Showing papers by "Bastiaan R. Bloem published in 2015"

MDS clinical diagnostic criteria for Parkinson's disease

Abstract: This document presents the Movement Disorder Society Clinical Diagnostic Criteria for Parkinson's disease (PD). The Movement Disorder Society PD Criteria are intended for use in clinical research but also may be used to guide clinical diagnosis. The benchmark for these criteria is expert clinical diagnosis; the criteria aim to systematize the diagnostic process, to make it reproducible across centers and applicable by clinicians with less expertise in PD diagnosis. Although motor abnormalities remain central, increasing recognition has been given to nonmotor manifestations; these are incorporated into both the current criteria and particularly into separate criteria for prodromal PD. Similar to previous criteria, the Movement Disorder Society PD Criteria retain motor parkinsonism as the core feature of the disease, defined as bradykinesia plus rest tremor or rigidity. Explicit instructions for defining these cardinal features are included. After documentation of parkinsonism, determination of PD as the cause of parkinsonism relies on three categories of diagnostic features: absolute exclusion criteria (which rule out PD), red flags (which must be counterbalanced by additional supportive criteria to allow diagnosis of PD), and supportive criteria (positive features that increase confidence of the PD diagnosis). Two levels of certainty are delineated: clinically established PD (maximizing specificity at the expense of reduced sensitivity) and probable PD (which balances sensitivity and specificity). The Movement Disorder Society criteria retain elements proven valuable in previous criteria and omit aspects that are no longer justified, thereby encapsulating diagnosis according to current knowledge. As understanding of PD expands, the Movement Disorder Society criteria will need continuous revision to accommodate these advances.

MDS research criteria for prodromal Parkinson's disease

Abstract: This article describes research criteria and probability methodology for the diagnosis of prodromal PD. Prodromal disease refers to the stage wherein early symptoms or signs of PD neurodegeneration are present, but classic clinical diagnosis based on fully evolved motor parkinsonism is not yet possible. Given the lack of clear neuroprotective/disease-modifying therapy for prodromal PD, these criteria were developed for research purposes only. The criteria are based upon the likelihood of prodromal disease being present with probable prodromal PD defined as ≥80% certainty. Certainty estimates rely upon calculation of an individual's risk of having prodromal PD, using a Bayesian naive classifier. In this methodology, a previous probability of prodromal disease is delineated based upon age. Then, the probability of prodromal PD is calculated by adding diagnostic information, expressed as likelihood ratios. This diagnostic information combines estimates of background risk (from environmental risk factors and genetic findings) and results of diagnostic marker testing. In order to be included, diagnostic markers had to have prospective evidence documenting ability to predict clinical PD. They include motor and nonmotor clinical symptoms, clinical signs, and ancillary diagnostic tests. These criteria represent a first step in the formal delineation of early stages of PD and will require constant updating as more information becomes available.

Freezing of gait: a practical approach to management

Abstract: Freezing of gait is a common and disabling symptom in patients with parkinsonism, characterised by sudden and brief episodes of inability to produce effective forward stepping. These episodes typically occur during gait initiation or turning. Treatment is important because freezing of gait is a major risk factor for falls in parkinsonism, and a source of disability to patients. Various treatment approaches exist, including pharmacological and surgical options, as well as physiotherapy and occupational therapy, but evidence is inconclusive for many approaches, and clear treatment protocols are not available. To address this gap, we review medical and non-medical treatment strategies for freezing of gait and present a practical algorithm for the management of this disorder, based on a combination of evidence, when available, and clinical experience of the authors. Further research is needed to formally establish the merits of our proposed treatment protocol.

Axial disability and deep brain stimulation in patients with Parkinson disease

Abstract: 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.

Reorganization of corticostriatal circuits in healthy G2019S LRRK2 carriers

Abstract: Objective: We investigated system-level corticostriatal changes in a human model of premotor Parkinson disease (PD), i.e., healthy carriers of the G2019S LRRK2 mutation that is associated with a markedly increased, age-dependent risk of developing PD. Methods: We compared 37 asymptomatic LRRK2 G2019S mutation carriers (age range 30–78 years) with 32 matched, asymptomatic nonmutation carriers (age range 30–74 years). Using fMRI, we tested the hypothesis that corticostriatal connectivity in premotor PD shifts from severely affected to less affected striatal subregions, as shown previously in symptomatic PD. Specifically, we predicted that in premotor PD, the shift in corticostriatal connectivity would follow the same gradient of striatal dopamine depletion known from overt PD, with the dorsoposterior putamen being more affected than the ventroanterior putamen. Results: The known parallel topology of corticostriatal loops was preserved in each group, but the topography of putamen connectivity shifted. In LRRK2 G2019S mutation carriers, the right inferior parietal cortex had reduced functional connectivity with the dorsoposterior putamen but increased connectivity with the ventroanterior putamen, as compared with noncarriers. This shift in functional connectivity increased with age in LRRK2 G2019S mutation carriers. Conclusions: Asymptomatic LRRK2 G2019S mutation carriers show a reorganization of corticostriatal circuits that mirrors findings in idiopathic PD. These changes may reflect premotor basal ganglia dysfunction or circuit-level compensatory changes.

The retropulsion test: a good evaluation of postural instability in Parkinson's disease?

Abstract: Postural instability is a disabling feature of Parkinson's disease (PD), contributing to recurrent falls and fall-related injuries. The retropulsion test is widely regarded as the gold standard to evaluate postural instability, and is therefore a key component of the neurological examination in PD. Many variants exist, which confuses both clinical practice and research. Here, we evaluate the merits of this test by discussing three common variants: (1) the pull test as described in the MDS-UPDRS scale; (2) using an unexpected shoulder pull, without prior warning; and (3) the push-and-release test. All variants are a quick method to index the degree of postural instability, but the outcome can vary considerably due to variability in test execution and -interpretation. This partially explains why the retropulsion test fails to predict future falls in PD. Another explanation is that falling results from the complex interplay between gait, balance, cognitive decline and environmental factors, and the retropulsion test captures only part of that. We conclude with several recommendations for current clinical practice.

Quantitative Motor Performance and Sleep Benefit in Parkinson Disease.

Abstract: STUDY OBJECTIVES: Many people with Parkinson disease experience "sleep benefit": temporarily improved mobility upon awakening. Here we used quantitative motor tasks to assess the influence of sleep on motor functioning in Parkinson disease. DESIGN: Eighteen Parkinson patients with and 20 without subjective sleep benefit and 20 healthy controls participated. Before and directly after a regular night sleep and an afternoon nap, subjects performed the timed pegboard dexterity task and quantified finger tapping task. Subjective ratings of motor functioning and mood/vigilange were included. Sleep was monitored using polysomnography. RESULTS: On both tasks, patients were overall slower than healthy controls (night: F2,55 = 16.938, P < 0.001; nap: F2,55 = 15.331, P < 0.001). On the pegboard task, there was a small overall effect of night sleep (F1,55 = 9.695, P = 0.003); both patients and controls were on average slightly slower in the morning. However, in both tasks there was no sleep*group interaction for nighttime sleep nor for afternoon nap. There was a modest correlation between the score on the pegboard task and self-rated motor symptoms among patients (rho = 0.233, P = 0.004). No correlations in task performance and mood/vigilance or sleep time/efficiency were found. CONCLUSIONS: A positive effect of sleep on motor function is commonly reported by Parkinson patients. Here we show that the subjective experience of sleep benefit is not paralleled by an actual improvement in motor functioning. Sleep benefit therefore appears to be a subjective phenomenon and not a Parkinson-specific reduction in symptoms.

Personal health communities: a phenomenological study of a new health-care concept.

Abstract: textContext: Fragmentation of care, complexity of diseases and the need to involve patients actively in their individual health care led to the development of the personal health community (PHC). In a PHC, patients can -regardless of the nature of their condition- invite all professionals that are involved in their health care process. Once gathered, the patient and health care team can exchange information about the patient's health and communicate through several functionalities, in a secured environment. Objectives: Exploring the use, first experiences and potential consequences of using PHCs in health care. Design: Qualitative phenomenological study. Participants: Eighteen respondents, consisting of women experiencing infertility (n = 5), persons with Parkinson's disease (n = 6), a gynaecologist, a fertility doctor, a fertility nurse, three Parkinson's specialist nurses and a neurologist. Results: First experiences with PHCs showed that patients use their PHC differently, dependending on their condition and people involved. Various (potential) advantages for future health care were mentioned relating to both organizational aspects of care (e.g. continuity of care) and the human side of care (e.g. personal care). Patient involvement in care was facilitated. Disadvantages were the amount of work that it took and technological issues. Conclusions: Using PHCs leads to promising improvements in both the organization of care and care experience, according to the participants in this study. They indicate that patients with different diseases and in different circumstances can benefit from these improvements. The PHC seem to be an online tool that can be applied in a personalized way. When (technically) well facilitated, it could stimulate active involvement of patients in their own health and health care. It warrants further research to study its effect on concrete health outcomes.

"Gunslinger's gait": a new cause of unilaterally reduced arm swing.

Abstract: Objective To postulate a new possible cause of a unilaterally reduced arm swing in addition to the known medical conditions such as shoulder pathology, Erb’s palsy, stroke, and Parkinson’s disease. Methods Analysis of YouTube videos depicting the gait of highly ranked Russian officials. Results We found a similar walking pattern in President Vladimir Putin, Prime Minister Dmitry Medvedev and three other highly ranked Russian officials, all presenting with a consistently reduced right arm swing in the absence of other overt neurological abnormalities. Conclusions We propose that this new gait pattern, which we term “gunslinger’s gait,” may result from a behavioural adaptation, possibly triggered by KGB or other forms of weapons training where trainees are taught to keep their right hand close to the chest while walking, allowing them to quickly draw a gun when faced with a foe. This should be included in the differential diagnosis of a unilaterally reduced arm swing.

Risk of Disabling Response Fluctuations and Dyskinesias for Dopamine Agonists Versus Levodopa in Parkinson’s Disease1

Abstract: BACKGROUND: Response fluctuations and dyskinesias develop during the use of both levodopa (LD) and dopamine agonists (DA), but may not be equally disabling. OBJECTIVE: To compare the risk and time of onset of disabling response fluctuations and dyskinesias (DRFD) among patients with Parkinson's disease (PD) who were initially treated with either LD or DA. METHODS: Open cohort study of all consecutive de-novo PD patients in routine clinical practice, included over a period of 15 years (median follow-up: 8.1 years, range 1.1-17.7), since embarking on LD or DA. Older patients and patients with more severe PD were started on LD (n = 77), younger patients on a DA (n = 50). Therapy was adjusted according to generally accepted guidelines. The primary endpoints were: the onset of response fluctuations, dyskinesias, and the moment when these complications became disabling (DRFD). RESULTS: LD-starters developed response fluctuations 0.8 years earlier than DA-starters (p = 0.07), while dyskinesias appeared around 2.5 years earlier (p = 0.003). However, the risk and time of onset of DRFD did not differ statistically between the groups (LD-starters: 60% , median interval 7.3 years, DA-starters: 52% , 6.1 years, p = 0.63). DA-starters displayed a 0.19 points lower adjusted mean improvement in motor scores than LD-starters (p = 0.002). Adjustments for age and severity of PD at start of dopaminergic therapy did not change these results. CONCLUSIONS: In routine clinical practice, the risk and time of onset of DRFD is comparable for LD-starters versus DA-starters, but motor functioning is worse in DA-starters. These results support the use of LD as initial therapy for PD.

Prospective assessment of subjective sleep benefit in Parkinson’s disease

Abstract: Background Parkinson’s disease (PD) patients may experience ‘sleep benefit’ (SB): a temporarily improved mobility upon awakening. SB has mainly been studied retrospectively using questionnaires, but it remains unclear whether it is associated with actual changes in motor functioning.

Overexpression of α-synuclein in oligodendrocytes does not increase susceptibility to focal striatal excitotoxicity.

Abstract: Multiple system atrophy (MSA) is a fatal adult-onset neurodegenerative disease characterized by α-synuclein (α-syn) positive oligodendroglial cytoplasmic inclusions. The latter are associated with a neuronal multisystem neurodegeneration targeting central autonomic, olivopontocerebellar and striatonigral pathways, however the underlying mechanisms of neuronal cell death are poorly understood. Previous experiments have shown that oligodendroglial α-syn pathology increases the susceptibility to mitochondrial stress and proteasomal dysfunction leading to enhanced MSA-like neurodegeneration. Here we analyzed whether oligodendroglial α-syn overexpression in a transgenic mouse model of MSA synergistically interacts with focal neuronal excitotoxic damage generated by a striatal injection of quinolinic acid (QA) to affect the degree of striatal neuronal loss.