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International audience; Objective: The aim of this study was the comprehensive characterisation of longitudinal clinical, electrophysiological and neuroimaging measures in type III and IV adult spinal muscular atrophy (SMA) with a view to propose objective monitoring markers for future clinical trials. Methods: Fourteen type III or IV SMA patients underwent standardised assessments including muscle strength testing, functional evaluation (SMAFRS and MFM), MUNIX (abductor pollicis brevis, APB; abductor digiti minimi, ADM; deltoid; tibialis anterior, TA; trapezius) and quantitative cervical spinal cord MRI to appraise segmental grey and white matter atrophy. Patients underwent a follow-up assessment with the same protocol 24 months later. Longitudinal comparisons were conducted using the Wilcoxon-test for matched data. Responsiveness was estimated using standardized response means (SRM) and a composite score was generated based on the three most significant variables. Results: Significant functional decline was observed based on SMAFRS (p = 0.019), pinch and knee flexion strength (p = 0.030 and 0.027), MUNIX and MUSIX value in the ADM (p = 0.0006 and 0.043) and in TA muscle (p = 0.025). No significant differences were observed based on cervical MRI measures. A significant reduction was detected in the composite score (p = 0.0005, SRM = −1.52), which was the most responsive variable and required a smaller number of patients than single variables in the estimation of sample size for clinical trials. Conclusions: Quantitative strength testing, SMAFRS and MUNIX readily capture disease progression in adult SMA patients. Composite multimodal scores increase predictive value and may reduce sample size requirements in clinical trials.

Objective To evaluate the relevance of transcranial magnetic stimulation (TMS) using triple stimulation technique (TST) to assess corticospinal function in amyotrophic lateral sclerosis (ALS) in a large-scale multicenter study. Methods Six ALS centers performed TST and conventional TMS in upper limbs in 98 ALS patients during their first visit to the center. Clinical evaluation of patients included the revised ALS Functional Rating Scale (ALSFRS-R) and upper motor neuron (UMN) score. Results TST amplitude ratio was decreased in 62% of patients whereas conventional TMS amplitude ratio was decreased in 25% of patients and central motor conduction time was increased in 16% of patients. TST amplitude ratio was correlated with ALSFRS-R and UMN score. TST amplitude ratio results were not different between the centers. Conclusions TST is a TMS technique applicable in daily clinical practice in ALS centers for the detection of UMN dysfunction, more sensitive than conventional TMS and related to the clinical condition of the patients. Significance This multicenter study shows that TST can be a routine clinical tool to evaluate UMN dysfunction at the diagnostic assessment of ALS patients.

The Nigerian Ministry of Health has been offering care for noma patients for many years at the Noma Children's Hospital (NCH) in Sokoto, northwest Nigeria, and Medecins Sans Frontieres has supported these initiatives since 2014. The comprehensive model of care consists of four main components: acute care, care for noma sequelae, integrated hospital-based services and community-based services. The model of care is based on the limited evidence available for prevention and treatment of noma and follows WHO's protocols for acute patients as well as best practice guidelines for the surgical treatment of noma survivors. The model is updated continually as new evidence becomes available, including evidence generated through the operational research studies performed at NCH. By describing the model of care, we wish to share the lessons learned with other actors working in the noma and neglected tropical disease sphere in the hope of guiding programme development.

Background and Objective In end-stage kidney disease, high urea levels promote the carbamylation of lysine side chains on a variety of proteins, including albumin. Albumin carbamylation has been identified as a risk factor for mortality and sevelamer led to a decrease in urea levels in dialysis patients. In the present secondary analysis of the NICOREN trial, we investigated the putative impacts of sevelamer and nicotinamide on albumin carbamylation, and the potential correlation between carbamylation and vascular calcifications. Methods All possible carbamylation of circulating albumin were screened for with high-resolution liquid chromatography-tandem mass spectrometry. Levels of three carbamylated peptides were then measured as a guide to the extent of albumin carbamylation. Carbamylation was measured at baseline in 55 patients included in the NICOREN trial and 29 patients at 24 weeks of treatment. Calcifications on plain radiographs were quantified as the Kauppila score and the Adragao score. Results Baseline albumin carbamylation was present at three different sites in subjects with end-stage kidney disease. At baseline, we observed only a correlation between urea and the KQTA carbamylation site in these patients. Albumin carbamylation levels did not decrease after 24 weeks of treatment with either sevelamer or nicotinamide. Furthermore, the proportion of carbamylated serum albumin was not correlated with vascular calcification scores in this population. Conclusions Our results confirmed the presence of carbamylated albumin in patients with end-stage kidney disease and demonstrated the presence of carbamylation beyond the LRVP residues. The results also demonstrated the lack of impact of sevelamer or nicotinamide on albumin carbamylation levels. Therapeutic strategies to lower carbamylation load should probably be focused on direct anti-carbamylation processes and/or potentially anti-inflammatory therapies. Supplementary Information The online version contains supplementary material available at 10.1007/s40268-021-00350-7.

Brentuximab vedotin (BV) is an antibody-drug conjugate composed by an anti-CD30 monoclonal antibody and the anti-microtubule agent monomethyl auristatin E, used for the treatment of relapsed/refractory Hodgkin's lymphoma and non-Hodgkin's lymphoma. Peripheral neuropathy is a frequent adverse event of BV treatment, affecting up to 60% to 70% of patients.1 It usually consists of a mild axonal, length-dependent, sensory neuropathy, characterised by numbness and tingling of fingers and toes,1 2 related to the toxic effect of monomethyl auristatin E on axonal microtubules.3 Nonetheless, immune-mediated peripheral neuropathies characterised by prominent motor impairment have also been described,4 suggesting that, similarly to other antineoplastic agents, BV might have the potential to induce or exacerbate inflammatory polyradiculoneuropathies. The aim of this study was to assess the characteristics of inflammatory demyelinating polyradiculoneuropathy associated with BV treatment. ### Patients and methods We performed a retrospective research in seven French neurology departments, for all patients who were admitted between January 2013 and December 2019 to investigate a peripheral neuropathy appeared during BV treatment. We selected patients meeting Sjevar et al criteria for the diagnosis of Guillain-Barre syndrome (GBS) (level 1 of diagnostic certainty) or meeting ‘definite’ criteria for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) according to 2010 European Federation of Neurological Societies/Peripheral Nerve Society guideline. We considered the onset as acute, subacute or chronic if the disease nadir was reached within 4 weeks, between 4 to 8 …

Platinum-based chemotherapy is commonly associated with toxic sensory neuropathies, but also, although rarely, with Guillain-Barré syndrome (GBS). We describe five patients who developed GBS while receiving platinum-based chemotherapy for a solid tumor and report the five cases published so far. Most patients had received cumulative platinum doses below known neurotoxic levels, and all of them had an optimal outcome after platinum discontinuation, associated in most cases with administration of intravenous immunoglobulin. Clinical presentation, electroneuromyography, and cerebrospinal fluid analysis help clinicians to differentiate GBS from toxic neuropathy. Platinum compounds are the only chemotherapeutic agents used for solid tumors that have been associated to GBS. Thus, we propose that GBS may constitute a non–dose-dependent side effect of platinum drugs and that awareness needs to be raised among oncologists on this rare but potentially life-threatening complication of platinum chemotherapy. Implications for Practice: Many patients on platinum-based chemotherapy for solid tumors develop sensory neuropathy, a common dose-dependent side effect. The authors propose that Guillain-Barré syndrome may constitute an immune-mediated, non-dose-related side effect of platinum-based chemotherapy. Prompt diagnosis of Guillain-Barré syndrome and distinction from classical toxic neuropathy are crucial for optimal treatment. Platinum discontinuation, associated if needed to intravenous immunoglobulin administration, radically changes the course of the disease and minimizes neurological sequelae.

Focal chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) is defined as involving the brachial or lumbosacral plexus, or one or more peripheral nerves in one upper or one lower limb (monomelic distribution). However, other auto-immune neuropathies such as Lewis-Sumner syndrome (LSS) and multifocal motor neuropathy (MMN) can also have a focal onset. From a retrospective cohort of 30 focal CIDP patients with a monomelic onset dating back at least 2 years, we distinguished patients with plexus involvement (focal demyelinating plexus neuropathy [F-PN], n = 18) from those with sensory or sensorimotor (F-SMN, n = 7), or purely motor (F-MN, n = 5) impairment located in one or several peripheral nerves. Few (39%) F-PN patients had motor nerve conduction abnormalities, but the majority showed proximal conduction abnormalities in somatosensory evoked potentials (80%), and all had focal hypertrophy and/or increased short tau inversion recovery image signal intensity on plexus MRI. Impairment remained monomelic in most (94%) F-PN patients, whereas abnormalities developed in other limbs in 57% of F-SMN, and 40% of F-MN patients (P = .015). The prognosis of F-PN patients was significantly better: none had an ONLS score > 2 at the final follow-up visit, vs 43% of F-SMN patients and 40% of F-MN patients (P = .026). Our findings from a large cohort of focal CIDP patients confirm the existence of different entities that are typically categorized under this one term: on the one hand, patients with a focal plexus neuropathy and on the other, patients with monomelic sensori-motor or motor involvement of peripheral nerves. These two last subgroups appeared to be more likely to evolve to LSS or MMN phenotype, when F-PN patients have a more distinctive long-term, focal, benign course.

Study objective Observational studies assessing direct oral anticoagulant (DOACs) dosage in atrial fibrillation (AF) reported that a lower proportion of patients received high-dose DOACs compared to those in randomized controlled trials (RCTs). Effectiveness and safety of high-dose DOACs relative to apixaban in a real-world AF population need to be addressed. The aim is to assess comparative effectiveness and safety of high-dose rivaroxaban relative to apixaban. Design We conducted a cohort study. Setting We built a cohort of patients hospitalized and discharged in community with a primary or secondary AF diagnosis from 2011-2017 using Quebec administrative databases (Med-Echo and RAMQ). Patients Cohort entry was defined as the first OAC claim in new users of high-dose rivaroxaban and apixaban, with no OAC claims in the prior year. Intervention To compare effectiveness and safety of high-dose rivaroxaban to apixaban. Measurement We ascertained patient demographics, comorbidities, CHA2DS2-VASc and HASBLED scores and Charlson score within 3 years prior to cohort entry. Primary effectiveness and safety were a composite of ischemic stroke/systemic thrombosis, death, myocardial infarction, and of intracranial bleeding (ICH), extracranial major bleeding, in the first year following drug initiation. We conducted propensity score matching and estimated hazard ratios (HRs) for outcomes using Cox proportional hazard models. All the analyses were conducted to account for competing risks. Main results The cohort consisted of 4,632 and 6,771 patients received high-dose rivaroxaban and apixaban, respectively. High-dose rivaroxaban users were younger with a mean age of 73.2 years, presented less associated comorbidities and had lower CHA2DS2-VASc scores compared to apixaban. High-dose rivaroxaban at the intention to treat was associated with a higher risk of stroke/SE/death (HR 1.21, 95% CI 1.04-1.40) and worse composite effectiveness (HR 1.21: 1.05-1.40); under treatment exposure, those values were at HR (1.66: 1.21-2.29) and HR (1.58:1.19-2.10), respectively. And, rivaroxaban presented a less favorable safety profile relative to apixaban. Conclusion In this study, composite effectiveness and safety varied between rivaroxaban and apixaban. High-dose apixaban was observed to have a better effectiveness and safety.

Background Anxiety is common in hospitalized patients and can worsen pain or lead to unsuccessful pain relief. Aims The purpose of this study was to evaluate the usefulness of measuring anxiety with a visual analog scale (VAS) in the hospitalized patient experiencing pain. Design We conducted a multiple-center cross-sectional study. Participants/Subjects Adult inpatients experiencing moderate to severe pain defined by a pain VAS score ≥40 of 100 were included. Methods Pain and anxiety data were collected using the following instruments: pain VAS, anxiety VAS, State Anxiety Scale of the Spielberger State-Trait Anxiety Inventory (STAI-YA) and Anxiety Subscale of the Hospital Anxiety and Depression Scale (HAD-A). Results Data were collected from 394 patients. Of those patients, 43.6% (171 of 392) and 36.6% (143 of 391) had significant anxiety according to STAI-Ya and HAD-A, respectively. Correlation was good between anxiety-VAS and STAI-YA (ρ = 0.67 [95% confidence interval 0.61-0.72]) and moderate between anxiety VAS and HAD-D (ρ = 0.48 [0.39-0.56]). The main factor predictive of situational anxiety was history of anxiety-depression symptoms (odds ratio = 2.95 [1.93-4.56]). For anxiety VAS score ≥ 40 of 100, the sensitivity for detecting anxiety was 81% with 70% specificity. Conclusion This study confirmed the high prevalence of anxiety among inpatients experiencing pain, demonstrated the capacity of a VAS to assess this anxiety, determined an anxiety VAS cutoff level to screen for significant anxiety, and identified risk factors of anxiety in this population. Anxiety VAS has been found to be an easy-to-use method familiar to caregivers, with all the advantages needed for an effective screening instrument. An anxiety VAS score ≥40 of 100 would thus warrant particular attention to adapt care to the patient's anxiety-related pain and initiate specific therapeutic interventions.

Objective: Friedreich ataxia (FRDA) is an inherited neurological disease defined by progressive movement incoordination. We undertook a comprehensive characterization of the spatial profile and progressive evolution of structural brain abnormalities in people with FRDA. Methods: A coordinated international analysis of regional brain volume using magnetic resonance imaging data charted the whole-brain profile, interindividual variability, and temporal staging of structural brain differences in 248 individuals with FRDA and 262 healthy controls. Results: The brainstem, dentate nucleus region, and superior and inferior cerebellar peduncles showed the greatest reductions in volume relative to controls (Cohen d= 1.5–2.6). Cerebellar gray matter alterations were most pronounced in lobules I–VI (d= 0.8), whereas cerebral differences occurred most prominently in precentral gyri (d= 0.6) and corticospinal tracts (d= 1.4). Earlier onset age predicted less volume in the motor cerebellum (rmax= 0.35) and peduncles (rmax= 0.36). Disease duration and severity correlated with volume deficits in the dentate nucleus region, brainstem, and superior/inferior cerebellar peduncles (rmax= −0.49); subgrouping showed these to be robust and early features of FRDA, and strong candidates for further biomarker validation. Cerebral white matter abnormalities, particularly in corticospinal pathways, emerge as intermediate disease features. Cerebellar and cerebral gray matter loss, principally targeting motor and sensory systems, preferentially manifests later in the disease course. Interpretation: FRDA is defined by an evolving spatial profile of neuroanatomical changes beyond primary pathology in the cerebellum and spinal cord, in line with its progressive clinical course. The design, interpretation, and generalization of research studies and clinical trials must consider neuroanatomical staging and associated interindividual variability in brain measures. ANN NEUROL 2021;90:570–583.

Introduction Child mortality has been linked to infectious diseases, malnutrition and lack of access to essential health services. We investigated possible predictors for death and patients lost to follow up (LTFU) for paediatric patients at the inpatient department (IPD) and inpatient therapeutic feeding centre (ITFC) of the Anka General Hospital (AGH), Zamfara State, Nigeria, to inform best practices at the hospital. Methods We conducted a retrospective cohort review study using routinely collected data of all patient admissions to the IPD and ITFC with known hospital exit status between 2016 and 2018. Unadjusted and adjusted rate ratios (aRR) and respective 95% confidence intervals (95% CI) were calculated using Poisson regression to estimate the association between the exposure variables and mortality as well as LTFU. Results The mortality rate in IPD was 22% lower in 2018 compared to 2016 (aRR 0.78; 95% CI 0.66–0.93) and 70% lower for patients coming from lead-affected villages compared to patients from other villages (aRR 0.30; 95% CI 0.19–0.48). The mortality rate for ITFC patients was 41% higher during rainy season (aRR 1.41; 95% CI 1.2–1.6). LTFU rates in ITFC increased in 2017 and 2018 when compared to 2016 (aRR 1.6; 95% CI 1.2–2.0 and aRR 1.4; 95% CI 1.1–1.8) and patients in ITFC had 2.5 times higher LTFU rates when coming from a lead-affected village. Conclusions Our data contributes clearer understanding of the situation in the paediatric wards in AGH in Nigeria, but identifying specific predictors for the multifaceted nature of mortality and LTFU is challenging. Mortality in paediatric patients in IPD of AGH improved during the study period, which is likely linked to better awareness of the hospital, but still remains high. Access to healthcare due to seasonal restrictions contributes to mortalities due to late presentation. Increased awareness of and easier access to healthcare, such as for patients living in lead-affected villages, which are still benefiting from an MSF lead poisoning intervention, decreases mortalities, but increases LTFU. We recommend targeted case audits and qualitative studies to better understand the role of health-seeking behaviour, and social and traditional factors in the use of formal healthcare in this part of Nigeria and potentially similar settings in other countries.

A variety of neuropsychiatric complications has been described in association with Covid-19 infection. Large scale studies presenting a wider picture of these complications and their relative frequency are lacking. The objective of our study was to describe the spectrum of neurological and psychiatric complications in patients with Covid-19 seen in a multidisciplinary hospital center over six months. We conducted a retrospective, observational study on all patients showing neurological or psychiatric symptoms in the context of Covid-19 seen in the medical and university neuroscience department of Assistance Publique Hopitaux de Paris -Sorbonne University. We collected demographic data, comorbidities, symptoms and severity of Covid-19 infection, neurological and psychiatric symptoms, neurological and psychiatric examination data and, when available, results from CSF analysis, MRI, EEG and EMG. A total of 249 Covid-19 patients with a de novo neurological or psychiatric manifestation were included in the database and 245 were included in the final analyses. One-hundred fourteen patients (47%) were admitted to the intensive care unit and 10 (4%) died. The most frequent neuropsychiatric complications diagnosed were encephalopathy (43%), critical illness polyneuropathy and myopathy (26%), isolated psychiatric disturbance (18%), and cerebrovascular disorders (16%). No patients showed CSF evidence of SARS-CoV-2. Encephalopathy was associated with older age and higher risk of death. Critical illness neuromyopathy was associated with an extended stay in the intensive care unit. The majority of these neuropsychiatric complications could be imputed to critical illness, intensive care and systemic inflammation, which contrasts with the paucity of more direct SARS-CoV-2-related complications or post-infection disorders., Graphical Abstract Graphical Abstract

The mechanisms contributing to increased expression of motor and cognitive impairment in people with Parkinson9s disease who lack muscle atonia during rapid eye movement (REM) sleep compared to those with muscle atonia are poorly understood. This study used tract-based spatial statistics to compare diffusion measures of white matter microstructure between people with Parkinson9s disease with and without REM sleep without atonia as well as the relationships of these measures to motor and cognitive function. Thirty-eight individuals with mild-to-moderate Parkinson9s disease and twenty-one matched control subjects underwent ultra-high-field MRI (7Tesla), quantitative motor assessments of gait and bradykinesia, and neuropsychological testing. The Parkinson9s disease cohort was separated post-hoc into those with and without elevated chin or leg muscle activity during REM sleep based on polysomnography findings. Fractional anisotropy was significantly higher, and radial and mean diffusivity significantly lower, in diffuse regions of the corpus callosum, projection, and association white matter pathways in the Parkinson9s group with normal REM sleep compared to controls. In contrast, there was no significant difference in fractional anisotropy between the Parkinson9s group with elevated muscle tone and controls. Fractional anisotropy was also significantly higher in a subset of pathways in the Parkinson9s disease group with normal REM sleep muscle tone compared to those with elevated REM sleep muscle tone. The group with elevated REM sleep muscle tone had significant impairments in gait and upper arm speed compared to controls and significantly worse scores in specific cognitive domains (executive function, visuospatial memory) compared to the Parkinson9s disease group with normal REM sleep muscle tone. Regression analyses showed that gait speed and step length in the Parkinson9s disease cohort were predicted by measures of mean fractional anisotropy of the anterior corona radiata, whereas elbow flexion velocity was predicted by fractional anisotropy of the superior corona radiata. Visuospatial memory task performance was predicted by the radial diffusivity of the posterior corona radiata. These findings demonstrate that people with mild-to-moderate severity of Parkinson9s disease who have normal muscle tone during REM sleep show alterations in white matter microstructure that are associated with preserved motor and cognitive function, but these adaptations are reduced or absent in those with increased REM sleep motor tone.

Purpose To evaluate adherence (as measured by the medication possession ratio) to the first ever course of oral antineoplasic treatment in cancer patients before and after the implementation of a multidisciplinary consultation program (involving an oncologist, a pharmacist, and a nurse) and to investigate the program's impact on adverse events and drug-related problems. Patients and Methods In a retrospective single-center study, we compared the medication possession ratio 2 months after treatment initiation in a control group (before multidisciplinary consultation program implementation) versus an interventional group (after multidisciplinary consultation program implementation). Results Two months after oral antineoplasic treatment initiation, the mean ± standard deviation medication possession ratio did not differ significantly when comparing the interventional (multidisciplinary consultation program) group ( n = 33; 0.99 ± 0.06) with the control group ( n = 64; 0.94 ± 0.16) ( p = 0.062). Patients in the multidisciplinary consultation program group had fewer adverse events in general (41, vs 109 in the control group; p = 0.048) and digestive adverse events in particular (6 vs 29, respectively; p = 0.007). A total of 53 and 40 drug-related problems were identified in the control and multidisciplinary consultation program groups, respectively ( p = 0.074). Conclusions Implementation of an multidisciplinary consultation program was not associated with a significant difference in drug adherence (as assessed by the medication possession ratio), which was good before and after implementation. The multidisciplinary consultation program was associated with a lower incidence of adverse events.

International audience; Riboflavin transporter deficiency (RTD) was recently characterized as a cause of genetic recessive childhood-onset motor neuron disease (MND) with hearing loss, formerly described as Brown-Vialetto-Van-Lear syndrome. We describe a 18-year-old woman with probable RTD mimicking juvenile Amyotrophic Lateral Sclerosis (ALS) who presented with an inaugural respiratory failure and moderate distal four limbs weakness. Only one heterozygous SLC52A3 mutation was detected, but presence of a sub-clinical auditory neuropathy and dramatic improvement under high dose riboflavin argued for a RTD. As RTD probably has a larger phenotypic spectrum than expected, a high dose riboflavin trial should be discussed in young-onset MND.

Objectives\ud\udWe analysed the concordance of rectal swab isolates and blood culture for Gram-negative bacteria (GNB) isolates in neonates with a suspicion of neonatal sepsis admitted to a neonatal care unit in Haiti.\udMethods\ud\udWe matched pairs of blood and rectal samples taken on the date of suspected sepsis onset in the same neonate. We calculated the proportion of rectal isolates in concordance with the blood isolates by species and genus. We calculated the negative predictive value (NPV) for GNB and extended-spectrum β-lactamase (ESBL)-producing GNB for all rectal and blood isolate pairs in neonates with suspected sepsis.\udResults\ud\udWe identified 238 blood and rectal samples pairs, with 238 blood isolate results and 309 rectal isolate results. The overall concordance in genus and species between blood and rectal isolates was 22.3% [95% confidence interval (CI) 17.4–28.0%] and 20.6% (95% CI 16.0–26.2%), respectively. The highest concordance between blood and rectal isolates was observed for samples with no bacterial growth (65%), followed byKlebsiella pneumoniae (18%) and Klebsiella oxytoca (12%). The NPV of detecting GNB bacterial isolates in rectal samples compared with those in blood samples was 81.6% and the NPV for ESBL-positive GNB was 92.6%.\udConclusions\ud\udThe NPV of rectal swab GNB isolates was high in all patient groups and was even higher for ESBL-positive GNB. Clinicians can use the results from rectal swabs when taken simultaneously with blood samples during outbreaks to inform the (de-)escalation of antibiotic therapy in those neonates that have an ongoing sepsis profile.

BackgroundNoma, a neglected disease mostly affecting children, with a 90% mortality rate if untreated, is an orofacial gangrene that disintegrates the tissues of the face in MethodsWe conducted 12 in-depth interviews with caretakers who were looking after noma patients admitted at the Noma Children's Hospital and 15 traditional healers in their home villages in Sokoto state, northwest Nigeria. We explored perceptions of noma, relationship dynamics, healthcare practices and intervention opportunities. Interviews were audiorecorded, transcribed and translated. Manual coding and thematic analysis were utilised.ResultsTraditional healers offered specialised forms of care for specific conditions and referral guidance. They viewed the stages of noma as different conditions with individualised remedies and were willing to refer noma patients. Caretakers trusted traditional healers.ConclusionsTraditional healers could play a crucial role in the early detection of noma and the health-seeking decision-making process of patients. Intervention programmes should include traditional healers through training and referral partnerships. This collaboration could save lives and reduce the severity of noma complications.

Ischemic stroke is highly prevalent in chronic kidney disease (CKD) patients and has been associated with a higher risk of neurological deterioration and in-hospital mortality. To date, little is known about the processes by which CKD worsens ischemic stroke. This work aimed to investigate the cellular and molecular mechanism associated with ischemic stroke severity in an in vivo model of CKD. CKD was induced through right kidney cortical electrocautery in 8-week-old female C57BL/6 J mice followed by left total nephrectomy. Transient middle cerebral artery occlusion (tMCAO) was performed 6 weeks after left nephrectomy. Twenty-four hours after tMCAO, the infarct volumes were significantly wider in CKD than in SHAM mice. CKD mice displayed decreased neuroscore, impaired ability to remain on rotarod device, weaker muscular strength and decreased prehensile score. Apoptosis, neuronal loss, glial cells recruitment and microglia/macrophages M1 signature genes CD32, CD86, IL-1β, IL-6, MCP1 and iNOS were significantly increased within ischemic lesions of CKD mice. This effect was associated with decreased AMP kinase phosphorylation and increased activation of the NFΚB pathway. Pharmacological targeting of AMP kinase activity, which is known to block microglia/macrophages M1 polarization, appears promising to improve stroke recovery in CKD.

Introduction and aims Calcific aortic valve disease (CAVD) is the most common heart valve disease in western countries. It has been reported that activation of the calcium-sensing receptor(CaSR) expressed by vascular smooth muscle cells prevents vascular calcification. However, to date, the CaSR's expression and function in cardiac valves have not been studied. The present study sought to evaluate the presence of the CaSR within human valvular interstitial cells (hVICs), assess the CaSR's functionality, and ascertain its involvement in hVIC calcification. Methods and results Data from Western blot, flow cytometry and immunocytochemistry experiments demonstrated that primary hVICs express the CaSR. The receptor was functional, since the incubation of hVICs with the calcimimetic R-568 significantly increased Ca2+-induced ERK1/2 phosphorylation, and exposure to the calcilytic NPS2143 reduced ERK1/2 activation. A reduction in endogenous CaSR expression by hVICs (using siRNA) was associated with significantly lower levels of Ca2+-induced mineralization (quantified using Alizarin Red staining). Similar data were obtained after the pharmacological inhibition of CaSR activity by the calcilytic NPS2143. In contrast, overexpression of a functional CaSR amplified Ca2+-induced calcification. Pharmacological activation of the CaSR with the calcimimetic R-568 showed similar effects. CaSR's procalcific properties are associated with increased osteogenic transition (as characterized by elevated mRNA expression of bone morphogenetic protein 2 and osterix), and reduced the expression of the calcification inhibitor osteopontin. Histological analysis of 12 human aortic tricuspid valves showed that CaSR expression was greater in calcified areas than in non-calcified areas. These data were confirmed by Western blots. Conclusions To the best of our knowledge, this study is the first to have demonstrated that hVICs express a functional CaSR. Taken as a whole, our data suggest that activation of the CaSR expressed by hVICs might be a key promoter of CAVD progression.

Mild traumatic brain injury (mTBI) is a significant cause of disability, especially when symptoms become chronic. This chronicity is often linked to oculomotor dysfunction (OMD). To our knowledge, this is the first prospective study to localize aberrations in brain function between mTBI cohorts, by comparing patients with mTBI with OMD with an mTBI control group without OMD, using task and resting-state functional magnetic resonance imaging (fMRI). Ten subjects with mTBI who had OMD (OMD group) were compared with nine subjects with mTBI who had no findings of OMD (control group). These groups were determined by a developmental optometrist using objective testing for OMD. The (convergence) task fMRI data demonstrated significantly decreased brain activity, measured as decreases in the blood oxygen level dependent (BOLD) signal, in the OMD group compared with the control group in three brain regions: the left posterior lingual gyrus, the bilateral anterior lingual gyrus and cuneus, and the parahippocampal gyrus. When doing a seed-based resting state fMRI analysis in the lingual/parahippocampal region, a large cluster covering the left middle frontal gyrus and the dorsolateral pre-frontal cortex (Brodmann areas 9 and 10), with decreased functional correlation in the OMD group, was identified. Together these observations provide evidence for neural networks of interactions involving the control of eye movement for visual processing, reading comprehension, spatial localization and navigation, and spatial working memory that appear to be decreased in mTBI patients with OMD compared with mTBI patients without OMD. The clinical symptomatology associated with post-traumatic OMD correlates well with these MRI findings.

Investigation of brain changes in functional connectivity and functional network topology from receiving 8-week selective serotonin reuptake inhibitor (SSRI) treatments is conducted in 12 unmedicated adolescents with major depressive disorder (MDD) by using wavelet-filtered resting-state functional magnetic resonance imaging (fMRI). Changes are observed in frontal-limbic, temporal, and default mode networks. In particular, topological analysis shows, at the global scale and in the 0.12–0.25 Hz band, that the normalized clustering coefficient and smallworldness of brain networks decreased after treatment. Regional changes in clustering coefficient and efficiency were observed in the bilateral caudal middle frontal gyrus, rostral middle frontal gyrus, superior temporal gyrus, left pars triangularis, putamen, and right superior frontal gyrus. Furthermore, changes of nodal centrality and changes of connectivity associated with these frontal and temporal regions confirm the global topological alternations. Moreover, frequency dependence is observed from FDR-controlled subnetworks for the limbic-cortical connectivity change. In the high-frequency band, the altered connections involve mostly frontal regions, while the altered connections in the low-frequency bands spread to parietal and temporal areas. Due to the limitation of small sample sizes and lack of placebo control, these preliminary findings require confirmation with future work using larger samples. Confirmation of biomarkers associated with treatment could suggest potential avenues for clinical applications such as tracking treatment response and neurobiologically informed treatment optimization.

In a companion paper by Cohen-Adad et al. we introduce the spine generic quantitative MRI protocol that provides valuable metrics for assessing spinal cord macrostructural and microstructural integrity. This protocol was used to acquire a single subject dataset across 19 centers and a multi-subject dataset across 42 centers (for a total of 260 participants), spanning the three main MRI manufacturers: GE, Philips and Siemens. Both datasets are publicly available via git-annex. Data were analysed using the Spinal Cord Toolbox to produce normative values as well as inter/intra-site and inter/intra-manufacturer statistics. Reproducibility for the spine generic protocol was high across sites and manufacturers, with an average inter-site coefficient of variation of less than 5% for all the metrics. Full documentation and results can be found at https://spine-generic.rtfd.io/. The datasets and analysis pipeline will help pave the way towards accessible and reproducible quantitative MRI in the spinal cord., Measurement(s)spinal cordTechnology Type(s)magnetic resonance imagingFactor Type(s)manufacturer • siteSample Characteristic - OrganismHomo sapiensSample Characteristic - LocationCanada • Switzerland • Australia • United States of America • United Kingdom • Germany • French Republic • Czech Republic • Italy • Japan • Kingdom of Spain • China Machine-accessible metadata file describing the reported data: 10.6084/m9.figshare.14052269

Chronic kidney disease (CKD) worsens ischemic stroke severity in both patients and animals. In mice, these poorer functional outcomes are associated with decreased brain activity of AMP-activated protein kinase (AMPK), a molecule that recently emerged as a potential therapeutic target for ischemic stroke. The antidiabetic drug metformin, a well-known activator of AMPK, has improved stroke outcomes in diabetic patients with normal renal function. We investigated whether chronic metformin pre-conditioning can rescue AMPK activity and prevent stroke damage in non-diabetic mice with CKD. Eight-week-old female C57BL/6J mice were assigned to CKD or SHAM groups. CKD was induced through right kidney cortical electrocautery, followed by left total nephrectomy. Mice were then allocated to receive metformin (200 mg/kg/day) or vehicle for 5 weeks until stroke induction by transient middle cerebral artery occlusion (tMCAO). The infarct volumes were lower in CKD mice exposed to metformin than in vehicle-treated CKD mice 24 h after tMCAO. Metformin pre-conditioning of CKD mice improved their neurological score, grip strength, and prehensile abilities. It also enhanced AMPK activation, reduced apoptosis, increased neuron survival and decreased microglia/macrophage M1 signature gene expression as well as CKD-induced activation of the canonical NF-κB pathway in the ischemic lesions of CKD mice.

PURPOSE/OBJECTIVE(S) To evaluate the efficacy and safety of radiotherapy (RT) of the primary salivary glands in a large series of patients with amyotrophic lateral sclerosis (ALS) and Parkinson's disease with sialorrhea. MATERIALS/METHODS Patients treated in our institution between 2010 and 2020 were retrospectively analyzed, including the first 50 patients prospectively analyzed. All patients included were refractory to conventional sialorrhea drug treatments. RT was delivered by a conventional LINAC, with 2 opposite beams including the two submandibular glands and two thirds of the two parotid glands before 2014, and from 2015 2 lateral beams including the submaxillary glands, and 2 opposite oblique beams directed to each parotid gland, with reduced oral cavity irradiation. The total dose delivered was 10 Gy in 2 fractions or 20 Gy in 4 fractions. RT efficacy was assessed using the 9-item Sialorrhea Scoring Scale (SSS), prospectively validated as the most effective and sensitive tool for measuring sialorrhea in ALS patients. RESULTS A total of 235 patients were included, and 281 treatments (45 reirradiations, 1 patient received 3 irradiations). Median age was 69 years (range: 38 - 95), 127 women (54%) and 126 men (46%), 212 had ALS (90%), 17 had Parkinson's disease (7%), and 5 patients (3%) had another neurological disorder. Median interval between the first and second radiotherapy course was 7.5 months (range: 1 - 37). The median SSS score before radiation therapy was 8 (range: 6 - 9), and the median SSS score at 1 month of irradiation was 2 (range: 1 - 6). There was no toxicity of > grade 1. At the end of RT, all but one patient had an improvement in SSS score: 272 had a complete response (CR) (97%, SSS 1-3) and 8 had a partial response (PR) (3%, SSS 4-5); one patient had a stable SSS score (< 1%). A 1-month CR after RT was achieved in 96% of the 235 patients who underwent a primary RT, and 100% of the 45 patients who received re-irradiation. Patients treated with 20Gy versus 10Gy during the first RT treatment were more likely to have a CR at 1 month (99% vs. 91%, P = 0.007), and had a greater decrease in SSS score (mean difference -6 vs. -5 points, P < 0.001). Also, the 45 patients who received reirradiation were more frequently previously treated with the RT 10Gy protocol (25/45 patients, 55%) versus 60/191 (31%) in patients who did not require reirradiation (P < 0.001). The 3-beam irradiation technique, used from 2014 and beyond, did not significantly improve treatment efficacy (reduction of the SSS score by -5.8 points on average versus -5.6 points previously, P = 0.3). Nevertheless, it reduced 1 month toxicity, in particular decreased saliva thickening discomfort (P < 0.001). CONCLUSION A 20 Gy irradiation in 4 fractions is an effective treatment for ALS patients with sialorrhea, with minimal toxicity, particularly by separately targeting parotid and submaxillary glands. A shorter RT (10 Gy in 2 fractions) may be proposed in patients with poor medical condition, subject to its lower efficacy and the greater need for reirradiation.

Background Low birthweight (LBW) infants are at higher risk of mortality and morbidity (growth, chronic disease and neurological problems) during their life. Due to the high incidence of (pre-) eclampsia in Haiti, LBW infants are common. We assessed the anthropometric growth (weight and length) and neurodevelopmental delay in LBW and normal birthweight (NBW) infants born at an obstetric emergency hospital in Port au Prince, Haiti, between 2014 and 2017. Methods Infants were followed at discharge and 3, 6, 12, 15, 18, 21 and 24 months of corrected gestational age. At each visit they underwent a physical checkup (weight, length, physical abnormalities, identification of morbidities). At 6, 12, 18 and 24 months they underwent a neurodevelopmental assessment using the Bayley Scale III (motor, cognitive and communication skills). We modelled the trajectories between birth and 24 months of age of NBW compared to LBW infants for weight, length, and raw scores for Bayley III assessments using mixed linear models. Results In total 500 LBW and 210 NBW infants were recruited of which 333 (46.7%) were followed up for 24 months (127 NBW; 60.5% and 206 LBW; 41.2%) and 150 died (LBW = 137 and NBW = 13). LBW and NBW babies gained a mean 15.8 g and 11.4 g per kg of weight from discharge per day respectively. The speed of weight gain decreased rapidly after 3 months in both groups. Both groups grow rapidly up to 6 months of age. LBW grew more than the NBW group during this period (22.8 cm vs. 21.1 cm). Both groups had WHZ scores Conclusion LBW babies that survive neonatal care in urban Haiti and live up to 24 months of age, perform similar to their NBW for weight, length and fine motor skills. LBW babies are delayed in gross motor, cognitive and communication skills development. Further research on the clinical significance of these findings and long term implications of this neurodevelopmental delay is needed.

BACKGROUND AND PURPOSE Non-myelopathic degenerative cervical spinal cord compression (NMDC) frequently occurs throughout aging and may progress to potentially irreversible degenerative cervical myelopathy (DCM). Whereas standard clinical magnetic resonance imaging (MRI) and electrophysiological measures assess compression severity and neurological dysfunction, respectively, underlying microstructural deficits still have to be established in NMDC and DCM patients. The study aims to establish tract-specific diffusion MRI markers of electrophysiological deficits to predict the progression of asymptomatic NMDC to symptomatic DCM. METHODS High-resolution 3 T diffusion MRI was acquired for 103 NMDC and 21 DCM patients compared to 60 healthy controls to reveal diffusion alterations and relationships between tract-specific diffusion metrics and corresponding electrophysiological measures and compression severity. Relationship between the degree of DCM disability, assessed by the modified Japanese Orthopaedic Association scale, and tract-specific microstructural changes in DCM patients was also explored. RESULTS The study identified diffusion-derived abnormalities in the gray matter, dorsal and lateral tracts congruent with trans-synaptic degeneration and demyelination in chronic degenerative spinal cord compression with more profound alterations in DCM than NMDC. Diffusion metrics were affected in the C3-6 area as well as above the compression level at C3 with more profound rostral deficits in DCM than NMDC. Alterations in lateral motor and dorsal sensory tracts correlated with motor and sensory evoked potentials, respectively, whereas electromyography outcomes corresponded with gray matter microstructure. DCM disability corresponded with microstructure alteration in lateral columns. CONCLUSIONS Outcomes imply the necessity of high-resolution tract-specific diffusion MRI for monitoring degenerative spinal pathology in longitudinal studies.

Contains fulltext : 244043.pdf (Publisher’s version ) (Open Access) Pediatric community-acquired bloodstream infections (CA-BSIs) in sub Saharan African humanitarian contexts are rarely documented. Effective treatment of these infections is additionally complicated by increasing rates of antimicrobial resistance. We describe the findings from epidemiological and microbiological surveillance implemented in pediatric patients with suspected CA-BSIs presenting for care at a secondary hospital in the conflict affected area of Zamfara state, Nigeria. Any child (> 2 months of age) presenting to Anka General Hospital from November 2018 to August 2020 with clinical severe sepsis at admission had clinical and epidemiological information and a blood culture collected at admission. Bacterial isolates were tested for antibiotic susceptibility. We calculated frequencies of epidemiological, microbiological and clinical parameters. We explored risk factors for death amongst severe sepsis cases using univariable and multivariable Poisson regression, adjusting for time between admission and hospital exit. We included 234 severe sepsis patients with 195 blood culture results. There were 39 positive blood cultures. Of the bacterial isolates, 14 were Gram positive and 18 were Gram negative; 5 were resistant to empiric antibiotics: methicillin-resistant Staphylococcus aureus (MRSA; n = 2) and Extended Spectrum Beta-Lactamase positive enterobacterales (n = 3). We identified no significant association between sex, age-group, ward, CA-BSI, appropriate intravenous antibiotic, malaria positivity at admission, suspected focus of sepsis, clinical severity and death in the multivariable regression. There is an urgent need for access to good clinical microbiological services, including point of care methods, and awareness and practice around rational antibiotic in healthcare staff in humanitarian settings to reduce morbidity and mortality from sepsis in children.

Spinocerebellar ataxia type 1 is a progressive neurodegenerative, movement disorder. With potential therapies on the horizon, it is critical to identify biomarkers that (i) differentiate between unaffected and spinocerebellar ataxia Type 1-affected individuals; (ii) track disease progression; and (iii) are directly related to clinical changes of the patient. Magnetic resonance imaging of volumetric changes in the brain may be a suitable source of biomarkers for spinocerebellar ataxia Type 1. In a previous report on a longitudinal study of patients with spinocerebellar ataxia Type 1, we evaluated the volume and magnetic resonance spectroscopy measures of the cerebellum and pons, showing pontine volume and pontine N-acetylaspartate-to-myo-inositol ratio were sensitive to change over time. As a follow-up, the current study conducts a whole brain exploration of volumetric MRI measures with the aim to identify biomarkers for spinocerebellar ataxia Type 1 progression. We adapted a joint label fusion approach using multiple, automatically generated, morphologically matched atlases to label brain regions including cerebellar sub-regions. We adjusted regional volumes by total intracranial volume allowing for linear and power-law relationships. We then utilized Bonferroni corrected linear mixed effects models to (i) determine group differences in regional brain volume and (ii) identify change within affected patients only. We then evaluated the rate of change within each brain region to identify areas that changed most rapidly. Lastly, we used a penalized, linear mixed effects model to determine the strongest brain predictors of motor outcomes. Decrease in pontine volume and accelerating decrease in putamen volume: (i) reliably differentiated spinocerebellar ataxia Type 1-affected and -unaffected individuals; (ii) were observable in affected individuals without referencing an unaffected comparison group; (iii) were detectable within ∼6–9 months; and (iv) were associated with increased disease burden. In conclusion, volumetric change in the pons and putamen may provide powerful biomarkers to track disease progression in spinocerebellar ataxia Type 1. The methods employed here are readily translatable to current clinical settings, providing a framework for study and usage of volumetric neuroimaging biomarkers for clinical trials., There is an urgent need for biomarkers that track neurodegenerative disease progression. Pontine and putamen volume decreases are specific to affected individuals, track disease progression within 6–9 months and are directly related to clinical changes in individuals affected by spinocerebellar ataxia Type 1, making them potential biomarkers for clinical trials., Graphical Abstract

An amendment to this paper has been published and can be accessed via a link at the top of the paper.

Background The prevalence of (pre-)eclampsia in pregnant women in Haiti is high and access to maternal health services is scarce. Limited evidence exists around negative maternal and neonatal outcomes in Haitian women and their offspring. We describe the patient profile of women admitted to an obstetric emergency hospital in Port-au-Prince between January 2013 and June 2018 and the estimated risk factors for maternal death, stillbirth and low birthweight (LBW). Methods We calculated frequencies of age groups, singleton vs. multiple pregnancies, delivery procedures and antenatal care (ANC) services for all maternal admissions. We estimated the associated risk between these factors and the three negative outcomes by calculating odds ratios (OR) and their 95% confidence intervals (CI) using univariate and multivariate logistic regression. We adjusted for an interaction between delivery procedure and pregnancy category in the regression models for maternal death and stillbirth. Results We included 31,509 women and 24,983 deliveries and documented 204 (0.6%) maternal deaths (648/100,000 women giving birth), 1,962 (7.9%) stillbirths and 11,008 (44.1%) LBW neonates. 34.9% of all admissions (n = 10,991) were women with (pre-)eclampsia. Maternal death was more likely in women with complicated pregnancies and/or deliveries and women with (pre-)eclampsia when undergoing a C-section compared to women with uncomplicated vaginal deliveries (OR 4.8; CI 1.7–13.8 and OR 2.3; CI 1.5–3.6 respectively). Stillbirth was more likely in women ≥ 35 years compared to women 20–34 years in complicated pregnancies and/or deliveries (OR 1.3; CI 1.1–1.6) and (pre-)eclampsia (OR 1.4; CI 1.2–1.7). C-sections in women with a complicated pregnancy and/or delivery and women with (pre-)eclampsia reduced the risk of stillbirth (OR 0.7; CI 0.6–0.9 and OR 0.3; CI 0.2–0.3 respectively). Not attending ANC was associated with a higher risk of stillbirth (OR 4.8; CI 3.6–6.6) and LBW (OR 1.4; CI 1.1–1.9) for women with complicated pregnancies and/or deliveries. Conclusion Maternal mortality in high-risk pregnancies in CRUO is higher than the national estimate of 529 per 100,000 deliveries. Attendance of ANC services is associated with a decrease in adverse neonatal outcomes including LBW and stillbirth. We recommend that access to maternal and neonatal healthcare facilities in Port-au-Prince is improved.

Introduction A phenotype of isolated parkinsonism mimicking Idiopathic Parkinson's Disease (IPD) is a rare clinical presentation of GRN and C9orf72 mutations, the major genetic causes of frontotemporal dementia (FTD). It still remains controversial if this association is fortuitous or not, and which clinical clues could reliably suggest a genetic FTD etiology in IPD patients. This study aims to describe the clinical characteristics of FTD mutation carriers presenting with IPD phenotype, provide neuropathological evidence of the mutation's causality, and specifically address their “red flags” according to current IPD criteria. Methods Seven GRN and C9orf72 carriers with isolated parkinsonism at onset, and three patients from the literature were included in this study. To allow better delineation of their phenotype, the presence of supportive, exclusion and “red flag” features from MDS criteria were analyzed for each case. Results Amongst the ten patients (5 GRN, 5 C9orf72), seven fulfilled probable IPD criteria during all the disease course, while behavioral/language or motoneuron dysfunctions occurred later in three. Disease duration was longer and dopa-responsiveness was more sustained in C9orf72 than in GRN carriers. Subtle motor features, cognitive/behavioral changes, family history of dementia/ALS were suggestive clues for a genetic diagnosis. Importantly, neuropathological examination in one patient revealed typical TDP-43-inclusions without alpha-synucleinopathy, thus demonstrating the causal link between FTD mutations, TDP-43-pathology and PD phenotype. Conclusion We showed that, altogether, family history of early-onset dementia/ALS, the presence of cognitive/behavioral dysfunction and subtle motor characteristics are atypical features frequently present in the parkinsonian presentations of GRN and C9orf72 mutations.

The robustness of brain structural networks, estimated from diffusion MRI data, may be relevant to cognition. We investigate whether measures of network robustness, such as Ollivier-Ricci curvature, can explain cognitive impairment in multiple sclerosis (MS). We assessed whether local (i.e., cortical area) and/or global (i.e., whole brain) robustness, differs between cognitively impaired (MSCI) and non-impaired (MSNI) MS patients. Fifty patients, with Expanded Disability Status Scale mean (m): 3.2, disease duration m: 12 years, and age m: 40 years, were enrolled. Cognitive impairment scores were estimated from the Minimal Assessment of Cognitive Function in Multiple Sclerosis. Images were obtained in a 3T MRI using a diffusion protocol with a 2 min acquisition time. Brain structural networks were created using 333 cortical areas. Local and global robustness was estimated for each individual, and comparisons were performed between MSCI and MSNI patients. 31 MSCI and 10 MSNI patients were included in the analyses. Brain structural network robustness and centrality showed significant correlations with cognitive impairment. Measures of network robustness and centrality identified specific cortical areas relevant to MS-related cognitive impairment. These measures can be obtained on clinical scanners and are succinct yet accurate potential biomarkers of cognitive impairment.

The manifestations of borreliosis in the peripheral nervous system (PNS) remain poorly described. As the symptoms of neuroborreliosis can be reversed with timely introduction of antibiotics, early identification could avoid unnecessary axonal loss. Our aim was to describe the characteristics of confirmed neuroborreliosis cases involving the PNS diagnosed between 2007 and 2017 in our neuromuscular disease center in a nonendemic area (La Pitié-Salpêtrière Hospital, Paris, France). Neuroborreliosis was defined as follows: compatible neurological symptoms without other cause of neuropathy; cerebrospinal fluid and serum analysis (positive serological tests with ELISA, confirmed by Western Blot); and improvement of symptoms with adapted antibiotherapy. All the patients consulting in our center between 2007 and 2017 underwent electrophysiological study. Sixteen confirmed cases of neuroborreliosis involving the PNS were included: 10 cases of meningoradiculoneuritis, 4 of axonal neuropathy, and 2 of demyelinating neuropathy (one acute and one chronic). Only 4 (25%) patients reported tick bites. Meningoradiculoneuritis was characterized by lymphocytic meningitis, intense pain, cranial nerve palsy, and contrast enhancement of nerve roots on imagery. The patients with axonal neuropathy presented sensory symptoms with intense pain but no motor deficit and meningitis was rare. Nerve biopsy of 1 patient revealed lymphocytic vasculitis. Electrophysiological testing showed sensory or sensorimotor axonal neuropathy (3 subacute and 1 chronic) of the lower limbs, with asymmetrical neuropathy in 1 patients, symmetrical neuropathy in one and monomelic sensory mononeuritis multiplex in another. We also found 1 case of acute demyelinating neuropathy, treated with antibiotherapy and immunoglobulins, and 1 chronic demyelinating neuropathy. Overall, diaphragmatic paralysis was frequent (18.6%). Antibiotherapy (mostly ceftriaxone 3–4 weeks) resulted in symptom resolution. This series gives an updated overview of the peripheral complications of neuroborreliosis to help identify this disease so that timely treatment could avoid axonal loss.