Cognitive safety of focused ultrasound thalamotomy for tremor: 1-year follow-up results of the COGNIFUS part 2 study.

Introduction: In the COGNitive in Focused UltraSound (COGNIFUS) study, we examined the 6-month cognitive outcomes of patients undergoing MRgFUS thalamotomy. This study endorsed the safety profile of the procedure in terms of cognitive functions that cannot be evaluated in real-time during the procedure unlike other aspects. The aim of the COGNIFUS Part 2 study was to investigate the cognitive trajectory of MRgFUS patients over a 1-year period, in order to confirm long-term safety and satisfaction. Methods: We prospectively evaluated the cognitive and neurobehavioral profile of patients with essential tremor (ET) or Parkinson's Disease (PD) related tremor undergoing MRgFUS thalamotomy at 1 year-follow-up following the treatment. Results: The sample consists of 50 patients (male 76%; mean age ± SD 69.0 ± 8.56; mean disease duration ± SD 12.13 ± 12.59; ET 28, PD 22 patients). A significant improvement was detected at the 1 year-follow-up assessment in anxiety and mood feelings (Hamilton Anxiety rating scale 5.66 ± 5.02 vs. 2.69 ± 3.76, p ≤ <0.001; Beck depression Inventory II score 3.74 ± 3.80 vs. 1.80 ± 2.78, p = 0.001), memory domains (Rey Auditory Verbal Learning Test, immediate recall 31.76 ± 7.60 vs. 35.38 ± 7.72, p = 0.001 and delayed recall scores 5.57 ± 2 0.75 vs. 6.41 ± 2.48), frontal functions (Frontal Assessment Battery score 14.24 ± 3.04 vs. 15.16 ± 2.74) and in quality of life (Quality of life in Essential Tremor Questionnaire 35.00 ± 12.08 vs. 9.03 ± 10.64, p ≤ 0.001 and PD Questionnaire -8 7.86 ± 3.10 vs. 3.09 ± 2.29, p ≤ 0.001). Conclusion: Our study supports the long-term efficacy and cognitive safety of MRgFUS treatment for ET and PD.

The Impact of Vocal Tremor on Deglutition: A Pilot Study.

OBJECTIVE: Vocal tremor (VT) poses treatment challenges due to uncertain pathophysiology. VT is typically classified into two phenotypes: isolated vocal tremor (iVT) and essential tremor-related voice tremor (ETvt). The impact of phenotypes on upper aerodigestive tract physiology during swallowing remains unclear. Qualitative and quantitative measures were employed to characterize tremor phenotypes and investigate the effects on swallowing physiology. METHODS: Eleven ETvt participants (1 Male, 10 Female; x̄ age = 74) and 8 iVT participants (1 Male, 7 Female; x̄ age = 71) swallowed 20 mL boluses in cued and uncued conditions under standardized fluoroscopic visualization. Sustained/a/productions were captured to assess the rate and extent of fundamental frequency (F0) modulation. Penetration and Aspiration Scale (PAS) scores were obtained and swallowing biomechanics were captured using Swallowtail™ software. Participants also completed the Swallowing Quality of Life (SWAL-QOL) questionnaire. RESULTS: Hypopharyngeal transit was faster in both VT phenotypes compared with Swallowtail™ normative reference data. Total pharyngeal transit times, however, were only faster in patients with iVT, relative to reference data. No significant differences were observed on the SWAL-QOL or PAS between tremor phenotypes. SWAL-QOL scores revealed that these patients rarely reported dysphagia symptoms. CONCLUSIONS: Subtle differences in swallowing patterns were observed across VT phenotypes, possibly related to adaptive mechanisms resulting in quicker pharyngeal bolus transit. Most patients did not report swallowing issues or dysphagia symptoms. This study is foundational for larger studies on this challenging population. LEVEL OF EVIDENCE: 4 Laryngoscope, 2024.

Systematic review-based guideline "Parkinson's disease" of the German Society of Neurology: diagnostic use of transcranial sonography.

BACKGROUND AND OBJECTIVE: Transcranial brain parenchyma sonography (TCS) has been recommended as a tool for the early and differential diagnosis of Parkinson's disease (PD) in German and European clinical guidelines. Still, the brain structures to be examined for the diagnostic questions and the requirements for being a qualified investigator were not specified in detail. These issues have now been addressed in the 2023 update of the clinical guideline on PD by the German Society of Neurology (DGN). METHODS: The recommendations were based on a systematic literature review following PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines. RESULTS: Three diagnostic questions were defined: (1) What is the accuracy of TCS in the differential diagnosis of PD versus atypical and secondary Parkinsonian syndromes? (2) What is the accuracy of TCS in the differential diagnosis of PD versus essential tremor? (3) What is the accuracy of TCS in the diagnosis of PD in persons with typical early symptoms, compared with the diagnosis established by clinical follow-up? The brain structures to be assessed and the level of recommendation were formulated for these questions. The training requirements for being regarded as qualified TCS investigator were stipulated by the responsible medical societies (German Society of Ultrasound in Medicine, DEGUM; German Society for Clinical Neurophysiology and Functional Imaging, DGKN). Finally, the recommendations for these diagnostic questions reached strong consensus (each ≥ 97%) of the guideline committee. Here, the details of review and recommendations are presented. CONCLUSION: The updated guideline clarifies the diagnostic uses and limitations of TCS in PD.

Staged magnetic resonance-guided focused ultrasound thalamotomy for the treatment of bilateral essential tremor and Parkinson's disease related tremor: a systematic review and critical appraisal of current knowledge.

Introduction: Essential tremor (ET) and Parkinson's Disease (PD) are debilitating neurodegenerative disorders characterized by tremor as a predominant symptom, significantly impacting patients' quality of life. Magnetic Resonance-guided Focused Ultrasound (MRgFUS) Thalamotomy is an innovative therapeutic option for the treatment of unilateral medically refractory tremor with fewer adverse effects compared to traditional surgical interventions. A recent CE approval allows appropriate patients to have their second side treated. Objective: The objective of this systematic review was to analyze available current knowledge about the use of MRgFUS for the treatment of bilateral ET and PD related tremor, to identify the effectiveness and the risks associated with bilateral treatment. Methods: Eligible studies were identified by searching published studies in PubMed and Scopus databases from May 2014 to January 2024 and by identifying ongoing studies registered on the clinicaltrials.gov website. Data were summarized by considering the following information topics: the number of patients involved, the selected lesion target, the assessment tool used to evaluate clinical changes, the observed improvement, the reported side effects, and the time interval between the two treatments. The study was registered in PROSPERO (ID: CRD42024513178). Results: Nine studies were eligible for this review, 7 for ET and 2 for PD. The involved population included a variable number of patients, ranging from 1 to 11 subjects for ET and from 10 to 15 subjects for PD. The main lesional targets were the ventral intermediate nucleus of the thalamus, the pallidothalamic tract and the cerebellothalamic tract bilaterally. All studies investigated the tremor relief through the Clinical Rating Scale for Tremor (CRST) in patients with ET, and through the Unified Parkinson's Disease Rating Scale (UPDRS) in patients with PD. A variable degree of improvement was observed, with all patients expressing overall satisfaction with the bilateral treatment. Adverse events were mild and transient, primarily involving gait disturbances, dysarthria, and ataxia. A standardized protocol for administering the two consecutive treatments was not identifiable; typically, the timing of the second treatment was delayed by at least 6 months. Conclusion: Available evidence supports the effectiveness and safety of staged bilateral MRgFUS treatments for ET and PD-related tremor.

Tremor-associated short tandem repeat intermediate and pathogenic expansions in familial essential tremor.

There is an obvious clinical-pathological overlap between essential tremor and some known tremor-associated short tandem repeat expansion disorders. The aim is to analyse whether these short tandem repeat genes, including ATXN1, ATXN2, ATXN3, CACNA1A, ATXN7, ATXN8OS, ATXN10, PPP2R2B, TBP, BEAN1, NOP56, DAB1, ATN1, SADM12 and FMR1, are associated with familial essential tremor patients. Genetic analysis of repeat sizes in tremor-associated short tandem repeat expansions was performed in a large cohort of 515 familial essential tremor probands and 300 controls. The demographic and clinical features among carriers of pathogenic expansions, intermediate repeats and non-carriers were compared. A total of 18 out of 515 (18/515, 3.7%) patients were found to have repeats expansions, including 12 cases (12/515, 2.5%) with intermediate repeat expansions (one ATXN1, eight TBP, two FMR1, one ATN1), and six cases (6/515, 1.2%) with pathogenic expansions (one ATXN1, one ATXN2, one ATXN8OS, one PPP2R2B, one FMR1, one SAMD12). There were no statistically significant differences in intermediate repeats compared to healthy controls. Furthermore, there were no significant differences in demographics and clinical features among individuals with pathogenic expansions, intermediate repeat expansions carriers and non-carriers. Our study indicates that the intermediate repeat expansion in tremor-associated short tandem repeat expansions does not pose an increased risk for essential tremor, and rare pathogenic expansion carriers have been found in the familial essential tremor cohort. The diagnosis of essential tremor based solely on clinical symptoms remains a challenge in distinguishing it from known short tandem repeat expansions diseases with overlapping clinical-pathological features.

Multiple system atrophy-cerebellar type: Diagnostic challenge in resource-limited settings case report.

Key Clinical Message: This case report highlights the challenges of diagnosing MSA-C in resource-limited settings. MRI findings like the "hot cross bun" sign can be supportive, but the unavailability of advanced tools like seed amplification assay may delay diagnosis. Early diagnosis is crucial for proper symptom management. Abstract: Multiple system atrophy is a rare neurodegenerative disorder affecting the pyramidal, autonomic, nigrostriatal, and cerebellar tracts. Multisystem atrophy should be considered in adults with progressive motor or autonomic dysfunctions. Clinical manifestations vary depending on the system, including bradykinesia, tremor, rigidity, cerebellar ataxia, and autonomic failure. Depending on the initial predominant manifestation, multisystem atrophy is classified as Parkinsonian (MSA-P) and cerebellar (MSA-C). Our patient presented with progressive loss of balance, rigidity, slurred speech, choking episodes, and loss of morning tumescence for 4 years, suggesting autonomic and cerebellar involvement. He was diagnosed with MSA after 4 years of initial presentation with combinations of magnetic resonant imaging findings and clinical manifestations. Diagnosing multiple system atrophy in such resource-limited areas is challenging. The unavailability of seed application tests and biomarkers significantly affected the delayed diagnosis.

Radiosurgical thalamotomy for the management of tremors: a systematic review and meta-analysis.

Medical treatment for tremors may include beta-blockers, primidone, dopaminergic, and anticholinergic drugs but it frequently leads to pharmacoresistance. Therefore, surgical treatment gained relevance as an alternative for those patients.We aim to evaluate radiosurgical thalamotomy as an effective and safe alternative to manage tremors. Pubmed (MEDLINE), Embase, Web of Science, and the Cochrane Library databases were systematically searched for potential articles that evaluated radiosurgical thalamotomy for the management of tremor. Our analysis included 12 studies with 545 patients, 226 of whom were female. Of these, 64.6% of patients were diagnosed with essential tremor (ET), 34.6% with Parkinson's disease (PD), and 0.8% with both ET and PD. The FTM-TRS global score (MD -5.46; 95% CI [-10.44]-[-0.47]; I2 = 52%) and the drawing (MD -1.40; 95% CI [-2.03]-[-0.76]; I2 = 93%), drinking (MD -1.60; 95% CI [-1.82]-[-1.37]; I2 = 40%), and writing (MD -1.51; 95% CI [-1.89]-[-1.13]; I2 = 89%) grades showed significantly lower mean differences, favoring radiosurgical thalamotomy. A pooled proportion of 12% presented with tremor unchanged, while 38% presented with total elimination of tremor. Adverse events included: major paresis, minor paresis, dysarthria, and numbness. Thus, radiosurgical thalamotomy is a safe alternative for tremors resistant to medication, particularly in high-risk patients for RF or DBS procedures. The recommended dose of 130 to 150 Gy is effective and well-tolerated. However, randomized controlled trials (RCTs) are needed to understand the unpredictability of tissue response to radiation.

Prescription Drug Utilization among Patients with Essential Tremor: A Cross-Sectional Study of More Than 36,000 Patients.

BACKGROUND: Essential tremor (ET) is a chronic, progressive neurological disease that affects an estimated 7 million individuals in the United States (ie, 2.2% of the entire U.S. population). Despite its high prevalence, there are a few published studies on patterns of prescription medication use among patients. OBJECTIVE: The aim was to examine prescription drug medication use among ET patients. METHODS: This is a cross-sectional study of ET patients, age ≥40, with at least 1 prescription medication fill using the Optum's de-identified Clinformatics Data Mart Database from 2018 through 2019. We examined patterns of fills of key agents used to treat ET. RESULTS: The final sample comprised 36,839 ET patients in the United States; 89% had at least 1 prescription drug claim over a 2-year period, indicating that 9 of 10 ET patients take a medication to treat their disease. For each of the 3 most frequently prescribed medications, only a modest fraction (1/5 to 1/4) of patients were taking that medication. Adherence to these agents was 52% to 61%. A high percentage of patients had fills for more than 1 of the main agents we studied. CONCLUSION: These data illustrate a need for medication in the ET population. There is only 1 FDA-approved medication to treat ET, propranolol, and less than 25% of ET patients used this drug during our study period. At the same time, no single agent was utilized by more than one quarter of ET patients, adherence was low, and use of multiple agents was common. For such a common disease, the pharmacotherapeutic landscape is impoverished.

Validation of the International Classification of Diseases, Tenth Revision-Clinical Modification Diagnostic Code for Essential Tremor.

Background: The positive predictive value (PPV) of the International Classification of Diseases, Ninth Revision-Clinical Modification (ICD-9-CM) code for "essential and other specified forms of tremor" in identifying essential tremor (ET) cases was found to be less than 50%. The ability of the ICD-10-CM G25.0 code for "essential tremor" to identify ET has not been determined. The study objective was to determine the PPV of the G25.0 code. Methods: Patients in a tertiary health system with a primary care encounter associated with ICD-10-CM code G25.0 in 2022 underwent medical record review to determine if the consensus criteria from the International Parkinson and Movement Disorder Society for an ET diagnosis were met. Results: 442 patients were included. The PPV of G25.0 in identifying probable ET cases was 74.7% (95% confidence interval (CI) 70.4-78.5%). Among patients prescribed propranolol, the PPV improved to 87.8% (95% CI 78.0-93.6%). Discussion: Compared to the ICD-9-CM code 333.1, G25.0 is superior for identifying ET cases. A potential limitation of this study is that the consensus criteria applied relies on nonspecific physical exam findings which may lead to an overestimation of the PPV of G25.0. Highlights: The ICD-10-CM diagnosis code for essential tremor has not been previously validated. The objective of this study was to determine the PPV of the G25.0 code. The PPV in identifying essential tremor cases was 74.7%. The PPV improved among patients prescribed propranolol.

An Eye on the First Surgical Side: Appreciating the Potential Impacts of a Second DBS Lead on Ipsilateral Symptoms.

Clinical Vignette: A 63-year-old man with severe essential tremor underwent staged bilateral ventralis intermedius (Vim) deep brain stimulation (DBS). Left Vim DBS resulted in improved right upper extremity tremor control. Months later, the addition of right Vim DBS to the other brain hemisphere was associated with acute worsening of the right upper extremity tremor. Clinical Dilemma: In staged bilateral Vim DBS, second lead implantation may possibly alter ipsilateral tremor control. While ipsilateral improvement is common, rarely, it can disrupt previously achieved benefit. Clinical Solution: DBS programming, including an increase in left Vim DBS amplitude, re-established and enhanced bilateral tremor control. Gap in Knowledge: The mechanisms underlying changes in ipsilateral tremor control following a second lead implantation are unknown. In this case, worsening and subsequent improvement after optimization highlight the potential impact of DBS implantation on the ipsilateral side. Expert Commentary: After staged bilateral Vim DBS, clinicians should keep an eye on the first or original DBS side and carefully monitor for emergent side effects or worsening in tremor. Ipsilateral effects resulting from DBS implantation present a reprogramming opportunity with a potential to further optimize clinical outcomes. Highlights: This case report highlights the potential for ipsilateral tremor worsening following staged bilateral DBS and provides valuable insights into troubleshooting and reprogramming strategies. The report emphasizes the importance of vigilant monitoring and individualized management in optimizing clinical outcomes for patients undergoing staged bilateral DBS for essential tremor.

Assessing ChatGPT Ability to Answer Frequently Asked Questions About Essential Tremor.

Background: Large-language models (LLMs) driven by artificial intelligence allow people to engage in direct conversations about their health. The accuracy and readability of the answers provided by ChatGPT, the most famous LLM, about Essential Tremor (ET), one of the commonest movement disorders, have not yet been evaluated. Methods: Answers given by ChatGPT to 10 questions about ET were evaluated by 5 professionals and 15 laypeople with a score ranging from 1 (poor) to 5 (excellent) in terms of clarity, relevance, accuracy (only for professionals), comprehensiveness, and overall value of the response. We further calculated the readability of the answers. Results: ChatGPT answers received relatively positive evaluations, with median scores ranging between 4 and 5, by both groups and independently from the type of question. However, there was only moderate agreement between raters, especially in the group of professionals. Moreover, readability levels were poor for all examined answers. Discussion: ChatGPT provided relatively accurate and relevant answers, with some variability as judged by the group of professionals suggesting that the degree of literacy about ET has influenced the ratings and, indirectly, that the quality of information provided in clinical practice is also variable. Moreover, the readability of the answer provided by ChatGPT was found to be poor. LLMs will likely play a significant role in the future; therefore, health-related content generated by these tools should be monitored.

Analysis of alpha-synuclein harvested from intracranial instruments used in deep brain stimulation surgery for Parkinson's disease.

Alpha-synuclein (αSyn) forms pathologic aggregates in Parkinson's disease (PD) and is implicated in mechanisms underlying neurodegeneration. While pathologic αSyn has been extensively studied, there is currently no method to evaluate αSyn within the brains of living patients. Patients with PD are often treated with deep brain stimulation (DBS) surgery in which surgical instruments are in direct contact with neuronal tissue; herein, we describe a method by which tissue is purified from DBS surgical instruments in PD and essential tremor (ET) patients and demonstrate that αSyn is robustly detected. 24 patients undergoing DBS surgery for PD (17 patients) or ET (7 patients) were enrolled; from patient samples, 81.2 ± 44.8 µg protein (n=15) is able to be purified, with immunoblot assays specific for αSyn reactive in all tested samples. Light microscopy revealed axons and capillaries as the primary components of purified tissue (n=3). Further analysis was conducted using western blot, demonstrating that truncated αSyn (1-125 αSyn) was significantly increased in PD (n=5) compared to ET (n=3), in which αSyn misfolding is not expected (0.64 ± 0.25 vs. 0.25 ± 0.12, P = 0.046), thus showing that pathologic αSyn can be reliably purified from living PD patients with this method.

Ventral intermediate nucleus of the thalamus, dentatorubrothalamic tract, and caudal zona incerta: stimulation of which structure provides ongoing tremor control in patients with essential tremor?

OBJECTIVE: Essential tremor (ET) is the most common movement disorder. Deep brain stimulation (DBS) targeting the ventral intermediate nucleus (VIM) is known to improve symptoms in patients with medication-resistant ET. However, the clinical effectiveness of VIM-DBS may vary, and other targets have been proposed. The authors aimed to investigate whether the same anatomical structure is responsible for tremor control both immediately after VIM-DBS and at later follow-up evaluations. METHODS: Of 68 electrodes from 41 patients with ET, the authors mapped the distances of the active contact from the VIM, the dentatorubrothalamic tract (DRTT), and the caudal zona incerta (cZI) and compared them using Friedman's ANOVA and the Wilcoxon signed-rank follow-up test. The same distances were also compared between the initially planned target and the final implantation site after intraoperative macrostimulation. Finally, the comparison among the three structures was repeated for 16 electrodes whose active contact was changed after a mean 37.5 months follow-up to improve tremor control. RESULTS: After lead implantation, the VIM was statistically significantly closer to the active contact than both the DRTT (p = 0.008) and cZI (p < 0.001). This result did not change if the target was moved based on intraoperative macrostimulation. At the last follow-up, the active contact distance from the VIM was always significantly less than that of the cZI (p < 0.001), but the distance from the DRTT was reduced and even less than the distance from the VIM. CONCLUSIONS: In patients receiving VIM-DBS, the VIM itself is the structure driving the anti-tremor effect and remains more effective than the cZI, even years after implantation. Nevertheless, the role of the DRTT may become more important over time and may help sustain the clinical efficacy when the habituation from the VIM stimulation ensues.

Tremor in Spinocerebellar Ataxia: A Scoping Review.

Background: Spinocerebellar ataxia (SCA) denotes an expanding list of autosomal dominant cerebellar ataxias. Although tremor is an important aspect of the clinical spectrum of the SCAs, its prevalence, phenomenology, and pathophysiology are unknown. Objectives: This review aims to describe the various types of tremors seen in the different SCAs, with a discussion on the pathophysiology of the tremors, and the possible treatment modalities. Methods: The authors conducted a literature search on PubMed using search terms including tremor and the various SCAs. Relevant articles were included in the review after excluding duplicate publications. Results: While action (postural and intention) tremors are most frequently associated with SCA, rest and other rare tremors have also been documented. The prevalence and types of tremors vary among the different SCAs. SCA12, common in certain ethnic populations, presents a unique situation, where the tremor is typically the principal manifestation. Clinical manifestations of SCAs may be confused with essential tremor or Parkinson's disease. The pathophysiology of tremors in SCAs predominantly involves the cerebellum and its networks, especially the cerebello-thalamo-cortical circuit. Additionally, connections with the basal ganglia, and striatal dopaminergic dysfunction may have a role. Medical management of tremor is usually guided by the phenomenology and associated clinical features. Deep brain stimulation surgery may be helpful in treatment-resistant tremors. Conclusions: Tremor is an elemental component of SCAs, with diverse phenomenology, and emphasizes the role of the cerebellum in tremor. Further studies will be useful to delineate the clinical, pathophysiological, and therapeutic aspects of tremor in SCAs.

Clinical neurophysiology in the treatment of movement disorders: IFCN handbook chapter.

In this review, different aspects of the use of clinical neurophysiology techniques for the treatment of movement disorders are addressed. First of all, these techniques can be used to guide neuromodulation techniques or to perform therapeutic neuromodulation as such. Neuromodulation includes invasive techniques based on the surgical implantation of electrodes and a pulse generator, such as deep brain stimulation (DBS) or spinal cord stimulation (SCS) on the one hand, and non-invasive techniques aimed at modulating or even lesioning neural structures by transcranial application. Movement disorders are one of the main areas of indication for the various neuromodulation techniques. This review focuses on the following techniques: DBS, repetitive transcranial magnetic stimulation (rTMS), low-intensity transcranial electrical stimulation, including transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS), and focused ultrasound (FUS), including high-intensity magnetic resonance-guided FUS (MRgFUS), and pulsed mode low-intensity transcranial FUS stimulation (TUS). The main clinical conditions in which neuromodulation has proven its efficacy are Parkinson's disease, dystonia, and essential tremor, mainly using DBS or MRgFUS. There is also some evidence for Tourette syndrome (DBS), Huntington's disease (DBS), cerebellar ataxia (tDCS), and axial signs (SCS) and depression (rTMS) in PD. The development of non-invasive transcranial neuromodulation techniques is limited by the short-term clinical impact of these techniques, especially rTMS, in the context of very chronic diseases. However, at-home use (tDCS) or current advances in the design of closed-loop stimulation (tACS) may open new perspectives for the application of these techniques in patients, favored by their easier use and lower rate of adverse effects compared to invasive or lesioning methods. Finally, this review summarizes the evidence for keeping the use of electromyography to optimize the identification of muscles to be treated with botulinum toxin injection, which is indicated and widely performed for the treatment of various movement disorders.

Exploring serum α­synuclein and its autoantibodies in essential tremor: implications for diagnosis and symptom correlations.

There is no definite biomarker for confirming the diagnosis of essential tremor (ET) or differentiating it from other diseases, particularly Parkinson's disease. The present study aimed to investigate the serum levels of the α-synuclein protein (α-syn) and its autoantibodies in patients with ET compared with healthy controls and its relation to motor and non-motor symptoms in patients with ET. Serum α-syn and its autoantibodies were measured in 32 patients with ET and 32 age- and sex-matched controls. Both groups were assessed using the non-motor symptoms scale, MoCA, Beck Depression Inventory, Hamilton Anxiety Rating Scale, and the Short Form 36 Health Survey Questionnaire. Tremor was assessed using the Fahn-Tolosa-Marin Tremor Rating Scale. The serum α-syn concentration in patients with ET was significantly lower than that in healthy controls (P<0.001), with a positive predictive value of 0.81 and a negative predictive value of 0.75, while the serum anti-a-syn autoantibody concentration was not significantly different between the two groups. There were no correlations between serum α-syn or its autoantibodies and patients' clinical characteristics. Furthermore, patients with ET had worse cognitive impairment, depression, anxiety, non-motor symptoms and quality of life. The serum α-syn concentration was lower in patients with ET than in controls, with favorable predictive values, suggesting that it could serve as a biomarker for ET diagnosis.

The Parkinson's Story of a Neurologist with 32 Years of Experience on Parkinson's Disease.

As a neurologist who has followed up countless Parkinson's patients over the last 32 years of my fifty-year career; I denied diagnosing myself with Parkinson's disease (PD), although the seldom mild involuntary "twitches" that occurred in the thumb of my right hand over a two-year period, resembled Parkinson's disease tremor. However, when these involuntary contractions became persistent; considering its similarity to characteristic resting tremor in typical PD, the positive effect of dopaminergic medications, the development of levodopa-induced dyskinesias and other non-motor symptoms, it was clear that the PD diagnosis was accurate. This situation naturally caused me anxiety, and for a year and a half, I kept my diagnosis hidden from everyone except a few close relatives. However, with the encouragement of a psychiatrist friend, when I was able to share my condition with my loved ones, I felt a relative reduction in the burden I was carrying and consequently experienced emotional relief. I am still able to carry out my daily activities independently with a rather low dose of medication, and my PD symptoms do not attract noticeable attention.

Subjective Sleep Disturbance and Lewy Pathology: Data from a Cohort of Essential Tremor Brain Donors.

INTRODUCTION: Sleep disturbances have been associated with essential tremor (ET). However, their pathophysiological underpinnings remain unknown. In this exploratory study, we examined the association between subjective sleep disturbances and the presence of Lewy pathology (LP) on postmortem brain examination in ET cases. METHODS: Fifty-two ET cases enrolled in a prospective, longitudinal study were assessed over an average period of 42 months. Cases completed the Pittsburgh Sleep Quality Index (PSQI), which yields seven component scores (e.g., sleep quality, sleep latency). For each component score, we calculated the difference between the last score and the baseline score. Brains were harvested at death. Each had a complete neuropathological assessment, including extensive α-synuclein immunostaining. We examined the associations between baseline PSQI scores and the change in PSQI scores (last - first), and LP on postmortem brain examination. RESULTS: ET cases had a mean baseline age of 87.1 ± 4.8 years. LP was observed in 12 (23.1%) of 52 cases; in 7 of these 12, LP was observed in the locus coeruleus (LC). Change in time needed to fall asleep (last - first sleep latency component score) was associated with presence of LP on postmortem brain examination - greater increase in sleep latency was associated with higher odds of LP (odds ratio = 2.98, p = 0.02). The greatest increase in sleep latency was observed in cases with LP in the LC (p = 0.04). CONCLUSION: In ET cases, increases in sleep latency over time could be a marker of underlying LP, especially in the LC.

Predictive Analysis of Yi-Gai-San's Multifaceted Mechanisms for Tremor-Dominant Parkinson's Disease via Network Pharmacology and Molecular Docking Validation.

INTRODUCTION: Based on comprehensive network-pharmacology and molecular docking analysis, this study was intended to unveil the multiple mechanisms of Yi-- Gai-San (YGS) in treating the tremor-dominant subtype of Parkinson's disease (PDDT). The compounds of YGS were meticulously analyzed, selected, and standardized with references to their pharmacological attributes. Its components included Gouteng (Uncaria rhynchophylla), Chaihu (Radix Bupleuri), Chuanxiong (Chuanxiong Rhizoma), Danggui (Angelicae Sinensis Radix), Fuling (Wolfiporia extensa), Baizhu (Atractylodis macrocephalae rhizoma), and Gancao (Licorice, Glycyrrhizae radix). METHOD: We identified 75 active compounds within YGS. From these, we predicted 110 gene targets, which exhibited a direct association with PD-DT. PPI network results highlighted core target proteins, including TP53, SLC6A3, GAPDH, MAOB, AKT, BAX, IL6, BCL2, PKA, and CASP3. These proteins potentially alleviate PD-DT by targeting inflammation, modulating neuronal cell apoptosis, and regulating the dopamine system. Furthermore, GO and KEGG enrichment analyses emphasized that YGS might influence various mechanisms, such as the apoptotic process, mitochondrial autophagy, Age- Rage signaling, and dopaminergic and serotonergic synapses. The core proteins from the PPI analysis were selected for the docking experiment. RESULT: The docking results demonstrated that the most stable ligand-receptor conformations were kaempferol with CASP3 (-9.5 kcal/mol), stigmasterol with SLC6A3 (-10.5 kcal/mol), shinpterocarpin with BCL2L1 (-9.6 kcal/mol), hirsutine with MAOB (-9.7 kcal/mol), hederagenin with PRKACA (-9.8 kcal/mol), and yatein with GAPDH (-9.8 kcal/mol). These results provide us with research objectives for future endeavors in extracting single compounds for drug manufacturing or in-depth studies on drug mechanisms. CONCLUSION: From these computational findings, we suggested that YGS might mitigate PD-DT via "multi-compounds, multi-targets, and multi-pathways."