Explore the vast range of titles available.

Background Chronic Dysimmune Polyneuropathies (CDP) encompass a group of conditions characterized by autoimmune etiology targeting myelin and/or axonal components. Subgroups include Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) and paraproteinemic neuropathies associated with IgM monoclonal gammopathy of undetermined significance, with anti-MAG antibodies (IgM-MGUS anti-MAG+) and without anti-MAG antibodies (IgM-MGUS anti-MAG-). Their identification is crucial for determining the most suitable treatment options, yet it poses significant challenges. In this study, an electrophysiological-based automatic classification through machine learning models is proposed. Methods This study included 67 patients, 29 diagnosed with CIDP, 20 with polyneuropathy associated with IgM-MGUS anti-MAG+, and 18 with CIDP-like polyneuropathy associated with IgM-MGUS anti-MAG-. Five different classification algorithms based on electrophysiological data (conduction velocity, latency, and amplitude of sensory and motor responses from different nerves) were implemented to classify three types of neuropathies and identify discriminative neurographic parameters. Results The best performance in stratifying the three classes was achieved by Random Forest in terms of both validation and test accuracy (86.5% and 80.6%). The predictor analysis on the best-performing model revealed the significance of F-wave latencies, distal latencies, and conduction velocities for group discrimination. Conclusions The study is the first to apply computational methods to identify electrophysiological parameters most frequently altered in different forms of polyneuropathy, to support clinical diagnosis and decision-making.

Objectives The aim of the study is to analyze the ALS disease progression and respiratory function of Italian patients treated with edaravone (EVN), as well as the adherence to, and the effects of, the therapy. Methods We performed an observational study of patients treated with EVN from May 2017 to May 2019, in 39 Italian ALS Centers. Taking into account ALS patients with at least 12 months of EVN treatment, we compared the decline of ALSFRS-R and FVC with a group of matched historical controls from the Pooled Resource Open-Access ALS Clinical Trials (PRO-ACT) database, using both descriptive and survival analysis approaches. Results A total of 331 ALS Italian patients treated with EVN and 290 matched historical controls were recruited in this study. No significant differences on disease progression or respiratory function were found comparing the two cohorts in both descriptive and survival analyses. The EVN treatment was overall well tolerated. Conclusions The study showed that EVN treatment was well tolerated. No significant differences were reported in ALS patients treated and not treated with EVN, in terms of both disease progression and respiratory function. These findings prove that further studies are required to better clarify whether EVN could be considered an effective treatment for ALS disease.

The mutations on microtubule associated protein tau (MAPT) gene manifest clinically with behavioural frontotemporal dementia (FTD), parkinsonism, such as progressive supranuclear palsy and corticobasal degeneration, and rarely with amyotrophic lateral sclerosis (ALS). FTD-parkinsonism and FTD-ALS are clinical overlaps included in the spectrum of MAPT mutation’s phenotypes. The mutations on MAPT gene cause the dysfunction of tau protein determining its accumulation in neurofibrillary tangles. Recent data describe frequently the co-occurrence of the aggregation of tau protein and α-synuclein in patients with parkinsonism and Parkinson disease (PD), suggesting an interaction of the two proteins in determining neurodegenerative process. The sporadic description of PD-ALS clinical complex, known as Brait–Fahn–Schwarz disease, supports the hypothesis of common neuropathological pathways between different disorders. Here we report the case of a 54-year-old Italian woman with idiopathic PD later complicated by ALS carrying a novel MAPT variant (Pro494Leu). The variant is characterized by an amino acid substitution and is classified as damaging for MAPT functions. The case supports the hypothesis of tau dysfunction as the basis of multiple neurodegenerative disorders.

ObjectivesTo compare the sensitivity and specificity of the 2021 European Academy of Neurology/Peripheral Nerve Society (EAN/PNS) diagnostic criteria for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) with those of the 2010 European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS).MethodsSensitivity and specificity of the two sets of criteria were evaluated in 330 patients with CIDP and 166 axonal peripheral neuropathy controls. Comparison of the utility of nerve conduction studies with different number of nerves examined and of the sensitivity and specificity of the two criteria in typical CIDP and its variants were assessed.ResultsEFNS/PNS criteria had a sensitivity of 92% for possible CIDP and 85% for probable/definite CIDP, while the EAN/PNS criteria had a sensitivity of 83% for possible CIDP and 74% for CIDP. Using supportive criteria, the sensitivity of the EAN/PNS criteria for possible CIDP increased to 85% and that of CIDP to 77%, remaining lower than that of the EFNS/PNS criteria. Specificity of the EFNS/PNS criteria was 68% for possible CIDP and 84% for probable/definite CIDP, while the EAN/PNS criteria had a specificity of 88% for possible CIDP and 98% for CIDP. More extended studies increased the sensitivity of both sets of criteria by 4%–7% but reduced their specificity by 2%–3%. The EFNS/PNS criteria were more sensitive for the diagnosis of typical CIDP while the EAN/PNS criteria were more specific for the diagnosis of distal and sensory CIDP.ConclusionsIn our population, the EAN/PNS criteria were more specific but less sensitive than the EFNS/PNS criteria. With the EAN/PNS criteria, more extended nerve conduction studies are recommended to obtain an acceptable sensitivity while maintaining a high specificity.

Background and Purpose This study was undertaken to compare the sensitivity and specificity of the 2010 European Federation of Neurological Societies/Peripheral Nerve Society (EFNS/PNS) diagnostic criteria for multifocal motor neuropathy (MMN) with those of the American Association of Electrodiagnostic Medicine (AAEM). Methods Sensitivity and specificity of the two sets of criteria were retrospectively evaluated in 53 patients with MMN and 280 controls with axonal peripheral neuropathy, inflammatory demyelinating polyneuropathy, or amyotrophic lateral sclerosis. Comparison of the utility of nerve conduction studies with different numbers of nerves examined was also assessed. Results The 2010 EFNS/PNS criteria had a sensitivity of 47% for definite MMN and 57% for probable/definite MMN, whereas the AAEM criteria had a sensitivity of 28% for definite MMN and 53% for probable/definite MMN. The sensitivity of the AAEM criteria was higher when utilizing area compared to amplitude reduction to define conduction block. Using supportive criteria, the sensitivity of the 2010 EFNS/PNS criteria for probable/definite MMN increased to 64%, and an additional 36% patients fulfilled the criteria (possible MMN). Specificity values for definite and probable/definite MMN were slightly higher with the AAEM criteria (100%) compared to the EFNS/PNS criteria (98.5% and 97%). Extended nerve conduction studies yielded slightly increased diagnostic sensitivity for both sets of criteria without significantly affecting specificity. Conclusions In our patient populations, the 2010 EFNS/PNS criteria demonstrated higher sensitivity but slightly lower specificity compared to the AAEM criteria. Extended nerve conduction studies are advised to achieve slightly higher sensitivity while maintaining very high specificity.

ObjectivesAnti-myelin-associated glycoprotein (MAG) antibody is associated with clinically heterogeneous polyneuropathies. Our purpose was to compare neuropathy phenotypes identified by different anti-MAG tests’ results.MethodsCohort study: Sera from 40 neuropathy anti-MAG EIA positive patients were tested for anti-MAG by Western blot (WB), for anti-peripheral nerve myelin (PNM) on monkey nerve by immunofluorescence assay (IFA), and for anti-HNK1 on rat CNS slices by IFA. Anti-sulfatide antibodies, for comparison, were also tested by EIA.ResultsAmong 40 anti-MAG EIA positive sera, 85% also had anti-PNM IFA reactivity and 67.5% bind HNK1 on rat CNS. Anti-HNK1 positive patients had the classical predominantly distal acquired demyelinating symmetric (DADS) neuropathy with a benign course, while anti-PNM positive but anti-HNK1 negative patients had predominantly axonal neuropathy with a high frequency of anti-sulfatide reactivity and the worst long-term prognosis. Anti-MAG EIA positive patients without anti-PNM or anti-HNK1 IFA reactivity had a CIDP-like polyneuropathy.ConclusionDifferent methods to test for anti-MAG antibodies identify different clinical and electrophysiological findings, as well as long-term outcome. HNK1 reactivity is the strongest marker of DADS.

Background Multifocal motor neuropathy (MMN) is a rare motor neuropathy diagnosed by identifying motor conduction block (CB), which may be absent or transient. This study aimed to evaluate nerve conduction abnormalities beyond CB and their diagnostic value. Methods A retrospective analysis included patients fulfilling the 2010 EFNS/PNS clinical criteria for MMN and controls with axonal polyneuropathy, lower motor neuron disease, or chronic inflammatory demyelinating polyradiculoneuropathy (CIDP). Electrophysiological studies evaluated motor distal latency prolongation, reduced motor conduction velocity, prolonged F‐wave latency, absence of F‐waves, abnormal temporal dispersion, and distal CMAP duration prolongation. The 2010 EFNS/PNS criteria for MMN were compared to an ‘extended’ set incorporating additional electrophysiological parameters. Results A total of 70 MMN patients and 359 controls were included. At least one nerve conduction abnormality, excluding motor CB, was detected in one or more nerve segments unaffected by CB in 71% of MMN patients, significantly more frequently than in axonal polyneuropathy or lower motor neuron disease patients. These parameters included abnormal temporal dispersion (47%), distal CMAP duration prolongation (31%), reduced motor conduction velocity (26%), absence of F‐waves (9%), prolonged F‐wave latency (6%), and motor distal latency prolongation (3%). Incorporating these parameters increased sensitivity for diagnosing probable/definite MMN by 26% (p < 0.001; compared to EFNS/PNS criteria), with minimal impact on specificity, even when compared to CIDP patients. Conclusion Including additional electrophysiological parameters into the diagnostic criteria for MMN may enhance diagnostic sensitivity while maintaining comparable specificity. The observation of nerve conduction abnormalities beyond CB indicates a broader electrophysiological profile for MMN. This multicenter study shows that nerve conduction abnormalities beyond conduction block occur frequently in multifocal motor neuropathy (MMN). These abnormalities are more prevalent than in axonal polyneuropathies or amyotrophic lateral sclerosis and involve nerves unaffected by conduction block. Incorporating these findings into diagnostic criteria increases sensitivity by 26% with minimal impact on specificity. The results support expanding electrodiagnostic definitions to better reflect the broader electrophysiological spectrum of MMN.

ALCAR (Acetyl-L-carnitine) is a donor of acetyl groups and increases the intracellular levels of carnitine, the primary transporter of fatty acids across the mitochondrial membranes. In vivo studies showed that ALCAR decrease oxidative stress markers and pro-inflammatory cytokines. In a previous double-blind placebo-controlled phase II trial showed positive effects on self-sufficiency (defined as a score of 3+ on the ALSFRS-R items for swallowing, cutting food and handling utensils, and walking) ALSFRS-R total score and FVC. We conducted an observational, retrospective, multicentre, case–control study to provide additional data on the effects of ALCAR in subjects with ALS in Italy. Subjects treated with ALCAR 1.5 g/day or 3 g/day were included and matched with not treated subjects by sex, age at diagnosis, site of onset, and time from diagnosis to baseline, (45 subjects per group). ALCAR 3 g/day vs not treated: 22 not treated subjects (48.9%) were still alive at 24 months after baseline, compared to 23 (51.1%) treated subjects (adj. OR 1.18, 95% CI 0.46–3.02). No statistically significant differences were detected in ALSFRS nor FVC nor self-sufficiency. ALCAR 1.5 g/day vs not treated: 22 not treated subjects (48.9%) were still alive at 24 months after baseline, compared to 32 (71.1%) treated subjects (adj. OR 0.27, 95% CI 0.10–0.71). For ALSFRS-R, a mean slope of − 1.0 was observed in treated subjects compared to − 1.4 in those not treated ( p  = 0.0575). No statistically significant difference was detected in the FVC nor self-sufficiency. Additional evidence should be provided to confirm the efficacy of the drug and provide a rationale for the dosage.

To study the possible implication of the two biomarkers, intermediate alleles (IAs) of the Huntingtin (HTT) gene and neurofilament light chain (NfL) levels in plasma, in amyotrophic lateral sclerosis (ALS) patients. We analyzed IAs in a cohort of 106 Italian ALS patients and measured the plasma NfL levels in 20% of the patients of the cohort. We correlated the two biomarkers with clinical phenotypes. Intermediate alleles were present in 7.5% of the patients of our cohort, a frequency higher than that reported in general population. Plasma NfL levels increased with age at onset ( < 0.05). Patients with bulbar onset (BO) had higher plasma NfL concentration (CI -0.61 to -0.06, = 0.02) and a later age at onset of the disease (CI -24.78 to -4.93, = 0.006) with respect to the spinal onset (SO) form. Additionally, two of the patients, with IAs and plasma NfL concentration lower with respect to normal alleles' carriers, presented an age at onset higher than the mean of the entire cohort. According to our findings, plasma NfL and IAs of HTT gene may represent potential biomarkers in ALS, providing evidence of a possible implication in clinical phenotype.