Eustachio D'Errico

Elevated cerebrospinal fluid neurofilament light levels in patients with amyotrophic lateral sclerosis: a possible marker of disease severity and progression

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.

Cerebrospinal fluid neurofilament light chain levels: marker of progression to generalized amyotrophic lateral sclerosis

To evaluate whether cerebrospinal fluid (CSF) neurofilament light chain (NFL) levels could predict the time to generalization (TTG) in amyotrophic lateral sclerosis (ALS).

Amyotrophic lateral sclerosis: a new missense mutation in the SOD1 gene

Copper-zinc superoxide dismutase-1 (SOD1) is the second most common mutated gene in amyotrophic lateral sclerosis (ALS). To date more than 150 missense mutations of SOD1 have been reported. The objective of this study was to describe a novel SOD1 mutation and its phenotypic expression. We describe a 74-year-old Caucasian man who began to complain of progressive weakness and atrophy of the right hand and over 10 months developed a severe tetraparesis, with atrophies of upper and lower limbs and neck muscles, dysphagia, and dyspnea that led to percutaneous endoscopic gastrostomy and tracheotomy. A diagnosis of ALS was made. Genetic analysis identified a heterozygous mutation in exon 4 of SOD1 that results in the amino acid substitution from arginine to cysteine at position 115 (p.R115C). We identified a novel pathogenic SOD1 mutation in a patient with a very rapid disease progression and aggressive phenotype providing additional information on the wide range of SOD1 mutations in apparently sporadic ALS and confirming the possibility of a strong genotype-phenotype correlation for distinct SOD1 mutations.

Laser evoked potentials in amyotrophic lateral sclerosis

The pathophysiological mechanism of the pain in ALS is still unclear. The aim of the study was to evaluate the laser evoked potentials (LEPs) in ALS patients in relation to their clinical features. Twenty-four ALS patients were selected. Pain features were assessed and their intensity was measured by a 0-10 VAS. LEPs were recorded in all patients and in 23 healthy subjects. The dorsum of both hands was stimulated, at laser stimuli intensity of 7.5 W, with 10s inter-stimulus interval and 25 ms duration. Four electrodes were placed at Cz, T3, T4 and Fz positions, with the reference electrode at the nasion; T3 and T4 electrodes were referred off-line to Fz, in order to detect the N1 component. Latencies of N2, P2 and N1 waves were significantly higher in ALS than in controls. N1 amplitude was significantly increased in ALS patients compared to controls, with a similar trend for the N2-P2 complex. No correlation was found between LEP abnormalities, pain intensity and clinical features. A degeneration of subcortical structures may subtend a delay in the afferent input to the nociceptive cortex in ALS. On the other hand, an increase of pain processing at the cortical level may derive from a potential sensory compensation to motor cortex dysfunction.

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.

Time to generalisation as a predictor of prognosis in amyotrophic lateral sclerosis

In amyotrophic lateral sclerosis (ALS), prognosis is usually based on death or tracheostomy as outcomes. Nevertheless, the early course is known to be a reliable indicator of the whole course of the disease.1 The identification of outcomes in early stages would determine better planning of interventions and more appropriate stratification of newly diagnosed patients for randomised clinical trials (RCTs). The time of disease spread is probably linked to the rate of progression and the intensity of neuro-axonal degeneration,2 and it has already been related to survival in ALS.3 The aim of the present study was to evaluate if time to generalisation (TTG) may predict survival in ALS. All patients with a diagnosis of possible, probable or definite ALS, according to El Escorial criteria,4 and an onset of the disease between January 2004 and December 2007, referred to the Centre of Motor Neuron Disease, University of Bari, were enrolled in the current study. The study was terminated in April 2012. Death or tracheostomy was used as outcome measure to study the 4-year and 5-year mortality. Considered clinical variables were: (1) age at symptom onset (AAO); (2) site of symptom onset (bulbar region or spinal region); (3) time of diagnosis; (4) onset-diagnosis interval (ODI), defined as the time from the onset of the first symptom to diagnosis of ALS; (5) score of the revised ALS Functional Rating Scale (ALSFRS-r) at baseline;5 (6) TTG, considered as the time of spreading of the clinical signs from spinal (cervical, thoracic, or lumbosacral regions), or bulbar localisation or both. To detect generalisation, all the lower and upper motor neuron signs listed in the El Escorial criteria for the four body regions were investigated;4 TTG was censored at the time of the last follow-up visit; (7) overall survival (OS), defined as …

Time to generalization and prediction of survival in patients with amyotrophic lateral sclerosis: a retrospective observational study.

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.

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

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.