Dopamine denervation in the functional territories of the striatum: a new MR and atlas-based 123I-FP-CIT SPECT quantification method.

Current quantification methods of 123I-FP-CIT SPECT rely on anatomical parcellation of the striatum. We propose here to implement a new method based on MRI segmentation and functional atlas of the basal ganglia (MR-ATLAS) that could provide a reliable quantification within the sensorimotor, associative, and limbic territories of the striatum. Patients with Parkinson's disease (PD), idiopathic rapid eye movement sleep behavioral disorder (iRBD), and healthy controls underwent 123I-FP-CIT SPECT, MRI, motor, and cognitive assessments. SPECT data were corrected for partial volume effects and registered to a functional atlas of the striatum to allow quantification in every functional region of the striatum (nucleus accumbens, limbic, associative, and sensorimotor parts of the striatum). The MR-ATLAS quantification method is proved to be reliable in every territory of the striatum. In addition, good correlations were found between cognitive dysexecutive tests and the binding within the functional (limbic) territories of the striatum using the MR-ATLAS method, slightly better than correlations found using the anatomical quantification method. This new MR-ATLAS method provides a robust and useful tool for studying the dopaminergic system in PD, particularly with respect to cognitive functions. It may also be relevant to further unravel the relationship between dopaminergic denervation and cognitive or behavioral symptoms.

Programming parameters of subthalamic deep brain stimulators in Parkinson's disease from a controlled trial.

BACKGROUND: Programming algorithms have never been tested for outcome. The EARLYSTIM study showed superior outcomes of deep brain stimulation of the subthalamic nucleus (STN-DBS) over best medical treatment in early Parkinson's disease (PD). Patients were programmed according to common guidelines but customized for each patient. METHODS: Stimulation parameters were systematically documented at 1, 5, 12, and 24 month in the cohort of 114 patients who had bilateral STN-DBS at 24 month. We investigated the influence of atypical programming, changes of stimulated electrode contacts and stimulation energy delivered. Outcomes were the Unified Parkinson's Disease Rating Scale (UPDRS) motor and ADL-subscores, health-related quality of life (PDQ-39) summary index and mobility- and ADL-subscores. RESULTS: At 1/5/12/24 months follow up, mean amplitude (1.8/2.5/2.6/2.8 V), impedance (1107/1286/1229/1189 Ω) and TEED (33.7/69.0/84.4/93.0 V2*µs*Hz/Ω) mainly increased in the first 5 months, while mean pulse width (60.0/62.5/65.1/65.8 µs), frequency (130/137.7/139.1/142.7 Hz) remained relatively stable. Typical programming (single monopolar electrode contact) was used in 80.7% of electrodes. Double monopolar (11/114) and bipolar (2/114) stimulation was only rarely required. There was no significant difference in clinical outcomes between the patient groups requiring contact changes (n = 32/28.1%) nor between typical (n = 83/72.8%) versus non-typical programming. Energy used for STN-DBS was higher for the dominant side of PD. CONCLUSION: In the first 5 months an increase in amplitude is required to compensate for various factors. Monopolar stimulation is sufficient in 80% of patients at 24 months. Homogeneous stimulation strategies can account for the favorable outcomes reported in the Earlystim study.

Comparative Study of MRI Biomarkers in the Substantia Nigra to Discriminate Idiopathic Parkinson Disease.

BACKGROUND AND PURPOSE: Several new MR imaging techniques have shown promising results in patients with Parkinson disease; however, the comparative diagnostic values of these measures at the individual level remain unclear. Our aim was to compare the diagnostic value of MR imaging biomarkers of substantia nigra damage for distinguishing patients with Parkinson disease from healthy volunteers. MATERIALS AND METHODS: Thirty-six patients and 20 healthy volunteers were prospectively included. The MR imaging protocol at 3T included 3D T2-weighted and T1-weighted neuromelanin-sensitive images, diffusion tensor images, and R2* mapping. T2* high-resolution images were also acquired at 7T to evaluate the dorsal nigral hyperintensity sign. Quantitative analysis was performed using ROIs in the substantia nigra drawn manually around the area of high signal intensity on neuromelanin-sensitive images and T2-weighted images. Visual analysis of the substantia nigra neuromelanin-sensitive signal intensity and the dorsolateral nigral hyperintensity on T2* images was performed. RESULTS: There was a significant decrease in the neuromelanin-sensitive volume and signal intensity in patients with Parkinson disease. There was also a significant decrease in fractional anisotropy and an increase in mean, axial, and radial diffusivity in the neuromelanin-sensitive substantia nigra at 3T and a decrease in substantia nigra volume on T2* images. The combination of substantia nigra volume, signal intensity, and fractional anisotropy in the neuromelanin-sensitive substantia nigra allowed excellent diagnostic accuracy (0.93). Visual assessment of both substantia nigra dorsolateral hyperintensity and neuromelanin-sensitive images had good diagnostic accuracy (0.91 and 0.86, respectively). CONCLUSIONS: The combination of neuromelanin signal and volume changes with fractional anisotropy measurements in the substantia nigra showed excellent diagnostic accuracy. Moreover, the high diagnostic accuracy of visual assessment of substantia nigra changes using dorsolateral hyperintensity analysis or neuromelanin-sensitive signal changes indicates that these techniques are promising for clinical practice.

Comparing ataxias with oculomotor apraxia: a multimodal study of AOA1, AOA2 and AT focusing on video-oculography and alpha-fetoprotein.

Whether the recessive ataxias, Ataxia with oculomotor apraxia type 1 (AOA1) and 2 (AOA2) and Ataxia telangiectasia (AT), can be distinguished by video-oculography and alpha-fetoprotein level remains unknown. We compared 40 patients with AOA1, AOA2 and AT, consecutively referred between 2008 and 2015 with 17 healthy subjects. Video-oculography revealed constant impairments in patients such as cerebellar signs, altered fixation, impaired pursuit, hypometric saccades and abnormal antisaccades. Horizontal saccade latencies could be highly increased reflecting oculomotor apraxia in one third of patients. Specific distinctive alpha-fetoprotein thresholds were determined for AOA1 (7-15 µg/L), AOA2 (15-65 µg/L) and AT (>65 µg/L). Early age onset, severe walking disability, movement disorders, sensori-motor neuropathy and cerebellar atrophy were all shared. In conclusion, alpha-fetoprotein level seems to permit a distinction while video-oculography does not and therefore is not mandatory, even if an appropriate oculomotor examination remains crucial. Our findings are that AOA1, AOA2 and AT form a particular group characterized by ataxia with complex oculomotor disturbances and elevated AFP for which the final diagnosis is relying on genetic analysis. These findings could guide genetic analysis, assist reverse-phenotyping and provide background for the interpretation of the numerous variants of unknown significance provided by next-generation sequencing.

"De-novo" consultation: Evaluation of an outpatient's clinic dedicated to early diagnosis of parkinsonian syndromes.

INTRODUCTION: In the absence of specific clinical signs, imaging or biomarkers, the differential diagnosis of degenerative parkinsonian syndromes may be difficult at early stages of the disease. To reduce the risk of misdiagnosis or delayed diagnosis and referral to multiple medical centers at disease onset, easier access to expert centers should be available. To improve the initial care of parkinsonian patients, the Parkinson's disease Expert Center (PEC) at Pitié-Salpêtrière Academic Hospital has set up a specific outpatients clinic with short waiting times dedicated to the diagnosis of early Parkinson's disease and related disorders. METHODS: The PEC setup first identifies requests for diagnostic confirmation of parkinsonian syndromes, then specific outpatients clinic visits are scheduled weekly, with examinations carried out by neurologists at the PEC on a rotating schedule. Data from the first year of the new procedure were analyzed retrospectively through self-administered questionnaires sent to patients seen during this period. The main outcomes were to confirm the ability to keep to short delays for patients' examinations and to assess patients' satisfaction with the setup. RESULTS: Both study outcomes were achieved. The creation of an outpatients clinic dedicated to the early diagnosis of parkinsonian syndromes allowed shorter delays before the first examination of 5 weeks instead of several months. Keeping to the weekly schedule and limited time taken for each visit was also achieved. Following this initial outpatients visit, diagnosis of a parkinsonian syndrome was clinically confirmed or further specified in 80% of cases. A survey of patients' satisfaction showed a rate of over 91% in terms of the timing and course of clinical examinations at our PEC. DISCUSSION/CONCLUSION: This study of our quality-improvement program for Parkinson's disease management has shown that specific consultations with shorter waiting times aiming to allow early specialized assessment of parkinsonian syndromes is beneficial for patients and reduces the risk of delayed diagnoses.

Vitamin A in pediatrics: An update from the Nutrition Committee of the French Society of Pediatrics.

Vitamin A (retinol) fulfills multiple functions in vision, cell growth and differentiation, embryogenesis, the maintenance of epithelial barriers and immunity. A large number of enzymes, binding proteins and receptors facilitate its intestinal absorption, hepatic storage, secretion, and distribution to target cells. In addition to the preformed retinol of animal origin, some fruits and vegetables are rich in carotenoids with provitamin A precursors such as ß-carotene: 6µg of ß-carotene corresponds to 1µg retinol equivalent (RE). Carotenoids never cause hypervitaminosis A. Determination of liver retinol concentration, the most reliable marker of vitamin A status, cannot be used in practice. Despite its lack of sensitivity and specificity, the concentration of retinol in blood is used to assess vitamin A status. A blood vitamin A concentration below 0.70µmol/L (200µg/L) indicates insufficient intake. Levels above 1.05µmol/L (300µg/L) indicate an adequate vitamin A status. The recommended dietary intake increases from 250µg RE/day between 7 and 36 months of age to 750µg RE/day between 15 and 17 years of age, which is usually adequate in industrialized countries. However, intakes often exceed the recommended intake, or even the upper limit (600µg/day), in some non-breastfed infants. The new European regulation on infant and follow-on formulas (2015) will likely limit this excessive intake. In some developing countries, vitamin A deficiency is one of the main causes of blindness and remains a major public health problem. The impact of vitamin A deficiency on mortality was not confirmed by the most recent studies. Periodic supplementation with high doses of vitamin A is currently questioned and food diversification, fortification or low-dose regular supplementation seem preferable.

Efficacy of pallidal stimulation in isolated dystonia: a systematic review and meta-analysis.

The aim of this review was to provide strong clinical evidence of the efficacy of deep brain stimulation (DBS) of the globus pallidus internus (GPi) in isolated inherited or idiopathic dystonia. Eligible studies were identified after a systematic literature review of the effects of bilateral GPi-DBS in isolated dystonia. Absolute and percentage changes from baseline in the Burke-Fahn-Marsden Dystonia Rating Scale (BFMDRS) motor and disability scores were pooled, and associations between treatment effect and patient characteristics were explored using meta-regression. In total, 24 studies were included in the meta-analysis, comprising 523 patients. The mean absolute and percentage improvements in BFMDRS motor score at the last follow-up (mean 32.5 months; 24 studies) were 26.6 points [95% confidence interval (CI), 22.4-30.8] and 65.2% (95% CI, 59.6-70.7), respectively. The corresponding changes in disability score at the last follow-up (mean 32.9 months; 14 studies) were 6.4 points (95% CI, 5.0-7.8) and 58.6% (95% CI, 50.3-66.9). Multivariate meta-regression of absolute scores indicated that higher BFMDRS motor and disability scores before surgery, together with younger age at time of surgery, were the main factors associated with significantly better DBS outcomes at the latest follow-up. Reporting of safety data was frequently inconsistent and could not be included in the meta-analysis. In conclusion, patients with isolated inherited or idiopathic dystonia significantly improved after GPi-DBS. Better outcomes were associated with greater dystonia severity at baseline. These findings should be taken into consideration for improving patient selection for DBS.

Management of dystonia in Europe: a survey of the European network for the study of the dystonia syndromes.

BACKGROUND AND PURPOSE: Dystonia is difficult to recognize due to its large phenomenological complexity. Thus, the use of experts in dystonia is essential for better recognition and management of dystonia syndromes (DS). Our aim was to document managing strategies, facilities and expertise available in various European countries in order to identify which measures should be implemented to improve the management of DS. METHODS: A survey was conducted, funded by the Cooperation in Science and Technology, via the management committee of the European network for the study of DS, which is formed from representatives of the 24 countries involved. RESULTS: Lack of specific training in dystonia by general neurologists, general practitioners as well as other allied health professionals was universal in all countries surveyed. Genetic testing for rare dystonia mutations is not readily available in a significant number of countries and neurophysiological studies are difficult to perform due to a lack of experts in this field of movement disorders. Tetrabenazine is only readily available for treatment of dystonia in half of the surveyed countries. Deep brain stimulation is available in three-quarters of the countries, but other surgical procedures are only available in one-quarter of countries. CONCLUSIONS: Internationally, collaboration in training, advanced diagnosis, treatment and research of DS and, locally, in each country the creation of multidisciplinary teams for the management of dystonia patients could provide the basis for improving all aspects of dystonia management across Europe.

Nutri-Bébé 2013 Study Part 2. How do French mothers feed their young children?

Nutri-Baby SFAE 2013 is the 5th edition of a survey conducted every 8 years since 1981 by SFAE (Secteur Français des Aliments de l'Enfance) in collaboration with an opinion poll institute (SOFRES) for the feeding behavior part of the study and with CREDOC for calculating nutrient intake: 1,188 mothers of infants and young children from 15 days to 3 years of age were interviewed in 2013. The present paper is limited to the behavioral part of the investigation on the observance by mothers of pediatric recommendations. Overall, the "2013 mother" is self-confident (76% declare being confident in their experience and instinct). They are aware of the recommendations of healthcare professionals, but the family circle is also influential. Although growing-up milk is more widely consumed than in 2005 (+8%), cow's milk (half-skimmed and not whole milk), even if it is introduced 2 months later than in 2005, is still consumed by 34% of children at 12-17 months of age and by 64% of 24 - to 29-month-old children. Milk is still frequently warmed up in a microwave oven. Breastfeeding mothers or those who breastfed more frequently give growing-up milk and home-cooked foods and afterwards their children refuse different foods less frequently. Adult foods that are not adapted for children are introduced too early. Foods in morsels are proposed very late. Fried foods and sweet foods appear too early in infant meals. Consumption of infant formulas and specific baby foods is increasing, but at around 1 year of age a decrease in the consumption of these adapted foods is observed.

Increased cortico-striatal connectivity during motor practice contributes to the consolidation of motor memory in writer's cramp patients.

Sensorimotor representations of movements are created in the sensorimotor network through repeated practice to support successful and effortless performance. Writer's cramp (WC) is a disorder acquired through extensive practice of finger movements, and it is likely associated with the abnormal acquisition of sensorimotor representations. We investigated (i) the activation and connectivity changes in the brain network supporting the acquisition of sensorimotor representations of finger sequences in patients with WC and (ii) the link between these changes and consolidation of motor performance 24 h after the initial practice. Twenty-two patients with WC and 22 age-matched healthy volunteers practiced a complex sequence with the right (pathological) hand during functional MRI recording. Speed and accuracy were measured immediately before and after practice (day 1) and 24 h after practice (day 2). The two groups reached equivalent motor performance on day 1 and day 2. During motor practice, patients with WC had (i) reduced hippocampal activation and hippocampal-striatal functional connectivity; and (ii) overactivation of premotor-striatal areas, whose connectivity correlated with motor performance after consolidation. These results suggest that patients with WC use alternative networks to reach equiperformance in the acquisition of new motor memories.

[Salt intake in children]. / Les enfants consomment-ils trop de sel ?

Very early in life, sodium intake correlates with blood pressure level. This warrants limiting the consumption of sodium by children. However, evidence regarding exact sodium requirements in that age range is lacking. This article focuses on the desirable sodium intake according to age as suggested by various groups of experts, on the levels of sodium intake recorded in consumption surveys, and on the public health strategies implemented to reduce salt consumption in the pediatric population. Practical recommendations are given by the Committee on nutrition of the French Society of Pediatrics in order to limit salt intake in children.

Lipid intake in children under 3 years of age in France. A position paper by the Committee on Nutrition of the French Society of Paediatrics.

Lipids are an important source of energy for young children and play a major role in the development and functioning of nervous tissue. Essential fatty acids and their long-chain derivatives also fulfill multiple metabolic functions and play a role in the regulation of numerous genes. The Food and Agriculture Organization of the United Nations (FAO), the World Health Organization (WHO), and the French Agency for Food, Environmental and Occupational Health & Safety (Agence nationale de sécurité sanitaire de l'alimentation, de l'environnement et du travail [ANSES]) have recently recommended a minimum daily intake in preformed long-chain polyunsaturated fatty acids (LC-PUFAs): arachidonic acid (ARA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA). Mother's milk remains the only reference, but the large variability in its DHA content does not guarantee that breastfed children receive an optimal DHA intake if the mother's intake is insufficient. For children fed with infant formulas, ARA and DHA intake is often below the recommended intake because only one-third of infant formulas available on the market in France are enriched in LC-PUFAs. For all children, linoleic acid (LA) intake is on average higher than the minimal recommended values. The consequences of these differences between intake and recommended values are uncertain. A cautious attitude is to come close to the current recommendations and to advise sufficient consumption of DHA in breastfeeding women. For bottle-fed children, infant formulas enriched in LC-PUFAs and with moderate levels of LA should be preferred. LC-PUFA-rich fish should be consumed during breastfeeding, and adapted vegetable oils when complementary foods are introduced.

GLUT1 deficiency syndrome: an update.

INTRODUCTION: Glucose transporter type 1 deficiency syndrome is caused by heterozygous, mostly de novo, mutations in the SLC2A1 gene encoding the glucose transporter GLUT1. Mutations in this gene limit brain glucose availability and lead to cerebral energy deficiency. STATE OF THE ART: The phenotype is characterized by the variable association of mental retardation, acquired microcephaly, complex motor disorders, and paroxysmal manifestations including seizures and non-epileptic paroxysmal episodes. Clinical severity varies from mild motor dysfunction to severe neurological disability. In patients with mild phenotypes, paroxysmal manifestations may be the sole manifestations of the disease. In particular, the diagnosis should be considered in patients with paroxysmal exercise-induced dyskinesia or with early-onset generalized epilepsy. Low CSF level of glucose, relative to blood level, is the best biochemical clue to the diagnosis although not constantly found. Molecular analysis of the SLC2A1 gene confirms the diagnosis. Ketogenic diet is the cornerstone of the treatment and implicates a close monitoring by a multidisciplinary team including trained dieticians. Non-specific drugs may be used as add-on symptomatic treatments but their effects are often disappointing. CONCLUSION: Glucose transporter type 1 deficiency syndrome is likely under diagnosed due to its complex and pleiotropic phenotype. Proper identification of the affected patients is important for clinical practice since the disease is treatable.

[Processed baby foods for infants and young children: a dietary advance? A position paper by the Committee on Nutrition of the French Society of Paediatrics]. / Les aliments industriels (hors laits et céréales) destinés aux nourrissons et enfants en bas âge : un progrès diététique ?

Processed baby foods designed for infants (4-12 months) and toddlers (12-36 months) (excluding infant formula, follow-on formula, the so-called growing-up milks, and cereal-based foods for infants), which are referred to as baby foods, are specific products defined by a European regulation (Directive 2006/125/CE). According to this Directive, such foods have a composition adapted to the nutritional needs of children of this age and should comply with specifications related to food safety in terms of ingredients, production processes, and prevention of infectious and toxicological hazards. Hence, they differ from ordinary foods and from non-specific processed foods. This market segment includes the full range of foods that can be part of children's diet: dairy products (dairy desserts, yoghurts, and fresh cheese), sweet products (nondairy desserts, fruit, and drinks), and salty products (soups, vegetable-based foods, meat, fish, and full dishes). This market amounted to 89,666 MT in France in 2011 and 83,055 MT in 2010 (a total of 325,524 MT in the 27 countries of the European Union in 2010, including 90,438 MT in Germany, 49,144 MT in Spain, and 40,438 MT in Italy). The consumption of baby foods in France varies with infant age and parental choice. Baby foods account for 7 % of total energy intake at 4-5 months, 28 % at 6-7 months, 27 % at 8-11 months, 17 % at 1-17 months, and 11 % at 18-24 months. Among parents, 24 % never offer their children any baby foods, 13 % do so 1-3 days/week and 63 % 4-7 days/week. Among consumers, 55 % of children eat more than 250 g/day of baby foods. As baby foods only account for a minor fraction of overall food intake, their impact on the quality of young children's diet is much less than that of growing-up milks, particularly for preventing insufficient iron and vitamin D intake. Their consumption, however, has an indirect benefit on the nutritional quality of the diet and on food safety, particularly regarding toxicological hazards, as it postpones the introduction of non-specific processed foods, which are inadequate for this age group owing to both their nutritional composition and lower food safety control. Baby foods represent a family of products meeting parents' expectations and adapted to infants and young children. They are clearly beneficial in terms of food safety, but the nutritional benefit to be expected from their consumption is minimal: their main advantage is postponing or decreasing the consumption of non-specific industrially processed foods.