Hemicrania continua …

Headache & Pain

Updated 07.18.2024
Released 10.01.2001
Expires For CME 07.18.2027

Hemicrania continua

Authors: Julish Selvy APRN, Aravindhan Veerapandiyan MD

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Editor: Shuu-Jiun Wang MD

Hemicrania continua

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Introduction

Overview

This article summarizes the clinical characteristics and treatment of hemicrania continua, a primary chronic headache disorder. It is one of the trigeminal autonomic cephalgias characterized by a strictly unilateral, continuous headache with ipsilateral cranial autonomic features and a complete response to indomethacin. Clinical history is important in the diagnosis. It is often misdiagnosed as migraine, cluster headache, sinus headache, or dental pain. Indomethacin is the gold standard treatment, but side effects may limit use, and many other treatments have reported efficacy. This update includes the final diagnostic criteria published in the 3rd edition of The International Classification of Headache Disorders (ICHD-3).

Key points

	• Hemicrania continua is an indomethacin-responsive trigeminal autonomic cephalalgia that is characterized by persistent, unilateral headaches with periodic exacerbations. Delays in the diagnosis can lead to unnecessary therapeutic interventions.
	• A therapeutic trial of indomethacin should be done in all strictly unilateral headache patients who are not responding to other medications.
	• A seasonal pattern with clustering is a diagnostic clue for hemicrania continua. The remitting type of hemicrania continua may mimic cluster headaches.
	• The important feature of hemicrania continua is continuous background pain.
	• Headache diaries must be kept to help identify the disorder by documenting details of both continuous background headaches and episodic exacerbations, respectively.
	• Although the cause of hemicrania continua is unknown, people suspected of having this condition should be assessed for an underlying cause. Tests should include neuroimaging to rule out a secondary cause.
	• Alternative treatment can be considered if the patient is unable to tolerate indomethacin. Options include melatonin, topiramate, verapamil, gabapentin, occipital nerve blocks, and occipital nerve stimulation.

Historical note and terminology

Hemicrania continua is one of the primary chronic daily headache disorders. It is characterized by a continuous unilateral headache of moderate intensity with exacerbations of severe pain and is often associated with migrainous and cranial autonomic features. Hemicrania continua almost invariably has a prompt and enduring response to indomethacin. The earliest recognition of a headache syndrome involving one side of the head is attributed to Aretaeus of Cappadocia (in the 2nd century AD) (63). However, Egyptian descriptions appear in papyri dating from 1500 BC (12). Galen introduced the term "hemicrania" for unilateral headache. It was later transformed into the old English megrim and the French migraine. We now accept the term migraine derived from hemicrania although migraine differs from hemicrania continua in its episodic nature.

Medina and Diamond probably were the first authors to describe hemicrania continua in a subset of 54 patients who had cluster headache variants as well as strictly unilateral, continuous headaches that responded to indomethacin (50). In 1983, Boghen and Desaulniers described a patient with a similar headache that they called "background vascular headache responsive to indomethacin” (10).

The term “hemicrania continua” was coined by Sjaastad and Spierings (92). They reported a woman aged 63 years and a man aged 53 years who developed a strictly unilateral headache that was continuous from onset and absolutely responsive to indomethacin. In 2006, Sjaastad reported the long-term follow-up of the first woman with hemicrania continua until her death at age 81. She was treated with indomethacin during the whole observation time; no tachyphylaxis was observed, but she developed gastric ulcers secondary to the indomethacin (90). In 1987, the first case of hemicrania continua with a remitting course was reported (94).

Debate is ongoing as to the existence of indomethacin-resistant hemicrania continua. Clinical experience has shown that a proportion of patients meeting all other criteria for hemicrania continua except an absolute indomethacin response are not uncommon. In 1 published series, 64% of patients were in this category (46), and in another, 31% (73). Currently, it is more widely believed that indomethacin response is sine qua non for a diagnosis of hemicrania continua and that hemicranial pain that does not respond is a different type of headache as yet unclassified but termed “hemicranias incerta” (60) or “NIRCH” (non-indomethacin responsive chronic hemicrania) (95; 06).

In the current ICHD-3, the trigeminal autonomic cephalgias group includes cluster headache; paroxysmal hemicrania; short-lasting unilateral neuralgiform headache attacks (SUNHAs); and their 2 subforms, SUNHAs with conjunctival injection and tearing (SUNCT) and SUNHAs with cranial autonomic symptoms (SUNA). Hemicrania continua is also now included in the trigeminal autonomic cephalgias group (82; 16).

Clinical manifestations

Presentation and course

Hemicrania continua is characterized by a strictly unilateral, continuous headache with absolute responsiveness to indomethacin. It exists in the unremitting (continuous) and remitting forms. The continuous variety can be subclassified into (1) an evolutive, unremitting form that arises from the remitting form and (2) an unremitting form characterized by continuous headache from the onset. About 82% to 88% of the clinical cases were the chronic form, and 12% to 15% were the remitting form (66; 21).

Bordini and colleagues reported a clear female preponderance (5:1) in 18 cases (11), whereas Espada and colleagues discovered a slight male preponderance (1.25:1) (26). A small female preponderance was found in other studies, with female-to-male ratios of 1.6:1 (21), 1.8:1 (56), 2.4:1 (66), and 1.75:1 (22; 53).

Mean age of onset appears to be around 30 to 50 years of age (66; Marura et al 2008; 21; 22; 53), but the condition onset has been recorded between 5 years and 67 years (66; 21; 53).

One of the essential features of hemicrania continua is unilateral headache; however, some bilateral (62; 96) or alternating side (55; Matharu et al 2005; 64; 21) cases have been reported. A patient with cranial autonomic symptoms contralateral to the headache was also reported (78).

In the update of the ICHD-3, hemicrania continua is categorized under the subcategory of trigeminal autonomic cephalgias. It was previously listed under “other primary headaches” in ICHD-2 (35). The associated autonomic features of hemicrania continua were expanded to include eyelid edema. Symptoms of forehead and facial sweating and flushing, and ear fullness had been proposed in the ICHD-3 beta, but were not ultimately included in the final criteria. A sense of agitation accompanying the pain, often described in cluster headache, or aggravation of pain by movement reminiscent of migraine, were also added.

The diagnostic criteria for hemicrania continua from the ICHD-3 are listed in Table 1.

Table 1. ICHD-3 Diagnostic Criteria for Hemicrania Continua

Hemicrania continua
A. Unilateral headache fulfilling criteria B-D
B. Present for > 3 months, with exacerbations of moderate or greater intensity
C. Either or both of the following:
	1. At least 1 of the following symptoms or signs, ipsilateral to the headache:
		a) conjunctival injection and/or lacrimation b) nasal congestion and/or rhinorrhea c) eyelid edema d) forehead and facial sweating e) miosis and/or ptosis
	2. A sense of restlessness or agitation, or aggravation of the pain by movement
D. Responds absolutely to therapeutic doses of indomethacin
E. Not better accounted for by another ICHD-3 diagnosis
Hemicrania continua, remitting subtype
A. Headache fulfilling the criteria for hemicrania continua and criterion B below
B. Headache is not daily or continuous, but interrupted (without treatment) by remission periods of ≥ 24 hours
Hemicrania continua, unremitting subtype
A. Headache fulfilling the criteria for hemicrania continua and criterion B below
B. Headache is daily and continuous for at least 1 year, without remission periods of ≥ 24 hours

Associated symptoms can be divided into 3 main categories: (1) cranial autonomic symptoms, (2) "stabbing headache," and (3) migrainous features. Cranial autonomic symptoms consist of ipsilateral conjunctival injection, tearing, rhinorrhea, nasal stuffiness, eyelid edema, ptosis, miosis, and forehead sweating. Some patients may develop bilateral cranial autonomic symptoms (21; 96). These symptoms are not as prominent in hemicrania continua as they are in cluster headache and chronic paroxysmal hemicrania. Symptoms of ocular discomfort, at times in premonitory phase, have been described. Some patients report a feeling of sand in the eye, which is no longer thought to be specific for hemicrania continua. Cranial autonomic symptoms are more common in the exacerbation period compared with the baseline in hemicrania continua; at least 1 autonomic symptom was found in 75% to 95% of patients (66; 21; 73).

Primary stabbing headache (“jabs and jolts syndrome”) is described as sharp pain that lasts for less than 1 minute; it occurs in patients with migraine and cluster headache or in headache-free individuals and responds to indomethacin. Stabbing pain occurs in hemicrania continua more frequently in the exacerbation periods. Jabs and jolts syndrome was found in 36% to 41% of cases of hemicrania continua (66; 21) whereas its prevalence in the general population is 30%. Because of its low sensitivity and specificity, it is not included in the diagnostic criteria for hemicrania continua.

Migrainous features (nausea, vomiting, photophobia, or phonophobia) are common in hemicrania continua, particularly in the exacerbation period (63; 21). Unilateral phonophobia or photophobia (or both) are more frequent in trigeminal autonomic cephalalgia and hemicrania continua than in migraine and new daily persistent headache and may be clinically useful in the differential diagnosis (37). Hemicrania continua with visual or olfactory auras has been described (63; 41; 30). Evers and colleagues reported a patient with hemicrania continua and attacks of hemiparesis and a familial history of hemiplegic migraines (29). Pasquier and colleagues reported a patient with unilateral paresthesias (62).

Prognosis and complications

Hemicrania continua is a chronic condition. There is limited information on the long-term prognosis. In a clinical study of 39 patients with hemicrania continua, the mean duration of the chronic (unremitting) phase of the disease was 12.3 years (21). The initial patient described by Sjasstad in 1984 was followed for 19 years after diagnosis until her death at age 81 years (90). She experienced the unremitting form of hemicrania continua for 56 years.

Clinical vignette

A 34-year-old man presented with a 13-year history of strictly unilateral left-sided headache with no significant remission period. He described a constant background pain of moderate intensity with an aching quality centered over the occiput. He got superimposed exacerbations of pain 1 to 2 times a day lasting between 1 to 10 hours. Exacerbations were severe and had an explosive or pressure quality and were focused around the left occiput radiating to the vertex, parietal, and retro-orbital regions. Pain was accompanied by ipsilateral lacrimation, ptosis, nasal blockage, rhinorrhea, and facial sweating. He became agitated with the exacerbations. He also had associated visual aura, nausea and vomiting, photophobia, and phonophobia. He had a positive Indotest and his headaches were controlled on up to 50 mg thrice daily of indomethacin. Unfortunately, he developed side effects from indomethacin and failed to respond to alternatives, including COX-2 inhibitors, topiramate, verapamil, and gabapentin. He had an occipital nerve stimulator inserted and became virtually pain-free off all medications.

Biological basis

Etiology and pathogenesis

Hemicrania continua is considered an idiopathic disorder, although secondary causes are recognized and discussed elsewhere. It has been speculated that hemicrania continua maybe a migraine variant as many patients have headaches with migrainous phenotype, including aura (63); however, it is well recognized that aura itself is not exclusive to migraine. Hemicrania continua has been reported to be coexistent with familial hemiplegic migraine (29). Hemicrania continua has also been reported to occur alongside other primary headaches, such as cluster headache and SUNCT (23; 81) and tension-type headache (01). This would perhaps suggest shared mechanisms in the etiology and pathophysiology of these conditions.

The mechanisms of indomethacin response are still unknown, but it is suspected to occur via inhibition of prostaglandin and neurohormone production in brain centers and peripheral pain-related structures. Theories have included decreased cerebral blood flow, reduced cerebrovascular permeability, decreased CSF pressure, an effect on melatonin secretion, and an antagonist effect on nitric oxide (19; 99).

Matharu and colleagues (49) studied 7 patients with hemicrania continua in 2 sessions. In 1 session, patients were pain-free after receiving indomethacin 100 mg intramuscularly. In the other session, patients were scanned with functional MRI during baseline pain and when still in pain after receiving intramuscular placebo. The control group included 7 age-matched and sex-matched non-headache subjects. Scans revealed significant activation of the contralateral posterior hypothalamus and ipsilateral dorsal rostral pons as well as activation of the ipsilateral ventrolateral midbrain, which extended over the red nucleus, the substantia nigra, and the bilateral pontomedullary junction. The scan exposed no obvious intracranial vessel dilation. This study demonstrated activation of various subcortical structures, particularly the posterior hypothalamus and the dorsal rostral pons. A single patient with hemicrania continua with no autonomic features but complete response to indomethacin underwent PET imaging (36). This study revealed activation of the brainstem regions as in Matharu and colleagues’ work above, but failed to show activation of the hypothalamus. Interestingly, these functional imaging studies are supported by a case of hemicrania continua found to be caused by a brainstem lesion ipsilateral to the side of pain (100). The brainstem is known to be important in regulating pain and cerebral blood flow and contains antinociceptive and trigeminal pain pathways as well as autonomic regulatory centers.

If posterior hypothalamic activations are considered to be markers of trigeminal autonomic cephalalgias (TAC) and brainstem activation specific for migrainous syndromes, the activation pattern demonstrated in hemicrania continua mirrors the overlapping clinical phenotype. However, the locality of activation is opposite to what is seen in trigeminal autonomic cephalalgias and migraine. In migraine, the brainstem activation is contralateral to the side of headache, but activation is ipsilateral in hemicrania continua. In cluster headache, the hypothalamus activation is ipsilateral to the side of pain, but contralateral in hemicrania continua.

This work has led to postulation that the hypothalamus may play an important role in headaches with prominent autonomic features and that clinical presentation may predict the pattern on brain activity in primary headache syndromes.

Differential diagnosis

Other primary chronic daily headache disorders (migraine, chronic tension-type headache, and new daily persistent headache) can be strictly unilateral, and other episodic TACs, such as cluster headache, can present with continuous interictal pain, especially in the chronic phase (47). Therefore, all patients who have strictly unilateral headaches, with or without cranial autonomic symptoms, should undergo an indomethacin trial to rule out a diagnosis of hemicrania continua.

Up to 71% of patients with hemicrania continua fulfil the diagnostic criteria for migraine during exacerbations, and migraine is the most common misdiagnosed condition for hemicrania continua (71). This makes it difficult to distinguish between the 2 conditions, which can impede treatment as the treatment modalities are different. The restlessness or agitation during attacks may be the best clinical clue to help differentiate as migraineurs prefer no movement or noise (71), but a patient with hemicrania continua cannot lie comfortably. Additionally, there may be a pain-free period noted with migraine but not with hemicrania continua.

Hemicrania continua needs to be differentiated from other trigeminal autonomic cephalalgias. Chronic paroxysmal hemicrania does not typically have the continuous baseline headache found in hemicrania continua; headache exacerbations are shorter (2 to 45 minutes), and frequency is usually more than 5 per day. Cluster headache is a severe, strictly unilateral headache that occurs predominantly at night. Attacks usually last 30 to 180 minutes and can occur as frequently as 8 times a day. Cluster headache does not typically have the continuous background headache found in hemicrania continua (although chronic patients often have background pain ipsilateral to their attacks), and the pain of exacerbations is much more severe. Smoking and sleep apnea are highly prevalent in cluster headache but not in hemicrania continua. Autonomic symptoms are more prominent in chronic paroxysmal hemicrania and cluster headache than in hemicrania continua.

There are a variety of pathologies related to secondary hemicrania continua in the literature (71). Secondary causes of hemicrania continua include intracranial structural lesions, head and neck vascular pathology, malignancy of lung, trauma, and infection. Posttraumatic headache is the most common type of secondary hemicrania continua, and postcraniectomy is the second most common secondary hemicrania continua (71). Getting a good history is crucial when these events precede the onset of hemicrania continua. The etiologies consist of a mesenchymal tumor of sphenoid (05), osteoid osteoma of ethmoid sinus (39), benign pineal cyst (69), prolactinoma (45), right brainstem ischemic lesion with secondary hemorrhage (100), several cases of carotid artery dissection (83; 07; 14), unruptured cavernous aneurysm of internal carotid artery (101), adenocarcinoma or small cell carcinoma of lung (Eross and Swanson 2001; 27; 80), head trauma (44; 79; 40), leprosy (72), HIV (15), and dental disease (57). Hemicrania continua has been described as being aggravated by a C7 root irritation due to a disc herniation (93). Indomethacin-responsive secondary hemicrania continua has also been rarely reported in association with lung tumors (25), but any case with systemic symptoms, atypical symptoms, or which becomes unresponsive to indomethacin over time should prompt a careful search for a secondary cause.

A large number of other primary headaches have been associated with hemicrania continua. There are 3 different types of association (71): (1) both headache disorders existing simultaneously (cluster headache is the most commonly associated headache) (87; 81); (2) other primary headaches evolving into hemicrania continua (there are cases where cluster headache, paroxysmal hemicrania, migraine, and SUNCT have evolved into hemicrania continua) (58; 23); and/or (3) hemicrania continua evolving into other primary headaches (there are 2 cases where hemicrania continua have evolved into other headaches) (20; 43). A case report of 2 patients with hemicrania continua–associated trigeminal neuralgia was coined HC-tic syndrome and expands on previous recognition of trigeminal neuralgia co-occurring with trigeminal autonomic cephalalgias (77).

Management

Indomethacin. Indomethacin remains the NSAID of choice for treatment of hemicrania continua. Whether hemicrania continua unresponsive to indomethacin exists remains a subject for debate. Indomethacin is usually started at a dose of 25 mg thrice daily and gradually titrated up to 100 mg thrice daily or until the patient gets complete relief. The dose required ranges from 25 to 500 mg per day. The mean indomethacin dose varies between 94 and 176 mg per day in various case series (75). A gradual dose reduction should be considered every 3 to 6 months to find out the lowest effective dose as about 60% of patients with hemicrania continua may need a lower dose over time (71).

Other medications. About 20% to 75% of patients with hemicrania continua who are taking indomethacin may potentially develop side effects requiring an alternate medication (71). Drugs other than indomethacin that are helpful include COX-2 inhibitors (celecoxib and rofecoxib), topiramate, melatonin, gabapentin, ibuprofen, piroxicam, naproxen, aspirin, acemetacin, verapamil, gabapentin, and steroids. Kumar and Bordiuk reported a complete response to ibuprofen 800 mg 2 times daily (42). Antonaci and Sjaastad found that 4 of 6 patients responded to piroxicam-beta-cyclodextrin 20 mg to 40 mg a day (05). Cases responsive to rofecoxib and celecoxib have also been reported (63; 70).

Melatonin may be an alternative treatment for indomethacin-responsive headaches. Its molecular structure is similar to that of indomethacin (68), and it tends to be more tolerable. Rozen updated prior reports of melatonin efficacy in hemicrania continua in a larger patient population (86). Of 11 patients treated with melatonin 3 to 30 mg at bedtime, 2 achieved complete pain freedom, and 3 noted partial response, which enabled substantial dose reduction of indomethacin. Several other publications also reported on the efficacy of melatonin (84; 85; 97).

Topiramate may be the best alternative to indomethacin in hemicrania continua patients and may be used as an indomethacin sparing agent (76). A number of cases responsive to topiramate have now been published (48; 13; 18; 74; 53). Topiramate is an effective drug in migraine and TACs, but the mechanism remains unknown. There is speculation of synergistic effects of topiramate in these patients. There are case reports of patients having a complete response with low-dose indomethacin and topiramate (76).

Surgical interventions. Surgical interventions can be considered in patients that do not respond to indomethacin (71). Different options include peripheral nerve blocks (24; 32); sphenopalatine ganglion block (02); occipital nerve stimulation (88; 17; 52); vagus nerve stimulation (54; 28); botulinum toxin type A (31; Khalil and Ahmed 2013; 51); radiofrequency ablation of supra orbital nerve (102); and radiofrequency ablation of C2 ventral ramus, C2 dorsal root ganglion, or sphenopalatine ganglion based on response to diagnostic blockade (08).

Lack of response to subcutaneous sumatriptan or oxygen has been reported in hemicrania continua (04; 21).

Outcomes

Espada and colleagues studied prognosis in 5 men and 4 women who had hemicrania continua (8 continuous, 1 remitting) (26). All 9 patients had initial relief with indomethacin (mean daily dose 94.4 mg, range 50 to 150). Follow-up was possible in 8 patients. Indomethacin could be discontinued after 3, 7, and 15 months, respectively, and patients remained pain-free. Three patients discontinued treatment because of side effects and had headache recurrence; 2 had relief with aspirin. Two other patients continued to take indomethacin with partial relief. Two cases of the remitting form hemicrania continua evolving from the chronic from have been published (61; 103). Both reported patients who began in the continuous stage, but 3 to 5 years later, after discontinuing regular indomethacin, remained virtually pain free. Pareja and colleagues (59) studied hemicrania continua and chronic paroxysmal hemicrania patients and found 42% of patients experienced a decrease of up to 60% in the dose of indomethacin required to maintain a pain-free state; 23% of patients reported gastrointestinal complaints that were relieved with ranitidine.

It is of note that indomethacin can, ironically, cause headache in some individuals. This adverse outcome was initially noted in the use of indomethacin for rheumatologic disease (09). This has been described as medication overuse headache in those with a migraine history (105; 21). Indomethacin was noted to induce a contralateral headache in a patient with hemicrania continua who initially experienced clinical benefit with indomethacin treatment (38; 34).

Indomethacin-induced headache is more common with higher doses. It has been proposed that gradual escalation in dose, avoiding peak blood levels with divided dosing, and taking the medication with a small meal can help limit the side effect of headaches (104).

Direct complications from the disease are not seen, but patients should be monitored for adverse effects from chronic indomethacin treatment (gastrointestinal bleeding, renal failure, neuropathy).

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Contributors

All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Authors

Julish Selvy APRN

Ms. Selvy of the Arkansas Children’s Hospital has no relevant financial relationships to disclose.
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Aravindhan Veerapandiyan MD

Dr. Veerapandiyan of University of Arkansas for Medical Sciences has no relevant financial relationships to disclose.
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Editor

Shuu-Jiun Wang MD

Dr. Wang of the Brain Research Center, National Yang-Ming University, and the Neurological Institute, Taipei Veterans General Hospital, has no relevant financial relationships to disclose.
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Former Authors

Mario F P Peres MD (original author), Shiang-Ru Lu MD, Sarah Miller MRCP, Manjit S Matharu PhD MRCP, and Carrie Dougherty MD

Patient Profile

Sex preponderance: female>male, >2:1

female>male, >1:1
Heredity: none
Population groups selectively affected: none selectively affected
Occupation groups selectively affected: none selectively affected

ICD & OMIM codes

ICD-9: Hemicrania continua: 339.41
ICD-10: Hemicrania continua: G44.51

Trigeminal autonomic cephalgias: G44.099

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Hemicrania continua

Associated Disorders

Hemicrania continua with aura
Migraine

Differential Diagnosis

migraine
carotid dissection
chronic daily headaches
chronic migraine
chronic tension-type headaches
- new daily persistent headaches
- chronic paroxysmal hemicrania
- cluster headache
- head trauma
- leprosy
- mesenchymal tumor
- HIV
- lung mass

Also Relevant

Chronic daily headache
Cluster headache
Indomethacin-responsive headache syndromes
Migraine
Paroxysmal hemicrania
- Primary stabbing headache
- SUNCT syndrome

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Headache & Pain

Patient Handouts

Web References

Guidelines

AAN: Headache

Hemicrania continua …

Hemicrania continua

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Table 1. ICHD-3 Diagnostic Criteria for Hemicrania Continua

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Diagnostic workup

Management

Outcomes

Special considerations

Pregnancy

Anesthesia

References

Contributors

Authors

Editor

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview.
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Also in This Category

Acupuncture

Migraine: pathogenesis and pathophysiology

New daily persistent headache

Headache associated with cervical spine dysfunction

Interventional options for cervicogenic headache

Pain

Ulnar neuropathy at the elbow

Vestibular migraine

Hemicrania continua

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Table 1. ICHD-3 Diagnostic Criteria for Hemicrania Continua

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Diagnostic workup

Management

Outcomes

Special considerations

Pregnancy

Anesthesia

References

Contributors

Authors

Editor

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Acupuncture

Migraine: pathogenesis and pathophysiology

New daily persistent headache

Headache associated with cervical spine dysfunction

Interventional options for cervicogenic headache

Pain

Ulnar neuropathy at the elbow

Vestibular migraine

This is an article preview.
Start a Free Account
to access the full version.