Our aim was to assess the incidence, survival and its prognostic factors in ALS patients from the area of the City of Belgrade, Serbia. A retrospective analysis included 325 probable or definite ALS cases from all five Belgrade neurology departments in the period 1992–2009. Each patient was regularly followed up during the disease until death or until 31 December 2009. Results showed that the average annual ALS incidence rate was 1.11 per 100,000 inhabitants. Male predominance was registered, except for patients with ALS onset after the age of 80 years. Mean survival from the first symptoms was 4.4 ± 0.2 years. Cumulative probability of survival was 71% for two years, 24% for five years, and 17% for seven years. Patients with diagnostic delay longer than 1.6 years had a 1.4-times better chance for survival (p <0.01). Spinal-onset patients on riluzole therapy had 1.8-times better survival (p < 0.01). Patients with early-onset ALS and higher ALSFRS-R score at initial evaluation also had somewhat better survival (p < 0.05). In conclusion, the average annual ALS incidence rate was 1.11 per 100,000 inhabitants. Longer survival was observed in patients with early onset, longer diagnostic delay, less functional impairment at the time of diagnosis, and riluzole treatment.

Innate and adaptive immune responses exert their role in CIDP pathogenesis through cytokine production. Single-nucleotide polymorphisms (SNPs) may alter cytokine gene expression, with a potential influence on the pathogenesis of autoimmune diseases. However, cytokine gene SNPs have not been assessed in CIDP patients yet. We assessed functional SNPs in the genes encoding IL-10 (rs1800896, rs1800871, rs1800872 and rs3024505), IL-6 (rs1800795), TNF (rs1800629 and rs361525), IL-12B (rs3212227), IFN-γ (rs2430561), GM-CSF (rs25882) and IL-17F (rs11465553) in a cohort of 88 CIDP patients and 486 healthy controls (HCs) via qPCR. We found an association of SNP in the IL10 promotor and CIDP occurrence. Major homozygotes (AA) were more frequent in the HCs compared to CIDP patients (p = 0.049), but the GA genotype prevailed among the patients (p = 0.032). A lower frequency of the C allele was observed for rs1800871 and rs1800872 in CIDP patients compared to the HCs (p = 0.048). A higher proportion of A carriers at position -1082 (rs1800896) (presumed to be a low IL-10 producer) was noted in patients with milder disability (low INCAT). All mild-INCAT patients were C carriers for rs1800871 and rs1800872 in IL10 (p = 0.038). Furthermore, the IL6 rs1800795 GG genotype was more frequent in patients (p = 0.049) and the CG heterozygote in the HCs (p = 0.013). Among the CIDP patients, being a G carrier for this SNP was associated with a higher frequency of type 2 diabetes (T2D) compared to being a non-carrier (p = 0.032). Our data indicate a possible association of the IL10 and IL6 SNPs with CIDP, but also with disease severity and T2D occurrence. Given the paucity of CIDP patients, multicentric studies are necessary to draw definite conclusions on these associations.

Introduction: Our trial (ClinicalTrials.gov Identifier: NCT04246619) evaluates the efficacy of two generic medications, pregabalin and duloxetine, for treating pain in PDPN patients. Methods: The patients were randomised either into the pregabalin (99) or the duloxetine (102) arm. Pain was evaluated using the DN-4 questionnaire, and visual analogue scales (VASs, 0–100 mm) were used to measure the average pain intensity (API), worst pain intensity (WPI) in the last 24 h and current pain intensity (CPI). Results: The proportion of patients with a clinically significant improvement in the API at Week 12 was 88.3% [CI 81.7%, 94.8%] in the pregabalin arm and 86.9% [CI 76.7%, 97.1%] in the duloxetine arm. After 12 weeks, the CPI, API, and WPI decreased by −35.3 [−40.5, −30.0], −37.0 [−41.4, −32.6], and −41.6 [−46.6, −36.5] in the pregabalin arm, and by −35.0 [−39.2, −30.7], −36.9 [−41.5, −32.3], and −40.0 [−44.8, −35.2] in the duloxetine arm (all in mm, all p < 0.001). Conclusion: Our results demonstrate that pregabalin and duloxetine are effective medications for treating pain in PDPN in more than 86% of all randomised patients.

Hereditary spastic paraplegia (HSP) is among the most genetically diverse of all monogenic diseases. The aim was to analyze the genetic causes of HSP among adult Serbian patients. The study comprised 74 patients from 65 families clinically diagnosed with HSP during a nine-year prospective period. A panel of thirteen genes was analyzed: L1CAM (SPG1), PLP1 (SPG2), ATL1 (SPG3A), SPAST (SPG4), CYP7B1 (SPG5A), SPG7 (SPG7), KIF5A (SPG10), SPG11 (SPG11), ZYFVE26 (SPG15), REEP1 (SPG31), ATP13A2 (SPG78), DYNC1H1, and BICD2 using a next generation sequencing-based technique. A copy number variation (CNV) test for SPAST, SPG7, and SPG11 was also performed. Twenty-three patients from 19 families (29.2%) had conclusive genetic findings, including 75.0% of families with autosomal dominant and 25.0% with autosomal recessive inheritance, and 15.7% of sporadic cases. Twelve families had mutations in the SPAST gene, usually with a pure HSP phenotype. Three sporadic patients had conclusive findings in the SPG11 gene. Two unrelated patients carried a homozygous pathogenic mutation c.233T>A (p.L78*) in SPG7 that is a founder Roma mutation. One patient had a heterozygous de novo variant in the KIF5A gene, and one had a compound heterozygous mutation in the ZYFVE26 gene. The combined genetic yield of our gene panel and CNV analysis for HSP was around 30%. Our findings broaden the knowledge on the genetic epidemiology of HSP, with implications for molecular diagnostics in this region.

Introduction. Histopathological findings of various inclusions were reported in the central nervous system of amyotrophic lateral sclerosis (ALS) patients, but not in the peripheral nerves. Case report. Our patient was a 66-year-old man with lower limb weakness later involvement of upper limbs, and loss of sphincter control. Neurological examination showed affection of both upper and lower motor neurons. He had paresthesia of the left side of his body and socks-distribution numbness. Histopathology of the sural nerve and genetic report showed basophilic periodic acid-Schiff (PAS)-positive intra-axonal inclusions and heterozygous L144F mutation in the exon 5 of the SOD1 gene. Conclusion. It seems that presence of the basophilic peripheral nerve inclusions may suggest diagnosis of SOD1 positive ALS.