Prism adaptation effects in complex regional pain syndrome: A therapo-physiological single case experimental design exploratory report.

Complex Regional Pain Syndrome (CRPS) is an invalidating chronic condition that can occur after an acute peripheral lesion. Prism adaptation therapy is regarded as a promising tool to improve chronic pain in this syndrome but the mechanisms which lead to pain amelioration remain unknown. In this exploratory report we performed a retrospective analysis of longitudinal data collected from a single, atypical patient, who showed hyper-attention toward her affected (left) hand. Repeated assessments of pain and spatial neglect made during the course of the prism adaptation treatment revealed differential contributions of the two hands to adaptation-induced pain reduction. Treatment response appeared to be associated with a relative modification of the spatial behaviour of the two hands. This case study provides a new example of pain relief following prismatic deviation away from the pathological side.

Impact of the COVID-19 outbreak on acute stroke pathways - insights from the Alsace region in France.

BACKGROUND AND PURPOSE: To date, no study has attempted to quantify the impact of the COVID-19 outbreak on the incidence and treatment of acute stroke. METHODS: This was a retrospective review of acute stroke pathway parameters in all three stroke units in the Alsace region during the first month of the outbreak (1-31 March 2020), using the similar period from 2019 as a comparator. A secondary detailed analysis of all stroke alerts and stroke unit admissions was performed in the centre with the largest case volume. RESULTS: Compared to the same period in 2019, in March 2020 there were 39.6% fewer stroke alerts and 33.3% fewer acute revascularization treatments [40.9% less intravenous thrombolysis (IVT) and 27.6% less mechanical thrombectomy (MT)]. No marked variation was observed in the number of stroke unit admissions (-0.6%). The proportion of patients with acute revascularization treatments (IVT or MT) out of the total number of stroke unit admissions was significantly lower in March 2020 (21.3%) compared to 2019 (31.8%), P = 0.034. There were no significant differences in time delays or severity of clinical symptoms for patients treated by IVT or MT, nor in the distribution of final diagnosis amongst stroke alerts and stroke unit admissions. CONCLUSION: These results suggest that the overall incidence of stroke remained the same, but fewer patients presented within the therapeutic time window. Increased public awareness and corrective measures are needed to mitigate the deleterious effects of the COVID-19 outbreak on acute stroke care.

[Impact of pharmaceutical interventions on antibiotic therapy of urinary tract infections in rehabilitation center]. / Impact des interventions pharmaceutiques sur l'antibiothérapie des infections urinaires en service de soins de suite et de réadaptation.

BACKGROUND: The aim of this study was to assess the impact of medico-pharmaceutical partnership on the quality of antibiotic treatment in urinary tract infection (UTI) within rehabilitation center. MATERIAL: All antibiotic prescriptions were validated by the pharmacist at the start of treatment and twice a week. All patients with symptomatic urinary tract infection between January 1, 2014 to December 31, 2015 were included in this study. Addition to awareness among specifiers to promoting the appropriate use of antibiotics, the pharmacist suggested pharmaceutical interventions (PI) in order to improve the quality of antibiotic treatments. At the same time, 3 quality indicators (QI) were followed: duration, dosage, antibiotic susceptibility. The compliance rates of this 3 QI allowed to assess the quality of the antibiotic treatment in urinary tract infection. RESULTS: The study population included 154 patients corresponding to 252 UTI. Sixty-eight PI were made by pharmacist about urinary tract infection treatment (overdosage or under-dosing, duration unknown, inadequate route of administration). These QI achieved 96.4% compliance with duration, 98.8% compliance with dosage and 99.2% with the antibiotic susceptibility. CONCLUSION: This study allowed showing the medico-pharmaceutical impact on the quality of antibiotic treatments in UTI. The awareness among specifiers with a daily validation of prescription by the pharmacist allowed to improve urinary tract infections care in rehabilitation center. LEVEL OF EVIDENCE: 4.

Mastering granular activated carbon filtration to remove organic micropollutants, antibiotic resistance and metals for municipal wastewater reuse.

GAC filtration of municipal wastewater was optimized and intensified, making its implementation and operation directly after secondary clarification possible and relevant. GAC was first selected based on laboratory tests. Performances on organic micropollutants were linked to the repartition of BET surface between micropores and meso/macropores. At pilot scale, in order to limit the impact of head loss, downflow declogging sequences (DCS) were implemented and upflow filtration tested. 6 to 12 DCS per day led to a 4.7-5.5-fold increase of particles retention capacity between backwashes (cycle duration of 20-120 h), and upflow operations improved head loss evolution profile with only a slight GAC (<15 %) expansion. DCS allows backwash frequency reduction, enabling significant water savings. Both adaptations maintained high organic micropollutants removals compared to a review of 16 GAC studies at pilot or full-scale, results being in the upper range. A specific dose of 2.0-2.5 g GAC/gC was necessary to obtain an average removal of pharmaceuticals and benzotriazole of 80 % at 20 min contact time, which is comparable to PAC and low granulometry GAC. Higher doses are needed for PFAS but >80 % removals are achievable. Particles, TKN, particulate phosphorus and organic matter are well removed by GAC filtration in both configurations. Biological activity is observed through nitrogen transformation in the GAC bed. Heavy metals are greatly removed in GAC filtration, in particular Cd, Cu, Ni and Pb, probably through biosorption onto the biofilm, developed within the GAC bed. For wastewater reuse applications, GAC filtration has an added value through physicochemical quality improvement and fecal contamination indicators removal of 1 log, facilitating the implementation and optimizing the design of a post-disinfection. Antibiotic resistant bacteria and antibiotic resistance genes are also partially retained in GAC filtration. Finally, biological wastewater treatments combined to GAC filtration is a good solution to effectively treat organic micropollutants together with heavy metals and preparing post-disinfection for reuse.

Bladder dysfunction in hereditary spastic paraplegia: a clinical and urodynamic evaluation.

OBJECTIVES: Hereditary spastic paraplegia (HSP) is a degenerative central nervous system disorder characterized by progressive spasticity and hyperreflexia of the lower limbs. Often, patients with HSP experience symptoms of voiding dysfunction. Urodynamic evaluations of these patients are rarely reported in the literature and the etiology of voiding dysfunction remains unclear. The present study characterizes lower urinary tract dysfunction in a large series of patients. METHODS: The medical records of 29 HSP patients who underwent urodynamic evaluation were retrospectively analyzed. The history of lower urinary tract symptoms was noted and the urodynamic findings analyzed. RESULTS: Urgency was the most dominant complaint (72.4%), followed by frequency (65.5%), urinary incontinence (55.2%) and hesitancy (51.7%). The urodynamic findings showed signs of central neurogenic bladder in 24 patients (82.7%), with detrusor overactivity (DO) in 15 patients (51.7%) and detrusor sphincter dyssynergia (DSD) in 19 (65.5%). Post-void residual (PVR) of >10% of the voided volume was found in 12 patients (41.4%). There were significant relationships between detrusor overactivity and PVR (P=0.005), frequency (P=0.046) and nocturia (P=0.045). Ultrasound examination revealed no upper urinary tract complications. CONCLUSION: Despite the presence of DO and DSD, HSP patients do not seem to have a high risk of developing ultrasonographically-assessed upper urinary tract complications after a mean follow-up of 22 years, contrary to spinal cord injury population. These results may guide practitioners in their decision-making about the appropriate evaluation and treatment of bladder disturbances that accompany hereditary spastic paraplegia.

[Importance of cognitive disorders in internal medicine: Pathophysiology, diagnosis, management. The example of systemic lupus erythematosus]. / Importance des troubles cognitifs en médecine interne : physiopathologie, évaluation, prise en charge. L'exemple du lupus systémique.

Systemic diseases, which are in France mainly monitored in internal medicine, affect multiple organs or tissues. While cutaneous or articular manifestations are the most common, neurological involvement is often associated with severity. Diagnosis of peripheral (e.g, neuropathies) or central (e.g, myelitis) nervous disorders is quite easy through clinical examination and dedicated complementary tests. However, neuropsychological manifestations that affect cognition, including memory, attention, executive functions or reasoning, are difficult to diagnose, sometimes trivialized by practitioners. Their causes are often numerous and interrelated. Nevertheless, these cognitive manifestations are closely related to patients' quality of life, affecting their social life, family dynamics and professional integration but also the treatment adherence. The purpose of this review, focused on the example of systemic lupus erythematosus, is to raise awareness of cognitive dysfunction in systemic diseases including their management from diagnosis to treatments. The final aim is to go further into setting up research groups and care programs for patients with cognitive impairment followed in internal medicine.

Effect of prism adaptation on left dichotic listening deficit in neglect patients: glasses to hear better?

Unilateral neglect is a disabling syndrome frequently observed following right hemisphere brain damage. Symptoms range from visuo-motor impairments through to deficient visuo-spatial imagery, but impairment can also affect the auditory modality. A short period of adaptation to a rightward prismatic shift of the visual field is known to improve a wide range of hemispatial neglect symptoms, including visuo-manual tasks, mental imagery, postural imbalance, visuo-verbal measures and number bisection. The aim of the present study was to assess whether the beneficial effects of prism adaptation may generalize to auditory manifestations of neglect. Auditory extinction, whose clinical manifestations are independent of the sensory modalities engaged in visuo-manual adaptation, was examined in neglect patients before and after prism adaptation. Two separate groups of neglect patients (all of whom exhibited left auditory extinction) underwent prism adaptation: one group (n = 6) received a classical prism treatment ('Prism' group), the other group (n = 6) was submitted to the same procedure, but wore neutral glasses creating no optical shift (placebo 'Control' group). Auditory extinction was assessed by means of a dichotic listening task performed three times: prior to prism exposure (pre-test), upon prism removal (0 h post-test) and 2 h later (2 h post-test). The total number of correct responses, the lateralization index (detection asymmetry between the two ears) and the number of left-right fusion errors were analysed. Our results demonstrate that prism adaptation can improve left auditory extinction, thus revealing transfer of benefit to a sensory modality that is orthogonal to the visual, proprioceptive and motor modalities directly implicated in the visuo-motor adaptive process. The observed benefit was specific to the detection asymmetry between the two ears and did not affect the total number of responses. This indicates a specific effect of prism adaptation on lateralized processes rather than on general arousal. Our results suggest that the effects of prism adaptation can extend to unexposed sensory systems. The bottom-up approach of visuo-motor adaptation appears to interact with higher order brain functions related to multisensory integration and can have beneficial effects on sensory processing in different modalities. These findings should stimulate the development of therapeutic approaches aimed at bypassing the affected sensory processing modality by adapting other sensory modalities.

Epidemiological, clinical, paraclinical and molecular study of a cohort of 102 patients affected with autosomal recessive progressive cerebellar ataxia from Alsace, Eastern France: implications for clinical management.

While Friedreich's ataxia (FRDA) and ataxia telangiectasia (AT) are known to be the two most frequent forms of autosomal recessive cerebellar ataxia (ARCA), knowledge on the other forms of ARCA has been obtained only recently, and they appear to be rarer. Little is known about the epidemiological features and the relative frequency of the ARCAs and only few data are available about the comparative features of ARCAs. We prospectively studied 102 suspected ARCA cases from Eastern France (including 95 from the Alsace region) between 2002 and 2008. The diagnostic procedure was based on a sequential strategic scheme. We examined the clinical, paraclinical and molecular features of the large cohort of patients and compared features and epidemiology according to molecular diagnosis. A molecular diagnosis could be established for 57 patients; 36 were affected with FRDA, seven with ataxia plus oculomotor apraxia type 2 (AOA2), four with AT, three with ataxia plus oculomotor apraxia type 1 (AOA1), three with Marinesco-Sjögren syndrome, two with autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS), one with ataxia with vitamin E deficiency (AVED) and one with autosomal recessive cerebellar ataxia type 2 (ARCA2). The group of patients with no identified mutation had a significantly lower spinocerebellar degeneration functional score corrected for disease duration (SDFS/DD ratio; p = 0.002) and comprised a significantly higher proportion of cases with onset after 20 years (p < 0.01). Extensor plantar reflexes were rarer and cerebellar atrophy was more frequent in the group of patients with a known non-Friedreich ARCA compared to all other patients (p < 0.0001 and p = 0.0003, respectively). Lower limb areflexia and electroneuromyographic evidences of peripheral neuropathy were more frequent in the Friedreich ataxia group than in the group with a known non-Friedreich ataxia and were more frequent in the later group than in the group with no identified mutation (p = 0.0001 and p = 0.01, respectively). The overall prevalence of ARCA in Alsace is 1/19,000. We can infer the prevalence of FRDA in Alsace to be 1/50,000 and infer that AT is approximately eight times less frequent than FRDA. MSS, AOA2 and ARSACS appear only slightly less frequent than AT. Despite the broad variability of severity, Friedreich ataxia patients are clinically distinct from the other forms of ARCA. Patients with no identified mutation have more often a pure cerebellar degenerative disease or a spastic ataxia phenotype. It appears that ARCA cases can be divided into two major groups of different prognosis, an early-onset group with a highly probable genetic cause and an adult-onset group with better prognosis for which a genetic cause is more difficult to prove but not excluded. ARCAs are rare, early-disabling and genetically heterogeneous diseases dominated by FRDA. Several of the recently identified ARCAs, such as AVED, ARSACS, AOA1, AOA2 and MSS, have a prevalence close to AT and should be searched for extensively irrespective of ethnic origins. The strategic scheme is a useful tool for the diagnosis of ARCAs in clinical practice.

Stroke Thrombectomy in Patients with COVID-19: Initial Experience in 13 Cases.

We performed a retrospective review in both comprehensive stroke units of a region affected early by the coronavirus disease 2019 (COVID-19) pandemic, between March 1 and April 26, 2020, including patients with COVID-19 who underwent mechanical thrombectomy for ischemic stroke. We identified 13 cases, representing 38.2% of 34 thrombectomies performed during this period. We observed increased mortality and a high incidence of thrombotic complications during hospitalization. Given the high rate of infected patients, systematic use of full personal protection measures seems justified.

Can you guess the colour of this moving object? A dissociation between colour and motion in blindsight.

Blindsight has been primarily and extensively studied by Lawrence Weiskrantz. Residual visual abilities following a hemispheric lesion leading to homonymous hemianopia encompass a variety of visual-perceptual and visuo-motor functions. Attention blindsight produces the more salient subjective experiences, especially for motion (Riddoch phenomenon). Action blindsight illustrates visuo-motor abilities despite the patients' feeling that they produce random movements. Perception blindsight seems to be the weakest residual function observed in blindsight, e.g. for wavelength sensitivity. Discriminating motion produced by isoluminant colours does not give rise to blindsight for motion but the outcome of the reciprocal test is not known. Here we tested whether moving stimuli could give rise to colour discrimination in a patient with homonymous hemianopia. It was found that even though the patient exhibited nearly perfect performances for motion direction discrimination his colour discrimination for the same moving stimulus remained at chance level. It is concluded that easily discriminated moving stimuli do not give rise to colour discrimination and implications for the 3 levels of blindsight taxonomy are discussed.

Construction and feasibility study of the SOFMER Activity Score (SAS), a new assessment of physical and cognitive activity.

OBJECTIVES: For hospitalizations in rehabilitation centers (RCs) in France, the quantification of healthcare givers' activity is based on the dependency of the patients, defined as a total or partial inability to perform activities required for daily living without help. The tools currently used to quantify dependency are not sufficiently precise. Here we describe the construction of a new tool, the SOFMER Activity Score (SAS scoring), which allows for a good description of the level of activity of patients hospitalized in RCs, and a feasibility study of the tool. METHODS: After a study group proposed the first version of the SAS, the validity of its content was studied by the Delphi consensus method: 26 physicians or healthcare professionals known for their expertise in PMR responded to the first round. The feasibility study was prospective and involved multi-site professionals. Data related to the SAS determined by a multidisciplinary team were collected and compared to the Activité de la Vie Quotidienne (AVQ) scale, which is administered to all patients and included in medical and administrative data. RESULTS: We included 81 patients in the feasibility study. The mean (SD) time to obtain the SAS was 4.5 (3.3) min. For 97.5% of scorings, the participating professionals judged that the SAS was compatible or fairly compatible with clinical practice. The internal structure of the SAS scale seemed better than that of the AVQ scale, for which the present study confirmed a floor effect for all items. CONCLUSIONS: The SAS allows for measuring the level of physical and cognitive activity of a patient hospitalized in an RC. If validation studies for the SAS, exploring its reliability, construct validity or criterion validity, confirm the tool's good metrological qualities, the SAS will allow for a good quantification of the burden of care.

Sp1 can displace GHF-1 from its distal binding site and stimulate transcription from the growth hormone gene promoter.

DNase I footprinting experiments showed that binding activities of Sp1 and of GHF-1 to its distal site on the human growth hormone gene promoter are mutually exclusive. The kinetics of GHF-1 binding were indicative of positive cooperativity. The Sp1 site did not affect promoter activity in cell-free transcription. Still, Sp1 could compensate partially for the decreased stimulation of transcription seen at low GHF-1 concentrations.

Low frequency of TSG101/CC2 gene alterations in invasive human breast cancers.

Large intragenic deletions of the TSG101/CC2 gene were recently reported in seven of 15 primary metastatic breast cancers. Although the number of samples was small, this observation suggested that TSG101/CC2 alterations were a major event in breast carcinogenesis. To study the frequency of these deletions in invasive breast cancers we analysed 189 primary invasive breast tumours and 59 breast cancer metastases. We detected intragenic rearrangements in only three samples (two primary tumours and one metastasis). Northern blot analysis of 43 tumours without rearrangements failed to detect any abnormalities. Furthermore, we studied TSG101/CC2 in 11 human breast adenocarcinoma cell lines by Southern blot, RT-PCR and sequencing of the entire coding region of the gene, and detected no abnormalities. These results show that genetic alteration of TSG101/CC2 is a rare event in breast cancer.

p21(WAF1/CIP1) response to genotoxic agents in wild-type TP53 expressing breast primary tumours.

Functional inactivation of the wild-type p53 protein has been described in different human cancers. Since a significant proportion of breast tumours express wild-type TP53, the p53 antiproliferative activity could be inactivated in transformed mammary epithelial cells by a mechanism independent on structural alteration of the gene. To test this hypothesis, we analysed the p53 activity in primary breast tumour cells. As a preliminary study, we demonstrated in breast adenocarcinoma cell lines that the nuclear accumulation of the inhibitor of cyclin dependent kinase p21(WAFl/CIP1), in response to adriamycin treatment, specifically reflected the activity of a functional wild-type p53 protein. Then, we used this strategy to study the p53 activity in 23 primary breast tumours. p21(WAF1/CIP1 accumulation was detected in all tumours expressing wild-type TP53. In contrast, no p21(WAF1/CIP1) response was detected in cells harboring a mutant TP53 gene. This report is the first functional study of p53 in primary breast tumours. The results demonstrate that TP53 mutation represents the only common mechanism leading to an irreversible inactivation of p53 functions in this cancer type.

Alteration of p53 damage response by tamoxifen treatment.

Hormone therapy is often used in association with chemotherapy in the treatment of estrogen-responsive breast cancers. By using breast adenocarcinoma cell lines, we show that antiestrogen treatment leads to a dramatic decrease of p53 protein levels. This effect leads to a loss of wild-type p53 response to genotoxic treatment. This inhibition is assessed by the lack of p53 protein accumulation and the loss of the p53-dependent induction of p21(WAF1/CIP1) expression. Given that the effects of several anticancer agents are mediated through DNA damage, these observations suggest that antiestrogen treatment could modulate cellular response to chemotherapeutic agents.

[Assessment of disability and quality of life in patients with cognitive disorders]. / Evaluation des incapacités et de la qualité de vie des patients présentant des troubles cognitifs.

OBJECTIVE: To identify disability, handicap and quality of life questionnaires available for patients with cognitive impairment. MATERIALS AND METHODS: We systematically reviewed the literature in Medline using the keywords assessment, evaluation, deficiency, disability, disadvantage, handicap, quality of life, scale, index, questionnaire, ICIDH-1, and ICIDH-2, combined with the cognitive deficits dysexecutive syndrome, memory deficits, attention deficits, neglect, apraxia, aphasia, agnosia and mood disorders. We focused on validated scales and distinguished scales dedicated to assess disability, handicap and quality of life. RESULTS: At the level of disability, global and specific scales are available. Specific scales exist for dysexecutive syndrome, memory deficits, attention deficits, unilateral neglect, aphasia and mood disorders. French adaptations of foreign language tests and original tests developed in French have been validated in these areas. No specific tool is available for isolated apraxia or agnosia. Generic scales and pathology-specific scales (for stroke, traumatic brain injury, and multiple sclerosis) are available for quality of life. For aphasia, specific tools are available for incapacity handicap and quality of life. CONCLUSION: Previous results show the impact of the ICIDH-1 framework on functional outcome assessment of cognitive impairments. This approach is often limited by the lack of theoretical background and by the difficulty to assess the involvement of environment and anosognosia.

Hemi-spatial neglect rehabilitation using non-invasive brain stimulation: or how to modulate the disconnection syndrome?

Hemi-spatial neglect syndrome is common and sometimes long-lasting. It is characterized by a deficit in the use and awareness of one side of space, most often consecutive to a right hemisphere injury, mainly in the parietal region. Acknowledging the different types and all clinical characteristics is essential for an appropriate evaluation and adapted rehabilitation care management, especially as it constitutes a predictive factor of a poor functional prognosis. Some new approaches have been developed in the last fifteen years in the field of hemi-spatial neglect rehabilitation, where non-invasive brain stimulation (TMS and tDCS) holds an important place. Today's approaches of unilateral spatial neglect modulation via non-invasive brain stimulation are essentially based on the concept of inter-hemispheric inhibition, suggesting an over-activation of the contralesional hemisphere due to a decrease of the inhibiting influences of the injured hemisphere. Several approaches may then be used: stimulation of the injured right hemisphere, inhibition of the hyperactive left hemisphere, or a combination of both. Results are promising, but the following complementary aspects must be refined before a more systematic application: optimal stimulation protocol, individual management according to the injured region, intensity, duration and frequency of care management, delay post-stroke before the beginning of treatment, combination of different approaches, as well as prognostic and efficacy criteria. An encouraging perspective for the future is the combination of several types of approaches, which would be largely facilitated by the improvement of fundamental knowledge on neglect mechanisms, which could in the future refine the choice for the most appropriate treatment(s) for a given patient.

Long-term sensorimotor and therapeutical effects of a mild regime of prism adaptation in spatial neglect. A double-blind RCT essay.

Spatial neglect (SN) is commonly associated with poor functional outcome. Adaptation to a rightward optical deviation of vision has been shown to benefit to SN rehabilitation. The neurophysiological foundations and the optimal modalities of prism adaptation (PA) therapy however remain to be validated. This study is aimed at exploring the long-term sensory-motor, cognitive and functional effects produced by weekly PA sessions over a period of four weeks. A double-blind, monocentric randomized and controlled trial (RCT) was carried out. Twenty patients with left SN secondary to stroke were included, 10 in the "prism" group and 10 in the "control" group. The sensory-motor effects of PA were evaluated by measurement of manual and visual straight-ahead, and also by precision of pointing without visual feedback before and after each PA session. The functional independence measure (FIM) was evaluated before and at 1, 3 and 6 months after PA, while SN severity was assessed using the Behavioural Inattention Test (BIT) before and 6 months after PA. Before the intervention, only manual straight-ahead pointing constituted a reproducible sensory-motor measurement. During prism exposure, a questionnaire showed that not a single patient were aware of the direct effects of optical deviation on pointing movement performance. The sensory-motor after-effects produced by the PA produced a more rapid reduction of the rightward manual straight-ahead, which was secondarily followed by visual straight-ahead. These sensory-motor effects helped to clarify the action mechanisms of PA on SN. At the conclusion of the 6-month follow-up, the two groups showed similar improvement, indicating that a weekly PA session over 4 weeks was not sufficient to produce long-term functional benefit. This improvement was correlated with the evolution of visual straight-ahead, which can be proposed as a marker for patients outcome.