Showing papers by "Bastiaan R. Bloem published in 2011"

Freezing of gait: Moving forward on a mysterious clinical phenomenon

Abstract: Freezing of gait (FoG) is a unique and disabling clinical phenomenon characterised by brief episodes of inability to step or by extremely short steps that typically occur on initiating gait or on turning while walking. Patients with FoG, which is a feature of parkinsonian syndromes, show variability in gait metrics between FoG episodes and a substantial reduction in step length with frequent trembling of the legs during FoG episodes. Physiological, functional imaging, and clinical-pathological studies point to disturbances in frontal cortical regions, the basal ganglia, and the midbrain locomotor region as the probable origins of FoG. Medications, deep brain stimulation, and rehabilitation techniques can alleviate symptoms of FoG in some patients, but these treatments lack efficacy in patients with advanced FoG. A better understanding of the phenomenon is needed to aid the development of effective therapeutic strategies.

Postural deformities in Parkinson's disease

Abstract: Postural deformities are frequent and disabling complications of Parkinson's disease (PD) and atypical parkinsonism. These deformities include camptocormia, antecollis, Pisa syndrome, and scoliosis. Recognition of specific postural syndromes might have differential diagnostic value in patients presenting with parkinsonism. The evidence to date suggests that postural deformities have a multifactorial pathophysiology. Contributing factors include muscular rigidity; axial dystonia; weakness caused by myopathy; body scheme defects due to centrally impaired proprioception; and structural changes in the spine. The relative contribution of these different factors varies between patients and across specific syndromes. Improved understanding of the mechanisms underlying postural deformities in PD might ultimately lead us to more effective management strategies for these disabling and drug-refractory complications.

Gait-related cerebral alterations in patients with Parkinson's disease with freezing of gait.

Abstract: Freezing of gait is a common, debilitating feature of Parkinson's disease. We have studied gait planning in patients with freezing of gait, using motor imagery of walking in combination with functional magnetic resonance imaging. This approach exploits the large neural overlap that exists between planning and imagining a movement. In addition, it avoids confounds introduced by brain responses to altered motor performance and somatosensory feedback during actual freezing episodes. We included 24 patients with Parkinson's disease: 12 patients with freezing of gait, 12 matched patients without freezing of gait and 21 matched healthy controls. Subjects performed two previously validated tasks--motor imagery of gait and a visual imagery control task. During functional magnetic resonance imaging scanning, we quantified imagery performance by measuring the time required to imagine walking on paths of different widths and lengths. In addition, we used voxel-based morphometry to test whether between-group differences in imagery-related activity were related to structural differences. Imagery times indicated that patients with freezing of gait, patients without freezing of gait and controls engaged in motor imagery of gait, with matched task performance. During motor imagery of gait, patients with freezing of gait showed more activity than patients without freezing of gait in the mesencephalic locomotor region. Patients with freezing of gait also tended to have decreased responses in mesial frontal and posterior parietal regions. Furthermore, patients with freezing of gait had grey matter atrophy in a small portion of the mesencephalic locomotor region. The gait-related hyperactivity of the mesencephalic locomotor region correlated with clinical parameters (freezing of gait severity and disease duration), but not with the degree of atrophy. These results indicate that patients with Parkinson's disease with freezing of gait have structural and functional alterations in the mesencephalic locomotor region. We suggest that freezing of gait might emerge when altered cortical control of gait is combined with a limited ability of the mesencephalic locomotor region to react to that alteration. These limitations might become particularly evident during challenging events that require precise regulation of step length and gait timing, such as turning or initiating walking, which are known triggers for freezing of gait.

Physical inactivity in Parkinson's disease.

Abstract: Patients with Parkinson's disease (PD) are likely to become physically inactive, because of their motor, mental, and emotional symptoms. However, specific studies on physical activity in PD are scarce, and results are conflicting. Here, we quantified daily physical activities in a large cohort of PD patients and another large cohort of matched controls. Moreover, we investigated the influence of disease-related factors on daily physical activities in PD patients. Daily physical activity data of PD patients (n = 699) were collected in the ParkinsonNet trial and of controls (n = 1,959) in the Longitudinal Aging Study Amsterdam (LASA); data were determined using the LAPAQ, a validated physical activity questionnaire. In addition, variables that may affect daily physical activities in PD were recorded, including motor symptoms, depression, disability in daily life, and comorbidity. Patients were physically less active; a reduction of 29% compared to controls (95% CI, 10-44%). Multivariate regression analyses demonstrated that greater disease severity, gait impairment, and greater disability in daily living were associated with less daily physical activity in PD (R (2) = 24%). In this large study, we show that PD patients are about one-third less active compared to controls. While disease severity, gait, and disability in daily living predicted part of the inactivity, a portion of the variance remained unexplained, suggesting that additional determinants may also affect daily physical activities in PD. Because physical inactivity has many adverse consequences, work is needed to develop safe and enjoyable exercise programs for patients with PD.

How might physical activity benefit patients with Parkinson disease

Abstract: Parkinson disease (PD) is a neurodegenerative disorder characterized by progressive motor and nonmotor impairments. These impairments incline many patients towards a sedentary lifestyle, which has many deleterious consequences. Accumulating evidence suggests that patients with PD might benefit from physical activity and exercise in a number of ways, from general improvements in health to disease-specific effects and, potentially, disease-modifying effects (suggested by animal data). Many issues remain to be addressed, including the need to perform clinical trials to demonstrate these presumed benefits of physical activity and exercise in patients with PD. These trials must also address safety issues, such as an increased risk of falls and cardiovascular complications in more-active patients. Identifying ways to induce a sustained behavioral change, using specifically tailored programs that address potential barriers such as depression, apathy and postural instability, may lead to an improved quality of life in individuals with PD.

Angiogenin variants in Parkinson disease and amyotrophic lateral sclerosis

Abstract: OBJECTIVE: Several studies have suggested an increased frequency of variants in the gene encoding angiogenin (ANG) in patients with amyotrophic lateral sclerosis (ALS). Interestingly, a few ALS pat ...

Causes and consequences of cerebral small vessel disease. The RUN DMC study: a prospective cohort study. Study rationale and protocol

Abstract: Cerebral small vessel disease (SVD) is a frequent finding on CT and MRI scans of elderly people and is related to vascular risk factors and cognitive and motor impairment, ultimately leading to dementia or parkinsonism in some. In general, the relations are weak, and not all subjects with SVD become demented or get parkinsonism. This might be explained by the diversity of underlying pathology of both white matter lesions (WML) and the normal appearing white matter (NAWM). Both cannot be properly appreciated with conventional MRI. Diffusion tensor imaging (DTI) provides alternative information on microstructural white matter integrity. The association between SVD, its microstructural integrity, and incident dementia and parkinsonism has never been investigated. The RUN DMC study is a prospective cohort study on the risk factors and cognitive and motor consequences of brain changes among 503 non-demented elderly, aged between 50-85 years, with cerebral SVD. First follow up is being prepared for July 2011. Participants alive will be included and invited to the research centre to undergo a structured questionnaire on demographics and vascular risk factors, and a cognitive, and motor, assessment, followed by a MRI protocol including conventional MRI, DTI and resting state fMRI. The follow up of the RUN DMC study has the potential to further unravel the causes and possibly better predict the consequences of changes in white matter integrity in elderly with SVD by using relatively new imaging techniques. When proven, these changes might function as a surrogate endpoint for cognitive and motor function in future therapeutic trials. Our data could furthermore provide a better understanding of the pathophysiology of cognitive and motor disturbances in elderly with SVD. The execution and completion of the follow up of our study might ultimately unravel the role of SVD on the microstructural integrity of the white matter in the transition from "normal" aging to cognitive and motor decline and impairment and eventually to incident dementia and parkinsonism.

Milestones in gait, balance, and falling

Abstract: Gait, balance, and falls have become increasingly common topics of published articles in the Movement Disorders journal since its launch in 1986. This growth represents an increasing awareness of the importance of mobility to patients' quality of life. New methods have become available that allow for accurate measurement of many aspects for gait and balance. This has led to new concepts of understanding gait and balance disorders. Neuroimaging has begun to reveal the neural circuitry underlying gait and balance. The physiology and pathophysiology of balance and gait are beginning to tease out the many processes involved in mobility and how they may be disrupted by disease processes. With these advances, the old therapeutic nihilism that characterized the clinician's approach to falls and gait disorders is disappearing, as innovative physiotherapy, exercise, drugs, and deep brain stimulation are being employed for gait and balance disorders.

Bicycling breaks the ice for freezers of gait

Abstract: Patients with freezing of gait (FOG) have episodic problems with generating adequate steps. This phenomenon is both common and debilitating in patients with Parkinson's disease (PD) or atypical parkinsonism. We recently presented a video case of a patient with longstanding PD and severe FOG, who showed a remarkably preserved ability to ride a bicycle. Here, we comment on the scientific and clinical implications of this single case observation, and show the video of a similar case. We first consider several pathophysiological explanations for this striking discrepancy between walking and cycling in PD. We then discuss the merits and shortcomings of cycling as a potential new avenue for rehabilitation and exercise training in patients grounded by FOG. Finally, we provide some directions for future research stimulated by this fascinating observation.

Multidisciplinary care for Parkinson's disease: not if, but how!

Abstract: Increasingly, many centres around the world are delivering multidisciplinary care for patients with Parkinson's disease (PD).1 2 Indeed, a multidisciplinary team approach currently seems inevitable for anyone who understands even a little about PD. After all, this really is a wretched disorder, with a complex and diverse phenotype. Patients become progressively incapacitated, not only because of the well known motor symptoms (bradykinesia, rigidity, tremor, gait impairment and postural instability), but also because of a wide variety of non-motor symptoms. These include neuropsychiatric disorders (cognitive disturbances, hallucinations, psychosis), sleep disorders (insomnia, rapid eye movement sleep behaviour disorder, periodic leg movements), autonomic dysfunction (orthostatic hypotension, constipation, urinary incontinence, erectile dysfunction) and pain from various sources (eg, central pain, painful off period dystonia). Not surprisingly, PD is regarded by patients as one of the most unbearable disorders around, ranked second on the respective lists for both motor and cognitive disorders.3 Perhaps even more telling is the fact that many immediate caregivers are on the brink of succumbing to the pressure of living with someone with PD.4–6 Moreover, conventional therapies—drug treatment and stereotactic deep brain surgery—offer only partial and temporary relief, particularly in more advanced disease.7 Against this background, any neurologist who still feels that a single discipline suffices to combat this debilitating disease must seem almost heartless, or at least a bit naive. And any potential critics should be consoled by the fact that multidisciplinary care has already won its spurs in other areas of neurology—for example, stroke units.8 Luckily for PD patients, help is on the way. Evidence is growing to support the effectiveness of various allied health disciplines. Thus far, the case is strongest for specific physiotherapy techniques, such as cueing.9 But there are also practice based guidelines—from accumulating research evidence, or sometimes merely expert …

Multidisciplinary care for Parkinson's disease: not if, but how!

Abstract: Increasingly, many centres around the world are delivering multidisciplinary care for patients with Parkinson's disease (PD).1 2 Indeed, a multidisciplinary team approach currently seems inevitable for anyone who understands even a little about PD. After all, this really is a wretched disorder, with a complex and diverse phenotype. Patients become progressively incapacitated, not only because of the well known motor symptoms (bradykinesia, rigidity, tremor, gait impairment and postural instability), but also because of a wide variety of non-motor symptoms. These include neuropsychiatric disorders (cognitive disturbances, hallucinations, psychosis), sleep disorders (insomnia, rapid eye movement sleep behaviour disorder, periodic leg movements), autonomic dysfunction (orthostatic hypotension, constipation, urinary incontinence, erectile dysfunction) and pain from various sources (eg, central pain, painful off period dystonia). Not surprisingly, PD is regarded by patients as one of the most unbearable disorders around, ranked second on the respective lists for both motor and cognitive disorders.3 Perhaps even more telling is the fact that many immediate caregivers are on the brink of succumbing to the pressure of living with someone with PD.4,–,6 Moreover, conventional therapies—drug treatment and stereotactic deep brain surgery—offer only partial and temporary relief, particularly in more advanced disease.7 Against this background, any neurologist who still feels that a single discipline suffices to combat this debilitating disease must seem almost heartless, or at least a bit naive. And any potential critics should be consoled by the fact that multidisciplinary care has already won its spurs in other areas of neurology—for example, stroke units.8 Luckily for PD patients, help is on the way. Evidence is growing to support the effectiveness of various allied health disciplines. Thus far, the case is strongest for specific physiotherapy techniques, such as cueing.9 But there are also practice based guidelines—from accumulating research evidence, …

Limb Amputations in Fixed Dystonia: A Form of Body Integrity Identity Disorder?

Abstract: Fixed dystonia is a disabling disorder mainly affecting young women who develop fixed abnormal limb postures and pain after apparently minor peripheral injury. There is continued debate regarding its pathophysiology and management. We report 5 cases of fixed dystonia in patients who sought amputation of the affected limb. We place these cases in the context of previous reports of patients with healthy limbs and patients with chronic regional pain syndrome who have sought amputation. Our cases, combined with recent data regarding disorders of mental rotation in patients with fixed dystonia, as well as previous data regarding body integrity identity disorder and amputations sought by patients with chronic regional pain syndrome, raise the possibility that patients with fixed dystonia might have a deficit in body schema that predisposes them to developing fixed dystonia and drives some to seek amputation. The outcome of amputation in fixed dystonia is invariably unfavorable.

Connectedness of healthcare professionals involved in the treatment of patients with Parkinson's disease: a social networks study

Abstract: Patients with chronic illness typically receive ambulatory treatment from multiple health professionals. Connectedness between these professionals may influence their clinical decisions and the coordination of patient care. We aimed to describe and analyze connectedness in a regional network of health professionals involved in ambulatory treatment of patients with Parkinson's disease (PD). Observational study with 104 health professionals who had joined a newly established network (ParkinsonNet) were asked to complete a pre-structured form to report on their professional contacts with others in the network. Using social networks methods, network measures were calculated for the total network and for the networks of individual health professionals. We planned to test differences between subgroups of health professionals regarding 12 network measures, using a random permutation method. Ninety-six health professionals (92%) provided data on 101 professionals. The reciprocity of reported connections was 0.42 in the network of professional contacts. Measures characterizing the individual networks showed a wide variation; e.g., density varied between 0 and 100% (mean value 28.4%). Health professionals with ≥10 PD patients had higher values on 7 out of 12 network measures compare to those with < 10 PD patients (size, number of connections, two step reach, indegree centrality, outdegree centrality, inreach centrality, betweenness centrality). Primary care professionals had lower values on 11 out of 12 network measures (all but reach efficiency) compared to professionals who were affiliated with a hospital. Our measure of professional connectedness proved to be feasible in a regional disease-specific network of health professionals. Network measures describing patterns in the professional contacts showed relevant variation across professionals. A higher caseload and an affiliation with a hospital were associated with stronger connectedness with other health professionals.

CSF tau, Aβ42, and MHPG differentiate dementia with Lewy bodies from Alzheimer's disease.

Abstract: Differentiating dementia with Lewy bodies (DLB) from Alzheimer's Disease (AD) can be difficult because of the substantial overlap in clinical features. Since deficits in serotonergic and dopaminergic pathways seem more pronounced in DLB patients, we investigated whether cerebrospinal fluid (CSF) analysis of neurotransmitter metabolites, in addition to brain-specific proteins, may improve the differentiation between DLB and AD. We retrospectively compared CSF concentrations of the neurotransmitter metabolites homovanillic acid (HVA), 5-hydroxyindolacetic acid (5-HIAA), and 3-methoxy-4-hydroxyphenylethyleneglycol (MHPG) and the brain-specific proteins total tau (t-tau), phosphorylated tau protein (p-tau), and amyloid-β42 (Aβ42) in 45 patients with AD (mean age 71.6 years; 34 (76%) men; 44 probable AD, 1 definite) and 23 patients with DLB (mean age 71.6 years; 18 (78%) men; 6 possible DLB, 16 probable, 1 definite). The concentrations of all neurotransmitter metabolites, as well as those for t-tau and p-tau protein, were significantly lower in DLB compared to AD, irrespective of the diagnostic certainty (i.e., possible or probable). The currently used combination of Aβ42, p-tau, and t-tau yielded a sensitivity of 92.9% and a specificity of 90%. The addition of MHPG resulted in an increased sensitivity of 97.6% and a specificity of 95% for the discrimination between DLB and AD. In conclusion, the combination of MHPG and the brain specific proteins t-tau, p-tau, and Aβ42 in CSF were associated with the clinical diagnosis of DLB and discriminated between AD and DLB with high diagnostic accuracy, suggesting this combination as a potential biomarker for DLB.

Levodopa is not a useful treatment for Lesch-Nyhan disease.

Abstract: Lesch-Nyhan disease (LND) is characterized by dystonia, cognitive abnormalities, and self-injurious behavior. No effective therapies are available. LND is associated with a presynaptic dopaminergic deficit, but the reported effects of dopamine replacement therapy are conflicting. The current prospective open-label study assesses the effects of levodopa on both neurological and behavioral features of LND. All 6 study participants discontinued levodopa early, due to lack of effect and sometimes worsening of motor function. The results provide important clues for pathophysiological mechanisms and suggestions for future treatment options.

"Silly Walks" in Parkinson's disease: Unusual presentation of dopaminergic-induced dyskinesias

Abstract: It is widely recognized that dopaminergic-induced dyskinesias can interfere with gait in advanced Parkinson’s disease (PD).1 However, levodopa-induced dyskinesias can sometimes take bizarre forms and may easily be mistaken for psychogenic movement disorders. Here, we present four PD patients with strikingly similar bizarre gaits related to the effects of levodopa. Patient 1 developed clumsiness of the left leg and hand at age 44. He was diagnosed with PD and levodopa treatment was initiated. Six years later, a psychogenic cause was suspected because of bizarre leg movements interfering with stability and gait. We discovered that these dyskinesias mainly occurred at the beginning and end of each levodopa dose effect (Video Patient 1, Segment 1 and 2). In between these periods, the patient experienced motor improvement (Video Patient 1, Segment 3). Patient 2 developed hypokinesia and rigidity in the left arm at age38. Levodopa was initiated, with a good effect on motor function. Three years later, he complained of a short and unpredictable effect of levodopa, usually with a period of immobility and abnormal leg movements preceding advent of the next dose effect (Video Patient 2, Segment 1). After overnight withdrawal of all medication, the patient showed generalized bradykinesia, plus dystonia of the right foot(Video Patient 2, Segment 2). Thirty five minutes after a levodopa dose, ballistic kicking and stamping appeared in the left leg on walking, along with persistent dystonic posturing of the left arm (Video Patient 2, Segment3). In his full “on” state, the patient showed only mild choreodystonia not interfering with gait(Video Patient 2, Segment 4). Patient 3 was diagnosed with PD beginning in his left arm at age 35. He started levodopa at age 36 with a good response. At age 41 he developed motor fluctuations and dyskinesias. During the “on” phase he exhibited a striking, stereotyped, kicking gait (Video Patient 3, Segment 1). When “off” he was slow with marked difficulty walking (Video Patient 3, Segment 2). Bilateral deep brain stimulation of the subthalamic nucleus (DBS STN)improved his parkinsonism and allowed reduction of his medications. He no longer exhibits this gait pattern. Patient 4 developed PD at the age of 39. He responded well to dopaminergic medication, but after four years he developed wearing off and dopaminergic-induced dyskinesias. In his best “on” phase, the patient shows violent choreatic dyskinesias involving the trunk, arms, and legs(Video Patient 4, Segment 1). In the practically defined “off” state, the patient’s gait is clearly bradykinetic, with small, slow and shuffling steps (Video Patient 4, Segment 2). The patient subsequently received bilateral DBS STN, with substantial improvement of dyskinesias and gait. There are several common elements to these case presentations. The first is the bizarre, yet fairly stereotyped, gait patterns. When videos of these patients were presented at conferences to experienced movement disorder specialists, the gait was generally thought to be psychogenic and reminiscent of the gaits shown in Monty Python’s classic TV sketch “The Ministry of Silly Walks” (http://www.youtube.com/watch?v=9ZlBUglE6Hc). The gait we present here indeed looks bizarre, but it is also remarkably stereotyped across patients seen in four different movement disorders clinics. Recurring characteristics include the stepping with kicks, high knee elevations and ballistic ‘stamping’ of one lower limb, generally on the side that was first affected by PD. In addition, dystonic postures of the contralateral foot and ipsilateral arm were seen in two patients, and dancing movements with hops and pelvis rotations in one case. A further shared feature was that all patients are men, whose PD began before the age of 45 years. In keeping with known experiences with such young-onset patients,2 they all developed early motor fluctuations and dyskinesias, starting only several years after initiation of dopaminergic treatment. Another important element was the timing of these abnormal movements in relation to the intake and clinical efficacy of dopaminergic medication. The two first patients clearly had a diphasic pattern: dyskinesias developed shortly following a levodopa dose, at the beginning of the therapeutic effect. When the levodopa effect increased further to reach a full “on” state, the dyskinesias largely disappeared, and gait improved considerably consistent with previous descriptions of biphasic levodopa-induced dyskinesias that mainly affect subjects with early-onset PD, and that are characterized by a stereotypic pattern, with a dystonic or ballistic form, and a violent expression.2–4 The predominance in the most affected leg corresponds to the observation that dyskinesias start and predominate in the leg contralateral to where dopaminergic denervation in the dorsal putamen is greatest.5 Optimizing dopaminergic therapy or DBS can be helpful in these patients, as was also demonstrated here. Most importantly, the bizarre gait pattern should not be misdiagnosed as a psychogenic movement disorder; even if voluntary movements are sometimes superimposed as a compensation for the dyskinesias interfering with gait(possibly in Patient 4). Another possibility is embellishment which, although not widely recognized, may occur as a superimposed movement abnormality in patients with otherwise genuine PD.6 Showing a similar case(#17), Hayes et al.7 appropriately warned about the danger of labeling a bizarre gait as psychogenic just on the basis that it is unlike anything one has seen before.

Evaluation of the Falls Telephone:: An Automated System for Enduring Assessment of Falls

Abstract: OBJECTIVES: To evaluate the reliability and user experiences of an automated telephone system to monitor falls during a prolonged period of time. DESIGN: Prospective cohort study. SETTING: Four neurological outpatient clinics in the Netherlands. PARTICIPANTS: One hundred nineteen community-dwelling people with Parkinson's disease without dementia, because falls are common in this population. MEASUREMENTS: Clinical and demographic data were obtained. The Falls Telephone is a computerized telephone system through which participants can enter the number of falls during a particular period. During a follow-up of 1 to 40 weekly calls, 2,465 calls were made. In total, 173 no-fall entries and 115 fall entries were verified using personal telephone interviews. User experiences were evaluated in 90 of the 119 participants using structured telephone interviews. RESULTS: All no-fall entries and 78% of fall entries were confirmed to be correct. Sensitivity to detect falls was 100%, and specificity was 87%. Users regarded the Falls Telephone as a convenient tool to monitor falls. CONCLUSION: The Falls Telephone is a convenient and reliable instrument to monitor falls. The automated system has high specificity, obviating the need for time-consuming personal follow-up calls in the majority of nonfallers. As such, the Falls Telephone lends itself well to data collection in large trials with prolonged follow-up in participants with Parkinson's disease.

A toxic shot from the hip

Abstract: A 26-year-old man developed a movement disorder characterised by bradyphrenia, bradykinesia, rigidity, tremor and dystonia, several years after having been shot by a gun in the hip. Laboratory investigations revealed anaemia and porphyria. The authors demonstrate that his neurological condition was a delayed manifestation of lead toxicity, caused by slow absorption of lead from persisting bullet fragments in the hip joint. Treatment with excision of the femoral head and debridement of the hip followed by a total hip, in combination with chelating therapy, led to a remarkable remission.

A new twist on turning movements in Parkinson's disease patients.

Abstract: Carpenter, Mark G Bloem, Bastiaan R Comment Editorial Research Support, Non-U.S. Gov't United States Mov Disord. 2011 Oct;26(12):2151-3. doi: 10.1002/mds.23980.

Diagnostic challenges in parkinsonism

Abstract: The presence of signs and symptoms of parkinsonism can be assessed in the clinical examination room, using a combination of history taking and neurological examination [1]. Parkinson’s disease (PD)...