EAL

CD: Neurological Outcomes (2006)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To assess whether patients with treated celiac disease carry an increased risk for neuropathy and characterize the type of possible neuropathy.

Inclusion Criteria:

Diagnosis of celiac disease established according to current ESPGHAN criteria. All celiac disease patients maintaining gluten-free diet since diagnosis for 3 years. Patients were in clinical and histological remission - no longer had small bowel mucosal atrophy.

Exclusion Criteria:

Excluded if not included above.

Description of Study Protocol:

Recruitment

Not mentioned.

Design

Nonrandomized Clinical Trial.

Blinding used (if applicable)

Not applicable.

Intervention (if applicable)

Gluten-free diet.

Statistical Analysis

Data were expressed as means with standard deviations or frequencies as indicated. Confidence intervals (95%) and contingency table with chi-square test and Mann-Whitney U test were used for statistical comparisons when appropriate.

Data Collection Summary:

Timing of Measurements

Electroneuromyographic findings and vibration, thermal and tactile thresholds of patients with celiac disease and reflux disease were analysed. Control biopsies were no older than 3 years before neurophysiological studies.

Dependent Variables

Neurophysiological exam included the measures of the function of both motor fibres and sensory large fibres and small myelinated and unmyelinated fibres
Electroneuromyography carried out using ENMG device on left or right extremities
Concentric needle electromyography (EMG) performed on one distal and one proximal muscle
Nerve conduction studies carried out in motor nerves and sensory nerves using surface electrodes and standard techniques
Vibration thresholds were measured from carpal and tarsal areas using the method of limits and Bio-Thesiometer

Independent Variables

Gluten-free diet. Strictness of diet assessed by interview.

Control Variables

Description of Actual Data Sample:

Initial N: 26 patients with celiac disease (7 male, 19 female), 23 patients with reflux disease (16 male, 7 female)

Attrition (final N): Same as above.

Age: Mean age of celiac patients: 51 years (range 22 - 77 years), mean age of reflux disease patients: 50 years (range 18 - 73 years).

Ethnicity: Not mentioned.

Other relevant demographics: Gluten-free diet for median of 3 years (range 2 - 28 years).

Anthropometrics: No significant differences between the groups in terms of predisposing factors to neuropathy.

Location: Finland

Summary of Results:

	Celiac Patients (n=26)	Reflux disease patients (n=23)	P-value
Warm threshold - left thenar (degrees C)	1.7 +/- 0.8	1.7 +/- 1.0	0.8895
Warm threshold - left foot (degrees C)	5.1 +/- 3.4	6.0 +/- 3.4	0.3760
Cold threshold - left thenar (degrees C)	1.0 +/- 0.3	0.9 +/- 0.3	0.3269
Cold threshold - left foot (degrees C)	1.3 +/- 0.8	1.8 +/- 1.8	0.2573
Heat pain threshold - left thenar (degrees C)	46.9 +/- 4.5	44.5 +/- 3.5	0.0454
Heat pain threshold - left foot (degrees C)	46.1 +/- 2.9	42.9 +/- 3.2	0.0005
Vibration threshold - left wrist (deviation from mean)	0.3 +/- 0.2	0.4 +/- 0.2	0.4451
Vibration threshold - left ankle (deviation from mean)	2.9 +/- 8.8	1.7 +/- 1.5	0.5889
Tactile threshold - Dermatome L3 (force)	3.9 +/-0.7	2.1 +/- 0.7	<0.001
Tactile threshold - Dermatome S1 (force)	4.1 +/- 0.7	2.9 +/- 0.8	<0.001

Other Findings

6 (23.1%) celiac disease patients and 1 (4.3%) reflux disease patient showed findings of chronic axonal neuropathy in quantitative needle EMG.

In addition, 2 celiac disease patients showed findings suggestive for myopathy.

There were no significant differences in warm, cold, or vibration thresholds between the groups but means of heat pain thresholds and tactile thresholds were significantly higher in celiac patients than in controls.

Author Conclusion:

We showed that even well treated patients with celiac disease carry an increased risk of nuropathy, to be seen in 23% of patients. Even more, 31% showed abnormalities in neurophysiological studies compared with 4.3% in controls. In conclusion, celiac patients have an increased frequency of chronic axonal neuropathy, even when adhering to a long term strict gluten free diet. This further indicates that neurological manifestations occur even in patients without overt malabsorption. Early detection of celiac disease might prevent the development of manifest neuropathy. The relation between gluten containing diet and the occurrence of neuropathy is a subject for further studies. Until that, it is reasonable to assume that a strict diet is warranted to prevent manifest neuropathy and follow up of dietary compliance would be indicated.

Funding Source:

University/Hospital:

Tampere University Hospital

Reviewer Comments:

Dietary adherence assessed through interview.

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?		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?		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?	Yes
	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?	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?		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?		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)?	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?	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