Nervous System Disorders and Their Molecular Mechanisms

Actuality of the lectureActuality of the lecture
 The nervous system as a main regulatory system of an organism in this orThe nervous system as a main regulatory system of an organism in this or
that measure participates in pathogenesis of each diseases. The earliest andthat measure participates in pathogenesis of each diseases. The earliest and
obligatory form of participation of the nervous system in pathology isobligatory form of participation of the nervous system in pathology is
defensive and adaptive the response. The protective reflexes (cough,defensive and adaptive the response. The protective reflexes (cough,
vomiting), protective inhibition, response hypotalamo-hypophysial-adrenalvomiting), protective inhibition, response hypotalamo-hypophysial-adrenal
system belong to such responses.system belong to such responses.
 At the same time during development of diseases the nervous systemAt the same time during development of diseases the nervous system
becomes the object of a defeat itself. It is defensive and adaptive thebecomes the object of a defeat itself. It is defensive and adaptive the
response of the damaged nervous system are reduced, and it becomes aresponse of the damaged nervous system are reduced, and it becomes a
source of pathological, harmful to an organism reflexes. Itself graving andsource of pathological, harmful to an organism reflexes. Itself graving and
character of violations of nervous activity depend on localization ofcharacter of violations of nervous activity depend on localization of
pathological process and appear as a complex of diverse symptoms.pathological process and appear as a complex of diverse symptoms.
Frequently there is a pain, which on the essence is typical pathologicalFrequently there is a pain, which on the essence is typical pathological
process, but at the same time has signal and adaptive significance. Theprocess, but at the same time has signal and adaptive significance. The
disturbance of nervous activity is always reflected in the function of internaldisturbance of nervous activity is always reflected in the function of internal
organs.organs.
 Several neurologic disorders in which some of the molecular mechanisms ofSeveral neurologic disorders in which some of the molecular mechanisms of
pathogenesis are known are discussed later in this chapter including motorpathogenesis are known are discussed later in this chapter including motor
neuron disease, Parkinson's disease, myasthenia gravis, epilepsy, Alzheimer'sneuron disease, Parkinson's disease, myasthenia gravis, epilepsy, Alzheimer's
disease, and stroke.disease, and stroke.
 Exciting advances in our understanding and overlap of these diseases areExciting advances in our understanding and overlap of these diseases are
leading to new therapeutic targets and the hope of better treating theseleading to new therapeutic targets and the hope of better treating these
devastating diseases.devastating diseases.

CONTENTCONTENT
• Nervous System: NeuronsNervous System: Neurons
• Division of the Nervous SystemDivision of the Nervous System
• Pain: features of pain as a kind of sensitivity. Etiology andPain: features of pain as a kind of sensitivity. Etiology and
pathogenesis of pain. Antinociceptive systemspathogenesis of pain. Antinociceptive systems
• Upper Motor NeuronsUpper Motor Neurons and Disordersand Disorders
• Sensory LossSensory Loss
• Spinal Cord InjuriesSpinal Cord Injuries
• DysphasiaDysphasia
• Diseases of the Basal GangliaDiseases of the Basal Ganglia
• Disorders of integrative function of CNS.Disorders of integrative function of CNS.
• Anxiety Disorders; Mood Disorders; SchizophreniaAnxiety Disorders; Mood Disorders; Schizophrenia
• Acute and chronic disturbances of brain circulation. StrokeAcute and chronic disturbances of brain circulation. Stroke
• Cerebral infarction and cerebral hemorrhage.Cerebral infarction and cerebral hemorrhage.
• Seizure disorders. Epilepsy; Sleep Disorders; AphasiasSeizure disorders. Epilepsy; Sleep Disorders; Aphasias
• Disorders of Memory. Alzheimer’s Disease. Creutzfeldt–Disorders of Memory. Alzheimer’s Disease. Creutzfeldt–
Jakob diseaseJakob disease

FunctionFunction of neuronsof neurons
 A). Sensory inputA). Sensory input
 B). IntegrationB). Integration
 C). ResponseC). Response

A). Non nervousA). Non nervous or glial cellsor glial cells..
1). Astrocytes1). Astrocytes
2). Microglia2). Microglia
3). Ependymal3). Ependymal
4). Oliodendrocytes4). Oliodendrocytes
5). Satellite cells5). Satellite cells
6).6). Schwann cellsSchwann cells form myelin sheathsform myelin sheaths
Types of cellsTypes of cells

Types ofTypes of
cellscellsB). NeuronsB). Neurons
1). Structure1). Structure
II).). cell bodycell body oror somasoma -- endoplasmicendoplasmic
reticulum called thereticulum called the nissl bodynissl body..
IIII).). ProcessesProcesses oror tracts (nerves)tracts (nerves)
a).a). Dendrites:Dendrites: input regioninput region
b).b). Axon:Axon: Carries information awayCarries information away
c).c). Synaptic knobsSynaptic knobs oror AxonalAxonal
terminalsterminals.. ReleasesReleases
neurotransmitters.neurotransmitters.
2).2). AxonsAxons
a).a). myelin sheathmyelin sheath -- protects andprotects and
electrically insulates fibers conductelectrically insulates fibers conduct
nerve impulses faster thannerve impulses faster than
nonmylenated fibers.nonmylenated fibers.
b).b). nodes of Ranviernodes of Ranvier::
spaces between the sheathsspaces between the sheaths
The action potential skips to the nodesThe action potential skips to the nodes

Nerve ImpulseNerve Impulse
A). TermsA). Terms
1).1). Resting membrane PotentialResting membrane Potential::
 PolarizedPolarized
2).2). DepolarizationDepolarization::
 Change in ion concentrationChange in ion concentration
3).3). HyperpolarizationHyperpolarization
 Change in ion concentration insideChange in ion concentration inside
becomes more negativebecomes more negative
4).4). Graded PotentialGraded Potential
 Localized change in ion; subthresholdLocalized change in ion; subthreshold
5).5). Action PotentialAction Potential
 Change in ion concentration thatChange in ion concentration that
does not decrease over distance.does not decrease over distance.
B).B). Action PotentialAction Potential
Stages of an Action PotentialStages of an Action Potential
polarized resting potentialpolarized resting potential
depolarizesdepolarizes
repolarizesrepolarizes
undershoot phaseundershoot phase
UndershooUndershoott :: the K+ channels stay openthe K+ channels stay open
once resting potential is reached;once resting potential is reached;
hyperpolarizing the cell.hyperpolarizing the cell.

NerveNerve ImpulseImpulse
C).C). PropagationPropagation
 Cannot be depolarized again until the membrane hasCannot be depolarized again until the membrane has
reached resting potential. The action potential moves at areached resting potential. The action potential moves at a
constant velocityconstant velocity
D).D). All or none phenomenonAll or none phenomenon
 Not all depolarizations result in action potentialsNot all depolarizations result in action potentials.. TheThe
depolarization must reach thedepolarization must reach the threshold pointthreshold point
E).E). Refractory periodRefractory period
 AAbsolute refractory periodbsolute refractory period cannot respond to anothercannot respond to another
stimuli.stimuli.
 RRelative refractory periodelative refractory period -- tthe threshold is higherhe threshold is higher
F). Impulse VelocityF). Impulse Velocity
 Strong stimuli result in more nerve impulses NotStrong stimuli result in more nerve impulses Not
stronger impulses or fasterstronger impulses or faster

SynapseSynapse –– junction that carriesjunction that carries
information between neuronsinformation between neurons
 A). TypesA). Types
1). Electrical synapse: ions to cross junction1). Electrical synapse: ions to cross junction
2). Chemical synapse2). Chemical synapse
 neurotransmittersneurotransmitters
B). Termination of neurotransmitterB). Termination of neurotransmitter
 1). Degradation enzymes1). Degradation enzymes
 2). Neurotransmitter reabsorbed2). Neurotransmitter reabsorbed
 3). Diffusion of the neurotransmitter3). Diffusion of the neurotransmitter
ImpulseImpulse
releasesreleases Ca++ (in neuron)Ca++ (in neuron)
± neurotransmitter released ± binds to receptors± neurotransmitter released ± binds to receptors ±±
ion channels open on postsynaptic membraneion channels open on postsynaptic membrane

Neurotransmitters
A). Acetylcholine (ACh)
B). Biogenic Amines
• 1). Dopamine
• 2). Norepinephrine
• 3). Epinephrine
• 4). Serotonin
C). Amino Acids
D). Peptides
• 1). endorphins
E). Novel or Miscellaneous

Division of the Nervous
System
A). Central Nervous
System: (CNS)
• Brain and Spinal Cord
only
B). Peripheral Nervous
System
• Outside CNS
1). Sensory or afferent
division:
• Carries impulses to CNS
2). Motor or efferent
division
• Carries impulses from the
CNS.
I). Somatic Nervous System
• voluntary
II). Autonomic Nervous
System
• involuntary
• a. Parasympathetic
• b. Sympathetic

The SympatheticThe Sympathetic
Nervous SystemNervous System
 TheThe first fibersfirst fibers of the sympathetic nerves, called theof the sympathetic nerves, called the
preganglionic fiberspreganglionic fibers, leave from the thoracic or lumbar, leave from the thoracic or lumbar
regions of the spine.regions of the spine.
 Soon afterSoon after leaving the spineleaving the spine, a preganglionic fiber, a preganglionic fiber joinsjoins
other preganglionic fibersother preganglionic fibers to form anto form an autonomic ganglionautonomic ganglion..
 At this point, theAt this point, the preganglionic fiber synapsespreganglionic fiber synapses on theon the
second nerve fiber of the systemsecond nerve fiber of the system, the, the postganglionic fiberpostganglionic fiber,,
andand releases acetylcholinereleases acetylcholine, which causes the, which causes the
postganglionic fiber to fire anpostganglionic fiber to fire an action potentialaction potential..
 From theFrom the autonomic gangliaautonomic ganglia, the postganglionic fiber travels, the postganglionic fiber travels
to itsto its target organtarget organ, the muscle or gland., the muscle or gland.
 TheThe sympathetic postganglionic fibersympathetic postganglionic fiber usually releases theusually releases the
neurotransmitter norepinephrineneurotransmitter norepinephrine.. Target organ receptors forTarget organ receptors for
norepinephrinenorepinephrine are calledare called adrenergic receptorsadrenergic receptors..

The Parasympathetic Nervous SystemThe Parasympathetic Nervous System
 The fibers of the parasympathetic nervous systemThe fibers of the parasympathetic nervous system (PNS)(PNS)
leave the brain in the cranial nervesleave the brain in the cranial nerves oror leave the spinal cordleave the spinal cord
from the sacral areafrom the sacral area..
 TheThe preganglionic fiberpreganglionic fiber of theof the PNSPNS is typically long and travelsis typically long and travels
to an autonomic ganglionto an autonomic ganglion locatedlocated near the target organnear the target organ..
 Preganglionic parasympathetic nervesPreganglionic parasympathetic nerves releaserelease acetylcholineacetylcholine
thatthat then stimulates the postganglionic fiberthen stimulates the postganglionic fiber..
 TheThe parasympathetic postganglionic fiberparasympathetic postganglionic fiber then travels a shortthen travels a short
distancedistance to its target tissueto its target tissue, a, a muscle or a glandmuscle or a gland. This nerve. This nerve
also releases acetylcholinealso releases acetylcholine..
 Preganglionic acetylcholine receptorsPreganglionic acetylcholine receptors for sympathetic andfor sympathetic and
parasympathetic fibersparasympathetic fibers are calledare called nicotinic receptorsnicotinic receptors ..
 Postganglionic acetylcholine receptorsPostganglionic acetylcholine receptors are calledare called muscarinicmuscarinic
receptorsreceptors. These names relate to the experimental. These names relate to the experimental
stimulation of the receptors bystimulation of the receptors by nicotinenicotine andand muscarinemuscarine (a(a
mushroom poison).mushroom poison).

The Autonomic Nervous System
Structure Sympathetic Stimulation Parasympathetic Stimulation
Iris (eye muscle) Pupil dilation Pupil constriction
Salivary Glands Saliva production reduced Saliva production increased
Oral/Nasal Mucosa Mucus production reduced Mucus production increased
Heart Heart rate and force increased Heart rate and force decreased
Lung Bronchial muscle relaxed Bronchial muscle contracted
Stomach Peristalsis reduced Gastric juice secreted; motility
increased
Small Intestine Motility reduced Digestion increased
Large Intestine Motility reduced Secretions and motility increased
Liver Increased conversion of glycogen to
glucose
---
Kidney Decreased urine secretion Increased urine secretion
Adrenal medulla Norepinephrine and epinephrine
secreted
---
Bladder Wall relaxed Sphincter closed Wall contracted Sphincter relaxed

THE SOMATOSENSORY SYSTEMTHE SOMATOSENSORY SYSTEM
■■ The somatosensory system relays information to theThe somatosensory system relays information to the
CNS about four major body sensations:CNS about four major body sensations:
touch,touch,
temperature,temperature,
pain,pain,
body positionbody position..
Stimulation of receptorsStimulation of receptors on regions of the body wall ison regions of the body wall is
required torequired to initiate the sensory response.initiate the sensory response.
■■ The system is organized intoThe system is organized into dermatomesdermatomes, with each, with each
segment supplied by asegment supplied by a single dorsal root ganglionsingle dorsal root ganglion thatthat
sequentially relays the sensory information tosequentially relays the sensory information to thethe
spinal cord, the thalamus, and the sensoryspinal cord, the thalamus, and the sensory cortexcortex..
■■ Two pathwaysTwo pathways carry sensory information throughcarry sensory information through thethe
CNSCNS. The. The discriminative pathwaydiscriminative pathway crosses in thecrosses in the
medulla and relaysmedulla and relays touchtouch andand body positionbody position. The. The
anterolateral pathwayanterolateral pathway crosses in the spinal cordcrosses in the spinal cord andand
relaysrelays temperaturetemperature andand pain sensationpain sensation fromfrom thethe
opposite side of the body.opposite side of the body.

Kinds of SensitivityKinds of Sensitivity
1.1. PainfulPainful
2.2. TemperatureTemperature
3.3. TactileTactile
4.4. ProprioceptiveProprioceptive

DEFINITION OF PAINDEFINITION OF PAIN
 PAINPAIN –– it is typical pathological processit is typical pathological process,,
whichwhich was generated during evolutionwas generated during evolution andand
which arise owing to action on an organismwhich arise owing to action on an organism
painfulpainful ((nociceptivenociceptive)) irritantirritant oror weakeningweakening
ofof antipainfulantipainful ((antinociceptiveantinociceptive)) systemsystem
 PainPain is an “unpleasant sensory andis an “unpleasant sensory and
emotional experience associatedemotional experience associated withwith
potential tissue damage, or described inpotential tissue damage, or described in
terms ofterms of such damage.”such damage.”

CLASSIFICATION OF
PAIN
• Physiological pain
• Pathological pain
• Acute pain
• Chronical pain
MEDIATORS OFMEDIATORS OF
PAINPAIN• Substanse Р
• Glutamic acid
• Cholecystokinin
• Neurotensin

TYPES OF PAINTYPES OF PAIN
 Pain can be classified according to
 location,
 site of referral, and
 duration.
 Cutaneous pain is a sharp, burning pain that has its
origin in the skin or subcutaneous tissues.
 Deep pain is a more diffuse and throbbing pain that
originates in structures such as the muscles, bones,
and tendons and radiates to the surrounding
tissues.
 Visceral pain is a diffuse and poorly defined pain
that results from stretching, distention, or ischemia
of tissues in a body organ.
 Referred pain is pain that originates at a visceral site
but is perceived as originating in part of the body
wall that is innervated by neurons entering the same
segment of the nervous system.
 Acute pain usually results from tissue damage and
is characterized by autonomic nervous system
responses.
 Chronic pain is persistent pain that is accompanied
by loss of appetite, sleep disturbances, depression,

PAIN SENSATION
■ Pain is both a protective and an unpleasant physical and emotionally
disturbing sensation originating in pain receptors that respond to a
number of stimuli that threaten tissue integrity.
■ There are two pathways for pain transmission:
• The fast pathway for sharply discriminated pain that moves directly
from the receptor to the spinal cord using myelinated Aδ fibers and from
the spinal cord to the thalamus using the neospinothalamic tract
• The slow pathway for continuously conducted pain that is transmitted
to the spinal cord using unmyelinated C fibers and from the spinal cord
to the thalamus using the more circuitous and slower-conducting
paleospinothalamic tract.
■ The central processing of pain information includes transmission to the
somatosensory cortex, where pain information is perceived and
interpreted; the limbic system, where the emotional components of pain
are experienced; and to brain stem centers, where autonomic nervous
system responses are recruited.
■ Modulation of the pain experience occurs by way of the endogenous
analgesic center in the midbrain, the pontine noradrenergic neurons,
and the nucleus raphe magnus in the medulla, which sends inhibitory
signals to dorsal horn neurons in the spinal cord.

Primary pain pathways
NociceptiveNociceptive
stimulistimuli
Somesthetic association cortexSomesthetic association cortex
(perception and meaning)(perception and meaning)
Limbic cortexLimbic cortex
(emotional experience)(emotional experience)
PontinePontine
noradrenergic neuronsnoradrenergic neurons
Primary somesthetic cortexPrimary somesthetic cortex
(discrimination: location and intensity)(discrimination: location and intensity)
Medullary raphe nucleusMedullary raphe nucleus
Thalamus (sensation)Thalamus (sensation)
Somesthetic nucleiSomesthetic nuclei
Spinal cord and dorsal hornSpinal cord and dorsal horn
pain modulating circuitspain modulating circuits
Periaqueductal gray (PAG)Periaqueductal gray (PAG)
(endogenous analgesic center)(endogenous analgesic center)
Medullary NRMMedullary NRM
NeospinothalamictractNeospinothalamictract
(sharp,brightpain)(sharp,brightpain)
PaleospinothalamictractPaleospinothalamictract
(dull,achingpain)(dull,achingpain)
Primary touch fibers
A-delta
(fast)
C-fiber
(slow)

Characteristics ofCharacteristics of
Acute and Chronic PainAcute and Chronic Pain
Characteristic Acute Pain Chronic Pain
Onset Recent Continuous or intermittent
Duration Short duration (<6 months) 6 months or more
Autonomic responses
Consistent with sympathetic fight-
or-flight response*
Increased heart rate
Increased stroke volume
Increased blood pressure
Increased pupillary dilation
Increased muscle tension
Decreased gut motility
Decreased salivary flow (dry mouth)
Absence of autonomic
responses
Psychological
component
Associated anxiety
Increased irritability
Associated depression
Somatic preoccupation
Withdrawal from outside
interests
Decreased strength of
relationships
Other types of
response
Decreased sleep
Decreased libido
Appetite changes

Pain Threshold and Tolerance
Cando Baseline Dolorimeter
 Pain threshold and tolerance affect an
individual’s response to a painful stimulus.
Although the terms often are used
interchangeably, pain threshold and pain
tolerance have distinct meanings. Pain
threshold is closely associated with tissue
damage and the point at which a stimulus is
perceived as painful.
 Pain tolerance relates more to the total pain
experience; it is defined as the maximum
intensity or duration of pain that a person is
willing to endure before the person wants
something done about the pain.
Psychological, familial, cultural, and
environmental factors significantly influence
the amount of pain a person is willing to
tolerate. The threshold to pain is fairly uniform
from one person to another, whereas pain
tolerance is extremely variable. Separation
and identification of the role of each of
these two aspects of pain continue to pose
fundamental problems for the pain
management team and for pain researchers.

Alterations in Pain Sensitivity
 Hypersensitivity (i.e., hyperesthesia) or increased painfulness (i.e.,
hyperalgesia)
 Primary hyperalgesia occurs at the site of injury.
 Secondary hyperalgesia occurs in nearby uninjured tissue.
 Hyperpathia is a syndrome in which the sensory threshold is raised,
but when it is reached, continued stimulation, especially if repetitive,
results in a prolonged and unpleasant experience. This pain can be
explosive and radiates through a peripheral nerve distribution. It is
associated with pathologic changes in peripheral nerves, such as
localized ischemia.
 Spontaneous, unpleasant sensations called paresthesias occur with
more severe irritation (e.g., the pins-and-needles sensation that
follows temporary compression of a peripheral nerve).
 The general term dysesthesia is given to distortions (usually
unpleasant) of somesthetic sensation that typically accompany partial
loss of sensory innervation.

Alterations in Pain Sensitivity
• Severe pathologic processes can result in reduced or lost
tactile (e.g., hypoesthesia, anesthesia), temperature (e.g.,
hypothermia, athermia), and pain sensation (i.e.,
hypalgesia).
• Analgesia is the absence of pain on noxious stimulation or
the relief of pain without loss of consciousness. The inability to
sense pain may result in trauma, infection, and even loss of a
body part or parts. Inherited insensitivity to pain may take the
form of congenital indifference or congenital insensitivity to
pain.
• Allodynia (Greek allo, “other,” and odynia, “painful”) is the
term used for the puzzling phenomenon of pain that follows a
non-noxious stimulus to apparently normal skin. This term is
intended to refer to instances in which otherwise normal
tissues may be abnormally innervated or may be referral sites
for other loci that give rise to pain with non-noxious stimuli.
• Trigger points are highly localized points on the skin or
mucous membrane that can produce immediate intense pain
at that site or elsewhere when stimulated by light tactile
stimulation.

CHRONICAL PAINFUL
SYNDROMES
Phantom pain
Causalgia
Neuralgia
Eccentric pain
Projectional pain

NeuralgiaNeuralgia
 NeuralgiaNeuralgia is characterized by severe, brief,is characterized by severe, brief,
often repetitive attacksoften repetitive attacks of lightning-like orof lightning-like or
throbbing pain. It occurs along the distributionthrobbing pain. It occurs along the distribution ofof
a spinal or cranial nerve and usually isa spinal or cranial nerve and usually is
precipitatedprecipitated by stimulation of the cutaneousby stimulation of the cutaneous
region supplied by that nerve.region supplied by that nerve.
 Trigeminal Neuralgia.Trigeminal Neuralgia.
Trigeminal neuralgia, orTrigeminal neuralgia, or tictic
douloureuxdouloureux,, is one of theis one of the
most common and severemost common and severe
neuralgias. It is manifestedneuralgias. It is manifested
byby facial ticsfacial tics oror grimacesgrimaces
and characterized byand characterized by
stabbing,stabbing, paroxysmalparoxysmal
attacks of pain that usuallyattacks of pain that usually
are limited to the unilateralare limited to the unilateral
sensory distribution of onesensory distribution of one
or more branches of theor more branches of the
trigeminal nerve, mosttrigeminal nerve, most
often the maxillary oroften the maxillary or
mandibular divisions.mandibular divisions.

Postherpetic Neuralgia.Postherpetic Neuralgia.
Postherpetic pain is painPostherpetic pain is pain
that persiststhat persists as aas a
complication of herpescomplication of herpes
zoster or shingles. Itzoster or shingles. It
describes thedescribes the presence ofpresence of
pain more than 1 monthpain more than 1 month
after the onset of theafter the onset of the
acuteacute attack.attack.
Postherpetic neuralgiaPostherpetic neuralgia
develops in from 10% todevelops in from 10% to
70% of70% of patients withpatients with
shingles; the riskshingles; the risk
increases with age.increases with age.
The pain ofThe pain of postherpeticpostherpetic
neuralgia occurs in theneuralgia occurs in the
areas of innervation ofareas of innervation of
thethe infected gangliainfected ganglia..
During the acute attack ofDuring the acute attack of
herpes zosterherpes zoster, the, the
reactivated virus travelsreactivated virus travels
from the ganglia to thefrom the ganglia to the
skin of the correspondingskin of the corresponding
dermatomes, causingdermatomes, causing
localized vesicularlocalized vesicular
eruptioneruption and hyperpathiaand hyperpathia
((i.e.i.e., abnormally, abnormally
exaggerated subjectiveexaggerated subjective
responseresponse to pain).to pain).

Phantom Limb Pain
• Phantom limb pain, a type of
neurologic pain, follows
amputation of a limb or part of a
limb. As many as 70% of those
who under amputation
experience phantom pain.
• The pain often begins as
sensations of tingling, heat and
cold, or heaviness, followed by
burning, cramping, or shooting
pain. It may disappear
spontaneously or persist for
many years. One of the more
troublesome aspects of phantom
pain is that the person may
experience painful sensations
that were present before the
amputation, such as that of a
painful ulcer or bunion.

• Several theories have been proposed as to the causes of phantom pain.
• One theory is that the end of a regenerating nerve becomes trapped in the scar
tissue of the amputation site. It is known that when a peripheral nerve is cut, the scar
tissue that forms becomes a barrier to regenerating outgrowth of the axon. The
growing axon often becomes trapped in the scar tissue, forming a tangled growth
(i.e., neuroma) of smalldiameter axons, including primary nociceptive afferents and
sympathetic efferents. It has been proposed that these afferents show increased
sensitivity to innocuous mechanical stimuli and to sympathetic activity and circulating
catecholamines.
• A related theory moves the source of phantom limb pain to the spinal cord,
suggesting that the pain is caused by the spontaneous firing of spinal cord neurons
that have lost their normal sensory input from the body. In this case, a closed
self-exciting neuronal loop in the posterior horn of the spinal cord is postulated to
send impulses to the brain, resulting in pain. Even the slightest irritation to the
amputated limb area can initiate this cycle.
• Other theories propose that the phantom limb pain may arise in the brain. In one
hypothesis, the pain is caused by changes in the flow of signals through
somatosensory areas of the brain.
• Treatment of
phantom limb pain
has been
accomplished by the
use of sympathetic
blocks, TENS of the
large myelinated
afferents innervating
the area, hypnosis,
and relaxation
training.

Antinociceptive systemsAntinociceptive systems
 NeuronalNeuronal opiate systemopiate system –– metmet-- and leuencephalinand leuencephalin
 NeuronalNeuronal unopiate systemunopiate system –– noradrenalinnoradrenalin,, serotoninserotonin,,
dopaminedopamine
 HormonalHormonal opiate systemopiate system –– hormoneshormones ofof
adenohypophysisadenohypophysis
 HormonalHormonal unopiate systemunopiate system –– vasopressinvasopressin

Hormonal unopiate systemHormonal unopiate system
 1.1. Adrenocorticotropic hormoneAdrenocorticotropic hormone
 2.2. MelanostimulatingMelanostimulating hormoneshormones
 3.3. ββ --LipotropicLipotropic hormonehormone
 4.4. LargeLarge endorphinesendorphines::
kitorphinkitorphin
ββ--kosomorphinkosomorphin
dinorphindinorphin

1.1. Opening of abscessOpening of abscess
2.2. Reposition ofReposition of
fragmentsfragments
3.3. Splintation of extremitySplintation of extremity
4.4. Section of scarsSection of scars
5.5. DesympathizationDesympathization
1.1. AcupunctureAcupuncture
2.2. ElectroacupunctureElectroacupuncture
3.3. LaseropunctureLaseropuncture
4.4. ElectrostimulationElectrostimulation
5.5. ElectrophoresisElectrophoresis
6.6. UltrasoundUltrasound
7.7. Magnetico-laserMagnetico-laser therapytherapy
8.8. MassageMassage
9.9. ManualManual therapytherapy
METHODS OFMETHODS OF
ANAESTIZATIONANAESTIZATION
 PsycologicalPsycological
 PhysicalPhysical
 PharmacologicalPharmacological
 SurgicalSurgical
 NeurosurgicalNeurosurgical
1.1. ConversationConversation
2.2. RelaxationRelaxation
3.3. HypnosisHypnosis
4.4. AutotrainingAutotraining
5.5. CorrectCorrect stereotypestereotype of motionof motion
6.6. Self-removel of painSelf-removel of pain

Upper Motor NeuronsUpper Motor Neurons
 Planned movements and those guided by sensory,
visual, or auditory stimuli are preceded by
discharges from prefrontal, somatosensory, visual,
or auditory cortices, which are then followed by
motor cortex pyramidal cell discharges that occur
several milliseconds before the onset of movement
 AnatomyAnatomy
 TheThe motor cortexmotor cortex is theis the
region from whichregion from which
movements can be elicitedmovements can be elicited
by electrical stimuli (Figure).by electrical stimuli (Figure).
 This includes:
 the primary motor area
(Brodmann area 4),
 premotor cortex (area 6),
 supplementary motor
cortex (medial portions of
6),
 primary sensory cortex
(areas 3, 1, and 2).
 In the motor cortex, groups
of neurons are organized in
vertical columns, and
discrete groups control
contraction of individual
muscles.

► Cortical motor neuronsCortical motor neurons contribute axons thatcontribute axons that
converge in the corona radiata and descend in theconverge in the corona radiata and descend in the
posterior limb of the internal capsule, cerebralposterior limb of the internal capsule, cerebral
peduncles, ventral pons, and medullapeduncles, ventral pons, and medulla. These fibers. These fibers
constitute theconstitute the corticospinalcorticospinal andand corticobulbarcorticobulbar
tractstracts and together areand together are known asknown as upper motorupper motor
neuron fibersneuron fibers. As they descend through the. As they descend through the
diencephalon and brainstem, fibers separate todiencephalon and brainstem, fibers separate to
innervate extrapyramidal and cranial nerve motorinnervate extrapyramidal and cranial nerve motor
nuclei. The lower brainstem motor neurons receivenuclei. The lower brainstem motor neurons receive
input from crossed and uncrossed corticobulbarinput from crossed and uncrossed corticobulbar
fibers, although neurons that innervate lower facialfibers, although neurons that innervate lower facial
muscles receive primarily crossed fibers.muscles receive primarily crossed fibers.
► In the ventral medullaIn the ventral medulla, the remaining corticospinal, the remaining corticospinal
fibers course in a tract that is pyramidal in shape infibers course in a tract that is pyramidal in shape in
cross section—thus, the namecross section—thus, the name pyramidal tractpyramidal tract.. AtAt
thethe lower end of the medullalower end of the medulla, most fibers, most fibers
decussate, although the proportion of crossed anddecussate, although the proportion of crossed and
uncrossed fibers varies somewhat betweenuncrossed fibers varies somewhat between
individuals. The bulk of these fibers descend as theindividuals. The bulk of these fibers descend as the
lateral corticospinal tractlateral corticospinal tract of the spinal cord.of the spinal cord.
► Different groups ofDifferent groups of neurons in the cortex controlneurons in the cortex control
muscle groupsmuscle groups of the contralateral face, arm, andof the contralateral face, arm, and
legleg. Neurons near the ventral end of the central. Neurons near the ventral end of the central
sulcus control muscles of the face, whereassulcus control muscles of the face, whereas
neurons on the medial surface of the hemisphereneurons on the medial surface of the hemisphere
control leg muscles. Because thecontrol leg muscles. Because the movements of themovements of the
face, tongue, and hand are complex in humans, aface, tongue, and hand are complex in humans, a
large share of the motor cortex is devoted to theirlarge share of the motor cortex is devoted to their
controlcontrol. A. A somatotopic organizationsomatotopic organization is also apparentis also apparent
in thein the lateral corticospinal tractlateral corticospinal tract of the cervicalof the cervical
cord, where fibers to motor neurons that control legcord, where fibers to motor neurons that control leg
muscles lie laterally and fibers to cervical motormuscles lie laterally and fibers to cervical motor
neurons lie medially.neurons lie medially.

Upper and Lower motoneurons innervate the skeletal
muscles and are essential for motor function.
Amyotrophic lateral sclerosis (ALS), fatal combined degeneration of
motoneurons and motor fiber tracts (i.e. combined gray and white matter disease).
Motoneurons of entire neuraxis! ALS - most devastating neurodegenerative
disease of aging CNS that so resembles Alzheimer and Parkinson diseases.

Upper and Lower motoneurons innervate the skeletal
muscles and are essential for motor function.
• Amyotrophic lateral sclerosis (ALS), also known as Lou
Gehrig’s disease after the famous New York Yankees
baseball player, is a devastating neurologic disorder that
selectively affects motor function. ALS is primarily a disorder
of middle to late adulthood, affecting persons between 55
and 60 years of age, with men developing the disease nearly
twice as often as women.
ETIOPATHOPHYSIOLOGY, PATHOLOGY
• Neuron degeneration, atrophy, and loss → glial replacement.
No inflammation! Degeneration of motoneurons:
• 1. Motor cortex (pyramidal cells in precentral cortex) → loss
of large myelinated fibers in anterior & lateral spinal
columns (gliotic sclerosis of lateral columns = LATERAL
SCLEROSIS)
N.B. posterior columns are usually spared in SALS.N.B. posterior columns are usually spared in SALS.
• 2. Brain stem - lower nuclei are more often / more
extensively involved than upper nuclei (e.g. oculomotor
nuclei loss is modest and rarely demonstrable clinically,
whereas hypoglossal nuclei are prominently degenerated).
• 3. Spinal anterior horns → loss of myelinated fibers in
anterior root →muscle denervation atrophy
(AMYOTROPHY); reinnervation is possible (but much less
extensive as in poliomyelitis, peripheral neuropathy).

Stephen Hawking's
EpidemiologyEpidemiology
a. ALS is a degenerative disease involving loss of upper and lower
motor neurons.
b. Symptoms usually appear between 40 and 60 years of age.
c. Most cases are sporadic (90%–95% of cases).
PathogenesisPathogenesis
• Possibly due to mutated superoxide dismutase (SOD) 1 (neuron
destruction by superoxide free radicals) or misfolded SOD 1 leading to
apoptosis of neurons (most likely mechanism)
Clinical findingsClinical findings
a. Upper motor neuron (UMN) signs  Spasticity, Babinski sign;
b. Lower motor neuron (LMN) signs:
1) Muscle weakness  Begins with atrophy of intrinsic muscles of the
hands;
2) Eventual paralysis of respiratory muscles.
c. No sensory changes.
d. Preservation of bowel and bladder function.
DiagnosisDiagnosis  Electromyography and nerve conduction studies.
TreatmentTreatment  Riluzole (glutamate antagonist).
Average survivalAverage survival time is 3 to 5 years.
Lower motor neuron disease that occurs in children.

DemyelinationDemyelination
 InIn myelinated nervesmyelinated nerves, the axon between two nodes of Ranvier (internodal, the axon between two nodes of Ranvier (internodal
segment) is surrounded by asegment) is surrounded by a myelin sheathmyelin sheath. This is a precondition for. This is a precondition for
saltatory conduction of the action potentials, i.e., the “jumping” propagationsaltatory conduction of the action potentials, i.e., the “jumping” propagation
of excitation from one nodal constriction (R1) to the next (R2). Theof excitation from one nodal constriction (R1) to the next (R2). The
internodal segment itself cannot generate an action potential, i.e.,internodal segment itself cannot generate an action potential, i.e.,
depolarization of the second node (R2) is completely dependent on thedepolarization of the second node (R2) is completely dependent on the
current from the first node (R1). However, the current is usually so strongcurrent from the first node (R1). However, the current is usually so strong
that it can even jump across the nodes.that it can even jump across the nodes.
 Nevertheless, on the way along the internodal segment the amplitude of theNevertheless, on the way along the internodal segment the amplitude of the
current will diminish. First of all, the membrane in the internodal segmentcurrent will diminish. First of all, the membrane in the internodal segment
must change its polarity, i.e., themust change its polarity, i.e., the membrane capacitancemembrane capacitance must bemust be
discharged, for which a current is needed. Secondly, current can alsodischarged, for which a current is needed. Secondly, current can also
escape through individualescape through individual ionic channelsionic channels in the axonal membrane (orangein the axonal membrane (orange
arrow). However, myelination of the internodal segment causes thearrow). However, myelination of the internodal segment causes the
membrane resistance (Rm) to be elevated and the capacity (Cm) of themembrane resistance (Rm) to be elevated and the capacity (Cm) of the
membrane condensor to be reduced.membrane condensor to be reduced.
 TheThe resistanceresistance of the axonal membrane of the internodal segment is veryof the axonal membrane of the internodal segment is very
high because of the low density of ionic channels there. Furthermore, thehigh because of the low density of ionic channels there. Furthermore, the
perimembranous space is insulated by a layer of fat from the freeperimembranous space is insulated by a layer of fat from the free
extracellular space. The lowextracellular space. The low capacitancecapacitance of the condensor is due to theof the condensor is due to the
large distance between the interior of the axon and the free extracellularlarge distance between the interior of the axon and the free extracellular
space as well as the low polarity of the fatty material in the space betweenspace as well as the low polarity of the fatty material in the space between
them.them.

DemyelinationDemyelination can becan be
caused by degenerative,caused by degenerative,
toxic, or inflammatorytoxic, or inflammatory
damage to the nerves,damage to the nerves,
or by a deficiency ofor by a deficiency of
vitamins B6 or B12.vitamins B6 or B12.
If this happens, Rm willIf this happens, Rm will
be reduced and Cmbe reduced and Cm
raised in the internodalraised in the internodal
segment.segment.
As a result, more currentAs a result, more current
will be required towill be required to
change the polarity ofchange the polarity of
the internodal segmentthe internodal segment
and, through opening upand, through opening up
the ionic channels, largethe ionic channels, large
losses of current maylosses of current may
occur.occur.

Multiple SclerosisMultiple Sclerosis
• Multiple sclerosis (MS), a demyelinating disease of the CNS, is a major cause of
neurologic disability among young and middleaged adults. Approximately two thirds
of persons with MS experience their first symptoms between 20 and 40 years of age.
In approximately 80% of the cases, the disease is characterized by exacerbations
and remissions over many years in several different sites in the CNS.
• Initially, there is normal or nearnormal neurologic function between exacerbations. As
the disease progresses, there is less improvement between exacerbations and
increasing neurologic dysfunction.

Pathogenesis
1. Autoimmune disease initiated by:
a) Genetic factors (e.g., HLA-DR2)
b) Environmental factors
• Microbial pathogens (e.g., Epstein-Barr virus, human herpesvirus 6,
Chlamydophila pneumoniae), vitamin D, sun exposure.
2. CD4 TH1 cells and TH17 cells react against self myelin antigens (e.g.,
myelin basic protein [MBP] and other antigens; type IV hypersensitivity
reaction).
3. CD4 TH1 cells secrete interferon γ (γ-IFN), which activates macrophages
(produce tumor necrosis factor-α; TNF-α) and TH17 cells release cytokines
that recruit neutrophils and monocytes.
4. Both leukocytes and TNF-α attack the myelin sheath and oligodendrocytes,
causing demyelination.
5. Antibodies produced by autoreactive B cells are directed against the myelin
sheath and oligodendrocytes as well (type II hypersensitivity reaction).
Gross and microscopic findings
1. Demyelinating plaques occur in white matter of brain/spinal cord.
• White matter looks like gray matter in areas of demyelination.
2. Inflammatory infiltrate in plaques is composed predominantly of CD4 T
cells, monocytes, and microglial cells with phagocytosed lipid.
MULTIPLE SCLEROSISMULTIPLE SCLEROSIS

Clinical findings
1) Episodic course punctuated by acute relapses and remissions (80%–90% of cases)
2) Sensory dysfunction:
a) Paresthesias
b) Loss of pain/temperature sensation
c) Loss of vibratory sensation
3) Upper motor neuron (UMN) dysfunction
a) Spasticity; b) Increased deep tendon reflexes (DTRs);
c) Muscle spasms; d) Extensor plantar response (Babinski);
e) Weakness  Shoulder abduction, finger extension, foot dorsiflexion, hip/knee flexion
4) Autonomic dysfunction:
a)Urge incontinence  Hyperactive detrusor muscle;
b)Sexual dysfunction; c) Bowel motility problems.
5) Optic neuritis
a) Inflammation of the optic nerve  MS is the most common cause of optic neuritis.
b) Blurry vision or sudden loss of vision
6) Cerebellar ataxia
7) Scanning speech (sound drunk)
8) Intention tremor, nystagmus
9) Bilateral internuclear ophthalmoplegia  Demyelination of medial longitudinal
fasciculus (MLF)
10) Flexion of the neck produces an electrical sensation down the spine.
MULTIPLE SCLEROSISMULTIPLE SCLEROSIS

Epidemiology
Most common acute peripheral neuropathy
Most common cause of acute flaccid paralysis
Predominantly motor involvement
Variants can be motor and sensory
Autoimmune demyelination syndrome:
a) Involves nerve roots and peripheral nerves;
b) Common preceding infections  Mycoplasma pneumoniae pneumonia,
Campylobacter jejuni enteritis, viral infection (HIV, EBV, cytomegalovirus, influenza)
b. Rapidly progressive ascending motor weakness:
Less commonly descending motor weakness.
Usually starts in the proximal muscles and eventually includes the distal muscles.
Danger of respiratory muscle paralysis and death.
c. Depressed or absent deep tendon reflexes in the arms and legs
d. Glove and stocking paresthesias/anesthesia
Laboratory findings: 1) Increased CSF protein Oligoclonal bands present on high-
resolution electrophoresis; 2) CSF glucose, cell count normal
Diagnosis:Diagnosis: 1) Spinal tap with increased CSF protein;
2) Electromyography and nerve conduction studies.
Treatment:Treatment: 1) Infusion IV immunoglobulin or plasma exchange;
2) Mechanical ventilation if required.
Prognosis: 1) Mortality 5% to 10% of cases; 2) Full motor recovery 60% of cases;
3) Residual weakness 15% of cases

Huntington'sHuntington's diseasediseaseEpidemiologyEpidemiology
a. Autosomal dominant diseasea. Autosomal dominant disease
b. Trinucleotide repeat disorder (CAG) involvingb. Trinucleotide repeat disorder (CAG) involving
chromosomechromosome
c. Delayed appearance of symptoms until 30 toc. Delayed appearance of symptoms until 30 to
40 years of age40 years of age
d. No gender dominanced. No gender dominance
Atrophy/loss of striatal neuronsAtrophy/loss of striatal neurons 
•• Caudate, putamen, globus pallidusCaudate, putamen, globus pallidus
Clinical findings:Clinical findings:
a.a. ChoreaChorea  1) Irregular, rapid, nonstereotyped1) Irregular, rapid, nonstereotyped
involuntary movements; 2) Calledinvoluntary movements; 2) Called
choreoathetosischoreoathetosis if it has a writhing quality.if it has a writhing quality.
b. Oculomotor abnormalitiesb. Oculomotor abnormalities
c. Parkinsonism in later stagesc. Parkinsonism in later stages
d. Depressiond. Depression
Diagnosis:Diagnosis: a. Genetic testing is availablea. Genetic testing is available
b. Imaging studies (CT, MRI)b. Imaging studies (CT, MRI)  Atrophy ofAtrophy of
caudate and putamencaudate and putamen
Treatment is supportive.Treatment is supportive.

HUNTINGTON DISEASEHUNTINGTON DISEASE
Classical familial,Classical familial,
genetic diseasegenetic disease
ProgressiveProgressive
motor loss andmotor loss and
dementiadementia
““chorea”, i.e.chorea”, i.e.
“jerky”“jerky”
movementsmovements
Progressive, fatalProgressive, fatal
Atrophy of basalAtrophy of basal
ganglia, i.e.,ganglia, i.e.,
corpus striatumcorpus striatum Cortical (basal ganglia) atrophyCortical (basal ganglia) atrophy
Ventricular enlargementVentricular enlargement

CNS DEGENERATIVE DISEASESCNS DEGENERATIVE DISEASES
• SPINOCEREBELLARSPINOCEREBELLAR
DEGENERATIONSDEGENERATIONS
(ATAXIAS)(ATAXIAS)
– Spinocerebellar ataxiasSpinocerebellar ataxias
– Friedrich AtaxiaFriedrich Ataxia
– Ataxia-TelangiectasiaAtaxia-Telangiectasia

EpidemiologyEpidemiology
a. Autosomal recessive (AR) disease
1)Trinucleotide repeat disorder (GAA);
2)Frataxin deficiency:
Deficiency leads to impaired mitochondrial iron homeostasis.
Cells are more prone to apoptosis.
b. Most common neurodegenerative hereditary ataxic disorder
c. Sites of degeneration:
1) Dorsal root ganglia; 4) Lateral corticospinal tracts
2) Posterior columns 5) Large sensory peripheral neurons
3) Spinocerebellar tract
d. Hypertrophic cardiomyopathy
e. Type 1 diabetes mellitus (10% of cases)
Clinical findingsClinical findings
a. Progressive gait ataxia
b. Loss of deep tendon reflexes  Initially at the ankles
c. Loss of vibratory sensation and proprioception
d. Muscle weakness in the legs
DiagnosisDiagnosis
a. Gene testing is available.
b. Imaging (MRI) shows spinal cord atrophy.
Treatment is supportive.Treatment is supportive.

ACQUIREDACQUIRED
TOXIC/METABOLICTOXIC/METABOLIC
CNS DISEASESCNS DISEASES VitaminVitamin B1B1 deficiency (Wernicke-Korsakoff)deficiency (Wernicke-Korsakoff)
 VitaminVitamin B12B12 deficiency (vibratory sense)deficiency (vibratory sense)
 DiabetesDiabetes Increased/Decreased GLUCOSEIncreased/Decreased GLUCOSE
 Hepatic FailureHepatic Failure (NH4+)(NH4+)
 COCO (Cortex, hippocampus, Purkinje cells)(Cortex, hippocampus, Purkinje cells)
 CH3-OHCH3-OH, Methanol (Retinal ganglion cells), Methanol (Retinal ganglion cells)
 CH3-CH2-OHCH3-CH2-OH (acute/chronic, direct/nutrit’l)(acute/chronic, direct/nutrit’l)
 RadiationRadiation (Brain MOST resistant to Rad. Rx.)(Brain MOST resistant to Rad. Rx.)
 ChemoChemo (Methotrexate + Radiation)(Methotrexate + Radiation)

Discriminative SensationDiscriminative Sensation
 Primary sensory cortex providesPrimary sensory cortex provides
awareness of somatosensory informationawareness of somatosensory information
and the ability to make sensoryand the ability to make sensory
discriminations.discriminations.
 Touch, pain, temperature, and vibrationTouch, pain, temperature, and vibration
sense are considered the primarysense are considered the primary
modalities of sensation and are relativelymodalities of sensation and are relatively
preserved in patients with damage topreserved in patients with damage to
sensory cortex or its projections from thesensory cortex or its projections from the
thalamus.thalamus.
 In contrast, complex tasks that requireIn contrast, complex tasks that require
integration of multiple somatosensoryintegration of multiple somatosensory
stimuli and of somatosensory stimuli withstimuli and of somatosensory stimuli with
auditory or visual information are impaired.auditory or visual information are impaired.
 These include the ability to distinguishThese include the ability to distinguish twotwo
pointspoints from one when touched on the skinfrom one when touched on the skin
((two-point discriminationtwo-point discrimination), localize tactile), localize tactile
stimuli, perceive the position of body partsstimuli, perceive the position of body parts
in space, recognize letters or numbersin space, recognize letters or numbers
drawn on the skin (drawn on the skin (graphesthesiagraphesthesia), and), and
identify objects by their shape, size, andidentify objects by their shape, size, and
texture (texture (stereognosisstereognosis).).

Anatomy of Sensory LossAnatomy of Sensory Loss
The patterns of sensory loss often indicate
the level of nervous system involvement.
Symmetric distal sensory loss in the limbs,
affecting the legs more than the arms,
usually signifies a generalized disorder of
multiple peripheral nerves
(polyneuropathy).
Sensory symptoms and deficits may be
restricted to the distribution of a single
peripheral nerve (mononeuropathy) or
two or more peripheral nerves
(mononeuropathy multiplex).
Symptoms limited to a dermatome indicate
a spinal root lesion (radiculopathy).

Alterations in Motor Responses andAlterations in Motor Responses and
MovementMovement
 Abnormal motor responses include inappropriate or absentAbnormal motor responses include inappropriate or absent
movements in response to painful stimuli. Brainstem reflexesmovements in response to painful stimuli. Brainstem reflexes
such as sucking and grasping responses will occur if highersuch as sucking and grasping responses will occur if higher
brain centers have been damaged.brain centers have been damaged.
 Flexion and rigidity of limbs also are motor responses indicativeFlexion and rigidity of limbs also are motor responses indicative
of brain damage.of brain damage.
 Muscle conditionsMuscle conditions that indicate abnormal brain function includethat indicate abnormal brain function include
hyperkinesiahyperkinesia ((excessive muscle movementsexcessive muscle movements),), hypokinesiahypokinesia
((decreased muscle movementsdecreased muscle movements),), paresisparesis ((muscle weaknessmuscle weakness),),
andand paralysisparalysis ((loss of motor functionloss of motor function).).
 Specific loss of cerebral cortex functioning, but no loss ofSpecific loss of cerebral cortex functioning, but no loss of
brainstem function, results in a particular body posture calledbrainstem function, results in a particular body posture called
flexor posturingflexor posturing..
 Flexor posturingFlexor posturing is characterized by flexion of the upperis characterized by flexion of the upper
extremities at the elbows and external rotation and extension ofextremities at the elbows and external rotation and extension of
the lower extremities. This posturethe lower extremities. This posture may be unilateral ormay be unilateral or
bilateralbilateral. Extensor posturing occurs with severe injury to higher. Extensor posturing occurs with severe injury to higher
brain centers and the brainstem and is characterized bybrain centers and the brainstem and is characterized by rigidrigid
extension of the limbs and neckextension of the limbs and neck..

Brown-Séquard syndrome
In the spinal cord, segregation of fiber tracts and the
somatotopic arrangement of fibers give rise to distinct
patterns of sensory loss. Loss of pain and
temperature sensation on one side of the body
and of proprioception on the opposite side occurs
with lesions that involve one half of the cord on the
side of the proprioceptive deficit (Brown-Séquard
syndrome).
Compression of the upper spinal cord causes loss of
pain, temperature, and touch sensation first in
the legs, because the leg spinothalamic fibers are
most superficial. More severe cord compression
compromises fibers from the trunk. In patients with
spinal cord compression, the lesion is often above
the highest dermatome involved in the deficit. Thus,
radiographic studies should be tailored to visualize
the cord at and above the level of the sensory deficit
detected on examination.
Intrinsic cord lesions that involve the central portions
of the cord often impair pain and temperature
sensation at the level of the lesion because the fibers
crossing the anterior commissure and entering the
spinothalamic tracts are most centrally situated.
Thus, enlargement of the central cervical canal in
syringomyelia typically causes loss of pain and
temperature sensation across the shoulders and
upper arms.

SPINAL CORD INJURIES (SCI)SPINAL CORD INJURIES (SCI)
CAUSES:CAUSES:
 TRAUMATRAUMA
 FALLSFALLS
 GSWGSW
 TUMORSTUMORS
TYPES:TYPES:
 CONCUSSIONCONCUSSION
 COMPRESSIONCOMPRESSION
 CONTUSION &CONTUSION &
TRANSECTIONTRANSECTION
 LACERATIONLACERATION
 HEMORRHAGEHEMORRHAGE
(HEMATOMYALIA)(HEMATOMYALIA)
 COMPRESSION OFCOMPRESSION OF
BLOOD SUPPLY TOBLOOD SUPPLY TO
THE CORDTHE CORD

Injury
Level
Segmental Sensorimotor Function Dressing, Eating Elimination Mobility
C1 Little or no sensation or control of head and
neck; no diaphragm control; requires
Continuous ventilation
Dependent Dependent Limited. Voice or sip-n-puff
controlled electric wheelchair
C2 to
C3
Head and neck sensation; some neck
control. Independent of mechanical
ventilation for short periods
Dependent Dependent Same as for C1
C4 Good head and neck sensation and motor
control; some shoulder elevation;
diaphragm movement
Dependent; may be
able to eat with
adaptive sling
Dependent Limited to voice, mouth, head,
chin, or shoulder-controlled
electric wheelchair
C5 Full head and neck control; shoulder
strength; elbow flexion
Independent with
assistance
Maximal assistance Electric or modified manual
wheel chair, needs transfer
assistance
C6 Fully innervated shoulder; wrist extension
or dorsiflexion
Independent or with
minimal assistance
Independent or with
minimal assistance
Independent in transfers and
wheelchair
C7 to
C8
Full elbow extension; wrist plantar flexion;
some finger control
Independent Independent Independent; manual
wheelchair
T1 to
T5
Full hand and finger control; use of
intercostal and thoracic muscles
wheelchair
T6 to
T10
Abdominal muscle control, partial to good
balance with trunk muscles
wheelchair
T11 to
L5
Hip flexors, hip abductors (L1–3); knee
extension (L2–4); knee flexion and ankle
dorsiflexion (L4–5)
Independent Independent Short distance to full
ambulation with assistance
S1 to
S5
Full leg, foot, and ankle control;
innervation of perineal muscles for
bowel, bladder, and sexual function
(S2–4)
Independent Normal to impaired
bowel and bladder
function
Ambulate independently with or
without assistance
Functional Abilities by Level of Cord InjuryFunctional Abilities by Level of Cord Injury

CLINICAL EFFECTS OF SCICLINICAL EFFECTS OF SCI
• SPINAL SHOCK
• REFLEX ACTIVITY
• WHIPLASH INJURY
• HERNIATED NUCLEUS PULPOSUS

• IMMEDIATE FLACCID PARALYSIS & SENSORY LOSS
BELOW THE LEVEL OF LESION
• PRIAPISM
• BULBOCAVERNOUS REFLEX IS LOST BUT REUTRNS
AFTER A FEW HRS
• OTHER REFLEXES REMAIN ABSENT
• 3-6 WKS
UTONOMIC DISTURBANCES:UTONOMIC DISTURBANCES:
WEATING IS ABOLISHED
BELOW THE LEVEL OF INJURY
RINE & FECES RETAINED
ASTRIC ATONY
RTHOSTATIC HYPOTENSION
LOW, & STEADY PULSE

REFLEX ACTIVITY
• REPLACE SPINAL SHOCK AFTER 2-3
WEEKS IF LUMBO-SACRAL SEGMENTS
ARE UNDAMAGED
• OCCURS IN ACUTE SPINAL INJURY,
NOT IN PROGRESSIVE ONES
• AUTOMATIC BLADDER; REFLEX
SWEATING & DEFECATION
• FIRST SIGN OF WEARING OFF:
– CONTRACTION OF HAMSTRING
– FLEXION/ EXTENSION OF TOES WITH
PLANTAR STIMULATION

ParalysisParalysis
 ParalysisParalysis is the loss of sensory and voluntary motoris the loss of sensory and voluntary motor
function. With spinal cord transection, paralysis isfunction. With spinal cord transection, paralysis is
permanent.permanent.
 ParalysisParalysis of theof the upper and lower extremitiesupper and lower extremities occurs withoccurs with
transection of the cord at level C6 or higher and is calledtransection of the cord at level C6 or higher and is called
quadriplegiaquadriplegia..
 ParalysisParalysis of the lower half of the body occurs withof the lower half of the body occurs with
transection of the cord below C6 and is calledtransection of the cord below C6 and is called
paraplegiaparaplegia..
 If only one half of the cord is transectedIf only one half of the cord is transected,, hemiparalysishemiparalysis
may occur.may occur.
 Permanent paralysisPermanent paralysis may occur even when the cord ismay occur even when the cord is
not transected, as a result of the destruction of thenot transected, as a result of the destruction of the
nerves following cordnerves following cord hemorrhage and swellinghemorrhage and swelling..
 In addition, demyelination of the axons in the cord canIn addition, demyelination of the axons in the cord can
lead to clinically complete lesions, even though thelead to clinically complete lesions, even though the
spinal cord may not be transected.spinal cord may not be transected.
 DemyelinationDemyelination of the axons most likely occurs as part ofof the axons most likely occurs as part of
the inflammatory response to cord injury.the inflammatory response to cord injury.

Clinical
Manifestations
of Paralysis
• Loss of sensation,
motor control, and
reflexes below the
level of injury, and
up to two levels
above, will occur.
• Body temperature
will reflect ambient
temperature, and
blood pressure will
be reduced.
• The pulse rate is
often normal, with
low blood pressure.

Complications
• If damage and swelling around the cord is in the
cervical spine (down to approximately C5),
respirations may cease because of compression of
the phrenic nerve, which exits between C3 and C5
and controls the movement of the diaphragm.
• Autonomic hyper-reflexia is characterized by high
blood pressure with bradycardia (low heart rate),
and sweating and flushing of the skin on the face
and upper torso.
• In the past, individuals suffering from a C2 or higher
transection invariably died as a result of respiratory
arrest. Although this is still true for many, recent
advances in treatment modalities and better
emergency rescue service responses have resulted
in the survival of many individuals with high cord
transection.
• A severe spinal cord injury affects virtually all
systems of the body to some degree. Commonly,
urinary tract and kidney infections, skin breakdown
and the development of pressure ulcers, and muscle
atrophy occur. Depression, marital and family
stress, loss of income, and large medical expenses
are some of the psychosocial complications.

DysphasiaDysphasia
 Dysphasia is impairment of language comprehension or production.is impairment of language comprehension or production.
AphasiaAphasia is total loss of language comprehension or production.is total loss of language comprehension or production.
Dysphasia usually results from cerebral hypoxia, which is oftenDysphasia usually results from cerebral hypoxia, which is often
associated with a stroke but can result from trauma or infection. Brainassociated with a stroke but can result from trauma or infection. Brain
damage leading to dysphasia usually involves the left cerebraldamage leading to dysphasia usually involves the left cerebral
hemisphere.hemisphere.
 Broca's dysphasia results from damage to Broca's area inresults from damage to Broca's area in the frontalthe frontal
lobelobe. Persons with. Persons with Broca's dysphasia will understand languageBroca's dysphasia will understand language, but, but
their ability to meaningfullytheir ability to meaningfully express words in speech or writing will beexpress words in speech or writing will be
impairedimpaired. This is called expressive dysphasia.. This is called expressive dysphasia.
 Wernicke's dysphasia results from damage to Wernicke's area in theresults from damage to Wernicke's area in the
leftleft temporal lobetemporal lobe. With Wernicke's dysphasia,. With Wernicke's dysphasia, verbal expression ofverbal expression of
language is intactlanguage is intact, but meaningful, but meaningful understanding of spoken or writtenunderstanding of spoken or written
words is impairedwords is impaired. This is called receptive dysphasia.. This is called receptive dysphasia.
 Agnosia is the failure to recognize an object because of the inabilityis the failure to recognize an object because of the inability
to make sense of incoming sensory stimuli.to make sense of incoming sensory stimuli. Agnosia may be visual,Agnosia may be visual,
auditory, tactile, or related to taste or smellauditory, tactile, or related to taste or smell. Agnosia develops from. Agnosia develops from
damage to a particular primary or associative sensory area in thedamage to a particular primary or associative sensory area in the
cerebral cortex.cerebral cortex.

Alterations in Pupil Responses
• The ability of our eyes to dilate or
constrict, rapidly and equally,
depends on an intact brainstem.
• Cerebral hypoxia and many drugs
change pupil size and reactivity.
Therefore, pupil size and reactivity
offer valuable information concerning
brain integrity and function.
• Important pupil changes seen with
brain damage are pinpoint pupils
seen with opiate (heroin) overdose
and bilaterally fixed and dilated pupils
usually seen with severe hypoxia.
• Fixed pupils are typically seen with
barbiturate overdose.
• Brainstem injury presents with pupils
fixed bilaterally in the midposition.

DISORDERS OFDISORDERS OF
THE MIDDLE EARTHE MIDDLE EAR
■ The middle ear is a small air-filled
compartment in the temporal bone.
It is separated from the outer ear
by the tympanic membrane,
contains tiny bony ossicles that aid
in the amplification and
transmission of sound to the inner
ear, and is ventilated by the
eustachian tube, which is
connected to the nasopharynx.
■■ The eustachian tube, which is lined with a mucousThe eustachian tube, which is lined with a mucous membrane that ismembrane that is
continuous with the nasopharynx,continuous with the nasopharynx, provides a passageway forprovides a passageway for
pathogens to enter thepathogens to enter the middle ear.middle ear.
■■ Otitis media (OM) refers to inflammation of the middleOtitis media (OM) refers to inflammation of the middle ear, usuallyear, usually
associated with an acute infectionassociated with an acute infection (acute OM) or an accumulation of(acute OM) or an accumulation of
fluid (OME). Itfluid (OME). It commonly is associated with disorders of eustachiancommonly is associated with disorders of eustachian
tube function.tube function.
■■ Impaired conduction of sound waves and hearingImpaired conduction of sound waves and hearing loss occur when theloss occur when the
tympanic membrane has beentympanic membrane has been perforated; air in the middle ear hasperforated; air in the middle ear has
been replacedbeen replaced with fluid (OME); or the function of the bonywith fluid (OME); or the function of the bony ossicles hasossicles has
been impaired (otosclerosis).been impaired (otosclerosis).

HEARING LOSS
■ Hearing loss represents
impairment of the ability
to detect and perceive
sound.
■ Conductive hearing loss is
caused by disorders in
which auditory stimuli are
not transmitted through
the structures of the outer
and middle ears to the
sensory receptors in the
inner ear.
■ Sensorineural hearing
loss is caused by
disorders that affect the
inner ear, auditory nerve,
or auditory pathways.

Diseases of the Basal GangliaDiseases of the Basal Ganglia
 The basal ganglia areThe basal ganglia are
made up of:made up of:
 –– thethe corpus striatumcorpus striatum
(consisting of the(consisting of the caudatecaudate
nucleusnucleus and theand the
putamenputamen););
 –– the inner and outerthe inner and outer
globus pallidusglobus pallidus
(pallidum, consisting of an(pallidum, consisting of an
internal and an externalinternal and an external
part);part);
 –– thethe subthalamicsubthalamic
nucleusnucleus; and; and
 –– thethe substantia nigrasubstantia nigra
(pars reticulata [p. r.] and(pars reticulata [p. r.] and
pars compacta [p. c.]).pars compacta [p. c.]).
 TheirTheir functionfunction is mainlyis mainly
to control movement into control movement in
conjunction with theconjunction with the
cerebellum,motor cortex,cerebellum,motor cortex,
corticospinal tracts, andcorticospinal tracts, and
motor nuclei in the brainmotor nuclei in the brain
stem.stem.

Parkinson’s Disease Parkinson’s diseaseParkinson’s disease is a diseaseis a disease
of theof the substantia nigrasubstantia nigra (p. c.)(p. c.)
which via dopaminergic tractswhich via dopaminergic tracts
influences GABAergic cells in theinfluences GABAergic cells in the
corpus striatumcorpus striatum. The. The causecause isis
frequently afrequently a hereditary dispositionhereditary disposition
that in middle to old age leads tothat in middle to old age leads to
degeneration of dopaminergicdegeneration of dopaminergic
neurons in the substantianeurons in the substantia
nigranigra. Further causes are. Further causes are traumatrauma
(e.g., in boxers),(e.g., in boxers), inflammationinflammation
(encephalitis),(encephalitis), impaired circulationimpaired circulation
(atherosclerosis),(atherosclerosis), tumorstumors andand
poisoningpoisoning (especially by CO,(especially by CO,
manganese, and 1-methyl-4-manganese, and 1-methyl-4-
phenyl-1,2,3,6-tetrahydropyridinephenyl-1,2,3,6-tetrahydropyridine
[MPTP], which was once used as[MPTP], which was once used as
a substitute for heroin). The cella substitute for heroin). The cell
destruction probably occurs partlydestruction probably occurs partly
by apoptosis; superoxides areby apoptosis; superoxides are
thought to play a causal role.thought to play a causal role.
 For symptoms to occur, over 70%For symptoms to occur, over 70%
of neurons in the substantia nigraof neurons in the substantia nigra
(p. c.) must have been destroyed.(p. c.) must have been destroyed.
 The loss of cells in the substantiaThe loss of cells in the substantia
nigra (p. c.) decreases thenigra (p. c.) decreases the
correspondingcorresponding dopaminergicdopaminergic
innervationinnervation of the striatum.of the striatum.

Brain centres and theirBrain centres and their
disorderdisorder
 The brain is conventionally considered in sixThe brain is conventionally considered in six main anatomicalmain anatomical
and functional areas:and functional areas:
1. Cerebrum1. Cerebrum – two hemispheres of cerebral– two hemispheres of cerebral cortex, containingcortex, containing
the limbic system andthe limbic system and basal ganglia.basal ganglia.
2. Diencephalon2. Diencephalon, containing the hypothalamus, containing the hypothalamus and thalamus.and thalamus.
3. Midbrain.3. Midbrain.
4. Pons.4. Pons.
5. Medulla oblongata.5. Medulla oblongata.
6. Cerebellum.6. Cerebellum.
 Alternatively, the brain may be subdividedAlternatively, the brain may be subdivided into distinct regions:into distinct regions:
•• TheThe forebrainforebrain, which includes areas 1 and 2., which includes areas 1 and 2.
•• TheThe hindbrainhindbrain, which includes areas 4, 5, which includes areas 4, 5 and 6.and 6.
•• TheThe brainstembrainstem, which includes the midbrain,, which includes the midbrain, medulla andmedulla and
pons.pons.
 Interconnections between these areas areInterconnections between these areas are manifold andmanifold and
complex, accounting for the richnesscomplex, accounting for the richness and diversity of humanand diversity of human
activity, experienceactivity, experience and achievement.and achievement.

Principal anatomical centresPrincipal anatomical centres
of brain functionof brain function
FunctionFunction CentreCentre
InputInput PerceptionPerception Sensory cortex, thalamus,Sensory cortex, thalamus,
reticular formationreticular formation
ProcessingProcessing Cognitive (intellectual)Cognitive (intellectual)
EmotionalEmotional
Cerebral cortexCerebral cortex
Limbic systemLimbic system
OutputOutput MotorMotor
HomeostasisHomeostasis
Motor cortex, cerebellum,Motor cortex, cerebellum,
basal gangliabasal ganglia
Medulla, hypothalamus,Medulla, hypothalamus,
pituitarypituitary

Cerebral cortexCerebral cortex
 The cerebral cortex is, in evolutionary terms, the youngest centre. It is
the principal distinguishing feature of higher mammals. Notably
developed in man, where it contains 90% of the total brain
neurones,
 the cerebral cortex is the location of:
 It functions like afunctions like a computercomputer,
providing an objective, logical assessment of the environment as
perceived via the senses,
 and then producing a plan for action depending on past experience
and biological goals.
 Specific areas of the cortex are dedicated to subsidiary functions,
such as the speech centre and the visual, auditory and motor
cortexes.
 Anatomically, the cerebral cortex is subdivided into various lobes, i.e.
abstract thought judgement
reasoning
memory
interpretation of
sensory inputcreativity
frontal temporal parietal occipital

Cortical disordersCortical disorders
 Cortical disorders usually have a profoundCortical disorders usually have a profound effect oneffect on
all CNS function. They are commonlyall CNS function. They are commonly manifested asmanifested as
disorders ofdisorders of intellectintellect, e.g., e.g.
 MentalMental handicaphandicap,, dementiadementia oror Alzheimer’sAlzheimer’s disease,disease,
or ofor of movementmovement, e.g., e.g. epilepsyepilepsy..
 StrokesStrokes are caused byare caused by obstruction of blood flowobstruction of blood flow
usually to discreteusually to discrete cortical areas.cortical areas.
 TheThe thought disorderthought disorder characteristiccharacteristic ofof schizophreniaschizophrenia
is partly cortical, but disorderedis partly cortical, but disordered limbic or thalamiclimbic or thalamic
influences on theinfluences on the ortex are probably more important.ortex are probably more important.
 Most proven and putative neurotransmittersMost proven and putative neurotransmitters areare
found in the cortex. Many of the morefound in the cortex. Many of the more recentlyrecently
discovered mediators, such as thediscovered mediators, such as the endorphinsendorphins andand
peptidespeptides, have yet to be definitely, have yet to be definitely linked withlinked with
specific CNS functions, disorders orspecific CNS functions, disorders or drug actions.drug actions.
They may modulate the action ofThey may modulate the action of the traditionalthe traditional
transmitters.transmitters.

 This interesting evolutionaryThis interesting evolutionary
development ofdevelopment of the higher mammalsthe higher mammals
providesprovides mental activitymental activity with anwith an
emotional dimensionemotional dimension ..
 TheThe limbiclimbic systemsystem is responsibleis responsible
forfor feelingsfeelings rather thanrather than objectiveobjective
reasoningreasoning and is perceivedand is perceived
consciouslyconsciously as anas an emotionalemotional
overlayoverlay, i.e. the, i.e. the affect or moodaffect or mood,,
which can modify the decisionswhich can modify the decisions
taken by thetaken by the cortex.cortex.
 The system mayThe system may mediate rage,mediate rage,
fear, pleasurefear, pleasure and loveand love and, byand, by
its influence on corticalits influence on cortical function, isfunction, is
responsible for beliefs as opposedresponsible for beliefs as opposed
toto rational thoughtrational thought ..
 A materialistic interpretationA materialistic interpretation of oneof one
of the objectives of some Easternof the objectives of some Eastern
philosophies,philosophies, especiallyespecially
meditationmeditation, would be that it, would be that it
attempts to achieve control or evenattempts to achieve control or even
eliminationelimination of limbic influencesof limbic influences (‘the(‘the
self’, ‘desire’)self’, ‘desire’) on theon the cortex.cortex.

 The contrast betweenThe contrast between limbiclimbic andand cortical functionscortical functions is illustrated by ouris illustrated by our
response to beingresponse to being caught for a motoring offence.caught for a motoring offence.
 One part of usOne part of us –– ourour limbic system – is angrylimbic system – is angry,, fearfulfearful oror ashamedashamed
(depending on our personality):(depending on our personality): at the sameat the same time, our cortextime, our cortex is calculatingis calculating
the effect on ourthe effect on our insurance premium,insurance premium, the most effective way tothe most effective way to appeaseappease
the policeman, or perhaps even how tothe policeman, or perhaps even how to manage without a drivingmanage without a driving
licencelicence..
 TheThe limbic systemlimbic system has evolved from a structurehas evolved from a structure in lower mammalsin lower mammals
concerned withconcerned with olfactionolfaction (sense of smell),(sense of smell), and indeed it retains thisand indeed it retains this
functionfunction in humans.in humans. Possibly this accounts for thePossibly this accounts for the emotional power thatemotional power that
smells have on humans.smells have on humans.
 TheThe limbic systemlimbic system is also involved inis also involved in memorymemory,, and we are all familiar withand we are all familiar with
how strongly smellshow strongly smells can evoke evencan evoke even distant memoriesdistant memories..
 The system isThe system is structurally complex with many componentstructurally complex with many component nuclei andnuclei and
important connections with theimportant connections with the frontalfrontal andand temporal lobes of the cortextemporal lobes of the cortex,,
withwith thethe reticular systemreticular system and with theand with the hypothalamushypothalamus (all of which are(all of which are
sometimes considered assometimes considered as partially within the limbic system).partially within the limbic system). DopamineDopamine isis
an important transmitter, as arean important transmitter, as are noradrenalinenoradrenaline (NA, norepinephrine) and(NA, norepinephrine) and
5-hydroxytryptamine5-hydroxytryptamine (5-HT, serotonin).(5-HT, serotonin). Gamma-aminobutyric acidGamma-aminobutyric acid
((GABA) is an inhibitory transmitter here.GABA) is an inhibitory transmitter here.

Disorders of theDisorders of the LLimbicimbic SSystemystem
 Disorders of the limbic systemDisorders of the limbic system are likely toare likely to
cause inappropriate emotions, such ascause inappropriate emotions, such as::
 depression,depression,
 mania ormania or
 excessive anxiety.excessive anxiety.
 DelusionsDelusions ((inappropriate beliefs) may arise ininappropriate beliefs) may arise in
the limbicthe limbic system. The now discreditedsystem. The now discredited
prefrontalprefrontal lobotomy (leucotomy), an operationlobotomy (leucotomy), an operation
to sever theto sever the links between the limbic systemlinks between the limbic system
and the cortexand the cortex in severe psychiatric disorders,in severe psychiatric disorders,
resulted in theresulted in the patient becoming emotionallypatient becoming emotionally
flat.flat.
 A similarA similar phenomenon is sometimes seen inphenomenon is sometimes seen in
patients onpatients on long-term antipsychoticslong-term antipsychotics..

Psychological DisordersPsychological Disorders
 Its mental processes and/or behavior patterns that causeIts mental processes and/or behavior patterns that cause
emotional distress and/or substantial impairment in functioningemotional distress and/or substantial impairment in functioning
 The presence of a constellation of symptoms that createThe presence of a constellation of symptoms that create
significant distress; impair work, school, family, relationships,significant distress; impair work, school, family, relationships,
or daily living; or lead to significant risk or harmor daily living; or lead to significant risk or harm
 SymptomsSymptoms
 CognitiveCognitive
 EmotionalEmotional
 BehavioralBehavioral
 What criteria can be used to determine whether behavior isWhat criteria can be used to determine whether behavior is
abnormal?abnormal?
 Behavior may be considered abnormal ifBehavior may be considered abnormal if
 It is considered strange within a person’s own cultureIt is considered strange within a person’s own culture
 It causes personal distressIt causes personal distress
 It is maladaptiveIt is maladaptive
 It is a danger to the self or othersIt is a danger to the self or others
 A person is not legally responsible for his or her actsA person is not legally responsible for his or her acts

Types/CategoriesTypes/Categories
 Organic Brain Syndromes (Caused by Damage)Organic Brain Syndromes (Caused by Damage)
 Developmental Disorders (autism, retardation)Developmental Disorders (autism, retardation)
 ““Psychoses” – Schizophrenia, Mood Disorders (Bipolar)Psychoses” – Schizophrenia, Mood Disorders (Bipolar)
 ““Neuroses” – Anxiety Disorders (Phobias, OCD, PTSD)Neuroses” – Anxiety Disorders (Phobias, OCD, PTSD)
 Somatoform Disorders (Ulcers)Somatoform Disorders (Ulcers)
 Dissociative Disorders – D.I.D.Dissociative Disorders – D.I.D.
 Personality Disorders – Antisocial Personality Disorder,Personality Disorders – Antisocial Personality Disorder,
Substances Abuse (problems with relationships)Substances Abuse (problems with relationships)
 Behavioral Disorders – Sleep Disorders, TurretsBehavioral Disorders – Sleep Disorders, Turrets
 General ProblemsGeneral Problems  Seek Counseling (relationships)Seek Counseling (relationships)

General Adaptation Syndrome
Three stages:
1. Alarm stage
- Emergency reaction (fight-or-flight)
1. Resistance stage
- Coping and adaptation
1. Exhaustion stage
- Termination of stress response and onset of
stress pathology
 StressStress refers to a number of
biological changes that can
be triggered by any
disturbance to our normal
physiology.
 Stress is neutral –Stress is neutral – the body
responds the same to
positive or negative
stressors.

Anxiety DisordersAnxiety Disorders
 Components of Anxiety ResponsesComponents of Anxiety Responses

Phobic DisordersPhobic Disorders
 PhobiaPhobia – an intense– an intense
and irrational fear ofand irrational fear of
particular object orparticular object or
situationsituation
Psychological DisorderPsychological Disorder
 InsanityInsanity is a legal term. Insanity is beingis a legal term. Insanity is being unableunable to appreciate theto appreciate the
nature and quality of the wrongfulness of his or her acts, because ofnature and quality of the wrongfulness of his or her acts, because of
mental disease or defect.mental disease or defect.
 AbnormalityAbnormality is a condition or behavior that deviates from the usualis a condition or behavior that deviates from the usual
physical or psychological state. Culture and context are important inphysical or psychological state. Culture and context are important in
defining abnormality. Talking to the dead is normal in some cultures.defining abnormality. Talking to the dead is normal in some cultures.

 PhobiasPhobias - strong and irrational fears of- strong and irrational fears of
certain objects or situationscertain objects or situations
 AgoraphobiaAgoraphobia: fear of open and public: fear of open and public
spaces from which escape would bespaces from which escape would be
difficultdifficult
 Social phobiasSocial phobias: fear of situations in: fear of situations in
which evaluation might occurwhich evaluation might occur
 Lifetime prevalence 13%Lifetime prevalence 13%
 Specific phobiasSpecific phobias: fear of specific: fear of specific
objects such as animals or situationsobjects such as animals or situations
 Animal fearsAnimal fears
 Blood-injection-injury fearsBlood-injection-injury fears
 Natural environment fearsNatural environment fears
 Situation fearsSituation fears
 Miscellaneous fearsMiscellaneous fears
 Lifetime prevalence 10%Lifetime prevalence 10%

 Panic DisorderPanic Disorder an extreme anxiety that manifestsan extreme anxiety that manifests
itself in the form of panic attacksitself in the form of panic attacks
 Panic occurs suddenly and unpredictablyPanic occurs suddenly and unpredictably
 Much more intense than typical anxietyMuch more intense than typical anxiety
 Panic attackPanic attack
 An episode of overwhelming anxiety, fear, or terrorAn episode of overwhelming anxiety, fear, or terror
 The brains of panic-attack sufferers respond to normal changes in the body as if they were lifeThe brains of panic-attack sufferers respond to normal changes in the body as if they were life
threateningthreatening

 Obsessive-Compulsive DisorderObsessive-Compulsive Disorder
 ObsessionsObsessions
 Repetitive and unwelcome thoughts, images, or impulsesRepetitive and unwelcome thoughts, images, or impulses
 CompulsionsCompulsions
 Repetitive behavioral responsesRepetitive behavioral responses
 CheckingChecking
 WashingWashing
 OrderingOrdering
 Lifetime prevalence 2-3%Lifetime prevalence 2-3%
 Caudate nucleusCaudate nucleus
 Obsession –Obsession – Constantly on your mindConstantly on your mind
 Compulsions –Compulsions – Keep repeating behaviorKeep repeating behavior

Posttraumatic Stress DisorderPosttraumatic Stress Disorder
• Severe anxiety disorderSevere anxiety disorder
– Can occur in people exposed to extreme traumaCan occur in people exposed to extreme trauma
• PTSD – disorder in which victims of traumatic eventsPTSD – disorder in which victims of traumatic events
experience the original event in the form of dreams orexperience the original event in the form of dreams or
flashbacksflashbacks
– SymptomsSymptoms
• Re-experience eventRe-experience event
• Avoidance and emotionalAvoidance and emotional
numbingnumbing
• Heightened arousalHeightened arousal
– Lifetime prevalence 8% (among Americans)Lifetime prevalence 8% (among Americans)
– Genetic predispositionGenetic predisposition

Somatoform DisordersSomatoform Disorders
 Used to be called “Used to be called “hysteriahysteria” by Freud” by Freud
 ““Physical symptoms for which there is noPhysical symptoms for which there is no
apparent physical causeapparent physical cause
 Two general typesTwo general types
1.1. Conversion DisordersConversion Disorders
2.2. HypochondriasisHypochondriasis

Conversion DisordersConversion Disorders
 Changing emotional difficulties into a lossChanging emotional difficulties into a loss
of specific voluntary body functionof specific voluntary body function
 Subconsciously doneSubconsciously done
 Reinforced by increased attentionReinforced by increased attention
 Motor Deficits or Sensory DeficitsMotor Deficits or Sensory Deficits
 RareRare

HypochondriasisHypochondriasis
 Good health but intense worry about smallGood health but intense worry about small
problems being really bigproblems being really big
 Extensive doctor visits, second opinions,Extensive doctor visits, second opinions,
self diagnosisself diagnosis
 From repressed emotions?From repressed emotions?
 Get more reinforcement (positiveGet more reinforcement (positive
attention)attention)

Mood DisordersMood Disorders
 Long-lasting, severeLong-lasting, severe  not just really sadnot just really sad
 BereavementBereavement  not necessarily depressionnot necessarily depression
Types:Types:
 Major Depressive DisorderMajor Depressive Disorder
 Bipolar DisorderBipolar Disorder
 Season Affective DisorderSeason Affective Disorder
 DysthymiaDysthymia
 Lifetime prevalence 6%Lifetime prevalence 6%
 SuicideSuicide
 Attempted by 30% of depressed peopleAttempted by 30% of depressed people

Major Depressive DisorderMajor Depressive Disorder
 Severe form of lowered mood, feelings ofSevere form of lowered mood, feelings of
worthlessness, apathy, disinterested inworthlessness, apathy, disinterested in
pleasurable activities, intense sadness,pleasurable activities, intense sadness,
hopelessnesshopelessness
 2+ weeks, can’t be due to bereavement2+ weeks, can’t be due to bereavement
(grieving)(grieving)
 Need 4 of following symptoms (consistently andNeed 4 of following symptoms (consistently and
higher in intensity) – problems eating, sleeping,higher in intensity) – problems eating, sleeping,
thinking, focusing, making decisions, low energy,thinking, focusing, making decisions, low energy,
suicidal thoughts, feel worthless/guilty, lack ofsuicidal thoughts, feel worthless/guilty, lack of
interest in enjoyable activitiesinterest in enjoyable activities

Bipolar Disorder (Manic Depression)Bipolar Disorder (Manic Depression)
Individual alternates between feelings of maniaIndividual alternates between feelings of mania
and depressionand depression
ManiaMania – little sleep, elation, confusion, delusions,– little sleep, elation, confusion, delusions,
distractibility, racing thoughts, overly optimisticdistractibility, racing thoughts, overly optimistic
DepressiveDepressive – feel worthless, sinful, despair, failure,– feel worthless, sinful, despair, failure,
lethargy, unresponsivenesslethargy, unresponsiveness

Seasonal Affective
Disorder
• Depression during certain seasons,
• increase sleep, eating
Causes
• Melatonin?
• Vitamin D?
• Conditioning?
• Social Learning?

What is SchizophreniaWhat is Schizophrenia
 Includes positive and negative symptomsIncludes positive and negative symptoms
 Positive – add – Negative – take awayPositive – add – Negative – take away
 Type IType I  mostly positive symptomsmostly positive symptoms
-delusions, hallucinations, disorders of thoughts and behavior-delusions, hallucinations, disorders of thoughts and behavior
 Type IIType II  mostly negative symptomsmostly negative symptoms
-flat affect (emotions), avolition (motivation), alogia (speech)-flat affect (emotions), avolition (motivation), alogia (speech)
• Disorders characterized by confused andDisorders characterized by confused and
disconnected thoughts, emotions,disconnected thoughts, emotions,
perceptionsperceptions
• Considered by many to be most severeConsidered by many to be most severe
disorderdisorder
• Often a variety of symptoms presentOften a variety of symptoms present

Types of SchizophreniaTypes of Schizophrenia
 CatatonicCatatonic – motor disturbances– motor disturbances
 ParanoidParanoid – preoccupied with– preoccupied with
delusions, people out to get themdelusions, people out to get them
 DisorganizedDisorganized – incoherent language,– incoherent language,
inappropriate emotion, delusions,inappropriate emotion, delusions,
hallucinationshallucinations
 UndifferentiatedUndifferentiated – many symptoms– many symptoms
 RemissionRemission – no current symptoms– no current symptoms
EtiologyEtiology
Biological Influences – 1% in population, 10% in familiesBiological Influences – 1% in population, 10% in families
Biochemistry – imbalance in neurotransmitters (dopamine/serotonin)Biochemistry – imbalance in neurotransmitters (dopamine/serotonin)
Family/interactionsFamily/interactions
““Diathesis-stress model” – biological, needs stress triggersDiathesis-stress model” – biological, needs stress triggers

StrokeStroke
 StrokeStroke is a clinical syndrome characterizedis a clinical syndrome characterized
by theby the suddensudden onset of a focal neurologiconset of a focal neurologic
deficit that persists fordeficit that persists for at least 24 hoursat least 24 hours andand
is due to anis due to an abnormality of the cerebralabnormality of the cerebral
circulationcirculation..
 TheThe incidence ofincidence of strokestroke increasesincreases
and isand is higherhigher
 Significant risk factors includeSignificant risk factors include::
hypercholesterolemiahypercholesterolemia
diabetesdiabetes
oral contraceptiveoral contraceptive
useuse
heavy alcoholheavy alcohol
consumptionconsumption
hypertensionhypertension
in men than in womenin men than in women
with age
smokingsmoking

PathophysiologyPathophysiology
The focal symptoms and signs that resultThe focal symptoms and signs that result
from stroke correlate with the area of brainfrom stroke correlate with the area of brain
supplied by the affected blood vessel.supplied by the affected blood vessel.
Strokes may be classified into two majorStrokes may be classified into two major
categories based on pathogenesis:categories based on pathogenesis:
hemorrhagehemorrhageischemicischemic
In ischemic stroke,
vascular occlusion
interrupts blood flow to a
specific brain region,
producing a fairly
characteristic pattern of
neurologic deficits
resulting from loss of
functions controlled by
that region.
The pattern of deficits resulting
from hemorrhage is less
predictable because it depends
on the location of the bleed and
also on factors that affect the
function of brain regions distant
from the hemorrhage (eg,
increased intracranial pressure,
brain edema, compression of
neighboring brain tissue, and
rupture of blood into ventricles
or subarachnoid space).

Classification of StrokeClassification of Stroke
Ischemic stroke
Large vessels
(major cerebral
arteries)
Small vessels
(lacunar stroke)
Venous occlusion
Cardioembolic
Artery to
artery
Thrombotic
occlusion
Embolic
Hemorrhage
Epidural
hemorrhage
Hemorrhagic ischemic
infarction
Subdural
hemorrhage
Subarachnoid
hemorrhage
Intraparenchymal
hemorrhage

Common Stroke SymptomsCommon Stroke Symptoms
 Weakness or paralysisWeakness or paralysis
 Numbness, tingling, decreasedNumbness, tingling, decreased
sensationsensation
 Vision changesVision changes
 Speech problemsSpeech problems
 Swallowing difficulties orSwallowing difficulties or
droolingdrooling
 Loss of memoryLoss of memory
 Vertigo (spinning sensation)Vertigo (spinning sensation)
 Loss of balance andLoss of balance and
coordinationcoordination
 Personality changesPersonality changes
 Mood changes (depression,Mood changes (depression,
apathy)apathy)
 Drowsiness, lethargy, or loss ofDrowsiness, lethargy, or loss of
consciousnessconsciousness
 Uncontrollable eye movementsUncontrollable eye movements
or eyelid droopingor eyelid drooping

 Hemiplegia - most common result of CVA
Paralysis of one side of the body
May affect other functions, such as hearing,
general sensation and circulation
The degree of impairment depends on the
part of the brain affected
Stages:
Flaccid – numbness and weakness of
affected side
Spastic – muscles contracted and tense,
movement hard
Recovery – therapy and rehab methods
successful

Ischemic StrokeIschemic Stroke
 Ischemic strokes result from thrombotic or
embolic occlusion of cerebral vessels.
 Neurologic deficits caused by occlusion of large
arteries result from focal ischemia to the area of
brain supplied by the affected vessel and produce
recognizable clinical syndromes (next slide).
 Not all signs are present in every patient, because
the extent of the deficit depends on the presence
of collateral blood flow, individual variations in
vascular anatomy, blood pressure, and exact
location of the occlusion.
 Thrombosis usually involves the internal
carotid, middle cerebral, or basilar arteries.
 Symptoms typically evolve over several minutes
and may be preceded by brief episodes of
reversible focal deficits known as transient
ischemic attacks.
 Emboli from the heart, aortic arch, or carotid
arteries usually occlude the middle cerebral
artery, because it carries more than 80% of blood
flow to the cerebral hemisphere.
 Emboli that travel in the vertebral and basilar
arteries commonly lodge at the apex of the
basilar artery or in one or both posterior
cerebral arteries.

Vascular Territories and Clinical Features in Ischemic StrokeVascular Territories and Clinical Features in Ischemic Stroke
Artery Territory Symptoms and Signs
Anterior
cerebral
Medial frontal and parietal
cortex, anterior corpus
callosum
Paresis and sensory loss of contralateral leg
and foot
Middle cerebral
Lateral frontal, parietal,
occipital, and temporal cortex
and adjacent white matter,
caudate, putamen, internal
capsule
Aphasia (dominant hemisphere), neglect
(nondominant hemisphere), contralateral
hemisensory loss, homonymous
hemianopia, hemiparesis
Vertebral
(posterior inferior
cerebellar)
Medulla, lower cerebellum Ipsilateral cerebellar ataxia, Horner's
syndrome, crossed sensory loss, nystagmus,
vertigo, hiccup, dysarthria, dysphagia
Basilar (including
anterior inferior
cerebellar,
superior
cerebellar)
Lower midbrain, pons, upper
and mid cerebellum
Nystagmus, vertigo, diplopia, skew deviation,
gaze palsies, hemi- or crossed sensory loss,
dysarthria, hemi- or quadriparesis, ipsilateral
cerebellar ataxia, Horner's syndrome, coma
Posterior cerebral
Distal territory: medial
occipital and temporal cortex
and underlying white matter,
posterior corpus callosum
Contralateral homonymous hemianopia,
dyslexia without agraphia, visual hallucinations
and distortions, memory defect, cortical
blindness (bilateral occlusion)
Proximal territory: upper
midbrain, thalamus
Sensory loss, ataxia, third nerve palsy,
contralateral hemiparesis, vertical gaze palsy,
skew deviation, hemiballismus, choreoathetosis,
impaired consciousness

Clinical features of a stroke involving the middle cerebral artery.
(From Weyhenmeyer, J, Gallman, E: Neuroscience, Rapid Review Series, 1st edition, 2007, Philadelphia, Mosby, p 28, Table 3-1.)

Clinical features of a stroke involving the anterior cerebral artery.Clinical features of a stroke involving the anterior cerebral artery.
(From Weyhenmeyer J, Gallman E: Neuroscience, Rapid Review Series, 1st ed, 2007, Philadelphia, Mosby, p 30, Table 3-2.)

Conditions Associated with Focal
Cerebral Ischemia.
Vascular disorders
Fibromuscular dysplasia
Vasculitis
Atherosclerosis
Systemic (polyarteritis nodosa,
lupus, giant cell, Wegner's,
Takayasu's)
Primary CNS
Meningitis (syphilis, tuberculosis,
fungal, bacterial, herpes zoster)
Drug induced (cocaine,
amphetamines)
Carotid or vertebral artery dissection
Lacunar infarction
Migraine
Multiple progressive intracranial
occlusions (moyamoya syndrome)
Venous or sinus thrombosis
Cardiac disorders
Hematologic disorders
Rheumatic heart disease
Mural thrombus
Arrhythmias
Endocarditis
Mitral valve prolapse
Paradoxic embolus
Atrial myxoma
Prosthetic heart valves
Thrombocytosis
Polycythemia Sickle cell disease
Leukocytosis
Hypercoagulable states
(homocysteinemia, protein S
deficiency, antiphospholipid
syndrome, sickle cell disease)

∗ Subarachnoid hemorrhage may occur
- from head trauma,
- extension of blood from another
compartment into the subarachnoid space,
- or rupture of an arterial aneurysm.
∗ Cerebral dysfunction occurs because of
increased intracranial pressure and from
poorly understood toxic effects of
subarachnoid blood on brain tissue and
cerebral vessels.
Hemorrhage Stroke
• The most common cause of spontaneous (nontraumatic) subarachnoid
hemorrhage is rupture of a berry aneurysm, which is thought to arise from
a congenital weakness in the walls of large vessels at the base of the brain.
• The aneurysms become symptomatic in adulthood, usually after the third
decade. Rupture suddenly elevates intracranial pressure, which can
interrupt cerebral blood flow and cause a generalized concussive injury. This
results in loss of consciousness in about half of patients.
• With very large hemorrhages, global cerebral ischemia can cause severe
brain damage and prolonged coma.
• Focal ischemia may later result from vasospasm of arteries at or near the
site of rupture. Recurrence of hemorrhage within the first few days is a
common and often fatal complication.

Nervous System Disorders and Their Molecular Mechanisms

Nervous System Disorders and Their Molecular Mechanisms

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