Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 8 de 8
Filtrar
1.
Eur Neurol ; 77(1-2): 87-90, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-27978519

RESUMEN

BACKGROUND/AIMS: To describe the use of peripherally inserted central catheter (PICC), in amyotrophic lateral sclerosis (ALS) at a later stage. METHODS: Twenty-five ALS patients in the later stages of the disease underwent PICC insertion followed by parenteral nutrition (PN). For all of them, gastrostomy was non-feasible. Patients were followed until death and monitored for complications. RESULTS: PICC insertion was successful in all patients. Three months after insertion, the mean body weight increased by 4.5% (p = 0.0057). PICC could be maintained until death in all but 1 patient. The mean delay between insertion and death was 4.5 months, but PN was administered for more than 1 year in 2 patients. Complications were noted in 6 patients: sepsis (n = 4), venous thrombosis (n = 1), and upper limb oedema (n = 1), none of them resulting in death. CONCLUSION: PICC insertion for PN at a later stage of ALS, in patients for whom gastrostomy is non-feasible, appears to be a useful option compared to the central venous catheter.


Asunto(s)
Esclerosis Amiotrófica Lateral , Cateterismo Periférico/efectos adversos , Cateterismo Periférico/métodos , Nutrición Parenteral/métodos , Adulto , Cateterismo Venoso Central/efectos adversos , Cateterismo Venoso Central/métodos , Femenino , Humanos , Masculino , Persona de Mediana Edad
2.
CNS Neurosci Ther ; 28(10): 1532-1538, 2022 10.
Artículo en Inglés | MEDLINE | ID: mdl-35751632

RESUMEN

BACKGROUND: Little is known about the influence of Riluzole on serum neurofilament light chain (sNfL) levels, a biomarker of prognosis in amyotrophic lateral sclerosis (ALS), and variations with time of sNfL concentrations are controversial. METHODS: Sera from ALS patients (n = 141) and controls (n = 33) were collected at inclusion (sNfL1) and second visit (sNfL2, mean delay 10.4 ± 8.7 months). sNfL levels, determined by single-molecule array, were compared between ALS and controls at both time points. sNfL concentration changes were compared between patients with Riluzole (w/Ril) at inclusion in the study and those who were treated by Riluzole following inclusion (w/o Ril). The factors influencing sNfL concentrations and changes were studied using linear regression and multivariate analysis. RESULTS: sNfL levels were higher in ALS patients than in controls at the two time points (p < 0.00001). In ALS patients, sNfL concentrations were higher in females for both sNfL1 (p = 0.014) and sNfL2 (p < 0.001). In the whole ALS group, sNfL levels were higher at sNfL2 than at sNfL1 (p < 0.001). sNfL1 and sNfL2 concentrations were similar between the two ALS subgroups (w/ and w/o Ril). ALS functional rating scale-revised rate of decline and gender were the two main factors significantly influencing both sNfL1 and sNfL2 levels (p < 0.01). However, only gender was shown to significantly influence sNfL changes with time (p = 0.003). CONCLUSIONS: In this study, sNfL levels increased with time in ALS patients and there was no difference between subjects already treated by Riluzole and those treated after sNfL1. Further studies with larger population samples and different sampling intervals are warranted to better determine the real potential of sNfL measurement as a tool to monitor treatment response in ALS.


Asunto(s)
Esclerosis Amiotrófica Lateral , Riluzol , Esclerosis Amiotrófica Lateral/diagnóstico , Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Biomarcadores , Femenino , Humanos , Filamentos Intermedios , Proteínas de Neurofilamentos , Pronóstico , Riluzol/uso terapéutico
3.
Artículo en Inglés | MEDLINE | ID: mdl-33576710

RESUMEN

Covid-19-related lockdown (LD) in France precluded in-person follow-up in referral ALS centers. ALS patients' evolution and worsening before and during LD were studied to analyze its impact. A total of 84 patients were identified. The monthly rate of ALSFRS-R decline during LD was 1.06 ± 1.42 and was significantly increased compared to the pre-LD period, 0.58 ± 0.73, corresponding to an 83% increase (p = 0.007). Weight loss was unchanged between pre-LD and LD, gender and site of onset did not influence the rates of change of ALSFRS-R score. Several factors may be implicated in this increased severity of ALS during LD, such as psychological consequences of LD, interruptions of physiotherapy and speech therapy, or in-patient visits both to the tertiary center and the GP. Physicians and health authorities should be aware of that, in order to prevent the consequences of future sanitary restrictions.


Asunto(s)
Esclerosis Amiotrófica Lateral , COVID-19 , Esclerosis Amiotrófica Lateral/epidemiología , Control de Enfermedades Transmisibles , Progresión de la Enfermedad , Francia/epidemiología , Humanos , SARS-CoV-2
4.
EClinicalMedicine ; 19: 100254, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32140672

RESUMEN

BACKGROUND: Oligodendrocytes (OGs) provide metabolic support to motor neurons (MNs) and are implicated in the pathophysiology of amyotrophic lateral sclerosis (ALS). MD1003, or high-dose Pharmaceutical grade Biotin (hdPB), may improve disability in progressive multiple sclerosis patients via augmentation of OG or MN energy levels. Here, we assessed the safety and efficacy of MD1003 in ALS patients. METHODS: This single centre, randomised, double-blind, placebo-controlled trial included patients aged 25-80 years with probable or definite ALS. Patients were assigned (2:1), using a computer-generated randomisation list, to receive oral MD1003 (300 mg/day) or placebo treatment for 24 weeks. The primary outcome, safety, was analysed in all patients who received at least one dose of study drug. This study, registered with ClinicalTrials.gov, NCT03114215, has been completed. FINDINGS: Between June and December 2016, 30 patients were enrolled (MD1003, n = 20; placebo, n = 10). Baseline characteristics were representative of the ALS population. MD1003 and placebo groups were not well balanced at screening, with the MD1003-treated group having a higher rate of ALSFRS-R decline prior to screening versus placebo (-6·0 IQR [-8·5, -5·0] vs. -5·0 IQR [-5·0, -3·0]) and a predominance of ALS with upper limb onset compared to placebo (35% vs. 10%). MD1003 had a favourable safety profile and was well tolerated. The occurrence of adverse events was similar in both groups (60%). Two deaths occurred in the MD1003 group versus 1 in the placebo group. ALSFRS-R median change from baseline to month 6 was not significantly different between the two groups (p = 0·49); the mean difference between groups was -1·6 (SEM=3·3). INTERPRETATION: MD1003 treatment was safe and well tolerated. It was not possible to establish MD1003 efficacy in this relatively small study. Given the favourable safety profile of MD1003 and an imbalance between treatment groups favouring placebo, additional, larger studies in ALS are warranted. FUNDING: MedDay Pharmaceuticals.

5.
Front Neurol ; 11: 363, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32547467

RESUMEN

Background: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder characterized by progressive degeneration of upper and lower motor neurons. Prognosis is highly variable, ranging from few months to more than 30 years. 25OH vitamin D (25OH VD) blood levels have been associated with worse prognosis of ALS, but these results remain in dispute. We addressed this controversy with a prospective study and multivariate analysis to study the influence of known clinical prognostic factors of the disease and 25OH VD levels on Revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) severity score (ALS-SS), as defined by the monthly rate of decline of ALSFRS-R score, to identify the factors most closely linked to the risk of worsening of the disease. Results:This prospective cohort of ALS patients recruited 127 individuals, and 105 of them met inclusion criteria. Mean age of onset was 62.2 ± 12.1 years, 32% of subjects had bulbar onset, and gender ratio was 1.44 (male/female). Mean 25OH VD level was 26.8 ± 10.8 ng/ml and was similar between males and females. Patients with 25OH VD levels <15 ng/ml had significantly higher ALS-SS at inclusion (ALS-SSi) than those with normal levels (>30 ng/ml), p = 0.011. The study of ALS-SS as calculated at the end of follow-up (ALS-SSe) was not found correlated to initial 25OH VD levels (r = -0.19; p = 0.084). Univariate analysis showed that ALS-SSe correlated with 25OH VD levels, ALS duration at inclusion, slow vital capacity (SVC) at inclusion, and SVC loss. Multivariate model showed that 25OH VD levels were independently associated with ALS-SSe: r = -0.0125, p = 0.033. Log rank test with Kaplan-Meier curves did not show significant differences of survival between the groups defined by 25OH VD levels: <15, >15 and <30, and > 30 ng/ml, p = 0.88. Conclusions: This prospective study in ALS patients confirmed previous retrospective results: ALS-SSi is significantly higher in patients with severe VD deficiency. For the first time, multivariate analysis showed that 25OH VD level was an independent prognostic factor correlated to ALS-SSe, suggesting that discrepancies between previous works could be due to confounders. It would be important that the present work be replicated in larger samples to confirm the present findings.

6.
Front Neurosci ; 14: 316, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32410933

RESUMEN

BACKGROUND: In familial amyotrophic lateral sclerosis (ALS) cases, the presence of an abnormal C9ORF72 repeat expansion (C9RE) is the most frequent genetic cause identified. Various clinical phenotypes have been described in relation to the presence of C9RE, including psychiatric disorders or Huntington-like symptoms. In a subset of sporadic ALS, C9RE has also been described. In the present study, all index cases with ALS and C9RE identified in our center and their clinical profile, as well as neurological and psychiatric characteristics of identified family members, were described. Clinical characteristics of ALS patients were compared to 999 patients with sporadic ALS (SALS) from our database. RESULTS: From the 70 index cases with ALS identified, a total of 200 individuals were studied, 118 with ALS, 32 with fronto-temporal lobe degeneration (FTD), 37 with ALS/FTD, and 13 with psychiatric disorders. A familial history was present in 57 of the index cases (81%). In ALS and ALS/FTD cases with C9RE, the age of onset (AoO) was earlier than that in SALS cases, p < 0.0001 and p = 0.008, respectively. Sporadic cases with C9REALS (n = 13) had an earlier AoO compared to familial C9REALS ones, p < 0.0001. Within families, there was an earlier AoO in index cases and their siblings compared to their parental generation (p < 0.01). There was also a significant intrafamilial correlation for bulbar onset of ALS. The parental generation had significant female predominance compared to index cases and their siblings (sex ratio 0.47 vs. 1.4, p = 0.004), and this predominance was also present when considering parent-child pairs. In the group with psychiatric disorders, suicide was prominent (n = 9) and mean age was 54 years. CONCLUSION: Although our sample size is rather limited, the earlier AoO in index cases and their siblings compared to the parental generation may suggest an anticipation. Reasons for predominance of female transmission are unclear, but the hypothesis that gender influences transmission of the genetic trait or C9RE size variation may be taken into account. Intrafamilial correlation suggests that genetic aspects underlie the occurrence of bulbar onset in ALS patients. Studies on larger samples are warranted to confirm those results.

7.
Cell Calcium ; 39(3): 237-46, 2006 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-16324742

RESUMEN

Changes in intracellular Ca(2+) concentration ([Ca(2+)](i)) control the setting up of the neuro-muscular synapse in vitro and probably in vivo. Dissociated cultures of purified embryonic (E15) rat motoneurons were used to explore the molecular mechanisms by which endoplasmic reticulum Ca(2+) stores, via both ryanodine-sensitive and IP(3)-sensitive intracellular Ca(2+) channels control [Ca(2+)](i) homeostasis in these neurons during ontogenesis. Fura-2 microspectrofluorimetry monitorings in single neurons showed that caffeine-induced responses of [Ca(2+)](i) increased progressively from days 1-7 in culture. These responses were blocked by ryanodine and nicardipine but not by omega-conotoxin-GVIA or omega-conotoxin-MVIIC suggesting a close functional relationship between ryanodine-sensitive and L-type Ca(v)1 Ca(2+) channels. Moreover, after 6 days in vitro, neurons exhibited spontaneous or caffeine-induced Ca(2+) oscillations that were attenuated by nicardipine. In 1-day-old neurons, both thapsigargin or CPA, which deplete Ca(2+) stores from the endoplasmic reticulum, induced an increase in [Ca(2+)](i) in 75% of the neurons tested. The number of responding motoneurons declined to 25% at 5-6 days in vitro. Xestospongin-C, a membrane-permeable IP(3) receptor inhibitor blocked the CPA-induced [Ca(2+)](i) response in all stages. RT-PCR studies investigating the expression pattern of RYR and IP(3) Ca(2+) channels isoforms confirmed the presence of their different isoforms and provided evidence for a specific pattern of development for RYR channels during the first week in vitro. Taken together, present results show that the control of motoneuronal [Ca(2+)](i) homeostasis is developmentally regulated and suggest the presence of an intracellular ryanodine-sensitive Ca(2+) channel responsible for a Ca(2+)-induced Ca(2+) release in embryonic motoneurons following voltage-dependent Ca(2+) entry via L-type Ca(2+) channels.


Asunto(s)
Canales de Calcio/fisiología , Señalización del Calcio/fisiología , Calcio/metabolismo , Neuronas Motoras/fisiología , Animales , Cafeína/farmacología , Canales de Calcio/biosíntesis , Canales de Calcio Tipo L/fisiología , Femenino , Indoles/farmacología , Receptores de Inositol 1,4,5-Trifosfato , Compuestos Macrocíclicos , Neuronas Motoras/efectos de los fármacos , Oxazoles/farmacología , Embarazo , Isoformas de Proteínas/biosíntesis , Ratas , Receptores Citoplasmáticos y Nucleares/biosíntesis , Rianodina/farmacología , Canal Liberador de Calcio Receptor de Rianodina/efectos de los fármacos , Canal Liberador de Calcio Receptor de Rianodina/fisiología , Médula Espinal/citología , Médula Espinal/embriología
8.
Neurobiol Aging ; 35(5): 1198-205, 2014 May.
Artículo en Inglés | MEDLINE | ID: mdl-24378089

RESUMEN

Amyotrophic lateral sclerosis (ALS) is an incurable paralytic disorder primarily typified by the selective and progressive degeneration of motoneurons in the brain and spinal cord. ALS causes muscle wasting and atrophy, resulting eventually in respiratory failure and death within 3-5 years of diagnosis. Vitamin D is a potent secosteroid hormone with diverse biological functions that include protection against neuronal damage. The detrimental consequences of vitamin D dietary deficiency have been documented in other neurodegenerative diseases. However, the protective effect of vitamin D on motoneuron and the influence of its levels on disease course remains elusive. Here we found that the biologically active form of vitamin D significantly potentiated the effect of neurotrophic factors and prevented motoneurons from a Fas-induced death, while electrophysiological properties of motoneurons were not affected. In ALS patients, we report that a severe vitamin D deficiency accelerates by 4 times the rate of decline and were associated with a marked shorter life expectancy. Our findings support a neuroprotective function of vitamin D on motoneurons and propose vitamin D as a reliable prognostic factor of ALS.


Asunto(s)
Esclerosis Amiotrófica Lateral/tratamiento farmacológico , Supervivencia Celular/efectos de los fármacos , Neuronas Motoras/efectos de los fármacos , Fármacos Neuroprotectores , Vitamina D/farmacología , Esclerosis Amiotrófica Lateral/mortalidad , Esclerosis Amiotrófica Lateral/patología , Animales , Células Cultivadas , Proteína Ligando Fas/fisiología , Femenino , Factor Neurotrófico Derivado de la Línea Celular Glial/farmacología , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Persona de Mediana Edad , Neuritas/fisiología , Tasa de Supervivencia , Factores de Tiempo , Vitamina D/administración & dosificación
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA