https://repositorio.fleni.org.ar/xmlui/handle/123456789/20 2026-09-27T04:01:42Z https://repositorio.fleni.org.ar/xmlui/handle/123456789/1590 Unravelling the Global Tapestry of Genetic Ataxias: Epidemiology and Genetic Testing Approaches Rossi, Malco Damián; Stephen, Christopher D.; Damásio, Joana; Pedroso, José Luiz; Kuo, Sheng-Han; Lin, Chi-Ying R.; Ojo, Oluwadamilola; El-Jaafary, Shaimaa; Lee, Woong-Woo; Madoev, Harutyun; Barsottini, Orlando G.; Srivastava, Achal Kumar; Klein, Christine; Van de Warrenburg, Bart The landscape of genetic ataxias is influenced by migration, population genetics, consanguinity, and founder effects, resulting in significant regional variation. Within the expanding domain of genetic ataxias, knowledge of regional epidemiology is scarce, particularly outside of North America and Europe. Understanding the epidemiology of genetic ataxias, together with deep phenotyping and knowledge of the appropriate ancillary studies, is crucial for the development and deployment of diagnostic testing strategies. This review offers a comprehensive, data-driven overview of 2932 articles with regional epidemiological estimates and the occurrence and prevalence of 548 genes associated with ataxia across 122 countries. Regional differences in epidemiology and phenotypic spectra are highlighted, driving an approach that incorporates complementary diagnostic test results and how these may inform cost-effective, region-specific genetic testing. All data are also publicly available as an online database, the MDSGene Global Genetic Ataxia Resource, accessible at https://www.mdsgene.org/ataxia.html. A phenotype-guided, tailored, and sequential testing approach is proposed, based on regional prevalence, to assist clinicians worldwide in diagnosing individuals with presumed genetic ataxia, of which at least 45 causes are treatable. This approach is particularly important in underserved regions, but also in developed countries where health systems limit access to genetic testing, improving the cost-effectiveness and feasibility of genetic testing in these areas. Future screening studies in high-income settings should adopt a more comprehensive approach, integrating broader genetic testing that covers the full range of genetic ataxias. Capacity building for genetic screening in underserved regions, particularly in Africa, South America, and the Middle East, should be prioritized. © 2025 International Parkinson and Movement Disorder Society. 2025-07-18T00:00:00Z https://repositorio.fleni.org.ar/xmlui/handle/123456789/1564 Systematic review of movement disorders mislabeled as functional: when incongruence misleads Marín-Medina, Daniel S.; Miño Zambrano, Joselyn; Espay, Alberto J.; Merello, Marcelo Background: Misdiagnosis of functional movement disorders (FMD) remains a concern for clinicians. We sought to review the phenomenology and clinical features associated with FMD misdiagnosis. Methods: We conducted a systematic review of case reports, case series, and observational studies of adults diagnosed with FMD and subsequently reclassified as having another neurological or medical condition. PubMed was searched from inception to September 13, 2025, focusing on reported features of inconsistency, incongruence with known diseases, and low-validity features. Isolated (iMD) and mixed (mMD) movement disorders were analyzed separately. Results: Forty-two included studies comprised 150 patients, of which 73 cases underwent detailed analysis. Gait disturbance (35%) and dystonia (27.5%) were the most common iMD phenomenologies (n = 40), while jerks and rigidity (24%) were the most common mMD phenomenology (n = 33). Incongruence with known diseases (50.7%), psychological factors (34.2%), and symptom variability (31.5%) were the main factors associated with misdiagnosis. Application of incongruence alone was associated with the highest rate of FMD misdiagnosis, similar to that of applying neither incongruence nor inconsistency (49% in both cases). Conversely, reliance on inconsistency alone was least associated with an FMD misdiagnosis (13.7%). Misdiagnoses of iMD were more likely in the absence of documented inconsistency (OR 3.94, 95% CI 1.32-12.82). Conclusions: FMD misdiagnoses, particularly of gait disorders and dystonia, were most commonly associated with the application of incongruence as diagnostic criterion. The lowest rate of FMD misdiagnosis was associated with ascertaining at least two positive neurological signs of inconsistency. 2026-04-08T00:00:00Z https://repositorio.fleni.org.ar/xmlui/handle/123456789/1556 Early motor response to dopamine replacement therapy in Parkinson's disease patients carrying GBA variants Rossi, Malco Damián; Castillo Torres, Sergio Andrés; Merello, Marcelo Background: Mutations in the glucocerebrosidase (GBA) gene represent the most common genetic risk factor for Parkinson's Disease (PD) and are associated with a more aggressive motor phenotype at late stages. However, the motor response at early stages of disease remains understudied. Methods: Retrospective study of PD patients that underwent next-generation sequencing panel tests for PD-related genes. We extracted demographic data and the MDS-UPDRS III response to an acute levodopa challenge (LDC), the best ON score, and the levodopa equivalent daily dose (LEDD) during the first six months after the LDC and initiation of DRT. We compared the response of GBA-PD patients to that of patients without pathogenic variants or rearrangements in other PD related genes (sporadic PD). Results: 13 GBA-PD and 48 sporadic PD patients were identified. Baseline MDS-UPDRS III score (24.6 ± 9.6 vs. 21.8 ± 9.3. p = 0.4), response to LDC (39.2% ± 7.9% vs. 32.7% ± 13.4%; p = 0.1), best ON score (36.9% ± 39.5% vs. 41.6% ± 20.8%; p = 0.6) and LEDD (188 mg ± 100 mg vs. 261.8 mg ± 164.8 mg; p = 0.2) during the first six months after initiation of DRT were not different between GBA-PD and sporadic PD patients. Conclusions: At early disease stages of GBA-PD, the motor response to acute levodopa challenge test and the initial response to DRT are similar to that of patients with sporadic PD. Although limited by small sample size, these preliminary findings should be confirmed by future prospective larger studies. 2022-09-15T00:00:00Z https://repositorio.fleni.org.ar/xmlui/handle/123456789/1544 Chapter 21 - Role of cerebellum in Parkinson's disease symptoms Varani, Andrés Pablo; Bagliani, María Camila; Rossi, Malco Damián Parkinson's disease is characterized by a variety of motor and non-motor symptoms that arise from different regions of the central nervous system. Growing evidence indicates that pathological alterations in Parkinson's disease extend beyond the basal ganglia to other areas of the brain, such as the cerebellum, even though the nigro-striatal system is primarily affected. It is now recognized that the cerebellum plays a significant role in cognition, sleep, and emotion in addition to its primary function in motor control. Clinical, pathological, neurophysiological, structural, and functional neuroimaging data have been gathered over the last 10 years, and these findings unequivocally demonstrate a connection between Parkinson's disease and the cerebellum. The involvement of the cerebellum in the pathophysiology and clinical features of Parkinson's disease is summarized and updated in this chapter. 2025-12-11T00:00:00Z