Quantitative brainstem and spinal MRI in amyotrophic lateral sclerosis: implications for predicting noninvasive ventilation needs.

BACKGROUND: Respiratory complications resulting from motor neurons degeneration are the primary cause of death in amyotrophic lateral sclerosis (ALS). Predicting the need for non-invasive ventilation (NIV) in ALS is important for advance care planning and clinical trial design. The aim of this study was to assess the potential of quantitative MRI at the brainstem and spinal cord levels to predict the need for NIV during the first six months after diagnosis. METHODS: Forty-one ALS patients underwent MRI and spirometry shortly after diagnosis. The need for NIV was monitored according to French health guidelines for 6 months. The performance of four regression models based on: clinical variables, brainstem structures volumes, cervical spinal measurements, and combined variables were compared to predict the need for NIV within this period. RESULTS: Both the clinical model (R2 = 0.28, AUC = 0.85, AICc = 42.67, BIC = 49.8) and the brainstem structures' volumes model (R2 = 0.30, AUC = 0.85, AICc = 40.13, BIC = 46.99) demonstrated good predictive performance. In addition, cervical spinal cord measurements model similar performance (R2 = 0.338, AUC = 0.87, AICc = 37.99, BIC = 44.49). Notably, the combined model incorporating predictors from all three models yielded the best performance (R2 = 0.60, AUC = 0.959, AICc = 36.38, BIC = 44.8). These findings are supported by observed positive correlations between brainstem volumes, cervical (C4/C7) cross-sectional area, and spirometry-measured lung volumes. CONCLUSIONS: Our study shows that brainstem volumes and spinal cord area are promising measures to predict respiratory intervention needs in ALS.

Comparison of spinal magnetic resonance imaging and classical clinical factors in predicting motor capacity in amyotrophic lateral sclerosis.

BACKGROUND: Motor capacity is crucial in amyotrophic lateral sclerosis (ALS) clinical trial design and patient care. However, few studies have explored the potential of multimodal MRI to predict motor capacity in ALS. This study aims to evaluate the predictive value of cervical spinal cord MRI parameters for motor capacity in ALS compared to clinical prognostic factors. METHODS: Spinal multimodal MRI was performed shortly after diagnosis in 41 ALS patients and 12 healthy participants as part of a prospective multicenter cohort study, the PULSE study (NCT00002013-A00969-36). Motor capacity was assessed using ALSFRS-R scores. Multiple stepwise linear regression models were constructed to predict motor capacity at 3 and 6 months from diagnosis, based on clinical variables, structural MRI measurements, including spinal cord cross-sectional area (CSA), anterior-posterior, and left-to-right cross-section diameters at vertebral levels from C1 to T4, and diffusion parameters in the lateral corticospinal tracts (LCSTs) and dorsal columns. RESULTS: Structural MRI measurements were significantly correlated with the ALSFRS-R score and its sub-scores. And as early as 3 months from diagnosis, structural MRI measurements fit the best multiple linear regression model to predict the total ALSFRS-R (R2 = 0.70, p value = 0.0001) and arm sub-score (R2 = 0.69, p value = 0.0002), and combined with DTI metric in the LCST and clinical factors fit the best multiple linear regression model to predict leg sub-score (R2 = 0.73, p value = 0.0002). CONCLUSIONS: Spinal multimodal MRI could be promising as a tool to enhance prognostic accuracy and serve as a motor function proxy in ALS.

Physical Activity and Changes in White Matter Hyperintensities over Three Years.

OBJECTIVES: Since physical activity (PA) has demonstrated benefits for cardiovascular health, it is possible to hypothesize that higher or increasing PA slows the progression of white matter hyperintensities (WMH). We investigated the association between PA and the progression of WMH in non-demented older adults with memory complaints. DESIGN: We included 152 participants (mean age 74.7±3.8 years; 63.8% women) in the analyses, in whom information on self-reported PA and MRI was available at both baseline and 3-year follow-up. From the PA questionnaire, the baseline metabolic equivalent of task (MET-minute/week) and changes in MET-minute/week over three years were separately calculated for overall, leisure-time, and non-leisure time PA. WMH volume at baseline and 3-year follow-up was obtained by using an automated segmentation algorithm. RESULTS: Mixed-effect linear regression models showed that none of the baseline PA variables was associated with progression of WMH over time. People who had decreased their PA levels over three years tended to show greater progression of WMH compared with those who had maintained PA levels of ≥1200 MET-min/week (roughly equivalent to ≥300 minutes of brisk walking) in the unadjusted model (ß±SE=4.85±2.42, p=0.045); however, this association was no longer significant after adjustment for confounders (ß±SE =3.63±2.18, p=0.096). CONCLUSIONS: We did not find any significant association between PA and WMH in non-demented older adults with memory complaints. However, decrease over time in PA levels tended to be associated with progression of WMH. A larger longitudinal study with data on PA assessed using objective measures would provide important information in this field.

Association between Red Blood Cells Omega-3 Polyunsaturated Fatty Acids and White Matter Hyperintensities: The MAPT Study.

OBJECTIVES: The association between circulating biomarkers of red blood cells (RBC) omega-3 polyunsaturated fatty acids (PUFAs) and cerebral white matter hyperintensities (WMH) on the brain MRI remains yet unclear. We investigated the cross-sectional and prospective associations of RBC omega-3 PUFAs with WMH in dementia-free older adults with subjective memory complaints. DESIGN: Participants were 234 older adults with assessments for both PUFA and MRI near to baseline; among them, 79 also had an MRI assessment at 3-year follow-up. The measurement of WMH volume was obtained by an automated segmentation algorithm. We related individual or combinational baseline RBC omega-3 PUFAs levels with baseline WMH volumes and WMH evolution over 3 years. We carried out multiple (cross-sectional) and mixed-effect (prospective analysis, with random effects at participant's level) linear regressions with adjustment for age, sex, time interval between date of blood draw for measurement of fatty acids and date of brain MRI, the status of APOE e4 carrier, body mass index, and vascular risk factors. Associations were considered significant at p ≤ 0.006 to take into account multiplicity (8 comparisons). RESULTS: None of the eight RBC omega-3 PUFAs tested was significantly associated with WMH at both cross-sectional and prospective analyses. CONCLUSIONS: We did not find any association between omega-3 PUFAs and WMH in non-demented older adults with memory complaints. A longer longitudinal study with data on omega-3 PUFAs and WMH would contribute important information to this field.

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.

Automatic segmentation of the hippocampus and the amygdala driven by hybrid constraints: method and validation.

The segmentation from MRI of macroscopically ill-defined and highly variable structures, such as the hippocampus (Hc) and the amygdala (Am), requires the use of specific constraints. Here, we describe and evaluate a fast fully automatic hybrid segmentation that uses knowledge derived from probabilistic atlases and anatomical landmarks, adapted from a semi-automatic method. The algorithm was designed at the outset for application on images from healthy subjects and patients with hippocampal sclerosis. Probabilistic atlases were built from 16 healthy subjects, registered using SPM5. Local mismatch in the atlas registration step was automatically detected and corrected. Quantitative evaluation with respect to manual segmentations was performed on the 16 young subjects, with a leave-one-out strategy, a mixed cohort of 8 controls and 15 patients with epilepsy with variable degrees of hippocampal sclerosis, and 8 healthy subjects acquired on a 3 T scanner. Seven performance indices were computed, among which error on volumes RV and Dice overlap K. The method proved to be fast, robust and accurate. For Hc, results with the new method were: 16 young subjects {RV=5%, K=87%}; mixed cohort {RV=8%, K=84%}; 3 T cohort {RV=9%, K=85%}. Results were better than with atlas-based (thresholded probability map) or semi-automatic segmentations. Atlas mismatch detection and correction proved efficient for the most sclerotic Hc. For Am, results were: 16 young controls {RV=7%, K=85%}; mixed cohort {RV=19%, K=78%}; 3 T cohort {RV=10%, K=77%}. Results were better than with the semi-automatic segmentation, and were also better than atlas-based segmentations for the 16 young subjects.

[Breast metastasis from a "tall cell variant" of papillary thyroid carcinoma]. / Métastase mammaire d'un carcinome papillaire à cellules hautes de la thyroïde.

The authors report a case of breast metastasis from a "tall cell" variant of papillary thyroid carcinoma in a 59-year-old woman. This metastasis was discovered two months after the diagnosis of an inextirpable thyroid tumor. Tall cell variant of papillary thyroid carcinoma is a sub-type of papillary carcinoma with an aggressive course and frequent metastases (in patients over 50 years of age). No mammary metastasis of this tumor type has been reported so far.

131I-6 beta-iodomethylnorcholesterol scintigraphy: an assessment of its role in the investigation of adrenocortical incidentalomas.

OBJECTIVE: Most incidentally discovered adrenal tumours ('incidentaloma') are benign adrenocortical adenomas. It has been suggested that 131I-6 beta-iodomethylnorcholesterol (IMC) scan could specify the degree of functional autonomy of such adenomas depending on whether they prevent contralateral adrenal tracer uptake. Our purpose was to examine this hypothesis in a correlated scintigraphic and endocrine study. DESIGN: Prospective study evaluating the prevalence of unilateral IMC uptake (tumour uptake with no visualization of the contralateral adrenal gland) and bilateral uptake (uptake in both the tumoral and the contralateral adrenal glands) in patients with unilateral incidentaloma. Comparison of adrenocortical function and of IMC scan after dexamethasone (DXM) in the two scintigraphic groups thus defined. PATIENTS: Thirty-five patients with a unilateral mass highly suggestive of benign adrenocortical adenoma on CT scan. MEASUREMENTS: The IMC scan was performed in basal conditions (baseline scan) and after DXM (suppression scan). Adrenocortical function assessment included basal measurements of 11-deoxycortisol, 17 alpha-hydroxyprogesterone (17-OHP), dehydroepiandrosterone sulphate (DHEAS), plasma cortisol and ACTH, urinary free cortisol (UFC), overnight and low-dose DXM suppression test, and CRH test. RESULTS: The baseline scan showed 16 patients (46%) with unilateral uptake (group A) and 19 (54%) with bilateral uptake (group B). Patients in group A exhibited lower ACTH values at 0800h (P = 0.05) and higher cortisol values after an overnight DXM suppression test (P = 0.02), than did patients in group B. In addition, 3 patients in group A failed the overnight and the low-dose DXM suppression tests. Adrenal masses were larger in group A than group B (P = 0.04) and an inverse correlation was found in the whole population between tumour size and ACTH value at 0800h (P = 0.05). On the suppression scan performed in 14 patients (7 in each group), patients in group A continued to exhibit unilateral tumour uptake and bilateral uptake was suppressed in 72% of patients in group B. An adrenal mass was removed in 3 patients of group A with confirmed benign adrenocortical adenomas. In the post-surgical period, the contralateral gland was again visualized in a baseline scan and the hormonal evaluation returned to the normal range. CONCLUSION: Unilateral 131I-6 beta-iodomethylnorcholesterol tumour uptake is a frequent feature in benign adrenocortical adenomas. Hormonal data and scintigraphic profiles obtained after dexamethasone, as well as hormonoscintigraphic changes observed after surgery, provide evidence that unilateral uptake is related to functioning adenomas with various degrees of autononomy and suggest that the 131I-6 beta-iodomethylnorcholesterol scan could be a valuable tool for screening 'subclinical' Cushing's adenomas.

[The role of adrenal gland x-ray computed tomography and scintigraphy using radiolabelled norcholesterol in the etiological diagnosis of primary hyperaldosteronism]. / Place respective de la tomodensitométrie surrénalienne et de la scintigraphie au norcholestérol radiomarqué dans le diagnostic étiologique des hyperaldostéronismes primaires.

The major etiologies of primary aldosteronism are aldosterone-producing adrenal adenoma, requiring a surgical treatment, and bilateral hyperplasia, usually managed with medical therapy. We only report a retrospective study on 22 patients with primary aldosteronism diagnosed by clinical and usual biochemical tests. All the patients were explored by computed tomography scan (CT) and iodomethyl-norcholesterol scintigraphy. The purpose of this study was to compare the capacity of the two methods to differentiate adrenal adenoma and hyperplasia. The CT scan was more sensitive (sensitivity: 88%) compare to scintigraphy (sensitivity: 64%) for the diagnosis of adrenal adenoma. However, the scintigraphy was a useful tool to detect asymmetric macronodular adrenal hyperplasia. Therefore, the catheterisation of adrenal venous would be only necessary for a few cases. We conclude from this study and the literature review that CT scan and iodomethyl-norcholesterol scintigraphy are complementary and both useful to increase diagnostic reliability of primary aldosteronism.

[Endocrine and metabolic disorders in anorexia nervosa. Their meaning]. / Les troubles endocriniens et métaboliques de l'anorexie mentale. Leur signification.

The authors distinguish among the hormonal and metabolic disturbances found in Anorexia nervosa those, numerous, which are the results of emaciation only, and others which could be signs of central neuro-chemical dysregulation. The disturbances of the gonadotropic function and of the control of the "hunger-fattening" phenomena are probably of the latter type; however the nature of those dysfunctions and of their corresponding neuro-mediators remain so far hypothetical.

[Eosinophilic fasciitis and Hodgkin's disease]. / Fasciite à éosinophiles et maladie de Hodgkin.

A case of eosinophilic fasciitis (EF) associated with Hodgkin disease is described. In eight previously published cases, EF was associated with immunologic diseases, such as autoimmune marrow aplasia. The relation between EF and Hodgkin disease should be studied by investigating the physiopathologic meaning of eosinophils in both conditions.

Pituitary function in idiopathic haemochromatosis: hormonal study in 36 male patients.

Thirty-six male patients with idiopathic haemochromatosis were subjected to measurements of basal plasma values of testosterone, LH and FSH and to an LRH test. Nineteen were also subjected to basal plasma determinations of T3, T4, cortisol, TSH and prolactin and to a TRH test. In 11 cases GH values were measured before, during and after an arginine infusion. Seventeen patients were found to hae low levels of testosterone, LH and FSH, and no gonadotrophin responses to LRH. Seventeen others had normal levels of these three hormones, with normal responses to LRH. The two remaining patients had normal testosterone values but very increased gonadotrophin values: a fact which remains unexplained. Basal levels of prolactin, GH, T3, T4, and TSH were normal: cortisol levels were either normal or increased in cases of poorly controlled diabetes. Prolactin responses to TRH were always normal. TSH responses to TRH were impaired in 2 cases, and GH responses to arginine in 3 cases. Considering that other factors may be involved in the few impairments found in TSH and GH stimulations, it is concluded that the only indisputable pituitary insufficiency in about half of the cases of idiopathic haemochromatosis is gonadotrophic.

C-peptide blood levels in keto-acidosis and in hyperosmolar non-ketotic diabetic coma.

For further evaluation of B-cell secretion in diabetic keto-acidosis (KA) and in non-ketotic hyperosmolar coma (NKHC), basal and post-i.v. tolbutamide blood CPR and IRI values were measured in 34 patients (22 KA and 12 NKHC). FFA, cortisol and HGH measurements were also performed. IRI was low in both KA and NKHC (0.07 +/- 0.01 and 0.082 +/- 0.01 nmol/l) as opposed to CPR which was significantly higher in NKHC (1.14 +/- 0.1 nmol/l) than in KA (0.21 +/- 0.03 nmol/l). After tolbutamide injection, CPR and IRI levels did not change in any of the KA cases, whereas they significantly increased in half of the NKHC cases. Cortisol and FFA values were similarly increased in both situations, as opposed to HGH which was significantly higher (6.1 +/- 1.2 ng/ml) in KA than in NKHC (1.9 +/- 0.2 ng/ml). These results suggest that B-cell function is less deficient in NKHC than in KA. Residual insulin amounts reaching the liver via the portal vein could partly account for the absence of ketosis in NKHC.

Adrenocortical function in idiopathic haemochromatosis.

In idiopathic haemochromatosis, excessive iron deposits include adrenal cortex, and mainly the zona glomerulosa. In this view, we measured basal and post-stimulative values of plasma cortisol, aldosterone and renin activity (RA) in two groups of patients: 1) 9 normal-salt repleted subjects (NSR) who were subjected to iv ACTH and furosemide tests, 2) 10 patients who were subjected to chronic salt depletion (CSD), to iv ACTH and furosemide tests. The results were compared with two groups of 7 healthy volunteers (NSR and CSD). In the patients, basal cortisol values were either normal or increased in cases of poorly controlled diabetes (21 +/- 2.1 microgram/100 ml, P < 0.01) and cortisol increase after ACTH injection was normal (to 43.3 +/- 4.3 microgram/100 ml). In the 9 NSR patients, basal aldosterone (7.75 +/- 1.5 ng/100 ml) and RA (1.55 +/- 0.27 ng/ml/h) values were normal; aldosterone and RA rose after furosemide injection: these increases were similar in these patients (respectively to: 13.5 +/- 2.2 ng/100 ml and 4.3 +/- 0.6 ng/ml/h) and in the 7 NSR controls. In the 10 CSD patients, basal aldosterone and RA values were always increased (26.5 +/- 3.2 ng/100 ml and 8.5 +/- 2.3 ng/ml/h) as much as in the 7 CSD controls. After ACTH administration, aldosterone values (26.1 +/- 4 in NSR patients, 54 +/- 8 ng/100 ml in CSD patients) were the same as in the two control groups. This study suggests that there is no adrenocortical deficiency in idiopathic haemochromatosis, in spite of excessive iron deposits in the adrenal cortex.

[Shulman's syndrome. A variant of scleroderma? Two cases (author's transl)]. / Syndrome de Shulman: une forme clinique des sclérodermie? A propos de deux cas.

Observations of two patients illustrating the problem of Shulman syndroma. The first had presented an oedema of the four limbs, without injury of the trunk, but with myalgias, histological fasciitis, eosinophilia and hypergammaglobulinemia. In spite of corticotherapy, evolution toward a generalized morphea. The second has presented the same oedema of the four limbs, with myalgias, but also Raynaud syndroma, histological fasciitis and eosinophilia. Evolution toward acrosclerosis in spite of corticotherapy. For the authors, Shulman's syndroma is apprehended as a particular clinical form of scleroderma.

[Regression under the influence of OP'DDD of a malignant cortico-adrenaloma and of its metastases (author's transl)]. / Régression par OP'DDD d'un cortico-surrénalome malin et de ses métastases.

Report of a case of metastatic adrenal cortical carcinoma with Cushing's syndrome treated with OP'DDD, 15 g per day. This therapy was followed by the regression of the adrenal tumour and of its metastases since three years.