Translation, cross-cultural adaptation and measurement proprieties of the German version of the Allodynia Symptom Checklist (ASC-12).

BACKGROUND: Cutaneous allodynia is highly prevalent among migraineurs and is associated with a poor prognosis. The Allodynia Symptom Checklist (ASC-12) is a comprehensive questionnaire to identify the presence and severity of allodynia. Our aim was to translate and adapt the ASC-12 to German and evaluate its measurement properties. METHODS: Following the COSMIN guidelines, 80 migraine patients were enrolled in the study to evaluate the stages of translation (n=30) and measurement propriety assessment (n=50), respectively. After reaching a final version, the German ASC-12 was assessed for structural validity, internal consistency, test-retest reliability, construct validity and absolute agreement, using mechanical and thermal pain thresholds as reference method. RESULTS: The German version of the ASC-12 presented an adequate structural validity compatible with the original version of the questionnaire. Its internal consistency ranged from 0.70 to 0.80 considering the total score and the thermic, static and dynamic mechanic subdomains. The total score presented excellent reliability (ICC: 0.85) with a standard error of measurement of 1.15 points and smallest detectable change of 3.40 points. ASC-12 total scores were correlated with headache intensity (r=0.38, p=0.004), headache disability (r=0.37, p=0.004) and cold pain thresholds (r=0.28, p=0.025). The thermic allodynia ASC-12 scores were correlated with cold (r=0.36, p=0.005) and heat (r=-0.30, p=0.010) pain thresholds, while the static mechanical allodynia ASC-12 scores correlated with mechanical pain threshold (r=0.29, p=0.019) and with mechanical pain sensitivity (r=0.24 to 0.28, p< 0.045). Despite no significant bias between methods, quantitative sensory testing (QST) results and ASC-12 scores tend to disagree. CONCLUSION: The German version of the ASC-12 is available for research and clinical settings and presented adequate measurement proprieties, as the original version. Despite the correlation between the ASC-12 and QST, one method cannot be replaced by the other.

Meta-analysis of associations of genetic polymorphisms with cerebral vasospasm and delayed cerebral ischemia after aneurysmal subarachnoid hemorrhage.

INTRODUCTION: Cerebral vasospasm (CV) and delayed cerebral ischemia (DCI) are among the most hazardous complications of aneurysmal subarachnoid hemorrhage (aSAH). Genetic factors are thought to play a significant role in the development of both complications. AIM: To perform a comprehensive meta-analysis of studies that study the association between different genetic polymorphisms and development of DCI and/or CV. METHODS: We searched MEDLINE and Science Direct databases on May 29, 2021, using iterations of the keywords "subarachnoid hemorrhage", "vasospasm", "delayed cerebral ischemia", and "gene". After duplicates were removed, the two reviewers screened the titles of the articles and abstracts independently. A random-effect model was used to calculate the relative risk with 95% CI; a fixed-effect model was additionally explored. RESULTS: We pooled data from 16 articles that reported an association between eNOS, apolipoprotein E4 (ApoE4), haptoglobin (Hp), or ryanodine-1 (RYR-1) and CV, DCI, or both. Presence of Hp 2-2 was associated both with CV (RR 2.10, 95% CI 1.33-3.31, p = 0.0014) and DCI (RR 1.57, 95%CI 1.06-2.34, p = 0.026). ApoE4 allele had a borderline association with CV (RR 1.48, 95%CI 0.99-2.21, p = 0.054). CONCLUSION: Our meta-analysis supports the association between the presence of the Hp2-2 allele and the occurrence of CV and DCI after aSAH. Further studies investigating this association are needed to reinforce this finding.

The impairment of the functional system and fatigue at the onset of the disease predict reaching disability milestones in relapsing-remitting multiple sclerosis differently in female and male patients.

Multiple sclerosis (MS) is a chronic demyelinating disease of the central nervous system with variable types of disability progression (DP). Previous studies, defining different disability milestones (DMs), have reported symptoms at MS onset to be the predictors of DP and sex as a risk factor. Meanwhile, accounting for sex differences in MS, predictors in female and male patients might differ. To investigate whether the symptoms at MS onset predict reaching DMs in patients with relapsing-remitting (RR) MS and whether the predictors vary between different DMs and female and male patients. Data from 128 RR MS patients (84 females, 44 males) was retrospectively studied. EDSS scores 4 and 6 (associated with impaired ambulation) were taken as DMs. Association between symptoms at MS onset and time to reach DMs was assessed with Cox multiple regression model. Pyramidal symptoms and fatigue at MS onset predicted the progression to EDSS 4 in the whole study population (HR 1.84, 95% CI 1.07-3.2, p = 0.028 and HR 2.01, 95% CI 1.12-3.4, p = 0.011, correspondingly). The same symptoms predicted reaching DM in female, but not male patients. Bowel/bladder symptoms predicted reaching EDSS 6 in the whole study population (HR 4.31, 95% CI 1.47-12.6, p = 0.008) and female patients only (HR 3.93, 95% CI 1.04-14.8, p = 0.043). In female patients, fatigue was also the predictor of reaching EDSS 6 (HR 3.54, 95% CI 1.16-10.8, p = 0.026). Impairment of functional symptoms at MS onset can predict reaching DMs in patients with RR-MS, but the predictors for EDSS 4 and EDSS 6 differ in female and male patients.

Is Initial Misdiagnosis Associated with Reaching Disability Milestones in Patients with Multiple Sclerosis?

Background and objectives: multiple sclerosis (MS) is a chronic demyelinating disorder of the CNS with a variable course and disability progression. The latter may be prevented with disease-modifying therapy (DMT). Initial misdiagnosis may postpone the use of DMT. There are no studies to explore whether initial misdiagnosis is indeed associated with a higher rate of reaching disability in MS patients. We aimed to investigate the association between initial misdiagnosis and reaching disability milestones in relapsing-remitting MS (RR-MS) patients. Materials and methods: Data from 128 RR-MS patients were retrospectively reviewed. EDSS 4 and EDSS 6 were chosen as disability milestones as those associated with a significant decrease in ambulation. Survival analysis was used, and Kaplan-Meier curves were generated to investigate how initial misdiagnosis affects reaching the defined milestones. Results: 53 patients (41.4%, 31 females, 22 males) were initially misdiagnosed. Initially misdiagnosed patients had a lesser risk of reaching EDSS 4 up to 11 years and EDSS 6 up to 22 years from the onset than non-misdiagnosed patients (p = 0.22 and p = 0.25 correspondingly). Median time to reaching EDSS 4 and 6 was eight years (95% CI 0.0-17.6) and 10 years (95% CI 4.25-20.75) in misdiagnosed and three years (95% CI 0.0-20.0 years) and five years (95% CI 0.0-13.73 years) in non-misdiagnosed patients correspondingly. Conclusions: Initially misdiagnosed RR-MS patients tended to reach disability milestones later than non-misdiagnosed ones, which might reflect an intrinsically milder disease. Individuals presenting with mild or non-specific symptoms suspicious of MS, must be deliberately managed.