Amyotrophic lateral sclerosis (ALS) is a devastating, uniformly lethal degenerative disease of motor neurons, presenting with relentlessly progressive muscle atrophy and weakness. More than fifty genes carrying causative or disease-modifying variants have been identified since the 1990s, when the first ALS-associated variant in the gene SOD1 was discovered. The most commonly mutated ALS genes in the European populations include the C9orf72, SOD1, TARDBP and FUS. Understanding the genetic causes of ALS within a population is becoming more significant, especially in light of the possible development of personalized medicine. Here, we provide clinical and genetic data on familial and sporadic ALS patients in a Greek-Cypriot population-based cohort. Eighty-nine ALS patients, including 21 familial ALS (fALS) (23.6%) and 68 sporadic ALS (sALS) (76.4%), provided the cohort for variant screening of the most common ALS-associated genes. Moreover, next-generation sequencing (NGS) was also performed to identify rare ALS variants, and in silico prediction tools were applied to predict the downstream effect of the variants detected in our study. The pathogenic hexanucleotide G₄C₂ repeat expansion in C9orf72 was the predominant genetic cause (22.47%) of ALS in our population, while variants in six additional ALS-associated genes were identified, including ALS2, TARDBP, FIG4, TBK1, GLT8D1, and BICD2.

Introduction: Amyotrophic lateral sclerosis (ALS) is a devastating, uniformly lethal degenerative disease of motor neurons, presenting with relentlessly progressive muscle atrophy and weakness. The etiology of ALS remains unexplained for over 85% of all cases, suggesting that besides the genetic basis of the disease, various environmental factors are implicated in the pathogenesis of ALS. This study aimed to investigate the contribution of known environmental risk factors of ALS in the Cypriot population.Methods: We conducted a case–control study with a total of 56 ALS cases and 56 healthy gender/age-matched controls of Cypriot nationality. Demographic, lifestyle characteristics, medical conditions, and environmental exposures were collected through the use of a detailed questionnaire. Statistical analyses using the R programming language examined the association between the above environmental factors and ALS.Results: A chi-square test analysis revealed a statistically significant (p = 0.000461) difference in smoking status between the two groups. In addition, univariate logistic regression analysis showed a statistically significant association between ALS cases for head trauma/injury (p = 0.0398) and exposure to chemicals (p = 0.00128), compared to controls.Conclusion: This case–control investigation has shed some light on the epidemiological data of ALS in Cyprus, by identifying environmental determinants of ALS, such as smoking, head trauma, and chemical exposure, in the Cypriot population.

Parkinson’s Disease (PD) is a multifactorial neurodegenerative disease characterized by motor and non-motor symptoms. The etiology of PD remains unclear. However, several studies have demonstrated the interplay of genetic, epigenetic, and environmental factors in PD. Early-onset PD (EOPD) is a subgroup of PD diagnosed between the ages of 21 and 50. Population genetic studies have demonstrated great genetic variability amongst EOPD patients. Hence, this study aimed to obtain a genetic landscape of EOPD in the Cypriot population. Greek-Cypriot EOPD patients (n = 48) were screened for variants in the six most common EOPD-associated genes (PINK1, PRKN, FBXO7, SNCA, PLA2G6, and DJ-1). This included DNA sequencing and Multiplex ligation-dependent probe amplification (MLPA). One previously described frameshift variant in PINK1 (NM_032409.3:c.889del) was detected in five patients (10.4%)—the largest number to be detected to date. Copy number variations in the PRKN gene were identified in one homozygous and 3 compound heterozygous patients (8.3%). To date, the pathogenic variants identified in this study have explained the PD phenotype for 18.8% of the EOPD cases. The results of this study may contribute to the genetic screening of EOPD in Cyprus.

Introduction: Restless Legs Syndrome (RLS) is a sensorimotor disorder characterized by an irresistible urge to move the legs. When resistant to pharmacological and psychotherapeutic treatments, RLS remains highly debilitating. This case study represents the first documented case of Transcranial Pulse Stimulation (TPS) applied in treatment-resistant RLS, exploring its feasibility, tolerability, and potential clinical effects. Methods: A 56-year-old male diagnosed with RLS with severe, persistent bilateral leg restlessness and neuropathic cramping pain underwent six sessions of TPS target cortical and subcortical network hubs within the Functional Network-Oriented Neuromodulation (FNON) framework. Results: At six-week follow-up, the patient reported improved sleep, a 95.2% reduction in RLS severity, a 66.7% decrease in pain/discomfort, and a 25% improvement in overall health status. Depression/Anxiety symptoms decreased by 25% while mobility and self-care remained stable at normal levels. Conclusion: In this single case, TPS was well tolerated and associated with meaningful symptomatic improvement. While no conclusions regarding safety or efficacy can be drawn from an individual observation, these findings suggest that TPS may warrant further investigation as non-invasive neuromodulatory approach for refractory RLS. This report expands the scientific literature by introducing a novel network-based neuromodulation modality to the RLS field and provides a foundation for future controlled studies to validate efficacy and optimize stimulation protocols.

Introduction: Cranial Electrotherapy Stimulation (CES) is a non-invasive brain stimulation (NIBS) technique used for anxiety and sleep disorders; however, case-level evidence linking clinical improvement with objective neurophysiological change remains limited. This case presents a multimodal examination of the therapeutic and neurophysiological effects of CES in a patient with sleep disturbances and chronic stress. Methods: A 51-year-old woman with chronic stress, anxiety, and persistent sleep disturbance following thyroid and parathyroid surgery, refractory to pharmacological treatment, underwent a 16-week CES intervention. Outcomes were assessed at baseline and follow-up using EQ-5D-5L, DASS-21, GAD-7, PSQI, and resting-state Electroencephalography (EEG). Results: Anxiety, stress, and depressive symptoms improved to within normal ranges, alongside significant improvements in mental health-related quality of life. EEG demonstrated increased posterior alpha activity and improved frontal symmetry. Sleep quality showed modest improvement. Conclusion: This case suggests that CES may be a safe adjunctive intervention associated with symptomatic improvement and changes in neurophysiological patterns in stress-related conditions, supporting further controlled investigation.