Neurosurg. Rev. 10 (1987) 191-196 lZ3I-amphetamine-SPECTin classical migraine and migraine accompagn6e Hans-Peter Schlake 1, Karl-Heinz Grotemeyer l, Ingolf B6ttger z, Ingo Wilhelm Husstedt 1, and Giinter Brune 1 1 Department of Neurology, University Hospital, and ~ Institute of Nuclear Medicine, Westffilische Wilhelms-Universitfit, Miinster, West Germany Abstract Migraine is considered to be a functional neurological disorder. In classical migraine (headache associated with prodromal visual field disturbances) and migraine accompagn6e (headache associated with transient neurological symptoms), disturbances of cerebral blood flow and amine metabolism are thought to be pathogenetic factors. However, conventional methods of neuroimaging (CAT, NMR) usually do not yield any pathological findings in patients. Since lZ3I-iodoamphetamine(123I-IMP) crosses the intact blood brain barrier, 123I-IMP-SPECTis used for the assessment of cerebral perfusion in various neurological diseases, including functional disorders. lz3I-IMP-SPECTwas performed on 5 patients with classical migraine and 18 patients with migraine accompagn6e. At the time of investigation, all patients were symptom-free. siologic information and complements anatomic and morphologic information provided by conventional methods of brain imaging [1, 2, 3]. Migraine, including classical migraine and migraine accompagn6e, is considered to represent a functional neurologic disorder. Classical migraine is clinically characterized by a migrainous headache associated with prodromal visual field disturbances. Migraine accompagn6e is characterized by migrainous headache associated with transient neurologic symptoms, i.e. hemiplegia. The pathogenesis of migraine is still obscure. Alterations of cerebral perfusion as well as disturbances of amine metabolism are considered to be pathogenetic factors. Keywords: Cerebral perfusion, migraine, SPECT. Investigations of cerebral blood flow (CBF) in patients with migraine were generally performed during prodromal and/or headache phases using conventional methods. In spite of some remarkable exceptions, these investigations support the concept of a reduction of CBF during the prodromal stage of migraine headache [5-10, 12, 13]. Only few studies have been carried out on CBF in pain-free intervals [4, 9, 11, 12]. These studies do not show any changes of CBF between migraine attacks with the exception of one case with severe complicated migraine reported by LAURITZENand OLESEN [4]. This patient demonstrated a minor low-flow region in the insula one week after an attack. 1 Introduction This paper reports on 123I-iodoamphetamine imaging of patients with classical migraine and migraine accompagn6e in symptom-free intervals. Cerebral blood flow was decreased in all patients with migraine accompagn6e, and often corresponded to the site of headache as well as to the topography of transient neurological symptoms. This reduction was most obvious in a patient with persisting neurological symptoms. Most patients with classical migraine, however, did not show any alteration of cerebral perfusion. It appears that migraine - and in particular migraine accompagn6e - is characterized by a permanent alteration not only of cerebral blood flow but also of neuronal activity. Migraine attacks may occur in connection with exacerbations of preexisting metabolic alterations. Radiolabeled amines such as 123I-iodoamphetamine are extracted by the brain in proportion to blood flow. In contrast to conventional radionuclides, 123Iiodoamphetamine crosses the intact blood brain barrier. 123I-iodoamphetamine imaging is therefore, used for the recording and assessment of cerebral perfusion in various neurologic diseases including functional disorders. The method provides phy© 1987 by Walter de Gruyter & Co. Berlin • New York 2 Patients and methods The investigation included 23 patients with migraine (14 female and 9 male patients). The average age was 28,0 + 10,4 S.D. years (range: 17 to 53 years of age). Five patients had classical migraine, while 18 patients were diagnosed as having migraine accom- 192 Schlake et al, mI-IMP-SPECT in migraine pagn6e (hemiplegic migraine: 15 patients, basilar artery migraine: 2 patients, 1 patient with persisting neurologic symptoms of hemiplegic as well as basilar artery migraine). All subjects were patients of the headache ambulance of the Department of Neurology of the University of Miinster. All patients received a neurological examination. 123I-IMP-SPECT and electroencephalography were performed in all patients during a headache-free interval. Additional investigations were performed when indicated by the results of the above examinations. 123I-IMP-SPECT was performed according to the following method: 15 min. (occasionally 3 h.) following I.V. administration of 185 MBq 123I-IMP, 64 single images were obtained within a full circle of 360 ° using a rotating gamma camera (General Electric 400ACT). Imaging time was 30 sec per image; the examinations lasted 40 min. Tomographic slices of 12 mm width were reconstructed in sagittal, coronal, and horizontal projections by filter-back-projection employing a Butterworth filter with a cut-off frequency of 0,2 cm -1 (STAR hard- and software by General Electric). Interpretation was qualitative. 3 Results Table I summarizes the results of the investigation with 123I-IMP-SPECT. Only 1 of the 5 patients with classical migraine showed a reduction of perfusion, the other 4 patients showed no alterations. All 16 patients with hemiplegic migraine demonstrated a reduction of perfusion. In most of the patients a slight or marked correlation with the site of headache and the topography of the focal transient neurologic symptoms could be observed. The two patients with basilar artery migraine showed deficits of perfusion with marked correlations to the site of headache but with no correlations to the neurologic symptoms. In the following, typical cases of the various diagnostic groups of migraine are described: Classical migraine: This 21-year-old woman had had migraine attacks since the age of seven years. The attacks show a frequency of 5 times per month with an average duration of 2 to 3 days. The headache is always initiated by typical scintillating scotoma. Her brother and one cousin also suffer from classical migraine. Neurologic examination did not reveal any pathology. The E E G yielded an alpha rhythm with some paroxysmally generalized dysrhythmic groups without any signs of focal abnormalities, 123I-IMPSPECT showed normal cerebral perfusion (Figure 1). Hemiplegic migraine: This 25-year-old man experienced his first migraine attack one year ago. The headache is localized in the left temporoparietal region and is accompagnied by a transient sensomotor paresis of the right arm and amnestic aphasia. Several attacks with the above symptoms have occurred. The mother of the patient and one brother also suffer from migraine accompagn6e. The neurologic examination yielded normal results. Electroencephalography was performed one day after the first attack. It showed a focal delta activity in the left occipitotemporal area. Four days after this examination, the E E G revealed normal patterns. Doppler sonography, CAT, NMR, and cerebral angiography did not show any pathological findings. Conventional brain scan with 99mTc-glucoheptonate performed 5 days after the attack was found to be normal. 123I-IMP-SPECT was carried out one month after the first attack. It showed a left-sided, occipitotemporal hypoperfusion corresponding to the localization of pain as well as to neurologic symptoms and E E G patterns (Figure 2). A repetition of the examination two months later still revealed a slight deficit of perfusion in this area. Basilar artery migraine: This 53 year-old woman has been suffering from migraine for 35 years. The pain Table I. Correlation between cerebral hypoperfusion and topography of symptoms in various types of migraine. Pathological Correlation SPECT findings (n) to headache localization to neurological symptoms marked slightly none marked slightly none Diagnosis n Classic migraine 5 1 0 0 5 0 0 5 Hemiplegic migraine 16" 16 6 5 5 8 6 2 Basilar artery migraine 2 2 2 0 0 0 0 2 * includes one patient with persisting neurologic symptoms. The symptoms indicate a combination of hemiplegic migraine and basilar artery migraine. Neurosurg. Rev. 10 (1987) Schlake et al, 123I-IMP-SPECTin migraine 880 193 X1 20 C 23 28 50 30 e 2J ,'Jc Q 31 Figure 1. Cerebral perfusion in a patient with classical migraine; normal symmetrical distribution of cerebral blood flow. is located in the frontal area of the left side of the head. For the last two years the headache has been initiated by transient scintillating scotoma, diplopia, vertigo, and cerebellar ataxia. Neurologic examination, E E G , Doppler sonography, visual evoked potentials and CAT revealed no abnormalities. 123IIMP-SPECT showed a slight hypoperfusion in the left-sided frontal area (Figure 3). Migraine accompagn6e with persisting neurologic symptoms (complicated migraine): This 37-year-old man had his first headache attack 5 years ago. His attacks are accompagnied by a right-sided sensomotor paresis, vertigo, and, sometimes, by dropattacks and/or loss of consciousness of short duration. The neurologic examination showed a slight sensomotor hemiparesis of the right side of the body. E E G , Doppler sonography acoustic and visual evoked potentials, electronystagmography, convenNeurosurg. Rev. 10 (1987) tional brain scintigraphy, CAT, NMR and examination of the cerebrospinal fluid did not demonstrate any abnormalities. 123I-IMP-SPECT revealed a marked hypoperfusion in the frontal and temporal regions of both sides of the head as well as in the right parietal area (Figure 4). 4 Discussion 123I-IMP-SPECT is used to determine cerebral perfusion, including brain metabolism [1, 2]. The results of this investigation clearly demonstrate that brain imaging with 123I-IMP-SPECT is able to show alterations of cerebral perfusion in functional neurologic disorders. This was possible for migraine even in symptom-free periods. There are, however, differences of perfusion in the various types of migraine. Most of the patients with classical migraine 194 Schlake et al, a231-IMP-SPECTin migraine 44 45 46 47 48 49 50 51 @ () // 0 74 .52 53 54 55 Figure 2. Cerebral perfusion in a patient with hemiplegic migraine; left sided, occipitotemporal hypoperfusion. did not exhibit any disturbances of cerebral perfusion. On the other hand, all patients with hemiplegic migraine showed deficits of perfusion and, in most patients, these deficits corresponded to the site of headache as well as to the topography of the transient focal neurologic symptoms. Patients with basilar artery migraine showed deficits of perfusion in the areas of headache; there was, however, no correlation to the topography of focal neurological symptoms. This may suggest that 123I-1MP-SPECT does not represent the basilar artery system adequately. On the whole, the investigation indicates that reductions of cerebral perfusion are more pronounced in migraine accompagn6e than in classical migraine. The deficit of cerebral perfusion was found to be most pronounced in a patient with persisting neurologic symptoms. In contrast to 12~I-IMPSPECT, conventional methods of brain imaging did not demonstrate any pathological alterations. The results obtained with 123I-IMP-SPECT indicate that migraine and in particular migraine accompagnde is characterized by a permanent alteration of cerebral perfusion and, perhaps, of neuronal activity which also exist in symptom-free intervals. 5 Conclusion This investigation of patients with migraine with 123-I-IMP-SPECT demonstrates that this method is able to show alterations of cerebral perfusion and, perhaps, alterations of neuronal activity in functional neurologic disorders even at times when no symptoms are apparent. The reduction of cerebral perfusion was observed in migraine accompagn6e; in classical migraine alteration of cerebral perfusion Neurosurg. Rev. 10 (1987) Schlake et al, 123I-IMP-SPECT in migraine I 857 195 XI FRUEH O 163 21 22 23 2~ 25 26 " a~- 29 30 31 3~ 34 35 ~e + @ 33 Figure 3. Cerebral perfusion in a patient with basilar artery migraine; slight hypoperfusion of the left frontal area with a strong correlation to the site of headache but with no correlation to the topography of neurological symptoms. was usually not seen. The most marked hypoperfusion was observed in a patient with persisting neurologic symptoms. It appears possible that mi- graine attacks occur in connection with exacerbations of existing metabolic alterations due to endogenous and/or exogenous factors. References [1] HOLMANBL, TC HILL, RGL LEE, RE ZIMMERMAN, STC MOORE, HD ROYAL: Brain Imaging with Radiolabeled Amines. In: FREEMANLM, HS WEISSMANN (eds): Nuclear Medicine Annual 1983. 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Cerebral perfusion of a patient with migraine accornpagn6e (hemiplegic and basilar artery migraine) with persisting neurologic symptoms; marked hypoperfusion of the frontal and temporal area, bilaterally, and of the right parietal region, slightly corresponding to the localization of pain and neurologic symptoms. [6] NORRISJW, VC HACHINSKI,PW COOPER:Changes in Cerebral Blood Flow during a Migraine Attack. Br Med J 3 (1975) 676-684 [7] O'BRIEN MD: Cerebral Blood Changes in Migraine. Headache 10 (1971) 139-143 [8] OLESEN J: Migraine and Regional Cerebral Blood Flow. Trends in Neurosci 8 (1985) 318-321 [9] OLESENJ, B LARSEN,M LAURITZEN:Focal Hyperemia Followed by Spreading Oligemia and Impaired Activation of rCBF in Classic Migraine. Ann Neurol 9 (1981) 344-352 [10] OLESENJ, M LAURITZEN,P TFELT-HANSEN,L HENRIKSEN, B LARSEN: Spreading Cerebral Oligemia in Classical- and Normal Cerebral Blood Flow in Common Migraine. 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