Pharmaceutical guidelines of patients with pathology of CNS organs. Symptomatic treatment of HEADACHE

1. Pharmaceutical guidelines of patients with pathology of CNS organs. Symptomatic treatment of HEADACHE

2. Headaches • Headache is an almost universal experience and one of themost common symptoms in medical practice. It varies froman infrequent and trivial nuisance to a pointer to seriousdisease.

3. Mechanisms Pain receptors are located at the base of the brain in arteries and veins and throughout meninges, extracranial vessels, scalp, neck and facial muscles, paranasal sinuses, eyes and teeth. Curiously, brain substance is almost devoid of pain receptors. Head pain is mediated by mechanical and chemical receptors (e.g. stretching of meninges, 5-HT and histamine stimulation). Nerve impulses travel centrally via the Vth and IXth cranial nerves and upper cervical sensory roots. Most headaches are benign, but the diagnostic issue – and usual concern – is the question of serious disease.

6. Chronic (benign) and recurrent headaches • Almost all recurring headaches lasting hours or days –band-like, generalized head pains, with a history for severalyears or months – are vaguely ascribed to muscle tensionand/or migraine • Depression is a commonaccompaniment. • In localized pain of short duration (minutes to hours),sinusitis, glaucoma and migrainous neuralgia shouldbe considered. • Headaches are not caused by essentialhypertension; malignant hypertension, with arterial damageand brain swelling, occasionally causes headache. • Eyestrain from refractive error does not cause headache,though new prescription lenses sometimes provoke pain.

7. Cluster Headache

8. Tension headache The vast majority of chronic daily headaches and recurrent headaches are thought to be generated by neurovascular irritation and referred to scalp muscles and soft tissues, although the exact pathogenesis remains unclear. Tight bandsensations, pressure behind the eyes, throbbing and burstingsensations are common. What is clear is that almost all headaches with these features are benign. There may be obvious precipitating factors such as worry, noise, concentrated visual effort or fumes. Depression is also a frequent co-morbid feature. Tension headaches are often attributed to cervical spondylosis, refractive errors or high blood pressure: evidence for such associations is poor. Headaches also follow even minor head injuries. Tenderness and tension in neck and scalp muscles are the only physical signs. Analgesic overuse is a prominent cause of headache.

9. Pressure headaches • Intracranial mass lesions displace and stretch meninges andbasal vessels. Pain is provoked when these structures areshifted either by a mass or by changes in cerebrospinal fluid(CSF) pressure, e.g. coughing. Cerebral oedema aroundbrain tumours causes further shift. These ‘pressure headaches’typically become worse on lying down. • Any headache present on waking and made worse bycoughing, straining or sneezing may be due to a mass lesion. • Vomiting often accompanies pressure headaches. Suchheadaches are caused early, over days or weeks, by posteriorfossa masses, but over alonger time scale – months or years – by hemispheretumours. • A rare cause of prostrating headache with lower limbweakness is an intraventricular tumour causing intermittenthydrocephalus.

10. Headache of subacute onset • The onset and progression of a headache over days or weekswith or without features of a pressure headache shouldalways raise suspicion of an intracranial mass or seriousintracranial disease. • Encephalitis, viral meningitisand chronic meningitis should also beconsidered.

11. Headaches with scalp tenderness • Patches of exquisite tenderness overlying superficial scalparteries are caused by giant cell arteritis in patientsover 50. Headache following head injury • The majority of post-trauma headaches lasting days, weeksor months are not caused by any serious intracranial pathology. • However, subdural haematoma must beconsidered.

12. A single episode of severe headache • This common emergency is caused by one of thefollowing: ■ subarachnoid haemorrhage (SAH) and cervical arterial dissection ■ migraine, or other benign headaches ■ meningitis (occasionally). • Particular attention should be paid to • suddenness of onset(suggestive of SAH). • The exact time of onset, • time to peak,duration, • associated symptoms and previous headachehistory should be documented. • Neck stiffness, vomiting(meningeal irritation) and a rash and/or fever suggest bacterialmeningitis.

14. Management Headache management involves: ■ explanation (imaging is often needed) ■ avoiding evident causes, e.g. bright lights ■ physical treatments – massage, ice packs, relaxation ■ antidepressants – when indicated ■ drugs for recurrent headache/migraine.

15. Migraine • Migraine is recurrent headache associated with visual andgastrointestinal disturbance. • The borderland betweenmigraine and tension headaches can be indistinct. Over 20%of any population world-wide report migrainous symptoms;in 90%, these began before 40 years of age.

16. Migraine. Mechanisms • Precise mechanisms remain unclear. Genetic factors playsome part – a rare form of familial migraine is associated withmutation in the alpha-1 subunit of the P/Q-type voltagegatedcalcium channel on chromosome 19. • The pathophysiology of migraine is now thought to involvechanges in the brainstem blood flow which have been foundon PET scanning during migraine attacks. • This leads to anunstable trigeminal nerve nucleus and nuclei in the basalthalamus. This results in release of calcitonin-related peptide(CGR8), substance P and other vasoactive peptides, leadingto neurogenic inflammation, which gives rise to pain, andvasodilation of cerebral and dural vessels which also contributetowards the headache. • Cortical spreading depression is also proposed as amechanism for the aura.

17. Some patients recognize precipitating factors: ■ weekend migraine (a time of relaxation) ■ chocolate (high in phenylethylamine) ■ cheese (high in tyramine) ■ noise and irritating lights ■ association with premenstrual symptoms. Migraine is common around puberty and at the menopause and sometimes increases in severity or frequency with hormonalcontraceptives, in pregnancy and occasionally withthe onset of hypertension or following minor head trauma. Migraine is not suggestive of any serious intracranial lesion. However, since migraine is so common, an intracranial massand migraine sometimes occur together by coincidence.

18. Clinical patterns • Migraine attacks vary from intermittent headaches indistinguishablefrom tension headaches to discrete episodes thatmimic thromboembolic cerebral ischaemia. • Distinctionbetween variants is somewhat artificial. • Migraine can beseparated into phases: ■ well-being before an attack (occasional) ■ prodromal symptoms ■ the main attack – headache, nausea, vomiting ■ sleep and feeling drained afterwards.

19. Migraine with aura (classical migraine) • Prodromal symptoms are usually visual and related to depression • of visual cortical function or retinal function. • Transient aphasia sometimesoccurs, with tingling, numbness, vague weakness of one sideand nausea. • The prodrome persists for a few minutes toabout an hour. • Headache then follows. This is occasionallyhemicranial (i.e. splitting the head) but often begins locallyand becomes generalized. • Nausea increases and vomitingfollows. The patient is irritable and prefers the dark. • Superficialscalp arteries are engorged and pulsating. • After severalhours the migraine settles, sometimes with a diuresis. • Deepsleep often ensues.

20. Migraine without aura (common migraine) • This is the usual variety. Prodromal visual symptoms arevague. • There is a similar headache often accompanied bynausea and malaise. Basilar migraine • Prodromal symptoms include circumoral and tongue tingling,vertigo, diplopia, transient visual disturbance,syncope, dysarthria and ataxia. • These occur alone orprogress to a typical migraine.

21. Hemiparetic migraine • This rarity is classical migraine with hemiparetic features,i.e. resembling a stroke, but with recovery within 24 hours. • Exceptionally, cerebral infarction occurs. Ophthalmoplegic and facioplegic migraine • These rarities are a IIIrd, VIth or VIIth nerve palsy with amigraine, and they are difficult to diagnose without investigationto exclude other conditions.

22. Differential diagnosis • A sudden migraine headache may resemble SAH or theonset of meningitis. • Hemiplegic, visual and hemisensorysymptoms must be distinguished from thromboembolic TIAs • In TIAs maximum deficit is present immediately andheadache is unusual. • Unilateral tingling or numbness mayresemble sensory epilepsy (partial seizures). In epilepsy, distinctmarch (progression) of symptoms is usual.

24. ManagementGeneral measures include: ■ avoidance of dietary factors – rarely helpful. • Patients taking hormonal contraceptives may benefit from abrand change, or trying without. Depot oestrogens are sometimesused. Severe hemiparetic symptoms are a potentialreason to stop hormonal contraceptives. • Premenstrualmigraine sometimes responds to diuretics.

25. At the start of an attack • Paracetamol or other analgesicsshould be taken, with an antiemetic such as metoclopramideif necessary. Repeated use of analgesics leads to furtherheadaches. • Triptans (5HT1 agonists) are also widely used,sometimes aborting an attack effectively. Sumatriptanwasthe first marketed; almotriptan, eletriptan, frovatriptan, naratriptan,rizatriptan and zolmitriptan are now available, withvarious routes of administration. • Triptans should be avoidedwhen there is vascular disease, and not overused.

27. Ergot Derivatives • cause constriction of cranial blood vessels and decrease the pulsation ofcranial arteries. As a result, they reduce the hyperperfusion of the basilar artery vascular bed. • Because these agents are associated with many systemic adverse effects, their usefulness islimited in some patients. The ergots are contraindicated during pregnancy because of the potential foradverse effects in the mother and fetus. • Dihydroergotamine (Migranal) can be used in the IM or IV form or as a nasal spray to provide rapid relief from migraine headache. This agent is the drug of choice if the oral route of administration is not possible. In 2003, the parenteral form was approved for the treatment of cluster headaches.

28. Ergot Derivatives (cont’d) • Ergotamine(generic), the prototype drug in this class, was the mainstay of migraine headache treatment before the triptans became available. This agent is administered sublingually for rapid absorption. Cafergot, the very popular oral form, combines ergotamine with caffeine to increase its absorption from the GI tract.

29. Contraindications and Cautions • Ergot derivatives are contraindicated in the following circumstances: presence of allergy to ergotpreparations; CAD, hypertension, or peripheral vascular disease, which could be exacerbated bythe CV effects of these drugs; impaired liver function, which could alter the metabolism andexcretion of these drugs; and pregnancy or lactation because of the potential for adverse effectson the fetus and neonate. Ergotism (vomiting, diarrhea, seizures) has been reported in affectedinfants. • Caution should be used in two instances: with pruritus, which could become worse withdrug-induced vascular constriction, and with malnutrition because ergot derivatives stimulate theCTZ and can cause severe GI reactions, possibly worsening malnutrition.

30. Adverse Effects • The adverse effects of ergot derivatives can be related to the drug-induced vascular constriction. • CNS effects include numbness, tingling of extremities, and muscle pain; • CV effects such aspulselessness, weakness, chest pain, arrhythmias, localized edema and itching, and MI may alsooccur. • the direct stimulation of the CTZ can cause GI upset, nausea, vomiting, anddiarrhea. Ergotism, a syndrome associated with the use of these drugs, causes nausea, vomiting,severe thirst, hypoperfusion, chest pain, blood pressure changes, confusion, drug dependency(with prolonged use), and a drug withdrawal syndrome.

32. Headaches are distributed in the general population in a definite gender-related pattern • Migraine headaches are three times more likely to occur in women than men. • Cluster headaches are more likely to occur in men than in women. • Tension headaches are more likely to occur in women than in men. • There is some speculation that the female predisposition to migraine headaches may berelated to the vascular sensitivity to hormones. Some women can directly plot migraineoccurrence to periods of fluctuations in their menstrual cycle. The introduction of the triptanclass of antimigraine drugs has been beneficial for many of these women.

33. Prophylaxis • The following are used continuously whenattacks are frequent: ■ pizotifen (5HT antagonist) 0.5 mg at night for several days, increasing to 1.5 mg (common side-effects are weight gain and drowsiness) ■ propranolol 10 mg three times daily, increasing to 40– 80 mg three times daily ■ amitriptyline 10 mg (or more) at night. • Sodium valproate, methysergide, SSRIs, verapamil, topiramate,nifedipine and naproxen are also used. • Gap junctionblockers are being used in trials.

34. Other benign headaches ■ Ice-cream headache. Sufferers describe intense, retropharyngeal head pain lasting for a few seconds or minutes following ice-cream or very cold foods. ■ Primary cough headache is a sudden sharp head pain on coughing. No underlying cause is found but intracranial pathology should be excluded. The problem often resolves spontaneously. Very rarely, for severe headache, a lumbar puncture with removal of CSF can help. ■ Primary low CSF volume headaches, seen typically on standing up, are also well recognized. The patient may give a history of some event, such as straining or orgasm, but these headachessometimes arise spontaneously. Treatment with an autologous intrathecal blood patch can be helpful. Secondary low CSF volume can follow lumbar puncture

35. Other benign headaches (cont’d) ■ Primary sex headache describes varieties of head pain that typically rise to a crescendo at orgasm, largely in males. Treatment with propranolol or diltiazem is said to be helpful, but these pains often resolve spontaneously after several attacks. Exceptionally, sex headaches occur with an unruptured intracranial aneurysm. ■ Many other varieties of primary headache are listed in the international classification, e.g. hemicrania continua, primary stabbing headache, primary exertional headache, hypnic headache, and primary thunderclap headache. ■ Post-traumatic headache is also a common problem. Headaches do sometimes follow a minor blow to the head; they tend to resolve, typically within 6–8 weeks. However, when there is third party involvement, and especially with litigation, these headaches can persist for long periods. Opinions vary about their cause.