Headache. Jeffrey L. Bennett, M.D., Ph.D. Professor of Neurology and Ophthalmology

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Headache Jeffrey L. Bennett, M.D., Ph.D. Professor of Neurology and Ophthalmology year-old obese woman Daily, throbbing HA x 4 mo MRI of brain - normal Visual
Headache Jeffrey L. Bennett, M.D., Ph.D. Professor of Neurology and Ophthalmology 29-year-old obese woman Daily, throbbing HA x 4 mo MRI of brain - normal Visual changes: sparkling lights on and off transient visual obscurations (blur out of vision on and off x seconds) Swollen optic nerve Normal optic nerve HA: Epidemiology and Cost $50 Billion/year missed work + medical benefits - US 15% of US pop seek consultation Lifetime prevalence Any HA Child - 72% Adult - 64% Elderly - 42% Migraine Child - 7% Adult - 11% Elderly - 6% Tension Child - 31% Adult - 46% Stovner et al., Cephalalgia, 2007; 27: Anatomy What Hurts? Trigeminal System and Cervical roots 2-4 Meninges Blood vessels Meningeal vessels Extracranial arteries & veins Dural Veins (aka dural sinuses) Proximal intracranial cerebral arteries Dermis V1 C2 V2 V3 C2/3/4 C3 HA: Classification 1. Primary recurrent no underlying pathology 2. Secondary underlying pathology HA: Classification Primary 1. Tension headache - 70% 2. Migraine - 16% 3. Trigeminal autonomic cephalalgia - 0.1% 4. Chronic Daily Headache Secondary 1. Head injury 2. Infection 3. Tumor 4. Vascular disorders (e.g. SAH, GCA) 5. Altered intracranial pressure 6. Trigeminal Neuralgia 7. Cervicogenic Headache Worrisome HA Red Flags SNOOP Systemic symptoms (fever, weight loss) or secondary risk factors (HIV, cancer) Neurologic symptoms or abnormal signs (confusion, impaired alertness or consciousness) Onset: sudden, abrupt, or split-second Older: new-onset and progressive, especially in middle age ( 50 yr old giant cell arteritis) Previous headache history: first headache or different (change in frequency, severity, or clinical symptoms) Danger Signs WHOL (worse headache of life) 2. Exertional 3. Neurologic symptom 4. Progressive 5. Changing 6. Infection (HIV, valve infection) 7. Metastases (person with cancer) 8. Acute - sudden or new onset 9. Greater than 50 y.o. 10. Exam abnormality HA: Diagnosis & Testing No Unusual Features Yes Causes of HA missed on routine CT Vascular Disease Aneurysm, Arteriorvenous malformation, Venous sinus thrombosis Carotid or vertebral artery dissection Infarct Vasculitis and White matter disease Subdural & epidural hematoma Neoplastic Disease Neoplasm Meningeal carcinomatosis Pituitary Tumor Infections Meningoencephalitis, abscess, cerebritis Others Intracranial hypotension, idiopathic hypertrophic pachymeningitis Adapted from RW Evans et al., Wolff s Headache, 2008 White matter lesions MRI in Migraine UBOs - Unidentified bright objects No difference in distribution & grade of lesions between migraineurs and controls Number of cerebellar & brainstem lesions may be higher Kruit et al, JAMA 2004; 921: Kruit et al, Stroke 2006; 37: UBOs in Migraine Cerebellar Lesion in Migraine Pontine Lesion in Migraine Lumbar Puncture MRI or CT before lumbar puncture Exception: High suspicion for meningitis Indication First or worst headache of life Fever or symptoms of infection Atypical, chronic, subacute or progressive headache Headache unresponsive to medications Medications & Headache Primary HA: Criteria International Headache Society -Criteria based on expert opinion Treatment Research Red flags Tension HA: Criteria A. 10 episodes B. 30 min 7 days C. 2 of following Pressing or tightening Mild Moderate Bilateral Not aggravated by PA D. Both: No nausea or vomiting Only one or none: photophobia or phonophobia Tension HA: Treatment Abortive Aspirin, acetaminophen, nonsteroidal antiinflammatory drug (NSAID) (e.g. ibuprofen) Combination agents Prophylactic Tricyclic antidepressants Selective serotonin reuptake inhibitors (e.g. Prozac) Biofeedback, acupuncture Migraine Without Aura At least 5 headache attacks lasting 4 to 72 hours No organic disease At least 2 of the following characteristics: Unilateral location Pulsating quality Moderate/severe intensity Aggravated by routine physical activity (eg, walking stairs) At least 1 of the following signs: Nausea/vomiting Photophobia/phonophobia Headache Classification Committee of the International Headache Society. Cephalalgia. 1988;8(Suppl 7):1-96. Migraine Aura: Criteria 15% of patients with Migraine 99% of aura is visual A. 2 episodes B. Reversible symptom of 1 of following: visual sensory language C. And 2 of the following: homonymous visual field or unilateral sensory change gradual development 5 min symptom lasts 5-60 min Inflammation of Meningeal Blood Vessels CGRP: calcitonin gene-related peptide Brainstem Activation Sensitization Peripheral Sensitization Central Sensitization Pain Meninges Continuous stimulation Innocuous stimuli (eg, light touching, touching scalp) Trigeminal nucleus caudalis Sensitized Bendtsen L. Curr Opin Investig Drugs. 2002;3: de Tommaso M, et al. Neurosci Lett. 2002;333: Skin, scalp, etc. Pain Migraine Triggers Migraine Triggers Migraine Triggers Migraine: Abortive Treatment 1. Aspirin / acetaminophen (650 mg / 1000 mg) Mild non-disabling HA (avoid ASA in children) 2. NSAID Ibuprofen, naproxin (Class I) Diclofenac, flurbuprofen (mild statistical benefit) Intramuscular ketorolac (severe HA) 3. Combination: Ibuprofen or acetaminophen/caffeine/butalbital/isometheptane Significant risk of medication overuse headache 4. *Triptans (selective 5HT-1B/1D agonists) Oral, SC, intranasal Initiate with maximum strength 40% of attacks and 25% of migraineurs do not respond 5. Ergotamine derivatives Ergotamine tartrate (1-2 mg; poorly absorbed; 2 days/week) Dihydroergotamine (0.5-1 mg; IV, IM, SC, intranasal) Good for refractory migraine, status migrainosus, NSAID/triptan refractory Triptan Agents 7 Triptans: Sumatriptan (Imitrex), zolmitriptan (Zomig), naratriptan (Amerge), rizatriptan (Maxalt), almotriptan (Axert), frovatriptan (Frova), eletriptan (Relpax) Differ pharmacologically by ½-life and onset of action Rapid onset; sumatriptan, zolmitriptan, rizatriptan, almotriptan, eletriptan Long ½-life: naratriptan, frovatriptan (menstrual migraine) Contraindications Heart disease, uncontrolled hypertension, Reynauds, basilar migraine, hemiplegic migraine Pregnancy: Category C MAO contraindication: sumatriptan, rizatriptan, zolmitriptan Rizatriptan reduce to 5 mg with propranolol Eletriptan Avoid within 72 hr of CYYP3A4 inhibitors Do not use within 48 hours of ergot SSRI: watch for serotonin syndrome Future Abortive Therapeutics Calcitonin gene-related peptide (CGRP) antagonists CGRP found in all regions related to migraine pathophysiology Released following stimulation in animal models & release inhibited by triptan agents Phase I & II Trials of IV (olcegepant) and oral (telcagepant): positive No vasoconstrictive or vascular side effects Vanilloid receptor (TRPV1) antagonists Receptor on small and medium trigeminal and DRG neurons Some colocalization with CGRP receptors in CNS Antagonists block capsacin-induced dural inflammation No results yet from clinical trials Serotonin 1F receptor agonists Located on trigeminal neurons in CNS; no cardiovascular effects Initial compounds with CN side effects Second generation in Phase II trials Nitric oxide (NO) blockers NO may be involved in migraine: vascular and nonvascular mechanisms GW274150: potent NO synthase inhibitor currently in early phase trials Migraine: Prophylactic Treatment 1. Beta Blockers Propranolol & timolol: Grade A & FDA approved Beta blocker related contraindications May result in exercise intolerance & erectile dysfunction 2. Calcium channel blockers Verapamil ( mg/day): Group B evidence Good for migraine with aura or migraine accompaniment Side effects: constipation, orthostasis, pedal edema, 1 o block 3. Tricyclic Antidepressants Amitriptylene, nortriptylene, doxepin, protriptylene Side effects: sedation, weight gain constipation, dry mouth & eyes, cardiac arrythmias, orthostatic hypotension, confusion & urinary retention in elderly Best evidence for amitriptylene: Group A Good for comorbid anxiety, depression, sleep disturbance Migraine: Prophylactic Treatment 1. Anti-epileptics Valproate ( mg/day): Grade A, FDA approved Side effects: nausea, alopecia, LFT changes, weight gain, pancreatitis, thrombocytopenia Topiramate (100 mg/day): Grade A, FDA approved Start low mg per day; increase by less than 25 mg/week Side effects: fatigue, weight loss, anorexia, cognitive slowing, paresthesias, renal stones, acute angle closure, oligohydrosis 2. Serotonin reuptake inhibitors Efficacy not proven in large scale trials Grade B Venlaxafine (serotonin norepinephrine reuptake inhibitor) Positive in 2 randomized trials (150 mg/day): Grade B Migraine: Evidence Based Alternative Treatment 1. Sleep! 2. Acupuncture 3. Biofeedback 4. OTC* Butterburr (150 mg/day) Riboflavin ( mg/day) Magnesium ( mg /day) Coenzyme Q (300 mg/day) * Grade B evidence Future Preventative Therapeutics Gap junction blockers Block cortical spreading depression Tonabersat: novel anticonvulsant in Phase IIb trials Neurostimulators Occipital neurostimulators in trials: ONSTIM & PRISM Botulinum Toxin Negative studies in episodic migraine and chronic tension-type headache 2 large studies negative in chronic daily headache Press releases tout positive results in chronic migraine! Trigeminal Autonomic Cephalgias Clinical symptoms Short, excruciating unilateral, paroxysmal head pain Trigeminal localization but may involve occiput or cervical region May alternate sides Cranial autonomic features: Lacrimation, conjucntival injection, nasal symptoms Classification Cluster headache Paroxysmal hemicrania Short-lasting unilateral neuralgiform headache attacks with conjunctival injection and tearing/cranial autonomic features (SUNCT/SUNA) Cluster HA: Criteria A. 5 episodes B. Severe, unilateral, periorbital and/or temporal, min C. 1 every other day up to 8/day *Autonomic Nervous System D. 1 of the following:* conjunctival injection lacrimation nasal congestion rhinorrhea eyelid edema ptosis miosis facial swelling restless/agitation Cluster HA: Other Men:Women - 3:1 Associated with OSA Triggers Alcohol Vasodilators Cluster HA: Treatment Abortive Therapy Oxygen (10 min by high flow mask) Triptans Ergots Lidocaine Transitional Therapy Corticosteroids Prednisone 60 mg/day for 1 week Cluster HA: Prophylactic Treatment 1. Calcium Channel blocker Verapamil 2. Lithium 3. Anti-epileptics Topiramate 4. Occipital nerve stimulation 50% efficacy in recalcitrant patients CPH and SUNCT/SUNA 1. CPH Female:male 2:1 Attack duration: ~15 min Frequency: per day Rx: Indomethacin ( mg/day) 2. SUNCT/SUNA Female:male 1:2 Attack duration: ~1 min Frequency: per day Rx: Lamotrigine, indomethacin Cluster HA: Differential Diagnosis Primary HA syndromes Paroxysmal hemicrania, SUNCT, hemicrania continua, migraine, hypnic headache Secondary Causes Dissection, AVM, infarction, hematoma Pituitary tumor, meningioma, nasopharyngeal carcinoma Sinusitis, zoster, orbital aspergillosis Facial trauma, enucleation Dental work: extraction, impaction Syringomyelia, Chiari I malformation Seondary HA syndromes Tolosa-Hunt Syndrome, giant cell arteritis Adapted from Matharu & Goadsby, Wolff s Headache, 2008 Chronic Daily Headache HA more than 15 days per month Primary HA syndromes (Divide by duration) 4 hours Cluster HA, CPH, SUNCT, idiopathic stabbing HA, hypnic HA 4 hours Chronic migraine (CM), hemicrania continua (HC), chronic tensiontype HA (CTTH), new daily persistent HA (NDPH) Secondary Issues to Consider Medication overuse Anxiety Depression Psychiatric disturbances Headache: Secondary Disorders ACRONYMS SNOOP WHENPCIMAGE New Daily Persistent Headache May be primary or secondary condition Triggering event Virus (EBV), trauma Differential Venous sinus thrombosis Meningitis (Lyme, fungal, TB, HIV) Pseudotumor cerebri Arterial dissection Sphenoid sinusitis Cervical facet syndrome Progressively Worsening Headache These generally do not present with rapid onset Differential Mass Lesion Intraaxial Extraaxial (epidural, subdural, abscess, empyema) Sphenoid sinusitis Giant cell arteritis Venous sinus thrombosis Meningitis Encephalitis Meningitis Infection of meninges Bacterial, fungal, viral Signs/Symptoms Headache Fever Stiff Neck Nausea/Vomiting Altered consciousness Kernig/Brudzinski signs Meningitis Diagnosis: Lumbar puncture Elevated WBC count ( 5 x 10 6 /L) Glucose (normal or low in bacterial meningitis) Protein (normal or high) Culture and gram stain (see an organism) Treatment Steroid (pneumococcal) Antibiotics Supportive care Thunderclap Headache HA that reaches max intensity in 1 min Think SAH! Differential Venous sinus thrombosis Arterial dissection Spontaneous Intracranial hypotension Pituitary apoplexy Stroke or intracranial hemorrhage Acute hypertensive crisis PRES Colloid cyst of IIIrd ventricle Intracranial infection Primary thunderclap HA Primary cough, sexual, exertional HA Subarachnoid Hemorrhage Most common cause of sudden, intense, incapacitating (WHOL worse headache of life) Mechanism Trauma Ruptured aneurysm (80% - if exclude trauma) Arteriorvenous malformation Up to 50% mortality rate Associated symptoms Stiff neck Photophobia Nausea/vomiting Neurologic findings/obtundation Diagnostic Sensitivity of CT and Lumbar Puncture for SAH Probability of Positive CT for SAH Day 0 95% Day 3 74% 1 week 50% 2 weeks 30% 3 weeks ~0% Probability of Xanthochromia 12 hours 100% 1 week 100% 2 weeks 100% 3 weeks 70% 4 weeks 40% Giant Cell Arteritis Inflammation of elastic lamina Risk Factor: Age 60 years (70-80 yrs) Associated Symptoms Jaw claudication Temporal artery tenderness Vision loss Constitutional symptoms (fever, malaise, wt loss) Giant Cell Arteritis: Diagnosis Laboratory findings - inflammatory Erythrocyte sedimentation rate C-reactive protein Diagnostic Studies Fluorescein angiogram Multifocal electroretinogram MRI: T1-weighted spin echo sequences Temporal artery biopsy MRI Imaging in GCA No Enhancement Slight Enhancement Normal GCA Prominent Enhancement Strong Enhancement Bley et al. 184 (1): 283. (2005) Giant Cell Arteritis: Treatment Glucocorticoids High dose (60-80 mg Prednisone) Treat for 1 year when vision loss if present Follow ESR or CRP if elevated If normal, do not taper faster than 10 mg every 2 weeks Late Life Headaches Secondary HA disorders Mass lesions Giant cell arteritis Medication-related headache Trigeminal neuralgia Systemic disease Disease of the head, neck, eyes, ears & nose Cerebrovascular disease Parkinson s Disease Primary HA disorders Migraine Tension-type headache Cluster headache Hypnic headache Adapted from RW Evans et al., Wolff s Headache, 2008 Elevated Intracranial Pressure: Symptoms Exertional headache Retrobulbar Pain Nausea/Vomiting Pulsatile Intracranial Noises Transient Visual Obscurations Photopsia Diplopia Vision Loss Elevated Intracranial Pressure: Signs Sixth Nerve Palsies (not common) Papilledema optic disc edema Vision Loss Differential Diagnosis of Elevated Intracranial Pressure Tumor Arteriovascular malformation Infection SAH Intracerebral hemorrhage Dural vein thrombosis Endocrine disorders Dural Fistula Trauma Pseudotumor Cerebri Elevated ICP Normal spinal fluid constituents Normal Neurologic exam except Papilledema Sixth nerve palsies Normal neuroimaging No other etiology Obese woman Low CSF Pressure Headache Etiology Spontaneous (spinal leak, rhinogenic) Iatrogenic (surgical, lumbar puncture) CSF Opening pressure 60 mm H 2 O May have pleocytosis May have elevated protein MRI Dural enhancement in intracerebral hypotension C.M. Lay, Curr Treatment Options Neurol, Before Rx After Rx Trigeminal Neuralgia Criteria: A. 1s 2 min, trigeminal nerve distribution B. Pain, 1 of following: intense, sharp, superficial, stabbing C. Precipitated by trigger area or factor D. Stereotyped Cause: Idiopathic (primary) Vascular compression (secondary) Demyelination multiple sclerosis (secondary) Treatment: Anti-epileptics Surgery HA: Concussion Very common ( 90%) Develop by 7d and resolve by 3mo Associated: Dizziness Poor concentration/cognition Irritability Insomnia Decreased likelihood for HA: Younger age Men Cervicogenic Headache Cervical spine may produce or worsen HA Usually unilateral without shifting Aggravated by neck movements or posture Exam is generally not localizing Shoulder & arm pain occasionally present Differential Lateral atlanto-axial joint pain Discogenic pain C2/3 Zygoapophyseal (facet) pain (C2/3)Myofascial pain syndrome Treatment: Local blocks Primary Causes of HA with Eye Pain Cluster headache Hemicrania continua Paroxysmal hemicrania Short-lasting unilateral neuralgiform headache attacks with conjunctival injection & tearing (SUNCT) Short-lasting unilateral neuralgiform headache attacks (SUNA) Trigeminal neuralgia (V I ) Idiopathic stabbing headache Secondary Causes of HA with Eye Pain Angle closure glaucoma Pain related to elevated intraocular pressure Dilated or irregular pupil Migrainous features: nausea & vomiting Trochleitis Inflammation of trochlea, tenderness on exam Painful elevation of eye (Brown s syndrome) Idiopathic, RA, SLE, psoriasis, enteric arthropathy Rx: NSAIDs, Steroids Primary trochlear headache Pain in trochlear area, other areas in 60% Imaging normal Local steroids helpful Relapses in 45%, average 8 months 68 year old woman Acute onset of headache, nausea, vomiting, and depressed mental status She is afebrile, but there is moderate nuchal rigidity. Neurologic exam reveals lethargy and complete ophthalmoplegia CT scan: normal LP: 180 WBC (97%), protein 59, glucose 50 Improves on broad spectrum antibodies What should you carefully examine now? Fields: Dense Bitemporal Hemianopsia, What is your next move? Pituitary Apoplexy Potentially life threatening 10-30% of episodes are asymptomatic Differential of acute neurologic deterioration (Arch Neurol 42;712, 1985) PITUITARY APOPLEXY (N=37) Headache 95% Ocular motor palsies 78% Visual field abnormality 64% Visual acuity loss 52% (Neurosurgery 33;602, 1993) COMPUTED TOMOGRAPHY IN APOPLEXY Pituitary tumor 94% Pituitary hemorrhage 46% Normal Sella Contents 6% (Neurosurgery 33:602, 1993) NEUROSURGICAL INTERVENTION Loss of vision Hypothalamic dysfunction Progression of signs Normal CT Scan of Brain 1. Subarachnoid Hemorrhage 2. Dural Vein Thrombosis 3. Temporal Arteritis 4. Meningitis 5. Pituitary Apoplexy Undiagnosed Secondary Headache 29-year-old obese woman Daily, throbbing HA x 4 months, nl MRI Sparkling lights on and off TVO (blur out of vision on and off x seconds) Other questions? What tests? What Diagnosis?
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