powerpoint presentation...2015 episodic and chronic migraine 63 gon injection (u or b) with 2.5 ml...

6/20/2018

1

Evidence for Headache Procedures

Matthew S Robbins, MD

Associate Professor of Neurology, Albert Einstein College of MedicineChief of Neurology, Jack D Weiler Hospital, Montefiore Medical Center

Director of Inpatient Services, Montefiore Headache Center

Disclosures• Contracted research: eNeura (site PI for study; funds to institution)

Off-label uses

• Local anesthetics generically approved for nerve blocks, infiltration

• Steroids generically approved for intramuscular, intra-articular, soft

tissue, or intra-lesional injection

Objectives

1. To evaluate the level of evidence for onabotulinumtoxinA, peripheral

nerve blocks, trigger point injections, and sphenopalatine ganglion

blocks

2. To appraise safety concerns and precautions with clinic-based

headache procedures

3. To examine the role of steroids in nerve blocks for migraine and

cluster headache

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Evidence for headache procedures

1. OnabotulinumtoxinA

2. Peripheral nerve blocks

3. Trigger point injections

4. Sphenopalatine ganglion blocks

5. Training

6. Summary

OnabotulinumtoxinA for chronic migraine

Dodick DW et al, Headache 2010

Blumenfeld AM et al, J Headache Pain 2018

Blumenfeld A et al, Headache 2008

Mathew NT et al, Headache 2009

versus other agents: similar efficacy, better tolerated

PREEMPT Phase 3 pooled COMPEL (long-term)

Safety in chronic migraine

• Neck pain 4-8%

• Muscle weakness 5-6%

• Rash* <0.5%

• Caution: patients with NMJ disorders

• One fatal case in use for pain (reconstituted in lidocaine)

Aurora S et al, Cephalalgia 2010Diener HC et al, Cephalalgia 2010Blumenfeld AM et al, J Headache Pain 2018Blumenfeld AM et al, Headache 2017Li M et al, J Forensic Sci 2005

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Response prediction: pain directionality

Jakubowski M et al, Pain 2006 Files JA et al, Headache 2014






5. Training

6. Summary


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Double-Blind, Placebo-Controlled RCTs of PNBs for Migraine Prevention

StudyHeadache

DisorderN

TreatmentPrimary Outcome Results

Active Placebo Frequency

Dilli et al

Cephalalgia

2015

Episodic and

chronic migraine63

GON injection (U or

B) with 2.5 ml 0.5%

bupivacaine + 0.5 ml

20 mg

methylprednisolone

GON injection

(U or B) with

2.75 ml saline +

0.25 ml 1%

lidocaine

OnceAfter 4 weeks ≥ 50% ↓ in frequency of moderate or severe HA

days was 30% for both groups but no differences

Palamar D

et al

Pain

Physician

2015

Chronic migraine 32

GON injection (B)

with 1.5 ml 0.5%

bupivacaine

GON injection

(B) with 1.5 ml

saline

Once

(ultrasound

guidance)

After 4 weeks significant ↓ average VAS score

Inan et al

Acta Neurol

Scand

2015

Chronic migraine 72

GON injection (U or

B) with 1.5 ml 0.5%

bupivacaine + 1 ml

saline

GON injection

(U or B) with 2.5

ml saline

Weekly x 4

weeks

After 1 month significant ↓ HA days, VAS score, though not

hours

Cuadrado

et al

Cephalalgia

2017

Chronic migraine 36

GON (B) injection

with

2 ml of 0.5%

bupivacaine

GON (B)

injection with 2

ml saline

Once After 1 week significant ↓ moderate-severe HA days

Gul et al

Acta Neurol

Scand

2017

Chronic migraine 44

GON (B) injection

with 1.5 ml 0.5%

bupivacaine + 1 ml

saline

GON (B)

injection with 2.5

ml saline

Weekly x 4

weeks

Significant headache day reduction at 2 months and 3 months

but not 1 month

Adapted from Robbins MS. Scientific American Neurology; 2016

Systematic reviews

RCT: GON blocks for acute migraine in ED

• Population:

– Acute migraine in ED with moderate-severe headache >1h post-IV metoclopramide

• Treatment:

– Active: B/L GONB with 6cc of 0.5% bupivacaine– Sham: B/L intradermal scalp injection with 1cc of 0.5% bupivacaine

• Outcome:

– Complete headache freedom 30 minutes after injections

• Enrollment:

– 32 month period

– 76 patients screened

– 28 patients enrolled

• 15 received sham injection• 13 received GONB

Friedman BW et al, AHS 2018 LBOR-07

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RCT: GON blocks for acute migraine in ED

Friedman BW et al, AHS 2018 LBOR-07

Outcome variableSham Injection

(n=15)

GON Block

(n=13)Difference (95%CI) p value

Headache freedom 30m 0 (0%) 4 (31%) 31% (6, 56%) 0.02

Sustained headache relief 0 (0%) 3 (23%) 23% (0, 46%) 0.09

Would want same injection

again

Yes 3 (20%) 5 (38%) 18% (-15, 52%) 0.31

No 6 (40%) 6 (46%)

Not sure 6 (40%) 2 (15%)

Headache intensity 60m

Severe 4 (27%) 2 (15%) 36% (1, 71%) 0.06

Moderate 6 (40%) 2 (15%)

Mild 5 (33%) 5 (38%)

None 0 (0%) 4 (31%)

Injection site pain (n=2, GONB)Neck pain (n=2, 1 GONB, 1 sham)Dizziness (n=1, sham)

Shingles (n=1, GONB)

Guessed correct treatmentActive: 62%Sham: 67%

RCT: GON blocks vs sham vs IV therapies

Korucu O et al, Acta Neurol Scand 2018

• N=60

• IV group

• Not blinded

• Dexketoprofen +

metoclopramide

• No side effects

Nerve blocks with steroids

• Migraine: no benefit versus anesthetic alone

• Cluster: should be used in GON injections

– 2 RCTs; Level A evidence

• Adverse effects

– Systemic if repetitive

– Local if dose high


Ashkenazi A et al, JNNP 2008

Kashipazha D et al, Glob J Health Sci 2014

Ambrosini A et al, Pain 2005

Shields KG et al, Neurology 2004

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Adding steroids to anesthetics for migraine

Ashkenazi A et al, J Neurol Neurosurg Psychiatry 2008

Kashipazha D et al, Glob J Health Sci 2014

Mean headache severity

before and 20m post-GONB + TPI

Variable Group A Group B P-value

Headache-

free days2.7±3.8 1.0±1.1 0.67

Headache

response days

14.3±15.1 5.5±4.9 0.60

Intervention (n=24)

B/L GON injectionsLidocaine + triamcinolone

Control (n=24)

B/L GON injections

Lidocaine + saline

GON injections have evidence for cluster

Reference Disorder N Active Placebo Primary outcome

Ambrosini A et al

Episodic and

chronic cluster

headache

16

2.5 ml suboccipital injection of

betamethasone dipropionate

12.46 mg + betamethasone

disodium phosphate 5.26 mg

+ 0.5 ml xylocaine 2%

2.5 ml suboccipital injection of 2 ml

saline

+ 0.5 ml xylocaine 2%

Active: 85% attack-free

in the 1st week vs 0% in

the placebo group

(p=0.0001)

Leroux E et al

Episodic and

chronic cluster

headache

43

3 unilateral suboccipital injections

(48-72 hours apart) of 1.5 ml

cortivazol 3.75 mg

3 suboccipital injections (48–72

hours apart) of 1.5 ml saline

Active: 95% ≤2

attacks/day versus 54%

controls

OR 14.5

(1.8-116.9; p=0.012)

2-4 days after 3rd

injection

Ambrosini et al. Pain. 2005

Leroux E et al. Lancet Neurol 2011

GON injection for cluster headache

• GON steroid injection is the only cluster headache

prophylactic therapy with 2 Class I studies and a Level A

recommendation

Robbins MS et al. Headache 2016

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GON injection versus oral steroid for cluster

• 43 patients received transitional therapy over a total of 151 encounters

• 16 patients received both

Wei J, Robbins MS, Headache 2018

Response Level

Oral steroid encounters n=81 (% total)

GON injection encountersn=59 (% total)

Complete * 41(50.6%) 21 (35.6%)

Partial ** 26 (32.1%) 17 (28.8%)

None 7 (8.6%) 11 (18.6%)

Unclear 7 (8.6%) 10 (16.9%)

Response to oral but

not injection

38%

Response to injection but not oral

6%

Response to both50%

Response to neither

6%

Other patient populations

Pediatrics

Pregnant women

Older adults






5. Training

6. Summary

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Trigger point injections: evidence

Robbins MS et al, Headache 2014






5. Training

6. Summary

Sphenopalatine ganglion blocks

http://tianmedical.com/europe/images/spgb_oldtechnique1.png

Maizels M et al. JAMA 1996

Robbins MS et al. Headache 2016

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SPG Blockade: RCTs

Chronic migraine (N=38)

• B/L SPG blocks twice per week for 6 weeks

• Sig. pain reductions vs placebo at 15m, 30m, 24h post-treatment

• HIT-6 scores significantly decreased from before treatment to the final treatment (P=0.005) vs NSD in the placebo group

• No significant or lasting adverse events (abnormal taste blinding?)

• 2° endpoints: Decreased headache days at 1 month, HIT-6 scores at 1 and 6 months, and medication usage; trends but NSD vs placebo

Emergency department: acute headache (N=87)

• 50% pain reduction: 48.8% bupivacaine vs 41.3% placebo (No SD)

• 24-hour headache-free: 24.7% difference (95% CI 2.6%–43.6%)

• 24-hour nausea free: 16.9% difference (95% CI 0.8% to 32.5%)

Cady R et al, Headache 2015

Cady R et al, Headache 2015

Schaffer JT et al, Ann Emerg Med 2015






5. Training

6. Summary

Training

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5. Training

6. Summary

Headache procedure evidence summary

Procedure Headache Disorders IndicationInjection Series

Best evidence

OnabotulinumtoxinA

Chronic migraine

Post-traumatic headache

NDPH

Nummular headache

Trigeminal neuralgia

ProphylaxisRepetitive

3 month intervalsChronic migraine

Peripheral nerve blocks /injections

Cluster

Migraine

Hemicrania continua

NDPH

Cervicogenic headache

Post-dural puncture headache

Acute treatment or

short-term prophylaxisSingle or repetitive

Cluster

Chronic migraine

Acute migraine

Trigger point injectionsETTH, CTTH

Migraine

Cervicogenic

Acute treatment or

short-term prophylaxisSingle or repetitive TTH

Sphenopalatineganglion blocks

Chronic migraine

Cluster

Hemicrania continua

Trigeminal neuralgia

Idiopathic facial pain

Acute treatment or

short-term prophylaxisSingle or repetitive Chronic migraine

Ashkenazi A et al, Headache 2013




Summary

1. Onabotulinumtoxin A is indicated for chronic migraine, and is effective, safe and with few contraindications.

2. Peripheral nerve injections have the best evidence for cluster headache followed by chronic migraine, but are useful for many headache disorders.

3. Adding a steroid to an occipital nerve block may be particularly effective for cluster headache but is of uncertain benefit for migraine.

4. Trigger point injections may be particularly effective in tension-type headache, are identified by physical examination, and should be restricted to local anesthetics only.

5. Sphenopalatine ganglion blocks are safe and potentially effective, though the evidence is emerging.

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Ongoing studies

NCT Number Title Conditions Interventions Location

NCT02665273

GON Block With

Bupivacaine for Acute Migraine in ED

Migraine Procedure: GON block

Procedure: Sham

Montefiore Medical

Center

NCT03159000

A Research Study of GON

Block as a Treatment for Acute Migraine Attacks

Migraine

Drug: Saline

Combination Product: lidocaine/ bupivacaine

Thomas Jefferson

University

NCT03066544

Status Migrainosus -

Differentiating Between Responders and Non-

responders

Migraine

Drug: Bupivacaine

Drug: Naratriptan Pill Drug: Dexamethasone

Drug: Ketorolac

Hartford HealthCare

Thank you

@mrobbinsmd

[email protected]

powerpoint presentation...2015 episodic and chronic migraine 63 gon injection (u or b) with 2.5 ml...

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