CD: Neurological Outcomes (2006)

Citation:
 
Study Design:
Class:
- Click here for explanation of classification scheme.
Quality Rating:
Research Purpose:
To screen for neurologic disorders in children and young adults who have celiac disease and presented with either the classical infantile intestinal form or the milder late forms, including some asymptomatic patients.
Inclusion Criteria:
Diagnosis of celiac disease.
Exclusion Criteria:
None specifically mentioned.
Description of Study Protocol:

Recruitment

Recruited from the local pediatric gastroenterology clinic all of the patients who had proven celiac disease and were enrolled in gastroenterology outpatient clinic between 1977 - 2001. 

Design

Case-Control Study.

Blinding used (if applicable)

 Not applicable.

Intervention (if applicable)

Medical chart review and questionnaire regarding presence of neurologic disorders or symptoms of celiac disease patients compared to controls.

Statistical Analysis

 Not defined.  Frequency data.

Data Collection Summary:

Timing of Measurements

 Questionnaires and medical chart review completed.

Dependent Variables

  • Neurologic disorders or symptoms requiring medical attention or treatment assessed through patient/caregiver questionnaire and medical chart review
  • Those with neurological manifestations underwent neurologic exam, brain imaging, or electroencephalogram 

Independent Variables

  •  Gluten-free diet not defined nor monitored

Control Variables

 

Description of Actual Data Sample:

Initial N: 322 subjects, 111 celiac disease patients (42.3% male, 57.7% female) and 211 controls (40.3% male, 59.7% female)

Attrition (final N):  See above

Age:  Celiac patients:  mean age 20.1 +/- 8.9 years, Controls:  mean age 20.1 +/- 9.0 years    

Ethnicity:  Not mentioned 

Other relevant demographics:  Not mentioned 

Anthropometrics:  Age- and sex-matched controls, differences between groups not significant

Location:  Israel 

 

Summary of Results:

 

  Celiac Disease Controls P-value
Hypotonia 21.6% 3.8% < 0.01

Developmental Delay

 15.5%

 3.3%

 < 0.01

Epileptic Disorders 7.2% 0.8% < 0.09
Learning Disabilities and ADHD 20.7% 10.5% < 0.01
Headache 27.9% 8.1% < 0.01
Ataxia 5.4% 0% < 0.01

Tics

 0.9%

 2.4%

 0.67

 Other Findings

 Patients with celiac disease were more prone to develop neurologic disorders (51.4%) in comparison with controls (19.9%); these disorders include hypotonia, developmental delay, learning disorders and ADHD, headache, and cerebellar ataxia.

Hypotonia:  16 patients had hypotonia and with the exception of 3 patients, the hypotonia resolved completely after years of a gluten-free diet.

Epileptic disorders were only marginally more common in celiac disease.

Headache:  In 16 patients (9 with migraine, 6 with nonspecific headache), symptoms resolved or significantly improved with institution of gluten-free diet.

In contrast, no difference was found in the prevalence of tic disorders in both groups.

Improvement through treatment with gluten-free diet was demonstrated only in patients with transient infantile hypotonia and migraine headache.

Author Conclusion:
This study suggests that the variability of neurologic disorders that occur in celiac disease is broader than previously reported and includes "softer" and more common neurologic disorders, such as chronic headache, developmental delay, hypotonia, and learning disorders or ADHD.  Future longitudinal prospective studies might better define the full range of these neurologic disorders and their clinical response to a gluten-free diet.
Funding Source:
University/Hospital: Technion - Israel Institute of Technology (Israel)
Reviewer Comments:
Inclusion/exclusion criteria not well defined.  Questionnaire not shown to be valid/reliable.  Statistics not described.  Gluten-free diet not defined nor monitored.
Quality Criteria Checklist: Primary Research
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? Yes
  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? Yes
  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? Yes
  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.) Yes
  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? N/A
  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? N/A
  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.) N/A
  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? N/A
  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? ???
  6.1. In RCT or other intervention trial, were protocols described for all regimens studied? N/A
  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? ???
  6.4. Was the amount of exposure and, if relevant, subject/patient compliance measured? ???
  6.5. Were co-interventions (e.g., ancillary treatments, other therapies) described? N/A
  6.6. Were extra or unplanned treatments described? N/A
  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? ???
  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? ???
  7.4. Were the observations and measurements based on standard, valid, and reliable data collection instruments/tests/procedures? ???
  7.5. Was the measurement of effect at an appropriate level of precision? ???
  7.6. Were other factors accounted for (measured) that could affect outcomes? ???
  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? ???
  8.1. Were statistical analyses adequately described and the results reported appropriately? No
  8.2. Were correct statistical tests used and assumptions of test not violated? ???
  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)? ???
  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