1. Migraine headaches

2. Pathophysiology of pain management in migraine
Cortical spreading depression activates the trigeminal and parasympathetic systems which causes vasodilatation and release of neuropeptides that cause inflammation.
Serotonin 5 HT receptors modulate the release of neurogenic peptides.
The goal of therapy is to prevent the neorogenic inflammation that occurs as a result of neuropeptide release. Triptans are 5 HT receptor agonists and block this release

3. Acute onset headache
Sufficient evidence from retrospective and prospective studies to support the association of an acute sudden onset headache with a vascular event.
Sudden onset headache is a red flag
Critical issues in the evaluation and management of patients presenting to the emergency department with acute headache: Annals of Emerg Med 2002 (1):39.

4. Life Threatening causes of acute headaches.
Intracranial hemorrhage
Subdural hemorrhage
Subarachnoid hemorrhage.
Meningitis
Hypertensive encephalopathy.
Temporal arteritis in patient over 50. Red flag is the first and the worst.

5. Subarachnoid hemorrhage:causes
80% of non traumatic hemorrhages from ruptured saccular aneurysms.
Other causes: AV malformations, neoplasms, blood dyscrasias.
Commonest ages yrs.

6. Subarachnoid hemorrhage:risk factors.
Estimated that 5% of population have a berry aneurysm.
HTN
Smoking and alcohol
Sympathomimetic drugs
Polycystic kidney disease
Coarctation of the aorta
Marfans syndrome

7. Risk factors for SDH
Age, alcohol, anticoagulation or anti-platelet treatment.
May be minimal trauma such as coughing
The signs and symptoms of brain compression may not appear until up to 2 weeks after the trauma..

8. Subdural hemorrhage Dull, mild generalized head pain.
Symptoms of chronic SDH may be subtle.
Up to 50% have altered level of consciousness
Headache is worse at night and same side as hematoma
On exam patient may have unilateral weakness and increased reflexes.

9. Hypertensive Encephalopathy
Associated with high blood pressure, nausea, vomiting and blurred vision
Usually associated with blood pressures of 200/130.
Headache diffuse and worse in the morning and subsides during the day.

10. Meningitis:useful signs and symptoms.
The absence of fever, neck stiffness and altered mental status in a patient with a headache virtually eliminates the diagnosis of meningitis.
In multiple studies the presence of neck stiffness on examination has a pooled sensitivity of 70%.
Does this adult patient have meningitis? Attia et al. JAMA 1999;281(2):
Fever is the most sensitive and then neck stiffness.Sensitivity is the proportino of paeple with the disease who have a positive result.

11. Signs of Meningism.
In a prospective study of young adult patients Kernigs sign had a sensitivity of 9% and a specificity of 100%.
Brudzinskis sign has not been evaluated since the original report .
Uchihara T, Tsukagoshi H. Headache 1991;31:
Specificity is number of people without the disease who have a negative test result.

12. Can response to therapy aid diagnosis?
No meta-analyses or RCTS to support or refute using response to therapy as an indicator of underlying pathology.
Case reports exist of patients whose headaches have significantly improved with analgesia and then subsequently died from an intracranial hemorrhage.
Bottom line: Level C recommendation that response to therapy should not be used as the sole diagnostic indicator of the etiology of the headache.
Case reports of patients presenting with headaches to the ER that have responded wel to ketoralac (toradol) and been discharged and then found dead at home secondary to intra cerebral hemorrhage, SAH,

13. Acute H/A: Factors in history associated with abnormality on neuroimaging.
Headache waking patient up.
Headache worsening with valsalva
Subjective sensory disturbance.
Rapidly increasing headache.
However the absence of these does not rule out positive findings on neuroimaging.
Annals of Emergency Medicine: Vol 39:1:Jan 2002.
Loss of headache free period. Above findings increase the probability of abnormal findings on neuroimaging but have very wide confidence intervals

14. Level B recommendations:
Clinical Policy of the ACEP for management of patients presenting with acute onset headache.
Level B recommendations:
Patients with headache and abnormal neuro exam should undergo an emergent non contrast CT.
Patients presenting with an acute sudden onset headache should be considered for an emergent CT scan.
HIV patients with a new headache should have urgent neuroimaging
Emergent means done at once to exclude life threstening condition. Urgent means arranged prior to disharge. HIV patinets have high incidence of space occupying lesions.

15. Clinical Policy of ACEP cont.
Level C recommendation:
Patients over 50 with a new headache should be considered for urgent neuroimaging.
Emergent means done immediately
Urgent means scan appointment is arranged prior to discharge and included in disposition.
Annals of Emergency Medicine: Vol 39:1:Jan 2002.

16. Overview Migraine and Statistics History Classification and symptoms
Etiology and Pathophysiology
Treatment

17. Migraine and statistics
Migraine is a neurovascular disease caused by neurogenic inflammation and characterized by severe, recurring headaches
It usually characterized by the severe pain on one side of the head as compare to the pain in rest of the head.
It occurs more often in Women than in men.

18. Sinus H/A vs. Migraine Summit study.
Prospective multi center observational study of 2,991 patient with self diagnosed or physician diagnosed sinus headache. Using the IHS migraine criteria 80% of them had migraine.
Schreiber CP, et al. Archives of Internal Medicine. In publication
To diagnose sinus headache must have purulent discharge on suction or spontaneous and simultaneous onset of headache and sinusitis and abnormal xray, CT or transillumination.

19. Phases of migraine
Premonition: eg hunger, energy surges, irritability.
Prodrome: aura.
Headache phase
Postdrome.

20. History History goes back to 9000 years.
First mode of treatment: trepanation
Medical intervention in which a hole is drilled or scraped into the human skull, exposing the dura mater in order to treat health problems related to intracranial diseases.

21. History cont.
In 2nd century AD, Pergamum a Greek physician used a term hemicrania.
The brain and stomach were connected
“Migraine” evolved from this term
However, this idea was replaced by blood flow in 17th century
In 80s, Dr. Harold G. Wolff said that dilation of blood vessels is the main cause of migraine.

22. Classification of Migraine headache.
1) Migraine without Aura or common migraine Does not give any warning signs before the onset of headache. It occurs in about 70 to 80% of migraine patients 2) Migraine with Aura Give some warning signs “ called aura” before the actual headache begins. Approximate, 20 to 30% migraine sufferers experience aura. The most common aura is visual and may include both positive and negative (visual field defects) features.

23. Negative scotoma. Loss of local awareness of local structure
Zigzag structure
Positive Scotoma. Additional structures One side loss of perception.

24. Classification of Migraine headache cont.
3) Retinal migraine It involves attacks of monocular scotoma or even blindness of one eye for less than an hour and associated with headache. 4) Childhood periodic syndromes that involve cyclical vomiting (occasional intense periods of vomiting), abdominal migraine (abdominal pain, usually accompanied by nausea), and benign paroxysmal vertigo of childhood (occasional attacks of vertigo). They may be precursors or associated with migraine.

25. Classification of Migraine headache cont.
5) Complications of migraine describe migraine headaches and/or auras that are unusually long or unusually frequent, or associated with a seizure or brain lesion.

26. Chronic Tension Type Headache.
Develops from episodic tension type headaches
The most common form of CDH.
Familial tendency.
Medication rebound headache may be a factor in the transformation of episodic headache to CDH.

27. Chronic Tension Type Headache
Affect women more than men
Most common in middle age
Stress is often a trigger
Average duration is 4-13 hours.
When see a patinet with CDH ask what their has were like before they became constant ie did they have episodic has before.ask about analgesic use.

28. Treatment of CTTH.
Treating each headache increases the frequency and severity of the headaches.
Reserve medications for worse than usual headache.
Expert opinion: treat 2 headaches a week.
Frequent headache sufferers are at risk of developing analgesic overuse or drug rebound headaches. Expert opinion: limit headache medication to 2 days per week.

29. Prevention of CTTH Tricyclic antidepressants. Stress management
Tizanidine
SSRIs:prozac
Anticonvulsants:gabapentin and topiramate.
Acupuncture

30. Rebound Headaches. IHS criteria.
Headache for 15 days/month with at least one of the following characteristics and 2,3 and 4.
Bilateral
Pressing/tight non pulsating quality
Mild/moderate intensity
Simple analgesic use >15 days a month for 3 months
Headache has increased during analgesic use
Headache resolves or reverts to previous pattern within 2 months after discontinuation of analgesia.

31. Rebound headaches
Most significant factor in their development is the lack of awareness by physicians and patients. “Prevention better than cure”
Triptans, all analgesics and ergotamines have been associated with medication rebound headaches.
Most significant factor in their development is the lack of awareness by physicians and patients.

32. Rebound headaches
If patient is unable to tolerate abrupt cessation of medication may need to titrate down over 2 weeks.
May need inpatient treatment to successfully withdraw
Various regimes including tizanidine, daily triptans, steroids and parenteral DHE have been used.
Most significant factor in their development is the lack of awareness by physicians and patients.

33. Etiology and Pathophysiology
The precise etiology and pathophysiology of migraine is unknown.
However, neuronal dysfunction theory is most acknowledged theory.
Activity in trigeminovascular system.

35. ‡ Abnormal Neuronal activity
Cerebral cortex, thalamus or hypothalamus in response to stress, emotion. ‡
Instability in release of neuropeptides e.g., Substance P, neurokinin A, calcitonin gene-related polypeptide, serotonin
Activates nociceptive trigeminovascular system and causes prolong pain
Activates trigeminovascular system, which in turn, stimulate pain stimulating neurons in brain stem and upper spinal cord
Initiate inflammatory response, sensitizes surrounding tissues and produce headache
Promote vasodilation and plasma protein extravasations.

36. Boss ‡ Abnormal Neuronal activity
Cerebral cortex, thalamus or hypothalamus in response to stress, emotion. ‡
Releases vasoactive neuropeptides e.g., Substance P, neurokinin A, calcitonin gene-related polypeptide, serotonin
Activates nociceptive trigeminovascular system and causes prolong pain
Boss
Activates trigeminovascular system, which in turn, stimulate pain stimulating neurons in brain stem and upper spinal cord
Initiate inflammatory response, sensitizes surrounding tissues and produce prolong headache
Promote vasodilation and plasma protein extravasations.

37. Serotonin Neurotransmittor
Serotonin ( 5- hydroxytryptamine) is thought to be an important mediator of migraine.
Unstable serotonergic neurotransmission , so has lower threshold for migraine.
There are 7 classes of 5-HT receptors
Out of 7, 2 involve in migraine pain.

38. Serotonin cont. It is basic as amines and Ammonia Changes Ph of blood
Serotonin causes
Vasodilation
Vasoconstriction
During migraine the level of serotonin is low in blood. (Low Ph)
Drug target

39. Serotonin binds to 5-HT1 and 5-HT2
5- HT1 Presynaptic receptor
Serotonin binds to 5-HT1 and 5-HT2
5- HT2 Postsynaptic receptor

40. How bad could migraine be…
It could distrub the normal life activities.
Could lead to brain damage
Recently, a woman in London had a migraine
Lost her accent

41. Treatment Identification and elimination of factors.
For example, Tobacco smoke, loud noise, stress, caffeine, emotions, contrasty light etc.
If they don’t work then move on to medicines
Prophylactic therapy
Abortive therapy

42. Prophylactic therapy Used in case of frequent migraines
Used when abortive therapy has failed
Medicines have to taken everyday to be effective
On the other hand, abortive medicine are taken during actual migraine pain.

43. Medicines used in this therapy
1) Medicines that block beta-adrenergic.
For example, Propranolol, nadodol, timolol, atenolol, and metoprolol.
Reduce the frequency of attacks by 50% in 60 to 80% patients.
Side effects- fatugue, sleep disturbance, depression, hypotension etc

44. Cont. 2) Tricyclic antidepressants
For example, amitryptiline, nortryptiline, doxepin, imipramine etc
Independent of antidepressant activity.
Antagonist of 5-HT2, thus stabelize serotonin neurotransmission
3) Methysergide:-
Semisynthetic ergot alkaloid and is 5-HT2 antagonist.
Gives best result when taken with meals
Side effects- gastrointestinal intolerence, insomnia, and muscle cramps.

45. Prophylactic therapy cont.
Calcium channel Blockers-
Verapmil
Takes up to 8 weeks to show any good effect
Side effects- Hypotension, constipation etc

46. Abortive therapy 1) simple analgesics:-
For mild and infrequent migraine- Aspirin and acetaminophen
Aspirin+acetaminophen+barbiturate butabital = To induce sleep
aspirin+acetaminophen+narcotics = Fiorinal
Aspirin+ acetaminophen+caffiene = Esgic
Drawback- Continuous use fails to provide pain relief.

47. Abortive Therapy cont. 2) NSAIDs:- Inhibit prostaglandin synthesis.
So may prevent inflammation in trigeminovascular system and alleviate migraine pain
They are effective for reducing the frequency, severity, and duration of migraine attacks. e,g. Aspirin, Ibuprofen, Naproxen etc.

48. Abortive therapy cont. 3) Ergot family Ergotamine-
It is secondary metabolite obtained from ergot fungus
Dihydroergotamine- available in inject able form.
The structure shares some similarit with neurotransmittor serotonin.
Acts as agonist, bind to 5-HT1,
More effective when given during early migraine attacks

49. Abortive therapy 5) Triptan Family 5-HT1 receptor agonists Examples-
Sumatriptan – Imitrex
Zolmitriptan – Zomig
Rizatriptan – Maxalt
Eletriptan – Relpax
Naratriptan - Amerge

50. Side Effects nausea, vomiting, dizziness, fatigue, and vertigo.
Not good for hypertensive patients at all.

51. Ergot and Triptan comparison
The rates of ergotamine and sumatriptan overuse were 14.2% and 3.5%, respectively
Drug-induced headache could be found more frequently in cases of ergotamine overuse then drugs of triptan family.

52. Miscellaneous agent
Midrin = Isometheptane+ dichlorophenazene+ acetaminophen
Used in patients who do not respond to ergot and triptan
Less effective then ergot and triptan family’s drugs
Most frequent side effects are nausea, dizziness, insomnia, and vomiting.

53. /sex-may-be-a-natural-way-to- treat-migraines-cluster-headaches/

54. Questions