Intractable migraine without aura and without status migrainosus

Status migrainosus

For many patients, an attack of migraine becomes a harrowing experience. After a variable period, they go to an emergency room or physician’s office for further treatment. Status migrainosus is described as a debilitating migraine attack lasting for more than 72 hours (IHS, 2018). While there are no concrete guidelines currently available for status migrainosus treatment, several strategies have been used by some in the past. At our institution we have developed consensus among headache specialists for adult status migrainosus management recommendations based on available evidence, guidelines, and clinical experience (Fig. 102.6;Garza and Cutrer, n.d.). These do not replace clinical judgment but may assist the provider with decision making when encountering status migrainosus. Although, strictly defined, status migrainosus is a migraine headache lasting >72 hours, treatment often needs to start earlier if associated with significant uncontrolled vomiting and/or dehydration. In this model, if IV access is present, initial treatment consists of IV hydration, IV ketorolac 30 mg, and a neuroleptic antiemetic of choice (commonly prochlorperazine, metoclopramide, or promethazine) as needed. Specific status migrainosus treatment protocols using neuroleptic antiemetics have been published (Bell et al., 1990;Fisher, 1995;Lane et al., 1989;McEwen et al., 1987;Richman et al., 2002;Tek et al., 1990;Wang et al., 1997). To avoid extrapyramidal reactions with neuroleptic antiemetics, consideration can be given to pretreating with 1 mg oral (PO), intramuscular (IM), or IV benztropine mesylate. Benztropine is typically given to patients with a history of an extrapyramidal reaction to the chosen antiemetic, but not routinely. If IV access is not available, IM ketorolac with or without promethazine may be a good alternative. Patients with significant dehydration, complex coexisting medical problems and those requiring prolonged parenteral treatment may need to be hospitalized (Garza and Cutrer, n.d.). If initial measures fail and proper expertise is available, consideration can be given to extracranial nerve blocks directed to the area or areas of pain such as occipital, supraorbital, or auriculotemporal nerves and/or the sphenopalatine ganglion. If DHE is needed for a patient in a short-term stay settingsuch as the emergency room, it is administered as a 0.5 mg IV test dose and if tolerated may repeat DHE 0.5 mg IV 30–60 minutes later (total 1 mg). If inpatient, however, DHE is administered instead with IV 0.5–1.0 mg doses (depending on tolerance every 8 hours as needed (“Raskin protocol”) (Raskin, 1990) for up to 2–5 days or via continuous IV DHE infusion (“Ford protocol”) (Ford and Ford, 1997). In the latter, DHE initiates at 3 mg in 1000 mL normal saline and is administered IV at 42 mL/h but if significant nausea the rate is reduced to 21–30 mL/h (may continue up to 7 days if needed). Patients getting IV DHE are commonly pretreated with IV metoclopramide (with or without benztropine mesylate as discussed above) if no other antiemetic has been given, and the antiemetic is repeated as needed while on IV DHEtreatment. When used, IV valproic acid starts with a loading dose of 15 mg/kg in D5W (5% dextrose in water) or normal saline at 20 mg/min and is followed by 5 mg/kg every 8 hours as needed (Schwartz et al., 2002). An alternative IV valproic acid protocol is 1 g in 250 mL normal saline over 1 hour (Edwards et al., 2001). A very common valproic acid IV dosing, however, is 500 mg at 20 mg/min × 1 dose (after 1000 mL normal saline) (Garza and Cutrer, n.d.). One of the main goals of this approach is to avoid opiate/opioid use as much as possible when managing status migrainosus, to minimize the risk of medication overuse headache. Dexamethasone (10 mg IV) may be given prior to dismissal to help prevent headache recurrence (Garza and Cutrer, n.d.).

Status Migrainosus

The IHS defines status migrainosus as an attack of migraine, the headache phase of which lasts more than 72 hr whether it is treated or not. The headache is continuous throughout the attack. Relief during periods of sleep or by medication is disregarded. No clear distinction is made between transformed migraine and prolonged status migrainosus because no time limit is given to status migrainosus. Factors responsible for triggering status migrainosus include emotional stress, depression, abuse of medications, anxiety, diet, hormonal factors, and multiple nonspecific factors. Status migrainosus may be secondary to an acute neurological disorder. However, acute central nervous system events can trigger an otherwise typical migraine.

Inpatient Management of Intractable Migraine and Status Migrainosus

Six to 7% of patients fail acute treatment in the emergency department. These patients are usually admitted for 3-5 days and receive extensive parenteral treatment. A child should be admitted to the hospital for a primary headache when the child is in status migrainosus, has an exacerbation of a chronic severe headache, or has an analgesic overuse headache with an acute exacerbation. The goal of inpatient treatment is to control a headache that has been unresponsive to other abortive therapy and is disabling to the child. Treatment protocols include the use of DHE, antiemetics, sodium valproate, and other drugs.

MIGRAINE AURA STATUS

Status migrainosus is not a true complication of migraine but rather a migraine headache that is beyond spontaneous resolution. The suggested time span of 72 hours is both arbitrary and too short; menstrual migraine headaches often last longer than that and still reverse spontaneously. Migrainous infarction can also occur as a complication of migraine without aura. In fact, a prospective stroke registry study of 3502 patients with ischemic stroke identified 27 cases of stroke that occurred during a migraine attack. Of the migraine attacks involved, 59% were without aura and 41% with aura. The neurologic symptoms of migraine can last beyond 7 days without being associated with cerebral infarction. This is the case with migraine aura status, characterized by the continuation of aura symptoms beyond their usual duration. Aura symptoms of migraine usually last less than 1 hour and often approximately 20 minutes. The International Headache Society speaks of prolonged aura when the symptoms last longer than 1 hour. However, they could be called migraine aura status when they last longer than 24 hours. This time boundary, although equally arbitrary, at least parallels that used to distinguish transient ischemic attack from stroke.

The following case study illustrates migraine aura status: A 41-year-old man had experienced headaches since childhood. The headaches occurred 12 to 15 times per year, often in flurries. They were always preceded by a visual disturbance, which lasted for 20 or 40 minutes. The visual disturbance consisted of bright white, flickering zigzag lines ("white snakes") in the periphery of both visual fields. It developed over 5 to 10 minutes and was immediately followed by headache. The headache built to its maximum intensity as the visual disturbance faded away and lasted for one half to 1 hour, treated with a nonprescription analgesic. The headache was severe, located in the anterior vertex as a throbbing pain, and was associated with photophobia. In October 1996, the patient was watching President Clinton's reelection on TV, which upset him greatly. He subsequently developed the visual disturbance as just described but much more intense. It came along with tingling of the left arm and hand, which developed without a march and lasted for 15 to 30 minutes. It was associated with severe headache, photophobia, and a general sense of weakness. In addition, he was confused and kept repeating the same sentence. The visual disturbance has been present since and makes him see everything as if through a veil. The "white snakes" in the periphery of both visual fields come and go. Cranial magnetic resonance imaging was normal, particularly without evidence of cerebral infarction.

Status Migrainosus

A debilitating migraine attack lasting more than 3 days is called status migrainosus. Brief remissions in pain with medications or sleep can occur. In some cases, treatment for status migrainosus may require outpatient or inpatient IV therapy.

Complications of Migraine

Complications of migraine include status migrainosus, persistent aura without infarction, migrainous infarction and migraine aura-triggered seizure. Status migrainosus is a headache attack fulfilling criteria for either migraine with aura or migraine without aura that lasts for greater than 72 h. In persistent aura without infarction aura symptoms persist for 1 or more weeks with no evidence of infarction on neuroimaging. Persistent aura symptoms are often bilateral and may last for months or years. Migrainous infarction is persistent migraine aura lasting greater than 60 min with correlating areas of infarct seen on neuroimaging. Migraine aura-triggered seizures occur during, or within 1 h after, a migraine with aura attack.

Indications

Sphenopalatine ganglion block may be used in the treatment of acute migraine headache, acute cluster headache, and a variety of facial neuralgias including Sluder's, Vail's, and Gardner's syndromes. This technique is also useful in the treatment of status migrainosus and chronic cluster headache. There is anecdotal evidence that sphenopalatine ganglion block may also be useful in the palliation of pain secondary to acute herpes zoster of the trigeminal nerve.

Neurodestructive procedures of the sphenopalatine ganglion using neurolytic agents, radiofrequency lesioning, or freezing may be indicated for the palliation of cancer pain and rarely for headache and facial pain syndromes that fail to respond to conservative management. Recent experience with electrical stimulation of the sphenopalatine ganglion has shown promising early results.

Temporal pattern

Headache development is often insidious and from a mild nonspecific ache to a typical migraine may take 0.5–2 hours (Zagami and Rasmussen 2000). Migraine is a periodic headache lasting 4–72 hours, and longer lasting attacks are considered ‘status migrainosus’ (Olesen et al 2004a). In about half of migraineurs pain duration was 5–24 hours and a third reported pain lasting more than 25 hours (Stewart et al 2003). In a small number (16.4%) duration was less than 5 hours (Solomon et al 1985; Stewart et al 2003).

For most migraineurs in the population headache frequency is less than one per month (Rasmussen et al 1991b; Pryse-Phillips et al 1992; Steiner et al 2003). However, attack frequency varies considerably from 6–12 per year (46%) to 1–2 per month (20%), up to 2–4 per month (16%) (Stewart et al 2003). Clinic populations report more frequent headaches with a third suffering more than 4 attacks monthly (Magnusson and Becker 2003). MWA has a higher average attack frequency and is usually more debilitating than MA. Seasonal or cyclic patterns have been associated with migraine attacks, often correlating with light hours (Fox and Davis 1998; Alstadhaug et al 2005).

Decreased quality of life between attacks (interictally) has been recognized in migraine patients (Cavallini et al 1995; Steiner 2000). Although comorbidity can partially explain some of the disability, migraineurs report significant interictal behavioural symptoms such as reduced activity, reduced vigour and a higher level of sleepiness (Stronks et al 2004).

A minority (15.6%) of migraineurs describe daily or near-daily headaches (Stewart et al 2003) and according to the IHS classification such frequent migraine attacks are distinguished as chronic migraine, as described below.

I.A.7.a Status Migrainosus

Previously, this condition was called intractable migraine or persistent (pernicious) migraine. It is distinguished as a migraine attack with the headache phase lasting more than 72 hr despite treatment. A headache-free interval of less than 4 hr may occur. Any episode of migraine, in any form of migraine, may evolve into an intractable, daily, continuous headache attack, unresponsive to standard treatments. The headache may be unilateral or global, pulsatile or pressure-like, or may have characteristics of both migraine and tension-type headaches. The headache progressively intensifies to a debilitating pain, accompanied by the usual characteristics of migraine. Typically, the associated nausea and vomiting are severe, leading to osmophobia, dehydration, refusal to eat, and prostration. The photophobia, phonophobia, and headache exacerbated by any movement forces the patient to remain in a dark and quiet room, unable to function at even a basic level. Some patients will even wear dark sunglasses indoors because of excessive sensitivity to light. Dehydration and anorexia may cause electrolyte disturbances, further complicating their condition. Emotional despair and depression with suicidal ideation are generally present. Status migrainosus is considered “headache urgency” requiring immediate care, preferably in an inpatient setting for rehydration, pain control, and reversal of continuous headache.

Status migrainosus, is often iatrogenically induced due to overuse or inappropriate use of analgesics, ergotamine preparations, narcotics, caffeine, or triptans or due to inadequate treatment of migraine. In susceptible patients, high stress, anxiety, and poor sleeping and eating habits may lead to this condition. Rebound headaches, transformed migraine, mixed headache, and chronic daily headaches may ultimately cause intractable debilitating headache. Status migrainosus is thought to be due to a sterile inflammation of the intracranial blood vessels involved in migraine process. The vasodilatation and inappropriate release of vasoactive neuropeptides, some of which are very potent vasodilators, as well as other active peptides that mediate neurogenic inflammation are self-perpetuating processes leading to endless activation of the trigeminal neurovascular system and fueling the central migraine generator. The plausible mechanism responsible for the refractoriness of status migrainosus is that the constant activation and release of neuropeptides downregulates serotonergic receptors and depletes endorphins.

Patients with acute status migrainosus may require hospitalization, particularly if the condition was induced by dependency on medication, is accompanied by dehydration, or if the patient is depressed or has a prior experience of adverse reactions to medications (Table I). The offending medication causing rebound headache phenomenon must be withdrawn. The withdrawal is usually done in an abrupt manner, but all precautions to prevent seizures and/or other withdrawal reactions should be instituted. Treatment for patients with status migrainosus should be aggressive and includes rest; rehydration and electrolyte replacement; detoxification; round-the-clock parenteral analgesic therapy; symptomatic treatment of nausea, anxiety, insomnia, and withdrawal symptoms; concurrent initiation of prophylactic therapy; and behavioral treatment. Corticosteroids and NSAIDs are used to reduce the neurogenic inflammation. Phenothiazine-based neuroleptics are utilized to control nausea and vomiting, reduce pain perception, and induce sedation. A series of intravenous dihydroergotamine (DHE) administered every 8 hr for 3 days is very effective in interrupting the painful cycle. It cannot be used when the patient is rebounding from ergotamine preparation or when DHE is contraindicated. Pain control is achieved by scheduled administration of parenteral narcotics, neuroleptics, benzodiazepines, and ketorolac. “As needed” pain control is not recommended because of reinforcement of dependency on analgesics. Appropriate prophylactic therapy, education, psychotherapy, and biofeedback should be concomitantly instituted.

Table I. Criteria for Admission to Inpatient Headache Unit

Nervous system

A woman with familial hemiplegic migraine experienced worsening of her symptoms after repeated doses of topiramate [303A].

A 33-year-old woman with familial hemiplegic migraine was given topiramate 25 mg/day for monthly attacks of migraine. She had never had status migrainosus. After a week she developed dysphasia, disorientation, and prolonged severe right-sided weakness complicating a migraine attack and lasting about 4 days. She had right-sided weakness involving the arm and leg and cortical sensory loss. All blood tests were normal and a brain MRI scan was unremarkable. Topiramate was withdrawn and her symptoms resolved within 48 hours. Six months later she took topiramate again and after 5 days had a new severe attack. Topiramate was immediately tapered off, with prompt resolution of the symptoms.

A 42-year-old woman developed tremor and myoclonus after topiramate 50 mg/day was added to fluvoxamine 300 mg/day as an antimigraine agent [304A].

Two cases of restless legs syndrome have been attributed to topiramate [305A].