550

MIGRAINE, SEROTONIN, AND THE CAROTID BODY SIR,-Dr Blaul has expressed admirably the controversy over the aetiology of migraine, yet one factor was not considered. Why is classical migraine usually one-sided-a feature that has earned it the name "hemicrania"? None of the standard works on migraine has attempted an explanation. We conceived the idea that the carotid body might trigger the migrainous attack on the ipsilateral side of the brain by releasing serotonin and other biogenic amines. To test our hypothesis, which is supported by the Wolff’s tracings of the temporal artery and carotid body pulse wave,2 we measured the serotonin content of the carotid body post mortem. Carotid bodies, including the bifurcation of the com-

carotid arteries, were removed from both sides within an hour of death from five patients chosen at random. The serotonin content was compared with that in material from the common-iliac-artery (control). The specimens were finely minced mon

SEROTONIN CONTENT OF CAROTID BIFURCATION POST MORTEM COMPARED WITH ILIAC BIFURCATION

(CONTROL)

S.E.M.=2 p.glg.

taken up in a fluid containing 0.06 ml of a solution with 0.2 mg/ml of potassium sorbate. The tubes were well shaken and placed on ice until assay.J and

immediately

15% K3

E.D.T.A.

The bifurcation of the

carotid contains serotonin in those in the common iliac than significantly higher bifurcation (P4mg/dl, we propose a single oral load with BH4 dihydrochloride, 2.5 mg/kg bodyweight 0-5—1 before a meal, and measurement of serum-phenylalanine beforehand and 4 or 6 h afterwards. A very significant decrease of serum-phenylalanine indicates BH4 deficiency. Localisation of the enzyme defect (deficiency in either DHPR or BH2 synthetase) is then possible by analysis of urinary pterins4,7 With this test it was possible to confirm the diagnosis of DHPR deficiency in two cases and to diagnose BH2 synthetase deficiency in five cases. (BH4 is available from A.N.) The first and second patient with BH2 synthetase deficiency4,7 have been under treatment for 12 and 7 months, respectively, with BH4 dihydrochloride at a daily dose of 1.25 mg/kg, under a normal phenylalanine unrestricted diet, but supplemented with DOPA, 5-hydroxytryptophan, and carbidopa. These children seem to develop much better under BH4 therapy than under phenylalanine-restricted diet with the same supplement of neurotransmitter precursors. Patients with DHPR deficiency require at least double the dose ofBH4.7 DHPR and BH2 synthetase deficiencies were grouped together in your editorial under the name "malignant hyperphenylalaninemia". However, since these diseases can be diagnosed and treated early, use of the term "malignant" should be discouraged. We suggest the term "BH4 deficiency." Other defects in BH2 biosynthesis can be expected (e.g., D-7,8-dihydroneopterin triphosphate synthetase deficiency and guanosine triphosphate cyclohydrolase deficiency). We are developing diagnostic techniques for these potential defects. Department of Pædiatrics, University of Zurich, 8032 Zurich, Switzerland,

Department of Organic Chemistry,

University of Zurich Children’s Hospital, University of Munich, Munich, West Germany Department of Pædiatrics, University of Heidelberg

Department of Pathology, Ichilov Hospital, Tel-Aviv University Medical School,

A. NIEDERWIESER H.-CH. CURTIUS

M. VISCONTINI

J. SCHAUB HILDGUND SCHMIDT

J. BEHAR

Israel

ALBERT

Bioclimatology Unit, Hebrew University-Hadassah Medical Centre, Jerusalem

ESTHER DEUTSCH EYTANA POMERANTZ YEHOUDA PFEIFER FELIX GAD SULMAN

Blau, J. N. Lancet, 1978, ii, 1136. Dalessio, D. J. Wolff’s Headache and Other Head Pain. London, 1972. 3. Yuwiler, A., Plotkin, S., Geller, E., Ritvo, E. R. Biochem. Med. 1970, 3,

1. 2.

426. 4.

PHENYLKETONURIA VARIANTS

Sulman, F. G., Pfeifer, Y., Superstine, E. Headache, 1977, 17, 203. 5. Everson-Pearse, A. G. Path. Ann. 1974, 9, 27.

1. 2.

Jervis, G. A. J. Biol. chem. 1947, 169, 651 Jervis, G. A. Proc. Soc. exp. Biol. Med. 1953, 82, 514. 3. Kaufman, S., Holtzman, N. A., Milstien, S., Butler, I. J., Krumholz, A. New Engl. J. Med. 1975, 293, 785. 4. Niederwieser, A., Curtius, H.-Ch., Bettoni, O., Bieri, J., Schircks, B., Viscontini, M., Schaub, J Lancet, 1979, i, 131. 5. Danks, D. M., and others J. inher. metab. Dis. 1978, 1, 49. 6. Schaub, J., Däumling, S., Curtius, H.-Ch., Niederwieser, A., Bartholomé. K., Viscontini, M., Schircks, B., Bieri, J. H., Archs Dis. Childh. 1978, 53, 674. 7. Curtius,

H.-Ch., Niederwieser, A., Viscontini, M., Otten, A., Schaub, J. Scheibenreiter, S., Schmidt, H. Clin. chim Acta, 1979, 93, 251.

Phenylketonuria variants.

550 MIGRAINE, SEROTONIN, AND THE CAROTID BODY SIR,-Dr Blaul has expressed admirably the controversy over the aetiology of migraine, yet one factor wa...
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