Article abstract
lnterictal regional cerebral blood flow was determined in 11 adult patients with partial epilepsy and lateralized electroencephalographicabnormalities by means of the xenon 133 intracarotid injection method. A hemispheric area demonstrating significantly low regional cerebral blood flow values as compared with the hemispheric mean cerebral blood flow was observed in each of the patients. In 10 of the 11 patients the localized reduced regional cerebral blood flow levels deviated significantly from levels obtained from parallel regions and hemispheres of normal controls. In the majority of patients, the site of low regional cerebral blood flow closely correlated with the clinical type of partial seizures and/or the site of main electroencephalographic abnormality. On the basis of these data, we suggest that the epileptogenic focus responsible for the partial seizures may be localized within the hemispheric area demonstrating the abnormal regional cerebral blood flow reduction.
lnterictal regional cerebral blood flow in patients with partial seizures SYLVAN LAVY, M.D., ELDAD MELAMED, M.D., ZIPORA PORTNOY, M.Sc., and AMIRAM CARMON, M.D.
B
0th early and recent experimental studies in animals and clinical studies in man have demonstrated that cerebral blood flow (CBF) increases during induced or spontaneous seizures.’-9 Little is known, however, about the blood flow in the epileptic brain during the seizure-free interval. It has been reported to be normal in adult epileptic patientslO and to be only slightly reduced in epileptic children.” Since only the mean CBF was recorded in these studies, focal circulatory abnormalities could not have been detected. Furthermore, these studies included patients with both focal and generalized seizures. Since it is plausible to assume that in the first instance, a localized cerebral pathology accounts for the focal seizures, it is also reasonable to expect regional cerebral blood flow (rCBF) abnormalities in this group of patients and not in patients with generalized ‘‘centrencephalic” seizures. The rCBF measurement allows the evaluation of the circulatory status in hemispheric epileptic foci, which might be altered by the From the Department of Neurology and Laboratory for Cerebral Vascular Research, Hadassah-UniversityHospitaland Hebrew University-Hadassah Medical School, Jerusalem, Israel. Received for publication July 25, 1975. Dr. Lavy’s address is Department of Neurology, Hadassah Medical Organization, Mayer de Rothschild Hadassah University Hospital, Kiryat Hadassah. Jerusalem, Israel.
418 NEUROLOGY 26: 418-422, May 1976
underlying structural or functional impairment. The present study was undertaken in order to determine the rCBF of patients with partial epilepsy during the interictal period by means of the xenon 133 (133Xe) intracarotid injection method .
Subjects and method. Eleven hospitalized adult epileptic patients were studied. Their ages ranged from 20 to 63 years (mean 41 years). Patient selection was determined both by the type of seizures and by the electroencephalographic findings. Gastaut’s’* classification served as a guideline in both criteria. Thus, only patients who had partial epilepsy were included in the present study. These were patients in whom seizures began locally with elementary or with complex symptomatology or patients with partial seizures that were secondarily generalized. In eight patients, the partial seizures were typical of temporal lobe epilepsy, e.g., absences, automatisms, uncinate fits, etc. In two patients, the partial epilepsy was manifested as focal motor seizures. One patient had a combination of temporal lobe and focal motor and sensory seizures. The time interval from onset of seizures to the present study ranged between 1 and 29 years. The table shows the pertinent clinical data. Eight-channel electroencephalographic recordings using the international 10 to 20 system of electrode placement disclosed interictal persistent or paroxysmal
lateralized abnormalities in all the patients. The lateralized electroencephalographic findings were either focal or regional and consisted of slow or sharp waves or spikes. Each patient underwent a detailed investigation, which included history, neurologic examination, lumbar puncture, technetium 99m brain scan, cerebral angiogram, and pneumoencephalogram. Despite this investigative procedure, no clear cause for the seizures could be determined in seven of the patients. A history of meaningful head trauma could be elicited in the remaining four patients (cases 4, 5, 10, 11). The pneumoencephalogram disclosed right parietal atrophy in one patient (case 4). Clinically, no interictal neurologic deficit was found in any of the 11 patients. The 133Xeintracarotid injection method13 was used to determine the C B F . Each patient consented to participate in the study after the nature of the procedure had been fully explained. The investigation was carried out not less than 72 hours following the last clinical seizure. Cerebral angiography was performed in these patients either during a previous hospitalization or immediately following the rCBF study. Anticonvulsants were not discontinued before the study. Patients were not anesthetized, and no premedication was administered. All received a local anesthetic (2 percent procaine hydrochloride) at the site of puncture. All patients remained fully alert throughout the period of 1 3 3 Xe clearance. The hemisphere studied was the one demonstrating the interictal electroencephalographic abnormalities. In six patients it was the right hemisphere, and in five the left. The clearance of the radioisotope was followed for 10 minutes by an array of 12 to 20 collimated scintillation detectors applied externally over the studied hemisphere, with the head relating to the probes in a standard position. Each detector is constructed from NaI crystal 12 mm in diameter and a photomultiplier and is incorporated into an on-line computerized system built by Beta Engineering and Development of Israel. The detectors, up to 22, are housed in Numetal shields and collimated by brass tubes that are placed in a honeycomb structure supported by a strong multipositional stand. The electronic circuitry consists of miniaturized pulse height analyzers and selectively permits measurements only around a peak of 81 kev. The counts are transferred to an electronic buffer system that allows multiplexing without any significant loss of data and from there, through a direct memory access, into an HP-2100 computer with 12/K words of memory. The computational results of the 10 minute rCBF1 were adjusted to hemoglobin levels and displayed on an oscilloscope. Arterial blood samples for partial pressure of carbon dioxide (PaCOz) and pH determinations were drawn immediately before the 133Xe injection. In these patients the PaCOz levels were 36.5 t 3.0 mm Hg SD, and the arterial pH 7.42-+ 0.05 SD. The mean arterial blood pressure ranged from 85 to 105 mm Hg. The mean flow values and the distribution of regional values were compared with those of a sample of 22 normal control subjects 20 to 68 years old. In these normal
patients, carotid angiography was indicated because of a suspected cerebral lesion, which was then ruled out. The rCBF measurement was carried out before the carotid angiogram in these patients. The right hemisphere was studied in 13 normal subjects and the left hemisphere in nine. The PaCOz in the control group was 3 8 . 0 t 3 . 4 mm Hg SD, and the arterial pH 7.41 5 0.04 SD. The mean arterial blood pressure ranged from 85 to 105 mm Hg.
Results. The hemispheric mean CBF of the group of patients with partial epilepsy was 47.5k 12.7 ml per 100 gm per minute SD. It did not differ significantly from the hemispheric mean CBF value of the normal control group, which was 43.7 5 8.8 ml per 100 gm per minute SD. The absolute C B F values in the epileptic patients were studied, and changes in the pattern of their distribution were analyzed. An area showing low C B F values in comparison with values in other hemispheric regions was observed in each of the patients (figure 1). This low-flow area differed in site among various patients and was observed in the frontal, temporal, or parietal regions or in border zones between them. It also varied in its diameter, i.e., the number of the detectors involved ranging from one to five in different patients. The degree of reduction from the hemispheric mean CBF ranged from 16 to 40 percent in this group of patients. The lowest rCBF value and also the mean CBF in the observed low-flow area deviated significantly from the hemispheric mean CBF (p < 0.01 and p < 0.026, respectively, by the sign test) in each of the studied patients. Since in normal controls C B F values are not equally distributed over various hemispheric regionsI4 and since C B F values from parallel regions in the left and right hemispheres differ as well,15 it was necessary to clarify whether the low-flow areas in the patients with partial epilepsy represent true pathologic rCBF reductions or a physiologic variation in flow patterns such as is found in normal hemispheres. Therefore, the rCBF values of our patients were compared with those obtained from 22 normal controls. The mean CBF was calculated for each hemisphere. In order to make data of the control and epileptic patients suitable for comparison, the rCBF values from each detector in each subject were transformed into percent deviation from individual hemispheric mean values. Subsequently, the mean and standard deviations of the new values for each specific detector within the array were calculated separately for two control groups, one including 13 right normal hemispheres and the second nine left normal ones (figure 2). The percent deviation obtained for each detector in each “epileptic” hemisphere was compared with the mean and standard deviations obtained for the parallel detector of the respective control group. Values that were unlikely to fall within the distribution of scores obtained from “normal” detectors (p < 0.05 or smaller) were considered significantly abnormal. Following this procedure, hemisphgic regions with significantly reduced rCBF as compared with normal controls have been demonstrated in 10 of the 11 patients NEUROLOGY May 1976 419
lnterictal regional cerebral blood flow in partial seizures
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with partial epilepsy (figure 3). In four patients (cases 1, 4, 6 , lo), these were identical with the low-flow areas depicted by observation of the absolute rCBF values (figure 1). In the other six patients (cases 2 , 3 , 4 , 5 , 7 , l l ) , the hemispheric regions with the significantly reduced rCBF were localized within the previously observed low-flow area. In two remaining patients (cases 2, 81, additional regions in the vicinity of the abnormal area showed significantly low rCBF levels. Clinical and electroencephalographic location of the epileptogenic focus closely correlated with the hemispheric region showing the significant low rCBF levels in the majority of patients (table, figure 2 ) . In one patient (case 4), whose partial seizures were of the temporal lobe type, the region with significantly low rCBF was localized within the parietal lobe. This area, which showed electroencephalographic abnormalities, also presented atrophy as demonstrated by the pneumoencephalogram.
Discussion. This study showed that in patients with partial seizures, an area with significantly low rCBF as compared with hemispheric mean CBF values can be identified in the interictal period. These low-flow values deviated significantly from those of parallel regions in normal cerebral hemispheres in the majority of patients. Although the site of low rCBF within the studied hemisphere can be only grossly designated anatomically, it closely correlated with the clinical symptomatology of the partial seizures a n d with the site o f main 420 NEUROLOGY May 1976
Figure 1. Absolute rCBF values (milliliters per 100 gm per minute) in hemispheres of patients with partial epilepsy. (Dotting designates the observed low-flow areas; empty circles represent nonoperating detectors within the array.)
electroencephalographic abnormality. These data suggest that the epileptogenic focus responsible for the partial seizures may be localized within the hemispheric area showing the abnormal ICBF reduction. The present findings are in accordance with those reported by Ingvar16 and may indicate permanent circulatory impairment within the site of the epileptogenic focus. Our data differ, however, from the findings recently reported by Hoogaard and Oikawa,17 who demonstrated interictal focal rCBF increase in nine of 10 patients with partial epilepsy. However, in this particular study, the rCBF increase occurred following activation procedures such as photostimulation in some of the patients. In addition, brain tumor was identified as the underlying cause of the
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Figure 2. Distribution of pooled rCBF values in normal control subjects; data from 13 right hemispheres and nine left hemispheres. (The rCBF values within circles are expressed as percentages of the hemispheric mean value i SD.)
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Figure 3. Localization of regions with significantly low rCBF as compared with normal controls; relationshipto site of main electroencephalographic abnormalities (star-shaped lines).
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Table. Correlation between type of seizures and site of main EEG abnormalitiesand hemispheric region with significantly low rCBF
NEUROLOGY May 1976 421
lnterictal regional cerebral blood flow in partial seizures
partial seizures in four patients. Our series, however, did not include cerebral tumors, infarctions, or abscesses. In all but one of our 11 patients, the clinical neurologic examination, as well as a variety of testing procedures, failed to demonstrate the cerebral pathology underlying the partial seizures. Although not detected, it is most likely that in each patient, a structural brain lesion was responsible for the seizures. This may be one of the “atrophic lesions,”18 such as focal cerebral infarction due to trauma or occlusive cerebral vascular disease; gliosis following trauma, anoxia, or infection; and simple atrophy from an unknown cause. In addition to neuronal loss and glial scar formation, these lesions are known to be associated with reduced vascular upp ply^^^'^ and may therefore be identified by the rCBF study as the low-flow areas. Indeed, in one of the epileptic patients in the present series, the low-flow area corresponded to the region of cerebral atrophy demonstrated by the air study. The rCBF values in the area of such a lesion must be interpreted with care. The computation of the rCBF involves a fixed value for the blood-to-brain partition coefficient of 133Xe.In the present study, as in most other rCBF studies, the value used was the one calculated for normal brain tissue.*O However, since this partition coefficient depends on the tissue lipid content, it may be subject to variations in cases of cerebral pathology, as O’Brien and Veallzl have shown in brain tumors. The present results suggest, however, that a localized cerebral pathology exists and that it is manifested either by low C B F value or by low partition coefficient.
Regulation and control of the rCBF are maintained mainly by the regional neuronal It has been proposed that increased cerebral neuronal metabolism induces elevation of CBF during active seizure^.^^^^^ It may therefore be suggested that owing to the neuronal loss and gliosis and during the seizure-free interval, a low metabolic rate exists in the cerebral lesion in which the epileptogenic focus is lodged, as compared with the other hemispheric regions. This may also contribute to the localized reduction of C B F levels apart from low blood supply to this area. However, since it has been shown that in patients with a variety of cerebral disease processes, the rCBF may at times correlate poorly with the regional cerebral metabolic rate of oxygen , 2 3 this assumption must be tested by further studies. The implications of this study will be determined only after careful physiologic and anatomic correlations in a larger number of patients. It seems that the rCBF study may at present serve as an additional tool in the evaluation of patients with partial seizures. This study may be particularly helpful in cases in which the scalp electroencephalogram can offer only crude localization of the epileptogenic focus and when the other commonly employed tests, including cerebral angiography, are nonrevealing . Acknowledgment S. Sadan, Ph.D., assisted in the statistical analysis, and Mrs. S. Alpern provided technical assistance.
REFERENCES 1. Penfield W: The evidence for a cerebral vascular mechanism in epilepsy. Ann Intern Med 7303-310, 1933 2. Gibbs FA, Lennox WG, Gibbs EL: Cerebral blood flow preceding and accompanyingepileptic seizures in man. Arch Neurol32:257-272,1934 3. Penfield W: The circulation of the epileptic brain. Res Pub1Assoc Res New Ment Dis 18:605-637,1937 4. PenfieldW, VonSantha K, Cipriani A: Cerebral blood flow during induced epileptiform selzures in animals and man. J Neurophysiol 2257-267, 1939 5. White PT, Grant P, Mosier J, et al: Changes in cerebral dynamics associated with seizures. Neurology (Minneap) 11 :354-361,1961 6. Meyer JS, Gotoh F, Favale E: Cerebral metabolism during epileptic seizures in man. ElectroencephalogrClin Neurophysiol21:lo-22, 1966 7. Plum F, Posner JB, Troy 8: Cerebral metabolic and circulatory responses to induced convulsions in animals. Arch Neurol 18:l-13, 1968 8. Posner JB, Plum F, Van Poznak A: Cerebral metabolism during electrically induced seizures in man. Arch Neurol 20:388-395, 1969 9. Brodersen P, Paulson 06, Bolwig TG, et al: Cerebral hypremia in electrically induced seizures in man. Arch Neurol 20:334338,1973 10. Grant FC, Spitz EG, Shenkin HA, et al: The cerebral blood flow and metabolism in idiopathic epilepsy. Trans Am Neurol Assoc 12:82-86, 1947 11. Kennedy C, Anderson W, Sokoloff L: Cerebral blood flow in epileptic children during the interseizure period. Neurology (Minneap), Suppl 1 , 8:lOO-105, 1958 12. Gastaut H: Clinical and electroencephalographic classification of epileptic seizures. Epilepsia 1 1 :102-113,1970
422 NEUROLOGY May 1976
13. H~edt-RasmussenK, Sveinsdottir E, Lassen NA: Regional cerebral blood flow in man determined by intra-arterial injection of radioactive inert gas. Circ Res 18:237-247, 1966 14. Wilkinson IMS, Bull JWO, DuBoulay GH, et al: Regional blood flow in the normal cerebral hemisphere. J Neurol Neurosurg Psychiatry 32:367-378, 1969 15. Carmon A, Lavy S, Gordon H,et al: Hemispheric differences in rCBF during verbal and non-verbal tasks. In lngvar DH, Lassen NA (Editors): Brain Work-The Coupling of Function, Metabolism, and Blood Flow in the Brain. Munskgaard, Copenhagen (in press) 16. lngvar DH: Regional cerebral blood flow in focal cortical epilepsy. (Abstr) Stroke 4359, 1973 17. Hoogaard K, Oikawa T: Regional cerebral blood flow estimation compared with EEG in focal epilepsy. Abstracts of the Seventh International Symposiumoncerebral Blood Flow and Metabolism, June 1975, Aviemore, Scotland 18. Penfield W, Jasper H: Epilepsy and the Functional Anatomy of the Human Brain. Boston, Little, Brown and Company, 1954, pp 302-349 19. Alexander L, Putnam T: Pathological alterations of cerebral vascular patterns. Res Pub1 A m Res Nerv Ment Dis 18:471-543,1938 20. Lassen NA, lngvar DH: Radioisotopic assessment of regional cerebral blood flow. Progr Nucl Med 1376-409, 1972 21. O’Brien MD, Veal1 N: Partition coefficients between various brain tumours and blood for 133Xe. Phys Med Biol 19:472-475, 1974 22. Lassen NA: Cerebral blood flow and oxygen consumption in man. Physiol Rev 39383-238, 1959 23. Carter CC, Eichlina JO. Davis DO. et a1:Correlation of reaional cerebral flood flow with oxygen uptake using ‘50method. Neuroigy (Minneap) 22:755-762, 1972
Interictal regional cerebral blood flow in patients with partial seizures SYLVAN LAVY, ELDAD MELAMED, ZIPORA PORTNOY, et al. Neurology 1976;26;418 DOI 10.1212/WNL.26.5.418 This information is current as of May 1, 1976 Updated Information & Services
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Neurology ® is the official journal of the American Academy of Neurology. Published continuously since 1951, it is now a weekly with 48 issues per year. Copyright © 1976 by the American Academy of Neurology. All rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.
lnterictal regional cerebral blood flow was determined in 11 adult patients with partial epilepsy and lateralized electroencephalographicabnormalities by means of the xenon 133 intracarotid injection method. A hemispheric area demonstrating significantly low regional cerebral blood flow values as compared with the hemispheric mean cerebral blood flow was observed in each of the patients. In 10 of the 11 patients the localized reduced regional cerebral blood flow levels deviated significantly from levels obtained from parallel regions and hemispheres of normal controls. In the majority of patients, the site of low regional cerebral blood flow closely correlated with the clinical type of partial seizures and/or the site of main electroencephalographic abnormality. On the basis of these data, we suggest that the epileptogenic focus responsible for the partial seizures may be localized within the hemispheric area demonstrating the abnormal regional cerebral blood flow reduction.
lnterictal regional cerebral blood flow in patients with partial seizures SYLVAN LAVY, M.D., ELDAD MELAMED, M.D., ZIPORA PORTNOY, M.Sc., and AMIRAM CARMON, M.D.
B
0th early and recent experimental studies in animals and clinical studies in man have demonstrated that cerebral blood flow (CBF) increases during induced or spontaneous seizures.’-9 Little is known, however, about the blood flow in the epileptic brain during the seizure-free interval. It has been reported to be normal in adult epileptic patientslO and to be only slightly reduced in epileptic children.” Since only the mean CBF was recorded in these studies, focal circulatory abnormalities could not have been detected. Furthermore, these studies included patients with both focal and generalized seizures. Since it is plausible to assume that in the first instance, a localized cerebral pathology accounts for the focal seizures, it is also reasonable to expect regional cerebral blood flow (rCBF) abnormalities in this group of patients and not in patients with generalized ‘‘centrencephalic” seizures. The rCBF measurement allows the evaluation of the circulatory status in hemispheric epileptic foci, which might be altered by the From the Department of Neurology and Laboratory for Cerebral Vascular Research, Hadassah-UniversityHospitaland Hebrew University-Hadassah Medical School, Jerusalem, Israel. Received for publication July 25, 1975. Dr. Lavy’s address is Department of Neurology, Hadassah Medical Organization, Mayer de Rothschild Hadassah University Hospital, Kiryat Hadassah. Jerusalem, Israel.
418 NEUROLOGY 26: 418-422, May 1976
underlying structural or functional impairment. The present study was undertaken in order to determine the rCBF of patients with partial epilepsy during the interictal period by means of the xenon 133 (133Xe) intracarotid injection method .
Subjects and method. Eleven hospitalized adult epileptic patients were studied. Their ages ranged from 20 to 63 years (mean 41 years). Patient selection was determined both by the type of seizures and by the electroencephalographic findings. Gastaut’s’* classification served as a guideline in both criteria. Thus, only patients who had partial epilepsy were included in the present study. These were patients in whom seizures began locally with elementary or with complex symptomatology or patients with partial seizures that were secondarily generalized. In eight patients, the partial seizures were typical of temporal lobe epilepsy, e.g., absences, automatisms, uncinate fits, etc. In two patients, the partial epilepsy was manifested as focal motor seizures. One patient had a combination of temporal lobe and focal motor and sensory seizures. The time interval from onset of seizures to the present study ranged between 1 and 29 years. The table shows the pertinent clinical data. Eight-channel electroencephalographic recordings using the international 10 to 20 system of electrode placement disclosed interictal persistent or paroxysmal
lateralized abnormalities in all the patients. The lateralized electroencephalographic findings were either focal or regional and consisted of slow or sharp waves or spikes. Each patient underwent a detailed investigation, which included history, neurologic examination, lumbar puncture, technetium 99m brain scan, cerebral angiogram, and pneumoencephalogram. Despite this investigative procedure, no clear cause for the seizures could be determined in seven of the patients. A history of meaningful head trauma could be elicited in the remaining four patients (cases 4, 5, 10, 11). The pneumoencephalogram disclosed right parietal atrophy in one patient (case 4). Clinically, no interictal neurologic deficit was found in any of the 11 patients. The 133Xeintracarotid injection method13 was used to determine the C B F . Each patient consented to participate in the study after the nature of the procedure had been fully explained. The investigation was carried out not less than 72 hours following the last clinical seizure. Cerebral angiography was performed in these patients either during a previous hospitalization or immediately following the rCBF study. Anticonvulsants were not discontinued before the study. Patients were not anesthetized, and no premedication was administered. All received a local anesthetic (2 percent procaine hydrochloride) at the site of puncture. All patients remained fully alert throughout the period of 1 3 3 Xe clearance. The hemisphere studied was the one demonstrating the interictal electroencephalographic abnormalities. In six patients it was the right hemisphere, and in five the left. The clearance of the radioisotope was followed for 10 minutes by an array of 12 to 20 collimated scintillation detectors applied externally over the studied hemisphere, with the head relating to the probes in a standard position. Each detector is constructed from NaI crystal 12 mm in diameter and a photomultiplier and is incorporated into an on-line computerized system built by Beta Engineering and Development of Israel. The detectors, up to 22, are housed in Numetal shields and collimated by brass tubes that are placed in a honeycomb structure supported by a strong multipositional stand. The electronic circuitry consists of miniaturized pulse height analyzers and selectively permits measurements only around a peak of 81 kev. The counts are transferred to an electronic buffer system that allows multiplexing without any significant loss of data and from there, through a direct memory access, into an HP-2100 computer with 12/K words of memory. The computational results of the 10 minute rCBF1 were adjusted to hemoglobin levels and displayed on an oscilloscope. Arterial blood samples for partial pressure of carbon dioxide (PaCOz) and pH determinations were drawn immediately before the 133Xe injection. In these patients the PaCOz levels were 36.5 t 3.0 mm Hg SD, and the arterial pH 7.42-+ 0.05 SD. The mean arterial blood pressure ranged from 85 to 105 mm Hg. The mean flow values and the distribution of regional values were compared with those of a sample of 22 normal control subjects 20 to 68 years old. In these normal
patients, carotid angiography was indicated because of a suspected cerebral lesion, which was then ruled out. The rCBF measurement was carried out before the carotid angiogram in these patients. The right hemisphere was studied in 13 normal subjects and the left hemisphere in nine. The PaCOz in the control group was 3 8 . 0 t 3 . 4 mm Hg SD, and the arterial pH 7.41 5 0.04 SD. The mean arterial blood pressure ranged from 85 to 105 mm Hg.
Results. The hemispheric mean CBF of the group of patients with partial epilepsy was 47.5k 12.7 ml per 100 gm per minute SD. It did not differ significantly from the hemispheric mean CBF value of the normal control group, which was 43.7 5 8.8 ml per 100 gm per minute SD. The absolute C B F values in the epileptic patients were studied, and changes in the pattern of their distribution were analyzed. An area showing low C B F values in comparison with values in other hemispheric regions was observed in each of the patients (figure 1). This low-flow area differed in site among various patients and was observed in the frontal, temporal, or parietal regions or in border zones between them. It also varied in its diameter, i.e., the number of the detectors involved ranging from one to five in different patients. The degree of reduction from the hemispheric mean CBF ranged from 16 to 40 percent in this group of patients. The lowest rCBF value and also the mean CBF in the observed low-flow area deviated significantly from the hemispheric mean CBF (p < 0.01 and p < 0.026, respectively, by the sign test) in each of the studied patients. Since in normal controls C B F values are not equally distributed over various hemispheric regionsI4 and since C B F values from parallel regions in the left and right hemispheres differ as well,15 it was necessary to clarify whether the low-flow areas in the patients with partial epilepsy represent true pathologic rCBF reductions or a physiologic variation in flow patterns such as is found in normal hemispheres. Therefore, the rCBF values of our patients were compared with those obtained from 22 normal controls. The mean CBF was calculated for each hemisphere. In order to make data of the control and epileptic patients suitable for comparison, the rCBF values from each detector in each subject were transformed into percent deviation from individual hemispheric mean values. Subsequently, the mean and standard deviations of the new values for each specific detector within the array were calculated separately for two control groups, one including 13 right normal hemispheres and the second nine left normal ones (figure 2). The percent deviation obtained for each detector in each “epileptic” hemisphere was compared with the mean and standard deviations obtained for the parallel detector of the respective control group. Values that were unlikely to fall within the distribution of scores obtained from “normal” detectors (p < 0.05 or smaller) were considered significantly abnormal. Following this procedure, hemisphgic regions with significantly reduced rCBF as compared with normal controls have been demonstrated in 10 of the 11 patients NEUROLOGY May 1976 419
lnterictal regional cerebral blood flow in partial seizures
020,d.L
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with partial epilepsy (figure 3). In four patients (cases 1, 4, 6 , lo), these were identical with the low-flow areas depicted by observation of the absolute rCBF values (figure 1). In the other six patients (cases 2 , 3 , 4 , 5 , 7 , l l ) , the hemispheric regions with the significantly reduced rCBF were localized within the previously observed low-flow area. In two remaining patients (cases 2, 81, additional regions in the vicinity of the abnormal area showed significantly low rCBF levels. Clinical and electroencephalographic location of the epileptogenic focus closely correlated with the hemispheric region showing the significant low rCBF levels in the majority of patients (table, figure 2 ) . In one patient (case 4), whose partial seizures were of the temporal lobe type, the region with significantly low rCBF was localized within the parietal lobe. This area, which showed electroencephalographic abnormalities, also presented atrophy as demonstrated by the pneumoencephalogram.
Discussion. This study showed that in patients with partial seizures, an area with significantly low rCBF as compared with hemispheric mean CBF values can be identified in the interictal period. These low-flow values deviated significantly from those of parallel regions in normal cerebral hemispheres in the majority of patients. Although the site of low rCBF within the studied hemisphere can be only grossly designated anatomically, it closely correlated with the clinical symptomatology of the partial seizures a n d with the site o f main 420 NEUROLOGY May 1976
Figure 1. Absolute rCBF values (milliliters per 100 gm per minute) in hemispheres of patients with partial epilepsy. (Dotting designates the observed low-flow areas; empty circles represent nonoperating detectors within the array.)
electroencephalographic abnormality. These data suggest that the epileptogenic focus responsible for the partial seizures may be localized within the hemispheric area showing the abnormal ICBF reduction. The present findings are in accordance with those reported by Ingvar16 and may indicate permanent circulatory impairment within the site of the epileptogenic focus. Our data differ, however, from the findings recently reported by Hoogaard and Oikawa,17 who demonstrated interictal focal rCBF increase in nine of 10 patients with partial epilepsy. However, in this particular study, the rCBF increase occurred following activation procedures such as photostimulation in some of the patients. In addition, brain tumor was identified as the underlying cause of the
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Figure 2. Distribution of pooled rCBF values in normal control subjects; data from 13 right hemispheres and nine left hemispheres. (The rCBF values within circles are expressed as percentages of the hemispheric mean value i SD.)
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Figure 3. Localization of regions with significantly low rCBF as compared with normal controls; relationshipto site of main electroencephalographic abnormalities (star-shaped lines).
.
.
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Table. Correlation between type of seizures and site of main EEG abnormalitiesand hemispheric region with significantly low rCBF
NEUROLOGY May 1976 421
lnterictal regional cerebral blood flow in partial seizures
partial seizures in four patients. Our series, however, did not include cerebral tumors, infarctions, or abscesses. In all but one of our 11 patients, the clinical neurologic examination, as well as a variety of testing procedures, failed to demonstrate the cerebral pathology underlying the partial seizures. Although not detected, it is most likely that in each patient, a structural brain lesion was responsible for the seizures. This may be one of the “atrophic lesions,”18 such as focal cerebral infarction due to trauma or occlusive cerebral vascular disease; gliosis following trauma, anoxia, or infection; and simple atrophy from an unknown cause. In addition to neuronal loss and glial scar formation, these lesions are known to be associated with reduced vascular upp ply^^^'^ and may therefore be identified by the rCBF study as the low-flow areas. Indeed, in one of the epileptic patients in the present series, the low-flow area corresponded to the region of cerebral atrophy demonstrated by the air study. The rCBF values in the area of such a lesion must be interpreted with care. The computation of the rCBF involves a fixed value for the blood-to-brain partition coefficient of 133Xe.In the present study, as in most other rCBF studies, the value used was the one calculated for normal brain tissue.*O However, since this partition coefficient depends on the tissue lipid content, it may be subject to variations in cases of cerebral pathology, as O’Brien and Veallzl have shown in brain tumors. The present results suggest, however, that a localized cerebral pathology exists and that it is manifested either by low C B F value or by low partition coefficient.
Regulation and control of the rCBF are maintained mainly by the regional neuronal It has been proposed that increased cerebral neuronal metabolism induces elevation of CBF during active seizure^.^^^^^ It may therefore be suggested that owing to the neuronal loss and gliosis and during the seizure-free interval, a low metabolic rate exists in the cerebral lesion in which the epileptogenic focus is lodged, as compared with the other hemispheric regions. This may also contribute to the localized reduction of C B F levels apart from low blood supply to this area. However, since it has been shown that in patients with a variety of cerebral disease processes, the rCBF may at times correlate poorly with the regional cerebral metabolic rate of oxygen , 2 3 this assumption must be tested by further studies. The implications of this study will be determined only after careful physiologic and anatomic correlations in a larger number of patients. It seems that the rCBF study may at present serve as an additional tool in the evaluation of patients with partial seizures. This study may be particularly helpful in cases in which the scalp electroencephalogram can offer only crude localization of the epileptogenic focus and when the other commonly employed tests, including cerebral angiography, are nonrevealing . Acknowledgment S. Sadan, Ph.D., assisted in the statistical analysis, and Mrs. S. Alpern provided technical assistance.
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Interictal regional cerebral blood flow in patients with partial seizures SYLVAN LAVY, ELDAD MELAMED, ZIPORA PORTNOY, et al. Neurology 1976;26;418 DOI 10.1212/WNL.26.5.418 This information is current as of May 1, 1976 Updated Information & Services
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Neurology ® is the official journal of the American Academy of Neurology. Published continuously since 1951, it is now a weekly with 48 issues per year. Copyright © 1976 by the American Academy of Neurology. All rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.
