Transcript Neurological Pathophysiology

Neurological
Pathophysiology
1
Edema in the CNS





Increase in tissue mass that results from the
excess movement of body fluid from the
vascular compartment or its abnormal retention
in the tissue.
Why is this a special problem in the brain and
spinal cord?
Enclosed space
Lack of lymphatics
Lack of anastomoses in venous drainage
2
Vasogenic edema



Occurs when the blood-brain barrier is upset
– Inflammation due to infection
– Toxic agents that damage capillary
endothelium
– Abnormal capillaries associated with
malignant neoplasm
Leakage of proteins fluid into interstitium →
swelling
Plasma filtrate accumulation alters ionic balance
and impairs function
3
Cytotoxic edema


Intracellular phenomenon
Hypoxia
– Cardiac arrest
– Near drowning
– Strangulation
– Focal edema due to blockage of an end artery

Toxic substances that:
– Impair sodium/potassium pump
– Impair production of ATP
4





In practice, swelling often caused by both
Treatment is different
If swelling is due to cytotoxicity, can give
I.V. bolus of a hypertonic solution such as
mannitol to draw water into the
vasculature and out of the brain
If the cause is vasogenic would this help?
No! would draw fluid into interstitial space
and increase swelling!!
5
Increased intracranial pressure (IICP)


Normal intracranial pressure is 5-15 mm Hg
May be due to:
– Tumor growth
– Edema
– Excess cerebrospinal fluid
– Hemorrhage
6
Contents of cranium





Tissue of the Central Nervous System
Cerebrospinal Fluid (CSF)
Blood
An increase in any one of these increases
intracranial pressure.
Clinical hallmarks of IICP:
– Headache
– Vomiting
– Papilledema – swelling of the optic discs
7
Since the brain is encased in the cranium,
the only way pressure can be relieved is by
decreasing cranial contents.
• Most readily displaced is CSF
• If ICP still high, cerebral blood volume is
altered:
•Stage 1 – vasoconstriction and external
compression of the venous system
•Compensating, so few symptoms
8
If ICP continues to increase, may exceed
brain’s ability to adjust.
• Stage 2:
•IICP (gradually rising) causes a decrease of
oxygenation of neural tissue
•Systemic vasoconstriction occurs to increase
blood pressure to get blood to brain
•Clinical manifestations transient: episodes of
confusion, restlessness, drowsiness, and slight
pupillary and breathing changes
9
When ICP begins to = arterial pressure, there is a lack
of compensation- beginning decompensation
Stage 3
•Hypoxia and hypercapnia → cytotoxic edema
•Decreasing levels of arousal
•Widened pulse pressure
•May begin Cheynes-Stokes respirations
•Bradycardia – due to increased pressure in carotid arteries
•Pupils small and sluggish
•Surgical or medical intervention needed
10
When all compensatory mechanisms have
been exhausted:
•Stage 4:
•Dramatic rise in ICP in a short time
•Autoregulation is lost, and get vasodilation, further
increasing intracranial volume
•↓ cerebral perfusion = severe hypoxia and acidosis
•Brain contents shift (herniate) from area of high pressure
to areas of lower pressure ↓ blood flow
11
•Small hemorrhages develop
•Ipsilateral pupil dilation and fixation,
progressing to bilateral fixed and dilated
pupils
•When mean systolic arterial pressure equal
ICP, cerebral blood flow ceases
12
Treatment





Remove the cause of the IICP
Mechanical hyperventilation to medicated and
comatose patient
Reduce blood pressure through diuretics, which
slows production of CSF and decreases bloodbrain volume
Drugs, us. Barbiturates to slow brain metabolism
and ↓ effects of hypoxia
Emergency craniotomy to relieve pressure
13
14
Brain Trauma

Highest risk:
– 15 to 30 years of age
– Infants 6 mo. to two years
– Young school age children
– Elderly persons

Male: female = 3:1
15
Most likely causes of head injury:
• Transportation accidents
• Falls
• Sports related events
• Violence
16
Two major categories of head trauma:
closed (blunt) trauma
open (penetrating) trauma
17
Open (penetrating) trauma
Break in dura results in exposure of brain tissues to
environment.
Results in focal (localized) injury
May be due to skull fracture or wound – intracerebral
hematoma
Traumatic pneumocephalus - injury to a nasal sinus that
allows air into brain or ventricles - cerebrospinal rhinorrhea
18
19
Blunt Head Trauma
More common than open trauma.
Involves head hitting hard surface or rapidly
moving object strikes head
Dura is intact – no brain tissue exposed
May cause focal or diffuse axonal injury (DAI)
20
Serious injury decrease due to :
Seat belt use
Improved management
21





Mild cerebral concussion
75- 90 % of all head injuries
Not severe
Diffuse axonal injury – no visible signs on
brain
May see transient dizziness, paralysis,
unconsciousness, unequal pupils and
shock.
Reactive period: vomiting, Temp 99 -100o,
rapid pulse, headache, and cerebral
irritation lasting 12 -24 hours.
22
Contusions (bruise) : impacts which lead to
hemorrhage and possibly hematoma
Coup (strike) – head strikes against object
shearing forces cause small tears in
blood vessels (subdural vessels)
edema
severity = force
smaller area = greater force
23
Contrecoup (rebound) – brain hits opposite
side of skull
shearing forces
and damage opposite to site of impact
24
25
Extradural (Epidural)
Hematomas





1-2% of major head injuries
Most common in 20-40 year olds
Often caused by temporal skull
fracture or injury
Artery is often the source of bleeding
Get herniation (shift) of temporal lobe
of brain through tentorial notch
26
27
Subdural hematomas





10 - 20 % of persons with traumatic
brain injury
Develop rapidly (within hours)
Typically on top of skull
Often due to tearing of veins or dural
sinuses
Acts as an expanding mass → IICP→
herniation of brain
28
Intracerebral hematomas







2-3% of head injuries
Single or multiple
Usually frontal and temporal lobes
May occur in deep white matter
Small blood vessels injured by shearing
forces
Acts as expanding mass, compresses
tissue, and causes edema
May appear 3- 10 days after head injury
29
Clinical manifestations of
contusions






Loss of consciousness, loss of reflexes
Transient cessation of breathing
Brief bradycardia
Decreased blood pressure
As hematoma enlarges:
headache, vomiting, drowsiness,
confusion, seizure, hemiparesis
30
Treatment


Contusions:
– Control intracranial pressure
 Drugs can relieve fluid pressures; may
alter Na+ conc. in brain fluids
– Manage symptoms
hematomas:
– Surgical ligation
31
Cerebrovascular Disease


Most frequent of all neurological problems
Due to blood vessel pathology:
– Lesions on walls of vessels leading to brain
– Occlusions of vessel lumen by thrombus or
embolus
– Vessel rupture
– Alterations of blood quality
32
CV disease leads to two types of brain
abnormalities :
Ischemia (with or without infarct)
Hemorrhage
33
Cerebrovascular Accident
(Stroke)


Clinical expression of cerebrovascular
disease: a sudden, nonconvulsive focal
neurological deficit
Incidence: third leading cause of
death in U.S. – half a million people a
year – one third will die from it
34
Incidence





Highest risk > 65 years of age
But about 1/3 (28%) are < 65 years
old
Tends to run in families
More often seen in females
More often seen in Blacks, perhaps
due to increased incidence of
hypertension
35
Three types :



Global hypoperfusion – shock
Ischemia – thrombotic and embolic
Hemorrhagic
36
Risk Factors


Arterial hypertension
Heart disease
– Myocardial infarction or endocarditis
– Atrial fibrillation





Elevated plasma cholesterol
Diabetes mellitus
Oral contraceptives
Smoking
Polycythemia and thrombocythemia
37
Occlusive strokes



Occurs with blockage of blood vessel by a
thrombus or embolus
May be temporary or permanent
Thrombotic stroke:
– 3 clinical types:
 TIAs
 Stroke-in-evolution
 Completed stroke
38
Transient Ischemic
Attacks



Last for only a few minutes, always
less than 24 hours
All neurological deficits resolve
Symptom of developing thrombosis
39
Causes:

Thrombus formation
– Atherosclerosis
– Arteritis
– Hypertension


Vasospasm
Other:
– Hypotension
– Anemia
– Polycythemia
40
Symptoms depend on
location


Ophthalmic branch of internal carotid
artery – amaurosis fugax – fleeting
blindness
Anterior or middle cerebral arteries –
contralateral monoparesis, hemiparesis,
localized, tingling numbness in one arm,
loss of right or left visual field or aphasia
41
Treatment


Without Tx 80% have a recurrence in
symptoms, and 1/3 go on to have a full
stroke within 5 years
Give anticoagulants prophylactically ,
usually ½ to 1 aspirin / day
42
Stroke-in-evolution


Can have abrupt onset, but develop in a
step-by-step fashion over minutes to
hours, occasionally, from days to weeks
Characteristic of thrombotic stroke or slow
hemorrhage
43
Thrombotic CVA



Involves permanent damage to brain due
to ischemia, hypoxia and necrosis of
neurons
Most common form of CVA
Causes:
– Atherosclerosis assoc. with hypertension
– Diabetes mellitus, and vascular disease
– Trauma
44





May take years to develop, often
asymptomatic until major narrowing of
arterial lumen
Anything that lowers systemic B.P. will
exacerbate symptoms (60 % during sleep)
Area affected depends on artery and
presence of anastomoses
Area affected initially is greater than
damage due to edema
Infarcted tissue undergoes liquifaction
necrosis
45
Embolic stroke


Second most common CVA
Fragments that break from a thrombus
outside the brain, or occasionally air, fat,
clumps of bacteria, or tumors
46
Common causes




Atrial fibrillation
Myocardial infarction
Endocarditis
Rheumatic heart disease and other defects
47



Impact is the same for thrombotic stroke
Rapid onset of symptoms
Often have a second stroke
48
Hemorrhagic Stroke


Third most common, but most lethal
Bleeding into cerebrum or subarachnoid
space
49
Causes:






Ruptured aneurysms
Vascular malformations
Hypertension
Bleeding into tumors
Bleeding disorders
Head trauma
50




Often a history of physical or emotional
exertion immediately prior to event
Causes infarction by interrupting blood
flow to region downstream from
hemorrhage
Further damage by hematoma or IICP
Onset less rapid than embolic CVA,
evolving over an hour or two
51



Usually chronic hypertension, and B.P.
may continue to rise
About half report severe headache
In about 70 % hematoma expands,
destroying vital brain centers, shifts of
brain tissue, and death
52
Degenerative Disorders





Progressive neurodisorders
Long-lasting
Permanent effects
Many present as syndromes
No cure, but much research
53
Alzheimer Disease
(Dementia of Alzheimer
Type)
54
Dementia is a loss of ordered
neural function









Discrimination and attending to stimuli
Storing new memories and retrieving old
Planning and delay of gratification
Abstraction and problem solving
Judgement and reasoning
Orientation in time and space
Language processing
Appropriate use of objects
Planning and execution of voluntary
movements
55
Course : slow progression
(5years or more)





At first affects only short term
memory, but gradually extends to long
term
Many experience restlessness
Many patients retain insight, which
leads to anxiety and depression
Personality may be lost
Ultimately, mute and paralyzed
Death comes from infection
56


Onset may be as young as 50, and
incidence increases with age:
– 6 % of people over 65 years have AD
– Almost half over 85 have AD

Diagnosis is by ruling out all other causes
–specific diagnosis only by biopsy or
autopsy
57


Pathology restricted to cerebral cortex,
hippocampus, amygdala, and another
basal nucleus called nucleus of Meynert
Nucleus of Meynert produces Acetylcholine
– loss results in impaired neural function
58
Pathology





Pyramidal cells die; loss of white
matter
Gyri shrink and and ventricles and
sulci expand – walnut like appearance
Neurofibrillary tangles
Neuritic (senile) plaques : filaments,
microglia, astrocytes around core of
amyloid
Amyloid angiopathy
59
http://www.ahaf.org/alzdis/about/plaques_tanglesBorder.jpg
60
61
www.infoaging.org/ d-alz-8-r-tangles.html
http://homepage.psy.utexas.edu/homepage/class/Psy332/Salinas/Disorders%20/62
Disorders.html





About 10 % of cases are familial, usually
early onset
Gene on chromosome 21 – carries gene
for amyloid protein
Almost all people with Down syndrome
who live beyond 45 years develop AD
Also linked to mutations on chromosomes
14 and 19
Prions have been isolated
63
Treatment






So far resistant
May revolve around amyloid protein
See high levels of aluminum – chelating agents
temporarily arrest or reverse some symptoms
THA(tetrahydroaminoacridine) used
experimentally – liver toxicity
Arthritics have lower incidence of AD
Therapy centers on problems of failing
cognitive skills
64
Parkinson Disease –
movement disorder




Described over 180 years ago by
James Parkinson
Combination of slowed, reduced
movements and restless tremoring
Paralysis agitans
Slowly degenerative CNS disorder
affecting 80,000 adults in North
America
65
Parkinson Disease



Degenerative disease of the basal
ganglia involving the failure of
dopamine-secreting neurons
(substantia nigra)
Can be primary or secondary
Secondary caused by trauma,
infection, neoplasm, atherosclerosis,
toxins and drug intoxication
66
67
Primary Parkinson
Disease



Begins after the age of 40, with peak age of
onset between 58 – 62
Course of 10- 20 years – slowly progressive
More prevalent in males (slightly to 2X)
68




Substantia nigra – two nuclei in midbrain
Outflow pathway from basal nuclei to
cortex via thalamus
Damage impairs flow of motor programs
Expressed as difficulty initiating
movements, general lack and slowing of
movement (bradykinesia)
69






Loss of feedback loop impairs flow of
programs and expresses as resting tremor
Most disabling symptoms are muscle
rigidity and bradykinesia
Muscle strength is more or less normal
Poor balance
Face becomes immobile and inexpressive
Autonomic function is decreased:
– orthostatic hypotension, excess sweating,
constipation, etc.
70


Some patients suffer dementia similar to
Alzheimer Disease
Not fatal, but shortens life expectancy
71
Treatment




Active exercise and good nutrition
Strategies to overcome bradykinesia
Only when symptoms are severe
are drugs given – levodopa
Side effects: cardiac arrhythmias,
gastrointestinal hemorrhage,
psychiatric problems, unpredictable
involuntary movement disorders
72
Possible therapies



Foreign or autograft of tissue still
experimental
Lesions in the subthalamic nucleus,
thalamus or internal segment of
globus pallidus promising
Stem cell research?
73
Multiple Sclerosis



Focal, chronic, progressive, usually
exacerbating and remitting
demyelination of CNS tracts.
Lesions can occur in a wide variety of
locations and give rise to complex
symptoms
Areas of demyelination are called
plaques, and can occur anywhere
oligodendrocytes provide myelin
sheath
74
Onset


Onset is between 20
and 40 years, rarely
before 15 or after 50
Females: Males 2:1
75



Clinical presentation depends on site of
lesion
Involvement of optic nerve produces
monocular visual disturbances – first
symptom in ¼ of patients
Half of people with optic neuritis are
diagnosed with MS
76
Common symptoms:



Double vision
Tingling in the back and anterior thigh
upon neck flexion – Lhermitte’s sign
Symptoms worsen when patient
becomes heated – Uhthoff’s sign
77
Diagnosis



CSF obtained by lumbar puncture
shows slight increase in protein; on
electrophoresis shows specific banding
pattern – antibodies within CSF
suggest immune reaction
Changes in velocities of visual and
auditory pathways
Plaques visible on MRI
78
Cause


Myelin undergoes breakdown and
phagocytic destruction – antibodies
may play a role
Decreased signal conduction due to
edema and demyelination that
exposes potassium channels that
short-circuit signal (edema resolves
and have partial remyelination)
79



Epidemiology hints at interaction between
a viral illness in the teen years and a
genetic predisposition
Growing up in northern temperate
climates increases rise
Non Asian heritage increases risk
80
Course





Pattern of exacerbation and remission
Stresses can trigger exacerbation:
infection, medication, stress, fatigue
Course is unstable and unpredictable
10 % undergo severe, rapid progressive
deterioration
Some have died with 7 months of first
symptom due to acute brain inflammation
and infection
81



A significant number never severely
incapacitated
Some experience only a single episode
Death is usually attributable to
complications of MS (infections due to
decreased function)
82
Symptoms





Increased urinary frequency
Lesions in frontal or temporal lobes
can cause emotional outbursts
Depression and euphoria can be
problems
Unpredictable progression taxes ability
to cope
Occasionally, plaques can cause
paraplegia or quadriplegia
83
Therapies



Only corticosteroids and ACTH appear
to have effects – reduce the duration
of exacrerbation, but have no impact
on long term outcome
Interferon β
Maintaining a healthy lifestyle and
outlook
84
Acute encephalopathies:




Reye’s Syndrome
First recognized in 1963
Characterized by encephalopathy and
fatty changes in several organs, esp.
liver
Incidence has declined in past 20
years due to awareness of ingestion of
aspirin during illness and development
of Reye’s syndrome.
85
Reye’s syndrome



Typically develops in a healthy child of 6
mo. to 15 years recovering from varicella,
influenza B, upper respiratory tract
infection, or gastroenteritis.
Stage I: vomiting, lethargy, drowsiness
Stage II: disorientation, delirium,
aggressiveness and combativeness,
central neurological hyperventilation,
shallow breathing, hyperactive reflexes,
stupor
86
Reye’s syndrome






Stage III: Insensitivity to pain, coma,
hyperventilation, rigidity
Stage IV: deepening coma, loss of ocular
reflexes; large, fixed pupils; divergent eye
movements
Stage V: seizures, loss of deep tendon
reflex, flaccidity, respiratory arrest
Mortality is 10 or more
Formerly 40 to as high as 80%
In a few cases death is due to liver failure
87
Reye’s syndrome

Cause:
– May have a genetic predisposition
– May be due in part to exhaustion of glycogen
stores and use of fatty acids -Mitochondrial
injury

Treatment:
– Aggressive intensive care
– Treatment for brain edema and IICP
– Fluids I.V. and control of blood electrolytes
– Prevent hyperthermia
88
Seizure disorders


Seizure is and abnormal discharge of
electrical activity within the brain. It is
a rapidly evolving disturbance of brain
function that may produce impaired
consciousness, abnormalities of
sensation or mental function or
convulsive movements.
Convulsions are episodes of
widespread and intense motor activity
89
Epilepsy



A recurrent disorder of cerebral function
marked by sudden, brief attacks of altered
consciousness, motor activity or sensory
phenomenon.
Convulsive seizures are the most common
form
Some, but not all, recurrent seizures are
due to epilepsy
90
Epilepsy



Second most common neurological
disorder
Incidence increases with age, with
30% initially occurring before 4 years
and 75 -80 % before 20 years.
Causes: brain tumor, scar tissue,
neurological disease, great majority of
cases are idiopathic.
91
Signs and symptoms vary:
petit mal – almost imperceptible
alterations in consciousness
grand mal – generalized tonic-clonic
seizures – dramatic loss of consciousness,
falling, generalized tonic-clonic
convulsions of all extremities,
incontinence, and amnesia for the event.
92



Some attacks are proceeded by a
prodrome – a set of symptoms that warn
of a seizure
As the seizure begins, the patient may
experience an aura – mental, sensory or
motor phenomena
Others have no warning
93
Phases of a grand mal
seizure
1.
Tonic phase ( 10 -20 seconds) –
muscle contraction
Epileptic cry – respiration stops
2.
3.
Clonic phase – (1/2 -2 minutes)
muscle spasms; respiration is
ineffective; autonomic nervous
system active
Terminal phase (about 5 minutes)
–limp and quiet, EEG flat lines
94


5-8 % are at risk of status epilepticus
– a series of GTCS without regaining
consciousness – medical emergency
Seizure activity lasts more than 30
minutes
– Acidosis
– Elevated pCO2
– Hypoglycemia
– Fall in blood pressure

Can lead to severe brain damage or death
95
Epileptogenic focus




Group of brain neurons susceptible to
activation
Plasma membranes may be more
permeable to ion movement
Firing of these neurons may be
greater in frequency and amplitude
Electrical activity can spread to other
hemisphere and then to the spinal
cord
96
Treatment




Treat any underlying metabolic disorders,
or tumors
Most cases can be controlled through
routine use of antiepileptic medications –
usually only one drug to minimize side
effects
Surgical intervention if drugs ineffective
Supportive therapy – patients learn to
cope effectively with stress, eat well, and
get sufficient rest and avoid triggers.
97
Eliciting stimuli:






Hypoglycemia
Fatigue
Emotional or physical stress
Fever
Hyperventilation
Environmental stimuli
98



Patients are normal between attacks
Can participate in sports, drive a car (if no
seizures for 6 mo – 1 year)
Should not drink alcohol
99