Empathy in medicine: A ritualistic healing function?

Marcel Réja (1873-1957) French alienist evokes in his book « Au pays des miracles ¼ this innumerable people of healers, mystics, empirics, magnetizers, mediums and fantasists. All operating "cures more wonderful than each other". This book questions in a very relevant way the role of the power of the spirit, of healing by the spirit and therefore of suggestion. This "art" of healers includes an affective and emotional coefficient which constitutes its essential spring. There is a mysterious force between the sick and the physician that goes "soul to soul". Current medicine is still very much borrowed from its past with a remnant of "magical" thought. Also, the empathetic dimension of the care relationship remains one of the most necessary dimensions for the exercise of the medical profession.

Laennecs' mediate auscultation: Child's play.

Before Laennec, respiratory diseases that we recognize today were often confused, because the heart and lung are locked inside the rib cage. Impressed by the autopsies performed by Xavier Bichat (1771-1802), Laennec maintained the importance of the anatomoclinical method. But he indicated in his early 1820s lectures at the Collège de France that the discovery of auscultation was fortuitous and empirical. Duffin demonstrates that medical discoveries hardly obey an implacable logic, they arise outside of pre-established projects. In this paper, we retrace the chronology and antecedents at the origin of the important medical invention that is the stethoscope.

Albert Pitres: Charcot's Brilliant Student.

Albert Pitres (1848-1928) was an internist, neuropsychiatrist, professor of anatomy, pathology, and histology. He never really had a biography in English. However, the development of neurology and neurosciences in Bordeaux owes a lot to him, as to the psychiatrist Emmanuel Régis (1855-1918). The fact that his career was so closely linked with Charcot (1825-1893) should have secured him a more prominent place in neurology and the history of aphasiology. Pitres went on to co-author clinical and experimental research papers with Charcot that are considered some of the most notable ones among Charcot's publications. Both carried out studies about pathological correlations between cortical lesions and hemiplegia, published series of articles and two major books about neurophysiology of motor control. To convey the atmosphere and the importance of the neurological clinic of Pitres in the heyday, we illustrate this article with unpublished photos of him.

Oligoclonal Band Straightening Based on Optimized Hierarchical Warping for Multiple Sclerosis Diagnosis.

The detection of immunoglobulin G (IgG) oligoclonal bands (OCB) in cerebrospinal fluid (CSF) by isoelectric focusing (IEF) is a valuable tool for the diagnosis of multiple sclerosis. Over the last decade, the results of our clinical research have suggested that tears are a non-invasive alternative to CSF. However, since tear samples have a lower IgG concentration than CSF, a sensitive OCB detection is therefore required. We are developing the first automatic tool for IEF analysis, with a view to speeding up the current visual inspection method, removing user variability, reducing misinterpretation, and facilitating OCB quantification and follow-up studies. The removal of band distortion is a key image enhancement step in increasing the reliability of automatic OCB detection. Here, we describe a novel, fully automatic band-straightening algorithm. The algorithm is based on a correlation directional warping function, estimated using an energy minimization procedure. The approach was optimized via an innovative coupling of a hierarchy of image resolutions to a hierarchy of transformation, in which band misalignment is corrected at successively finer scales. The algorithm's performance was assessed in terms of the bands' standard deviation before and after straightening, using a synthetic dataset and a set of 200 lanes of CSF, tear, serum and control samples on which experts had manually delineated the bands. The number of distorted bands was divided by almost 16 for the synthetic lanes and by 7 for the test dataset of real lanes. This method can be applied effectively to different sample types. It can realign minimal contrast bands and is robust for non-uniform deformations.

Oral nomegestrol acetate and transdermal 17-beta-estradiol for preventing post-partum relapses in multiple sclerosis: The POPARTMUS study.

BACKGROUND: Sex steroids could explain the course of multiple sclerosis (MS) in pregnancy. OBJECTIVE: To compare the annualized relapse rate (ARR) 12 weeks post-partum in women treated with nomegestrol acetate (NOMAc) and 17-beta-estradiol (E2) versus placebo. METHODS: POPARTMUS is a randomized, proof-of-concept trial in women with MS, receiving oral NOMAc 10 mg/day and transdermal estradiol 75 µg/week, or placebo. RESULTS: Recruitment was stopped prematurely due to slow inclusions (n = 202). No treatment effect was observed on ARR after 12 weeks (sex steroids = 0.90 (0.58-1.39), placebo = 0.97 (0.63-1.50) (p = 0.79)). CONCLUSION: POPARTMUS failed showing efficacy of a NOMAc-E2 combination in preventing post-partum relapses.

Jacques Jean Lhermitte and Lhermitte's sign.

Jacques Jean Lhermitte, a forefather of modern clinical neurology, was a French neurologist conducting the majority of his research between 1908 and 1957. Although less well known than his contemporaries at the time, Lhermitte eventually was famously recognized for his eponymously named "Lhermitte's sign." Lhermitte's contributions to the field of neurology spanned that of monographic clinical descriptions of syndromes to exquisitely detailed descriptions of neuropathology, finally delving into the realm of modern neuropsychiatry in his later years. Lhermitte laid the groundwork for the burgeoning field of neurology, developing the reputation of a renaissance physician by both his contemporaries and current neurologists. Here, we take an extensive look into the life and career of Lhermitte and the legacies that he left behind.

Hysteria or epilepsy?

Hysteria and epilepsy have long been compounded by the term "hysteria-epilepsy" among neurologists and physchiatrists, including Jean Martin Charcot. In a 114 page unpublished manuscript written circa 1815, Jean-Baptiste Louyer Villermay, French physician and student of Philippe Pinel, considered the signs that would differentiate hysteria from epilepsy. This differential diagnosis approach was proposed long before Charcot's lecture in 1868 at Salpêtrière hospital.

Neuraxial analgesia is not associated with an increased risk of post-partum relapses in MS.

BACKGROUND: Obstetrical analgesia remains a matter of controversy because of the fear of neurotoxicity of local anesthetics on demyelinated fibers or their potential relationship with subsequent relapses. OBJECTIVE: To assess the impact of neuraxial analgesia on the risk of relapse during the first 3 months post-partum, with a focus on women who experienced relapses during pregnancy. METHODS: We analyzed data of women followed-up prospectively during their pregnancies and at least 3 months post-partum, collected in the Pregnancy in Multiple Sclerosis (PRIMS) and Prevention of Post-Partum Relapses with Progestin and Estradiol in Multiple Sclerosis (POPARTMUS) studies between 1992-1995 and 2005-2012, respectively. The association of neuraxial analgesia with the occurrence of a post-partum relapse was estimated by logistic regression analysis. RESULTS: A total of 389 women were included, 215 from PRIMS and 174 from POPARTMUS. In total, 156 women (40%) had neuraxial analgesia. Overall, 24% experienced a relapse during pregnancy and 25% in the 3 months post-partum. Women with a pregnancy relapse were more likely to have a post-partum relapse (odds ratio (OR) = 1.83, p = 0.02), independently of the use of neuraxial analgesia. There was no association between neuraxial analgesia and post-partum relapse (OR = 1.08, p = 0.78). CONCLUSION: Neuraxial analgesia was not associated with an increased risk of post-partum relapses, whatever multiple sclerosis (MS) activity during pregnancy.

The Practice of Sport in Multiple Sclerosis: Update.

The practice of sport by multiple sclerosis patients has long been controversial. Recent studies, however, show that both sport and physical activity are essential for these patients. Indeed, they help to cope with the effects of multiple sclerosis, such as fatigue, reduced endurance, loss of muscle mass, and reduction of muscle strength. The beneficial effects of physical activity on these patients have been underlined in several studies, whereas those of practicing sport have been the subject of fewer evaluations and assessments. The aim of this update is to report on the effects of sport on multiple sclerosis patients. The benefits of sport have been demonstrated in several studies. It helps multiple sclerosis patients to increase their balance, resistance to fatigue, mobility and quality of life. Several biases in these studies do not enable us to recommend the practice of some of these sports on a routine basis.

Social participation in patients with multiple sclerosis: correlations between disability and economic burden.

BACKGROUND: Economic costs related to treatment of multiple sclerosis (MS) must be justified by health state, quality of life (QOL) and social participation improvement. This study aims to describe correlations between social participation, economic costs, utility and MS-specific QOL in a sample of patients with MS (pwMS). METHODS: We interviewed 42 pwMS receiving natalizumab and collected clinical data, direct medical costs, productivity loss, utility (EQ5D-VAS), MS-specific QOL (SEP-59), social participation with the Impact on Participation and Autonomy questionnaire (IPA). We performed descriptive and correlation analyses. RESULTS: 41 pwMS, with a mean Expanded Disability Status Scale (EDSS) score of 4.0, completed questionnaires. Mean annual global cost per patient was 68448 +/-33374 Euros and increased with EDSS (r = 0.644), utility (r = -0.456) and IPA (r = 0.519-0.671) worsening. Mean utility was 0.52 +/- 0.28. Correlations between IPA and QOL (EQ5D-VAS or SEP-59) were observed (r = -0.53 to -0.78). Association between QOL and EDSS was smaller (EQ5D-VAS) or absent. Productivity losses were poorly correlated to EDSS (r = 0.375). CONCLUSION: Moderate to strong correlations of social participation with clinical status (EDSS), QOL, utility and economic costs encourage exploring better these links in larger cohorts. The stronger correlation between social participation and QOL than between EDSS and QOL needs to be confirmed.

Who was the first to visualize the malaria parasite?

Human malaria, an ancient tropical disease, is caused by infection with protozoan parasites belonging to the genus Plasmodium and is transmitted by female mosquitoes of the genus Anopheles. Our understanding of human malaria parasites began officially in 1880 with their discovery in the blood of malaria patients by Charles Louis Alphonse Lavéran (1845-1922), a French army officer working in Algeria. A claim for priority was made by Philipp Friedrich Hermann Klencke (1813-1881) in 1843, who wrote a chapter entitled: "Marvellous parallelism between the manifestations of vertigo and the presence of animalcule vacuoles in living blood." We should not lose sight of this old controversy, which is rarely mentioned in historical reviews on malaria.

125 years of the Wertheim operation. What next?

The Austrian gynecologist Ernst Wertheim (1864-1920) was a pioneer in the surgical treatment of cancer. The principle of Wertheim's hysterectomy was to remove the uterus and the cervix with appropriate parametrium and tissues surrounding the upper vagina and pelvic lymph nodes. However, in the early 2000s, a meta-analysis of randomized trials revealed that radiotherapy and concomitant chemotherapy without surgical removal of the uterus were more effective in the historical treatment of advanced cervical cancer. This finding challenged the use of radical abdominal hysterectomy (RAH) in such cases and demonstrated the superiority of radiotherapy and chemotherapy in terms of overall survival.

Assessing cognitive changes in multiple sclerosis: criteria for a reliable decision.

INTRODUCTION: Quantifying a significant cognitive change on a neuropsychological battery is essential to assess patients' decline or recovery and offer appropriate care. The reliability of change indices is particularly important in multiple sclerosis (MS), as the course of cognitive impairment is quite unpredictable, due at least in part to substantial interindividual variability. The main objective of this study was to compare six different methods for assessing cognitive change in an MS sample: the SD method, two reliable change indices, two standardized regression-based methods (SRB), and the generalized regression-based method (GSRB). METHOD: One hundred and twenty-three patients with clinically definite MS and 89 healthy controls underwent a battery of standardized neuropsychological tests assessing cognitive functions that are frequently affected in this disease (i.e., verbal episodic memory, working memory, processing speed and verbal fluency). RESULTS: We observed fairly similar proportions of improvement, decline or stability in the control group whatever the method. By contrast, in the MS sample, regression-based methods with one predictor (i.e., score at T1) and four predictors (i.e., score at T1 and demographic factors: age, sex, education level) detected a significant worsening more often than the reliable change indices while the GSRB method was more consistent with the RCI methods in tasks associated with ceiling effects. CONCLUSIONS: The interpretation of a patient's cognitive changes depends on which method is used. The (G)SRB methods appear to be relevant indicators for assessing cognitive change in MS. The addition of demographic factors does not seem to play an important role in the prediction of significant worsening in the MS sample, regardless of cognitive domain. For clinicians, an easy-to-use free shiny app is provided.

Tear analysis in clinically isolated syndrome as new multiple sclerosis criterion.

In clinically isolated syndrome (CIS), the detection of oligoclonal bands (OCBs) in cerebrospinal fluid (CSF) is critical for space dissemination validation when magnetic resonance imaging (MRI) diagnostic criteria are not fulfilled. However, lumbar puncture for CSF collection is considered relatively invasive. Previous studies have demonstrated applicability of OCB detection in tears to the diagnosis of multiple sclerosis (MS). The objective of the present study was to assess concordance between OCB detection in tears and in CSF. We have prospectively included patients with CIS and compared results of CSF and tear OCB detection by isoelectric focusing (IEF). Tears were collected using a Schirmer strip. We included 82 patients. For 69 of them, samples were analysable. OCBs were detected in CSF for 63.8% and in tears for 42% of patients. All patients with tear OCBs had CSF OCBs. We suggest that tear OCB detection may replace CSF OCB detection as a diagnostic tool in patients with CIS. This would circumvent the practice of invasive lumbar punctures currently used in MS diagnosis.

Toward an automatic tool for oligoclonal band detection in cerebrospinal fluid and tears for multiple sclerosis diagnosis: lane segmentation based on a ribbon univariate open active contour.

The latest revision of multiple sclerosis diagnosis guidelines emphasizes the role of oligoclonal band detection in isoelectric focusing images of cerebrospinal fluid. Recent studies suggest tears as a promising noninvasive alternative to cerebrospinal fluid. We are developing the first automatic method for isoelectric focusing image analysis and oligoclonal band detection in cerebrospinal fluid and tear samples. The automatic analysis would provide an accurate, fast analysis and would reduce the expert-dependent variability and errors of the current visual analysis. In this paper, we describe a new effective model for the fully automated segmentation of highly distorted lanes in isoelectric focusing images. This approach is a new formulation of the classic parametric active contour problem, in which an open active contour is constrained to move from the top to the bottom of the image, and the x-axis coordinate is expressed as a function of the y-axis coordinate. The left and right edges of the lane evolved together in a ribbon-like shape so that the full width of the lane was captured reliably. The segmentation algorithm was implemented using a multiresolution approach in which the scale factor and the active contour control points were progressively increased. The lane segmentation algorithm was tested on a database of 51 isoelectric focusing images containing 419 analyzable lanes. The new model gave robust results for highly curved lanes, weak edges, and low-contrast lanes. A total of 98.8% of the lanes were perfectly segmented, and the remaining 1.2% had only minor errors. The computation time (1 s per membrane) is negligible. This method precisely defines the region of interest in each lane and thus is a major step toward the first fully automatic tool for oligoclonal band detection in isoelectric focusing images. Graphical abstract.

Socioeconomic deprivation increases the risk of disability in multiple sclerosis patients.

BACKGROUND: Little is known about the association between the socioeconomic status (SES) and disability risk of patients with Multiple Sclerosis (MS). OBJECTIVE: The aim of this study was to assess the influence of low SES, otherwise known as socioeconomic deprivation, on the disability risk of MS patients. METHODS: 4498 patients with a relapsing MS disease onset between 1982 and 2017 were included from the databases of three MS expert centres (Caen, Rouen, Lille) of the French Observatory for MS (OFSEP). Sociodemographic and clinical data of 3641 patients were used for the analysis. The EDI (European Deprivation Index), an ecological and composite indicator was used to assess the level of socioeconomic deprivation. Comparisons of time to reach EDSS 4 and EDSS 6, chosen as disability milestones, according to EDI quintiles were performed by Kaplan-Meier analysis. Cox proportional hazard models were also conducted to assess the risk according to EDI quintiles with adjustment to sex, MS type and age at disease onset. RESULTS: In the study population (n = 3641), most patients were women (71.9%; n = 2664). The mean age at disease onset was 32.2 years (SD =9.7). 1684 (46%) patients reached EDSS 4 and 1005 (28%) reached EDSS 6. The risk of reaching EDSS 4 and EDSS 6 in more socioeconomically deprived patients (EDI Q5) was independently higher than in the less socioeconomically deprived patients (EDI Q1) (HR=1.37 95%CI [1.15-1.64]) to reach EDSS 4 and (HR=1.42 95%CI [1.13-1.75]) to reach EDSS 6. CONCLUSIONS: In this study, socioeconomic deprivation was significantly associated to the disability risk in MS patients. Better knowledge of socioeconomic disparities in MS may help adapt care to settings and improve the quality of care given to patients in the future.

Evaluation of emotional disorders before and during treatment with interferon beta in patients with multiple sclerosis.

BACKGROUND: Domains encompassing emotional disorders in relapsing-remitting MS (RRMS) patients are still unclear. METHODS: We performed a 24-month, multicenter, single-arm, prospective study. RRMS patients started IFN-ß treatment at baseline. The primary endpoint was lack of emotional control, measured using the "Echelle d'HumeurDépressive" (EHD) scale three times at baseline and at 10 post-treatment visits. Secondary endpoints were emotional blunting, irritability, fatigue, depression and anxiety. A linear mixed covariance model assessed change from baseline on an intention-to-treat basis, under the assumption of no mood disorder effect (one-sided 97.5% level), in which autoregressive type of autocorrelation was tested. RESULTS: Out of 79 recruited patients, 70 were analyzed: 80% female; mean (SD) age, 37.0 (11.5) years. Mean (SD) lack of emotional control score at baseline and Month 24 was 12.7 (4.4) and 12.6 (5.5), respectively, versus 10.1 (3.2) in a healthy control population matched for age and sex. Stepwise analysis identified younger age, male sex and antidepressant use as significant predictors of higher lack of emotional control values. CONCLUSIONS: Based on 24 months of prospective follow-up, the results of this study highlights a broad spectrum of emotional disorders in the MS population at the time of disease modifying drugs initiation but no major IFN-ß-related emotional disorders (mood dyscontrol, anxiety, depression) were observed. However, sporadic occurrences of severe mood disorders and suicidality cannot be excluded.