Search Results (139)

Background/Objectives: Tacrolimus is the most used immunosuppressive agent in solid organ transplantation due to its efficacy in preventing acute rejection, but it has a narrow therapeutic range, and overexposure often leads to toxicities, including neurological side effects like tremors. Tremor affects up to 54% of renal transplant patients under tacrolimus. Extended-release tacrolimus (LCPT) has demonstrated efficacy in reducing tremor severity, as evidenced by studies employing quality of life (QoL) questionnaires, the Fahn–Tolosa–Marin (FTM) scale, and Accelerometer devices. The objectives of this study were to evaluate the benefits of the conversion to LCPT formulation in kidney transplant recipients experiencing tremors on prolonged-release tacrolimus (PR-TAC) treatment and to validate the DyCare device, a wearable wireless sensor for tremors. Results: The DyCare device measured tremor frequencies of 8.74 ± 0.11 Hz and 1.36 ± 0.08° and 17.38 ± 1.16°, as root mean square (RMSx100 for accelerometer and Gyroscope, respectively) in PR-TAC patients. After switching ten patients to LCPT, tremor severity significantly decreased, as confirmed by DyCare and the QoL in the Essential Tremor Questionnaire (QUEST). Additionally, LCPT allowed a 34% reduction in tacrolimus dosage while maintaining therapeutic trough concentrations. Immunological and pharmacodynamic biomarkers (p-miR-210-3p, p-IL10, p-IL12p70, p-IFNγ uCXCL10, NFAT-regulated gene expression) confirmed stable immunosuppression post-conversion. Conclusions: The conversion to the LCPT formulation significantly reduced tremors in kidney transplant recipients without altering their immunological status, as confirmed through a panel of immunologic and pharmacodynamic biomarkers. The DyCare device enables a precise quantification of tremors in transplant recipients, allowing physicians to optimize treatment strategies. Full article

Deep brain stimulation (DBS) is an evolving neurosurgical treatment, originally developed for movement disorders such as Parkinson’s disease, essential tremor, and dystonia. In recent years, it has been increasingly applied to psychiatric and cognitive disorders. This review aimed to summarize the psychological and neuroethical dimensions of DBS, with particular attention to cognitive, emotional, and personality-related outcomes. While DBS can significantly enhance quality of life, it may also lead to subtle or overt changes in cognition, affect, and self-perception, especially in patients with neuropsychiatric comorbidities. Comprehensive psychological evaluation, both pre- and post-operatively, is essential. Findings from recent trials highlight a balance of potential risks and benefits that must be communicated transparently to patients. From a neuroethical perspective, DBS raises important questions regarding personal identity and autonomy, concerns that will become increasingly relevant as the technology advances. This paper underscores the need for more systematic research and the development of personalized care protocols that address not only motor outcomes but also psychosocial well-being. Full article

Background: Differentiating Parkinson’s disease (PD) from essential tremor (ET) is often challenging, especially in early or atypical cases. Dopamine transporter (DAT) single-photon emission computed tomography (SPECT) with ¹²³I-Ioflupane supports diagnosis, and semi-quantitative tools such as DaTQUANT^® and BasGanV2™ provide objective measures. This study compared their diagnostic performance when integrated with supervised machine learning. Methods: We retrospectively analysed ¹²³I-Ioflupane SPECT scans from 169 patients (133 PD, 36 ET). Semi-quantitative analysis was performed using DaTQUANT^® v2.0 and BasGanV2™ v.2. Classification tree (ClT), k-nearest neighbour (k-NN), and support vector machine (SVM) models were trained and validated with stratified shuffle split (250 iterations). Diagnostic accuracy was compared between the two software packages. Results: All classifiers reliably distinguished PD from ET. DaTQUANT^® consistently achieved higher accuracy than BasGanV2™: 93.8%, 93.2%, and 94.5% for ClT, k-NN, and SVM, respectively, versus 90.9%, 91.7%, and 91.9% for BasGanV2™ (p < 0.001). Sensitivity and specificity were also consistently higher for DaTQUANT^® than BasGanV2. Class imbalance (PD > ET) was addressed using Synthetic Minority Over-sampling Technique (SMOTE). Conclusions: Machine learning analysis of ¹²³I-Ioflupane SPECT enhances differentiation between PD and ET. DaTQUANT^® outperformed BasGanV2™, suggesting greater suitability for AI-driven decision support. These findings support the integration of semi-quantitative and AI-based approaches into clinical workflows and highlight the need for harmonised methodologies in movement disorder imaging. Full article

Background: Epilepsy is a chronic, non-communicable brain disorder characterized by recurrent seizures. Some derivatives of 1,2,3,4-tetrahydroisoquinolines have demonstrated anticonvulsant effects. This study aims to investigate the effects of 33 derivatives of 1-aryl-1,2,3,4-tetrahydroisoquinoline on seizures induced by nicotine and strychnine. Methods: The anticonvulsant effects of 1-aryl-1,2,3,4-tetrahydroisoquinoline derivatives were evaluated in white male mice. Convulsant agents were administered subcutaneously at doses of 10.0 mg/kg for nicotine and 1.5 mg/kg for strychnine, 60 min after the oral administration of the test compounds at doses ranging from 0.1 to 10 mg/kg. The onset time, duration of tremors and seizures, and survival rate of the animals were recorded. The docking studies were conducted for 32 tested compounds targeting the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor (PDB ID: 1FTL). Furthermore, a predictive ADMET study was conducted to evaluate the pharmacokinetic and toxicity profiles of the compounds. Results: Compounds 20 and 25 exhibited the highest activity against strychnine-induced seizures. When evaluating the effects of 1-aryl-1,2,3,4-tetrahydroisoquinolines and reference drugs on the tremorogenic and convulsive actions of nicotine at doses of 0.1–5 mg/kg, compounds 3, 6, 8, 14, 16, 25, 27, 29, 30, 31, and 34 demonstrated comparable activity to the reference drugs. The docking results targeting AMPA (PDB ID: 1FTL) revealed comparable binding interactions for most of the compounds, with a (−)C-Docker interaction energy range of 33.82–45.41 Kcal/mol, compared to that of the ligand (41.60 Kcal/mol). The structural requirements of the studied scaffold were analyzed to identify the essential pharmacophoric features for anticonvulsant activity. Furthermore, a predictive ADMET study was conducted to evaluate the pharmacokinetic and toxicity profiles of the compounds. Conclusions: Certain derivatives of 1,2,3,4-tetrahydroisoquinolines may serve as potential anticonvulsant agents for epilepsy. Full article

Background: Medically unexplained oral symptoms/syndromes (MUOS), such as Burning Mouth Syndrome and Persistent Idiopathic Facial Pain, present significant management challenges due to the lack of standardized treatments and high-level evidence. While pharmacotherapy is often employed, real-world data on treatment adherence—a pragmatic proxy for effectiveness and tolerability—remain sparse, especially in Japan. This study aimed to describe the real-world prescribing patterns of antidepressants and dopamine receptor partial agonists (DPAs) for MUOS and retrospectively investigate their association with treatment continuation. Methods: This retrospective observational study analyzed data from patients initiating pharmacotherapy for MUOS at a specialized clinic in Japan (April 2021–March 2023). We used Cox proportional hazards models to evaluate treatment continuation for amitriptyline monotherapy and antidepressant–aripiprazole adjunctive therapy. The primary outcome was the time to discontinuation. Dosage effects were modeled using B-splines to capture nonlinearity. Results: Among 702 MUOS patients who started pharmacotherapy, 493 received amitriptyline as the first prescription, and 108 received aripiprazole as an adjunctive therapy. For amitriptyline monotherapy, a nonlinear relationship was observed between dosage and discontinuation risk, with a relatively lower hazard around 25 mg/day across age groups. In the antidepressant–aripiprazole adjunctive group, the overall hazard ratio for discontinuation was higher (HR = 4.75, p < 0.0005) compared to non-adjunctive therapy, likely due to indication bias reflecting more treatment-resistant cases. However, within the aripiprazole adjunctive group, a U-shaped relationship was identified between maximum aripiprazole dosage and discontinuation risk, with the lowest hazard (HR ≈ 0.30) observed at approximately 1.7–1.8 mg/day. Mild side effects such as drowsiness, dry mouth, constipation, tremor, insomnia, and weight gain were noted, but no severe adverse events occurred. Conclusions: This real-world data analysis suggests specific dosage ranges (amitriptyline ≈ 25 mg/day; aripiprazole augmentation ≈ 1.7–1.8 mg/day) are associated with longer treatment continuation in MUOS patients. Treatment continuation reflects a crucial balance between symptom relief and tolerability, essential for managing these chronic conditions. It is critical to emphasize that these findings are descriptive and observational, derived from a specialized setting, and do not constitute prescriptive recommendations. They highlight the importance of individualized dosing. Definitive evidence-based strategies require validation through prospective randomized controlled trials. Full article

Background/Objectives: Essential tremor (ET) is the most common movement disorder worldwide. It negatively affects patients’ activities of daily living (ADL) and quality of life. Unilateral transcranial magnetic resonance-guided focused ultrasound (tcMRgFUS) thalamotomy has been proven as a highly effective and safe treatment option for patients with refractory ET. The aims of this study are to explore the effectiveness and safety of tcMRgFUS thalamotomy in patients with ET in a real-world setting. Methods: Patients who underwent tcMRgFUS thalamotomy at the University Hospital of Palermo were prospectively enrolled. Scores obtained by Quality of Life in Essential Tremor Questionnaire (QUEST) and The Essential Tremor Rating Assessment Scale (TETRAS) were compared before and after tcMRgFUS thalamotomy. Predictors of tcMRgFUS thalamotomy effectiveness were explored by multivariable Cox regression analyses. All the adverse events (AEs) during and after the procedure were collected. Results: Fifty patients were included (80% male; median age at tcMRgFUS 67.4 years). After procedure, the QUEST score decreased by 46.2%, while TETRAS-ADL and TETRAS Performance (TETRAS-PE) decreased by 52.2% and 51.8%, respectively. Temperature peak and longitudinal lesion diameter positively correlated with the magnitude of QUEST and TETRAS-PE reduction. A higher baseline TETRAS-PE score predicted a good prognosis (HR = HR 6.6 [95% CI: 2.1–21.3]; p = 0.001). AEs were mild to moderate and transient, while permanent AE was observed only in one case. Conclusions: This real-world study confirms the higher effectiveness and the favorable safety profile of tcMRgFUS thalamotomy in patients with ET by reducing the tremor-related interference in quality of life, disability in ADL, and tremor severity. Full article

Parkinson’s disease (PD) is a common neurodegenerative disorder caused by progressive loss of dopaminergic neurons in the substantia nigra and the presence of Lewy bodies. While PD is most recognized by its motor symptoms (resting tremor, rigidity, bradykinesia, and postural instability), cognitive decline (CD) may become apparent as PD progresses, leading to Parkinson’s disease dementia (PDD). Type 2 diabetes mellitus (T2DM) and insulin resistance (IR) are risk factors for dementia, especially Alzheimer’s disease; however, their influence on dementia in PD is underexplored. Therefore, we sought to determine the effect of T2DM and IR on dementia in PD. A systematic search of articles from 2005 to March 2025 was undertaken using Embase, PubMed, Scopus, Web of Science, and citation searching. Case–control, cross-sectional, longitudinal, and non-human population studies assessing cognitive outcomes in individuals with PD, with and without T2DM and IR, were included (PROSPERO registration number CRD420251013367). In total, 27 studies met the inclusion criteria, with clinical sample sizes ranging from 23 to 544,162 participants. Among the 23 clinical studies, 15 identified T2DM as a contributor to cognitive decline (CD) in PD, and 4 specifically examined insulin resistance (IR). Elevated HbA1c was consistently associated with poorer cognitive performance and increased risk of Parkinson’s disease dementia (PDD); HbA1c ≥ 7% independently predicted cognitive impairment (OR = 4.25, 95% CI: 1.59–11.34). Vascular and inflammatory markers, including elevated LDL-C, fibrinogen, and hs-CRP, further exacerbated CD. MoCA and MMSE scores were the most common cognitive measures, consistently showing worse outcomes in PD patients with T2DM. Preclinical studies supported these associations, showing that high-fat-diet-induced T2DM and IR aggravated dopaminergic neuronal loss by 38–45%, increased α-synuclein by 35%, and heightened microglial activation, providing mechanistic evidence for the observed clinical associations. This systematic review, the first to examine the impact of T2DM and IRs on the occurrence and advancement of CD in PD patients, demonstrates a possible association between the two. However, these results demonstrate the need for larger sample sizes and the inclusion of additional clinical variables, such as HbA1c levels and pharmacological interventions, providing further information about the link between metabolic dysfunction and CD in PD. To further strengthen this link, longitudinal studies with systematic follow-ups are essential to establish causal links and avoid misdiagnosis in clinical practice. Full article

Introduction: Hypertrophic olivary degeneration (HOD) is a rare form of trans-synaptic degeneration involving the Guillain–Mollaret triangle, characterized by enlargement of the inferior olivary nucleus—unlike the atrophy typical of most neurodegenerative processes. It is usually associated with stroke, surgical injury, or demyelination, but rarely follows hemorrhage from a cavernous malformation (CM). This report presents a case of HOD secondary to a mesencephalic CM hemorrhage, with emphasis on imaging findings and diagnostic considerations. Case Description: A 55-year-old woman presented with acute-onset, right-sided facial, torso, and limb hypoesthesia, along with gait instability. Neurological examination revealed sensory impairment in the right maxillary (V2) and mandibular (V3) trigeminal territories, as well as diminished pain and temperature sensation throughout the right hemibody. MRI revealed a hemorrhage in the posterior mesencephalon near the left red nucleus, leading to the diagnosis of a CM with an associated venous angioma. She was managed conservatively and improved clinically. Six months later, MRI showed hypertrophy and T2/FLAIR hyperintensity of the left inferior olive, consistent with developing HOD. At 1.5 years follow-up, olivary enlargement had progressed—now consistent with stage 2 HOD—and a bilateral palatal tremor was observed, more pronounced on the right side. DTI revealed asymmetric volume loss in the left brainstem fiber pathways at the level of the medulla oblongata, confirming trans-synaptic degeneration. Conclusions: This case highlights HOD as a rare but important complication of mesencephalic CM hemorrhage. Recognition of its characteristic imaging features—olivary hypertrophy with persistent T2/FLAIR hyperintensity—is essential for accurate diagnosis. DTI supports the trans-synaptic mechanism, helping distinguish HOD from other pathologies and preventing unnecessary investigations. Full article

Tremor, an oscillatory movement disorder, is commonly encountered in clinical practice in the setting of a variety of etiologies, such as essential tremor and Parkinson’s disease. Despite its high prevalence, treatment options are somewhat limited. Oral medications are often ineffective or limited by side effects, and other treatments, such as deep brain stimulation, are more invasive and costly. Botulinum toxin (BoNT) injections are a well-established therapy in the treatment of dystonia, but its use in the treatment of tremors has not been fully explored. In this review, we discuss the available randomized controlled trials and open-label evidence for the use of BoNT in various tremor etiologies, as well as its injection techniques. While essential tremor is the most studied condition, other tremor etiologies and tremor types such as Parkinson’s disease, head tremor, voice tremor, proximal tremor, and tremor due to dystonia and multiple sclerosis have been studied as well. Botulinum toxin injections have provided evidence of significant benefit in outcomes in several trials among these indications, but transient weakness remains a common adverse effect. There is a paucity of well-designed trials as many published studies have relatively small cohorts and results are additionally limited by heterogenous outcome measures, dosages, muscle selection techniques and methods of injection. Full article

Background: Tremor is a common but diagnostically challenging movement disorder due to its clinical heterogeneity and overlapping aetiologies. The 2018 consensus introduced a two-axis classification system that redefined tremor syndromes by distinguishing between clinical phenomenology and underlying causes, and introduced new diagnostic categories, such as essential tremor plus. Methods: This review synthesises recent advances in the epidemiology, classification, pathophysiology, and treatment of tremor syndromes, aiming to provide an integrated and clinically relevant framework that aligns with emerging diagnostic and therapeutic paradigms. Results: We discuss how electrophysiology, neuroimaging, wearable sensors, and artificial intelligence are reshaping diagnostic precision. Syndromes such as essential tremor, parkinsonian tremor, dystonic tremor, task-specific tremor, orthostatic tremor, and functional tremor are examined through syndromic, aetiological, and mechanistic lenses. The limitations of current rating scales and the promise of emerging biomarkers are critically assessed. Conclusions: As therapeutic approaches evolve toward neuromodulation and precision medicine, the need for pathophysiologically grounded diagnostic criteria becomes more urgent. Integrating network-based frameworks, digital diagnostics, and individualised treatment holds promise for advancing tremor care. Full article

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by the selective loss of dopaminergic neurons in the substantia nigra, resulting in motor symptoms such as bradykinesia, tremor, rigidity, and postural instability, as well as a wide variety of non-motor manifestations. Branched-chain amino acids (BCAAs)—leucine, isoleucine, and valine—are essential nutrients involved in neurotransmitter synthesis, energy metabolism, and cellular signaling. Emerging evidence suggests that BCAA metabolism is intricately linked to the pathophysiology of PD. Dysregulation of BCAA levels has been associated with energy metabolism, mitochondrial dysfunction, oxidative stress, neuroinflammation, and altered neurotransmission. Furthermore, the branched-chain ketoacid dehydrogenase kinase (BCKDK), a key regulator of BCAA catabolism, has been implicated in PD through its role in modulating neuronal energetics and redox homeostasis. In this review, we synthesize current molecular, genetic, microbiome, and clinical evidence on BCAA dysregulation in PD to provide an integrative perspective on the BCAA–PD axis and highlight directions for future translational research. We explored the dualistic role of BCAAs as both potential neuroprotective agents and metabolic stressors, and critically examined the therapeutic prospects and limitations of BCAA supplementation and BCKDK targeting. Full article

Background and Objectives: Essential tremor (ET) is a common neurological disorder, typically presenting as bilateral, rhythmic, and symmetric kinetic or postural tremors. In contrast, Parkinson’s disease (PD) is a progressive neurodegenerative disorder, characterized by resting tremor, rigidity, bradykinesia, and postural instability. Although both disorders involve tremor, ET and PD differ in clinical presentation and pathophysiology: ET generally involves action tremor and has a strong familial component, while PD more commonly presents with resting tremor and a weaker family history. A subset of ET patients may develop Parkinsonian features over time, although the relationship between ET and subsequent PD remains unclear. Genetic studies have identified only a few pathogenic variants in ET, suggesting it develops as a result of multifactorial genetic and environmental influences rather than simple Mendelian inheritance. ET is also recognized as a risk factor for developing PD, although the underlying mechanisms remain poorly understood. This study aimed to clarify potential genetic overlaps and distinctions in patients diagnosed with both ET and PD. Materials and Methods: We retrospectively analyzed 40 patients with a family history of ET or PD who were initially diagnosed with ET and later developed PD. Genetic screening and clinical assessments were conducted to investigate associated variants and clinical features. Results: Among these 40 patients, 17 different mutations were detected in 16 individuals. Three pathogenic or likely pathogenic variants were identified. The clinical characteristics and treatment responses of these patients were reviewed in relation to their genetic findings. Notably, none of the identified variants had previously been reported in association with PD following ET. Conclusions: A comprehensive clinical and genetic evaluation of ET patients who develop PD may offer insights into the underlying pathophysiology and inform future therapeutic strategies. Our findings support the need for further studies to explore the genetic landscape of patients with overlapping ET and PD features. Full article

Introduction: Cerebellar transcranial magnetic stimulation (TMS) has emerged as a promising neuromodulatory intervention for addressing motor, cognitive, and socio-affective deficits across a range of clinical populations. Materials and Methods: This systematic review aimed to synthesize recent evidence (2015–2025) on the efficacy, safety, and methodological characteristics of multi-session cerebellar TMS protocols used in rehabilitation settings. Following PRISMA guidelines, a comprehensive search of PubMed and Scopus was conducted to identify peer-reviewed studies applying multi-session cerebellar TMS in clinical populations for motor, cognitive, or affective rehabilitation. A total of 1750 records were screened, and 46 studies met the inclusion criteria. Data extraction included sample characteristics, study design, TMS protocol, targeted symptoms, outcomes, and risk of bias. Results: The results show that repeated sessions of cerebellar TMS are safe, well-tolerated, and associated with functional improvements primarily in motor disorders—such as spinocerebellar ataxia, Parkinson’s disease, multiple system atrophy, essential tremor, and post-stroke deficits—as well as in psychiatric populations, particularly patients with schizophrenia. Discussion: Evidence regarding the effects of cerebellar TMS on cognitive functions remains limited, though promising. Despite overall positive findings, the literature is limited by variability in stimulation parameters, protocol designs, and outcome measures, small sample sizes and potential publication bias. Conclusions: The review highlights the need for further large-scale and well-controlled trials to refine stimulation protocols, explore long-term effects, and clarify the underlying mechanisms of cerebellar TMS across motor, cognitive, and affective domains. This systematic review has been registered on PROSPERO (registration number: CRD420251067308). Full article

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterized by motor symptoms such as tremors, rigidity, and bradykinesia. The accurate and continuous monitoring of these symptoms is essential for optimizing treatment strategies and improving patient outcomes. Traditionally, clinical assessments have relied on scales and methods that often lack the ability for continuous, real-time monitoring and can be subject to interpretation bias. Recent advancements in wearable technologies, such as smartphones, smartwatches, and activity trackers (ATs), present a promising alternative for more consistent and objective monitoring. This review aims to evaluate the use of smartphones and smart wrist devices, like smartwatches and activity trackers, in the management of PD, assessing their effectiveness in symptom evaluation and monitoring and physical performance improvement. Studies were identified by searching in PubMed, Scopus, Web of Science, and Cochrane Library. Only 13 studies of 1027 were included in our review. Smartphones, smartwatches, and activity trackers showed a growing potential in the assessment, monitoring, and improvement of motor symptoms in people with PD, compared to clinical scales and research-grade sensors. Their relatively low cost, accessibility, and usability support their integration into real-world clinical practice and exhibit validity to support PD management. Full article

Background/Objectives: Parkinson’s disease (PD) is a neurodegenerative disorder with a prolonged prodromal phase and progressive symptom burden. Traditional monitoring relies on clinical visits post-diagnosis, limiting the ability to capture early symptoms and real-world disease progression outside structured assessments. Social media provides an alternative source of longitudinal, patient-driven data, offering an opportunity to analyze both pre-diagnostic experiences and later disease manifestations. This study evaluates the feasibility of using Facebook to analyze PD-related discourse and disease timelines. Methods: Participants (N = 60) diagnosed with PD, essential tremor, or atypical parkinsonism, along with caregivers, were recruited. Demographic and clinical data were collected during structured interviews. Participants with Facebook accounts shared their account data. PD-related posts were identified using a Naïve Bayes classifier (recall: 0.86, 95% CI: 0.84–0.88, AUC = 0.94) trained on a ground-truth dataset of 6750 manually labeled posts. Results: Among participants with PD (PwPD), Facebook users were significantly younger but had similar Movement Disorder Society-United Parkinson’s Disease Rating Scale scores and disease duration compared to non-users. Among Facebook users with PD, 90% had accounts before diagnosis, enabling retrospective analysis of pre-diagnostic content. PwPD maintained 14 ± 3 years of Facebook history, including 5 ± 6 years pre-diagnosis. On average, 3.6% of all posts shared by PwPD were PD-related, and 1.7% of all posts shared before diagnosis were PD-related. Overall, 69% explicitly referenced PD, and 93% posted about PD-related themes. Conclusions: Facebook is a viable platform for studying PD progression, capturing both early content from the premorbid period and later-stage symptoms. These findings support its potential for disease monitoring at scale. Full article