The PRIAMO study: age- and sex-related relationship between prodromal constipation and disease phenotype in early Parkinson's disease.

OBJECTIVES: To explore the impact of sex and age on relationship between prodromal constipation and disease phenotype in Parkinson's disease at early stages. METHODS: A total of 385 Parkinson's disease patients from the PRIAMO study were classified according to the presence of prodromal constipation and followed for 24 months. Multivariable mixed-effect models were applied. All analyses were performed separately for sex (64.1% men) and median age (different by sex: 67 years-old in men and 68 years-old in women). RESULTS: As for sex, prodromal constipation was associated with greater odds of attention/memory complaints and apathy symptoms in women only. As for age, prodromal constipation was associated with lower cognitive and higher apathy scores in older patients only. CONCLUSIONS: Prodromal constipation anticipates lower cognitive performances and more severe apathy since the earliest stages in women and older patients. Sex- and age-related heterogeneity of prodromal markers of Parkinson's disease may impact disease phenotype

Effect of alirocumab on mortality after acute coronary syndromes. An analysis of the ODYSSEY OUTCOMES randomized clinical trial

Background: Previous trials of PCSK9 (proprotein convertase subtilisin-kexin type 9) inhibitors demonstrated reductions in major adverse cardiovascular events, but not death. We assessed the effects of alirocumab on death after index acute coronary syndrome. Methods: ODYSSEY OUTCOMES (Evaluation of Cardiovascular Outcomes After an Acute Coronary Syndrome During Treatment With Alirocumab) was a double-blind, randomized comparison of alirocumab or placebo in 18 924 patients who had an ACS 1 to 12 months previously and elevated atherogenic lipoproteins despite intensive statin therapy. Alirocumab dose was blindly titrated to target achieved low-density lipoprotein cholesterol (LDL-C) between 25 and 50 mg/dL. We examined the effects of treatment on all-cause death and its components, cardiovascular and noncardiovascular death, with log-rank testing. Joint semiparametric models tested associations between nonfatal cardiovascular events and cardiovascular or noncardiovascular death. Results: Median follow-up was 2.8 years. Death occurred in 334 (3.5%) and 392 (4.1%) patients, respectively, in the alirocumab and placebo groups (hazard ratio [HR], 0.85; 95% CI, 0.73 to 0.98; P=0.03, nominal P value). This resulted from nonsignificantly fewer cardiovascular (240 [2.5%] vs 271 [2.9%]; HR, 0.88; 95% CI, 0.74 to 1.05; P=0.15) and noncardiovascular (94 [1.0%] vs 121 [1.3%]; HR, 0.77; 95% CI, 0.59 to 1.01; P=0.06) deaths with alirocumab. In a prespecified analysis of 8242 patients eligible for ≥3 years follow-up, alirocumab reduced death (HR, 0.78; 95% CI, 0.65 to 0.94; P=0.01). Patients with nonfatal cardiovascular events were at increased risk for cardiovascular and noncardiovascular deaths (P<0.0001 for the associations). Alirocumab reduced total nonfatal cardiovascular events (P<0.001) and thereby may have attenuated the number of cardiovascular and noncardiovascular deaths. A post hoc analysis found that, compared to patients with lower LDL-C, patients with baseline LDL-C ≥100 mg/dL (2.59 mmol/L) had a greater absolute risk of death and a larger mortality benefit from alirocumab (HR, 0.71; 95% CI, 0.56 to 0.90; Pinteraction=0.007). In the alirocumab group, all-cause death declined wit h achieved LDL-C at 4 months of treatment, to a level of approximately 30 mg/dL (adjusted P=0.017 for linear trend). Conclusions: Alirocumab added to intensive statin therapy has the potential to reduce death after acute coronary syndrome, particularly if treatment is maintained for ≥3 years, if baseline LDL-C is ≥100 mg/dL, or if achieved LDL-C is low. Clinical Trial Registration: URL: https://www.clinicaltrials.gov. Unique identifier: NCT01663402

Trattamento della sindrome parkisoniana con Levo-Dopa Treatment of Parkinsonian syndrome with levo-DOPA. Case reports

To evaluate the effect of L-DOPA in parkinsonism 35 patients (17 men and 18 women, mean age 64 years) were selected for study. L-dopa therapy was given at a mean daily dose of 3 mg. 31 patients were followed more than 1 year during treatment. 4 patients were withdrawn from the study owing to intolerable side effects. All patients were receiving anticholinergic drugs before the study period. Such medications were discontinued in 16 patients and continued in the remaining 15. The results of this study confirm the effectiveness of L-Dopa in ameliorating the major manifestations of parkinsonism particularly rigidity and bradykinesia and to a lesser extent tremor which appeared somewhat more resistant to L-DOPA therapy. Neurological improvement was usually evident on the first few weeks of treatment and continued to progress during the ensuing months even though the daily dose of L-Dopa could be reduced. Prolonged treatment with L-DOPA increased the degree of improvement of major parkinsonian symptoms and of functional and social rehabilitation whereas did not seem to increase the number of improved cases

Voluntary lid closing inability. Release of a compulsive reaction to the exploration of the environment.

Voluntary lid closing inability has been observed in two patients with right-sided frontal ischemic damage. The patients developed a transient inability to close their eyelids voluntarily at the same time as a transient forced grasping in the left hand and left hemiparesis not affecting the face. Automatic and reflex lid closures were retained as well as the ability to keep the eyes closed and to reopen them readily on command. In previous reports, inability to close eyelids voluntarily has been attributed to apraxia, paralysis, or motor impersistence. The localization of the lesion observed in our patients suggests other pathogenetic hypotheses similar to compulsive gaze. It is conceivable that the voluntary lid closing inability produced by frontal lobe lesions is due to the release of a compulsion to maintain the lids elevated in the waking state, because of the overactive effect of the visual stimuli

Angiographic study of the arteries of the internal auditory canal

Studio sull'anatomia dell'arteria uditiva interna e delle sue varianti attraverso analisi di angiografie dei vasi arteriosi intracranic