Plasticity-Induced Effects of Theta Burst Transcranial Ultrasound Stimulation in Parkinson's Disease.

BACKGROUND: Low-intensity transcranial ultrasound stimulation (TUS) is a noninvasive brain stimulation (NIBS) technique with high spatial specificity. Previous studies showed that TUS delivered in a theta burst pattern (tbTUS) increased motor cortex (MI) excitability up to 30 minutes due to long-term potentiation (LTP)-like plasticity. Studies using other forms of NIBS suggested that cortical plasticity may be impaired in patients with Parkinson's disease (PD). OBJECTIVE: The aim was to investigate the neurophysiological effects of tbTUS in PD patients off and on dopaminergic medications compared to healthy controls. METHODS: We studied 20 moderately affected PD patients in on and off dopaminergic medication states (7 with and 13 without dyskinesia) and 17 age-matched healthy controls in a case-controlled study. tbTUS was applied for 80 seconds to the MI. Motor-evoked potentials (MEP), short-interval intracortical inhibition (SICI), and short-interval intracortical facilitation (SICF) were recorded at baseline, and at 5 minutes (T5), T30, and T60 after tbTUS. Motor Unified Parkinson's Disease Rating Scale (mUPDRS) was measured at baseline and T60. RESULTS: tbTUS significantly increased MEP amplitude at T30 compared to baseline in controls and in PD patients on but not in PD patients off medications. SICI was reduced in PD off medications compared to controls. tbTUS did not change in SICI or SICF. The bradykinesia subscore of mUPDRS was reduced at T60 compared to baseline in PD on but not in the off medication state. The presence of dyskinesia did not affect tbTUS-induced plasticity. CONCLUSIONS: tbTUS-induced LTP plasticity is impaired in PD patients off medications and is restored by dopaminergic medications. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Management of Impulse Control and Related Disorders in Parkinson's Disease: An Expert Consensus.

BACKGROUND: Impulse-control and related behavioral disorders (ICBDs) significantly impact the lives of Parkinson's disease (PD) patients and caregivers, with lasting consequences if undiagnosed and untreated. While ICBD pathophysiology and risk factors are well-studied, a standardized severity definition and treatment evidence remain elusive. OBJECTIVE: This work aimed to establish international expert consensus on ICBD treatment strategies. To comprehensively address diverse treatment availabilities, experts from various continents were included. METHODS: From 2021 to 2023, global movement disorders specialists engaged in a Delphi process. A core expert group initiated surveys, involving a larger panel in three iterations, leading to refined severity definitions and treatment pathways. RESULTS: Experts achieved consensus on defining ICBD severity, emphasizing regular PD patient screenings for early detection. General treatment recommendations focused on continuous monitoring, collaboration with significant others, and seeking specialist advice for legal or financial challenges. For mild to severe ICBDs, gradual reduction in dopamine agonists was endorsed, followed by reductions in other PD medications. Second-line treatment strategies included diverse approaches like reversing the last medication change, cognitive behavior therapy, subthalamic nucleus deep brain stimulation, and specific medications like quetiapine, clozapine, and antidepressants. The panel reached consensus on distinct treatment pathways for punding and dopamine dysregulation syndrome, formulating therapy recommendations. Comprehensive discussions addressed management strategies for the exacerbation of either motor or non-motor symptoms following the proposed treatments. CONCLUSION: The consensus offers in-depth insights into ICBD management, presenting clear severity criteria and expert consensus treatment recommendations. The study highlights the critical need for further research to enhance ICBD management. © 2024 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Communication board in locked-in syndrome: a practical interaction method with the patient.

Locked-in syndrome is a neurological condition characterized by tetraplegia, mutism, preservation of vertical eye movement, superior eyelid movement, and intact consciousness, making it impossible for the patient to communicate properly. We herein describe a case to analyze the practice of developing a method of communication for a patient with locked-in syndrome. Two communication boards were created, adapted to the Portuguese language, as well as a shortcut to inquire about the physical and emotional patient's well-being. We had difficulty with the initial communication board, due to the patient's low education level, so we adapted a new one to the patient's social context, including a shortcut to inquire about physical and emotional well-being. The communication board had a positive impact on treatment development and the patient's life.

A síndrome do encarceramento é uma condição neurológica caracterizada por tetraplegia, mutismo, preservação do movimento vertical dos olhos, movimento palpebral superior e consciência intacta, impossibilitando a comunicação adequada do paciente. Descrevemos um caso para analisar a prática de criação de um método de comunicação em um paciente com síndrome do encarceramento. Foram criadas duas pranchas de comunicação, adaptadas à língua portuguesa, e um atalho para indagar sobre o bem-estar físico e emocional do paciente. Tivemos dificuldade com a prancha de comunicação inicial em razão da baixa escolaridade do paciente, então criamos uma nova prancha de comunicação adaptada ao seu contexto social. A nova prancha tinha um atalho para indagar sobre o bem-estar físico e emocional do paciente. A prancha de comunicação teve impacto positivo no desenvolvimento do tratamento e na vida do paciente.

Average annual cost of Parkinson's disease in a Brazilian multiethnic population.

INTRODUCTION: With the current demographic transition, it is estimated that by 2050 Brazil will have a population of 90 million people aged 60 years or more, and in parallel Parkinson's disease (PD) will bring a considerable economic burden to our society. Brazil is considered multiracial due to its colonization, generating important social and regional inequalities. Knowing the costs of the PD may aid to improve local public policies. However, in Brazil, no estimates of these values have been made so far. OBJECTIVES: To evaluate direct, indirect, and out-of-pocket costs in Brazilian people with PD (PwP). METHODS: Categorical and numerical data were collected through a customized and standardized cost-related-questionnaire from 1055 PwP nationwide, from 10 tertiary movement disorders centers across all Brazilian regions. RESULTS: The estimated average annual cost of PwP was US$ 4020.48. Direct and indirect costs accounted for 63% and 36% of the total, respectively, and out-of-pocket costs were 49%. There were no evidence of differences in the total cost of PD across the regions of the country; however, differences were reported between the stages of the Hoehn and Yahr scale (H&Y). CONCLUSION: This data suggests a considerable burden of PD for Brazilian society in general, not only for the public health system, but mainly for those with PD.

Influence of unilateral eyelid spasms and botulinum toxin treatment on intraocular pressure measured by transpalpebral tonometer.

PURPOSE: Eyelid spasms might be associated with elevated intraocular pressure (IOP) in hemifacial spasm (HFS) patients. IOP assessment using a Goldmann applanation tonometer (GAT) is often compromised by eyelid spasms. This study aimed to assess the effect of HFS on IOP measurements using the transpalpebral tonometer Diaton® before and after treatment with botulinum toxin type A (BTX-A) and compared Diaton® and GAT measurements after treatment with BTX-A. METHODS: IOP measurements were obtained with Diaton® in 27 patients with moderate-to-severe HFS before and after treatment with BTX-A. After treatment, the IOP was also measured using GAT and the results were compared with the ones measured with a Diaton®. The patients underwent automated perimetry, OCT, and pachymetry for screening to glaucoma. RESULTS: Mean IOP with Diaton® was 11 ± 3.42 mmHg before treatment in the affected eye and 9 ± 2.98 mmHg in the contralateral eye. This difference was statistically significant (P = 0.012). However, after treatment with BTX-A, no interocular difference was found in IOP obtained with Diaton® (P = 0.204) or GAT (P = 0.971). Comparison between GAT and Diaton® measurements showed no significant differences after BTX-A treatment between the affected (P = 0.212) and contralateral eye (P = 0.971). CONCLUSIONS: A significant reduction in IOP measurements on the affected side of HFS patients was observed after treatment with BTX-A, demonstrating that eyelid spasms may increase the IOP. No significant difference was observed between Diaton® and GAT measurements after the application of BTX-A. No differences were found in automated perimetry, OCT, and CCT when comparing affected eyes with contralateral eyes.

Hearts and Minds: Emotion Recognition and Mentalizing in Parkinson's Disease and Progressive Supranuclear Palsy.

OBJECTIVE: There are scarce data comparing Parkinson's disease (PD) and Progressive Supranuclear Palsy (PSP) in social cognition (SC). We aimed to compare patients with PSP and PD in SC. METHODS: We included three groups: PD (n = 18), PSP (n = 20) and controls (n = 23). Participants underwent neuropsychological exams, including the mini-version of the Social and Emotional Assessment, which is composed of the facial emotion recognition test (FERT) and the modified faux-pas (mFP) test, which assesses Theory of Mind (ToM). RESULTS: Patients with PD scored lower than controls in the FERT, but not in the mFP test. Patients with PSP performed worse than controls in both the mFP and FERT. PD and PSP groups did not differ in the FERT, but PSP performed worse than PD in the mFP test. The mFP test distinguished PSP from PD with 89% accuracy. CONCLUSION: The assessment of ToM may contribute to the differentiation between PD and PSP.

Handicap as a Measure of Perceived-Health Status in Parkinson's Disease.

Background: Handicap is a patient-centered measure of health status that encompasses the impact of social and physical environment on daily living, having been assessed in advanced and late-stage Parkinson's Disease (PD). Objective: To characterize the handicap of a broader sample of patients. Methods: A cross-sectional study of 405 PD patients during the MDS-UPDRS Portuguese validation study, using the MDS-UPDRS, Unified Dyskinesias Rating Scale, Nonmotor symptoms questionnaire, PDQ-8 and EQ-5D-3L. Handicap was measured using the London Handicap Scale (LHS). Results: Mean age was 64.42 (±10.3) years, mean disease duration 11.30 (±6.5) years and median HY 2 (IQR, 2-3). Mean LHS was 0.652 (±0.204); "Mobility," "Occupation" and "Physical Independence" were the most affected domains. LHS was significantly worse in patients with longer disease duration, older age and increased disability. In contrast, PDQ-8 did not differentiate age groups. Handicap was significantly correlated with disease duration (r = -0.35), nonmotor experiences of daily living (EDL) (MDS-UPDRS-I) (r = -0.51), motor EDL (MDS-UPDRS-II) (r = -0.69), motor disability (MDS-UPDRS-III) (r = -0.49), axial signs of MDS-UPDRS-III (r = -0.55), HY (r = -0.44), presence of nonmotor symptoms (r = -0.51) and PDQ-8 index (r = -0.64) (all P < 0.05). Motor EDL, MDS-UPDRS-III and PDQ-8 independently predicted Handicap (adjusted R 2 = 0.582; P = 0.007). Conclusions: The LHS was easily completed by patients and caregivers. Patients were mild-moderately handicapped, which was strongly determined by motor disability and its impact on EDL, and poor QoL. Despite correlated, handicap and QoL seem to differ in what they measure, and handicap may have an added value to QoL. Handicap seems to be a good measure of perceived-health status in a broad sample of PD.

X-Chromosome Association Study in Latin American Cohorts Identifies New Loci in Parkinson's Disease.

BACKGROUND: Sex differences in Parkinson's disease (PD) risk are well-known. However, the role of sex chromosomes in the development and progression of PD is still unclear. OBJECTIVE: The objective of this study was to perform the first X-chromosome-wide association study for PD risk in a Latin American cohort. METHODS: We used data from three admixed cohorts: (1) Latin American Research consortium on the Genetics of Parkinson's Disease (n = 1504) as discover cohort, and (2) Latino cohort from International Parkinson Disease Genomics Consortium (n = 155) and (3) Bambui Aging cohort (n = 1442) as replication cohorts. We also developed an X-chromosome framework specifically designed for admixed populations. RESULTS: We identified eight linkage disequilibrium regions associated with PD. We replicated one of these regions (top variant rs525496; discovery odds ratio [95% confidence interval]: 0.60 [0.478-0.77], P = 3.13 × 10-5 replication odds ratio: 0.60 [0.37-0.98], P = 0.04). rs5525496 is associated with multiple expression quantitative trait loci in brain and non-brain tissues, including RAB9B, H2BFM, TSMB15B, and GLRA4, but colocalization analysis suggests that rs5525496 may not mediate risk by expression of these genes. We also replicated a previous X-chromosome-wide association study finding (rs28602900), showing that this variant is associated with PD in non-European populations. CONCLUSIONS: Our results reinforce the importance of including X-chromosome and diverse populations in genetic studies. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

"I don't have Huntington's disease": the boundaries between acceptance and understanding.

Huntington's disease (HD) is an inherited disease that leads to an inexorable progression of motor, cognitive and psychiatric disturbances. In the initial stages, the symptoms are not clearly disabling, and the patient may present a lack of awareness about the symptoms themselves, which we call anosognosia. However, anosognosia might not justify all passivity of the HD patient in face of the diagnosis. Patients may also experience the denial of illness, as a stage of grief, expected to happen in the face of the diagnosis of any neurodegenerative disorder. In addition, people with HD tend to be more apathetic, and more silent, in regular consultations. In the present article, the authors express a point of view, discussing the behavior of the HD patient, in which there is a multifactorial passivity, in the face of the diagnosis and of the disease itself. Having the proper knowledge of this situation may prepare the neurologist to better understand the patient and the evolution of the disease.

A doença de Huntington (DH) é uma doença hereditária que leva a uma progressão inexorável de distúrbios motores, cognitivos e psiquiátricos. Nos estágios iniciais, os sintomas não são claramente incapacitantes e há uma falta de consciência sobre os próprios sintomas, o que chamamos de anosognosia. No entanto, anosognosia pode não justificar toda a passividade do paciente de HD diante do diagnóstico. Os pacientes também podem vivenciar a negação da doença, como um estágio de luto, o que é esperado acontecer diante do diagnóstico de qualquer doença neurodegenerativa. Além disso, as pessoas com DH tendem a ficar mais apáticas, mais silenciosas, nas consultas regulares. No presente artigo, os autores expressam um ponto de vista, discutindo acerca do comportamento do paciente com DH, em que há uma passividade multifatorial, frente ao diagnóstico e diante da doença em si. Ter conhecimento sobre essa situação pode preparar o neurologista para entender melhor o paciente e a evolução da doença.

Clinical and functional correlates of parkinsonism in a population-based sample of individuals aged 75 + : the Pietà study.

BACKGROUND: Parkinsonism is strongly associated with ageing, and many studies have suggested that parkinsonian signs may affect up to half of older adults and is associated with a wide range of adverse health outcomes. We compared clinical and functional characteristics of oldest-old community-dwelling individuals with parkinsonism (parkinsonian group [PG]) to individuals without parkinsonism (non-parkinsonian group [NPG]. METHODS: The Pietà study is a population-based study conducted in Caeté, southeast Brazil, involving 607 individuals aged 75 + years submitted to an extensive clinical evaluation. A subset of 65 PG individuals (61.5% women, median age of 82 years) was compared to 542 NPG individuals (64.8% women, median age of 80 years). RESULTS: PG individuals had significantly more functional impairment, clinical comorbidities (including number of falls, loss of bladder control and dysphagia) and major depression. Multivariate analysis revealed that older age, higher UPDRSm scores, lower category fluency test (animals/minute) and delayed recall memory scores were associated with PG. This group was also more cognitively impaired, with lower performance than NPG individuals in the Mini-Mental State Examination, category fluency test (animals/minute), clock drawing and in delayed recall (p < 0.001 for all tests). UPDRSm scores were the most contributing factor to cognition that independently explained variability in functionality of the entire sample. CONCLUSION: Individuals aged 75 + years with parkinsonism were significantly more clinically and functionally impaired in this population-based sample. Cognitive dysfunction explained most of the loss of functionality in these patients. UPDRS-m scores contributed independently to explain variability in functionality in the whole sample.

"I don't have Huntington's disease": the boundaries between acceptance and understanding / "Eu não tenho doença de Huntington": os limites entre aceitação e compreensão

Abstract Huntington's disease (HD) is an inherited disease that leads to an inexorable progression of motor, cognitive and psychiatric disturbances. In the initial stages, the symptoms are not clearly disabling, and the patient may present a lack of awareness about the symptoms themselves, which we call anosognosia. However, anosognosia might not justify all passivity of the HD patient in face of the diagnosis. Patients may also experience the denial of illness, as a stage of grief, expected to happen in the face of the diagnosis of any neurodegenerative disorder. In addition, people with HD tend to be more apathetic, and more silent, in regular consultations. In the present article, the authors express a point of view, discussing the behavior of the HD patient, in which there is a multifactorial passivity, in the face of the diagnosis and of the disease itself. Having the proper knowledge of this situation may prepare the neurologist to better understand the patient and the evolution of the disease.

Resumo A doença de Huntington (DH) é uma doença hereditária que leva a uma progressão inexorável de distúrbios motores, cognitivos e psiquiátricos. Nos estágios iniciais, os sintomas não são claramente incapacitantes e há uma falta de consciência sobre os próprios sintomas, o que chamamos de anosognosia. No entanto, anosognosia pode não justificar toda a passividade do paciente de HD diante do diagnóstico. Os pacientes também podem vivenciar a negação da doença, como um estágio de luto, o que é esperado acontecer diante do diagnóstico de qualquer doença neurodegenerativa. Além disso, as pessoas com DH tendem a ficar mais apáticas, mais silenciosas, nas consultas regulares. No presente artigo, os autores expressam um ponto de vista, discutindo acerca do comportamento do paciente com DH, em que há uma passividade multifatorial, frente ao diagnóstico e diante da doença em si. Ter conhecimento sobre essa situação pode preparar o neurologista para entender melhor o paciente e a evolução da doença.

Levodopa Dose Equivalency in Parkinson's Disease: Updated Systematic Review and Proposals.

BACKGROUND: To compare drug regimens across clinical trials in Parkinson's disease (PD) conversion formulae between antiparkinsonian drugs have been developed. These are reported in relation to levodopa as the benchmark drug in PD pharmacotherapy as 'levodopa equivalent dose' (LED). Currently, the LED conversion formulae proposed in 2010 by Tomlinson et al. based on a systematic review are predominantly used. However, new drugs with established and novel mechanisms of action and novel formulations of longstanding drugs have been developed since 2010. Therefore, consensus proposals for updated LED conversion formulae are needed. OBJECTIVES: To update LED conversion formulae based on a systematic review. METHODS: The MEDLINE, CENTRAL, and Embase databases were searched from January 2010 to July 2021. Additionally, in a standardized process according to the GRADE grid method, consensus proposals were issued for drugs with scarce data on levodopa dose equivalency. RESULTS: The systematic database search yielded 3076 articles of which 682 were eligible for inclusion in the systematic review. Based on these data and the standardized consensus process, we present proposals for LED conversion formulae for a wide range of drugs that are currently available for the pharmacotherapy of PD or are expected to be introduced soon. CONCLUSIONS: The LED conversion formulae issued in this Position Paper will serve as a research tool to compare the equivalence of antiparkinsonian medication across PD study cohorts and facilitate research on the clinical efficacy of pharmacological and surgical treatments as well as other non-pharmacological interventions in PD. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Defining the Riddle in Order to Solve It: There Is More Than One "Parkinson's Disease".

BACKGROUND: More than 200 years after James Parkinsondescribed a clinical syndrome based on his astute observations, Parkinson's disease (PD) has evolved into a complex entity, akin to the heterogeneity of other complex human syndromes of the central nervous system such as dementia, motor neuron disease, multiple sclerosis, and epilepsy. Clinicians, pathologists, and basic science researchers evolved arrange of concepts andcriteria for the clinical, genetic, mechanistic, and neuropathological characterization of what, in their best judgment, constitutes PD. However, these specialists have generated and used criteria that are not necessarily aligned between their different operational definitions, which may hinder progress in solving the riddle of the distinct forms of PD and ultimately how to treat them. OBJECTIVE: This task force has identified current in consistencies between the definitions of PD and its diverse variants in different domains: clinical criteria, neuropathological classification, genetic subtyping, biomarker signatures, and mechanisms of disease. This initial effort for "defining the riddle" will lay the foundation for future attempts to better define the range of PD and its variants, as has been done and implemented for other heterogeneous neurological syndromes, such as stroke and peripheral neuropathy. We strongly advocate for a more systematic and evidence-based integration of our diverse disciplines by looking at well-defined variants of the syndrome of PD. CONCLUSION: Accuracy in defining endophenotypes of "typical PD" across these different but interrelated disciplines will enable better definition of variants and their stratification in therapeutic trials, a prerequisite for breakthroughs in the era of precision medicine. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

Development and Validation of the Dystonia-Pain Classification System: A Multicenter Study.

BACKGROUND: Dystonia is associated with disabling nonmotor symptoms like chronic pain (CP), which is prevalent in dystonia and significantly impacts the quality of life (QoL). There is no validated tool for assessing CP in dystonia, which substantially hampers pain management. OBJECTIVE: The aim was to develop a CP classification and scoring system for dystonia. METHODS: A multidisciplinary group was established to develop the Dystonia-Pain Classification System (Dystonia-PCS). The classification of CP as related or unrelated to dystonia was followed by the assessment of pain severity score, encompassing pain intensity, frequency, and impact on daily living. Then, consecutive patients with inherited/idiopathic dystonia of different spatial distribution were recruited in a cross-sectional multicenter validation study. Dystonia-PCS was compared to validated pain, mood, QoL, and dystonia scales (Brief Pain Inventory, Douleur Neuropathique-4 questionnaire, European QoL-5 Dimensions-3 Level Version, and Burke-Fahn-Marsden Dystonia Rating Scale). RESULTS: CP was present in 81 of 123 recruited patients, being directly related to dystonia in 82.7%, aggravated by dystonia in 8.8%, and nonrelated to dystonia in 7.5%. Dystonia-PCS had excellent intra-rater (Intraclass Correlation Coefficient - ICC: 0.941) and inter-rater (ICC: 0.867) reliability. In addition, pain severity score correlated with European QoL-5 Dimensions-3 Level Version's pain subscore (r = 0.635, P < 0.001) and the Brief Pain Inventory's severity and interference scores (r = 0.553, P < 0.001 and r = 0.609, P < 0.001, respectively). CONCLUSIONS: Dystonia-PCS is a reliable tool to categorize and quantify CP impact in dystonia and will help improve clinical trial design and management of CP in patients affected by this disorder. © 2023 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

COVID19-associated new-onset movement disorders: a follow-up study.

BACKGROUND: Neurological symptoms are common manifestation in acute COVID-19. This includes hyper- and hypokinetic movement disorders. Data on their outcome, however, is limited. METHODS: Cases with new-onset COVID-19-associated movement disorders were identified by searching the literature. Authors were contacted for outcome data which were reviewed and analyzed. RESULTS: Movement disorders began 12.6 days on average after the initial onset of COVID-19. 92% of patients required hospital admission (mean duration 23 days). In a fraction of patients (6 of 27; 22%; 4 males/2 females, mean age 66.8 years) the movement disorder (ataxia, myoclonus, tremor, parkinsonism) was still present after a follow-up period of 7.5 ± 3 weeks. Severe COVID-19 in general and development of encephalopathy were risk factors, albeit not strong predictors, for the persistence. CONCLUSIONS: The prognosis of new-onset COVID-19-associated movement disorder appears to be generally good. The majority recovered without residual symptoms within several weeks or months. Permanent cases may be due to unmasking of a previous subclinical movement disorder or due to vascular/demyelinating damage. Given the relatively low response rate of one third only and the heterogeneity of mechanisms firm conclusions on the (long-term) outome cannot, however, be drawn.