CD: Neurological Outcomes (2006)
Citation:
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
To assess the prevalence of celiac disease in patients with migraine by means of serology and intestinal biopsy samples and to compare this prevalence with a control group, to determine whether regional cerebral blood flow abnormalities are present in migraine patients with celiac disease compared to migraine patients without celiac disease, and to test, in these patients, the effects of a gluten-free diet on migraine symptoms and regional cerebral blood flow.
Inclusion Criteria:
Patients with idiopathic migraine, diagnosed according to criteria of International Headache Society.
Exclusion Criteria:
None specifically mentioned.
Description of Study Protocol:
Recruitment
Consecutive enrollment of patients at the Headache Center of La Sapienza University.
Design
Case-Control.
Blinding used (if applicable)
Single photon emission CT imaging was interpreted blindly by 3 different experienced specialists.
Intervention (if applicable)
Single photon emission CT imaging.
Statistical Analysis
Differences between groups assessed by Fisher test.
Data Collection Summary:
Timing of Measurements
Migraine patients found to have celiac disease underwent a brain single photon emission CT study before and after 6 months of gluten-free diet. 5 patients without celiac disease were also evaluated. Serological tests and jejunal biopsies repeated at end of follow-up for those with celiac disease.
Dependent Variables
- Serum IgG antitransglutaminase antibodies assessed by ELISA
- IgA antiendomysial antibodies were detected by indirect immunofluorescence
- Diagnosis confirmed by presence of villous atrophy on jejunal biopsy samples for antibody-positive subjects
- Single photon emission CT brain study performed
- Self-evaluation test to assess clinical characteristics of migraine and daily diary recording intensity, duration and frequency of headaches
Independent Variables
- Gluten-free diet for 6 months, not defined.
Control Variables
- Patients did not receive any migraine-preventing treatment and were told to use common, over-the-counter, NSAIDs for migraine attacks
Description of Actual Data Sample:
Initial N: 90 patients with idiopathic migraine (63 female, 27 male) and 236 blood donors as controls (89 men, 147 women)
Attrition (final N): See above
Age: Patients: mean age 37 +/- 8 years, Controls: mean age 35 +/- 9 years
Ethnicity: Not mentioned
Other relevant demographics: Not mentioned
Anthropometrics: Controls were not matched
Location: Rome, Italy
Summary of Results:
Other Findings
4 of 90 (4.4%, 95% CI = 1.2 - 11.0) migraine patients were found to have celiac disease compared with 1 of 236 (0.4%, 95% CI = 0.01 - 2.3) blood donor controls (p < 0.05).
Prior to gluten-free diet, all 4 patients with celiac disease showed evident abnormalities in regional cerebral blood flow and a circumscribed area of cortical hypoperfusion was present, while there were no abnormalities in the controls.
After 6 months of gluten-free diet, antibodies were negative and jejunal biopsy showed normal villi in all 4 subjects.
During the 6 months of gluten-free diet, 1 of 4 patients had no migraine attacks, and the remaining 3 patients experienced an improvement in frequency, duration and intensity of migraine. All patients showed significant improvement in brain perfusion.
Author Conclusion:
The present study showed an association of migraine with celiac disease, and found that a gluten-free diet may lead to amelioration of migraine symptoms. Also, this study showed that abnormalities of regional cortical blood flow improved after 6 months on a gluten-free diet. Our results suggest that a significant proportion of patients with migraine may have celiac disease, and that a gluten-free diet may lead to an improvement in the migraine in these patients.
Funding Source:
| Not-for-profit |
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Reviewer Comments:
Single photon emission CT only completed on 9 patients, 4 with celiac disease. Gluten-free diet not defined but monitored through antibodies and jejunal biopsy after 6 months. Controls not matched.
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Quality Criteria Checklist: Primary Research
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| Relevance Questions | |||
| 1. | Would implementing the studied intervention or procedure (if found successful) result in improved outcomes for the patients/clients/population group? (Not Applicable for some epidemiological studies) | Yes | |
| 2. | Did the authors study an outcome (dependent variable) or topic that the patients/clients/population group would care about? | Yes | |
| 3. | Is the focus of the intervention or procedure (independent variable) or topic of study a common issue of concern to dieteticspractice? | Yes | |
| 4. | Is the intervention or procedure feasible? (NA for some epidemiological studies) | Yes | |
| Validity Questions | |||
| 1. | Was the research question clearly stated? | Yes | |
| 1.1. | Was (were) the specific intervention(s) or procedure(s) [independent variable(s)] identified? | Yes | |
| 1.2. | Was (were) the outcome(s) [dependent variable(s)] clearly indicated? | Yes | |
| 1.3. | Were the target population and setting specified? | Yes | |
| 2. | Was the selection of study subjects/patients free from bias? | ??? | |
| 2.1. | Were inclusion/exclusion criteria specified (e.g., risk, point in disease progression, diagnostic or prognosis criteria), and with sufficient detail and without omitting criteria critical to the study? | ??? | |
| 2.2. | Were criteria applied equally to all study groups? | ??? | |
| 2.3. | Were health, demographics, and other characteristics of subjects described? | ??? | |
| 2.4. | Were the subjects/patients a representative sample of the relevant population? | ??? | |
| 3. | Were study groups comparable? | ??? | |
| 3.1. | Was the method of assigning subjects/patients to groups described and unbiased? (Method of randomization identified if RCT) | Yes | |
| 3.2. | Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline? | ??? | |
| 3.3. | Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.) | Yes | |
| 3.4. | If cohort study or cross-sectional study, were groups comparable on important confounding factors and/or were preexisting differences accounted for by using appropriate adjustments in statistical analysis? | N/A | |
| 3.5. | If case control study, were potential confounding factors comparable for cases and controls? (If case series or trial with subjects serving as own control, this criterion is not applicable.) | ??? | |
| 3.6. | If diagnostic test, was there an independent blind comparison with an appropriate reference standard (e.g., "gold standard")? | N/A | |
| 4. | Was method of handling withdrawals described? | Yes | |
| 4.1. | Were follow-up methods described and the same for all groups? | Yes | |
| 4.2. | Was the number, characteristics of withdrawals (i.e., dropouts, lost to follow up, attrition rate) and/or response rate (cross-sectional studies) described for each group? (Follow up goal for a strong study is 80%.) | Yes | |
| 4.3. | Were all enrolled subjects/patients (in the original sample) accounted for? | Yes | |
| 4.4. | Were reasons for withdrawals similar across groups? | Yes | |
| 4.5. | If diagnostic test, was decision to perform reference test not dependent on results of test under study? | N/A | |
| 5. | Was blinding used to prevent introduction of bias? | Yes | |
| 5.1. | In intervention study, were subjects, clinicians/practitioners, and investigators blinded to treatment group, as appropriate? | N/A | |
| 5.2. | Were data collectors blinded for outcomes assessment? (If outcome is measured using an objective test, such as a lab value, this criterion is assumed to be met.) | Yes | |
| 5.3. | In cohort study or cross-sectional study, were measurements of outcomes and risk factors blinded? | N/A | |
| 5.4. | In case control study, was case definition explicit and case ascertainment not influenced by exposure status? | Yes | |
| 5.5. | In diagnostic study, were test results blinded to patient history and other test results? | N/A | |
| 6. | Were intervention/therapeutic regimens/exposure factor or procedure and any comparison(s) described in detail? Were interveningfactors described? | Yes | |
| 6.1. | In RCT or other intervention trial, were protocols described for all regimens studied? | Yes | |
| 6.2. | In observational study, were interventions, study settings, and clinicians/provider described? | N/A | |
| 6.3. | Was the intensity and duration of the intervention or exposure factor sufficient to produce a meaningful effect? | Yes | |
| 6.4. | Was the amount of exposure and, if relevant, subject/patient compliance measured? | Yes | |
| 6.5. | Were co-interventions (e.g., ancillary treatments, other therapies) described? | Yes | |
| 6.6. | Were extra or unplanned treatments described? | Yes | |
| 6.7. | Was the information for 6.4, 6.5, and 6.6 assessed the same way for all groups? | Yes | |
| 6.8. | In diagnostic study, were details of test administration and replication sufficient? | N/A | |
| 7. | Were outcomes clearly defined and the measurements valid and reliable? | Yes | |
| 7.1. | Were primary and secondary endpoints described and relevant to the question? | Yes | |
| 7.2. | Were nutrition measures appropriate to question and outcomes of concern? | Yes | |
| 7.3. | Was the period of follow-up long enough for important outcome(s) to occur? | Yes | |
| 7.4. | Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? | Yes | |
| 7.5. | Was the measurement of effect at an appropriate level of precision? | Yes | |
| 7.6. | Were other factors accounted for (measured) that could affect outcomes? | Yes | |
| 7.7. | Were the measurements conducted consistently across groups? | Yes | |
| 8. | Was the statistical analysis appropriate for the study design and type of outcome indicators? | Yes | |
| 8.1. | Were statistical analyses adequately described and the results reported appropriately? | Yes | |
| 8.2. | Were correct statistical tests used and assumptions of test not violated? | Yes | |
| 8.3. | Were statistics reported with levels of significance and/or confidence intervals? | Yes | |
| 8.4. | Was "intent to treat" analysis of outcomes done (and as appropriate, was there an analysis of outcomes for those maximally exposed or a dose-response analysis)? | N/A | |
| 8.5. | Were adequate adjustments made for effects of confounding factors that might have affected the outcomes (e.g., multivariate analyses)? | N/A | |
| 8.6. | Was clinical significance as well as statistical significance reported? | Yes | |
| 8.7. | If negative findings, was a power calculation reported to address type 2 error? | N/A | |
| 9. | Are conclusions supported by results with biases and limitations taken into consideration? | Yes | |
| 9.1. | Is there a discussion of findings? | Yes | |
| 9.2. | Are biases and study limitations identified and discussed? | Yes | |
| 10. | Is bias due to study's funding or sponsorship unlikely? | Yes | |
| 10.1. | Were sources of funding and investigators' affiliations described? | Yes | |
| 10.2. | Was the study free from apparent conflict of interest? | Yes | |