COMPLEXITIES OF MIGRAINE HEADACHES

Transcription

1

2 COMPLEXITIES OF MIGRAINE HEADACHES Michael A. Rogawski, MD, PhD Professor and Chair Department of Neurology University of California, Davis Sacramento, CA

3 MICHAEL A. ROGAWSKI, MD, PHD Disclosures Research/Grants: Congressionally Directed Medical Research Programs; Eisai Inc.; Epilepsy Research Foundation (Epilepsy Foundation); Forest Research Institute, Inc.; Gilead Sciences, Inc.; National Institute of Neurological Disorders and Stroke (NIH); People Against Childhood Epilepsy, Inc. Speakers Bureau: None Consultant: Eli Lilly and Company; GlaxoSmithKline; Merck & Co., Inc.; Novartis Corporation; Pfizer Inc. Stockholder: Marinus Pharmaceuticals Other Financial Interest: None Advisory Board: None

4 LEARNING OBJECTIVE Describe the various migraine types, and factors related to common triggers, comorbidities, and clinical manifestations.

5 WHAT DO THESE GROUPS OF DISORDERS HAVE IN COMMON? Long QT syndrome Myotonia congenita/ paramyotonia congenita/ potassium-aggravated myotonia Periodic paralysis (hypokalemic/ hyperkalemic) Episodic ataxia/ myokymia Paroxysmal dyskinesias Migraine Epilepsy Bipolar disorder

6 EPISODIC DISORDERS REPRESENT A UNIQUE TYPE OF MEDICAL SYNDROME Dramatic events occur paroxysmally, often in otherwise normal individuals Diverse symptoms: cardiac arrhythmia, myotonia, periodic paralysis, paroxysmal dyskinesia (dystonia, chorea, ballismus), paroxysmal dystonia, seizure, migraine headache Often non-progressive; full recovery between attacks

7 EPISODIC DISORDERS REPRESENT A UNIQUE TYPE OF MEDICAL SYNDROME Often have inciting factor, but may not be obvious: Rest after exercise, fasting, foods that raise or lower serum K+ (periodic paralyses, potassium-aggravated myotonia) Exercise (swimming), emotion (startle) (long QT syndrome) Caffeine, alcohol (migraine, PNKD stress, fatigue) Hormones, pregnancy (migraine, epilepsy, hyperkpp)

8 EPISODIC DISORDERS ARE COMMONLY CHANNELOPATHIES Cardiac muscle: Long QT syndrome (K +, Na +, Ca 2+ ) Skeletal muscle: HyperPP, PC, PAM, myotonia congenita, HypoPP (Na +, Cl, Ca 2+ ) Cerebellum/NMJ: Episodic ataxia and myokymia EA1 (K + ); episodic ataxia EA2/ FHM1/SCA6 (Ca 2+ ) Spinal cord: Hyperekplexia (glycine receptor) Brain: Hemiplegic migraine/ episodic ataxia (Ca 2+, Na +, Na + -K + -ATPase) DRG/spinal cord: Neuropathic pain (acquired Na + /Ca 2+ )? Brain region: Depression, bipolar disorder (? channel)

9 PAROXYSMAL ELECTRICAL DISCHARGES IN CHANNELOPATHIES Torsades de Pointes Long QT Syndrome EKG Myotonia Paramyotonia Congenita Spike and Wave Absence Seizure EEG EMG

10 SEASONAL AND TEMPORAL PATTERN IN EPISODIC CLUSTER HEADACHE Metronomic regularity: attacks strike at a precise time of day each morning or night. 90 min attack late in evening 2 attacks disturbing sleep Courtesy of: American Headache Society.

11 LIFE CHART SHOWING CONTINUOUS CYCLING IN A WOMAN WITH BIPOLAR I DISORDER 4 years 6 years Acknowledgment: Post R, NIMH.

12 FUNCTIONAL AND STRUCTURAL CHANGES IN THE HYPOTHALAMUS IN CLUSTER HEADACHE PET Activation in 9 Cluster Headache Patients with Respect to Headache-free State Voxel-based Morphometry in 25 Cluster Headache Patients Compared with 29 Healthy Volunteers (images mirrored with respect to side of headache) Inferior posterior hypothalamus May A, et al. Nat Med. 1999;5(7):

13 HYPOTHALAMIC ABNORMALITIES IN BIPOLAR DISORDER Depression is often episodic; can be seasonal (biological clock/circadian system plays a role) Abnormal HPA function (blunted DST)

14 COMORBIDITY OF MIGRAINE, EPILEPSY, DEPRESSION Comorbidity = greater-than-coincidental association of two or more conditions in the same person

15 COMORBIDITY OF MIGRAINE AND EPILEPSY 0.5% in general population have epilepsy; 6% of patients with migraine have epilepsy 1 People with epilepsy 2.4 times more likely to have migraine 2 1. Andermann F. Epilepsy Res. 1987;1(4): Lipton RB. Adv Stud Med. 2005;(6E):S649-S657.

16 COMORBIDITY OF MIGRAINE AND DEPRESSION Migraine and Psychopathology: Results of the Zurich Cohort Study of Young Adults One-Year Prevalence (n = 61) (n = 396) p <.05 Rates/100 p <.05 p <.001 p <.05 Bipolar Spectrum Merikangas KR, et al. Arch Gen Psychiatry. 1990;47(9):

17

18 Courtesy of: International Headache Society (IHS). ESTIMATES OF MIGRAINE PREVALENCE USING IHS CRITERIA

19 META-ANALYSIS OF 18 POPULATION-BASED STUDIES Migraine is Prevalent Even at Age 15 Onset After Age 50 Rare

20 IHS DIAGNOSTIC CRITERIA FOR MIGRAINE WITHOUT AURA (MO) At least 5 headache attacks lasting 4-72 hours (untreated or unsuccessfully treated), which have at least 2 of the 4 characteristics: Unilateral location Pulsating quality Moderate or severe intensity Aggravation by or causing avoidance of routine physical activity (e.g., walking or climbing stairs) During headache at least 1 of the 2 following symptoms occur: Nausea and/or vomiting Phonophobia and photophobia Not attributed to another disorder International Headache Society (IHS) Classification ICHD-II.

21 IHS DIAGNOSTIC CRITERIA FOR TENSION-TYPE HEADACHE Headache lasting from 30 minutes to 7 days At least 2 of the following criteria: Pressing/tightening (non-pulsatile) quality Mild or moderate intensity (may inhibit, but does not prohibit activity) Bilateral No aggravation by routine physical activity (walking, stairs or similar) No nausea or vomiting (anorexia may occur) Only one but not both: photophobia and phonophobia (both may be absent) Not attributable to another disorder International Headache Society (IHS) Classification ICHD-II.

22 MIGRAINE CHARACTERISTICS FROM POPULATION STUDIES OF MIGRAINE EPIDEMIOLOGY

23 SOME COMMON MIGRAINE CLINICAL FEATURES Goes to dark room Benefited by sleep Relation to menstruation (2 days before or 3 days after; migraine without aura; more severe, disabling, and refractory to abortive therapy) Positive family history (migraine with aura KCNK18 TRESK 2-pore K + channel) Childhood precursors (motion sickness, episodic vomiting, episodic vertigo)

24 PHASES OF A MIGRAINE ATTACK Headache Moderate to Severe Premonitory/ Prodrome Symptoms : Food cravings Mood changes Yawning Fatigue Aura Focal neurological symptoms preceding headache Symptoms: Flashing lights or wavy lines Numbness Tingling in face Disturbed senses Mild Symptoms: Unilateral throbbing headache Photophobia Phonophobia Nausea/vomiting Symptoms: Same as mild but more intense Postdrome Symptoms: Tiredness Confusion Lowered appetite Scalp tenderness May feel refreshed Hours/days prior to headache <1 hour 4 72 hours Hours/days after headache resolution

25 TRIGGER FACTORS Stress or relief of stress Foods: aged cheese, dairy, red wine, nuts, shellfish Caffeine withdrawal Vasodilators (nitroglycerin) Perfumes, strong odors Light (bright sunlight) Irregular diet Lack of sleep or excessive sleep Weather changes (hot/cold, high humidity, dry air, wind/storm, changes in barometric pressure)

26 AURA Appear over 5 to 20 min and last < 60 min Can be visual (most common), sensory, or motor Visual aura may include both positive and negative features; blurred, shimmering or cloudy vision; tunnel vision Somatosensory aura consists of digitolingual or cheiro-oral paresthesias (hand and arm as well as in the ipsilateral nosemouth area) Paresthesia migrate up the arm and then extend to involve the face, lips, and tongue Other aura symptoms Auditory or olfactory hallucinations Aphasia Vertigo Hypersensitivity to touch

27

28 ARTIST S REPRESENTATION Progressive Central Scotoma with Jagged Edge Scotoma gradually increases to fill most of the central field

29

30

31 PARESTHESIAS SECOND MOST COMMON MIGRAINE AURA

32

33

34 VPM trigeminal ganglion

35

36 BASILAR-TYPE MIGRAINE Little evidence that the basilar artery necessarily involved so no longer called basilar migraine Aura consisting of 2 of the following fully reversible symptoms, but no motor weakness: 1. dysarthria; 2. vertigo; 3. tinnitus; 4. hypacusia; 5. diplopia; 6. visual symptoms simultaneously in both temporal and nasal fields of both eyes; 7. ataxia; 8. decreased level of consciousness; 9. simultaneously bilateral paraesthesias At least one of the following: At least one one aura symptom develops gradually over 5 min and/or different aura symptoms occur in succession over 5 min Each aura symptom lasts 5 and 60 min

37 RETINAL MIGRAINE Ophthalmic Migraine, Ocular Migraine Repeated monocular scotomata or blindness < 1 hr Confirmed by patient s drawing of monocular field defect during attack Associated with or followed by a headache within 60 min (headache may precede visual symptoms) Normal ophthalmological exam outside of attack (diagnosis of exclusion) Normally does not require treatment A. During amaurotic episode. Note dusky appearance of fundus, increased retinal opacity (edema?), and dark, narrowed veins (arrows). Disc is hyperemic. B. Fundus after episode. Note normal caliber of veins (arrows).

38 CERVICOGENIC HEADACHE? Rich overlap between ophthalmic n. V and high cervical dorsal roots (esp. C2) IHS classification does recognize cervicogenic headache requires clear neck pathology Most patients with neck discomfort and headache have migraine (neck stiffness is a premonitory sign that can persist)

39 UNUSUAL HEADACHE SYNDROMES IN CHILDREN Most common headache syndromes in children: migraine, tension-type, chronic daily headache Basilar-type; hemiplegic migraine Periodic syndromes in children that are precursors to migraine Movement disorders (benign paroxysmal torticolis) Cyclical vomiting (5 per hr for at least 1 hr); attacks last 1 5 days Ataxia Benign paroxysmal vertigo of childhood Abdominal migraine

40 IHS DIAGNOSTIC CRITERIA FOR CLUSTER HEADACHE A Trigeminal Autonomic Cephalgia At least 5 attacks of severe unilateral orbital, supraorbital, and/or temporal pain lasting min untreated, with one or more of the following signs occurring on the same side as the pain: Conjunctival injection Lacrimation Nasal congestion Rhinorrhea Forehead and facial sweating Miosis Ptosis Eyelid edema Frequency of attacks from q.o.d. to 8/day

41 CLUSTER PATIENT OF BAYARD T. HORTON Right-Sided Cluster Headache with Autonomic (Parasympathetic) Symptoms Temporal artery bulging and pulsating Severe headache pain behind eye Unilateral ptosis, swelling, and redness of eyelid Miosis, conjunctival injection Tearing Nasal congestion, rhinorrhea Flushing of side of face, sweating Leonine facies (deep nasolabial folds, peau d orange skin, squared jaw)

42 SUNCT Short-Lasting, Unilateral, Neuralgiform Headache with Conjunctival Injection and Tearing (a TAC) Short, sustained, unilateral, sharp, stabbing pain Localized to orbital, periorbital, temporal region Conjunctival injection; tearing (94%) May have rhinorrhea and congestion, eyelid edema, ptosis, miosis, facial sweating, facial flushing 5 sec to 4 min; peak intensity within seconds Can have multiple attacks per day; up to 30 per hour; 200 per day

43 QUESTIONS AND ANSWERS

44