Transcranial Sonography Characteristics of Cerebellar Neurodegenerative Ataxias.

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.

RFC1 and FGF14 Repeat Expansions in Serbian Patients with Cerebellar Ataxia.

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.

ANO10-Related Spinocerebellar Ataxia: MDSGene Systematic Literature Review and a Romani Case Series.

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.

The Impact of Demographic and Clinical Factors on the Quality of Life in Patients with Neurodegenerative Cerebellar Ataxias.

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.

Adherence to Medication among Parkinson's Disease Patients Using the Adherence to Refills and Medications Scale.

Objectives: Adherence to medication is an important factor that can influence Parkinson's disease (PD) control. We aimed to explore patients' adherence to antiparkinsonian medication and determine factors that might affect adherence to medications among PD patients. Methods: A cross-sectional, exploratory survey of PD patients treated with at least one antiparkinsonian drug and with a total score of MoCA (Montreal Cognitive Assessment) ≥26 was conducted. The final sample included 112 PD patients. A patient's adherence was assessed through ARMS (Adherence to Refills and Medications Scale). ARMS scores higher than 12 were assumed lower adherence. In addition, each patient underwent neurological examination, assessment of depression, anxiety, and evaluation of the presence of PD nonmotor symptoms. Results: The mean ARDS value in our cohort was 14.9 ± 2.5. Most PD patients (74.1%) reported lower adherence to their medication. Participants in the lower adherence group were younger at PD onset, had significantly higher UPDRS (Unified PD Rating Scale) scores, as well as UPDRS III and UPDRS IV subscores, HARS (Hamilton Anxiety Rating Scale), and NMSQuest (Non-Motor Symptoms Questionnaire for PD) scores compared to the fully adherent group (p=0.013, p=0.017, p=0.041, p=0.043, and p=0.023, respectively). Among nonmotor PD symptoms, the presence of cardiovascular, apathy/attention-deficit/memory disorders, hallucinations/delusions, and problems regarding changes in weight, diplopia, or sweating were associated with lower adherence. Multivariate regression analysis revealed depression as the strongest independent predictor of lower adherence. Conclusion: Depressed PD patients compared to PD patients without clinical depression had a three times higher risk for lower adherence to pharmacotherapy. Recognition and adequate treatment of depression might result in improved adherence.

The correlation between genetic factors and freezing of gait in patients with Parkinson's disease.

BACKGROUND: Clinical-related risk factors to freezing of gait (FOG) in Parkinson's disease (PD) have been identified. Still, the influence of genetic variations on the FOG occurrence has been poorly studied thus far. AIM: We aimed to evaluate the association of six selected polymorphisms of DRD2, ANKK1, and COMT genes with the FOG occurrence and explore the influence of ANNK1/DRD2 haplotypes on the onset of FOG in the group of PD patients. METHOD: PD patients (n = 234), treated with levodopa for at least two years, were genotyped for the rs4680 in COMT, rs6277, rs1076560, and rs2283265 in DRD2, and rs1800497 and rs2734849 polymorphisms in ANKK1 genes. FOG was evaluated by posing a direct question. In addition, a comprehensive set of clinical scales was applied to all patients. RESULTS: FOG occurred in 132 (56.4%) PD patients in our cohort. Freezers were younger at PD onset, had longer disease duration, used higher levodopa daily doses and dopaminergic agents, and had higher motor and non-motor scales scores than non-freezers. FOG was more frequent among AA rs4680 COMT carriers than AG and GG rs4680 COMT carriers. Independent predictors of FOG were: disease duration of more than ten years, levodopa daily dose higher than 500 mg/day, motor status, and COMT AA genotype. AGGAA and GGAAA haplotypes were revealed as protective and vulnerability factors for FOG occurrence. CONCLUSION: In addition to previously identified disease- and therapy-related risk factors, our results suggested a possible contribution of dopamine-related genes to the FOG occurrence.

Autosomal recessive adult onset ataxia.

Autosomal recessive ataxias (ARCA) represent a complex group of diseases ranging from primary ataxias to rare and complex metabolic disorders in which ataxia is a part of the clinical picture. Small number of ARCA manifest exclusively in adulthood, while majority of typical childhood onset ARCA may also start later with atypical clinical presentation. We have systematically searched the literature for ARCA with adult onset, both in the group of primary ataxias including those that are less frequently described in isolated or in a small number of families, and also in the group of complex and metabolic diseases in which ataxia is only part of the clinical picture. We propose an algorithm that could be used when encountering a patient with adult onset sporadic or recessive ataxia in whom the acquired causes are excluded. ARCA are frequently neglected in the differential diagnosis of adult-onset ataxias. Rising awareness of their clinical significance is important, not only because some of these disorders may be potentially treatable, but also for prognostic implications and inclusion of patients to future clinical trials with disease modifying agents.

Social Cognition in Patients With Cerebellar Neurodegenerative Disorders.

OBJECTIVE: Cerebellar neurodegenerative disorders (CDs) are a heterogeneous group of disorders. It is known that the cerebellum plays a role not only in motor, but also in cognitive and social cognitive functions. The aim of this study was to investigate social cognition in patients with different CDs. MATERIALS AND METHODS: Social cognition was examined in 34 patients, 12 with spinocerebellar ataxia type 1 (SCA1), 6 with spinocerebellar ataxia type 2 (SCA2), and 16 with idiopathic late onset cerebellar ataxia (ILOCA). All patients were clinically evaluated using the Scale for the Rating and Assessment of Ataxia. In addition, 34 age, sex, and education-matched healthy control (HC) subjects were similarly analyzed. Social cognition was studied using two tests: the Faux Pas Recognition Test and the Reading the Mind in the Eyes Test (RMET). An appropriate array of neuropsychological tests was used to assess the global cognitive status as well as the frontal functions and mood. RESULTS: CD patients achieved significantly worse results on both tests of social cognition compared to the HCs. The SCA1 + 2 group achieved the poorest results on the Faux Pas Recognition Test and exhibited poor performance on all cognitive tests, but was only significantly worse compared to the ILOCA group on the Free and Cued Selective Reminding Test (FCSRT) - recognition. The patients in the SCA1 + 2 and ILOCA groups obtained similar scores on RMET. In the SCA1 + 2 group the findings significantly correlated with clinical parameters of disease severity and duration and executive functions (EFs), and with mood and executive functions in the ILOCA group. In the SCA group EFs appeared as the only significant predictor of RMET achievement. The Boston Naming Test (BTN) was a significant predictor of the CD patients' achievement on RMET, while the BTN, the Trail Making Test Part A and FCSRT - Delayed free recall predicted their performance on the Faux Pas Recognition Test. CONCLUSION: Patients with CD have social cognitive impairments as demonstrated by the Faux Pas Test and the RMET test results. The SCA1 and 2 patients exhibited a more pronounced impairment compared with the ILOCA patients. The independent cognitive predictors of social cognition impairment were EFs and language.

Clinical and Genetic Analysis of Psychosis in Parkinson's Disease.

BACKGROUND: Recent studies explored polymorphisms of multiple genes as contributing to genetic susceptibility to psychosis in Parkinson's disease (PDP). OBJECTIVE: We aimed to examine the association of seven selected polymorphisms of genes related to dopamine pathways with PDP development. At the same time, demographic and clinical correlates of PDP were assessed. METHODS: PD patients (n = 234), treated with levodopa for at least two years, were genotyped for the rs4680 in COMT, rs6277, rs1076560, and rs2283265 in DRD2, and rs1800497 and rs2734849 polymorphisms in ANKK1 genes. Also, variable number of tandem repeats polymorphism in the DAT gene was examined. Each patient underwent comprehensive neurological examination, assessment of psychosis, as defined by the NINDS/NIMH criteria, as well as screening of depression, anxiety, and cognitive status. RESULTS: Diagnostic criteria for PDP were met by 101 (43.2%) patients. They had longer disease duration, were taking higher doses of dopaminergic agents, and had higher scores of the motor and non-motor scales than the non-PDP group. Multivariate regression analysis revealed LEDD≥900 mg, Unified Parkinson's Disease Rating Scale III part score, the Hamilton Depression Rating Scale score≥7, the Hamilton Anxiety Rating Scale score > 14,and GG homozygotes of rs2734849 ANKK1 as independent predictors of the onset of PDP. CONCLUSION: Besides previous exposure to dopaminergic drugs, impairment of motor status, depression and anxiety, as well-established clinical risk factors for the development of PDP, GG rs2734849 ANKK1 could also be a contributing factor, which requires addressing by future longitudinal studies.