My last minute MRCP facts

Discussion in 'MRCP Forum' started by sawsan s, Jan 23, 2006.

  1. sawsan s

    sawsan s Guest

    **Fibrosing alveolitis is the most common pulmonary manifestation of rheumatoid arthritis.

    **impairment in renal function in Hepatorenal syndrome The hallmark is oliguria and progressive decline in renal function. The urine is typically free of protein or any other sediment.

    **Long-term haemodialysis is associated with carpal tunnel syndrome. is the most common complication

    **the most likely cause of bacterial meningitis in adult patients with neutropenia :
    Listeria monocytogenes.

    **the most frequent cause of a nosocomial wound infection: Insufficient hand disinfection

    **Osteoporosis is the most common cause of fracture of neck of femur and is not associated with any specific abnormality in the standard bone biochemistry profile.

    **Tuberculous arthritis usually affects children aged 2–5 years. The hip is one of the most frequently affected joints.

    **Meningitis due to enterovirus and meningococcus (N. meningitidis) are the most likely in this age group(28 yrs0

    **Tuberculous meningitis is rare in the UK and the CSF typically shows a markedly raised protein (> 1 g/l), a low glucose (< 50% serum) and a lymphocytosis.

    **Streptococcus meningitis is the commonest cause of meningitis in those over 40 years of age; very high neutrophil counts are often seen in the CSF, which has a high protein and low glucose level.

    **Factors predisposing to digitalis toxicity are advanced age, hypoxia, hypokalaemia, hypomagnesaemia, hypercalcaemia, hypothyroidism, amyloidosis and renal failure. The most common precipitating factor is hypokalaemia.

    ** In Hodgkin’s disease Lymphocyte depleted has the worst prognosis. It is the least common variant and typically occurs in older people.

    **The commonest mutation in patients with cystic fibrosis (CF) is the Delta-F508 mutation.

    **in systemic lupus erythematosus Recurrent pleurisy and pleural effusions are the most common manifestations and are often bilateral

    **Cryptosporidium infection in HIV-positive patients along with cytomegalovirus, is the commonest cause of HIV-related diarrhoea and tends to present when the CD4 count is less than 100.

    **Diarrhoea and flushing, occurring separately or together, are the most frequent presenting features of carcinoid syndrome (approximately half of all patients).

    **Focal necrotising glomerulonephritis is the characteristic renal lesion of generalised Wegener’s granulomatosis. Typically, it presents with deteriorating renal function that progresses to renal failure within 3 months,

    **Glomerulonephritis is a common occurrence in chronic Schistosoma mansoni infection in Brazil, especially in patients with hepatosplenic disease

    **Tremor in the legs is a useful sign as it is almost always associated with idiopathic Parkinson’s disease. The tremor is typically a rest tremor unlike benign essential tremor, where actions such as drinking a cup of tea make the tremor worse.

    **Pericardial effusions are more common in patients with rheumatoid arthritis than constrictive pericarditis and acute pericarditis.

    **The earliest lesions to be detected in diabetic retinopathy are usually dot haemorrhages (capillary microaneurysms) and venous dilatation.

    **Hypertrophic cardiomyopathy is the single, most common cause of sudden death in young athletes.

    **the most common cause of paranoid psychosis with visual hallucination :Alcohol withdrawal

    **Basal cell carcinomas are the most common malignant skin tumour and are related to excessive skin exposure. They are common later in life and may present as a slow-growing nodule or papule.

    **The most common type of thyroid cancer is papillary cancer, which accounts for approximately 70% of all thyroid cancers

    ***Open angle glaucoma is 100 times more common than angle closure glaucoma, and is asymptomatic until central visual loss appears at the end stage.

    **a high white cell count with smear cells and mature lymphocytes. This is characteristic of chronic lymphocytic leukaemia...

    **Chronic lymphocytic leukaemia
    · Constitutes 25% of all leukaemias. It is chiefly a disease of the elderly
    · It is characterised by an accumulation of mature lymphocytes in the peripheral blood, bone marrow, spleen, liver and lymph nodes
    · Clinical findings include painless, symmetrical lymphadenopathy, hepatosplenomegaly, pruritus and symptoms due to bone marrow failure
    · Blood film will show large numbers of mature lymphocytes and smear or smudge cells. Anaemia and thrombocytopenia are common
    · Hypogammaglobulinaemia is common and monoclonal paraproteins are occasionally seen
    · Staging is by the Binet or Rai systems and depends on number of areas involved and full blood count results
    · Median survival is 3–5 years and one-third die of causes other than the leukaemia
    · In early stages no treatment is required. In later stages and in rapidly progressive disease treatment is with oral or intravenous chemotherapy such as chlorambucil or fludarabine. Stem cell transplantation is an option in younger patients


    **IgG is the most common paraprotein in myeloma.

    **Myeloma
    · Median age of diagnosis is 70 years
    · Diagnosis is made in the presence of two of monoclonal protein in blood or urine, 10% plasma cells in bone marrow and lytic bone lesions
    · Other clinical features are bone disease, hypercalcaemia, renal failure, bone marrow failure and immune paresis
    · 5 year survival is only 25%
    · Treatment is supportive, chemotherapy (which can be oral or intravenous) and autologous or allogeneic stem cell transplantation
    · Thalidomide has recently been used in relapsed and refractory disease


    ***Adrenergic inhibitors used in hypertension:
    Peripheral neuronal inhibitors: Reserpine, Guanethedine
    Central adrenergic inhibitors: M-dopa, Clonidine, Guananbenz, Guanafacine
    Alpha-receptor blockers:
    o Alpha 1 and 2 receptor blockers: Phenoxybenzamine, phentolamine
    o Alpha 1 blockers: Doxazosin, Terazosin
    Beta blockers
    Alpha and beta blockers: Labetalol

    **Polycythaemia rubra vera:
    · Splenomegaly
    · Aquagenic pruritus
    · Bleeding
    · Gout
    · Peptic ulcer
    · Conversion to myelofibrosis or leukaemia in 10%


    **Causes of Chorea
    Neurodegenerative: Huntington’s disease
    Benign hereditary chorea
    Dentatorubropallidoluysian atrophy
    Inherited metabolic: Wilson’s disease
    Lesch-Nyhan disease
    Neuroacanthosis
    Hypoxic/ischaemic: Stroke
    Hypotension
    Vasculitis Sickle cell disease
    Polycythaemia
    Toxic: Copper
    Mercury
    Drug induced: Oral contraceptive pill
    L-Dopa
    Neuroleptics
    Anticholinergics
    Cocaine
    Amphetamines
    Infection: Sydenham’s chorea
    Meningitis
    Viral encephalitis
    Mycoplasma pneumoniae
    Legionella
    Toxoplasmosis
    Creutzfeld-Jacob disease
    Autoimmune: SLE
    Primary anti-phospholipid syndrome
    Vasculitis Behcet’s
    Hashimoto’s thyroiditis (unrelated to hyperthyroidism)
    Endocrine: Thyrotoxicosis
    Chorea gravidarum
    Addison’s disease
    Metabolic: Hypocalcaemia
    Hypomagnesaemia
    Hyper/hypoglycaemia
    Hyper/hyponatraemia


    **Causes of sudden cardiac death
    · Arrhythmia
    -Acute myocardial infarction
    -Long-QT syndromes
    -Hypertrophic cardiomyopathy
    -Commotio cardis
    -Coronary anomalies
    -Myocarditis
    · Obstruction
    -Atrial myxoma
    -Infective endocarditis
    -Dissection


    **In Hypertrohpic Cardiomyopathy
    · Combination of palpable LVS4 and then double systolic apical impulse due to the mid systolic outflow obstruction
    · It increases in phase II of the valsalva maneouver (the straining phase) and decreases in phase IV (post release phase)
    · Severe diastolic dysfunction
    · Children have a worse prognosis than affected adults because of greater incidence of SCD
    · As in severe AS (because of greater myocardial oxygen demand)


    **5 histological stages have been described (WHO Classification) and treatment depends on this. There is a lack of clear correlation between clinical manifestations and the severity of renal involvement. Biopsy findings guide the selection of immunosuppressive therapy.

    WHO Classification of Lupus Nephritis

    Stage I ¡V Lupus nephritis without histological changes
    Stage II ¡V Mesangial lupus nephritis
    Stage III ¡V Focal proliferative lupus nephritis
    Stage IV ¡V Diffuse proliferative lupus nephritis (commonest & most severe form)
    Stage V ¡V Membranous lupus nephritis


    Conditions that recur in the transplanted kidney

    Focal glomerulosclerosis
    Mesangiocapillary glomerulonephritis
    Rapidly progressive (Crescentic) glomerulonephritis
    IgA nephropathy
    Alport¡¦s syndrome
    Cystinosis
    Oxalosis
    Lupus nephritis
    Goodpastures syndrome
    Wegner¡¦s granulomatosis



    **The most common renal disease in HIV is collapsing FSGS in which there is focal sclerosis associated with collapse down of the glomerulus leaving a space in Bowman’s capsule. It has a poor prognosis and usually leads to ESRF.


    **The indications for a native nephrectomy prior to renal transplant are:
    1. Uncontrolled hypertension where a differential renin study shows that one or the other kidney is significantly contributing to hypertension
    2. Pyonephrosis
    3. Recurrent attacks of clinically significant UTI


    **Budd Chiari classically results in a very high protein ascites but may cause a transudate.

    **Transudates (protein < 30gdl or 75% of the serum albumin) are due to:
    - Reduced intravascular oncotic pressure (hypoalbuminaemia)
    - Increased intravascular hydrostatic pressure (cirrhosis, portal hypertension, CCF)


    **Teaching Notes for Question 15
    Theme: Pancreatic Secretion

    The roles of individual gut hormones are not completely defined, but
    cholecystokinin (duodenum & jejunum) increases gall bladder contraction, increases colonic motility.
    Gastrin (gastric antrum & duodenum) increases gastric acid secretion,increases GI mucosal growth.
    Secretin(duodenum & Jejunum) increases pancreatic bicarbonate production.
    VIP(enteric nerves)increased intestinal secretion, splanchnic vasodilation.
    Motilin(whole gut) increases small bowel motility.
    Bombesin (gut & Pancreas)stimulates pancreatic exocrine activity.

    Neuropeptide Y (enteric nerves)regulates intestinal blood flow.

    Somatostatin (stomach & pancreas) inhibits secretion and action of gut hormones.
    Glucagon(pancreas)reduces GI motility


    **In systemic lupus erythematosus (SLE). Joint involvement is the most common clinical feature (> 90%).

    **Prolactinoma is the commonest pituitary tumour, making up 30% of all adenomas. Microadenomas occur with increasing frequency in women, macroadenomas more commonly in men.

    **ASDs account for about 10-15% of all congenital cardiac anomalies and are the second commonest congenital heart disease seen in adults.

    **VSDs are the commonest adult congenital heart disease.

    **Frontal lobe dementia------>a failure to generate list rapidly is the test of frontal lobe+difficulties with task sequencing and executive skills. EXPRESSIVE aphasia, primitive reflexes, perseveration, anosmia and changes in personality.

    Parietal lobe--------------->Dyscalculia(inability to perform mentalarithmetic) is a manifestation of the dominant parietal lobe
    Sensory inattention, apraxia, neglect, astereognosis(unable to recognise an object by feeling it) and visual field defects( typically homonymous inferior quadrantanopia).

    Temporal lobe-----------> typical homonymous superior quadrantanopia), Wernike's (RECEPTIVE) aphasia, auditory agnosia, and memory impairment

    Occipital lobe---------->cortical blindness(blindness due to damage to the visual cortex and may present as Anton syndrome where there is blindness but the patient is unaware or denies blindness), homonymous hemianopia, and visual agnosia( seeing but not percieving objects - it is diffirent to neglect since in agnosia the objects are seen and followed but cannot be named).

    Homonymous hemianopia----------> occipital lobe
    superior quanranopia---------------->temporal lobe
    inferior quanrtanopia------------------->parietal lobe

    **AUTOIMMUNE ASSOCIATIONS
    Thyroid disease, IDDM, Addison disease, pernicious anaemia, alopecia, vitiligo.

    MULTIPLE ENDOCRINE NEOPLASIA
    Autosomal dominant. The association of a number of endocrine tumours.

    MEN I MEN IIa
    Parathyroid Adrenal (phaeochromocytoma, Cushing)
    Pituitary (prolactin or GH or ACTH) Thyroid (medullary carcinoma)
    Pancreas Parathyroid hyperplasia
    (Thyroid)
    (Adrenal)
    Fasting calcium level (??) Calcitonin level ? (medullary ca. thyroid)
    Look for phaeochromocytoma



    MEN IIb is the same as MEN IIa, with Marfanoid features and multiple neuromas.

    Prophylactic total thyroidectomy is performed if the child is known to carry the gene for MEN II.

    **Adrenergic inhibitors used in hypertension:
    Peripheral neuronal inhibitors: Reserpine, Guanethedine
    Central adrenergic inhibitors: M-dopa, Clonidine, Guananbenz, Guanafacine
    Alpha-receptor blockers:
    o Alpha 1 and 2 receptor blockers: Phenoxybenzamine, phentolamine
    o Alpha 1 blockers: Doxazosin, Terazosin
    Beta blockers
    Alpha and beta blockers: Labetalol

    **Mixed connective tissue disease (MCTD) is an overlap connective tissue disease with features of SLE, polymyositis and progressive systemic sclerosis. The characteristic auto-antibody pattern is of high titre anti-RNP and speckled pattern ANA.

    **The antiphospholipid syndrome is one of the commoner causes of hypoadrenalism and may precipitate adrenal infarction and haemorrage through adrenal vein thrombosis.

    **Biphasic high amplitude sharp waves are characteristic of ceutzfeld-jacob disease.

    **Causes of dilated pupils: Holme's adie(myotonic pupils)
    Third nerve palsy
    drug poisons(atropine, CO, Ethylene glycol)

    Causes of small pupils : horner;s syndrome
    old age
    pontine haemorrhage
    Argyl Robertson pupil
    Drug poisons(opiate, organophosphate)

    **Optic neuropathy------------->central scotoma.
    Optic tract lesion--------------->incongrous homontmous hemianopia.
    Chiasmal lesion---------------->bitemporal hemianopia.
    optic radiation and occipital lobe---------------->congrous hemianopia.

    **Listeria meningitis is typically associated with brain stem signs. CSF shows neutrophilic pleocytosis, low glucose and high protein.

    **Nystagmus is defind as involuntary oscillations of the eyes.
    THis may be
    1-Pendular: when the oscillations are equal in rate and amplitude.
    2-Jerking: when there are quick and slow phases(the quick phase is used to define the direction).
    pendular nystagmus is usually duee to loss of macular vision, but maybe seen in diffuse brain stem lesions.

    jerking nustagmus which is of constant direction regardless of the direction of gaze, suggests a labyrinthine or cerebellar lesion.

    Nystagmus which changes with the direction of gaze suggests a widspread central involvement of vestibular nuclei.

    Jerking nystagmus present only on lateral gaze, and who's fast component is in the direction of gaze, indicates a lesion of brain stem or cerebellum.

    Nystagmus confined to one eye suggests a peripheral lesion of the nerve or mucsle, or a lesion of the mediallongitudinal bundle.

    Nystagmus restricted to the abducting eye on lateral gaze(ataxic nystagmus) is due to a lesion of the medial longitudinal bundle between the ponds and midbrain as in MS.

    Nystagmus occuring on upward gaze with the fast component upwards( upbeat nystagmus) maybe due to a lesion in the mid-brain at the level of the superior colliculus.

    Downbeat nystagmus(fast phase downward) suggests a lesion in the lower part of the medulla. It's therefore, typical of the Arnold Chiari malformation.

    **Causes of absent ankle reflexes and extensor plantars:
    subacute combined degeneration of the cord
    syphilitic taboparesis
    friedreich's ataxia
    motor neuron disease

    **Bicuspid aortic valve is perhaps the most common form of congenital heart disease in adults(1-2% of population).

    **hyporeflexia is a common clinical sign in patients with hypercalceamia. Biphosphanates inhibit bone resorption and are the first line pharmacological treatment of hypercalceamia of malignancy.

    **Premature epiphysial closure is a classical finding of CAH.

    **Flecainide is the drug most likely to restore sinus rhythm in atrial fibrillation.

    **Lithium can produce Diabetes Insipidus and hypercalceamia.

    **Constrictive pericarditis produces an elevated JVP, with prominent x & y descent.Pulsus paradoxus occurs less frequently than in tamponade.

    **Streptococcus bovis is a normal commensal of the GI tract. However, S.bovis bactereamia and endocarditis has a strong association with GI malignancy.

    **Neisseria meningitidis( Gram negative diplococci)
    Streptocuccus pneumonia(gram positive diplococci)

    Rx:
    gram stain unavailable: cefotaxime+- ampicillin
    g +ve cocci: Cefotaxime +vancomycin( S.pneumonia)
    G +ve bacilli:Ampicillin +gentamicin.(listeria)
    G -ve cocci: Benzyl penicillin.(N.meningitidis)
    G -ve bacilli: Cefotaxime + gentamicin(heamophilus influenza)

    **Anaplastic carcinoma carries the worst prognosis in thyroid cancer followed by thyroid medullary carcinoma in MEN 2B.\

    **ANCA ab are of 2 types:

    1- C-ANCA which correlates with antiproteinase 3 antibodies--->most specific for wegener's granulomatosis.
    2- P-ANCA which correlates with anti myeloperoxidase ab. P-ANCA/MPO ab. are highly sensitive and specific for rapidly progressive glomerulonephritis and haemorrhagic alveolar capillaritis.

    AMA ab--------> PBC
    Anticentromere ab.--------> CREST/scleroderma syndrome
    ANA and anticardiolipin ab.----------->SLE.

    **Clozapine is associated with agranulocytosis in app.1-2% of patients

    **Acute pancreatitis with worse prognosis:
    Age>55
    WCC>16,000
    LDH>600
    AST>120
    Glu>10

    **Pendred's syndrome


    Pendred's syndrome is a rare autosomal recessive condition characterised by incomplete oxidation of trapped iodide prior to organification.

    It may be confirmed by a positive perchlorate discharge test.


    **Anti 21 hydroxylase ab. found in about 80% of cases of addison's disease.

    **SSRIs are a recognised cause of SIADH.

    **Astimulatory mutation of thr Gs protein alpha subunit has been noted in approx.30% of GH secreting pituitary tumours.

    **Carcinoid tumours of the foregut unlike tumours of the midgut are not associated with carcinoid syndrome but may secret CRF/ACTH resulting in ectopic cushing's syndrome.Other associated conditions include somatostatinoma, Zollinger -Ellison syndrome and Acromegaly.

    **The antiphospholipid syn. is one of the commoner causes of hypoadrenalism and may precipitate adrenal infarction and haemorrhage through adrenal vein thrombosis.

    **Osteopenia is defined as a T score of between -1 and -2.5 standard deviation below the bone mineral density of a young female.Osteoporosis is defined as <2.5 SD.

    **bcl-2 is an inhibitor of apoptosis.
    fas and caspases promote apoptosis but are nottumour supressor genes
    p53 is a tumour supressor gene that inhibits mitosis and promotes apoptosis.
    ras is oncogene.

    **Congenital adrenal hyperplasia is autosomal recessive disorder.

    **beta blockers are the mainstay of treatment in long QT interval. The most commonly used drugs are propranolol and nadolol.

    **pulmonary complications of reumatoid arthritis"
    Fibrosing alveolitis
    pleural effusions
    empyema
    cryptogenic organising pneumonia
    bronchiectasis
    pulmonary ndules

    **Fetal alcohol syn., Down's syn., and congenital rubella syn. are ass. with an ASD(Loud 2nd sound plus fixed splitting.

    **VIP
    Achlorhydria
    profuse diarrhea
    hypokalaemic acidosis
    hyperglycaemia

    **Cavitations on pulmonary x ray:
    squamous cell carcinoma
    abscess(staph. aureus, Klebsiella, and pseudomonas aeruginosa0
    lymphoma
    rheumatoid nodule
    pulmonary infarction
    wegener's granolumatosis

    **p-ANCA is present in approx. 70% with UC and less than 20% of Crohn.
    85% of untreated subjects with wegener's will have c-ANCA

    **prerenal failure:
    urinary Na<20
    urine osmolality> 500
    urine/plasma ratio>8and
    urine/plasma creatinine >40\

    Renal failure:
    Na>40
    osmolality urine<350
    U/P ratio<3
    U/P creat.<20

    **Vitamin D resistant rickets is x linked dominant.

    **infection is the commonest cause of death in multiple myeloma.

    **Antimicrosomal antibodies------>Hashimoto's thyroiditis

    **Behchet's disease is associated with HLA B5

    **Venous beading, loops and soft exudates(cotton wool spots) are ccharacteristic of preproliferative retinopathy.

    Microaneurysms, Hard exudates and Macular edema suggests background diabetic retinopathy

    New vessels suggests proliferative retinopathy.

    **Hexosaminidase A deficiency is ass. Tay-Sachs disease
    Sphingomyelinase deficiency ->Nieman-Pick disease
    Arylsulphatase-A Def. ass. with metachromic leucodystrophy
    Iduronidase def. ass. with Hurler's syn.
    B-glucosidase def.--->Gaucher's disease.

    **Methotrexate is a well known cause of acute pneumonitisand interstitial lung disease.

    **Clopidegrol prevent platelet aggregation through antagonism of the ADP receptor.

    **Patients with painful, isolated third nerve palsy with pupillary involvement are assumed to have posterior communicating artery aneurysm until proven otherwise.
  2. Guest

    Guest Guest

    very helpul,doctor.Thanks a lot for the effort. I am posting some more imp topics for benifit of future candidates ,radha


    TOPAMAX has been associated with serious adverse events, including:

    * Hyperchloremic, non-anion gap metabolic acidosis–lowering of bicarbonate levels in the blood. Measurement of baseline and periodic serum bicarbonate is recommended.
    * Acute myopia and secondary angle-closure glaucoma–patients should be cautioned to seek medical attention if they experience blurred vision or ocular pain.
    * Oligohidrosis and hyperthermia–decreased sweating and increased body temperature, especially in hot weather. The majority of reports have been in children.
    * Cognitive/psychiatric side effects, including cognitive dysfunction, psychiatric/behavioral disturbances, and somnolence and fatigue.

    Most common adverse events associated with TOPAMAX 100 mg vs placebo were: paresthesia, 51% vs 6%; anorexia, 15% vs 6%; fatigue, 15% vs 11%; nausea, 13% vs 8%; diarrhea, 11% vs 4%; weight decrease, 9% vs 1%; taste alteration, 8% vs 1%.

    The possibility of decreased contraceptive efficacy and increased breakthrough bleeding should be considered in patients taking combination oral contraceptive products with TOPAMAX.

    Patients should be instructed to maintain an adequate fluid intake in order to minimize the risk of renal stone formation.


    Migraine Headache


    Synonyms and related keywords: complex migraine, migraine equivalent, migraine variant, classic migraine, cluster headache, aura

    Background: Although migraine is a term applied to certain headaches with a vascular quality, overwhelming evidence suggests that migraine is a dominantly inherited disorder characterized by varying degrees of recurrent vascular-quality headache, photophobia, sleep disruption, and depression.


    Pathophysiology: The mechanisms of migraine remain not completely understood. However, the advent of new technologies has allowed formulation of current concepts that may explain parts of the migraine syndrome.

    Vascular theory

    For many years, headache pain during a migraine attack was thought to be a reactive hyperemia in response to vasoconstriction-induced ischemia during aura. This explained the throbbing quality of the headache, its varied localization, and the relief obtained from ergots; however, it did not explain the prodrome and associated features, the efficacy of some drugs used to treat migraines that have no effect on blood vessels, and the fact that most patients do not have an aura.

    Also, intracarotid and single-photon emission computed tomography (SPECT) studies revealed that the headache is dissociated from hyperperfusion at its onset and termination in patients suffering from migraine headache with aura. They also revealed that regional cerebral blood flow (rCBF) decreases in the posterior area of the relevant cerebral hemisphere even before the aura is noted and that headache occurred while rCBF remained decreased; rCBF gradually increased throughout the remainder of the headache phase. No consistent flow changes have been identified in patients suffering from migraine headache without aura, but rCBF remains normal in the majority. However, bilateral decrease in rCBF beginning at the occipital cortex and spreading anteriorly has been reported.

    Cortical spreading depression

    The spread of hypoperfusion propagates at a speed similar to that of cortical spreading depression (CSD) and migraine aura. This suggests not only that CSD is the disturbance resulting in the clinical manifestation of migraine aura but also that this spreading oligemia can be clinically silent (ie, migraine without aura). Perhaps a certain threshold is required to produce symptoms in patients having aura but not in those without aura. CSD with or without clinical manifestation (aura) may be a key trigger for the headache of migraine. Although this question is unsettled, CSD has been postulated to directly excite trigeminovascular afferents by promoting release of nociceptive substances from neocortex into the interstitial space, causing direct firing of the nociceptive stimulus.

    Vasoactive substances and neurotransmitters

    Perivascular nerve activity also results in release of substances such as substance P (SP), neurokinin A (NKA), calcitonin gene-related peptide (CGRP), and nitric oxide (NO), which interact with the blood vessel wall to produce dilatation, protein extravasation, and sterile inflammation, stimulating the trigeminocervical complex as shown by induction of c-fos antigen by positron emission tomography (PET) scan. Information then is relayed to the thalamus and cortex for registering of pain. Involvement of other centers may explain the associated autonomic symptoms and affective aspects of this pain.

    Is the neurologically mediated sterile plasma extravasation the cause of this pain? Neurogenic plasma extravasation is inhibited by 5-HT1 agonists, GABA agonists, neurosteroids, prostaglandin inhibitors, SP antagonists, and the endothelin antagonist bosentan; the latter 2 are ineffective as antimigraine drugs, showing that blockade of neurogenic plasma extravasation is not completely predictive of antimigraine efficacy in humans. Neurogenically induced plasma extravasation may play a role in expression of pain in migraine, but whether this in itself is sufficient to cause pain is not clear; the presence of other stimulators may be required. Also, the pain process needs not only the activation of nociceptors of pain-producing intracranial structures but also reduction in the normal functioning of endogenous pain control pathways that gate the pain.

    Migraine center

    What generates a migraine episode? A potential "migraine center" in the brain stem has been proposed based on findings on PET of persistently elevated rCBF in the brain stem (ie, periaqueductal gray, midbrain reticular formation, locus ceruleus) even after sumatriptan produced resolution of headache and related symptoms in 9 patients who had experienced spontaneous attack of migraine without aura. This increased rCBF was not observed outside of the attack, suggesting that this activation is not due to pain perception or increased activity of the endogenous antinociceptive system.

    That sumatriptan reversed the concomitant increased rCBF in the cerebral cortex but not the brainstem centers suggests dysfunction in the regulation involved in antinociception and vascular control of these centers. Thalamic processing of pain is known to be gated by ascending serotonergic fibers from the dorsal raphe nucleus and from aminergic nuclei in the pontine tegmentum as locus ceruleus and that the latter can alter brain flow and blood-brain barrier permeability. Perhaps when these modulatory controls are timed to dysfunction, the migrainous process ensues.


    Frequency:


    In the US: More than 23 million people in the United States suffer from migraine. This roughly corresponds to 17.6% of females and 6.0% of males.
    Mortality/Morbidity: Headaches may serve as a warning: not all severe headaches are due to migraine; they can be a warning sign of more serious conditions. Headache characteristics that should raise concern include the following:

    Change in character of the headache over the time should raise a red flag. Headaches associated with other neurological signs or symptoms (eg, diplopia, loss of sensation, weakness, ataxia) or those of unusually abrupt onset.
    Headaches that are persistent (especially beyond 72 hours), that first occur after the age of 55 years, or that develop after head injury or major trauma. Headaches that are persistent on one side of the head (persistent one sided throbbing headaches mimicking like migraines: arteriovenous malformation should be excluded with imaging).
    Headaches that are associated with stiff neck or fever
    Headaches without a clear family history of migraine headache
    Race: The prevalence of migraine appears to be lower among African Americans and Asian Americans than among whites.

    Sex:

    Migraine headaches are reported to affect women more than men.
    Approximately 75% of all persons who experience migraines are women.
    Age:

    The prevalence of migraine appears to be similar for boys and girls in the prepubescent years.
    The prevalence of migraine is higher in adolescent girls than in boys of similar age.
    By early adulthood, migraine is 3 times as frequent in women as it is in men.




    CLINICAL Section 3 of 10
    Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Pictures Bibliography



    History: The typical headache of migraine is throbbing or pulsatile. It is initially unilateral and localized in the frontotemporal and ocular area, then builds up over a period of 1-2 hours, progressing posteriorly and becoming diffuse. It typically lasts from several hours to a whole day. Pain intensity is moderate to severe, prompting the patient to remain still as it intensifies even with routine physical activity.

    The attack commonly occurs when the patient is already awake, although it may have already started upon awakening and less commonly may awaken the patient at night.
    Nausea and vomiting usually occur later in the attack in about 80% and 50% of patients, respectively, along with anorexia and food intolerance.
    Some patients have been noted to be pale and clammy, especially if nausea develops.
    Photophobia and/or phonophobia also commonly are associated with the headache.
    The headache usually subsides gradually within a day and after a period of sleep; a majority of patients report being tired and weak afterwards.
    About 60% of people who experience migraines report a prodrome, often occurring hours to days before headache onset. Patients describe a change in mood or behavior that may include psychological, neurological, constitutional, or autonomic features.
    These symptoms may be difficult to diagnose as part of the migraine complex if they occur in isolation from the headache or if they are mild. The prodrome of migraine has yet to receive significant investigational attention.

    Because of the set periodicity of migraine, linkage to the suprachiasmatic nucleus of the hypothalamus that governs circadian rhythm has been proposed. Discovering the central trigger for migraine would help identify better prophylactic agents.
    The migraine aura is a complex of neurological symptoms that may precede or accompany the headache phase or may occur in isolation.

    It usually develops over 5-20 minutes and lasts less than 60 minutes.

    The aura can be visual, sensory, motor, or any combination of these.

    The most characteristic visual aura of migraine is a scintillating scotoma (occurring in about 64% of cases), beginning as a hazy spot from the center of a visual hemifield followed by shimmering light of different patterns expanding peripherally to involve a greater part of the hemifield with scotoma.

    Paresthesias, occurring in 40% of cases, constitute the next most common aura; they are often cheiro-oral with numbness starting in the hand then migrating to the arm and then jumping to involve the face, lips, and tongue.

    As with visual auras, positive symptoms typically are followed by negative symptoms; paresthesias may be followed by numbness.
    Sensory aura rarely occurs in isolation and usually follows visual aura.

    The rate of spread of sensory aura is helpful in distinguishing it from transient ischemic attack (TIA) or a sensory seizure.

    Just as a visual aura spreads across the visual field slowly, the paresthesias may take 10-20 minutes to spread, which is slower than the spread of sensory symptoms of TIA.

    The migrainous aura generally resolves within a few minutes and then is followed by a latent period before the onset of headache, although merging of the 2 also is reported.

    Motor symptoms may occur in 18% of patients and usually are associated with sensory symptoms.

    Motor symptoms often are described as a sense of heaviness of the limbs before a headache but without any true weakness.

    Speech and language disturbances have been reported in 17-20% of patients, commonly associated with upper extremity heaviness or weakness.

    Whether migraine with and without aura (prevalences, 36% and 55%, respectively) represent 2 distinct processes remains debatable; however, the similarities of the prodrome, headache, and resolution phases of the attacks, similarity in therapeutic response, and the fact that 9% of patients experience both suggest that they are the same entity.
    When an aura is not followed by a headache, it is called a migraine equivalent or acephalic migraine. This is reported most commonly in patients older than 40 years who have a history of recurrent headache. Scintillating scotoma has been considered to be diagnostic of migraine even in the absence of a headache; however, paresthesias, weakness, and other transient neurological symptoms are not. In the absence of a prior history of recurrent headache and first occurrence after age 45 years, TIA should be considered and must be investigated fully.

    Although headache is a very common reason for physician visits, the majority of headache complaints are benign in origin. However, migraine with its protean manifestation may simulate or be simulated by primary and secondary headache disorders. Also, it can coexist with a secondary headache disorder. When headache is episodic, recurrent, and with a well-established pattern, a primary headache disorder is likely. Differentiating between migraine, tension-type, and cluster headaches is important, as optimal treatment may differ.
    Any of the following features suggest a secondary headache disorder and warrant further investigation:

    Atypical history or unusual character that does not fulfill the criteria for migraine

    Occurrence of a new, different, or truly "worst" headache

    Change in frequency of episodes or major characteristics of the headache

    Abnormal neurological examination

    Inadequate response to optimal therapy

    When patients are seen shortly after the initial headache and their level of anxiety is such that more than reassurance is needed, further diagnostic studies may be necessary.
    Severe headache of sudden onset is a concern despite its occurrence in primary headache disorders. Typically, migraine is gradual in onset, peaking within 2 hours, although some have abrupt onset; these are termed "crash" migraine and are similar to a "thunderclap" headache.
    Cluster headache also may be sudden and excruciating, but it lasts only 15-180 minutes and is recognized easily if the patient has had previous attacks. Exertional headache builds in intensity over minutes and occurs with sustained physical exertion. Coital headache can develop at the height of orgasm or it may build up through intercourse.
    Despite these possibilities, a ruptured intracranial aneurysm is the primary consideration if the headache is severe with sudden onset and reaches maximum intensity in minutes. The classical presentation of an aneurysmal subarachnoid hemorrhage (SAH) is a severe headache with sudden, explosive onset, stiff neck, photophobia, nausea and vomiting, and possibly alteration of consciousness. An extensive evaluation is indicated in this case, including initial CT scan of the head without contrast. Lumbar puncture (LP) should be considered if CT scan is negative, as 25% of cases are missed by CT.
    The question persists of whether an angiogram should be performed after normal findings of neurological examination, cerebrospinal fluid (CSF) examination, and CT or MRI. In one study, acute severe thunderclap headache comparable to that of SAH without the nuchal rigidity occurred in 6.3% of patients with unruptured aneurysm. Other studies have revealed that in patients with severe thunderclap headache with normal CT and CSF findings, none developed SAH, leading to more confusion. If the CT scan and LP are performed late after symptom onset, so that negative results are unreliable, and if clinical features such as family history or past medical history, classic SAH-like symptoms, or the presence of neurological signs (in particular a third cranial nerve palsy affecting the pupil) suggest that the patient is at risk, such patients probably should undergo angiography if an experienced angiographer is available. In patients with unrevealing studies in whom the diagnosis of aneurysmal SAH is possible but very
    unlikely, MRI and magnetic resonance angiography (MRA) are screening tests, and close follow-up is appropriate if the findings of these tests are negative.
    Another concern is the possibility of a space-occupying lesion mimicking migraine. In a series of 111 patients with primary (34%) or metastatic (66%) brain tumor, headache was reported in 48%; the headache had characteristics similar to migraine in 9% and to tension-type headache in 77%, while the so-called classic brain tumor headache occurred in only 17%. Headache was intermittent in 62%, usually lasting a few hours, and was constant in 36%. It was bilateral in 72% and was moderate to severe in intensity in most patients. All patients with headaches similar to migraine had other neurological symptoms or abnormal signs. Of note is that 32% had history of headache; in 36% of those, the headache was of identical character to prior headaches but was more severe or frequent and was associated with other symptoms such as seizures, confusion, prolonged nausea, and hemiparesis.
    These data indicate that patients with a history of headache should have further diagnostic workup if the headache is accompanied by new symptoms or abnormal signs or differs in any way from their usual headache. With new-onset headache, imaging should be obtained if headache is severe or occurs with nausea, vomiting, or abnormal signs.

    Other space-occupying lesions must be considered in the appropriate clinical setting. Large intraparenchymal hemorrhage presents dramatically with headache and neurological symptoms or signs shortly after onset. Of patients with chronic, subacute, or acute subdural hematoma, 81%, 53%, and 11%, respectively, have headaches. In brain abscesses, a progressive, severe, intractable headache is common, and headache is reported in 70-90% of patients.
    Cerebral venous thrombosis involves the sagittal sinus in about 70% of cases; these patients present with signs and symptoms of increased intracranial pressure (ICP), such as headache and papilledema. Should the thrombus extend to the superficial cortical veins, then focal findings may be noted. In the appropriate setting with known risk factors, cerebral venous thrombosis must be considered and evaluated with MRI, MRA, or magnetic resonance venography (MRV).

    Spontaneous internal carotid artery dissection is an uncommon cause of headache and acute neurological deficit, but it must be considered in the younger individuals who have unilateral, severe, persistent head pain of sudden onset preceding neurological signs, most commonly Horner syndrome, differentiating it from traumatic causes, in which cerebral ischemic symptoms are more common.
    Other secondary causes of alarming headaches should be sought in the presence of the "red flags" mentioned above and must be sought in the appropriate clinical setting. Other features needing further diagnostic workup include positional headaches, which may occur in colloid cysts or other ventricular tumors such as ependymomas, Chiari malformations, and low CSF pressure headache. Headaches after age 50 years must be investigated to consider temporal or giant cell arteritis. Headaches associated with systemic disease require consideration of infectious and non-infectious inflammatory processes.
    Bear in mind that sumatriptan and related compounds, by virtue of being able to block expression of c-fos by their action on 5-HT1 receptors, decrease headaches with diverse pathogenesis. These agents may be effective in decreasing headache pain associated with meningovascular irritation, such as viral and bacterial infections and subarachnoid hemorrhage. Hence, response to 5-HT1 agonists is not diagnostic of a migraine headache.
    Physical:

    Most patients with headache have a normal neurological examination.
    Some abnormal findings suggest a secondary cause, which would necessitate a different diagnostic and treatment approach.
    The presence of papilledema suggests increased ICP and warrants a diagnostic imaging study to rule out a mass lesion.
    Nuchal rigidity due to meningeal irritation is seen with meningitis and subarachnoid or intraparenchymal hemorrhage.
    Causes: See Pathophysiology. DIFFERENTIALS Section 4 of 10
    Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Pictures Bibliography




    Arteriovenous Malformations
    Atypical Facial Pain
    Cerebral Aneurysms
    Childhood Migraine Variants
    Chronic Paroxysmal Hemicrania
    Cluster Headache
    Craniopharyngioma
    Dissection Syndromes
    Glioblastoma Multiforme
    Headache: Pediatric Perspective
    Herpes Simplex Encephalitis
    Intracranial Hemorrhage
    Meningioma
    Meningococcal Meningitis
    Migraine Headache: Pediatric Perspective
    Migraine Variants
    Muscle Contraction Tension Headache
    Oligodendroglioma
    Pituitary Tumors
    Polyarteritis Nodosa
    Postherpetic Neuralgia
    Subarachnoid Hemorrhage
    Systemic Lupus Erythematosus
    Temporal/Giant Cell Arteritis
    Tolosa-Hunt Syndrome
    Viral Encephalitis
    Viral Meningitis



    Other Problems to be Considered:

    Cerebral venous thrombosis



    Migraine Resource Center
    Migraine Resource Center

    View all Migraine Articles

    Migraine CME

    Migraine Multimedia Library




    Quick Find
    Author Information
    Introduction
    Clinical
    Differentials
    Workup
    Treatment
    Medication
    Follow-up
    Pictures
    Bibliography

    Click for related images.

    Related Articles
    Arteriovenous Malformations

    Atypical Facial Pain

    Cerebral Aneurysms

    Childhood Migraine Variants

    Chronic Paroxysmal Hemicrania

    Cluster Headache

    Craniopharyngioma

    Dissection Syndromes

    Glioblastoma Multiforme

    Headache: Pediatric Perspective

    Herpes Simplex Encephalitis

    Intracranial Hemorrhage

    Meningioma

    Meningococcal Meningitis

    Migraine Headache: Pediatric Perspective

    Migraine Variants

    Muscle Contraction Tension Headache

    Oligodendroglioma

    Pituitary Tumors

    Polyarteritis Nodosa

    Postherpetic Neuralgia

    Subarachnoid Hemorrhage

    Systemic Lupus Erythematosus

    Temporal/Giant Cell Arteritis

    Tolosa-Hunt Syndrome

    Viral Encephalitis

    Viral Meningitis




    Continuing Education
    CME available for this topic. Click here to take this CME.


    Patient Education
    Headache Center

    Causes and Treatments of Migraine and Related Headaches

    Migraine Headache Overview

    Migraine Headache Causes

    Migraine Headache Symptoms

    Migraine Headache Treatment

    Alternative and Complementary Approaches to Migraine and Cluster Headaches

    Migraine Headache FAQs

    Understanding Migraine and Cluster Headache Medications


    Lab Studies:


    Diagnostic investigations are performed for the following reasons:
    Exclude structural, metabolic, and other causes of headache that can mimic or coexist with migraine
    Rule out comorbid diseases that could complicate headache and its treatment
    Establish a baseline for treatment and exclude contraindications to drug administration
    Measure drug levels to determine compliance, absorption, or medication overdose
    Imaging Studies:


    Neuroimaging is indicated for any of the following:
    First or worst headache of the patient's life
    Change in frequency, severity, or clinical features of the headache
    Abnormal neurological examination
    Progressive or new daily, persistent headache
    Neurological symptoms that do not meet the criteria for migraine with typical aura or that themselves warrant investigation
    Persistent neurological deficit
    Hemicrania that is always on the same side and associated with contralateral neurological symptoms
    Inadequate response to routine therapy
    Atypical clinical presentation
    Neuroimaging studies that may be appropriate include CT scan and MRI. Other studies such as angiography, MRA, and MRV also may be indicated. See History for more information on selection of imaging studies.
    Procedures:


    Indications for LP include the following:
    First or worst headache of a patient's life
    Severe, rapid-onset, recurrent headache
    Progressive headache
    Atypical chronic intractable headache
    Neuroimaging (CT scan or MRI) should precede LP to rule out a mass lesion and/or increased ICP.

    TREATMENT Section 6 of 10
    Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Pictures Bibliography



    Medical Care: Approach to migraine treatment involves acute (abortive) and preventive (prophylactic) therapy; patients with frequent attacks usually require both. Acute treatment aims to stop or prevent the progression of a headache or reverse a headache that has started. Preventive treatment, which is given even in the absence of a headache, aims to reduce the frequency and severity of the migraine attack, make acute attacks more responsive to abortive therapy, and perhaps also improve the patient's quality of life.

    Numerous abortive medications are used for migraine, and the choice for each patient depends upon the severity of the attacks, associated symptoms such as nausea and vomiting, comorbid problems, and the patient's treatment response. A stratified approach based on the patient's therapeutic needs has been advanced (see Table 1), as has a step-care approach. Simple analgesics alone or in combination with other compounds have provided relief for mild to moderately severe and even at times severe headaches. 5-HT1 agonists and/or opioid analgesics alone or in combination with dopamine antagonists are used for more severe pain. The use of abortive medications must be limited to 2-3 days a week to prevent development of a rebound headache phenomenon.

    Table 1. Abortive Medication Stratification by Severity

    Moderate Severe Extremely Severe
    NSAIDs
    Isometheptene
    Ergotamine
    Naratriptan
    Rizatriptan
    Sumatriptan
    Zolmitriptan
    Almotriptan
    Frovatriptan
    Eletriptan
    Dopamine antagonists Naratriptan
    Rizatriptan
    Sumatriptan (SC,NS)
    Zolmitriptan
    Almotriptan
    Frovatriptan
    Eletriptan
    DHE (NS/IM)
    Ergotamine
    Dopamine antagonists DHE (IV)
    Opioids
    Dopamine antagonists




    Rebound headache has been defined as perpetuation of head pain in chronic headache sufferers secondary to frequent and excessive use of symptomatic medication. Analgesic overuse may be responsible in part for the transformation of episodic migraine or tension-type headache into daily headache and for the perpetuation of the syndrome; however, it is not the absolute cause of transformed migraine or chronic tension-type headache. Although the actual doses and duration of analgesic overuse needed to develop rebound headache have not been defined clearly, the use of abortive medications more than 2 days a week often is cited. Also, no major difference is known among various types of analgesics used in the treatment of headache in producing analgesic rebound headache.

    In some US headache centers, 50-80% of patients with chronic daily headaches reported analgesic overuse. In a survey, 40% of responders reported that 20% of headache patients experience analgesic rebound. The following are clinical features of analgesic rebound:
    Headache occurs daily or near daily

    Occurs in a patient with primary headache disorder who uses immediate relief medications very frequently, often in excessive quantities

    Headache varies in intensity, type, severity, and location from time to time

    Slight physical or intellectual effort bring on headaches; threshold for pain low

    Headache accompanied by asthenia, nausea and other GI symptoms, restlessness, anxiety, irritability, memory problems, difficulty in intellectual concentration, and depression

    Drug-dependent rhythmicity of headaches

    Evidence of tolerance to analgesics over a period of time

    Withdrawal symptoms when taken off the medications abruptly

    Spontaneous improvement of headache on discontinuing the medications

    Concomitant prophylactic medications are relatively ineffective while the patient is consuming excessive amounts of immediate relief medications. Its pathogenesis is not understood clearly, but it may be partly due to a defective mechanism of 5-HT uptake caused by analgesic overuse.
    To facilitate understanding of the mechanisms of action of the various medications, the relationship between serotonin and migraine is reviewed here briefly, as some of these studies partly define the current understanding of migraine. Stimulation of the trigeminal nerve releases SP, CGRP, and NKA from the sensory C-fibers, resulting in neurogenic inflammation that then interacts with the blood vessel wall, producing dilatation, plasma extravasation, and sterile inflammation. Plasma extravasation has been shown to be blocked by ergots, sumatriptan, and the newer 5-HT1B/D agonists, indomethacin, acetylsalicylic acid, GABA agonists such as valproic acid and benzodiazepines, neurosteroids, substance P antagonists, and the endothelin antagonist bosentan.
    Immunohistochemical studies have detected 5-HT1D receptors in trigeminal sensory neurons, including peripheral projections to the dura and within the trigeminal nucleus caudalis (TNC) and solitary tract, while 5-HT1B receptors are present on smooth muscle cells in meningeal vessels; however, both can be found in both tissues to some extent and even in coronary vessels. These findings suggest that sumatriptan and other selective 5-HT1 agonists decrease headache by abolishing neuropeptide release in the periphery and blocking neurotransmission by acting on second-order neurons in the trigeminocervical complex. All the currently available "triptans" are selective 5-HT1B/D full agonists. The major differences among these agents lie in their pharmacokinetic properties, which may affect onset of action (eg, rizatriptan with lesser tmax leading to faster onset), duration of action (eg, naratriptan with longer half-life leading to lower recurrence rate), bioavailability (eg, naratriptan with higher oral bioavailability leading to more consistent response), and CNS penetration (eg, sumatriptan not shown to cross the intact blood-brain barrier).

    GABA-A receptor is suggested to reside on the parasympathetic fibers emanating from the sphenopalatine ganglia, as the effects of valproic acid, benzodiazepines, and steroids are abolished when these projections are sectioned. The possible relationship of dopamine and migraine has been shown by a direct relationship between dopamine concentration and migraine symptomatology and the demonstrated efficacy of dopamine antagonists in the acute treatment of migraine.

    Prophylactic therapy can be considered under the following conditions:
    Two or more attacks each month with significant disability that lasts 3 or more days

    Contraindication to or ineffectiveness of symptomatic medications

    Use of abortive medications more than twice a week

    Migraine variants such as hemiplegic migraine or rare headache attacks producing profound disruption or risk of permanent neurological injury

    Currently, the major prophylactic medications for migraine work via one of the following mechanisms:

    5-HT2 antagonism - Methysergide

    Regulation of voltage-gated ion channels - Calcium channel blockers

    Modulation of central neurotransmitters - Beta-blockers, tricyclic antidepressants

    Enhancing GABAergic inhibition - Valproic acid, gabapentin

    Another notable mechanism is through alteration of neuronal oxidative metabolism by riboflavin and reducing neuronal hyperexcitability by magnesium replacement.
    Like that of abortive medications, the selection of a preventive medication must take into consideration comorbid conditions and side effect profile (see Table 2 and Table 3). Most preventive medications have modest efficacies and have therapeutic gains less than 50% when compared to placebo. The latency between initiation of therapy and onset of positive treatment response can be quite prolonged. Furthermore, the scientific bases for using most of these medications are wanting. Propranolol, timolol, methysergide, and valproic acid have been approved by the US Food and Drug Administration (FDA) in the past, and recently topiramate has also been approved for migraine prophylaxis. Refer to Table 2 and Medication for further information on prophylaxis.
    Table 2. Preventive Drugs

    First line High efficacy Beta-blockers
    Tricyclic antidepressants
    Divalproex
    Topiramate
    Low efficacy Verapamil
    NSAIDs
    SSRIs
    Second line High efficacy Methysergide
    Flunarizine
    MAOIs
    Unproven efficacy Cyproheptadine
    Gabapentin
    Lamotrigine




    Table 3. Preventive Medication for Comorbid Conditions

    Hypertension Beta-blockers
    Angina Beta-blockers
    Stress Beta-blockers
    Depression Tricyclic antidepressants, SSRIs
    Underweight Tricyclic antidepressants
    Epilepsy Valproic acid, Topiramate
    Mania Valproic acid




    Surgical Care: Besides the medical management, surgical treatments have also been tried for the prevention of migraines. Guyuron and colleagues have shown that surgical deactivation of migraine headache trigger sites can help eliminate or significantly reduce the symptoms of migraine.

    Corrugator muscle resection has a much better chance for improvement with the mild form of migraine headache compared with more worse forms as shown by Dirnberger and Becker.

    BOTOX® has been used in multiple trials for the prophylaxis of migraine headaches. Some mixed results have occurred on the use of BOTOX® for the migraine headaches.
    Pericranial injection of 50-U BTX-A has shown good efficacy and tolerability as a prophylactic agent. BOTOX® therapy has been tried for refractory chronic migraine in those who previously have failed to respond to at least 3 prophylactic medications.
    A recent report from Schulte-Mattler and Martinez-Castrillo has shown no evidence for a beneficial effect of botulinum toxin and thus, they have not supported the widespread use of botulinum toxin therapy in headaches.
    Diet:

    A fraction of persons who experience migraines have dietary triggers. Common triggers include chocolate, aged cheeses and meats, wine and beer (ie, sulfites), and citrus fruits.
    Obviously, the avoidance of dietary triggers plays an important role in the treatment of these patients.




    (Advertisement)

    TOPAMAX is contraindicated in patients with a history of hypersensitivity to any component of this product.

    Important Safety Information

    TOPAMAX has been associated with serious adverse events, including:

    Hyperchloremic, non-anion gap metabolic acidosis–lowering of bicarbonate levels in the blood. Measurement of baseline and periodic serum bicarbonate is recommended.
    Acute myopia and secondary angle-closure glaucoma–patients should be cautioned to seek medical attention if they experience blurred vision or ocular pain.
    Oligohidrosis and hyperthermia–decreased sweating and increased body temperature, especially in hot weather. The majority of reports have been in children.
    Cognitive/psychiatric side effects, including cognitive dysfunction, psychiatric/behavioral disturbances, and somnolence and fatigue.
    Most common adverse events associated with TOPAMAX 100 mg vs placebo were: paresthesia, 51% vs 6%; anorexia † , 15% vs 6%; fatigue, 15% vs 11%; nausea, 13% vs 8%; diarrhea, 11% vs 4%; weight decrease, 9% vs 1%; taste alteration, 8% vs 1%.

    The possibility of decreased contraceptive efficacy and increased breakthrough bleeding should be considered in patients taking combination oral contraceptive products with TOPAMAX.

    Patients should be instructed to maintain an adequate fluid intake in order to minimize the risk of renal stone formation.

    †Anorexia is defined as loss of appetite.

    Please review the TOPAMAX full Prescribing Information.

    MEDICATION Section 7 of 10
    Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Pictures Bibliography



    Pharmacologic agents used for the treatment of migraine can be classified as abortive (ie, symptomatic) drugs and prophylactic (ie, preventive) agents.


    Drug Category: Abortive medications/Selective serotonin receptor (5-HT1) agonists -- The following serotonin receptor (5-HT1) agonists/triptans are used as abortive medications for moderately severe to severe migraine headaches.Drug Name
    Sumatriptan (Imitrex); naratriptan (Amerge, Naramig) -- zolmitriptan (Zomig, Zomig-ZMT); rizatriptan (Maxalt, Maxalt-MLT); almotriptan (Axert); frovatriptan (Frova)-- Efficacy of SC sumatriptan is 82% at 20 min, that of inhaled is 62% at 2 h, and that of PO is 60-70% at 4 h.
    Zolmitriptan at initial dose of 2.5 mg PO has efficacy of 62% at 2 h and 75-78% within 4 h.
    Naratriptan at 2.5 mg PO has higher bioavailability and longer half-life than sumatriptan, which may contribute to lower rate of headache recurrences. Pain relief experienced by 60-68% of patients within 4 h of treatment and maintained up to 24 h in 49-67% of patients.
    Rizatriptan 10 mg PO has reported early onset of action (30 min) and efficacy of 71% at 2 h.
    Almotriptan induces cranial vessel constriction, inhibition of neuropeptide release, and reduces pain transmission in trigeminal pathways.
    Frovatriptan possesses long half-life (ie, 26-30 h), thus, decreases recurrence of migraine within 24 h after treatment.
    Eletriptan's onset is within 1 h, and the half-life is 18 h.
    Adult Dose Sumatriptan:
    25-100 mg PO; second dose up to 100 mg may be taken after 2 h; additional doses may be taken at 2-h intervals; not to exceed 300 mg/d
    5-20 mg NS inhaled into 1 nostril; second dose may be given after 2 h if headache returns or if response is partial; not to exceed 40 mg in 24 h
    6 mg SC; not to exceed 2 6-mg injections separated by minimum interval of 1 h
    Zolmitriptan:
    2.5-5 mg PO; if headache returns after initial dose, second dose may be given any time after 2 h of first dose; not to exceed 10 mg/d
    Naratriptan:
    2.5 mg PO; may be repeated after 4 h if headache recurs or if only partial relief with initial dose
    Rizatriptan:
    5-10 mg PO disintegrating tab initially; may be repeated every 2 h; not to exceed 30 mg within 24 h
    Almotriptan:
    6.25-12.5 mg PO at onset of migraine; may repeat once, not to exceed 25 mg/d
    Frovatriptan:
    2.5 mg PO once at onset of migraine attack
    Eletriptan:
    20-40 mg PO at onset of migraine; if initial dose ineffective, may repeat dose once after 2 h; not to exceed 80 mg/d
    Pediatric Dose Sumatriptan:
    Tab: 12.5-25 mg PO prn; not to exceed 100 mg qd
    Nasal spray: 5 mg NS prn
    Injection: 0.02 mg/kg SC prn
    Zolmitriptan: 2.5 mg PO prn; not to exceed 10 mg qd
    Naratriptan: 1 mg PO prn; not to exceed 5 mg qd
    Rizatriptan: 5 mg PO prn; not to exceed 30 mg qd
    Almotriptan: Not established
    Frovatriptan: <18 years: Not established
    >18 years: Administer as in adults
    Eletriptan: <18 years: Not established
    >18 years: Administer as in adults
    Contraindications Documented hypersensitivity; age >65 y; angina or other signs or symptoms of ischemic heart disease or coronary vasospasm; uncontrolled hypertension; stroke of any type; peripheral vascular disease; severe renal or hepatic impairment; concurrent ergotamine-containing preparations or MAOIs; hemiplegic or basilar migraine
    Additionally, for eletriptan: severe hepatic impairment; administration within 72 h of potent CYP450 3A4 inhibitors
    Interactions Theoretical interactions with ergotamine-containing drugs, MAOIs, and SSRIs; propranolol increases plasma concentration of rizatriptan by 70%; concurrent administration with ergot-containing drugs or other 5-HT1 agonists may increase vasospastic reactions
    Eletriptan: Potent CYP450 3A4 inhibitors (eg, ketoconazole, itraconazole, nefazodone, troleandomycin, clarithromycin, ritonavir, nelfinavir) may increase toxicity
    Pregnancy C - Safety for use during pregnancy has not been established.
    Precautions Limited data available concerning use during breastfeeding
    Patients with known or suspected coronary artery disease may have increased risk of myocardial ischemia, infarction, or other cardiac or cerebrovascular events (5-HT1 agonists may cause coronary vasospasm)
    May cause tingling, sensation of heat, dizziness, flushing, sensation of burning, pressure, and heaviness; in patients receiving propranolol, rizatriptan single dose should not exceed 5 mg and total daily dose should not exceed 15 mg in 24 h
    Drug Category: Abortive medications/Ergot alkaloids -- These are nonselective 5-HT1 agonists that have a wider spectrum of receptor affinities outside of the 5-HT1 system, including dopamine receptors. They can be used for the abortive treatment of moderately severe to severe migraine headache.Drug Name
    Ergotamine tartrate (Cafatine, Cafergot, Cafetrate), Dihydroergotamine (DHE-45) -- Counteract episodic dilation of extracranial arteries and arterioles.
    DHE differs from ergotamine tartrate in that it is weaker arterial constrictor, has less emetic and less uterine effects, and is less likely to produce drug-rebound headache. DHE 1 mg IM yielded 72% improvement of symptoms (ie, mild pain or no pain) after 1 h.
    Adult Dose Ergotamine tartrate
    1 mg PO initially; q30min prn; not to exceed 6 mg per attack
    1-2 mg SL initially; q30min prn; not to exceed 6 mg per attack
    1-2 mg PR initially; q30min prn; not to exceed 4 mg per attack
    DHE
    1 spray (0.5 mg) NS inhaled in each nostril, repeated after 15 min; not to exceed 2 mg
    0.5-1 mg IM/SC, repeat dose at 1-h intervals; not to exceed 3 mg
    IV route used when more rapid results desired: 1 mg IV q8h with or without metoclopramide is safe and effective for treatment of status migrainosus
    Pediatric Dose Not established
    Contraindications Documented hypersensitivity; peripheral vascular disease; coronary artery disease; thrombophlebitis; severe hypertension; bradycardia; hepatic or renal impairment; hyperthyroidism; malnutrition; sepsis; pregnancy; breastfeeding; age >60 y
    Interactions Increase effects of heparin; increase toxicity of nitroglycerin, propranolol, erythromycin, vasoconstrictors, 5-HT1 agonists, and clarithromycin
    Pregnancy X - Contraindicated in pregnancy
    Precautions Ergotamine tartrate not recommended for prolonged use and may cause significant rebound headache
    Avoid using prolonged regimens due to danger of causing gangrene as well as dependency
    Drug Category: Abortive medications/analgesics -- These agents are used as initial abortive therapy for patients with infrequent migraines.Drug Name
    Acetaminophen (Tylenol), propoxyphene (Darvon), oxycodone (OxyContin) -- morphine (Duramorph, MS Contin), meperidine (Demerol), hydromorphone (Dilaudid), butorphanol (Stadol)--Used as 'rescue' medications if migraine headache not controlled with standard treatment, or if 5-HT1 agonists contraindicated.
    Acetaminophen (with or without metoclopramide) in particular is the first choice for treatment of migraine attacks during pregnancy and breastfeeding.
    Adult Dose Acetaminophen
    650-1000 mg PO initially, may be repeated after 1-2 h prn
    Propoxyphene
    Propoxyphene HCl: 65 mg PO q4h prn; not to exceed 390 mg/d
    Propoxyphene napsylate: 100 mg PO q4h prn; not to exceed 600 mg/d
    (Propoxyphene napsylate 100 mg = propoxyphene HCl 65 mg)
    Oxycodone
    5 mg PO q6h prn
    Morphine
    10-30 mg PO q4h prn
    5-20 mg/70 kg IM/SC q4h prn
    Meperidine
    50-150 mg PO/IM/SC q3-4h prn
    Hydromorphone
    2-4 mg PO q4-6h prn
    1-4 mg IM/SC q4-6h prn
    Butorphanol
    1 mg NS inhaled into 1 nostril; if sufficient relief not obtained in 60-90 min, give additional 1 mg; repeat initial 2-dose sequence in 3-4 h prn
    Pediatric Dose Acetaminophen: 10 mg/kg/dose PO; not to exceed 720 mg/d (children aged 3-6 y) or 2.6 g/d (children aged 6-12 y)
    Meperidine: 1-1.8 mg/kg PO/IM/SC q3-4h; not to exceed recommended adult dosage
    Other drugs: Not established
    Contraindications Documented hypersensitivity; intracranial lesion associated with impaired intracranial pressure (hydromorphone); recent or concurrent MAOIs; depressed respiration; COPD; cor pulmonale; emphysema; status asthmaticus; kyphoscoliosis
    Interactions Increase CNS depressant properties of other drugs including alcohol, antihistamines, antidepressants, sedative/hypnotics, and MAOIs
    Rifampin can reduce analgesic effects of acetaminophen; coadministration with barbiturates, carbamazepine, hydantoins, and isoniazid may increase acetaminophen hepatotoxicity
    Pregnancy C - Safety for use during pregnancy has not been established.
    Precautions Common adverse effects are dose related and include respiratory depression, sedation, confusion, nausea, vomiting, constipation, urinary retention, multifocal myoclonus, and seizures
    Long-term administration associated with pharmacological effects of tolerance and physical and psychological dependence; limit use to not more than 2 d per wk, except around menses, to prevent drug-induced headache
    Hepatotoxicity possible in chronic alcoholics following various dose levels of acetaminophen; severe or recurrent pain or high or continued fever may indicate a serious illness; acetaminophen is contained in many OTC products and combined use with these products may result in cumulative acetaminophen doses exceeding recommended maximum dose
    Drug Category: Abortive medications/Nonsteroidal anti-inflammatory drugs (NSAIDs) -- Generally used as abortive therapy in mild to moderately severe type of migraine headaches; however, they also may be effective for severe headaches, especially ketorolac.Drug Name
    Aspirin (Bayer Aspirin, Anacin), Ibuprofen (Motrin, Ibuprin) -- naproxen (Naprosyn, Naprelan), ketorolac (Toradol)--Mild analgesics that can be used to treat infrequent migraine episodes.
    Adult Dose Aspirin
    900-1000 mg PO initially; repeat same dose after 1-2 h prn
    Ibuprofen
    400-1200 mg/attack PO; may be repeated at dose of 400-800 mg in 1-2 h; not to exceed 3200 mg/d
    Naproxen sodium
    Up to 825 mg PO initially; may give 550 mg after 1-2 h prn
    Ketorolac
    10 mg PO q4h prn; not to exceed 40 mg/d; limit use to 5 consecutive days
    30-60 mg IM initially; repeat q6h prn; not to exceed 120 mg/d; limit use to 3 consecutive days
    IV administration similar to IM but dose used is 30 mg
    Pediatric Dose Not recommended
    Contraindications Documented hypersensitivity; active peptic ulcer disease; renal or hepatic impairment; concomitant or recent use of anticoagulants; hemophilia or other hemorrhagic conditions
    Interactions Aspirin: Activated charcoal, ammonium chloride, ascorbic acid, methionine, antacids, urinary alkalizers, carbonic anhydrase inhibitors, corticosteroids, nizatidine, alcohol, ACE inhibitors, oral anticoagulants, beta-blockers, heparin, loop diuretics, methotrexate, nitroglycerin, other NSAIDs, probenecid, sulfinpyrazone, spironolactone, sulfonylureas, insulin, valproic acid
    Ibuprofen: ACE inhibitors, anticoagulants, beta-blockers, cimetidine, cyclosporine, digoxin, dipyridamole, hydantoins, lithium, loop diuretics, methotrexate, penicillamine, probenecid, salicylates, sympathomimetics, thiazide diuretics
    Naproxen: Other NSAIDs, anticoagulants, thrombolytic agents, probenecid, glucocorticoids, methotrexate and other antineoplastic agents, cephalosporins, insulin and oral hypoglycemic agents
    Ketorolac: Coadministration with aspirin increases risk of inducing serious NSAID-related adverse effects; probenecid may increase concentrations and, possibly, toxicity of NSAIDs; may decrease effect of hydralazine, captopril, and beta-blockers; may decrease diuretic effects of furosemide and thiazides; may increase PT when taking anticoagulants (instruct patients to watch for signs of bleeding); may increase risk of methotrexate toxicity; phenytoin levels may be increased when administered concurrently
    Pregnancy C - Safety for use during pregnancy has not been established.
    Precautions Aspirin: The elderly may be more susceptible to CNS effects; should not be used in last trimester of pregnancy
    NSAIDs: GI effects such as dyspepsia, nausea, and vomiting are common adverse effects
    Drug Category: Abortive medications/Combination analgesics -- Combination analgesics may be used when simple analgesics are not effective and the patient is not a candidate for treatment with 5-HT1 agonists or when the patient needs an alternative drug.Drug Name
    Butalbital (Fiorinal), Isometheptene and dichloralphenazone (Midrin) -- Combination drugs effective for mild to moderately severe migraine headache.
    Adult Dose Butalbital: 1-2 tab PO q4h prn; not to exceed 6 tabs/d
    Isometheptene and dichloralphenazone: 2 caps PO initially then 1 capsule q1h until symptoms relieved; not to exceed 5 capsules in 12-h period
    Pediatric Dose Butalbital: Not established in patients <12 years
    Isometheptene and dichloralphenazone: Not established
    Contraindications Butalbital: Documented hypersensitivity; porphyria
    Isometheptene and dichloralphenazone: Documented hypersensitivity; glaucoma; severe renal or hepatic impairment or disease; organic heart disease; concomitant MAOIs
    Interactions Butalbital: Effects decreased by coadministration of phenothiazines, quinidine, tricyclic antidepressants, theophylline, haloperidol, chloramphenicol, ethosuximide, corticosteroids, warfarin, doxycycline, and beta-blockers; effects are increased with coadministration of CNS depressants, methylphenidate, valproic acid, propoxyphene, and benzodiazepines
    Isometheptene and dichloralphenazone: Concurrent use of MAOIs with isometheptene may result in severe headache, hypertension and hyperpyrexia, which in turn may result in hypertensive crisis
    Pregnancy C - Safety for use during pregnancy has not been established.
    Precautions Butalbital: Not recommended for prolonged use because of potential for drug dependency; limit use to not more than 2 d per wk, except around menses, to prevent drug-induced headache
    Isometheptene and dichloralphenazone: Use with caution in patients with hypertension, peripheral vascular disease, or recent cardiovascular episodes; safety in pregnancy not known for isometheptene and dichloralphenazone
    Drug Category: Abortive medications/Antiemetics -- As dopamine antagonists, these agents are effective if nausea and vomiting are prominent features and also may act as prokinetics to increase gastric motility and enhance absorption.Drug Name
    Droperidol (Inapsine), chlorpromazine (Thorazine), metoclopramide (Reglan) -- Used alone or in combination with other analgesics as adjuncts, especially if migraine attack associated with significant nausea and vomiting. Its role in migraine based on findings that increased dopamine concentration is associated with prominent migraine symptomatology.
    Adult Dose Droperidol: 2.5-10 mg (alone or with an antihistamine) given IM or slow IV
    Chlorpromazine: 10-25 mg PO q4-6h prn; 50-100 mg PR q6-8h prn; 25-50 mg IM q3-4h; 5-50 mg IV
    Metoclopramide: 10-20 mg PO/IM
    Pediatric Dose Droperidol: 1-1.5 mg/9-11 kg IM for children aged 2-12 y
    Chlorpromazine: 0.55 mg/kg PO/IM q6-8h; not to exceed 75 mg/d for children aged 5-12 y
    Metoclopramide: Not established
    Contraindications Documented hypersensitivity; concurrent drugs that are likely to cause extrapyramidal reactions
    Interactions Anticholinergic drugs, narcotic analgesics, alcohol, sedatives, hypnotics, tranquilizers, MAOIs, and barbiturates
    Pregnancy C - Safety for use during pregnancy has not been established.
    Precautions Sedation, hypotension, tachycardia, extrapyramidal reactions, hyperactivity, anxiety, and dizziness are common adverse effects, which must be given consideration especially for very young and elderly patients
    Metoclopramide classified as category B for use in pregnancy
    Drug Category: Prophylactic therapy/Antiepileptics -- These drugs are effective in prophylaxis of migraine headache.Drug Name
    Divalproex sodium/valproate (Depakote, Depacon, Depakene) -- Topiramate (Topamax)-- Valproic acid: Now considered first-line preventive medication for migraine. Believed to enhance GABA neurotransmission, which may suppress events related to migraine that occur in cortex, perivascular sympathetics, or trigeminal nucleus caudalis. Has been shown to reduce migraine frequency by 50%.
    Topiramate: Indicated for migraine headache prophylaxis. Precise mechanism unknown, but the following properties may contribute to its efficacy: (1) electrophysiological and biochemical evidence showing blockage of voltage-dependent sodium channels, (2) augments activity of the neurotransmitter GABA at some GABA-A receptor subtypes, (3) antagonizes AMPA/kainate subtype of the glutamate receptor, and (4) inhibits the carbonic anhydrase enzyme, particularly isozymes II and IV.

    Adult Dose Valproic acid: 125-250 mg/d PO initially; titrate dose prn; not to exceed 1500 mg/d; doses higher than 250 mg/d should be divided bid
    Topiramate: Slowly titrateupward at a minimum of 1-wk
    intervals as follows:
    Week 1: 25 mg PO qhs
    Week 2: 25 mg PO bid
    Week 3: 25 mg PO every am
    and 50 mg PO qhs
    Week 4: 50 mg PO bid

    Pediatric Dose Valproic acid: Limit use in children <10 y because of increased risk of fatal hepatotoxicity
    Topiramate: Not established
    Contraindications Valproic acid: Documented hypersensitivity; children aged <10 y (because of risk of fatal hepatotoxicity); hepatic disease; thrombocytopenia
    Topiramate: Documented hypersensitivity
    Interactions Valproic acid: Coadministration with cimetidine, salicylates, felbamate, and erythromycin may increase toxicity; rifampin may significantly reduce valproate levels; in pediatric patients, protein binding and metabolism of valproate decrease when taken concomitantly with salicylates; coadministration with carbamazepine may result in variable changes of carbamazepine concentrations with possible loss of seizure control; valproate may increase diazepam and ethosuximide toxicity (monitor closely); valproate may increase phenobarbital and phenytoin levels while either one may decrease valproate levels; valproate may displace warfarin from protein binding sites (monitor coagulation tests); may increase zidovudine levels in HIV seropositive patients
    Topiramate: Phenytoin, carbamazepine, and valproic acid can significantly decrease topiramate levels; topiramate reduces digoxin and norethindrone levels, when administered concomitantly; concomitant use with carbonic anhydrase inhibitors may increase risk of renal stone formation and should be avoided; use topiramate with extreme caution when administering concurrently with CNS depressants since may have an additive effect in CNS depression, as well as other cognitive or neuropsychiatric adverse events

    Pregnancy D - Unsafe in pregnancy
    Precautions Valproic acid: Common adverse effects include nausea and/or vomiting and indigestion, which are usually self-limited; tremor, hair loss, weight gain, and hepatic toxicity also have been reported; periodic clinical assessment and occasional blood tests to evaluate hematopoietic, renal, and hepatic systems should accompany prolonged therapy
    Topiramate: Risk of developing a kidney stone formation is increased 2-4 times that of untreated population; risk may be reduced by increasing fluid intake; caution in renal or hepatic impairment; patients taking topiramate should seek immediate medical attention if they experience blurred vision or periorbital pain; continued usage after symptoms develop, can lead to glaucoma; primary treatment is discontinuation of topiramate; if left untreated, serious sequelae, including permanent vision loss, may occur; oligohidrosis and hyperthermia has been reported predominantly in children during vigorous exercise or exposure to warm environmental temperatures (ensure proper hydration prior and during activity and warm temperatures); may cause hyperchloremic, nonanion gap metabolic acidosis acute or chronic metabolic acidosis resulting in hyperventilation, and nonspecific symptoms, such as fatigue and anorexia, or more severe adverse effects including cardiac arrhythmias or stupor; chronic, untreated metabolicacidosis may increase nephrolithiasis or nephrocalcinosis risk, osteomalacia (ie, rickets in pediatric patients), or osteoporosis with an increased risk for bone fractures; chronic metabolic acidosis in pediatric patients may also reduce growth rates; measure baseline and periodic serum bicarbonate; sprinkle cap should be swallowed whole, or carefully open cap and sprinkle contents on soft food immediately before ingestion, do not chew or crush

    Drug Name
    Gabapentin (Neurontin) -- Initial open study showed efficacy in migraine and transformed migraine. Randomized, double-blind, placebo-controlled trial showed lower migraine headache rate in gabapentin group than in placebo group; more patients in gabapentin group had >50% reduction in frequency.
    Adult Dose 300 mg PO tid; titrate gradually prn; not to exceed 2400 mg/d
    Pediatric Dose <12 years: Not established
    >12 years: Administer as in adults
    Contraindications Documented hypersensitivity
    Interactions Antacids may significantly reduce bioavailability of gabapentin (administer at least 2 h following antacids); may increase norethindrone levels significantly
    Pregnancy C - Safety for use during pregnancy has not been established.
    Precautions Somnolence, fatigue, dizziness, and coordination problems reported
    Drug Category: Prophylactic therapy/Beta-blockers -- Propranolol and timolol are both FDA-approved prophylactic agents, but propranolol has more scientific evidence of efficacy than timolol. Atenolol, metoprolol, and nadolol are not FDA-approved preventive agents. Significant to their activity as migraine prophylactic agents is the lack of partial agonistic activity. Latency from initial treatment to therapeutic results may be as long as 2 months.Drug Name
    Propranolol (Inderal), timolol (Blocadren), nadolol (Corgard) -- atenolol (Tenormin)-- Are effective in prophylactic therapy possibly by blocking vasodilators, decreasing platelet adhesiveness and aggregation, stabilizing the membrane, and increasing the release of oxygen to tissues.
    Adult Dose Propranolol: Start with low dose, 60 mg PO qd (sustained release) or 40 mg in divided doses; titrate prn; not to exceed 320 mg/d
    Timolol: 10 mg/d PO initially; titrate prn; not to exceed 30 mg/d
    Nadolol: 20 mg/d PO qd initially; titrate prn; not to exceed 240 mg/d
    Atenolol: 50 mg/d PO qd initially; titrate prn; not to exceed 200 mg/d
    Metoprolol: 50 mg PO qd or bid initially; titrate prn; not to exceed 200 mg/d
    Pediatric Dose Only propranolol has been used for children
    0.5 mg/kg PO bid initially; may be increased every 3-5 d; not to exceed 1 mg/kg bid
    Contraindications Documented hypersensitivity; asthma; COPD; CHF; partial or complete AV conduction defects; Raynaud disease; peripheral vascular disease; brittle diabetes; severe depression
    Interactions Decreases effect of diuretics and increases toxicity of methotrexate, lithium, and salicylates; may diminish reflex tachycardia, resulting from nitroglycerin use, without interfering with hypotensive effects; cimetidine may increase labetalol blood levels; glutethimide may decrease labetalol effects by inducing microsomal enzymes
    Pregnancy C - Safety for use during pregnancy has not been established.
    Precautions May cause bradycardia, dizziness, nausea, fatigue, depression, memory disturbance, impotence, and diminished exercise tolerance; caution in impaired hepatic function; discontinue therapy if there are signs of liver dysfunction; in elderly patients, a lower response rate and higher incidence of toxicity may be observed
    Drug Category: Prophylactic therapy/Tricyclic antidepressants -- Amitriptyline, nortriptyline, doxepin, and protriptyline have been used for migraine prophylaxis, but only amitriptyline has proven efficacy and appears to exert its antimigraine effect independent of its effect on depression.Drug Name
    Amitriptyline (Elavil), doxepin (Adapin), nortriptyline (Aventyl) -- protriptyline (Vivactil) -- Migraine prophylaxis that is effective (independent of antidepressant effect). Mechanism of action is unknown. Inhibits activity of such diverse agents as histamine, 5-HT, and acetylcholine.
    Adult Dose Amitriptyline, doxepin, nortriptyline: 10-25 mg PO qhs initially; increase by 10-25 mg q1-2wk based on efficacy and tolerance; not to exceed 150-175 mg/d
    Protriptyline: 15 mg/d PO initially; titrate prn; not to exceed 40 mg/d given tid or qid
    Pediatric Dose <12 years: Not recommended
    >12 years: Administer as in adults
    Contraindications Documented hypersensitivity; pregnancy or lactation; narrow-angle glaucoma; urinary retention; cardiac arrhythmias or defects in bundle-branch conduction; concomitant MAOIs
    Interactions Phenobarbital may decrease effects; coadministration with CYP2D6 enzyme system inhibitors (eg, cimetidine, quinidine) may increase tricyclic antidepressant levels; tricyclic antidepressants inhibit hypotensive effects of guanethidine; may interact with thyroid medications, alcohol, CNS depressants, barbiturates, and disulfiram
    Pregnancy D - Unsafe in pregnancy
    Precautions Concurrent MAOIs may cause hypertension, hyperpyrexia, seizures, and death—should not be given within 2 wk of using MAOIs
    Adverse effects are dose related and include sedation, agitation, tremor, seizures, anticholinergic effects such as dry mouth, constipation, delayed micturition, blurred vision, increased appetite with weight gain, decreased libido, and excessive sweating
    Drug Category: Prophylactic therapy/Calcium channel blockers -- This group is commonly used as prophylactic medication, although studies of their effectiveness have shown mixed results. Flunarizine has the best-documented efficacy but is not available in the United States. The efficacy of verapamil is supported by studies.

    This group is particularly useful in patients with comorbid hypertension and in those with contraindications to beta-blockers such as asthma and Raynaud disease. This group may have particular advantage in patients with prolonged aura, vertebrobasilar migraine, or hemiplegic migraine.Drug Name
    Verapamil (Calan, Covera) -- During depolarization, inhibits calcium ion from entering slow channels or voltage-sensitive areas of vascular smooth muscle.
    Adult Dose 120 mg/d PO qd (sustained release) initially or 40 mg tid; increase gradually; not to exceed 480 mg/d
    Pediatric Dose Not established
    Contraindications Documented hypersensitivity; bradycardia; second-and third-degree heart block; sick-sinus syndrome; concomitant beta-blockers
    Interactions Phenobarbital may decrease effects; coadministration with CYP2D6 enzyme system inhibitors (e.g., cimetidine and quinidine) may increase tricyclic antidepressant levels; amitriptyline inhibits hypotensive effects of guanethidine; may interact with thyroid medications, alcohol, CNS depressants, barbiturates, and disulfiram
    Pregnancy C - Safety for use during pregnancy has not been established.
    Precautions Patients may report an initial increase in headache, which improves after weeks of treatment; hypotension and dizziness also reported secondary to vasodilatation; increase in peripheral edema may be associated with nifedipine and decrease with nimodipine and verapamil
    Drug Category: Prophylactic therapy/Selective serotonin reuptake inhibitors -- These may be considered first-line drugs, but they have low efficacy.Drug Name
    Fluoxetine (Protac), Sertraline (Zoloft), Paroxetine (Paxil) -- Fluoxetine has been shown by anecdotal reports and small, double-blind, placebo-controlled study to be of benefit in migraine prophylaxis. Atypical, nontricyclic antidepressant with potent specific 5-HT-uptake inhibition with fewer anticholinergic and cardiovascular side effects than TCAs.
    Adult Dose Fluoxetine: 10 mg/d PO on waking initially; can be increased every 2 wk; not to exceed 60 mg/d
    Sertraline: 50 mg/d PO initially; increase at weekly interval over several wk; not to exceed 200 mg/d
    Paroxetine: 10 mg/d PO initially; titrate prn; not to exceed 50 mg/d
    Pediatric Dose Not established
    Contraindications Documented hypersensitivity; pregnancy and lactation; severe renal or hepatic disease
    Interactions Increases toxicity of MAO inhibitors, diazepam, tolbutamide, and warfarin; serotonin syndrome (ie, myoclonus, rigidity, confusion, nausea, hyperthermia, autonomic instability, coma, eventual death) occurs with simultaneous use of other serotonergic agents (eg, anorectic agents, tramadol, buspirone, trazodone, clomipramine, nefazodone, tryptophan), discontinue other serotonergic agents at least 2
  3. Guest

    Guest Guest

    Sleep Disorders

    Sleep Disorders

    Synonyms and related keywords: sleep disorders, primary sleep disorders, disorders of initiating and maintaining sleep, DIMS, dyssomnias, insomnia, parasomnias, sleep-wake cycle disturbances, sleep apnea, obstructive sleep apnea, OSA, REM sleep, non-REM sleep, polysomnography, sleep maintenance, sleep onset, circadian rhythm, circadian cycle, nightmare, sleepwalk, sleepwalking, hypersomnia, narcolepsy, somnambulism


    Background: Sleep disorders are among the most common clinical problems encountered in medicine, including in Psychiatry . The Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, Text Revision (DSM-IV-TR) divides all sleep disorders into 3 general groups: primary, secondary to a mental disorder, and others, namely those related to a general medical condition or substance abuse.

    Primary sleep disorders are presumed to result from an endogenous disturbance in sleep-wake generating or timing mechanisms, often complicated by behavioral conditioning. Primary sleep disorders are further subdivided into parasomnias and dyssomnias. Parasomnias are characterized by abnormal behavioral or physiological events in association with sleep, sleep stages, or sleep-wake transitions, rather than increased or decreased sleep. Parasomnias include nightmare disorder, sleep terror disorder, and sleepwalking disorder. Dyssomnias are characterized by abnormalities in the amount, quality, or timing of sleep. These include primary insomnia and hypersomnia, narcolepsy, breathing-related sleep disorder (ie, sleep apnea), and circadian rhythm sleep disorder. This article focuses primarily on insomnia, rather than the numerous other sleep disorders.

    Primary insomnia is the general term for difficulty in initiating or maintaining sleep. Because sleep requirements vary from individual to individual, insomnia is considered clinically significant when a patient perceives the loss of sleep as a problem. Insomnia may be characterized further as acute (transient) or chronic.


    Pathophysiology:


    Rapid eye movement and nonrapid eye movement

    Sleep is divided into 2 categories, rapid eye movement (REM) and nonrapid eye movement (NREM). Each of these sleep states is associated with distinct central nervous system activity.

    NREM sleep is further divided into 4 progressive categories, termed stages 1-4 sleep. The arousal threshold rises with each stage of sleep, with stage 4 (delta) being the sleep state from which a person is least able to be aroused, characterized by high-amplitude slow waves.

    REM sleep is characterized by muscle atonia, episodic REMs, and low-amplitude fast waves on electroencephalogram (EEG) readings. Dreaming occurs mainly during REM sleep.

    Disturbances in the pattern and periodicity of REM and NREM sleep are often found when people aver to experiencing sleep disorders.

    Sleep-wake cycles

    Sleep-wake cycles are governed by a complex group of biological processes that serve as internal clocks.

    The suprachiasmatic nucleus, located in the hypothalamus, is thought to be the body's anatomic timekeeper, responsible for the release of melatonin on a 25-hour cycle.

    The pineal gland secretes less melatonin when exposed to bright light; therefore, the level of this chemical is lowest during the daytime hours of wakefulness.

    Multiple neurotransmitters are thought to play a role in sleep. These include serotonin from the dorsal raphe nucleus, norepinephrine contained in neurons with cell bodies in the locus ceruleus, and acetylcholine from the pontine reticular formation. Dopamine, on the other hand, is associated with wakefulness.

    Abnormalities in the delicate balance of all of these chemical messenger systems may disrupt various physiologic, biologic, behavioral, and EEG parameters responsible for REM (ie, active) sleep and NREM (slow-wave) sleep.


    Frequency:


    In the US: Approximately one third of all Americans have sleep disorders at some point in their lives. Approximately 20-40% of adults report difficulty sleeping at some point each year. Approximately 17% of adults consider the problem to be serious. Sleep disorders are a common reason for patient visits throughout medicine. Approximately one third of adults have insufficient sleep syndrome. Twenty percent of adults report chronic insomnia.
    Mortality/Morbidity:

    Chronic insomnia is associated with an increased risk of depression and accompanying danger of suicide, anxiety, excess disability, reduced quality of life, and increased use of health care resources.
    Insufficient sleep can result in industrial and motor vehicle crashes, somatic symptoms, cognitive dysfunction, depression, and decrements in daytime work performance owing to fatigue or sleepiness.
    Sex:

    Primary insomnia is more common in women, with a female-to-male ratio of 3:2. Hormonal variations during the menstrual cycle or during menopause may cause disruptions in sleep.
    Obstructive sleep apnea is more common in men (4%) than in women (2.5%).
    Age:

    Increasing age predisposes to sleep disorders (5% in persons aged 30-50 y and 30% in those aged 50 y or older).
    People who are elderly experience a decrease in total sleep time, with more frequent awakenings during the night.
    People who are elderly have a higher incidence of general medical conditions and are more likely to be taking medications that cause sleep disruption.




    CLINICAL Section 3 of 10
    Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography



    History: Insomnia may present as decreased sleep efficiency or decreased total hours of sleep, with some associated decrease in productivity or well-being. Sleep quality is more important than the total number of hours slept because sleep requirements vary from person to person. Compare the total number of hours slept with each individual's lifelong normal night sleep time.

    Initial insomnia is characterized by difficulty falling asleep, with increased sleep latency (time between going to bed and falling asleep). Initial insomnia is frequently related to anxiety disorders.
    Middle insomnia refers to difficulty maintaining sleep. Decreased sleep efficiency is present, with fragmented unrestful sleep and frequent waking during the night. Middle insomnia may be associated with medical illness, pain syndromes, or depression.
    In terminal insomnia, also referred to as early morning wakening, patients consistently wake up earlier than needed. This symptom is frequently associated with major depression.
    Alterations of the sleep-wake cycle may be a sign of circadian rhythm disturbances, such as those caused by jet lag and shift work.
    Hypersomnia, or excessive daytime sleepiness, is often attributable to ongoing sleep deprivation or poor quality sleep for reasons ranging from sleep apnea to substance abuse or medical problems.
    In delayed sleep phase syndrome, the patient is unable to fall asleep until very early morning. As time progresses, the onset of sleep becomes progressively delayed.
    Sleepwalking, also called somnambulism, refers to episodes of complex behaviors during NREM sleep (stages 3 and 4) of which the patient is amnestic afterward.
    Nightmares are repeated awakenings from sleep caused by vivid and distressing recall of dreams. Nightmares usually occur during the second half of the sleep period. Upon wakening from the dream, the person rapidly reorients to time and place.
    Night terrors are recurrent episodes of abrupt awakening from sleep characterized by a panicky scream, with intense fear and autonomic arousal. The individual usually has no recall of the details of the event and is unresponsive during the episode. Night terrors occur during the first third of the night, during stages 3 and 4 of NREM sleep.
    The bed partner of patients who snore may provide a history of snoring. Such a history may help identify whether a patient experiences obstructive sleep apnea.
    Causes: The major causes of insomnia may be divided into medical conditions, psychological conditions, and environmental problems.

    Medical conditions
    Cardiac conditions include ischemia and congestive heart failure.
    Neurologic conditions include stroke, degenerative conditions, dementia, peripheral nerve damage, myoclonic jerks, restless leg syndrome, hypnic jerk, and central sleep apnea.
    Endocrine conditions affecting sleep are related to hyperthyroidism, menopause, the menstrual cycle, pregnancy, and hypogonadism in elderly men.
    Pulmonary conditions include chronic obstructive pulmonary disease, asthma, central alveolar hypoventilation (the Ondine curse), and obstructive sleep apnea syndrome (associated with snoring).
    Gastrointestinal conditions include gastroesophageal reflux disease.
    Hematological conditions include paroxysmal nocturnal hemoglobinuria, which is a rare, acquired, hemolytic anemia associated with brownish-red morning urine.
    Substances that may result in insomnia include stimulants, opioids, caffeine, and alcohol, or, withdrawal from any of these also may cause insomnia.
    Medications implicated in insomnia include decongestants, corticosteroids, and bronchodilators.
    Other conditions include fever, pain, and infection.
    Psychiatric conditions: Bear in mind that the major psychiatric conditions now are known to have a biological basis and constitute a subset of medical conditions.
    Depression may cause alterations in REM sleep. As many as 40% of people with depression have insomnia.

    Posttraumatic stress disorder (PTSD) can produce vivid and terrifying nightmares.
    Anxiety disorders predispose to insomnia. The most common of these are generalized anxiety disorder, panic disorder, and anxiety disorders not otherwise specified.
    Thought disorders and misperception of sleep state are other potential states that cause insomnia.
    Psychotropic medications, such as antidepressants, may interfere with normal REM sleep patterns.
    Rebound insomnia from benzodiazepines or other hypnotic agents is common.
    Environmental problems
    Stressful or life-threatening events (eg, bereavement, PTSD) may cause insomnia.
    Shift work may disturb the sleep cycle, as might jet lag or changes in altitude.
    Sleep deprivation may occur as a result of an overly warm sleeping environment, environmental noise, or frequent intrusions (such as in an intensive care unit setting).
    DIFFERENTIALS Section 4 of 10
    Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography



    Alcoholism
    Anxiety Disorders
    Bipolar Affective Disorder
    Breathing-Related Sleep Disorder
    Chronic Obstructive Pulmonary Disease
    Depression
    Emphysema
    Hyperthyroidism
    Hypoparathyroidism
    Obstructive Sleep Apnea-Hypopnea Syndrome
    Opioid Abuse
    Posttraumatic Stress Disorder



    Other Problems to be Considered:

    Stimulant abuse (eg, amphetamine abuse)



    Sleep Disorders Learning Center
    Sleep Disorders Learning Center

    View all Sleep Disorders Articles

    Sleep Disorders CME

    Sleep Disorders Multimedia Library




    Quick Find
    Author Information
    Introduction
    Clinical
    Differentials
    Workup
    Treatment
    Medication
    Follow-up
    Miscellaneous
    Bibliography

    Click for related images.

    Related Articles
    Alcoholism

    Anxiety Disorders

    Bipolar Affective Disorder

    Breathing-Related Sleep Disorder

    Chronic Obstructive Pulmonary Disease

    Depression

    Emphysema

    Hyperthyroidism

    Hypoparathyroidism

    Obstructive Sleep Apnea-Hypopnea Syndrome

    Opioid Abuse

    Posttraumatic Stress Disorder




    Continuing Education
    CME available for this topic. Click here to take this CME.


    Patient Education
    Mental Health and Behavior Center

    Sleep Disorders Center

    Disorders That Disrupt Sleep (Parasomnias) Overview

    Insomnia Overview

    Primary Insomnia Overview

    REM Sleep Disorder Overview

    Understanding Insomnia Medications

    Sleep Disorders in Women Overview

    Sleep Disorders and Aging Overview

    Sleeplessness and Circadian Rhythm Disorder Overview









    WORKUP Section 5 of 10
    Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography




    Lab Studies:


    Hemoglobin and hematocrit
    Arterial blood gases
    Thyroid function tests
    Drug and alcohol toxicology screening
    Imaging Studies:


    Although no imaging studies are indicated directly for the workup of insomnia, underlying medical conditions require appropriate investigation using suitable studies.
    Other Tests:


    Oximetry may be performed during sleep to examine blood oxygen levels for clinically important desaturations suggestive of sleep apnea or other sleep-disordered breathing.
    A Beck Depression Index or similar clinical screening tool may be used to detect an underlying depressive illness as a contributing factor in insomnia.
    An Epworth Sleepiness Score or other objective measure of daytime sleepiness may lead to clues of another underlying sleep disorder. For example, approximately 20% of patients with sleep apnea present with a history of nighttime insomnia; however, patients are excessively sleepy by day and have an abnormal score on the Epworth Sleepiness Scale.
    Procedures:


    Subjective measures of sleep are obtained by means of a sleep journal.
    A sleep journal kept for approximately 2 weeks may help determine the extent of the sleep disturbance.
    Patients should record the total hours slept per night, frequency of nighttime awakenings, and level of restfulness provided after sleep.
    Further objective history might be available if patients have a sleep partner who keeps a 2-week journal or provides history.
    Objective measures of sleep may be obtained using EEG monitoring or polysomnography.
    Monitored polysomnography is the criterion standard for evaluating measures of sleep. This study includes measures of multiple channels of electroencephalogram (EEG), electrooculogram (EOG), chin and leg electromyogram, nasal and oral airflow, oximetry, abdominal and chest movements, and ECG. Monitored polysomnography can help the physician discriminate between REM and NREM sleep, as well as causes of sleep arousal.
    Polysomnogram may be useful in determining the etiology of the sleep disturbance.
    These studies may be helpful in determining sleep and wakefulness in the intensive care unit or in the sleep laboratory.
    Patients with chronic medical conditions, such as fibromyalgia or anxiety disorders, often have characteristic alpha brain-wave activity that intrudes into the deeper stages of sleep. This activity can readily be seen on the EEG during the polysomnogram (PSG).
    Patients with insomnia often have some degree of sleep-state misperception, wherein they perceive and believe that they achieve significantly less sleep than they actually do. This can be documented by correlating the EEG findings from the PSG with patient subjective reports of sleep duration and onset.
    TREATMENT Section 6 of 10
    Author Information Introduction Clinical Differentials Workup Treatment Medication Follow-up Miscellaneous Bibliography



    Medical Care: Evaluate patients for other primary sleep disorders (eg, sleep apnea) and for underlying medical, psychiatric, and substance abuse disorders, and institute appropriate treatment. Sleep hygiene and behavioral strategies are used in combination with medication to treat insomnia, particularly primary insomnia.

    Educating the patient on good sleep practices is essential for the effective treatment of insomnia. Cognitive behavior therapy (CBT) targeted at debunking myths and misconceptions about sleep and sleep loss has been proven to be as effective as pharmacotherapy in the treatment of acute insomnia.
    Use the bed for sleep and sex only (no television watching or reading in bed).
    Do not watch the clock while in bed. Practice relaxation techniques before bedtime. Avoid stimulating activities during the 3 hours before bedtime, such as heavy exercise, tense or thrilling reading or television, or arguments.
    Maintain a regular schedule for bedtime and wakening; avoid naps. Early to rise and early to bed is the most effective schedule. A "night owl" schedule is poor sleep hygiene.
    Avoid struggling to fall asleep in bed. Instead, get up and spend quiet time out of bed until sleep comes.
    Light-phase shift therapy is useful for sleep disturbances associated with circadian rhythm abnormalities. Patients may be exposed to bright light, from either a light box or natural sunlight, to help normalize the sleep schedule.
    Surgical Care: Surgical referral may be indicated to correct some underlying medical conditions that cause insomnia, such as for palate surgery in some cases of sleep apnea.

    Consultations: Consultation can help evaluate patients for medical (including psychiatric) causes of insomnia. The evaluation team optimally should include a psychiatrist, neurologist, pulmonologist, sleep medicine specialist, and dietitian.

    Diet:

    No special diet is needed to treat insomnia, but large meals and spicy foods should be avoided in the 3 hours before bedtime.
    Patients should avoid sleep-disturbing substances such as alcohol, nicotine, and caffeine. Alcohol creates the illusion of good sleep, but sleep architecture is affected adversely. Nicotine and caffeine are stimulating and should be avoided in the second half of the day, from late afternoon on.
    Consumption of tryptophan-containing foods may help induce sleep. The classic example is warm milk.
    Activity:

    Strenuous exercise during the day may promote better sleep, but this same exercise during the 3 hours before bedtime can cause initial insomnia.
    Stimulating activities should be avoided 3 hours before bedtime. Examples include tense movies, exciting novels, thrilling television shows, arguments, and vigorous physical exercise
  4. Guest

    Guest Guest

    execuse me but u mentionned that Long-term haemodialysis is associated with carpal tunnel syndrome. is the most common complication
    could you explain me how ???
  5. sawsan s

    sawsan s Guest

    it can be due to the shunt or amyloidosis
  6. Nath

    Nath Guest

    hi
    its mainly because of the deposition of beta 2 amyloid in the carpal tunnel

    cheers
  7. Guest

    Guest Guest

    THANKS A LOT FOR THIS WONDERFUL EFFORT
  8. Guest

    Guest Guest

    thanks a lot for this painful task.
  9. Guest

    Guest Guest

    thank you very much
  10. Guest

    Guest Guest

    thanx alot
  11. Guest

    Guest Guest

    very helpfull facts

    thankyou very much :)

Share This Page