Epidemiology of amyotrophic lateral sclerosis in the north east Tuscany in the 2018-2021 period.

Background: The incidence of Amyotrophic Lateral Sclerosis (ALS) varies among different geographical areas and seems to increase over time. This study aimed to examine the epidemiologic data of ALS in the north-east Tuscany and compare the results with those of similar surveys. Methods: Data from ALS cases diagnosed in Florence and Prato Hospitals were prospectively collected from 1st June 2018 to 31st May 2021. Results: The age- and sex-adjusted incidence rate of ALS in cases per 100,000 population was 2.71 (M/F ratio: 1.21), significantly higher as compared to that reported in the 1967-1976 decade in the same geographical area (0.714). The age- and sex-adjusted incidence rate among resident strangers was similar to that of the general population (2.69). A slightly higher incidence rate (4.36) was observed in the north-east area of Florence province, which includes the Mugello valley. The mean prevalence was of 7.17/100,00. The mean age at diagnosis was 69.7 years, with a peak between 70 and 79 years among men and a smoother age curve among women. Conclusions: ALS epidemiological features in north-east Tuscany are in line with other Italian and European Centers. The dramatic increase of the local disease burden over the last decades probably reflects better ascertainment methods and health system.

Neurofilament Light Chain and Intermediate HTT Alleles as Combined Biomarkers in Italian ALS Patients.

OBJECTIVE: 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. METHODS: 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. RESULTS: 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 (p < 0.05). Patients with bulbar onset (BO) had higher plasma NfL concentration (CI -0.61 to -0.06, p = 0.02) and a later age at onset of the disease (CI -24.78 to -4.93, p = 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. CONCLUSION: 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.

Polyneuropathy and monoclonal gammopathy of undetermined significance (MGUS); update of a clinical experience.

BACKGROUND AND PURPOSE: Polyneuropathies associated with monoclonal gammopathy of undetermined significance (MGUS) encompass a group of phenotypically and immunologically heterogeneous neuropathies. While the best characterized is that associated with anti-myelin glycoprotein (MAG) antibodies, there are phenotypical and immunological neuropathy variants that still lack a clear classification. We analyzed a significant number of patients, in order to better evaluate the distribution of neuropathy phenotypes and to look for some common characteristics. METHODS: Clinical, neurophysiological, and laboratory data from 87 consecutive MGUS patients with peripheral neuropathy were analyzed and compared among patient groups with different MGUS classes and autoantibody reactivity. RESULTS: Anti-MAG neuropathy cases account for the most homogeneous group with regard to clinical and neurophysiological findings. Patients with anti-gangliosides or sulfatide (GS) antibodies, despite a marked phenotype heterogeneity, still share several common features, including a younger age at diagnosis, a more severe disease, and a prompt and sustained response to both immunoglobulin and rituximab therapies, mostly requiring chronic administration of immune treatment. CONCLUSIONS: Although heterogeneous, MGUS-associated, anti-GS antibody positive neuropathies have important similar features possibly resulting from a similar biological background.

Anti-MAG IgM: differences in antibody tests and correlation with clinical findings.

OBJECTIVES: Anti-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. METHODS: Cohort 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. RESULTS: Among 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. CONCLUSION: Different 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.

Association of the New Variant Tyr424Asp at TBK1 Gene with Amyotrophic Lateral Sclerosis and Cognitive Decline.

A new risk gene associated with amyotrophic lateral sclerosis (ALS) has recently been identified: the Tank-binding kinase 1 (TBK1) gene. Up to now, 90 TBK1 variants have been described in ALS patients with or without frontotemporal dementia (FTD), thus making TBK1 the third or fourth most frequent genetic cause of ALS and FTD. A point mutation analysis in a cohort of 69 Italian ALS patients was performed in order to analyze the frequency of TBK1 mutations and the correlation with clinical phenotypes. The analysis identified the novel variant p.Tyr424Asp in a patient with a rapid progression of the disease. Our data supports the implication of TBK1 in ALS pathogenesis in Italy.