Abstract
Familial Dysautonomia (FD) is an autosomal recessive genetic disease where autonomic and sensory functions are defective affecting many body systems including the vascular. Plasma level of the neurotransmitter Calcitonin Gene Related Peptide (CGRP) is decreased in FD patients. This compound has been implicated to take part in the pathogenesis of migraine. We aimed to evaluate the symptoms of headaches in FD patients and to test the hypothesis that these patients will have a low incidence of migrainous headache. Sixty-five FD patients were evaluated by a medical headache questionnaire. Mean age was 23.73 + 10.82 years (mean 21 years) and there were 37 males (57 %).Thirty-eight patients (58.5 %) described having episodic headache conforming to criteria of tension headache, and in 17 of those 38 (44.7 %) headache were dependent on changes in blood pressure, except from one patient who had complaints that matched diagnosis of acephalic migraine. None of the patients had symptoms compatible with migraine or cluster headache. Results show that the headache is a very common complaint in FD, there is lack of migraine symptoms in this group. This might be attributed to defective sensory innervation and deficiency of CGRP. FD could be regarded as a human model for CGRP deficiency when studying the pathogenesis of migraine.
Similar content being viewed by others
References
Aguayo AJ, Nair CP, Bray GM (1971) Peripheral nerve abnormalities in the Riley-Day syndrome. Findings in a sural nerve biopsy. Arch Neurol 24:106–116
Anderson SL, Coli R, Daly IW, Kichula EA, Rork MJ, Volpi SA, Ekstein J, Rubin BY (2001) Familial dysautonomia is caused by mutations of the IKAP gene. Am J Hum Genet 68:753–758
Asghar MS, Hansen AE, Kapijimpanga T, van der Geest RJ, van der Koning P, Larsson HB, Olesen J, Ashina M (2010) Dilation by CGRP of middle meningeal artery and reversal by sumatriptan in normal volunteers. Neurology 75:1520–1526
Axelrod FB, Goldberg JD, Ye XY, Maayan C (2002) Survival in familial dysautonomia: impact of early intervention. J Pediatr 141:518–523
Benemei S, Nicoletti P, Capone JA, Geppetti P (2007) Pain pharmacology in migraine: focus on CGRP and CGRP receptors. Neurol Sci 28(Suppl 2):S89–S93
Doods H, Arndt K, Rudolf K, Just S (2007) CGRP antagonists: unravelling the role of CGRP in migraine. Trends Pharmacol Sci 28:580–587
Edvisson I, Ho TW (2010) CGRP receptor antagonism and migraine. Neurotherapeutics 7:164–175
Gold-von Simson G, Axelrod FB (2006) Familial dysautonomia: update and recent advances. Curr Probl Pediatr Adolesc Health Care 36:218–237
Grover-Johnson N, Pearson J (1976) Deficient vascular innervation in familial dysautonomia, an explanation for vascular instability. Neuropathol Appl Neurobiology 2:217–224
Hansen JM, Hauge AW, Olesen J, Ashina M (2010) Calcitonin gene-related peptide triggers migraine-like attacks in patients with migraine with aura. Cephalalgia 30:1179–1186
Headache Classification Subcommittee of the International Headache Society (2004) The International Classification of Headache Disorders 2nd edition. Cephalalgia 24(Suppl 1):9–160
Ho TW, Ferrari MD, Dodick DW, Galet V, Kost J, Fan X, Leibensperger H, Froman S, Assaid C, Lines C, Koppen H, Winner K (2008) Efficacy and tolerability of MK-9074 (telcagepant), a new oral antagonist of calcitonin gene-related peptide receptor, compared with zolmitriptan for acute migraine: a randomized, placebo-controlled, parallel-treatment trial. Lancet 372:2115–2123
Jang MU, Park JW, Kho HS, Chung SC, Chung JW (2011) Plasma and saliva levels of nerve growth factor and neuropeptides in chronic migraine patients. Oral Dis 17:187–193
Jansen-Olesen J, Mortensen A, Edvinsson I (1996) Calcitonon gene-related peptide is released from capsaicin-sensitive nerve fibers and induces vasodilation of human cerebral arteries concomitant with activation of adnyl cyclase. Cepahalalgia 16:310–316
Jensen R, Stovner LJ (2008) Epidemiology and comorbidity of headache. Lancet Neurol 7:354–361
Lassen LH, Haderslev PA, Jacobsen VB, Iversen HK, Sperling B, Olesen J (2002) CGRP may play a causative role in migraine. Cephalalagia 22:54–61
Maayan C, Kaplan E, Shachar S, Godfrey S (1987) Incidence of familial dysautonomia in Israel 1977–1981. Clin Genet 32:106–108
Maayan C, Becker Y, Gesundheit B, Girgis SI (2001) Calcitonin gene related peptide in familial dysautonomia. Neuropeptides 35:189–195
Olesen J (2001) CGRP in migraine. Cephalalgia 31:638
Olesen J, Diener HC, Hussted IW, Goadsby PJ, Hall D, Meier U, Pollentier S, Lesko LM, BIBN 4096 BS Clinical Proof of Concept Study Group (2004) Calcitonin gene-related peptide receptor antagonist BIBN 4096 BS for the acute treatment of migraine. N Eng J Med 350:1104–1110
Pearson J, Pytel BA (1978a) Quantitative studies of sympathetic ganglia and spinal cord intermedio-lateral gray columns in familial dysautonomia. J Neurol Sci 39:47–59
Pearson J, Pytel BA (1978b) Quantitative studies of ciliary and sphenopalatine ganglia in familial dysautonomia. J Neurol Sci 39:123–130
Pearson J, Pytel BA, Grover-Johnson N, Axelrod F, Dancis J (1978) Quantitative studies of dorsal root ganglia and and neuropathologica observations on spinal cords in familial dysautonomia. J Neurol Sci 35:77–92
Rapoport AM (2010) New acute treatments for headache. Neurol Sci 31(Suppl 1):129–132
Recober A, Russo AF (2009) Calcitonin gene-related peptide: an update on the biology. Curr Opin Neurol 22:241–246
Russo AF, Kuburas A, Kaiser EA, Raddant AC, Recober AA (2009) Potential Preclinical Migraine Model: CGRP-Sensitized Mice. Mol Cell Pharmacol 1:264–270
Slaugenhaupt SA, Blumenfeld A, Gill SP et al (2001) Tissue-specific expression of a splicing mutation in the IKBKAP gene causes familial dysautonomia. Am J Hum Genet 68:598–605
Sprenger T, Goadsby PJ (2009) Migraine pathogenesis and state of pharmacological treatment options. BMC Med 7:71
Stewart WF, Staffa J, Lipton RB, Ottman R (1997) Familial risk of migraine: a population-based study. Ann Neurol 41:166–172
Acknowledgments
Dr. Steiner and Dr. Maayan conceived the project, designed the study and wrote the manuscript. Dr. Shihman interviewed the patients and analyzed the data. Dr.Yovchev collected data from the clinical charts.
Prof. Steiner serves on the editorial boards of the Journal of Neurovirology, the Journal of Neurological Sciences, and Medicine Neurology (Hebrew); serves on a data safety monitoring board for Actelion Pharmaceuticals Ltd. And Hoffmann-La Roche Ltd; and has received research support from the Israel Science Foundation and the Israeli Ministry of Health Chief Scientist.
Dr. Shihman, Dr. Maayan and Dr. Yovchev have nothing to disclose.
Author information
Authors and Affiliations
Corresponding author
Rights and permissions
About this article
Cite this article
Shihman, B., Steiner, I., Yovchev, I. et al. Lack of migraine in headaches of familial dysautonomia patients. J Neural Transm 120, 399–402 (2013). https://doi.org/10.1007/s00702-012-0903-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00702-012-0903-y