Chronic pain characteristics in COVID-19 survivors after an ICU stay. A cross-sectional study.

BACKGROUND: The onset and characteristics of chronic pain following an intensive care unit (ICU) stay for COVID-19 have never been thoroughly investigated. STUDY DESIGN: A multicenter cohort study was conducted to describe chronic pain, according to ICD-11, among COVID-19 survivors. The chronic pain was assessed during face-to-face consultations with a pain specialist. RESULTS: Among 204 COVID-19 ICU survivors, 143 patients with mean age of 60 ± 14 years were included nine months after discharge from the ICU. More than half (54%) of patients experienced new-onset chronic pain. In total, 102 different forms of pain were reported in these patients. Secondary pain was the most frequent type, comprising musculoskeletal (40%), post-traumatic (34%), neuropathic (25%), and visceral (13%). Primary chronic pain was rare (7%). The three most common sites of pain were the shoulders, chest, and head. Pain was moderate to severe in 75% of cases, and higher intensity was associated with a greater impact on daily life. Anxiety, depression, post-traumatic stress, perceived stress, and debilitating pain were frequently associated. Intubation was more frequent in patients with chronic pain. Specialized pain centre follow-up was required for 21% of the survivors, which represented 40% of the patients who developed new-onset chronic pain. CONCLUSION: New-onset chronic pain is common after an ICU stay for COVID-19 and may manifest in various forms. Secondary pain caused by ICU management is the most frequent. Patients should undergo screening after ICU discharge to facilitate prompt, thorough, and personalized pain management. CLINICAL TRIAL REGISTRATION: NCT04940208.

Disentangling molecular and clinical stratification patterns in beta-galactosidase deficiency.

INTRODUCTION: This study aims to define the phenotypic and molecular spectrum of the two clinical forms of ß-galactosidase (ß-GAL) deficiency, GM1-gangliosidosis and mucopolysaccharidosis IVB (Morquio disease type B, MPSIVB). METHODS: Clinical and genetic data of 52 probands, 47 patients with GM1-gangliosidosis and 5 patients with MPSIVB were analysed. RESULTS: The clinical presentations in patients with GM1-gangliosidosis are consistent with a phenotypic continuum ranging from a severe antenatal form with hydrops fetalis to an adult form with an extrapyramidal syndrome. Molecular studies evidenced 47 variants located throughout the sequence of the GLB1 gene, in all exons except 7, 11 and 12. Eighteen novel variants (15 substitutions and 3 deletions) were identified. Several variants were linked specifically to early-onset GM1-gangliosidosis, late-onset GM1-gangliosidosis or MPSIVB phenotypes. This integrative molecular and clinical stratification suggests a variant-driven patient assignment to a given clinical and severity group. CONCLUSION: This study reports one of the largest series of b-GAL deficiency with an integrative patient stratification combining molecular and clinical features. This work contributes to expand the community knowledge regarding the molecular and clinical landscapes of b-GAL deficiency for a better patient management.

A clinical screening tool for objective and subjective cognitive disorders in multiple sclerosis.

BACKGROUND: Cognitive dysfunction is common in multiple sclerosis (MS). Deficits can affect attention, concentration, planning, and memory. They can have severe functional consequences in many domains. Cognitive complaints are frequently associated with other confounding factors (fatigue, anxiety, depression, or treatment side effects). In most cases, cognitive assessment is proposed after a spontaneous complaint, but determining the extent of discomfort perceived by the patient, the influence of coexisting factors, or the optimal timing for a more complete neuropsychological assessment is difficult. OBJECTIVE: The objective of this work was to evaluate the feasibility and relevance of a fast global assessment of both objective and subjective cognitive dysfunction in MS. METHODS: MS patients underwent a brief cognitive assessment including 7 visual analogue scales (VASs) asking about the patient's subjective level of discomfort in various domains, a memory test (Barbizet's lion story), a commonly used test of information processing speed (Symbol Digit Modalities Test [SDMT]) and self-reporting questionnaires for fatigue and mood (Fatigue Severity Scale [FSS] and Hospital Anxiety and Depression Scale [HADS]). Spearman correlation coefficients among scores were estimated. RESULTS: The mean age of the 73 patients included was 48.3 (SD 11.1) years; 78% were females and 52.8% had the remittent-recurrent MS form, 8.3% the primary progressive form, and 38.9% the secondary progressive form. In less than 20min, this brief cognitive assessment was able to identify symptoms and quantify discomfort level. Symptoms of fatigue and anxiety frequently coexisted with cognitive complaints. We found modest correlations between scores on the VAS fatigue and the FSS and between scores on the VAS mood and the HADS. Analytical evaluation revealed that most patients had similar SDMT and recall profiles; however, a small proportion showed a dissociation between these 2 tests, which validated the inclusion of both tests in the assessment. Accounting for coexisting factors (e.g., anxiety and fatigue) and their functional repercussions is essential for prioritizing these problems within the context of multidisciplinary patient treatment. CONCLUSION: Considering the possible multifactorial character of cognitive dysfunction in MS, it is essential to ask patients about their experiences and to take into account cognitive complaints in the follow-up of patients. The assessment tool we propose is simple and easy to use in a clinical setting and provides the information necessary for requesting (or not) a more complete neuropsychological assessment.

History of multiple sclerosis in 2 successive pregnancies: A French and Italian cohort.

OBJECTIVE: To evaluate the risk of relapses during pregnancy and in the first 3 months after delivery in 2 successive pregnancies in a cohort of French and Italian women with multiple sclerosis (MS). METHODS: A total of 93 women were included if they had had 2 pregnancies followed prospectively after MS onset between January 1993 and 2013. The association of a relapse during pregnancy or the first postpartum trimester in pregnancy 1 and pregnancy 2 was evaluated by univariate logistic regression. RESULTS: A majority of women did not experience any exacerbation in the 3 months after delivery (31.2% and 23.7%, respectively, relapsed after pregnancy 1 and 2; p = 0.32). A total of 7.6% had a relapse after both pregnancies. The risk of relapse after pregnancy 2 was not associated with the number of relapses in the prepregnancy year (odds ratio [OR] 1.52 [0.57-4.05]) or during pregnancy (OR 1.57 [0.52-4.79]) or with the occurrence of a relapse after pregnancy 1 (OR 0.86 [0.29-2.50]). CONCLUSIONS: Our work provides original data on the evolution of successive pregnancies in MS, showing a similar (and even lower) disease activity in the second pregnancy. There was no correlation of activity in successive pregnancies. Therefore, counseling of women with MS who consider having a second baby should be the same as for the first one.

[New therapies in multiple sclerosis]. / Actualités thérapeutiques dans la sclérose en plaques.

Due to the autoimmune nature of multiple sclerosis (MS), the current disease modifying treatments aim at reducing the immune system activity or at interfering with it. Immune modulators from the interferon Beta and glatiramer acetate families are widely used as first line treatments. They often prove sufficient for moderately active forms of the disease. For more active forms, powerful immunosuppressants such as mitoxantrone or a monoclonal antibody (natalizumab), selective inhibitor of the T cell adhesion molecule on the cerebral endothelium, are used. Several new promising oral medications should be added to this therapeutic arsenal shortly. Most of the times, these various treatments are already effective for preventing relapses. However, they remain rather ineffective for progression which is the second clinical constituent of the disease. Improvements are urgently needed in this area.

Assessment of disease activity in multiple sclerosis phenotypes with combined gadolinium- and superparamagnetic iron oxide-enhanced MR imaging.

PURPOSE: To compare magnetic resonance (MR) imaging features of multiple sclerosis (MS) lesions after the administration of a gadolinium-based contrast agent and ultrasmall superparamagnetic iron oxide (USPIO) particles among the clinical phenotypes of MS and over time. MATERIALS AND METHODS: This study was approved by the local ethics committee, and written informed consent was obtained from all patients. Twenty-four patients with MS (10 with relapsing and 14 with progressive forms) underwent clinical and gadolinium- and USPIO-enhanced MR examinations at baseline and 6-month follow-up. The number of lesions that enhanced with gadolinium alone, USPIO alone, or both was compared with the Pearson χ2 or Fisher exact test, and lesion sizes were compared with the Wilcoxon Mann-Whitney U test. At 6-month follow-up, the lesion signal intensity on precontrast T1-weighted images and the enhancement after repeat injection of the contrast agent were compared with the baseline postcontrast imaging features by using the McNemar test. RESULTS: Fifty-six lesions were considered active owing to contrast enhancement at baseline; 37 lesions (66%) in 10 patients enhanced with gadolinium. The use of USPIO helped detect 19 additional lesions (34%), and two additional patients were classified as having active disease. Thus, the use of both agents enabled detection of 51% (19 of 37 lesions) more lesions than with gadolinium alone. Enhanced lesions were more frequently observed in the relapsing compared with the progressive forms of MS (P<.0001). USPIO enhancement, in the form of ringlike patterns, could also be observed on T1-weighted images in patients with progressive MS, enabling the detection of five lesions in addition to the five detected with gadolinium in this phenotype. Lesions that enhanced with both contrast agents at baseline were larger (mean size, 6.5 mm±3.8; P=.001) and were more likely to persistently enhance at 6-month follow-up (seven of 27 lesions, P<.0001) compared with those that enhanced only with gadolinium (mean size, 4.9 mm±2.2; one of nine lesions) or USPIO (mean size, 3.5 mm±1.5; 0 of 17 lesions). CONCLUSION: The combination of gadolinium and USPIO in patients with MS can help identify additional active lesions compared with the current standard, the gadolinium-only approach, even in progressive forms of MS. Lesions that enhance with both agents may exhibit a more aggressive evolution than those that enhance with only one contrast agent.

Recurrent cerebral venous thrombosis revealing paraneoplastic angiitis in Hodgkin's lymphoma.

Recurrent cerebral venous thrombosis (CVT), as a manifestation of paraneoplastic angiitis and revealing of nodular lymphocyte predominant Hodgkin's disease (NLPHD), is an extremely rare condition. We herein report a 55-year-old man who developed recurrent CVT despite efficacious anticoagulant therapy and subsequent stenting of the superior longitudinal sinus. Progressive neurological deterioration ensued and a body scan revealed axillary lymph nodes. Pathological analysis led to a diagnosis of NLPHD. Conventional angiography showed CVT and multiple arterial narrowings. A paraneoplastic primary cerebral angiitis with prominent venous structure involvement was suspected. Immunotherapy using rituximab and steroids provided a dramatic recovery. This case of CVT due to paraneoplastic cerebral angiitis is a rare condition and represents a new, very rare manifestation of nodular lymphocyte predominant Hodgkin's disease.