NEUROLOGICAL

DISORDERS
NOR FIRDOUS MOHAMED
LECTURER (CLINICAL PSYCHOLOGY)
 Chapter Outline

1 Cerebrovascular Accidents
2 Traumatic Brain Injury
3 Degenerative Disorders: Dementia
 1. CEREBROVASCULAR ACCIDENTS
Produces permanent brain damage, but amount of the
damage depending on the size of the affected blood
vessels.

Strokes consequences can produces impairment in

perception, emotional recognition and expression, memory
and language.
• Strokes
Causes
a) Ischemic Stroke
 Cerebrovascular accident
caused by occlusion of
blood vessel.
 Thrombus (Blood clot
that forms in blood
vessels) or embolus
(Piece of material that
floats from one part of
vascular system until it
reaches an artery too
small to pass through);
both block a blood vessels
and obstruct the blood
flow.
• Strokes
Causes
b) Hemorrhagic Strokes
 Cerebrovascular
accident caused by
rupture or malformed of
cerebral blood vessel by
high blood pressure
causing bleeding within
the brain.
 The blood that leaks
out of the defective
blood vessels
accumulates within the
brain. Putting pressure
on the surrounding
brain tissue and
damaging it.
1) Surgery: Treatments
• Using mechanical medical device by
inserting these tools to the cerebral
blood vessel and extended until its
reach the obstruction by pulling out or
sucking out the clot.
• Hemorrhagic strokes caused by weak
or malformed blood vessels, brain
surgery maybe used to seal off the
faulty vessels in preventing another
hemorrhage.
• Ischemic strokes involves surgery in
removing the blood clot.

2) Anticoagulant drugs:
• To make the blood less likely to clot,
reducing the likelihood of another
strokes.
 Treatments (Continued)
1) Tissue plasminogen activator (tPA),
• To minimize the amount of brain damage caused by strokes, by
administering drugs that dissolve blood clots by dissolution of fibrin (a protein
that involves in clot formation) in an attempt to reestablish circulation to an
ischemic brain region.
• tPA – administering a clot dissolving drug after the onset of strokes is
beneficial, but only used in 3 hours.
• Mixed results, issues of significant side effects and complications such as
toxic in the central nervous system, further damage the blood brain barriers
and may cause cerebral hemorrhage.

2) Desmoteplase (anticoagulant enzyme from the bat’s saliva)

• Causing no excitotoxic injury when injected directly to brain. Desmoteplase
restored blood flow and reduced clinical symptoms in a majority of patients if
given up to nine hours after occurrence of a stroke.
Treatments (Continued)
How strokes can be Prevented?
• Lifestyle risks: blood pressure, smoking, diabetes,
cholesterol – Atherosclerotic plaques (precursor to
heart attacks)
• Atherosclerotic plaques cause severe narrowing of
the interior of the artery which greatly increase the
risk of a massive strokes.
• Carotid endarterectomy (inserting shunt in the
artery and removing plaque) & Placing a Stent in a
narrowed carotid artery to expand and hold open a
partially occluded artery (mixed results)

• The best secondary prevention:

• Cardiac Rehabilitation
2. TRAUMATIC BRAIN INJURY
(TBI)
 1) Penetrating brain injuries (open-head injuries)

Causes – cause damage of the portion of the brain that is injured

by the object or bone. Traumatic brain injury can be
caused by a projectile or a fall against a sharp object that
fractures the skull, causing the brain to be wounded by
• Serious health problem the object or a piece of the broken skull.
– US: 1.4 million annually
treated in emergency
department  death.

– Damage to blood vessels can

deprive the normal blood
supply, and accumulation of
blood within the brain cause
further damage by exerting
pressure within the brain.

2) Closed-head injuries
- do not involve penetration of the brain, but these
injuries can also cause severe injury or death.
- Blow with blunt object can cause Coup and contrecoup.
 I M PA C T

o Bundles of axons can be

twisted, blood vessels can
be ruptured and
cerebrospinal fluid can
distort the walls of the
ventricles.

o Traumatic brain injuries

can be followed with
several months later by
seizures.
 – Form of TBI
– Neurodegeneration due to repeated head trauma, and
received media attention due to prevalence in athletes
who participated in sports and experience frequent and
repeated head trauma.
– Confirmed by postmortem examination
– CTE symptoms of moods and cognitive impairments
appears years after the injury was sustained.
 15-33
Chronic Traumatic Encephalopathy:
Neurodegeneration Following Repetitive Concussive And Sub concussive Brain
Trauma.

(a) This image shows a brain section from a patient with CTE (right) compared to a control section (left). The dark
regions in the CTE section are areas where abnormal tau protein accumulated following brain injury. The white
asterisk denotes dense accumulation of these proteins in the amygdala. (b) This image shows a diffusion tensor
image scan of the corpus callosum from a control brain (in green, left) and the brain of a former professional boxer
with CTE in (pink, right). The corpus callosum in the CTE patient’s brain shows damage (shorter and less extensive
white matter tracts) associated with the brain injury.
 Treatment
• Primary treatment:
– Reduce swelling and intracranial pressure, as well as ensuring
adequate blood flow to the injured region.
• Secondary treatment:
– Treat symptoms that develop after injury (likelihood of Alzheimer's
diseases)
– Drugs: to inhibit the release of glutamate. Glutamate and adenosine
are increasingly produced during the brain injury as inflammatory
agent. However, the increase glutamate promotes inflammatory and
causing more damage.
– Other potential drug not yet established tested in randomized clinical
trials.
• The long term behavioral and cognitive intervention involves
same strategies as in cerebrovascular accidents.
 3. DEGENERATIVE DISORDERS:
DEMENTIA
AD i s a n e u r o d e g e n e r a t i v e
p r o g ressi ve c o n d itio n c h a ra cterize d
b y c o g n i ti ve imp a ir men t a n d
fu n c ti on al d e c lin e . Mo s t p e o p le w ith
a d w i l l d e m o nstrate n e u r opsych iatric
fe a tu res, b e tte r k n o w n a s b e h a vio ral
a n d p s yc ho log ical s ymp toms o f
d e m e n tia ( BPSD ) .

Ea r l y r e c o gni tio n a n d tr e a tmen t o f

BPSD a r e e s s en tia l, a s th e s e c a u s e
c o n s i de rabl e d is tr e ss a n d c a r er
bur den. W h ile th e r e a r e ma n y
d i s e a se -mod i fyin g th e r apie s fo r th e
c o g n i ti ve s ymp toms s till in th e
r e s e arch s ta g e, o n ly s ymp toma tic
tr e a tmen ts a r e c u r ren tly a va ila b le fo r
thes e a n d th e BPSD .
 15-64

DEMENTIA
• Dementia caused by several neurological disorders which characterized by a deterioration
of intellectual disabilities resulting from organic disorders.
• Lewy bodies which is an abnormal circular structures with dense core consisting of -
synuclein protein; found in cytoplasm of nigrostriatal neurons in people with Parkinson’s
disease; also frequently found to be associated with dementia (20%).
• Alzheimer’s disease is most common form of dementia, which occurs in 10% of the
population over 65, almost 50% over age 85 – most common cause of dementia
• Degenerative brain disorder of unknown origin; causes progressive memory loss and other
cognitive functions, motor deficits, and eventual death

Memory deficit
critically involves Fatal diseases
Have difficulty
Confusion, difficult remembering progresses, the
remembering
with task such as recent events symptoms become
appointments, fail to
managing money. (anterograde more severe.
think other people’
amnesia) which
names
cause them easily to
get lost
 • 15-68

ALZHEIMER’S DISEASE
•Figure shows photographs of the brain of a
patient with Alzheimer’s disease and of a normal
brain.

• Figures shows wider the sulci are in the patient’s

brain, especially in the frontal and temporal lobes,
indicating substantial loss of cortical tissue

Alzheimer’s disease produces severe

degeneration of the hippocampus, entorhinal
cortex, neocortex (especially the association cortex
of the frontal and temporal lobes), nucleus basalis,
locus coeruleus, and raphe nuclei.
 • 15-69

MICROSCOPIC FEATURES OF
ALZHEIMER’S DISEASE

The photomicrographs from deceased patients with Alzheimer’s disease show (a) an
amyloid plaque, filled with β-amyloid protein, and (b) neurofibrillary tangles.
ABNORMAL BRAIN STRUCTURES
1) Amyloid Plaque (amm i loyd)
– Extracellular deposit containing dense core of -amyloid protein surrounded by
degenerating axons and dendrites and activated microglia and reactive astrocytes.
-Amyloid (A) is a protein found in excessive amounts in brains of patients with
Alzheimer’s disease.
– In patients with Alzheimer diseases the proportion of long A rises to as much as
40% of the total. Consequently, high concentration of the long form have a tendency
to fold and aggregate improperly which is toxic to the cells.

2) Neurofibrillary Tangle
– consists of dying neuron containing intracellular accumulations of twisted filaments
of hyperphosphorylated tau-protein. Normal tau protein serves as a component of
microtubules that important in cells’ transport mechanism. During the progression of
Alzheimer's diseases causing excessive amount of phosphate interrupt with the
transportation of substance within the cells.
 15-66

Alzheimer’s Disease: Causes

1) Hereditary forms of Alzheimer's
diseases involve defective genes for
the -Amyloid Precursor Protein
(APP).
2) Numerous mutations of APP gene
that produce familial Alzheimer's
diseases such as:

•Apolipoprotein E (ApoE) (ay po lye po proh teen)

• Glycoprotein that transports cholesterol in blood and plays role in cellular repair:
presence of the E4 allele of apoE gene increases the risk of late-onset Alzheimer’s
disease
•Presenilin (pree sen ill in)
• Protein produced by faulty gene that causes -amyloid precursor protein to be
converted to abnormal short form; may be a cause of Alzheimer’s disease
 3. Traumatic Brain injuries – CTE
CAUSES 4. Obesity, hypertension. High
cholesterol levels, and diabetes also are
risk factors for Alzheimer's diseases.

5. Education
• Level of education.
• A report by Bennett et al. (2003)
found a positive relationship
between increased number of
years of formal education and
cognitive performance, even in
people whose brains contained
significant concentrations of
amyloid plaques.
• Thus, formal education appears to
enable the person to maintain
higher level of cognitive
performance even in the face of
brain degeneration.
 15-67

ALZHEIMER’S DISEASE: TREATMENT

– Acetylcholinesterase inhibitors
 Acetylcholinesterase inhibitors (donepezil, rivastigmine, and galantamine)
 Helps to inhibit the destruction of Ach and enhance its activity have been found to
provide a modest increase in cognitive measures among patients with Alzheimer's
diseases.

– NMDA receptor antagonist

 NMDA receptor antagonist (memantine), helps to produce slight imporvements in
symptoms of dementia by slowing the excitoxic destruction of acetylcholinergic
neurons caused by the entry of excessive amounts of calcium.

– Immunological research with AD mice is promising.

 Administration of the vaccine suppressed the development of amyloid
plaques in the brain of mice that received vaccine from early age,
and halted the development of amyloid plaques in mice that received
the vaccine in later life.
 • 15-71

IMMUNIZATION AGAINST AΒ

• Clinical trial with Alzheimer patients attempted to destroy AB by sensitizing the patient’s immune
systems to the protein. The graph shows the effect of immunization against Aβ on the cognitive
decline of patients who generated Aβ antibodies (successfully immunized patients) and those who
did not (controls).
 END
T H A N K YO U