The enduring enigma of sporadic chorea: A single center case series.

Chorea can have a wide variety of causes including neurodegenerative, pharmacological, structural, metabolic, infectious, immunologic and paraneoplastic processes. We reviewed the clinical records of patients with apparently sporadic choreic movements and no relevant family history, who presented to our neurology department (Hospital Fundación Jimenez Diaz) between 1991 and 2022. We detected 38 cases of apparent sporadic chorea (ASC); Our analysis revealed 5 cases of genetic chorea (including 3 cases with Huntington's disease) while 6 cases were autoimmune/hematological; 6 drug-related chorea, 5 metabolic-vascular, 5 due to miscellaneous conditions and 4 were of mixed etiology. No clear etiology was identified in 8 cases. The differential diagnosis of ASC is extensive and challenging. Highlights: Chorea can have a wide variety of genetic and sporadic causesWe reviewed the clinical records of patients with apparently sporadic chorea (ASC), who presented to our neurology department over the last 30 yearsWe detected 38 cases of apparent ASC; Our analysis revealed a wide array of different sporadic conditions and 5 cases of genetic choreaThe differential diagnosis of ASC is extensive and challenging.

Perampanel: Medical Alternative for Essential Tremor?

OBJECTIVES: The aim of this study was to assess the safety and efficacy of perampanel in patients with refractory essential tremor (ET). METHODS: We recruited patients from our movement disorders clinic with the diagnosis of severe refractory ET, and perampanel 4 mg at night was initiated.Assessments were conducted at baseline and after 1 month of treatment with perampanel 4 mg/d. Details about tolerance and effectiveness were collected. Clinical evaluation was conducted with the Fahn-Tolosa-Marín scale, and statistical analysis was carried out with Wilcoxon matched pairs signed rank test. RESULTS: This study included 18 patients with severe ET (11 females, 7 males; mean age: 75.1 ± 12.03 years; mean duration of ET: 17.4 ± 17.03 years). Perampanel significantly improved patients' average score with refractory ET ( P ≤ 0.0001). This improvement has been occasionally quite relevant. However, a proportion of patients did not tolerate perampanel because of several adverse effects including dizziness, ataxia, irritability, and instability. CONCLUSIONS: Perampanel had a markedly positive antitremor effect in patients with ET and could be an alternative treatment. However, this drug is not devoid of adverse effects.

Clinical and structural brain correlates of hypomimia in early-stage Parkinson's disease.

BACKGROUND AND PURPOSE: Reduced facial expression of emotions is a very frequent symptom of Parkinson's disease (PD) and has been considered part of the motor features of the disease. However, the neural correlates of hypomimia and the relationship between hypomimia and other non-motor symptoms of PD are poorly understood. METHODS: The clinical and structural brain correlates of hypomimia were studied. For this purpose, cross-sectional data from the COPPADIS study database were used. Age, disease duration, levodopa equivalent daily dose, Unified Parkinson's Disease Rating Scale part III (UPDRS-III), severity of apathy and depression and global cognitive status were collected. At the imaging level, analyses based on gray matter volume and cortical thickness were used. RESULTS: After controlling for multiple confounding variables such as age or disease duration, the severity of hypomimia was shown to be indissociable from the UPDRS-III speech and bradykinesia items and was significantly related to the severity of apathy (ß = 0.595; p < 0.0001). At the level of neural correlates, hypomimia was related to motor regions brodmann area 8 (BA 8) and to multiple fronto-temporo-parietal regions involved in the decoding, recognition and production of facial expression of emotions. CONCLUSION: Reduced facial expressivity in PD is related to the severity of symptoms of apathy and is mediated by the dysfunction of brain systems involved in motor control and in the recognition, integration and expression of emotions. Therefore, hypomimia in PD may be conceptualized not exclusively as a motor symptom but as a consequence of a multidimensional deficit leading to a symptom where motor and non-motor aspects converge.

Present and Future of Parkinson's Disease in Spain: PARKINSON-2030 Delphi Project.

Parkinson's disease (PD) is a chronic progressive and irreversible disease and the second most common neurodegenerative disease worldwide. In Spain, it affects around 120.000-150.000 individuals, and its prevalence is estimated to increase in the future. PD has a great impact on patients' and caregivers' lives and also entails a substantial socioeconomic burden. The aim of the present study was to examine the current situation and the 10-year PD forecast for Spain in order to optimize and design future management strategies. This study was performed using the modified Delphi method to try to obtain a consensus among a panel of movement disorders experts. According to the panel, future PD management will improve diagnostic capacity and follow-up, it will include multidisciplinary teams, and innovative treatments will be developed. The expansion of new technologies and studies on biomarkers will have an impact on future PD management, leading to more accurate diagnoses, prognoses, and individualized therapies. However, the socio-economic impact of the disease will continue to be significant by 2030, especially for patients in advanced stages. This study highlighted the unmet needs in diagnosis and treatment and how crucial it is to establish recommendations for future diagnostic and therapeutic management of PD.

Electroconvulsive Therapy and Movement Disorders. New Perspectives on A Time-Tested Therapy.

Electroconvulsive therapy (ECT) has been a very well known therapy in Psychiatry for over 80 years. ECT is considered useful in treating acute mania, severe depression and other psychiatric conditions. Over time, this therapy has also been used in several movement disorders including Parkinson disease (PD) and Huntington disease (HD). In this brief review, I summarize the recent History and evolution of ECT, its proven and potential applications in movement disorders as well as its potential mechanisms.

Consensus guidelines for botulinum toxin therapy: general algorithms and dosing tables for dystonia and spasticity.

Botulinum toxin (BT) therapy is a complex and highly individualised therapy defined by treatment algorithms and injection schemes describing its target muscles and their dosing. Various consensus guidelines have tried to standardise and to improve BT therapy. We wanted to update and improve consensus guidelines by: (1) Acknowledging recent advances of treatment algorithms. (2) Basing dosing tables on statistical analyses of real-life treatment data of 1831 BT injections in 36 different target muscles in 420 dystonia patients and 1593 BT injections in 31 different target muscles in 240 spasticity patients. (3) Providing more detailed dosing data including typical doses, dose variabilities, and dosing limits. (4) Including total doses and target muscle selections for typical clinical entities thus adapting dosing to different aetiologies and pathophysiologies. (5) In addition, providing a brief and concise review of the clinical entity treated together with general principles of its BT therapy. For this, we collaborated with IAB-Interdisciplinary Working Group for Movement Disorders which invited an international panel of experts for the support.

Sexual Dysfunction in Early-Onset Parkinson's Disease: A Cross-Sectional, Multicenter Study.

BACKGROUND: Sexual dysfunction (SD) is one of the least studied non-motor symptoms in Parkinson's disease (PD). OBJECTIVES: To assess sexual function in a cohort of patients with early-onset PD (EOPD) and compare it to a group of healthy controls. METHODS: In this cross-sectional multicenter study, SD was assessed with gender-specific multi-dimensional self-reported questionnaires: The Brief Male Sexual Function Inventory (BSFI-M) and the Female Sexual Function Index (FSFI). Scores between patients and controls were compared and associations between SD and demographical and clinical variables were studied. RESULTS: One hundred and five patients (mean age 47.35±7.8, disease duration 6 (3-11) years, UPDRS part III 17 (10-23) and 90 controls were recruited. The BSFI-M total score was lower in EOPD men than in controls, and specific items were also significantly lower, such as drive, erections, ejaculation, and satisfaction. EOPD women had lower scores than controls in totalFSFI, and certain domains such as lubrication and pain. SD was present in 70.2% of patients and 52.5% of controls. Sexual satisfaction in 35.2% of patients and 81.2% of controls. By gender, male and female patients had more SD than controls but only male patients had more dissatisfaction than controls. Gender, higher depression scores and urinary dysfunction were associated with SD in multivariate analysis; and gender, UPDRS and urinary dysfunction with sexual satisfactionConclusion:In this Spanish cohort, SD and sexual dissatisfaction was more prevalent in EOPD patients than in the general population. Gender and urinary disfunction were associated with SD and sexual dissatisfaction.

Benign versus malignant Parkinson disease: the unexpected silver lining of motor complications.

OBJECTIVE: We sought to evaluate demographic, clinical, and habits/occupational variables between phenotypic extremes in Parkinson's disease (PD). METHODS: Databases from nine movement disorders centers across seven countries were retrospectively searched for subjects meeting criteria for very slowly progressive, benign, PD (bPD) and rapidly progressive, malignant, PD (mPD). bPD was defined as Hoehn and Yahr (H&Y) stage ≤ 3, normal cognitive function, and Schwab and England (S&E) score ≥ 70 after ≥ 20 years of PD (≥ 10 years if older than 60 at PD onset); mPD as H&Y > 3, S&E score < 70, and cognitive impairment within 10 years from PD onset. We performed between-group analysis of demographic, habits/occupational, and clinical features at baseline and follow-up and unsupervised data-driven analysis of the clinical homogeneity of bPD and mPD. RESULTS: At onset, bPD subjects (n = 210) were younger, had a single limb affected, lower severity and greater asymmetry of symptoms, and lower prevalence of depression than mPD (n = 155). bPD was associated with active smoking and physical activity, mPD with agricultural occupation. At follow-up, mPD showed higher prevalence of depression, hallucinations, dysautonomia, and REM behaviour disorder. Interestingly, the odds of mPD were significantly reduced by the presence of dyskinesia and wearing-off. Data-driven analysis confirmed the independent clustering of bPD and mPD, with age at onset emerging as a critical discriminant between the two groups (< 46-year-old vs. > 68-year-old). CONCLUSIONS: Phenotypic PD extremes showed distinct demographic, clinical, and habits/occupational factors. Motor complications may be conceived as markers of therapeutic success given their attenuating effects on the odds of mPD.

Hypomimia in Parkinson's Disease: What Is It Telling Us?

Introduction: Amimia is one of the most typical features of Parkinson's disease (PD). However, its significance and correlation with motor and nonmotor symptoms is unknown. The aim of this study is to evaluate the association between amimia and motor and nonmotor symptoms, including cognitive status, depression, and quality of life in PD patients. We also tested the blink rate as a potential tool for objectively measuring upper facial bradykinesia. Methods: We prospectively studied amimia in PD patients. Clinical evaluation was performed using the Unified Parkinson's Disease Rating Scale (UPDRS) and timed tests. Cognitive status, depression, and quality of life were assessed using the Parkinson's Disease Cognitive Rating Scale (PD-CRS), the 16-Item Quick Inventory of Depressive Symptomatology (QIDS-SR16), and the PDQ-39, respectively. Amimia was clinically evaluated according to item 19 of UPDRS III. Finally, we studied upper facial amimia by measuring resting blink frequency and blink rate during spontaneous conversation. Results: We included 75 patients. Amimia (item 19 UPDRS III) correlated with motor and total UPDRS (r: 0.529 and 0.551 Spearman), and its rigidity, distal bradykinesia, and motor axial subscores (r: 0.472; r: 0.252, and r: 0.508, respectively); Hoehn and Yahr scale (r: 0.392), timed tests, gait freezing, cognitive status (r: 0.29), and quality of life (r: 0.268) correlated with amimia. Blinking frequency correlated with amimia (measured with item 19 UPDRS), motor and total UPDRS. Conclusion: Amimia correlates with motor (especially axial symptoms) and cognitive situations in PD. Amimia could be a useful global marker of overall disease severity, including cognitive decline.

Long-term Apomorphine Infusion Users Versus Short-term Users: An International Dual-center Analysis of the Reasons for Discontinuing Therapy.

OBJECTIVES: A retrospective analysis at 2 specialist centers was undertaken to determine the long-term efficacy of subcutaneous apomorphine infusion (APO), rates and reasons for discontinuation, and factors that might contribute to discontinuation. METHODS: Demographics, clinical outcomes data, and reasons for discontinuation were collected for patients treated with APO at Chulalongkorn Centre of Excellence for Parkinson's Disease and Related Disorders, Bangkok, Thailand (n = 36) and Fundacion Jimemez Diaz Universidad Autonoma de Madrid, Spain (n = 16). RESULTS: There were 19 (52.7%) patients in the Thai cohort and 10 (62.5%) patients in the Spanish cohort who discontinued treatment within around 6 months of initiation, most commonly due to skin nodules (Thai cohort) and perceived lack of efficacy (Spanish cohort). Those who continued APO tended to stay on treatment. In both cohorts, APO resulted in significant reductions in Unified Parkinson's Disease Rating Scale 3 motor scores, daily OFF time, and levodopa-equivalent dose in patients who subsequently stopped therapy, suggesting APO is clinically effective even when "lack of efficacy" is stated as a reason for discontinuing. Daily OFF hours after APO therapy was found to be a significant predictive factor for APO discontinuation with an odds ratio of 5.952 (P = 0.040). The cutoff point that determined APO discontinuation was calculated to be 1.75 or more OFF hours (sensitivity, 84.6%; specificity, 63.2%). CONCLUSIONS: Apomorphine infusion is a minimally invasive therapy and therefore very easy to discontinue if difficulties arise. This fact might explain the high dropout rate of this technique. Successful long-term adherence to APO therapy requires a multidisciplinary health care team approach including regular patient follow-up and assessment and prompt resolution of queries and concerns.

Creativity related to dopaminergic treatment: A multicenter study.

Impulse control disorder (ICD), including pathological gambling, hypersexuality, and compulsive shopping has been linked to dopaminergic treatment, especially treatment with dopamine agonists (DAs). However, patients with Parkinson's disease (PD) may experience enhanced creativity during DA therapy, often manifesting as newfound artistic pursuits. Though ICD is very well recognized in the literature, enhanced creativity remains underreported, probably because, unlike ICD, enhanced creativity is often positive and rarely disruptive for patients and relatives. We studied 21 patients (20 patients with PD and one patient with restless-legs syndrome) with enhanced creativity. These individuals engaged in artistic activities after dopaminergic treatment; all but one were treated with DA (pramipexole, 14/21; ropinirole, 4/21; rotigotine 2/21). Most patients preferred painting as their main activity, but many were engaged in several activities, usually in combination. We hypothesize that by facilitating a stimulating environment for parkinsonian patients, this positive phenomenon may present more frequently.

Impulse Control Disorders and Dopamine-Related Creativity: Pathogenesis and Mechanism, Short Review, and Hypothesis.

Impulse control disorder (ICD), including pathological gambling, hypersexuality, and compulsive shopping has been linked to antiparkinsonian medication, especially dopamine agonists. The mechanism of ICD is not completely clear, but it seems that ICD is the result of an activation of dopamine receptors, mostly D3 in the ventral striatum. Patients treated with dopamine agonists that have preferential affinity for D3 (including ropinirole and pramipexole) are much more prone to develop ICD. In addition, a genetic component is probably present, especially in young patients. Finally, environment and lifestyle may also play a role: those patients engaged in physical, social, and artistic activities are probably less likely to develop ICD compared to those patients with poor physical activity living in isolated environments.

Estimulación cerebral profunda en pacientes parkinsonianos con intolerancia a levodopa / Deep brain stimulation in parkinsonian patients with dopa intolerance

La estimulacion cerebral profunda (ECP) es un tratamiento eficaz para pacientes con enfermedad de Parkinson con complicaciones motoras. El elemento más importante que predice la respuesta a la ECP es la respuesta a la levodopa. Mostramos dos casos de pacientes con enfermedad de Parkinson de comienzo precoz con intolerancia severa a la levodopa y excelente respuesta a ECP. La ECP puede ser una alternativa en pacientes parkinsonianos con intolerancia a la levodopa siempre que la respuesta a apomorfina sea positiva

Deep brain stimulation (DBS) is at present, a useful treatment for patients with advanced Parkinson's disease and motor complications. The crucial step toward consistent DBS outcomes remains careful patient selection; several conditions must be fulfilled including excellent levo dopa response. We report two cases of early onset Parkinson's disease with severe intolerance to levo dopa but excellent and sustained response to DBS. DBS can be a useful alternative for parkinsonian patients with severe intolerance to levo dopa, provided a positive acute response to levo dopa or apomorphine is obtained

Mitos y evidencias en el empleo de la toxina botulínica: neurofarmacología y distonías / Myths and evidence on the use of botulinum toxin: neuropharmacology and dystonia

Introducción. La toxina botulínica de tipo A (TBA) ha supuesto una verdadera revolución terapéutica en neurología, y en la actualidad es el tratamiento rutinario en las distonías focales y la espasticidad. Objetivo. Plantear, revisar y responder cuestiones controvertidas en relación con la neurofarmacología de a TBA y su uso en las distonías en la práctica clínica habitual. Desarrollo. Un grupo de expertos en trastornos del movimiento revisó una lista de temas controvertidos relacionados con la farmacología de la TBA y su uso en las distonías. Revisamos la bibliografía e incluimos artículos relevantes especialmente en inglés, pero también, si su importancia lo merece, en castellano y en francés, hasta junio de 2016. El documento se estructuró como un cuestionario que incluyó las preguntas que podrían generar mayor controversia o duda. El borrador inicial del documento fue revisado por los miembros del panel y se realizaron las modificaciones necesarias hasta alcanzar el mayor grado de consenso. Incluimos preguntas sobre diferentes aspectos de la neurofarmacología, especialmente el mecanismo de acción, la bioequivalencia de los diferentes preparados y la inmunogenicidad. En relación con el subapartado de las distonías, se incluyeron aspectos sobre la evaluación y el tratamiento de las distonías focales. Conclusiones. Esta revisión no pretende ser una guía, sino una herramienta práctica destinada a neurólogos y médicos internos residentes interesados en esta área, dentro de diferentes ámbitos específicos del manejo de la TBA (AU)

Introduction. Botulinum toxin type A (BTA) is a bacterial endotoxin, whose therapeutic use has had a dramatic impact on different neurological disorders, such as dystonia and spasticity. Aim. To analyze and summarize different questions about the use of BTA in our clinical practice. Development. A group of experts in neurology developed a list of topics related with the use of BTA. Two groups were considered: neuropharmacology and dystonia. A literature search at PubMed, mainly for English language articles published up to June 2016 was performed. The manuscript was structured as a questionnaire that includes those questions that, according to the panel opinion, could generate more controversy or doubt. The initial draft was reviewed by the expert panel members to allow modifications, and after subsequent revisions for achieving the highest degree of consensus, the final text was then validated. Different questions about diverse aspects of neuropharmacology, such as mechanism of action, bioequivalence of the different preparations, immunogenicity, etc. were included. Regarding dystonia, the document included questions about methods of evaluation, cervical dystonia, blepharospasm, etc. Conclusion. This review does not pretend to be a guide, but rather a tool for continuous training of residents and specialists in neurology, about different specific areas of the management of BTA (AU)

Behavioral addictions in early-onset Parkinson disease are associated with DRD3 variants.

BACKGROUND: Impulse control disorders (ICDs) comprise abnormal behaviors frequently found in patients with Parkinson's disease (PD) receiving antiparkinsonian medication. ICDs in PD would develop when dopaminergic treatment overstimulates the dopamine receptor D3 (DR3). Here we studied whether DR3 gene (DRD3) is associated to ICD in PD patients with early-onset (EOPD). METHODS: We performed association analysis of the rs6280 DRD3 single nucleotide variation (SNV) (Ser9Gly) in a clinical sample of 126 non early-onset PD (NEOPD) and 73 EOPD (age at onset < 45). ICD was evaluated using the Questionnaire for Impulsive-Compulsive Disorders (QUIP) in PD. RESULTS: In the total sample, we found that a younger onset of PD is linked to ICD traits with a potentially addictive reinforcement (ICDARs, behavioral addictions) (p = .017) and a trend for total ICDs (p = .078) while punding was not associated (p = .75). EOPD sample showed an increase of DRD3 C+ genotype for ICD (p = .022) and ICDARs (p = .043) but not for punding (p = .170). The post-hoc analyses including the time of evolution and Pramipexol or Ropinirole treatments, confirmed the independent effect of the DRD3 upon ICDs (p = .028) and ICDARs (p = .041) as well as the interaction between DRD3 and Pramipexol treatment upon ICDARs (OR = 4.60, 95% CI 1.20-17.632, p = .026). The NEOPD group showed no association between DRD3 and ICDs. CONCLUSIONS: We found that behavioral addictions in PD are associated with an early onset of the disease, the rs6280 DRD3 SNV and the type of dopamine agonist. Further investigation in independent samples is warranted.