Pharmaceutical guidelines of patients with pathology of CNS organs. Headaches Headache is an almost universal experience and one of the most common symptoms in medical practice. It varies from an infrequent and trivial nuisance to a pointer to serious disease. 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. Chronic (benign) and recurrent headaches Almost all recurring headaches lasting hours or days band-like, generalized head pains, with a history for several years or months are vaguely ascribed to muscle tension and/or migraine Depression is a common accompaniment. In localized pain of short duration (minutes to hours), sinusitis, glaucoma and migrainous neuralgia should be considered. Headaches are not caused by essential hypertension; malignant hypertension, with arterial damage and brain swelling, occasionally causes headache. Eyestrain from refractive error does not cause headache, though new prescription lenses sometimes provoke pain. Cluster Headache 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 band sensations, pressure behind the eyes, throbbing and bursting sensations 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. Pressure headaches Intracranial mass lesions displace and stretch meninges and basal vessels. Pain is provoked when these structures are shifted either by a mass or by changes in cerebrospinal fluid (CSF) pressure, e.g. coughing. Cerebral oedema around brain tumours causes further shift. These pressure headaches typically become worse on lying down. Any headache present on waking and made worse by coughing, straining or sneezing may be due to a mass lesion. Vomiting often accompanies pressure headaches. Such headaches are caused early, over days or weeks, by posterior fossa masses, but over a longer time scale months or years by hemisphere tumours. A rare cause of prostrating headache with lower limb weakness is an intraventricular tumour causing intermittent hydrocephalus. Headache of subacute onset The onset and progression of a headache over days or weeks with or without features of a pressure headache should always raise suspicion of an intracranial mass or serious intracranial disease. Encephalitis, viral meningitis and chronic meningitis should also be considered. Headaches with scalp tenderness Patches of exquisite tenderness overlying superficial scalp arteries are caused by giant cell arteritis in patients over 50. Headache following head injury The majority of post-trauma headaches lasting days, weeks or months are not caused by any serious intracranial pathology. However, subdural haematoma must be considered. A single episode of severe headache This common emergency is caused by one of the following: 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 headache history should be documented. Neck stiffness, vomiting (meningeal irritation) and a rash and/or fever suggest bacterial meningitis. 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. Migraine Migraine is recurrent headache associated with visual and gastrointestinal disturbance. The borderland between migraine 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. Migraine. Mechanisms Precise mechanisms remain unclear. Genetic factors play some part a rare form of familial migraine is associated with mutation in the alpha-1 subunit of the P/Q-type voltagegated calcium channel on chromosome 19. The pathophysiology of migraine is now thought to involve changes in the brainstem blood flow which have been found on PET scanning during migraine attacks. This leads to an unstable trigeminal nerve nucleus and nuclei in the basal thalamus. This results in release of calcitonin-related peptide (CGR8), substance P and other vasoactive peptides, leading to neurogenic inflammation, which gives rise to pain, and vasodilation of cerebral and dural vessels which also contribute towards the headache. Cortical spreading depression is also proposed as a mechanism for the aura. 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 hormonal contraceptives, in pregnancy and occasionally with the 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 mass and migraine sometimes occur together by coincidence. Clinical patterns Migraine attacks vary from intermittent headaches indistinguishable from tension headaches to discrete episodes that mimic thromboembolic cerebral ischaemia. Distinction between 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. Migraine with aura (classical migraine) Prodromal symptoms are usually visual and related to depression of visual cortical function or retinal function. Transient aphasia sometimes occurs, with tingling, numbness, vague weakness of one side and nausea. The prodrome persists for a few minutes to about an hour. Headache then follows. This is occasionally hemicranial (i.e. splitting the head) but often begins locally and becomes generalized. Nausea increases and vomiting follows. The patient is irritable and prefers the dark. Superficial scalp arteries are engorged and pulsating. After several hours the migraine settles, sometimes with a diuresis. Deep sleep often ensues. Migraine without aura (common migraine) This is the usual variety. Prodromal visual symptoms are vague. There is a similar headache often accompanied by nausea and malaise. Basilar migraine Prodromal symptoms include circumoral and tongue tingling, vertigo, diplopia, transient visual disturbance, syncope, dysarthria and ataxia. These occur alone or progress to a typical migraine. 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 a migraine, and they are difficult to diagnose without investigation to exclude other conditions. Differential diagnosis A sudden migraine headache may resemble SAH or the onset of meningitis. Hemiplegic, visual and hemisensory symptoms must be distinguished from thromboembolic TIAs In TIAs maximum deficit is present immediately and headache is unusual. Unilateral tingling or numbness may resemble sensory epilepsy (partial seizures). In epilepsy, distinct march (progression) of symptoms is usual. Management General measures include: avoidance of dietary factors rarely helpful. Patients taking hormonal contraceptives may benefit from a brand change, or trying without. Depot oestrogens are sometimes used. Severe hemiparetic symptoms are a potential reason to stop hormonal contraceptives. Premenstrual migraine sometimes responds to diuretics. At the start of an attack Paracetamol or other analgesics should be taken, with an antiemetic such as metoclopramide if necessary. Repeated use of analgesics leads to further headaches. Triptans (5HT1 agonists) are also widely used, sometimes aborting an attack effectively. Sumatriptan was the first marketed; almotriptan, eletriptan, frovatriptan, naratriptan, rizatriptan and zolmitriptan are now available, with various routes of administration. Triptans should be avoided when there is vascular disease, and not overused. Ergot Derivatives cause constriction of cranial blood vessels and decrease the pulsation of cranial 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 is limited in some patients. The ergots are contraindicated during pregnancy because of the potential for adverse 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. Ergot Derivatives (contd) 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. Contraindications and Cautions Ergot derivatives are contraindicated in the following circumstances: presence of allergy to ergot preparations; CAD, hypertension, or peripheral vascular disease, which could be exacerbated by the CV effects of these drugs; impaired liver function, which could alter the metabolism and excretion of these drugs; and pregnancy or lactation because of the potential for adverse effects on the fetus and neonate. Ergotism (vomiting, diarrhea, seizures) has been reported in affected infants. Caution should be used in two instances: with pruritus, which could become worse with drug-induced vascular constriction, and with malnutrition because ergot derivatives stimulate the CTZ and can cause severe GI reactions, possibly worsening malnutrition. 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 as pulselessness, weakness, chest pain, arrhythmias, localized edema and itching, and MI may also occur. the direct stimulation of the CTZ can cause GI upset, nausea, vomiting, and diarrhea. 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. Asthenia Asthenia: Weakness. Lack of energy and strength. Loss of strength. The word asthenia is not much used in medicine today, although it is a prominent part of myasthenia, a loss of muscle strength, as in myasthenia gravis. Asthenia It is a frequent cause of consult, almost 30% in ambulatory settings. The chronic fatigue represents up to 10% of these cases, and the % belongs to the chronic fatigue syndrome. It is very important to differentiate asthenia from weakness, dizziness or dyspnoea, since patients may confuse them. The factor time in asthenia is very useful for its characterization, it was defined to the prolonged fatigue when it lasts for more than a month and chronic when the duration is greater than 6 months. The depression is the commonest fatigue cause, representing approximately half of the cases. Asthenia General asthenia occurs in many chronic wasting diseases anemia and cancer, is probably most marked in diseases of the adrenal gland. Asthenia may be limited to certain organs or systems of organs, as in asthenopia, characterized by ready fatiguability. Asthenia is also a side effect of Ritonavir (Protease Inhibitor used in HIV treatment) and fentanyl patches (an opioid used to treat pain). The condition is also commonly seen in patients suffering from chronic fatigue syndrome, sleep disorders or chronic disorders of the heart, lungs or kidneys. Differentiating between psychogenic asthenia and true asthenia with muscular weakness is often difficult, and in time apparent psychogenic asthenia accompanying many chronic disorders is seen to progress into a primary weakness. Chronic fatigue syndrome (CFS) functional syndrome uncertain classification as neurasthenia in the psychiatric classification and myalgic encephalomyelitis (ME) under neurological diseases. It occurs most commonly in women between the ages of 20 and 50 years. The cardinal symptom is chronic fatigue made worse by minimal exertion. The fatigue is usually both physical and mental, associated most commonly with poor concentration, impaired registration of memory, alteration in sleep pattern (either insomnia or hypersomnia), and muscular pain. Mood disorders are present in a large minority of patients, and can cause problems in diagnosis because of the large overlap in symptoms.These mood disorders may be secondary, independent (co- morbid), or primary (with a misdiagnosis of CFS). The most effective treatment of the asthenia is to solve the underlying cause, although up to 20% of the patients remain without diagnosis. The diagnosis of the chronic fatigue syndrome is of exclusion and the criteria of the international consensus of year 1994 are due to use. The high frequency of the symptom entails an enormous social and economic cost and it is for that reason so important for physicians to have a correct manage of this symptom. Treatment of asthenic syndrome includes a variety of approaches: psychotherapy, lifestyle changes, the ordering of work and leisure modes of wakefulness and sleep, regular meals, eliminating the causes of emotional stress, physical therapy, spa treatment. In some cases, such events can bring tangible benefits and rights to withdraw from the state of fatigue. However, for obvious reasons, these recommendations are not always feasible. On the other hand, in some cases, these measures are insufficient, and the doctor had to resort to medication. Anxiety Anxiety is a feeling of constant, inappropriate or excessive worry, fear, apprehension, tension or inner restlessness, seen in anxiety and depressive disorders as well as drug withdrawal. ANXIETY DISORDERS are classified according to whether the anxiety is persistent (general anxiety) or episodic, with the episodic conditions classified according to whether the episodes are regularly triggered by a cue (phobia) or not (panic disorder). Anxiety disorder caused by physical diseases Thyrotoxicosis Hypoglycaemia (transient) Phaeochromocytoma Complex partial seizures (transient) Alcohol withdrawal