Deciphering the causes of sporadic late-onset cerebellar ataxias: a prospective study with implications for diagnostic work.

The management of sporadic late-onset cerebellar ataxias represents a very heterogeneous group of patients and remains a challenge for neurologist in clinical practice. We aimed at describing the different causes of sporadic late-onset cerebellar ataxias that were diagnosed following standardized, exhaustive investigations and the population characteristics according to the aetiologies as well as at evaluating the relevance of these investigations. All patients consecutively referred to our centre due to sporadic, progressive cerebellar ataxia occurring after 40 years of age were included in the prospective, observational study. 80 patients were included over a 2 year period. A diagnosis was established for 52 patients (65%) corresponding to 18 distinct causes, the most frequent being cerebellar variant of multiple system atrophy (n = 29). The second most frequent cause was inherited diseases (including spinocerebellar ataxias, late-onset Friedreich's disease, SLC20A2 mutations, FXTAS, MELAS, and other mitochondrial diseases) (n = 9), followed by immune-mediated or other acquired causes. The group of patient without diagnosis showed a slower worsening of ataxia (p < 0.05) than patients with multiple system atrophy. Patients with later age at onset experienced faster progression of ataxia (p = 0.001) and more frequently parkinsonism (p < 0.05) than patients with earlier onset. Brain MRI, DaT scan, genetic analysis and to some extent muscle biopsy, thoracic-abdominal-pelvic tomodensitometry, and cerebrospinal fluid analysis were the most relevant investigations to explore sporadic late-onset cerebellar ataxia. Sporadic late-onset cerebellar ataxias should be exhaustively investigated to identify the underlying causes that are numerous, including inherited causes, but dominated by multiple system atrophy.

Robotic-assisted thymectomy with Da Vinci II versus sternotomy in the surgical treatment of non-thymomatous myasthenia gravis: early results.

BACKGROUND: The role of thymectomy in myasthenia gravis remains controversial. The remission rate 5years after surgery varies from 13 to 51% in the literature. Sternotomy is the standard technique, though unacceptable by patients because of significant esthetic sequelae. Our objective was to demonstrate that the robot-assisted technique using the Da Vinci Surgical Robot II is at least as efficient and leaves fewer scars than the standard surgical technique. METHODS: We retrospectively reviewed the data of 31 consecutive patients suffering from myasthenia gravis who underwent surgery in our center from January 1998 to March 2010. Ten patients with thymoma were excluded from this study. Two groups were formed: group 1 corresponding to patients treated with sternotomy, group 2 patients with robot-assisted technique. The duration of the hospital stay, the pain on D1, the degree of improvement at 1year according to Myasthenia Gravis Foundation of America (MGFA) classification, the frequency of relapses, and perioperative treatment were studied. RESULTS: Our sample consisted of 14 women and seven men. The mean age was 31.3years. The mean delay before surgery was 24months. Group 1 included 15 patients and group 2 had six patients. The complete remission rate at 1year was 9.5% (n=2). Surgery decreased the frequency of relapses after surgery (P=0.08) equally in the two groups. The duration of hospital stay and the pain level on D1 in group 2 were significantly lower than those in group 1 (P=0.02 and P<0.001). The degree of postoperative improvement was not significantly different between the two groups (P=0.31). CONCLUSION: The results at 1year are fully comparable for sternotomy and the robot-assisted technique. The robot provides additional benefits of minimally invasive techniques: minimal esthetic sequelae in often young patients, less parietal morbidity (including pain), shorter hospital stays. Our complete remission rate, lower than those in the literature, must be considered taking into account the early nature of these results. The surgical robot, because of its many advantages, appears to be a promising technique and should facilitate the early management of these patients.

Inflammatory demyelinating events following treatment with anti-tumor necrosis factor.

BACKGROUND: Tumor necrosis factor alpha (TNF-alpha) is an inflammatory cytokine involved in certain inflammatory diseases including multiple sclerosis (MS), rheumatoid arthritis (RA), and Crohn's disease. The anti-TNF-alpha treatments used for RA may be associated with inflammatory demyelinating events affecting the central nervous system and may possibly aggravate known MS. OBJECTIVE: We report here three new cases of inflammatory demyelinating events of the central nervous system following treatment with anti-TNF-alpha. RESULTS: The neurological symptoms appeared on average 5 months after initiation of the treatment. For all patients, the inflammatory process was confirmed by brain magnetic resonance imaging. The symptoms totally or partially regressed as soon as anti-TNF-alpha treatment was stopped except for one patient who developed clinically defined MS. CONCLUSIONS: Inflammatory demyelination of the central nervous system may be associated with the use of anti-TNF-alpha. Patients with rheumatoid arthritis treated with these treatments should benefit from a follow-up which includes brain MRI.

[Thyroid nodules: assay of serum thyrotropin and cytopuncture versus scintigraphy as first-line tests. Prospective study with 150 cases]. / Nodules thyroïdiens: dosage d'hormone thyréotrope sérique et cytoponction versus scintigraphie comme examens de première intention. Etude prospective sur 150 observations.

OBJECTIVE: Fine-needle aspiration (FNA) is now considered as the first-line investigation for the diagnosis of thyroid nodules. We searched for a more accurate and cost-effective methodology as this technique fails to recognized hot nodules, frequent in certain countries. PATIENTS AND METHODS: A prospective study was conducted in 150 patients to compare two diagnostic procedures: scintigraphy first combined with FNA in case of cold nodules versus TSH measurement plus FNA when TSH measurement plus FNA when TSH was not depressed. The results were subjected to cost/benefit analysis. RESULTS: Cystic nodules were found in 28 cases (including 3 hyperfunctionning nodules, with 5 suspicious smears (1 carcinoma). FNA was non-diagnostic in 26 patients; 12 were operated on (1 carcinoma), 14 had further FNA (5 suspicious, 9 benign). Altogether 56 nodules were removed, for toxic adenoma (n = 5), for suspicious (n = 21) or malignant (n = 12) smear, or on personal (n = 18) demand; 16 carcinomas were found (2 medullary, 13 capillary, 1 follicular carcinomas). With scintigraphy first, the cost was 787 French francs (FF) per patient. With TSH measurement and FNA, the cost was 554 FF per patient. In both cases, the same number of carcinomas were removed, and all the hot nodules (11 including 5 toxic adenomas) were detected. CONCLUSION: Serum TSH measurement, with scintigraphy if TSH is low, and FNA in all the other cases, is accurate and more cost-effective than scintigraphy as a first-line investigation for the diagnosis of thyroid nodule.

[Rapid peroperative assay of intact parathormone in primary hyperparathyroidism. Evaluation and comparison with the long method]. / Dosage per-opératoire rapide de la parathormone intacte dans l'hyperparathyroïdie primaire. Evaluation et comparaison avec la méthode longue.

OBJECTIVES: To evaluate the efficacy of rapid peroperative assay of parathormone in patients with primary hyperparathyroidism compared with the longer standard assay. METHODS: Primary hyperthyroidism was diagnosed in 10 patients (8 males, 2 females, mean age 55 +/- 8.6 years, range 36-99) (preoperative tests: serum calcium 290 +/- 8.9 nmol/l, range 274-311; intact parathormone 137 +/- 31.3 pg/ml, range 87-250). First intention cervicotomy was performed. Blood samples were drawn at induction of anaesthesia, at palpation of the adenoma, and 15, 30 and 45 minutes after ablation. Each sample was assayed with a rapid radioimmunoassay and the longer standard laboratory methods. RESULTS: There was a good correlation between the two assay methods. In the 9 patients with a solitary adenoma, serum levels of parathormone were normalized 15 (n = 8) or 30 minutes (n = 1) after resection. CONCLUSION: Rapid radioimmunoassay is a reliable method for evaluating serum parathormone level peroperatively. Although financial implications may limit its use, this rapid assay is clearly indicated for patients in poor clinical condition undergoing first intention surgery and in those undergoing a second cervicotomy.

[Changes in plasma binding protein of sex steroids and transcortin during the treatment of menopause with oral estrogens]. / Etude des variations de la protéine de liaison plasmatique des stéroïdes sexuels et de la transcortine au cours du traitement de la ménopause par les estrogènes par voie orale.

Sex steroid binding protein (SBP) and transcortin (CBG) plasma concentrations were measured in 15 postmenopausal women before and during oral administration of estradiol 2 mg plus estriol 1 mg given alone for one month and in sequential combination with noresthisterone 1 mg for the following months. The results were compared with those obtained in a group of 13 premenopausal women who were studied during the early follicular phase or during administration of estroprogestagens. The oral administration of estrogens slightly increased CBG levels (56.1 +/- 11.4 vs 46.0 +/- 5.2 mg/l, P less than 0.05) which in 4 patient were higher than in premenopausal women. The mean SBP level was lower in postmenopausal women than in premenopausal women (1.02 +/- 0.40 vs 1.35 +/- 0.38 micrograms/dl, P less than 0.02), and SBP correlated negatively and significantly with the body mass index (r = 0.794, P less than 0.02). On average, SBP increased twofold during the estrogen treatment. In 6 patients the concentrations of estrogen-stimulated SBP were higher than the upper limit for premenopausal women. Lowered SBP levels were normalized during estrogen therapy. During estrogen substitution in the postmenopausal women, the mean E2 to SBP ratio (an index of free estradiol) was within the normal limits for premenopausal women. These results demonstrate that SBP is highly sensitive to oral estrogens. The increase in SBP is associated with a free E2 index which is within the physiological range of premenopausal women. The risk(s) or benefit(s) associated with the increase in SBP during estrogen therapy in postmenopausal women deserve to be evaluated by further investigations.

Effects of drug administration on gonadotropins, sex steroid hormones and binding proteins in humans.

The possible mechanisms by which the administration of drugs may alter the gonadal function in humans are considered in this review. Based on personal data, and on data published in the literature, the following events may occur: (1) blockade of gonadal steroidogenesis; (2) interaction of drug(s) with the steroid-binding protein system in plasma, and (3) interference of drug(s) at the level of the feedback control of gonadotropin secretion. Representative examples of the above mechanisms are as following: (1) Ketoconazole possesses inhibitory effects in vitro on cytochrome P-450. When given in adult males, it decreased the plasma concentrations of testosterone (T) and androstenedione and increased 17 alpha-hydroxyprogesterone levels, suggesting that this drug acts in vivo on gonadal steroidogenesis by blocking the 17,20-lyase. (2) Danazol is a progestagen with high affinity for sex steroid-binding protein (SBP); when given in high dosages in normal males, it increased rapidly the dialyzable fraction (percent protein unbound or free fraction) of T. This suggests that by interacting with the binding sites of SBP, danazol and/or its metabolites displace the fraction of T bound to SBP. However, in males as well as in females, the long-term administration of danazol decreased also the binding capacity of SBP, and consequently increased the free fraction of sex steroid hormones. (3) Dihydrotestosterone (DHT), the most active androgen in many target cells, given at therapeutic dosages to adult males, resulted in a decrease in plasma concentrations of luteinizing hormone (LH) and T, without any significant change in the percent of free T, even though the affinity of DHT for SBP is higher than that of T. This suggests that the main effect of DHT is to inhibit gonadotropin secretion at the central level. (4) Flutamide, a nonsteroidal antiandrogen, increased both LH and T levels, demonstrating its pure antiandrogenic activity on gonadotropin secretion. The consequence(s) of the effects of such drugs on the production, the metabolic clearance rate and the bioavailability of sex steroid hormones are discussed.

[Effect of estrogens on the value of serum thyroglobulin]. / Influence des oestrogènes sur la valeur de la thyroglobuline sérique.

Serum thyroglobulin (TG) is considered as a useful index of differentiated thyroid carcinoma evolution. Previous studies have suggested that TG levels might be dependent upon oestrogens. Here TG levels were determined in volunteers , free of any thyroid disease, divided into 5 groups according to estrogen level. Results (mean +/- s.d.) indicated that Tg levels in men group A (n = 9): 6,6 +/- 2,8 ng/ml in women undergoing oestroprogestagen treatment group B (n = 10) 3,7 +/- 1,5 ng/ml; in women free of oestroprogestaten treatment group C (n = 10): 5,9 +/- 4,0 ng/ml; in pregnant women group D (n = 40): 4,6 +/- 2,7 ng/ml, and in parturient women group E (n = 4): 7,2 +/- 2,2 ng/ml; were not correlated to estrogen levels. However, in a group where thyroid gland was not carefully examined i.c. a "blood doners group", a difference (p less than 0,005) was found between women (29 +/- 15) and men (14 +/- 9). Sex and estrogen levels there fore do not influence the TG index which as a result can be used in the monitoring of thyroid carcinoma in pregnant women.