Background: The newly discovered intronic repeat expansions in the genes encoding replication factor C subunit 1 ( RFC1 ) and fibroblast growth factor 14 ( FGF14 ) frequently cause late‐onset cerebellar ataxia. Objectives: To investigate the presence of RFC1 and FGF14 pathogenic repeat expansions in Serbian patients with adult‐onset cerebellar ataxia. Methods: The study included 167 unrelated patients with sporadic or familial cerebellar ataxia. The RFC1 repeat expansion analysis was performed by duplex PCR and Sanger sequencing, while the FGF14 repeat expansion was tested for by long‐range PCR, repeat‐primed PCR, and Sanger sequencing. Results: We identified pathogenic repeat expansions in RFC1 in seven patients (7/167; 4.2%) with late‐onset sporadic ataxia with neuropathy and chronic cough. Two patients also had bilateral vestibulopathy. Repeat expansions in FGF14 were found in nine unrelated patients (9/167; 5.4%) with ataxia, less than half of whom presented with neuropathy and two‐thirds with global brain atrophy. Tremor and episodic features were the most frequent additional characteristics in carriers of uninterrupted FGF14 repeat expansions. Among the 122 sporadic cases, 12 (9.8%) carried an expansion in either RFC1 or FGF14 , comparable to 4/45 (8.9%) among the patients with a positive family history. Conclusions: Pathogenic repeat expansions in RFC1 and FGF14 are relatively frequent causes of adult‐onset cerebellar ataxia, especially among sporadic patients, indicating that family history should not be considered when prioritizing ataxia patients for testing of RFC1 or FGF14 repeat expansions.

Background: Biallelic pathogenic variants in the ANO10 gene cause autosomal recessive progressive ataxia (ATX‐ANO10).Methods: Following the MDSGene protocol, we systematically investigated genotype–phenotype relationships in ATX‐ANO10 based on the clinical and genetic data from 82 published and 12 newly identified patients.Results: Most patients (>80%) had loss‐of‐function (LOF) variants. The most common variant was c.1150_1151del, found in all 29 patients of Romani ancestry, who had a 14‐year earlier mean age at onset than patients homozygous for other LOF variants. We identified previously undescribed clinical features of ATX‐ANO10 (e.g., facial muscle involvement and strabismus) suggesting the involvement of brainstem pathology, and we propose a diagnostic algorithm that may aid clinical ATX‐ANO10 diagnosis.Conclusions: The early disease onset in patients with c.1150_1151del may indicate the existence of genetic/environmental disease‐modifying factors in the Romani population. Our findings will inform patient counseling and may improve our understanding of the disease mechanism. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

In neurodegenerative cerebellar ataxias, not only ataxia but also extra-cerebellar signs have a significant impact on patients’ health related to quality of life (HRQoL). The aim of this study was to evaluate the various aspects of HRQoL and predictors of QoL in patients with neurodegenerative cerebellar ataxias. We included a total of 107 patients with cerebellar degenerative ataxia. Patients filled out the validated Serbian version of the SF-36 used for the assessment of HRQoL. All patients were clinically evaluated using SARA, INAS, and neuropsychological tests to assess their global cognitive status and different psychiatric scales. The most frequent types of neurodegenerative cerebellar ataxias were autosomal dominant ataxias (38.3%) and sporadic ataxias (32.7%). Mean age at diagnosis was 35.3 ± 16.23 years, and disease duration was on average 12.1 ± 9.91 years. Mean total SF-36 score was 50.63 ± 20.50. Hierarchical regression analysis showed that in the case of the PHC score, the most significant predictors are the patient’s actual age, severity of ataxia, and ACE total score. For MHC, the Hamilton depression score was the most important predictor. Our study has shown that HRQoL measured by SF-36 in patients with neurodegenerative cerebellar disorders is strongly influenced by impaired mobility and depression.

Background/Objectives: Certain aspects of retinal thickness assessed by optical coherence tomography (OCT) in patients with Parkinson’s disease (PD) require additional clarification. It is supposed that attributing reduced retinal thickness in PD to dopaminergic loss may not be acceptable as it also happens in diseases where dopaminergic loss does not occur. The objective of our study is to compare the ganglion cell/inner plexiform layer (GCIPL), peripapillary retinal nerve fiber layer (pRNFL), and macular thickness of PD and dopa responsive dystonia (DRD) patients with healthy controls (HC), to investigate whether DRD patients, as a distinctive model of genetically induced dopamine deficiency, have reduced retinal thickness in comparison with PD, and to analyze correlation between retinal thickness and various PD clinical parameters. Methods: We analyzed 86 patients with PD, 10 patients with DRD, and 96 age- and sex-matched HC. Results: GCIPL, pRNFL, and central macula thickness (CMT) are statistically significantly thinner in PD patients compared to HC (p < 0.001, all). GCIPL and CMT are also statistically significantly thinner in DRD patients compared to HC (p = 0.012, p = 0.001, respectively). GCIPL thickness correlates positively with the daily dose of levodopa (r = 0.244, p < 0.01). The thickness of GCIPL and pRNFL correlate negatively with current age (r = −0.219; p < 0.01 and r = −0.358; p < 0.05, respectively). All retinal parameters are statistically significantly thinner in females than in males (p < 0.05). Conclusions: Patients with PD and DRD did not differ in GCIPL and pRNFL thickness when compared to one another. These results, supported by positive correlation of levodopa dose and GCIPL thickness in PD patients, emphasize the importance of dopamine in maintaining retinal thickness.

Background/Objectives: Degenerative cerebellar ataxias (DCA) present a group of complex neurological disorders primarily affecting the cerebellum and its pathways. Classic manifestations include motor symptoms of cerebellar ataxia. However, emerging evidence suggests that the cerebellum also plays a crucial role in various cognitive and emotional processes. The objective was to assess the psychiatric profile of a heterogeneous group of patients with degenerative cerebellar ataxia. Methods: Our sample comprised 107 participants diagnosed with cerebellar degenerative ataxia. All patients were clinically evaluated using SARA, INAS, and different neuropsychiatric scales (ACE-R, HAMA, HAMD, AS, and GAF). Results: The majority of patients had autosomal dominant ataxia (38.3%) followed by sporadic ataxia (32.7%) with an average age at the moment of diagnosis of 35.3 ± 16.23 years, while the mean duration of disease at the study beginning was 12.1 ± 9.9 years. Psychiatric disorders were present in 40 patients (37.4%), with dysthymia (14.2%), major depressive disorder (9.4%), and MDD with melancholic features (7.6%). The presence of MDD with melancholic features was statistically significantly correlated with a lower ACE-R total score (r = −0.223; p = 0.022), while dysthymia was statistically significantly associated with a shorter duration of the disease (r = −0.226; p = 0.020) and older age (r = 0.197; p = 0.043). Statistically significant differences were observed between MSA-C patients and those with sporadic ataxia (HDRS p < 0.001, HARS p < 0.001, Apathy Scale p = 0.003, and GAF p = 0.004). Conclusions: Based on our findings, we can conclude that the degree of motor deficit has a significant impact on the development of psychiatric disorders, including depression, anxiety, and apathy. However, it is not the only factor, and the impact also depends on the type of DCA.

Cerebellar neurodegenerative ataxias are a group of disorders affecting the cerebellum and its pathways with different neurological structures. Transcranial sonography (TCS) has been used for the evaluation of brain parenchymal structures in various diseases because of its fast and safe utilization, especially in neuropsychiatric and neurodegenerative diseases. The aim of our study was to investigate TCS characteristics of patients with neurodegenerative cerebellar ataxias. In our study, we included 74 patients with cerebellar degenerative ataxia; 36.5% had autosomal dominant onset, while 33.8% had sporadic onset. Standardized ultrasonographic planes were used for the identification of brain structures of interest. The SARA, INAS, neuropsychological and psychiatric scales were used for the further clinical evaluation of our study participants. The brainstem raphe was discontinued in 33.8% of the patients. The substantia nigra (SN) hyperechogenicity was identified in 79.7%. The third and fourth ventricle enlargement had 79.7% and 45.9% of patients, respectively. A positive and statistically significant correlation was found between SN hyperechogenicity with dystonia (p < 0.01), rigidity and dyskinesia (p < 0.05). The higher SARA total score is statistically significantly correlated with the larger diameter of the III (r = 0.373; p = 0.001) and IV ventricles (r = 0.324; p = 0.005). In such patients, the echogenicity of substantia nigra has been linked to extrapyramidal signs, and raphe discontinuity to depression. Furthermore, ataxia and its clinical subtypes have positively correlated with the IV ventricle diameter, indicating brain atrophy and brain mass reduction.