Inclusion of motor evoked abnormalities in amyotrophic lateral sclerosis: a diagnostic algorithm to early classify lower motor neuron phenotypes

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Motor-evoked potentials in amyotrophic lateral sclerosis: potential implications in detecting subclinical UMN involvement in lower motor neuron phenotype

Background: In amyotrophic lateral sclerosis (ALS), the involvement of lower motor neuron is well defined by electromyography, whereas a reliable marker of upper motor neuron (UMN) damage still lacks. Aim of the study was to estimate the role of transcranial magnetic stimulation (TMS)-induced motor-evoked potentials (MEPs) as marker of subclinical UMN involvement. Methods: Clinical evidence of UMN damage was prospectively compared to MEPs in 176 ALS patients diagnosed between 2011 and 2014, and classified according to existing diagnostic criteria. Finally, we evaluated the appearance of clinical UMN signs and the level of diagnostic certainty in ALS after 1 year of follow-up. Results: At presentation, abnormal MEPs were found in 80% of patients with clinical evidence of UMN damage and in 72% of patients without clinical involvement of UMN. Among these latter, 61% showed appearance of UMN clinical signs after 1 year. Approximately 70% of patients with clinical lower motor neuron (LMN) phenotype showed MEP abnormalities, while they were considered not classifiable ALS according to Airlie house or Awaji criteria. Furthermore, abnormal MEPs in absence of clinical UMN signs at baseline were found in 80% of spinal ALS that after 1-year developed UMN signs at limbs, compared to 50% of bulbar ALS. Conclusions: TMS is a reliable marker of subclinical UMN damage particularly among LMN phenotype and ensure an early ALS diagnosis in ~ 70% of such cases

Adherence to riluzole in patients with amyotrophic lateral sclerosis: an observational study

Alessandro Introna, Eustachio D’Errico, Boris Modugno, Antonio Scarafino, Angela Fraddosio, Eugenio Distaso, Irene Tempesta, Antonella Mastronardi, Isabella Laura Simone Neurology Unit, Department of Basic Medical Sciences, Neurosciences and Sense Organs, University of Bari “Aldo Moro,” Bari, Italy Objective: Riluzole is the first drug approved to treat amyotrophic lateral sclerosis (ALS). Recently, an oral suspension (OS) of riluzole was made available. Thus, the aim of our study was to evaluate the adherence to 2 formulations of riluzole in patients with ALS.Patients and methods: We enrolled 45 consecutive patients with ALS. At disease diagnosis, riluzole was prescribed in 2 different formulations depending on the severity of dysphagia (27/45 patients received tablets and 18/45 patients received OS). Side effects (SEs) and treatment adherence were investigated using a clinical questionnaire including the ©Morisky 8-item Medication Adherence Questionnaire.Results: Gastroenteric complaints were the most frequent SEs (58% in the tablet group and 48% in the OS group), followed by those at the nervous system (29% and 40%, respectively). No serious SEs related to treatment were reported. The rate of adherence to riluzole was independent of the formulation of the drug and consistent with other medications assumed for comorbidities (p=0.004). In the tablet group, low adherence was caused by SEs in 55.6% and by dysphagia in 44.4% of patients. In the OS group, SEs caused low adherence in 75% of patients. Independently of the drug formulation, patients with high or medium adherence to riluzole had a higher progression rate (p=0.002 and p=0.009, respectively) and a shorter time to generalization (TTG; p=0.01), compared to those with low adherence.Conclusion: Gastroenteric symptoms were the most frequent SE related to tablet as well as OS. The rate of adherence was independent of the formulation of riluzole and the number of medications assumed for comorbidities, and it was consistent with the severity of the disease. The low adherence was caused by dysphagia and SEs in the tablet group, whereas it was caused prevalently by SEs in the OS group. Keywords: adherence, riluzole, oral suspension, tablet, side effect

Nutritional prognostic factors for survival in amyotrophic lateral sclerosis patients undergone percutaneous endoscopic gastrostomy placement

Objective: There are conflicting data on nutritional factors influencing survival in amyotrophic lateral sclerosis (ALS) patients after percutaneous endoscopic gastrostomy (PEG) placement. We performed an observational cross-sectional study evaluating body mass index (BMI) categories and cholesterol levels as prognostic factors for survival after PEG. Moreover, we assessed body composition in a subgroup of patients to better explain the influence of BMI on survival. Methods: Neurological and nutritional parameters were evaluated at the time of PEG implantation in 47 consecutive patients. Moreover, body composition was evaluated in a subgroup of 22 patients by bioelectrical impedance analysis. Survival was calculated as the time from the PEG placement to death. Results: Underweight patients had a significantly increased risk of death as compared to normal-weight patients using Cox regression analysis [HR = 3.37 (1.29-8.81); p = 0.04]. Similarly, older age at the onset of symptoms significantly increased the risk of death [HR = 1.07 (1.02-1.12); p = 0.001]. Neither overweight/obesity nor hypercholesterolemia affected survival. All ALS patients showed an altered body composition compared to the general population. In addition, a BMI <18.5 kg/m(2) identified patients with a significant reduction of body cell mass (BCM) and phase angle (PhA) compared to patients with normal BMI taken as the reference value. Conclusions: In the later stages of the disease, only a BMI < 18.5 kg/m(2) and older age at symptom onset had a prognostic value on survival. Dyslipidemia did not affect survival. The low BCM and PhA characterizing underweight patients support the role of BMI as a predictor of survival

Multiparametric unconventional MRI study in early stage of ALS disease

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Diagnostic and prognostic power of CSF Tau in amyotrophic lateral sclerosis

Abstract BACKGROUND: Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that still lacks reliable diagnostic biomarkers. This study aims to evaluate the diagnostic and prognostic potential of CSF total Tau (t-Tau), phospho-Tau (p-Tau) and p-Tau/t-Tau ratio in ALS patients using CSF neurofilament light (NFL) as the reference biomarker. METHODS: Eighty-five incident ALS, 30 ALS-mimicking (AM) diseases and 51 other non-neurodegenerative diseases (ONND) were included in the study. RESULTS: ALS patients had higher levels of CSF t-Tau and lower p-Tau/t-Tau ratio than AM (p = 0.005 and p = 0.006) and ONND (p < 0.001). CSF t-Tau levels discriminated ALS from AM with a sensitivity of 69% and specificity of 60%, and from ONND with a sensitivity of 88% and specificity of 51%. These values were lower than the accuracy of CSF NFL in ALS (sensitivity 86% and specificity 87% in distinguishing ALS from AM and sensitivity 83% and specificity 75% from ONND); CSF t-Tau correlated with progression rate and SNIP. CSF p-Tau did not show relation with any ALS clinical features. CSF NFL significantly correlated with all considered clinical parameters. High levels of CSF t-Tau and NFL were related to poor survival. CONCLUSION: CSF t-Tau showed no reliable diagnostic significance but the relation between the high levels of CSF t-Tau and short survival suggests the potential prognostic role of this biomarker in ALS. However, CSF NFL was confirmed to be the most reliable and efficient tool for diagnosis and prediction of clinical progression and survival in ALS patients

A novel KIF5A mutation in an Italian family marked by spastic paraparesis and congenital deafness

Hereditary spastic paraplegia (HSP) includes a group of diseases characterized by progressive spastic weakness of the lower limbs (pure forms) with possible additional signs (complicated forms). The SPG10 form is due to alteration in the kinesin1A gene (KIF5A) that encodes the neuronal kinesin heavy chain, a protein required for the anterograde axonal transport. We performed clinical, neurophysiological and molecular studies in two siblings affected by AD-HSP complicated by deafness. The screening of the KIF5A gene revealed the novel mutation p.Leu259Gln in two affected siblings and in their father with a pure form of HSP. © 2014 Elsevier B.V

Common cardiovascular risk factors and in-hospital mortality in 3,894 patients with COVID-19: survival analysis and machine learning-based findings from the multicentre Italian CORIST Study

Background and aims: There is poor knowledge on characteristics, comorbidities and laboratory measures associated with risk for adverse outcomes and in-hospital mortality in European Countries. We aimed at identifying baseline characteristics predisposing COVID-19 patients to in-hospital death. Methods and results: Retrospective observational study on 3894 patients with SARS-CoV-2 infection hospitalized from February 19th to May 23rd, 2020 and recruited in 30 clinical centres distributed throughout Italy. Machine learning (random forest)-based and Cox survival analysis. 61.7% of participants were men (median age 67 years), followed up for a median of 13 days. In-hospital mortality exhibited a geographical gradient, Northern Italian regions featuring more than twofold higher death rates as compared to Central/Southern areas (15.6% vs 6.4%, respectively). Machine learning analysis revealed that the most important features in death classification were impaired renal function, elevated C reactive protein and advanced age. These findings were confirmed by multivariable Cox survival analysis (hazard ratio (HR): 8.2; 95% confidence interval (CI) 4.6\u201314.7 for age 6585 vs 18\u201344 y); HR = 4.7; 2.9\u20137.7 for estimated glomerular filtration rate levels <15 vs 65 90 mL/min/1.73 m2; HR = 2.3; 1.5\u20133.6 for C-reactive protein levels 6510 vs 64 3 mg/L). No relation was found with obesity, tobacco use, cardiovascular disease and related-comorbidities. The associations between these variables and mortality were substantially homogenous across all sub-groups analyses. Conclusions: Impaired renal function, elevated C-reactive protein and advanced age were major predictors of in-hospital death in a large cohort of unselected patients with COVID-19, admitted to 30 different clinical centres all over Italy