Drug-induced sarcoidosis: an overview of the WHO pharmacovigilance database.

BACKGROUND: There is a documented association between drug exposure and sarcoidosis-like reactions. In this study, we used the largest pharmacovigilance database to describe drug-induced sarcoidosis. METHODS: Data were collected from the World Health Organization (WHO) pharmacovigilance database (VigiBase). We excluded steroids and vaccines from the analysis. The primary end-point was the lower end-point of the 95% credibility interval for the information component (IC025 ). RESULTS: A total of 127 reports had significant IC025 values for drug-induced sarcoidosis, and 110 were included in the final analysis, accounting for 2425 adverse drug reactions. Overall, 2074 (85.5%) reactions were considered 'serious' and 86 (3.5%) were fatal. Most of the drugs that led to sarcoidosis adverse reactions were TNF-alpha antagonists, interferon or peg-interferon therapeutics, and immune checkpoint inhibitors. Other biologic drugs were less frequently associated with sarcoidosis adverse events. Cancer-targeted therapies such as BRAF or MEK inhibitors were associated with sarcoidosis reactions in 37 cases. Pulmonary hypertension drugs were also reported for drug-induced sarcoidosis. Amongst the 55 drugs considered as potential sarcoidosis inducers, 25 (45.4%) were never reported in Medline as drug-induced sarcoidosis. CONCLUSIONS: We provide a detailed list of suspected drugs associated with drug-induced sarcoidosis that will improve the recognition of this drug-induced adverse event.

The cerebrospinal fluid CD4/CD8 ratio and interleukin-6 and -10 levels in neurosarcoidosis: a multicenter, pragmatic, comparative study.

BACKGROUND AND PURPOSE: Neurosarcoidosis is a rare inflammatory disorder of unknown cause. The aim of this study was to evaluate the value of T/B lymphocyte population counts and the concentrations of the cytokines interleukin (IL) 6 and IL-10 in the cerebrospinal fluid (CSF) of neurosarcoidosis patients. METHODS: A retrospective study CSF biomarkers was conducted in patients with neurosarcoidosis who underwent CSF analysis between 2012 and 2017 as well as various control populations. RESULTS: Forty-three patients with neurosarcoidosis, 14 with multiple sclerosis (MS) and 48 with other inflammatory disorders were analyzed. The CSF IL-6 levels were higher in sarcoidosis patients than in MS patients (median 8 vs. 3 pg/ml, P = 0.006). The CSF CD4/CD8 ratio was higher in sarcoidosis patients than in MS patients and in patients with other inflammatory disorders (median 3.18 vs. 2.36 and 2.10, respectively, P = 0.008). The CSF IL-6 level was higher in patients with active neurosarcoidosis than in non-active neurosarcoidosis patients (median 13 vs. 3 pg/ml, P = 0.0005). In patients with neurosarcoidosis, a CSF IL-6 concentration >50 pg/ml was associated with a higher risk of relapse or progression-free survival (hazard ratio 3.60; 95% confidence interval 1.78-23.14). A refractory neurosarcoidosis patient was treated with an anti-IL-6 monoclonal antibody that produced a complete neurological response. CONCLUSIONS: The CSF CD4/CD8 ratio and IL-6 concentration are increased in neurosarcoidosis compared to MS and other inflammatory disorders. A CSF IL-6 concentration >50 pg/ml is associated with relapse or progression of neurosarcoidosis. IL-10 levels may be elevated in neurosarcoidosis.

[Association between students' clinical performance and their success in the computerized national ranking tests: A single-center retrospective cohort study]. / Association entre les performances cliniques des étudiants et leur réussite aux Épreuves classantes nationales informatisées : une étude de cohorte rétrospective monocentrique.

INTRODUCTION: Before attending residency, 6th-year French medical students must validate a final examination including a practical clinical test in their faculty. However, the national ranking that determines their future specialty and region solely relies on a computerized knowledge test. Our goal was to investigate the association between the final faculty test and the national ranking test. METHODS: In our faculty, the final examination includes a computerized theoretical test (similar to the national one) and a practical test: a standardized evaluation of semiology skills at the bedside and a standardized assessment of relational skills with role plays. The agreements between the national test and faculty computerized and practical tests were analyzed by intraclass correlation coefficients (ICC). RESULTS: Data from 1806 students who underwent the three examinations from 2017 to 2021 were analyzed. There was a good agreement between the ranks in the faculty and national computerized tests: ICC 0.83 (95% CI 0.81-0.85). By contrast, the agreement between the ranks in the faculty practical test and the national computerized test was poor: ICC 0.13 (95% CI 0.08-0.17). Results were stable over the years. CONCLUSION: The agreement between the ranking of the current national test and the clinical skills assessed by a specific faculty test is poor. This could relate to a true independence or to different levels of motivation to perform well. Indeed, the result of the national test is the most important one as it determines their career. Incorporating a clinical assessment into the national ranking test will motivate students to acquire clinical skills and value those who perform well this practical dimension.

[Splenic lymphoma, diagnosis and treatment]. / Lymphomes spléniques : diagnostic et prise en charge.

Some common clinical situations, such as splenomegaly or lymphocytosis, or less common, such as autoimmune hemolytic anemia, cold agglutinin disease, or cryoglobulinemia can lead to the diagnosis of splenic lymphoma. Splenic lymphoma is rare, mainly of non-hodgkinian origin, encompassing very different hematological entities in their clinical and biological presentation from an aggressive form such as hepato-splenic lymphoma to indolent B-cell lymphoma not requiring treatment such as marginal zone lymphoma, the most frequent form of splenic lymphoma. These entities can be challenging to diagnose and differentiate. This review presents different clinical and biological manifestations suspicious of splenic lymphoma and proposes a diagnosis work-up. We extended the strict definition of splenic lymphoma (lymphoma exclusively involving the spleen) to lymphoma thant can be revealed by a splenomegaly and we discuss the differential diagnosis of splenomegaly.

Isolated CNS Sarcoidosis Versus Systemic Sarcoidosis With CNS Involvement: A Same Disease?

Neurological involvement occurs in 5 to 15% of patients with sarcoidosis. It rarely represents the sole manifestation of the disease, a condition called isolated neurosarcoidosis. Objectives: To describe patients with definite isolated central neurosarcoidosis. To compare their characteristics to a group of systemic sarcoidosis with central neurologic involvement. Methods: Monocentric retrospective study of all patients presenting with central neurosarcoidosis (NS) over a 10 year period, subsequently divided into 2 groups: isolated neurosarcoidosis (INS) and systemic neurosarcoidosis (SNS). Results: We report 10 cases of INS and subsequently, we compared their characteristics to a group of 30 patients with SNS. INS patients exhibited brain parenchymal involvement (8/10), meningeal disease (8/10), myelitis (3/10), cranial neuropathy (3/10), neuroendocrine impairment (1/10). Cerebro-spinal fluid (CSF) analysis was conducted in 8/10 patients and showed pleocytosis in 6/8 (75%), elevated protein level in (4/8) 50%, oligoclonal intrathecal synthesis in 1/5 (20%). All patients received steroids, 7/10 (70%) required associated immunosuppressive therapy, 5 of which TNFα inhibitors. When compared to patients with SNS, INS patients were more likely to experience seizures (60% vs 23.3%); display encephalic parenchymal enhancing lesions (80% vs 39.3%) or encephalic leptomeningeal involvement (80% vs 35.7%). Serum angiotensin converting enzyme (ACE) was elevated in a third of patients with SNS but none of those with INS. Conclusion: The phenotypes of patients with INS are similar to the ones described in SNS. Serum ACE should not be regarded as a diagnostic test in patients with isolated neurosarcoidosis but could be useful in detecting subclinical extra neurologic involvement during follow up.

Off-label use of biologics for the treatment of refractory and/or relapsing granulomatosis with polyangiitis.

OBJECTIVE: To describe the efficacy and safety of off-label use of biologics for refractory and/or relapsing granulomatosis with polyangiitis (GPA). METHODS: We conducted a French retrospective study including GPA patients who received off-label biologics for refractory and/or relapsing disease after failure of conventional immunosuppressive regimens. RESULTS: Among 26 patients included, 18 received infliximab (IFX), 2 adalimumab (ADA) and 6 abatacept (ABA). Biologics were initiated in median as 4th-line therapy (IQR 3-6) for relapsing and/or refractory disease in 23 (88%) and/or significant glucocorticoid-dependency in 8 cases (31%). At biologics initiation, median (IQR) BVAS and prednisone dose in anti- TNF-α and ABA recipients were 7 (3-8) and 2 (1-6), and 20 (13-30) mg/day and 20 (15-25) mg/day, respectively. Clinical manifestations requiring biologics were mainly pulmonary and ENT manifestations in 58% each. Anti-TNF-α and ABA were continued for a median duration of 8 months (IQR 6-13) and 11 months (IQR 6-18) respectively. Anti-TNF-α recipients showed remission, partial response and treatment failure in 10%, 30% and 60% at 6 months, and 25%, 20% and 55% at 12 months, respectively. ABA recipients showed remission, partial response and treatment failure in 17%, 33% and 50% at 6 months and 17%, 33% and 50% at 12 months. One patient treated with IFX experienced life-threatening reaction while one patient treated with ABA experienced a severe infection. CONCLUSION: This real-life study suggests that off-label use of anti-TNF-α and abatacept shows efficacy in less than 50% of refractory and/or relapsing GPA.

Are script concordance tests suitable for the assessment of undergraduate students? A multicenter comparative study.

INTRODUCTION: Script concordance tests (SCTs) have been developed to assess clinical reasoning in uncertain situations. Their reliability for the evaluation of undergraduate medical students has not been evaluated. METHODS: Twenty internal medicine SCT cases were implemented in undergraduate students of two programs. The results obtained on the SCTs were compared to those obtained by the same students on clinical-based classical multiple-choice questions (MCQs). RESULTS: A total of 551/883 students (62%) answered the SCTs. The mean aggregate score (based on a total 20 points) was 11.54 (3.29). The success rate and mean score for each question did not differ depending on the modal response but the discrimination rate did. The results obtained by the students on the SCT test correlated with their scores on the MCQ tests. Among students, 446/517 (86%) considered the SCTs to be more difficult than classical MCQs, although the mean score did not differ between the SCT and MCQ tests. CONCLUSION: The use of SCTs is a feasible option for the evaluation of undergraduate students. The SCT scores correlated with those obtained on classical MCQ tests.

[Infection associated cerebral vasculitis]. / Vascularites cérébrales associées aux infections.

Infections are a frequent cause of cerebral vasculitis, important to diagnose because a specific treatment may be required. Infection-associated vasculitis can be caused by angiotropic pathogens (varicella zoster virus, syphilis, aspergillus). They can be associated with subarachnoidal meningitis (tuberculosis, pyogenic meningitis, cysticercosis). They can appear contiguously to sinuses or orbital infection (aspergillosis, mucormycosis). Finally, they also may be due to an immune mechanism in the context of chronic infections (hepatitis B virus, hepatitis C virus, human immunodeficiency virus). Cerebral vasculitis are severe conditions and their prognosis is directly linked to early recognition and diagnosis. Infectious causes must therefore be systematically considered ahead of cerebral vasculitis, and the appropriate investigations must be determined according to the patient's clinical context. We propose here an update on the infectious causes of cerebral vasculitis, their diagnosis modalities, and therapeutic options.

Progressive clinical case-based multiple-choice questions: An innovative way to evaluate and rank undergraduate medical students.

INTRODUCTION: In France, at the end of the sixth year of medical studies, students take a national ranking examination including progressive clinical case-based multiple-choice questions (MCQs). We aimed to evaluate the ability of these MCQs for testing higher-order thinking more than knowledge recall, and to identify their characteristics associated with success and discrimination. METHODS: We analysed the 72 progressive clinical cases taken by the students in the years 2016-2019, through an online platform. RESULTS: A total of 72 progressive clinical cases (18 for each of the 4 studied years), corresponding to 1059 questions, were analysed. Most of the clinical cases (n=43, 60%) had 15 questions. Clinical questions represented 89% of all questions, whereas basic sciences questions accounted for 9%. The most frequent medical subspecialties were internal medicine (n=90, 8%) and infectious diseases (n=88, 8%). The most frequent question types concerned therapeutics (26%), exams (19%), diagnosis (14%), and semiology (13%). Level 2 questions ("understand and apply") accounted for 59% of all questions according to the Bloom's taxonomy. The level of Bloom's taxonomy significantly changed over time with a decreasing number of level 1 questions ("remember") (P=0.04). We also analysed the results of the students among 853 questions of training ECNi. Success and discrimination significantly decreased when the number of correct answers increased (P<0.0001 both). The success, discrimination, mean score, and mean number of discrepancies did not differ according to the diagnosis, exam, imaging, semiology, or therapeutic type of questions. CONCLUSION: Progressive clinical case-based MCQs represent an innovative way to evaluate undergraduate students.

[Use of targeting therapy in Erdheim-Chester disease: A case report with neurologic involvement]. / Utilisation de thérapie ciblée dans la maladie d'Erdheim-Chester : à propos d'un cas avec atteinte du système nerveux central.

INTRODUCTION: Erdheim-Chester disease (ECD) is a rare multisystemic disease characterised by an infiltration of various organs by CD68+ CD1a- histiocytes. The clinical and radiological presentation is very variable. CASE REPORT: We report the case of a 71-year-old woman with ECD which was revealed by neurological and cutaneous manifestations. The diagnosis was confirmed by skin biopsy and the BRAFV600E mutation was identified in skin tissue, leading to the use of combined therapy targeting the RAS-RAF-ERK-MEK pathway. This therapy allowed an improvement of cutaneous manifestations but neurological manifestations lead to death, underlying their notable severity. CONCLUSION: Our case report shows the persistent diagnostic difficulty of the ECD and the particular gravity of neurologic involvement.

Diagnosis issues in sarcoidosis.

Multiple problems may be encountered during the diagnosis of sarcoidosis: at first diagnose sarcoidosis in an appropriate clinical setting, secondly, identify any manifestation to be linked to sarcoidosis at diagnosis work-up and during evolution; thirdly, recognize "danger" in sarcoidosis and parasarcoidosis syndromes, and finally, diagnose sarcoidosis recovery. Diagnosis is often delayed as presentation may be diverse, non-specific, or atypical. Diagnosis of sarcoidosis is based on three criteria: a compatible presentation; evidence of non-caseating granulomas and exclusion of any alternative diagnosis. However, even when all criteria are fulfilled, the probability of sarcoidosis diagnosis varies from definite to only possible depending upon the presence of more or less characteristic radio-clinical and histopathological findings and on the epidemiological context. Bilateral hilar lymphadenopathy and/or diffuse lung micronodules mainly along lymphatics are the most frequent highly suggestive findings. Evidence of granulomas relies on superficial biopsies of clinically suspected lesion when present or most often by bronchial endoscopy. The diagnosis of sarcoidosis may be difficult in absence of thoracic or skin manifestations and may require the benefit of hindsight before being definitive. Differential diagnoses, mainly tuberculosis, must be considered. The diagnosis of events during evolution relies on serial clinical, pulmonary function, radiographic evaluation and on extrapulmonary manifestations work-up, including electrocardiogram and blood biology. Affected organs need to be related to sarcoidosis using an appropriate diagnostic assessment instrument. To declare the recovery of sarcoidosis, all manifestations must have disappeared spontaneously or after 3-5 years post-treatment without relapse.

[Reliability and validity of a workbook for assessment of professional competencies of internal medicine residents]. / Évaluation multicentrique de la reproductibilité et de la validité d'un carnet d'évaluation des compétences professionnelles des internes de médecine interne.

INTRODUCTION: Though several assessment tools for resident professional skills based on workplace direct observation have been validated, they remain scarcely used in France. The objective of this study was to evaluate the reliability and the validity of a workbook including several assessment forms for different components of the professional competency. METHODS: Three assessment forms have been tested over a period of 6 months in a multicentric study including 12 French internal medicine departments: the French version of the mini-CEX, an interpersonal skills assessment form (OD_CR) and the multisource feedback form (E_360). Reliability has been assess using the intra-class correlation coefficient (ICC) and the Cronbach alpha coefficient. Arguments for validity have been provided looking at the ability of the forms to detect an increase in the scores over time and according to the level of experience of the resident. RESULTS: Twenty-five residents have been included. The Cronbach alpha was of 0.90 (n=70) with the mini-CEX, 0.89 with the OD_CR (n=62) and 0.77 with the E_360 (n=86). ICC showed a wide variation according to the items of the mini-CEX and the OD-CR probably due to the poor number of observations performed by residents. The scores of most of the items of these two forms increased between M1 and M6. The scores of the E_360 were high: 7.3±0.8 to 8.3±2.4 (maximum 9) and did not vary according to the level of experience. CONCLUSION: This study suggest that it would be difficult to ensure a sufficient reliability for professional skills assessment using these tools given our available current human and material resources. However, these assessment forms could be added to the resident portfolio as supports for the debriefing in order to document their progression during their formation.

[Coronary involvement and nephrotic syndrome in systemic lupus: A case report]. / Atteinte coronarienne et syndrome néphrotique au cours du lupus systémique : à propos d'une observation.

INTRODUCTION: Heart failure during systemic lupus erythematosus has various causes. CASE REPORT: A 29-year-old female presented with a systemic lupus flare and a nephrotic syndrome, followed by cardiogenic shock requiring extra-corporeal membranous oxygenation. Ventricular dysfunction was related to massive myocardial infarction due to an anterior interventricular artery thrombosis and an underlying atheroma. The young age and the absence of chest pain were not suggestive of coronary artery disease initially. Coronary thrombosis was probably favored by the nephrotic syndrome, in which the arterial thrombotic risk is increased. CONCLUSION: Coronary artery disease should be systematically evoked in the presence of ventricular dysfunction in patients with systemic lupus, including when they are young and in the absence of chest pain. Nephrotic syndrome should be identified as a risk factor for arterial thrombosis.

[Acute pericarditis in the modern era: a diagnostic challenge]. / La péricardite aiguë en 2007: un défi diagnostique.

BACKGROUND: Diagnosis of acute pericarditis remains difficult in clinical practice. OBJECTIVES: The purpose of this study was to evaluate the clinical and biological features of patients presenting with acute pericarditis, and to determine the incidence and significance of troponin I (cTnI) elevation in that context. PATIENTS AND METHODS: We retrospectively included 55 patients with acute idiopathic pericarditis. We analyzed clinical presentation, ECG recordings, biologic results, echocardiography findings and cTnI level. RESULTS: Fifty-five consecutive patients (41 men, 54+/-18 years) with idiopathic acute pericarditis were included. There was a typical chest pain in 90% of cases, whereas fever and pericardial friction rub were present in 25 and 18%, respectively. ST-segment elevation was observed in 58% of the patients. A rise of cTnI and C-reactive protein was detectable in 27 and 78% of cases respectively. The following characteristics were more frequently associated with a positive cTnI test: younger patients, recent infection and higher length-of-stay. Pericardial effusion was observed in 58% of patients. Cardiac tamponade and ventricular tachycardia both occurred in 3 patients (5%). After a mean follow-up of 33 months, recurrent pericarditis occurred in 13% of patients. A similar rate of complications was found in patients with a positive or a negative cTnI. CONCLUSION: Clinical spectra of acute pericarditis have changed and some classic assumptions and descriptions, perpetuated in some publications, are outdated. Clinical presentation implies a 45-55 year-old man, with a chest pain and ST-segment elevation, without fever or pericardial friction rub, and a positive cTnI test in 27% of cases. Therefore, misinterpretation as other disease, especially acute myocardial infarction, is common and diagnosis of acute pericarditis remains often retrospective. In our series, a cTnI rise did not appear as a negative prognostic marker.

[Rosai-Dorfman disease: Diagnosis and therapeutic challenges]. / La maladie de Destombes-Rosai-Dorfman : évolution du concept, classification et prise en charge.

Rosai-Dorfman disease (RDD) was first described by the French pathologist Paul Destombes in 1965. It frequently affects children or young adults and is characterized by the presence of large histiocytes with emperipolesis. More than 50 years after this first description, the pathogenesis of this rare disease is still poorly understood. The revised classification of histiocytoses published in 2016 identified various forms of RDD, from familial RDD to IgG4-associated RDD. Almost 90% of the patients with RDD have cervical lymph nodes involvement although all the organs may virtually be involved. Outcomes are typically favorable. Treatments may be necessary in case of compression or obstruction, and are not well codified. The main therapeutic strategies rely on surgery, radiotherapy, steroids, immunosuppressive drugs or interferon-alpha and cladribine.

[Validity and reproducibility of two direct observation assessment forms for evaluation of internal medicine residents' clinical skills]. / Validité et reproductibilité de deux grilles d'observation des compétences cliniques des internes en DES de médecine interne.

INTRODUCTION: The revision of the French medical studies' third cycle ought to be competency-based. In internal medicine, theoretical and practical knowledge will be assessed online with e-learning and e-portfolio. In parallel, a reflection about clinical skills assessment forms is currently ongoing. In this context, our aim was to assess the reproducibility and validity of two assessment forms based on direct clinical observation. METHOD: A prospective and multicentric study has been conducted from November 2015 to October 2016 aiming at evaluating the French translations of the MINI-Clinical Examination Exercice (MINI-CEX) and the Standardized Patient Satisfaction Questionnaire (SPSQ). Included residents have been assessed 2 times over a period of 6 months by the same binoma of judges. RESULTS: Nineteen residents have been included. The inter-judge reproducibility was satisfactory for the MINI-CEX: intraclass coefficients (ICC) between 0.4 and 0.8 and moderate for the SPSQ: ICC between 0.2 and 0.7 with a good internal coherence for both questionnaires (Cronbach between 0.92 and 0.94). Significant differences between the distributions of the scores given by the judges and a significant inter-center variability have been found. CONCLUSION: If the absolute value of the scores should not be taken into account in the evaluation process given its high variability, it could be of interest for the follow-up of the progression in the competencies. These forms could support the residents' debriefing based on the general trends given by the scores.

[Subclinical hypothyroidism: a cardiovascular risk factor?]. / L'hypothyroidie infracinique: facteur de risque cardiovasculaire?

Although patent hypothyroidism is clearly associated with increased cardiovascular risk, the relationship between infraclinical hypothyroidism and cardiovascular disease remains controversial though probable. This relationship is mediated by the traditional risk factors (lipids, hypertension), by changes in parameters of inflammation and haemostasis, and by a direct effect of thyroid hormones on the vessel wall. The authors review the epidemiological evidence and the mechanisms underlying the association between infraclinical hypothyroidism and cardiovascular risk and the therapeutic implications of this association.

[Prevalence of sleep apnea in men with metabolic syndrome and controlled hypertension]. / Prévalence et déterminants du syndrome d'apnée du sommeil chez des hommes ayant un syndrome métabolique et une hypertension artérielle contrôlée.

BACKGROUND: Abdominal obesity and high blood pressure (HBP) are known to be associated with sleep apnea syndrome (SAS). Resistant hypertension commonly leads physicians to prescribe a sleep record because the prevalence of SAS is high in patients with resistant hypertension. Data on the prevalence of SAS in patients with treated and controlled hypertension are lacking. Moreover, while the metabolic syndrome (MS) and insulin resistance frequently occur in association with SAS, few studies have evaluated the prevalence of SAS in patients with MS. Epworth sleepiness scale (ESS) is often proposed to identify patients at high risk for sleep disorders and for which a sleep record should be prescribed. The reliability of this test to identify SAS has not been studied in patients with MS. OBJECTIVES: (i) To assess the prevalence of SAS in men with MS, (ii) to study the relationship between controlled hypertension and SAS in patients with MS, (iii) to assess the reliability of the ESS to diagnose SAS in patients with MS. METHODS: Among 135 men hospitalized for MS, the 125 who had no history of SAS were systematically evaluated by a nocturnal polygraphy was systematically performed in the 125 men without known SAS at the admission. An excessive daytime sleepiness was assessed by the ESS. Results of analyses in patients with controlled HBP (<130/85 mmHg with antihypertensive drug(s), n=41) were compared with those in patients with normotension (<130/85 mmHg without treatment, n=32). RESULTS: The prevalence of SAS (apnea-hypopnea index (AHI) >or=15/h) in men with MS was 44% in the whole population, 28.1% in the subgroup of patients with normotension and 61.0% in patients with treated and controlled HBP. A severe SAS (AHI >or=30/h) was respectively present in 6.3% and 34.1% of patients with normotension and controlled HTA (p<0.01). Compared with patients without SAS, those with SAS displayed higher blood pressure and BMI. Logistic regression analysis showed that controlled HTA was a determinant of SAS which persisted after adjustment for BMI. As suggested by the ROC curve, the ESS is not a good tool to identify patients with SAS. With a threshold of 11/24 the positive and negative values of this scale were of 0.20 and 0.47. CONCLUSION: The prevalence of SAS is high in men with MS. The ESS does not identify patients who should undergo a nocturnal record. Because a severe SAS is found in nearly one third of patients with MS and controlled HBP, we suggest that a nocturnal record should be systematically proposed to these patients irrespective of the degree of daytime sleepiness assessed by questionnaires.

[Cystathionine betasynthase and MTHFR deficiencies in adults]. / Déficit en cystathionine bêta-synthase et déficit en MTHFR chez l'adulte.

INTRODUCTION: Homocysteine lies at an important metabolic branch point; it may be either converted to cystathionine through the transsulfuration pathway, or methylated to form methionine. Hyperhomocysteinemia may result from hereditary defects affecting one of these reactions. STATE OF ART: Cystathionine beta synthase or 5,10-methylenetetrahydrofolate deficiency can both result in homocystinuria. Current knowledge about biochemical mechanisms leading to hyperhomocysteinemia, clinical and radiological features, pathogenesis and treatment are reviewed, focusing on late onset forms of these diseases which can be diagnosed in adulthood. CBS deficiency is characterized by lens dislocation, skeletal abnormalities, neurologic disturbances and thromboembolism. MTHFR deficiency leads to various neurological symptoms, ranging from developmental delay to encephalopathy, including motor and gait abnormalities, seizures, psychiatric manifestations and rarely strokes. The treatment of CBS deficiency depends on vitamin B6, whereas MTHFR deficiency can be efficiently treated by vitamin B12, folic acid, and betaine. PERSPECTIVES: Homocysteinemia should be measured in patients with unexplained neurological manifestations or thromboembolism.