Hereditary angioedema with normal C1 inhibitor and factor XII mutation: a series of 57 patients from the French National Center of Reference for Angioedema.

Hereditary angioedema (HAE) is a rare disease associated with either a quantitative or qualitative deficiency in C1-inhibitor (C1-INH) or normal C1-INH. HAE with normal C1-INH is associated in 20% of cases with mutations in the gene for factor XII (FXII) or FXII-HAE. A recent review described 41 families, including 14 German and 15 Spanish families. We have constructed a register of French patients and their characteristics. A national survey was launched through the French National Center of Reference for Angioedema (CREAK) to study the clinical, biological and therapeutic characteristics of patients with HAE linked to a mutation of FXII gene. Fifty-seven patients were identified from 24 different families. In most cases they were young women (mean age at diagnosis: 31 years, mean age at first symptom: 21 years, female/male ratio: 76%). Twenty-one per cent of the patients experienced angioedema attacks only during pregnancy or when on oestrogen contraception. Sixty-three per cent had attacks at all times, but they were more severe during these same periods. Male carriers of the mutation were more frequently asymptomatic than females (P = 0·003). C1-INH concentrate and icatibant were both effective for treating attacks. The prophylactic use of tranexamic acid led to a 64% decrease in the number of attacks. This is one of the largest series reported of HAE patients with FXII mutation. The therapeutic management appeared to be identical to that of HAE with C1-INH deficiency.

Idiopathic histaminergic angioedema without wheals: a case series of 31 patients.

Idiopathic histaminergic acquired angioedema (IH-AAE) is a common cause of recurrent angioedema without wheals. It is a mast cell-mediated disease thought to belong to the same clinical entity as chronic urticaria (CU). The objective of this study was to describe the clinical and epidemiological characteristics of IH-AAE patients. From 2014 to 2015, 534 patients were seen at our national reference centre for angioedema and/or urticaria. Among them, we identified 31 patients with idiopathic histaminergic acquired angioedema without wheals (IH-AAE). Thirty-one patients (15 men and 16 women) with a mean age of 50 years met the criteria for IH-AAE. The average delay in diagnosis was 6·3 years. A history of allergy was found in 12 patients (38·7%), nine suffering from allergic rhinitis. The mean duration of attacks was 28·1 h. The AE attack was located in the upper respiratory tract in 54·8% of cases (17 patients). A lingual location was found in 29% of patients. Men were more likely than women to have an upper airway involvement. No intubations or admissions to intensive care units were reported. The dosage of anti-histamines to control the symptoms was onefold the recommended dose in 51·6% of patients (16 patients), twofold in 32% (10 patients) and three-fourfold in 16·1% (five patients). IH-AAE is characterized by an important delay in diagnosis, a frequent involvement of the upper airway and a benign course during attacks. As in CU, a trial of up to fourfold dose of H1-anti-histamines may be necessary to control symptoms.

MAPT STUDY: A MULTIDOMAIN APPROACH FOR PREVENTING ALZHEIMER'S DISEASE: DESIGN AND BASELINE DATA.

OBJECTIVE: The Multidomain Alzheimer Preventive Trial (MAPT study) was designed to assess the efficacy of isolated supplementation with omega-3 fatty acid, an isolated multidomain intervention (consisting of nutritional counseling, physical exercise, cognitive stimulation) or a combination of the two interventions on the change of cognitive functions in frail subjects aged 70 years and older for a period of 3 years. Ancillary neuroimaging studies were additionally implemented to evaluate the impact of interventions on cerebral metabolism (FDG PET scans) and atrophy rate (MRIs), as well as brain amyloïd deposit (AV45 PET scans). DESIGN PATIENTS: 1680 subjects (mean age: 75.3 years; female: 64.8 %), enrolled by 13 memory clinics, were randomized into one of the following four groups: omega-3 supplementation alone, multidomain intervention alone, omega-3 plus multidomain intervention, or placebo. Participants underwent cognitive, functional and biological assessments at M6, M12, M24 and M36 visits. The primary endpoint is a change of memory function at 3 years, as assessed by the Free and Cued Selective Reminding test. All participants will be followed for 2 additional years after the 3-years intervention (MAPT PLUS extension study). INTERVENTIONS: 1/Omega-3 supplementation: two soft capsules daily as a single dose, containing a total of 400 mg docosahexaenoic acid (DHA), i.e., 800 mg docosahexaenoic acid per day, for 3 years. 2/ Multidomain intervention: collective training sessions conducted in small groups (6-8 participants) in twelve 120-minute sessions over the first 2 months (two sessions a week for the first month, and one session a week the second month) then a 60-minute session per month in the following three areas: nutrition, physical activity, and cognition until the end of the 3 years. In addition to the collective sessions, individualized preventive outpatient visits exploring possible risk factors for cognitive decline are performed at baseline, M12 and M24. BASELINE POPULATION: For cognition, the mean MMSE at baseline was 28.1 (± 1.6). About 58% and 42% of participants had a CDR score equal to 0 and 0.5, respectively. Regarding mobility status, 200 (11.9%) had a 4-m gait speed lower or equal to 0.8 m/s. According to the Fried criteria, 673 (42.1%) participants were considered pre frail, and 51 (3.2%) frail. The red blood cell DHA content was 26.1 ± 8.1 µg/g. Five hundred and three participants underwent baseline MRI. AV45 PET scans were performed in 271 individuals and preliminary results showed that 38.0% had a cortical SUVR > 1.17, which gave an indication of significant brain amyloïd deposit. DISCUSSION: The MAPT trial is presently the first largest and longest multidomain preventive trial relevant to cognitive decline in older adults with subjective memory complaints. The multidomain intervention designed for the MAPT trial is likely to be easily implemented within the general population.

[Cerebral trunk abscess due to Neisseria meningitidis in a 28-year-old immunocompetent patient]. / Abcès du tronc cérébral àNeisseria meningitidis chez une patiente de 28ans, immunocompétente.

Meningococcal disease can manifest in very different clinical situations. Meningococcal meningitis and fulminant meningococcemia (or purpura fulminans) are the most common forms of these infections, but many other manifestations can be seen including septic arthritis, pericarditis, pleurisy and conjunctivitis. Brain abscesses have also been described; they are a rare complication of meningococcal disease. We report the case of a 28-year-old immunocompetent patient who developed meningococcal infection associated with brain abscesses and oligo-arthritis.

The nutritional intake of a free-living healthy French population : a four-year follow-up.

OBJECTIVE: To contribute to a better definition of the nutritional requirements of the healthy elderly and to improved knowledge the effects of age on these requirements. METHODS: We studied the nutritional intake of 96 elderly persons who had met criteria of good health status in 1993 at a four-year interval. The nutritional intake of the elderly subjects who remained healthy during the four-year interval (18 men and 64 women), was considered to globally correspond to their nutritional needs. The nutritional intake was evaluated by a three-day food record. RESULTS: The mean baseline weight of the subjects who remained in good health during the four years was 72,6 +/- 9,5 kg for men and 60,1 +/- 9,3 kg for women. In four years, mean weight remained globally stable. But in cross-sectional analysis, weight tended to decrease with the age of the subjects. This decrease was significant for women in 1993. Mean baseline intake was nearly 29 kcal/kg. Longitudinal and cross-sectional analyses showed that it changed only slightly with age. Though global energy intake varied slighlty in four years, we have observed some changes in the composition of this caloric intake. For men and women, protein intake tended to decrease in four years (respectively -0,4% and -0,6%), carbohydrate intake to decrease (respectively -1,1% and -2,7%) and fat intake to increase (respectively +2,1% and +2,9%). These variations were not significant except for fat and carbohydrate intakes in women. In 1993, for a majority of subjects, the intakes of iron, and vitamins C and B12 were higher and the intakes of calcium, zinc, vitamins A, B1, B6 and B9 were lower than the French recommendations. In four years, mean intake did not change significantly, except for calcium intake in women (-8,8%). CONCLUSION: In this study, healthy aging was associated with a mean caloric intake close to 29 kcal/kg which is near the upper limits of recommendations (between 25 and 30 kcal/kg/d). These intakes, like those of macronutrients and micronutrients changed little with advancing age. These results suggest that the needs of the elderly remain quite stable with aging. Nevertheless a tendency to weight loss with aging is observed, especially in older subjects, suggesting that even if food intake contributes to the maintenance of healthy aging, aging processes are multidimensional and frailty that is often associated with weight loss is ineluctable for older subjects.

One-leg standing balance and functional status in a population of 512 community-living elderly persons.

The objective of this cross-sectional study (whose baseline data were drawn from a longitudinal population study) was to determine if one-leg standing balance might be a useful marker of functional status in elderly persons independently living in an urban community (N = 512, mean age 73 +/- 7.0, 71.4% women). One-leg standing balance (ascertained by the Tinetti test) and functional status were obtained from a baseline gerontological assessment and follow-up questionnaires. Correlations were tested between one-leg balance and physical health and functional measurements. One-leg standing balance (OLSB) was abnormal in 24.7% of the population. At least one incapacity in instrumental activities of daily living (IADL) was found in 60.6% of those with OLSB abnormality, vs 45.5% in those with OLSB "adaptive" (borderline abnormal), and 33.3% in those with normal one-leg standing balance (p < 0.0001). Multivariate analysis showed 3 independent factors related to one-leg balance abnormality: age > 71 years (OR = 5.11, CI = 1.99-13.10); IADL deficit requiring help with transportation (OR = 3.61; CI = 1.15-11.40); and "poor" health status on the Iowa Self-Assessment Inventory (OR = 2.67, CI = 1.35-5.27). We conclude that one-leg standing balance may be a simple, predictive and inexpensive marker helpful in screening for low functional level and frailty in clinical practice.

Nutrition and successful aging: a study of 520 elderly persons from the Toulouse and New-Mexico Aging Process Study.

Epidemiological studies of aging are usually confronted with the presence of numerous pathologies or environmental factors which make it difficult to identify the effects of aging individually. One way of reducing the variability among individuals is to use well defined criteria to select the study population. This is the choice that was made for the New Mexico and Toulouse Aging Process Studies, which were particularly turned towards successful aging. In this study we have sought to explain the diversity of states of health of the subjects of these two studies by means of an aging classification exploring the medical history, balance and walking, and the cognitive functions. This reveals that the poorer health of certain subjects (about 10% and 30% of the populations of Toulouse and Albuquerque respectively) is slightly associated with changes in eating behaviour relative to subjects who age successfully. We have, however observed a decrease in vitamin E intake in Toulouse associated with a reduction of lipids in the food. But the poorer state of health is predominantly explained by advancing age and the occurrence of pathological states. This study confirms that aging was generally successful in the two populations studied.