Jean-Claude Desport

Hypermetabolism in ALS: correlations with clinical and paraclinical parameters.

Despite a reduction in fat-free mass (FFM), a hypermetabolism has been reported with an average of 10% in amyotrophic lateral sclerosis (ALS) patients as compared with a healthy population. The objectives of this study were to confirm the level of hypermetabolism determined by using indirect calorimetry in 168 patients with a probable or a definite ALS and to study correlations with survival. Consecutive evaluations of resting energy expenditure (REE) were performed from diagnosis to the proximity of death in 44 ALS patients. Differences with the calculated value determined a ΔREE. FFM was given by bioimpedance. At T1, REE was significantly increased by an average of 14% as compared with the calculated value. 62.3% of ALS patients were considered as hypermetabolic. REE was correlated in univariate analysis with age, sex, clinical form at onset, presence of a denutrition, weight, FFM, phase angle and ALS Functional Rating Scale (ALSFRS). In multivariate analysis, REE was linked to age and FFM. ΔREE was correlated in univariate analysis with sex, phase angle and manual muscle testing (MMT). In multivariate analysis, age and sex remained significantly correlated. During progression of ALS, REE levels remained higher than calculated values with a trend to decrease at proximity of death, whereas FFM remained stable. From T1, survival was linked to MMT, ALSFRS, vital capacity, REE and phase angle. We confirmed the existence of a stable hypermetabolic state in ALS which depends mainly on age, sex and FFM. REE is a prognostic factor for survival in univariate analysis.

High metabolic level in patients with familial amyotrophic lateral sclerosis

An abnormally elevated level of resting energy expenditure (REE, measured by indirect calorimetry) has been reported in a subset of patients with sporadic amyotrophic lateral sclerosis (SALS). Hypermetabolism (measured REE/calculated REE (cREE)≥1.1, or 110%) has also been observed in transgenic mice harbouring ALS-causing mutations in the SOD1 gene. By contrast, the REE of patients with familial amyotrophic lateral sclerosis (FALS) has never been assessed. Our objective was to evaluate the metabolic and nutritional parameters of FALS patients and to compare them with those of SALS patients, and search for correlations with clinical parameters. Eleven patients with FALS (from 10 different families, none carrying a SOD1 mutation) were evaluated by indirect calorimetry in our centre. As a control group, we used a sample of 33 patients with SALS, matched for age and sex with the FALS patients. 11/11 (100%) patients with FALS were hypermetabolic, compared to 17/33 (52%) patients with SALS (p=0.009). Measured REE (mREE) and mREE/cREE (metabolic level) were significantly higher in FALS patients than in SALS patients (p=0.03 and p=0.0008, respectively). No correlation was found between metabolic measures and neurological or respiratory parameters. In conclusion, hypermetabolism appears to be a common feature of subjects with FALS, suggesting that this impairment of energy homeostasis may be genetically driven. The high metabolic level of FALS patients should be taken into account for their nutritional management (need for a high-energy diet to prevent malnutrition).

Value of magnetic resonance cholangiography in the preoperative diagnosis of common bile duct stones

OBJECTIVE:The aim of this study was to assess the performance of magnetic resonance cholangiography (MRC) in the preoperative diagnosis of choledocholithiasis.METHODS:A total of 147 consecutive patients underwent MRC for clinical and biological signs of common bile duct stones. ERCP was then carried out in 101 patients in whom there was a past history of cholecystectomy. The remaining 46 patients without a past history of biliary surgery underwent cholecystectomy and intraoperative cholangiography (IOC). The diagnosis obtained by MRC was compared with the final diagnosis established after endoscopic or surgical removal of calculi.RESULTS:A total of 113 patients had choledocholithiasis (single or multiple, including 15 cases of microlithiasis). There were no false-positive results with MRC. The false-negative results were caused mainly by small stones <3 mm in diameter, and to a lesser extent, cholangitis. Overall, the sensitivity was 93% and the specificity 100% for MRC in detecting common bile duct stones. The sensitivity and specificity of ERCP were respectively 94% and 100%, versus 93.5% and 93.3% for IOC. There was no statistically significant difference, however, between MRC and the other techniques.CONCLUSION:MRC is a key technique in the preoperative diagnosis of choledocholithiasis. Its diagnostic value is comparable to ERCP, but it appears to be more specific than IOC. Nevertheless, its diagnostic capability remains limited in cases of microlithiasis and cholangitis.

Complications and survival following radiologically and endoscopically-guided gastrostomy in patients with amyotrophic lateral sclerosis

In the natural progression of amyotrophic lateral sclerosis (ALS), a state of malnutrition often develops, associated with reduced oral intake, caused by difficulties with swallowing, adequate salivation, and/or anorexia. The placement of a feeding tube should be considered at the point where patients demonstrate swallowing difficulty and/or alteration in nutritional status. The goal of this prospective work was to compare, in 50 patients having definite or probable ALS, the complications after endoscopic (PEG), or radiologically-guided gastrostomy (RIG) and to evaluate their effects on survival. RIG was proposed as first-line therapy when patients had a slow vital capacity (SVC) less than 50% of the theoretical value, or in a case where PEG was refused by the patient. Thirty patients underwent PEG procedure, and 20 had RIG. Among the decisional criteria for placing a gastrostomy tube, risk of aspiration demonstrated by using videofluoroscopy was more frequently observed in the RIG group (65%) than in the PEG group (19.2%) (p=0.002). The two patient populations at time of gastrostomy placement were comparable with respect to age, gender ratio, disease duration before gastrostomy, the form and the gravity of neurological involvement as well as for nutritional criteria. The only significant difference observed between the two groups was the level of the SVC, much lower for patients undergoing RIG: 51.6±25.0% versus 67.4±26.7% than for the PEG group (p=0.03). The frequency of all complications observed at the moment of placement of gastrostomy tube and during the first month of follow-up was not significantly different between the two groups. Kaplan- Meier survival curves from the date of gastrostomy placement were not different in univariate analysis (p=0.85). In multivariate analysis, survival was not different between one group and the other (p=0.28). The major interest of the RIG technique rests on its greater feasibility and on the possibility of utilizing it in ALS patients who have significant ventilatory compromise.

Link between Epilepsy and Malnutrition in a Rural Area of Benin

Summary:  Purpose: Epilepsy and malnutrition are both important public health problems in sub‐Saharan Africa. A relationship between epilepsy and malnutrition has been suspected for many years. Our objective was to investigate the association between epilepsy and malnutrition in Djidja, Benin.

Phase angle is a prognostic factor for survival in amyotrophic lateral sclerosis.

Malnutrition is a well-known independent survival factor in ALS patients. Total body impedance analysis (BIA) has been validated for the measurement of fat-free mass. Another physical value obtained by BIA is phase angle (PA) that has been proposed to be an index of malnutrition or a survival prognostic factor in several diseases. We measured PA in a sample of 168 ALS patients and analysed the relationships between PA and neurological, respiratory and nutritional status, and determined whether PA is an independent prognostic factor for survival in ALS. BIA was performed using an Analycor3 instrument with surface electrodes at 50 kHz and 800 µA. PA was obtained using the formula: PA =arctan (Xc/R) (in degrees) where Xc is the body reactance and R the bioelectric resistance. Relationships between quantitative variables were assessed by linear correlation coefficients and through univariate and multivariate linear regression analyses. To assess the prognostic role of PA on survival of patients, we performed survival analyses based on the Kaplan-Meier method using the log rank test, and on univariate and multivariate Cox proportional hazard model. Baseline time was time from multidisciplinary visit (T1) to death or censoring time. PA was always significantly lower in ALS patients than in healthy control subjects published in the literature. PA was lower in our ALS malnourished patients than in non-malnourished patients (3.3±1.1° versus 2.5±0.6°, p =0.003). In multivariate linear regression analysis, manual muscle testing (p<0.0001), vital capacity (p<0.001), fat-free mass (p<0.0001), time between initial signs and T1 (p<0.002) and age (p<0.001) were independently significantly linked with PA and explained 48% of PA variation. The survival of ALS patients from T1 was significantly linked with PA after adjustment on BMI, CV and time between initial signs and multidisciplinary visit, clinical form, age and sex. Patients with a PA <2.5° had a significantly poorer survival rate than patients with a PA >2.5°. We concluded that in ALS patients, PA is greatly decreased. It is related to the nutritional status of patients, and is also an independent prognostic factor of survival.

Nutritional assessment and follow-up of residents with and without dementia in nursing homes in the Limousin region of France: A health network initiative

IntroductionLimousin in France has the second oldest regional population in Europe, with people over 65-years-old who have Alzheimer’s disease accounting for more than 9%. In France as a whole, a large number of residents in nursing homes (NH) have dementia, leading to many nutritional problems. LINUT is a health network that assesses the nutritional status of elderly NH residents and provides support where necessary. Aims of the present study were to use this network to evaluate the nutritional status of NH residents with and without dementia and to review changes after 4 months of intervention.MethodsA cross-sectional survey was conducted by a doctor and a dietician at baseline (T0) and 4 months (T4) among residents at the 26 NH in Limousin that agreed to take part. The evaluation criteria included presence of dementia, depression and autonomy, weight, height, body mass index, Mini Nutritional Assessement (MNA™), and a 3-day survey of food intake.ResultsThe 346 residents assessed at T0 were aged 87.9±6.9 years, 83.4% were women, 66.8% had dementia, 53.3% were malnourished and 27.4% obese. Autonomy was not affected by obesity. Residents with dementia had a lower Activities of Daily Living score and a lower weight than non-demented individuals (2.2±1.2 vs. 2.7±1.7 p=0.03 and 60.1±16.3 vs. 64.7±20.0 kg p=0.03, respectively), were more often malnourished (56.1% vs. 46.4% p=0.004) and less often obese (22.0% vs. 39.1% p=0.004) but consumed more protein (62.6±17.8 vs. 58.2±16.9 g/d p=0.04, 1.1±0.4 vs. 1.0±0.4 g/kg/d p=0.005). Energy intake was at the lower limit of French recommendations (26.4±8.8 vs. >25.0 kcal/kg/d). Assessment of all residents at T4 showed improved MNA™ (+0.4 points/month p=0.02), protein intake (+3.3 g/d p=0.0007), and energy intake (+41.4 kcal/d p=0.01 and 0.1 kcal/kg/d p=0.03). Variations in prevalences of malnutrition and obesity were not statistically significant. MNA™ increased in the dementia group (+0.29±0.8 points/month p=0.003). All other changes were comparable, and nutritional status did not differ more between the two groups at T4 than at T0.ConclusionThe prevalence of dementia was high in the population studied. Malnutrition was the main problem, particularly if residents had dementia. Protein intake was satisfactory, but energy intake often insufficient. The nutritional status of dementia patients improved after 4 months of follow-up, suggesting that effective action to support such services would be worthwhile.

Malnutrition and epilepsy: A two-way relationship

BACKGROUND & AIMS A link between malnutrition and epilepsy has been suspected for many years. METHODS Different aspects of the question were studied with a review of previous published data. RESULTS Several studies performed on animal models or humans highlight the possible adverse effects of malnutrition in the onset of seizures. Protein-energy, electrolyte, vitamin or trace element deficiencies may be involved. Conversely, several determinants of epilepsy could lead to malnutrition: food taboos and social exclusion in developing countries as well as some adverse effects of antiepileptic treatments. CONCLUSIONS Two different hypotheses exist as a vicious circle: malnutrition predisposing to epilepsy or epilepsy predisposing to malnutrition. A better understanding of these interactions is necessary. In the mean time, malnutrition has to be prevented and treated.

Disease progression and survival in ALS: First multi‐state model approach

Although several prognostic factors have been identified in ALS, there remains some discordance concerning the prognostic significance of the age and clinical form at onset. In order to clarify these findings, we have analysed already known prognostic factors using a multi‐state model. Two hundred and twenty‐two sporadic ALS patients were followed. A simple unidirectional three‐states model was used to summarize clinical course of ALS. States 1 and 2 reflected the progression of neurological impairment and state 3 represented the end of follow‐up (tracheotomy or death). Gender, diagnostic delay, body mass index (BMI) and slow vital capacity (SVC) were also recorded. A time‐inhomogeneous Markov model with piecewise constant transition intensities was used to estimate the effect of the covariates in each transition. The bulbar form at onset was only correlated with a more rapid clinical progression between state 1 and state 2. In contrast, an advanced age at diagnosis affected only survival from state 2. This methodological approach suggests that these two factors have a different prognostic significance: age at onset is related to patients survival and the clinical form at onset predicts the progression of motoneuronal impairment in different regions.

Prise en charge nutritionnelle et respiratoire des patients atteints de Sclérose Latérale Amyotrophique (SLA)

Resume Au cours de la sclerose laterale amyotrophique (SLA), la qualite de vie et la survie des patients sont correlees a l’etat respiratoire et nutritionnel. La prise en charge des patients doit donc etre multi-disciplinaire et coordonnee par le neurologue referent. Elle necessite l’acquisition de competences nouvelles de la part du neurologue qui doit connaitre les moyens d’evaluation de l’etat nutritionnel et respiratoire, les avantages et les limites des explorations utilisees ainsi que les situations a risque. L’information des patients sur certaines therapeutiques, comme la ventilation assistee ou la mise en place d’une sonde de gastrostomie, vecues le plus souvent avec beaucoup d’angoisse, doit etre precoce et precise, basee sur un climat de confiance. Les choix eclaires des patients seront respectes. La prise en charge des troubles nutritionnels et respiratoires repose actuellement sur les recommandations publiees en 1999 par l’Academie Americaine de Neurologie. Le but de cette revue est de presenter les connaissances actuelles de la prise en charge nutritionnelle et respiratoire des patients atteints de SLA.