Jacques Fermanian

Comparison of pain syndromes associated with nervous or somatic lesions and development of a new neuropathic pain diagnostic questionnaire (DN4)

&NA; Few studies have directly compared the clinical features of neuropathic and non‐neuropathic pains. For this purpose, the French Neuropathic Pain Group developed a clinician‐administered questionnaire named DN4 consisting of both sensory descriptors and signs related to bedside sensory examination. This questionnaire was used in a prospective study of 160 patients presenting with pain associated with a definite neurological or somatic lesion. The most common aetiologies of nervous lesions (n=89) were traumatic nerve injury, post herpetic neuralgia and post stroke pain. Non‐neurological lesions (n=71) were represented by osteoarthritis, inflammatory arthropathies and mechanical low back pain. Each patient was seen independently by two experts in order to confirm the diagnosis of neuropathic or non‐neuropathic pain. The prevalence of pain descriptors and sensory dysfunctions were systematically compared in the two groups of patients. The analysis of the psychometric properties of the DN4 questionnaire included: face validity, inter‐rater reliability, factor analysis and logistic regression to identify the discriminant properties of items or combinations of items for the diagnosis of neuropathic pain. We found that a relatively small number of items are sufficient to discriminate neuropathic pain. The 10‐item questionnaire developed in the present study constitutes a new diagnostic instrument, which might be helpful both in clinical research and daily practice.

Development and validation of the neuropathic pain symptom inventory

&NA; This study describes the development and validation of the Neuropathic Pain Symptom Inventory (NPSI), a new self‐questionnaire specifically designed to evaluate the different symptoms of neuropathic pain. Following a development phase and a pilot study, we generated a list of descriptors reflecting spontaneous ongoing or paroxysmal pain, evoked pain (i.e. mechanical and thermal allodynia/hyperalgesia) and dysesthesia/paresthesia. Each of these items was quantified on a (0–10) numerical scale. The validation procedure was performed in 176 consecutive patients with neuropathic pain of peripheral (n=120) or central (n=56) origin, recruited in five pain centers in France and Belgium. It included: (i) assessment of the test–retest reliability of each item, (ii) determination of the factorial structure of the questionnaire and analysis of convergent and divergent validities (i.e. construct validity), and (iii) evaluation of the ability of the NPSI to detect the effects of treatment (i.e. sensitivity to change). The final version of the NPSI includes 10 descriptors (plus two temporal items) that allow discrimination and quantification of five distinct clinically relevant dimensions of neuropathic pain syndromes and that are sensitive to treatment. The psychometric properties of the NPSI suggest that it might be used to characterize subgroups of neuropathic pain patients and verify whether they respond differentially to various pharmacological agents or other therapeutic interventions.

Neuropathic pain: are there distinct subtypes depending on the aetiology or anatomical lesion?

&NA; Neuropathic pain can be caused by a variety of nerve lesions and it is unsettled whether it should be categorised into distinct clinical subtypes depending on aetiology or type of nerve lesion or individualised as a specific group, based on common symptomatology across aetiologies. In this study, we used a multivariate statistical method (multiple correspondence analyses) to investigate associations between neuropathic positive symptoms (assessed with a specific questionnaire, the Neuropathic Pain Symptom Inventory [NPSI]) and aetiologies, types of nerve lesion and pain localisations. We also examined the internal structure of the NPSI and its relevance to evaluation of symptoms of evoked pains by exploring their relationships with clinician‐based quantified measures of allodynia and hyperalgesia. This study included 482 consecutive patients (53% men; mean age: 58 ± 15 years) with pain associated with peripheral or central lesions. Factor analysis showed that neuropathic symptoms of the NPSI can be categorised into five dimensions. Spearman correlation coefficients indicated that self‐reported pain evoked by brush, pressure and cold stimuli strongly correlated to allodynia/hyperalgesia to brush, von Frey hairs and cold stimuli (p < 0.0001, n = 90). Multiple correspondence analyses indicated few associations between symptoms (or dimensions) and aetiologies, types of lesions, or pain localisations. Exceptions included idiopathic trigeminal neuralgia and postherpetic neuralgia. We found that there are more similarities than differences in the neuropathic positive symptoms associated with a large variety of peripheral and central lesions, providing rationale for subgrouping aetiologically diverse neuropathic patients into a specific multidimensional category for therapeutic management.

Capacity of the Clinical Picture to Characterize Low Back Pain Relieved by Facet Joint Anesthesia: Proposed Criteria to Identify Patients With Painful Facet Joints

Study Design. Prospective randomized study to compare the efficacy of facet joint injection with lidocaine and facet joint injection with saline in two groups of patients with low back pain, with and without clinical criteria that were determined in a previous study to implicate the facet joint as the primary source of the pain. Objectives. To assess the efficacy of single facet joint anesthesia versus placebo (saline injections) and to determine clinical criteria that are predictive of significant relief of LBP after injection. Summary of Background Data. There is no syndrome that discriminates between lower back pain caused by facet joint and that caused by other structures. Single or double facet joint anesthesia, and single photon emission computed tomography are expensive and time‐consuming procedures for selecting patients in controlled clinical trials with large populations. Methods. Results of a previous study showed that seven clinical characteristics were more frequent in patients who responded to facet joint anesthesia than in those who did not. In the current study, a group of 43 patients with lower back pain who met at least five criteria were compared with 37 patients who met fewer criteria. Patients randomly received injection of either lidocaine or saline into the lower facet joints. The result was considered positive if more than 75% pain relief was determined by visual analog scale. The patient, the radiologist, and the investigator were blinded. An analysis of variance was used to seek an interaction between clinical group effect and injection effect, and logistic regression analysis to select the best set of variables that would be predictive of minimum pain relief of 75% after the injection. Results. There was a significant interaction between clinical group and injection effect (P= 0.003). In patients with back pain, lidocaine provided greater lower‐back pain relief than saline (P = 0.01). Lidocaine also‐provided greater pain relief in the back pain group than in the the nonpain group (P = 0.02). The presence of five among seven variables (age greater than 65 years and pain that was not exacerbated by coughing, not worsened by hyperextension, not worsened by forward flexion, not worsened when rising from flexion, not worsened by extension‐rotation, and well‐relieved by recumbency), always including the last item, distinquished 92% of patients responding to lidocaine injection and 80% of those not responding in the lidocaine group. Conclusions. A set of five clinical characteristics can be used in randomized studies to select lower back pain that will be well relieved by facet joint anesthesia. These characteristics should not, however, be considered as definite diagnostic criteria of lower back pain originating from facet joints.

A motor function measure scale for neuromuscular diseases. Construction and validation study

A new scale for motor function measurement has been developed for neuromuscular diseases. The validation study included 303 patients, aged 6-62 years. Seventy-two patients had Duchenne muscular dystrophy, 32 Becker muscular dystrophy, 30 limb-girdle muscular dystrophy, 39 facio-scapulo-humeral dystrophy, 29 myotonic dystrophy, 21 congenital myopathy, 10 congenital muscular dystrophy, 35 spinal muscular atrophy and 35 hereditary neuropathy. The scale comprised 32 items, in three dimensions: standing position and transfers, axial and proximal motor function, distal motor function. Agreement coefficients for inter-rater reliability were excellent (kappa=0.81-0.94) for nine items, good (kappa=0.61-0.80) for 20 items and moderate (kappa=0.51-0.60) for three items. High correlations were found between the total score and other scores: Vignos (r=0.91) and Brooke (r=0.85) grades, Functional Independence Measure (r=0.91), the global severity of disability evaluated with visual analog scales by physicians (r=0.88) and physiotherapists (r=0.91). This scale is reliable, does not require any special equipment and is well-accepted by patients. Its sensitivity to change is being assessed to permit its use in clinical trials of neuromuscular diseases.

Methodological Approaches to Shortening Composite Measurement Scales

Composite measurement scales (CMSs) have contributed to improving the measurement of complex medical phenomena such as physical and psychological functioning or health-related quality of life. However, their use in patient care and research is often limited by their length and excessive respondent burden. In such situations, short instruments should be made available. Efforts to develop short instruments have largely focused on shortening existing instruments. To investigate the methodology currently used in the shortening of CMS, we assessed 42 studies reported in medical, psychological, and educational journals between 1984 and 1994. A number of methodological and statistical considerations important in the CMS shortening procedure were found to have been ignored or neglected by authors developing short forms from existing CMS. Serious flaws appear mainly to result from inadequate conceptualization of the shortening process, and inappropriate use and excess credit given to statistical techniques used to select items to be retained in short forms. When performed, the assessment of measurement properties of the short form was often inappropriate, and cross validation studies were seldom conducted. We propose recommendations for shortening existing CMS, to help authors and investigators develop and choose, respectively, shortened measurement instruments. These recommendations address the preliminary choice of the original CMS to be shortened, and the two successive phases to be considered in the development of short forms: the shortening process itself, where items are selected, and the validation of the shortened CMS, which should be conducted independently using independent subject samples.

Anxiety disorders in subjects seeking treatment for eating disorders: a DSM-IV controlled study

Women who were referred with an eating disorder (ED) were compared with a matched normal control group to answer the following questions: What are the frequencies of anxiety disorders in cases of anorexia and bulimia nervosa diagnosed according to DSM-IV criteria? Are anxiety disorders significantly more frequent among women with an eating disorder than among women from the community? We assessed the frequencies of six specific anxiety disorders among 271 women with a current diagnosis of anorexia or bulimia nervosa and 271 controls, using the Mini-International Neuropsychiatric Interview, French DSM-IV version. A lifetime comorbidity with at least one anxiety disorder was found in 71% of both the anorexic and the bulimic subjects, significantly higher than the percentage of controls with an anxiety disorder. The prevalence was significantly higher in the eating disorder groups than in controls for most types of anxiety disorder, and between 41.8 and 53.3% of comorbid cases had an anxiety disorder preceding the onset of the eating disorder. Anxiety disorders are significantly more frequent in subjects with eating disorders than in volunteers from the community, a finding that has important etiological and therapeutic implications.

The specific disease burden of neuropathic pain: Results of a French nationwide survey

Summary This nationwide survey of the French general population indicates that pain with neuropathic characteristics induces a specific disease burden as compared to nonneuropathic pain. ABSTRACT We report the first nationwide survey of the impact of neuropathic pain, as opposed to nonneuropathic pain, on quality of life and health care utilization in the French general population. A postal questionnaire was sent to a representative sample of 4554 respondents from an initial nationwide survey of 30,155 subjects with or without chronic pain. It included pain characteristics (Neuropathic Pain Symptom Inventory, DN4), quality of life (Medical Outcomes Short Form 12, SF‐12), sleep, anxiety/depressive symptoms (Hospital Anxiety and Depression Scale) and health care utilization. In total, 3899 (85.6%) questionnaires were returned, 3816 (97.9%) could be assessed and 3165 subjects (82.9%) confirmed their pain status. Subjects reporting pain and neuropathic characteristics based on the DN4 displayed a higher degree of impairment of all dimensions relating to quality of life and sleep and had higher anxiety/depression scores than those reporting pain without neuropathic characteristics and those without pain (P < .01). They also made greater use of health care facilities, particularly as concerned neurological treatments and visits to neurologists (21% vs 9%; P < .01). Multivariate analyses showed that the neuropathic characteristics of pain made an independent contribution to quality‐of‐life impairment (P < .0001 and P = .0005 for the physical and mental scores of the SF‐12 respectively). Our study indicates that the disease burden of chronic pain depends on the nature of the pain, independently of its intensity and duration.

Validation of the French version of the fear avoidance belief questionnaire.

Study Design. Observational prospective study. Objective. To assess the reliability, validity, and responsiveness of the French version of the Fear Avoidance Belief Questionnaire. Summary of Background Data. Fear, avoidance attitudes, and belief play pivotal roles in disability perceived by patients with chronic low back pain. The Fear Avoidance Belief Questionnaire is a two-part questionnaire assessing fear, avoidance, and beliefs about professional activity and physical activity. Methods. The Fear Avoidance Belief Questionnaire was translated by use of the forward and backward translation procedure. Test-retest reliability was assessed in 31 patients (Group 1) with the intraclass correlation coefficient and the Bland and Altman method. Construct validity was assessed in two groups of patients (Group 2, n = 147; Group 3, n = 70) with the Spearman rank correlation coefficient and factor analysis. Responsiveness was assessed in Group 3, after they underwent a functional restoration program, by the effect size and the standardized response mean. Results. Test-retest reliability was good, with an intra-class correlation coefficient value of 0.88 and 0.72 for fear, avoidance, and beliefs about professional activity and physical activity, respectively. Use of the Bland and Altman method produced a homogeneous distribution of the differences, with no systematic trend observed. The expected divergent validity was observed in Groups 2 and 3. Factor analysis extracted four factors in Group 2 and the two original factors of the English Fear Avoidance Belief Questionnaire in Group 3. The lowest effect size and standardized response mean values (0.30 and 0.31, respectively) were observed with the fear, avoidance, and beliefs about professional activity. Conclusions. The psychometric properties (test-retest reliability, construct validity, and responsiveness) of the French version of the Fear Avoidance Belief Questionnaire are acceptable, and fear, avoidance, and belief can now be assessed in French-speaking patients with low back pain.

Antibodies to fibroblasts in idiopathic and scleroderma-associated pulmonary hypertension

The aim of the present study was to investigate the presence of anti-fibroblast antibodies in patients with idiopathic or scleroderma-associated pulmonary arterial hypertension (PAH) and healthy controls. PAH was documented by right-heart catheterisation (mean pulmonary artery pressure at rest >25 mmHg). Serum immunoglobulin (Ig)G and IgM reactivities of patients with idiopathic PAH (n = 35), scleroderma-associated PAH (n = 10), diffuse (n = 10) or limited cutaneous (n = 10) scleroderma without PAH and age- and sex-matched healthy individuals (n = 65) were analysed by cell-based ELISA and immunoblotting on normal human fibroblasts. As assessed by ELISA, 14 out of 35 (40%) patients with idiopathic PAH and three out of 10 (30%) patients with scleroderma-associated PAH expressed anti-fibroblast IgG antibodies. IgG from all individuals bound to one major 40-kDa protein band. IgG from patients with idiopathic PAH bound to two 25- and 60-kDa bands with a higher intensity than IgG from other individuals. In conclusion, immunoglobulin G anti-fibroblast antibodies are present in the serum of patients with pulmonary arterial hypertension. Immunoglobulin G from patients with idiopathic pulmonary arterial hypertension or scleroderma-associated pulmonary arterial hypertension express distinct reactivity profiles with fibroblasts antigens, suggesting distinct target antigens.