EAL

CD: Neurological Outcomes (2006)

Citation:

Study Design:

Class:

- Click here for explanation of classification scheme.

Quality Rating:

Research Purpose:

To investigate the prevalence of gluten sensitivity in patients with both sporadic and familial cerebellar ataxia.

Inclusion Criteria:

Patients presenting with cerebellar ataxia.

Exclusion Criteria:

None specifically mentioned.

Description of Study Protocol:

Recruitment

Methods not described.

Design

Cohort Study.

Blinding used (if applicable)

Not used - lab tests.

Intervention (if applicable)

Antibody screening and other lab tests.

Statistical Analysis

Descriptive statistics and frequency data.

Data Collection Summary:

Timing of Measurements

Patients underwent testing.

Dependent Variables

Serum immunoglobulin A (IgA) and IgG anti-gliadin antibodies using ELISA
Anti-reticulin (ARA) and anti-endomysial antibodies (EmA) using indirect immunofluorescence
Anti-tissue transglutaminase (anti-tTG) antibodies using ELISA
Typical lymphocyte antigen (HLA) genotypes
CBC
Erythrocyte sedimentation rate
Serum immunoglobulin assay
Vitamin E, B12, folic acid
Methylmalonic acid
Plasma homocysteine
Routine renal, liver and thyroid function tests
Rheumatoid factor
Sjogren syndrome
Antinuclear, thyroid and paraneoplastic antibodies
MRI
Electromyography and nerve conduction studies

Independent Variables

Control Variables

Description of Actual Data Sample:

Initial N: 50 patients, 26 with sporadic cerebellar ataxia (12 male, 14 female) and 24 with hereditary cerebellar ataxia (7 male, 17 female)

Attrition (final N): See above

Age: range 13 - 79 years

Ethnicity: Not mentioned

Other relevant demographics:

Anthropometrics:

Location: Maryland

Summary of Results:

Other Findings

A high prevalence of gluten sensitivity (high IgG, IgA, or both ADA > 25 U/mL) was found in patients with sporadic (7/26, 27%) and autosomal dominant (9/24, 37%) ataxias, including patients with known ataxia genotypes indicating an unrecognized association between hereditary ataxias and gluten sensitivity.

There was no apparent difference in gastrointestinal symptoms, age of ataxia onset, incidence of peripheral neuropathy, myoclonus, or other neurological findings between AGA-positive and AGA-negative or between hereditary and sporadic ataxia groups.

Cerebellar atrophy (with or without brain stem or global brain atrophy) was evident on brain MRI.

Author Conclusion:

In agreement with previous studies, our results indicate a high prevalence of gluten sensitivity (as indicated by positive AGA) in patients with cerebellar ataxia (16/50, 32%). The new and unexpected finding is that the prevalence of gluten sensitivity was similarly high in both sporadic and hereditary ataxias including those with identified gene defects. Further studies are needed to determine whether gluten sensitivity contributes to cerebellar degeneration in patients with hereditary cerebellar ataxia. Patients with hereditary ataxia (including asymptomatic patients with known ataxia genotype) should be considered for screening for gluten sensitivity and gluten-free diet trials.

Funding Source:

Government:

National Institute of Neurological Disorders & Stroke, NIDDK, NIH

Reviewer Comments:

Recruitment methods and cohort not well described. Statistics not sophisticated.

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)	N/A
	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?	N/A
	4.	Is the intervention or procedure feasible? (NA for some epidemiological studies)	N/A

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)	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?	???
	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?		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?		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?	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?		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?		???
	8.1.	Were statistical analyses adequately described and the results reported appropriately?	???
	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