Chronic vagus nerve stimulation in Crohn's disease: a 6-month follow-up pilot study.

The vagus nerve (VN) is a link between the brain and the gut. The VN is a mixed nerve with anti-inflammatory properties through the activation of the hypothalamic-pituitary-adrenal axis by its afferents and by activating the cholinergic anti-inflammatory pathway through its efferents. We have previously shown that VN stimulation (VNS) improves colitis in rats and that the vagal tone is blunted in Crohn's disease (CD) patients. We thus performed a pilot study of chronic VNS in patients with active CD. Seven patients under VNS were followed up for 6 months with a primary endpoint to induce clinical remission and a secondary endpoint to induce biological (CRP and/or fecal calprotectin) and endoscopic remission and to restore vagal tone (heart rate variability). Vagus nerve stimulation was feasible and well-tolerated in all patients. Among the seven patients, two were removed from the study at 3 months for clinical worsening and five evolved toward clinical, biological, and endoscopic remission with a restored vagal tone. These results provide the first evidence that VNS is feasible and appears as an effective tool in the treatment of active CD.

The type of fortificant and the leaf matrix both influence iron and zinc bioaccessibility in iron-fortified green leafy vegetable sauces from Burkina Faso.

Leafy vegetable sauces from Burkina Faso were assessed as a potential vehicle for food fortification. First, iron and zinc bioaccessibility were measured by dialysability method in amaranth and Jew's mallow sauces and in traditional whole dishes consisting of maize paste plus leafy vegetable sauces. Iron dialysability and solubility were higher in amaranth than in Jew's mallow sauce, pointing to a marked effect of the matrix. Iron dialysability was hardly affected by the maize paste contrary to zinc dialysability, which was reduced. Second, iron and zinc bioaccessibility was assessed in the same sauces fortified with NaFeEDTA or iron sulfate. Added iron, i.e. iron supplied by fortification, represented 60% of total iron at the low fortification level and 80% at high level. In amaranth sauces with the high level of fortification using NaFeEDTA and iron sulfate, fractional dialysable iron reached respectively 66% and 26% compared to only 8.1% in the unfortified sauce. Similarly, in Jew's mallow sauces, fractional dialysable iron was 57% and 5% respectively with NaFeEDTA and iron sulfate and less than 1% in the unfortified sauce. Concomitantly, fractional dialysable zinc increased by respectively 20% and 40% in amaranth and Jew's mallow sauces fortified with NaFeEDTA whereas it remained unchanged with iron sulfate. Iron fortification could be an efficient way to greatly increase the available iron content of green leafy vegetable sauces and for this purpose NaFeEDTA is more effective than iron sulfate whatever the food matrix.

Vagus nerve stimulation: from epilepsy to the cholinergic anti-inflammatory pathway.

BACKGROUND: The brain and the gut communicate bidirectionally through the autonomic nervous system (ANS). The vagus nerve (VN), a major component of the ANS, plays a key role in the neuro-endocrine-immune axis to maintain homeostasia through its afferents (through the activation of the hypothalamic pituitary adrenal axis and the central ANS) and through its efferents (i.e. the cholinergic anti-inflammatory pathway; CAP). The CAP has an anti-TNF effect both through the release of acetylcholine at the distal VN acting on macrophages and through the connection of the VN with the spleen through the splenic sympathetic nerve. Vagus nerve stimulation (VNS) of vagal afferents at high frequency (20-30 Hz) is used for the treatment of drug-resistant epilepsy and depression. Low-frequency (5 Hz) VNS of vagal efferents activates the CAP for an anti-inflammatory effect that is as an anti-TNF therapy in inflammatory diseases were TNF is a key cytokine as represented by experimental sepsis, postoperative ileus, burn-induced intestinal barrier injury, colitis. However, both vagal afferents and efferents are activated by VNS. PURPOSE: The objective of this review was to explore the following: (i) the supporting evidence for the importance of VNS in epilepsy (and depression) and its mechanisms of action, (ii) the anti-inflammatory characteristics of the VN, (iii) the experimental evidence that VNS impact on inflammatory disorders focusing on the digestive tract, and (iv) how VNS could potentially be harnessed therapeutically in human inflammatory disorders such as inflammatory bowel diseases, irritable bowel syndrome, postoperative ileus, rheumatoid arthritis as an anti-inflammatory therapy.

Anti-inflammatory effect of vagus nerve stimulation in a rat model of inflammatory bowel disease.

Vagus nerve stimulation of afferents is used as an adjunctive treatment for drug-resistant epilepsy and depression. In addition, anti-inflammatory properties of vagus nerve stimulation have been reported in various experimental models of inflammation but not in colitis. These effects are thought to be mediated via peripheral release of acetylcholine from the vagus and subsequent activation of macrophages. Our aim was to evaluate in rats the anti-inflammatory effects of chronic vagus nerve stimulation on colonic inflammation. Colitis was induced by intracolonic instillation of trinitrobenzene sulfonic acid. Vagus nerve stimulation (left cervical) was performed in freely moving animals 3 h per day for five consecutive days. Assessment of colonic inflammation was obtained using physiological (e.g. body weight, temperature and locomotor activity) parameters, macroscopical (area of lesions), histological, and biological parameters (e.g. myeloperoxidase activity, cytokine and cytokine-related mRNAs), both at the level of the damaged colon and the colon immediately above. A global multivariate index of colitis was then generated for a better characterization of colonic inflammation. Vagus nerve stimulation reduced the degree of body weight loss and inflammatory markers as observed above the lesion by histological score and myeloperoxidase quantification. This anti-inflammatory effect was also demonstrated by the improvement of the multivariate index of colitis. These data argue for an anti-inflammatory role of vagus nerve stimulation chronically performed in freely moving rats with colitis and provide potential therapeutic applications for patients with inflammatory bowel diseases.

Neurological sequelae after cerebral anoxia.

PRIMARY OBJECTIVE: Cardiac arrest can cause neurological impairment. The aim of this study is to confirm the disability and the predominant part of executive and behavioural impairments after cardiac arrest. RESEARCH DESIGN: A retrospective study is proposed. METHODS AND PROCEDURES: All consecutive patients admitted to the Department of Rehabilitation for Neurological Impairments following cerebral anoxia after cardiac arrest between 1995-2007 were included. Clinical and neuropsychological assessment was proposed. MAIN OUTCOMES AND RESULTS: Thirty patients, 19 men, were examined. Ages ranged from 16-58 (mean = 39.5). Fourteen patients presented with severe disability and 16 patients presented with moderate disability. In the first group (severe disability) no patients were autonomous for daily life activities. They presented with dysexecutive syndrome and behavioural disorders associated with amnesia syndrome; 64% of them presented with motor disorders. In the second group, patients with moderate disability were autonomous in daily life but not for the complex activities or functioning. They had no motor impairment but suffered from executive and memory impairments. Behavioural changes were noted. Medical history or demographic data did not differ between the two groups. CONCLUSION: The study confirms the predominant part of executive, memory and behavioural impairments after cardiac arrest. This retrospective study cannot provide prognosis factors and further prognosis studies are needed.

[The effect of age on executive functioning after acquired brain injury in adults]. / Effet de l'âge sur le fonctionnement exécutif après lésion cérébrale chez l'adulte.

INTRODUCTION: Executive functioning deficits have often been described in normal aging. They are also known to be a frequent sequel of traumatic brain injury, where patients may exhibit severe long-standing impairments in instrumental activities of daily living. One could therefore expect that cerebral lesions affecting executive functioning would result in more severe impairments in older patients. We previously developed an ecological assessment of executive functions, consisting of a cooking task, requiring multitasking abilities and known to be sensitive to a dysexecutive syndrome [Cortex 36 (2000) 649-669]. The aim of this study was to analyze the effect of age on the cognitive and ecological assessments of executive functions in a group of patients with acquired brain injury (ABI) resulting in a dysexecutive syndrome. Studies in this area usually focus on patients older than 60 or 65, but we chose to analyze the effect of age in a younger population. We hypothesized that older patients would have poorer performances on the cognitive and ecological tests of executive functioning, when compared to younger patients. METHODS: Forty-five patients with ABI resulting in frontal lesions and a dysexecutive syndrome participated in this study. Patients underwent a comprehensive battery of cognitive tests assessing executive functioning, as well as the cooking task. We also studied a group of 12 control subjects who performed the cooking task. RESULTS: No effect of age was found on performance in the cooking task in the control group. Age was not related to demographic parameters or injury severity in the ABI group. Although the ABI group was relatively young (mean age: 40.3 years (S.D.=12.5), ranging from 17 to 63), results indicated a significant deleterious effect of age on the cognitive tests of executive functioning in the ABI group. We also highlighted a significant worsening of patients' performance in the cooking task with age, and this effect was found on several variables of task analysis: the number of errors and occurrence of dangerous behaviors. CONCLUSION: Our study demonstrates the deleterious effect of aging on cognitive and ecological assessment of executive functioning after ABI. The strength of this study is that it deviated from the traditional age considered in studies of elderly populations and focused on younger patients. It is therefore important to consider the implication that this may have on a patient's rehabilitation program and postinjury discharge.

[Fantastic confabulations or delusion?]. / Confabulations fantastiques ou délire ?

INTRODUCTION: Confabulations are inaccurate narratives purporting to convey information about the world or the self. Fantastic utterances from brain-injured patients are difficult to interpret as confabulation or delusion. METHODS: Starting from two clinical observations, we analyse the terms "spontaneous confabulations" and "delusion". RESULTS: Two brain-injured patients presented with fantastic utterances; the adhesion was complete for both patients. They also suffered from amnesic and executive disorders. Clinical interviews with neuropsychologist and psychopathologist could not distinct between spontaneaous confabulations and delusion. DISCUSSION: Neuropsychological interpretations of spontaneous confabulations are (1) the deficient strategic retrieval process arising from executive failures and (2) confusion of the temporal order of information within memory. These hypotheses cannot explain the fantastic utterances described. Are spontaneous fantastic confabulations a specific entity or did these patients present a morbid association of neurological and psychiatric disorders? Fantastic confabulations are very scarcely described and the association of neurological and psychiatric impairments enables us to better describe the clinical observations. Spontaneous confabulations reported after amnesic and executive disorders are indeed typically composed of the patient's past experiences and do not usually comprehend fantastic utterances. CONCLUSION: Neurological and psychological analyses of the fantastic utterances from two brain-injured patients do not respond to the definition of spontaneous confabulation. Fantastic confabulations are a rare entity and we propose another explanation consisting of the association of neurological and psychiatric disorders.

Ecological assessment of the dysexecutive syndrome using execution of a cooking task.

Patients with a dysexecutive syndrome often have severe disabilities in daily life activities. The aims of this study were to use a naturalistic experimental task to assess patients' disabilities, and to study the nature of the cognitive disorders underlying them. Execution of a cooking task involving multi-tasking (Chevignard et al., 2000) was studied in 45 patients with a dysexecutive syndrome following acquired brain injury. Patients made significantly more errors and were slower than controls; more than half of the patients did not achieve the goal and demonstrated dangerous behaviours. Those results were significantly correlated to the results of the Six Elements Task and to a behavioural questionnaire. They were also correlated to brain injury severity and to patients' cooking habits. This naturalistic assessment is clinically relevant to better assess patients' dysexecutive impairments in complex activities of daily living. Correlations of the results in the cooking task with the neuropsychological assessment highlighted the role of the dysexecutive syndrome in patients' disabilities, indicating control alterations rather than planning disorders, difficulty in dealing with the environment, and inhibiting inappropriate actions. The role of attention and prospective memory was also underlined, whereas other cognitive functions did not influence task performance.

[Ecological assessment of executive functions in a patient with acquired brain injury]. / Evaluation écologique des fonctions exécutives chez un patient traumatisé crânien.

UNLABELLED: Dysexecutive syndrome is one of the most frequent sequel of severe traumatic brain injury. It causes severe disabilities and it is incompletely assessed by the classical "paper and pencil" neuropsychological tests. We developed an ecological assessment conducted in a naturalistic situation, consisting of a cooking task, and we described a classification of errors. This assessment is very sensitive, even to a mild dysexecutive syndrome. OBJECTIVE: To describe the disabilities in activities of daily living of a traumatic brain-injured patient and to demonstrate the sensitivity of an ill-structured ecological assessment. METHOD: We report a single case study illustrating how the ecological assessment by the cooking task helped better understand and characterize the patient's disabilities. RESULTS: The patient presented severe disabilities in daily life activities, which were well described by his family. His cognitive disorders were mild in the cognitive tests, even those supposed to be more ecological, such as the Six Elements Task or script generation. He exhibited very severe disorders in the cooking task, with a very high number of errors. Moreover, duration of the cooking task was very long; he did not achieve the goal and exhibited dangerous behaviour. DISCUSSION AND CONCLUSION: The cooking task involves abilities to deal with multitasking, which particularly involve executive functions. The most severe disorders were observed during the patient's interaction with the environment while conducting a complex goal-directed action plan, indicating control disorders. This type of naturalistic assessment provides very useful information to help patients organise their familial, social or professional reintegration.

Neurological complications of primary Sjögren's syndrome.

OBJECTIVE: To better delineate the spectrum of neurological complications of primary Sjögren's syndrome (PSS). METHODS: A detailed neurological investigation was prospectively performed in a group of 25 consecutive patients with PSS followed in an internal medicine department between June 1996 and December 1997 (Internal Medicine group). In addition, eleven patients with neurological complications of PSS were identified in the Neurological Department of the same institution during the same period (Neurological group). RESULTS: In the Internal Medicine group, neurological complications were discovered in 10/25 (40%) patients. Peripheral nervous system involvement was present in 4/25 patients from the Internal Medicine group and in 10/11 patients from the Neurological group and consisted mainly of axonal sensorimotor/sensory polyneuropathy. A motor neuron syndrome was identified in two patients. CNS involvement occurred in 7/25 patients from the Internal Medicine group and in 4/11 patients from the Neurological group. Three patients had spinal cord involvement. Cognitive dysfunction was the most frequent finding (5/25 in the Internal Medicine group, 3/11 in the Neurological group) characterized either by subcortical or corticosubcortical dysfunction. Cognitive impairment was not attributed to mood disturbance and was not associated with specific laboratory or radiological abnormalities. CONCLUSION: Neurological complications of PSS are frequent since they were present in 40% (10/25) of patients in a consecutive series of patients from a department of Internal Medicine. Although PNS involvement predominates, complications of PSS affecting the brain or spinal cord are not rare, with subcortical dysfunction as the main finding.

Lipid content and fatty acid composition in foods commonly consumed by nursing Congolese women: incidences on their essential fatty acid intakes and breast milk fatty acids.

The fat content and fatty acid (FA) composition of nearly 40 foods, currently consumed by 102 nursing Congolese mothers living in Brazzaville, were determined to assess their impact on mothers' essential fatty acid (EFA) intakes and breast milk FA. Data on mothers' milk FA and dietary habits which allowed food selection were recently published (Rocquelin et al., 1998). Most foods were locally produced. Food samples were collected at local markets, bleached if necessary to avoid microbial degradation, and stored at +4 degrees C or -20 degrees C. They were lyophilized upon their arrival in the laboratory before lipid analyses. FA composition of food lipids was determined by capillary gas chromatography. Staple diets included low-fat, high-carbohydrate foods (processed cassava roots, wheat bread) and high-polyunsaturated fatty acid (PUFA) foods: soybean oil (high in 18 : 2 n-6 and alpha-18 : 3 n-3), bushbutter (dacryodes edulis), peanuts, avocado (high in fat and 18 : 2 n-6), freshwater and salt-water fish (high in LC n-3 and/or n-6 PUFA), and leafy green vegetables (low in fat but very high in alpha-18 : 3 n-3). Their frequent consumption by nursing mothers provided enough EFA to meet requirements due to lactation. It also explains why mothers' breast milk was rich in C8-C14 saturated FA (26% of total FA) and in n-6, n-3 PUFA (respectively 15.0% and 2.4% of total FA) highly profitable for breastfed infants' development. From this point of view, dietary habits of Congolese mothers have to be sustained for they are more adequate than most Western-type diets.

[Electrophysiologic study in a patient presenting with expanding cerebral lacunae]. / Etude électrophysiologique chez un patient présentant des lacunes cérébrales expansives.

A 42-year-old man was affected with multiple cerebral lesions suggesting expanding lacunae. He had suffered for about 15 years of headaches and blurred vision. Neurological examination showed a Parinaud syndrome and a skew deviation. Magnetic resonance imaging showed an enlargement of the third and lateral ventricles and multiple intraparenchymatous lesions with a signal similar to that of the cerebrospinal fluid. These lesions were located in the mesencephalon and right thalamic region. Important discrepancies between the topography of the lesion and the clinical data were observed. Neurological examination, ocular movements during wake and neuropsychological testing suggested sub-cortical dysfunction. These results suggest functional rather than lesional repercussion of expansive lacunae.

[Comparative study of nitrogen sparing during parenteral feeding as a function of carbohydrate intake]. / Etude comparative de l'épargne azotée au cours de la nutrition parentérale en fonction de l'apport glucidique.

The nitrogen balance of two groups of patients, A and B, was studied during the first four post-operative days. Groups A (31) received a daily intake of one liter of Totamine concentrée glucidique with glucose 10 p. 100 1,5 liter. Groups B received Totamine concentrée glucidique with glucose 30 p. 100 1,5 liter. There was no statistically significant difference in nitrogen balance between both groups. On the other hand, the cumulative nitrogen balance was positive for both groups for the first four post-operative days.