Persistence of Basal Ganglia Oscillatory Activity During Tremor Attenuation by Movement in Parkinson's Disease Patients.

BACKGROUND: One of the characteristics of parkinsonian tremor is that its amplitude decreases with movement. Current models suggest an interaction between basal ganglia (BG) and cerebello-thalamo-cortical circuits in parkinsonian tremor pathophysiology. OBJECTIVE: We aimed to correlate central oscillation in the BG with electromyographic activity during re-emergent tremor in order to detect changes in BG oscillatory activity when tremor is attenuated by movement. METHODS: We performed a prospective, observational study on consecutive parkinsonian patients who underwent deep brain stimulation surgery and presented re-emergent tremor. Coherence analysis between subthalamic nucleus/globus pallidus internus (STN/GPi) tremorous activity measured by microrecording (MER) and electromyogram (EMG) from flexor and extensor wrist muscles during rest, posture, and re-emergent tremor pause was performed during surgery. The statistical significance level of the MER-EMG coherence was determined using surrogate data analysis, and the directionality of information transfer between BG and muscle was performed using entropy transfer analysis. RESULTS: We analyzed 148 MERs with tremor-like activity from 6 patients which were evaluated against the simultaneous EMGs, resulting in 296 correlations. Of these, 26 presented a significant level of coherence at tremor frequency, throughout rest and posture, with a complete EMG stop in between. During the pause, all recordings showed sustained MER peaks at tremor frequency (±1.5 Hz). Information flows preferentially from BG to muscle during rest and posture, with a loss of directionality during the pause. CONCLUSIONS: Our results suggest that oscillatory activity in STN/GPi functionally linked to tremor sustains firing frequency during re-emergent tremor pause, thus suggesting no direct role of the BG circuit on tremor attenuation due to voluntary movements. © 2024 International Parkinson and Movement Disorder Society.

Correlation between 99mTc-TRODAT-1 SPECT and 18F-FDOPA PET in patients with Parkinson's disease: a pilot study / Correlação entre 99mTc-TRODAT-1 SPECT e 18F-FDOPA PET em pacientes com doença de Parkinson: um estudo piloto

Abstract Objective: To determine whether technetium-99m-labeled tropane derivative single-photon emission computed tomography (99mTc-TRODAT-1 SPECT) provides results comparable to those of the less widely available, less accessible tool fluorine-18-labeled fluorodopa positron-emission tomography (18F-FDOPA PET) in the setting of a movement disorders clinic. Materials and Methods: In this prospective pilot study, eight subjects with a clinical diagnosis of Parkinson's disease were randomly selected from among patients under treatment at a movement disorders clinic and submitted to 99mTc-TRODAT-1 SPECT and 18F-FDOPA PET. The results were read by two experienced observers, and a semiquantitative analysis was performed. Results: The visual and semiquantitative analyses were concordant for all studies, showing that radiotracer uptake in the contralateral striatum on the most affected side was lower when 99mTc-TRODAT-1 SPECT was employed. The semiquantitative analysis demonstrated a significant correlation between 18F-FDOPA PET and 99mTc-TRODAT-1 SPECT (r = 0.73; p < 0.01). Conclusion: It appears that 99mTc-TRODAT-1 SPECT is a valid option for the study of dopaminergic function in a clinical setting.

Resumo Objetivo: Determinar se a 99mTc-TRODAT-1 SPECT fornece resultados comparáveis aos da 18F-FDOPA PET, ferramenta menos acessível e menos amplamente disponível, no contexto de uma clínica de distúrbios do movimento. Materiais e Métodos: Neste estudo prospectivo, oito indivíduos com diagnóstico clínico de doença de Parkinson foram selecionados aleatoriamente entre pacientes em tratamento em uma clínica de distúrbios do movimento e submetidos a 99mTc-TRODAT-1 SPECT e 18F-FDOPA PET. Os resultados foram lidos por dois observadores experientes e uma análise semiquantitativa foi realizada. Resultados: As análises visual e semiquantitativa foram concordantes para todos os estudos, mostrando que a captação do radiotraçador no estriado contralateral do lado mais afetado foi menor quando a 99mTc-TRODAT-1 SPECT foi empregada. A análise semiquantitativa demonstrou uma correlação significativa entre 18F-FDOPA PET e 99mTc-TRODAT-1 SPECT (r = 0,73; p < 0,01). Conclusão: A 99mTc-TRODAT-1 SPECT parece ser uma opção válida para o estudo da função dopaminérgica em um ambiente clínico.

Cardiac Involvement in Movement Disorders.

BACKGROUND: Several conditions represented mainly by movement disorders are associated with cardiac disease, which can be overlooked in clinical practice in the context of a prominent primary neurological disorder. OBJECTIVES: To review neurological conditions that combine movement disorders and primary cardiac involvement. METHODS: A comprehensive and structured literature search following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses criteria was conducted to identify disorders combining movement disorders and cardiac disease. RESULTS: Some movement disorders are commonly or prominently associated with cardiac disease. Neurological and cardiac symptoms may share underlying physiopathological mechanisms in diseases, such as Friedreich's ataxia and Wilson's disease, and in certain metabolic disorders, including Refsum disease, Gaucher disease, a congenital disorder of glycosylation, or cerebrotendinous xanthomatosis. In certain conditions, such as Sydenham's chorea or dilated cardiomyopathy with ataxia syndrome (ATX-DNAJC19), heart involvement can present early in the course of disease, whereas in others such as Friedreich's ataxia or Refsum disease, cardiac symptoms tend to present in later stages. In another 68 acquired or inherited conditions, cardiac involvement or movement disorders are seldom reported. CONCLUSIONS: As cardiac disease is part of the phenotypic spectrum of several movement disorders, heart involvement should be carefully investigated and increased awareness of this association encouraged as it may represent a leading cause of morbidity and mortality.

Challenges in PD Patient Management After DBS: A Pragmatic Review.

BACKGROUND: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) or internal globus pallidus (GPi) represents an effective and universally applied therapy for Parkinson's disease (PD) motor complications. However, certain procedure-related problems and unrealistic patient expectations may detract specialists from indicating DBS more widely despite significant clinical effects. METHODS: This review provides a pragmatic educational summary of the most conflicting postoperative management issues in patients undergoing DBS for PD. RESULTS: DBS in PD has been associated with certain complications and post-procedural management issues, which can complicate surgical outcome interpretation. Many PD patients consider DBS outcomes negative due to unfulfilled expectations, even when significant motor symptom improvement is achieved. Speech, gait, postural stability, and cognition may worsen after DBS and body weight may increase. Although DBS may induce impulse control disorders in some cases, in others, it may actually improve them when dopamine agonist dosage is reduced after surgery. However, apathy may also arise, especially when dopaminergic medication tapering is rapid. Gradual loss of response with time suggests disease progression, rather than the wearing off of DBS effects. Furthermore, implantable pulse generator expiration is considered a movement disorder emergency, as it may worsen parkinsonian symptoms or cause life-threatening akinetic crises due to malignant DBS withdrawal syndrome. CONCLUSION: Major unsolved issues occurring after DBS therapy preclude complete patient satisfaction. Multidisciplinary management at experienced centers, as well as careful and comprehensive delivery of information to patients, should contribute to make DBS outcome expectations more realistic and allow post procedural complications to be better accepted.

A Treatable Rare Cause of Progressive Ataxia and Palatal Tremor.

Background: Cerebrotendinous xanthomatosis is a rare autosomal recessive neurometabolic disorder characterized by chronic diarrhea, tendon xanthomas, juvenile cataracts, and neurological symptoms. Case Report: An adult patient with cerebrotendinous xanthomatosis exhibited ataxia and palatal tremor in the absence of tendon xanthomas and cataracts. Discussion: The importance of this case resides on the fact that cerebrotendinous xanthomatosis should be considered as a possible etiology of the syndrome of progressive ataxia with palatal tremor, even in the absence of tendon xanthomas and cataracts. Early diagnosis is critical to the institution of specific treatment with chenodeoxycholic acid.

A multifactorial study on nutritional status, binge eating and physical activity as main factors directly influencing body weight in Parkinson's disease.

Weight lossisa multifactorial disorder commonly affecting Parkinson's disease patients. The aim of this study was to investigate the relationship between body weight, nutritional status, physical activity, and Parkinson's disease-related factors. A total of 114 consecutive Parkinson's disease patients without dietary restrictions were evaluated prospectively with respect to: nutritional status (Mini Nutritional Assessment), physical activity level (Yale Physical Activity Survey), MDS-UPDRS score, olfactory function, depression, cognitive functionand impulse-control disorders, among other variables. Structural equation modeling was used to build multivariate models and to calculate standardized regression weights (srw) for pairs of variables, which are homologous to correlation coefficients, taking into account the effects of all other variables in the model. Sixty (53%) patients were males. Mean age was 66.1 ± 9.8 years and mean disease duration was 8.3 ± 5.6 years. Longer disease duration was negatively related to nutritional status (srw = -0.25; p = 0.01). UPDRS II + III score was associated with reduced cognitive function (srw = -0.39; p = 0.01), which was positivelyrelated to nutritional status (srw = 0.23; p = 0.01). Finally, nutritional status was positively related to body weight (srw = 0.22, p < 0.01). Binge eating and physical activity were also directly and positively related to body weight (srw = 0.32; p = 0.001 and srw = 0.23; p = 0.001). Nutritional status, binge eating and physical activity were directly and independently related to body weight in our sample of Parkinson's disease patients. Therefore, physicians should actively explore nutritional status and binge eating in Parkinson's disease patients to avoid alterations in body weight regulation. Effects of physical activity should be further explored.

Two new adenosine receptor antagonists for the treatment of Parkinson's disease: istradefylline versus tozadenant.

INTRODUCTION: Adenosine A2A receptors are localized in the brain, mainly within the caudate and putamen nuclei of the basal ganglia. Their activation leads to stimulation of the 'indirect' pathway. Conversely, administration of A2A receptor antagonists leads to inhibition of this pathway, which was translated into reduced hypomotility in several animal models of parkinsonism. AREAS COVERED: In this review, the effects of two A2A receptor antagonists, istradefylline and tozadenant, on parkinsonian symptoms in animal and humans will be discussed. EXPERT OPINION: Animal studies have shown potent antiparkinsonian effects for several A2A receptor antagonists, including istradefylline. In clinical trials, istradefylline reduced OFF time when administered with levodopa, but results are inconclusive. Results with tozadenant are scarce. Modification of thalamic blood flow compatible with reduced inhibition was noted in one small trial, followed by a significant reduction in OFF time in a larger one. Therefore, both drugs show promising efficacy for the reduction of OFF time in levodopa-treated Parkinson's disease patients, but further research is needed in order to obtain definitive conclusions.

Historias del cerebro: la cocinera que perdió el olfato y la chica que no podía parar de correr

Contenido: El hombre que se creía Adrián Suar. La mano con vida propia. La cocinera sin olfato. La estudiante que no podía bajar las escaleras. La tenista que revolvía la basura. La periodista que perdió las palabras. El ciego que ignoraba su ceguera. El golpeador sonámbulo. La madre que olvidó a su hija. La moza que hacía gestos obscenos. Corre, Laura, corre. La niña que sabía que iba a morir

Sialorrhoea and drooling in patients with Parkinson's disease: epidemiology and management.

Although often less recognized than motor symptoms, non-motor effects represent an important source of disability for many parkinsonian patients. Of these non-motor symptoms, sialorrhoea, defined as the inability to control oral secretions resulting in excessive saliva accumulation in the oropharynx, constitutes perhaps one of the most bothersome and troubling problems, often causing social embarrassment and isolation. In patients with Parkinson's disease (PD), this symptom is thought to be due to restricted swallowing and dysfunction, rather than to hypersecretion of saliva. Only a few well designed studies have been conducted to determine the optimal treatment for sialorrhoea in PD. A combination of approaches appears to be necessary to obtain successful results.

Neuronal activity of the zona incerta in Parkinson's disease patients.

The objective of this study was to describe the firing characteristics of the zona incerta (ZI) in Parkinson's disease patients. The ZI constitutes a band of gray matter lying dorsal to the subthalamic nucleus, whose firing properties have not been well defined in humans yet. ZI proved to become hyperactive in 6-OHDA-lesioned rats as compared to normal rats, and regarding these noticeable changes in the discharge patterns it was suggested that ZI could be a putative target for the surgical treatment of Parkinson's disease. Twelve patients who underwent microrecording-guided subthalamic surgery consented to the study. Neurons from different tracts were classified as belonging to the ZI according to their firing features, background extracellular activity, anatomical mapping of trajectories, and atlas confirmation. Fifty-nine neurons were classified as belonging to ZI. The mean firing rate proved to be 29.5 Hz, with a broad dispersion band, even covering subthalamic nucleus (STN) frequency ranges. Pattern analysis showed heterogeneous neuronal signals ranging from tonic to burst and paused neurons. A decrease in extracellular background activity in the defined ZI was also observed. Five of the recorded neurons showed rhythmical spike trains with oscillations of 8 to 14 Hz, and two units were found to discharge trains at 4 Hz. None of the recorded ZI neurons responded to proprioceptive maneuvers. ZI presented firing activities with a broad spectrum in terms of frequency and tonicity. It is differentiated from STN recordings in Parkinson's disease patients mainly because of absent proprioceptive-related units and diminished extracellular background activity.

Pallidotomy in Parkinson's disease improves single-joint, repetitive, ballistic movements, but fails to modify multijoint, repetitive, gestural movements.

We studied 12 non-demented PD patients in on state before and 3 months after posteroventral pallidotomy (PVP), in order to evaluate the effects of surgery upon an unconstrained, multijoint skilled movement as well as a single joint, repetitive, ballistic movement. A Selspot II System was used for three-dimensional data acquisition, processing and reconstruction of limb trajectories. Specific wrist kinematic features of spatial accuracy (linearity and planarity), temporal attributes (acceleration and velocity), spatiotemporal relationships (velocity-curvature coupling), and joint kinematic variables (relationships between wrist and elbow velocities and relative arm angle amplitudes) for each cycle of movement were graphically and numerically analysed. QMC was applied to single joint, repetitive, ballistic movements. QMC significantly improved after PVP (P < 0.0006). However, wrist as well as joint kinematic variables of the gestural movements failed to change significantly after PVP. The lack of improvement of the kinematic abnormalities of the gestural movement in PD patients would indicate that they are unrelated to the basic motor deficit; most likely they are the result of a disruption of a complex of sensorimotor integration processes due to abnormal parieto-frontal basal ganglia interaction.

Tratamiento de las fluctuaciones motoras de la enfermedad de Parkinson con inyecciones subcutaneas de apomorfina / Treatment of motor fluctuations in Parkinson's disease with subcutaneous injections of apomorfine

Dieciseis pacientes con enfermedad de Parkinson y severas fluctuaciones motoras fueron tratados con inyecciones subcutáneas de apomorfina y seguidos prospectivamente durante un año. La utilización de la droga mejoró el número de hroas "off" diarias en un 52 por ciento; la eficacia del tratamiento se mantuvo constante al cabo de un año sin la aparición de tolerancia (ANOVA con mediciones repetidas p=0.0002). No se registraron efectos adversos severos que justificaran la suspensión del tratamiento. La apomorfina demostró ser una droga segura y eficaz en el tratamiento de las fluctuaciones motoras