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Migraine Headache in Patients With Tourette Syndrome
Carolyn Kwak, MS, PA-C;
Kevin Dat Vuong, MA;
Joseph Jankovic, MD
Arch Neurol. 2003;60:1595-1598.
ABSTRACT
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Background Tourette syndrome (TS) is recognized as one of the most common childhood movement disorders, characterized by motor and phonic tics often associated with neurobehavioral comorbidities, such as obsessive-compulsive disorder. Neurotransmitter dysregulation, particularly involving the serotonin system, has been implicated in the pathogenesis of TS, obsessive-compulsive disorder, and migraine headache.
Objectives To investigate the possible association between migraine headache and TS and to report preliminary findings of family history of migraine headache in patients with TS.
Methods Subjects diagnosed as having TS at the Baylor College of Medicine Parkinson's Disease Center and Movement Disorders Clinic were administered a migraine headache questionnaire based on the migraine criteria established by the Headache Classification Committee of the International Headache Society.
Results Of 100 patients with TS, 25 (25.0%) satisfied the diagnostic criteria for migraine headache, significantly greater than the estimated 10% to 13% in the general adult population (P<.001) and the estimated 2% to 10% in the general pediatric population (P<.04). There was no significant (P = .44) difference in the presence of comorbid obsessive-compulsive traits in the TS migraine and TS nonmigraine sample groups. Furthermore, our TS group with migraines was not more likely to have features of obsessive-compulsive disorder compared with attention-deficit/hyperactivity disorder. Of patients with TS, 56.0% reported a family history of migraines, 44.0% of whom were first-degree relatives.
Conclusions The frequency of migraine headache in a clinic sample of TS subjects was nearly 4-fold more than the frequency of migraines reported in the general population. Contrary to previous reports, the co-occurrence of migraines and TS in our sample group may possibly be attributed to another TS comorbidity, other than obsessive-compulsive traits.
INTRODUCTION
GILLES DE LA TOURETTE syndrome (TS) is among the most common childhood genetic movement disorders, with a reported frequency in children as high as 3%.1 The condition is characterized by motor and phonic tics that fluctuate in distribution, severity, and frequency, often preceded by premonitory sensations.2-4 Tourette syndrome is commonly associated with attention deficit with or without hyperactivity, obsessive-compulsive traits, and other neurobehavioral comorbidities, such as poor impulse control, self-injurious behavior, anxiety, and mood disorders.5-7
In addition to the various neurobehavioral comorbidities, patients with TS have been described as having a high frequency of headaches. Barabas8-9 and colleagues reported that 27% of children with TS met the diagnostic criteria for migraine headache, significantly higher than the estimated prevalence of 3% to 13% in the general population of school-aged children, adolescents, and adults.10-15 Migraines may be as debilitating as symptoms of TS, accounting for school absences and disruption of daily functioning. Commonly described as pulsatile unilateral headaches, migraines are often associated with nausea, vomiting, photophobia, auras, or other sensory phenomena.16-17 In the pediatric and adolescent populations, migraine variants may present as abdominal pain with cyclic vomiting, benign paroxysmal torticollis, or paroxysmal vertigo.18 Migraines in the younger population have also been commonly reported to be of shorter duration and bilateral in distribution.19
5-Hydroxytryptamine receptor dysfunction has been implicated in obsessive-compulsive disorder (OCD) and migraine headache.20-21 However, to our knowledge, the occurrence of migraine headache in TS patients, or their family members who may have a high incidence of OCD, has not been well studied. This study determines the prevalence of migraines in our sample of TS subjects and in their first-degree family members, and explores whether the TS comorbid features of attention-deficit/hyperactivity disorder and OCD correlate with the occurrence of migraines.
METHODS
One hundred one subjects diagnosed as having TS according to the TS Classification Study Group criteria22 were included in the study. All subjects were diagnosed at the Baylor College of Medicine Parkinson's Disease Center and Movement Disorders Clinic. A written consent form, approved by the Institutional Review Board for Human Research for the Baylor College of Medicine, was reviewed and signed by all subjects or their legal guardians. Questionnaires were designed based on the diagnostic criteria for migraine headache, established by the Headache Classification Committee of the International Headache Society.23 The questionnaires were administered to all new or follow-up consecutive patients seen during the study period at the Baylor College of Medicine Parkinson's Disease Center and Movement Disorders Clinic, and were completed through either a personal interview in the clinic or telephone contact. Data collected included the following information: (1) demographic data; (2) age at onset of TS symptoms; (3) occurrence of comorbidities, such as attention deficit with or without hyperactivity and obsessive-compulsive traits based on Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria24; (4) age at onset of migraine headache; (5) the presence of aura with migraine; (6) family history of migraine headache; and (7) other information. To ensure data accuracy and reliability, all but one patient was interviewed again through repeated administration of the questionnaire by telephone. Each subject's medical record was also reviewed for accuracy of age of onset of TS symptoms and presence of comorbid attention-deficit or obsessive-compulsive traits. All data analysis was performed on 100 verified subjects.
Nonparametric analyses were performed using the  2 exact test based on the Goodman and Kruskal ( <.05) statistic, comparing the variables of TS patients with migraine headache, family history of migraine headache, and obsessive-compulsive and attention-deficit traits. A univariate analysis of variance was also used to compare the age at onset of TS symptoms between both sex and TS migraine and nonmigraine groups. All analyses are performed using SPSS version 10 (SPSS Inc, Chicago, Ill).
RESULTS
One hundred TS patients (78 males), whose mean age was 20.2 ± 14.2 (range, 7-69) years, were included in this study. Of the 100 patients with TS, 25 satisfied the diagnostic criteria for migraine headache based on International Headache Society criteria. Sixteen percent of pediatric and 39% of adult patients with TS had migraines, significantly greater than the 6% (range, 2%-10%) reported in otherwise healthy children10-13 (2 = 0.03, P<.04) and the 11% (range, 10%-13%) reported in the general adult population14-15 (2 = 0.11, P<.001), respectively (Table 1). Of the 25 TS patients with migraine, 12 (48%) reported migraine with aura.
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Table 1. Comparison of Patients With TS and Without Migraines*
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Also, of the 25 TS patients with migraine, 6 (24%) were females and 19 (76%) were males; this difference did not reach statistical significance (P>.99). The mean age at onset of migraine headache between sexes was also not significantly different (P = .91). Of the 25 subjects with migraine, 24 (96%) also had comorbid obsessive-compulsive traits. However, our TS patients with migraines did not have a significantly greater comorbidity of obsessive-compulsive traits or attention deficit compared with the TS group without migraine (P = .44 and P>.99, respectively). Fifty-six percent of patients with TS had a family member with migraine, 44% of whom were first-degree relatives; 46.0% of a non–first-degree relative reported migraines.
COMMENT
Our study shows that the frequency of migraine headache in a clinic sample of subjects with TS is 25.0% (39% of adults and 16% of children with TS), which suggests nearly a 4-fold increase over the frequency of migraines reported in a comparable sample group of otherwise healthy individuals10-15 (Table 2). Although these findings are comparable to those of Barabas8-9 and colleagues, who reported a frequency of 27% of migraines in their TS sample, our results must be interpreted cautiously because we used reported control data on the frequency of headaches collected from the general population rather than from a specialty clinic.10-14 Control data from an age-matched group to assess the prevalence of migraines in a sample group with other neurological disorders are being collected. Although other types of headache, including tension, sinus, and medication-related headaches, were reported in our TS sample, the objective of the questionnaire was to diagnose migraine headache.
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Table 2. Comparison of Migraine Studies in TS and Non-TS Populations
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A primary defect in serotonin metabolism has been proposed for TS and migraine.25-26 Serotonin abnormalities have been suggested in OCD, a hypothesis supported by marked improvement of OCD symptoms with selective serotonin reuptake inhibitors.27 In TS patients, cerebrospinal fluid studies28 have shown reduced levels of 5-hydroxyindoleacetic acid and tryptophan in the basal ganglia, decreased plasma tryptophan levels, and decreased 24-hour serotonin excretion and whole-blood serotonin. However, in contrast to the Barabas et al8 pilot study, our study showed that TS patients with migraines did not have significantly greater obsessive-compulsive features. While 96% of TS patients with migraines had obsessive-compulsive traits, the frequency of these traits in our sample of TS subjects without migraines was also high (88%) (Table 1), indicating that obsessive-compulsive traits are not a predictor of migraine headache. Other biochemical abnormalities have been proposed in TS, including involvement of the cholinergic, dopaminergic, GABAergic, noradrenergic, and opioid systems.29-30 In migraines, mutations in genes involving calcium channels, mitochondrial DNA, dopamine receptors, and prothrombic risk factors have also been detected.31-32
Although genetic linkage analyses have excluded 5-hydroxytryptamine receptor genes in the TS population,33-34 until the TS gene is located, it is unknown whether migraine, TS, obsessive-compulsive traits, and other comorbidities are genetically linked. To our knowledge, our study is the first to support a possible genetic component of TS manifesting as migraine headache. Of the patients with TS, 45.0% reported one or more parents with migraine headache. Also, of the TS patients in our study, 3 had both parents with migraine headaches. Previous studies35 suggest a bilinear mode of transmission of TS symptoms in 25% of patients with TS. Our data, however, must be interpreted cautiously, because the reported risk in the general population for migraine headache if one parent is affected is high for the offspring.
A recent review36 on migraine headache in patients with psychiatric disorders concluded an association between affective disorders, particularly anxiety and depression. Further studies should investigate whether TS subjects with migraines also have an increased prevalence of anxiety, depression, or other psychiatric comorbidities. Furthermore, studies should determine if TS patients with migraine respond more favorably to adjunctive therapy designed to treat TS psychiatric comorbidities, compared with those without psychiatric conditions.
In summary, TS is a spectrum disorder, with varying degrees of severity in individual patients. Because the complexity of the TS gene has yet to be determined, the presence of migraine headache, if present also in family members of patients with TS, may be used as a clinical marker for this complex genetic disorder.
AUTHOR INFORMATION
Corresponding author: Joseph Jankovic, MD, Parkinson's Disease Center and Movement Disorders Clinic and Department of Neurology, Baylor College of Medicine, 6550 Fannin St, Suite 1801, Houston, TX 77030.
Accepted for publication April 21, 2003.
Author contributions: Study concept and design (Ms Kwak and Dr Jankovic); acquisition of data (Dr Jankovic); analysis and interpretation of data (Mr Vuong and Dr Jankovic); drafting of the manuscript (Ms Kwak and Dr Jankovic); critical revision of the manuscript for important intellectual content (Mr Vuong); statistical expertise (Mr Vuong); study supervision (Ms Kwak and Dr Jankovic).
From the Parkinson's Disease Center and Movement Disorders Clinic and the Department of Neurology, Baylor College of Medicine, Houston, Tex.
REFERENCES
1. Mason A, Banerjee S, Eapen Z, Zeitlin H, Robertson M. The prevalence of Tourette syndrome in a mainstream school population. Dev Med Child Neurol. 1998;40:292-296.
ISI
| PUBMED
2. Jankovic J. Tourette's syndrome. N Engl J Med. 2001;345:1184-1192.
FREE FULL TEXT
3. Leckman J, Peterson B, King R, Scahill L, Cohen D. Phenomenology of tics and natural history of tic disorders. In: Cohen D, Jankovic J, Goetz C, eds. Tourette Syndrome, Advances in Neurology. Vol 85. Philadelphia, Pa: Lippincott Williams & Wilkins; 2001:1-14.
4. Leckman J, Walker D, Goodman W. "Just-right" perceptions associated with compulsive behavior in Tourette's syndrome. Am J Psychiatry. 1994;151:675-680.
FREE FULL TEXT
5. Coffey BJ, Park KS. Behavioral and emotional aspects of Tourette syndrome. Neurol Clin. 1997;15:277-289.
FULL TEXT
|
ISI
| PUBMED
6. Spencer T, Biederman J, Harding M. Disentangling the overlap between Tourette's disorder and ADHD. J Child Psychol Psychiatry. 1998;39:1037-1044.
FULL TEXT
|
ISI
| PUBMED
7. Eapen V, Robertson M, Alsobrook J. Obsessive-compulsive symptoms in Gilles de la Tourette's syndrome and obsessive-compulsive disorder: differences by diagnoses and family history. Am J Med Genet. 1997;74:432-438.
FULL TEXT
|
ISI
| PUBMED
8. Barabas G, Matthews W, Ferrari M. Tourette's syndrome and migraine. Arch Neurol. 1984;41:871-872.
FREE FULL TEXT
9. Barabas G, Matthews W. Homogenous clinical subgroups in children with Tourette syndrome. Pediatrics. 1985;75:73-75.
FREE FULL TEXT
10. Aromaa M, Sillanpaa M, Rautava P. Childhood headache at school entry: a controlled clinical study. Neurology. 1998;50:1729-1736.
ABSTRACT
11. Guidetti V, Galli F. Evolution of headache in childhood and adolescence: an 8-year follow-up. Cephalalgia. 1998;18:449-454.
FULL TEXT
|
ISI
| PUBMED
12. Metsahonkala L, Sillanpaa M, Tuominen J. Outcome of early school-age migraine. Cephalalgia. 1997;17:662-665.
FULL TEXT
|
ISI
| PUBMED
13. Mavromichalis I, Anagnostopaulos D, Metaxas N, Papanastassiou E. Prevalence of migraine in schoolchildren and some clinical comparisons between migraine with and without aura. Headache. 1999;39:728-736.
PUBMED
14. Breslau N, Rasmussen BK. The impact of migraine: epidemiology, risk factors, and co-morbidities. Neurology. 2001;56(suppl 1):S4-S12.
FREE FULL TEXT
15. Lipton R, Scher A, Kolodner K, Liberman J, Steiner T, Stewart W. Migraine in the United States: epidemiology and patterns of health care use. Neurology. 2002;58:885-894.
FREE FULL TEXT
16. Ferrari M. Migraine. Lancet. 1998;351:1043-1051.
FULL TEXT
|
ISI
| PUBMED
17. Turk W. Childhood migraine. Adv Pediatr. 2000;47:161-197.
PUBMED
18. Al-Twaijri W, Shevell M. Pediatric migraine equivalents: occurrence and clinical features in practice. Pediatr Neurol. 2002;27:410-411.
FULL TEXT
|
ISI
| PUBMED
19. deGrauw T, Hershey A, Powers S, Bentti A. Diagnosis of migraine in children attending a pediatric headache clinic. Headache. 1999;39:481-485.
FULL TEXT
|
ISI
| PUBMED
20. Slassi A. Recent advances in 5-HT1B/1D receptor antagonists and agonists and their potential therapeutic applications. Curr Top Med Chem. 2002;2:559-574.
FULL TEXT
| PUBMED
21. Kennett G, Lightowler S, deBiasi V, et al. Effect of chronic administration of selective 5-hydroxytryptamine and noradrenaline uptake inhibitors on a putative index of 5-HT2C/2B receptor function. Neuropharmacology. 1994;33:1581-1588.
FULL TEXT
|
ISI
| PUBMED
22. Tourette Syndrome Classification Study Group. Definitions and classification of tic disorders. Arch Neurol. 1993;50:1013-1016.
FREE FULL TEXT
23. International Headache Society. Classification and diagnostic criteria for headache disorders, cranial neuralgia and facial pain. Cephalalgia. 1988;8(suppl 7):1-96.
24. American Psychiatric Association. Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition. Washington, DC: American Psychiatric Association; 1994.
25. Cath D, Spinhoven P, Landman A, van Kempen G. Psychopathology and personality characteristics in relation to blood serotonin in Tourette's syndrome and obsessive-compulsive disorder. J Psychopharmacol. 2001;15:111-119.
FREE FULL TEXT
26. deGroot C, Bornstein R, Baker G. Obsessive-compulsive symptom clusters and urinary amine correlates in Tourette syndrome. J Nerv Ment Dis. 1995;183:224-230.
ISI
| PUBMED
27. Micallef J, Blin O. Neurobiology and clinical pharmacology of obsessive-compulsive disorder. Clin Neuropharmacol. 2001;24:191-207.
FULL TEXT
|
ISI
| PUBMED
28. Comings D. Blood serotonin and tryptophan in Tourette syndrome. Am J Med Genet. 1990;36:418-430.
FULL TEXT
|
ISI
| PUBMED
29. Singer H, Wendlandt J. Neurochemistry and synaptic neurotransmission in Tourette syndrome. In: Cohen D, Jankovic J, Goetz C, eds. Tourette Syndrome, Advances in Neurology. Vol 85. Philadelphia, Pa: Lippincott Williams & Wilkins; 2001:1163-1178.
30. Riddle M, Carlson J. Clinical psychopharmacology for Tourette syndrome and associated disorders. In: Cohen D, Jankovic J, Goetz C, eds. Tourette Syndrome, Advances in Neurology. Vol 85. Philadelphia, Pa: Lippincott Williams & Wilkins; 2001:343-354.
31. Fanciullacci M, Alessandra M, Del Rosso A. Dopamine involvement in the migraine attack. Funct Neurol. 2000;15:171-181.
32. Montagna P. Molecular genetics of migraine headaches: a review. Cephalalgia. 2000;20:3-14.
FULL TEXT
|
ISI
| PUBMED
33. Gelernter J, Rao PA, Pauls DL. Assignment of the 5HT7 receptor gene (HTR7) to chromosome 10q and exclusion of genetic linkage with Tourette syndrome. Genomics. 1995;26:207-209.
FULL TEXT
|
ISI
| PUBMED
34. Brett P, Curtis D, Robertson M, Gurling H. Neuroreceptor subunit genes and the genetic susceptibility to Gilles de la Tourette syndrome. Biol Psychiatry. 1997;42:941-947.
FULL TEXT
|
ISI
| PUBMED
35. Hanna P, Janjua F, Contant C. Bilineal transmission in Tourette syndrome. Neurology. 1999;53:813-818.
FREE FULL TEXT
36. Sheftell F, Atlas S. Migraine and psychiatric comorbidity: from theory and hypothesis to clinical application. Headache. 2002;42:934-944.
FULL TEXT
|
ISI
| PUBMED
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