Huntington’s Disease
Progressive autosomal dominant neurodegenerative
disorder caused by expansion of a CAG (cytosine
,adenine , guanine ) repeat coding for polyglutamine
in the huntingtin protein.
Genetics Review
• Chromosomes - are located in the nucleus
• They provide the instructions for all the
information necessary for the living
organism to grow and function
• These instructions come in form of a
complex molecule called DNA
(Deoxyribonucleic Acid).
DNA- Blueprint of life
• DNA comes in compact form, a twisted
ladder shaped molecule called a double
helix.
• Composed of a string of nucleotides. The 4
units are adenine (A), thymine (T), cytosine
(C), and guanine (G).
Genes
• “Functional” regions of DNA that contain
specific instructions are called genes.
• Example would be regions of DNA that code
for making proteins.
Huntingtin Protein
• Cytoplasmic protein found in almost all
tissues of the body and brain
• Normal function is not well understood, yet
implicated in cell membrane recycling and
neuroprotection.
• Studies suggest that huntingtin protein
regularly interacts with other proteins found
in the brain
• The altered form of huntingtin protein leads
to nerve cell death in brain.
Genetic Mechanism of HD:
Unstable Trinucleotide repeat
• The gene responsible for causing HD is
located in chromosome 4. The gene
regulates the production of huntingtin
protein.
• Huntingtin protein contains within it the
amino acid glutamine (C-A-G). In people
with HD, however, there is an excess
number of glutamine.
• That is why HD is often referred to as a
trinucleotide repeat disorder
HD = Huntingtin protein with expanded CAG
(glutamine) tract
CAG repeat
• 10 – 35 in normal individuals
• More than 40 repeats in diseased patients
Proteins must be folded normally to function. Mutant
expansion of CAG causes an unusual huntingtin
protein which clumps together in the cell and causes
neuronal cell death (in the brain only)
How much CAG expansion is too much?
• People with 10 to about 35 copies of CAG
have a normal functioning form of the
huntingtin protein.
• Expansion of 40 or more CAG repeats is
often full penetrance and the person will
develop HD.
• For people who have 36 to 39 copies of
CAG, the outcome is less clear. Some will
develop the symptoms of Huntington's
disease and some will not.
Neuropathology of HD
• HD involve atrophy and cell death of the
basal ganglia, the complex subcortical
structures involved in control of motor
movement, cognition and sensory
pathways.
• Specifically, there is a progressive and
marked degeneration of the caudate and
putamen (striatum).
Neuropathology
• There are different types of neurons and
neurotransmitters in the striatum, and the
balanced interaction between dopamine,
acetylcholine, and GABA play a vital role in
regulating motor movements.
.
• Striatal gamma aminobutyric acid (GABA-
ergic) medium spiny neurons are most
vulnerable to cell death in HD.
.
• GABA normally has inhibitory effects on the
thalamus and tells the cortex to ‘brake’
movement.
 Degeneration of Basal Ganglia

The brain of a person with HD has bigger

openings due to death of nerve cells in that region

Brain Imaging studies in HD:

Striatal degeneration and atrophy

• Caudate and putamen hypometabolism and

volume loss begins before onset of
symptoms.

• Some evidence of patchy cortical thinning

• Selective loss of these specialized cells
result in decreased inhibition (i.e., increased
activity) of the thalamus.
• Atrophy of thalamic subnuclei projecting to
• Thalamus increases output to certain
regions of the cerebral cortex. This may
lead to the disorganized, excessive
(hyperkinetic) movement patterns of
chorea.
are more prominent over the posterior
cortical regions and proceed to the anterior
cortical regions with disease progression,
and more evident in the left striatum.
the prefrontal areas, substantia nigra, nuclei
of hypothalamus, small regions of the
hippocampus, and Purkinje cells of the
cerebellum.

Clinical Features of Huntington’s Disease

• As disease progresses, damage to other
pathways and dopamine receptors causes a
decreased stimulation to the cortex and
thus rigid bradykinetic features.
Risk factor: GENETICS
Altered chromosome 4
Overproduction of huntingtin protein
↓
Clumping of huntingtin protein
↓ Asian and African populations.
Neuronal cell death in the basal ganglia
↓ mean age onset of 35-44 years (range 2 to
Imbalance of neurotransmitters in striatum (GABA)
• Progressive neurodegenerative disorder
characterized by atrophy of the basal
ganglia causing triad of cognitive, motor
and psychiatric impairments. There is no
cure for HD.
• Inherited autosomal dominant disorder with
a 50% chance of inheriting the mutant gene
from an affected parent.
• In western Europe and USA prevalence is
higher at about 7-10 per 100, 000. Lower in
• Typically an adult onset disorder with a
80 years).

↓ • <20% first display symptoms after age 50

Decreased inhibition of the thalamus and have a slower progression of the
disease
↓
Disrupts critical interneural pathways • <10% of cases are juvenile HD with onset
before age 20 years.
↓
Thalamus increases output to regions of the cerebral • Survival after onset is 15-18 years (range
cortex 5-25 years) the average age of death is 54
years old.
↓
Excessive movement patterns of chorea Motor Abnormalities: Early/Mid HD
(Hyperkinesia)

↓
• Chorea – is the hallmark of the disease
onset, present in most adult cases.
Decreased stimulation to the cortex (bradykinesia)
- Abnormal, rapid, involuntary,
unpredictable movements
 - appears as prominent uncontrolled
jerking movements of the limbs,
trunk, face and oral motor
structures.
• Motor impersistence - inability to maintain
voluntary muscle contractions at a constant
level.
• Motor speed and coordination, fine motor
control, postural stability/balance and gait
progressively worsens.
Nsg. Dx: Risk for fall r/t inability to maintain
voluntary muscle contraction.
Motor Abnormalities: Later Disease
• Dystonia - Prolonged involuntary twisting
movements caused by slow muscle
contraction
- may be caused by lack of appropriate
reciprocal inhibition to the
muscle
• Bradykinesia and rigidity often increases
causing inability to move or care for oneself.
• Ocular motor disturbances may be seen in
as much as 75% of individuals.
• Subgroup of adult-onset HD patients has
more predominant dystonia and rigidity,
and paucity of chorea throughout the course
of disease sometimes referred to ‘rigid-
akinetic’ subtype.
Nsg. Dx: Self Care Deficit r/t uncoordinated
movement and cognitive change.
Motor Speech Impairments:
Hyperkinetic Dysarthria of Speech
• Oral mechanism exam often reveals normal
structure, symmetry of face, lips, tongue,
jaw and palate.
• Speech tasks such as conversation, oral
reading, AMRs, vowel prolongation, are very
useful to detect articulatory breakdown,
rate and prosody changes, phonatory-
respiratory discoordination
• Choreiform movements characterized by
quick, unpatterned involuntary head/neck,
jaw, face, tongue, palate, pharyngeal,
laryngeal, and/or thoracic and abdominal
movements at rest and during movement
• Dystonia or slower waxing/waning
movements or posture
Nsg. Dx: Impaired motor speech r/t quick
unpatterned involuntary tongue movement.
Primary Hyperkinetic Dysarthria in HD
• Articulation: Imprecise consonants,
distortions and irregular breakdowns, slow
& irregular AMRs
• Phonation-Respiration: Sudden forced
inhalation/exhalation, voice stoppages,
transient breathiness or strained-harsh
voice quality, excess pitch or loudness
variation
• Resonance: Intermittent hypernasality
• Prosody: Prolonged phonemes, variable
rates and stress patterns, inappropriate
silences, short phrases
Dysphagia: Common and Progressive
• Hyperextension of head and trunk
• Lingual chorea and decreased ability to
orally control bolus
• Rigidity of neck and/or mandible in
bradykinetic subgroup
• Absent or inefficient chewing
• Intraoral retention and segmented bolus
transfer
• Premature loss of control and bolus spillage
into pharynx
• Swallow timing and coordination deficits
Nsg Dx: Dysphagia r/t absent or inefficient chewing
Swallowing impairments
• Delayed swallow onset with advanced
disease
• Decreased pharyngeal contraction and
clearance
• Laryngeal penetration and aspiration
• Unpredictable inhalation/ respiratory-
swallow discoordination
• Frequent belching (especially those with
chorea)
• Intra-oral sensory deficits
• ‘Tachyphagia’ or behavioral impulsivity
very common thus increasing risks for
choking and airway obstruction
Nsg Dx: Risk for Aspiration r/t Inspiratory-swallow
discoordination

Cognitive Impairments
• Visuospatial (scanning and perceptual
skills)
• Executive Function: cognitive planning
and sequencing, spatial working memory,
cognitive flexibility and shifting set
• Memory: slowed learning rates, impaired
or delayed free recall which improves
significantly with cued recall/recognition,
preserved retention rates
• Language: Word finding deficits, decreased
phrase length and syntactic complexity,
decreased comprehension of complex
information
• Cognitive-communication impairments vary
in onset and severity in early-mid disease
and progresses to dementia in advanced HD
Psychiatric Symptoms
• Can occur in any stage of the disease and
do not follow clear progression (or relation
to CAG repeat)
• May be present before motor symptoms and
mistaken for other primary psychiatric
illnesses (such as schizophrenia or bipolar)
• Dysfunction of frontostriatal pathways
implicated in psychiatric symptoms
Psychiatric Manifestations
• Depression
• Apathy
• Irritability/Outbursts
• Anxiety
• Impulsivity
• Obsessive-compulsive disorder
• Aggressive Behavior
• Disinhibition
• Psychosis
• Suicide
Myasthenia Gravis
“Descending Paralysis”
(NMJ –AI destruction of AChR)
• Skeletal (voluntary) muscles disorder
characterized by weakness and easy
fatigability due to autoimmune destruction
of the AChR in
the postsynaptic membrane of the
NMJ
• Progressive muscle paralysis without
sensory loss or atrophy.
• Neuromuscular Junction (NMJ)
– Components:
• Presynaptic membrane
• Synaptic cleft
• Postsynaptic membrane
– Presynaptic membrane contains
vesicles with Acetylcholine (ACh)
which are released into synaptic
cleft in a calcium dependent
manner
– ACh attaches to ACh receptors
(AChR) on postsynaptic membrane
• Neuromuscular Junction (NMJ)
– The Acetylcholine receptor (AChR) is a
sodium channel that opens when bound
by ACh
• There is a partial depolarization of
the postsynaptic membrane and
this causes an excitatory
postsynaptic potential (EPSP)
• If enough sodium channels open and
a threshold potential is reached, a
muscle action potential is
generated in the postsynaptic
membrane
Background:
• Acquired autoimmune disorder
• Clinically characterized by:
– Weakness of skeletal (voluntary)
muscles
– Fatigability on exertion.
• First clinical description in 1672 by Thomas
Willis.
Grade Levels of MG:
classification by disease severity
Grade I: Focused and specific such as Ocular
Myasthenia Gravis (Weakness of the eye
muscles)
Grade II a: Generalized mild weakness
II b: Generalized moderate weakness
Grade III: Generalized severe weakness
Grade IV: Myasthenia Crisis
a severe exacerbation of the disease an depletion of
ACh
receptors at the NMJ causing severe muscle
weakness,
respiratory insufficiency and SOB , extreme
difficulty swallowing, may cause quadriplegia or
quadriparesis (incomplete paralysis).
Generalized autoimmune MG
Myasthenia Gravis has several courses:
 1. periodic remissions • Chloroquine
2. A slowly progressive course • Prednisone
3. A rapidly progressive course • Timolol
4. A fulminating course • Anticholinergics
(exploding in a sudden manner) • Disease without recognizable cause as of
spontaneous origin.
Etiology:
Pathophysiology
Thymoma
 it gives an incorrect instructions to • In MG, antibodies are directed toward the
acetylcholine receptor at the neuromuscular
developing immune cells, ultimately
junction of skeletal muscles
resulting in autoimmunity and the
• Results in:
production of the AChR antibodies,
setting the stage for the attack on the – Decreased number of nicotinic
NMJ. AChR at the motor end-plate
– Reduced postsynaptic membrane
folds
– Widened synaptic cleft

Etiology : Ideopathic
Thymoma
Virus (HSV)
Autoimmune

IgG antibody Reduced receptor by

interact blocking,
AChR at the NMJ. degradation, damage

Reduced AChR
density

Decrease binding of ACh to AChR

Diminished transmission of nerve

impulses at NMJ

Decrease amplitude of AP

Failure in muscle fiber contraction

Weakness muscle
(Voluntary)

Drugs
• Antibiotics
(Aminoglycosides, Grade Levels of MG:
ciprofloxacin, ampicillin, Classification by Severity
erythromycin)
• B-blocker (propranolol) Grade I: Focused and specific such as Ocular
• Lithium MS (weakness of the eye muscles)
• Magnesium SO4 Grade II a: Generalized mild weakness
• Procainamide II b: Generalized moderate weakness
• Verapamil Grade III: Generalized severe weakness
• Quinidine
Grade IV: Myasthenia Crisis a severe
exacerbation of the disease and depletion
of ACh receptors at the NMJ causing
severe muscle weakness, respiratory
insufficiency and SOB, extreme difficulty
swallowing may cause quadriplegia or
quadriparesis (incomplete paralysis).
Generalized autoimmune MG
Myasthenia gravis has several courses:
1. Periodic remissions
2. Slowly progressive course
3. Rapidly progressive course
4. Fulminating course
(exploding in a sudden manner)
Clinical presentation:
Ocular muscle weakness
• Orbicularis Oculi- muscle that controls
eyelid movement
• Masseter- jaw muscle used for chewing
Occular muscle weakness
– Asymmetric
• Usually affects more than one
extraocular muscle and is not
limited to muscles innervated by
one cranial nerve
• Weakness of lateral and medial
recti may produce a
pseudointernuclear opthalmoplegia
– Limited adduction of one eye with
nystagmus of the abducting eye on
attempted lateral gaze
– Ptosis caused by eyelid weakness
– Diplopia is very common
Risk for Eye Infection r/t exposure of cornea
• Facial muscle weakness is almost always
present
– Ptosis and bilateral facial muscle
weakness
– Sclera below limbus may be
exposed due to weak lower lids
Altered body image r/t changes in anatomical
contour of the face & neck
• Basic physical exam findings
– Muscle strength testing
– Recognize patients who may
develop respiratory failure (i.e.
difficult breathing)
– Sensory examination and DTR’s
are normal
• Bulbar muscle weakness
– Palatal muscles
• “Nasal voice”, nasal
regurgitation
• Chewing may become
difficult
• Severe jaw weakness may
cause jaw to hang open
• Swallowing may be
difficult and aspiration
may occur with fluids—
coughing and choking
while drinking
– Neck muscles
• Neck flexors affected
more than extensors
• Respiratory muscle weakness
– Weakness of the intercostal
muscles and the diaghram may
result in CO2 retention due to
hypoventilation
• May cause a
neuromuscular emergency
– Weakness of pharyngeal muscles
may collapse the upper airway
• Monitor negative
inspiratory force, vital
capacity and tidal volume
• Do NOT rely on pulse
oximetry
• Arterial blood
oxygenation may
be normal while
CO2 is retained
• Ineffective breathing pattern r/t collapse of
upper airway
• Ineffective airway clearance r/t inability to
cough
• Fluctuating weakness increased by exertion
– Weakness increases during the day
and improves with rest
• Extraocular muscle weakness
– Ptosis is present initially in 50% of
patients and during the course of
disease in 90% of patients
• Head extension and flexion weakness
– Weakness may be worse in
proximal muscles
• Progression of disease
– Mild to more severe over weeks to
months
• Usually spreads from ocular to
facial to bulbar to truncal and limb
muscles
• Often, symptoms may remain
limited to EOM and eyelid muscles
for years
• The disease remains ocular in
16% of patients
• Remissions
– Spontaneous remissions rare
– Most remissions with treatment
occur within the first three years
• Limb muscle weakness
– Upper limbs more common than
lower limbs
Upper Extremities
Deltoids
 Wrist extensors
Finger extensors
Triceps > Biceps
Lower Extremities
Hip flexors (most common) Plantar Flexors
Quadriceps
Hamstrings
Foot dorsiflexors
• Co-existing autoimmune diseases
– Hyperthyroidism
• Occurs in 10-15% MG
patients
– Exopthalamos
and tachycardia
point to
hyperthyroidism
– Weakness may
not improve with
treatment of MG
alone in patients
with co-existing
hyperthyroidism
– Rheumatoid arthritis
– Scleroderma
– Lupus
Work-up
• Electrodiagnostic studies
– Repetitive nerve stimulation
– Single fiber electromyography
(SFEMG)
– SFEMG is more sensitive than RNS
in MG
Electrodiagnostic studies:
Repetitive Nerve Stimulation
• Low frequency RNS (1-5Hz)
– Locally available Ach becomes
depleted at all NMJs and less
available for immediate release
• Results in smaller EPSP’s
• Patients w/ MG
– AchR’s are reduced and during RNS
EPSP’s may not reach threshold and no
action potential is generated
» Results in a decrease in the
compound muscle action potential
» Any decrement over 10% is
considered abnormal
» Should not test clinically normal
muscle
» Proximal muscles are better tested
than unaffected distal muscles
Train 1 - Decremental response
Train 2 - Post-tetanic potentiation
Train 3 – Post-activation exhaustion
• Most common employed stimulation rate is
3Hz
• Several factors can affect RNS results
– Lower temperature increases the
amplitude of the compound muscle
action potential
• Many patients report
clinically significant
improvement in cold
temperatures
– AChE inhibitors prior to testing
may mask the abnormalities and
should be avoided for at least 1
day prior to testing
Single-fiber electromyography
• Concentric or monopolar needle electrodes
that record single motor unit potentials
– Findings suggestive of NMF transmission
defect
 Increased jitter and normal fiber
density
 SFEMG can determine jitter
» Variability of the interpotential
interval between two or more
single muscle fibers of the same
motor unit
Generalized MG
Abnormal extensor digiti minimi found in 87%
Examination of a second abnormal muscle will
increase sensitivity to 99%
Occular MG
• Frontalis muscle is abnormal in
almost 100%
• More sensitive than EDC (60%)
Lab studies
– Interleukin-2 receptors
• Increased in generalized and
bulbar forms of MG
• Increase seems to correlate to
progression of disease
Imaging studies
– Chest x-ray
• Plain anteroposterior and
lateral views may identify
a thymoma as an anterior
mediastinal mass
– Chest CT scan is mandatory to
identify thymoma
– MRI of the brain and orbits may
help to rule out other causes of
cranial nerve deficits but should
not be used routinely
Pharmacological testing
• Edrophonium (Tensilon test)
– Patients with MG have low
numbers of AChR at the NMJ
– Ach released from the motor nerve
terminal is metabolized by
Acetylcholine esterase
– Edrophonium is a short acting
Acetylcholine Esterase Inhibitor
that improves muscle weakness
 – Evaluate weakness (i.e. ptosis and
opthalmoplegia) before and after • Acute autoimmune disorder
administration
• There is involvement of T and B
lymphocytes –↑cytokines and cytokine
Steps:
receptors in serum (IL 2, soluble IL 2
1. 0.1ml of a 10 mg/ml edrophonium solution
receptor) and CSF (IL 6, TNF α, interferon)
is administered as a test
• Brain is unable to send messages
2. If no unwanted effects are noted (i.e. sinus
• Legs and arms are commonly affected
bradychardia), the remainder of the drug is
injected
3. Consider that Edrophonium can improve
Etiology
weakness in diseases other than MG such as
ALS, poliomyelitis, and some peripheral
neuropathies  75% of cases are preceded by an acute
infectious process usually GI or Respiratory
Complications of MG in origin
• Respiratory failure  20-35% of cases are preceded by a
• Dysphagia Campylobacter jejuni, HV, EBV infection.
• Complications secondary to drug treatment  Recent: swine influenza vaccine
– Long term steroid use
• Osteoporosis, cataracts,
 Destruction most often occurs in segments
between the Nodes of Ranvier
hyperglycemia, HTN
• Gastritis, peptic ulcer
Why Nodes of Ranvier are the target of attack?
disease
• Neural targets are likely to be gangliosides
• Pneumocystis carinii
• Gangliosides are complex glycosphingolipids
that contain one or more sialic acid
residue
• Gangliosides are present in large quantities
Guillain-Barré Syndrome
in human nervous tissues and in key
“Ascending Paralysis “
sites: NODES OF RANVIER
AI-Destruction-Nodes of Ranvier

Acute inflammatory demyelinating polyneuropathy

Pathophysiology of GBS
(AIDP) caused by an autoimmune disorder
affecting the peripheral nervous system, usually
Etiology
triggered by an acute infectious process
characterized by ascending paralysis.  Autoimmue
 Campylobacter jejuni
Demyelination of Nerve Fibers  Virus
 Negative conduction abnormalities  EBV
- Slowed axonal conduction, variable conduction  HV
blocks occur in the presence of high- but not  SIV
-low frequency volleys of impulse.
Antigens enter into the body by multifenestrated
 Positive conduction abnormalities cells
- Generations of ectopic impulses, spontaneous
and abnormal “crosstalk” between
demyelinated axons
Innate immune response results in the uptake
of the pathogens by immature APC

Production of antibodies and Phagocytosis of

the bacteria

Immunopathogenesis
 Cranial Nerves and Their Functions Test

B cells are activated by newly activated Th2 No.Name General FunctionSpecific Function
cells. This produces a cell-mediated and I Olfactory Sensory Smell
humoral response against the pathogen. II Optic Sensory Vision
IIIOculomotor Motor, Motor to four of six
Parasympathetic eye muscles and
Migration to lymph nodes, a mature, upper eyelid;
differentiated APC activate CD4 T cells that parasympathetic:
recognize antigen from the infectious pathogen constricts pupil;
thickens lens
IV Trochlear Motor Motor to one eye
muscle
Molecular mimicry V Trigeminal Sensory, Motor Sensory to cornea
face and teeth;
motor to muscles of
mastication

VI Abducens Motor Motor to one eye

muscle
VII Facial Sensory,Motor, Sensory: taste;
Lymphocytes and macrophages Parasympathetic motor to muscles of
circulate in the blood and facial expression;
eventually find myelin. parasympathetic to
salivary and tear
glands
Lymphocytic infiltration of spinal roots and VIII Vestibulo- Sensory Hearing and
peripheral nerves, followed by cochlear balance
macrophage-mediated, multifocal IX Glossopha- Sensory,Motor, Sensory: taste and
stripping of myelin causing axonal ryngeal Parasympathetic touch to back of
damage tongue; motor to
pharyngeal
muscles;
parasympathetic to
Defects in the propagation of salivary glands
electrical nerve impulses with X Vagus Sensory,Motor, Sensory to pharynx,
eventual conduction blocks Parasympathetic larynx, and viscera;
motor to palate,
pharynx, and
Guillain–Barré syndrome larynx;
parasympathetic to
viscera of thorax
and abdomen
XI Accessory Motor Motor to 2 neck and
upper back muscles
Sensory Dull aching
Acute
changes: pains of the
progressive
Paresthesia/ lower back, XII Hypoglossal motor Motor to tongue
ascending
numbness flank or muscles
weakness
in the lower legs
hands/feet
Fatigue Scale Assessment
Muscle Strength Assessment

Complications
M. Fishers Cranial nerve  Breathing difficulties
Syndrome involvement:  Residual numbness or other sensations
facialdroop Long term complications:
(VII),  Serious, permanent problems with
dysphagia (V), sensation and coordination, including some
cases of severe disability
 A relapse of Guillain-Barre syndrome
  Rarely, death from complications such as
respiratory distress syndrome
Nursing Diagnosis
1. Acute Pain r/t stimulation of free nerve endings
2ndary to nonsynaptic transmission of nerve
axons.
2. Self care deficit r/t decrease strength and
endurance.
3. Low Self–Esteem r/t disruption in how client
perceive one’s own body.
4.Ineffective airway clearance r/t neuromuscular
dysfunction
5. Bathing/hygiene, feeding, toileting self-care
deficit related to decrease energy production.
6. Fear related to sudden onset of illness.
7. Impaired spontaneous ventilation r/t
denervation of intercostal muscles.
Diagnosis
 Diagnosis is made by recognizing the pattern of
rapidly evolving paralysis with areflexia.
 Absence of fever or other systemic symptoms
and characteristics of antecedent events.
Diagnostics
Lumbar Puncture
In lumbar puncture “LP” CSF is withdrawn through a
needle inserted into the subarachnoid space of the
spinal canal between the L3-L4 or L4-L5 lumbar
vertebrae.
• Measure CSF pressure
• determine viral or bacterial origin
• Increase in WBC count
• presence of cytokines (IL 6, TNF α, interferon)
• Cx: inc. ICP → rapid decrease in pressure within CSF
around spinal cord→ brain herniation
Electromyography
- Needle electrodes inserted into the muscle .
- Pattern of electrical activity in the muscle
both at rest and during activity may be
recorded.
- Relaxed muscles are normally electrically
silent except in motor end plates.
- Abnormal spontaneous activity with
denervation or inflammatory changes in the
affected muscle.
- Fibrillation potentials and positive sharp
waves – reflect muscle irritability.
Serum Antibody titer
IgM and IgG are highest in the early course of
the disease.
Diagnostic Tests
• Nerve conduction studies
• (Sensory) determining the conduction
velocity and amplitude of APs where
these fibers are stimulated at one point.
• Helpful in determining whether sensory
symptoms arising from pathology are
proximal or distal to the root of ganglia
Normal conduction:
- Arms: 50-70 m/s
- Legs: 40-60 m/s
Treatment
There is no cure for Guillain-Barré Syndrome, but
there are treatments available…
 Plasmapharesis
 Immunoglobulins
Multiple Sclerosis (MS)
Multiple Sclerosis (MS) is a chronic progressive,
non-contagious, degenerative disease of the
CNS characterized by demyelinization of
neurons.
Areas affected by MS
 Brain
 Spinal cord
 Optic nerves
Pathologic triad
 CNS inflammation
 Demyelination
 Gliosis (scarring)
History of Multiple Sclerosis
 The earliest description of MS was recorded in
Holland on August 4, 142. But the history of
the disease really begins in the 19th century
with the first clear illustrations and clinical
description of the disease beginning to appear
in 1838.
 The first actual case was diagnosed in 1849.
It was Dr. Jean-Martin Charcot who is credited
for giving the first signs and symptoms of
Multiple Sclerosis.
Multiple Sclerosis - Epidemiology
 Worldwide occurrence:1.1 – 2.5 million
cases
 Female: male ratio = 2:1
 In Canada an estimated that 55,000-75,000
people have multiple sclerosis
 Affects nearly 500,000 individuals in the US
 Occurs most frequently between ages 25 –
35
Genetic and the Immune System

Factors Contributing for MS
Genetic Factors
 Gender: Women are 2 to 3 times more
likely to get the disease.
 Family history of MS: A family history
increases the risk
 Race: MS appears more in Caucasians than
in other groups
Environmental factors
 Latitude: As you increase latitude, mainly
above and below 40° latitude. MS is more
common. It is five times more likely in
temperate and cooler climate regions.
 Socioeconomic status: Least common in
rural and lower class.
 Migration: The age at which you may
move may also be an important factor. “If
you move before the age of 15, your risk is
likely to that of the people in the country
you move to. If you move after the age of
15, your risk stays fixed at that of the
country you grew up in”.
 Infection:
“They believe MS is a delayed reaction to a
viral infection contracted during childhood by a
genetically susceptible person” (O’Connor 13).
The viral infections may include shingles,
chicken pox, measles, or certain herpes. An
idea they also have concerns the age at which
you get the infection. The older you are the
higher the risk for MS.
***Remember that in warm countries, children
contract viruses at a younger age.
Not Everyone with a Genetic Risk Will Develop MS –
Why?
• Risk is modified by Environmental factors
o Sunlight
o Diet (e.g., vitamin D)
o Other lifetime experiences
(infections?)
Multiple Sclerosis - Causes
o The exact cause of multiple sclerosis is not clear
o MS patients, have a higher number of immune
cells which suggests there might be an
immune response; this is suspected to be
due to a virus or genetic defect
o Other causes are environmental and hereditary
How Does it work?
Demyelination of Nerve Fibers in MS
 Positive conduction abnormalities
generations of spontaneous ectopic impulses and
abnormal “crosstalk” between demyelinated
axons
 Negative conduction abnormalities
slowed axonal conduction, variable conduction
blocks occur in the presence of high- but
not -low frequency volleys of impulse.
The destruction of the myelin sheath leads to
impaired communication between nerve cells
Mode of Action
 The immune system attacks axons,
XX
causing destruction of the myelin sheath
resulting in a Conduction Block which
leads to permanent loss of function.
MS is an Immune-Mediated Disease
Pathophysiology
2
 Autoimmune response results in damage
and loss of fibers.
 Nerves can regain myelin, but the process is
not fast enough to avoid the deterioration
that occurs
 Astrocytes form scars where myelin
formerly existed
 Inflammation, loss of myelin of nerve fibers,
XX
and the scarring that follows result in
reduced transmission of nerve signals within
XX
the CNS.
 Type of symptoms and severity vary widely
due to the location of the scar tissue and
the extent of demyelination
9
Multiple Sclerosis Signs and Symptoms
1
 Vision impairment
 Lhermitte‘s sign- momentary paresthesia
 Difficulty in walking
 Weakness and exhaustion
 Memory loss
 Depression
 Urinary and bowel problems
XX XX
 + Babinski’s reflex
Nursing Diagnosis
1. Pain chronic r/t stimulations of free nerve
ending 2 to destructions of myelinated
axons.
13 7
 2. Impaired sensory perception r/t nonsynaptic
3. transmission of demyelinated axons.
4. Fatigue r/t decrease energy production
5. Paralysis r/t conduction block of demyelinated
axons.
6. Low self Esteem r/t change in brain
structure/function.
7. Ineffective coping r/t multiple life changes.
8. Risk for care givers role train r/t severity of
the care receiver, duration of care giving
required
9. Deficient knowledge regarding condition,
prognosis, complications, treatment and
need r/t unfamiliarity of information
resources.
Multiple Sclerosis - Types
There are 4 major types of MS
 Relapsing-remitting MS (RR-MS)
 Primary-progressive MS (PP-MS)
 Progressive-relapsing MS (PR-MS)
 Secondary-progressive MS (SP-MS)
Relapsing-remitting MS (RR-MS)
 More than 80%
 Defined clinical exacerbation of neurological
symptoms
 Followed by complete or incomplete
remission during which the person fully or
partially recovers from the deficits acquired
during relapse
Primary-progressive MS (PP-MS)
 10 to 20%
 Gradual progression of the disease
 No overlapping relapses and remissions
Progressive-relapsing MS (PR-MS)
 Rare
 Initially presenting as PP-MS, however during
the course of the disease the individuals
develop true neurologic exacerbations
 Steady progression of clinical neurological
damage with superimposed relapses and
remissions.
Secondary Progressive MS (SP-MS)
 SP-MS is characterized by a steady
progression of neurological damage with or
without superimposed relapses and minor
remissions
 Individuals with SP-MS will have experienced
a period of RR-MS, which may have lasted
from 2 to 40 years
 Any super-imposed relapses and remissions
fade over time
How Is MS Diagnosed?
 At least two episodes of symptoms
a) Occur at different point in time
b) Result from involvement of different areas
of the central nervous system
 Absence of other treatable causes for the
symptoms
 Results of neurological testing
DIAGNOSTIC WORKUP
Radiologic studies
 It is diagnosed by neurological examination
and brain MRI scans
o Signs of two separate attacks with
demyelination of CNS supports the
diagnosis.
Magnetic Resonance Imaging (MRI)
Is a noninvasive diagnostic scanning technique in
which the client is placed in a magnetic field. MRI
provides a better contrast between normal and
abnormal tissue than the CT scan. For visualization
of the brain, spine, limbs, and joints, heart, blood
vessels, abdomen and pelvis.
Brain Atrophy (Shrinkage) in Untreated MS
Images acquired over the course of 7 years from a
single person with untreated MS Brain atrophy is
seen as the enlargement of the ventricle and sulcal
spaces. In untreated MS, by year 2, up to 6% of
brain volume can be lost.
Serum and CSF Analysis
 Blood tests
 Lumbar Puncture (spinal tap)
- If MS is present, persistent elevated of CSF
protein IgG (oligoclonal antibody) bands can
be seen in spinal fluid which is an additional
confirmatory test.
Symptom Management – Examples
 Pain control
 Management of impaired bladder and bowel
function
 Anti-spasmodic drugs
 Treatment of fatigue
 Splinting for contractures
 Counseling
CNS TUMOR
Glioma
Stem cells are unspecialized immature cells that can
renew themselves through cell division for long
periods of time.
** A glioma is a type of tumor that start in the brain
or spine. It is called a glioma because it arises from
glial cells. The most common site of gliomas is the
brain.
Types of CNS tumor
n Intracranial
n Intraspinal

Main Types of Brain Tumor
Primary – tumor starts in the brain
Types of Primary Tumor
1. Benign - do not contain cancer cells
2. Malignant- do contain cancer cells.
GRADE 4
A tumor are very malignant and are often difficult
to treat, also known as Glioblastoma Multiforme,
usually requires operation to take as much tumor as
possible followed by radiation therapy and
sometimes chemotherapy

Metastatic – Tumor starts somewhere else in the Another Grading System

body. Earlier Stages GRADE I
GRADE II
Cell Types and Associated Tumors of the GRADE III
Central Nervous System.
Advanced Stages GRADE IV

Associated Tumors Function Cell Type

Oligodendroglioma Provides insulation Oligodendrocyte
Oligoastrocytoma to neuronal axons
to facilitate signal Astrocytoma Provides nutrition, Astrocyte
conduction Pilocytic insulation,
Ependymoma Forms lining of the Ependymal cell astrocytoma and structural
ventricular Diffuse support for neurons
System astrocytoma
Anaplastic
astrocytoma
GLIOMAS Glioblastoma
Oligoastrocytoma
Classification: Pleomorphic
Astrocytomas xanthoastrocytoma
from astrocyte, invasive, slow growing in the Subependymal giant-
brain and spinal cord cell
Glioblastoma Multiforme astrocytoma
extremely malignant, highly vascular tumors that Ganglioglioma Conducts electrical Neuron
arise from Gangliocytoma signals
undifferentiated astrocytomas Central neurocytoma within neural
Oligodendrocytomas systems
from oligodendroglia, avascular, encapsulated,
malignant
form is oligodendroblastoma
Location
Ependymoma
Supratentorial
from ependymal cells, more common in children,
Above the tentorium, in the
malignant form is called ependymoblastoma.
cerebrum, most common in adults.
Grading
Infratentorial
 Low-grade - Well-differentiated (benign) Below the tentorium, in the
with a better prognosis. cerebellum, most common in
children.
 High-grade - Undifferentiated (malignant)
Neural stem cells are multipotent and self-
with worst prognosis.
renewing, have been isolated from the
subventricular zone,
WHO grading system for astrocytoma
GLIAL PROGENITOR CELLS — self-renewing
GRADE 1
precursors capable of producing astrocytes and
Least malignant and slowest to grow. If they are
oligodendrocytes
surgically totally removed they can be associated
with long-term remission.
INTRASPINAL TUMORS
Classified according to location in relation to
GRADE 2
the dura and spinal cord
Have more malignant cells in them, they grow
faster and have the tendency to recur, often more
Extradural- arising from the extradural space
cancerous than the first time.
Intradural - originating within the neural tissue.
GRADE 3
Malignant cells undergoing mitosis, infiltrating and
1. Extramedullary
may recur at a higher grade.
arising from the blood vessels, meninges or
nerve roots, forming an intradural tumor
 Diagnostics
Neurofibromas (Nerve sheath tumor) Bone Scan
grow in the nerve root that extends into the PET scan
extradural space CT- guided needle biopsy
Open biopsy
Meningiomas
tumor originates from the dura matter and
arachnoid membranes Parkinson’s Disease (PD)
Dopamine depletion-
2. Intramedullary Substantia Nigra
tumors arising from within the substance of
the spinal cord itself Degenerative disorder resulting in dysfunction of
extrapyramidal system caused by dopamine
Ex. depletion which interferes with inhibition of
Ependymomas, Astrocytomas, Glioblastomas, excitatory impulses.
Oligodendrogliomas, Ganglioneuromas,
Medulloblastomas, Hemangioma, Extrapyramidal pathways:
Hemangioblastomas cerebral cortex, thalamus, cerebellum and brain
stem.
RISK FACTOR
Genetics Nitroglial dysfunctions produce by syndrome of
abnormal movement called Parkinsonism.
- Cells contain genetic material called
chromosomes. Extrapyramidal Tracts: uncrossed tract of motor
- Controls growth of the cells nerves from the brain to the anterior horn of the
- When the genetic material becomes spinal cord. Within the brain extrapyramidal
pathways comprise of various relays of
abnormal, it can loose its ability to control
motorneurons between motor areas of cerebral
its growth.
cortex and basal nuclie, the thalamus, the
cerebellum and brain stem.
Infections
Diet: Nitrate C
Exposure to Chemicals:
Historical Perspective
Formaldehyde
• Dr. James Parkinson (1755-1828)
Vinyl Chloride
- 1817
Acrylonitrile
• “involuntary tremulous motion”
• “pass from a walking to a running
pace”
Multi hit hypothesis
Cellular telephones • “shaking palsy”
Exposure to high tension wires • London home
Hair dyes
Head trauma Epidemiology
• Ave. age of onset 60
Causes • Men and women affected equally but more
Unknown prevalent in males
Radiation therapy • Genetic Link—chromosomes 4
• Environmental Toxin (MPTP)
Pathophysiology • African-Americans and Asians less likely
INTRACRANIAL TUMOR than Caucasians to develop Parkinson’s
INTRASPINAL TUMOR
Pathogenesis
Nursing Diagnosis • Four Theories
- Ineffective breathing pattern r/t denervation  Oxidative damage
of the intercostals • Impaired protection
- Impaired tissue perfusion r/t damage of (↓gluthatione, ↑reactive
SNS. iron)
- Impaired physical mobility r/t loss of muscle  Environmental toxins
control/function. • MPTP-Methyl-phenyl
- Altered Sensory Perception r/t tetrahydropyridine-->
neuromuscular deficit with loss of sensory MAO B–> MPP--> death
reception and transmission. in nigrostriatal neurons
- Impaired Urinary Elimination r/t loss of  Genetic predisposition
nerve conduction above the level of reflex • Mutations in the gene for the
arc. protein alpha- synuclein
 located on chromosome Walking often difficult to initiate and patient
4 may have to lean forward increasingly until
they can advance. They walk with small
 Accelerated aging
shuffling steps, have no arm swings, and
may have difficult in stopping. Some
Pathophysiology
patient may walk with festinating gait
• Imbalance of dopamine and acetylcholine
example: at an increasing speed to prevent
• Loss of 80 to 90% of dopaminergic
themselves from falling because of there
production in the substantia nigra pars
center of gravity.
compacta.
• Lewy Bodies
Characteristic Problems
Risk factors
Aging 60 • Hypophonia-soft speech
Gender: Male • Dysarthria-unclear pronunciation
Race: Caucasian
Genetic • Festination-shuffling gait
Exposure: toxins, free radicals • Micrographia – small handwriting

Degeneration substantia nigra * The combination of tremor, rigidity and

pars compacta neurons
Death of dopamine cells
Striatal dopamine depletion
Reduce thalamic
excitation of motor cortex
bradykenisia result in small tremolous
and often eligible handwriting. Patients
have difficulty in writing or and hand to
assume flexed posture when erect.
• Hypomimia – decreased facial animation
• Blepharospasm – involuntary eyelid
closure
• Blepharoclonus – fluttering of close
eyelids
• Myerson’s sign – tap in between eyebrows

Hoehn and Yahr Staging of Severity of

Parkinson’s Disease

Stage Description
0 No clinical signs evident

I Unilateral involvement

II Bilateral involvement but no postural

abnormalities
Imbalance Dopamine - Acetylcholine
Mechanism III Bilateral involvement with mild
postural imbalance on examination or
history of poor balance or falls;
patient leads independent life
T – remor IV Bilateral involvement with postural
R - igidity instability; patient requires substantial
A - kinesia/ help
Bradykinesia
P - ostural instability V Severe, fully developed disease;
patient restricted to bed or wheelchair

Diagnostic Features
• Four Cardinal Signs
Nursing Diagnosis
• T- remor 1. Impaired Physical Mobility r/t increase
• R igidity resistance to passive motion with
generalized rythmic flexion and extension
• A kinesia and bradykinesia of the limbs
• P ostural instability 2. Risk for Fall r/t Loss control of movements
 3. Self Care Deficit r/t loss of muscle tone and Movements of brain
coordination inside skull
4. Impaired (verbal, written) communication r/t
loss of motor control , r/t loss of oral
muscle tone control
5. Activity intolerance r/t neuromuscular Brain damage and nerve injuries
impairment result in frequent and severe
6. Bathing/hygiene, dressing/grooming self-care headache
deficit r/t neuromuscular impairment
7. Risk for aspiration related to impaired muscles
of swallowing Risks Factor
8. Risk for falls related to impaired gait and Falls
balance. Firearms

Diagnosis Traumatic Brain Injury

• History and Physical examination
• Bradykinesia must be present with atleast two
of the following: limb muscle rigidity,
resting tremor, or postural instability.
Diagnostics
Radiologic study
• No specific diagnostic available
• (PET) Positron Emission tomography
- Computerize tomographic technique that uses
radioactive substance to examine
metabolic activity of various structures.
- given by inhalation or injection.
- Radioactive (FDG) Fluoro-2- deoxy-D-glucose.
HEAD TRAUMA
Neurologic Assessment
• Levels of consciousness
• Glassgow coma scale
• Cranial nerve assessment
Definition – Traumatic Brain Injury (TBI)
- is a result of an external mechanical force to the
brain that leads in a change to cognitive, physical,
psychosocial functioning associated with altered
state of consciousness. The impairments can be
temporary or permanent.
Brain floating with CSF
 Primary Brain Injury
 Results from what has occurred to the brain
at the time of the injury
Secondary Brain Injury
 Physiologic and biochemical events which
follow the primary injury
Categories of Brain Injuries
Closed (Blunt) Brain Injury
 Acceleration/Deceleration
 If a moving object hits a movable
head (e.g. head gets hit with a bat)
 If a moving head hits something
stationary
 Shaken type of movement
(E.g., when head rocks back and forth in skull).
 Non-Acceleration
 Much more rare, referred to as a
crushing injury
 If a moving object hits a head that is
fixed (e.g. car falls on head while
you are working under it).
Categories of Brain Injuries
Open Brain Injury
 Low Velocity
o Skull is no longer intact, part of
skull or debris gets into the brain.

 High Velocity
External forces transmitted to o Bullets penetrate the skull and
the brain goes into the brain matter.

CAUSES OF BRAIN INJURIES

Direct injury to brain • Coup and Countercoup Injuries
tissue • Concussion vs Contusion
• Diffuse Axonal Injury
• Epidural Hematoma
• Subdural Hematoma
• Intracerebral Hemorrhage
• Compound fracture
• Penetrating injury

COUP
 The energy of impact from a small hard object
tends to dissipate at the impact site, leading to a
COUP contusion
COUNTERCOUP
Impact from a larger object causes less injury at
the impact site, since the energy is dissipated at the
beginning or end of the head motion.
Contusion
Bruising type of injury to the brain resulting to
sudden loss of consciousness or coma. Contusion
may occur with subdural/ extradural collection of
blood, intracerebral hemorrhage.
Contusion is considered severe form of axonal injury
with shearing of blood.
Concussion
Mild bruising to the cerebral tissue cause by jarring
of the brain resulting in transient
loss of consciousness.
Concussion is considered a mild form of diffuse
axonal injury
Categories of Diffuse Brain Injury
Mild Concussion (without LOC)
 Grade I confusion disorientation with
amnesia
 Grade II confusion and retrograde amnesia
(5-10 min)
 Grade III confusion with retrograde and
anterograde.
 Immediate but transitory clinical
manifestation.
 CSF pressure rises, ECG, EEG changes.
 Confusion last for several minutes.
 with amnesia for events preceding the
trauma.
 Head pain, nervousness and not being
themselves.
 (grade IV) Classic Cerebral Concussion
 diffuse cerebral disconnection from
brain
 retrograde and anterograde amnesia
 May experience post-concussive
syndrome
 Vital signs quickly stabilized
 Confusion for hours to days
 Head pain, fatigue, nausea, inability to
concentrate and
 Forgetfulness, mood and affect changes
Diffuse Axonal Injury
Diffuse axonal injury is characterized by extensive
generalized damage to the white matter of the brain
Strains during high-speed acceleration/deceleration
produced in lateral motions of the head may cause
the injury.
Categories of Diffuse Brain Injury
DAI
Mild (coma > 6 -24 hrs)
Persistent residual cognitive, phsychologic,
sensorimotor deficit
 Decorticate and decerebrate posturing
 Experience prolonged period of stupor
 Permanent deficit in memory, attention,
abstraction, reasoning, problem solving,
executive function, vision or perception and
language
Decorticate
Decerebrate
Moderate
Widespread impairment cerebral cortex,
diencephalon, tearing of axons both
hemispheres
 Transitory decortication or decerebration
 Unconsciousness lasting days or weeks
 On awakening the person is confused and
suffer long period of post-traumatic
anterograde and retrograde amnesia
Severe (LOC > week)
Severe mechanical disruptions of axons in both
hemisphere, diencephalon and brain stem
 Immediate autonomic dysfunction that
disappear in few weeks
 IICP 4-6 days after injury
 compromised coordinated movements with
verbal and written communication, inability
to learn and reason, inability to modulate
behavior
Compound Fracture
Object strikes the head with great force or head
strike the object forcefully temporal or occipital blow
upward impact of cervical vertebrae (basilar skull
fracture)
Penetrating Injury
Missile (bullets) or sharp projectile (knives, axes,
screwdriver)
CENTRIPETAL APPROACH
(outside to inside)
• –Scalp
• –Cranium
• –Epidural
• –Subdural
• –Subarachnoid
• –Intra-parenchymal
 • –Intra-ventricular Acute Severe within Rapid deterioration
Head hours to drowsiness,
Injury agitation, stuporous,
Traumatic Hemorrhage: coma, signs of brain
 Subgaleal stem compression,
pupil dilation
 Cephalohematoma contralateral
-Subperiosteal Outer Table hemiparesis.
 Epidural (Extradural)
-Subperiosteal Inner Table
Subacute Moderate 2 hours Lucid , Drowsiness,
 Subdural- Epi-arachnoid Head to weeks stuporous coma,
 Subarachnoid Injury after Increase ICP
 Parenchymal Hemorrhage
Chronic Mild Head weeks - Dull headache,
 Intra-ventricular Injury months slowness in thinking,
after apathy, drowsiness,
contralateral
EPIDURAL HEMATOMA
hemipareresis,
Source of Bleeding progressive
neurologic changes,
MENINGEAL VESSELS aphasia,
 Arterial (high pressure) papilledema, LOC
 Venous (low pressure) changes.
DURAL SINUS
 High flow, low pressure INTRACEREBRAL HEMATOMA
 Diploic veins (Fx)
 Marrow sinusoids  Usually frontal and temporal lobes
 May occur in hemispheric deep white matter
EPIDURAL HEMATOMA
 Small blood vessels injured by shearing
forces
 Trauma -> fracture & concussion
 Acts as expanding mass, compresses tissue,
 Tearing/stripping of both layers from inner and causes edema
table
 May appear 3- 10 days after head injury
 Laceration of outer periosteal layer
 Laceration of meningeal vessels
 Inner (meningeal dura) intact Meningitis and Encephalitis
 Blood between naked bone and dura

NORMAL arterial pressure continues to dissect  Meningitis is an inflammation of the

protective membranes covering the brain and
 Significant trauma spinal cord, known collectively as the meninges.
 Fracture & concussion (l.o.c)
 Lucid Interval  The inflammation may be caused by
– pt Wakes Up infection with viruses, bacteria, fungus and
– 40% pts. less commonly by certain drugs.
 Delayed neurologic Sx (hrs. Later)
 Herniation, coma and death Etiology
 Bacterial
 Fungi
 Parasites
 Rickettsia
 Viral
- Arboviruses, Herpes viruses, Enterovirus
Retroviruses, Paramyxoviruses

Septic Meningitis: common causes

SUBDURAL HEMATOMA  Neonates: Group B Streptococci, Escherichia

coli, Listeria monocytogenes
 Infants: Neisseria meningitidis, Haemophilus
HEMATOMA TYPES OF ONSET CLINICAL influenzae, Streptococcus pneumoniae
INJURY OF S/S MANIFESTATION  Children: N. meningitidis, S. pneumoniae
 Choroid plexus/Altered
BBB

 Adults: S. pneumoniae, N. meningitidis,

Mycobacteria, Cryptococce
Produce exudates and thickens
CSF
Risk Factors:
 Cerebral shunt
 Extraventricular drain
o infections with staphylococci and
pseudomonas
 Children younger than 5 Produce Inflammation
exudates and of brain
 Pregnancy
thickens CSF parenchyma
 Working with animals
 Compromised immune system

Pathophysiology:
IICP Hydrocephalus Seizures Meningeal
Bacteria reach the meninges through: Irritation
 Bloodstream
 Direct contact between the meninges Headache Macewen’
through either the nasal cavity or the skin Vomiting sign +kernig’s/Brudzinki’s
papill- sign
Bacterial Meningitis edema

 Mechanism of invasion is not completely Complications of Bacterial Meningitis (IMMEDIATE)

understood  Dehydration
 Host defense mechanisms within the CSF  Pericardial Effusion
are often ineffective.  Death
 Bacterial proliferation stimulates a  coma
convergence of leukocytes into theCSF.  loss of airway reflexes
 seizures
 Meningeal and subarachnoid space
 cerebral edema
inflammation
 vasomotor collapse
 release of cytokines into the CSF (TNF,
 DIC
interleukin 1, 6)
 Respiraytory arrest

Infectious agent enters

Blood circulation Complications of Bacterial Meningitis (DELAYED)
 Snhl
 Ataxia
 Blindness
Induce a meningeal Fever, chills,  Bilateral adrenal hemorrhage
inflammatory reaction tachycardia  Death
 Seizure disorder
 Focal paralysis
Meningeal vessels become  Subdural effusion
Hyperemic-Permeable  Hydrocephalus
 Intellectual deficits

Encephalitis
Neutrophils migrate
Into SAS ‡ Inflammation of the brain parenchyma, present as
diffuse and/or focal neuropsychological dysfunction
most commonly a viral infection with parenchymal
damage varying from mild to profound.

Etiology
 Arboviruses and herpes simplex virus are
the most common causes of endemic and
sporadic cases of encephalitis, respectively.
 Varicella, herpes zoster and Epstein-Barr
virus - cause of encephalitis in
uncompromised hosts. ‡
 Severe and Fatal Encephalitis-
Arthropodborne viruses and HSV
 Viral replication

 Hematogenous spread to CNS ‡ Diagnostic Strategies

 Retrograde transmission along
neuronal axon
 Direct invasion of the subarachnoid
space through infection in the olfactory
submucosa
Vectors and Reservoirs
 Humans are the reservoir for
enteroviruses, mumps, measles, herpes
simplex, and varicella viruses.
 H. capsulatum and C. neoformans are
organisms found in soil contaminated
with bird droppings
Vectors and Reservoirs
 Cats are the definitive host for T. gondii; they
acquire the parasite from eating infected rodents or
other infected meat.
 Monkeys are the reservoir for simian B virus
(cercopithecine herpesvirus 1).
Modes of Transmission
 Brain Abscess: CT Scan
-Ring enhancement. Surrounding area of
inflammation & edema
 Hydrocephalus:
Lumbar Puncture Contraindication
 Presence of infection on the skin or soft
tissues at the puncture site
 Likelihood of brain herniation
Indication for CT Puncture LP in Lumbar scan
before suspected Bacterial meningitis
 Immunocompromised state
 Hx of stroke, mass lesion, focal infection,
head trauma
 Seizure occurring 7 days prior
 Abnormal LOC
 Inability to answer questions or follow
commands
 Abnormal visual fields or paresis of gaze
 Focal weakness
 Abnormal speech

 Enteroviruses: transmitted from person CSF ANALYSIS

to person
 through ingestion of materials
contaminated by the feces of an
infected person
 through exposure to infectious
respiratory droplets
 indirectly via fomites
 Opening pressure 50-200 mm H2O
 Lateral recumbent position and sitting
position ay increase it several fold
 Elevated in bacterial, TB, fungal infections
 Falsely elevated in tense and obese patients
or when there is marked muscle contraction

 Some causes of encephalitis, such as

Listeria sp. and T. gondii, may be
acquired through consumption of
contaminated food

 Measles and varicella viruses are

transmitted from person to person
through airborne route.

 Simian B disease is transmitted to

humans:
 through monkey bites
 exposure of naked skin or mucous
membranes to infectious monkey
saliva or monkey tissue culture

Pathogenesis: Meningeal irritation

 + kernig’s sign
 + brudzinki’s sign
 Nucchal rigidity (neck stiffness)

COMPLICATIONS
 IICP
 Hydrocephahus
 Seizures