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Original Contribution |

Migraine Headache in Patients With Tourette Syndrome FREE

Carolyn Kwak, MS, PA-C; Kevin Dat Vuong, MA; Joseph Jankovic, MD
[+] Author Affiliations

From the Parkinson's Disease Center and Movement Disorders Clinic and the Department of Neurology, Baylor College of Medicine, Houston, Tex.


Arch Neurol. 2003;60(11):1595-1598. doi:10.1001/archneur.60.11.1595.
Text Size: A A A
Published online

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.

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.24 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.57

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.1015 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.

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 χ2 exact test based on the Goodman and Kruskal (α<.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).

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 children10132 = 0.03, P<.04) and the 11% (range, 10%-13%) reported in the general adult population14,152 = 0.11, P<.001), respectively (Table 1). Of the 25 TS patients with migraine, 12 (48%) reported migraine with aura.

Table Graphic Jump LocationTable 1. Comparison of Patients With TS and Without Migraines*

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.

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 individuals1015 (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.1014 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.

Table Graphic Jump LocationTable 2. Comparison of Migraine Studies in TS and Non-TS Populations

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.

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).

Mason  ABanerjee  SEapen  ZZeitlin  HRobertson  M The prevalence of Tourette syndrome in a mainstream school population. Dev Med Child Neurol.1998;40:292-296.
PubMed
Jankovic  J Tourette's syndrome. N Engl J Med.2001;345:1184-1192.
PubMed
Leckman  JPeterson  BKing  RScahill  LCohen  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.
Leckman  JWalker  DGoodman  W "Just-right" perceptions associated with compulsive behavior in Tourette's syndrome. Am J Psychiatry.1994;151:675-680.
PubMed
Coffey  BJPark  KS Behavioral and emotional aspects of Tourette syndrome. Neurol Clin.1997;15:277-289.
PubMed
Spencer  TBiederman  JHarding  M Disentangling the overlap between Tourette's disorder and ADHD. J Child Psychol Psychiatry.1998;39:1037-1044.
PubMed
Eapen  VRobertson  MAlsobrook  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.
PubMed
Barabas  GMatthews  WFerrari  M Tourette's syndrome and migraine. Arch Neurol.1984;41:871-872.
PubMed
Barabas  GMatthews  W Homogenous clinical subgroups in children with Tourette syndrome. Pediatrics.1985;75:73-75.
PubMed
Aromaa  MSillanpaa  MRautava  P Childhood headache at school entry: a controlled clinical study. Neurology.1998;50:1729-1736.
PubMed
Guidetti  VGalli  F Evolution of headache in childhood and adolescence: an 8-year follow-up. Cephalalgia.1998;18:449-454.
PubMed
Metsahonkala  LSillanpaa  MTuominen  J Outcome of early school-age migraine. Cephalalgia.1997;17:662-665.
PubMed
Mavromichalis  IAnagnostopaulos  DMetaxas  NPapanastassiou  E Prevalence of migraine in schoolchildren and some clinical comparisons between migraine with and without aura. Headache.1999;39:728-736.
PubMed
Breslau  NRasmussen  BK The impact of migraine: epidemiology, risk factors, and co-morbidities. Neurology.2001;56(suppl 1):S4-S12.
PubMed
Lipton  RScher  AKolodner  KLiberman  JSteiner  TStewart  W Migraine in the United States: epidemiology and patterns of health care use. Neurology.2002;58:885-894.
PubMed
Ferrari  M Migraine. Lancet.1998;351:1043-1051.
PubMed
Turk  W Childhood migraine. Adv Pediatr.2000;47:161-197.
PubMed
Al-Twaijri  WShevell  M Pediatric migraine equivalents: occurrence and clinical features in practice. Pediatr Neurol.2002;27:410-411.
PubMed
deGrauw  THershey  APowers  SBentti  A Diagnosis of migraine in children attending a pediatric headache clinic. Headache.1999;39:481-485.
PubMed
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.
PubMed
Kennett  GLightowler  SdeBiasi  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.
PubMed
Tourette Syndrome Classification Study Group Definitions and classification of tic disorders. Arch Neurol.1993;50:1013-1016.
PubMed
International Headache Society Classification and diagnostic criteria for headache disorders, cranial neuralgia and facial pain. Cephalalgia.1988;8(suppl 7):1-96.
PubMed
American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition.  Washington, DC: American Psychiatric Association; 1994.
Cath  DSpinhoven  PLandman  Avan 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.
PubMed
deGroot  CBornstein  RBaker  G Obsessive-compulsive symptom clusters and urinary amine correlates in Tourette syndrome. J Nerv Ment Dis.1995;183:224-230.
PubMed
Micallef  JBlin  O Neurobiology and clinical pharmacology of obsessive-compulsive disorder. Clin Neuropharmacol.2001;24:191-207.
PubMed
Comings  D Blood serotonin and tryptophan in Tourette syndrome. Am J Med Genet.1990;36:418-430.
PubMed
Singer  HWendlandt  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.
Riddle  MCarlson  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.
Fanciullacci  MAlessandra  MDel Rosso  A Dopamine involvement in the migraine attack. Funct Neurol.2000;15:171-181.
PubMed
Montagna  P Molecular genetics of migraine headaches: a review. Cephalalgia.2000;20:3-14.
PubMed
Gelernter  JRao  PAPauls  DL Assignment of the 5HT7 receptor gene (HTR7) to chromosome 10q and exclusion of genetic linkage with Tourette syndrome. Genomics.1995;26:207-209.
PubMed
Brett  PCurtis  DRobertson  MGurling  H Neuroreceptor subunit genes and the genetic susceptibility to Gilles de la Tourette syndrome. Biol Psychiatry.1997;42:941-947.
PubMed
Hanna  PJanjua  FContant  C Bilineal transmission in Tourette syndrome. Neurology.1999;53:813-818.
PubMed
Sheftell  FAtlas  S Migraine and psychiatric comorbidity: from theory and hypothesis to clinical application. Headache.2002;42:934-944.
PubMed

Figures

Tables

Table Graphic Jump LocationTable 1. Comparison of Patients With TS and Without Migraines*
Table Graphic Jump LocationTable 2. Comparison of Migraine Studies in TS and Non-TS Populations

References

Mason  ABanerjee  SEapen  ZZeitlin  HRobertson  M The prevalence of Tourette syndrome in a mainstream school population. Dev Med Child Neurol.1998;40:292-296.
PubMed
Jankovic  J Tourette's syndrome. N Engl J Med.2001;345:1184-1192.
PubMed
Leckman  JPeterson  BKing  RScahill  LCohen  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.
Leckman  JWalker  DGoodman  W "Just-right" perceptions associated with compulsive behavior in Tourette's syndrome. Am J Psychiatry.1994;151:675-680.
PubMed
Coffey  BJPark  KS Behavioral and emotional aspects of Tourette syndrome. Neurol Clin.1997;15:277-289.
PubMed
Spencer  TBiederman  JHarding  M Disentangling the overlap between Tourette's disorder and ADHD. J Child Psychol Psychiatry.1998;39:1037-1044.
PubMed
Eapen  VRobertson  MAlsobrook  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.
PubMed
Barabas  GMatthews  WFerrari  M Tourette's syndrome and migraine. Arch Neurol.1984;41:871-872.
PubMed
Barabas  GMatthews  W Homogenous clinical subgroups in children with Tourette syndrome. Pediatrics.1985;75:73-75.
PubMed
Aromaa  MSillanpaa  MRautava  P Childhood headache at school entry: a controlled clinical study. Neurology.1998;50:1729-1736.
PubMed
Guidetti  VGalli  F Evolution of headache in childhood and adolescence: an 8-year follow-up. Cephalalgia.1998;18:449-454.
PubMed
Metsahonkala  LSillanpaa  MTuominen  J Outcome of early school-age migraine. Cephalalgia.1997;17:662-665.
PubMed
Mavromichalis  IAnagnostopaulos  DMetaxas  NPapanastassiou  E Prevalence of migraine in schoolchildren and some clinical comparisons between migraine with and without aura. Headache.1999;39:728-736.
PubMed
Breslau  NRasmussen  BK The impact of migraine: epidemiology, risk factors, and co-morbidities. Neurology.2001;56(suppl 1):S4-S12.
PubMed
Lipton  RScher  AKolodner  KLiberman  JSteiner  TStewart  W Migraine in the United States: epidemiology and patterns of health care use. Neurology.2002;58:885-894.
PubMed
Ferrari  M Migraine. Lancet.1998;351:1043-1051.
PubMed
Turk  W Childhood migraine. Adv Pediatr.2000;47:161-197.
PubMed
Al-Twaijri  WShevell  M Pediatric migraine equivalents: occurrence and clinical features in practice. Pediatr Neurol.2002;27:410-411.
PubMed
deGrauw  THershey  APowers  SBentti  A Diagnosis of migraine in children attending a pediatric headache clinic. Headache.1999;39:481-485.
PubMed
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.
PubMed
Kennett  GLightowler  SdeBiasi  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.
PubMed
Tourette Syndrome Classification Study Group Definitions and classification of tic disorders. Arch Neurol.1993;50:1013-1016.
PubMed
International Headache Society Classification and diagnostic criteria for headache disorders, cranial neuralgia and facial pain. Cephalalgia.1988;8(suppl 7):1-96.
PubMed
American Psychiatric Association Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition.  Washington, DC: American Psychiatric Association; 1994.
Cath  DSpinhoven  PLandman  Avan 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.
PubMed
deGroot  CBornstein  RBaker  G Obsessive-compulsive symptom clusters and urinary amine correlates in Tourette syndrome. J Nerv Ment Dis.1995;183:224-230.
PubMed
Micallef  JBlin  O Neurobiology and clinical pharmacology of obsessive-compulsive disorder. Clin Neuropharmacol.2001;24:191-207.
PubMed
Comings  D Blood serotonin and tryptophan in Tourette syndrome. Am J Med Genet.1990;36:418-430.
PubMed
Singer  HWendlandt  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.
Riddle  MCarlson  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.
Fanciullacci  MAlessandra  MDel Rosso  A Dopamine involvement in the migraine attack. Funct Neurol.2000;15:171-181.
PubMed
Montagna  P Molecular genetics of migraine headaches: a review. Cephalalgia.2000;20:3-14.
PubMed
Gelernter  JRao  PAPauls  DL Assignment of the 5HT7 receptor gene (HTR7) to chromosome 10q and exclusion of genetic linkage with Tourette syndrome. Genomics.1995;26:207-209.
PubMed
Brett  PCurtis  DRobertson  MGurling  H Neuroreceptor subunit genes and the genetic susceptibility to Gilles de la Tourette syndrome. Biol Psychiatry.1997;42:941-947.
PubMed
Hanna  PJanjua  FContant  C Bilineal transmission in Tourette syndrome. Neurology.1999;53:813-818.
PubMed
Sheftell  FAtlas  S Migraine and psychiatric comorbidity: from theory and hypothesis to clinical application. Headache.2002;42:934-944.
PubMed

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