Secondary Generalized (West
syndrome, Lennox-Gastaut syndrome)

IDIOPATHIC EPILEPSY
primary epilepsy
there is no underlying cause
identified other than a
hereditary predisposition
Presumed to be of genetic
origin
Often with a (+) family
history
As a rule, begin early in life
Not associated with evidence
of structural, nervous or
mental disorders
Normal interictal EEG
background
Favorable response to antiepileptic therapy
Benign prognosis with
spontaneous resolution in time

SECONDARY EPILEPSY
secondary epilepsy
Seizures have an identifiable &
acquired structural cause
There is evidence for focal or
generalized neurological
disease
Mental retardation or
deterioration may occur
Epilepsy may evolve with in
frequency, duration or spread
of the seizures
Interictal EEg background is
abnormally slow
Spontaneous resolution of
epilepsy is unusual
Prognosis depends on the
underlying neurologic
condition

PARTIAL SEIZURES
A. SIMPLE PARTIAL SEIZURES
- Begin with motor, sensory or autonomic phenomena
depending on the cortical region affected
- May involve contiguous regions of the brain
(JACKSONIAN MARCH)
- Consciousness is usually preserved
- Autonomic symptoms (pallor, flushing, sweating,
piloerection, vomiting, incontinence)
- May cause transient hemiparesis (TODDS)
COMPLEX PARTIAL SEIZURES (TEMPORAL LOBE
SEIZURE)
- Aura followed by impaired consciousness; patient may
appear awake but lost contact with environment & do
not respond to instructions or questions for few
minutes; usually stare or remain motionless, or engage in
repetitive semi-purposeful motor behaviors called
AUTOMATISMS chewing, grimacing, gesturing, lip
smacking, snapping fingers, may become hostile or
aggressive if restrained
- Seizure discharge arise from the temporal lobe or medial
frontal lobe
- Symptoms take many forms but usually are stereotyped
- Epigastric symptoms are common
- Affective (fear), cognitive (dj vu), sensory (olfactory
hallucinations)

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GENERALIZED TONIC-CLONIC SEIZURES

TONIC PHASE
CLONIC PHASE
RELAXING
PHASE
Initial
Alternating muscle
Regaining
manifestations are contraction &
consciousness
unconsciousness & relaxation of
maybe followed
tonic contractions symmetric limb jerking by postictal
of limb muscles
(30-60 sec)
confusion &/or
(10-30 sec)
Ventilator efforts
headache
Expirationreturn immediately
Full orientation
induced
after cessation of tonic in 10-30 mins
vocalizations (cry
phase & cyanosis clears (longer with
or moan)
Mouth my froth with
status or preCyanosis
saliva
existing structural
(blue/violet)
Muscles becomes
or metabolic
Contraction of
flaccid
brain disorders)
masticatory
Sphincter relaxation
muscles
may produce urinary
Patients falls to
incontinence
the ground
May remain
unconscious for
variable period of time
- PE usually normal in IDIOPATHIC EPILEPSY or
SEIZURES OF METABOLIC ORIGIN
- Pupils always react to light
- Transient unilateral weakness in post-ictal period
ABSENCE, PETIT MAL SEIZURES
- Petit mal seizures; pyknoepilepsy (pykno compact or
dense)
- FEATURES: brevity, frequency, paucity of motor activity
- a moment of absentmindedness or day dreaming
- Without a warning sudden interruption of
consciousnessstares & briefly stops talking or ceases
to respond
- 10% are completely motionless; the rest have fine clonic
(myoclonic) movements of eyelids, facial muscles or
fingers, at a rate of 3 per second
- EEG pattern of generalized 3 per second spike & wave
pattern
- After 2-10 seconds, or longer, patient reestablishes full
contact with the environment & resumes pre-seizure
activity
- Hyperventilation may induce an attack
- Rarely begins before 4 yrs, or after puberty
- As many as several hundred may occur in a day
- Attacks tend to diminish during adolescence & then
disappear, to be replaced by other forms of generalized
seizures

OTHER GENERALIZED SEIZURE TYPES

- Tonic seizures
- Clonic Seizures
- Myoclonic Seizures
- Atonic seizures

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