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Ottar Sjaastad - One of the best experts on this subject based on the ideXlab platform.
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indomethacin responsive headache syndromes Chronic Paroxysmal Hemicrania and Hemicrania continua how they were discovered and what we have learned since
Functional Neurology, 2010Co-Authors: Ottar Sjaastad, Maurice B VincentAbstract:In the indomethacin responsive headaches (IRHs), Chronic Paroxysmal Hemicrania (CPH) and Hemicrania continua (HC), the indomethacin (INDO) response is swift, absolute, and permanent, with moderate doses. Traditionally, CPH has been linked to cluster headache (CH) due to clinical similarities: unilaterality, intensity, and some autonomic phenomena. However, other clinical features differ essentially between these two headaches: sex ratio, mean attack frequency (CPH: 13.6 versus CH: 1.7 attacks/day), and duration of attacks. The therapeutic profile in CPH (indomethacin effect: ++; triptan effect: generally non-existent) is reversed in CH. The autonomic phenomena also differ clearly, a forehead supersensitivity sweating pattern and Horner-like pupil being present only in CH. The Chronic/non-Chronic stage ratio is 3.9 in CPH, against 0.14 in CH, a >25 times difference. Conversely, CPH and HC are very similar, clinically speaking. Accordingly, we should probably sever the link between CH and CPH and favour, instead, a linking together of CPH and HC, the two principal IRHs.
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Chronic Paroxysmal Hemicrania from the index patient to the disease
Current Pain and Headache Reports, 2006Co-Authors: Ottar SjaastadAbstract:The first patient with Chronic Paroxysmal Hemicrania (CPH), a 41-year-old woman, first seen in 1961, was followed until an adequate treatment was found, 12 years later. Clinically, attack frequency and duration differed widely from the general pattern of cluster headache. Ocular variables, such as intraocular pressure and corneal indentation pulse amplitudes, also differed in our case (clear symptomatic side increment during attacks) and cluster headache. Pupil reactions to directly and indirectly acting sympathicomimetic drugs were also vastly different in our case and cluster headache: no signs of Horner’s syndrome in our patient, while cluster headache exhibits a "Horner-like pattern." In cluster headache, there is a relative hypohidrosis in the forehead on the symptomatic side if body temperature is increased, and a clear hyperhidrosis on direct parasympathomimetic stimulation. This was not so in our case. Indomethacin was highly effective in our case, while "cluster headache drugs," such as ergotamine/sumatriptan, were ineffective. Indomethacin was inactive in cluster headache. Accordingly, our case seemed to differ decisively from cluster headache: CPH had been discovered.
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Chronic Paroxysmal Hemicrania Hemicrania continua and sunct the fate of the three first described cases
Journal of Headache and Pain, 2006Co-Authors: Ottar SjaastadAbstract:The first patient with Chronic Paroxysmal Hemicrania has been followed for 45 years, and for 33 years with indomethacin treat- ment. The headache became less severe with time; there was no indomethacin tachyphylaxis. The first patient with SUNCT was fol- lowed for 28 years, until his demise at 89. Pain became worse with time. No adequate therapy was found. The first patient with Hemicrania continua was followed for 19 years, until her demise at 81. She was treated with indomethacin during the whole observation time. There was no tachyphylaxis. Both patients treated with indomethacin developed gastric ulcer. And both had gastric surgery. Indomethacin therapy may be a life-long affair. The risk of gastric complications may be substantial.
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Chronic Paroxysmal Hemicrania and Hemicrania continua lack of efficacy of sumatriptan
Headache, 1998Co-Authors: Fabio Antonaci, Juan A Pareja, A B Caminero, Ottar SjaastadAbstract:Attacks of Chronic Paroxysmal Hemicrania are prevented by the continuous administration of indomethacin. Sumatriptan, an agonist of 5-HT1-like receptors, has proven effective in the treatment of cluster headache attacks. There are clear clinical similarities between Chronic Paroxysmal Hemicrania and cluster headache. A natural consequence of these considerations would be to establish whether Chronic Paroxysmal Hemicrania also responds similarly to sumatriptan. Since Hemicrania continua is another unilateral headache responsive to indomethacin, it would be meaningful to also include Hemicrania continua in such a study. Sumatriptan, 6 mg subcutaneous, was tried in an open fashion in 7 patients (6 women and 1 man) with Chronic Paroxysmal Hemicrania and 7 patients (5 women and 2 men) with Hemicrania continua. In Chronic Paroxysmal Hemicrania, the mean interval between the last three attacks prior to sumatriptan treatment (40 ± 23 minutes) was not statistically different from the mean interval between the three attacks subsequent to sumatriptan treatment of an attack (32 ± 20 minutes). In none of the patients did the mean duration of the “test attack” decrease as compared to the attacks antedating the test attach (25 ± 11 minutes and 19 ± 9 minutes, respectively) (P=0.027, Wilcoxon). In 2 patients with Chronic Paroxysmal Hemicrania, placebo (saline) administration did not lead to any change in the interval between attacks. There was a mild, but statistically significant reduction in visual analog scale values for headache intensity in Hemicrania continua (P=0.04, Wilcoxon). There was no clear, ie, clinically meaningful, reduction in visual analog scale values in any particular patient with Hemicrania continua. Taken together, these results seem to show that sumatriptan is of no benefit in Chronic Paroxysmal Hemicrania, but may have a partial efficacy in Hemicrania continua. However, the latter effect is clinically unimportant This minor difference in regard to the clinical effect may, nevertheless, be of some interest pathogenetically, indicating minor differences between the two headaches. The lack of sumatriptan effect in Chronic Paroxysmal Hemicrania clearly and markedly strengthens the nonalignment concept in regard to Chronic Paroxysmal Hemicrania and cluster headache.
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Chronic Paroxysmal Hemicrania and Hemicrania continua parenteral indomethacin the indotest
Headache, 1998Co-Authors: Fabio Antonaci, Juan A Pareja, A B Caminero, Ottar SjaastadAbstract:The interval between indomethacin administration and clinical response may be clinically relevant in the assessment of Chronic Paroxysmal Hemicrania and Hemicrania continua and other unilateral headache disorders with which they can be confounded. Eight patients with Chronic Paroxysmal Hemicrania (6 women and 2 men) and 12 patients with Hemicrania continua (8 women and 4 men) were entered into the study. The patients were given 50 mg of indomethacin intramuscularly (IM) on day 1 and some of them 100 mg IM on day 2 in an open fashion. The usual attack pattern was reestablished prior to the second test. The mean interval between attacks before the two injections (51 ± 18 minutes) in Chronic Paroxysmal Hemicrania was significantly shorter than the mean after each of the two indomethacin injections (50 mg = 493 ± 251 minutes; 100 mg = 668 ± 211 minutes; P0.001; Mann-Whitney test). In every patient, there was a clear refractory period after indomethacin. Since the first “expected” attack after indomethacin administration did not occur, it can, with reasonable certainty, be assumed that the protective phase was initiated already prior to the time of the next “anticipated” attack. The mean attack duration was 22 minutes (last three attacks prior to test). The mean interval between the onset of two consecutive pretest attacks was 73 minutes. Since the interval between attacks was rather stable, one is, therefore, probably allowed to assume that the absolute protective effect of indomethacin on average had begun somewhere between 22 (mean attack duration) and 73 minutes after indomethacin injection. Similarly, in Hemicrania continua, the time between 50-mg indomethacin injection and complete pain relief was 73 ± 66 minutes. The pain-free period after indomethacin injection was around 13 hours (ie, 13 ± 8 hours after 50 mg and 13 ± 10 hours after 100 mg). The use of a test dosage of 50 mg of indomethacin IM (‘indotest’) gives a clear-cut answer and may be a useful tool in the diagnostic arsenal in every unilateral headache for a proper clinical assessment. A diagnosis of Chronic Paroxysmal Hemicrania or Hemicrania continua is a serious matter because it may imply life-long treatment with a potentially noxious drug. It is, therefore, of the utmost importance that an ‘indotest’ is carried out in a standard fashion. In the future, the rules set forth in the present context should be followed, at least in scientific studies. Pain pressure thresholds at cranial and extracranial levels were not significantly modified after indomethacin injection in any of the headaches.
Juan A Pareja - One of the best experts on this subject based on the ideXlab platform.
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dose efficacy and tolerability of long term indomethacin treatment of Chronic Paroxysmal Hemicrania and Hemicrania continua
Cephalalgia, 2001Co-Authors: Juan A Pareja, A B Caminero, E Franco, J L Casado, Julio PascualAbstract: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.
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Chronic Paroxysmal Hemicrania tic syndrome
Cephalalgia, 1998Co-Authors: A B Caminero, Juan A Pareja, J L DobatoAbstract:We report the coexistence of both Chronic Paroxysmal Hemicrania (CPH) and trigeminal neuralgia (tic douloureux) in a female patient. The clinical features combined to make a configuration of CPH-tic syndrome. The two components of the syndrome appeared synchronously in the same orbital region—first branch of the trigeminal nerve—with a latency of several years after the onset of isolated tic attacks of the second and third trigeminal divisions. The concurrence of both types of pain in the same symptomatic area may have some significance for pathogenic, clinical, and pharmacological aspects of such a syndrome. We discuss all these and postulate a provisional distinction between CPH-V2,3 tic and CPH-V1 tic.
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Chronic Paroxysmal Hemicrania and Hemicrania continua lack of efficacy of sumatriptan
Headache, 1998Co-Authors: Fabio Antonaci, Juan A Pareja, A B Caminero, Ottar SjaastadAbstract:Attacks of Chronic Paroxysmal Hemicrania are prevented by the continuous administration of indomethacin. Sumatriptan, an agonist of 5-HT1-like receptors, has proven effective in the treatment of cluster headache attacks. There are clear clinical similarities between Chronic Paroxysmal Hemicrania and cluster headache. A natural consequence of these considerations would be to establish whether Chronic Paroxysmal Hemicrania also responds similarly to sumatriptan. Since Hemicrania continua is another unilateral headache responsive to indomethacin, it would be meaningful to also include Hemicrania continua in such a study. Sumatriptan, 6 mg subcutaneous, was tried in an open fashion in 7 patients (6 women and 1 man) with Chronic Paroxysmal Hemicrania and 7 patients (5 women and 2 men) with Hemicrania continua. In Chronic Paroxysmal Hemicrania, the mean interval between the last three attacks prior to sumatriptan treatment (40 ± 23 minutes) was not statistically different from the mean interval between the three attacks subsequent to sumatriptan treatment of an attack (32 ± 20 minutes). In none of the patients did the mean duration of the “test attack” decrease as compared to the attacks antedating the test attach (25 ± 11 minutes and 19 ± 9 minutes, respectively) (P=0.027, Wilcoxon). In 2 patients with Chronic Paroxysmal Hemicrania, placebo (saline) administration did not lead to any change in the interval between attacks. There was a mild, but statistically significant reduction in visual analog scale values for headache intensity in Hemicrania continua (P=0.04, Wilcoxon). There was no clear, ie, clinically meaningful, reduction in visual analog scale values in any particular patient with Hemicrania continua. Taken together, these results seem to show that sumatriptan is of no benefit in Chronic Paroxysmal Hemicrania, but may have a partial efficacy in Hemicrania continua. However, the latter effect is clinically unimportant This minor difference in regard to the clinical effect may, nevertheless, be of some interest pathogenetically, indicating minor differences between the two headaches. The lack of sumatriptan effect in Chronic Paroxysmal Hemicrania clearly and markedly strengthens the nonalignment concept in regard to Chronic Paroxysmal Hemicrania and cluster headache.
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Chronic Paroxysmal Hemicrania and Hemicrania continua parenteral indomethacin the indotest
Headache, 1998Co-Authors: Fabio Antonaci, Juan A Pareja, A B Caminero, Ottar SjaastadAbstract:The interval between indomethacin administration and clinical response may be clinically relevant in the assessment of Chronic Paroxysmal Hemicrania and Hemicrania continua and other unilateral headache disorders with which they can be confounded. Eight patients with Chronic Paroxysmal Hemicrania (6 women and 2 men) and 12 patients with Hemicrania continua (8 women and 4 men) were entered into the study. The patients were given 50 mg of indomethacin intramuscularly (IM) on day 1 and some of them 100 mg IM on day 2 in an open fashion. The usual attack pattern was reestablished prior to the second test. The mean interval between attacks before the two injections (51 ± 18 minutes) in Chronic Paroxysmal Hemicrania was significantly shorter than the mean after each of the two indomethacin injections (50 mg = 493 ± 251 minutes; 100 mg = 668 ± 211 minutes; P0.001; Mann-Whitney test). In every patient, there was a clear refractory period after indomethacin. Since the first “expected” attack after indomethacin administration did not occur, it can, with reasonable certainty, be assumed that the protective phase was initiated already prior to the time of the next “anticipated” attack. The mean attack duration was 22 minutes (last three attacks prior to test). The mean interval between the onset of two consecutive pretest attacks was 73 minutes. Since the interval between attacks was rather stable, one is, therefore, probably allowed to assume that the absolute protective effect of indomethacin on average had begun somewhere between 22 (mean attack duration) and 73 minutes after indomethacin injection. Similarly, in Hemicrania continua, the time between 50-mg indomethacin injection and complete pain relief was 73 ± 66 minutes. The pain-free period after indomethacin injection was around 13 hours (ie, 13 ± 8 hours after 50 mg and 13 ± 10 hours after 100 mg). The use of a test dosage of 50 mg of indomethacin IM (‘indotest’) gives a clear-cut answer and may be a useful tool in the diagnostic arsenal in every unilateral headache for a proper clinical assessment. A diagnosis of Chronic Paroxysmal Hemicrania or Hemicrania continua is a serious matter because it may imply life-long treatment with a potentially noxious drug. It is, therefore, of the utmost importance that an ‘indotest’ is carried out in a standard fashion. In the future, the rules set forth in the present context should be followed, at least in scientific studies. Pain pressure thresholds at cranial and extracranial levels were not significantly modified after indomethacin injection in any of the headaches.
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Chronic Paroxysmal Hemicrania and Hemicrania continua : anaesthetic blockades of pericranial nerves
Functional Neurology, 1997Co-Authors: Fabio Antonaci, Juan A Pareja, Caminero, Ottar SjaastadAbstract:Greater occipital nerve (GON), supraorbital nerve (SON), and minor occipital nerve (MON) blockades-in this sequence-were carried out on the symptomatic side in patients with Chronic Paroxysmal Hemicrania (CPH) (no = 6) and Hemicrania continua (HC) (no = 7). Prior to the blockade, indomethacin was discontinued for a sufficiently long time (24 h) to allow a constant flow of attacks/constant pain. The local anaesthetic agent used was lidocaine. The blockades were invariably negative in CPH. In HC, the GON and MON blockades generally had no positive influence. The pattern as regards SON blockades was slightly different, in that the pre-test average VAS-value of 7.3 decreased to 4.6 (p < 0.05, Student's t-test, and p = 0.065 Wilcoxon) and-on an individual basis-decreased in 4 out of 7 patients. GON/MON blockades will help distinguish CPH/HC from cervicogenic headache. SON blockade will have to be carried out in a good-sized series of HC patients in order to establish more concrete evidence of the putative effect in HC. SON blockades may eventually also aid in the distinction between HC and supraorbital nerve neuralgia (where the blockade effect generally seems to be complete).
Peter J Goadsby - One of the best experts on this subject based on the ideXlab platform.
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The Paroxysmal Hemicrania‐tic syndrome
Cephalalgia, 2020Co-Authors: Christopher J Boes, Matharu, Peter J GoadsbyAbstract:Two cases of Paroxysmal Hemicrania (PH) associated with trigeminal neuralgia are reviewed. The Paroxysmal Hemicrania component in one patient was episodic, while it was Chronic in the other. Each headache type responded completely to separate treatment, highlighting the importance of recognizing this association. We review the six other cases of Chronic Paroxysmal Hemicrania-tic (CPH-tic) reported, and suggest that the term Paroxysmal Hemicrania-tic syndrome (PH-tic) be used to describe this association.
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post traumatic Chronic Paroxysmal Hemicrania cph with aura
Neurology, 2001Co-Authors: Manjit Matharu, Peter J GoadsbyAbstract:The authors describe a patient who developed Chronic Paroxysmal Hemicrania (CPH) in close temporal relationship to a head injury. The subsequent attacks of CPH were associated with a typical migrainous sensory and motor aura. Administration of indomethacin 75 mg daily resulted in isolated occurrence of autonomic and aura symptoms in the absence of pain symptoms. The patient became completely asymptomatic on indomethacin 100 mg daily. Migrainous aura may be seen with trigeminal-autonomic headaches and may represent the expression of an aura-susceptibility gene rather than typical migraine headache biology.
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neuropeptide changes in a case of Chronic Paroxysmal Hemicrania evidence for trigemino parasympathetic activation
Cephalalgia, 1996Co-Authors: Peter J Goadsby, Lars EdvinssonAbstract:Chronic Paroxysmal Hemicrania (CPH) is a rare headache syndrome of short-lasting attacks of pain, characterized clinically by trigemino-parasympathetic activation. The features of the headache are severe attacks of pain that generally last no more than minutes in association with autonomic activation, such as lacrimation or rhinorrhea. We report a patient fulfilling International Headache Society guidelines for the diagnosis of CPH in whom levels of calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) were elevated in the cranial circulation during attacks. Moreover, successful treatment of the problem with indomethacin leads to normalization of the levels of both CGRP and VIP. Given that similar neuropeptide changes are seen in cluster headache the data suggest a shared underlying pathophysiology between CPH and cluster headache.
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Neuropeptide changes in a case of Chronic Paroxysmal Hemicrania—evidence for trigemino‐parasympathetic activation
Cephalalgia, 1996Co-Authors: Peter J Goadsby, Lars EdvinssonAbstract:Chronic Paroxysmal Hemicrania (CPH) is a rare headache syndrome of short-lasting attacks of pain, characterized clinically by trigemino-parasympathetic activation. The features of the headache are severe attacks of pain that generally last no more than minutes in association with autonomic activation, such as lacrimation or rhinorrhea. We report a patient fulfilling International Headache Society guidelines for the diagnosis of CPH in whom levels of calcitonin gene-related peptide (CGRP) and vasoactive intestinal polypeptide (VIP) were elevated in the cranial circulation during attacks. Moreover, successful treatment of the problem with indomethacin leads to normalization of the levels of both CGRP and VIP. Given that similar neuropeptide changes are seen in cluster headache the data suggest a shared underlying pathophysiology between CPH and cluster headache.
F Jose A C P L Medina - One of the best experts on this subject based on the ideXlab platform.
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organic headaches mimicking Chronic Paroxysmal Hemicrania
Headache, 1992Co-Authors: F Jose A C P L MedinaAbstract:SYNOPSIS 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.
A B Caminero - One of the best experts on this subject based on the ideXlab platform.
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dose efficacy and tolerability of long term indomethacin treatment of Chronic Paroxysmal Hemicrania and Hemicrania continua
Cephalalgia, 2001Co-Authors: Juan A Pareja, A B Caminero, E Franco, J L Casado, Julio PascualAbstract: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.
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Chronic Paroxysmal Hemicrania tic syndrome
Cephalalgia, 1998Co-Authors: A B Caminero, Juan A Pareja, J L DobatoAbstract:We report the coexistence of both Chronic Paroxysmal Hemicrania (CPH) and trigeminal neuralgia (tic douloureux) in a female patient. The clinical features combined to make a configuration of CPH-tic syndrome. The two components of the syndrome appeared synchronously in the same orbital region—first branch of the trigeminal nerve—with a latency of several years after the onset of isolated tic attacks of the second and third trigeminal divisions. The concurrence of both types of pain in the same symptomatic area may have some significance for pathogenic, clinical, and pharmacological aspects of such a syndrome. We discuss all these and postulate a provisional distinction between CPH-V2,3 tic and CPH-V1 tic.
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Chronic Paroxysmal Hemicrania and Hemicrania continua lack of efficacy of sumatriptan
Headache, 1998Co-Authors: Fabio Antonaci, Juan A Pareja, A B Caminero, Ottar SjaastadAbstract:Attacks of Chronic Paroxysmal Hemicrania are prevented by the continuous administration of indomethacin. Sumatriptan, an agonist of 5-HT1-like receptors, has proven effective in the treatment of cluster headache attacks. There are clear clinical similarities between Chronic Paroxysmal Hemicrania and cluster headache. A natural consequence of these considerations would be to establish whether Chronic Paroxysmal Hemicrania also responds similarly to sumatriptan. Since Hemicrania continua is another unilateral headache responsive to indomethacin, it would be meaningful to also include Hemicrania continua in such a study. Sumatriptan, 6 mg subcutaneous, was tried in an open fashion in 7 patients (6 women and 1 man) with Chronic Paroxysmal Hemicrania and 7 patients (5 women and 2 men) with Hemicrania continua. In Chronic Paroxysmal Hemicrania, the mean interval between the last three attacks prior to sumatriptan treatment (40 ± 23 minutes) was not statistically different from the mean interval between the three attacks subsequent to sumatriptan treatment of an attack (32 ± 20 minutes). In none of the patients did the mean duration of the “test attack” decrease as compared to the attacks antedating the test attach (25 ± 11 minutes and 19 ± 9 minutes, respectively) (P=0.027, Wilcoxon). In 2 patients with Chronic Paroxysmal Hemicrania, placebo (saline) administration did not lead to any change in the interval between attacks. There was a mild, but statistically significant reduction in visual analog scale values for headache intensity in Hemicrania continua (P=0.04, Wilcoxon). There was no clear, ie, clinically meaningful, reduction in visual analog scale values in any particular patient with Hemicrania continua. Taken together, these results seem to show that sumatriptan is of no benefit in Chronic Paroxysmal Hemicrania, but may have a partial efficacy in Hemicrania continua. However, the latter effect is clinically unimportant This minor difference in regard to the clinical effect may, nevertheless, be of some interest pathogenetically, indicating minor differences between the two headaches. The lack of sumatriptan effect in Chronic Paroxysmal Hemicrania clearly and markedly strengthens the nonalignment concept in regard to Chronic Paroxysmal Hemicrania and cluster headache.
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Chronic Paroxysmal Hemicrania and Hemicrania continua parenteral indomethacin the indotest
Headache, 1998Co-Authors: Fabio Antonaci, Juan A Pareja, A B Caminero, Ottar SjaastadAbstract:The interval between indomethacin administration and clinical response may be clinically relevant in the assessment of Chronic Paroxysmal Hemicrania and Hemicrania continua and other unilateral headache disorders with which they can be confounded. Eight patients with Chronic Paroxysmal Hemicrania (6 women and 2 men) and 12 patients with Hemicrania continua (8 women and 4 men) were entered into the study. The patients were given 50 mg of indomethacin intramuscularly (IM) on day 1 and some of them 100 mg IM on day 2 in an open fashion. The usual attack pattern was reestablished prior to the second test. The mean interval between attacks before the two injections (51 ± 18 minutes) in Chronic Paroxysmal Hemicrania was significantly shorter than the mean after each of the two indomethacin injections (50 mg = 493 ± 251 minutes; 100 mg = 668 ± 211 minutes; P0.001; Mann-Whitney test). In every patient, there was a clear refractory period after indomethacin. Since the first “expected” attack after indomethacin administration did not occur, it can, with reasonable certainty, be assumed that the protective phase was initiated already prior to the time of the next “anticipated” attack. The mean attack duration was 22 minutes (last three attacks prior to test). The mean interval between the onset of two consecutive pretest attacks was 73 minutes. Since the interval between attacks was rather stable, one is, therefore, probably allowed to assume that the absolute protective effect of indomethacin on average had begun somewhere between 22 (mean attack duration) and 73 minutes after indomethacin injection. Similarly, in Hemicrania continua, the time between 50-mg indomethacin injection and complete pain relief was 73 ± 66 minutes. The pain-free period after indomethacin injection was around 13 hours (ie, 13 ± 8 hours after 50 mg and 13 ± 10 hours after 100 mg). The use of a test dosage of 50 mg of indomethacin IM (‘indotest’) gives a clear-cut answer and may be a useful tool in the diagnostic arsenal in every unilateral headache for a proper clinical assessment. A diagnosis of Chronic Paroxysmal Hemicrania or Hemicrania continua is a serious matter because it may imply life-long treatment with a potentially noxious drug. It is, therefore, of the utmost importance that an ‘indotest’ is carried out in a standard fashion. In the future, the rules set forth in the present context should be followed, at least in scientific studies. Pain pressure thresholds at cranial and extracranial levels were not significantly modified after indomethacin injection in any of the headaches.