There is growing evidence of activated microglia and inflammatory processes in the cerebral cortex in amyotrophic lateral sclerosis (ALS). Activated microglia is characterized by increased expression ...of the 18 kDa translocator protein (TSPO) in the brain and may be a useful biomarker of inflammation. In this study, we evaluated neuroinflammation in ALS patients using a radioligand of TSPO, (18)F-DPA-714. Ten patients with probable or definite ALS (all right-handed, without dementia, and untreated by riluzole or other medication that might bias the binding on the TSPO), were enrolled prospectively and eight healthy controls matched for age underwent a PET study. Comparison of the distribution volume ratios between both groups were performed using a Mann-Whitney's test. Significant increase of distribution of volume ratios values corresponding to microglial activation was found in the ALS sample in primary motor, supplementary motor and temporal cortex (p = 0.009, p = 0.001 and p = 0.004, respectively). These results suggested that the cortical uptake of (18)F-DPA-714 was increased in ALS patients during the "time of diagnosis" phase of the disease. This finding might improve our understanding of the pathophysiology of ALS and might be a surrogate marker of efficacy of treatment on microglial activation.
ABSTRACT
Introduction
We evaluated clinical and bioelectrical impedance (BIA) parameters at the time of diagnosis and during follow‐up and associated these parameters with survival in amyotrophic ...lateral sclerosis (ALS) patients.
Methods
One hundred seventeen patients were enrolled and were evaluated prospectively every 3 months. All patients underwent at least 1 BIA‐based assessment, and 73 underwent at least 2 assessments. Data regarding the site of onset, age at onset, weight, body mass index (BMI), amyotrophic lateral sclerosis functional rating scale score (ALSFRS), fat‐free mass (FFM), fat mass (FM), and phase angle (PA) were collected.
Results
At the time of diagnosis, weight loss exceeding 5% of the premorbid weight and low PA were poor prognostic factors. During follow‐up, a decrease of PA and FFM were associated with shorter survival, regardless of weight loss.
Conclusions
These results confirm that BIA is useful to identify poor prognostic factors at the time of diagnosis and during follow‐up and thus could be used to monitor patients during follow‐up. Early identification of poor prognostic factors enables nutritional management and might improve patient survival. Muscle Nerve 51: 479–484, 2015
Purpose: The aim of this study was to determine the clinical, social, and/or professional and cognitive outcomes in adulthood of the continuous spike–waves during slow sleep (CSWS) and ...Landau–Kleffner syndromes, which are two rare epileptic syndromes occurring in children.
Methods: We enrolled seven young adults, five who had a CSWS syndrome, and two, a Landau–Kleffner syndrome in childhood. We evaluated their intellectual level as well as their oral and written language and executive functions.
Results: This study confirmed that the epilepsy associated with these syndromes has a good prognosis. Only one patient still had active epilepsy. However, the neuropsychological disorders particular to each syndrome persisted. Only two patients had followed a normal pathway in school. Three of the five patients with a CSWS syndrome during childhood remained globally and nonselectively mentally deficient. We found no evidence of the persistence of a dysexecutive syndrome in this study group. The intellectual functions of the two patients with Landau–Kleffner syndrome were normal; however, their everyday lives were disrupted by severe, disabling language disturbances. We discuss the role of some prognostic factors such as the location of the interictal electric focus and the age at onset of CSWS.
Conclusions: These two epileptic syndromes of childhood are very similar in many respects, but their clinical outcomes in adulthood are different.
Abstract Purpose The purpose of this study was to evaluate the effectiveness and safety of PER as add-on treatment in patients with severe refractory epilepsy with a particular focus on patients with ...learning disability and/or psychiatric comorbidity. Method We pooled retrospective data from adult patients with refractory epilepsy prescribed perampanel from a tertiary center in France between 1st May 2014 and 3rd June 2015. Data collection was done on February 2016. Results One hundred and one patients were included (mean age: 41.2 years, 37.6% with learning disability and 49.5% with psychiatric comorbidity). Mean retention was 8.1 months (range: 14 days to 17 months). On final evaluation, a > 50% reduction in seizure frequency was reached in 41.6% of patients, and 7 patients (6.9%) became seizure-free. Sixty-three patients (62.4%) experienced adverse effects. The most common adverse effects were irritability, asthenia, aggression, and sedation. Efficacy, retention of treatment, and safety were equally similar in patients with learning disability or psychiatric comorbidity as for those without. The only significant difference was in percentage of seizure-free patients: 11.1% in the group without learning disability compared with 0% in the group with (p = 0.043). Conclusion Adjunctive PER can achieve clinically meaningful improvement, or even seizure freedom, in more than one-third of patients suffering from severe refractory epilepsies. It seems similarly safe and effective in the subgroup of these patients with learning disability or with psychiatric comorbidity. However, the rate of psychiatric side effects is high,; of note, we asked both patient and caregivers at each visit especially focusing on psychiatric side effects. Patients, caregivers, and families should be informed of potential psychiatric/behavioral risks associated with taking perampanel especially during the initial titration period.
Pathophysiological mechanisms involved in amyotrophic lateral sclerosis (ALS) are complex and none has identified reliable markers useful in routine patient evaluation. The aim of this study was to ...analyze the CSF of patients with ALS by (1)H NMR (Nuclear Magnetic Resonance) spectroscopy in order to identify biomarkers in the early stages of the disease, and to evaluate the biochemical factors involved in ALS.
CSF samples were collected from patients with ALS at the time of diagnosis and from patients without neurodegenerative diseases. One and two-dimensional (1)H NMR analyses were performed and metabolites were quantified by the ERETIC method. We compared the concentrations of CSF metabolites between both groups. Finally, we performed principal component (PCA) and discriminant analyses.
Fifty CSF samples from ALS patients and 44 from controls were analyzed. We quantified 17 metabolites including amino-acids, organic acids, and ketone bodies. Quantitative analysis revealed significantly lower acetate concentrations (p = 0.0002) in ALS patients compared to controls. Concentration of acetone trended higher (p = 0.015), and those of pyruvate (p = 0.002) and ascorbate (p = 0.003) were higher in the ALS group. PCA demonstrated that the pattern of analyzed metabolites discriminated between groups. Discriminant analysis using an algorithm of 17 metabolites revealed that patients were accurately classified 81.6% of the time.
CSF screening by NMR spectroscopy could be a useful, simple and low cost tool to improve the early diagnosis of ALS. The results indicate a perturbation of glucose metabolism, and the need to further explore cerebral energetic metabolism.
L’amylose AL est une pathologie systémique caractérisée par un dépôt extracellulaire de chaînes légères secondaire à une gammapathie monoclonale, maligne dans 10–15 % des cas. L’atteinte musculaire ...est rare et constitue un défi diagnostique.
Nous rapportons le cas d’un patient de 70 ans, aux antécédents de myélome IgG lambda considéré en rémission depuis 9 ans. Depuis 18 mois, le patient rapportait une dégradation fonctionnelle rapide avec démarche dandinante, difficultés à la montée des escaliers puis à la marche, plainte masticatoire et troubles de la déglutition. L’examen objectivait un déficit moteur amyotrophiant des ceintures symétriques entre 2 et 3/5 MRC avec un décollement majeur des omoplates, un déficit axial abdominal et des fléchisseurs du cou, une diplégie faciale franche et une macroglossie. À noter parallèlement une altération de l’état général (−7kg, recrudescence des œdèmes des membres inférieurs). L’ENMG était myogène, y compris dans la face (muscle masséter). L’IRM musculaire révélait une amyotrophie sévère des ceintures pelviennes et scapulaires (Mercuri stade IV) avec présence d’hypersignaux en séquence STIR. La biopsie musculaire présentait un tableau de nécrose/régénération très sévère avec dépôts de substance amyloïdes dans les vaisseaux musculaires. On notait l’existence d’un pic IgG lambda avec majoration des chaines légères libres lambda sériques, ainsi qu’une discrète élévation des CPK (355 U/L).
L’amylose musculaire est rare. Décrite pour la première fois en 1929, deux phénotypes cliniques se distinguent : une forme hypertrophique associant infiltration sous cutanée pseudo-tumorale, macroglossie, signe de l’épaulette et une forme atrophique (20 %) se caractérisant par un déficit moteur des ceintures et de la face rapidement progressive, en imposant pour une myosite. L’IRM montre classiquement un pattern de réticulations de la graisse sous-cutanée.
Ce cas alerte sur l’intérêt du diagnostic précoce de l’amylose musculaire considérant l’enjeu fonctionnel et thérapeutique. L’inconstance des signes caractéristiques rend indispensable la biopsie musculaire au diagnostic.
Summary Objectives The objective of the present study was to evaluate the prevalence of obstructive sleep apnea (OSA) in patients with late-onset epilepsy (LOE) who were considered at higher risk of ...cardiovascular disease. Methods Polysomnography was performed on 27 patients with LOE. Berlin questionnaires and Epworth sleepiness score were performed on all patients. We compared clinical, demographic and anthropometric characteristics, questionnaire scores on the patients with no or mild OSA (group 1) and the patients with moderate or severe OSA (group 2). Patients eligible for continuous positive airway pressure (CPAP) therapy were reviewed in consultation. Results Twenty-four patients (88.9%) had OSA and 55.6% had moderate or severe OSA. Patients in group 2 ( n = 15) were older than patients in group 1 ( n = 12). The two groups were similar in terms of body mass index (BMI), neck circumference, nocturnal seizure frequency, vascular cardiovascular risk factors and excessive daytime sleepiness. Leukoaraiosis in MRI was highly prevalent in our patients (40.7%), especially in group 2 patients. Eighty percent of the patients who had begun CPAP therapy experienced decreased seizure frequency. Conclusion Patients with LOE should be screened for the presence of OSA and treated accordingly.
Somatosensory evoked potentials (SEPs) offer complementary results to those of nerve conduction studies and contribute to the electrodiagnostic criteria of chronic inflammatory demyelinating ...polyradiculoneuropathy.
We performed nerve conduction studies and SEPs in patients with symmetrical motor weakness, areflexia, and/or sensory disturbances lasting for at least 8 weeks. We determined two groups according to the electrodiagnostic criteria of the European Federation of Neurological Societies. Group 1 included patients who met the definite or probable electrodiagnostic criteria, and group 2 included patients who met the possible electrodiagnostic criteria. We also compared SEPs results with those of controls (group of healthy subjects).
Sixteen patients (14 men; mean age, 59 ± 17.3 years) were included in the study. The latencies of potentials N9, N13, N7, and N22 and the intervals N9-N13 and N7-N22 were significantly increased in patients compared with controls. The N9/iP14 amplitude ratio was significantly lower in patients. There was no significant difference in the latencies of SEPs between the two groups of patients.
We confirm the contribution of SEPs as complementary information to nerve conduction studies in chronic inflammatory demyelinating polyradiculoneuropathy diagnosis. In addition to the usual abnormalities, a decrease in the N9/iP14 amplitude ratio could potentially be used as an electrodiagnostic criterion.
Abstract Background Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. During the course of the illness, malnutrition can occur and may shorten survival. The aim of our study ...was to determine whether clinical nutritional parameters that are used in daily practice are associated with prognosis and whether they can help guide therapeutic decisions. Methods We retrospectively reviewed a cohort of ALS patients in our institution between January 2002 and January 2006. Clinical and demographic outcomes were compiled. To evaluate predictors of survival, we analyzed several clinical nutritional parameters available in daily practice (body mass index, weight loss exceeding 10% of premorbid weight at the time of diagnosis and during the course of the disease and the use of technical supports such as percutaneous endoscopic gastrostomy (PEG) and non-invasive ventilation). Results Sixty-three patients were retrospectively studied. Thirteen patients had weight loss exceeding 10% of premorbid weight at the time of diagnosis and thirty patients had weight loss meeting this criterion at final examination. Weight loss exceeding 10% at the time of diagnosis was associated with a shorter duration of disease (17 ± 6 months versus 35 ± 26 months; p = 0.002). A linear correlation was found between mean disease duration and time between onset and diagnosis ( p < 0.0001). The subgroup of patients with a PEG had a longer survival time than the other subgroup of patients ( p = 0.02). Conclusions In ALS patients, early and marked weight loss significantly predicts a worse prognosis. The percentage of premorbid weight loss is a suitable and useful measure that can be used in daily practice to identify patients with a poor prognosis.
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