Transcript CM-Neuro Exam 4, Lectures 37-44

There are about 50 title slides this time
Enjoy!
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)
1. Anatomic locations of disease
processes
a. NM
jxn
b. Spinal cord anterior horn
c. Nerve root
d. Peripheral nerves
e. Muscle
1a. NM jxn

Abnormal nerve
conduction at the
neuromuscular junction
(NMJ)

Typical presentation
 Ocular muscles affected first
 Ptosis and diplopia
 Fluctuating muscle weakness
 No associated sensory loss

Common causes
 Myasthenia gravis
 Lambert-Eaton syndrome
 Toxins
1b. Spinal cord anterior horn
Damage to ventral
gray matter of the S.C.
effects motor outputs
Common causes

 i.e. infarct of anterior spinal a.
Tumors
 Adult onset spinal muscular
atrophy (genetic defect)
 Motor neuron disease
 Polio
 Transverse myelopathy

Typical presentation



Bilateral paresis
Tetraparesis
DTR to confirm
Strokes
1c. Nerve root
Radiculopathies can be associated with
pain and paresis.
 Nerve root compression can cause pain

 Pain follows dermatomal distribution
 Parestheias/sensory loss follow dermatomal
distribution
1d. Peripheral nerves
Summary of next 5 slides
Glove and stocking distribution sensory
loss and sensory changes
 Distal weakness
 Absent DTR’s is distal extremity mm.

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.

Typical presentation:
 Sensory changes in





the hands and feet
Burning pain
Sensitivity to touch
Lack of coordination
Muscle weakness
Bowel or bladder
function

Common causes:
 Diabetes Mellitus
 Alcoholism
 Medication induced
 Infections
Peripheral Neuropathy
Local vs systemic causes

Local

Systemic
 Trauma/impingement
 Diabetes
 Tumors
 Nutritional deficits
 Autoimmune diseases
○ Guillian-Barre
○ CIDP
 Infection
 Medications
Peripheral Neuropathy
Symptoms of peripheral neuropathy



Numbness and tingling in distal extremities
Distal extremity weakness
Impaired proprioception
Presentation


Systemic – presented in all 4 limbs
Weakness is worse distally
Peripheral neuropathy
Evaluation


H&P
Electrodiagnostic testing
 EMG - Electromyography
 Nerve conduction test


Blood work
LP - Lumbar puncture
Peripheral Neuropathy
Treatment




Manage Diabetes
Correct nutritional deficits
Supplement metabolic insufficiencies
Meds
 Anti-seizure meds (AEDs)
 Immuno suppressive meds
 Antidepressants (TCAs, SSRIs, SNRIs)
Prognosis
AED – antiepileptic drug
TCA – tricyclic antidepressant
SSRI – selective serotonin reuptake inhibitor
SNRI – serotonin norepinephrine reuptake inhibitor
1e. Muscle
Muscle- Myopathy
Neuromuscular disorder with
primary symptom of muscle
weakness due to dysfunction
of muscle fibers
Other common presenting symptom
What else would we want to
ask the patient?
Common causes





Rate of symptom onset
Constitutional ROS (recent
illness?)
Comorbidities?
Family history
Vaccine/immunization history









Cramps
Stiffness
Spasms
Inflammatory  HIV, dermatomyositis
Infectious myopathies
Endocrine myopathies
Toxic myopathies  alcohol,
corticosteroids, narcotics
Metabolic myopathies
Etc.
2. Weakness differential:
a.
b.
c.
d.
e.
f.
g.
h.
MG
ALS
Pick
Heavy metals
Friedrichs
PMFL
Polymyositis
MD
2a. MG…myasthenia gravis
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
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)
2b. ALS
Amyotrophic Lateral Sclerosis (ALS)
Called Lou Gherig’s Disease
 Males > females; age of onset = 40-60
 Progressive demylination of PNS
 UMN and LMN lesions
 Symptoms - fasciculations, slurred speech,
weakness, difficulty swallowing, spared mental status
 Treatment: riluzole, baclofen (spasticity)
 NO cure

2c. Pick
Pick Disease
A type of fronto-temporal dementia characterized
by personality and language disturbances.
PRESENTATION:
 Slurred speech
 Personality and behavioral changes
 Language disturbances
2d. Heavy metals
Arsenic Poisoning

General
 Toxicity caused by arsenic, a toxic trace metal that is a key component
of herbicides, insecticides, rodenticides, wood preservatives and used in
manufacturing glass and paints.
 The usual fatal dose is 100–200 mg; there are ± 1900 arsenic
poisonings/year (US), 85% of which are accidental by children < age 6;
the rest are adult suicides.

Clinical findings
 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 diarrhoea, then by renal and cardiac failure and circulatory
collapse.

Treatment
 Dimercaprol (BALS).
2e. Friedrichs
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)
2f. PMFL…progressive multi-focal
leukoencephalopathy
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
2g. Polymyositis
Polymyositis
Titer = Group A Strep, post streptococcal
complication
 Blood test = elevated Creatinine kinase,
aldolase, and ESR
 Electromyography
 ELISA for anti-Jo 1

Symptoms
Symmetrical & progressive muscle
weakness: hips, thighs, shoulders, upper
arms/neck.
 Dysphasia, dysphonia, mild join/muscle
tenderness, fatigue, SOB
 Post streptococcal complication

Tx

Corticosteroid (prednisone)
 + Calcium & Vit D




IVIG
PT & Speech therapy
Other immunosuppressants
EXPERIMENTAL: Rituximab
 Improves muscle strength, lung function, skin
rash.
2h. MD…myotonic dystrophy
Overview



Myotonic dystrophy is a chronic, slowly
progressive and highly variable inherited
multisystem disease
Characterized by a constellation of clinical
findings including muscle wasting (muscular
dystrophy), cataracts, heart conduction
abnormalities, endocrine pathology, and
myotonia.
The disease can occur in patients of any age.
Etiology
Autosomal dominant inheritance pattern
 Trinucleotide repeat disorders

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 produce a characteristic facial
appearance in these patients .
Myotonia (prolonged muscle contraction) occurs
spontaneously or is elicited by voluntary activity or by mild
stimulation, such as tapping on a muscle (percussion
myotonia).
Morphology
The skeletal muscle
biopsy shows
characteristic central
nuclei, atrophy (smaller
myofibers) and ring
myofibers (designated
by R).
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
1. Two Major Types of pain
1. NOCICEPTIVE PAIN
- Visceral pain
- Deep somatic pain
- Superficial somatic pain
2. NEUROPATHIC PAIN
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.
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.
It is usually described as dull or aching.
Aggravated by activity and relieved by rest.
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, and malaise, and
pain.

Characteristics – vague/dull, poorly localized/diffuse,
pressure-like, deep squeezing
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.

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
2. Best outcome measure for
pain plans
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
Goals of pain treatments
1.
2.
Improve function
Improve quality of life
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
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
3. Addiction vs. pseudoaddicition
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.
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.
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

Addiction

Physical dependence and tolerance are
normal physiological consequences of
extended opioid therapy for pain and are not
the same as addiction.
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.
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
4. Plan for prescribing to patients
with substance abuse hx
Basically…
Document the h/o substance abuse
 Use informed consent & agreements
 Use extra care, monitoring,
documentation and referral/consultation
with or referral to an expert in the
management of such patients.

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)
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.
5. Define physical dependence
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.
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
1. Distinguish cluster v. migraine
v. tension type headache (also
episodic vs. chronic)
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
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
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
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
Diagnostic Criteria

Migraine with aura
 Reversible visual symptoms  Reversible sensory symptoms – numbness,
tingling
 Motor weakness –
 Headache with or within 60 minutes of aura
Chronic Daily Headaches
Greater than 15 per month
 Use of prophylactic medication is key to
treatment
 Can result in rebound headaches from
medication overuse

2. Evidence based OMT effects
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

3. Outside induced causes of
headaches
Secondary headaches
Sinus related
 Post trauma

Look for “red flag” signs or symptoms
Secondary headache causes
Tumors or masses
 Cerebral venous thrombosis
 Giant cell arteritis
 Bleeding aneurysms
 Low or high cerebrospinal pressure
 Preeclampsia

History

Medications
 Birth control / hormones (♀)
 Nitrates
 Others

Treatments tried
 Frequency
 Efficacy
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
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
4. Diagnostic testing (imaging /
labs) best suited for different
secondary headaches
Diagnostic Testing

Labs
 Usually of little value
 Look for causes of secondary headaches
Diagnostic Testing

Lumbar puncture
 Meningitis or encephalitis
○ WBC
○ organisms
 Subarachnoid bleed
○ RBC’s
 Pseudotumor cerebri
○ Elevated opening pressure
 Systemic diseases such as sarcoid, lupus
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
Diagnostic Testing

Other testing
 EEG – rare use
 Thermography, transcranial doppler not
indicated in work up
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
1. Define fever
Fever
 Fever is a 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 systemsPugh MB (ed): Stedman's Medical Dictionary, ed 27. Baltimore, Lippincott, Williams, and Wilkins, 2000
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
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
2. Work ups based on age
FEVER
Fever in infants less than 3 months of age is a
medical emergency.
 Infants less than 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
3. Prevention with vaccines
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
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
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
4. Maternal-fetal transmission of
serious bacterial infections
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
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%
HSV-2
Infant with scalp vesicles
Seen with perinatal
transmission of HSV-2
5. Define complex febrile seizure
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.
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
1. Associated findings in
Neurofibromatosis
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/higher frx
risk
 Scoliosis
 Seizures
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
Neurofibromas





Cutaneous most common type
Dermal lesions
Appear before/during
adolescence
Increase in number and size
with age
Not associated with malignant
transformation
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
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
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
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
Neurofibromatosis II
Café au lait macules,
 Neurofibromas of skin, and
 Seizures CAN occur with NF II


Occur much LESS commonly than with
Neurofibromatosis I
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
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

2. Incidence of tuberous sclerosis
and most common presenting
feature
Tuberous Sclerosis
•
•
•
Autosomal dominant
1 in 5,000-10,000 live births
Mutations in two separate genes
• TSC1
• TSC2
Several potential answers

I think the answer is epilepsy (slide 7)
 Mentioned again on slide 17

But he does have a couple of phrases
discussing “____ is the most common …”
 “Characteristic skin findings: Hypopigmented
macules (most common)” (Slide 8)
 “Rhabdomyoma is the most common cardiac
manifestation of TSC” (Slide 14)
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
Tuberous Sclerosis
Characteristic skin findings
 Hypopigmented
macules (most
common)
 Ash-leaf spots

Angiofibromas
 Malar region of face

Shagreen patches
 Lower trunk

Fibrous plaques
 Forehead
Tuberous Sclerosis

Rhabdomyoma is the most common
cardiac manifestation of tuberous
sclerosis
 Heart failure
 Murmur
 Arrhythmia
3. Sturge-weber disease findings
4. VHL disease associated
tumors
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
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
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)
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
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 during adolescence
Baseline audiometry during adolescence
Further testing if/when symptoms develop
 Tinnitus, ear pain, or changes in hearing acuity
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
1. Principles of Palliative care
***Five Principles of Palliative
Care***
1.
2.
3.
4.
5.
Respect 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
Robert Wood Johnson Foundation. Last Acts Task Force on Palliative Care and the Family: five
principles of palliative care. 2000.
2. Hospice primary caregiver
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
3. Enteral feedings in terminally
ill patients
***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
137
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.

138
Are we starving this patient to death?

Cognitively intact patients dying of
progressive malignancy frequently lose
interest in eating and drinking.
 Deny hunger and thirst - some do report
xerostomia

Hunger strikers deny hunger/thirst after
several days of volitional abstinence from
food/drink.
140
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
Less choking on oral secretions
 Fewer diaper changes
 Less skin breakdown

141
4. Define patient decisional
capacity
Capacity

Should be
assessed by the
primary physician
Does not require
legal or psychiatric
expertise
Judicial
determination
 Required when
assessing a patients
global decision
making capacity for
non-medical
issues(ie. financial
matters)

Up-To-Date

Competence
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
Decisions Near the End of Life
Patients have the right to refuse
recommended life-sustaining
medical treatments.
 Based on the philosophical concept of
respect for patient autonomy, the
common-law right of self determination
and the patient’s liberty interest under
the US Constitution.

ACP Ethics Manual
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
ACP Ethics Manual
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
ACP Ethics Manual

Physician disagrees:
○ Respond with empathy
○ Offer thoughtful exploration of all possibilities

Decisions violate the physicians 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
5. Define beneficence
Beneficence –
 Implies we should always do the best for our
patients.
 What if we have no clue? – obligated to
refer.
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
Doyle, Derek, et al. The Oxford Textbook of Palliative Medicine, 3rd ed. New York: Oxford University Press, Inc., 2005.
Dr. Gould’s Notes on 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…..
6. Define autonomy
Autonomy –
 Each individual has a right to make
decisions about his/her own life and is
capable of doing so.
Dr. Gould’s Notes on 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…..
7. Brain death exam findings
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
•
Motor & brain reflexes…read the
notes section
Motor Examination – absence
of brain-originating motor
responses
•
•
•
•
Muscle tone
Spontaneous movement
Elicited movement
Reflexes
Brain stem reflexes
•
•
•
Absence of pupillary light reflex
Absence of corneal reflex
Absence of oculovestibular
reflexes
•
•
•
•
•
Doll’s eyes
Caloric testing
Absence of masseter reflex
Absence of gag reflex
Absence of cough with tracheal
suctioning
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
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
8. Features of Death with Dignity
act
Physician Assisted Suicide

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
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
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

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

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