Migraine Mimics

Randolph W. Evans, MD

www.maxmyinterest.com

Disclosures

• Speaker’s bureau: Allergan (migraine); Depomed (migraine); Pernix (migraine); Teva (migraine).

• Royalties: Elsevier, Lippincott Williams&Wilkins, Medscape Neurology, Oxford, UpToDate

• I have migraine• My wife and 3 children have migraine

Physician Insurers Association of America 2004-2013 National Closed Claim Data for Neurologists

• 1. Errors in diagnosisHeadacheOcclusion and stenosis of cerebral arteriesMigraines

Case history

• 48 year old woman with a 20 year history of menstrual migraine with visual aura lasting 2-3 days with ibuprofen

• 3.5 month history of a daily and constant headache since onset. Left sided pressure or throbbing with an intensity of 1-10/10, avg 6/10 with light and noise sensitivity but no nausea, aura or cranial autonomic sxs. No triggers. Normal exam. MRI brain and MRA of brain and neck neg. Blood tests normal.

• Sumatriptan po and sc, diclofenac powder, ketorolac oral and IM, DHE NS, and occipital nerve block without help. Gabapentin and pregabalin no help. Indomethacin 75 mg SR/d for 8 d no help. Prednisone 60/d for 10 d no help. IV DHE regimen for 5 days no help.

• What’s the diagnosis and what would you do next?

Case (continued)

I saw her as a third opinion after she had seen 2 other headache specialists. She was placed on indomethacin titrated up to 75 mg tid with omeprazole and became headache free. The pain resolved for 9 months after about 2 months without medication and then recurred and has been pain free with indomethacin 75 mg/d for 3 years.

Primary headache mimics: Hemicrania continua (HC):easy to misdiagnosis

• HC is easy to misdiagnosis: in a study of 52 pts, 52% were misdiagnosed with migraine and 40% met migraine criteria during exacerbations; the mean time until correct dx was 5 years with the average # of physicians seen 4.6 including neurologists and headache specialists

• Other studies have reported a delay until dx of 86.1 months to 12 years and up to 70% meeting migraine criteria during exacerbations

• Pts with HC may undergo unnecessary dental extractions, TMJ treatment, or sinus surgery

• 11% of new daily persistent headaches are unilateral with 50% having migraine features

HC: epidemiology

• Rare disorder but prevalence may be up to 1% of population• Females: males=1.6:1• Onset often third decade with range of first to seventh decade

HC: clinical features

• Pain almost always unilateral but occasionally can switch sides and rare bilateral cases; throbbing in 69%

• Triggers for exacerbations: stress, 51%; alcohol, 38%; irregular sleep,38%; bright lights, 36%; exercise, 31%; warm environment, 28%; skipping meal, 23%; strong smell, 15%; weather change, 13%; tiredness, 13%; and period, 10%

• Similar to chronic migraine, 75% have exacerbations of severe throbbing or stabbing pain lasting 20” to several days (causing awakening from sleep in 1/3) which can be associated with photophobia (59%), phonophobia, which is often unilateral 59%), nausea (53%), and vomiting (24%)

• Rarely, visual auras occur

HC: clinical features (continued)

• Cranial autonomic symptoms present in up to 75% with tearing and then conjunctival injection the most common compared with 56% of migraineurs

• Prior hx of migraine common• Primary stabbing headache (ice pick headache) in 41% especially

during exacerbations and in 40% of migraineurs

HC: clinical features (continued)

• Chronic when daily and continuous without pain-free periods for a minimum of 1 year

• Episodic when there are pain-free intervals of at least a day without treatment

• In one series, 82% had chronic (unremitting) HC, which was chronic from the onset in 69%. Evolution from the episodic form occurred in 28% after a latency of 7.9 years (range of 2 weeks to 26 years). Some of the patients with the initial episodic form had headaches that were not daily initially and one patient had about 10 headache days per month. 15% had the episodic form, which was episodic from the onset in 33% and evolved from the chronic form in 66%.

HC: treatment

• HC defined by complete headache freedom on indomethacin in divided doses from 25 to 300 mg (rare) daily, usually 150 mg/d or less

• Most patients respond to an indomethacin trial increasing the dose if not headache free: 25 mg tid x 3 d, 50 mg tid x 3 d, 75 mg tid x 3 d, 100 mg tid x 3 d

• Indomethacin taken with PPI• Multiple possible side effects of indomethacin

HC: treatment (continued)

• If can’t take or tolerate indomethacin, alternatives not nearly as effective

• In 1 series, greater occipital nerve block and IV DHE effective as short-term treatment in 35% and 33% and topiramate as prevention in 41% (100-200 mg/d in different case reports)

HC treatment (continued)

• Effective in case reports: occipital nerve block alone, melatonin 9-15 mg hs, ibuprofen 1600-2400 mg/d, celecoxib 200 mg bid, botulinum toxin A (PREEMPT migraine paradigm), verapamil 120–480 mg daily, gabapentin 600-3600 mg daily, pregabalin 150 mg daily, valproic acid 750 mg/d, intravenous methylprednisolone

• Case reports of occipital nerve stimulation• Case reports of patients undergoing diagnostic blockade of either the atlanto-

axial joint, C2 dorsal root ganglion or sphenopalantine ganglion depending on their clinical examination and presence of cranial autonomic symptoms. positive response led to a radiofrequency ablation of the C2 ventral ramus, C2 dorsal root ganglion or sphenopalantine ganglion, which provided headache relief in all case patients as complete as indomethacin (Beams et al. Cephalalgia 2015)

Cluster headache (CH)

• By ICHD-3-beta definition, duration is 15”-3 hours. One study found attack duration of 4 hours or more in pts who met all other criteria

• Prospective series of 155 pts with CH, migraine features with each attack: nausea/vomiting, 18.1%; bilateral photophobia, 12.3%; phonophobia, 5.2%;osmophobia, 0.6%; and aura (3 visual, 1 somatosensory), 2.6% (14% in another series)

• In another series of 209 CH, light and noise sensitivity in 70% and vomiting or nausea in 20%; but 83% were restless unlike migraineurs

• CH may be confused with migraine when duration of headache provided by pt is not accurate-may provide duration of 2 or 3 headaches combined

Cluster-Migraine

• For occasional patients who present with features of migraine and cluster that do not meet ICHD-3 criteria for either or both diagnoses to be present, the terms “cluster-migraine” or “migraine-cluster” have been used

New daily persistent headache (NDPH)• Commonly misdiagnosed by neurologists as chronic migraine• NDPH is defined as daily from onset with pain becoming continuous

and unremitting within 24 hours present for more than 3 months, unlike chronic migraine, which evolves or transforms from episodic migraine and is not daily from onset

• Migraine features present in almost 50% plus rare visual aura• 20% have a pre-existing history of migraine• NDPH with migraine features may respond to same acute and

preventive medications as chronic migraine

Secondary headaches: AVMs

• Prevalence about 0.5% in postmortem studies• Headache is presenting sx in up to 48%• Migraine-like headaches with and without visual sxs can be associated especially

with occipital lobe AVMs (20% of parenchymal AVMs)• Headaches always on the same side (side-locked) occur in 95% with AVMs and

about 15% with migraine• AVM headaches usually do not meet migraine criteria. In a series of 109 pts: non-

pulsating, 95%; nausea, vomiting, light, or noise sensitivity, 4.1%; unilateral and homolateral to the AVM, 70%; duration less than 3 hours, 77%; 1-2 per month, 82.5%; and usually mild responding to simple analgesics

• Seizures may occur in 25% and scintillating scotoma may be brief; field cuts may be present

Vascular malformations

• The following brainstem malformations have been associated with migraine meeting ICHD criteria: a hemorrhagic midbrain cavernoma resulting in a contralateral headache; a pontine bleed from a cavernous angioma with initially ipsilateral headache then bilateral with aura; pontine capillary telangiectasia with signs of residual hemorrhage with bilateral headaches initially with aura; and a midbrain/upper pons hemorrhagic AVM/cavernous malformation resulting in a contralateral headache with aura.

• Provide evidence for the involvement of the brainstem in the initiation of migraine

Case history 1

• This is a 60 year old male with a history of migraine with and without aura since his 40s up to 25 days per month decreased to about 5 per month on gabapentin 600 mg tid I had followed for 3 years. The headaches could be back of the head or generalized or occasionally bitemporal pressure with an intensity of 3-10/10 associated with light and noise sensitivity but no vomiting relieved by eletriptan in 2 hours. He would have a visual aura of flashing lights in both eyes for 20 minutes before the headache occasionally.

• He presented with a 12 day history of a right temporal, behind the right eye and occasionally right back of the head sharp pain with an intensity of 4/10 at onset and 7-9/10 since associated with nausea, light and noise sensitivity but no vomiting on a daily basis lasting 2-8 hours with ibuprofen or eletriptan. He reported blurred vision with things missing in the right eye intermittently for 3-5 hours daily from the day of onset of the headache for 10 days. He had no fever. His pcp placed him on a Medrol dose pak. Exam by an ophthalmologist was normal. Neurological exam was normal.

• What is your diagnosis?

Case 1 (continued)

• ESR 2• MRI of the brain showed small acute/subacute right cerebral white

matter infarcts• MRA of the neck showed a dissection of the right ICA beginning about

1 cm distal to the bifurcation extending to the skull base with about 60% maximum stenosis

• He had frequent coughing 3 wks before onset due to allergies-? relationship

Case history 2

• This is a 35 year old female with a history of occasional migraine with visual aura as a teen and migraine without aura since her 20s 1-2 per month (bifrontal aching with light and noise sensitivity).

• She looked behind the seat in the car and developed a mild crick in her neck. A few hours later, she developed a constant nuchal-occipital and generalized pressure and throbbing with an intensity of 9-10/10without associated symptoms. Her pcp gave her Imitrex and Midrin which helped a little. Over a couple of weeks, the headaches were only bifrontal. After one month, the headaches were still constant, bifrontal and right temporal with an intensity of 3-10/10. Neuro exam normal.

• What is the diagnosis?

Case history 2 (continued)

• MRI of the brain showed several prominent foci of increased T2 FLAIR signal in subcortical and periventricular white matter and one in corpus callosum. MRA of the neck was suggestive of dissection. CTA was not diagnostic. Cerebral arteriogram showed a left vertebral artery aneurysm at C6 level with pseudoaneurysm just distal to the narrowing with 50% stenosis. Coagulopathy and collagen vascular blood tests normal. LP neg for oligo bands.

• Treated with heparin and then warfarin for 3 months until MRA showed recanalization and then asa.

• Headaches persisted daily for 8 months p onset-decreased on topiramate and then 1/month on Pristiq alone

• 3 yrs later, developed MS

Cervical artery dissection

• Headache or neck pain is the only symptom of spontaneous CAD in 8% and can mimic migraine with and without aura and migraine status

• Thunderclap onset in 20%• Average annual incidence rate for spontaneous dissectionsInternal carotid: 2.6/100,000 and vertebral: 1.5/100,000May be higher since many cases not detectedMean age of 44-46, males=femalesCan occasionally result in new daily persistent headache as in this case (more often with cervical carotid artery dissection)

Factors Associated With Cervical Dissection

• Migraineurs have a two-fold increased risk which does not differ by migraine aura status or gender

• Mild or trivial trauma estimated to be antecedent in 12-36% of cases• Arterial hypertension• Young age• Current use of oral contraceptives• Fibromuscular dysplasia• Ultrastructural connective tissue abnormalities• Vascular subtype of Ehlers-Danlos syndrome• Marfan syndrome

Factors Associated With Cervical Dissection (contd)

• Turner syndrome• Williams syndrome• Familial cases• Hereditary hemochromatosis• Osteogenesis imperfect type I• α1-Antitrypsin deficiency• 677T genotype MTHFR• Hyperhomocysteinemia• Cystic medial necrosis of intracranial vessels

Factors Associated With Cervical Dissection (contd)• Styloid process length• Autosomal-dominant polycystic kidney disease• Infections• Moyamoya disease• Lentiginosis• Vessel redundancies (coils, kinks, loops) especially if bilateral

Internal carotid artery dissection

• Headache initial symptom in 47% and occurs in 60-95% preceding other neurological sxs and/or signs by a median of 9 days (range 1-90 days)

• Pain is ipsilateral in 91% of cases, typically localized to the frontal or temporal area, jaw, ear, and/or orbit and is more often aching than throbbing.

• A partial Horner syndrome occurs in about 25% of cases with ptosis and miosis• Can have migraine features including nausea and vomiting.• Can mimic migraine with aura with a visual aura only or a march or aura sxs (such as

visual then sensory then dysphasia) with a migraine-like headache• In those with prior migraine, dissection could be incidental or could be trigger for

migraine with aura or cause of sxs• Median duration of headache is 3 days (range 1 hour to 4 years; 90% resolve within 1

week)

Vertebral artery dissection

• Presenting symptom in 70% and occurs in 88% with head or neck pain preceding other neurological sxs and/or signs by a median time of about 2 weeks (range .5 hour to 30 days)

• Typically a severe ipsilateral occipital or posterior neck throbbing or steady and sharp pain but can be bilateral. Rarely frontal or generalized.

• Rarely associated with migraine features such as nausea, vomiting, photophobia, or phonophobia, and visual aura

• Easily and often misdiagnosed as musculoskeletal pain or tension headache

• Mean duration of headache is 8.3 days (range 2-35 days)

Cerebral venous thrombosis

• Incidence in adults perhaps 1.32/100,000, 3:1 females:males (preg, postpartum, ocp’s, hrt)

• Headache in 80-90% of cases: most frequent manifestation and often only presenting sx-can be only manifestation at onset and during the course with a normal neuro exam

• In a series of 123 patients with CVT, 14% presented with headache as the only neurological symptom and had the following migraine features: throbbing, 76%; severe, 76%; unilateral, 76%;nausea, vomiting, and/or phono/photophobia, 59%

Cerebral venous thrombosis (continued)• Rarely, can have visual phenomena similar to migraine aura• Raise suspicion of CVT: recent persistent headache, thunderclap

headache or pain worsening with straining, sleep/lying down, or Valsalva maneuvers even in the absence of papilledema or focal signs

Reversible cerebral artery vasoconstriction• 60% develop postpartum or after exposure to vasoactive drugs

(cannabis, ecstasy, SSRI, triptans, cocaine, amphetamine, IVIG)• Female:male=3:1, typically between ages 20-50 (range 10-76 yrs)• Multiple severe bilateral throbbing thunderclap headaches (average

of 4 although single attacks can occur), which can be associated with nausea and/or vomiting and photophobia, are a presenting feature in 94% of cases over a mean period of 1 week that may occur spontaneously or be triggered by cough, exertion, or Valsalva

• Visual blurring, scotomas, and blindness are commonly associated• Transient cerebral vasoconstriction resolves within 1-3 months

Temporal arteritis

• Consider with new onset headaches over age 50• In a Canadian study of 141 consecutive patients presenting to a neuro-

ophthalmology practice, there was one patient under the age of 50 (age 47)

• Female:male =3:1 with incidence of 29.6/100,000 in 70s• Headache most common sx, in 72%, initial sx in 33%• May be throbbing or aching with an acute or subacute onset, can be

persistent or intermittent, mild to severe intensity, and in any location• A scintillating scotoma most often monocular similar to a migraine aura

is rarely reported

Subarachnoid hemorrhage

• Can mimic crash migraine (severe sudden onset), severe migraine upon awakening, and worst migraine ever

• May be the only symptom of SAH in about one third of patients and is usually bilateral but can be any location, mild at onset, gradually increasing in intensity in 19%, often associated with nausea and vomiting but with the absence of a stiff neck in 36%

• SAH can be the trigger for a migrainous aura• SAH headache may improve with triptans

Cerebral autosomal dominant arteriopathy with subcortical infarcts with leukoencephalopathy (CADASIL)

• Middle-aged onset of cerebrovascular disease demonstrated on MRI scans showing white matter hyperintensities with or without lacunar infarctions and microbleeds that often progresses to dementia

• Prevalence of mutation carriers is 0.8-2/100,000• Caused by mutations in the NOTCH3 gene located on chromosome 19

CADASIL (continued)

• About 30% are affected by migraine attacks often as the first symptom with 80-90% having migraine with aura

• Of those with migraine with aura, 56% have uncommon features including aura without headache, hemiplegic aura, migraine with brainstem aura, prolonged aura (including one case with prolonged headache), and acute-onset aura

Hypertension

• An often bilateral and pulsating headache may be associated with an acute rise in a systolic blood pressure to ≥180 mmHg and/or diastolic to ≥120 mmHg, which remits after normalization of blood pressure

• Mild or moderate chronic hypertension does not appear to cause headache

Cardiac cephalalgia or angina headache• A unilateral or bilateral headache in any part of the head brought on by

exercise and relieved by rest due to cardiac ischemia. Pain may occur at rest in cases of unstable angina.

• Chest pain, pain in the left arm which can radiate to the mandible, or epigastric pain are present in 50% of cases

• Cardiac cephalalgia is the only manifestation of angina in 27% of cases• Thirty percent have associated symptoms such as photophobia,

phonophobia, osmophobia, and nausea. • 36 cases have been reported, 58.3% males, usually over the age of 50 years,

although 22% younger than 50 with the youngest 35

Neoplasms

• Migraine-like headaches occur in up to 15% of patients with primary and metastatic tumors and can present with nonacute migrainous headaches with a normal neurological examination without seizures

• Reported with colloid cysts of the third ventricle, craniopharyngioma, cerebral metastasis, brainstem glioma, and pituitary tumors

• Pituitary hemorrhage can produce a migraine-like acute headache with a normal neurologic examination which can be missed on routine CT

Stroke-Like Migraine Attacks After RadiationTherapy (SMART) Syndrome• About 40 cases reported of migraine-like headaches associated with

neurological deficits including dysphasia, visual loss, confusion, hemiparesis, hemisensory change, and/or seizures occurring in children and adults 1-35 years after radiation treatment for intracranial neoplasms lasting less than 2 hours to 2.5 months with full recovery in most, but some have an incomplete recovery

• MRI shows thick unilateral gyriform cortical enhancement in previously irradiated areas developing after 2-7 days and typically resolving in 14-35 days but can last between 11 and 84 days

• Pathophysiology not known

Acute and chronic isolated sphenoid sinusitis• Usually causes a frontal, occipital, temporal, vertex, or retro-orbital

pain in single locations or a combination of these locations, which is often associated with nausea and vomiting worse with standing, walking, bending, or coughing and not relieved with sleep

• Fever is present in more than half while purulent nasal discharge or nasal obstruction is present in 40%.

Viral meningitis

• Can present with a severe bilateral throbbing headache associated with nausea, vomiting, and photophobia without fever or stiff neck

• Recurrent benign meningitis or Mollaret’s meningitis, which has been attributed to many different causes, most commonly herpes virus, can occur without fever

Headache Associated with Neurological Deficits and cerebrospinal Lymphocytosis (HaNDL or Pseudomigraine With Temporary Neurological Symptoms)• May be caused by activation of the immune system by a viral infection.

A viral prodrome is reported in up to 40% of cases. Some 100 cases have been reported ranging in age from 7 to 50 years

• The headache is typically throbbing, moderate to severe, and bilateral or hemicranial, which may be associated with nausea, vomiting, photophobia, or phonophobia with a duration of 1 hour to 1 week with a mean of 19 hours.

• Eighty percent have transient neurological deficits restricted to one hemisphere (75% left hemisphere) and 6% to the basilar artery territory lasting between 5 minutes and 1 week and may recur several times over days to week.

HaNDL (continued)

• The most frequent focal deficits are sensory symptoms, language disorders, and hemiparesis

• The lumbar puncture opening pressure is elevated in 60-70%. The cerebrospinal fluid shows a lymphocytic pleocytosis (10-760 cells/mL) and protein is elevated in up to 96% (up to 250 mg/dL)

• All patients recover completely within 1 to 84 days• Those with suspected HaNDL syndrome associated with confusion

and agitation, which are not typical features, should be tested for neuronal antibodies as anti-N-methyl-D-aspartate receptor encephalitis can mimic HaNDL.

Brain abscess

• In a meta-analysis of 9484 patients with brain abscess with a mean age of 33.6 years, headache was present in 69%, fever in 53%, and focal neurological deficits in 48% but all 3 in 20% with a mean duration of symptoms of 8.3 days

• Nausea and vomiting was present in 47%• Headache is typically moderate to severe and aggravated by straining

or other Valsalva maneuver• Can mimic migraine status

Pseudotumor cerebri syndrome

• In one prospective study, headache daily in 73% with an increasing pulsatile headache different and more severe than prior headaches associated with nausea

• 70% had headaches with focal unilateral pain (retro-orbital, frontal, temporal, occipital, or vertex pain) but often had a generalized headache as well. The headache has a typically frontal and bilateral location with an intensity that may range from mild to severe-cannot distinguish from migraine on clinical features

• In another series, 41% had a premorbid hx of migraine and 17% had migraine with aura

Hydrocephalus

• Obstructive hydrocephalus can cause a migraine-like visual aura• Idiopathic aqueductal stenosis may cause episodic severe headaches

with transient visual scotomas• Recurrent migraine-like headaches have been reported in slit ventricle

syndrome

Spontaneous intracranial hypotension• Can cause a migraine-like headache that can be associated with

nausea ± vomiting, light and noise sensitivity• Although an orthostatic headache is the most common clinical

manifestation, the headache can gradually evolve into a nonorthostatic chronic daily headache or be a nonorthostatic chronic daily headache from onset or be intermittent

• Headache may be dull, throbbing or pressure, mild to severe, usually but not always bilateral and can be frontal, fronto-occipital, generalized, or occipital

Epilepsy

• Preictal headaches (occur in 5-15% of patients with epilepsy); ictal headache (reported by 3–5% of patients with epilepsy); and can occur immediately after a seizure, a postictal headache (10–50% of patients with epilepsy)

• Ictal epileptic headache is a rare disorder where a migrainous or tension-type headache is the sole manifestation of a seizure

• Has been reported in patients with focal seizures arising predominantly from the occipital lobes, with nonconvulsive status epilepticus, and in generalized idiopathic epilepsy

Occipital lobe seizures

• Can resemble a migraine aura with visual hallucinations, illusions, and reduced vision with about 50% having migraine-like post-ictal headaches

• Epileptic visual hallucinations usually occur within a few seconds, last a few minutes, and are usually colored and circular

• Migraine visual aura develops over minutes and typically lasts 5-60 minutes and is often uncolored and linear

• In difficult cases, an ictal EEG may be diagnostic

Glaucoma

• Rarely, with a normal scan of the brain and a white eye, subacute angle closure glaucoma can mimic migraine with and without aura

• Can even recur over a period of years

Alice in Wonderland Syndrome

• A rare migraine aura usually where patients experience distortion in body image characterized by enlargement, diminution, or distortion of part of or the whole body, which they know is not real

• The syndrome can occur at any age but is more common in children• The cause may be migrainous ischemia of the nondominant posterior

parietal lobule

Alice in Wonderland Syndrome (continued)• In a review of 81 cases, migraine was the cause in 11% and Epstein–

Barr virus in 48%• Other causes included other infections, toxic encephalopathy, major

depression, epileptic seizures, and medications• Topiramate, used for migraine prevention, can cause