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The phosphorylated neurofilament heavy chain (pNfH) is a promising biomarker in amyotrophic lateral sclerosis (ALS). We examined plasma pNfH concentrations in order to corroborate its role as a diagnostic and prognostic biomarker in ALS. Incident ALS cases enrolled in a population-based registry were retrospectively selected and matched by sex and age with a cohort of healthy volunteers. Plasma pNfH levels were measured by an ELISA kit and correlated with clinical parameters. Discrimination ability of pNfH was tested using receiving operating characteristic (ROC) curves. Kaplan-Meier (KM) analysis and Cox proportional hazard models were used for survival analysis. Plasma pNfH was significantly higher in patients compared to controls. An optimal cut-off of 39.74 pg/ml discriminated cases from controls with an elevated sensitivity and specificity. Bulbar-onset cases had higher plasma pNfH compared to spinal onset (p = 0.0033). Furthermore, plasma pNfH positively correlated with disease progression rate (r = 0.19, p = 0.031). Baseline plasma pNfH did not influence survival in our cohort. Our findings confirmed the potential utility of plasma pNfH as a diagnostic biomarker in ALS. However, further studies with longitudinal data are needed to corroborate its prognostic value.

Background and purpose A strong association between time to generalization (TTG), considered as the time of spreading of the clinical signs from spinal or bulbar localization to both, and survival was recently identified in patients with amyotrophic lateral sclerosis (ALS). Thus, TTG may be used as an early to intermediate end-point in survival studies. The aim of the present study was to test TTG as a predictor of survival in ALS. Methods This was an observational retrospective study of ALS patients from a tertiary referral centre over a 5-year follow-up period. Results In 212 ALS patients, TTG was associated with time to death/tracheostomy [R 0.62, 95% confidence interval (CI) 0.53–0.70; P < 0.001]. In a time-to-event analysis, longer TTG resulted in lower risk to reach a composite outcome (death or tracheostomy) both in univariate [hazard ratio (HR) 0.98, 95% CI 0.97–0.99] and multivariate Cox analyses (HR 0.98, 95% CI 0.96–0.99). TTG predicted death/tracheostomy at 4 years (C-statistic 0.58; 95% CI 0.53–0.63) and at 5 years (C-statistic 0.58; 95% CI 0.53–0.62). Conclusions Based on the present results from a large clinical cohort, TTG may be used as a new early to intermediate end-point to describe the ALS natural history. TTG may be potentially useful as a new primary outcome measure for clinical trials.

Background To date there are no biomarkers with proven reliability as a measure of disease burden in amyotrophic lateral sclerosis (ALS). The aim of our study is to assess the neurofilament light chain (NFL) in cerebrospinal fluid (CSF) samples as a measure of disease activity and progression in ALS. Methods Thirty-seven consecutive patients with ALS, 25 with chronic inflammatory demyelinating polyneuropathy and 21 with other neurodegenerative diseases were evaluated. CSF NFL levels were assayed by two-site solid-phase sandwich ELISA. In patients with ALS, neurological status was assessed by the revised ALS Functional Rating Scale (ALSFRS-r) and the Medical Research Council scale, and the progression of the disease was evaluated using the ‘diagnostic delay’ and the ‘progression rate’. Results Cerebrospinal fluid NFL levels were higher in ALS cases than in controls (P

Sir, Progressive muscular atrophy is a motor neuron disease (MND) characterized by selective lower motor neuron involvement [1]. MND pathogenesis is unknown and different mechanisms, including oxidative stress, may be involved [2]. Mitochondrial (mt) abnormalities have been observed in motor neurons of patients with MND [2], and MND patients carrying pathogenic mtDNA alteration have been reported [3]. A 63-year-old woman presented with a 4-year history of proximal upper limb muscle weakness and hypotrophy. Informed consent was obtained. Neurological examination revealed muscle weakness, hypotrophy and fasciculations with the absence of deep tendon reflexes in upper limbs. Cranial nerves and lower limbs function were normal. Laboratory examinations, SOD1, and SMA analysis were normal. Electromyography of the four limb muscles showed diffuse chronic denervation with fibrillations. Motor, sensory evoked potentials were normal. Magnetic Resonance Imaging (MRI) of brain was normal, whilst MRI of the spinal cord revealed cervical and lumbar disks protrusion. The muscular weakness slowly