UPDATED VERSION, My apologies for any missing info and typos There are about 50 title slides this time 1

1. Anatomic locations of disease processes: (NM jxn, spinal cord anterior horn, nerve root, peripheral nerves, muscle) 2. 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 Trauma / impingement Tumors Autoimmune diseases ○ Guillian-Barré Syndrome No steroid Tx! ○ CIDP IV steroids!  Systemic Diabetes Nutritional deficits Infection Medications Alcoholism Local vs systemic causes 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, 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. MG…myasthenia gravis b. ALS…amyotrophic lateral sclerosis c. Pick d. Heavy metals…arsenic poisoning e. Friedrich’s ataxia f. PMFL…progressive multi-focal leukoencephalopathy g. Polymyositis h. 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

 Called Lou Gehrig's Disease  Males > females; age of onset =  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 Amyotrophic Lateral Sclerosis (ALS) 24

2c. Pick Disease 25

A type of fronto-temporal dementia characterized by personality and language disturbances. PRESENTATION:  Slurred speech  Personality and behavioral changes  Language disturbances Pick Disease 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

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 Progressive Multi-Focal Leukoencephalopathy 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 Heliotrope rash Shawl signV 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. Types of pain 2. Best outcome measure for pain plans 3. Addiction vs. Pseudoaddiction 4. Plan for prescribing to patients with substance abuse hx 5. 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 activation of pain receptors in either the body surface or musculoskeletal tissues  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  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). in the dorsal root ganglion of the T2-T6 spinal segments  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. Effective patient evaluation 2. Creating a treatment plan 3. Informed consents & agreements 4. Periodic review 5. Referral & patient management 6. Documentation 50

Goals of pain treatments 1. Improve function 2. 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 (Withdrawal)  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. uses it compulsively  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 (Seen as “drug seeking” behavior)  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. discriminate between the two pseudoaddiction resolves addictive behavior does not  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 risks and benefits  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. high risk for medication abuse history of substance abuse  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 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 (Withdrawal)  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. Distinguish cluster v. migraine v. tension type headache (also episodic vs. chronic) 2. Evidence based OMT effects 3. Outside induced causes of headaches 4. 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 SymptomMigraineTensionCluster LocationMainly UnilateralBilateralAlways unilateral CharacterGradual in onset, pulsating, worse with activity Pressure or tightness – comes and goes Quick onset, deep, explosive pain Patient appearance Needs quiet darkness No specific pattern Patient can remain active Duration4-72 hoursVariable½ - 3 hours Other symptomsNausea, vomiting, photophobia, phonophobia, aura, neuro deficits NoneIpsilateral lacrimation and redness of eye, stuffy nose, Horner’s, sweating EXAM!!!! 69

Diagnostic Criteria  Cluster headache Description (all four) ○ Severe headache ○ Unilateral ○ Duration 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, T1- T4 76

3. Outside induced causes of headaches 77

Secondary headaches  Sinus related  Post trauma 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 Vasodilators 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. Define fever 2. Work ups based on age 3. Prevention with vaccines 4. Maternal-fetal transmission of serious bacterial infections 5. 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,

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 TreatmentBenefit 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 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 polysaccharide- protein 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, 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

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, 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

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. 10 day old with rectal temperature of 101 and a vesicular rash on the scalp. b. 60 day old with axillary temperature of 101 and cough for 2 days c. 2 year old with a rectal temperature of 103 and a 2 minute generalized tonic clonic seizure d. 3 year old with temporal temperature of 104 for 4 days, defervescence and then a erythematous blanching rash on his trunk and extremities e. 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. Associated findings in Neurofibromatosis 2. Incidence of tuberous sclerosis and most common presenting feature 3. Sturge-weber disease findings 4. 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,

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. Principles of Palliative care 2. Hospice primary caregiver 3. Enteral feedings in terminally ill patients 4. Define patient decisional capacity 5. Define beneficence 6. Define autonomy 7. Brain death exam findings 8. Features of Death with Dignity act 144

1. Principles of Palliative care 145

***Five Principles of Palliative Care*** 1. Respects the goals, likes and choices of the dying 2. Looks after the medical, emotional, social and spiritual needs of the dying 3. Supports the needs of family members 4. Helps gain access to needed health care providers and appropriate care settings 5. 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 Patients personal physician o Hospice physician/Medical director o Nurses o Home health aides o Social Workers o Clergy and bereavement counselors o 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 168 Read the Notes Section in the next 4 Slides

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 – 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 170

Apnea Test Performed after all other criteria for brain death are met Prerequisites Core temperature ≥36°C Systolic BP ≥100 mmHg Eucapnia (PaCO 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 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: