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OBJECTIVE: The corticospinal tract (CST) reveals progressive microstructural alterations in ALS measurable by DTI. The aim of this study was to evaluate fractional anisotropy (FA) along the CST as a longitudinal marker of disease progression in ALS. METHODS: The study cohort consisted of 114 patients with ALS and 110 healthy controls from the second prospective, longitudinal, multicentre study of the Canadian ALS Neuroimaging Consortium (CALSNIC-2). DTI and clinical data from a harmonized protocol across 7 centres were collected. Thirty-nine ALS patients and 61 controls completed baseline and two follow-up visits and were included for longitudinal analyses. Whole brain-based spatial statistics and hypothesis-guided tract-of-interest analyses were performed for cross-sectional and longitudinal analyses. RESULTS: FA was reduced at baseline and longitudinally in the CST, mid-corpus callosum (CC), frontal lobe, and other ALS-related tracts, with alterations most evident in the CST and mid-CC. CST and pontine FA correlated with functional impairment (ALSFRS-R), upper motor neuron function, and clinical disease progression rate. Reduction in FA was largely located in the upper CST; however, the longitudinal decline was greatest in the lower CST. Effect sizes were dependent on region, resulting in study group sizes between 17 and 31 per group over a 9-month interval. Cross-sectional effect sizes were maximal in the upper CST; whereas, longitudinal effect sizes were maximal in mid-callosal tracts. CONCLUSIONS: Progressive microstructural alterations in ALS are most prominent in the CST and CC. DTI can provide a biomarker of cerebral degeneration in ALS, with longitudinal changes in white matter demonstrable over a reasonable observation period, with a feasible number of participants, and within a multicentre framework.
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This study aimed to investigate the clinical stratification of amyotrophic lateral sclerosis (ALS) patients in relation to in vivo cerebral degeneration. One hundred forty-nine ALS patients and one hundred forty-four healthy controls (HCs) were recruited from the Canadian ALS Neuroimaging Consortium (CALSNIC). Texture analysis was performed on T1-weighted scans to extract the texture feature "autocorrelation" (autoc), an imaging biomarker of cerebral degeneration. Patients were stratified at baseline into early and advanced disease stages based on criteria adapted from ALS clinical trials and the King's College staging system, as well as into slow and fast progressors (disease progression rates, DPR). Patients had increased autoc in the internal capsule. These changes extended beyond the internal capsule in early-stage patients (clinical trial-based criteria), fast progressors, and in advanced-stage patients (King's staging criteria). Longitudinal increases in autoc were observed in the postcentral gyrus, corticospinal tract, posterior cingulate cortex, and putamen; whereas decreases were observed in corpus callosum, caudate, central opercular cortex, and frontotemporal areas. Both longitudinal increases and decreases of autoc were observed in non-overlapping regions within insula and precentral gyrus. Within-criteria comparisons of autoc revealed more pronounced changes at baseline and longitudinally in early- (clinical trial-based criteria) and advanced-stage (King's staging criteria) patients and fast progressors. In summary, comparative patterns of baseline and longitudinal progression in cerebral degeneration are dependent on sub-group selection criteria, with clinical trial-based stratification insufficiently characterizing disease stage based on pathological cerebral burden.
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Esclerosis Amiotrófica Lateral , Progresión de la Enfermedad , Imagen por Resonancia Magnética , Humanos , Esclerosis Amiotrófica Lateral/diagnóstico por imagen , Esclerosis Amiotrófica Lateral/patología , Masculino , Femenino , Persona de Mediana Edad , Anciano , Adulto , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Índice de Severidad de la Enfermedad , Estudios Longitudinales , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patologíaRESUMEN
BACKGROUND: Increased morbidity in many patients with myasthenia gravis (MG) on long-term immunosuppression highlights the need for improved treatments. The aim of this study is to investigate the safety and efficacy of iscalimab (CFZ533), a fully human anti-CD40 monoclonal antibody, in patients with moderate-to-severe MG receiving standard-of-care (SoC) therapies. METHODS: In this double-blind, placebo-controlled phase 2 study, symptomatic patients (n = 44) despite SoC were randomized 1:1 to receive intravenous iscalimab (10 mg/kg; n = 22) or placebo (n = 22) every 4 weeks for 6 doses in total. Patients were followed up for 6 months after the last dose. The total duration of the study was 52 weeks. RESULTS: In total, 34 of 44 patients (77.3 %) completed the study. The primary endpoint, Quantitative MG score, did not change significantly between baseline and week 25 for iscalimab (median [90 % CI], -4.07 [-5.67, -2.47]) versus placebo (-2.93 [-4.53, -1.33]); however, non-thymectomized patients (n = 29) showed more favorable results (iscalimab, -4.35 [-6.07, -2.64] vs placebo, -2.26 [-4.16, -0.36]). A statistically significant difference between iscalimab and placebo groups was observed in MG Composite score (adjusted mean change: -4.19 [-6.67, -1.72]; p = 0.007) at week 13, and MG-Activities of Daily Living score (-1.93 [-3.24, -0.62]; p = 0.018) at week 21. Adverse events were comparable between the iscalimab (91 %) and placebo (96 %) groups. CONCLUSION: Iscalimab showed favorable safety and improvements compared with placebo in non-thymectomized patients with moderate-to-severe MG. It did not show any protective effect in patients with moderate-to-severe MG.
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Actividades Cotidianas , Miastenia Gravis , Humanos , Resultado del Tratamiento , Anticuerpos Monoclonales/efectos adversos , Miastenia Gravis/tratamiento farmacológico , Miastenia Gravis/inducido químicamente , Método Doble CiegoRESUMEN
PURPOSE: The primary objective of this study was to determine if speech and pause measures obtained using a passage reading task and timing measures from a monosyllabic diadochokinesis (DDK) task differ across speakers of Canadian French diagnosed with amyotrophic lateral sclerosis (ALS) presenting with and without bulbar symptoms, and healthy controls. The secondary objective was to determine if these measures can reflect the severity of bulbar symptoms. METHOD: A total of 29 Canadian French speakers with ALS (classified as bulbar symptomatic [n = 14] or pre-symptomatic [n = 15]) and 17 age-matched healthy controls completed a passage reading task and a monosyllabic DDK task (/pa/ and /ta/), for up to three follow-up visits. Measures of speaking rate, total duration, speech duration, and pause events were extracted from the passage reading recordings using a semi-automated speech and pause analysis procedure. Manual analysis of DDK recordings provided measures of DDK rate and variability. RESULT: Group comparisons revealed significant differences (p = < .05) between the symptomatic group and the pre-symptomatic and control groups for all passage measures and DDK rates. Only the DDK rate in /ta/ differentiated the pre-symptomatic and control groups. Repeated measures correlations revealed moderate correlations (rrm = > 0.40; p = < 0.05) between passage measures of total duration, speaking rate, speech duration, and number of pauses, and ALSFRS-R total and bulbar scores, as well as between DDK rate and ALSFRS-R total score. CONCLUSION: Speech and pause measures in passage and timing measures in monosyllabic DDK tasks might be suitable for monitoring bulbar functional symptoms in French speakers with ALS, but more work is required to identify which measures are sensitive to the earliest stages of the disease.
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Esclerosis Amiotrófica Lateral , Habla , Humanos , Esclerosis Amiotrófica Lateral/complicaciones , Canadá , Medición de la Producción del Habla/métodos , LenguajeRESUMEN
Amyotrophic Lateral Sclerosis (ALS) is a complex neurodegenerative disorder characterized by motor neuron degeneration. Significant research has begun to establish brain magnetic resonance imaging (MRI) as a potential biomarker to diagnose and monitor the state of the disease. Deep learning has emerged as a prominent class of machine learning algorithms in computer vision and has shown successful applications in various medical image analysis tasks. However, deep learning methods applied to neuroimaging have not achieved superior performance in classifying ALS patients from healthy controls due to insignificant structural changes correlated with pathological features. Thus, a critical challenge in deep models is to identify discriminative features from limited training data. To address this challenge, this study introduces a framework called SF2Former, which leverages the power of the vision transformer architecture to distinguish ALS subjects from the control group by exploiting the long-range relationships among image features. Additionally, spatial and frequency domain information is combined to enhance the network's performance, as MRI scans are initially captured in the frequency domain and then converted to the spatial domain. The proposed framework is trained using a series of consecutive coronal slices and utilizes pre-trained weights from ImageNet through transfer learning. Finally, a majority voting scheme is employed on the coronal slices of each subject to generate the final classification decision. The proposed architecture is extensively evaluated with multi-modal neuroimaging data (i.e., T1-weighted, R2*, FLAIR) using two well-organized versions of the Canadian ALS Neuroimaging Consortium (CALSNIC) multi-center datasets. The experimental results demonstrate the superiority of the proposed strategy in terms of classification accuracy compared to several popular deep learning-based techniques.
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Esclerosis Amiotrófica Lateral , Humanos , Esclerosis Amiotrófica Lateral/diagnóstico por imagen , Canadá , Imagen por Resonancia Magnética/métodos , Neuroimagen , Encéfalo/diagnóstico por imagen , Encéfalo/patologíaRESUMEN
The absence of disease modifying treatments for amyotrophic lateral sclerosis (ALS) is in large part a consequence of its complexity and heterogeneity. Deep clinical and biological phenotyping of people living with ALS would assist in the development of effective treatments and target specific biomarkers to monitor disease progression and inform on treatment efficacy. The objective of this paper is to present the Comprehensive Analysis Platform To Understand Remedy and Eliminate ALS (CAPTURE ALS), an open and translational platform for the scientific community currently in development. CAPTURE ALS is a Canadian-based platform designed to include participants' voices in its development and through execution. Standardized methods will be used to longitudinally characterize ALS patients and healthy controls through deep clinical phenotyping, neuroimaging, neurocognitive and speech assessments, genotyping and multisource biospecimen collection. This effort plugs into complementary Canadian and international initiatives to share common resources. Here, we describe in detail the infrastructure, operating procedures, and long-term vision of CAPTURE ALS to facilitate and accelerate translational ALS research in Canada and beyond.
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Esclerosis Amiotrófica Lateral , Humanos , Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Canadá , Biomarcadores , Progresión de la Enfermedad , NeuroimagenRESUMEN
Although speech declines rapidly in some individuals with amyotrophic lateral sclerosis (ALS), longitudinal changes in speech have rarely been characterized. The study objectives were to model the rate of decline in speaking rate and speech intelligibility as a function of disease onset site, sex, and age at onset in 166 individuals with ALS; and estimate time to speech loss from symptom onset. We also examined the association between clinical (speaking rate/intelligibility) measures and patient-reported measures of ALS progression (ALSFRS-R). Speech measures declined faster in the bulbar-onset group than in the spinal-onset group. The rate of decline was not significantly affected by sex and age. Functional speech was still maintained at 60 months since disease onset for most patients with spinal onset. However, the time to speech loss was 23 months based on speaking rate < 120 (w/m) and 32 months based on speech intelligibility < 85% in individuals with ALS-bulbar onset. Speech measures were more responsive to functional decline than were the patient-reported measures. The findings of this study will inform future work directed toward improving speech prognosis in ALS, which is critical for determining the appropriate timing of interventions, providing appropriate counseling for patients, and evaluating functional changes during clinical trials.
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Esclerosis Amiotrófica Lateral , Humanos , Pronóstico , Trastornos del Habla/etiología , Inteligibilidad del HablaRESUMEN
Amyotrophic lateral sclerosis (ALS) is a multisystem neurodegenerative disorder characterized by progressive degeneration of upper motor neurons and lower motor neurons, and frontotemporal regions resulting in impaired bulbar, limb, and cognitive function. Magnetic resonance imaging studies have reported cortical and subcortical brain involvement in the pathophysiology of ALS. The present study investigates the functional integrity of resting-state networks (RSNs) and their importance in ALS. Intra- and inter-network resting-state functional connectivity (Rs-FC) was examined using an independent component analysis approach in a large multi-center cohort. A total of 235 subjects (120 ALS patients; 115 healthy controls (HC) were recruited across North America through the Canadian ALS Neuroimaging Consortium (CALSNIC). Intra-network and inter-network Rs-FC was evaluated by the FSL-MELODIC and FSLNets software packages. As compared to HC, ALS patients displayed higher intra-network Rs-FC in the sensorimotor, default mode, right and left fronto-parietal, and orbitofrontal RSNs, and in previously undescribed networks including auditory, dorsal attention, basal ganglia, medial temporal, ventral streams, and cerebellum which negatively correlated with disease severity. Furthermore, ALS patients displayed higher inter-network Rs-FC between the orbitofrontal and basal ganglia RSNs which negatively correlated with cognitive impairment. In summary, in ALS there is an increase in intra- and inter-network functional connectivity of RSNs underpinning both motor and cognitive impairment. Moreover, the large multi-center CALSNIC dataset permitted the exploration of RSNs in unprecedented detail, revealing previously undescribed network involvement in ALS.
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Esclerosis Amiotrófica Lateral , Encéfalo/diagnóstico por imagen , Mapeo Encefálico , Canadá , Humanos , Imagen por Resonancia Magnética , Estados UnidosRESUMEN
Objective: Amyotrophic lateral sclerosis (ALS) is a multi-system disorder characterized primarily by motor neuron degeneration, but may be accompanied by cognitive dysfunction. Statistically appropriate criteria for establishing cognitive impairment (CI) in ALS are lacking. We evaluate quantile regression (QR), that accounts for age and education, relative to a traditional two standard deviation (SD) cutoff for defining CI. Methods: QR of cross-sectional data from a multi-center North American Control (NAC) cohort of 269 healthy adults was used to model the 5th percentile of cognitive scores on the Edinburgh Cognitive and Behavioral ALS Screen (ECAS). The QR approach was compared to traditional two SD cutoff approach using the same NAC cohort (2SD-NAC) and to existing UK-based normative data derived using the 2SD approach (2SD-UK) to assess the impact of cohort selection and statistical model in identifying CI in 182 ALS patients. Results: QR-NAC models revealed that age and education impact cognitive performance on the ECAS. Based on QR-NAC normative cutoffs, the frequency of CI in the 182 PENN ALS patients was 15.9% for ALS specific, 12.6% for ALS nonspecific, and 15.4% for ECAS total. This frequency of CI is substantially more conservative in comparison to the 2SD-UK (20.3%-34.6%) and modestly more conservative to the 2SD-NAC (14.3%-16.5%) approaches for estimating CI. Conclusions: The choice of normative cohort has a substantial impact and choice of statistical method a modest impact on defining CI in ALS. This report establishes normative ECAS thresholds to identify whether ALS patients in the North American population have CI.
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Esclerosis Amiotrófica Lateral , Disfunción Cognitiva , Adulto , Humanos , Esclerosis Amiotrófica Lateral/complicaciones , Esclerosis Amiotrófica Lateral/diagnóstico , Esclerosis Amiotrófica Lateral/psicología , Pruebas Neuropsicológicas , Estudios Transversales , Disfunción Cognitiva/diagnóstico , Disfunción Cognitiva/etiología , Escolaridad , Cognición/fisiologíaRESUMEN
Progressive cerebral degeneration in amyotrophic lateral sclerosis (ALS) remains poorly understood. Here, three-dimensional (3D) texture analysis was used to study longitudinal gray and white matter cerebral degeneration in ALS from routine T1-weighted magnetic resonance imaging (MRI). Participants were included from the Canadian ALS Neuroimaging Consortium (CALSNIC) who underwent up to three clinical assessments and MRI at four-month intervals, up to 8 months after baseline (T0 ). Three-dimensional maps of the texture feature autocorrelation were computed from T1-weighted images. One hundred and nineteen controls and 137 ALS patients were included, with 81 controls and 84 ALS patients returning for at least one follow-up. At baseline, texture changes in ALS patients were detected in the motor cortex, corticospinal tract, insular cortex, and bilateral frontal and temporal white matter compared to controls. Longitudinal comparison of texture maps between T0 and Tmax (last follow-up visit) within ALS patients showed progressive texture alterations in the temporal white matter, insula, and internal capsule. Additionally, when compared to controls, ALS patients had greater texture changes in the frontal and temporal structures at Tmax than at T0 . In subgroup analysis, slow progressing ALS patients had greater progressive texture change in the internal capsule than the fast progressing patients. Contrastingly, fast progressing patients had greater progressive texture changes in the precentral gyrus. These findings suggest that the characteristic longitudinal gray matter pathology in ALS is the progressive involvement of frontotemporal regions rather than a worsening pathology within the motor cortex, and that phenotypic variability is associated with distinct progressive spatial pathology.
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Esclerosis Amiotrófica Lateral , Sustancia Blanca , Esclerosis Amiotrófica Lateral/diagnóstico por imagen , Esclerosis Amiotrófica Lateral/patología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Canadá , Humanos , Imagen por Resonancia Magnética/métodos , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patologíaRESUMEN
Objective: To understand current genetic testing practices at Canadian ALS clinics. Methods: An online survey and phone interviews, with clinicians practicing in 27 ALS clinics in Canada, were employed to collect data. Quantitative and qualitative analyses were conducted. Results: Ninety-three percent (25/27) of ALS clinics in Canada are routinely ordering genetic testing for familial ALS, while 33% (9/27) of clinics are routinely ordering genetic testing for sporadic ALS. Barriers to genetic testing include a perceived lack of an impact on treatment plan, difficulty in obtaining approvals, primarily from provincial Ministries of Health, and limited access to genetic counseling. Predictive testing practices were found to be the most variable across the country. The average wait time for a symptomatic patient living with ALS to see a genetic counselor in Canada is 10 months (range 0-36 months). Conclusions: Access to genetic testing, and testing practices, vary greatly across Canadian ALS clinics. There may be patients with a monogenetic etiology to their ALS who are not being identified given that genetic testing for patients diagnosed with ALS is not routinely performed at all clinics. This study highlights potential inequities for patients with ALS that can arise from variability in health care delivery across jurisdictions, in a federally-funded, but provincially-regulated, health care system. Clinical trials for both symptomatic ALS patients and pre-symptomatic ALS gene carriers are ongoing, and ALS clinicians in Canada are motivated to improve access to genetic testing for ALS.
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Esclerosis Amiotrófica Lateral , Esclerosis Amiotrófica Lateral/diagnóstico , Esclerosis Amiotrófica Lateral/epidemiología , Esclerosis Amiotrófica Lateral/genética , Canadá/epidemiología , Asesoramiento Genético , Pruebas Genéticas , Humanos , Encuestas y CuestionariosRESUMEN
OBJECTIVE: To evaluate safety, dose response, and preliminary efficacy of reldesemtiv over 12 weeks in patients with amyotrophic lateral sclerosis (ALS). Methods: Patients (≤2 years since diagnosis) with slow upright vital capacity (SVC) of ≥60% were randomized 1:1:1:1 to reldesemtiv 150, 300, or 450 mg twice daily (bid) or placebo; active treatment was 12 weeks with 4-week follow-up. Primary endpoint was change in percent predicted SVC at 12 weeks; secondary measures included ALS Functional Rating Scale-Revised (ALSFRS-R) and muscle strength mega-score. Results: Patients (N = 458) were enrolled; 85% completed 12-week treatment. The primary analysis failed to reach statistical significance (p = 0.11); secondary endpoints showed no statistically significant effects (ALSFRS-R, p = 0.09; muscle strength mega-score, p = 0.31). Post hoc analyses pooling all active reldesemtiv-treated patients compared against placebo showed trends toward benefit in all endpoints (progression rate for SVC, ALSFRS-R, and muscle strength mega-score (nominal p values of 0.10, 0.01 and 0.20 respectively)). Reldesemtiv was well tolerated, with nausea and fatigue being the most common side effects. A dose-dependent decrease in estimated glomerular filtration rate was noted, and transaminase elevations were seen in approximately 5% of patients. Both hepatic and renal abnormalities trended toward resolution after study drug discontinuation. Conclusions: Although the primary efficacy analysis did not demonstrate statistical significance, there were trends favoring reldesemtiv for all three endpoints, with effect sizes generally regarded as clinically important. Tolerability was good; modest hepatic and renal abnormalities were reversible. The impact of reldesemtiv on patients with ALS should be assessed in a pivotal Phase 3 trial. (ClinicalTrials.gov Identifier: NCT03160898).
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Esclerosis Amiotrófica Lateral , Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Método Doble Ciego , Humanos , Fuerza MuscularRESUMEN
The spinal muscular atrophies (SMA) affect lower motor neurons leading to important muscle atrophy and paralysis. Some cases of SMA affect mostly the lower limbs and are called autosomal dominant spinal muscular atrophy, lower extremity predominant (SMALED). So far, two genes have been identified to cause this phenotype, DYNC1H1 (SMALED1) and BICD2 (SMALED2). This pathology is rare, but patients exhibit classical features which should be recognised by physicians. We present two unrelated cases of SMALED2 with previously described c.320C>T BICD2 mutations. Our cases exhibit non-progressive weakness and atrophy of the lower limbs associated with contractures and unique muscle MRI findings suggestive of classical SMALED2. We also performed an extensive review of the literature to present the classical and atypical phenotypes of BICD2. Indeed, some features appear to be highly suggestive of the disease, including upper limb sparing, sparing of the adductors muscles on physical examination and MRI, congenital contractures and normal nerve conductions studies.
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Proteínas Asociadas a Microtúbulos/genética , Mutación/genética , Fenotipo , Atrofias Musculares Espinales de la Infancia/diagnóstico , Adulto , Femenino , Humanos , Extremidad Inferior/patología , Masculino , Persona de Mediana Edad , Músculo Esquelético/patología , Atrofia Muscular/patología , Atrofias Musculares Espinales de la Infancia/genéticaRESUMEN
Loss-of-function mutations in the potassium-chloride cotransporter KCC3 lead to Andermann syndrome, a severe sensorimotor neuropathy characterized by areflexia, amyotrophy and locomotor abnormalities. The molecular events responsible for axonal loss remain poorly understood. Here, we establish that global or neuron-specific KCC3 loss-of-function in mice leads to early neuromuscular junction (NMJ) abnormalities and muscular atrophy that are consistent with the pre-synaptic neurotransmission defects observed in patients. KCC3 depletion does not modify chloride handling, but promotes an abnormal electrical activity among primary motoneurons and mislocalization of Na+/K+-ATPase α1 in spinal cord motoneurons. Moreover, the activity-targeting drug carbamazepine restores Na+/K+-ATPase α1 localization and reduces NMJ denervation in Slc12a6-/- mice. We here propose that abnormal motoneuron electrical activity contributes to the peripheral neuropathy observed in Andermann syndrome.
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Agenesia del Cuerpo Calloso/metabolismo , Neuronas Motoras/metabolismo , Unión Neuromuscular/metabolismo , Enfermedades del Sistema Nervioso Periférico/metabolismo , Terminales Presinápticos/metabolismo , Simportadores/deficiencia , Transmisión Sináptica/fisiología , Agenesia del Cuerpo Calloso/tratamiento farmacológico , Agenesia del Cuerpo Calloso/patología , Animales , Carbamazepina/farmacología , Células Cultivadas , Cloruros/metabolismo , Modelos Animales de Enfermedad , Ratones Endogámicos C57BL , Ratones Transgénicos , Neuronas Motoras/efectos de los fármacos , Neuronas Motoras/patología , Unión Neuromuscular/efectos de los fármacos , Unión Neuromuscular/patología , Neurotransmisores/farmacología , Enfermedades del Sistema Nervioso Periférico/tratamiento farmacológico , Enfermedades del Sistema Nervioso Periférico/patología , Terminales Presinápticos/efectos de los fármacos , Terminales Presinápticos/patología , ATPasa Intercambiadora de Sodio-Potasio/metabolismo , Médula Espinal/efectos de los fármacos , Médula Espinal/metabolismo , Médula Espinal/patología , Simportadores/genética , Transmisión Sináptica/efectos de los fármacosAsunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/complicaciones , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico , Hemorragia Cerebral/etiología , Anciano , Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos/diagnóstico por imagen , Hemorragia Cerebral/diagnóstico por imagen , Humanos , MasculinoRESUMEN
INTRODUCTION: In recent studies on ultrasound-guided infraclavicular block (ICB), the authors have favoured a single injection posterior to the axillary artery rather than multiple injections; however, procedural complications and success rates associated with single-injection ultrasound-guided ICB are not well known. We undertook an observational study to evaluate the success rates of experienced and non-experienced operators performing ICBs and to identify the complications associated with ultrasound-guided single-injection ICB. METHODS: We conducted an observational cohort study of all ultrasound-guided single-injection ICBs performed over a two-year period (2008-2010). We identified the subjects for our study using a local database and excluded patients younger than 18 yr and those who received a continuous ICB. Complications (non-neurological and neurological) and ICB success rates were the primary and secondary end points, respectively. We collected the following data from patients' charts: patient demographics, types of complications and their respective frequencies, and the experience of the clinician performing the ICBs, and we identified potential late complications by telephone interview. Using a seven-point Likert scale, two experts in regional anesthesia evaluated the likelihood of a relationship between the identified neurological signs or symptoms and the ICB. A neurologist then evaluated the complications identified as being potentially related to the ICB. Summary data were collated, and 95% confidence intervals (CI) were calculated. RESULTS: We reviewed 627 ICB procedures, and 496 (79%) patients received telephone interviews. Most patients were males who had undergone either plastic or orthopedic surgery. Mepivacaine 1.5% was used in 96% of cases with a median volume of 30 mL [interquartile range 30-38]. We identified 131 cases of neurological signs or symptoms. Four cases were retained as possible links to the ICB, but they underwent complete resolution of symptoms at the time of evaluation. Two possible cases of local anesthetic toxicity were observed. There was a 93% success rate (95% CI 91 to 95) and the results were comparable between the experienced and the non-experienced operators (94% vs 93%, respectively). DISCUSSION: We observed few complications associated with a single-injection ultrasound-guided ICB and a high success rate regardless of the operator's expertise. The technique appears to be reliable, easy to perform, and safe.
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Anestésicos Locales/administración & dosificación , Bloqueo Nervioso/métodos , Ultrasonografía Intervencional/métodos , Adulto , Anciano , Anestésicos Locales/efectos adversos , Plexo Braquial , Estudios de Cohortes , Femenino , Humanos , Inyecciones , Masculino , Mepivacaína/administración & dosificación , Mepivacaína/efectos adversos , Persona de Mediana Edad , Bloqueo Nervioso/efectos adversos , Procedimientos Ortopédicos/métodos , Procedimientos de Cirugía Plástica/métodos , Factores de Tiempo , Resultado del TratamientoRESUMEN
Up to 16% of chronic inflammatory demyelinating polyneuropathy (CIDP) patients may present acutely. We performed a retrospective chart review on 30 acute inflammatory demyelinating polyneuropathy (AIDP) and 15 acute-onset CIDP (A-CIDP) patients looking for any clinical or electrophysiological parameters that might differentiate AIDP from acutely presenting CIDP. A-CIDP patients were significantly more likely to have prominent sensory signs. They were significantly less likely to have autonomic nervous system involvement, facial weakness, a preceding infectious illness, or need for mechanical ventilation. With regard to electrophysiological features, neither sural-sparing pattern, sensory ratio >1, nor the presence of A-waves was different between the two groups. This study suggests that patients presenting acutely with a demyelinating polyneuropathy and the aforementioned clinical features should be closely monitored as they may be more likely to have CIDP at follow-up.
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Fenómenos Electrofisiológicos/fisiología , Síndrome de Guillain-Barré/diagnóstico , Síndrome de Guillain-Barré/fisiopatología , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/diagnóstico , Polirradiculoneuropatía Crónica Inflamatoria Desmielinizante/fisiopatología , Potenciales de Acción/fisiología , Adulto , Sistema Nervioso Autónomo/fisiopatología , Diagnóstico Diferencial , Músculos Faciales/fisiopatología , Femenino , Humanos , Infecciones/fisiopatología , Masculino , Persona de Mediana Edad , Debilidad Muscular/fisiopatología , Respiración Artificial , Estudios RetrospectivosRESUMEN
BACKGROUND: This study aims to validate the fitting of contact lenses derived from refractive and keratometric values in a group of subjects with moderate (2.50 diopters [D] to 5.00 D) to severe (>5.00 D) astigmatism. It aims also to show whether soft or rigid gas-permeable (GP) contact lenses offer the best correction and to determine which modality is preferred by subjects. METHODS: Twenty subjects were randomly fitted with both soft and GP lenses. Group A was first fitted with soft lenses then switched to GPs and vice versa for group B. For each type of lens worn, low- and high-contrast visual acuity (VA) and stereoscopy were evaluated at both near and far. Each subject was asked to select the lens type of choice and to rate quality of vision in day-to-day activities through a questionnaire. RESULTS: There was no significant difference in objective binocular VA between current spectacles and empirically calculated soft toric lenses and GP toric/bi-toric contact lenses at all distances. That was also true for stereoscopy. Subjectively, most of the subjects preferred rigid contact lenses because of the quality of their vision in day-to-day activities, and a majority of them decided to continue with that modality. CONCLUSION: Empirical fitting of toric soft or GP contact lenses leads to very good results, which suggests that each type of lens might constitute a viable option.
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Astigmatismo/fisiopatología , Astigmatismo/rehabilitación , Lentes de Contacto , Ajuste de Prótesis/métodos , Ajuste de Prótesis/normas , Adulto , Lentes de Contacto Hidrofílicos , Estudios Cruzados , Anteojos , Gases , Humanos , Permeabilidad , Índice de Severidad de la Enfermedad , Agudeza VisualRESUMEN
To determine the optimal recording site for phrenic nerve conduction studies, six different recording techniques were compared in 11 healthy volunteers (22 phrenic nerves). The mean diaphragm compound muscle action potential (CMAP) amplitude, side-to-side difference, and the number of studies with a false-positive result (CMAP amplitude <0.30 mV) were compared for each technique. The largest amplitude (0.65 +/- 0.23 mV, range 0.30-1.2 mV) with good right-left agreement (mean difference 0.15 mV) and no false positives was obtained using technique 1, where the G1 electrode was positioned 5 cm above the xiphoid process and G2 16 cm from G1 along the costal margin. This was also the easiest technique to perform. It does not require rib counting, which may be difficult and inaccurate, especially in overweight patients. At least one false positive occurred with each of the remaining five techniques.
Asunto(s)
Potenciales de Acción/fisiología , Diafragma/fisiología , Electrodos , Adulto , Análisis de Varianza , Estimulación Eléctrica/métodos , Electromiografía/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad , Conducción Nerviosa/fisiología , Nervio Frénico/fisiología , Adulto JovenRESUMEN
We present a case of subacute weakness of one hand with unusual sensory involvement including the upper thorax. Despite normal distal conduction studies, a clinical diagnosis of Lewis-Sumner syndrome was made and the patient responded well to intravenous immunoglobulins. Repeated studies after clinical exacerbation finally proved the demyelinating nature of the neuropathy using proximal magnetic nerve stimulation. This case underlies the importance of seeking proximal conduction blocks in patients with suspected demyelinating neuropathy.