Secondary Headaches

Rashmi Halker MD FAHS Mayo Clinic Phoenix, AZ

halker.rashmi@mayo.edu Twitter: @rashmihalker

Disclosures

• No financial disclosures • Many medications used in the treatment of

headache disorders are off label

Outline

• Thunderclap headache • Abnormalities of ICP • Medication overuse headache • Other secondary headaches that may be

tested

Thunderclap Headache

(Primary) Thunderclap Headache: ICHD-3

• A. Severe head pain fulfilling criteria B and C • B. Abrupt onset, reaching maximum intensity

in <1 min • C. Lasting for ≥5 min • (D. Not better accounted for by another ICHD-

3 diagnosis)

Thunderclap Headache Differential Diagnosis

• Subarachnoid hemorrhage • RCVS • CVST • Cervical artery dissection • Acute hypertensive crisis • Ischemic stroke • Pituitary apoplexy • Cardiac Cephalgia • Giant Cell Arteritis

• Idiopathic TCH • Sexual activity • Exertion • Cough

• CSF Leak • Lesion (colloid cyst) • Meningitis

RCVS = reversible cerebral vasoconstriction syndrome CVST = cerebral venous sinus thrombosis

Subarachnoid Hemorrhage (SAH) • 90% present with headache

• In ED: account for 25% of “worst headache” presentations with abnormal examinations

– In 18%, headache is absent, mild, or gradual in onset, or overshadowed by other symptoms

• Aneurysmal SAH = 80% of non-traumatic SAH

• 1 month case-fatality rate = 30-40%

• Accounts for 3% of stroke but 5% of all stroke deaths

• Survivors:

– Functionally dependent = 10-20%

– Reduced quality of life = 60%

Polmear A. Cephalalgia 2003

Linn FH et al. Lancet 1994;344:590-593 Morgenstern LB et al. Ann Emerg Med 1998;32:297-304

Edlow JA, et al. J Emerg Med 2008;34:237–251

Aneurysmal SAH: Risk Factors for Aneurysm Rupture

Patient-specific • Cigarette smoking • Hypertension • Race/Ethnicity

– African race (2.1xbaseline risk)

– Japanese, Finnish descent

• Family history • F > M (1.6:1) • Age > 60

Aneurysm-specific • Size: > 5 mm AC, > 3 mm PC • Posterior circulation • Multiple aneurysms • Multiple lobes (daughter

sacs) • Growth during follow up

imaging

Wermer MJH et al. Stroke. 2007;38:1404-1410 Weibers DO, et al. Lancet 2003, 362:103–110.

Diagnosis of Aneurysmal SAH Sensitivity of CT

Sensitivity Specificity Negative predictive

value

Positive predictive

value CT < 6h 100% 100% 100% 100%

CT overall 93% 100% 99.5% 100%

Perry JJ, et al. BMJ 2011;343:d4277 doi: 10.1136/bmj.d4277

Bottom line: Modern 3rd generation CT is extremely sensitive in identifying subarachnoid hemorrhage when it is carried out within six hours of headache onset and interpreted by a qualified radiologist.

CSF XANTHOCHROMIA AFTER SAH

Perry JJ, et al. Ann Emerg Med. 2008;51:707-713. Vermulen M et al. J Neurol Neurosurg Psychiatry. 1989; 52(7): 826–828.

71 4 WEEKS

90 3 WEEKS

100 2 WEEKS

100 1 WEEK

100 12 HOURS

PROBABILITY (%)

TIME AFTER HEMORRHAGE

A negative CT and negative CSF is sufficient to rule out SAH.

Cerebral Venous Sinus Thrombosis (CVST)

• Thunderclap HA in 10% (Headache 75%)

• CT normal in 25%

• CSF: normal in 70% (lymphocytosis, rbcs, and/or increased protein in 30%)

• Up to 40% may have elevated CSF opening pressure alone

• If CVST suspected, MRI/MRV study of choice

• Tx: Anticoagulation

Filipidis A et al. Neurosurg Focus 2009; 27(5):E3.

CVST Risk Factors

Transient • Infections

– CNS (empyema, meningitis) – ENT, Face/neck (otitis,

mastoiditis, sinusitis, etc) • Pregnancy & puerperium • Physical precipitants

– Head trauma – Jugular/subclavian catheters

• Prothrombotic drugs – OCPs, HRT, Lithium, tamoxifen,

etc • Dehydration • Diabetic ketoacidosis

Permanent • Genetic/acquired prothrombotic

conditions – Protein C, S, antithrombin

deficiencies, factor V Leiden, prothrombin mutations

– APLS, nephrotic syndrome, congenital heart disease

• Malignancy • Dural fistula • Inflammatory diseases

– Behcet’s, SLE, Sjogren’s, Wegener’s, GCA, Sarcoidosis, IBD

• Thyroid disease (hyper & hypothyroidism)

Ferro JM & Canhao P. Curr Cardiol Rep 2014;16:523.

Arterial Dissection

• Thunderclap HA 13% (Headache 75%)

• CT/CSF usually normal

• MRI/MRA diagnostic procedures of choice

• Tx: remains controversial, Anticoagulation vs antiplatelet therapy

Jensen MD et al. Neurologist 2008;14(1):5-8. Redecop GJ. Can J Neurol Sci 2008;35(2):146-52.

Pituitary Apoplexy • Acute clinical syndrome: headache, vision loss,

ophthalmoplegia, altered MS, and variable endocrine abnormalities

• Hemorrhage or infarction of pituitary gland • Pre-existing pituitary (macro)adenoma is common • Clinical risk factors:

– trauma, increased ICP, postpartum (Sheehan syndrome), anticoagulation, bromocriptine therapy, diabetic ketoacidosis, conventional angiography, radiation therapy, and open heart surgery

• Treatment: surgical decompression or steroids • Complications: coma, death (over weeks)

Rogga JM. AJNR 2002 23: 1240-1245.

Pituitary Apoplexy MRI • Imaging features:

– If acute, T1 iso or hyperintense

– If acute, T2 hypointense enlarged pituitary gland

– T2 blooming artifact if hemorrhage

– Restricted diffusion may be early sign of hemorrhage

– Rim enhancement common – May see adjacent dural

thickening and mucosal thickening of sphenoid sinus

Images: http://emedicine.medscape.com/article/1198279-overview

Reversible Cerebral Vasoconstriction Syndrome

(RCVS) • Most commonly precipitated

post-partum or with the use of vasoactive substances – Cannabis – Cocaine – SSRIs – Binge drinking – Nasal decongestants

• “Strings & beads” on imaging • May result in:

– PRES – SAH – ICH – Ischemic stroke

• Treated with IV/PO calcium channel blockers

Ducros et al. Brain 2007; 130:3091-3101

Thunderclap Headache Summary

• Ask about mode of onset of headache, especially for patients presenting with “a headache” or patients in the ED

• Know the differential diagnosis of TCH

• All patients should be aggressively evaluated with CT, CSF, and if negative, MRI/MRA/MRV

Pseudotumor Cerebri Syndrome (Idiopathic Intracranial Hypertension)

A. Papilledema B. Normal neurological examination except cranial nerve

abnormalities C. Normal gad-enhanced brain MRI (female/obese) and MRV

(atypical) [ contrast enhanced CT if contraindication for MRI] D. Normal CSF composition E. Elevated opening CSF pressure (>250 mm CSF adults; >280

mm CSF children; >250 mm CSF children if not sedated or obese)

Freidman DI, et al. Neurology 2013;81:1159-1165 Friedman DI, et al. Neurology 2013;81:1159-1165

PTCS without papilledema (B-E plus VI nerve palsy) PTCS without papilledema or VI nerve palsy (B-E plus 3 of the following)

– Empty sella (65%) – Flattening posterior globe – Distention perioptic subarachnoid space + tortuous optic nerve – Transverse venous sinus stenosis

• PTCS without papilledema is uncommon!

Freidman DI, et al. Neurology 2013;81:1159-1165

Friedman DI, et al. Neurology 2013;81:1159-1165

Flattening posterior globe

Distention perioptic subarachnoid space, tortuous optic nerve

Empty sella Transverse venous sinus stenosis

PCTS: Symptoms

• Headache: 94% – Usually daily, bilateral, retro-ocular, may be most

severe in AM – Often migraine phenotype

• Transient visual obscurations: 75% • Intracranial noises: 60% • Diplopia: 38% • Sustained visual loss: 30%

Wall et al. JAMA Neurol 2014.

PTCS: MRV for All?

• Yes, when possible • Definitely for:

– “Atypical” patients, including non-obese women, men, children

– Patients not responding to treatment should be thoroughly evaluated for a possible underlying cause • Contrast-enhanced MR imaging and MRV • CSF cytology (repeat CSF analysis if needed)

Friedman DI, et al. Neurology 2013;81:1159-1165

Secondary PTCS: Risk Factors • Cerebral venous

abnormalities, CVST • Hypercoaguable states • Anemia • Vitamin A and retinoids

– Hypervitaminosis A, isotretinion, excessive liver ingestion, all trans retinoic acid for polymyelocytic leukemia

• Antibiotics – Tetracycline, minocycline,

doxycycline, sulfa drugs, nalidixic acid

• Withdrawal from chronic corticosteroids

• Hormones – HGH, thyroxine (in children),

anabolic steroids, leuprorelin acetate, levonorgestrel

• Lithium • Chlordecone • Encocrine disorders

– Addison, hyperPTH • Hypercapnea

– OSA, Pickwickian syndrome • Renal failure • Turner Syndrome • Down Syndrome

Friedman DI, et al. Neurology 2013;81:1159-1165

General Principles of Management

• Not all patients need to be treated • Goal of treatment: preserve vision • Decisions dictated by status of vision • Document field & disc appearance • Team approach - neurologist and ophthalmologist

Medical Treatment

• Eliminate contributing/causative factors – Tetracycline, vitamin A

• Low sodium diet – 1,500-2,400mg/day; 1tsp=2,300 mg

• Weight loss > 10% body weight

– Bariatric surgery (morbid obesity)

• ICP management

• Headache management

Headache Management: Similar to Chronic Primary Headache Disorder

Symptomatic • Triptans • DHE-45 • NSAIDs (ie – Indomethacin)

Preventive • Topiramate • ARBs • Protriptyline • SNRI • Indomethacin • OnabotulinumtoxinA

Avoid: Valproate, steroids, and TCAs can cause weight gain; opioids; β and Ca++ CBs may reduce perfusion to optic nerve head

Role of Steroids

• Work initially, but not recommended for chronic treatment – Weight gain, fluid retention – Withdrawal associated with PTCS – Raise intraocular pressure – Serious side effects with long-term use

• One role: to “buy some time” while arranging for surgical procedure, etc.

Diuretics

• Acetazolamide (0.5-2g bid with meals) – CSF flow not affected until 99.5% of CA inhibited (may take

up to 4g); Serum HCO3 measure of compliance – Renal stones ~3% – Aplastic anemia 1/15000 patient treatment years and

almost always within first 6 months of therapy • Furosemide 20mg bid; up to 40mg tid (K+ supplementation

required) • Triamterene • Spironolactone: Aldosterone antagonist • Be careful if combining diuretics!

Surgical Treatment

Indications – Progressive visual loss despite maximally

tolerated medical therapy – Severe visual loss at presentation – Severe visual loss and unreliable follow-up

Procedures: Optic nerve sheath fenestration Lumbo-peritoneal shunt Ventriculo-peritoneal shunt

Intracranial Hypotension

Spontaneous Intracranial Hypotension (SIH): ICHD-3

• 7.2.3 Headache attributed to SIH A. Any headache fulfilling criterion C B. Low CSF pressure (<60 mm CSF) and/or evidence

of CSF leakage on imaging C. Headache has developed in temporal relation to

the low CSF pressure or CSF leakage, or has led to its discovery

D. Not better accounted for by another ICHD-3 diagnosis

Intracranial Hypotension: MRI findings

Intracranial Hypotension: MRI findings

radiopaedia.org Venous distention sign

Intracranial Hypotension: Imaging Findings

• CT head – Subdural collection – Cerebellar tonsillar herniation

into foramen magnum (acquired Chiari I malformation)

– Dural venous sinus distention

• MRI brain with contrast – Venous sinus engorgement – Pachymeningeal

enhancement (infra- and supra tentorial)

– Pituitary gland enlargement

• MRI brain without contrast – Diffuse brain swelling – Sagging brainstem – Subdural effusions – Increased fluid around optic

nerves – Bulbous dilatation of the

sheath behind globes – Rounding of cross section of

venous sinuses

Medication Overuse Headache

8.2 Medication-overuse headache (MOH)

A. Headache occurring on ≥15 d/mo in a patient with a pre-

existing headache disorder B. Regular overuse for >3 mo of one or more drugs that can be

taken for acute and/or symptomatic treatment of headache C. Not better accounted for by another ICHD-3 diagnosis

8.2 Medication-overuse headache (MOH)

8.2.1 Ergotamine-overuse headache (>10 days/month) 8.2.2 Triptan-overuse headache (>10 days/month) 8.2.3 Simple analgesic-overuse headache (>15 days/month) 8.2.4 Opioid-overuse headache (>10 days/month) 8.2.5 Combination -analgesic-overuse headache (>10 days/month)

Note: “Combination-analgesic” is used specifically for formulations combining drugs of two or more classes, each with analgesic effect or acting as adjuvants

8.2.6 MOH attributed to multiple drug classes not individually overused (>10 days/month)

8.2.7 MOH headache attributed to unverified overuse of multiple drug classes (>10 days/month)

8.2.8 MOH attributed to other medication (>10 days/month)

Other Testable Tidbits

8.1.2 Phosphodiesterase (PDE) inhibitor-induced headache

A. Any headache fulfilling criterion C B. A single dose of a phosphodiesterase (PDE) inhibitor has been

taken C. Evidence of causation demonstrated by all of the D. following:

1. Headache has developed within 5 hours of intake of the PDE inhibitor

2. Headache has resolved within 72 hours of onset 3. Headache has at least one of the following four characteristics:

a. Bilateral b. Mild to moderate intensity c. Pulsating quality d. Aggravated by physical activity

E. Not better accounted for by another ICHD-3 diagnosis.

11.3.1 Headache attributed to acute glaucoma

A. Any headache fulfilling criterion C B. Acute narrow-angle glaucoma diagnosed C. Evidence of causation demonstrated by ≥2 of: 1. headache has developed in temporal relation to onset of

glaucoma 2. headache has significantly worsened in parallel with

progression of glaucoma 3. headache has significantly improved or resolved in

parallel with improvement in or resolution of glaucoma 4. pain location includes affected eye D. Not better accounted for by another ICHD-3 diagnosis

Headache due to subacute angle-closure glaucoma

• Intermittent episodes of transient elevations of intraocular pressure

• Headache often the only presenting complaint – Blurred vision, eye pain, redness – 1/3 describe seeing halos

• 2/3rds of patients misdiagnosed with migraine – Later age of onset (per one study, avg age 50 years) – Most attacks last <1 hour

• Diagnosed by gonioscopy (narrow, occludable angles) • Treatment: laser peripheral iridotomy (LPI)

Schindler et al, Neurology 2005; 65(5):757-758.

Secondary Headaches SNOOP4 Red Flags

• Systemic symptoms (fever, weight loss) or Systemic disease (malignancy)

• Neurologic symptoms or signs • Onset sudden (acute or thunderclap

headache) • Onset after age 40 years • Previous headache history (new or different) • Progressive • Precipitation by Valsalva (cough, bend) • Postural • Pregnancy

Dodick DW. Adv. Stud Med 2003;3:550-555

THANK YOU