The p.A382T TARDBP gene mutation in Sardinian patients affected by Parkinson's disease and other degenerative parkinsonisms

Based on our previous finding of the p.A382T founder mutation in ALS patients with concomitant parkinsonism in the Sardinian population, we hypothesized that the same variant may underlie Parkinson's disease (PD) and/or other forms of degenerative parkinsonism on this Mediterranean island. We screened a cohort of 611 patients with PD (544 cases) and other forms of degenerative parkinsonism (67 cases) and 604 unrelated controls for the c.1144G > A (p.A382T) missense mutation of the TARDBP gene. The p.A382T mutation was identified in nine patients with parkinsonism. Of these, five (0.9 % of PD patients) presented a typical PD (two with familiar forms), while four patients (6.0 % of all other forms of parkinsonism) presented a peculiar clinical presentation quite different from classical atypical parkinsonism with an overlap of extrapyramidal–pyramidal–cognitive clinical signs. The mutation was found in eight Sardinian controls (1.3 %) consistent with a founder mutation in the island population. Our findings suggest that the clinical presentation of the p.A382T TARDBP gene mutation may include forms of parkinsonism in which the extrapyramidal signs are the crucial core of the disease at onset. These forms can present PSP or CBD-like clinical signs, with bulbar and/or extrabulbar pyramidal signs and cognitive impairment. No evidence of association has been found between TARDBP gene mutation and typical PD.     

When to perform bone scan in patients with newly diagnosed prostate cancer: external validation of a novel risk stratification tool

Purpose

To externally validate the performance characteristics of the Briganti’s risk stratification tool for baseline staging bone scan in patients with newly diagnosed prostate cancer (PCa).

Methods

From 2009 onwards, a consecutive series of patients with PCa were enrolled. All patients were staged to evaluate the presence of bone metastasis (BM) with a conventional total-body Tc 99 m MDP scintigraphy performed regardless of baseline PCa characteristics. The area under the curve (AUC) estimates were used to test the accuracy of the Briganti’s risk stratification tool that recommended staging baseline bone scan for patients with a biopsy Gleason score >7 or with a prostate-specific antigen (PSA) >10 ng/ml and palpable disease (cT2/T3). The new tool was compared to the European Association of Urology (EAU) guideline.

Results

A total of 313 patients were consecutively enrolled. Median age was 68 (range 49–95 years), and median PSA was 7 ng/ml (range 0.81–2,670). Twenty (6.4 %) patients presented BMs. Patients with BMs were significantly older, with higher PSA and a higher Gleason score (p = 0.001). The novel Briganti’s model was significantly (p = 0.001) more accurate (AUC: 0.75; CI: 0.632–0.859) than the EAU guideline (AUC: 0.64; CI: 0.52–0.761) for the prediction of BMs.

Conclusions

Our study validated in a group of patients with PCa the novel risk stratification tool proposed by Briganti, which presented a higher accuracy for baseline staging bone scan when compared with the EAU guideline. In our experience, this approach would further reduce (about 60 %) the use of staging baseline bone scan without compromising the ability to detect BMs in patients with PCa.     

Prostaglandin E2 type 1 receptors contribute to neuronal apoptosis after transient forebrain ischemia

Cyclooxygenase-2-derived prostaglandin E₂ (PGE₂) contributes to excitotoxic and ischemic neuronal cell death by engaging neuronal PGE₂ type 1 receptors (EP1R). Our previous studies have shown that EP1R signaling resulted in disturbances of intracellular Ca²⁺ homeostasis and suppression of the pro-survival protein kinase AKT. The aim of this study was to investigate whether these pathophysiological mechanism have a role in the neuronal cell death after transient forebrain ischemia. Mice were subjected to ischemia/reperfusion by bilateral common carotid artery occlusion. Hippocampal cornu ammonis area 1 (CA1) neuronal cell death was determined 5 days after reperfusion. Animals treated with the EP1R antagonist SC51089 or EP1R-deficient mice (EP1^−/−) showed significantly less neuronal injury as compared to vehicle-treated wild-type controls. Benefits of EP1R blockage were still evident 14 days after injury. Better neuronal survival was correlated with reduced neuronal caspase-3 activity and decreased nuclear translocation of the apoptosis-inducing factor . Neuroprotection could be reverted by intracerebroventricular administration of the phosphoinositide 3-kinase inhibitor {"type":"entrez-nucleotide","attrs":{"text":"LY294002","term_id":"1257998346","term_text":"LY294002"}}LY294002 and was not further increased by the calcineurin inhibitor FK506. These data implicate EP1R in postischemic neuronal apoptosis possibly by facilitating AKT inhibition.     

Neuropsychiatric Functioning in CDLS: A Detailed Phenotype and Genotype Correlation

Journal of Autism and Developmental Disorders - Behavioural phenotype and autism-related traits of 38 patients affected by Cornelia de Lange syndrome (CdLS) were assessed using a specific...     

Body composition and resting metabolic rate of perimenopausal women using continuous progestogen contraception

Objective The effect on body composition and in particular on fat mass (FM) of 12 months’ use of a desogestrel (DSG)-only contraceptive pill or the levonorgestrel-releasing intrauterine system (LNG-IUS) was evaluated in women in the perimenopause.

Methods An observational study comprised 102 perimenopausal women: 42 received a 75 μg DSG pill, 34 received the 52 mg LNG-IUS, and 26 received no treatment. Body composition, body weight and resting metabolic rate (RMR) were evaluated at baseline and again after 12 months.

Results FM did not change in the control group (? 0.5 ± 1.6%) but significantly increased in the LNG-IUS group (+ 1.1 ± 2.9%; p = 0.02 vs. controls) and in the DSG group (+ 2.8 ± 3.5%; p = 0.0001 vs. controls; p = 0.02 vs. LNG-IUS). Women treated with DSG or the LNG-IUS showed a non-significant increase in body weight, body mass index and waist circumference. RMR did not significantly vary in the control group (? 3.8 ± 292.9 kJ/ 24 h) and tended to decrease but not significantly in the LNG-IUS (115.5 ± 531.8 kJ/ 24 h) and DSG groups (305.9 ± 556.9 kJ/24 h).

Conclusions The results of this preliminary study seem to indicate that in perimenopausal women continuous use of the DSG-only pill and to a lesser extent the LNG-IUS may favour FM accumulation.     

Palliative embolization for metastases of the spine

Background

To present palliative selective and superselective arterial embolization with N-butyl-cyanoacrylate for cancer patients with spinal metastases.

Materials and methods

We studied the files of 164 cancer patients (94 men and 70 women; mean age 57.6 years; range 35–81 years) treated from March 2003 to March 2013 with 178 selective arterial embolization procedures for metastases of the spine from variable primary cancers. We evaluated the technical success of the embolization procedure with post-procedural angiography, the clinical effect in pain relief, need for analgesics and tumor size reduction, and the embolization-related complications.

Results

Post-embolization angiography showed complete occlusion of the pathological feeding vessels in all procedures. Pain score and need for analgesics reduced by 50 % in 159 patients (97 %); no response was achieved in five patients with metastases of the sacrum. The mean duration of pain relief was 9.2 months (range 1–12 months). Metastatic tumor size reduced from a mean of 5.5 cm (range 3.5–7.5 cm) pre-embolization to a mean of 4.5 cm (range 3–5 cm) at the 6-month follow-up; the difference was not statistically significant. Ninety-three patients (56.7 %) experienced embolization-related complications the most common being post-embolization syndrome (80 patients, 48.8 %) followed by leg paresthesias (ten patients, 6 %), and rupture of a lumbar artery (one patient, 0.6 %).

Conclusion

Selective arterial embolization with N-butyl-cyanoacrylate should be considered for pain palliation of patients with metastases of the spine. However, pain relief is temporary, and complications, although minor may occur.