1. Headache 5

2. Definition
Headache is a symptom that can be caused by many disorders for example, traction and inflammation of pain-sensitive structures within the head, or it can be due to disorders of extracranial structures such as the eyes, ears, or sinuses.

3. Classification of headache
Headache can be categorized on the basis of the underlying etiology into one of two major types (primary and secondary).
Primary headache disorders are characterized by the lack of an identifiable and treatable underlying cause. Migraine, tension-type, and cluster headaches are examples of primary headache disorders.
Secondary headache disorders are those associated with a variety of organic causes such as trauma, cerebrovascular malformations, and brain tumors.

4. Classification of primary Headache
Migraine 
Migraine without aura 
Migraine with aura 
Tension-Type Headache
Episodic tension-type headache 
Chronic tension-type headache 
Cluster Headache and other trigeminal autonomic cephalalgias
Episodic cluster headache 
Chronic cluster headache 

5. Classification of secondary Headache
1- Headache Associated with Head or neck Trauma 
2- Headache Associated with cranial or cervical Vascular Disorders
Acute ischemic cerebrovascular disease ( stroke)
Intracranial hematoma
Subarachnoid hemorrhage

6. 3- Headache Associated with Metabolic Disorder
(e.g., hypoxia, hypercapnia, hypoglycemia)
4- Headache associated with nonvascular intracranial disorder
Benign intracranial HTN
Intracranial infection
Low CSF pressure (e.g., headache subsequent to LP)

7. 8- Headache attributed to psychiatric disorders
5- Headache associated with substance use or withdrawal.
6- Headache associated with non-cephalic infection (viral infection, bacterial infection).
7- Headache or facial pain associated with disorder of cranium, neck, eyes, ears, nose, sinuses, teeth or mouth.
8- Headache attributed to psychiatric disorders

8. Pathophysiology
Intracranially, only a limited number of structures are sensitive to pain.
Headache may result from dilation, distention, or traction of the large intracranial vessels.
The brain itself is insensitive to pain. Whereas scalp arteries and muscles are capable of registering pain and have been implicated in the pathophysiology of migraine and tension-type headache.
Extracranially, most of the structures outside the skull (e.g., eye, ear, teeth, skin, deeper tissues) have pain afferents.

9. Historically, the primary headache disorders have been thought to be related either to vascular disturbances (migraine and cluster headache) or muscular tension (tension-type headache).
However, a neurovascular hypothesis proposed that headache is triggered by disturbances in central pain processing pathways leading to the release of serotonin, a vasoactive neurotransmitter which plays a role in migraine pathogenesis.
That is why, drugs that alter serotonergic function are highly effective for the symptomatic treatment of migraine and cluster headache. 

10. Primary Headache Migraine Headaches
Migraine is a common, recurrent, sever headache that interferes with normal functioning.
Symptoms of migraine
It is characterized by recurring episodes of throbbing head pain, frequently unilateral.
Migraine headaches can be severe and associated with nausea, vomiting, and sensitivity to light, sound, &/or movement.
The migraine headache may occur at any time of day or night but usually occurs in the early morning hours on awakening.

11. Pain is usually gradual in onset, peaking in intensity over minutes to hours, and lasting between 4 and 72 hours that when untreated.
Pain may occur anywhere in the face or head but most often involves the frontotemporal region.
The headache is typically unilateral and throbbing or pulsating in nature; however, pain may be bilateral at onset or become generalized during the course of an attack.

12. Neurologic symptoms: ( phonophobia , photophobia, hyperosmia, difficulty concentrating) .
Psychological symptoms:( anxiety, depression, euphoria, irritability & drowsiness, hyperactivity & restlessness) .
Autonomic symptoms: ( polyuria, diarrhea & constipation).
Constitutional symptoms( stiff neck, thirst, food cravings, anorexia).

13. 1- A migraine with aura
is experienced by approximately 31% of migraineurs patient. The aura typically evolves over 5 to 20 minutes and lasts less than 60 minutes.
Headache usually occurs within 60 minutes of the end of the aura. Visual auras can include both: positive features (e.g., scintillations, photopsia, fortification spectrum) and negative features (e.g., scotoma, hemianopsia). 
Sensory and motor symptoms such as paresthesias or numbness involving the arms & face, dysphasia or aphasia & weakness, may also occur.

14. Many patients seek a dark, quiet place for rest and relief.
Once the headache pain wanes, patients may experience a resolution phase characterized by feeling tired, exhausted and irritability .
Aura may signal the migraine headache but is not required for diagnosis.

15. 2- Migraine without aura
Headache attacks lasting 4-72 hours ( untreated or unsuccessfully treated )
Headache has at least 2 of the following characteristics :
Unilateral location
Pulsating quality
Moderate or severe pain intensity
Aggravation by or causing avoidance of routine physical activity ( eg, walking or climbing stairs ).

16. During headache at least 1 of the following :
Nausea and / or vomiting
Photophobia and phono phobia.

17. Diagnostic tests Check for abnormalities:
Vital signs (fever, hypertension),
Funduscopy (papilledema, hemorrhage),
Palpation and auscultation of the head and neck( sinus tenderness, hardened or tender temporal arteries …)
neurologic examination (identify abnormalities or deficits in mental status, cranial nerves…)
Neuroimaging (computed tomography or magnetic resonance imaging) should be considered in patients with unexplained findings on the neurologic exam & those with additional risk factors.

18. Commonly Reported Triggers of Migraine
Food triggers
Alcohol
Caffeine/caffeine withdrawal
Chocolate
Fermented and pickled foods
Nitrate-containing foods (e.g., processed meats)
Tyramine-containing foods

19. Strong smells and fumes Tobacco smoke Weather changes
Environmental triggers
Glare lights
High altitude
Loud noises
Strong smells and fumes
Tobacco smoke
Weather changes
Behavioral–physiologic triggers
Excess or insufficient sleep
Fatigue
Menstruation, menopause

20. Skipped meals
Physical activity (e.g., prolonged overexertion)
Stress or post-stress
Medications
(Analgesic overuse, benzodiazepine withdrawal, cimetidine, decongestant overuse, ergotamine overuse, estrogen therapy, indomethacin, nifedipine, nitrates, oral contraceptive, theophylline).

21. Treatment
Non-pharmacologic Treatment • Application of ice to the head and periods of rest or sleep, usually in a dark, quiet environment. • Preventive management should begin with the identification and avoidance of factors that provoke migraine attacks. • Behavioral interventions (relaxation therapy) are preventive options for patients who prefer nondrug therapy or when drug therapy is contraindicated, ineffective or not tolerated.

22. Pharmacologic Treatment of Acute Migraine
Acute migraine therapies are most effective when administered at the onset of migraine.
The frequent or excessive use of acute migraine medications can result in a pattern of increasing headache frequency and drug consumption known as medication-overuse headache. This occurs commonly with overuse of simple or combination analgesics, opiates, ergotamine tartrate, and triptans.
This may be avoided by limiting use of acute migraine therapies to 2 days per week.

23. 1- Antiemetic
Dopamine antagonist (prochlorperazine,metoclopramide)
Should be given15 to 30 minutes prior to administering oral acute migraine therapy.
Non oral treatments (rectal suppositories, nasal spray, injections) may be advisable when nausea and vomiting are severe.
metoclopramide can enhance absorption of oral medications.
Dopamine antagonist drugs also have been used successfully as monotherapy for the treatment of intractable headache.
Side effects of dopamine antagonist ( drowsiness, dizziness and extrapyramidal side effects).

24. 2- Analgesics and Nonsteroidal Anti-inflammatory Drugs
Simple analgesics and (NSAIDs) are effective as first-line treatment for mild to moderate migraine attacks.
E.g., aspirin, ibuprofen, naproxen sodium, tolfenamic acid.
Combination therapy with metoclopramide can speed the absorption of analgesics and NSAIDs and alleviate migraine related nausea and vomiting.
The combination of acetaminophen plus aspirin with caffeine or with short-acting barbiturate (butalbital) are also effective.
In general, NSAIDs with a long half-life are preferred as less frequent dosing is needed.
Rectal suppositories and intramuscular ketorolac are options for patients with severe nausea and vomiting.

25. 3- Opioids
Narcotic analgesic drugs(oxycodone,hydromorphone. meperidine, butorphanol) are effective but generally should be reserved for patients with moderate to severe infrequent headaches in whom conventional therapies are contraindicated or as (rescue medication )after failure to respond to conventional therapies.
Frequent use of narcotic analgesics may lead to the development of dependency and rebound headache.

26. 4- Corticosteroids
• Corticosteroids may be an effective rescue therapy for status migrainosus (a severe, continuous migraine that may last up to 1 week).
5- Ergot Alkaloids and Derivatives
Ergot alkaloids are useful for moderate to severe migraine attacks.
They are nonselective 5HT1 receptor agonists that constrict intracranial blood vessels.
Venous and arterial constriction occurs with therapeutic doses, but ergotamine tartrate exerts more potent arterial effects than dihydroergotamine.
They also have activity at α -adrenergic, β-adrenergic, and dopaminergic receptors.

27. Ergotamine tartrate Dihydroergotamine (DHE)
It is available for oral, sublingual, and rectal administration.
Oral and rectal preparations contain caffeine to enhance absorption and potentiate analgesia.
Dihydroergotamine (DHE)
It is available for intranasal and parenteral (IM, IV & SC) administration.
Nausea and vomiting are common adverse effects of ergotamine derivatives, pretreatment with an antiemetic should be considered with ergotamine and IV DHE therapy.

28. DHE does not appear to cause rebound headache.
Occasionally symptoms of severe peripheral ischemia (ergotism) include cold, painful extremities; continuous paresthesias; diminished peripheral pulses; and claudication may result from the vasoconstrictor effects of the ergot alkaloid.
Gangrenous extremities, myocardial infarction & bowel and brain ischemia have been reported rarely with ergotamine.
Ergotamine derivatives and triptans should not be used within 24 hours of each other.

29. 6- Serotonin Receptor Agonists (Triptans)
Sumatriptan, zolmitriptan ,naratriptan, rizatriptant ---- etc., are appropriate first-line therapies for patients with moderate to severe migraine or as (rescue therapy)when nonspecific medications are ineffective.
These drugs are selective agonists of the 5HT1B and 5HT1D receptors.
Sumatriptan
It is available for oral, intranasal, and SC administration.
When compared with the oral formulation, SC administration offers enhanced efficacy and a more rapid onset of action (10 vs. 30 minutes).

30. Also intranasal sumatriptan has a faster onset of effect (15 minutes) than the oral formulation.
Approximately 30% to 40% of patients who respond to sumatriptan experience headache recurrence within 24 hours; a second dose given at the time of recurrence is usually effective.
Side effects of triptans include paresthesias, fatigue, dizziness, flushing, warm sensations, and drowsiness. Minor injection site reactions are reported with SC use, and taste perversion and nasal discomfort may occur with intranasal administration.

31. Contraindications include ischemic heart disease, uncontrolled hypertension, cerebrovascular disease.
Triptans should not be given within 24 hours of ergotamine derivative administration.
Concomitant use of the triptans with selective serotonin reuptake inhibitors or the serotonin norepinephrine reuptake inhibitors can cause serotonin syndrome, a potentially life-threatening condition.

32. Prevention of therapy
Prevention therapies are administered on a daily basis to reduce the frequency, severity, and duration of attacks, as well as to increase responsiveness to acute symptomatic therapies.
Prophylaxis should be considered in:
Patient with recurring migraines that produce significant disability.
Those with frequent attacks requiring symptomatic medication more than twice per week.
Those with symptomatic therapies that are ineffective, contraindicated, or produce serious side effects.

33. Preventive therapy may also be administered intermittently when headaches recur in a predictable pattern (e.g., exercise-induced or menstrual migraine).
Because efficacy of various prophylactic agents appears to be similar, drug selection is based on side-effect profiles and comorbid conditions of the patient.

34. 1- β-Adrenergic Antagonists
β-Blockers (propranolol, nadolol , timolol , atenolol and metoprolol )are the most widely used treatment for migraine prophylaxis.
β–Blockers are reported to reduce the frequency of attacks by 50% in 60% to 80% of patients.
 2- Antidepressants
Amitriptyline , imipramine, nortriptyline, doxepin and protriptyline.
TCAs are usually well tolerated at the lower doses used for migraine prophylaxis, but anticholinergic effects may limit use, especially in elderly patients or those with benign prostatic hyperplasia or glaucoma.
Evening doses are preferred because of sedation.

35. 3- Anticonvulsants
Valproic acid and divalproex
The extended release formulation of divalproex sodium is administered once daily and is better tolerated than the enteric-coated formulation.
Topiramate
It is recently approved by the FDA for migraine prophylaxis.
Dose is initiated at 25 mg/day and increased slowly to minimize side effects, which may include paresthesias, fatigue & anorexia.

36. 4- Calcium Channel Blockers
Verapamil provided only modest benefit in decreasing the frequency of attacks .
It is generally considered a second- or third-line prophylactic agent.

37. 5- Methysergide
it is a semisynthetic ergot alkaloid that is a potent 5HT2 receptor antagonist. It can stabilize serotonergic neurotransmission in the trigeminovascular system to block the development of neurogenic inflammation.
Its use is limited by the rare development of pulmonary fibrosis during long-term administration.
It is reserved for patients with refractory headaches that do not respond to other preventive therapies.

38. Dosage should be tapered over 1 week to prevent rebound headaches.
Methysergide is best tolerated when taken with meals.
It is contraindicated in pregnancy, peripheral vascular disorder, coronary artery disease, sever hypertension, peptic ulcer, liver or renal dysfunction and vascular heart disease.

39. 6- Nonsteroidal Anti inflammatory Drugs
NSAIDs are modestly effective for reducing the frequency, severity, and duration of migraine attacks, but potential GI and renal toxicity limit daily or prolonged use.
They may be used intermittently to prevent headaches that recur in a predictable pattern (e.g., menstrual migraine). Treatment should be initiated1 to 2 days before the time of headache and continued until attack is passed.

40. Cluster Headaches
Cluster headaches derive their name from a characteristic pattern of recurrent headaches that are separated by periods of remission that last from months to even years. During those periods the headaches usually occur at least once daily.
The headache generally is unilateral, occurs behind the eye, reaches maximal intensity over several minutes, and lasts for <3hrs.

41. Unilateral lacrimation, rhinorrhea, and facial flushing may accompany the cluster headache. During cluster periods, headache is commonly precipitated by alcohol, naps, and vasodilating drugs.
In contrast to migraine headaches, cluster headaches are more common in males than females.

42. Tension-Type Headaches
It is the most common type of primary headache and is more common in women than men.
Pain is usually mild to moderate and non pulsating. It is persistent headache, occurring bilaterally in a hatband distribution around the head. The headache may fluctuate in intensity throughout the day.
Tension-type headaches often occur during or after stress, but chronic tension-type headaches may persist for months even in the absence of recognizable stress.

43. Skeletal muscle over contraction, depression, and occasionally nausea may accompany the headache. Neurologic symptoms do not occur in association with tension-type headache.
Mild photophobia or phonophobia occur in some patient.