Transcript CM-Neuro Exam 4, Lectures 37-44

UPDATED VERSION,
My apologies for any missing info and typos
There are about 50 title slides this time
1
1.
2.
Anatomic locations of disease processes:
(NM jxn, spinal cord anterior horn, nerve root, peripheral
nerves, muscle)
Weakness differential:
(MG, ALS, Pick, heavy metals, Friedrichs, PMFL,
Polymyositis, MD)
2
1. Anatomic locations of disease
processes
a. NM
jxn
b. Spinal cord anterior horn
c. Nerve root
d. Peripheral nerves
e. Muscle
3
1a. NM jxn
4

Abnormal nerve
conduction at the
neuromuscular junction
(NMJ)
Common causes

Myasthenia gravis
 Eye fatigue
 Muscle weakness during
period of activity
 Ptosis & diplopia

Lambert-Eaton syndrome
 Muscle weakness (leg)
 Ptosis
 Difficulty swallowing

Toxins
5
1b. Spinal Cord (S.C.) anterior horn
6
Damage to ventral
gray matter of the S.C.
effects motor outputs
Typical presentation





Bilateral paresis
Tetraparesis
DTR absent
Atrophy
Fasciculation
Common causes

Strokes
 i.e. infarct of anterior spinal a.
& sulcal a.
Tumors
Adult onset spinal muscular
atrophy (genetic defect)
 Motor neuron disease
 Polio
 Transverse myelopathy


7
1c. Nerve root
8
Radiculopathies can be associated with
pain and paresis.
 Nerve root compression can cause pain

 Pain follows dermatomal distribution
 Parestheias/sensory loss follow dermatomal
distribution
Unilateral
 Sensory deficits > motor deficits

9
1d. Peripheral nerves
10
Peripheral NERVES
Glove and stocking distribution sensory
loss (and other sensory changes)
 Distal weakness
 Absent DTR’s in distal extremity mm.
 Unilateral

11
Peripheral NEUROPATHY
Damage or disease of the peripheral nerves that
can cause weakness, numbness and pain,
usually in your hands and feet, but it may also
occur in other areas of your body. The disease
can affect all three types of nerves:
 Sensory,
 Motor, and
 Autonomic
12
Peripheral NEUROPATHY
Local vs systemic causes

Local

Systemic
 Trauma / impingement
 Diabetes
 Tumors
 Nutritional deficits
 Autoimmune diseases
○ Guillian-Barré Syndrome
 Infection
 No steroid Tx!
 Medications
 Alcoholism
○ CIDP
 IV steroids!
13
Peripheral NEUROPATHY
Symptoms / Presentation of peripheral neuropathy

Sensory changes
 Paresthesias - numbness and tingling in distal extremities
 Impaired proprioception
 Burning pain
 Sensitivity to touch




Distal extremity weakness
If systemic – presented in all 4 limbs
Lack of coordination
Bowel or bladder function
14
Peripheral NEUROPATHY
Evaluation


H&P
Electrodiagnostic testing
 EMG - Electromyography
 Nerve conduction test


Blood work
LP - Lumbar puncture
15
Peripheral NEUROPATHY
Treatment
Manage Diabetes (control glucose, 80-120
mg/dL)
 Correct nutritional deficits
 Supplement metabolic insufficiencies
 Meds for neuropathic pain

 Anti-seizure meds (AEDs)
 Immuno suppressive meds
 Antidepressants (TCAs)
AED – antiepileptic drug
TCA – tricyclic antidepressant
16
1e. Muscle
17
Muscle - Myopathy
Neuromuscular disorder with
primary symptom of muscle
weakness due to dysfunction of
muscle fibers
What else would we want to ask
the patient?
Onset…rapid vs. gradual
General ROS (myalgia from recent
illness)
 Comorbidities
 Family history
 Vaccine/immunization history


Other common presenting
symptom



Cramps
Stiffness
Spasms
Common causes
Inflammatory  HIV,
dermatomyositis
 Infectious myopathies
 Endocrine/Metabolic myopathies
 Toxic myopathies  alcohol,
corticosteroids, narcotics

18
2. Weakness differential:
a.
b.
c.
d.
e.
f.
g.
h.
MG…myasthenia gravis
ALS…amyotrophic lateral sclerosis
Pick
Heavy metals…arsenic poisoning
Friedrich’s ataxia
PMFL…progressive multi-focal
leukoencephalopathy
Polymyositis
MD…myotonic dystrophy
19
2a. MG…myasthenia gravis
20
Myasthenia Gravis
Pathogenesis

Autoimmune disease in which antibodies bind to ACh (acetylcholine)
receptors at NMJ
Signs/Symptoms




Drooping eyelids (ptosis) and double vision (diplopia)
Generalized weakness
Ocular symptoms worsen as day progresses, worse w/ driving
Relieved with rest, aggravated with activity
21
Myasthenia Gravis
Dx = ephodronium


Short acting, reversible/competitive inhibitor anticholinesterase
inhibitor
Temporarily relieves symptoms by increasing ACh in the synaptic
cleft
Tx = neostigmine


Increases [acetylcholine] at NMJ
Other Tx options:
 Prednisone, plasmapheresis, and thymectomy (to remove thymic
lesions)
22
2b. ALS
23
Amyotrophic Lateral Sclerosis (ALS)
Called Lou Gehrig's Disease
 Males > females; age of onset = 40-60
 Progressive demyelination of PNS
 UMN and LMN lesions
 Symptoms - fasciculations, slurred speech,
weakness, difficulty swallowing (dysphagia),
 Mental status – intact
 Treatment: riluzole, baclofen pump (spasticity)
 NO cure

24
2c. Pick Disease
25
Pick Disease
A type of fronto-temporal dementia characterized
by personality and language disturbances.
PRESENTATION:
 Slurred speech
 Personality and behavioral changes
 Language disturbances
26
2d. Heavy metals
27
Arsenic Poisoning

General
 Found in herbicides, insecticides, rodenticides, wood
preservatives and used in manufacturing glass and paints.

Clinical findings
 CHOLINERGIC SYMPTOMS (muscarinic receptors 





secretions!)
Vague gastrointestinal (nausea, vomiting) and neurologic
(apprehension and shortness of breath) symptoms, and a
Classic sign—“garlic” breath
Followed by dysphagia, tachycardia, severe abdominal pain and
bloody diarrhea,
Then by renal and cardiac failure and circulatory collapse.
Treatment
 Dimercaprol (BALS).
28
2e. Friedrich’s Ataxia
29
Friedreich’s Ataxia
PRESENTATION:



Loss of balance and coordination
Ataxia: wide-based gate
UMN problems:





Weakness:
Hyperreflexia - DTR’s
Hypertonia
No fasciculations
No atrophy (can be disuse atrophy)
30
2f. PMFL…progressive multi-focal
leukoencephalopathy
31
Progressive Multi-Focal Leukoencephalopathy
Preceded by viral infection (JCV - polyomavirus) which attacks
myelin-producing cells, often occurring in immunocompromised
people. Location of lesion is variable and correlated with symptoms
(frequently parietal and occipital lobes).






Clumsiness
Weakness or paralysis
Vision loss
Impaired speech
Cognitive deterioration
Alien-hand syndrome
32
2g. Polymyositis
33
Polymyositis
An inflammatory myopathy
 Titer = Group A Strep, post streptococcal
complication
 Blood test = elevated Creatinine kinase,
aldolase, and ESR
 Electromyography
 ELISA for anti-Jo 1

34
Symptoms
Symmetrical & progressive, PROXIMAL muscle
weakness: hips, thighs, shoulders, upper
arms/neck.
 Dysphagia, dysphonia, mild join/muscle
tenderness, fatigue, SOB, weight loss
 Rashes - Gottrons papules, heliotrope, Shawl,
Vsign, periungual erythema
 Post streptococcal complication

35
Gottrons papules
Shawl sign
Heliotrope rash
V sign
36
Tx

Corticosteroid (prednisone)
 + Calcium & Vit D




IVIG
PT & Speech therapy
Other immunosuppressants
EXPERIMENTAL: Rituximab
 Improves muscle strength, lung function, skin
rash.
37
2h. MD…myotonic dystrophy
38
Overview
Chronic, slowly progressive and highly
variable inherited multisystem disease
 No age predilection
 Autosomal dominant inheritance
 Trinucleotide repeat disorders

39
Clinical Manifestation










Muscle weakness and stiffness, more pronounced in facial and distal
muscles
Increased muscle excitability.
Atrophy and weakness of facial muscles
Ptosis
Frontal baldness
Myotonia (prolonged muscle contraction) occurs spontaneously or is
elicited by voluntary activity or by mild stimulation, such as tapping on
a muscle (percussion myotonia).
Muscle wasting (muscular dystrophy)
Cataracts
Cardiac conduction abnormalities
Endocrine pathology
40
Morphology
The skeletal muscle
biopsy shows
characteristic central
nuclei, atrophy (smaller
myofibers) and ring
myofibers (designated
by R).
41
1.
2.
3.
4.
5.
Types of pain
Best outcome measure for pain plans
Addiction vs. Pseudoaddiction
Plan for prescribing to patients with substance abuse hx
Define physical dependence
42
1. Two Major Types of pain
1. NOCICEPTIVE PAIN
- Superficial somatic pain
- Deep somatic pain
- Visceral pain
2. NEUROPATHIC PAIN
43
NOCICEPTIVE PAIN
Think spinothalamic tract
1. Superficial somatic pain
 Skin or superficial tissues
2.
Deep somatic pain
 Ligaments, bones, blood vessels, and muscles.
3.
Visceral pain
 Within body organs.
44
Somatic Pain

Caused by the activation of pain receptors in either the body
surface or musculoskeletal tissues.

Caused by a combination of factors (i.e. underlying, pre-existent
abnormalities)




Inflammation, repetitive trauma,
Excessive activity, vigorous stretching,
Contractions due to paralysis,
Spasticity, flabbiness, disuse and misuse.

Usually described as dull or aching.

Aggravated by activity and relieved by rest.
45
Visceral Pain

Caused by the activation of pain receptors in the chest,
abdomen or pelvic areas when the internal organs are
damaged, injured or stretched, specifically:

MOI - distension, perforation, inflammation, impaction,
constipation

Associated symptoms - nausea, fever, malaise, and pain.

Characteristics – vague/dull, poorly localized/diffuse,
pressure-like, deep squeezing
46
Referred Pain




The axons of primary afferent nociceptors enter the spinal cord
through the dorsal root ganglion.
Multiple sensory nerves converge onto ascending spinal nerves
of the spinothalamic tract on their way to the thalamus.
This convergence gives rise to the concept of referred pain, whereby
pain signals originating in one part of the body may be felt in the
dermatomal distribution of another nerve (shown).
For example, patients with ischemic chest pain feel pain in their
left shoulder because the sympathetic afferent nerve fibers of the
heart are concentrated in the dorsal root ganglion of the T2-T6 spinal
segments.
47
Neuropathic Pain

Complex, chronic pain state involving:
 Shooting and burning pain or tingling and numbness
 Usually is accompanied by tissue injury (nerve fibers
damaged, dysfunction, or injury and then send incorrect
signals to other pain centers.

Causes:





Amputation (phantom limb syndrome),
Diabetes,
Multiple Sclerosis,
Shingles,
Spinal cord injury
48
2. Best outcome measure for
pain plans
49
Follow a pattern
1.
2.
3.
4.
5.
6.
Effective patient evaluation
Creating a treatment plan
Informed consents & agreements
Periodic review
Referral & patient management
Documentation
50
Goals of pain treatments
1.
2.
Improve function
Improve quality of life
51
From Analgesia to Functioning: A
Necessary Paradigm Shift
Use a function-based paradigm at diagnosis;
and follow up with a function-based treatment
plan
 “What is it you want to do on this
medicine that you cannot do now?”
 Develop a list of functional losses and gains
that will be impacted by care, then track and
modify them throughout care.

Relate,

Walk,

Sleep,

Activity,

Mood,

Work,

Enjoy
52
From Analgesia to Functioning

For example, the patient might wish to sleep in his bed instead of
the easy chair, attend function at his son’s elementary school,
attend a pain education class, and begin a program of gentle but
long-term physical therapy sessions and have his wife confirm his
progress in the other areas.

Simply “feeling better,” without improving functioning in some
aspect of an individual’s life, may not reflect improvement in
quality of life.

Modest reductions in pain score may actually be extremely
significant in terms of reclaimed function
53
3. Addiction vs. pseudoaddicition
54
Tolerance

Physiologic state resulting from regular use
of a drug in which an increased dosage is
needed to produce a specific effect, or a
reduced effect is observed with a constant
dose over time.

Tolerance may or may not be evident
during opioid treatment and does not
equate with addiction.
55
Physical Dependence

State of adaptation that is manifested by drug
class-specific signs and symptoms
(Withdrawal) that can be produced by





Abrupt cessation,
Rapid dose reduction,
Decreasing blood level of the drug, and/or
Administration of an antagonist
Physical dependence, by itself, does not
equate with addiction.
56
Addiction
Primary, chronic, neurobiologic disease, with
genetic, psychosocial, and environmental
factors influencing its development and
manifestation.
 Occurs when a person loses control over the
use of a substance, experiences cravings,
uses it compulsively, and continues to use it
despite harm and dysfunction

57
Addiction

Physical dependence and tolerance are
normal physiological consequences of
extended opioid therapy for pain and are not
the same as addiction.
58
Pseudoaddiction

Iatrogenic syndrome resulting from the
misinterpretation of relief seeking behaviors as
though they are drug-seeking behaviors that
are commonly seen with addiction.

The relief seeking behaviors resolve upon
institution of effective analgesic therapy.
59
Pseudoaddiction

Patients receiving an inadequate dose of opioid medication often seek
more to obtain relief. (Seen as “drug seeking” behavior)

Signs of pseudoaddiction:







Requesting analgesics by name
Demanding or manipulative behavior
Clock watching
Taking opioid drugs for an extended period
Obtaining opioid drugs from more than one physician, and
Hoarding opioids.
One way to discriminate between the two is to observe the functional
consequences of opioid use. Whereas pseudoaddiction resolves when
the patient obtains adequate analgesia, addictive behavior does not
60
4. Plan for prescribing to patients
with substance abuse hx
61
Basically…
Document the h/o substance abuse
 Use informed consent & agreements
 Use extra care, monitoring,
documentation and consultation with or
referral to an expert in the management
of such patients.

62
Informed Consent and Agreements

The physician should discuss the risks and benefits of the use of
controlled substances with the patient, persons designated by the
patient or with the patients' surrogate or guardian

The patient should receive prescriptions from one physician and one
pharmacy whenever possible.

If the patient is a high risk for medication abuse or has a history of
substance abuse, the physician should consider the use of a written
agreement between physician and patient outlining patient
responsibilities, including:
 Urine/serum medication levels screening when requested;
 Number and frequency of all prescription refills;
 Reasons for which drug therapy may be discontinued (violation of agreement)
63
Referral and Patient Management

Refer the patient PRN for additional evaluation /
treatment.

The management of pain in patients with a
history of substance abuse or with a comorbid
psychiatric disorder may require extra care,
monitoring, documentation and consultation with
or referral to an expert in the management of
such patients.
64
5. Define physical dependence
65
Physical Dependence…repeat


State of adaptation that is manifested by
Drug class-specific signs and symptoms
(Withdrawal) that can be produced by




Abrupt cessation,
Rapid dose reduction ,
Decreasing blood level of the drug, and/or
Administration of an antagonist
 Physical dependence, by itself, does not equate with
addiction.
66
1.
2.
3.
4.
Distinguish cluster v. migraine v. tension type headache (also episodic vs.
chronic)
Evidence based OMT effects
Outside induced causes of headaches
Diagnostic testing (imaging / labs) best suited for different secondary
headaches
67
1. Distinguish cluster v. migraine
v. tension type headache (also
episodic vs. chronic)
68
COMMON PRESENTATIONS
EXAM!!!!
Symptom
Migraine
Tension
Bilateral
Cluster
Location
Mainly Unilateral
Always unilateral
Character
Gradual in onset, Pressure or
pulsating, worse tightness –
with activity
comes and goes
Quick onset,
deep, explosive
pain
Patient
appearance
Needs quiet
darkness
No specific
pattern
Patient can
remain active
Duration
4-72 hours
Variable
½ - 3 hours
Other symptoms
Nausea,
vomiting,
photophobia,
phonophobia,
aura, neuro
deficits
None
Ipsilateral
lacrimation and
redness of eye,
stuffy nose,
Horner’s,
sweating
69
Diagnostic Criteria

Cluster headache
 Description (all four)
○ Severe headache
○ Unilateral
○ Duration 15-180 minutes
○ Orbital, periorbital or temporal location
 Autonomic symptoms (any two)
•Lacrimation
•Rhinorrhea
•Facial sweating
•Ptosis
•Miosis
•Eyelid edema
•Conjunctivae injection
70
Diagnostic Criteria

Tension-type headache
 Description (any two)
○ Pressing or tightening (tightening vice around head)
○ Mild to moderate intensity
○ Bilateral location
○ No worsening with exertion
 Associated symptoms (one)
○ No nausea or vomiting
○ Phonophobia or photophobia
 Episodic (<15/month) vs. Chronic
71
Diagnostic Criteria

Migraine without aura
 Description (any two)
○ Unilateral
○ Pulsatile quality
○ Moderate to severe pain intensity (> 6 of 10)
○ Aggravation by physical activity
 With one of the associated symptoms
○ Nausea
○ Photophonia or phonophobia
 5 attacks of the above criteria which last 4-72 hours
72
Diagnostic Criteria

Migraine with aura
 Reversible visual symptoms  Reversible sensory symptoms – numbness,
tingling
 Motor weakness –
 Headache with or within 60 minutes of aura
73
Chronic Daily Headaches
Greater than 15 per month
 Use of prophylactic medication is key to
treatment
 Can result in rebound headaches from
medication overuse

74
2. Evidence based OMT effects
75
OMT for Headaches
Shown to be effective in evidence based
studies for prevention of tension type
headaches (TTH)
 Some efficacy in acute treatment of TTH
and migraines (not evidence based)
 Direct treatment at OA, cervical spine, T1T4

76
3. Outside induced causes of
headaches
77
Secondary headaches
Sinus related
 Post trauma

Look for “red flag” signs or symptoms
78
Secondary headache causes
Tumors or masses
 Cerebral venous thrombosis
 Giant cell arteritis
 Bleeding aneurysms
 Low or high cerebrospinal pressure
 Preeclampsia

79
History

Medications
 Birth control / hormones (♀)
 Nitrates
 Others

Treatments tried
 Frequency
 Efficacy
80
Pathophysiology - TTH
Multifactorial
 Current Model

 Increased nociceptive input from pericranial
myofascial tissue
 Sensitization of dorsal horn neurons
 Increased pain transmission centrally

Not from tight pericranial muscles
81
Pathophysiology - Migraine

Multifactorial – theories
 Cortical spreading depression/depolarization
 Trigeminovascular inflammation/activation
○ Calcitonin gene-related peptide release
○ Substance P release
○ Neurokinin A
 Neuronal sensitization
 Serotonin deficit
82
4. Diagnostic testing (imaging /
labs) best suited for different
secondary headaches
83
Diagnostic Testing

Labs
 Usually of little value
 Look for causes of secondary headaches
84
Diagnostic Testing

Lumbar puncture
 Meningitis or encephalitis
○ WBC
○ organisms
 Subarachnoid bleed
○ RBC’s
 Pseudotumor cerebri
○ Elevated opening pressure
 Systemic diseases such as sarcoid, lupus
85
Diagnostic Testing

Imaging
 Usually not indicated unless secondary or red
flag symptoms
 Head MRI with MRA most sensitive for vascular
lesions or posterior fossa lesions
 Head CT is usually sufficient
○ Bleed
○ Tumor
86
Diagnostic Testing

Other testing
 EEG – rare use
 Thermography, transcranial doppler not
indicated in work up
87
1.
2.
3.
4.
5.
Define fever
Work ups based on age
Prevention with vaccines
Maternal-fetal transmission of serious bacterial infections
Define complex febrile seizure
88
1. Define fever
89
Fever
Complex physiologic response to disease,
 Mediated by pyrogenic cytokines, and
 Characterized by a

 Rise in core temperature,
 Generation of acute phase reactants, and
 Activation of immune systems
Pugh MB (ed): Stedman's Medical Dictionary, ed 27.
Baltimore, Lippincott, Williams, and Wilkins, 2000
90
Fever
What temperature is
considered a fever…
 Rectal temperature
greater than 38° C
(100.4° F) ****
 Tympanic temperature
greater than 38° C
(100.4° F)
 Oral temperature greater
than 37.8° C (100° F)
 Axillary temperature
greater than 37.2° C (99°
F)
Rideout ME, First LR: Fever: Measuring and managing a sizzling symptom. Contemporary Pediatrics
2001;18(5):42
91
Fever
Symptoms

Infants








Irritability
Fussiness
Lethargy
Poor feeding
Crying
Tachycardia
Tachypnea
Sleep changes

Older children







Body aches
Headaches
Difficulties sleeping
Poor appetite
Feeling hot or cold
Chills/shivering
Hallucinations
92
2. Work ups based on age
93
FEVER
Fever in infants less than 3 months of age is a
medical emergency.
 Infants < 1 month of age
 Full sepsis workup, including blood work, urine,
LP and empiric antibiotics

Infants 1-3 months of age
 Evaluate, labs and ? to treat or observe
94
Fever - Treatment
Benefit of Treatment
Benefit of Not Treating



Child generally feels better
Gives parents reassurance
and the feeling of “helping
their child”
 Decrease risk of
dehydration
 May help to prevent
decompensation in child
with heart or lung disease
 Unproven decrease risk of
febrile seizure
Fever is natural infection
fighter
 Slows the growth of viruses
and bacteria
 Aid the body in producing
acute phase reactants and
other immune defenses

“Artificial” absence fever
may obscure the signs of
worsening illness or illness
at all.
95
FEVER

Treatment
 Acetominophen (i.e.Tylenol)
○ 10-15mg/kg/dose, po, q4h
○ Danger of overdosage and liver toxicity
○ 2011 infant drops removed from market
 Ibuprofen (i.e. Motrin, Advil)
○ 5-10mg/kg/dose, po, q6h
96
3. Prevention with vaccines
97
Streptococcus pneumoniae vaccine




Licensed in the US in 2000
7 valent polysaccharide protein conjugate
vaccine
PCV13 – 2010 Licensure
Give at 2mo, 4mo, 6mo, and 12-15mo
98
Streptococcus pneumoniae




Gram positive diplococcus
Virulence factor is a polysaccharide capsule
Risk factors include ear infection, sinusitis,
pneumonia, immunodefiency, HIV, asplenia
Vaccine: Licensed in the US in 2000
 7 valent polysaccharide protein conjugate vaccine
 PCV13 – 2010 Licensure
 Give at 2mo, 4mo, 6mo, and 12-15mo

Developing resistance to antibiotics including
penicillin, cephalosporin, TMP-SMX, Macrolides and
fluroquinolones
99
Neisseria meningitidis vacinne


Menactra/Menveo - quadrivalent
meningococcal polysaccharide-protein
conjugate vaccine – Serogroups A, C, Y and
W-135
Routine vaccination between ages 11-12yo,
booster at 16yo
100
Neisseria meningitidis
Gram-negative aerobic diplococcus
polysaccharide capsule
serogroups associated with disease in humans are A, B, C, Y, and
W135
 Meningococcemia- blood infection,



 petechial or purpuric rash
Fulminant meningococcemia occurs in 5 to 15% of patients
with meningococcal disease and has a high mortality rate
 highest incidence during late winter and early spring
 Think about college dormitories, military barracks.
 Menactra/Menveo - quadrivalent meningococcal polysaccharideprotein conjugate vaccine – Serogroups A, C, Y and W-135

 Routine vaccination between ages 11-12yo, booster at 16yo
101
Hib vaccine


HIB at 2mo, 4mo, 6mo, 12-15 mo
The incidence of Hib invasive disease among
children aged 4 years or younger has declined
by 98% since the introduction of Hib conjugate
vaccines in 1985
102
Haemophilus Influenzae B






nonmotile Gram-negative
Polysaccharide capsule
Type B causes bacteremia, acute bacterial meningitis,
epiglottitis cellulitis, osteomyelitis, and joint infections.
Nontypable H. influenzae causes ear infections (otitis
media) and sinusitis in children, and is associated with
respiratory tract infections
Vaccine : HIB at 2mo, 4mo, 6mo, 12-15 mo
The incidence of Hib invasive disease among children
aged 4 years or younger has declined by 98% since the
introduction of Hib conjugate vaccines in 1985
103
4. Maternal-fetal transmission of
serious bacterial infections
104
HSV-2 (see next slide)
 GBS (Not testable…just an FYI)

 Prior to delivery, OB/GYN obtains culture of
mother’s anus and vagina
 If (+) culture, mother placed on abx and
prophylactic abx at delivery
105
Encephalitis - Herpes Simplex Virus


Most commonly diagnosed
HSV-1
 Severe, sporadic encephalitis in children and adults. Brain
involvement usually is focal; progression to coma and death occurs
in 70% of cases without antiviral therapy.

HSV-2
 Severe encephalitis with diffuse brain involvement in neonates who
usually contract the virus from their mothers at delivery



Temporal lobe involvement
Diagnostic TOC: HSV PCR on the CSF
Treatment: Acyclovir
 Decreased mortality from 70% to 19%
106
HSV-2
Infant with scalp vesicles
Seen with perinatal
transmission of HSV-2
107
5. Define complex febrile seizure
108
Febrile Seizure





Most common seizure disorder in childhood
associated with a core temperature that increases
rapidly to ≥38 C (100.4F) without CNS infection
Infants 6 months to children 6 years of age, peak
18 months of age
Occur in 5% of children
Two types
 Simple – generalized, <15 minutes in duration
 Complex
○ Prolonged (longer than 15 minutes), multiple
occurring within 24 hours or are focal in nature.
109
Lecture 41 - iClicker Questions
Maybe they’ll on the test?
110
Clicker Question
Which of the following children has the most concerning
presentation?
a.
b.
c.
d.
e.
10 day old with rectal temperature of 101 and a vesicular rash
on the scalp.
60 day old with axillary temperature of 101 and cough for 2
days
2 year old with a rectal temperature of 103 and a 2 minute
generalized tonic clonic seizure
3 year old with temporal temperature of 104 for 4 days,
defervescence and then a erythematous blanching rash on
his trunk and extremities
10 year old with subjective fever (mom felt with back of hand)
and 2 days of vomiting and diarrhea
111
Clicker Question
Which of the following bacteria is not treated by
Vancomycin?
a. Streptococcus pneumonia
b. Staph Aureus
c. MRSA (methicillin-resistant staph aureus)
d. Enterococcus
e. E. Coli
112
Clicker Question
Which of the following should be done following a
simple febrile seizure in a 2 year old ?
A. EEG
B. Head CT
C. Lumbar Puncture
D. Anticonvulsant prophylaxis
E. Follow-up exam in 24 hours
113
1.
2.
3.
4.
Associated findings in Neurofibromatosis
Incidence of tuberous sclerosis and most common presenting
feature
Sturge-weber disease findings
VHL disease associated tumors
114
1. Associated findings in
Neurofibromatosis
115
Neurofibromatosis I
Physical exam findings
(usually all benign)
 Café au lait macules
 Neurofibromas
 Lisch nodules
 Axillary or inguinal
freckling
Other, more concerning
findings:
 Long bone dysplasia
with higher frx risk
 Scoliosis
 Seizures
116
Café Au Lait Macules




Flat, uniformly
hyperpigmented macules
Appear in first year of life
Increase during childhood
Six or more highly suggests
NF I
 25% of normal population
have 1-3 macules
117
Neurofibromas





Cutaneous most common type
Dermal lesions
Appear before/during
adolescence
Increase in number and size
with age
Not associated with malignant
transformation
118
Optic Pathway Gliomas




Occur in 15% of
children < 6 years with
NF1
Rare in older children
and adults
Low grade gliomas,
involving optic nerve
pathway
Vision often preserved
119
Axillary Freckling
120
Lisch Nodules
121
Neurofibromatosis I
•
High rate of brain tumor development
– Rarely malignant
•
Hearing loss, headaches, seizures, scoliosis,
and facial sensory symptoms and/or pain
common
• Mental retardation in 1% of NF I cases
• Learning disability and hyperactivity common
122
Neurofibromatosis I

Other clinical associations
 Long bone dysplasia and risk of fractures
 Scoliosis in 10-25% of patients
 Seizures twice as common compared to
general population
123
Neurofibromatosis II
•
Abnormalities in the NF 2 gene
– NF 2 gene produces merlin
– Merlin is a cell membrane-related protein
that suppresses tumors
– Merlin dysfunction results in tumor growth
•
Affects approximately 1:25,000
124
Neurofibromatosis II
Café au lait macules,
 Neurofibromas of skin, and
 Seizures CAN occur with NF II


Occur much LESS commonly than with
Neurofibromatosis I
125
Neurofibromatosis II
•
Almost all patients develop bilateral
vestibular schwannomas
– Most common manifestation of NF II
– Hearing loss, headaches, facial movement
difficulty, ataxia, and vertigo
•
Schwannomas of other cranial nerves,
spinal tumors, and intracranial
meningiomas may also occur
126
Schwannomatosis…not that
important for us
Recently recognized form of
neurofibromatosis
 Genetically distinct from NF1 and NF2
 Majority of cases are due to genetic
mutation
 Rarely occurs by inheritance

127
2. Incidence of tuberous sclerosis
and most common presenting
feature
128
Tuberous Sclerosis…incidence
•
•
•
Autosomal dominant
1 in 5,000-10,000 live births
Mutations in two separate genes
• TSC1
• TSC2
129
Most common presentation…

I think the answer is epilepsy (lecture 42,
slide 7)
 Mentioned again on lecture 42, slide 17

But he does have a couple of phrases
discussing “____ is the most common …”
 “Characteristic skin findings: Hypopigmented macules
(most common)” (lecture 42, slide 8)
 “Rhabdomyoma is the most common cardiac
manifestation of TSC” (, lecture 42, slide 14)
130
Tuberous Sclerosis

Epilepsy
 Most frequent presenting feature
 Affects 80-90% of tuberous sclerosis
patients
 Seizures in first year of life in 60% of
patients
○ Adults can develop new onset seizures
131
Tuberous Sclerosis
Characteristic skin findings
 Hypopigmented
macules (most
common)
 Ash-leaf spots

Angiofibromas
 Malar region of face

Shagreen patches
 Lower trunk

Fibrous plaques
 Forehead
132
Tuberous Sclerosis

Rhabdomyoma is the most common
cardiac manifestation of tuberous
sclerosis
 Heart failure
 Murmur
 Arrhythmia
133
3. Sturge-weber disease findings
134
Sturge-Weber Disease

Etiology is unknown
 Deemed to occur sporadically

Classic sign is the port wine
stain
 Cutaneous capillary malformations
 Facial area most common
○ Forehead and upper eyelid
○ Distribution of first and second
division of trigeminal nerve
135
Sturge Weber Disease
Leptomeningeal angiomas
(capillary-venous malformations) in 10-20%
of patients with port wine stain
 Intracranial angiomas often on same side as
port wine stain
 Parietal and occipital lobes most common

136
Sturge-Weber Disease
•
Other common clinical features
– Glaucoma
– Seizures
– Visual field defects
– Stroke-like events
– Mental retardation
137
4. VHL disease associated
tumors
138
Von Hippel-Lindau Disease
•
•
•
•
Autosomal dominant
Variety of benign and malignant tumors
Management goal is early diagnosis and
treatment of tumors
Goal to avoid disability or death
139
Von Hippel-Lindau Disease
Hemangioblastomas most common tumor
 Tend to be multiple
 Annual retinal exams from infancy
 Preserve vision

Every other year MRI brain and spinal cord
after age 15
 Early diagnosis and intervention
140
Von Hippel-Lindau Disease
Clear cell renal cell carcinomas (RCCs)
 Seventy percent of patients who survive 60
years of age
 Annual renal MRI or CT
 Tumor removal indicated (not nephrectomy)
141
Von Hippel-Lindau Disease
Pheochromocytomas:
 Abnormal tumor secretion of adrenergic hormones
(epi, NE…)
 More common in younger patients
 Usually multiple
 Commonly extra-adrenal locations
 Annual plasma metanephrines (childhood)
 Annual abdominal MRI or CT (adolescence)
 Diagnose pheochromocytoma and/or pancreatic tumors
142
Von Hippel-Lindau Disease
Endolymphatic sac tumors:





Endolymph - the bodily fluid that fills the
membranous labyrinth of the inner ear
Slow growing
Hearing loss
Baseline ENT exam and audiometry during
adolescence
Further testing if/when symptoms develop
 Tinnitus, ear pain, or changes in hearing acuity
143
1.
2.
3.
4.
5.
6.
7.
8.
Principles of Palliative care
Hospice primary caregiver
Enteral feedings in terminally ill patients
Define patient decisional capacity
Define beneficence
Define autonomy
Brain death exam findings
Features of Death with Dignity act
144
1. Principles of Palliative care
145
***Five Principles of Palliative
Care***
1.
2.
3.
4.
5.
Respects the goals, likes and choices of the dying
Looks after the medical, emotional, social and
spiritual needs of the dying
Supports the needs of family members
Helps gain access to needed health care providers
and appropriate care settings
Builds ways to provide excellent care at the end of
life
146
2. Hospice primary caregiver
147
Who Makes Up the Hospice Team?
• Family member is primary caregiver
• Interdisciplinary team
o
o
o
o
o
o
o
Patients personal physician
Hospice physician/Medical director
Nurses
Home health aides
Social Workers
Clergy and bereavement counselors
Volunteers
148
3. Enteral feedings in terminally
ill patients
149
***Important Facts***


Evidenced based studies DO NOT support the use
of PEG tubes in this setting.
Some studies even indicate higher aspiration
risks and higher mortality rates in patients with
feeding tubes compared to those without.
 Higher risks due to decreased esophageal sphincter
pressure and altered GE angle.
 Placement of feeding tubes does nothing for
aspiration of secretions
150
Other studies suggest that enteral feeding
does little to improve the nutritional status or
pressure ulcer rates.
 Chronic care facilities in the southeast US
have higher rates of feeding tube utilization
compared to the midwest or northeast.

151
Are we starving this patient to death?
152
Cognitively intact patients dying of progressive
malignancy frequently lose interest in eating
and drinking - deny hunger and thirst
 Some do report xerostomia (abnormal dryness
of the mouth resulting from decreased secretion
of saliva)
 Hunger strikers deny hunger/thirst after several
days of volitional abstinence from food/drink.

153
Benefits of Not Placing the Tube

Focus on other needs of the patient
 frequent oral care
 family may experience intimacy of hand feeding
 pleasure foods…give him bon-bons
Less choking on oral secretions
 Fewer diaper changes
 Less skin breakdown

154
4. Define patient decisional
capacity
155
Capacity


Should be
assessed by the
primary physician
Does not require
legal or psychiatric
expertise
Competence
Judicial
determination
 Required when
assessing a patients
global decision
making capacity for
non-medical
issues(i.e. financial
matters)

Physicians have recognized the right of the patient to participate in medical
decision making for the last 25 years. The principle of autonomy, or the right to
make choices about one's own life, has now become the centerpiece of
modern American biomedical ethics
156
Decisions Near the End of Life
Patients have the right to refuse
recommended life-sustaining medical
treatments.
 Based on the philosophical concepts of:

 Respect for patient autonomy
 Common-law right of self determination
 Patient’s liberty interest under the US Constitution.
157
Patients without decisional capacity




Same rights at mentally (legally) competent patients
Treatment should conform to what the patient would
want on the basis of written or oral advanced care
planning
If the patient’s beliefs are not known, care decisions
should be based on evidence of what the patient would
have chosen based on known values, previous choices
and beliefs.
All else fails – best interest of the patient
158
Advanced Care Planning

Allows a patient to develop and indicate preferences
for care and/or choose a surrogate to act on his/her
behalf.
This should be discussed with regularity with patient
prior to an acute event (ie. At the yearly physical)
The Patient Self-Determination Act of 1990

Two important patient documents:


 Durable power of attorney for health care
 Living will
159
Impacts on the Physician

Physician disagrees:
○ Respond with empathy
○ Offer thoughtful exploration of all possibilities

Decisions violate the physician’s sense of professional
integrity:
○ Referral to another qualified physician
○ Never abandon the patient
○ Ethics committee consultation may be an option

Time limited trials and further consultation
160
5. Define beneficence
161
Beneficence
 Implies we should always do the best for our
patients.
 What if we have no clue? – obligated to
refer.
162
Key Concepts in Medical Ethics








A duty to alleviate suffering
Respect for people
Autonomy
Non-Maleficence – do no harm
Beneficence – do what’s best
Utility – greatest good for the most ppl
Justice – fairness / equality
Human Rights
163
Dr. Gould’s Notes on Lecture 43-44, Slide 67






Autonomy – Each individual has a right to make decisions about his/her
own life and is capable of doing so.
Non-maleficence – We should not do anything which may cause
potential harm to the patient; difficult sometimes – chemo hurts people.
Beneficence – Implies we should always do the best for our patients.
What if we have no clue? – obligated to refer.
Utility – Basis for care should be for the greatest good for the greatest
number; not always easy – what about when resources are limited – your
time is a resource!
Justice – Implies fairness for all and equity and equality of care
Human rights. A good case can be made for using a rights based
approach. What are rights, how are they enfored? Right to life, right to
respect, education…..
164
6. Define autonomy
165
Autonomy
 Each individual has a right to make decisions
about his/her own life and is capable of doing so.
166
Dr. Gould’s Notes on Lecture 43-44, Slide 67






Autonomy – Each individual has a right to make decisions about his/her
own life and is capable of doing so.
Non-maleficence – We should not do anything which may cause
potential harm to the patient; difficult sometimes – chemo hurts people.
Beneficence – Implies we should always do the best for our patients.
What if we have no clue? – obligated to refer.
Utility – Basis for care should be for the greatest good for the greatest
number; not always easy – what about when resources are limited – your
time is a resource!
Justice – Implies fairness for all and equity and equality of care
Human rights. A good case can be made for using a rights based
approach. What are rights, how are they enfored? Right to life, right to
respect, education…..
167
7. Brain death exam findings
Read the Notes Section
in the next 4 Slides
168
Neurological Examination…
(Must demonstrate absent cerebral and brainstem function)
Establish level of consciousness
• Patient must be comatose
• Patient arousability
• Response to noise – clap hands in face; response?
• Somatosensory stimulation
• Motor Examination
• No brain-originating motor responses
• Assess muscle tone
• Assessment of brain stem reflexes
• Pupils
•
169
Motor & brain reflexes…read the
notes section
Motor Examination –
Brain stem reflexes
absence of brain-originating • Absence of pupillary light reflex
motor responses
• Absence of corneal reflex
•
•
•
•
Muscle tone
Spontaneous movement
Elicited movement
Reflexes
•
Absence of oculovestibular
reflexes
•
•
•
•
•
Doll’s eyes
Caloric testing
Absence of masseter reflex
Absence of gag reflex
Absence of cough with tracheal
suctioning
170
Apnea Test
•
•
•
•
•
•
•
Performed after all other criteria for brain death are met
Prerequisites
• Core temperature ≥36°C
• Systolic BP ≥100 mmHg
• Eucapnia (PaCO2 35-45 mmHg)
Preoxygenation eliminates stores of nitrogen
• Fraction of inspired O2 should be 1.0 for 10 minutes up to a
maximum PaO2 200 mmHg or until PaCO2 exceeds 40 mmHg.
Ventilation rate reduced to eucapnia
PEEP reduced to 5 cm H20
SaO2 > 95 = ABG
Patient disconnected from ventilator
171
Apnea Test
•
•
•
•
Observe for respiratory movement for 8-10 minutes
PaCO2 measured just prior to reconnection to ventilator
Positive test
• No respiratory response to a PaCO2 > 60 mmHg or 20 mmHg
greater than baseline values
• Final arterial pH < 7.28
Reasons to abort test
• Hemodynamic instability - SBP < 90 mmHg
• Hypoxemia – SaO2 <85% for > 30 seconds
• Cardiac arrhythmia
172
8. Features of Death with Dignity
act
173
Physician Assisted Suicide (PAS)

Oregon Death With Dignity Act (DWDA) passed in
1994 and re-affirmed in 1997
 Citizens initiative which passed in 1994 with 51% of the vote
 Legal injunction followed and voters, given the option to reject,
voted in favor of DWDA in 1997



Washington Death With Dignity Act, initiative 1000
passed November 4, 2008
PAS referenda have failed in Maine and California
Belgium, Switzerland and the Netherlands all have
laws in regard to PAS or euthanasia
174
DWDA Facts
Highly controversial
 Allows terminally ill Oregon residents to obtain
and use prescriptions from their physicians for
self-administered legal medications
 Under the Act, ending one’s life in accordance
with the law is not considered suicide

 Life insurance still has to pay out to beneficiary

The DWDA specifically prohibits euthanasia
175
Legal Requirements for Patients
Adult and a legal resident of Oregon
 Diagnosed with a terminal illness with life
expectancy of six months or less
 Make two oral requests to his personal
physician separated by at least 15 days
 Provide a written request to his physician
signed in the presence of two witnesses

176
Legal Requirements for Physicians
Prescribing physician and a consulting physician
must confirm the diagnosis and prognosis and
determine whether the patient is capable of
making the decision
 Prescribing physician must inform patient of
alternatives – comfort care, hospice care and
pain control
 Prescribing physician must request (but not
require) patient to inform next of kin

177
DWDA Stats
2012 : 61 physicians wrote 115 RXs
resulting in 77 deaths.
 Diagnoses:

 Top 2 : Malignancy NOS and ALS

Men : 39 Women: 38 Median age: 69
178