1,721,122 research outputs found
Are environmental exposures to selenium, heavy metals, and pesticides risk factors for amyotrophic lateral sclerosis ?
Full text linkThe etiology of sporadic amyotrophic lateral sclerosis (ALS), the most common form of this degenerative disease of the motor neurons, is still unknown, despite extensive investigation of several genetic and environmental potential risk factors. We have reviewed laboratory and epidemiological studies assessing the role of exposure to neurotoxic chemicals (metalloid selenium; heavy metals mercury, cadmium, and lead; pesticides) in ALS etiology by summarizing the results of these investigations and examining their strengths and limitations. Despite limitations in the exposure assessment methodologies typically used in human studies, we found suggestive epidemiological evidence and biologic plausibility for an association between ALS and antecedent overexposure to environmental selenium and pesticides. The relation with mercury, cadmium, and lead appears weaker
Amyotrophic lateral sclerosis: Prognostic indicators of survival
No full textAmyotrophic lateral sclerosis (ALS) has a fatal outcome in about three years, but survival is known to vary considerably, making it difficult to predict disease duration in individual cases. The aim of this study was to investigate possible early prognostic factors of ALS survival. We included 123 probable or definite cases of ALS, with disease onset between 1989 and 1998, and with a follow-up of at least one year. Survival functions were obtained using both the Kaplan-Meier and the actuarial methods. Subgroups, formed on the basis of gender, area of residence, work, and age at and site of onset, were compared using the logrank test and Cox's proportional hazards method (survival functions), and applying the Grizzle, Starmer, Koch (1969), and Koch, Johnson, Tolley (1972) methods (one-year survival probability trends). The survival curves dipped sharply in the first three years, followed by a flattening trend, with 50% of patients dying within 2.5 years, and 89% over seven years. The clinical form with lower limb onset was associated with longer survival than the upper limb onset and bulbar forms (median survival: 39, 27, and 25 months, respectively). Survival was also affected by age at onset (median survival: 34, 27, and 23 months for onset 75 years, respectively), area of residence (median survival: 24 months in mountainous areas, 32 elsewhere), and type of work (median survival: 25 months in agricultural workers, 33.5 in others). Gender did not influence survival, whereas percutaneous endoscopic gastrostomy placement and invasive ventilation did. The estimation of individual ALS survival is important to allow the patient to plan for his future and to make optimal use of medical and community resources. Although age at and site of onset, area of residence, and agricultural work were found to influence survival, there remains an unexplained heterogeneous progression of the disease, suggesting the influence of other, as yet unknown, prognostic factors. The identification of a definite set of prognostic factors may allow physicians to make more reliable survival predictions at diagnosis
Sensory Loss Mimicking Cauda Equina Syndrome due to Cervical Spinal Lesion in a Patient with Clinically Isolated Syndrome
No full textWe describe the case of a 39-year-old woman with signs and symptoms suggesting cauda equina syndrome. Lumbosacral magnetic resonance imaging (MRI) demonstrated no lesion at this level, while cervical MRI showed a T2-hyperintense lesion in the middle-right anterolateral region of the cervical spinal cord, which may explain the symptoms by involving the anterior spinothalamic tract. We suggest that in cases with cauda equina syndrome presentation and normal lumbosacral MRI, a cervicodorsal lesion should be considered during diagnostic assessment
Central pontine myelinolysis and poorly controlled diabetes: MRI’s hints for pathogenesis
No full textDear Sir,
Central pontine myelinolysis (CPM) is usually associated with a rapid correction of hyponatremia [1, 2]. In a patient with chronic hyponatremia, oligodendrocytes in the pons decrease their inner osmolarity to protect them from swelling. Thereafter, any rapid osmotic shift in the opposite direction caused by the hypertonic fluid can induce the swollen cells to shrink, leading to osmotic demyelination [1, 2]. Typical MRI features in CPM are characterized by cytotoxic edema (DWI hyperintensity and ADC hypointensity) consistent with shrinkage of the pontine cells [3]. We describe a case of CPM due to poorly controlled diabetes with brain MRI features compatible with vasogenic edema (DWI and ADC hyperintensity) that may suggest an extracellular space expansion rather than shrinkage of the pontine cell
Percutaneous endoscopic gastrostomy, body weight loss and survival in amyotrophic lateral sclerosis: a population-based registry study
No full textAbstract
Objective: To assess the role of percutaneous endoscopic gastrostomy (PEG) insertion, and its timing, on ALS survival, and
to study prognostic factors of survival before and after PEG placement in a population-based setting. Methods: In this
observational population-based, registry study, we enrolled patients with newly- diagnosed ALS, according to the El
Escorial revised criteria, who were resident in the Emilia Romagna Region, and who developed severe dysphagia needing
enteral nutritional support. The primary outcome measure was tracheostomy-free survival after PEG recommendation.
Results: There were 210 patients needing PEG, out of an incident cohort of 545 patients from the Emilia Romagna Registry
for ALS, who were diagnosed between 2009 and 2013. One hundred and ninety-three patients were included in the study,
and 17 were excluded because they were already tracheostomized at the time of PEG placement. Of the 193 patients
included in the study, 152 underwent PEG, whereas 41 did not undergo the procedure. Patients who did not undergo
PEG, among the eligible ones, had the same tracheostomy-free survival from onset as patients who did (25 vs. 32 months,
p1⁄40.21). Tracheostomy-free survival from PEG recommendation was greater in patients who underwent PEG placement
than in patients who did not (6 vs. 2 months, p1⁄40.008). Median tracheostomy-free survival from PEG insertion was eight
months (95% CI5–12); 30 days after PEG placement, survival was 89.60%. At Cox multivariable analysis, the hazard of
death or tracheostomy after PEG insertion was significantly influenced by the difference between BMI at the time of the
PEG procedure and BMI at diagnosis (HR 1.05, 95% CI 1.02–1.08; p1⁄40.002). The hazard of death or tracheostomy was
not affected by the timing of PEG insertion. Conclusions: The present study, although it has some limitations, suggests a
gain of tracheostomy-free survival from the time of PEG recommendation for patients who undergo PEG placement, and,
among patients who undergo PEG, a greater survival if PEG is inserted before a significant weight loss occurs, and if
nutritional support avoids further weight loss. Should this association between prevention of weight loss and better clinical
outcome be confirmed by further studies, it would have important implications for disease management
Cerebrospinal Fluid Neurofilaments May Discriminate Upper Motor Neuron Syndromes: A Pilot Study
No full textPatients presenting with upper motor neuron (UMN) signs may widely diverge in prognosis, ranging from amyotrophic lateral sclerosis (ALS) to primary lateral sclerosis (PLS) and hereditary spastic paraplegia (hSP). Neurofilaments are emerging as potential diagnostic and prognostic biomarkers for ALS, but the diagnosis of UMN syndromes still relies mostly on clinical long-term observation and on familiarity or genetic confirmation
Potential Peptide Biomarkers and Etiological Factors in the Cerebrospinal Fluid of Amyotrophic Lateral Sclerosis Patients
No full textRisk stratification of non-traumatic headache in the emergency department
No full textOBJECTIVE: To determine the diagnostic accuracy of an algorithm structured in four clinical scenarios to discriminate benign primary headaches from serious secondary non-traumatic headaches (NTH) in the emergency department (ED). BACKGROUND: NTH is usually a benign symptom but can occasionally result in serious outcome making the disposition of patients with NTH difficult in the ED. DESIGN AND METHODS: Consecutive adults patients referring to 8 EDs of the Emilia-Romagna region in Italy for NTH as the chief complaint were recruited in the study for a 30-day period. ED physicians attributed to each patient one of the four clinical scenarios (1, 2 and 3 identifying serious secondary headaches and scenario 4 identifying benign primary headaches) or an undetermined scenario when none of the four scenarios applied. Reference standards of the study were the head CT scan and a follow-up telephone interview after three months by the ED admission. RESULTS: The test was administered to 256 out of 302 (85%) eligible patients. The analysis (scenario 1,2,3 vs scenario 4) was based on 180 patients who completed the follow-up showing a sensitivity of 100% (95% confidence interval, 81% to 100%) and a specificity of 64% (56% to 71%). The likelihood ratio for a positive test was 2.67 (2.15 to 3.31) and the likelihood ratio for a negative test was 0.04 (0.003 to 0.64). CONCLUSIONS: An algorithm based on four clinical scenarios can be administered to the majority of patients presenting to the ED with the chief complaint of NTH. The algorithm showed a good accuracy in identifying patients with non-life threatening causes of headache and could be used as a risk stratification tool to improve clinical decision- making. Further studies are required to validate this diagnostic algorithm
Predictors from systemic and neuro-inflammation in amyotrophic lateral sclerosis: A monocentric experience
No full textWhile the role of systemic and neuroinflammatory players is actually consolidated in amyotrophic lateral sclerosis (ALS) pathogenesis, a representative and reliable panel of inflammatory prognostic biomarkers is still lacking. This retrospective study on 182 ALS patients from the Modena ALS Center, investigates biomarkers of axonal injury (neurofilaments) and microglial and astrocytic activation (SerpinA1, TREM2, CHI3L1, OPN and S100B, respectively). In a subpopulation of patients, we examined blood count-derived parameters, including the Systemic-Immune-Inflammation index (SII), Systemic Inflammation Response Index (SIRI) and Aggregate Systemic Inflammation Index (AISI). All variables were analyzed for association with clinical features in the entire cohort and then in sex- and age-based subgroups. SerpinA1CSF was significantly lower in females [4.43 μg/ml (IQR 2.76–6.3) vs 5.61 μg/ml (IQR 3.39–9.16),p = 0.032], while SII indexes was oppositely distributed [higher in females, 540.67 (IQR 363.05–807.24) vs 384.89 (IQR 307.5–578.52),p = 0.015]. In univariate survival analysis, without overcoming neurofilaments, SIRI (HR 1.43, 95 %CI 1.03–1.966,p = 0.03), AISI (HR 1.002, 95 %CI 1.001–1.003, p = 0.002) and SII (HR 1.001, 95 %CI 1.0003–1.001,p = 0.003) impact negatively on survival, with AISI retaining its power at multivariate analysis (HR 1.002, 95 %CI 1.0004–1.001,p = 0.012). SerpinA1CSF levels influenced survival only for females (HR 1.042, 95 %CI 1.0065–1.078,p = 0.02), in a similar manner of SIRI (HR 1.483, 95 %CI 1.082–2.0334,p = 0.014) and SII (HR 1.00099, 95 %CI 1.0008–1.003,p = 0.001). Our data revealed the influence of sex on survival by SerpinA1CSF, CHI3L1CSF and systemic biomarkers in females. However, both neurofilaments and CHI3L1CSF outperform the other neuroinflammatory biomarkers at predicting rate of disease progression, so the prognostic meaning of these measure alone remains unconclusive, requiring larger collaborative studies
Neurofilaments in motor neuron disorders: towards promising diagnostic and prognostic biomarkers
Full text linkMotor neuron diseases (MNDs) are etiologically and biologically heterogeneous diseases. The pathobiology of motor neuron degeneration is still largely unknown, and no effective therapy is available. Heterogeneity and lack of specific disease biomarkers have been appointed as leading reasons for past clinical trial failure, and biomarker discovery is pivotal in today's MND research agenda.In the last decade, neurofilaments (NFs) have emerged as promising biomarkers for the clinical assessment of neurodegeneration. NFs are scaffolding proteins with predominant structural functions contributing to the axonal cytoskeleton of myelinated axons. NFs are released in CSF and peripheral blood as a consequence of axonal degeneration, irrespective of the primary causal event. Due to the current availability of highly-sensitive automated technologies capable of precisely quantify proteins in biofluids in the femtomolar range, it is now possible to reliably measure NFs not only in CSF but also in blood.In this review, we will discuss how NFs are impacting research and clinical management in ALS and other MNDs. Besides contributing to the diagnosis at early stages by differentiating between MNDs with different clinical evolution and severity, NFs may provide a useful tool for the early enrolment of patients in clinical trials. Due to their stability across the disease, NFs convey prognostic information and, on a larger scale, help to stratify patients in homogenous groups. Shortcomings of NFs assessment in biofluids will also be discussed according to the available literature in the attempt to predict the most appropriate use of the biomarker in the MND clinic
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