The feasibility and usability of a personal health record for patients with multiple sclerosis: a 2-year evaluation study.

Background: Multiple sclerosis (MS) is a persistent inflammatory condition impacting the brain and spinal cord, affecting globally approximately 2.8 million individuals. Effective self-management plays a crucial role in the treatment of chronic diseases, including MS, significantly influencing health outcomes. A personal health record (PHR) is a promising tool to support self-management, potentially empowering patients and enhancing their engagement in treatment and health. Despite these promising aspects, challenges in implementation persist and PHRs are still a relatively new concept undergoing rapid development. Objective: This study aimed to assess the feasibility and usability of the PHR. Secondary objectives included evaluating implementation determinants, and exploring preliminary effects on quality of care for both patients and healthcare professionals (HCPs), self-management, self-efficacy for patients, job satisfaction, efficiency, and demand for HCPs, and preliminary effects on costs and health-related quality of life. Methods: This study had a mixed-methods design. Quantitative data of patients (n = 80) and HCPs (n = 12) were collected via self-reported questionnaires at baseline (T0), after one year (T1), and after two years (T2). One focus group interview was conducted at T2 with patients (n = 7), and another one with HCPs (n = 4), to get a more in-depth understanding of the feasibility and usability of the PHR via the Unified Theory of Acceptance and Use of Technology framework, and to further explore the secondary objectives in-depth. Results: Most patients never logged in during the first year and logged in a couple of times per year during the second year, averaging around 15 min per log-in session. The HCPs mainly logged in a couple of times per year over the two years with an average use of six minutes per session. Patient usability and satisfaction scores were below average and moderate, respectively: with SUS-scores of 59.9 (SD = 14.2, n = 33) at T1 and 59.0 (SD = 16.3, n = 37) at T2, and CSQ-8 scores of 21.4 (SD = 5.0, n = 34) at T1, and 22.1 (SD = 5.0, n = 39) at T2. HCPs had similar usability and satisfaction scores. Multiple facilitators and barriers were identified by both patients and HCPs, such as (in)sufficient knowledge of how to use the PHR, lack of staff capacity and ICT obstacles. No significant differences were found in the preliminary effects. Qualitative data showed, among others, that both patients and HCPs saw the benefit of the PHR in terms of performance expectancy, by gaining more insight into health and health data, but challenges remained regarding effort expectancy, such as log-in issues and experiencing difficulties with information retrieval. Conclusion: The feasibility and usability were considered moderate by patients and HCPs; however, potential regarding the performance of the PHR was observed. Implementation challenges, such as the complexity of usage, lowered the adoption of the PHR. The evolving nature of PHRs requires ongoing evaluation and adaptation to optimize their potential benefits. Utilizing a participatory design approach and a dedicated implementation team could help in achieving this optimization, ultimately enhancing their adoption.

Prospective trial of natalizumab personalised extended interval dosing by therapeutic drug monitoring in relapsing-remitting multiple sclerosis (NEXT-MS).

BACKGROUND: Extended interval dosing (EID) of natalizumab is a promising strategy to optimise treatment in multiple sclerosis (MS). Personalised EID by therapeutic drug monitoring can enable further extension of treatment intervals. METHODS: The NEXT-MS trial is an investigator-initiated prospective phase IV non-randomised study. Adults with a diagnosis of relapsing-remitting MS who received ≥6 natalizumab infusions were included in three groups: personalised EID with a target drug trough concentration of 10 µg/mL (EID10), an exploratory group of personalised EID with a target of 5 µg/mL (EID5) and standard interval dosing (SID) of 4 weeks. The primary outcome is radiological disease activity (new/newly enlarged T2 lesions) comparing the EID10 group to a historical cohort of SID (HSID). RESULTS: Results of the first phase of the NEXT-MS trial are reported here (n=376) as the study will continue with an amended protocol. In the EID10 group (n=251), incidence rate of radiological activity was 10.0 per 1000 person-years, which was non-inferior to the HSID cohort (24.7 per 1000 person-years (n=87), incidence rate difference 14.7, 90% CI -4.5 to 34.0). Incidence rate of radiological activity was 10.0 per 1000 person-years in the EID5 group (n=65), and 47.0 per 1000 person-years in the SID group (n=60). Serum neurofilament light levels did not increase over time within the EID groups. There were no cases of progressive multifocal leukoencephalopathy. CONCLUSIONS: MS disease activity is adequately controlled with personalised natalizumab EID. Interval extension to a drug trough concentration of 5 µg/mL is likely a safe target to extend natalizumab treatment intervals >6 weeks. TRIAL REGISTRATION NUMBER: NCT04225312.

Decrease of natalizumab drug levels after switching from intravenous to subcutaneous administration in patients with multiple sclerosis.

BACKGROUND: Natalizumab is effective in the treatment of multiple sclerosis (MS). In 2021, the European Medicines Agency approved the subcutaneous (SC) variant of natalizumab which can be used instead of intravenous administration. However, the course of drug levels varies between administration routes, and the Food and Drug Administration rejected the request for approval of natalizumab SC for reasons that were not disclosed. Our objective was to evaluate the course of natalizumab trough drug levels in patients who switched from natalizumab intravenous to SC on various treatment intervals. METHODS: The NEXT-MS trial (N=382) investigates personalised treatment of natalizumab, in which infusion intervals are prolonged based on individual natalizumab trough drug levels. In 2021, an amendment was approved allowing participants to switch from intravenous to SC administration with frequent measurements of natalizumab drug levels and antidrug antibodies (ADAs). Results were compared with linear mixed model analyses. RESULTS: Until December 2022, 15 participants switched to SC natalizumab. Natalizumab drug levels with SC administration were on average 55% lower compared with intravenous administration (Exp (estimate) 0.45, 95% CI 0.39 to 0.53, p<0.001), leading to very low trough drug levels in three patients on extended treatment intervals. No natalizumab ADAs were detected during intravenous or SC treatment. None of the participants on natalizumab SC showed evidence of MS disease activity. CONCLUSIONS: Natalizumab trough drug levels can decrease after switching from natalizumab intravenous to SC administration. We advise to monitor trough drug levels in patients with low natalizumab drug levels during intravenous treatment, patients with higher body mass index or patients on extended treatment intervals who switch to SC administration of natalizumab.

Determining the minimal important change of the 6-minute walking test in Multiple Sclerosis patients using a predictive modelling anchor-based method.

BACKGROUND: The minimal important change (MIC) of the 6-minute walk test (6MWT) is not clear for patients with Multiple Sclerosis (MS), hampering treatment evaluation. The aim of our study was therefore to determine the MIC of the 6MWT in MS patients. METHODS: MS patients did the 6MWT using the instruction to walk at comfortable speed twice with approximately one year in between. After the second 6MWT they completed 3-point anchor question. The MICadjusted with a 95% confidence interval (CI) was calculated with the predictive modelling method with bootstrapping. RESULTS: 118 MS patients (mean age 48.2 years, 23.7% men) were included between September 2018 and October 2019. Mean 6MWT distance was 468 ± 112 m at baseline and 469 ± 115 m one year later. Twenty-three (19.5%) patients answered their walking distance improved, 43 (36.4%) answered it worsened. A MICadjusted for improvement of 19.7 m (95%CI 9.8-30.9 m) was found, and for deterioration of 7.2 m (95%CI -3.3-18.2 m). CONCLUSIONS: Using the most sophisticated statistical method, the MICadjusted of the 6MWT in MS patients was 19.7 m for improvement, and 7.2 m for deterioration. This knowledge allows physiotherapists and physicians to evaluate if their treatment has led to a meaningful improvement for their MS patients or if walking of their patients has deteriorated.

A Dutch validation study of the Multiple Sclerosis Work Difficulties Questionnaire in relapsing remitting multiple sclerosis.

PURPOSE: The current study aimed to evaluate the psychometric properties of the Dutch version of the Multiple Sclerosis Work Difficulties Questionnaire-23 (MSWDQ-23). METHODS: Two hundred and thirty-nine employed persons with multiple sclerosis (MS) and 59 healthy controls completed the MSWDQ-23. To verify the factor structure, a confirmatory factor analysis was conducted. To assess construct validity, the MSWDQ-23 scores were correlated to measures of physical disability, fatigue, cognitive and neuropsychiatric problems, depression, health-related quality of life, and work-related variables. MSWDQ-23 scores were compared within different age groups, gender, education levels, and job types. Predictive validity was assessed using a logistic regression analysis to predict a deterioration in employment status after one year based on MSWDQ-23 scores. RESULTS: The internal consistency of the MSWDQ-23 was acceptable (α = 0.913, 95% CI = 0.897-0.928) and the results indicated a fair fit. The MSWDQ-23 showed acceptable construct validity, confirming 94% of the hypotheses. The total scale and the psychological/cognitive subscale were able to predict a deterioration in employment status after one year (χ2(1)=18.164, p < 0.001). CONCLUSIONS: The Dutch version of the MSWDQ-23 is a valid and internally consistent instrument to measure self-reported work difficulties in persons with MS.Implications for rehabilitationThe Dutch version of the 23-item Multiple Sclerosis Work Difficulties Questionnaire (MSWDQ-23) is a reliable and valid tool to measure self-reported work difficulties in people with multiple sclerosis (MS).More psychological and cognitive work difficulties are predictive of a deteriorated employment status after one year.The MSWDQ-23 is a helpful tool for researchers and (occupational) health professionals to identify current work difficulties in persons with MS and identify persons at risk for a deterioration in employment one year later.

COVID-19 in multiple sclerosis: The Dutch experience.

Here, we provide an extensive overview of all reported COVID-19 cases in multiple sclerosis (MS) patients in the Netherlands between 27 February and 9 June 2020, gathered by the Dutch MS Taskforce of the Netherlands Society of Neurology. A total of 86 MS patients were reported, 43 of whom tested positive for COVID-19. Of 43 patients who tested positive, 22 patients were hospitalized. Three intensive care unit (ICU) admissions and four deaths were reported. Our findings show no apparent difference in disease-modifying treatment (DMT) use and COVID-19 disease course in Dutch MS patients. In addition, a clear link between low lymphocyte count and severe disease was not observed.

Cognitive functioning as a predictor of employment status in relapsing-remitting multiple sclerosis: a 2-year longitudinal study.

BACKGROUND: Cognitive functioning has been linked to employment outcomes in multiple sclerosis (MS) in cross-sectional studies. Longitudinal studies are however lacking and previous studies did not extensively examine executive functioning. OBJECTIVES: We examined whether baseline cognitive functioning predicts a change in employment status after 2 years, while taking into account mood, fatigue and disability level. METHODS: A total of 124 patients with relapsing-remitting MS (pwMS) and 60 healthy controls were included. They underwent neurological and neuropsychological examinations and completed online questionnaires. PwMS were divided into a stable and deteriorated employment status group (SES and DES), based on employment status 2 years after baseline. We first examined baseline differences between the SES and DES groups in cognitive functioning, mood, fatigue and disability level. A logistic regression analysis was performed, with change in employment status (SES/DES) as dependent variable. RESULTS: The DES group included 22% pwMS. Group differences were found in complex attention, executive functioning, self-reported cognitive functioning, fatigue and physical disability. More physical disability (OR = 1.90, p = 0.01) and lower executive functioning (OR = 0.30, p = 0.03) were retained as independent predictors of DES (R2 = 0.22, p ≤ 0.001). CONCLUSIONS: Baseline physical disability and executive functioning, but none of the other variables, moderately predicted a deterioration in employment status 2 years later. TRIAL REGISTRATION: This observational study is registered under NL43098.008.12: 'Voorspellers van arbeidsparticipatie bij mensen met relapsing-remitting Multiple Sclerose'. This study is registered at the Dutch CCMO register (https://www.toetsingonline.nl).

Outcome of Carpal Tunnel Release and the Relation With Depression.

PURPOSE: To examine the relation between depressive symptoms and outcome of carpal tunnel release (CTR). METHODS: Prospective study in a general hospital with data collection at baseline and 3 and 12 months after CTR. We quantified depressive symptoms using the Center for Epidemiologic Studies Depression (CES-D) scale and performed multivariable analyses on 2 outcome measures: (1) carpal tunnel syndrome (CTS) symptoms (Boston Carpal Tunnel Questionnaire [BCTQ]) and (2) palmar pain, focusing on preoperative CES-D and BCTQ score, sex, age, alcohol use, diabetes, and severity of nerve conduction abnormalities. RESULTS: We included 227 patients. Before surgery, patients with depression had a higher BCTQ score than patients without depression. After 1 year, depressed patients had a higher BCTQ score and more palmar pain. The CES-D decreased by a median of 2 points from baseline to 1 year. This correlated with the decrease in BCTQ score. Multivariable analyses showed that preoperative depression had a small but statistically significant influence on palmar pain, but not on postoperative BCTQ score. CONCLUSIONS: Depression is not an independent predictor of residual CTS symptoms 1 year after CTR. Depressive symptoms in patients with CTS decrease after CTR, along with a decrease in CTS symptoms. The nature of this relationship is unknown. Patients with CTS and depression may expect a somewhat higher degree of palmar pain after CTR, the clinical relevance of which is small. TYPE OF STUDY/LEVEL OF EVIDENCE: Prognostic II.

Determination of the smallest detectable change (SDC) and the minimal important difference (MID) for the Small Fiber Neuropathy Screening List (SFNSL) in sarcoidosis.

Background: Previous studies found that 40-60% of the sarcoidosis patients suffer from small fiber neuropathy (SFN), substantially affecting quality of life. SFN is difficult to diagnose, as a gold standard is still lacking. The need for an easily administered screening instrument to identify sarcoidosis-associated SFN symptoms led to the development of the SFN Screening List (SFNSL). The usefulness of any questionnaire in clinical management and research trials depends on its interpretability. Obtaining a clinically relevant change score on a questionnaire requires that the smallest detectable change (SDC) and minimal important difference (MID) are known. Objectives: The aim of this study was to determine the SDC and MID for the SFNSL in patients with sarcoidosis. Methods: Patients with neurosarcoidosis and/or sarcoidosis-associated SFN symptoms (N=138) included in the online Dutch Neurosarcoidosis Registry participated in a prospective, longitudinal study. Anchor-based and distribution-based methods were used to estimate the MID and SDC, respectively. Results: The SFNSL was completed both at baseline and at 6-months' follow-up by 89/138 patients. A marginal ROC curve (0.6) indicated cut-off values of 3.5 points, with 73% sensitivity and 49% specificity for change. The SDC was 11.8 points. Conclusions: The MID on the SFNSL is 3.5 points for a clinically relevant change over a 6-month period. The MID can be used in the follow-up and management of SFN-associated symptoms in patients with sarcoidosis, though with some caution as the SDC was found to be higher. (Sarcoidosis Vasc Diffuse Lung Dis 2018; 35: 333-341).

Validation of the King's Sarcoidosis Questionnaire (KSQ) in a Dutch sarcoidosis population.

BACKGROUND: The King's Sarcoidosis Questionnaire (KSQ) is a brief questionnaire assessing health status using five modules (General Health Status, Lung, Eyes, Skin, Medication) in patients with sarcoidosis. The KSQ was only validated in one English sarcoidosis cohort. OBJECTIVE: The aim of this study was to validate the KSQ in a Dutch sarcoidosis population. METHODS: The KSQ was translated according to international guidelines and tested in interviews with patients. Consecutive outpatients completed multiple questionnaires twice, two weeks apart. Construct validity, internal consistency and repeatability were determined. RESULTS: Of the 98 patients included 85 had lung, 22 skin and 24 eye disease. There was good construct validity of the KSQ General Health Status module against the World Health Organization Quality of Life-BREF questionnaire. The Medication module correlated weak to moderate with most questionnaires. The correlations with organ-specific questionnaires varied from strong for Eyes (r=0.75), Skin (r=-0.62) to moderate for Lung (r=-0.45 with MRC breathlessness scale). Internal consistency was good for all KSQ modules (Cronbach's α 0.72-0.93). Intraclass correlation coefficients (0.70-0.90) and Bland-Altman plots showed good repeatability of the KSQ. CONCLUSION: The Dutch KSQ is the first translation of the English KSQ, validated in a Dutch sarcoidosis population.

The Tinel sign has no diagnostic value for nerve entrapment or neuropathy in the legs.

INTRODUCTION: The presence of a Tinel sign in leg nerves has been proposed as a criterion for decompressive surgery in polyneuropathy. We investigated the diagnostic yield of the Tinel sign for nerve entrapment and for distal symmetrical peripheral neuropathy (DSPN). METHODS: We prospectively tested for the Tinel sign at 3 sites of possible nerve entrapment per leg in 91 patients. Entrapment was defined using nerve conduction data. We also investigated whether the number of sites at which the Tinel sign was present identified patients with DSPN. RESULTS: Sensitivity of the Tinel sign for nerve entrapment was low (29%, 44%, and 17%) for the 3 sites, and specificity was moderate (86%, 75%, and 81%). In the subgroup with DSPN, sensitivity was extremely low (0%, 20%, and 8%), and specificity was moderate (91%, 79%, and 73%). The number of sites with a Tinel sign did not identify patients with DSPN. CONCLUSION: The Tinel sign does not reliably indicate nerve entrapment or DSPN. Muscle Nerve 54: 25-30, 2016.

Consequences of Sarcoidosis.

Sarcoidosis is a multisystem disorder of unknown cause(s). Less specific disabling symptoms, including fatigue and physical impairments, may have a major influence on the daily activities and the social and professional lives of the patients, resulting in a reduced quality of life. A multidisciplinary approach focusing on somatic and psychosocial aspects is recommended. Patients self-perceived knowledge about the importance of exercise and lifestyle should be improved. Developing the most appropriate therapeutic approach for sarcoidosis requires careful consideration of the possible impact of fatigue, small fiber neuropathy related symptoms, pain, cognitive functioning, and coping strategies. Personalized medicine and appropriate communication are beneficial.

[Neurosarcoidosis and paraneurosarcoidosis: new online registration of patients]. / Neurosarcoïdose en paraneurosarcoïdose: nieuwe onlineregistratie van patiënten.

The clinical spectrum of neurosarcoidosis is highly diverse; virtually any neurological syndrome can present, depending upon granuloma localization. There are indications that neurosarcoidosis is insufficiently recognized as a separate clinical entity. In the absence of major prospective clinical trials, we launched a large national online registry of neurosarcoidosis patients in the Netherlands in June 2014 at www.neurosarcoidose.nl. When a patient with sarcoidosis presents with neurological symptoms that may compatible with sarcoidosis, it is important to locate sites of disease activity accessible for biopsy outside the nervous system. Small nerve fibre neuropathy is a common neurological complication of sarcoidosis. It is considered an epiphenomenon, and therefore classified as 'para-neurosarcoidosis'. Neurological symptoms causing disability are an indication for immunosuppressive therapy. There is increasing evidence for the effective treatment of refractory neurosarcoidosis using biologicals. Whether the intravenous administration of immunoglobulins or ARA290, an erythropoietin derivative with TNF-α-antagonistic and tissue-protective characteristics, is effective for small nerve fibre neuropathy in sarcoidosis is subject for study.

Association of the TNF-α G-308A polymorphism with TNF-inhibitor response in sarcoidosis.

Responsiveness to tumour necrosis factor (TNF) inhibitors has been associated with the TNF-α G-308A polymorphism in rheumatoid arthritis. The aim of this study was to examine the association between the presence of this polymorphism and the response to TNF inhibitors in patients with refractory sarcoidosis. Patients (n=111) who started TNF-inhibitor treatment (76 infliximab, 35 adalimumab) were followed for at least 1 year. The main symptoms in these patients were fatigue (n=100, 90.1%), small fibre neuropathy (n=91, 82.0%), pulmonary involvement (n=69, 62.2%), and/or uveitis (n=31, 27.9%). Patients were additionally genotyped for the presence of the TNF-α G-308A polymorphism. Treatment response was assessed using clinical outcome measures and questionnaires. Three-quarters (n=83, 74.8%) of the patients responded well. Of the patients without the variant A-allele 93.6% (73 out of 78, p<0.001) improved, while 30.3% (10 out of 33) of variant A-allele carriers responded favourably to TNF inhibitors. For patients with the GG-genotype, the probability of improving compared with remaining stable or deteriorating was three times higher (risk ratio 3.09, 95% CI 1.84-5.20). Sarcoidosis patients without the TNF-α -308A variant allele (GG-genotype) had a three-fold higher response to TNF inhibitors (adalimumab or infliximab). Further research is needed to evaluate the value of genotyping for the TNF-α G-308A polymorphism in order to tailor TNF-inhibitor treatment.

Safety and efficacy of ARA 290 in sarcoidosis patients with symptoms of small fiber neuropathy: a randomized, double-blind pilot study.

ARA 290 (a peptide designed to activate the innate repair receptor that arrests injury and initiates cytoprotection, antiinflammation and healing) reduces allodynia in preclinical neuropathy models. We studied the safety and efficacy of ARA 290 to reduce symptoms of small fiber neuropathy (SFN) in patients with sarcoidosis. A total of 22 patients diagnosed with sarcoidosis and symptoms of SFN were enrolled in a double-blind, placebo-controlled exploratory trial consisting of three times weekly intravenous dosing of ARA 290 (2 mg; n = 12) or placebo (n = 10) for 4 wks. Inclusion criteria were a diagnosis of neuropathy and a spontaneous pain score of ≥5 (Brief Pain Inventory [BPI]). Endpoints assessed were changes in pain intensity and the small fiber neuropathy screening list (SFNSL) score, quality of life (SF-36), depressive symptoms (Inventory of Depressive Symptomatology [IDS]) and fatigue (Fatigue Assessment Scale [FAS]). No safety concerns were raised by clinical or laboratory assessments. The ARA 290 group showed significant (p < 0.05) improvement at wk 4 in SFNSL score compared with placebo (Δ -11.5 ± 3.04 versus Δ -2.9 ± 3.34 [standard error of the mean]). Additionally, the ARA 290 group showed a significant change from baseline in the pain and physical functioning dimensions of the SF-36 (Δ -23.4 ± 5.5 and Δ -14.6 ± 3.9, respectively). The mean BPI and FAS scores improved significantly but equivalently in both patient groups. No change was observed in the IDS. ARA 290 appears to be safe in patients with sarcoidosis and can reduce neuropathic symptoms.

The diagnostic value of water immersion skin wrinkling and Neuropads in small fiber neuropathy.

OBJECTIVE: To investigate the diagnostic yield of two simple tests for small fiber neuropathy (SFN): Neuropads® and water immersion skin wrinkling (WISW). METHODS: We studied 35 patients clinically diagnosed with SFN and 61 age- and sex-matched healthy controls. Wrinkling was judged as absent (abnormal), or present (normal) after immersion of the hands for 30 min. Neuropads are plasters impregnated with cobalt blue that are applied with to the soles of the feet. These remain blue when feet are dry (abnormal) or turn pink when there is some moisture (normal). RESULTS: The sensitivity of the Neuropad was 29% and its specificity 93%. The sensitivity of WISW was 66% and its specificity 70%. Regarding abnormality of at least one test to define the combination as abnormal yielded a sensitivity of 71% and specificity 67%. When both tests had to be abnormal to judge the combination abnormal, sensitivity was 23% and specificity 97%. CONCLUSIONS: The Neuropad has a high specificity, so an abnormal result can be used to confirm SFN. WISW has a moderate sensitivity and specificity. Combining these two tests can be helpful: when both tests are abnormal the diagnosis SFN is highly likely. SIGNIFICANCE: The Neuropad and WISW can be helpful in daily practice by supporting the diagnosis SFN.

Sarcoidosis and pain caused by small-fiber neuropathy.

Sarcoidosis is a chronic inflammatory illness and small-fiber neuropathy (SFN) is one of the disabling and often chronic manifestations of the disease. SFN presents with peripheral pain and symptoms of autonomic dysfunction. The character of the pain can be burning or shooting. Besides, allodynia and hyperesthesia can exist. Diagnosis is usually made on the basis of clinical features, in combination with abnormal specialized tests. The aim of treatment is often to reduce pain; however, total pain relieve is seldom achieved. The role of TNF-α in the pathogenesis of SFN in sarcoidosis appears interesting to explore. Novel therapeutic agents such as ARA 290, a nonhematopoietic erythropoietin analogue with potent anti-inflammatory and tissue protective properties, are interesting to explore in the treatment of SFN in sarcoidosis.

Offset analgesia in neuropathic pain patients and effect of treatment with morphine and ketamine.

BACKGROUND: Offset analgesia, in which a disproportionally large amount of analgesia becomes apparent upon a slight decrease in noxious heat stimulation, has not been described previously in patients with chronic pain. METHODS: Offset analgesia responses in 10 patients with neuropathic pain (in both legs) were compared with 10 matched healthy controls and volunteers from a convenience sample (n = 110) with an age range of 6-80 yr. Offset analgesia was defined by the reduction in electronic pain score upon the 1°C decrease in noxious heat stimulus relative to the peak pain score where pain was administered at the volar side of the arm. RESULTS: Offset analgesia was present in healthy volunteers irrespective of age and sex (pain score decrease = 97 ± 1% [mean ± SEM]). In contrast, a reduced or absent offset analgesia response was observed in patients with neuropathic pain (pain score decrease = 56 ± 9% vs. controls 98 ± 1%, P < 0.001). Intravenous treatment with ketamine, morphine, and placebo had no effect on offset analgesia in patients, despite sharp reductions in spontaneous pain scores. CONCLUSIONS: These data indicate that offset analgesia is fully developed at the age of 6 yr and does not undergo additional maturation. The reduced or absent responses observed in patients with chronic neuropathic pain indicate the inability to modulate changes in pain stimulation, with perseverance of pain perception in situations in which healthy subjects display signs of strong analgesia. Both central and peripheral sites may be involved in the altered offset analgesia responses in these patients.

The small fiber neuropathy screening list: Construction and cross-validation in sarcoidosis.

BACKGROUND: Small fiber neuropathy (SFN) appears to be relatively common in sarcoidosis patients. However, there is no golden standard to establish SFN and diagnostic tests for SFN are not widely available. There is a need for an easy to administer SFN screening instrument for clinical assessment, research or therapeutic trials. The aim of the present study was to develop a screening list to identify sarcoidosis patients with SFN in general clinical practice. METHODS: We studied 139 sarcoidosis patients. The first consecutive 84 patients (Group 1) underwent temperature threshold testing (TTT) and completed an extensive SFN-symptoms-questionnaire. Based on data from Group 1 and using distribution measures and discriminant analyses, a screening list for SFN in sarcoidosis consisting of 21 questions was constructed: the Small Fiber Neuropathy Screening List (SFNSL). Subsequently, this SFNSL was crossvalidated in the next 55 consecutive patients (Group 2). RESULTS: The same cut-off scores as found for Group 1 were appropriate in Group 2. The SFNSL was found to have high levels of internal consistency (Cronbach's alpha 0.90) and exploratory factor analysis showed that it measures only one underlying factor. Convergent validity seems good. CONCLUSION: To assess the presence of SFN in clinical practice the SFNSL, a brief and easy to administer questionaire, was developed in a sarcoidosis population. The results of the present study support the idea that SFN is a serious problem in chronic sarcoidosis. Future studies are needed to establish the broad usefulness of this SFN screening list and expand knowledge on the psychometric properties.