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Biomedical subjects

Bastiaan R Bloem

Publications and source records attributed to Bastiaan R Bloem.

At least 19 recordsLinked to original sources

Blue light therapy delivered through light glasses improves sleep quality and daytime sleepiness in Parkinson's disease: A randomized trial.

BackgroundSleep disturbances, including excessive daytime sleepiness (EDS) and fragmented nocturnal sleep, are common in Parkinson's disease (PD) and significantly reduce quality of life. This pilot study evaluated the efficacy of a novel approach using blue light, delivered via dedicated glasses with integrated LED lights, to improve sleep and non-motor symptoms.MethodsRandomised, placebo-controlled, single-blind pilot study with a 2-week light intervention. Participants were assessed at baseline, two weeks, and five weeks. The study was designed to evaluate between- and within-group changes. Participants were randomly allocated to receive blue light therapy (n&#x2009;=&#x2009;15) or red light placebo (n&#x2009;=&#x2009;15), delivered via LED-integrated glasses for one hour, twice daily, given for a 2-week period. Primary outcome was improvement in sleep quality, assessed via the Pittsburgh Sleep Quality Index. Secondary outcomes included diary-based sleep outcomes, excessive daytime sleepiness, mood, anxiety, and motor symptoms.ResultsThere was a significant group&#x2009;&#xd7;&#x2009;time effect with blue light therapy leading to better Pittsburgh Sleep Quality Index scores (p&#x2009;=&#x2009;0.021). Between-group analyses showed that at two weeks a trend toward significance was observed (p&#x2009;=&#x2009;0.065), while sleep quality significantly improved at five weeks compared to placebo (p&#x2009;=&#x2009;0.029) with a large effect size (0.896). Excessive sleepiness improved in the blue light group (p&#x2009;<&#x2009;0.001), with a reduction in clinically relevant sleepiness from 50.0% to 6.7% (p&#x2009;=&#x2009;0.005).ConclusionsBlue light therapy delivered through dedicated glasses appeared to show an improvement in sleep quality and daytime sleepiness in individuals with PD. Blue light therapy offers a promising alternative to traditional light therapy utilising lower light intensities and eliminating the need for light boxes.

Aged↗

Genome-wide association study of copy number variations in Parkinson's disease.

OBJECTIVE: To investigate the impact of copy number variations (CNVs) on Parkinson's disease (PD) pathogenesis using genome-wide data and explore their role in sporadic PD. METHODS: We analyzed CNV data from 11,035 PD patients (including 2,731 early-onset PD (EOPD)) and 8,901 controls from the COURAGE-PD consortium using a sliding window CNV-GWAS and genome-wide burden analysis. The independent dataset from the Global Parkinson Genetics Program (GP2) consisted of 23,089 cases and 18,824 controls were used to validate our initial findings. RESULTS: The exploratory dataset identifies multiple CNV regions associated with PD risk. The nominated CNV loci were not confirmed in an independent dataset, except that only a deletion in the PRKN gene, a well-established EOPD locus, remained genome-wide significant and robustly supported. CNV burden analysis showed a higher prevalence of CNVs in PD-related genes in patients compared to controls (OR=1.56 [1.18-2.09], p=0.0013), with PRKN showing the highest burden (OR=1.47 [1.10-1.98], p=0.026). Patients with CNVs in PRKN had an earlier disease onset. Burden analysis with controls and EOPD patients showed similar results. INTERPRETATION: The largest CNV-based GWAS on PD highlights both the promise and pitfalls of array-based CNV detection in PD and underscores the relevance of whole-genome sequencing approaches in resolving the role of CNV in PD. The array-based findings are prone towards false positive findings that might arise either from platform limitations and/or cohort biases. Future studies require improved genotyping resolution and rigorous cross-cohort validation to reliably assess CNV contributions to PD risk.

Journal Article↗

Evidence-based analysis of physical therapy in Parkinson's disease with recommendations for practice and research.

Physical therapy is often prescribed in Parkinson's disease. To facilitate the uniformity and efficacy of this intervention, we analyzed current evidence and developed practice recommendations. We carried out an evidence-based literature review. The results were supplemented with clinical expertise and patient values and translated into practice recommendations, developed according to international standards for guideline development. A systematic literature search yielded 6 systematic reviews and 23 randomized controlled trials of moderate methodological quality with sufficient data. Six specific core areas for physical therapy were identified: transfers, posture, reaching and grasping, balance, gait, and physical capacity. We extracted four specific treatment recommendations that were based on evidence from more than two controlled trials: cueing strategies to improve gait; cognitive movement strategies to improve transfers; exercises to improve balance; and training of joint mobility and muscle power to improve physical capacity. These practice recommendations provide a basis for current physical therapy in Parkinson's disease in everyday clinical practice, as well as for future research in this field.

Biomedical Research↗

Neurological gait disorders in elderly people: clinical approach and classification.

Gait disorders are common and often devastating companions of ageing, leading to reductions in quality of life and increased mortality. Here, we present a clinically oriented approach to neurological gait disorders in the elderly population. We also draw attention to several exciting scientific developments in this specialty. Our first focus is on the complex and typically multifactorial pathophysiology underlying geriatric gait disorders. An important new insight is the recognition of gait as a complex higher order form of motor behaviour, with prominent and varied effects of mental processes. Another relevant message is that gait disorders are not an unpreventable consequence of ageing, but implicate the presence of underlying diseases that warrant specific diagnostic tests. We next discuss the core clinical features of common geriatric gait disorders and review some bedside tests to assess gait and balance. We conclude by proposing a practical three-step approach to categorise gait disorders and we present a simplified classification system based on clinical signs and symptoms.

Aging↗

Online maintenance of sensory and motor representations: effects on corticospinal excitability.

Flexible behavior requires the ability to delay a response until it is appropriate. This can be achieved by holding either a sensory or a motor representation online. Here we assess whether maintenance of sensory or motor material drives the motor system to different functional states, as indexed by alterations of corticospinal excitability. We used single-pulse TMS to measure corticospinal excitability evoked during the delay period of a novel paradigm in which task contingencies, rather than explicit verbal instructions, induced participants to use either sensory or motor codes to solve a delay-nonmatch-to-sample (DNMS) task. This approach allowed us to probe the state of the motor system while the participants were retaining either sensory or motor codes to cross the delay period, rather than the control of short-term storage driven by verbal instructions. When participants could prepare the movement in advance (preparation trials), the excitability of the motor cortex contralateral to the moving hand increased, whereas the excitability of the ipsilateral motor cortex decreased. The increase in excitability was confined to the prime mover, whereas the decrease in excitability extended to cortical territories controlling muscles unrelated to the response. Crucially, these changes in excitability were evoked only during preparation trials and not during trials in which subjects needed to maintain sensory items online (memory trials). We infer that short-term storage of sensory information and preparation of motor responses have differential and specific access to the output stage of the motor system.

Adult↗

Gender differences in Parkinson's disease.

OBJECTIVE: To investigate gender differences in basic disease characteristics, motor deterioration and nigrostriatal degeneration in Parkinson's disease (PD). METHODS: We studied 253 consecutive PD patients who were not receiving levodopa or dopamine agonists (disease duration < or = 10 years). We investigated the influence of gender and oestrogen status on: (1) age at onset, (2) presenting symptom, (3) severity and progression of motor symptoms (Unified Parkinson's Disease Rating Scale III (UPDRS-III) scores) and (4) amount and progression of nigrostriatal degeneration ([123I]FP-CIT single photon emission computed tomography measurements). RESULTS: Age at onset was 2.1 years later in women (53.4 years) than in men (51.3 years). In women, age at onset correlated positively with parity, age at menopause and fertile life span. Women more often presented with tremor (67%) than men (48%). Overall, patients presenting with tremor had a 3.6 year higher age at onset and a 38% slower UPDRS-III deterioration. Mean UPDRS-III scores at disease onset were equal for both genders, as was the rate of deterioration. Women had a 16% higher striatal [123I]FP-CIT binding than men at symptom onset and throughout the course of PD. CONCLUSIONS: Our results suggest that, in women, the development of symptomatic PD may be delayed by higher physiological striatal dopamine levels, possibly due to the activity of oestrogens. This could explain the epidemiological observations of a lower incidence and higher age at onset in women. Women also presented more often with tremor which, in turn, is associated with milder motor deterioration and striatal degeneration. Taken together, these findings suggest a more benign phenotype in women with PD.

Adult↗

Disentangling the contribution of the paretic and non-paretic ankle to balance control in stroke patients.

During stroke recovery, restoration of the paretic ankle and compensation in the non-paretic ankle may contribute to improved balance maintenance. We examine a new approach to disentangle these recovery mechanisms by objectively quantifying the contribution of each ankle to balance maintenance. Eight chronic hemiparetic patients were included. Balance responses were elicited by continuous random platform movements. We measured body sway and ground reaction forces below each foot to calculate corrective ankle torques in each leg. These measurements yielded the Frequency Response Function (FRF) of the stabilizing mechanisms, which expresses the amount and timing of the generated corrective torque in response to sway at the specified frequencies. The FRFs were used to calculate the relative contribution of the paretic and non-paretic ankle to the total amount of generated corrective torque to correct sway. All patients showed a clear asymmetry in the balance contribution in favor of the non-paretic ankle. Paretic balance contribution was significantly smaller than the contribution of the paretic leg to weight bearing, and did not show a clear relation with the contribution to weight bearing. In contrast, a group of healthy subjects instructed to distribute their weight asymmetrically showed a one-on-one relation between the contribution to weight bearing and to balance. We conclude that the presented approach objectively quantifies the contribution of each ankle to balance maintenance. Application of this method in longitudinal surveys of balance rehabilitation makes it possible to disentangle the different recovery mechanisms. Such insights will be critical for the development and evaluation of rehabilitation strategies.

Adult↗

Postural responses to multidirectional stance perturbations in cerebellar ataxia.

Previous studies of patients with focal cerebellar damage underscored the importance of the cerebellum for balance control. These studies were restricted to postural control in the pitch plane, and focused mainly on leg muscle responses. Here, we examined the effect of degenerative cerebellar lesions on postural control in multiple directions, and studied how such lesions affect intersegmental coordination of the legs, trunk and arms. We formulated two main questions. (a) Do patients with cerebellar ataxia predominantly have balance problems in the sagittal or frontal planes? (b) Is instability in cerebellar ataxia associated with increased joint motion or with reduced joint motion? We selected nine patients with autosomal dominant spinocerebellar ataxia (SCA)--three with pure ataxia and six with mild extra-cerebellar features--and 12 matched controls. Upright standing subjects received support surface rotations (7.5 degrees at 60 degrees /s) that were randomly delivered in eight different directions of pitch or roll. We used full body kinematics to determine displacements of the center of mass (COM) and of individual body segments. We also collected surface EMG from 10 leg, trunk and arm muscles. Primary variables of interest were COM displacement and trunk control (angles and muscle responses). Secondary analyses focused on angles and muscle responses of the legs and arms. COM analysis demonstrated that SCA patients had greatest instability following backward and laterally directed perturbations. Major factors in causing this instability were, first, a marked reduction of stimulus-induced knee flexion and, second, excessive "hypermetric" motion of the pelvis (in roll) and trunk (in pitch). Muscle responses of SCA patients were characterized by increased late balance correcting activity. Responses of patients with pure ataxia were comparable to those of patients with mild extra-cerebellar features. A main underlying cause of postural instability in SCA patients appears to be "locking" of the knees, which may reflect compensation (by reducing interaction between body links) or reduced vestibulocerebellar control over leg muscles. The observed pathophysiology is very different from that seen in other patient populations.

Adult↗

The "posture second" strategy: a review of wrong priorities in Parkinson's disease.

Falls are common in Parkinson's disease. It remains difficult to predict these falls, presumably because clinical balance tests assess single components of postural control, whereas everyday fall mechanisms are typically more complicated. A substantial proportion of everyday falls appears to occur while Parkinson patients attempt to perform multiple tasks at the same time. Furthermore, little attention is generally paid to the possible contribution of cognitive impairments to falls. The importance of mental dysfunction is supported by the fact that cognitive loading while walking or balancing can lead to marked deteriorations in postural performance, and there is some evidence to suggest that such "dual tasking" is particularly difficult for elderly persons with dementia or depression. We examined what strategies Parkinson patients used when a basic walking task became increasingly challenging by adding additional tasks (both motor and cognitive). Most patients could perform a simple "dual task" test: simultaneously walking and answering simple questions. However, as the walking task became more complex, patients' performance began to deteriorate. Interestingly, this was reflected not only by failure to answer questions, but also by an increasing number of blocks in motor performance (walking and balancing). This behaviour was different from that of both young and elderly controls, who appeared to sacrifice performance on the cognitive task in order to optimise their gait and balance ("posture first" strategy). Preliminary evidence suggest that impaired multiple task performance is associated with a two-fold increased risk of sustaining falls in daily life. We conclude that Parkinson patients are less inclined than healthy persons to maintain a safe gait. Instead, Parkinson patients use a "posture second" strategy and treat all elements of a complex task with equal priority, which in daily life may go at the expense of maintaining balance and lead to falls.

Accidental Falls↗

Repetitive transcranial magnetic stimulation to improve mood and motor function in Parkinson's disease.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive brain stimulation technique that can produce lasting changes in excitability and activity in cortical regions underneath the stimulation coil (local effect), but also within functionally connected cortical or subcortical regions (remote effects). Since the clinical presentation of Parkinson's disease (PD) is related to abnormal neuronal activity within the basal ganglia and cortical regions, including the primary motor cortex, the premotor cortex and the prefrontal cortex, several studies have used rTMS to improve brain function in PD. Here, we review the studies that have investigated the possible therapeutic effects of rTMS on mood and motor function in PD patients. We highlight some methodological inconsistencies and problems, including the difficulty to define the most effective protocol for rTMS or to establish an appropriate placebo condition. We finally propose future directions of research that may help to improve the therapeutic efficacy of rTMS in PD.

Affect↗

CSF neurofilament light chain and tau differentiate multiple system atrophy from Parkinson's disease.

BACKGROUND: In early disease stages it can be clinically difficult to differentiate idiopathic Parkinson's disease (IPD) from patients with multiple system atrophy predominated by parkinsonism (MSA-P). METHODS: In CSF of 31 patients with IPD, 19 patients with MSA-P, we analyzed tau, neurofilament light chain (NFL) and heavy chain (NFHp35) and the noradrenergic metabolite 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG). RESULTS: CSF levels of NFL, NFHp35, and tau were significantly increased in MSA-P (all p<0.0001), whereas, MHPG levels were significantly decreased in MSA-P (p<0.0001). Optimal discriminative cut-off values for the differentiation between MSA-P and IPD were calculated resulting in high sensitivity (76-94%) and specificity (83-97%) levels. Multivariate logistic regression resulted in the combination of NFL and tau as independent contributors in differentiating between MSA-P and IPD. DISCUSSION: Higher CSF levels of axonal biomarkers could reflect advanced axonal degeneration in MSA-P. Differentiating MSA-P from IPD could be accurately possible with CSF analysis of a combination of axonal and neurotransmitter biomarkers.

Adult↗

Delineation of the motor disorder of Lesch-Nyhan disease.

Lesch-Nyhan disease (LND) is caused by deficiency of the purine salvage enzyme hypoxanthine-guanine phosphoribosyltransferase (HPRT). Affected individuals exhibit over-production of uric acid, along with a characteristic neurobehavioural syndrome that includes mental retardation, recurrent self-injurious behaviour and motor disability. Prior studies involving relatively small numbers of patients have provided different conclusions on the nature of the motor disorder. The current study includes the results of a multi-centre international prospective study of the motor disorder in the largest cohort of patients studied to date. A total of 44 patients ranging from 2 to 38 years presented a characteristic motor syndrome that involved severe action dystonia superimposed on baseline hypotonia. Although some patients also displayed other extrapyramidal or pyramidal signs, these were always less prominent than dystonia. These results are compared with a comprehensive review of 122 prior reports that included a total of 254 patients. Explanations for the differing observations available in the literature are provided, along with a summary of how the motor disorder of LND relates to current understanding of its pathophysiology involving the basal ganglia.

Adolescent↗

Secondary parkinsonism in childhood: A rare complication after radiotherapy.

Secondary parkinsonism is uncommon in children and exceedingly rare after cranial radiotherapy. This report describes a 14-year-old female who presented with growth retardation as a result of a craniopharyngioma, which was partially resected. A secondary hydrocephalus responded well to shunting. She gradually developed a severe hypokinetic-rigid syndrome 6 months after radiotherapy (54 Gray in 30 daily fractions of 1.8 Gray). In addition, her vigilance decreased. Magnetic resonance imaging revealed increased signal intensity on T2-weighted images in the globus pallidus bilaterally. Nuclear scans indicated only a marginal striatal dopaminergic deficit and revealed decreased metabolism in the thalamus bilaterally. Treatment with dopamine agonists resulted in minor improvement in motor function. Magnetic resonance imaging investigations 3 months later disclosed a decrease of signal intensity changes of the globus pallidus. Gradually, bradykinesia diminished slightly and vigilance increased little. In conclusion, secondary and partially reversible parkinsonism can occur in children after radiotherapy. We suggest that focal encephalopathy resulting from postradiation edema secondary to microangiopathy led to dysfunction of the globus pallidus and thalamus.

Adolescent↗

Fallacious falls.

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Accidental Falls↗

Falls in degenerative cerebellar ataxias.

We retrospectively and prospectively assessed the frequency and characteristics of falls in patients with degenerative cerebellar ataxias. The results show that falls occur very frequently in patients with degenerative cerebellar ataxias and that these falls are serious and often lead to injuries or a fear of falling. Clinicians should be aware of this problem in ataxia patients and should try to prevent falls.

Accidental Falls↗

Trunk sway in patients with spinocerebellar ataxia.

We investigated whether quantified measurements of trunk sway during stance and gait tests in patients with autosomal dominant spinocerebellar ataxia (SCA) could be a useful approach to assess ataxia, which is highly relevant for adequate follow-up and future intervention studies. Examined were 11 SCA patients and 11 age-matched, healthy controls. Postural and balance control were quantified using peak-to-peak measurements of trunk angle and angular velocity, in the roll (lateral) and pitch (anterior-posterior) directions, during a battery of stance and gait tasks. In all stance tasks, trunk angle displacement and angular velocity in both the pitch and roll planes were significantly larger in the SCA group compared with the control group. Among the ataxia patients instability was more increased in the pitch than in the roll direction for two-legged stance tasks, especially when standing on foam, with pronounced oscillations in the pitch plane at 1.4 and 2.5 Hz. A similar dominance of pitch over roll instability was also observed in most gait tasks, especially for tandem gait and while walking with simultaneous head rotations. Trunk sway measurements were effective in detecting and quantifying the gait and balance abnormalities in SCA patients, suggesting that this method might be used for follow-up studies of SCA patients. Furthermore, the method might help to identify early symptomatic individuals and those patients at risk of falling. The postural instability in SCA was found to be multidirectional, although there is generally more pitch than roll instability corresponding with predominant involvement of the spinocerebellum.

Adult↗

Role of the basal ganglia in balance control.

In this review paper, we summarize the important contributions of the basal ganglia to the regulation of postural control. After a brief overview of basal ganglia circuitries, the emphasis is on clinical observations in patients with focal lesions in parts of the basal ganglia, as the impairments seen here can serve to highlight the normal functions of the basal ganglia nuclei in postural control. Two particularly relevant functions are discussed in detail: first, the contribution of the basal ganglia to flexibility and to gaining control of balance-correcting responses, including the ability to lend priority to the elements of a postural task; and second, processing afferent information by the basal ganglia, which is increasingly recognized as being highly relevant for postural control.

Adaptation, Physiological↗