Canadian Society of Internal Medicine

Annual Meeting Quebec City, October 2012

Headaches in pregnancy Dr Elizabeth Leroux, MD, FRCPC Centre Hospitalier Universitaire de

Montréal, Neurology department

Canadian Society of Internal Medicine

Annual Meeting Quebec City, October 2012

Leroux: Headaches in pregnancy

The following presentation represents the views of the speaker

at the time of the presentation. This information is meant for

educational purposes, and should not replace other sources

of information or your medical judgement.

A selection of slides from this talk will be available

on the CSIM website in PDF format.

Canadian Society of Internal Medicine

Annual Meeting Quebec City, October 2012

Dr Leroux: Pregnancy Headaches

The speaker has received fees/honoraria from the following sources:

Pfizer, Merck, Allergan, Tribute Pharmaceuticals, Teva Neuroscience,

Johnson and Johnson, Purdue Pharma.

Conflict Disclosures

Some of the drugs, devices, or treatment modalities mentioned in this

presentation are:

Objectives Dr Anne E. Mac Gregor, Neurol Clin 2012

Diminish the stress response when you see a pregnant woman with headaches

Give the pregnant migraineur ways to control the migraines

Recognize secondary headaches

Review reversible vasoconstriction syndrome

Rachel has migraines

27 years old woman

History of migraine

Treats with Relpax

Has 3 attacks per month

Some related to menses

Otherwise healthy

Wants to get pregnant…what will happen with her migraines?

How do I diagnose migraine (quickly)?

POUND: pulsatile, one day, unilateral, nausea, disabling.

SULTANS: severe, unilateral, throbbing, activity worsens, nausea, sensitivity to light and sounds

5-4-3-2-1: 5 episodes, >4h to 3 days, 2, 1 day

ID Migraine: moderate to severe, nausea, photophobia.

Recurring attacks with free intervals

How do I diagnose migraine (quickly)?

POUND: pulsatile, one day, unilateral, nausea, disabling.

SULTANS: severe, unilateral, throbbing, activity worsens, nausea, sensitivity to light and sounds

5-4-3-2-1: 5 episodes, >4h to 3 days,

2 of moderate/severe, unilateral, throbbing, increased by activity

1 of photo/phonophobia or nausea

How do I diagnose migraine (quickly)?

ID Migraine:

Recurring attacks

No warning signs

Moderate to severe

Nausea

Photophobia.

Migraine spectrum

Episodic migraine

Frequent migraine

Chronic migraine

More impairment More depression More anxiety Medication overuse

Needs prophylaxis Avoid overuse

Work on triggers Find acute treatment Improve lifestyle

2%

5%

8%

15% of people 3-4 F/ 1 M

Pathophysiology Puzzle

Edith Hamel, J Appl Physiol 2005

Goadsby, NEJM 2002

Hadjikhani PNAS 2001

Weiller, Nature 1995

Pathophysiology Puzzle Cortex Neurons, glia

CSD

Pons Serotonin Trigeminal

nucleus

Meningeal arteries CGRP, NO Neurogenic

inflammation

Mac Gregor Neurol Clin 2012

Check for menstrually related migraine It will most likely improve…

Mac Gregor Neurol Clin 2012

Acute treatment: non pharmacological

Hydration

Rest

Darkness

Warm or cold

Sleep

Relaxation

Biofeedback

Pregnancy

privilege

Airola, Neurol Sci 2010

Category Drug FDA Lactation Comment Analgesics (65% will use OTC during pregnancy)

Acetaminophen B Minimal risk First line

Aspirin C* Caution Keep low dose

Ibuprofen B* Minimal risk

Diclofenac B* Minimal risk

Naproxen B* Caution

Indomethacin B* Caution

Anti-emetics Promethazine C Minimal risk Increase lactation Dystonic reaction Sedation Metoclopramide B Minimal risk

Prochlorperazine C Concern

Dimenhydrinate B Caution

Domperidone C Minimal risk

Others Prednisone C* Compatible Short term OK

IV Magnesium 1g A Caution First line in ER

Caffeine B Minimal risk May help

Diphenhydramine B Caution

Opiates Morphine C Caution May increase nausea Not first line Tramadol C Caution

Codeine C** Caution

NSAIDs and spontaneous abortion Nakhai Pour CMAJ 2011 (RAMQ registry), Briggs 2005

4705 spontaneous abortion / 47 050 controls

7,5% vs 2,6% had PRESCRIPTION NSAID.

Around 17% of pregnant women use NSAIDs.

NSAIDs recommendations Ostensen, Res Ther 2006

1) Non-selective and selective COX inhibitors can prevent or retard ovulation but frequency of ovulation inhibition is unknown;

2) Non-selective COX inhibitors are not teratogenic and can be continued during the first and second trimester of pregnancy;

3) After gestational week 20, all non-selective COX inhibitors (except aspirin at doses less than 100 mg/day) can cause constriction of the ductus arteriosus and impair fetal renal function;

4) All non-selective COX inhibitors except low-dose of aspirin (less than 325 mg/day) should be withdrawn at gestational week 32;

5) The aspirin treatment should be stopped one week before delivery with epidural anesthesia or could be prolonged until the end of pregnancy in patients with antiphospholipid syndrome.

Safety of triptans: birth defects General population 3-5%

All class C. Ergots and DHE contra-indicated

Suma Imitrex

Zolmi Zomig

Eletriptan Relpax

Rizatriptan Maxalt

FDA class C C C C

Major birth defects Registries

494 exp (4,5%)

No data No data 51 exp (3,1%)

Norwegian study OR MBD 1

653 243 179 328

Swedish registry First trimester

2257 OR 0,99

362 OR 0,76

14 OR 5,17

157 OR 1.01

Breastfeeding Low excretion AAP: safe

No data 0,02% excreted (metabolite?)

No data

Being practical

Emphasize non-pharmacological approaches

Acetaminophen first line

Anti-emetics

NSAIDs first trimester possible, second trimester OK, third trimester no.

Avoid narcotics for migraine

Anti-histamines may help sleeping over it

Sumatriptan for severe attacks only

Prophylaxis: non pharmacological

Avoid triggers

Stop caffeine

Regular lifestyle

Biofeedback

Acupuncture

Education is the key…before the pregancy! www.migrainequebec.com www.headachenetwork.ca Airola, Neurol Sci 2010

Biofeedback for pregnant migraineurs Marcus, Psychosom Med 1995

79% versus 23% improvement in Headache Index

From 8 days of headache per 2 weeks to 2 days.

Sustained benefit up to 1 year post-partum.

Cost: 90-110$ per session

At least 5 sessions to learn.

Frequent practice necessary

Find an experienced therapist

Acupuncture

Many trials now

Older studies: better than nothing

Better methodology: not different from sham

Probably a placebo effect..but it may help

Repeated sessions are costly

Linde Cochrane Review 2009, Diener editorial Ev Based Med 2012, Li Headache 2009, Yang Cephalalgia 2009, Wang Pain Med 2012

Drug Posology FDA B. feeding Comment

Propanolol 40-120 mg qd C Low levels First line.

Metoprolol 25-50 mg BID C Low levels Second line

Nadolol 40-120 mg qd C Higher levels Avoid

Atenolol 25-50 BID D Higher levels Avoid

Verapamil 120-420mg/d C Low levels May use second line (or cluster)

Flunarizine 5-10 mg qd Not class. No data Avoid

Candesartan 8-16 mg qd C or D No data Avoid. Teratogenic.

Lisinopril 5-10 mg qd C or D No data Avoid. Teratogenic.

Amitriptyline 10-50 mg HS C Low levels Most experts use low dose

Nortriptyline 10-50 mg HS Not class. Low levels May use

Venlafaxine 75-150 qd C Excreted Not if migraine only

Topiramate 25-75 BID D Caution Avoid. Teratogenic oral clefts

Valproate 250-500 BID D Avoid Avoid. Teratogenic

Gabapentin 600-3600 mg C Caution May use during breasfeeding

Magnesium 300 mg BID No data on high doses

Vitamin B2 400 mg die No data on high doses

Botox 150-200 ui C No data Do not use during pregnancy.

Rachel has an aura!

She is 13 weeks pregnant

She describes a progressive blurred vision with shimmering spots, for 20 minutes. Maybe some tingling in the right arm.

She had a headache just after, with nausea.

Now she is normal.

Should you worry?

Migraine auras: 122 pts Queiroz, Cephalalgia 2011

28% of migraineurs have auras

33% have more than visual symptoms

70% before the headache, 27% during 3% after

66% last 5-30 minutes (may be more)

75% progression (25% sudden)

50% bilateral visual field involvement

40% coloured

50% dot and blurry (not only complex)

Queiroz, Cephalalgia 2011

Migraine with aura during pregnancy

Mac Gregor Neurol Clin 2012

Vascular causes of auras: emboli

Cortical subarachnoid

Cerebral venous thrombosis

Cervical artery dissection

Stroke

Dalkara, Lancet Neurol 2010

Rachel’s pregnancy goes on

She is worried she might be at increased risk for eclampsia

Migraine and hypertensive disorders

Increased risk gestational hypertension OR 1,6 (1,2-2,1) Scher 2005

Increased risk of pre-eclampsia OR 2,8 (1,4-5,8) Fachinetti Cephalalgia 2009 OR 1,4 (1,1-1,8) 11,4% vs 8,4% Banhidy 2006

Depression also worsens the risk! Mood disorder OR 3,57 Mood and migraine OR 3,49 Cripe 2011 Migraine only no increased risk

Worse if obese migraineur OR 12 Adeney 2005

Allais, Neurol Sci 2007

A disturbing article Bushnell, BMJ 2008

Stroke risk higher if migraineur 34/100 000 deliveries

OR 16 if migraine James 2005 (0,5%)

Diagnosis of migraine: 0,18% of sample Most diagnosed at delivery…

Many migraineurs NOT diagnosed

Erroneous diagnosis of migraine in patients with a secondary headache who stroke after!

Rachel will soon deliver

Second trimester was really fine

37 weeks now

She presents to hospital for a headache

She is sent back home after some improvement with Maxeran

She comes back, and is given Dilaudid

Third time, the neurologist is called for chronic migraine.

Do you know this headache?

Known? (more intense OK) History of similar headaches PRIMARY

Unknown? First episode, pt worried SECONDARY

Thunderclap Progressive Unclear

Headache >15/30 Episodic attacks

No overuse With overuse

Meningitis High ICP Venous thrombosis Many others

Be prudent

SAH RCVS Sheehan Sinusitiis Venous thrombosis High ICP Others

Look for overuse if chronic

Nausea photophobia Pulsatile, etc

No migrainous sx

Migraine or tension type?

Episodic or chronic

What is a thunderclap headache?

Severe intensity over 1 min. or so

Lasts more than 30 minutes

DO NOT SUGGEST ANYTHING

The worse headache is not very helpful

What were you doing when the headache appeared?

Look for vomiting, LOC, grabbing the head, fear of the headache, neck pain.

Thunderclap differential Schwedt Lancet 2006

Particularities of pregnant women Subarachnoid (Bateman Anesthesiology 2012)

5,8/100 000 deliveries Half post partum, 6% coiling rate…NO aneurysm 40% with HTA disorders

Venous thrombosis (1-10/10 000 pregnancies?) VT of any kind, incidence ratio 4,29 (Heit 2005) In a serie of 19 cases, NONE had only headache. Look for vomiting and papilledema (Demir 2012)

AVM rupture: 3,5% outside of pregnancy

Pituitary apoplexy and Sheehan: rare

Reversible vasoconstriction syndrome: prevalence?

Rachel’s story

Had 5 major thunderclaps Triggered by defecation and effort

Clearly different from her migraines

5 others, less intense (stopped activity)

Lingering diffuse headache between episodes

NO neurological deficits

NO criteria for pre-eclampsia

6.7.2: Reversible Angiopathy of the CNS

Recurrent thunderclap headaches (80-100%)

Multifocal arterial spasms, reversible at 3 months Start distal to proximal Bleed first, stroke after

0 5 10 15 20

ICH 1.7 ± 2

cSAH 5 ± 5

Last thunderclap 7.4 ± 5.6

Infarction 12 ± 3

TIA 11.6 ± 4.9

Ducros, Brain 2007

Déclencheur Exemples (From Russell, Lancet Neurology 2011)

Pregnancy Eclampsia or Post-partum 10% of cases Vasoactive Illicit Ergots Sympathomimetics Immunosuppressants Others

Cannabis, cocaine, ecstasy, amphetamines, LSD Ergotamine tartrate, methergine, methylergometrine, lisuride, bromocriptine Ephedrine, isometheptene, pseudoephedrine, diet pills, phenylpropanolamine Selective serotonin-reuptake inhibitors, triptans Tacrolimus (FK-506), cyclophosphamide, IFN-a Nicotine patches, Ginseng, licorice, indomethacin, binge drinking, oral contraceptive pills, hormonal ovarian stimulation for intrauterine insemination

Catecholamines tumors

Pheochromocytoma, bronchial carcinoid tumor, glomus tumors

Vascular interventions

Cervical artery dissection, aortic dissection, unruptured intracranial aneurysm, fibromuscular dysplasia, postcarotid endarterectomy

Blood products Erythropoietin, intravenous immunoglobulin, massive blood transfusion

Intracranial pressure changes

Intracranial hypotension, intracranial hemorrhage, spinal subdural hematoma, neurosurgery, head trauma

Others Hypercalcemia, systemic lupus erythematosus, porphyria, microangiopathic hemolytic anemia, triplet cesarean delivery, ascent to high altitude, tonsillectomy, autonomic dysreflexia

Triggers for each headache

Cough

Sex

Exercise

Urinating, defecating

Emotions

Sudden movements

Bathing

Multifocal spasms Angio CT, angio MRI or Trans Cranial Doppler May be normal early on, control 7-10 days

Complications of RCVS Chen, Exp Rev Neurother 2011, Fletcher, Neurocrit Care 2009,

Fugate Stroke 2012

Complication RCVS in general

Puerperium RCVS 28 cases

Post partum angiopathy 18 cases over 2 years

Hypertension 30% 60% 50% proteinuria

PRES 9-14% 54% 35%

TIA 15% NA NA

Ischemic stroke 4-54% 29% 27%

Hemorrhage 20% 39% 39%

Subarachnoid Up to 34% 6 cases reported No aneurysm

22%

Seizure Up to 21% 54% 28%

Permanent deficit 3-0% 2 deaths, 3 severe 4 deaths, 1 severe 3 mild

PRES No TCH 30/43 vasospasm

RCVS TCH Vasospasm HTN 30-50%

Eclampsia: HTN, proteinuria, Headache 80%, vasospasm

SAH TCH

CNS vasculitis Vasospasm Progressive HA

Calabrese, 2009 Chen, Exp Rev Neurother 2011

RCVS treatment Rest

Avoid triggers

Stop offending drug

Hospitalize (possibly)

Avoid hypotension

Magnesium IV tocolysis is an option in the post-partum pt

Calcium channel blockers Nimodipine 30-60 mg q4h IV nimodipine 0,5-2 mg /hour

No steroids

What happened to Rachel?

Brain parenchyma was normal

She was given Nimotop 60 QID and Magnesium IV

The headaches did not recur with treatment

She developed hypertension and proteinuria

Labor was induced

She delivered safely a healthy baby.

Control angio-MRI was normal 7 days later

7 days after first MRI

Angio MRI 3D TOF Time of flight NO contrast

First MRI 15 days after first HA

Conclusions Migraine is likely to improve during pregnancy

Menstrual migraine

Migraine without aura

Acute treatment can be planned

Prophylaxis can be used if needed

An unusual headache is secondary until proven otherwise

ALL thunderclaps headaches should be investigated

RCVS is part of a spectrum with PRES and eclampsia