EAL

CD: Neurological Outcomes (2006)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To present clinical and MRI data on a cohort of patients attending the gluten sensitivity and neurology clinic, in whom MRI showed otherwise unexplained white matter abnormalities.

Inclusion Criteria:

Patients with gluten sensitivity and abnormal MRI
Gluten sensitivity was defined by the presence of anti-gliadin antibodies as well as evidence of genetic susceptibility for this disease.

Exclusion Criteria:

None specifically mentioned.

Description of Study Protocol:

Recruitment: All patients were seen at the gluten sensitivity and neurology clinic at the Royal Hallamshire Hospital over the last four years
Design: Cohort study
Intervention: Patients with symptoms and signs of CNS dysfunction underwent MRI and other tests, as well as treatment with gluten-free diet
Statistical analysis: Descriptive statistics, frequencies.

Data Collection Summary:

Timing of Measurements

All patients underwent MRI, medical, neurological and neurophysiologic examination.

Dependent Variables

Anti-nuclear antibodies
Double-stranded DNA
Anti-nuclear cytoplasmic antibodies
Extractable nuclear antibodies
C-reactive protein
Immunoglobulins
Electrophoresis
Rheumatoid factor
Complement levels
Thrombophilia screen (anti-cardiolipin antibodies, lupus anti-coagulant)
Vitamins B₁₂, E, E and red cell folate
Full blood count
Erythrocyte sedimentation rate
Urea and electrolytes
Liver function tests
Thyroid function tests
Calcium and magnesium
Random glucose
Angiotensin-converting enzyme levels
Endoscopy and distal duodenal biopsy.

Independent Variables

Gluten-free diet for unspecified length of time
Not defined or monitored.

Description of Actual Data Sample:

Initial N: 105 patients attending the clinic. 40 patients with symptoms and signs of CNS dysfunction underwent MRI.
Attrition (final N): Selection of 10 patients, based on presence of white matter abnormalities; six females and four males
Age: Mean, 52 years
Ethnicity: Not mentioned
Location: United Kingdom.

Summary of Results:

Other Findings

All patients experienced episodic headache often associated with visual or sensory disturbances
Six had unsteadiness when walking and four had gait ataxia. Two also had distal sensory distrubance affecting feet and hands.
MRI abnormalities varied from extensive confluent areas of high signal throughout the white matter to foci of high signal scattered in both hemispheres
Introduction of gluten-free diet in nine patients resulted in complete resolution of the headaches in seven, with partial improvement in two. One patient would not try the diet.

Author Conclusion:

We describe 10 patients with gluten-sensitivity and CNS white matter abnormalities without evidence of an alternative cause
The complete resolution of headaches in seven of the nine patients on a gluten-free diet and partial improvement in the remaining two suggests a link between gluten-sensitivity and migraine-like headaches in these cases
Further studies of the effect of gluten-free diet are needed to confirm these preliminary observations.

Funding Source:

University/Hospital:

Royal Hallamshire Hospital, Leicester Royal Infirmary

Reviewer Comments:

Gluten free diet for unspecified length of time, not defined or monitored
Small sample size.

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)	N/A
	3.2.	Were distribution of disease status, prognostic factors, and other factors (e.g., demographics) similar across study groups at baseline?	N/A
	3.3.	Were concurrent controls or comparisons used? (Concurrent preferred over historical control or comparison groups.)	N/A
	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.)	N/A
	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?		N/A
	4.1.	Were follow-up methods described and the same for all groups?	N/A
	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%.)	N/A
	4.3.	Were all enrolled subjects/patients (in the original sample) accounted for?	N/A
	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?	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?	???
	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?	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?		???
	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?	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?	???
	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?		No
	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?	No
	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?	No
	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