Axial motor signs-including gait impairment, postural instability and postural abnormalities-are common and debilitating symptoms in patients with advanced Parkinson disease. Dopamine replacement ...therapy and physiotherapy provide, at best, partial relief from axial motor symptoms. In carefully selected candidates, deep brain stimulation (DBS) of the subthalamic nucleus or globus pallidus internus is an established treatment for 'appendicular' motor signs (limb tremor, bradykinesia and rigidity). However, the effects of DBS on axial signs are much less clear, presumably because motor control of axial and appendicular functions is mediated by different anatomical-functional pathways. Here, we discuss the successes and failures of DBS in managing axial motor signs. We systematically address a series of common clinical questions associated with the preoperative phase, during which patients presenting with prominent axial signs are considered for DBS implantation surgery, and the postoperative phase, in particular, the management of axial motor signs that newly develop as postoperative complications, either acutely or with a delay. We also address the possible merits of new targets-including the pedunculopontine nucleus area, zona incerta and substantia nigra pars reticulata-to specifically alleviate axial symptoms. Supported by a rapidly growing body of evidence, this practically oriented Review aims to support decision-making in the management of axial symptoms.
Alzheimer's disease (AD) and Parkinson's disease (PD) are the first and second most common neurodegenerative disorders, respectively. Both are proteinopathies with inexorable courses and no approved ...disease-modifying therapies. A substantial effort has been made to identify interventions that could slow down the progression of AD and PD; to date, with no success. The advances in biomarker research improved the identification of individuals at risk for these disorders before symptom onset, recognizing the pre-clinical stage, in which there is abnormal protein accumulation but no clinical symptoms of the disease, and the prodromal stage, in which mild symptoms are present but the clinical diagnostic criteria for disease cannot be fulfilled. The ability to detect pre-clinical and prodromal stages of these diseases has encouraged clinical trials for disease-modification at earlier phases, seeking to slow or prevent phenoconversion into clinical disease. Clinical trials at these stages have several challenges, such as the identification of the eligible population, the appropriate choice of biomarkers, the definition of clinical endpoints, the duration of follow-up, and the statistical analysis. This article aims to discuss some of the methodological challenges in the design of trials for pre-clinical and prodromal phases of AD and PD, to critically review the recent studies, and to discuss methodological approaches to mitigate these challenges in trial design.
We report a 37-year-old Caucasian male with history of developmental delay, childhood onset Intellectual Disability (ID) and attention deficit hyperactivity disorder (ADHD) who presented at the age ...of 34 with tremor-dominant parkinsonism. Next Generation Sequencing (NGS) revealed pathogenic hemizygous sequence variant, c.200G > T, in the RAB39B gene. This report expands the number of described individuals with young onset PD associated with RAB39B mutation.
IMPORTANCE: Symptoms in the genital region, such as pain, discomfort, tingling, and burning sensations, have rarely been reported in Parkinson disease (PD), and the previous cases were attributed to ...nonmotor off symptoms. We report a patient with PD and severe genital discomfort unrelated to motor fluctuations but compatible with restless genital syndrome. OBSERVATIONS: A 65-year-old woman with PD experienced a disabling discomfort in her pelvis and genital region for 3 years. The episodes occurred in the evening and were triggered by sitting or lying down for a period. Gynecological investigation was unrevealing. She experienced improvement with a low dose of a dopamine agonist. CONCLUSION AND RELEVANCE: Restless genital syndrome is a rare disorder that can be a source of distress and disability. In patients with PD, restless genital syndrome should be included in the differential diagnosis of genital symptoms and restlessness, along with nonmotor wearing off and akathisia. A detailed clinical history is essential for this diagnosis and treatment with dopamine agonists can provide benefit.
Summary Tardive syndromes (TS) encompass a broad spectrum of abnormal movements due to chronic exposure to dopamine receptor blocking agents. This review provides a compiled update on TS, including ...phenomenology, epidemiology, pathophysiology, genetic correlations and therapeutics, highlighting the emerging experience with atypical antipsychotics. The advent of atypical antipsychotics, which have lower affinity for dopamine receptors and act on 5-HT2A and 5-HT2C serotonin receptors, was expected to dramatically reduce the prevalence and incidence of this iatrogenic problem. Recent studies have shown that the reduction has been more modest than expected and TS remains an important challenge. Recent insights on pathophysiology, risk factors and genetic correlations have raised the hope for further individualized treatment for schizophrenic patients, and more strict use of antipsychotics. Up to now, there is no definite treatment for TS, but options range from relatively innocuous low doses of propranolol to more invasive procedures such as deep brain stimulation.
Maternal educational attainment has been identified as relevant to several child health and development outcomes. This study aimed to evaluate the association of sociodemographic and maternal ...education factors with child development in families living below the poverty line. A cross-sectional study was conducted through telephone contact from May to July 2021 in Ceará, a state in Northeastern Brazil. The study population comprised families with children up to six years of age participating in the cash transfer program "Mais infância". The families selected to participate in this program must have a monthly per capita income of less than US$16.50. The Ages and Stages Questionnaire version 3 was applied to assess the children's development status. The mothers reported maternal educational attainment as the highest grade and or degree obtained. The final weighted and adjusted model showed that maternal schooling was associated with the risk of delay in all domains except for the fine motor domain. The risk of delay in at least one domain was 2.5-fold higher in mothers with a lower level of schooling (95% CI: 1.6-3.9). The findings of this study suggest that mothers with higher educational attainment have children with better child development outcomes.
ABSTRACT
Background
Deep Brain Stimulation (DBS) is an increasingly popular therapy for Parkinson's Disease (PD). Despite the experience gained over time with DBS of either the subthalamus or the ...globus pallidus pars interna, there is still no consensus regarding the age limit for DBS indication.
Objectives
This narrative review of the literature discusses the issues of age and DBS, emphasizing the critical need for good quality evidence to support the surgical management of elderly patients with PD.
Methods
We searched PubMed using the terms Parkinson's Disease; Parkinson's Disease therapy; deep brain stimulation; antiparkinsonian agents therapeutic use; age factors; aged; aged, 80 and over; middle aged; treatment outcome; and risk assessments.
Results
We identified several limitations of the available evidence, such as under‐representation of older patients in DBS studies, small sample sizes in studies with older participants, heterogeneity of outcomes, and conflicting results.
Conclusions
Despite preliminary suggestions that age might affect the outcomes of DBS, the evidence to support the hypothesis of age as an independent predictor of DBS outcomes is limited and results are controversial. Ultimately, finding an age‐independent biomarker predicting DBS outcome is the final goal to expand this powerful treatment to all patients age in an effective and safe manner.
Deep brain stimulation (DBS) is recognized as an established therapy for Parkinson's disease (PD) and other movement disorders in the light of the developments seen over the past three decades. ...Long-term efficacy is established for PD with documented improvement in the cardinal motor symptoms of PD and levodopa-induced complications, such as motor fluctuations and dyskinesias. Timing of patient selection is crucial to obtain optimal benefits from DBS therapy, before PD complications become irreversible. The objective of this first part review is to examine the fundamental concepts of DBS for PD in clinical practice, discussing the historical aspects, patient selection, potential effects of DBS on motor and non-motor symptoms, and the practical management of patients after surgery.
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