Performance of ChatGPT 3.5 and 4 as a tool for patient support before and after DBS surgery for Parkinson's disease.

Deep brain stimulation (DBS) is a neurosurgical procedure that involves implanting electrodes into specific areas of the brain to treat a variety of medical conditions, including Parkinson's disease. Doubts and questions from patients prior to or following surgery should be addressed in line with the most recent scientific and clinical practice. ChatGPT emerges as an example of how artificial intelligence can be used, with its ability to comprehend and answer medical questions in an understandable way, accessible to everyone. However, the risks of these resources still need to be fully understood.ChatGPT models 3.5 and 4 responses to 40 questions in English and Portuguese were independently graded by two experienced specialists in functional neurosurgery and neurological movement disorders and resolved by a third reviewer. ChatGPT 3.5 and 4 demonstrated a good level of accuracy in responding to 80 questions in both English and Portuguese, related to DBS surgery for Parkinson's disease. The proportion of responses graded as correct was 57.5% and 83.8% for GPT 3.5 and GPT 4, respectively. GPT 3.5 provided potentially harmful answers for 6.3% (5/80) of its responses. No responses from GPT 4 were graded as harmful. In general, ChatGPT 3.5 and 4 demonstrated good performance in terms of quality and reliability across two different languages. Nonetheless, harmful responses should not be scorned, and it's crucial to consider this aspect when addressing patients using these resources. Considering the current safety concerns, it's not advisable for patients to use such models for DBS surgery guidance. Performance of ChatGPT 3.5 and 4 as a tool for patient support before and after DBS surgery for Parkinson's disease.

An exome study of Parkinson's disease in Sardinia, a Mediterranean genetic isolate.

Parkinson's disease (PD) is a common neurodegenerative disorder of complex aetiology. Rare, highly penetrant PD-causing mutations and common risk factors of small effect size have been identified in several genes/loci. However, these mutations and risk factors only explain a fraction of the disease burden, suggesting that additional, substantial genetic determinants remain to be found. Genetically isolated populations offer advantages for dissecting the genetic architecture of complex disorders, such as PD. We performed exome sequencing in 100 unrelated PD patients from Sardinia, a genetic isolate. SNPs absent from dbSNP129 and 1000 Genomes, shared by at least five patients, and of functional effects were genotyped in an independent Sardinian case-control sample (n = 500). Variants associated with PD with nominal p value <0.05 and those with odds ratio (OR) ≥3 were validated by Sanger sequencing and typed in a replication sample of 2965 patients and 2678 controls from Italy, Spain, and Portugal. We identified novel moderately rare variants in several genes, including SCAPER, HYDIN, UBE2H, EZR, MMRN2 and OGFOD1 that were specifically present in PD patients or enriched among them, nominating these as novel candidate risk genes for PD, although no variants achieved genome-wide significance after Bonferroni correction. Our results suggest that the genetic bases of PD are highly heterogeneous, with implications for the design of future large-scale exome or whole-genome analyses of this disease.

Substantia nigra neuromelanin-MR imaging differentiates essential tremor from Parkinson's disease.

BACKGROUND: Essential tremor (ET) is a very common movement disorder that has no diagnostic markers. Differentiation with Parkinson's disease (PD) can be clinically challenging in some cases, with a high rate of misdiagnosis. Magnetic resonance imaging (MRI) studies have been able to identify neuromelanin changes in the substantia nigra (SN) of PD patients, but they have thus far not been investigated in ET. In this study, we aimed to characterize neuromelanin-MR signal changes in ET and evaluate its diagnostic accuracy in the differential diagnosis with PD. METHODS: The inclusion criteria were patients with ET and untreated "de novo" PD patients; in addition, age-matched controls were enrolled. These were studied with a high-resolution T1-weighted MRI sequence at 3.0 Tesla to visualize neuromelanin. The primary outcomes were the area and width of the SN region with high signal. RESULTS: A total of 15 ET patients and 12 "de novo" PD patients were evaluated. The area and width of the T1 high signal in the SN region were markedly decreased in the PD group compared with the ET and age-matched controls, and a greater decrease was seen in the ventrolateral segment. The neuromelanin measures in the ET group, although slightly lower, were not significantly different from the healthy control group. We obtained a sensitivity of 66.7% and a specificity of 93.3% in discriminating ET from early-stage PD. CONCLUSIONS: Neuromelanin-sensitive MRI techniques can discriminate ET from early-stage tremor-dominant PD and can be a useful clinical tool in the evaluation of tremor disorders. © 2015 International Parkinson and Movement Disorder Society.

Long-term follow-up of subthalamic nucleus deep brain stimulation in patients with Parkinson's disease: An analysis of survival and disability milestones.

BACKGROUND: Data on the long-term survival and incidence of disability milestones after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson's disease (PD) is limited. OBJECTIVES: To estimate mortality and assess the frequency/time-to-development of disability milestones (falls, freezing, hallucinations, dementia, and institutionalization) among PD patients post STN-DBS. METHODS: A longitudinal retrospective study of patients undergoing STN-DBS. For mortality, Cox proportional hazards regression analysis was performed. For disease milestones, competing risk analyses were performed and cumulative incidence functions reported. The strength of association between baselines features and event occurrence was calculated based on adjusted hazard ratios. RESULTS: The overall mortality for the 109 patients was 16 % (62.1 ± 21.3 months after surgery). Falls (73 %) and freezing (47 %) were both the earliest (40.4 ± 25.4 and 39.6 ± 28.4 months, respectively) and most frequent milestones. Dementia (34 %) and hallucinations (32 %) soon followed (56.2 ± 21.2 and mean 60.0 ± 20.7 months after surgery, respectively). Higher ADL scores in the OFF state and higher age at surgery were associated with falls, freezing, dementia and institutionalization. CONCLUSIONS: Long-term mortality rate is low after STN-DBS. Disease milestones occur later during the disease course, with motor milestones appearing first and at a higher frequency than cognitive ones.

Molecular Characterization of Portuguese Patients with Hereditary Cerebellar Ataxia.

Hereditary cerebellar ataxia (HCA) comprises a clinical and genetic heterogeneous group of neurodegenerative disorders characterized by incoordination of movement, speech, and unsteady gait. In this study, we performed whole-exome sequencing (WES) in 19 families with HCA and presumed autosomal recessive (AR) inheritance, to identify the causal genes. A phenotypic classification was performed, considering the main clinical syndromes: spastic ataxia, ataxia and neuropathy, ataxia and oculomotor apraxia (AOA), ataxia and dystonia, and ataxia with cognitive impairment. The most frequent causal genes were associated with spastic ataxia (SACS and KIF1C) and with ataxia and neuropathy or AOA (PNKP). We also identified three families with autosomal dominant (AD) forms arising from de novo variants in KIF1A, CACNA1A, or ATP1A3, reinforcing the importance of differential diagnosis (AR vs. AD forms) in families with only one affected member. Moreover, 10 novel causal-variants were identified, and the detrimental effect of two splice-site variants confirmed through functional assays. Finally, by reviewing the molecular mechanisms, we speculated that regulation of cytoskeleton function might be impaired in spastic ataxia, whereas DNA repair is clearly associated with AOA. In conclusion, our study provided a genetic diagnosis for HCA families and proposed common molecular pathways underlying cerebellar neurodegeneration.

Neuromelanin Magnetic Resonance Imaging of the Substantia Nigra in Huntington's Disease.

BACKGROUND: Huntington's disease (HD) is an autosomal-dominant neurodegenerative disorder inducing motor, psychiatric changes and cognitive decline, characterized pathologically by striatal atrophy. Pathological changes in the extra-striatal structures, such as the substantia nigra (SN), and abnormalities in pre-synaptic striatal dopamine neurotransmission are also known to occur. Neuromelanin (NM)-sensitive magnetic resonance imaging (NM-MRI) is an innovative technique that was recently developed allowing the in vivo study of pathological changes in the dopaminergic neurons of the SN. OBJECTIVE: To investigate the SN MR signal in HD patients. METHODS: We performed a cross-sectional study using a specific T1-weighted MR sequence to visualize NM. The areas and signal intensity contrast ratios of the T1 hyperintense SN regions were obtained using a semi-automatic segmentation method. RESULTS: A total of 8 HD patients and 12 healthy subjects were evaluated. The SN area was markedly reduced in the HD group compared with the control group (p = 0.02), even after normalization of the SN area with the midbrain area and age correction (p = 0.01). There was a significant reduction in the intensity contrast ratio of the hyperintense SN areas to crus cerebri in HD patients comparing with controls (p = 0.04) after correction for age. CONCLUSIONS: NM-sensitive MR techniques were used for the first time to study the SN in HD patients, showing loss of NM in this region, supporting the implication of dopaminergic neuronal changes in disease pathology. Future research needs to be conducted to evaluate the potential of SN area and intensity contrast as biomarkers for HD.

Patients and Health Professional's Perspective of Functional Mobility in Parkinson's Disease.

Background: Functional mobility (FM) is the person's ability to move to accomplish daily living tasks and activities. FM limitations are common in Parkinson's disease, increase with disease progression, and can be highly disabling. Although several studies in Parkinson's disease (PD) field use this concept, only recently, a formal definition has been proposed. Objective: We aimed to explore patient's and health professional's perspectives of FM in PD. Methods: A focus group methodology has been used. Four focus groups, with a total of 10 patients and 10 health professionals, were performed. Six patients were early stage and four advanced stage. The health professional's group was composed of five neurologists and five physiotherapists. The suitability of the new concept, the impact of FM limitations in PD patient's daily routine, and the potential benefit of walking aids have been discussed. Results: All participants were able to provide a spontaneous definition of FM, matching with the proposed concept. All agreed that PD affects patient's FM, increasing the limitations with disease progression, and with the existence of a serious prejudice with walking aids that hinders its use. Early-stage patient's perspective seems to be more in line with neurologist's perspective, while the views of advanced-stage patients were closer to physiotherapist's views. Conclusion: FM concept was considered as intuitive and useful. FM limitations have an important physical and social impact in the advanced stage of the disease. Although patients and health professionals acknowledge walking aid's benefit improving patient's FM, the prejudice associated with this type of tools limits its recommendation and use.