Transcript Case Based Teaching for IM Residents

Three Cases
Vanja Douglas, MD
Sara & Evan Williams Foundation Endowed Neurohospitalist Chair
Associate Professor of Clinical Neurology
UCSF Department of Neurology
Neurohospitalist Program
No Disclosures
Case
• A 72 year-old man comes to your office for routine
yearly follow-up. You notice that his walking has
gotten slower and he takes a lot more time in getting
up from his chair in the waiting room. He is a stoic
man and has never mentioned a problem with walking.
When you ask him about it he says:
• “You know, maybe I have gotten a little slower. I always
assumed that’s just what happens when you get older.
Now that you mention it - I did lose my balance and fall
the other day when I turned around to answer the
phone. Why do you ask, doc?”
Case #2
• An 83 year-old woman is brought to the
emergency department for trouble walking
and falls.
• She has had increasing difficulty with gait for
the past 2 months and fell at home today. She
was unable to get up and, her family says she
can no longer walk without a family member
assisting her, so they brought her to the ED.
Gait Disorder and Falls
Rubenstein and Josephson, Med Clin N Am 2006; photo by Robert Caplin, NY Times
Gait Disorder and Falls
Rubenstein and Josephson, Med Clin N Am 2006; photo by Robert Caplin, NY Times
Gait Disorder and Falls
Single Fall
Check for
gait/balance
problem
No gait/balance
problem
No further
evaluation
Gait/balance
problem
Recurrent Falls
Fall evaluation
• Fall evaluation: “…an examination of basic neurological
function, including mental status, muscle strength, lower
extremity peripheral nerves, proprioception, reflexes, tests of
cortical, extrapyramidal, and cerebellar function…”
Guideline for the Prevention of Falls in Older Persons, J Amer Ger Soc 2001
Gait Disorder and Falls
Most common neurological cause of falls in the
elderly:
1.
2.
3.
4.
Peripheral neuropathy – 18%
Myelopathy – 17%
Stroke – 15%
Parkinson disease – 12%
Samuels and Feske eds, Office Practice of Neurology 2nd Edition, p 26
Gait Disorder: from top to bottom
Cerebral Hemispheres (Stroke)
Ventricular System (Hydrocephalus)
Basal Ganglia (Parkinsonism)
Cerebellum (Alcohol)
Spinal Cord (Cervical Spinal Stenosis)
Cauda Equina (Lumbar Spinal Stenosis)
Peripheral Neuropathy (Diabetes, Alcohol)
Illustration from Wikipedia Commons, by William Crochot
Gait Disorder: from top to bottom
• High Yield Neurological Exam:
– Talk to patient
– Visual fields
– Pyramidal weakness in 2 minutes:
• Pronator drift (20 seconds)
• Finger taps and foot taps (40 seconds)
• Finger extensor and big toe strength (1 minute)
–
–
–
–
Check for spasticity and rigidity
Sensation: vibration sense and Romberg test
Reflexes: biceps, knee, and ankle
Coordination: finger-nose-finger, heel-knee-shin and tandem
gait
– Gait: tandem, toe and heel walking, Romberg and pull test
Image from Wikipedia Commons
Scenario 1…
• Increased urinary frequency at night and
urgency during the day, but no incontinence.
• On exam, full strength and normal tone in the
arms, but foot taps are slow and both EHLs are
mildly weak. There is mild spasticity in the
legs. Reflexes are brisk in the knees and
ankles. Vibratory sensation is reduced to the
knees.
• Localization?
Cervical Stenosis
Myelopathy
• Common causes:
– Structural
• Cervical Stenosis
• Tumors (bony metastases, foramen magnum tumors)
• Infections (vertebral osteomyelitis/epidural abscess)
– Medical
•
•
•
•
•
B12 deficiency
Multiple sclerosis
HIV myelopathy
Tabes dorsalis (syphilis)
Dural arteriovenous fistula
Image from Wikipedia Commons
Scenario 2…
• On further questioning, the patient reports
that his trouble walking is more severe at
night. He also says his feet tingle almost
constantly.
• On exam, he has diminished vibratory
sensation to the knees and absent ankle jerks.
Deciding to investigate further, you find he
also has decreased pinprick sensation below
the ankles.
Peripheral Neuropathy
• Prevalence:
– 2.4% of the population
– 8% of people over age 55
• Etiology can be identified in 74-82% of cases
England et al, AAN Practice Parameter, Neurology 2009
Physical Examination
– Hair loss
– Shiny, tight skin
– Muscular atrophy
– Ulcers; Charcot joints
– Pes cavus
– Hammer toes
Ly, J. Q. et al. Am. J. Roentgenol. 2004;182:147-154
Laforet, P. et al. Neurology 2004;63:1535
Neurological Examination
(specific for neuropathy; not mentioned on prior slide)
– Check for atrophy (hands, feet)
– Sensation: pain OR temperature, vibration sense
OR joint position sense, and Romberg test
– Reflexes: biceps, knee, and ankle jerks
Peripheral Neuropathy: Approach
HPI,
Exam
Symmetric?
EMG
NCS
Polyneuropathy
Asymmetric?
Work up causes of
mononeuropathy
multiplex
Peripheral Neuropathy: Approach
HPI,
Meds,
FH,
screening
Labs
Symmetric?
Polyneuropathy
Asymmetric?
Work up causes of
mononeuropathy
multiplex
EMG
Peripheral Neuropathy: Approach
NCS
HPI,
Meds,
FH,
screening
Labs
Axonal?
Large Fiber?
Demyelinating?
Symmetric?
Small Fiber?
Motor/Sensory/
Autonomic
Involvement?
Polyneuropathy
Asymmetric?
Work up causes of
mononeuropathy
multiplex
Distal Symmetric
Polyneuropathy
Most Common and Treatable Causes of
Symmetric Polyneuropathy
Diabetes (11%)
Fasting glucose, Hgb A1c
Alcohol
History
B12 deficiency (3.6%)
B12, homocysteine, MMA, folate
Monoclonal Gammopathy (9%)
SPEP/UPEP
Uremia
Creatinine/BUN
Liver disease
Liver Function Tests
HIV
HIV Ab
Hypothyroidism
TSH, free T4
Vasculitis or connective tissue disease
ESR (OK as screening tool in symmetric
polyneuropathy… maybe)
Toxin/drug exposure
Careful history
England et al, AAN Practice Parameter, Neurology 2009; Image from Wikipedia Commons
Neuropathy and Paraproteins
• 30% of patients with MGUS have neuropathy
– 60% IgM, 30% IgG, 10% IgA
– ½ of those with IgM MGUS and neuropathy have
MAG antibodies
•
•
•
•
Primary systemic amyloidosis
Multiple myeloma
Waldenstrom’s macroglobulinemia
POEMS syndrome/plasmacytoma
Distal Symmetric Polyneuropathy
• CIDP
• MMN (Multifocal Motor
Neuropathy)
• Paraproteinemic
• Hereditary
GM1 antibodies
SPEP/UPEP, MAG antibodies
Examine Family members
Large Fiber
Axonal
• Causes listed in prior table
• Vitamin deficiency (E, B1,
B6, folate)
• Infectious (Hepatitis, Lyme)
• Hereditary
• Inflammatory: sarcoid,
Sjogren’s, celiac disease
Thorough medication, toxin,
and dietary history
Hepatitis serologies (B and C),
cryoglobulins, Lyme Ab
Examine Family members
ANA, SSA, SSB
Small Fiber
• Diabetes
• Alcohol
• Amyloid (often + autonomic)
• HIV
Abdominal fat pad biopsy
Demyelinating
The Role of EMG
EMG
NCS
EMG
NCS
EMG
NCS
Axonal?
Large Fiber?
Symmetric?
Demyelinating?
Small Fiber?
Polyneuropathy
Asymmetric?
Work up causes of
mononeuropathy
multiplex
Nerve Conduction Study
distance = velocity
time
myelin
Images from Wikipedia Commons
Electromyogram
Image from Wikipedia Commons
Electromyogram
Normal
Neuropathy
Myopathy
Mononeuropathy Multiplex
Inflammatory
Infectious
Neoplastic
Compressive/
Ischemic
Differential Diagnosis
Workup
Vasculitis
Aggressive vasculitis workup
including LP and biopsy
Sarcoid
CXR, Chest CT, serum ACE
CIDP (Chronic Inflammatory
Demyelinating Polyneuropathy)
EMG/NCS and LP
Leprosy
Skin smear or biopsy
HIV (especially with CMV)
HIV Ab
Lyme
Lyme Ab
Lymphoma
Directed workup
Waldenstrom’s Macroglobulinemia
SPEP/UPEP
Diabetes
Fasting glucose, OGTT
Hypothyroidism
TSH, free T4
HNPP (Hereditary Neuropathy with
susceptibility to Pressure Palsies)
Family history, Genetic testing
The Role of Nerve Biopsy
•
•
•
•
Vaculitis
Sarcoid
Leprosy
Amyloid
neuromuscular.wustl.edu
Another Case
• A 57 year-old man comes to clinic after a
recent hospitalization for stroke.
• He has a mild right hemiparesis.
• He says he had some tests in the hospital and
was told to take an aspirin every day.
• What is your job as his PCP to make sure his
stroke workup and treatment meets the
standard of care?
Overview of Stroke Treatment
Acute Treatment?
Determine Stroke Source and Assess Risk
Factors
Secondary Prevention
Risk Factor Modification
Rehabilitation and Prevent Complications
Stroke Workup
Risk Factors
• Tobacco smoking
• Diabetes
• Hypercholesterolemia
• Hypertension
Embolic Source
• (Small vessel ischemia)
• Intracranial atherosclerosis
• Carotid/vertebral arteries
• Aortic arch
• Heart
–
–
–
–
–
Atrial fibrillation
Valves
Myocardial infarction
Cardiomyopathy
Patent foramen ovale
Intracranial Atherosclerosis
• Antiplatelet vs. Anticoagulation?
• WASID: aspirin vs. warfarin
– Equivalent rates of ischemic stroke, intracranial
hemorrhage, or death from vascular causes
– More major hemorrhage with warfarin
Chimowitz et al., NEJM 2005
Intracranial Atherosclerosis: Stenting?
Chimowitz et al., NEJM 2011
Intracranial Atherosclerosis
• Medical management > stenting
• Antiplatelet therapy > anticoagulation
• Warfarin alone OK if there is another
indication (e.g., atrial fibrillation)
• Risk factor modification
The Bottom Line
Carotid Endarterectomy
Rothwell et al., Lancet 2003
Carotid Endarterectomy
• When should we be operating?
Rothwell et al., Lancet 2004
Endarterectomy vs. Stenting
Roffi et al., Eur Heart J 2009
Endarterectomy vs. Stenting
• Increased odds of stroke or death within 30
days of treatment with stenting
– OR 1.72 (1.29-2.31)
• Equivalent risk of stroke during follow up
– OR 0.93 (0.60-1.45)
• Risk difference only seen in patients >70 years
– <70: OR for stenting 1.16 (0.80-1.67)
– ≥70: OR for stenting 2.20 (1.47-3.29)
Bonati et al., Cochrane Database Syst Rev 2012
Endarterectomy and Stenting
• CEA indicated for 70-99% stenosis
• Consider CEA for 50-69% stenosis if periprocedural risk is <6%
• Perform CEA within 2 weeks if possible
• Stenting an acceptable alternative in:
– Patients <70 years old
– Certain high risk surgical patients
The Bottom Line
Cardioembolic Stroke
• Atrial fibrillation causes ~20% of ischemic
strokes
20
EKG
15
Telemetry
10
5
Telemetry +
Event Monitor
0
Rizos et al., Stroke 2012; Gladstone et al., NEJM 2014
Evidence-based Reasons to
Anticoagulate a Stroke Patient
• Atrial Fibrillation
• Mechanical Heart Valves*
• Rare indications:
– Stroke due to dural venous sinus thrombosis
– LV thrombus (no definitive clinical trial data)
– Antiphospholipid antibody syndrome (no clinical
trial data)
*Only indication for anticoagulation + aspirin
The ACTIVE Trials
• Warfarin reduces stroke risk by 50 to 68%
• Aspirin reduces stroke risk by 21%
• ACTIVE A
– Aspirin + clopidogrel: 2.4% per year
– Aspirin: 3.3% per year
• ACTIVE W
– Aspirin + clopidogrel: 5.6% per year
– Warfarin: 3.93% per year
Connolly et al., NEJM 2009; Connolly et al., Lancet 2006; Image from Wikimedia Commons
Role of the NOACs
1.6
Events Per Year (%)
1.4
1.2
1
Stroke (drug)
0.8
Stroke (warfarin)
0.6
ICH (drug)
ICH (warfarin)
0.4
0.2
0
Dabigatran
(n=18,113)
Rivaroxaban
(n=14,264)
Apixaban
(n=18,201)
Anticoagulation
• Atrial fibrillation is key indication
– Anticoagulation superior to antiplatelets
• Long term event monitors (>21 days) double
rate of detection
• Start oral anticoagulation within 2 weeks
• Bridge with aspirin (no heparin)
• Transition to NOACs in the outpatient setting
The Bottom Line
Echocardiography
Transthoracic Echo
• Left ventricle
Transesophageal Echo
• Left atrial appendage
• Aortic arch
• Patent foramen ovale
• Atrial septal aneurysm
• Spontaneous atrial echo
contrast
Image from Wikimedia Commons
More Cardioembolic Strokes
• Patent Foramen Ovale
– 3 randomized trials show no benefit of closure
• Cardiomyopathy (EF < 35%)
– Warfarin = aspirin
• Left Ventricular Thrombus
– Current guidelines recommend warfarin for 3 months
• Aortic Arch Atheroma
– 1 randomized trial stopped due to lack of enrollment
and low event rate (aspirin + clopidogrel vs. warfarin)
Kumar et al., J Stroke Cerebrovasc Dis 2013; Amarenco et al., Stroke 2014; Kernan et al., Stroke
2014; Image from Wikimedia Commons
More Cardioembolic Strokes
• Antiplatelet therapy unless:
– Atrial fibrillation
– LV thrombus
• If echo shows a PFO:
– Ultrasound legs for DVT
• If no DVT: Antiplatelet therapy and no closure
• If DVT: Anticoagulate temporarily for DVT and consider
closure if high risk of recurrent DVT
The Bottom Line
Cervical Artery Dissection and
Vertebral Atherosclerosis
• Cervical Artery Dissection
– CADISS Trial: heparin +
warfarin vs. antiplatelet
– Low event rate (2% in
antiplatelet and 1% in
anticoagulation group)
• Vertebral artery stenting
– No phase III randomized
trial data
– Antiplatelet therapy and
risk factor control is
mainstay
CADISS Trial Investigators, Lancet Neurol 2015
All This Talk of Antiplatelets…
• Acutely use 325 mg aspirin; long term doses
ranging 50 to 1500 mg are equivalent
• Clopidogrel 75 mg daily
• Aggrenox 25 mg aspirin + 200 mg extended
release dipyridamole BID
All This Talk of Antiplatelets…
• CAPRIE: plavix vs. aspirin
– RRR 8.7%; ARR 5.83% -> 5.32% (NNT 200)
• ESPRIT: aggrenox vs. aspirin
– HR 0.80 favoring aggrenox, ARR 1% (NNT 100)
• PROFESS: plavix vs. aggrenox
– HR 1.01 (more GI bleeding with aggrenox)
• MATCH and CHARISMA: plavix + aspirin vs. plavix
alone or aspirin alone
– No difference in stroke prevention with increase in
major bleeding in combination therapy
Kernan et al., Stroke 2014
Risk Factor Modification: All Patients
• Blood pressure (risk begins at SBP ≥140)
– Treat for SBP ≥140 and DBP ≥90
– Start after 72 hours of permissive hypertension
– Thiazide or ACE inhibitors are preferred
• Statin
– SPARCL trial: 80 mg atorvastatin if LDL ≥100
– Treat regardless of LDL level if stroke due to
atherosclerosis
• Smoking cessation
• Diabetes management
The Bottom Line
Kernan et al., Stroke 2014
Stroke Workup
Risk Factors
• Tobacco smoking
• Diabetes
• Hypercholesterolemia
• Hypertension
Embolic Source
• Intracranial atherosclerosis
• Carotid/vertebral arteries
• Aortic arch
• Heart
–
–
–
–
–
Atrial fibrillation
Valves
Myocardial infarction
Cardiomyopathy
Patent foramen ovale
Stroke Workup
Risk Factors
• Tobacco smoking
• Diabetes
– Fasting glucose, Hgb A1c
• Hypercholesterolemia
– Fasting lipid panel
• Hypertension
• Unnecessary: B12, TSH, ESR
• In select situations:
– RPR, hypercoagulable
conditions
Embolic Source
CTA, MRA
• Intracranial atherosclerosis
• Carotid/vertebral arteries
• Aortic arch
CTA, MRA,
US
• Heart
–
–
–
–
–
Atrial fibrillation
ECG, Tele,
Valves
Event
Myocardial infarction
Cardiomyopathy
Patent foramen ovale
TTE with
shunt study
Stroke Center Quality Metrics
•
•
•
•
•
•
•
Thrombolysis
Antithrombotic within 48 hrs & at discharge
VTE prophylaxis within 48 hrs
Anticoagulation for atrial fibrillation
Discharged on statin
Assessed for rehab
Stroke education
Bonus Case
TIA
Case
• Your patient calls your office because he
experienced 2 hours of right arm weakness
and trouble speaking earlier in the day. He is
now back to normal. He is a 63 year-old man
with hypertension and diabetes, taking
aspirin, lisinopril, and metformin.
TIA: Unstable Angina of the Brain
• 10% will have a stroke in 90 days
• Half of these will occur in the first 2 days
• Is there a way to identify who is at highest
risk?
• Is there anything you can do to prevent stroke
after TIA?
High Risk TIA: The ABCD2 Score
Clinical Features
Age ≥ 60
Blood pressure ≥ 140/90
Clinical Symptoms
Speech impairment without weakness
Unilateral weakness
Diabetes
Duration
10 to 59 minutes
≥ 60 minutes
Points
1 point
1 point
1 point
2 points
1 point
1 point
2 points
Johnston et al, Lancet 2007
ABCD2 Score
Johnston et al, Lancet 2007
Modifying Recurrence Risk
Rothwell et al, Lancet 2007
Cumulative Incidence of the Composite Outcome in the
Overall Population.
Amarenco P et al. N Engl J Med 2016;374:1533-1542.
A Role for Dual Antiplatelet Therapy?
• CHANCE:
– 5,170 patients within 24 hours of TIA or minor
stroke
– Aspirin for 90 days vs. clopidogrel (300 mg loading
dose followed by 75 mg daily) for 90 days
combined with aspirin 75 mg for 21 days
– 8.2% vs. 11.7% with stroke at 90 days
– Favored combination therapy; HR 0.68 (p<0.001)
• POINT Trial ongoing
Wang et al, NEJM 2013
TIA
• Work up and treat emergently; admit if
necessary to expedite workup
• Treatment
– Antiplatelets, anticoagulation or endarterectomy
Risk factor modification
• Dual antiplatelet therapy may be an option in
the future
The Bottom Line