Chronic Paroxysmal Hemicrania and Hemicrania Continua: Orbital Phlebography and MRI Studies

SYNOPSIS
Six patients with chronic paroxysmal hemicrania (CPH) and 10 patients with hemicrania continua (HC), two indomethacin-responsive, unilateral, headache syndromes, were investigated with orbital phlebography and magnetic resonance imaging of the brain. Orbital phlebography apparently showed pathological findings more frequently in CPH than in HC. Such abnormalities did not always show preference for the side of headache. MR scans were grossly normal in these headaches.     

Hemicrania continua changed to chronic paroxysmal hemicrania after treatment with cyclooxygenase-2 inhibitor

Remission of hemicrania continua (HC) and transformation from HC to chronic paroxysmal hemicrania (CPH) are unusual. We report a patient with left-sided HC who, after a period of remission, presented as CPH. The continuous HC headache disappeared completely after initiating treatment with cyclooxygenase (COX)-2 inhibitor, but reappeared on the same side after 14 months remission with paroxysmal, frequent, intense and short-lasting headache attacks accompanied by ipsilateral cranial autonomic symptoms. This happened shortly after the treatment was discontinued because of withdrawal of the COX-2 inhibitor from the market. The response to indomethacin was prompt, and the patient became completely free from her paroxysmal headache with a dose of 50 mg 2 times daily. This case questions a possible modification effect on the course of HC by use of COX-2 inhibitor, as well as further supporting that some aspects of the pathophysiology of HC may resemble those of CPH, and may argue for common biological mechanisms in HC and CPH.     

Hemicrania continua: diagnostic criteria and nosologic status

Proposals for the diagnostic criteria for hemicrania continua (HC) and also for the nosological status of HC are set forth. The clinical constellation of symptoms and signs making up HC consists of: unilaterality without side shift; absolute indomethacin effect; and long-lasting repetitive attacks of varying duration, eventually with a chronic pattern, the pain being mild to severe. For the typical clinical picture of HC, including a positive 'indotest', we propose the term hemicrania continua vera. More or less analogous, but 'indotest-negative' clinical pictures have provisionally been termed hemicrania generis incerti (of undetermined nature). At the present level of knowledge, the diagnosis of hemicrania generis incerti should be made mostly by exclusion. HC may possibly best be classified along with chronic paroxysmal hemicrania (CPH) as this is the only other headache absolutely responsive to indomethacin. The bond between these two headaches on the one hand and cluster headache on the other should, at most, be a loose one. Interrelationships of these four classifiable headaches are briefly discussed.     

CPH and Hemicrania Continua: Requirements of High Indomethacin Dosages -An Ominous Sign?

Two female patients, one with chronic paroxysmal hemi-crania and one with hemicrania continua, had a continuously high requirement of indomethacin, ie, ³ 225 mg per day, for 4 and 7 years, respectively. In the hemicrania continua patient, a right (symptomatic side) C7 root affection due to disc herniation was demonstrated. Removal of the disc relieved the arm pain completely, and reduced the head pain and indomethacin requirement considerably initially. The other patient suffered from the unremitting form of chronic paroxysmal hemicrania with right-sided attacks from the age of 16. Indomethacin, 200 to 250 mg per day generally kept the headache at bay, but during exacerbations, especially during menstrual periods, the dosage transitorily had to be increased to 250 to 350 mg per day. ACT scan with contrast at aged 18 (1987) was negative. In 1992, she started having new symptoms, including numbness on the ipsilateral side of the face and arm and difficulty swallowing. An MR scan showed a meningioma originating in the roof of the cavernous sinus on the symptomatic side. The meningioma was surgically removed. The postoperative indomethacin requirement was reduced, but only transiently. Patients with chronic paroxysmal hemicrania (CPH) and hemicrania continua (HC) with a continuously high indomethacin requirement may have grave additional disorders and should consequently be followed closely.     

"Hemicrania Continua": A Clinical Review

Hemicrania continua (HC) is a headache entity completely responsive to indomethacin. Since 1984, 18 cases have been described, 15 females and 3 males, i.e. a F:M ratio of 5.0. The finding of a female preponderance, like that in chronic paroxysmal hemicrania, is a new observation. HC is, in general, a unilateral headache in the sense that it sets in on one side and subsequently sticks to this side. In two cases, both sides might possibly be involved, when the pain was at its maximum. In another (somewhat dubious) case the headache was bilateral. The pain was continuous from the beginning in 8 of 18 cases (early stage ratio continuous: non-continuous = 0.8). Over time, the headache developed a continuous character in 16 of the 18 cases, producing a "continuous: non-continuous ratio" of 8:1. The intensity of pain generally was moderate and was not reported as excruciatingly severe by any patient. The autonomic involvement from a clinical point of view, was clearly less pronounced than that of other unilateral headaches, such as cluster headache and chronic paroxysmal hemicrania.     

Dose, efficacy and tolerability of long-term indomethacin treatment of chronic paroxysmal hemicrania and hemicrania continua

Indomethacin has consistently been proven to provide complete and sustained relief of symptoms in hemicrania continua (HC) and chronic paroxysmal hemicrania (CPH), but is not devoid of side-effects. The goal of this retrospective study is to assess the dose and side-effects of prolonged indomethacin treatment of HC and CPH. Twenty-six patients with either HC or CPH were followed during an average of 3.8 years after onset of treatment with indomethacin. Relief of symptoms occurred within 3 days of treatment, with 84 +/- 32 mg/day of indomethacin. With time, 42% of patients experienced a decrease of up to 60% in the dose of indomethacin required to maintain a pain-free state. Six (23%) patients showed adverse events, mostly gastrointestinal and relieved with ranitidine. No major side-effects were observed. These results indicate that prolonged indomethacin treatment of HC or CPH has a good safety and tolerability profile with a reduction of up to 60% in the initial dose.     

Hemicrania continua: who responds to indomethacin?

Hemicrania continua (HC) is a primary headache disorder characterized by a continuous, moderate to severe, unilateral headache and defined by its absolute responsiveness to indomethacin. However, some patients with the clinical phenotype of HC do not respond to indomethacin. We reviewed the records of 192 patients with the putative diagnosis of HC and divided them into groups based on their headaches' response to indomethacin. They were compared for age, gender, presence or absence of specific autonomic symptoms, medication overuse, rapidity of headache onset, and whether or not the headaches met criteria for migraine when severe. Forty-three patients had an absolute response and 122 patients did not respond to adequate doses of indomethacin. The two groups did not differ significantly in terms of age, sex, presence of rapid-onset headache, or medication overuse. Autonomic symptoms, based on a questionnaire, did not predict response. Eighteen patients could not complete a trial of indomethacin due to adverse events. Nine patients could not be included in the HC group despite improvement with indomethacin: one patient probably had primary cough headache, another paroxysmal hemicrania; three patients improved but it was uncertain if they were absolutely pain free, and four patients dramatically improved but still had a baseline headache. We found no statistically significant differences between patients who did and did not respond to indomethacin. All patients with continuous, unilateral headache should receive an adequate trial of indomethacin. Most patients with unilateral headache suggestive of HC did not respond to indomethacin.     

Coexisting Trigeminal Autonomic Cephalalgias and Hemicrania Continua

The trigeminal autonomic cephalalgias (TACs) and hemicrania continua (HC) share many clinical characteristics including unilateral pain and ipsilateral autonomic features. We report a patient with a history of migraine without aura who developed cluster headache and HC simultaneously. The distinctive clinical features and differential response profiles to various treatments indicates that they are distinct disorders. We then review previous reports of patients with coexisting TACs and HC and discuss the relationship between these families of primary headache disorders.     

Chronic paroxysmal hemicrania

Pupillometric studies were carried out in eight patients with chronic paroxysmal hemicrania (CPH) and in age- and sex-matched controls in the basal condition and after instillation of 2% tyramine (CPH, n = 5; controls, n = 17), 1% OH-amphetamine (CPH, n = 6; controls, n = 12), and 1% phenylephrine (CPH, n = 6; controls, n = 17). The pupil on the symptomatic and non-symptomatic sides in CPH patients was significantly smaller in the basal condition than in controls, particularly on the symptomatic side. The mydriatic responses to pharmacologic stimulation were essentially similar on the symptomatic and non-symptomatic sides. An evaporimetric study of the forehead sweat glands, using the body heating and pilocarpine tests, was also carried out in these patients and in age- and sex-matched controls. "Early", "intermediate", and "late" measurements demonstrated symmetry of forehead sweating. The findings for both methods of examination thus contrast with those in cluster headache patients. Pupillometric and forehead sweating patterns therefore suggest differences in the pathogenesis of the two headache entities. These tests may be used to distinguish CPH and cluster headache clinically.     

A Piroxicam Derivative Partly Effective in Chronic Paroxysmal Hemicrania and Hemicrania Continua

Piroxicam beta-cyclodextrin has recently been observed to be equal to, or even possibly to be superior to, indomethacin (mainly with regard to side effects) in a single case of hemicrania continua. Piroxicam beta-cyclodextrin, 20 to 40 mg per day, was, accordingly, tried in six patients with chronic paroxysmal hemicrania and six patients with hemicrania continua with a previously proven response to indomethacin. The study was conducted over a period of 3 weeks and in an open fashion. A placebo effect is considered to be negligible in these disorders. In such a comparison, piroxicam beta-cyclodextrin seemed inferior to indomethacin, in particular in chronic paroxysmal hemicrania.     

Chronic Paroxysmal Hemicrania and Hemicrania Continua. Interval Between Indomethacin Administration and Response

The interval between indomethacin dosage and clinical response was assessed in hemicrania continua (n=12) and chronic paroxysmal hemicrania (n=11) sufferers. The number of trials per patient ranged from I to 30. At the time of testing, the patients had "considerable" pain after discontinuation of the drug. The dosage used was the usual one for that patient at the given pain level; ie, 25 or 50 mg tid. All the patients had a complete, long-term response to treatment. Nevertheless, the average interval between drug intake and pain relief during the present study ranged beween 30 minutes and 48 hours in both disorders. In most patients (10 in both groups), the indomethacin effect was complete within 24 hours, and frequently within 8 hours. It is suggested that interindividual differences in dosage and timing to abolish the headaches may be due to different bioavailability or individual sensitivity. Recommendations on indomethacin testing in unilateral headaches are given.     

Transcranial Doppler Sonography in Chronic Paroxysmal Hemicrania

SYNOPSIS
Three patients with chronic paroxysmal hemicrania (CPH) (1 M, 2 F) and 9 healthy controls (8 M I F) were studied with transcranial Doppler (TCD) sonography. One patient who was studied during the spontaneous attacks hyperventilated markedly. Middle cerebral artery velocity (V_MCA) was measured in the first attack, and anterior cerebral artery velocity (V_ACA) in the second attack, respectively. V_MCA and V_ACA decreased bi-laterally during attack. V_MCA started to decrease at an early stage of the attack, i.e. prior to the major hyperventilation that was observed during the attack. V_ACA on the symptomatic side decreased less than that on the other side (P<0.05). Cerebral vasomotor reactivity (VMR) was expressed as the percentage change in mean blood flow velocity as a function of end-tidal PCO₂ (P_ETCO₂) reduction induced by voluntary hyperventilation (DV/DP_ETCO₂). In the 3 patients, a slightly lowered VMR was observed in the MCA and posterior cerebral artery on both sides, and in the ACA on the symptomatic side IP>0.05) in comparison with controls. These observations may imply an abnormal vascular reactivity in CPH.     

Chronic paroxysmal hemicrania, hemicrania continua and SUNCT syndrome in association with other pathologies: a review

We present a review of 22 cases of headache mimicking chronic paroxysmal hemicrania (CPH) (17 female and five male; F : M ratio 3.4), nine cases mimicking hemicrania continua (HC) (seven female and two male) and seven cases mimicking SUNCT syndrome (five male and two female) found in association with other pathologies published from 1980 up to the present. All case reports were discussed with respect to diagnostic criteria proposed by International Headache Society (IHS) for CPH, by Goadsby and Lipton for HC and SUNCT, and evaluated to identify a possible causal relationship between the pathology and the onset of headache. The aim of the present review was to evaluate if the presence of associated lesions and their location could help elucidate the pathogenesis of trigeminal autonomic cephalalgias (TACs).     

Organic Headaches Mimicking Chronic Paroxysmal Hemicrania

The article describes two women who had headaches that mimicked chronic paroxysmal hemicrania (CPH). The first patient had a collagen vascular disorder; and the second one, a large malignant tumor in the right frontal lobe. The similarity of the headaches of the first patient to CPH included an absolute response to indomethacin. The existence of these cases may lead to a better understanding of the pathophysiology of CPH. At the same time, their existence also calls for caution in the diagnosis of CPH.     

Hemicrania Continua‐Like Headache Related to Transdermal Nitroglycerine Therapy

Several cases of symptomatic hemicrania continua (HC) have been reported. A 66‐year‐old man, suffering from migraine without aura, presented with a four month history of a new headache fulfilling the ICHD 3beta clinical criteria for HC. HC onset was strictly related to the use of transdermal nitroglycerine patch (TNP). In agreement with the cardiologist, TNP was discontinued and the headache promptly disappeared; symptoms reappeared within 6‐12 hours after nitroglycerine reintroduction. After permanent discontinuation of TNP, headache disappeared at one year follow‐up. To the best of our knowledge, this is the first report of the occurrence of an HC‐like headache related to TNP.     

Asymmetrical reduction of the nociceptive flexion reflex threshold in cluster headache

The nociceptive flexion reflex (NFR) of the lower limbs (RIII reflex) was examined bilaterally in 54 cluster headache (CH) patients suffering from episodic CH (ECH) and chronic CH (CCH). Fifteen ECH patients were examined in both remission and active phases. The RIII reflex threshold (Tr) and the threshold of pain sensation (Tp) were significantly reduced on the symptomatic side in patients with episodic CH during the bout. During the active phase of episodic CH an inverse correlation was found between the severity of CH (ratio: number of cluster periods/years of illness duration) and the Tp, which may suggest a role for secondary central sensitization in pain pathways. The lower Tr and Tp on the symptomatic side is in keeping with previous observations exploring pain mechanisms using different methods (i.e. corneal reflex, pain pressure threshold). On the whole, these data tie in with the view of an impairment of the pain control system, which parallels the periodicity of the disorder in the episodic form.     

Intracranial Hypertension and Sumatriptan Efficacy in a Case of Chronic Paroxysmal Hemicrania Which Became Bilateral. (The Mechanism ofIndomethacin in CPH.)

SYNOPSIS
A female patient is described who had a four year long period of unilateral chronic paroxysmalhemicrania (CPH) which then became bilateral. For some years before the CPH started she suffered fromperiods of about one month with chronic hemicrania without nerve involvement. She also suffered fromchronic fatigue, back pain, arthralgia, vertigo, chronic constipation and spontaneous ecchymoses. Bloodtests showed chronic leukocytosis, low serum iron, and signs of inflammation in serum electrophoresisduring the five years she was studied. CPH attacks could be provoked by breathing 6% carbon dioxide inair. Lumbar cerebrospinal fluid pressure was pathologically increased (30 cm water). The attacksdecreased during indomethacin treatment but 275 mg was needed for satisfactory control of the attacks,i.e., more than the 150 mg which, according to the criteria for CPH, should be absolutely effective.Sumatriptan was found to suppress the CPH attacks as well as indomethacin. Due to these findings CPH isconsidered to be another manifestation of venous vasculitis. The beneficiary mechanism of indomethacinin CPH is considered to be due partly to its anti-inflammatory effects and partly to its reduction of theintracranial blood flow.     

Alternatives in Drug Treatment of Chronic Paroxysmal Hemicrania

Indomethacin is the drug of first choice in chronic paroxysmal hemicrania with clear relief of pain as a diagnostic criterion. In a few cases, indomethacin is not tolerated because of side effects. Therefore, the efficacy of carbamazepine, verapamil. sumatriptan. acetylsalicylic acid, and oxygen as drugs in the prophylactic or acute treatment of chronic paroxysmal hemicrania was studied in a prospective open trial with 10 patients suffering from chronic paroxysmal hemicrania. The trial results, in accordance with a review of the literature. suggest that acetylsalicylic acid (and probably naproxen and diclofenac) and verapamil are the most effective drugs of second choice in chronic paroxysmal hemicrania. The efficacy of sumatriptan in this condition needs still to be clarified. although there is evidence for partial efficacy. Carbamazepine and oxygen did not show any significant influence on chronic paroxysmal hemicrania.     

Trait- and Frequency-Dependent Dysfunctional Habituation to Trigeminal Nociceptive Stimulation in Trigeminal Autonomic Cephalalgias

We investigated whether the stimulation frequency (SF), the pain phases, and different diagnoses of trigeminal autonomic cephalalgias (TACs) may influence the habituation to pain. We studied the habituation of the nociceptive blink reflex R2 responses at different SFs (.05, .1, .2, .3, .5, and 1?Hz), in 28 episodic cluster headache (ECH) patients, 16 during and 12 outside the bout; they were compared with 16 episodic paroxysmal hemicrania (EPH) during the bout and 21 healthy subjects. We delivered 26 electrical stimuli and subdivided stimuli 2 to 26 in 5 blocks of 5 responses for each SF. Habituation values for each SF were expressed as the percentages of the mean area value of second through fifth blocks with respect to the first one. A significant lower mean percentage decrease of the R2 area across all blocks was found at .2 to 1?Hz SF during ECH, outside of the ECH, and EPH compared with healthy subjects. We showed a common frequency-dependent deficit of habituation of trigeminal nociceptive responses at higher SFs in ECH and EPH patients, independently from the disease phase. This abnormal temporal pattern of pain processing may suggest a trait-dependent dysfunction of some underlying pain-related subcortical structures, rather than a state-dependent functional abnormality due to the recurrence of the headache attacks during the active period.