Disclosures & 2016 Vanja Douglas, MD None Sara & Evan - - PDF document

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Neurology Headlines from 2015 & 2016

Vanja Douglas, MD Sara & Evan Williams Foundation Endowed Neurohospitalist Chair Associate Professor of Clinical Neurology UCSF Department of Neurology Neurohospitalist Program

Disclosures

None

Objectives

• Describe the treatments available for acute

ischemic stroke

• Compare and contrast carotid endarterectomy

and stenting

• Explain why TIA should be treated urgently
• Discuss evidence-based treatments for back pain
• List treatment options for agitation in dementia
• Identify emerging treatments for migraine
• Effectively examine patients with possible

concussion

Case

• 73 y/o man with sudden onset right sided

weakness and aphasia

• Eating breakfast with wife at 9:00 AM
• Arrived in ED at 9:55 AM

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Which of the following is NOT an evidence-based treatment option for this patient?

• Intravenous tissue plasminogen activator (IV

tPA)

• Intra-arterial tPA
• Mechanical embolectomy
• Combination of IV tPA and mechanical

embolectomy

• Clopidogrel

Acute Stroke Management

• IV tPA: 0 to 3 hours
• IV tPA: 3 to 4.5 hours*
• Embolectomy: 0 to 6 hours
• Clock starts:

– Last seen normal

*Not FDA approved; approved in Europe

Image By Sun Ladder - Own work, CC BY-SA 3.0, https://commons.wikimedia.org/w/index.php?curid=10959166

Acute Stroke Management

• IV tPA: 0 to 3 hours

– 39% no disability vs. 26% no disability – Number needed to treat: 7

• IV tPA: 4 to 4.5 hours

– 52% no disability vs. 45% no disability – NNT : 14

Jauchet al, Stroke 2013 Public Domain, https://commons.wikimedia.org/w/index.php?curid=244840 9

Acute Stroke Management

• Embolectomy: 0 to 6 hours

– Large vessel occlusions only (20% of all ischemic stroke patients) – 19-40% independent vs. 33-71% independent – NNT 3 to 7.5

• Up to 12 hours for basilar occlusions

Powers et al, Stroke 2015

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Non-contrast CT head 10:03 AM CT Angiogram Groin puncture 11:40 AM

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TICI 3 recanalization: 12:13 PM 4 days post-thrombectomy: Mild right hemiparesis

Case

• During the angiogram, 80% narrowing of the

left internal carotid artery is confirmed.

• The 73 y/o patient asks what he can do to

prevent a future stroke.

In which patient is carotid stenting NOT an evidence-based alternative to endarterectomy?

• 64 year-old woman with 80% stenosis
• 64 year-old man with 80% stenosis
• 76 year-old man with 80% stenosis
• 71 year-old man with 80% stenosis and prior

neck radiation and NYHA Class III heart failure

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Symptomatic Carotid Stenosis

Roffiet al., Eur Heart J 2009

Carotid Endarterectomy

Rothwell et al., Lancet 2003

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)

Bonatiet al., Cochrane Database Syst Rev 2012

Endarterectomy vs. Stenting: 10 year follow-up

• Stroke or

periprocedural death

– Stenting: 98 (11.0%) – CEA: 71 (7.9%) – Hazard ratio 1.37 (1.01 – 1.86)

• All risk difference

seen in patients 70 and older

B Stroke or Death

Patients (%) 100 80 60 40 20 1 2 3 4 5 6 7 8 9 10 Follow-up (yr)

• No. at Risk

Endarterectomy Stenting 1240 1262 1127 1111 1056 1049 967 979 848 889 744 777 703 741 624 679 442 479 245 265 67 68 20 Stenting Endarterectomy 15 10 5 1 2 3 4 5 6 7 8 9 10

Brott et al., NEJM 2016; Howard et al., Lancet 2016

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Case

• You are called to admit a patient who

experienced 2 hours of right arm weakness and trouble speaking earlier in the day. He was normal by the time he got to the ED. He is a 63 year-old man with hypertension and diabetes, taking aspirin, lisinopril, and metformin.

• Blood pressure at triage was 150/85.

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 Points Age ≥ 60 1 point Blood pressure ≥ 140/90 1 point Clinical Symptoms Speech impairment without weakness Unilateral weakness 1 point 2 points Diabetes 1 point Duration 10 to 59 minutes ≥ 60 minutes 1 point 2 points

Johnston et al, Lancet 2007

ABCD2 Score

Johnston et al, Lancet 2007

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Modifying Recurrence Risk

Rothwell et al, Lancet 2007

Ama re nco P e t a

• l. N E

ngl J Me d 2 0 1 6 ;3 7 4 :1 5 3 3 -1 5 4 2 .

Cumulative Incidence of the Composite Outcome in the Overall Population.

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, NEJM2013

TIA: Unstable Angina of the Brain

• Work up and treat emergently; admit if

necessary to expedite workup

• Treatment

– Antiplatelets, anticoagulation or endarterectomy Risk factor modification

• Consider dual antiplatelet therapy for 21 days

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Case

• A 47 year-old man presents to your office with

several days of severe low back pain.

• He has a history of chronic low back pain for

the past 5 years.

• His neurological examination is normal.

Which of the following is an evidence- based therapy for acute low back pain?

• Physical therapy
• Naproxen
• Oxycodone
• Naproxen + cyclobenzaprine

Low Back Pain in the ED

323 patients randomized

Naproxen 9.8 (7.9-11.7) Naproxen + cyclobenzaprine 10.1 (7.9-12.3) Naproxen +

• xycodone/acetaminophen

11.1 (9.0-13.2) Improvement on RMDQ at 1 week

Friedman et al., JAMA 2015

Physical therapy? Wait a month.

PT x4 weeks (n=108) 3 months: ODI 41.3 -> 6.6 1 year: ODI 7.0 Education & No PT x4 weeks (n=112) 3 months: ODI 40.9 -> 9.8 1 year: ODI 9.0

Fritz et al., JAMA 2015

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Do you prescribe steroids for acute radicular pain due to lumbar disk herniation (sciatica)?

• Yes
• No

Steroids for Sciatica?

Steroids (n=181; baseline ODI 51.2)

3-week ODI 32.2 1 year ODI 13.4

Placebo (n=88); baseline ODI 51.1)

3-week ODI 37.5 1 year ODI 20.7

Goldberg et al., JAMA 2015; image from Wikimedia Commons

No significant change in pain No difference in surgery rates

For Low Back Pain, Treat the Brain

• 342 patients randomized to

– Mindfulness based stress reduction – Cognitive behavioral therapy – Usual care

Cherkinet al., JAMA 2016 Richmond et al., PLOS One 2015

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Case

• One of your 84 year-old patients with

Alzheimer Dementia is brought in by his wife for an urgent appointment.

• In the past several months he has become

paranoid, aggressive and occasionally agitated.

Which of the following is associated with excess mortality when used in patients with dementia?

• Donepezil
• Citalopram
• Valproate
• Dextromethorphan-Quinidine
• Quetiapine
• 220 patients randomized
• Uncertain clinical benefit but…
• Improvement on multiple outcome

measures

• Serious adverse events:
• 7.9% with dextromethorphan
• 4.7% with placebo

Cummings et al., JAMA 2015

Case

• A 56 y/o woman comes to your office

complaining of headaches. She has 4 severe headaches per month and usually misses 2 days of work per month as a result.

• Sumatriptan works well for the headaches but

sometimes she runs out before she is eligible for refills.

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Which of the following are NOT evidence based prophylactic therapies for migraine headaches?

• Valproate
• T
• piramate
• Propranolol
• Verapamil
• Metoprolol
• Petasites (butterbur)
• Amitriptyline
• Riboflavin
• Venlafaxine
• Gabapentin

Change in Headache Days: Episodic Migraine

Bigalet al., Lancet Neurol2015

Change in Headache Days: Chronic Migraine

Bigalet al., Lancet Neurol2015

Bonus Case

• A 19 year-old college student comes into your
• ffice the day after hitting his head against the

goalpost during soccer practice. There was no loss of consciousness.

• He is complaining of a headache and is

worried he had a concussion that may affect his performance on his upcoming final exams.

• He has a history of migraines.

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Post- concussive Baseline

• Orthostatic vitals
• Head/neck exam

– Cervical ROM & proprioception – Spurling’s maneuver

• Cognitive assessment

– Orientation – 5-item delayed recall – Concentration: reverse digit span and months backward

• Mood/affect
• Cranial nerves I, VII
• Eyes

– Smooth pursuits & saccades – Convergence (wnl = 6-10 cm) – Nystagmus

• Vestibular

– Head impulse test – Dynamic visual acuity

• Cerebellar
• UMN weakness screen

– Pronator drift – Finger & foot taps – Distal extensor power

Matuszak et al., Sports Health 2016

References

• Meta-Analysis of Endovascular Thrombectomy after Large-vessel ischemic Stroke:

Goyal M et al. Lancet 2016 Apr 23;387(10029):1723

• Long-T

erm Results of Stenting versus Endarterectomy for Carotid-Artery Stenosis: Brott TG et al., N Engl J Med 2016 Mar 17; 374(11):1021

• One-Year Risk of Stroke after TIA or Minor Stroke: AmarencoP et al., N EnglJ Med

2016 Apr 21; 374(16):1533

• Naproxen with Cyclobenzaprine or Oxycodone for Acute Low Back Pain: Friedman

BW et al., JAMA 2015;314(15):1572

• Early PT for Acute Low Back Pain: Fritz JM et al., JAMA 2015;314(14):1459
• Oral Steroids for Sciatica: Goldberg H et al., JAMA2015;313(19):1915
• Mindfulness and Cognitive Behavioral Therapy for Back Pain: CherkinDC et al.,

JAMA 2016; 315(12):1240

• Dextromethorphan-Quinidine on Agitation in Patients with AD: Cummings et al.,

JAMA 2015;314(12):1242

• CGRP Antibody for Migraine: BigalME et al., Lancet Neurol2015;14:1081
• A Practical Concussion Physical Examination T
• olbox: Matuszak JM et al., Sports

Health 2016 Mar 28; 8:260

EXTRA SLIDES

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Criteria for High CEA Risk – Stenting may be Preferred

Severe comorbidities

• class III/IV congestive heart

failure

• class III/IV angina
• left main CAD
• >/= 2 vessel CAD
• left ventricular ejection

fraction </=30%

• recent MI
• severe lung disease
• severe renal disease

Challenging technical or anatomic factors

• prior neck operation (ie., radical

neck dissection) or neck irradiation

• postendarterectomy

restenosis

• surgically inaccessible lesions (ie.,

above C2, below the clavicle)

• contralateral carotid occlusion
• contralateral vocal cord palsy
• presence of a tracheostomy

Kernanet al, Stroke 2014