Anna Tagliabue

Multi-frequency impedance for the prediction of extracellular water and total body water

The relationship between total body water (TBW) and extracellular water (ECW), measured by deuterium oxide dilution and bromide dilution respectively, and impedance and impedance index (height2/impedance) at 1, 5, 50 and 100 kHz was studied. After correction for TBW, ECW was correlated only with the impedance index at 1 and 5 kHz. After correction for ECW, TBW was best correlated with the impedance index at 100 kHz. The correlation of body-water compartments with impedance values obtained with modelling programs was lower than with measured impedance values. Prediction formulas for ECW (at 1 and 5 kHz) and TBW (at 50 and 100 kHz) were developed. The prediction errors for ECW and TBW were 1.0 and 1.7 kg respectively (coefficient of variation 5%). The residuals of both ECW and TBW were related to the ECW/TBW value. Application of the prediction formulas in a population, independently measured, revealed a slight overestimation of TBW and ECW, which could be largely explained by differences in the validation group in body-water distribution and in body build. The ratio of impedance at 1 kHz to impedance at 100 kHz was correlated with body-water distribution (ECW/TBW). The relation is however not strong enough to be useful as a predictor. It is concluded that an independent prediction of ECW and TBW, using impedance at low and high frequency respectively, is possible, but that the bias depends on the body-water distribution and body build of the measured subject.

The ketogenic diet in children, adolescents and young adults with refractory epilepsy: An Italian multicentric experience

PURPOSE This collaborative study by three Italian groups of child neuropsychiatrists was carried on to evaluate the efficacy and safety of the classic 4:1 ketogenic diet as add-on treatment in refractory partial or generalized epilepsy in children, adolescents and young adults. METHODS We performed a prospective add-on study in 56 refractory epilepsy young patients (age 1-23 years, mean 10.4 years), all with both symptomatic and cryptogenic, generalized or partial epilepsies. Child neuropsychiatrists worked with nutritional team for sample selection and patients management. The ketogenic diet was added to the baseline antiepileptic drugs and the efficacy was rated according to seizure type and frequency. During treatment, seizure frequency, side effects, urine and blood ketone levels and other parameters were systematically evaluated. RESULTS Patients have been treated for 1-18 months (mean 5 months). A >50% reduction in seizure frequency was gained in 37.5 and 26.8% of patients after 3 and 6 months, respectively, at 12 months, this number fell by 8.9%. No significant relationship between diet efficacy and seizure or epilepsy type, age at diet onset, sex and etiology of epilepsy was noted. Nevertheless, it seems noteworthy that 64% of our patients with neuronal migration disorders improved on this diet. Adverse effects occurred, mainly in the first weeks of treatment, in 32 patients (57.1%), but were generally mild and transient. In seven patients (12.5%) it was possible to withdraw one to two AED after 3-4 months on ketogenic diet. CONCLUSION This initial experience with the ketogenic diet was effective in difficult-to-treat patients with partial and generalized epilepsies, though its efficacy dropped significantly by 9-12 months.

Intentional weight loss in overweight and obese individuals and cognitive function: a systematic review and meta-analysis

High adiposity in middle age is associated with higher dementia risk. The association between weight loss and cognitive function in older adults is still controversial. A meta‐analysis was undertaken to estimate the effectiveness of intentional weight loss on cognitive function in overweight and obese adults. A structured strategy was used to search randomized and non‐randomized studies reporting the effect of intentional and significant weight loss on cognitive function in overweight and obese subjects. Information on study design, age, nutritional status, weight‐loss strategy, weight lost and cognitive testing was extracted. A random‐effect meta‐analysis was conducted to obtain summary effect estimates for memory and attention–executive domains. Twelve studies met inclusion criteria. Seven were randomized trials and the remaining five included a control group. A low‐order significant effect was found for an improvement in cognitive performance with weight loss in memory (effect size 0.13, 95% CI 0.00–0.26, P = 0.04) and attention/executive functioning (effect size 0.14, 95% CI 0.01–0.27, P < 0.001). Studies were heterogeneous in study design, sample selection, weight‐loss intervention and assessment of cognitive function. Weight loss appears to be associated with low‐order improvements in executive/attention functioning and memory in obese but not in overweight individuals.

Evaluation of nutritional status in children with refractory epilepsy

Backgroundchildren affected by refractory epilepsy could be at risk of malnutrition because of feeding difficulties (anorexia, chewing, swallowing difficulties or vomiting) and chronic use of anticonvulsants, which may affect food intake and energy metabolism. Moreover, their energy requirement may be changed as their disabilities would impede normal daily activities. The aim of the present study was to evaluate nutritional status, energy metabolism and food intake in children with refractory epilepsy.Methods17 children with refractory epilepsy (13 boys and 4 girls; mean age 9 ± 3,2 years; Body Mass Index 15,7 ± 3,6) underwent an anthropometric assessment, body composition evaluation by dual-energy X-ray absorptiometry, detailed dietetic survey and measurement of resting energy expenditure by indirect calorimetry. Weight-for-age, height-for-age (stunting) and weight-for-height (wasting) were estimated compared to those of a reference population of the same age.Results40% of children were malnourished and 24% were wasted. The nutritional status was worse in the more disabled children. Dietary intake resulted unbalanced (18%, 39%, 43% of total daily energy intake derived respectively from protein, lipid and carbohydrate). Adequacy index [nutrient daily intake/recommended allowance (RDA) × 100] was < 60% for calcium iron and zinc.Conclusionmany children with refractory epilepsy would benefit from individual nutritional assessment and management as part of their overall care.

A pilot study of a ketogenic diet in patients with Lafora body disease

PURPOSE Lafora body disease (LBD) is severe and rapidly worsening progressive myoclonus epilepsy (PME), not treatable with specific therapy. In LBD patients, typical polyglucosan accumulations result from alterations of proteins involved in the regulation of glycogen metabolism. Thus, a ketogenic regimen might reasonably be expected to counteract the disease progression. We set out to assess the feasibility and tolerability of a long-term ketogenic diet (KD) in LBD patients and to make a preliminary evaluation of its effect on the disease course. METHODS We treated five LBD patients with KD and evaluated the changes in the clinical, neuropsychological and neurophysiological findings over 10-30 months. RESULTS The KD was well tolerated in all the patients for the first 16 months. Nutritional measures and laboratory findings remained substantially stable. The disease progressed in all the patients, reaching an advanced stage in one. Electrophysiological findings indicated the presence of increased cortical excitability in four patients, paralleling the worsening of the myoclonus. CONCLUSION KD was unable to stop the disease progression. However, given the considerable heterogeneity of the natural history of LBD, we cannot exclude the possibility that KD has the potential to slow down the disease progression. The application of this nutritional approach should be further evaluated in larger case series.

Effects of the ketogenic diet on nutritional status, resting energy expenditure, and substrate oxidation in patients with medically refractory epilepsy: A 6-month prospective observational study

BACKGROUND & AIMS This 6-month prospective, single-arm observational study was designed to assess the effects of the KD on the nutritional status, resting energy expenditure (REE), and substrate oxidation in patients with drug-resistant epilepsy. METHODS Eighteen patients with medically refractory epilepsy underwent assessment of body composition, REE, and substrate oxidation rates before and after 6 months of KD. RESULTS Compared with baseline, there were no statistically significant differences at 6 months in terms of height, weight, BMI z-scores, and REE. However, the respiratory quotient decreased significantly (from 0.80 ± 0.06 to 0.72 ± 0.05, p < 0.001) whereas fat oxidation was significantly increased (from 50.9 ± 25.2 mg/min to 97.5 ± 25.7 mg/min, p < 0.001). Interestingly, we found that the increase in fat oxidation was the main independent predictor of the reduction in seizure frequency (beta = -0.97, t = -6.3, p < 0.05). CONCLUSIONS Administering a KD for 6 months in patients with medically refractory epilepsy increases fat oxidation and decreases the respiratory quotient, without appreciable changes in REE.

The ketogenic diet for Dravet syndrome and other epileptic encephalopathies: an Italian consensus

Ketogenic diet is a nonpharmacologic treatment for childhood epilepsy not amenable to drugs. At the present time, two works based on national research, one in Germany and one in the United States provide international guidelines to ensure a correct management of the ketogenic diet. Our Italian collaborative study group was set up in order to formulate a consensus statement regarding the clinical management of the ketogenic diet, patient selection, pre–ketogenic diet, counseling, setting and enforcement of dietary induction of ketosis, follow‐up management, and eventual discontinuation of the diet.

A common core microbiota between obese individuals and their lean relatives? Evaluation of the predisposition to obesity on the basis of the fecal microflora profile

Obesity represents a crucial social problem in developed countries as a cause of multiple metabolic abnormalities. The exact etiology of this multifactorial disease is still unknown. The impact of dietary habits and lifestyle is currently under investigation but the role of other predisposing factors, such as genetic determinants and familial history, needs still to be elucidated. Significant alterations in the composition of the intestinal microbiota have been recently identified in obese mice, suggesting an involvement of gut microbes in obesity. In humans, obese subjects are supposed to have a more efficient flora in energy extraction from food, due to the detection of quantitative differences in the major bacterial groups in obese subjects compared to lean ones. Despite these observations, the homologies in gut microbiota between obese adults and their lean relatives have never been investigated in details. Few reports about the detection of common microbial profiles between members of the same family have been published in the past but only one recent scientific article, investigating the presence of a common core microbiota between obese and lean twins, correlates genetic background and gut microflora as significant variables in obesity. The hypothesis suggested herein is that the identification of a familial-specific core microbiota could be precious in order to identify key-bacterial groups to be used as biomarkers for the evaluation of predisposition to obesity.

To treat or not to treat: comparison of different criteria used to determine whether weight loss is to be recommended

BackgroundExcess body fat is a major risk factor for disease primarily due to its endocrine activity. In recent years several criteria have been introduced to evaluate this factor. Nevertheless, treatment need is currently assessed only on the basis of an individuals Body Mass Index (BMI), calculated as body weight (in kg) divided by height in m2. The aim of our study was to determine whether application of the BMI, compared to adiposity-based criteria, results in underestimation of the number of subjects needing lifestyle intervention.MethodsWe compared treatment need based on BMI classification with four adiposity-based criteria: percentage body fat (%BF), considered both alone and in relation to metabolic syndrome risk (MS), waist circumference (WC), as an index of abdominal fat, and Body Fat Mass Index (BFMI, calculated as fat mass in kg divided by height in m2) in 63 volunteers (23 men and 40 women, aged 20 – 65 years).ResultsAccording to the classification based on BMI, 6.3% of subjects were underweight, 52.4% were normal weight, 30.2% were overweight, and 11.1% were obese. Agreement between the BMI categories and the other classification criteria categories varied; the most notable discrepancy emerged in the underweight and overweight categories. BMI compared to almost all of the other adiposity-based criteria, identified a lower percentage of subjects for whom treatment would be recommended. In particular, the proportion of subjects for whom clinicians would strongly recommend weight loss on the basis of their BMI (11.1%) was significantly lower than those identified according to WC (25.4%, p = 0.004), %BF (28.6%, p = 0.003), and MS (33.9%, p = 0.002).ConclusionThe use of the BMI alone, as opposed to an assessment based on body composition, to identify individuals needing lifestyle intervention may lead to unfortunate misclassifications. Population-specific data on the relationships between body composition, morbidity, and mortality are needed to improve the diagnosis and treatment of at-risk individuals.

Glucose transporter type 1 deficiency: Ketogenic diet in three patients with atypical phenotype

Glucose transporter type I deficiency syndrome (GLUT-1 DS) is an inborn error of glucose transport characterized by seizures, developmental delay, spasticity, acquired microcephaly and ataxia. Diagnosis is based on the finding of low cerebrospinal fluid glucose, in the absence of hypoglycemia, and identification of GLUT-1 gene mutation on chromosome 1. The classic phenotype is a severe form of early onset epileptic encephalopathy, but patient with different clinical presentation have been reported expanding the clinical spectrum. In particular, many patients show a prominent movement disorder other than epilepsy. It is known that this disease represents a treatable condition and ketogenic diet (KD) is the elective treatment in GLUT-1 DS patients. We report on KD in three unrelated Italian GLUT-1 DS female patients, diagnosed in early adulthood, all presenting with an atypical phenotype. Preliminary results seem to demonstrate efficacy of KD on paroxysmal movement disorder while positive effect on cognitive impairment result less evident.