<style> .reveal { font-size:32px; } </style> ###### 大哈讀書會 # Headache ### PGY 林協霆 --- ### Outline * GENERAL PRINCIPLES * ANATOMY AND PHYSIOLOGY OF :exploding_head: * CLINICAL EVALUATION OF ACUTE, NEW-ONSET :exploding_head: * SECONDARY :exploding_head: * PRIMARY :exploding_head: DISORDERS * CHRONIC DAILY OR NEAR-DAILY :exploding_head: * APPROACH TO THE :mask: * PRIMARY CARE AND :exploding_head: MANAGEMENT --- ### GENERAL PRINCIPLES ##### A classification system developed by the International Headache Society (www.ihs-:exploding_head:.org/ichd-guidelines) characterizes :exploding_head: as primary or secondary (Table 13-1).  --- ### Primary vs Secondary * Primary : disorder itself * Secondary :exploding_head: : exogenous disorders * Primary: considerable disability and a decrease in quality of life. * Mild secondary :exploding_head:, 如 upper respiratory tract infections, :point_right: common but rarely worrisome. * Life-threatening :exploding_head: :point_right: rela-tively uncommon, but vigilance :point_right: recognize and appropriately treat --- ### ANATOMY AND PHYSIOLOGY OF :exploding_head: ##### Pain usually occurs when peripheral nociceptors :point_right: stimulated in response to tissue injury, visceral distension, or other factors (Chap 10). * pain perception :point_right: normal physiologic response * pain-producing pathways of the peripheral or central nervous system (CNS) :point_right: damaged or activated inappropriately. --- ### Relatively few cranial structures :point_right: pain-producing; * scalp, meningeal arteries, dural sinuses, falx cerebri, and proximal segments of the large pial arteries. * The ventricular ependyma, choroid plexus, pial veins, and much of the brain parenchyma :point_right: not pain-producing. --- ### The key structures involved in primary :exploding_head: appear to be the following: * ==large intracranial vessels== and ==dura mater== and ==the peripheral terminals of the CN5== that innervate * ==caudal portion of the CN5== :point_right: extends into the dorsal horns of the upper cervical spinal cord :heavy_plus_sign: receives input from the first and second cervical nerve roots (the trigeminocervical complex) * ==Rostral pain-processing regions==, 如 the ventroposteromedial thalamus and the cortex * ==pain-modulatory systems== in the brain that modulate input from trigeminal nociceptors at all levels of the pain-processing pathways :heavy_plus_sign: influence vegetative functions, 如 hypothalamus :heavy_plus_sign: brainstem structures ---  --- * The innervation of the large intracranial vessels and dura mater by the trigeminal nerve :point_right: known as the trigeminovascular system. * ==Cranial autonomic symptoms==, 如 lacrimation, conjunctival injection, nasal congestion, rhinorrhea, periorbital swelling, aural fullness, and ptosis, :point_right: prominent in the trigeminal autonomic cephalalgias (TACs), including cluster :exploding_head: and paroxysmal hemicrania, and may also be seen in migraine, even in children. * often be mistaken for cranial sinus inflammation, which :point_right: thus overdiagnosed and inappropriately managed. * Migraine and other primary :exploding_head: types :point_right: not “vascular :exploding_head:"; these disorders do not reliably manifest vascular changes, and Rx outcomes cannot be predicted by vascular effects. --- ### CLINICAL EVALUATION OF ACUTE, NEW-ONSET :exploding_head: * In new-onset and severe :exploding_head:, the probability of finding a potentially serious cause :point_right: considerably greater than in recurrent :exploding_head:. * :mask: with recent onset of pain require prompt evaluation and appropriate Rx. * :sos: :arrow_right: meningitis, subarachnoid hemorrhage, epi-dural or subdural hematoma, glaucoma, tumor, and purulent sinusitis. --- * NE :point_right: essential :one: step in the evaluation. * :mask: with an abnormal examination or a history of recent-onset :exploding_head: :point_right: CT / MRI * As an initial screening procedure for intracranial pathology in this setting, CT and MRI methods appear to be ==equally sensitive.== * :mag:lumbar puncture (LP) --- ### PE * cranial arteries :point_right: ==palpation== * cervical spine :point_right: passive movement of the head * cardiovascular and renal status :point_right: blood pressure monitoring and urine examination; * eyes by funduscopy, intraocular pressure, and refraction. * psy :mask: a relationship exists between head pain, depression, and anxiety. * This :point_right: intended to identify comorbidity rather than provide an explanation for the :exploding_head:, because troublesome :exploding_head: :point_right: seldom simply caused by mood change. * Although it :point_right: notable that medicines with antidepressant actions :point_right: also effective in the preventive Rx of both tension-type :exploding_head: and migraine, each symptom must be treated optimally. --- * Underlying recurrent :exploding_head: disorders may be activated by pain that follows otologic or endodontic surgical procedures. * :arrow_right:Thus, pain about the head as the result of diseased tissue or trauma may reawaken an otherwise quiescent migraine syndrome. * Rx of the :exploding_head: :point_right: largely ineffective until the cause of the primary problem :point_right: addressed. * Serious underlying conditions that :point_right: associated with :exploding_head: :point_right: described below. * Brain tumor :point_right: a rare cause of :exploding_head: and even less commonly a cause of severe pain. * The vast majority of :mask: s presenting with severe :exploding_head::u6709:a benign cause. --- ### SECONDARY :exploding_head: * MENINGITIS * INTRACRANIAL HEMORRHAGE * BRAIN TUMOR * TEMPORAL ARTERITIS * GLAUCOMA --- ### SECONDARY :exploding_head: The management of secondary :exploding_head: focuses on diagnosis and Rx of the underlying condition. --- ### MENINGITIS * Acute, severe :exploding_head: with stiff neck and fever suggests meningitis. * LP :point_right: mandatory. * Often there :point_right: striking accentuation of pain with ==eye movement.== * Meningitis can be easily mistaken for migraine in that the cardinal symptoms of pounding :exploding_head:, ==photophobia, nausea, and vomiting== :point_right: frequently present, perhaps reflecting the underlying biology of some of the :mask:. --- ### INTRACRANIAL HEMORRHAGE * Acute, maximal in <5 min, severe :exploding_head: lasting >5 min with stiff neck but ==without fever== suggests subarachnoid hemorrhage. * A ruptured aneurysm, arteriovenous malformation, or intraparenchymal hemorrhage may also present with :exploding_head: alone. * Rarely, if the hemorrhage :point_right: small or below the foramen magnum, the head CT scan can be normal. * Therefore, LP may be required --- ### BRAIN TUMOR * 30% :mask: with brain tumors consider :exploding_head: to be their chief complaint. * The head pain :point_right: usually nondescriptan intermittent deep, dull aching of moderate intensity, which may worsen with exertion or change in position and may be associated with nausea and vomiting. * This pattern of symptoms results from migraine far more often than from brain tumor. * :exploding_head: of brain tumor disturbs sleep in 10% of :mask: * Vomiting that precedes the appearance of :exploding_head: by ==weeks== :point_right: highly ==posterior fossa brain tumors==. --- * ==amenorrhea or galactorrhea== :point_right: :interrobang: a prolactin-secreting pituitary adenoma (or the polycystic ovary syndrome). * Headache arising de novo in a :mask: with known malignancy suggests either cerebral metastases or carcinomatous meningitis, or both. * Head pain appearing abruptly after bending, lifting, or coughing can be due to a posterior fossa mass, a Chiari malformation, or low cerebrospinal fluid (CSF) volume. Brain tumors :point_right: discussed in Chap. 86. --- ### TEMPORAL ARTERITIS * Temporal (giant cell) arteritis :point_right: an inflammatory disorder of arteries that frequently involves the extracranial carotid circulation. * 77 per 100,000 individuals aged ≥50. * The average age 70 years * women account for 65% of cases. * half of :mask: untreated :arrow_right: blindness due to involvement of the ophthalmic artery and its branches; * indeed, the ischemic optic neuropathy induced by giant cell arteritis :point_right: the major cause of rapidly developing bilateral blindness in :mask: s >60 years. * :pill:==glucocorticoids== :point_right: effective in preventing this complication, prompt recognition of the disorder :point_right: important. --- ### TEMPORAL ARTERITIS - Presentation * Typical presenting symptoms: :exploding_head:, polymyalgia rheumatica, jaw claudication, fever, and weight loss. * :exploding_head: :point_right: the dominant symptom and often appears in association with malaise and muscle aches. * unilateral or bilateral and :point_right: located temporally in 50% of :mask: s but may involve any and all aspects of the cranium. * Pain usually appears gradually over a ==few hours==before peak intensity :point_right: reached; occasionally, it :point_right: explosive in onset. * The quality of pain :point_right: infrequently throbbing; it :point_right: almost invariably described as dull and boring, with superimposed episodic stabbing pains similar to the sharp pains that appear in migraine. --- * :mask: head pain :point_right: ==superficial, external to the skull==, rather than originating deep within the cranium (the pain site usually identified migraineurs). * Scalp tenderness :point_right: brushing the hair or resting the head on a pillow may be impossible because of pain. * :exploding_head: :point_right: usually worse at night :moon: and often aggravated by exposure to cold. * :triangular_flag_on_post: reddened, tender nodules or red streaking of the skin overlying the temporal arteries, and tenderness of the temporal or, less commonly, the occipital arteries. --- ### TEMPORAL ARTERITIS - Management * ESR :point_right: often, although not always, elevated; a normal ESR does not exclude giant cell arteritis. * A temporal artery biopsy followed by immediate Rx with :pill:prednisone 80 mg daily for the first 4–6 weeks should be initiated when clinical suspicion :point_right: high :arrow_up:. * The prevalence of migraine among the elderly :point_right: substantial, considerably higher than that of giant cell arteritis. * Migraineurs often report amelioration of their :exploding_head:s with prednisone; thus, caution must be used when interpreting the therapeutic response. --- ### GLAUCOMA * Glaucoma may present with a prostrating :exploding_head: associated with nausea and vomiting. * The :exploding_head: often starts with severe eye pain. * On physical examination, the eye :point_right: often red with a fixed, moderately dilated pupil. Glaucoma :point_right: discussed in Chap. --- ### PRIMARY :exploding_head: DISORDERS * absence of any exogenous cause. * The most common :point_right: migraine, tension-type :exploding_head:, and the TACs, notably cluster :exploding_head:. * These entities :point_right: discussed in detail in Chap. 422. --- ### CHRONIC DAILY OR NEAR-DAILY :exploding_head: * chronic daily :exploding_head: (CDH) can be applied when a :mask: experiences :exploding_head: on 15 days or more per month. * CDH :point_right: not a single entity; it encompasses a number of different :exploding_head: syndromes, both primary and secondary (Table 13-3). * In aggregate, this group presents considerable disability * Population-based estimates suggest that about 4% of adults:u6709:daily or near-daily :exploding_head:. ---  --- ### APPROACH TO :mask: * Chronic Daily Headache * MANAGEMENT OF MEDICALLY INTRACTABLE DISABLING PRIMARY CHRONIC DAILY :exploding_head: * MEDICATION-OVERUSE :exploding_head: * NEW DAILY PERSISTENT :exploding_head: * Clinical Presentation * Secondary NDPH * Low CSF Volume Headache * Raised CSF Pressure Headache * Posttraumatic Headache * Other Causes * Rx --- ### APPROACH TO :mask: #### Chronic Daily Headache * :one: management of :mask: s with CDH :point_right: to diagnose any secondary :exploding_head: and treat that problem (Table 13-3). * This can sometimes be a challenge where the underlying cause triggers a worsening of a primary :exploding_head:. * For :mask: s with primary :exploding_head:s, diagnosis of the :exploding_head: type will guide therapy. --- * Preventive Rxs 如 tricyclics, either amitriptyline or nortriptyline at doses up to 1 mg/kg, :point_right: very useful in :mask: with CDH arising from migraine or tension-type :exploding_head: or where the secondary cause:u6709:activated the underlying primary :exploding_head:. * Tricyclics :point_right: started in low doses (10–25 mg) daily and may be given 12 h before the expected time of awakening in order to avoid excess morning sleepiness. * Medicines including topiramate, valproate, propranolol, flunarizine (not available in the United States), and candesartan :point_right: also useful in migraine. --- ### MANAGEMENT OF MEDICALLY INTRACTABLE DISABLING #### PRIMARY CHRONIC DAILY :exploding_head: * The management of medically intractable :exploding_head: :point_right: difficult, although developments in therapy :point_right: at hand. * Monoclonal antibodies to ==calcitonin gene-related peptide (CGRP)== :+1: in phase II/III randomized placebo-controlled trials. * Non-invasive neuromodulatory approaches, 如 * ==single pulse transcranial magnetic stimulation== and non-invasive vagal nerve stimulation, which appear to modulate thalamic processing or brainstem mechanisms, respectively, in migraine have, or are, entering clinical practice, respectively. --- * Non-invasive ==vagal nerve stimulation== :u6709:also shown promise in chronic cluster :exploding_head:, chronic paroxysmal hemicrania, short-lasting unilateral neuralgiform :exploding_head: attacks with cranial autonomic symptoms (SUNA), short-lasting unilateral neuralgiform :exploding_head: attacks with conjunctival injection and tearing (SUNCT), and hemicrania continua --- ### :pill:MEDICATION-OVERUSE :exploding_head: * Overuse of analgesic medication for :exploding_head: can aggravate :exploding_head: frequency, markedly impair the effect of preventive medicines, and induce a state of refractory daily or near-daily :exploding_head: called medication-overuse :exploding_head:. * A proportion of :mask: s who stop taking analgesics will experience substantial improvement in the severity and frequency of their :exploding_head:. * However, even after cessation of analgesic use, many :mask: s continue to:u6709::exploding_head:, although they may feel clinically improved in some way, especially if they:u6709:been using opioids or barbiturates regularly. * The residual symptoms probably represent the underlying primary :exploding_head: disorder, and most commonly, this issue occurs in :mask: s prone to migraine. Management of Medication Overuse: Out :mask: s For :mask: s who overuse medications, it :point_right: often helpful that analgesic use be reduced and eliminated. --- * One approach :point_right: to reduce the medication dose by 10% every 1–2 weeks. * Immediate cessation of analgesic use :point_right: possible for some :mask: s, provided there :point_right: no contraindication. * Both approaches :point_right: facilitated by the use of a medication diary maintained during the month or two before cessation; this helps to identify the scope of the problem. * A small dose of a nonsteroidal anti-inflammatory drug (NSAID) 如 naproxen, 500 mg bid, if tolerated, will help relieve residual pain as analgesic use :point_right: reduced. * NSAID overuse :point_right: not usually a problem for :mask: s with daily :exploding_head: when a NSAID with a longer half-life :point_right: taken once or twice daily; however, overuse problems may develop with more frequent dosing schedules or shorter acting NSAIDS. --- * Once the :mask: :u6709:substantially reduced analgesic use, a preventive medication should be introduced, although another equally widely used approach :point_right: to commence the preventive at the same time as the analgesic reduction :point_right: started. * It must be emphasized that preventives often do not work in the presence of analgesic overuse. * The most common cause of unresponsiveness to Rx :point_right: the use of a preventive when analgesics continue to be used regularly. * For some :mask: s, discontinuing analgesics :point_right: very difficult; often the best approach :point_right: to inform the :mask: that some degree of pain :point_right: inevitable during this initial period. --- * Management of Medication Overuse: In :mask: s Some :mask: s will require hospitalization for detoxification. * Such :mask: s:u6709:typically failed efforts at out :mask: withdrawal or:u6709:a significant medical condition, 如 diabetes mellitus or epilepsy, which would complicate withdrawal as an out :mask: . * Following admission to the hospital, acute medications :point_right: withdrawn completely on the first day, in the absence of a contraindication. * Antiemetics and fluids :point_right: administered as required; clonidine :point_right: used for opioid withdrawal symptoms. * For acute intolerable pain during the waking hours, aspirin, 1 g IV (not approved in United States), :point_right: useful. * IM chlorpromazine can be helpful at night; :mask: s must be adequately hydrated. --- * Three to five days into the admission, as the effect of the withdrawn substance wears off, a course of IV dihydroergotamine (DHE) can be used. * DHE, administered every 8 h for 5 consecutive days, can induce a significant remission that allows a preventive Rx to be established. * Serotonin 5-HT3 receptor antagonists, 如 ondansetron or granisetron, or the neurokinin receptor antagonist, aprepitant, may be required with DHE to prevent significant nausea, and domperidone (not approved in the United States) orally or by suppository can be very helpful. * Avoiding sedating or otherwise side effect–prone antiemetics :point_right: helpful. ---  --- ### NEW DAILY PERSISTENT :exploding_head: * New daily persistent :exploding_head: (NDPH) :point_right: a clinically distinct syndrome with important secondary causes; these :point_right: listed in Table 13-4. --- ### Clinical Presentation The :mask: with NDPH presents with :exploding_head: on most if not all days, and the :mask: can clearly, and often vividly, recall the moment of onset. * :exploding_head: usually begins abruptly, but onset may be more gradual; evolution over 3 days has been proposed as the upper limit for this syndrome. * :mask: typically recall the exact day and circumstances of the onset of :exploding_head:; the new, persistent head pain does not remit. * The first priority :point_right: to distinguish between a primary and a secondary cause of this syndrome. * Subarachnoid hemorrhage :point_right: the most serious of the secondary causes and must be excluded either by history or appropriate investigation --- ### Secondary NDPH Low CSF Volume Headache In these syndromes, head pain :point_right: positional: it begins when the :mask: sits or stands upright and resolves upon reclining. * The pain, which :point_right: occipitofrontal, :point_right: usually a dull ache but may be throbbing. * :mask: s with chronic low CSF volume :exploding_head: typically present with a history of :exploding_head: from 1 day to the next that :point_right: generally not present on waking but worsens during the day. * Recumbency usually improves the :exploding_head: within minutes, and it can take only minutes to an hour for the pain to return when the :mask: resumes an upright position. --- * The most common cause of :exploding_head: due to persistent low CSF volume :point_right: CSF leak following LP. * Post-LP :exploding_head: usually begins within 48 h but may be delayed for up to 12 days. * Its incidence :point_right: between 10 and 30%. * Beverages with caffeine may provide temporary relief. * Besides LP, index events may include epidural injection or a vigorous Valsalva maneuver, 如 from lifting, straining, coughing, clearing the eustachian tubes in an airplane, or multiple orgasms. * Spontaneous CSF leaks :point_right: well recognized, and the diag-nosis should be considered whenever the :exploding_head: history :point_right: typical, even when there :point_right: no obvious index event. --- * As time passes from the index event, the postural nature may become less apparent; cases in which the index event occurred several years before the eventual diagnosis:u6709:been recognized. * Symptoms appear to result from low volume rather than low pressure: although low CSF pressures, typically 0–50 mm CSF, :point_right: usually identified, a pressure as high as 140 mm CSF:u6709:been noted with a documented leak. * Postural orthostatic tachycardia syndrome (POTS)can present with orthostatic :exploding_head: similar to low CSF volume :exploding_head: and :point_right: a diagnosis that needs consideration in this setting. --- * When imaging :point_right: indicated to identify the source of a presumed leak, an MRI with gadolinium :point_right: the initial study of choice (Fig. 13-1). * A striking pattern of diffuse meningeal enhancement :point_right: so typical that in the appropriate clinical context the diagnosis :point_right: established. * Chiari malformations may sometimes be noted on MRI; in such cases, surgery to decompress the posterior fossa :point_right: not indicated and usually worsens the :exploding_head:. --- * Spinal MRI with T2 weighting may reveal a leak, and spinal MRI may demonstrate spinal meningeal cysts whose role in these syndromes :point_right: yet to be elucidated. * The source of CSF leakage may be identified by spinal MRI with appro-priate sequences, by CT, or increasingly by MR myelography. * Less used now, 111In-DTPA CSF studies in the absence of a directly identified site of leakage, may demonstrate early emptying of 111In-DTPA tracer into the bladder or slow progress of tracer across the brain suggesting a CSF leak. --- * Initial Rx for low CSF volume :exploding_head: :point_right: bed rest. * For :mask: s with persistent pain, IV caffeine (500 mg in 500 mL of saline administered over 2 h) can be very effective. * An electrocardiogram (ECG) to screen for arrhythmia should be performed before administration. * It :point_right: reasonable to administer at least two infusions of caffeine before embarking on additional tests to identify the source of the CSF leak. --- * Because IV caffeine :point_right: safe and can be curative, it spares many :mask: s the need for further investigations. * If unsuccessful, an abdominal binder may be helpful. * If a leak can be identified, an autologous blood patch :point_right: usually curative. * A blood patch :point_right: also effective for post-LP :exploding_head:; in this setting, the location :point_right: empirically determined to be the site of the LP. * In :mask: s with intractable :exploding_head:, oral theophylline :point_right: a useful alternative; however, its effect :point_right: less rapid than caffeine. --- ### Raised CSF Pressure Headache Raised CSF pressure :point_right: well recognized as a cause of :exploding_head:. * Brain imaging can often reveal the cause, 如 a space-occupying lesion. * NDPH due to raised CSF pressure can be the presenting symptom for :mask: s with idiopathic intracranial hypertension (pseudotumor cerebri) without visual problems, particularly when the fundi :point_right: normal. * Persistently raised intracranial pressure can trigger chronic migraine. * These :mask: s typically present with a history of generalized :exploding_head: that :point_right: present on waking and improves as the day goes on. * It :point_right: generally worse with recumbency. * Visual obscurations :point_right: frequent. --- * The diagnosis :point_right: relatively straightforward when papilledema :point_right: present, but the possibility must be considered even in :mask: s without funduscopic changes. * Formal visual field testing should be performed even in the absence of overt ophthalmic involve-ment. * Headache on rising in the morning or nocturnal :exploding_head: :point_right: also characteristic of obstructive sleep apnea or poorly controlled hypertension. * Evaluation of :mask: s suspected to:u6709:raised CSF pressure requires brain imaging. * It :point_right: most efficient to obtain an MRI, including an MR venogram, as the initial study. * If there :point_right: no contraindications, the CSF pressure should be measured by LP; this should be done when the :mask: :point_right: symptomatic so that both the pressure and the response to removal of 20–30 mL of CSF can be determined. --- * An elevated opening pressure and improvement in :exploding_head: following removal of CSF :point_right: diagnostic in the absence of fundal changes. * Initial Rx :point_right: with acetazolamide (250–500 mg bid); the :exploding_head: may improve within weeks. * If ineffective, topiramate :point_right: the next Rx of choice; it:u6709:many actions that may be useful in this setting, including carbonic anhydrase inhibition, weight loss, and neuronal membrane stabilization, likely mediated via effects on phosphorylation pathways. * Severely disabled :mask: s who do not respond to medical Rx require intracranial pressure monitoring and may require shunting. --- ### Posttraumatic Headache A traumatic event can trigger a :exploding_head: process that lasts for many months or years after the event. * The term trauma :point_right: used here in a very broad sense: :exploding_head: can develop following an injury to the head, but it can also develop after an infectious episode, typically viral meningitis, a flulike illness, or a parasitic infection. * Complaints of dizziness, vertigo, and impaired memory can accompany the :exploding_head:. * Symptoms may remit after several weeks or persist for months and even years after the injury. * Typically the neurologic examination :point_right: normal and CT or MRI studies :point_right: unrevealing. --- * Chronic subdural hematoma may on occasion mimic this disorder. * Posttraumatic :exploding_head: may also be seen after carotid dissection and subarachnoid hemorrhage and after intracranial surgery. * The underlying theme appears to be that a traumatic event involving the pain-producing meninges can trigger a :exploding_head: process that lasts for many years. --- ### Other Causes In one series, one-third of :mask: s with NDPH reported :exploding_head: beginning after a transient flulike illness characterized by fever, neck stiffness, photophobia, and marked malaise. * Evaluation typically reveals no apparent cause for the :exploding_head:. * There :point_right: no convincing evidence that persistent Epstein-Barr virus infection plays a role in NDPH. * A complicating factor :point_right: that many :mask: s undergo LP during the acute illness; iatrogenic low CSF volume :exploding_head: must be considered in these cases. --- ### Rx * Rx :point_right: largely empirical and directed at the :exploding_head: phenotype. * Tricyclic antidepressants, notably amitriptyline, and anticonvulsants, 如 topiramate, valproate, and gabapentin,:u6709:been used with reported benefit. * The monoamine oxidase inhibitor phenelzine may also be useful in carefully selected :mask: s. * The :exploding_head: usually resolves within 3–5 years, but it can be quite disabling. --- ### PRIMARY CARE AND :exploding_head: MANAGEMENT * Most :mask: s with :exploding_head: will be seen first in a primary care setting. * The task of the primary care physician :point_right: to identify the very few worri-some secondary :exploding_head:s from the very great majority of primary and less troublesome secondary :exploding_head:s (Table 13-2). * Absent any warning signs, a reasonable approach :point_right: to treat when a diagnosis :point_right: established. * As a general rule, the investigation should focus on identifying worrisome causes of :exploding_head: or on gaining confidence if no primary :exploding_head: diagnosis can be made. * After Rx:u6709:been initiated, follow-up care :point_right: essential to identify whether progress:u6709:been made against the :exploding_head: complaint. --- * Not all :exploding_head:s will respond to Rx, but, in general, worrisome :exploding_head:s will progress and will be easier to identify. * When a primary care physician feels the diagnosis :point_right: a primary :exploding_head: disorder, it :point_right: worth noting that >90% of :mask: s who present to primary care with a complaint of :exploding_head: will:u6709:migraine * In general, :mask: s who do not:u6709:a clear diagnosis,:u6709:a primary :exploding_head: disorder other than migraine or tension-type :exploding_head:, or :point_right: unresponsive to two or more standard therapies for the considered :exploding_head: type should be considered for referral to a specialist. * In a practical sense, the threshold for referral :point_right: also determined by the experience of the primary care physician in :exploding_head: medicine and the availability of secondary care options.