Population density and risk of Amyotrophic Lateral Sclerosis: an Italian population-based study.

Population density and risk of Amyotrophic Lateral Sclerosis: an Italian population-based study

Selenium species and heavy metals in cerebrospinal fluid and risk of amyotrophic lateral sclerosis: a hospital-based case-control study

Background Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disease which has been ascribed to overexposure to selenium and some heavy metals, on the basis of epidemiologic evidence and laboratory observations. However, no data are available on the specific involvement of single selenium species, all of which have distinctive biological activities, and limited evidence has also been provided for lead, mercury and cadmium in the human. Methods In a hospital-admitted case-control series, we determined the Se compounds and the levels of Cd, Hg and Pb in cerebrospinal fluid samples of thirty-six ALS patients and of thirty-six reference neurological patients. Determinations of Se compounds and of the heavy metals was performed using high pressure liquid chromatography coupled with inductively coupled plasma - dynamic reaction cell - mass spectrometry according to methodologies previously established and described by one of the coauthors (B.M.). Results We found an excess concentration of inorganic Se forms, particularly of the hexavalent and tetravalent ones, while organic Se compounds levels were considerably decreased in ALS cases. These differences were more pronounced in older patients and in females. On the converse, no substantial differences in Cd, Hg and Pb concentrations emerged. Conclusions These results suggest the occurrence of overexposure to inorganic Se species and decreased levels of Se-containing enzymes in ALS, while they offer little evidence of an involvement of three heavy metals, Cd, Hg and Pb, in the etiopathogenesis of this disease. However, caution must be used when inferring etiological clues from analytical results in patients affected by a severe disease such as ALS, and in hospital-referred controls. Further research on the involvement of Se in ALS etiology is clearly warranted

Comment on 'Huntington's disease presenting as ALS'

This is a case report of patient with concurrent Huntington disease and Amyotrophic Lateral Sclerosi

The impact of clinical factors, riluzole and therapeutic interventions on ALS survival: A population based study in Modena, Italy

The prognostic role of riluzole, enteral nutrition (EN), non-invasive ventilation (NIV) and interdisciplinary care in ALS is still debated. A population based study has been performed focusing on ALS survival, with particular attention to prognostic factors and therapeutic intervention. All patients diagnosed with ALS between 2000 and 2009 and residing in Modena, Italy, have been registered. A centre for motor neuron disease (MND) has been active in our province since 2000, in addition to a prospective registry collecting all incident cases. One hundred and ninety-three incident cases have been collected during the 10 years of the study. Results demonstrated that median survival was 41 months (the overall three-year and five-year survival rates being 54.36% and 28.81%, respectively). Based on univariate analysis, factors related to survival were: age at diagnosis, gender, site of onset, phenotype, riluzole treatment and tracheostomy. In the Cox multivariable model, the factors independently related to a longer survival were age (p < 0.01), site of onset (p = 0.02) and riluzole treatment (p < 0.01), with a median gain in survival of 29 months (patients aged < 55 years compared with patients ≥ 55 years), 20 months (spinal versus bulbar onset), and 12 months (riluzole, yes vs. no), respectively. In conclusion, the study has confirmed the prognostic role of clinical features, but has surprisingly demonstrated that riluzole prolonged life significantly longer than NIV and EN. This observational study described the effects of ALS management in a setting that may approximate routine clinical practice more closely than randomized controlled trial (RCT); effects of uncontrolled potential confounders, however, cannot be excluded. The prognostic role of riluzole, enteral nutrition (EN), non-invasive ventilation (NIV) and interdisciplinary care in ALS is still debated. A population based study has been performed focusing on ALS survival, with particular attention to prognostic factors and therapeutic intervention. All patients diagnosed with ALS between 2000 and 2009 and residing in Modena, Italy, have been registered. A centre for motor neuron disease (MND) has been active in our province since 2000, in addition to a prospective registry collecting all incident cases. One hundred and ninety-three incident cases have been collected during the 10 years of the study. Results demonstrated that median survival was 41 months (the overall three-year and five-year survival rates being 54.36% and 28.81%, respectively). Based on univariate analysis, factors related to survival were: age at diagnosis, gender, site of onset, phenotype, riluzole treatment and tracheostomy. In the Cox multivariable model, the factors independently related to a longer survival were age (p < 0.01), site of onset (p = 0.02) and riluzole treatment (p < 0.01), with a median gain in survival of 29 months (patients aged < 55 years compared with patients ≥ 55 years), 20 months (spinal versus bulbar onset), and 12 months (riluzole, yes vs. no), respectively. In conclusion, the study has confirmed the prognostic role of clinical features, but has surprisingly demonstrated that riluzole prolonged life significantly longer than NIV and EN. This observational study described the effects of ALS management in a setting that may approximate routine clinical practice more closely than randomized controlled trial (RCT); effects of uncontrolled potential confounders, however, cannot be excluded

Changing incidence and subtypes of ALS in Modena, Italy: A 10-years prospective study

We performed a prospective population-based study to describe the temporal pattern of the incidence and prevalence and the clinical features and phenotypes of ALS in Modena, Italy, from 2000 to 2009. From 2000 onwards, a prospective registry has been collecting all cases of incident ALS among residents in the province of Modena. This source was implemented by cases resulting from the provincial hospitals, and by death certificates. Based on 193 newly diagnosed cases, the crude average annual incidence rate of ALS was 2.9 cases per 100,000 person years (py); adjusted incidence rate was 2.8/100,000. The age-standardized incidence rates increased from 2.6 per 100,000 py in 2000-2004 to 2.9 per 100,000 py in 2005-2009, representing an annual increase of approximately 2% throughout the 10-year period. There was a constant increase in prevalence rates throughout the years of the study (from 5.8/100,000 on 31 December 2000 to 11.2/100,000 on 31 December 2009). Median life time was 29 months for patients diagnosed before the year 2000 and 36 months for patients diagnosed from 1 January 2000 (p < 0.01). Thus, we report incidence rates similar to those reported by recent European population based studies, but we observed an increasing trend over the 10 years of the study. The increasing incidence is not explained by aging of the population, and our study raises the question as to whether local environmental or genetic factors are driving this temporal trend. Along with an increasing incidence, we found an important increase in prevalence and survival probably related to access to mutidisciplinary clinics and improvements in symptomatic care of ALS

Pearls & Oy-sters: rapidly progressive dementia: prions or immunomediated?

The paper presentes a case report of a patient with rapidly progressive dementia. The discussion is focused on the differential diagnosis between Voltage-gated potassium channel antibody\u2013associated encephalitis and sporadic Creutzfeldt-Jakob disease

Heterogeneity in ALSFRS-R decline and survival: a population-based study in Italy

Very few studies examined trend over time of the revised Amyotrophic Lateral Sclerosis Functional Rating Scale (ALSFRS-R) and factors influencing it; previous studies, then, included only patients attending tertiary ALS Centres. We studied ALSFRS-R decline, factors influencing this trend and survival in a population-based setting. From 2009 onwards, a prospective registry records all incident ALS cases among residents in Emilia Romagna (population: 4.4 million). For each patient, demographic and clinical details (including ALSFRS-R) are collected by caring physicians at each follow-up. Analysis was performed on 402 incident cases (1279 ALSFRS-R assessments). The average decline of the ALSFRS-R was 0.60 points/month during the first year after diagnosis and 0.34 points/month in the second year. ALSFRS-R decline was heterogeneous among subgroups. Repeated measures mixed model showed that ALSFRS-R score decline was influenced by age at onset (p < 0.01), phenotype (p = 0.01), body mass index (BMI) (p < 0.01), progression rate at diagnosis (ΔFS) (p < 0.01), El Escorial Criteria-Revised (p < 0.01), and FVC% at diagnosis (p < 0.01). Among these factors, at multivariate analysis, only age, site of onset and ΔFS independently influenced survival. In this first population-based study on ALSFRS-R trend, we confirm that ALSFRS-R decline is not homogeneous among ALS patients and during the disease. Factors influencing ALSFRS-R decline may not match with those affecting survival. These disease modifiers should be taken into consideration for trials design and in clinical practice during discussions with patients on prognosis