Motor function in multiple sclerosis assessed by navigated transcranial magnetic stimulation mapping.

INTRODUCTION: Impaired motor function is a major cause of disability in multiple sclerosis (MS), involving various neuroplasticity processes typically assessed by neuroimaging. This study aimed to determine whether navigated transcranial magnetic stimulation (nTMS) could also provide biomarkers of motor cortex plasticity in patients with MS (pwMS). METHODS: nTMS motor mapping was performed for hand and leg muscles bilaterally. nTMS variables included the amplitude and latency of motor evoked potentials (MEPs), corticospinal excitability measures, and the size of cortical motor maps (CMMs). Clinical assessment included disability (Expanded Disability Status Scale, EDSS), strength (MRC scale, pinch and grip), and dexterity (9-hole Pegboard Test). RESULTS: nTMS motor mapping was performed in 68 pwMS. PwMS with high disability (EDSS ≥ 3) had enlarged CMMs with less dense distribution of MEPs and various MEP parameter changes compared to pwMS with low disability (EDSS < 3). Patients with progressive MS had also various MEP parameter changes compared to pwMS with relapsing remitting form. MRC score correlated positively with MEP amplitude and negatively with MEP latency, pinch strength correlated negatively with CMM volume and dexterity with MEP latency. CONCLUSIONS: This is the first study to perform 4-limb cortical motor mapping in pwMS using a dedicated nTMS procedure. By quantifying the cortical surface representation of a given muscle and the variability of MEP within this representation, nTMS can provide new biomarkers of motor function impairment in pwMS. Our study opens perspectives for the use of nTMS as an objective method for assessing pwMS disability in clinical practice.

High-Efficacy Therapy Discontinuation vs Continuation in Patients 50 Years and Older With Nonactive MS.

Importance: A recent randomized clinical trial concluded that discontinuing medium-efficacy therapy might be a reasonable option for older patients with nonactive multiple sclerosis (MS), but there is a lack of data on discontinuing high-efficacy therapy (HET). In younger patients, the discontinuation of natalizumab and fingolimod is associated with a risk of rebound of disease activity. Objective: To determine whether discontinuing HET in patients 50 years and older with nonactive MS is associated with an increased risk of relapse compared with continuing HET. Design, Setting, and Participants: This observational cohort study used data from 38 referral centers from the French MS registry (Observatoire Français de la Sclérose en Plaques [OFSEP] database). Among 84704 patients in the database, data were extracted for 1857 patients 50 years and older with relapsing-remitting MS treated by HET and with no relapse or magnetic resonance imaging activity for at least 2 years. After verification of the medical records, 1620 patients were classified as having discontinued HET or having remained taking treatment and were matched 1:1 using a dynamic propensity score (including age, sex, disease phenotype, disability, treatment of interest, and time since last inflammatory activity). Patients were included from February 2008 to November 2021, with a mean (SD) follow-up of 5.1 (2.9) years. Data were extracted in June 2022. Exposures: Natalizumab, fingolimod, rituximab, and ocrelizumab. Main Outcomes and Measures: Time to first relapse. Results: Of 1620 included patients, 1175 (72.5%) were female, and the mean (SD) age was 54.7 (4.8) years. Among the 1452 in the HET continuation group and 168 in the HET discontinuation group, 154 patients in each group were matched using propensity scores (mean [SD] age, 57.7 [5.5] years; mean [SD] delay since the last inflammatory activity, 5.6 [3.8] years; mean [SD] follow-up duration after propensity score matching, 2.5 [2.1] years). Time to first relapse was significantly reduced in the HET discontinuation group compared with the HET continuation group (hazard ratio, 4.1; 95% CI, 2.0-8.5; P < .001) but differed between HETs, with a hazard ratio of 7.2 (95% CI, 2.1-24.5; P = .001) for natalizumab, 4.5 (95% CI, 1.3-15.5; P = .02) for fingolimod, and 1.1 (95% CI, 0.3-4.8; P = .85) for anti-CD20 therapy. Conclusion and Relevance: As in younger patients, in patients 50 years and older with nonactive MS, the risk of relapse increased significantly after stopping HETs that impact immune cell trafficking (natalizumab and fingolimod). There was no significant increase in risk after stopping HETs that deplete B-cells (anti-CD20 therapy). This result may inform decisions about stopping HETs in clinical practice.

Highly Effective Therapies as First-Line Treatment for Pediatric-Onset Multiple Sclerosis.

Importance: Moderately effective therapies (METs) have been the main treatment in pediatric-onset multiple sclerosis (POMS) for years. Despite the expanding use of highly effective therapies (HETs), treatment strategies for POMS still lack consensus. Objective: To assess the real-world association of HET as an index treatment compared with MET with disease activity. Design, Setting, and Participants: This was a retrospective cohort study conducted from January 1, 2010, to December 8, 2022, until the last recorded visit. The median follow-up was 5.8 years. A total of 36 French MS centers participated in the Observatoire Français de la Sclérose en Plaques (OFSEP) cohort. Of the total participants in OFSEP, only treatment-naive children with relapsing-remitting POMS who received a first HET or MET before adulthood and at least 1 follow-up clinical visit were included in the study. All eligible participants were included in the study, and none declined to participate. Exposure: HET or MET at treatment initiation. Main Outcomes and Measures: The primary outcome was the time to first relapse after treatment. Secondary outcomes were annualized relapse rate (ARR), magnetic resonance imaging (MRI) activity, time to Expanded Disability Status Scale (EDSS) progression, tertiary education attainment, and treatment safety/tolerability. An adapted statistical method was used to model the logarithm of event rate by penalized splines of time, allowing adjustment for effects of covariates that is sensitive to nonlinearity and interactions. Results: Of the 3841 children (5.2% of 74 367 total participants in OFSEP), 530 patients (mean [SD] age, 16.0 [1.8] years; 364 female [68.7%]) were included in the study. In study patients, both treatment strategies were associated with a reduced risk of first relapse within the first 2 years. HET dampened disease activity with a 54% reduction in first relapse risk (adjusted hazard ratio [HR], 0.46; 95% CI, 0.31-0.67; P < .001) sustained over 5 years, confirmed on MRI activity (adjusted odds ratio [OR], 0.34; 95% CI, 0.18-0.66; P = .001), and with a better tolerability pattern than MET. The risk of discontinuation at 2 years was 6 times higher with MET (HR, 5.97; 95% CI, 2.92-12.20). The primary reasons for treatment discontinuation were lack of efficacy and intolerance. Index treatment was not associated with EDSS progression or tertiary education attainment (adjusted OR, 0.51; 95% CI, 0.24-1.10; P = .09). Conclusions and Relevance: Results of this cohort study suggest that compared with MET, initial HET in POMS was associated with a reduction in the risk of first relapse with an optimal outcome within the first 2 years and was associated with a lower rate of treatment switching and a better midterm tolerance in children. These findings suggest prioritizing initial HET in POMS, although long-term safety studies are needed.

Multiple sclerosis imaging in clinical practice: a European-wide survey of 428 centers and conclusions by the ESNR Working Group.

OBJECTIVES: To evaluate compliance with the available recommendations, we assessed the current clinical practice of imaging in the evaluation of multiple sclerosis (MS). METHODS: An online questionnaire was emailed to all members and affiliates. Information was gathered on applied MR imaging protocols, gadolinium-based contrast agents (GBCA) use and image analysis. We compared the survey results with the Magnetic Resonance Imaging in MS (MAGNIMS) recommendations considered as the reference standard. RESULTS: A total of 428 entries were received from 44 countries. Of these, 82% of responders were neuroradiologists. 55% performed more than ten scans per week for MS imaging. The systematic use of 3 T is rare (18%). Over 90% follow specific protocol recommendations with 3D FLAIR, T2-weighted and DWI being the most frequently used sequences. Over 50% use SWI at initial diagnosis and 3D gradient-echo T1-weighted imaging is the most used MRI sequence for pre- and post-contrast imaging. Mismatches with recommendations were identified including the use of only one sagittal T2-weighted sequence for spinal cord imaging, the systematic use of GBCA at follow-up (over 30% of institutions), a delay time shorter than 5 min after GBCA administration (25%) and an inadequate follow-up duration in pediatric acute disseminated encephalomyelitis (80%). There is scarce use of automated software to compare images or to assess atrophy (13% and 7%). The proportions do not differ significantly between academic and non-academic institutions. CONCLUSIONS: While current practice in MS imaging is rather homogeneous across Europe, our survey suggests that recommendations are only partially followed. CLINICAL RELEVANCE STATEMENT: Hurdles were identified, mainly in the areas of GBCA use, spinal cord imaging, underuse of specific MRI sequences and monitoring strategies. This work will help radiologists to identify the mismatches between their own practices and the recommendations and act upon them. KEY POINTS: • While current practice in MS imaging is rather homogeneous across Europe, our survey suggests that available recommendations are only partially followed. • Several hurdles have been identified through the survey that mainly lies in the areas of GBCA use, spinal cord imaging, underuse of specific MRI sequences and monitoring strategies.

Improving the decision to switch from first- to second-line therapy in multiple sclerosis: A dynamic scoring system.

BACKGROUND: In relapsing-remitting multiple sclerosis (RRMS), early identification of suboptimal responders can prevent disability progression. OBJECTIVE: We aimed to develop and validate a dynamic score to guide the early decision to switch from first- to second-line therapy. METHODS: Using time-dependent propensity scores (PS) from a French cohort of 12,823 patients with RRMS, we constructed one training and two validation PS-matched cohorts to compare the switched patients to second-line treatment and the maintained patients. We used a frailty Cox model for predicting individual hazard ratios (iHRs). RESULTS: From the validation PS-matched cohort of 348 independent patients with iHR ⩽ 0.69, we reported the 5-year relapse-free survival at 0.14 (95% confidence interval (CI) 0.09-0.22) for the waiting group and 0.40 (95% CI 0.32-0.51) for the switched group. From the validation PS-matched cohort of 518 independent patients with iHR > 0.69, these values were 0.37 (95% CI 0.30-0.46) and 0.44 (95% CI 0.37-0.52), respectively. CONCLUSIONS: By using the proposed dynamic score, we estimated that at least one-third of patients could benefit from an earlier switch to prevent relapse.

Investigating the Long-term Effect of Pregnancy on the Course of Multiple Sclerosis Using Causal Inference.

BACKGROUND AND OBJECTIVES: The question of the long-term safety of pregnancy is a major concern in patients with multiple sclerosis (MS), but its study is biased by reverse causation (women with higher disability are less likely to experience pregnancy). Using a causal inference approach, we aimed to estimate the unbiased long-term effects of pregnancy on disability and relapse risk in patients with MS and secondarily the short-term effects (during the perpartum and postpartum years) and delayed effects (occurring beyond 1 year after delivery). METHODS: We conducted an observational cohort study with data from patients with MS followed in the Observatoire Français de la Sclérose en Plaques registry between 1990 and 2020. We included female patients with MS aged 18-45 years at MS onset, clinically followed up for more than 2 years, and with ≥3 Expanded Disease Status Scale (EDSS) measurements. Outcomes were the mean EDSS score at the end of follow-up and the annual probability of relapse during follow-up. Counterfactual outcomes were predicted using the longitudinal targeted maximum likelihood estimator in the entire study population. The patients exposed to at least 1 pregnancy during their follow-up were compared with the counterfactual situation in which, contrary to what was observed, they would not have been exposed to any pregnancy. Short-term and delayed effects were analyzed from the first pregnancy of early-exposed patients (who experienced it during their first 3 years of follow-up). RESULTS: We included 9,100 patients, with a median follow-up duration of 7.8 years, of whom 2,125 (23.4%) patients were exposed to at least 1 pregnancy. Pregnancy had no significant long-term causal effect on the mean EDSS score at 9 years (causal mean difference [95% CI] = 0.00 [-0.16 to 0.15]) or on the annual probability of relapse (causal risk ratio [95% CI] = 0.95 [0.93-1.38]). For the 1,253 early-exposed patients, pregnancy significantly decreased the probability of relapse during the perpartum year and significantly increased it during the postpartum year, but no significant delayed effect was found on the EDSS and relapse rate. DISCUSSION: Using a causal inference approach, we found no evidence of significantly deleterious or beneficial long-term effects of pregnancy on disability. The beneficial effects found in other studies were probably related to a reverse causation bias.

Outcomes of coronavirus disease 2019 in patients with neuromyelitis optica and associated disorders.

BACKGROUND: Outcomes of coronavirus disease 2019 (COVID-19) in patients with neuromyelitis optica spectrum disorders (NMOSD) or myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD), often treated with immunosuppressive therapies, are still unknown. METHODS: We conducted a multicenter, retrospective, observational cohort study among all French expert centers for neuromyelitis optica and related disorders. Patients with NMOSD or MOGAD included in the study received a confirmed or highly suspected diagnosis of COVID-19 between 1 March 2020 and 30 June 2020. Main outcome was COVID-19 severity score assessed on a seven-point ordinal scale ranging from 1 (not hospitalized with no limitations on activities) to 7 (death). RESULTS: Fifteen cases (mean [SD] age: 39.3 [14.3] years, 11 female) were included. Five patients (33.3%) were hospitalized, all receiving rituximab. A 24-year-old patient with positive aquaporine-4 antibody, with obesity as comorbidity, needed mechanical ventilation. Outpatients were receiving anti-CD20 (5), mycophenolate mofetil (3) or azathioprine (3). They were younger (mean [SD] age: 37.0 [13.4] years), with a longer disease duration (mean [SD]: 8.3 [6.3] years) and had a lower expanded disability severity score (EDSS) score (median [range] EDSS: 2.5 [0-4]) relative to patients requiring hospitalization (mean [SD] age: 44.0 [16.4] years, mean [SD] disease duration: 5.8 [5.5] years, median [range] EDSS: 4 [0-6.5]). CONCLUSIONS: COVID-19 outcome was overall favorable in this cohort. Larger international studies are needed to identify risk factors of severe COVID-19; however, we recommend personal protective measures to reduce risk of SARS-CoV-2 infection in this immunocompromised population.

High effector-memory CD8+ T-cell levels correlate with high PML risk in natalizumab-treated patients.

BACKGROUND: Progressive multifocal leukoencephalopathy (PML) is a severe complication of natalizumab (NTZ) treatment in multiple sclerosis (MS) patients. Based on the analysis of cryopreserved cells, several reports have showed that CD62L+ CD4+ T-cells percentage drops before PML onset. OBJECTIVE: To analyze CD62L and CD45RA expression on fresh-blood CD4+ and CD8+ T-cells from NTZ-treated patients, according to their estimated PML risk. METHODS: We prospectively enrolled 74 MS patients, including 62 NTZ-treated, and stratified them into low, intermediate and high PML risk groups. Circulating naïve and memory T-cell subsets were analyzed by flow cytometry. RESULTS: We found no correlation between the percentage of CD62L+ CD4+ T-cells and PML risk. In contrast, the repartition of CD8+ T-cells subpopulations was altered in the high risk group: both the percentage and absolute count of CD8+ CD62L- CD45RA- effector memory T- cells (TEM) was significantly higher compared to patients at lower risk despite similar CD3+ and CD8+ T-cell counts. One high-risk patient with elevated CD8+ TEM and CD62L+ CD4+ T-cell levels developed PML six months after sampling. CONCLUSION: Our results suggest that CD8+ TEM cells should be evaluated in larger studies as a potential surrogate marker of PML risk in NTZ-treated patients.

Clinical Characteristics and Outcomes in Patients With Coronavirus Disease 2019 and Multiple Sclerosis.

Importance: Risk factors associated with the severity of coronavirus disease 2019 (COVID-19) in patients with multiple sclerosis (MS) are unknown. Disease-modifying therapies (DMTs) may modify the risk of developing a severe COVID-19 infection, beside identified risk factors such as age and comorbidities. Objective: To describe the clinical characteristics and outcomes in patients with MS and COVID-19 and identify factors associated with COVID-19 severity. Design, Setting, and Participants: The Covisep registry is a multicenter, retrospective, observational cohort study conducted in MS expert centers and general hospitals and with neurologists collaborating with MS expert centers and members of the Société Francophone de la Sclérose en Plaques. The study included patients with MS presenting with a confirmed or highly suspected diagnosis of COVID-19 between March 1, 2020, and May 21, 2020. Exposures: COVID-19 diagnosed with a polymerase chain reaction test on a nasopharyngeal swab, thoracic computed tomography, or typical symptoms. Main Outcomes and Measures: The main outcome was COVID-19 severity assessed on a 7-point ordinal scale (ranging from 1 [not hospitalized with no limitations on activities] to 7 [death]) with a cutoff at 3 (hospitalized and not requiring supplemental oxygen). We collected demographics, neurological history, Expanded Disability Severity Scale score (EDSS; ranging from 0 to 10, with cutoffs at 3 and 6), comorbidities, COVID-19 characteristics, and outcomes. Univariate and multivariate logistic regression models were used to estimate the association of collected variables with COVID-19 outcomes. Results: A total of 347 patients (mean [SD] age, 44.6 [12.8] years, 249 women; mean [SD] disease duration, 13.5 [10.0] years) were analyzed. Seventy-three patients (21.0%) had a COVID-19 severity score of 3 or more, and 12 patients (3.5%) died of COVID-19. The median EDSS was 2.0 (range, 0-9.5), and 284 patients (81.8%) were receiving DMT. There was a higher proportion of patients with a COVID-19 severity score of 3 or more among patients with no DMT relative to patients receiving DMTs (46.0% vs 15.5%; P < .001). Multivariate logistic regression models determined that age (odds ratio per 10 years: 1.9 [95% CI, 1.4-2.5]), EDSS (OR for EDSS ≥6, 6.3 [95% CI. 2.8-14.4]), and obesity (OR, 3.0 [95% CI, 1.0-8.7]) were independent risk factors for a COVID-19 severity score of 3 or more (indicating hospitalization or higher severity). The EDSS was associated with the highest variability of COVID-19 severe outcome (R2, 0.2), followed by age (R2, 0.06) and obesity (R2, 0.01). Conclusions and Relevance: In this registry-based cohort study of patients with MS, age, EDSS, and obesity were independent risk factors for severe COVID-19; there was no association found between DMTs exposure and COVID-19 severity. The identification of these risk factors should provide the rationale for an individual strategy regarding clinical management of patients with MS during the COVID-19 pandemic.

Progressive Multifocal Leukoencephalopathy Incidence and Risk Stratification Among Natalizumab Users in France.

Importance: Risk of developing progressive multifocal leukoencephalopathy (PML) is the major barrier to using natalizumab for patients with multiple sclerosis (MS). To date, the association of risk stratification with PML incidence has not been evaluated. Objective: To describe the temporal evolution of PML incidence in France before and after introduction of risk minimization recommendations in 2013. Design, Setting, and Participants: This observational study used data in the MS registry OFSEP (Observatoire Français de la Sclérose en Plaques) collected between April 15, 2007, and December 31, 2016, by participating MS expert centers and MS-dedicated networks of neurologists in France. Patients with an MS diagnosis according to current criteria, regardless of age, were eligible, and those exposed to at least 1 natalizumab infusion (n = 6318) were included in the at-risk population. A questionnaire was sent to all centers, asking for a description of their practice regarding PML risk stratification. Data were analyzed in July 2018. Exposures: Time from the first natalizumab infusion to the occurrence of PML, natalizumab discontinuation plus 6 months, or the last clinical evaluation. Main Outcomes and Measures: Incidence was the number of PML cases reported relative to the person-years exposed to natalizumab. A Poisson regression model for the 2007 to 2016 period estimated the annual variation in incidence and incidence rate ratio (IRR), adjusted for sex and age at treatment initiation and stratified by period (2007-2013 and 2013-2016). Results: In total, 6318 patients were exposed to natalizumab during the study period, of whom 4682 (74.1%) were female, with a mean (SD [range]) age at MS onset of 28.5 (9.1 [1.1-72.4]) years; 45 confirmed incident cases of PML were diagnosed in 22 414 person-years of exposure. The crude incidence rate for the whole 2007 to 2016 period was 2.00 (95% CI, 1.46-2.69) per 1000 patient-years. Incidence significantly increased by 45.3% (IRR, 1.45; 95% CI, 1.15-1.83; P = .001) each year before 2013 and decreased by 23.0% (IRR, 0.77; 95% CI, 0.61-0.97; P = .03) each year from 2013 to 2016. Conclusions and Relevance: The results of this study suggest, for the first time, a decrease in natalizumab-associated PML incidence since 2013 in France that may be associated with a generalized use of John Cunningham virus serologic test results; this finding appears to support the continuation and reinforcement of educational activities and risk-minimization strategies in the management of disease-modifying therapies for multiple sclerosis.

Comparative effectiveness of teriflunomide vs dimethyl fumarate in multiple sclerosis.

OBJECTIVE: In this study, we compared the effectiveness of teriflunomide (TRF) and dimethyl fumarate (DMF) on both clinical and MRI outcomes in patients followed prospectively in the Observatoire Français de la Sclérose en Plaques. METHODS: A total of 1,770 patients with relapsing-remitting multiple sclerosis (RRMS) (713 on TRF and 1,057 on DMF) with an available baseline brain MRI were included in intention to treat. The 1- and 2-year postinitiation outcomes were relapses, increase of T2 lesions, increase in Expanded Disability Status Scale score, and reason for treatment discontinuation. Propensity scores (inverse probability weighting) and logistic regressions were estimated. RESULTS: The confounder-adjusted proportions of patients were similar in TRF- compared to DMF-treated patients for relapses and disability progression after 1 and 2 years. However, the adjusted proportion of patients with at least one new T2 lesion after 2 years was lower in DMF compared to TRF (60.8% vs 72.2%, odds ratio [OR] 0.60, p < 0.001). Analyses of reasons for treatment withdrawal showed that lack of effectiveness was reported for 8.5% of DMF-treated patients vs 14.5% of TRF-treated patients (OR 0.54, p < 0.001), while adverse events accounted for 16% of TRF-treated patients and 21% of DMF-treated patients after 2 years (OR 1.39, p < 0.001). CONCLUSIONS: After 2 years of treatment, we found similar effectiveness of DMF and TRF in terms of clinical outcomes, but with better MRI-based outcomes for DMF-treated patients, resulting in a lower rate of treatment discontinuation due to lack of effectiveness. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with RRMS, TRF and DMF have similar clinical effectiveness after 2 years of treatment.

The Clinical Features of Painful Small-Fiber Neuropathy Suggesting an Origin Linked to Primary Sjögren's Syndrome.

OBJECTIVE: We attempted to determine whether clinical features could differentiate painful small-fiber neuropathy related to primary Sj€ogren's syndrome (pSS-SFN) from idiopathic SFN (idio-SFN). METHODS: Validated clinical questionnaires and neurophysiological investigations specific for pain and SFN assessment were performed in 25 patients with pSS-SFN and 25 patients with idio-SFN. RESULTS: Patients with idio-SFN had more frequent severe burning sensations and higher mean anxiety scores and daily pain intensity compared to patients with pSSSFN. Conversely, patients with pSS-SFN had reduced electrochemical skin conductance measured by Sudoscan_, and almost half of them had the sensation of walking on cotton wool. CONCLUSION: Our results suggest that idio-SFN more specifically involved small sensory fibers than pSS-SFN, in which subtle dysfunction of larger sensory fibers and damage of distal autonomic sudomotor innervation may occur. A practical algorithm is proposed to help to differentiate SFN associated with pSS from idio-SFN, based on information very easy to obtain by clinical interview.

Coaching of lifestyle recommendations improves sensory neurophysiological parameters in neuropathies related to glycemic disorder or metabolic syndrome. A pilot study.

OBJECTIVES: Metabolic abnormalities, such as, glycemic disorders and metabolic syndrome (GDMS) are one of the main causes of peripheral neuropathies. The objective of this study was to evaluate the impact of adding specific coaching care (CC) to standard care (SC) of therapeutic education based on lifestyle recommendations for neuropathies associated with GDMS. METHODS: This prospective randomized study included two groups of four patients (SC vs. CC) with examiners blinded to group allocation. The SC group had one day of therapeutic education on lifestyle measures (physical activity and diet recommendations) followed by only one phone call of reinforcement. The CC group received an additional weekly phone call of reinforcement for 3 months. Clinical, biological and neurophysiological variables were compared between the two groups at baseline and for the percentage of change at 3 months. RESULTS: All patients (4 men and 4 women) had diabetes or pre-diabetes, which was associated with metabolic syndrome in 5 cases. There was no difference on any variable at baseline, but at 3 months, Mann-Whitney test showed a difference (P=0.0008) between the two groups regarding the sensory neurophysiological variable, which deteriorated in the SC group (median: -6.0%) and improved in the CC group (median: +12.4%). No significant difference was observed between the two groups for the other variables at 3 months. CONCLUSION: The weekly coaching of recommendations for lifestyle measures over a period of three months allows an improvement of GDMS neuropathies, at least in terms of sensory aspects, as evidenced by neurophysiological assessments.

Characterization of Neuropathic Pain in Primary Sjögren's Syndrome with Respect to Neurophysiological Evidence of Small-Fiber Neuropathy.

OBJECTIVE: To determine whether clinical features of neuropathic pain differ with respect to the presence of small-fiber neuropathy (SFN) in patients with primary Sjögren's syndrome (pSS). METHODS: We compared the clinical presentation of neuropathic pain between 15 patients with pSS and SFN detected by neurophysiological tests (laser-evoked potentials, cold and warm detection thresholds, sympathetic skin responses, and electrochemical skin conductance) and 15 patients with pSS but no neurophysiological evidence of SFN. RESULTS: The patients with SFN had more intense squeezing and pressure sensations and more frequent dynamic mechanical allodynia (pain provoked by brushing) than the patients without SFN. Restless leg syndrome was also more frequently observed in patients with SFN, who had pain aggravated at rest that improved by moving. CONCLUSIONS: These findings are in favor of the sensitization of relatively spared large Aß-fibers and second-order nociceptive neurons in patients with SFN. On the other hand, burning sensations, which rather reveal sensitization of small nociceptive fibers, were observed whether SFN was present or not. Thus, some discriminating clinical features may help to suggest the presence of SFN in patients with pSS and chronic neuropathic pain.