REGIONAL CEREBRAL BLOOD FLOW IN THE DIAGNOSIS OF VASCULAR HEADACHE
Ninan T. Mathew, M.D., F.R.C.P. (C) Franc Hrastnik, M.D. John S. Meyer, M.D.
Department of Neurology, Baylor College of Medicine, Baylor-Methodist Center for Cerebrovascular Research, Houston, Texas 77025 This work was supported by Grant NS 09287 from the National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, Maryland 20014 Presented at The Bergen Migraine Symposium, June 1975 Submitted for Publication: 7/28/75 Accepted: 8/4/75 SYNOPSIS
Potential availability of a reliable non-invasive system for measuring regional cerebral blood flow (rCBF) prompted measurement of rCBF in patients with vascular headache in order to assess its diagnostic value. The rCBF in migraine varied with the clinical phase. During the prodrome phase the blood flow was reduced; whereas during the headache phase, a striking cortical hyperperfusion was noted. Patients who continued to have neurologic symptoms of the prodrome in the headache phase showed a mixed pattern of reduced and increased blood flow. The rCBF was found normal in the headache phase in patients with muscle contraction and psychogenic headache. In patients with headache as a prominent symptom of cerebrovascular insufficiency, rCBF was reduced but was not significantly different from rCBF in patients with cerebrovascular insufficiency without headache. THE DIAGNOSIS OF VARIOUS types of vascular headaches is based primarily on clinical history and examination. While clinical diagnosis proves to be correct in the majority of cases, the differential diagnosis is complicated in some patients. Difficulties occur in atypical patients with mixed pattern of headache, vascular headache of late onset, in patients with chronic dependency or addiction to narcotics and in cases with status migrainosus. There is no investigative procedure which provides a positive diagnosis for vascular headache and the diagnosis is usually established by exclusion. The majority of vascular headaches are related to episodic functional changes in the dynamics of the cephalic circulation but currently available neuroradiologic procedures including axial tomography (EMI scanner), are incapable of identifying them. Nevertheless, these procedures are used to exclude structural lesions which may produce headache simulating migraine. Although the electroencephalogram (EEG) in patients with migraine may show nonspecific dysrhythmias, the EEG abnormalities are not diagnostic.1 Regional cerebral blood flow (rCBF) measurements are reportedly capable of detecting hemodyamic changes associated with migraine.2,3,4,5, However, the feasibility of utilizing rCBF measurements as a positive diagnostic test in vascular headache has not been fully explored. A recent modification of 133Xenon inhalation method with provisions for correcting for recirculation and extracranial contamination of the radioisotope6,7,8,9,10 yields rCBF values comparable to intracarotid 133Xe technique9,10,11 and is non-invasive. The availability of non-invasive 133Xenon inhalation rCBF measurements for screening out-patient populations with headache, prompted us to examine the diagnostic value of rCBF in various types of vascular headache. However, the present study was undertaken using the intracarotid technique, because the laboratory has only recently become equipped with non-invasive methods for measuring rCBF. PATIENTS AND METHODS
Patients who presented with headaches as a major complaint were included in this study. All patients had detailed neurologic and general medical examinations to detect the cause of headache. Psychiatric consultation was obtained for patients with ten-
sion, anxiety and depression. Patients with fever, brain tumors, intracranial aneurysms, arteriovenous malformations, and intracranial infections were excluded. The diagnostic categories are given in Table 1. The criteria used for diagnosis and classification of the patients (Group A, Table 1) were based on the classification of headache of the National Institute of Nervous Disease and Blindness.12 The diagnosis of cerebrovascular insufficiency in Group B was based on history of associated focal or diffuse cerebral symptoms, signs attributed to chronic and/or intermittent ischemia and the presence of risk factors for cerebrovascular disease. Diagnosis was confirmed in all cases in Group B by arteriographic demonstration of stenotic or occlusive atherosclerotic lesions in the extra and/or intracranial cerebral circulation. Psychogenic factors such as tension, anxiety and depression was supported in Group C by psychiatric consulation. rCBF measurements were made after obtaining informed consent from the patient TABLE I Clinical Diagnosis Diagnosis A. Migraine Common Migraine Classic Migraine Hemiplegic Migraine
Number in Each Category 13 10 1
B. Cerebrovascular Insufficiency With Prominent Headache Without Headache C. Other Headache Muscle Contraction Psychogenic Post Traumatic Syndrome
Total in Each Sub-Group 24
20 10 10 8 3 2 2
With Endogenous Depression TOTAL
1 52
or their responsible relative. All vasoactive medications were stopped at least 3 days prior to the initial rCBF measurements. An attempt was made to obtain rCBF measurements during the prodrome and headache phases and the symptom free interval in migraineurs. In patients with dietary migraine, attacks were induced by giving them four to six ounces of red wine and in some a bar of chocolate was also given. Wine and chocolate are known to have a high content of vasoactive substances, including tyramine in red wine.13,14 Thirteen patients had rCBF measurements during the headache phase. In three prodromal symptoms continued after they had entered the headache phase when measurements were made. In three patients (#19, 20, and 21; Table III) rCBF was measured during the prodrome. rCBF and regional cerebral blood volume (rCBF) were measured utilizing the intra-arterial radioisotope technique15 and a gamma camera.16,17 Details of the technique and reproducibility of measurements of rCBF after intracarotid injection of 133Xenon have been reported.18 Short term variations in rCBF and inter-regional differences have been established for the method.19,20 With intracarotid injection of 133Xenon the gamma camera gives rCBF values comparable to the multiple probe system.21 Serial intracarotid injections of 133Xe and 99mTc were made to measure rCBF and regional transit time, respectively. In calculating regional transit time after intracarotid injection of 9mTc the methods of Fazio et a122 and Oldendorf23 were used. Regional transit time was calculated as the interval between increment and decrement of the 99mTc curve at the midpoint of the maximal vertical axis. Theoretical aspects of the calculation of rCBF from transit time and rCBF have been described24 based on the central volume principle of Meier and Zierler.25 The clearance of 133Xe was monitored from the lateral surface of the head for 10 minutes. Later the clearance of 99mTc was recorded for 1 minute after its injection. The data was stored on magnectic tape. A computer analysed the clearance curve of both radioisotopes and provided automatic
print-out of rCBF expressed as rCBF for 10 minutes (rCBF10), flow in gray matter (Fg), flow in white matter (Fw) and rCBF.16,17 Regional cerebral blood volume was computed using rCBF10 and the transit time of cerebral circulation obtained from injecting the nondiffusible 99mTc. On an average, rCBF and rCBV from 12-15 different regions of the hemisphere were obtained in each case. Arterial blood pressure and arterial pCO2 (PaCO2) were recorded during the procedure. RESULTS
Migraine: Results of rCBF and rCBV in patients with migraine are summarized in Tables II and III. In 13 out of 24 patients rCBF measurements were obtained during headache. The headache was spontaneous in 5 and precipitated by ingestion of red wine and chocolate in 8. In three patients rCBF measurements were carried out during prodromes consisting of hemianopic scintillating scotomas and paresthesia. Ten rCBF measurements were obtained in 9 patients during symptom free periods. Three patients (no. 2, 3 and 4) had measurements both during the headache phase and symptom free periods when given propranolol 40 mg thrice daily. During the headache phase rCBF10 (p
Ninan T. Mathew, M.D., F.R.C.P. (C) Franc Hrastnik, M.D. John S. Meyer, M.D.
Department of Neurology, Baylor College of Medicine, Baylor-Methodist Center for Cerebrovascular Research, Houston, Texas 77025 This work was supported by Grant NS 09287 from the National Institute of Neurological and Communicative Disorders and Stroke, Bethesda, Maryland 20014 Presented at The Bergen Migraine Symposium, June 1975 Submitted for Publication: 7/28/75 Accepted: 8/4/75 SYNOPSIS
Potential availability of a reliable non-invasive system for measuring regional cerebral blood flow (rCBF) prompted measurement of rCBF in patients with vascular headache in order to assess its diagnostic value. The rCBF in migraine varied with the clinical phase. During the prodrome phase the blood flow was reduced; whereas during the headache phase, a striking cortical hyperperfusion was noted. Patients who continued to have neurologic symptoms of the prodrome in the headache phase showed a mixed pattern of reduced and increased blood flow. The rCBF was found normal in the headache phase in patients with muscle contraction and psychogenic headache. In patients with headache as a prominent symptom of cerebrovascular insufficiency, rCBF was reduced but was not significantly different from rCBF in patients with cerebrovascular insufficiency without headache. THE DIAGNOSIS OF VARIOUS types of vascular headaches is based primarily on clinical history and examination. While clinical diagnosis proves to be correct in the majority of cases, the differential diagnosis is complicated in some patients. Difficulties occur in atypical patients with mixed pattern of headache, vascular headache of late onset, in patients with chronic dependency or addiction to narcotics and in cases with status migrainosus. There is no investigative procedure which provides a positive diagnosis for vascular headache and the diagnosis is usually established by exclusion. The majority of vascular headaches are related to episodic functional changes in the dynamics of the cephalic circulation but currently available neuroradiologic procedures including axial tomography (EMI scanner), are incapable of identifying them. Nevertheless, these procedures are used to exclude structural lesions which may produce headache simulating migraine. Although the electroencephalogram (EEG) in patients with migraine may show nonspecific dysrhythmias, the EEG abnormalities are not diagnostic.1 Regional cerebral blood flow (rCBF) measurements are reportedly capable of detecting hemodyamic changes associated with migraine.2,3,4,5, However, the feasibility of utilizing rCBF measurements as a positive diagnostic test in vascular headache has not been fully explored. A recent modification of 133Xenon inhalation method with provisions for correcting for recirculation and extracranial contamination of the radioisotope6,7,8,9,10 yields rCBF values comparable to intracarotid 133Xe technique9,10,11 and is non-invasive. The availability of non-invasive 133Xenon inhalation rCBF measurements for screening out-patient populations with headache, prompted us to examine the diagnostic value of rCBF in various types of vascular headache. However, the present study was undertaken using the intracarotid technique, because the laboratory has only recently become equipped with non-invasive methods for measuring rCBF. PATIENTS AND METHODS
Patients who presented with headaches as a major complaint were included in this study. All patients had detailed neurologic and general medical examinations to detect the cause of headache. Psychiatric consultation was obtained for patients with ten-
sion, anxiety and depression. Patients with fever, brain tumors, intracranial aneurysms, arteriovenous malformations, and intracranial infections were excluded. The diagnostic categories are given in Table 1. The criteria used for diagnosis and classification of the patients (Group A, Table 1) were based on the classification of headache of the National Institute of Nervous Disease and Blindness.12 The diagnosis of cerebrovascular insufficiency in Group B was based on history of associated focal or diffuse cerebral symptoms, signs attributed to chronic and/or intermittent ischemia and the presence of risk factors for cerebrovascular disease. Diagnosis was confirmed in all cases in Group B by arteriographic demonstration of stenotic or occlusive atherosclerotic lesions in the extra and/or intracranial cerebral circulation. Psychogenic factors such as tension, anxiety and depression was supported in Group C by psychiatric consulation. rCBF measurements were made after obtaining informed consent from the patient TABLE I Clinical Diagnosis Diagnosis A. Migraine Common Migraine Classic Migraine Hemiplegic Migraine
Number in Each Category 13 10 1
B. Cerebrovascular Insufficiency With Prominent Headache Without Headache C. Other Headache Muscle Contraction Psychogenic Post Traumatic Syndrome
Total in Each Sub-Group 24
20 10 10 8 3 2 2
With Endogenous Depression TOTAL
1 52
or their responsible relative. All vasoactive medications were stopped at least 3 days prior to the initial rCBF measurements. An attempt was made to obtain rCBF measurements during the prodrome and headache phases and the symptom free interval in migraineurs. In patients with dietary migraine, attacks were induced by giving them four to six ounces of red wine and in some a bar of chocolate was also given. Wine and chocolate are known to have a high content of vasoactive substances, including tyramine in red wine.13,14 Thirteen patients had rCBF measurements during the headache phase. In three prodromal symptoms continued after they had entered the headache phase when measurements were made. In three patients (#19, 20, and 21; Table III) rCBF was measured during the prodrome. rCBF and regional cerebral blood volume (rCBF) were measured utilizing the intra-arterial radioisotope technique15 and a gamma camera.16,17 Details of the technique and reproducibility of measurements of rCBF after intracarotid injection of 133Xenon have been reported.18 Short term variations in rCBF and inter-regional differences have been established for the method.19,20 With intracarotid injection of 133Xenon the gamma camera gives rCBF values comparable to the multiple probe system.21 Serial intracarotid injections of 133Xe and 99mTc were made to measure rCBF and regional transit time, respectively. In calculating regional transit time after intracarotid injection of 9mTc the methods of Fazio et a122 and Oldendorf23 were used. Regional transit time was calculated as the interval between increment and decrement of the 99mTc curve at the midpoint of the maximal vertical axis. Theoretical aspects of the calculation of rCBF from transit time and rCBF have been described24 based on the central volume principle of Meier and Zierler.25 The clearance of 133Xe was monitored from the lateral surface of the head for 10 minutes. Later the clearance of 99mTc was recorded for 1 minute after its injection. The data was stored on magnectic tape. A computer analysed the clearance curve of both radioisotopes and provided automatic
print-out of rCBF expressed as rCBF for 10 minutes (rCBF10), flow in gray matter (Fg), flow in white matter (Fw) and rCBF.16,17 Regional cerebral blood volume was computed using rCBF10 and the transit time of cerebral circulation obtained from injecting the nondiffusible 99mTc. On an average, rCBF and rCBV from 12-15 different regions of the hemisphere were obtained in each case. Arterial blood pressure and arterial pCO2 (PaCO2) were recorded during the procedure. RESULTS
Migraine: Results of rCBF and rCBV in patients with migraine are summarized in Tables II and III. In 13 out of 24 patients rCBF measurements were obtained during headache. The headache was spontaneous in 5 and precipitated by ingestion of red wine and chocolate in 8. In three patients rCBF measurements were carried out during prodromes consisting of hemianopic scintillating scotomas and paresthesia. Ten rCBF measurements were obtained in 9 patients during symptom free periods. Three patients (no. 2, 3 and 4) had measurements both during the headache phase and symptom free periods when given propranolol 40 mg thrice daily. During the headache phase rCBF10 (p
