75
17. Mills BG, Masuoka LS, Graham CC, Singer FR, Waxman AD. Gallium-67 citrate localization in osteoclast nuclei of Paget’s disease of
bone. J Nucl Med 1988; 29:
1083-67.
18. Krakoff IH, Newman RA, Goldberg RS. Clinical toxicologic and pharmacologic studies of gallium nitrate. Cancer 1979; 44: 1722-27. 19. Warrell RP, Bockman RS, Coonley CJ, Isaacs M, Staszewski H. Gallium nitrate inhibits calcium resorption from bone and is effective treatment for cancer-related hypercalcaemia. J Clin Invest 1984; 72: 1487-90. 20. Warrell RP, Israel R, Frisone M, Snyder T, Gaynor JJ, Bockman RS. Gallium nitrate for acute treatment of cancer related hypercalcaemia. Ann Intern Med 1988; 108: 669-74. 21. Dudley HC, Marrer HH. Studies of the metabolism of gallium. III. Deposition in and clearance from bone. J Pharmacol Exp Ther 1952; 106: 129-34. 22. Walton RJ, Preston CJ, Bartlett M, Smith R, Russell GG. Biochemical measurements in Paget’s disease of bone. Eur J Clin Invest 1977; 7: 37-39. 23. Goverde BC, Veenkamp FJN. Routine assay of total urinary hydroxyproline based on resin-catalysed hydrolysis. Clin Chim Acta 1972; 41: 29-40. 24. Nussbaum SR, Zahradnik RJ, Lavigne JR, et al. Highly sensitive two-site immunoradiometric assay of parathyrin, and its clinical utility in evaluating patients with hypercalcaemia Clin Chem 1987; 33: 1364-67. 25. Walton RJ, Bijvoet OLM. Nomogram for derivation of renal threshold phosphate concentration. Lancet 1975; i: 309-10.
Papapoulos SE, Frolich M, Mudde AH, Harinck HIJ, Berg HVD, Bojvoet OLM. Serum osteocalcin in Padget’s disease of bone: bone concentrations and response to bisphosphonate treatment., J Endocrinol Metab 1987; 65: 89-94. 27. Bockman RS, Boskey AL, Blumenthal NC, Alcock NW, Warrell RP. Gallium increases bone calcium and crystallite perfection of hydroxyapatite. Calcif Tissue Int 1986; 39: 376-81. 28. Blumenthal NC, Cosma V, Levine S. Effect of gallium on the in vitro formation, growth, and solubility of hydroxyapatite. Calcif Tissue Int 1989; 45: 81-87. 29. Donnelly R, Boskey A. The effect of gallium on seeded hydroxyapatite growth. Calcif Tissue Int 1989; 44: 138-42. 30. Chitambar CR, Matthaeus WG, Antholine WE, Graff K, O’Brien WJ. Inhibition of leukemic HL60 cell growth by transferrin-gallium: effects on ribonucleotide reductase and demonstration of drug synergy with hydroxyurea. Blood 1988; 72: 1930-36. 31. Larson SM, Rasey JS, Allen DR, et al. Common pathway for tumor cell uptake of gallium-67 and iron-59 via a transferrin receptor. J Natl 26.
Cancer Inst 1980; 64: 41-53.
Anghileri LJ, Crone-Escanye M-C, Thouvenot P, Brunotte F, Robert J. Mechanisms of gallium-67 accumulation by tumors: role of cell membrane permeability. J Nucl Med 1988; 29: 663-68. 33. Pioli G, Girasole G, Pedrazzoni M, et al. Spontaneous release of interleukin-1 (IL-1) from medullary mononuclear cells of pagetic subjects. Calcif Tissue Int 1989; 45: 257-59. 32.
Visual evoked responses in children with a
migraine:
diagnostic test
The visual evoked responses (VERs) to both flash and pattern stimulation were recorded in 44 children with migraine, with or without aura, and 8 with periodic syndrome. The controls were 50 age and sex matched children. VERs of 50 sex matched adults with migraine were also recorded. The fast wave amplitude in children with migraine was higher than that in controls. The amplitude was higher in younger children with migraine (under 13 years) than that in older children or adults with migraine. Children with periodic syndrome had VERs similar to those of children with migraine. The VER, especially in children, may prove to be a useful test in the diagnosis of migraine.
Introduction The aetiology of migraine (vasculogenic or neurogenic) has been debated for years. Peatfield1 has stated that "migrainous headache is believed to be initiated within the brainstem, expressed in the external carotid circulation and then perceived back in the brain stem, thalamus and cortex". The pathogenesis of migraine may involve the opening of arteriovenous anastomoses in the carotid circulation ;2 this theory is supported by the finding that a new 5hydroxytryptamine-like receptor agonist, a selective vasoconstrictor of this circulation in animals, relieves migraine in adults.3 Migraine headache affects 2.7% of children by the age of 7 and 10-6% by age 14.4,5 Because there have been no
diagnostic tests for migraine, most epidemiological data has been based on questionnaires.6 Many attempts have been made to find an objective marker.7 The diagnosis of migraine, with and without aura, and migraine equivalents is made from clinical history, physical examination, and elimination of alternatives;.8,9 the differential diagnosis is multiple and complex."* Despite the view that childhood periodic syndromes are migraine equivalents without headache they are not included in the International Headache Society classification of migraine.8,9 Electrophysiological techniques have been used to analyse the hypothalamic content of a migraine attack. Differences in both electroencephalograms (EEGs) and visual evoked responses (VERs) have been found between groups of children with migraine and controls,l1-13 but, to date, there has not been an electrophysiological test for diagnostic use. In an earlier study of adults, 14 we found that there was a difference in background fast wave activity of the VER between those with migraine and controls. We have studied VERs, with frequences over 14 Hz, in children with migraine and controls, and looked at the possible use of this test in the diagnosis of migraine.
ADDRESS: Birminghamand Midland Eye Hospital, Birmingham B32NS, UK (M. J. Mortimer, MRCGP, P A. Good, BSc, J. B. Marsters, PhD, D P. Addy, FRCP). Correspondence to Mr P. A Good.
76
Patients and methods 52 children, attending the Birmingham Migraine clinic, were assessed clinically; 44 had migraine with aura or migraine without aura,8 and 8 had periodic syndrome (paroxysmal abdominal pain with nausea and/or vomiting, but no headache). The district ethical committee approved the study. With informed parental consent, we recorded VERs for each child.
The 44 children with migraine headache were separated into two (10 boys and 12 girls) under 13 yr (range 3-12 yr, mean 9-2 yr), and 22 (5 boys and 17 girls) aged 13-16 yr (mean 14-11 yr). 13 yr was chosen as an approximation of puberty. In the younger group, 7 had migraine with aura and 15 had no aura. In the older children, 15 had experienced aura and 7 had not. All the children with periodic syndrome were 12 yr or younger (range 4-12 yr); 4 were girls and 4 boys. age groups: 22
A control group of 50 children, who were age and sex matched with the migraine subgroups, were volunteers from general practice; they had no history of migraine, and no ophthalmological or neurological abnormality. The adult migraine control group consisted of 50 sex-matched patients with migraine over 16 yr, selected at random from a group of adults with migraine referred from the Birmingham Migraine Clinic for investigation. 25 of these patients had migraine with aura and 25 migraine without aura. All controls were investigated under exactly the same conditions as the children with migraine.
The VERs were recorded to both diffuse flash and pattern stimulation (reversing checkerboard). Flash stimulation was generated by a Grass P5 22 photic stimulator with a blue/white light source of intensity 200 candella/m2 and with peak wavelength 510 nm. The stimulus rate was 2 Hz. Pattern stimulation was provided by a 2 Hz reversing black and white checkerboard displayed on a television screen. The pattern subtended an angle of 1°at the eye. The stimulus field size was 16°, contrast 90%, and mean luminance 350 candella/m2. Sources of both flash and pattern stimuli were 50 cm from the children’s eyes. Both eyes were stimulated at the same time. The recording electrodes were bipolar silver,/silver chloride electrodes put on the scalp at positions Fz and Oz, in accordance with international convention. Frequencies in the EEG &bgr; range, 10-50 Hz, were recorded (Nicolet C4 clinical averager). Analysis time was 500 ms. The amplitude and frequency of at least four different waveforms from five consecutive stimuli were used to calculate the means. The amplitudes of waves with frequency greater than 16 Hz occurring in the last 250 ms of the recording (fastwaves) were used to calculate the mean amplitude of fast wave activity. No child had a migraine at the time the VER was recorded.
Fig 1-Examples of VER recordings
to flash and pattern
stimulation. Note increased fast
wave
activity
in
patients.
Statistical analysis of the data was by analysis of (ANOVA) and Bonferroni’s procedure was applied.
variance
Results The visual evoked responses for control groups and migraine groups are shown in the table. Children with migraine or periodic syndrome who were younger than 13 and lower years had higher fast wave amplitude (p
17. Mills BG, Masuoka LS, Graham CC, Singer FR, Waxman AD. Gallium-67 citrate localization in osteoclast nuclei of Paget’s disease of
bone. J Nucl Med 1988; 29:
1083-67.
18. Krakoff IH, Newman RA, Goldberg RS. Clinical toxicologic and pharmacologic studies of gallium nitrate. Cancer 1979; 44: 1722-27. 19. Warrell RP, Bockman RS, Coonley CJ, Isaacs M, Staszewski H. Gallium nitrate inhibits calcium resorption from bone and is effective treatment for cancer-related hypercalcaemia. J Clin Invest 1984; 72: 1487-90. 20. Warrell RP, Israel R, Frisone M, Snyder T, Gaynor JJ, Bockman RS. Gallium nitrate for acute treatment of cancer related hypercalcaemia. Ann Intern Med 1988; 108: 669-74. 21. Dudley HC, Marrer HH. Studies of the metabolism of gallium. III. Deposition in and clearance from bone. J Pharmacol Exp Ther 1952; 106: 129-34. 22. Walton RJ, Preston CJ, Bartlett M, Smith R, Russell GG. Biochemical measurements in Paget’s disease of bone. Eur J Clin Invest 1977; 7: 37-39. 23. Goverde BC, Veenkamp FJN. Routine assay of total urinary hydroxyproline based on resin-catalysed hydrolysis. Clin Chim Acta 1972; 41: 29-40. 24. Nussbaum SR, Zahradnik RJ, Lavigne JR, et al. Highly sensitive two-site immunoradiometric assay of parathyrin, and its clinical utility in evaluating patients with hypercalcaemia Clin Chem 1987; 33: 1364-67. 25. Walton RJ, Bijvoet OLM. Nomogram for derivation of renal threshold phosphate concentration. Lancet 1975; i: 309-10.
Papapoulos SE, Frolich M, Mudde AH, Harinck HIJ, Berg HVD, Bojvoet OLM. Serum osteocalcin in Padget’s disease of bone: bone concentrations and response to bisphosphonate treatment., J Endocrinol Metab 1987; 65: 89-94. 27. Bockman RS, Boskey AL, Blumenthal NC, Alcock NW, Warrell RP. Gallium increases bone calcium and crystallite perfection of hydroxyapatite. Calcif Tissue Int 1986; 39: 376-81. 28. Blumenthal NC, Cosma V, Levine S. Effect of gallium on the in vitro formation, growth, and solubility of hydroxyapatite. Calcif Tissue Int 1989; 45: 81-87. 29. Donnelly R, Boskey A. The effect of gallium on seeded hydroxyapatite growth. Calcif Tissue Int 1989; 44: 138-42. 30. Chitambar CR, Matthaeus WG, Antholine WE, Graff K, O’Brien WJ. Inhibition of leukemic HL60 cell growth by transferrin-gallium: effects on ribonucleotide reductase and demonstration of drug synergy with hydroxyurea. Blood 1988; 72: 1930-36. 31. Larson SM, Rasey JS, Allen DR, et al. Common pathway for tumor cell uptake of gallium-67 and iron-59 via a transferrin receptor. J Natl 26.
Cancer Inst 1980; 64: 41-53.
Anghileri LJ, Crone-Escanye M-C, Thouvenot P, Brunotte F, Robert J. Mechanisms of gallium-67 accumulation by tumors: role of cell membrane permeability. J Nucl Med 1988; 29: 663-68. 33. Pioli G, Girasole G, Pedrazzoni M, et al. Spontaneous release of interleukin-1 (IL-1) from medullary mononuclear cells of pagetic subjects. Calcif Tissue Int 1989; 45: 257-59. 32.
Visual evoked responses in children with a
migraine:
diagnostic test
The visual evoked responses (VERs) to both flash and pattern stimulation were recorded in 44 children with migraine, with or without aura, and 8 with periodic syndrome. The controls were 50 age and sex matched children. VERs of 50 sex matched adults with migraine were also recorded. The fast wave amplitude in children with migraine was higher than that in controls. The amplitude was higher in younger children with migraine (under 13 years) than that in older children or adults with migraine. Children with periodic syndrome had VERs similar to those of children with migraine. The VER, especially in children, may prove to be a useful test in the diagnosis of migraine.
Introduction The aetiology of migraine (vasculogenic or neurogenic) has been debated for years. Peatfield1 has stated that "migrainous headache is believed to be initiated within the brainstem, expressed in the external carotid circulation and then perceived back in the brain stem, thalamus and cortex". The pathogenesis of migraine may involve the opening of arteriovenous anastomoses in the carotid circulation ;2 this theory is supported by the finding that a new 5hydroxytryptamine-like receptor agonist, a selective vasoconstrictor of this circulation in animals, relieves migraine in adults.3 Migraine headache affects 2.7% of children by the age of 7 and 10-6% by age 14.4,5 Because there have been no
diagnostic tests for migraine, most epidemiological data has been based on questionnaires.6 Many attempts have been made to find an objective marker.7 The diagnosis of migraine, with and without aura, and migraine equivalents is made from clinical history, physical examination, and elimination of alternatives;.8,9 the differential diagnosis is multiple and complex."* Despite the view that childhood periodic syndromes are migraine equivalents without headache they are not included in the International Headache Society classification of migraine.8,9 Electrophysiological techniques have been used to analyse the hypothalamic content of a migraine attack. Differences in both electroencephalograms (EEGs) and visual evoked responses (VERs) have been found between groups of children with migraine and controls,l1-13 but, to date, there has not been an electrophysiological test for diagnostic use. In an earlier study of adults, 14 we found that there was a difference in background fast wave activity of the VER between those with migraine and controls. We have studied VERs, with frequences over 14 Hz, in children with migraine and controls, and looked at the possible use of this test in the diagnosis of migraine.
ADDRESS: Birminghamand Midland Eye Hospital, Birmingham B32NS, UK (M. J. Mortimer, MRCGP, P A. Good, BSc, J. B. Marsters, PhD, D P. Addy, FRCP). Correspondence to Mr P. A Good.
76
Patients and methods 52 children, attending the Birmingham Migraine clinic, were assessed clinically; 44 had migraine with aura or migraine without aura,8 and 8 had periodic syndrome (paroxysmal abdominal pain with nausea and/or vomiting, but no headache). The district ethical committee approved the study. With informed parental consent, we recorded VERs for each child.
The 44 children with migraine headache were separated into two (10 boys and 12 girls) under 13 yr (range 3-12 yr, mean 9-2 yr), and 22 (5 boys and 17 girls) aged 13-16 yr (mean 14-11 yr). 13 yr was chosen as an approximation of puberty. In the younger group, 7 had migraine with aura and 15 had no aura. In the older children, 15 had experienced aura and 7 had not. All the children with periodic syndrome were 12 yr or younger (range 4-12 yr); 4 were girls and 4 boys. age groups: 22
A control group of 50 children, who were age and sex matched with the migraine subgroups, were volunteers from general practice; they had no history of migraine, and no ophthalmological or neurological abnormality. The adult migraine control group consisted of 50 sex-matched patients with migraine over 16 yr, selected at random from a group of adults with migraine referred from the Birmingham Migraine Clinic for investigation. 25 of these patients had migraine with aura and 25 migraine without aura. All controls were investigated under exactly the same conditions as the children with migraine.
The VERs were recorded to both diffuse flash and pattern stimulation (reversing checkerboard). Flash stimulation was generated by a Grass P5 22 photic stimulator with a blue/white light source of intensity 200 candella/m2 and with peak wavelength 510 nm. The stimulus rate was 2 Hz. Pattern stimulation was provided by a 2 Hz reversing black and white checkerboard displayed on a television screen. The pattern subtended an angle of 1°at the eye. The stimulus field size was 16°, contrast 90%, and mean luminance 350 candella/m2. Sources of both flash and pattern stimuli were 50 cm from the children’s eyes. Both eyes were stimulated at the same time. The recording electrodes were bipolar silver,/silver chloride electrodes put on the scalp at positions Fz and Oz, in accordance with international convention. Frequencies in the EEG &bgr; range, 10-50 Hz, were recorded (Nicolet C4 clinical averager). Analysis time was 500 ms. The amplitude and frequency of at least four different waveforms from five consecutive stimuli were used to calculate the means. The amplitudes of waves with frequency greater than 16 Hz occurring in the last 250 ms of the recording (fastwaves) were used to calculate the mean amplitude of fast wave activity. No child had a migraine at the time the VER was recorded.
Fig 1-Examples of VER recordings
to flash and pattern
stimulation. Note increased fast
wave
activity
in
patients.
Statistical analysis of the data was by analysis of (ANOVA) and Bonferroni’s procedure was applied.
variance
Results The visual evoked responses for control groups and migraine groups are shown in the table. Children with migraine or periodic syndrome who were younger than 13 and lower years had higher fast wave amplitude (p
