[Mortality in an Italian factory producing tetraethyl lead]. / Mortalità alla SLOI di Trento, un'azienda che produceva piombo tetraetile.

The Società Lavorazioni Organiche Inorganiche (SLOI) in Trento (North-Eastern Italy) produced tetraethyl lead from 1941 to 1978, when it was closed following an explosion, luckily with no fatalities. Working conditions were very bad. During the 1960s, 325 acute lead intoxications were reported and over 100 workers were hospitalized for neurological conditions attributable to tetraethyl lead. At least 12 SLOI workers were hospitalized in the mental asylum (psychiatric wards).The present work describes the first formal epidemiological study ever carried out on SLOI workers. In the absence of any original SLOI employee registers, a list of 1,742 workers hired since factory startup was assembled using the files of the Italian National Social Security Agency (digitalized in 1974 and perused manually by one of the Authors for the previous period). To date, follow-up for mortality has been completed for the 580 male employees at work in 1961 or hired subsequently and who worked at SLOI for at least 12 months. Twenty-two (3.8%) were lost to follow-up. Mortality in this sub-cohort was compared with that of the population of the province of Trento, gathered since 1986 by the Institute of Statistics of the Trento Province. Excluding deaths occurring at age 90+ years, during the 1986-2016 period, deaths in the SLOI sub-cohort were 295 vs 229.0 deaths expected from age- and period-specific rates in the reference population (standardazied mortality ratio 1.29; 95%CI 1.15-1.44). In the absence of individual data, the possible contribution to the mortality excess by non-occupational risk factors cannot be estimated. Identification of causes of death is underway.

Leptomeningeal metastasis from solid tumors: a diagnostic and therapeutic challenge.

Leptomeningeal metastasis (LM) is a severe complication in the natural history of malignancies that occurs in 4-15 % of patients (pts) with solid tumors. Clinical presentation, cerebrospinal fluid cytology (CSF), and gadolinium magnetic resonance imaging (gdMRI) of the brain and spine are the methods routinely used to diagnose LM. Treatment encompasses involved-field radiotherapy of bulky or symptomatic disease sites and chemotherapy; however, no standard therapy has been established yet. We collected and reviewed retrospectively the clinical, pathological, radiological findings as well as the outcomes of 50 consecutive patients with LM from solid tumors to determine whether the diagnostic modalities and therapeutic procedures affected the outcomes. The results of this study confirm the role of gdMRI in the diagnosis of LM in clinical practice and suggest that an aggressive treatment may improve survival in patients with this debilitating and increasingly frequent neurological complication.

Change in myasthenia gravis epidemiology in Trento, Italy, after twenty years.

BACKGROUND: The recent literature suggests that the incidence and prevalence of myasthenia gravis (MG) are changing. We performed a population-based study of MG in the province of Trentino (524,826 inhabitants) and compared the results with those collected 20 years ago. METHODS: Multiple sources of information (discharge diagnosis, antibody tests and anticholinesterase drugs) were analyzed. Incidence was calculated from 2005 to 2009. Prevalence was calculated on December 31, 2009. Comparison was made with descriptive statistics for 1981-1990 for the identical region. RESULTS: Incidence and prevalence greatly increased in comparison with 1981-1990 data. The prevalence rate increased from 82.9 (95% confidence interval, CI, 58.4-114.3) in 1990 to 129.6 (95% CI 100.6-164.3) per million population, whereas the average annual incidence increased from 7.4 (95% CI 5-10.4) per million person-years in 1981-1990 to 14.8 (95% CI 10.5-20.3) in 2005-2009. This increase was mainly due to male patients with late-onset MG. CONCLUSIONS: The study confirms the increase in incidence and prevalence of late-onset MG in the same region 20 years apart. So we should consider MG also as a disease of the elderly.

Gene dosage sensitivity of a novel mutation in the intracellular domain of P0 associated with Charcot-Marie-Tooth disease type 1B.

Autosomal dominant Charcot-Marie-Tooth disease type 1B (CMT1B) is caused by heterozygous mutations in the extracellular domain of P0. Here, we investigated clinically, electrophysiologically and pathologically a pedigree with a novel mutation in the intracellular domain of P0 (P0ic). The mutational analysis included denaturing high performance liquid chromatography (DHPLC) and nucleotide sequencing. Two patients from subsequent generations were homozygous for an Asp195Tyr mutation in the intracellular domain of P0 (P0ic), whereas two healthy individuals with minimal electrophysiological changes were heterozygous for the same mutation. The authors conclude that mutations of P0ic may undergo a gene dosage effect manifesting semidominant inheritance.

Palatal tremor suppressed by mouth opening: clinical and neurophysiological correlations in two patients.

We report clinical and neurophysiological findings in two patients with palatal tremor (PT). In both patients a prompt and persistent suppression of palatal movements and clicking sounds is caused by slight passive or active mouth opening. One patient has a typical essential palatal tremor (EPT) according to current classification criteria. The other one has a PT characterized by involuntary activation of levator veli palatini and genioglossus muscles. Objective clicking sounds were observed late during the course of the disease. A symptomatic aetiology was excluded, suggesting a diagnosis of atypical EPT. Our observations further confirm that unusual features of some cases may not fit current PT classification criteria. These two cases have several features that distinguish them from voluntary PT and from psychogenic PT. We emphasize that clear cut modulating phenomena may be relevant features in both typical and atypical involuntary EPT. We finally focus on the significance of jaw posture in determining PT suppression in our patients.

The THRombolysis and STatins (THRaST) study.

OBJECTIVE: To assess the impact on stroke outcome of statin use in the acute phase after IV thrombolysis. METHODS: Multicenter study on prospectively collected data of 2,072 stroke patients treated with IV thrombolysis. Outcome measures of efficacy were neurologic improvement (NIH Stroke Scale [NIHSS] ≤ 4 points from baseline or NIHSS = 0) and major neurologic improvement (NIHSS ≤ 8 points from baseline or NIHSS = 0) at 7 days and favorable (modified Rankin Scale [mRS] ≤ 2) and excellent functional outcome (mRS ≤ 1) at 3 months. Outcome measures of safety were 7-day neurologic deterioration (NIHSS ≥ 4 points from baseline or death), symptomatic intracerebral hemorrhage type 2 with NIHSS ≥ 4 points from baseline or death within 36 hours, and 3-month death. RESULTS: Adjusted multivariate analysis showed that statin use in the acute phase was associated with neurologic improvement (odds ratio [OR] 1.68, 95% confidence interval [CI] 1.26-2.25; p < 0.001), major neurologic improvement (OR 1.43, 95% CI 1.11-1.85; p = 0.006), favorable functional outcome (OR 1.63, 95% CI 1.18-2.26; p = 0.003), and a reduced risk of neurologic deterioration (OR: 0.31, 95% CI 0.19-0.53; p < 0.001) and death (OR 0.48, 95% CI 0.28-0.82; p = 0.007). CONCLUSION: Statin use in the acute phase of stroke after IV thrombolysis may positively influence short- and long-term outcome.

k-Nearest neighbour local linear prediction of scalp EEG activity during intermittent photic stimulation.

The characterization of the EEG response to photic stimulation (PS) is an important issue with significant clinical relevance. This study aims to quantify and map the complexity of the EEG during PS, where complexity is measured as the degree of unpredictability resulting from local linear prediction. EEG activity was recorded with eyes closed (EC) and eyes open (EO) during resting and PS at 5, 10, and 15 Hz in a group of 30 healthy subjects and in a case-report of a patient suffering from cerebral ischemia. The mean squared prediction error (MSPE) resulting from k-nearest neighbour local linear prediction was calculated in each condition as an index of EEG unpredictability. The linear or nonlinear nature of the system underlying EEG activity was evaluated quantifying MSPE as a function of the neighbourhood size during local linear prediction, and by surrogate data analysis as well. Unpredictability maps were obtained for each subject interpolating MSPE values over a schematic head representation. Results on healthy subjects evidenced: (i) the prevalence of linear mechanisms in the generation of EEG dynamics, (ii) the lower predictability of EO EEG, (iii) the desynchronization of oscillatory mechanisms during PS leading to increased EEG complexity, (iv) the entrainment of alpha rhythm during EC obtained by 10 Hz PS, and (v) differences of EEG predictability among different scalp regions. Ischemic patient showed different MSPE values in healthy and damaged regions. The EEG predictability decreased moving from the early acute stage to a stage of partial recovery. These results suggest that nonlinear prediction can be a useful tool to characterize EEG dynamics during PS protocols, and may consequently constitute a complement of quantitative EEG analysis in clinical applications.

Carotid stenosis as predictor of stroke after transient ischemic attacks.

ABCD2 score identifies high-risk TIAs but its validity in different countries and hospitals is unknown. Doubts remain also about the role of diagnostic work up for patients with TIAs in the emergency department. The present study was undertaken to confirm the usefulness of ABCD2 score in the emergency department of Trento Hospital and to evaluate if other exams (carotid ultrasound or CT scan) commonly performed in TIA patients are helpful. We retrospectively analysed discharge diagnosis of around 120,000 patients seen at the first aid of Trento Hospital over a 28 month period. ABCD2 score, carotid ultrasound and CT scan were recorded and were correlated with recurrence of stroke at different time points (mean follow-up period of 11.4 months) in all patients with TIA. We identified 965 patients with focal neurologic deficit and 502 could be classified as TIA. An ischemic stroke recurred in 30 patients at the end of the follow-up (30% in the first two days). ABCD2 score confirmed its value. A significant carotid stenosis (>70%) was an independent risk factor for stroke at any time point. Our study confirms the role of ABCD2 in a large Italian cohort of TIA patients but also suggests the importance of performing a carotid ultrasound as soon as possible.

An identifiable model to assess frequency-domain granger causality in the presence of significant instantaneous interactions.

We present a new approach for the investigation of Granger causality in the frequency domain by means of the partial directed coherence (PDC). The approach is based on the utilization of an extended multivariate autoregressive (MVAR) model, including instantaneous effects in addition to the lagged effects traditionally studied, to fit the observed multiple time series prior to PDC computation. Model identification is performed combining standard MVAR coefficient estimation with a recent technique for instantaneous causal modeling based on independent component analysis. The approach is first validated on simulated MVAR processes showing that, in the presence of instantaneous effects, only the extended model is able to interpret the imposed Granger causality patterns, while the traditional MVAR approach may yield strongly biased PDC estimates. The subsequent application to multichannel EEG time series confirms the potentiality of the approach in real data applications, as the importance of instantaneous effects led to significant differences in the PDC estimated after traditional and extended MVAR identification.