CD: Neurological Outcomes (2006)
Recruitment
Patients with celiac disease were consecutively referred to us by the Gastroenterology Unit of the hospital over a 1 year period. Controls recruited among the members of the patient's household.
Design
Nonrandomized Clinical Trial.
Blinding used (if applicable)
Neurologist blinded to subject condition.
Intervention (if applicable)
Gluten free diet.
Statistical Analysis
The frequency of neurological abnormalities was recorded and analyzed versus controls in all patients affected by celiac disease and according to diet observance, distinguishing patients who adhered to a strict gluten-free diet or to a gluten-free diet with indiscretions, or who were on an unrestricted diet. The chi-square test with Yates' correction was used to compare frequencies between groups, the t test to compare means between groups, and linear regression to correlate the findings both with duration of disease and with treatment. Two-tailed p-values were used throughout.
Timing of Measurements
Patients and controls underwent semistructured interview and neurologic exam. Medical records were reviewed and routine laboratory tests completed.
Dependent Variables
- Laboratory tests included hemoglobin, mean corpuscular volume, serum cholesterol, total serum protein, serum albumin, plasma electrolytes and vitamin levels.
- Neurological exam
- Semistructured interview specifically focused on seizures, headache, ataxia, mood disorders and signs of peripheral neuropathy (weakness, hyporeflexia, cramps, paresthesia, reduced vibratory sense). A score for the neurological abnormalities obtained by adding number of single symptoms and signs for each patient.
- Computed tomography (CT) of the head was performed in subgroup consisting of 25 consecutive patients. 4 patients suffering from seizures also underwent CT and EEG exams.
Independent Variables
- Gluten-free diet not described or monitored, although subjects were divided into groups of strict adherence, some indiscretions, or unrestricted diet.
Control Variables
Initial N: 184 patients recruited and 52 controls. 8 patients excluded since they had no clinical improvement on gluten-free diet during 6 months.
Attrition (final N): 176 patients (45 men, 131 women), 52 age-matched controls.
Age: Mean age of patients at study entry: 30.9 +/- 13.5 years (range 16 - 76), and controls: 31.7 +/- 10.3 years (range 19 - 67)
Ethnicity: Not mentioned.
Other relevant demographics: 127 had classic form, 49 had subclinical form of celiac disease.
Anthropometrics: Age-matched controls.
Location: Italy
|
|
Controls (n=52) |
Total CD (n=176) |
Classic CD (n=127) |
Subclinical CD (n=49) |
|
Headache |
15 (29%) |
80 (46%), P < 0.05 |
60 (47%), P < 0.05 |
20 (41%) |
|
Migraine |
13 (25%) |
56 (32%) |
45 (35%) |
11 (22%) |
|
Tension |
1 (2%) |
10 (6%) |
6 (5%) |
4 (8%) |
|
Mixed |
1 (2%) |
14 (8%) |
9 (7%) |
5 (10%) |
|
Mood Disorders |
9 (17%) |
50 (29%) |
36 (28%) |
14 (28%) |
|
Depression Episodes |
7 (13%) |
24 (14%) |
17 (13%) |
7 (14%) |
|
Dysthymia |
2 (4%) |
26 (15%), P < 0.05 |
19 (15%) |
7 (14%) |
|
Epilepsy |
0 (0%) |
4 (2.3%) |
2 (1.6%) |
2 (4.1%) |
|
Ataxia |
0 (0%) |
0 (0%) |
0 (0%) |
0 (0%) |
|
Cramps |
6 (11%) |
87 (49%), P < 0.001 |
63 (50%), P < 0.001 |
24 (49%), P < 0.001 |
|
Paresthesia |
9 (17%) |
78 (44%), P < 0.001 |
55 (43%), P < 0.001 |
23 (47%), P < 0.01 |
|
Weakness |
0 (0%) |
55 (31%), P < 0.001 |
38 (30%), P < 0.001 |
17 (35%), P < 0.001 |
|
Reduced Vibratory Sense |
2 (4%) |
32 (18%), P < 0.05 |
26 (20%), P < 0.05 |
6 (12%) |
|
Hyporeflexia |
8 (15%) |
92 (52%), P < 0.001 |
68 (53%), P < 0.001 |
24 (49%), P < 0.001 |
Other Findings
Of the 176 patients, 92 (52%) had been on a strict gluten-free diet for a mean of 6.5 years and reported no symptoms of malabsorption at the study entry. Remaining patients still had symptoms of malabsorption at study entry. 51 subjects (29%) were eating an unrestricted diet and 33 (19%) were following a gluten-free diet with frequent dietary indiscretions.
The occurrence of headache (P < 0.05), dysthymia (P < 0.05) and signs of peripheral neuropathy was significantly higher in patients with celiac disease than in control subjects.
There was no significant differences in the frequency of peripheral signs between the subgroups of patients with classic and subclinical forms of the disease.
Adherence to a gluten-free diet was associated with a significant reduction of headache, dysthymia (p < 0.05), cramps (p < 0.001) and weakness (p < 0.05), but did not modify the occurrence of paresthesia or hyporeflexia.
There was a significant correlation (p < 0.05, F = 6.8) between the duration of celiac disease preceding treatment and the number of neurological signs and symptoms. Conversely, neurological abnormalities were inversely correlated with the duration of the dietary gluten restriction (P < 0.005, F = 10).
| University/Hospital: | Federico II University of Naples (Italy) |
|
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? | Yes | |
| 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? | Yes | |
| 2.2. | Were criteria applied equally to all study groups? | Yes | |
| 2.3. | Were health, demographics, and other characteristics of subjects described? | Yes | |
| 2.4. | Were the subjects/patients a representative sample of the relevant population? | Yes | |
| 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? | ??? | |
| 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? | Yes | |
| 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? | Yes | |
| 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? | 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? | No | |
| 6.5. | Were co-interventions (e.g., ancillary treatments, other therapies) described? | ??? | |
| 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? | ??? | |
| 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? | ??? | |
| 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? | 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)? | Yes | |
| 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? | No | |
| 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 | |