Showing papers by "Bastiaan R. Bloem published in 2014"
TL;DR: A task force to consider a redefinition of Parkinson's disease identified several critical issues that challenge current PD definitions, and there is a need to create new MDS diagnostic criteria that take these changes in disease definition into consideration.
Abstract: With advances in knowledge disease, boundaries may change. Occasionally, these changes are of such a magnitude that they require redefinition of the disease. In recognition of the profound changes in our understanding of Parkinson's disease (PD), the International Parkinson and Movement Disorders Society (MDS) commissioned a task force to consider a redefinition of PD. This review is a discussion article, intended as the introductory statement of the task force. Several critical issues were identified that challenge current PD definitions. First, new findings challenge the central role of the classical pathologic criteria as the arbiter of diagnosis, notably genetic cases without synuclein deposition, the high prevalence of incidental Lewy body (LB) deposition, and the nonmotor prodrome of PD. It remains unclear, however, whether these challenges merit a change in the pathologic gold standard, especially considering the limitations of alternate gold standards. Second, the increasing recognition of dementia in PD challenges the distinction between diffuse LB disease and PD. Consideration might be given to removing dementia as an exclusion criterion for PD diagnosis. Third, there is increasing recognition of disease heterogeneity, suggesting that PD subtypes should be formally identified; however, current subtype classifications may not be sufficiently robust to warrant formal delineation. Fourth, the recognition of a nonmotor prodrome of PD requires that new diagnostic criteria for early-stage and prodromal PD should be created; here, essential features of these criteria are proposed. Finally, there is a need to create new MDS diagnostic criteria that take these changes in disease definition into consideration.
392 citations
TL;DR: The benefits of a model of integrated care provided by a network of specialists and suggest it has promise for other long term conditions.
Abstract: Patients with Parkinson’s disease need long term support to manage their condition. Bastiaan Bloem and Marten Munneke describe the benefits of a model of integrated care provided by a network of specialists and suggest it has promise for other long term conditions
123 citations
TL;DR: This project produced a set of consensus-based clinical practice recommendations that systematically address potential fall risk factors in PD and may be used in two ways: for pragmatic use in current clinical practice, pending further evidence; and as the active intervention in clinical trials, aiming to evaluate the effectiveness and cost-effectiveness of large scale implementation.
119 citations
TL;DR: Delayed onsets in HSP were normalized when the imperative stimulus was combined with a SAS, presumably through release of a subcortically stored motor program conveyed by the preserved reticulospinal tract.
Abstract: Startling acoustic stimuli (SAS) can accelerate reaction times ("StartReact" effect), but the underlying mechanism remains unclear. Both direct release of a subcortically stored motor program and a subcortically mediated trigger for a cortically stored motor program have been hypothesized. To distinguish between these hypotheses, we examined the StartReact effect in humans with pure hereditary spastic paraplegia (HSP). Delayed reaction times in HSP patients in trials both with and without a SAS would argue in favor of a cortically stored response. We instructed 12 HSP patients and 12 matched controls to respond as rapidly as possible to a visual imperative stimulus, in two different conditions: dorsiflexion of the dominant ankle; or flexion of the dominant wrist. In 25% of trials, a SAS was delivered simultaneously with the imperative stimulus. Before these tests, subjects received five SAS while standing to verify normal function of the reticulospinal tract in HSP. Latencies of startle responses in sternocleidomastoid and tibialis anterior muscles were comparable between patients and controls. During the ankle dorsiflexion task, HSP patients had an average 19 ms delay in reaction times compared with controls. Administration of a SAS accelerated ankle dorsiflexion in both groups, but more so in the patients, which completely normalized their latencies. The wrist flexion task yielded no differences in onset latencies between HSP patients and controls. The reticulospinal tract seems unaffected in HSP patients, because startle reflex onsets were normal. The corticospinal tract was affected, as reflected by delayed ankle dorsiflexion reaction times. These delayed onsets in HSP were normalized when the imperative stimulus was combined with a SAS, presumably through release of a subcortically stored motor program conveyed by the preserved reticulospinal tract.
82 citations
TL;DR: Scanning Parkinson's disease patients using functional magnetic resonance imaging extended the dopamine overdose hypothesis, according to which dopamine-induced changes in dorsal and ventral striatal processing lead to cognitive improvement and impairment respectively.
57 citations
TL;DR: This review underscores that designing multispecialty care within the setting of a modern healthcare system is almost as complex as PD itself, and that its scientific evaluation comes with significant challenges.
51 citations
TL;DR: The relationship between weight bearing and balance control seems to be less pronounced in freezers, compared to healthy controls and non-freezers, however, this relationship should be investigated further in larger groups of patients.
Abstract: Balance control (the ability to maintain an upright posture) is asymmetrically controlled in a proportion of patients with Parkinson’s disease. Gait asymmetries have been linked to the pathophysiology of freezing of gait. We speculate that asymmetries in balance could contribute to freezing by a) hampering the unloading of the stepping leg and/or b) leading to a preferred stance leg during gait, which then results in asymmetric gait. To investigate this, we examined the relationship between balance control and weight-bearing asymmetries and freezing. We included 20 human patients with Parkinson (tested OFF medication; nine freezers) and nine healthy controls. Balance was perturbed in the sagittal plane, using continuous multi-sine perturbations, applied by a motion platform and by a force at the sacrum. Applying closed-loop system identification techniques, relating the body sway angle to the joint torques of each leg separately, determined the relative contribution of each ankle and hip joint to the total amount of joint torque. We also calculated weight-bearing asymmetries. We determined the 99-percent confidence interval of weight-bearing and balance-control asymmetry using the responses of the healthy controls. Freezers did not have larger asymmetries in weight bearing (p = 0.85) nor more asymmetrical balance control compared to non-freezers (p = 0.25). The healthy linear one-to-one relationship between weight bearing and balance control was significantly different for freezers and non-freezers (p = 0.01). Specifically, non-freezers had a significant relationship between weight bearing and balance control (p = 0.02), whereas this relation was not significant for freezers (p = 0.15). Balance control is asymmetrical in most patients (about 75 percent) with Parkinson’s disease, but this asymmetry is not related to freezing. The relationship between weight bearing and balance control seems to be less pronounced in freezers, compared to healthy controls and non-freezers. However, this relationship should be investigated further in larger groups of patients.
49 citations
TL;DR: Suggestions for improvement are to improve education for therapists with respect to theories about behavioral change, formulate concrete and specific examples of exercise goals, and pay more specific attention to patients with co morbidities, cognitive dysfunction and a lack of motivation during education.
40 citations
TL;DR: It is concluded that dopaminergic medication does not improve underscaling of stepping responses in PD, and other interventions are needed to improve these important defense postural reactions.
Abstract: In this study, we investigated the effect of dopaminergic medication on reactive stepping responses to forward and backward balance perturbations in patients with moderately severe Parkinson's disease (PD). Twelve PD patients, Hoehn and Yahr stage ranging from 2 to 3, and 15 healthy controls were exposed to multidirectional translational stance perturbations on a moveable platform. Perturbations were unpredictable in terms of amplitude, timing and direction. Patients were tested in the medication ON and OFF (at least 12 h of dopaminergic medication withdrawal) state on two separate days. Forward and backward stepping responses were quantified in terms of (1) presence, onset and amplitude of anticipatory postural adjustments (APAs); (2) spatiotemporal step variables (step onset, length and velocity); and (3) leg inclination angle at first stepping-foot contact. When perturbed forward, patients performed worse than controls in terms of step length (0.32 ± 0.07 vs. 0.38 ± 0.05 m, p = 0.01) and step velocity (1.21 ± 0.16 vs. 1.37 ± 0.13 m/s, p = 0.01), while step onset was not different. The number of steps with an APA was larger in patients in the OFF state than in controls which was, however, only significant after forward perturbations (43 vs. 20%, p = 0.01). Following backward perturbations, leg angles at foot contact were smaller in patients compared to controls (-2.71° ± 4.29° vs. 0.26° ± 2.80°, p = 0.04) reflecting a poorer mechanical efficiency of the step. Dopaminergic medication had no significant effect on any of these outcomes. In conclusion, dopaminergic medication does not improve underscaling of stepping responses in PD. Therefore, other interventions are needed to improve these important defense postural reactions.
35 citations
TL;DR: PD patients compensate for balance control asymmetries by increasing the relative contribution of the leg of their least affected body side, which appears to be successful at the ankle but is accompanied by an increased stiffness at the hip.
Abstract: In Parkinson's disease (PD) subtle balance abnormalities can already be detected in early-stage patients. One feature of impaired balance control in PD is asymmetry: one leg produces more corrective joint torque than the other. We hypothesize that in mild to moderately affected PD patients, the least impaired leg compensates for the more impaired leg. Twenty PD patients and eleven healthy matched control subjects participated. Clinical asymmetry was determined by the difference between the left and right body side scores on the Unified Parkinson's Disease Rating Scale. Balance was perturbed with two independent continuous multisine perturbations in the forward-backward direction. Subsequently, we applied closed-loop system identification, which determined the spectral estimate of the stabilizing mechanisms, for each leg. Balance control behavior was similar in PD patients and control subjects at the ankle, but at the hip stiffness was increased. Control subjects exhibited symmetric balance control, but in PD patients the balance contribution of the leg of the clinically least affected body side was higher whereas the leg of the clinically most affected body side contributed less. The ratio between the legs helped to preserve a normal motor output at the ankle. Our results suggest that PD patients compensate for balance control asymmetries by increasing the relative contribution of the leg of their least affected body side. This compensation appears to be successful at the ankle but is accompanied by an increased stiffness at the hip. We discuss the possible implications of these findings for postural stability and fall risk in PD patients.
34 citations
TL;DR: There was no PD-related deficit to switch to an alternative response strategy, neither in patients with FOG nor in patients without FOG, and difficulty to adapt the step trial-by-trial might have contributed to the absence of switch deficits in PD.
TL;DR: PD patients with RBD showed a significantly higher number of bouts scored as “wake” using actigraphy, compared to patients without RBD.
Abstract: Background: Rapid eye movement (REM) sleep behavior disorder (RBD) is a common parasomnia in Parkinson’s disease (PD) patients. The current International Classification of Sleep Disorders (ICSD-II) requires a clinical interview combined with video polysomnography (video-PSG) to diagnose. The latter is time consuming and expensive and not always feasible in clinical practice. Here we studied the use of actigraphy as a diagnostic tool for RBD in PD patients. Methods: We studied 45 consecutive PD patients (66.7% men) with and without complaints of RBD. All patients underwent one night of video-PSG and eight consecutive nights of actigraphy. Based on previous studies, the main outcome measure was the total number of bouts classified as “wake”, compared between patients with (PD + RBD) and without RBD (PD- RBD). Results: 23 (51.1%) patients had RBD according to the ICSD-II criteria. The total number of wake bouts was significantly higher in RBD patients (PD + RBD 73.2±40.2 vs. PD-RBD 48.4±23.3, p =.016). A cut off of 95 wake bouts per night resulted in a specificity of 95.5%, a sensitivity of 20.1% and a positive predictive value of 85.7%. Seven patients were suspected of RBD based on the interview alone, but not confirmed on PSG; six of whom scored below 95 wake bouts per night on actigraphy. Conclusion: PD patients with RBD showed a significantly higher number of bouts scored as “wake” using actigraphy, compared to patients without RBD. In clinical practice, actigraphy has a high specificity, but low sensitivity in the diagnosis of RBD. The combination of actigraphy and previously reported RBD questionnaires may be a promising method to diagnose RBD in patients with PD.
TL;DR: PD care in Dutch nursing homes is suboptimal according to residents, informal caregivers, and health care workers, and three core areas for improvement were identified, including greater attention for psychosocial problems, improved PD-specific knowledge among nursing home staff, and better collaboration with hospital staff trained in movement disorders.
TL;DR: This is the first evidence that impulsivity, in particular in the attentional domain, is related to fall risk in Parkinson’s disease.
Abstract: OBJECTIVE: Impulsivity is a "tendency to act prematurely without foresight." Clinical experience suggests that such impulsive behavior can impact on the fall risk in Parkinson's disease (PD), but this has never been tested. We investigated whether trait impulsivity is related to fall risk in a large cohort of PD patients. We also investigated whether trait impulsivity affects the fall risk differently for patients with more or less postural instability and gait disability (PIGD). METHODS: 388 patients with PD (HY p = .012). This effect was predominantly driven by higher scores on the subscale for attentional impulsivity (p = .003). The difference in attentional impulsivity was independent of gender, disease severity, dopaminergic medication, and cognitive function. Motor and non-planning impulsivity did not differ between recurrent fallers and non-fallers. There was no evidence that impulsivity modulated the association between PIGD and fall risk. DISCUSSION: This is the first evidence that impulsivity, in particular in the attentional domain, is related to fall risk in PD.
TL;DR: Surprisingly, gait was associated with a paradoxical improvement of phonological verbal fluency in the patients with levodopa-resistant freezing whilst walking determined a worsening of episodic memory in the other patient groups.
TL;DR: Patients with Parkinson's disease have reduced gray matter volume and fractional anisotropy in both cortical and sub‐cortical structures, yet changes in the pre‐motor phase of the disease are unknown.
Abstract: Background: Patients with Parkinson’s disease have reduced gray matter volume and fractional anisotropy in both cortical and sub-cortical structures, yet changes in the pre-motor phase of the disease are unknown. Methods: A comprehensive imaging study using voxelbased morphometry and diffusion tensor imaging tract-based spatial statistics analysis was performed on 64 Ashkenazi Jewish asymptomatic first degree relatives of patients with Parkinson’s disease (30 mutation carriers), who carry the G2019S mutation in the leucine-rich repeat kinase 2 (LRRK2) gene. Results: No between-group differences in gray matter volume could be noted in either whole-brain or volume-of-interest analysis. Diffusion tensor imaging analysis did not identify group differences in white matter areas, and volume-of-interest analysis identified no differences in diffusivity parameters in Parkinson’s disease-related structures. Conclusions: G2019S carriers do not manifest changes in gray matter volume or diffusivity parameters in Parkinson’s disease-related structures prior to the appearance of motor symptoms. V C 2014 Interna
TL;DR: Fast support surface rotations caused greater instability and discriminated Parkinson patients better from controls than slow rotations, and ankle torques were weaker for patients than controls on the most affected side, but were stronger than controls for the least affected side.
Abstract: Underlying somatosensory processing deficits of joint rotation velocities may cause patients with Parkinson’s disease (PD) to be more unstable for fast rather than slow balance perturbations. Such deficits could lead to reduced proprioceptive amplitude feedback triggered by perturbations, and thereby to smaller or delayed stabilizing postural responses. For this reason, we investigated whether support surface perturbation velocity affects balance reactions in PD patients. We examined postural responses of seven PD patients (OFF medication) and eight age-matched controls following backward rotations of a support-surface platform. Rotations occurred at three different speeds: fast (60 deg/s), medium (30 deg/s) or slow (3.8 deg/s), presented in random order. Each subject completed the protocol under eyes open and closed conditions. Full body kinematics, ankle torques and the number of near-falls were recorded. Patients were significantly more unstable than controls following fast perturbations (26% larger displacements of the body’s centre of mass; P<0.01), but not following slow perturbations. Also, more near-falls occurred in patients for fast rotations. Balance correcting ankle torques were weaker for patients than controls on the most affected side, but were stronger than controls for the least affected side. These differences were present both with eyes open and eyes closed (P<0.01). Fast support surface rotations caused greater instability and discriminated Parkinson patients better from controls than slow rotations. Although ankle torques on the most affected side were weaker, patients partially compensated for this by generating larger than normal stabilizing torques about the ankle joint on the least affected side. Without this compensation, instability may have been greater.
TL;DR: For instance, the authors found that the right posterior superior temporal sulcus (pSTS) is involved when people understand the intended meaning of novel communicative actions using transcranial magnetic stimulation (rTMS).
TL;DR: Cell survival assays show that wild type ANG is capable of rescuing cells containing ANG mutations from death when challenged with toxic agents, suggesting ANG is a potent neuroprotective factor.
Abstract: Mice lacking the hypoxia responsive element in the promoter of vascular endothelial growth factor ( VEGF ) develop a phenotype with weakness and pathological reflexes that resemble amyotrophic lateral sclerosis (ALS). A subsequent study demonstrated an association between polymorphisms in the promoter of VEGF and ALS in humans. Therefore other angiogenic genes were investigated in ALS, which showed mutations in angiogenin ( ANG ) in patients with familial and sporadic ALS.1 A recent study confirmed this association and also demonstrated that ANG mutations predispose to Parkinson's disease (PD).2 The association with PD has independently been replicated.
It is not known how mutations in ANG lead to neurodegeneration. The ANG protein is involved in the transcription of ribosomal DNA, RNA metabolism, neurite outgrowth and axonal pathfinding. Cell survival assays show that wild type ANG is capable of rescuing cells containing ANG mutations from death when challenged with toxic agents, suggesting ANG is a potent neuroprotective factor.3 Functional studies have demonstrated that most mutations result in a loss of function.3
A small study demonstrated elevated serum ANG levels in patients with ALS,4 which could however not be replicated in a later study.5 Here, we compared serum ANG levels in a large cohort of patients with ALS and PD with controls.
Two hundred and sixty-five serum samples were available from patients with sporadic ALS, all of which were referred to the University Medical Center Utrecht (UMCU) and diagnosed according to the revised El Escorial criteria. One hundred and sixty-three serum samples were available from …