Single photon emission computed tomography (SPECT) with 99mTc-HMPAO (hexamethyl propylenamino oxime) in chronic paroxysmal hemicrania-a case report
Hans-Peter Schlake, Ingolf Gerhard Böttger, Karl-Heinz Grotemeyer, Ingo Wilhelm Husstedt, Otmar Schober
CEPHALALGIA Schlake H-P, Böttger IG, Grotemeyer K-H, Husstedt IW, Schober O. Single photon emission computed tomography (SPECT) with 99mTc-HMPAO (hexamethyl propylenamino oxime) in chronic paroxysmal hemicrania-a case report. Cephalalgia 1990;10;311-15. Oslo. ISSN 0333-1024 The case of a 69-year-old woman with chronic paroxysmal hemicrania (CPH) is presented in whom cerebral perfusion was investigated using the flow tracer 99mTc-hexamethyl propylenamino oxime (HMPAO) and single photon emission tomography (SPECT). There was a bilateral hypoperfusion in the fronto-parietal region between attacks-without medication as well as under effective treatment with verapamil. During an attack, however, SPECT investigation showed a normal cerebral perfusion. Further investigation is required to find out whether these SPECT findings are due to primary alterations of brain perfusion in CPH or are only of epiphenomenological nature. The observed effectiveness of verapamil in the prophylactic treatment of CPH should be verified in a greater number of patients. • Cerebral perfusion, chronic paroxysmal hemicrania, hexamethyl propylenamino oxime, SPECT, technetium-99m, verapamil Hans-Peter Schlake, Karl-Heinz Grotemeyer, Ingo Wilhelm Husstedt, Department of Neurology; Ingolf Gerhard Böttger, Otmar Schober, Department of Nuclear Medicine, University of Münster, Albert-Schweitzer-Strasse 33, D-4400 Münster, Federal Republic of Germany; Accepted 23 July, 1990 In 1974 Sjaastad and Dale (1) described a "new treatable headache entity", which they called "chronic paroxysmal hemicrania"(2). The clinical symptoms of chronic paroxysmal hemicrania (CPH)-a strictly unilateral headache associated with rhinorrhoea, lacrimation and conjunctival injection-are similar to those of cluster headache. However, CPH shows clear-cut differences in respect of its shorter duration (5-20 min) and higher frequency (4-38 per 24 h) of attacks, its sex distribution (females > males) and its absolute therapeutic response to indomethacin treatment (3-6). Although more than 80 cases with this new headache syndrome have been published up to now (6), its aetiology and pathogenesis are still unknown. Only few and relatively inconclusive results have been reported on the cerebral haemodynamics of both cluster headache (7-11) and chronic paroxysmal hemicrania (3). On the basis of our previous findings in migraine (7-9) and cluster headache (7, 8), we have now investigated a female patient with severe CPH. The investigation was carried out during different clinical stages using single photon emission computed tomography (SPECT) and the flow tracer 99mTc-HMPAO (hexamethyl propylenamino oxime). In contrast to radiopharmaceuticals used in conventional brain scintigraphy, this lipophilic compound is able to cross the intact blood brain barrier. It shows a high first-pass extraction into the brain proportional to blood flow with a maximum of cerebral uptake after 1-2 min and a nearly constant maintenance of the regional distribution over several hours (12-14). These radio-
pharmacokinetic properties make it possible to study cerebral perfusion even during short-lasting clinical events such as CPH attacks. Case report
This 69-year-old woman has been suffering for about 13 years from a recurring, strictly unilateral headache in the left-sided fronto-parietal region. It is associated with oedema ot the eyelid, tearing, conjunctival injection and rhinorrhoea and/or nasal congestion. Without treatment, an attack frequency of > 30 per day-sometimes 5-8 per hour-and an average duration of 5 (2-8) min were observed. The attacks were triggered by exposure to cold and draught. Pain was characterized as being "wild and burning"; for the last two years a persisting dull headache of lower intensity has occurred in the affected region between attacks (without medication). Among various prophylactic pre-treatments (for example, carbamazepine, flunarizine, lisuride, ß-blockers, dihydroergotamine), only acetyl salicylic acid and diclofenac had a moderate effect, whereas indomethacin (3 x 50 mg per day) led to a prompt and complete relief of pain, which occurred again when medication was interrupted. She had a left-sided mastectomy for breast cancer in 1972 followed by radiation. Following this she developed lymphoedema in the left upper limb. In 1976 she had a hysterectomy and appendectomy, and since 1985 she has been getting pilocarpine treatment for her glaucoma. Family history showed a similar headache in the patient's mother, but there was no evidence of a family history of migraine or other neurological disorder. In August 1989 the patient was admitted to our hospital because she had developed abdominal symptoms with chronic indomethacin treatment in a dosage of 150 mg per day. Neurological examination was normal. EEG showed an alpha-activity with repeatedly occurring dysrhythmic paroxysms without any side or focal preference. Doppler sonography was normal. Further investigations showed no evidence of a local or distant relapse of breast cancer. CAT (computer-assisted tomography) of the brain was normal. Cerebral MR tomography, which was performed with and without application of a paramagnetic contrast medium (Gadolinium-DTPA), showed a few pinhead-sized vascular lesions within the white matter (maximal diameter: 1-2 mm), mostly in the centrum semiovale and the bilateral periventricular region. These findings were considered to be age-related, probably representing small arteriosclerotic alterations. SPECT investigations
99mTc-HMPAO-SPECT investigation of regional cerebral blood flow (rCBF) was carried out under standardized environmental conditions (quiet room, dimmed light, eyes opened) according to the method described below. Fifteen minutes following iv administration of 400-600 MBq 99mTc-HMPAO 64 single images were obtained within a full circle of 360° using a rotating gamma camera (General Electric 400 ACT). Imaging time per projection was 30 sec and 40 min per examination. Tomographic slices of 12 mm width were reconstructed in sagittal, coronal and horizontal projections by filtered back-projection employing a Butterworth filter with a cut-off frequency of 0.2 cm-1. Interpretation was performed qualitatively and semi-quantitatively by visual evaluation of regional changes of tracer uptake on the colour scale, one step representing a difference of perfusion of 7%. According to 99mTc-HMPAO SPECT findings in healthy volunteers reported in the literature (14), a regional difference of cerebral tracer uptake exceeding two steps »14%) was considered to be significant. Fig. 1 shows 99mTc-HMPAO SPECT findings during the pain-free state without medi-cation. Compared to the cerebellum (maximal perfusion), a regional reduction of tracer uptake was observed bilaterally in the fronto-parietal region, the difference amounting to three to four steps on the colour
scale, representing a decrease of rCBF of » 21-28%. Fig. 2 represents the results of 99mTc-HMPAO SPECT, the tracer being injected just after the beginning of a typical CPH attack. At the time of investigation the patient was free of any medication. There is no essential regional hypoperfusion. A slight difference of regional per-fusion (in favour of the cerebellum) does not exceed one to two steps (»7-14%), which is within normal limits (14). Based on the proposed analogies between cluster headache and chronic paroxysmal hemicrania, we started a prophylactic treatment with verapamil in increasing doses up to 3 x 120 mg per day, as this drug has been proved to be effective in the prophylaxis of cluster headache (15). In our patient, verapamil led to prompt and nearly complete relief from CPH attacks for two months. After this period the attacks began to occur again, but with less frequency and pain intensity than previously. With a combined treatment of verapamil (3 x 120 mg) and a low dosage of indomethacin (1 x 50 mg per day) the patient has been almost free of any complaints for over four months. Fig. 3 shows the results of 99mTc-HMPAO-SPECT during the attack-free period under a monotherapy with verapamil (360 mg per day). Compared with cerebellar perfusion, the tracer uptake in the bilateral fronto-parietal region seems to be decreased. The difference amounts to two to four steps on the colour scale, representing a hypoperfusion of » 14-28%, which is nearly comparable to the value obtained during the headache-free period without medication. Discussion
The clinical picture of the presented case shows all the characteristics of chronic paroxysmal hemicrania, i.e. its strict unilaterality, its frequency and duration of attacks, its concomitant symptoms and its clear-cut response to indomethacin treatment. In addition, clinical neurologic examination as well as technical investigations gave no evidence of a symptomatic pathogenesis. Although in CPH normal electroencephalographic findings have been reported throughout (6), our patient revealed slight paroxysmally dysrythmic EEG alterations. As these findings did not show any side or focal preference, there is no correspondence to clinical symptoms-i.e. the strict unilaterality of pain-nor could such a relation be detected to the observed alterations of cerebral perfusion in the bilateral fronto-parietal region. It therefore appears unlikely that these unspecific electroencephalographic findings are of any significance in this case. There have been only a few reports on the investigation of the cerebral vascular system in CPH patients. Recently, Antonaci and Sjaastad (6) reviewed 16 angiograms in the literature, two of which revealed small aneurysms of the anterior communicating artery. In the present case, such vascular malformations could be excluded by means, of MR tomography, which was also done by the use of a paramagnetic contrast medium (Gadolinium-DTPA). This investigation showed a few pinhead-sized vascular lesions within the white brain matter, which were considered to be related to the patient's age (69 years), probably representing small ischaemic infarctions. It seems unlikely that the observed transitory changes of cerebral perfusion between and during CHP attacks were influenced by these minimal but permanent alterations. Up until now, rCBF measurements in CPH have been reported in only two cases by Sjaastad et al. (3) during and between CPH attacks, using intra-arterial 133Xe technique. One patient showed no alterations of rCBF, whereas a slight (but not significant) increase of cerebral blood flow was observed in the other one. Using orbital phlebography, Hannerz et al. (16) demonstrated a narrowing of the ophthalmic vein and a reduced filling of the cavernous sinus in one patient with CPH on the affected side. In our patient the investigation of cerebral perfusion by means of SPECT and the flow tracer 99mTc-HMPAO yielded a hypoperfusion (»14-28%) in the bilateral fronto-
parietal region during the pain-free interval-without medication as well as under effective treatment with verapamil. However, during an attack (without treatment), these hypoperfused areas were not detectable and SPECT was entirely normal. These alterations of brain perfusion between CPH attacks were only slight, and their significance has still to be established in a greater number of patients. On the other hand, the observed regional changes of fronto-parietal tracer uptake clearly exceed the values, which have been reported by Podreka et al. (14) for healthy persons, ranging between 0.42 ± 2.45% (SD) and 5.57 ± 3.11% in different cerebral regions. In addition, the intraindividual instability of regional tracer distribution was found to be 3.6% at most in one healthy volunteer in six 99mTc-HMPAO SPECT investigations (14). It is difficult to explain why rCBF alterations in this strictly unilateral headache syndrome were bilateral. It should be mentioned that similar regional changes of tracer uptake could also be detected in the majority of patients with migraine with aura during the pain-free interval (6-9, 17, 18) and in (pain-free) cluster headache patients during the cluster period (7, 8). These areas of regional hypoperfusion did not show any clear-cut relationship to pain localization, but mostly corresponded to the topography of transient focal neurological symptoms in migraine with aura (6-9). During migraine attacks, however, SPECT investigations gave contradictory results (19-21). Finally, it could also be argued that the increase in cerebral perfusion during a CPH attack might be caused by an unspecific pain-induced activation of rCBF. Up to now, such a mechanism remains hypothetical and has not been proved in other kinds of pain syndromes. Based on the presented SPECT findings in one patient, it therefore remains obscure whether the observed changes in cerebral perfusion were only an epiphenomenon, or are part of the primary pathogenetic process in CPH-possibly due to similar changes in regional brain metabolism and/or neuronal activity. In order to investigate these questions, the favourable properties of 99mTc-HMPAO and SPECT should enable the study of cerebral perfusion in a greater number of patients with chronic paroxysmal hemicrania. To our knowledge, the observed usefulness of verapamil in the prophylactic treatment of CPH has not been reported in the literature until now. Based on our observations, it would also be worthwhile to systematically investigate the therapeutic effectiveness of verapamil in chronic paroxysmal hemicrania. References
1.
Sjaastad O, Dale I. Evidence for a new (?) treatable headache entity. A preliminary report. Headache 1974;14:105-8
2.
Sjaastad O, Dale I. A new (?) clinical headache entity "Chronic Paroxysmal Hemicrania" 2. Acta Neurol Scand 1976;54:140-59
3.
Sjaastad O. Chronic paroxysmal hemicrania (CPH). In: Vinken PJ, Bruyn GW, Klawans HL, Clifford Rose F Eds Handbook of clinical neurology, vol. 48 (Headache). Amsterdam-New York: North Holland 1986:257-66
4.
Sjaastad O. Chronic paroxysmal hemicrania: Recent developments. Cephalalgia 1987;7:179-88
5.
Russell D. Chronic paroxysmal hemicrania: severity, duration and time of occurrences of attacks. Cephalalgia 1984;4:53-6
6.
Antonaci F, Sjaastad O. Chronic paroxysmal hemi-crania (CPH): A review of the clinical manifestations. Headache 1989;29:648-59
7.
Schlake H-P, Böttger IG, Grotemeyer K-H, Husstedt IW, Schober O. Tc-99m HMPAO SPECT during the pain-free interval of migraine and cluster headache. Cephalalgia 1989;9(suppl 10):33-4
8.
Schlake H-P, Böttger IG, Grotemeyer K-H, Husstedt IW, Vollet B, Schober O, Brune GG. Single photon emission computed tomography with Technetium-99m hexamethyl propylenamino oxime in the pain-free interval of migraine and cluster headache. Eur Neurol (1990);30:153-6
9.
Schlake H-P, Böttger IG, Grotemeyer K-H, Husstedt IW. Brain imaging with 123I-IMP-SPECT in migraine between attacks. Headache 1989;29:344-9
10.
Wesseley P, Suess E, Koch G, Wöber C, Deecke D. SPECT (99m)Tc-HMPAO findings in acute headache and during symptom-free interval. Cephalalgia 1989;9(suppl 10):62-3
11.
Gawel MJ, Krajewski A. Intracranial hemodynamics in cluster headache. Headache 1988;28: 484-7
12.
Ell PJ, Hocknell JML, Jarrit PH, Cullum I, Lui D, Campos-Costa D, Nowotnik DP, Pickett RD, Canning LR, Neirinckx RD. A 99mTc-labelled
radiotracer for the investigation of cerebral vascular disease. Nucl Med Commun 1985;6:437-41 13.
Sharp PF, Smith FW, Gemmell HG, Lyall D, Evans NTS, Gvozdanovic D, Davidson J, Tyrell DA, Pickett RD, Neirinckx RD. Technetium-99m HM-PAO stereoisomers as potential agents for imaging regional cerebral blood flow: human volunteer studies. J Nucl Med 1986;27:171-7
14.
Podreka E, Suess E, Goldenberg G, Steiner M, Brücke T, Müller C, Lang W, Neirinckx JD, Deecke D. Initial experience with Technetium-99m HM-PAO brain SPECT. J Nucl Med 1987;29:1657-66
15.
Meyer JS, Mathew N, Walker M, Zetusky WJ, Dowell RE, jr. Migraine and cluster headache treatment with calcium antagonists support a vascular pathogenesis. Headache 1985;25:358-67
16.
Hannerz J, Ericson K, Bergstrand G. Chronic paroxysmal hemicrania: orbital phlegmography and steroid treatment. A case report. Cephalalgia 1987;7:189-92
17.
Lagréze HL, Dettmers C, Hartmann A. Abnormalities of interictal perfusion in classic but not common migraine. Stroke 1988;19:1108-11
18.
Levine SR, Welch KMA, Ewing JR, Joseph R, D'Andrea G. Cerebral blood flow asymmetries in headache-free migraineurs. Stroke 1987;18:245-8
19.
Grünwald F, Durwen H, Ruhlmann J, Penin H, Biersack H-J. HM-PAO-SPECT bei Migraine Accompagnée. NucCompact 1988;19:210-13
20.
Davies PTG, Steiner TJ, Costa DC, Jones BE, Jewkes RF, Clifford Rose F. Regional cerebral blood flow during acute migraine attacks: latest results of imaging using 99 m-Tc-HMPAO and the NOVO 810 high-resolution spet scanner. 7th Migraine Trust International Symposium, 5th-8th September 1988 (Abstracts)
21.
Friberg L, Olesen J, Iversen H. Regional cerebral blood flow during attacks and when free of symptoms in a large group of migraine patients. Cephalalgia 1989;9(suppl 10):62-3
Hans-Peter Schlake, Ingolf Gerhard Böttger, Karl-Heinz Grotemeyer, Ingo Wilhelm Husstedt, Otmar Schober
CEPHALALGIA Schlake H-P, Böttger IG, Grotemeyer K-H, Husstedt IW, Schober O. Single photon emission computed tomography (SPECT) with 99mTc-HMPAO (hexamethyl propylenamino oxime) in chronic paroxysmal hemicrania-a case report. Cephalalgia 1990;10;311-15. Oslo. ISSN 0333-1024 The case of a 69-year-old woman with chronic paroxysmal hemicrania (CPH) is presented in whom cerebral perfusion was investigated using the flow tracer 99mTc-hexamethyl propylenamino oxime (HMPAO) and single photon emission tomography (SPECT). There was a bilateral hypoperfusion in the fronto-parietal region between attacks-without medication as well as under effective treatment with verapamil. During an attack, however, SPECT investigation showed a normal cerebral perfusion. Further investigation is required to find out whether these SPECT findings are due to primary alterations of brain perfusion in CPH or are only of epiphenomenological nature. The observed effectiveness of verapamil in the prophylactic treatment of CPH should be verified in a greater number of patients. • Cerebral perfusion, chronic paroxysmal hemicrania, hexamethyl propylenamino oxime, SPECT, technetium-99m, verapamil Hans-Peter Schlake, Karl-Heinz Grotemeyer, Ingo Wilhelm Husstedt, Department of Neurology; Ingolf Gerhard Böttger, Otmar Schober, Department of Nuclear Medicine, University of Münster, Albert-Schweitzer-Strasse 33, D-4400 Münster, Federal Republic of Germany; Accepted 23 July, 1990 In 1974 Sjaastad and Dale (1) described a "new treatable headache entity", which they called "chronic paroxysmal hemicrania"(2). The clinical symptoms of chronic paroxysmal hemicrania (CPH)-a strictly unilateral headache associated with rhinorrhoea, lacrimation and conjunctival injection-are similar to those of cluster headache. However, CPH shows clear-cut differences in respect of its shorter duration (5-20 min) and higher frequency (4-38 per 24 h) of attacks, its sex distribution (females > males) and its absolute therapeutic response to indomethacin treatment (3-6). Although more than 80 cases with this new headache syndrome have been published up to now (6), its aetiology and pathogenesis are still unknown. Only few and relatively inconclusive results have been reported on the cerebral haemodynamics of both cluster headache (7-11) and chronic paroxysmal hemicrania (3). On the basis of our previous findings in migraine (7-9) and cluster headache (7, 8), we have now investigated a female patient with severe CPH. The investigation was carried out during different clinical stages using single photon emission computed tomography (SPECT) and the flow tracer 99mTc-HMPAO (hexamethyl propylenamino oxime). In contrast to radiopharmaceuticals used in conventional brain scintigraphy, this lipophilic compound is able to cross the intact blood brain barrier. It shows a high first-pass extraction into the brain proportional to blood flow with a maximum of cerebral uptake after 1-2 min and a nearly constant maintenance of the regional distribution over several hours (12-14). These radio-
pharmacokinetic properties make it possible to study cerebral perfusion even during short-lasting clinical events such as CPH attacks. Case report
This 69-year-old woman has been suffering for about 13 years from a recurring, strictly unilateral headache in the left-sided fronto-parietal region. It is associated with oedema ot the eyelid, tearing, conjunctival injection and rhinorrhoea and/or nasal congestion. Without treatment, an attack frequency of > 30 per day-sometimes 5-8 per hour-and an average duration of 5 (2-8) min were observed. The attacks were triggered by exposure to cold and draught. Pain was characterized as being "wild and burning"; for the last two years a persisting dull headache of lower intensity has occurred in the affected region between attacks (without medication). Among various prophylactic pre-treatments (for example, carbamazepine, flunarizine, lisuride, ß-blockers, dihydroergotamine), only acetyl salicylic acid and diclofenac had a moderate effect, whereas indomethacin (3 x 50 mg per day) led to a prompt and complete relief of pain, which occurred again when medication was interrupted. She had a left-sided mastectomy for breast cancer in 1972 followed by radiation. Following this she developed lymphoedema in the left upper limb. In 1976 she had a hysterectomy and appendectomy, and since 1985 she has been getting pilocarpine treatment for her glaucoma. Family history showed a similar headache in the patient's mother, but there was no evidence of a family history of migraine or other neurological disorder. In August 1989 the patient was admitted to our hospital because she had developed abdominal symptoms with chronic indomethacin treatment in a dosage of 150 mg per day. Neurological examination was normal. EEG showed an alpha-activity with repeatedly occurring dysrhythmic paroxysms without any side or focal preference. Doppler sonography was normal. Further investigations showed no evidence of a local or distant relapse of breast cancer. CAT (computer-assisted tomography) of the brain was normal. Cerebral MR tomography, which was performed with and without application of a paramagnetic contrast medium (Gadolinium-DTPA), showed a few pinhead-sized vascular lesions within the white matter (maximal diameter: 1-2 mm), mostly in the centrum semiovale and the bilateral periventricular region. These findings were considered to be age-related, probably representing small arteriosclerotic alterations. SPECT investigations
99mTc-HMPAO-SPECT investigation of regional cerebral blood flow (rCBF) was carried out under standardized environmental conditions (quiet room, dimmed light, eyes opened) according to the method described below. Fifteen minutes following iv administration of 400-600 MBq 99mTc-HMPAO 64 single images were obtained within a full circle of 360° using a rotating gamma camera (General Electric 400 ACT). Imaging time per projection was 30 sec and 40 min per examination. Tomographic slices of 12 mm width were reconstructed in sagittal, coronal and horizontal projections by filtered back-projection employing a Butterworth filter with a cut-off frequency of 0.2 cm-1. Interpretation was performed qualitatively and semi-quantitatively by visual evaluation of regional changes of tracer uptake on the colour scale, one step representing a difference of perfusion of 7%. According to 99mTc-HMPAO SPECT findings in healthy volunteers reported in the literature (14), a regional difference of cerebral tracer uptake exceeding two steps »14%) was considered to be significant. Fig. 1 shows 99mTc-HMPAO SPECT findings during the pain-free state without medi-cation. Compared to the cerebellum (maximal perfusion), a regional reduction of tracer uptake was observed bilaterally in the fronto-parietal region, the difference amounting to three to four steps on the colour
scale, representing a decrease of rCBF of » 21-28%. Fig. 2 represents the results of 99mTc-HMPAO SPECT, the tracer being injected just after the beginning of a typical CPH attack. At the time of investigation the patient was free of any medication. There is no essential regional hypoperfusion. A slight difference of regional per-fusion (in favour of the cerebellum) does not exceed one to two steps (»7-14%), which is within normal limits (14). Based on the proposed analogies between cluster headache and chronic paroxysmal hemicrania, we started a prophylactic treatment with verapamil in increasing doses up to 3 x 120 mg per day, as this drug has been proved to be effective in the prophylaxis of cluster headache (15). In our patient, verapamil led to prompt and nearly complete relief from CPH attacks for two months. After this period the attacks began to occur again, but with less frequency and pain intensity than previously. With a combined treatment of verapamil (3 x 120 mg) and a low dosage of indomethacin (1 x 50 mg per day) the patient has been almost free of any complaints for over four months. Fig. 3 shows the results of 99mTc-HMPAO-SPECT during the attack-free period under a monotherapy with verapamil (360 mg per day). Compared with cerebellar perfusion, the tracer uptake in the bilateral fronto-parietal region seems to be decreased. The difference amounts to two to four steps on the colour scale, representing a hypoperfusion of » 14-28%, which is nearly comparable to the value obtained during the headache-free period without medication. Discussion
The clinical picture of the presented case shows all the characteristics of chronic paroxysmal hemicrania, i.e. its strict unilaterality, its frequency and duration of attacks, its concomitant symptoms and its clear-cut response to indomethacin treatment. In addition, clinical neurologic examination as well as technical investigations gave no evidence of a symptomatic pathogenesis. Although in CPH normal electroencephalographic findings have been reported throughout (6), our patient revealed slight paroxysmally dysrythmic EEG alterations. As these findings did not show any side or focal preference, there is no correspondence to clinical symptoms-i.e. the strict unilaterality of pain-nor could such a relation be detected to the observed alterations of cerebral perfusion in the bilateral fronto-parietal region. It therefore appears unlikely that these unspecific electroencephalographic findings are of any significance in this case. There have been only a few reports on the investigation of the cerebral vascular system in CPH patients. Recently, Antonaci and Sjaastad (6) reviewed 16 angiograms in the literature, two of which revealed small aneurysms of the anterior communicating artery. In the present case, such vascular malformations could be excluded by means, of MR tomography, which was also done by the use of a paramagnetic contrast medium (Gadolinium-DTPA). This investigation showed a few pinhead-sized vascular lesions within the white brain matter, which were considered to be related to the patient's age (69 years), probably representing small ischaemic infarctions. It seems unlikely that the observed transitory changes of cerebral perfusion between and during CHP attacks were influenced by these minimal but permanent alterations. Up until now, rCBF measurements in CPH have been reported in only two cases by Sjaastad et al. (3) during and between CPH attacks, using intra-arterial 133Xe technique. One patient showed no alterations of rCBF, whereas a slight (but not significant) increase of cerebral blood flow was observed in the other one. Using orbital phlebography, Hannerz et al. (16) demonstrated a narrowing of the ophthalmic vein and a reduced filling of the cavernous sinus in one patient with CPH on the affected side. In our patient the investigation of cerebral perfusion by means of SPECT and the flow tracer 99mTc-HMPAO yielded a hypoperfusion (»14-28%) in the bilateral fronto-
parietal region during the pain-free interval-without medication as well as under effective treatment with verapamil. However, during an attack (without treatment), these hypoperfused areas were not detectable and SPECT was entirely normal. These alterations of brain perfusion between CPH attacks were only slight, and their significance has still to be established in a greater number of patients. On the other hand, the observed regional changes of fronto-parietal tracer uptake clearly exceed the values, which have been reported by Podreka et al. (14) for healthy persons, ranging between 0.42 ± 2.45% (SD) and 5.57 ± 3.11% in different cerebral regions. In addition, the intraindividual instability of regional tracer distribution was found to be 3.6% at most in one healthy volunteer in six 99mTc-HMPAO SPECT investigations (14). It is difficult to explain why rCBF alterations in this strictly unilateral headache syndrome were bilateral. It should be mentioned that similar regional changes of tracer uptake could also be detected in the majority of patients with migraine with aura during the pain-free interval (6-9, 17, 18) and in (pain-free) cluster headache patients during the cluster period (7, 8). These areas of regional hypoperfusion did not show any clear-cut relationship to pain localization, but mostly corresponded to the topography of transient focal neurological symptoms in migraine with aura (6-9). During migraine attacks, however, SPECT investigations gave contradictory results (19-21). Finally, it could also be argued that the increase in cerebral perfusion during a CPH attack might be caused by an unspecific pain-induced activation of rCBF. Up to now, such a mechanism remains hypothetical and has not been proved in other kinds of pain syndromes. Based on the presented SPECT findings in one patient, it therefore remains obscure whether the observed changes in cerebral perfusion were only an epiphenomenon, or are part of the primary pathogenetic process in CPH-possibly due to similar changes in regional brain metabolism and/or neuronal activity. In order to investigate these questions, the favourable properties of 99mTc-HMPAO and SPECT should enable the study of cerebral perfusion in a greater number of patients with chronic paroxysmal hemicrania. To our knowledge, the observed usefulness of verapamil in the prophylactic treatment of CPH has not been reported in the literature until now. Based on our observations, it would also be worthwhile to systematically investigate the therapeutic effectiveness of verapamil in chronic paroxysmal hemicrania. References
1.
Sjaastad O, Dale I. Evidence for a new (?) treatable headache entity. A preliminary report. Headache 1974;14:105-8
2.
Sjaastad O, Dale I. A new (?) clinical headache entity "Chronic Paroxysmal Hemicrania" 2. Acta Neurol Scand 1976;54:140-59
3.
Sjaastad O. Chronic paroxysmal hemicrania (CPH). In: Vinken PJ, Bruyn GW, Klawans HL, Clifford Rose F Eds Handbook of clinical neurology, vol. 48 (Headache). Amsterdam-New York: North Holland 1986:257-66
4.
Sjaastad O. Chronic paroxysmal hemicrania: Recent developments. Cephalalgia 1987;7:179-88
5.
Russell D. Chronic paroxysmal hemicrania: severity, duration and time of occurrences of attacks. Cephalalgia 1984;4:53-6
6.
Antonaci F, Sjaastad O. Chronic paroxysmal hemi-crania (CPH): A review of the clinical manifestations. Headache 1989;29:648-59
7.
Schlake H-P, Böttger IG, Grotemeyer K-H, Husstedt IW, Schober O. Tc-99m HMPAO SPECT during the pain-free interval of migraine and cluster headache. Cephalalgia 1989;9(suppl 10):33-4
8.
Schlake H-P, Böttger IG, Grotemeyer K-H, Husstedt IW, Vollet B, Schober O, Brune GG. Single photon emission computed tomography with Technetium-99m hexamethyl propylenamino oxime in the pain-free interval of migraine and cluster headache. Eur Neurol (1990);30:153-6
9.
Schlake H-P, Böttger IG, Grotemeyer K-H, Husstedt IW. Brain imaging with 123I-IMP-SPECT in migraine between attacks. Headache 1989;29:344-9
10.
Wesseley P, Suess E, Koch G, Wöber C, Deecke D. SPECT (99m)Tc-HMPAO findings in acute headache and during symptom-free interval. Cephalalgia 1989;9(suppl 10):62-3
11.
Gawel MJ, Krajewski A. Intracranial hemodynamics in cluster headache. Headache 1988;28: 484-7
12.
Ell PJ, Hocknell JML, Jarrit PH, Cullum I, Lui D, Campos-Costa D, Nowotnik DP, Pickett RD, Canning LR, Neirinckx RD. A 99mTc-labelled
radiotracer for the investigation of cerebral vascular disease. Nucl Med Commun 1985;6:437-41 13.
Sharp PF, Smith FW, Gemmell HG, Lyall D, Evans NTS, Gvozdanovic D, Davidson J, Tyrell DA, Pickett RD, Neirinckx RD. Technetium-99m HM-PAO stereoisomers as potential agents for imaging regional cerebral blood flow: human volunteer studies. J Nucl Med 1986;27:171-7
14.
Podreka E, Suess E, Goldenberg G, Steiner M, Brücke T, Müller C, Lang W, Neirinckx JD, Deecke D. Initial experience with Technetium-99m HM-PAO brain SPECT. J Nucl Med 1987;29:1657-66
15.
Meyer JS, Mathew N, Walker M, Zetusky WJ, Dowell RE, jr. Migraine and cluster headache treatment with calcium antagonists support a vascular pathogenesis. Headache 1985;25:358-67
16.
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