Showing papers in "Movement Disorders Clinical Practice in 2016"

Developing a Tool for Remote Digital Assessment of Parkinson's Disease

Abstract: BACKGROUND: The natural fluctuation of motor symptoms of Parkinson's disease (PD) makes judgement of any change challenging and the use of clinical scales such as the International Parkinson and Movement Disorder Society (MDS)-UPDRS imperative. Recently developed commodity mobile communication devices, such as smartphones, could possibly be used to assess motor symptoms in PD patients in a convenient way with low cost. We provide the first report on the development and testing of stand-alone software for mobile devices that could be used to assess both tremor and bradykinesia of PD patients. METHODS: We assessed motor symptoms with a custom-made smartphone application in 14 patients and compared the results with their MDS-UPDRS scores. RESULTS: We found significant correlation between five subscores of MDS-UPDRS (rest tremor, postural tremor, pronation-supination, leg agility, and finger tapping) and eight parameters of the data collected with the smartphone. CONCLUSIONS: These results provide evidence as a proof of principle that smartphones could be a useful tool to objectively assess motor symptoms in PD in clinical and experimental settings.

Elastic Abdominal Binders Attenuate Orthostatic Hypotension in Parkinson's Disease.

Abstract: Background and Methods To investigate the possible efficacy of an elastic abdominal binder to control orthostatic hypotension (OH) associated with Parkinson's disease (PD), 15 patients with PD and OH were enrolled in a single-blind crossover study with elastic abdominal versus placebo binder on two different days, separated by a 1-day interval, followed by a 4-week open-label follow-up. Results Intervention significantly reduced blood pressure fall upon tilting. The mean difference (standard deviation; 95% confidence intervals) between abdominal binder versus placebo was +10 mm Hg (10.2; +3.5, +16.5; P = 0.006). No significant effect on supine mean blood pressure values was observed compared to placebo (P = 0.3). Symptoms of OH decreased significantly during follow-up (P = 0.003), as assessed by means of the Orthostatic Hypotension Questionnaire. Conclusions Our findings suggest that elastic abdominal binders may be a simple complementary tool to alleviate OH in PD.

High Botulinum Toxin-Neutralizing Antibody Prevalence Under Long-Term Cervical Dystonia Treatment

Abstract: Background The aim of this study was to determine the prevalence of neutralizing antibodies in a large cohort of long-term treated patients with cervical dystonia (CD) still responding to repetitive injections with botulinum toxin (BoNT). Methods Consecutively recruited CD patients (n = 221) under long-term BoNT treatment (≥2-21 years) underwent a clinical examination at the same time blood samples were taken for neutralizing antibody determination. Collected data included demographics, mean dose of the last 10 botulinum injections, treatment duration, Tsui score for CD severity, and patients' subjective impression of treatment effect. Blood samples were screened for antibody presence by ELISA; positive samples were further analyzed by mouse hemidiaphragm test. The two laboratories performing antibody testing were blinded to the coded samples. Results Antibody status could be determined for 212 patients; 39 (18.4%) were ELISA positive and 31 (14.6%) additionally positive in the mouse hemidiaphragm test. Patients with positive neutralizing antibody titers had significantly higher Tsui scores and were treated for a significantly longer time with significantly higher doses. There were no differences between male and female patients and between onabotulinumtoxinA- and abobotulinumtoxinA-treated patients. When BoNT preparations had been switched during the last 10 injections, a significantly higher proportion of neutralizing antibody-positive patients was detected. Conclusions Neutralizing antibody prevalence in long-term treated, still responding CD patients is substantially higher than suggested by follow-up studies with a shorter time frame. It should therefore be emphasized that antigenicity of BoTN preparations is still a relevant problem and should be taken into account in long-term treatment decisions.

The Pathophysiology of Fatigue in Parkinson's Disease and its Pragmatic Management.

Abstract: Background Fatigue is 1 of the most common and most disabling symptoms among patients with Parkinson's disease (PD) and has a significant impact on their quality of life. Yet the pathophysiology of fatigue is poorly understood, while its treatment is “limited to an empirical approach based on plausible hypotheses.” Methods PubMed was searched for articles with the key words “Parkinson's disease” or “parkinsonism” and “fatigue” that were published by or before August 2015. The analysis of articles, which were selected on subjective grounds, was used to review the current knowledge of pathophysiology and treatment outcomes in studies focused on fatigue in PD. Conclusions Clinical and experimental findings support the view that fatigue is a primary manifestation of PD. The main hypothesized pathophysiological mechanisms include abnormal basal ganglia (BG)-cortical mechanisms, particularly frontal loops, and an imbalance between neurotransmitters (e.g., dopamine [DA] and serotonin), along with an altered hypothalamus-pituitary-adrenal axis, neuroinflammation, cardiac sympathetic denervation, etc. Pragmatic treatment of fatigue in patients with PD includes various pharmacological (dopaminergic and psychostimulant drugs, antidepressants) and nonpharmacological strategies, although current knowledge suffers from insufficient evidence to support the use of any drug or nondrug therapy.

Rating Scales for Pain in Parkinson's Disease: Critique and Recommendations.

Abstract: Background We aimed at critically appraising the clinimetric properties of existing pain scales or questionnaires and to give recommendations for their use in Parkinson's disease (PD). Methods Clinimetric properties of pain scales used in PD were systematically evaluated. A scale was classified as ‘recommended’ if was used in PD, showed adequate clinimetric properties, and had been used by investigators other than the original developers; as ‘suggested’ if it was used in PD and fulfilled only one other criterion; and as ‘listed’ if it was used in PD but did not meet the other criteria. Only scales rating pain intensity or for syndromic classification were assessed. Results Eleven of the 34 scales initially considered fulfilled inclusion criteria. Among the scales rating pain intensity, the “Brief Pain Inventory short form,” “McGill Pain Questionnaire short and long forms,” “Neuropathic Pain Symptoms Inventory,” “11-point Numeric Rating Scale,” “10-cm Visual Analog Scale,” and “Pain-O-Meter” were “recommended with caution” because of lack of clinimetric data in PD, whereas the “King's PD Pain Scale” was “recommended.” Among scales for pain syndromic classification, the “DN4” was “recommended with caution” because of lack of clinimetric data in PD; the “Leeds Assessment of Neuropathic Symptoms and Signs,” “Pain-DETECT,” and the “King's PD Pain Scale” were “suggested.” Conclusions King's PD pain scale can be recommended for the assessment of pain intensity in PD. Syndromic classification of pain in PD may be achieved by the DN4, but clinimetric data in PD are needed for this scale.

Huntington's Disease, Huntington's Disease Look-Alikes, and Benign Hereditary Chorea: What's New?

Abstract: Background The differential diagnosis of chorea syndromes is complex. It includes inherited forms, the most common of which is autosomal dominant Huntington's disease (HD). In addition, there are disorders mimicking HD, the so-called HD-like (HDL) syndromes. Methods and Results Here we review main clinical, genetic, and pathophysiological characteristics of HD and the rare HD phenocopies in order to familiarize clinicians with them. Molecular studies have shown that HD phenocopies account for about 1% of suspected HD cases, most commonly due to mutations in C9orf72 (also the main cause of frontotemporal dementia and amyotrophic lateral sclerosis syndromes), TATA box-binding protein (spinocerebellar ataxia type 17 [SCA17]/HDL4), and JPH3 (HDL2). Systematic screening studies also revealed mutations in PRNP (prion disease), VPS13A (chorea-acanthocytosis), ATXN8OS-ATXN8 (SCA8), and FXN (late-onset Friedreich's Ataxia) in single cases. Further differential diagnoses to consider in patients presenting with a clinical diagnosis consistent with HD, but without the HD expansion, include dentatorubral-pallidoluysian atrophy and benign hereditary chorea (TITF1), as well as the recently described form of ADCY5-associated neurodegeneration. Lastly, biallelic mutations in RNF216 and FRRS1L have recently been reported as autosomal recessive phenocopies of HD. Conclusion There is a growing list of genes associated with chorea, yet a substantial percentage of patients remain undiagnosed. It is likely that more genes will be discovered in the future and that the clinical spectrum of the described disorders will broaden.

Genetic and Clinical Predictors of Deep Brain Stimulation in Young-Onset Parkinson's Disease.

Abstract: Objective In a cohort of patients with young-onset Parkinson's disease (PD), the authors assessed (1) the prevalence of genetic mutations in those who enrolled in deep brain stimulation (DBS) programs compared with those who did not enroll DBS programs and (2) specific genetic and clinical predictors of DBS enrollment. Methods Subjects were participants from 3 sites (Columbia University, Rush University, and the University of Pennsylvania) in the Consortium on Risk for Early Onset Parkinson's Disease (CORE-PD) who had an age at onset < 51 years. The analyses presented here focus on glucocerebrosidase (GBA), leucine-rich repeat kinase 2 (LRRK2), and parkin (PRKN) mutation carriers. Mutation carrier status, demographic data, and disease characteristics in individuals who did and did not enroll in DBS were analyzed. The association between mutation status and DBS placement was assessed in logistic regression models. Results Patients who had PD with either GBA, LRRK2, or PRKN mutations were more common in the DBS group (n = 99) compared with the non-DBS group (n = 684; 26.5% vs. 16.8%, respectively; P = 0.02). In a multivariate logistic regression model, GBA mutation status (odds ratio, 2.1; 95% confidence interval, 1.0–4.3; P = 0.05) was associated with DBS surgery enrollment. However, when dyskinesia was included in the multivariate logistic regression model, dyskinesia had a strong association with DBS placement (odds ratio, 3.8; 95% confidence interval, 1.9–7.3; P < 0.0001), whereas the association between GBA mutation status and DBS placement did not persist (P = 0.25). Conclusions DBS populations are enriched with genetic mutation carriers. The effect of genetic mutation carriers on DBS outcomes warrants further exploration.

Amyloid-Beta Positron Emission Tomography Imaging of Alzheimer's Pathology in Parkinson's Disease Dementia.

Abstract: Background Neuronal loss and alpha-synuclein (α-syn) pathology are diagnostic of PD in the appropriate clinical context. However, some Parkinson's disease (PD) patients have comorbid Alzheimer's disease (AD) pathology on autopsy, including amyloid-beta (Aβ) plaques and neurofibrillary tangles. Florbetapir (18F) is a PET ligand that detects Aβ pathology. We hypothesized that florbetapir (18F) imaging could detect Aβ pathology in PD dementia (PDD) patients before death. The aim of this study was to determine the utility of florbetapir (18F) PET imaging in detecting Aβ pathology in patients with autopsy-confirmed PDD. Methods Five participants with PDD had florbetapir (18F) PET imaging before death as a part of a longitudinal research study of cognitive decline in PD. PET scans were evaluated by expert raters blinded to clinical and neuropathological information. At autopsy, all 5 participants underwent semiquantitative assessments of regional Aβ and tau immunohistochemistry. Results All participants met neuropathological criteria for PD. Two had both positive florbetapir (18F) scans and Aβ-positive plaques in multiple brain regions. Regional florbetapir (18F) binding correlated with regional semiquantitative Aβ pathology in these cases. Three cases had negative florbetapir (18F) scans. Two of these had significant tau pathology without Aβ pathology, consistent with PSP in 1 case and argyrophilic grain disease in the other. The last case had a low level of AD neuropathological change. Conclusions Florbetapir (18F) Aβ imaging can detect the presence of Aβ neuropathology in patients with PDD. This imaging technique may aid the clinical evaluation of PDD patients to determine whether cognitive decline is occurring in the setting of Aβ accumulation.

Impact of Cervical Dystonia on Work Productivity: An Analysis From a Patient Registry

Abstract: Background Cervical dystonia is thought to result in high disease burden, but limited information exists on its impact on employment and work productivity. We utilized data from the Cervical Dystonia Patient Registry for the Observation of OnabotulinumtoxinA Efficacy (ClinicalTrials.gov identifier: NCT00836017) to assess the impact of cervical dystonia on employment and work productivity and examine the effect of onabotulinumtoxinA treatments on work productivity. Methods Subjects completed a questionnaire on employment status and work productivity at baseline and final visit. Baseline data were examined by severity of cervical dystonia, predominant subtype, presence of pain, prior exposure to botulinum toxin, and/or utility of a sensory trick. Work productivity results at baseline and final visit were compared in subjects who were toxin-naive at baseline and received three onabotulinumtoxinA treatments. Results Of 1,038 subjects, 42.8% were employed full- or part-time, 6.1% unemployed, 32.7% retired, and 11.8% disabled. Of those currently employed, cervical dystonia affected work status of 26.0%, caused 29.8% to miss work in the past month (mean, 5.1 ± 6.4 days), and 57.8% reported decreased productivity. Half of those unemployed were employed when symptoms began, and 38.5% attributed lost employment to cervical dystonia. Pain, increasing severity, and anterocollis/retrocollis had the largest effects on work status/productivity. Preliminary analyses showed that absenteeism and presenteeism were significantly decreased following onabotulinumtoxinA treatments in the subpopulation that was toxin-naive at baseline. Conclusions This analysis confirms the substantial negative impact of cervical dystonia on employment, with cervical dystonia-associated pain being a particularly important driver. OnabotulinumtoxinA treatment appears to improve work productivity.

Nocturia in Parkinson's Disease: Why Does It Occur and How to Manage?

Abstract: Background Nocturia is one of the commonest nonmotor symptoms in Parkinson's disease (PD) and has a significant impact on quality of life both for patients and their carers. There exists a relation between nocturia and poor sleep quality, falls, and institutionalization. Nocturia may manifest as a result of reduced functional bladder capacity or nocturnal polyuria; however, most often the cause is multifactorial. Disorders of circadian rhythm regulation are known to occur with sleep disturbances in PD may also contribute to nocturia. Methods and Results In this review, an overview of the assessment and management of nocturia in patients with PD is presented. History taking, medication review, and a bladder diary form the cornerstone of the evaluation. Urinalysis, ultrasonography, and urodynamic studies help to assess the cause for lower urinary tract symptoms and exclude concomitant pathologies, such as bladder outlet obstruction. Antimuscarinic medications are the first-line treatment for the overactive bladder; however, caution is needed when using these medications in individuals predisposed to cognitive impairment. Desmopressin is effective for managing nocturnal polyuria. Conclusions An individualized approach is recommended to optimize the management of nocturia in PD.

Malignant Subthalamic Nucleus-Deep Brain Stimulation Withdrawal Syndrome in Parkinson's Disease.

Abstract: Abrupt cessation of STN-DBS is an under-recognized cause of life-threatening akinetic crisis in Parkinson's disease (PD) and can present as a movement disorder emergency. We report on 2 patients who survived severe and prolonged akinetic crisis after abrupt cessation of STN stimulation for PD (malignant STN-DBS withdrawal syndrome). We discuss the clinical similarities and possible differences in pathophysiology from the akinetic crisis in medically-treated PD. Although early implantable pulse generator (IPG) replacement is the definitive treatment, medical and economic considerations may preclude early surgery and strategies for medical management assume importance. We reflect upon the socioeconomic concerns surrounding DBS in countries lacking health care coverage and the need for user-independent monitors and indicators of low IPG battery status.

Dopamine Transporter (DaT) Scan Utilization in a Movement Disorder Center

Abstract: Background The aim of this work was to describe utilization patterns of dopamine transporter (DaT) scan and its influence on patient management at a single movement disorders center. DaT scan helps differentiate between neurodegenerative from non-neurodegenerative parkinsonism and essential tremor (ET). It has been recently approved in the United States in 2011. Methods We conducted a retrospective review of all patients, observed by movement disorders neurologists, who received a DaT scan. Demographic data, medication use, and prescan diagnosis were collected. Results A total of 216 DaT scans were performed at our center from 1 June 2011 to 31 October 2012. A total of 175 scans were included for analysis. Rates of DaT scan utilization varied from 5 to 33 per 100 new patients observed. When our specialists suspected neurodegenerative parkinsonism before the scan (N = 70), the scan was abnormal in 57%. When non-neurodegenerative parkinsonism was prescan diagnosis (N = 46), the scan was normal in 65%. When essential/dystonic tremor was suspected (N = 14), the scan was normal in 79%. When psychogenic disorder was the prescan diagnosis (N = 15), the scan was normal in only 47%. Only 4% of patients with abnormal scan remained off anti-PD medications, whereas 24% of patients with negative scan were still on anti-PD medications. Conclusions DaT scan utilization among specialists varied greatly. Scan results correlated most when prescan diagnosis was ET than when working diagnosis was neurodegenerative parkinsonism or other non-neurodegenerative parkinsonism. Scan result was least consistent when prescan diagnosis was psychogenic disorder. Finally, DaT scans influenced medical treatment more when it was abnormal, compared to when it was normal.

GNAO1‐Associated Movement Disorder

Abstract: Keywords: chorea; whole-exome sequencing; guanine nucleotide-binding protein; α-activating activity polypeptide O (GNAO1)

Parkinson's Impulse-Control Scale for the Severity Rating of Impulse-Control Behaviors in Parkinson's Disease: A Semistructured Clinical Assessment Tool

Abstract: Background Impulse-control behaviors (ICBs) are increasingly recognized in Parkinson's disease (PD) as drug-related effects of dopaminergic mediation that occur in 15% to 35% of patients with PD. The authors describe the design and evaluation of a new, clinician-rated severity scale for the assessment of syndromal and subsyndromal forms of impulse-control disorders (ICDs), simple (punding) and complex (hobbyism) repetitive behaviors, and compulsive overuse of medication (dopamine dysregulation syndrome). Methods The Parkinson's Impulse-Control Scale (PICS), the first PD-specific, semistructured interview to cover the full range of PD-related ICBs, is described along with initial evidence on its clinimetric properties including interrater reliability, discriminant validity and sensitivity to change. A convenience sample of PD patients with ICBs and those without were administered a semistructured interview (n = 92). Results The scale distinguished between those with and without clinically detected ICBs and between patients with syndromal ICD and subsyndromal ICB (receiver operating characteristic areas under the curve, 92%–95%). Cutoff values were suggested, and substantial agreement was reported on weighted kappa (Κ) values for clinician-clinician rating of severity (Κ = 0.92). Significant improvements were detected on the scale after a randomized controlled trial of cognitive-behavioral therapy and medication adjustment (t[22] = 5.47; P < 0.001). Conclusions The PICS appears to be a reliable measure of the full range of PD ICBs with good levels of interrater reliability. It may provide a useful measure to assess the severity of ICBs and monitor change in clinical and research settings; although, given the specialized centers used for recruitment of this sample, further psychometric evaluation is required.

Clozapine in Parkinsonian Rest Tremor: A Review of Outcomes, Adverse Reactions, and Possible Mechanisms of Action

Abstract: Background The pathogenesis of rest tremor in Parkinson's disease (PD) is incompletely understood. This symptom can be resistant to typical anti-PD medications. Therefore, new treatments are needed given the concern that this symptom causes to patients and family. Limited experience suggests that clozapine can have an important antitremor effect in PD. The mechanism(s) underlying this effect is not well understood, but could provide insight and impetus to the development of more-effective and safer antitremor therapies. Methods and Results Exemplifying the antitremor effects of clozapine, we describe a patient with tremor-predominant PD who obtained prominent reduction of rest tremor with clozapine treatment. We review the responses to this treatment in another 7 of our PD patients with treatment-resistant rest tremor. We also review the published literature on clozapine for tremor in PD and discuss its potential mechanisms of action and possible adverse effects. In our case series, there was a 64% reduction of tremor score after clozapine was initiated. The mechanism of tremor reduction remains unclear with possible involvement of anticholinergic, serotonergic, antihistaminergic, antiadrenergic, and antidopaminergic effects. Clozapine does have potential serious adverse effects. Conclusions Clozapine may be effective in controlling rest tremor in PD. Given the potential fatal side effects, if clozapine is to be initiated in PD patients, it has to be used cautiously with proper monitoring, preferably in specialized centers. We acknowledge that the number of patients in this case series is small. Further studies are needed to understand clozapine's mechanism of action in reducing tremor.

Associations and Implications of Low Health Literacy in Parkinson's Disease

Abstract: Background Low health literacy (HL) indicates a limited ability to understand and use basic information to make appropriate health care decisions. Whereas low HL is associated with higher morbidity, mortality, and health care costs in multiple chronic conditions, little is known about HL and its associations in Parkinson's disease (PD). Methods This was a cross-sectional study of nondemented adults with PD participating in the National Parkinson Foundation Parkinson's Outcomes Project at the University of Pennsylvania. Subjects were administered two brief HL assessments—the Rapid Estimate of Adult Literacy in Medicine-Short Form (REALM-SF), a word-recognition test, and the Newest Vital Sign (NVS), a test of literacy, numeracy, and understanding of health information—as well as demographic and clinical questionnaires. Adverse outcomes included falls in the 3 months preceding the study visit and hospital admissions, emergency room visits, infections, or injuries in the preceding year. Caregiver burden was measured using the Multidimensional Caregiver Strain Index. Results A total of 168 subjects completed both HL screens (mean, 65.8 years; 65.5% male; 65.2% H & Y stage 2). Using the REALM-SF, 97.6% of subjects had adequate HL. Using the NVS, however, 29.8% had low HL, which was associated with older age, lower education, male sex, greater disease severity, and poorer cognition. Low HL was associated with hospital admission and increased caregiver burden. Conclusions Low HL is common and associated with greater caregiver burden and a higher likelihood of hospitalization in patients with PD. Because HL is associated with both disease severity and adverse outcomes, it may be an important, modifiable contributor to morbidity.

DRUM-PD: The use of a drum circle to improve the symptoms and signs of Parkinson's disease (PD).

Abstract: Background Physical therapy can improve motor function in patients with Parkinson's disease (PD). Music performance may be used to improve motor skills by rhythmic entrainment. Drumming has long been a part of traditional healing rituals worldwide and is increasingly being utilized as a therapeutic strategy. Methods This pilot controlled prospective and cohort trial assessed feasibility and effects of twice-weekly group West African drum circle classes for 6 weeks on PD patients’ quality of life, symptoms, motor findings, cognition, and mood. Ten patients with PD were recruited into the drum circle group. Ten patients with PD were matched pairwise to each of the drum circle participants and enrolled in a no-intervention control group. Both groups completed the PD-specific Parkinson Disease Questionnaire (PDQ)-39 quality of life assessment and the Geriatric Depression Scale and underwent motor and cognitive assessments by a rater blinded to group at baseline, 6 weeks, and 12 weeks. Results Drummers had significantly improved PDQ-39 scores from baseline to 6 weeks (−5.8; P = 0.042), whereas the control group's scores were unchanged. Walking performance was significantly faster at baseline for controls; after 6 weeks of drumming, this difference was no longer significant and remained nonsignificant at 12 weeks. The drummers trended (P = 0.069) toward improvement in walking from baseline to 12 weeks. Other outcomes did not significantly change from baseline to 6 or 12 weeks. Conclusions Drum circle classes significantly and reversibly improved quality of life in patients with PD. This pilot trial's findings merit larger controlled investigations comparing drumming classes to established interventions in PD, such as physical therapy.

Nocturia in Patients With Parkinson's Disease

Abstract: Background Waking up from sleep more than once to pass urine, known as nocturia, is an important nonmotor symptom in Parkinson's disease (PD). Very little is known about the cause for nocturia. The aim of this work was to evaluate lower urinary tract (LUT) symptoms in patients with PD reporting nocturia using standardized validated questionnaires and bladder diaries and to assess the impact of nocturia on quality of life and sleep. Methods Twenty-three consecutive patients with PD (17 males, 6 females; mean age: 68.5 years; range, 50–85) referred to a specialist uro-neurology clinic reporting nocturia according to the International Continence Society definition were included. Patients measured their daily fluid intake, urinary output per void, and recorded these with the timing of voids on a 3-day bladder diary. Standardized questionnaires were used to assess LUT symptoms (Urinary Symptom Profile, International Prostate Symptom Score, and Qualiveen Short Form) and sleep quality (Parkinson's Disease Sleep Scale). Results Mean duration of PD was 10.1 years, and mean severity on H & Y scale was 3.0 (range, 1.0–5.0). Median duration of LUT symptoms was 6.0 years. Mean night-time urinary frequency was 3.5 (range, 1.0–7.3), and mean nocturnal maximum voided volume was 242 mL. Mean Nocturnal Polyuria Index (NPi) was 0.4 (range, 0.13–0.75), and 13 patients (56.5%) had nocturnal polyuria (NPi > 0.33). Patients with nocturnal polyuria reported more-severe LUT symptoms that impacted quality of life and sleep. Conclusions In this preliminary study, nocturnal polyuria seems to be common in patients with PD reporting nocturia and appears to affect quality of life and sleep, though this was not statistically significant. The bladder diary is an essential tool in the assessment of nocturia in patients with PD.

Postural, Bone, and Joint Disorders in Parkinson's Disease.

Abstract: Background Stooped posture was mentioned in the original description of the characteristic features of Parkinson's disease (PD). Since then, a variety of postural, bone, and joint problems have become recognized as common aspects of the illness and deserve attention. Methods A Medline literature search for the period from 1970 to 2016 was performed to identify articles relevant to this topic. Keywords for the search included posture, spine, bone disorders, fractures, joint disorders, kyphosis, scoliosis, stooping, camptocormia, Pisa syndrome, frozen shoulder, anterocollis, dropped head syndrome, and pain in combination with PD. The articles were then reviewed to summarize clinical features, frequency, impact, pathophysiology, and treatment options for these conditions. Results Postural disorders (kyphoscoliosis, camptocormia, Pisa syndrome, dropped head syndrome), bone mineralization disorders (osteoporosis, bone fractures), and joint disorders (frozen shoulder, dystonia involving joints, joint pain) are often seen in association with PD. Treatment options for these conditions are varied and may include medications, physical therapy, or surgical interventions. Conclusions Posture, bone, and joint disorders are common in patients with PD; they often produce added disability, and they may be treatable.

Banisteriopsis caapi, a Forgotten Potential Therapy for Parkinson's Disease?

Abstract: Banisteriopsis caapi, a liana indigenous to the Amazon basin with metagnomigenic properties and possible anti-depressant effects is one of the natural sources of harmala alkaloids. A summary of early trials with extracts of Banisteriopsis caapi and Peganum harmala (from which harmine was first isolated) in the 1920s and 1930s on various forms of parkinsonism is given as well as a brief overview of the known pharmacological properties of harmine. Despite its earlier abandonment because of perceived weaker efficacy than solanaceous alkaloids like scopolamine and hyoscine we propose that harmine should be reconsidered as a potential rapidly acting anti-Parkinsonian agent.

Deep Brain Stimulation Battery Longevity: Comparison of Monopolar Versus Bipolar Stimulation Modes.

Abstract: Background Deep brain stimulation is an effective treatment for movement disorders, but it is relatively complex, invasive, and costly. Little is known about whether stimulation mode alters pulse generator (battery) longevity in routine clinical care. Objective To compare battery longevity during monopolar versus bipolar stimulation in patients who underwent deep brain stimulation for movement disorders. Methods We evaluated 2,902 programming adjustments and calculated the average stimulator settings for 393 batteries in 200 unique patients with Parkinson's disease and essential tremor. We classified the pulse generators into different stimulation modes (monopolar, bipolar, tripolar, double monopolar) and compared battery longevity with Kaplan Meier survival analyses using the log rank test. We exclusively implanted the Medtronic 3387 lead with adjacent electrode contacts separated by 1.5 mm. Results The mean pulse generator longevity was 47.6±1.6 months regardless of diagnosis or stimulation mode. Bipolar stimulation mode was associated with greater longevity than monopolar stimulation (56.1±3.4 versus 44.2±2.1 months, p=0.006). This effect was most pronounced when stimulation parameters were at low to moderate intensity settings. Double monopolar configuration was associated with less pulse generator longevity than conventional stimulation modes (37.8±5.6 versus 49.7±1.9, p=0.014). Conclusion IPGs initially programmed in bipolar mode provided one year of additional battery longevity versus monopolar mode in this large retrospective series of patients with essential tremor and Parkinson's disease. Given satisfactory efficacy for motor symptoms, bipolar stimulation mode is a feasible alternative programming strategy at the initiation of DBS therapy.

How Do I Examine for Re-Emergent Tremor?

Abstract: Although rest tremor is the typical form of tremor associated with Parkinson's disease (PD), particularly the tremor-dominant subtype,1 parkinsonian patients may also exhibit postural tremor. In many parkinsonian patients, this postural tremor emerges after a latency of a few seconds or even minutes. In our original description, we coined the term "re-emergent tremor" to differentiate this postural tremor from essential tremor, which occurs without any latency, and to link it to PD rest tremor that is "reset" after some latency when a new holding posture is assumed.2 The relationship of this re-emergent tremor to the typical rest tremor is supported by the observation that this tremor shares many characteristics with the typical rest tremor, such as the same, 3 to 5-Hz frequency, occasional supinating-pronating component, and relatively good response to dopaminergic therapy. Rarely, postural tremor, occurring after a brief (2-4 seconds) latency can be seen even without observable rest tremor.3 In most patients with PD, it is the postural (re-emergent) tremor that is more troublesome for them than the typical rest tremor, because this re-emergent tremor interferes with their ability to hold objects, such as newspapers, against gravity and results in spilling of liquids. Postural tremor of PD is often misdiagnosed as essential tremor, and this diagnostic challenge can be further confounded when both conditions coexist.4 When that occurs, the postural tremor is present without latency, although the amplitude may gradually increase as the underlying re-emergent tremor becomes more evident.

Mitochondrial Respiratory Function in Peripheral Blood Cells from Huntington's Disease Patients

Abstract: BackgroundPatients with Huntington's disease display symptoms from both the central nervous system and peripheral tissues. Mitochondrial dysfunction has been implicated as part of the pathogenesis of the disease and has been reported in brain tissue and extracerebral tissues, such as muscle and blood cells, but the results are inconsistent. Therefore, the authors performed a refined evaluation of mitochondrial function in 2 types of peripheral blood cells from 14 patients with Huntington's disease and 21 control subjects. Several hypotheses were predefined, including impaired mitochondrial complex II function (primary), complex I function (secondary), and maximum oxidative phosphorylation capacity (secondary) in patient cells.MethodsHigh-resolution respirometry was applied to viable platelets and mononuclear cells. Data were normalized to cell counts, citrate synthase activity, and mitochondrial DNA copy numbers.ResultsNormalized to citrate synthase activity, platelets from patients with Huntington's disease displayed respiratory dysfunction linked to complex I, complex II, and lower maximum oxidative phosphorylation capacity. No difference was seen in mononuclear cells or when platelet data were normalized to cell counts or mitochondrial DNA. The ratio of complex I respiration through maximum oxidative phosphorylation was significantly decreased in patients compared with controls. The corresponding ratio for complex II was unaffected.ConclusionsThe data indicate decreased function of mitochondrial complex I in peripheral blood cells from patients with Huntington's disease, although this could not be uniformly confirmed. The results do not confirm a systemic complex II dysfunction and do not currently support the use of mitochondrial function in blood cells as a biomarker for the disease.

The Accessibility of Parkinson's Disease Medication in Kenya: Results of a National Survey.

Abstract: Background There is a dearth of knowledge about the availability and affordability of the different drug treatments for Parkinson's disease (PD) across sub-Saharan Africa (SSA). We aimed to determine the availability and affordability of drugs for treating PD in Kenya. Methods A facility-based survey was conducted in selected medicine outlets (pharmacies) in what were formerly the headquarter towns of the eight provinces of Kenya. We used the World Health Organization/Health Action International methodology to obtain data for drugs used to treat PD. Unit price for each drug was obtained. Results Forty-eight outlets were visited in total, six in each of Kenya's eight provinces. Levodopa (L-dopa) was available in only 24 (50.0%) outlets. Only one public pharmacy sold l-dopa (14 were private and nine were other types of outlet). Ergot-derived dopamine agonists (DAs) and anticholinergics were available in 37 and 35 outlets, respectively. Monoamine-oxidase inhibitors, non-ergot-derived DAs, and catechol-O-methyl transferase inhibitors were available in four, two and zero outlets, respectively. Mean cost of 100 l-dopa tablets was $48.2, though costs varied widely (range, $28.2–$82.4). Only five outlets considered l-dopa affordable, all of which sold 100 tablets for less than $31. Conclusion There is a lack of availability of PD drugs in Kenya, particularly in public pharmacies, where costs are generally lower. Few pharmacists consider the drugs available to be affordable. If PD is to be effectively managed in Kenya, then strategies are needed to increase the availability and affordability of medication.

Inpatient Physiotherapy for Functional (Psychogenic) Gait Disorder: A Case Series of 35 Patients

Abstract: Patients with functional gait disorder (FGD) are often referred for physiotherapy, but data on their outcome is limited. The authors present a case series of 35 patients who received targeted physiotherapy for FGD at a regional neuroscience center (mean number of sessions, 11). Significant improvements in the Modified Rivermead Mobility Index (score range, 0-40) were recorded between pretreatment and posttreatment (mean pretreatment vs. posttreatment score, 20 vs. 37, respectively). Improvements also were seen in patients who had chronic symptoms, including those with symptom duration over 6 months (mean pretreatment vs. posttreatment score, 21 vs. 33, respectively) and in patients who had no psychological intervention. These data support the hypothesis that specific physiotherapy for FGD can be surprisingly effective and further encourage the development of larger randomized trials to test efficacy.

Once STN DBS, Always STN DBS?—Clinical, Ethical, and Financial Reflections on Deep Brain Stimulation for Parkinson's Disease

Abstract: Once STN DBS, Always STN DBS?-Clinical, Ethical, and Financial Reflections on Deep Brain Stimulation for Parkinson's Disease

Spinal Movement Disorders in Neuromyelitis Optica: An Under-recognized Phenomenon.

Abstract: Background Spinal cord demyelination can cause several movement disorders. Although these abnormal movements could be the presenting symptom of the disease and, at times, the major source of disability, they are often overlooked, mislabeled, or undertreated. The aims of this study were to clearly define and establish common terminology for spinal movement disorders (SMDs) and characterize their full spectrum in patients with neuromyelitis optica (NMO). Methods We chart reviewed 37 patients with NMO or NMO spectrum disorder. We classified spinal movement disorders under five categories: tonic spasms; focal dystonia; spinal myoclonus; spontaneous clonus; and tremors of spinal origin. We examined clinical, MRI, and medication data of symptomatic patients. Results Of the 37 patients (86.4% female; mean age: 51 ± 17 years; mean disease duration: 9.4 ± 5.3 years), 16 (43.2%) had one or more form of SMDs. Compared to those without SMDs, patients with SMDs were generally older at presentation and were less likely to be African Americans. An abnormal movement was the main complaint in at least one posthospitalization visit in all symptomatic patients. Thirteen (35.1%) patients had paroxysmal tonic spasms, 2 (5.4%) had focal dystonia, 3 (8%) had postural/action tremors, and no patient had spinal myoclonus or spontaneous clonus. In 9 patients, spasms were painful. There was no signal abnormality in the basal ganglia or the brainstem/cerebellum in any of the symptomatic patients. Conclusions SMDs are common in NMO and are often a major source of disability. Using clear, unified terminology to describe SMDs is crucial for both clinical and research purposes.

Outcome Measures for Parkinson's Disease Dementia: A Systematic Review

Abstract: Background Parkinson's disease (PD) dementia (PDD) is a major cause of morbidity and mortality in PD, which severely affects patient functioning and quality of life and increases the risk for nursing home admission. Unfortunately, current treatment options for PDD are limited and have only marginal therapeutic effects. As novel treatments are developed, there will be a need to assess their efficacy in well-designed, randomized, controlled trials. However, there is no consensus on the optimal outcome measures for use in PDD clinical trials. Methods A systematic review of PDD clinical trials and empirical studies of outcome measures used in PDD was performed. Outcome measures were divided into 5 categories: (1) cognitive; (2) behavioral and mood; (3) activities of daily living and quality of life; (4) global; and (5) caregiver burden. Findings A total of 20 PDD pharmacological clinical trials were identified. These trials incorporated a broad array of outcome measures, which were used inconsistently across trials. We summarize the psychometric properties and other relevant data on outcome measures used, including their diagnostic utility, inter-rater reliability, test-retest reliability, responsiveness, clinically meaningful change, and availability of alternate forms. Conclusions We have identified the best-evidenced PDD outcome measures in each domain. Further research is needed to assess the validity, reliability, and clinically meaningful change of these measures in PDD to inform the design of future clinical trials and enhance the ability of clinicians, researchers, and policy makers to interpret study results. In addition, the development of outcome measures specific to PDD may be warranted.

Long-term Thalamic Deep Brain Stimulation for Essential Tremor: Clinical Outcome and Stimulation Parameters

Abstract: Background The reasons underlying the loss of efficacy of deep brain stimulation (DBS) of the thalamic nucleus ventralis intermedius (VIM-DBS) over time in patients with essential tremor are not well understood. Methods Long-term clinical outcome and stimulation parameters were evaluated in 14 patients with essential tremor who underwent VIM-DBS. The mean ± standard deviation postoperative follow-up was 7.7 ± 3.8 years. At each visit (every 3–6 months), tremor was assessed using the Fahn-Tolosa-Marin tremor rating scale (FTM-TRS) and stimulation parameters were recorded (contacts, voltage, frequency, pulse width, and total electrical energy delivered by the internal generator [TEED1sec]). Results The mean reduction in FTM-TRS score was 73.4% at 6 months after VIM-DBS surgery (P < 0.001) and 50.1% at the last visit (P < 0.001). The gradual worsening of FTM-TRS scores over time fit a linear regression model (coefficient of determination [R2] = 0.887; P < 0.001). Stimulation adjustments to optimize tremor control required a statistically significant increase in voltage (P = 0.01), pulse width (P = 0.01), frequency (P = 0.02), and TEED1sec (P = 0.008). TEED1sec fit a third-order polynomial curve model throughout the follow-up period (R2 = 0.966; P < 0.001). The initial exponential increase (first 4 years of VIM-DBS) was followed by a plateau and a further increase from the seventh year onward. Conclusions The current findings suggest that the waning effect of VIM-DBS over time in patients with essential tremor may be the consequence of a combination of factors. Superimposed on the progression of the disease, tolerance can occur during the early years of stimulation.

OnabotulinumtoxinA and AbobotulinumtoxinA Dose Conversion: a Systematic Literature Review.

Abstract: Objective This systematic review was performed to elucidate dosing practices, dosing conversions, and related outcomes from randomized, controlled trials that directly compared onabotulinumtoxinA (ONA) and abobotulinumtoxinA (ABO) at various dose conversion ratios for therapeutic use in movement disorders. Methods A systematic review of three medical literature databases (PubMed, the Cochrane Library, and EMBASE) was performed to identify relevant comparative clinical studies, systematic reviews, and meta-analyses published in the English language between January 1991 and January 2015. Studies that met predefined inclusion criteria were selected for formal data extraction and quality assessment. Results A total of 182 manuscripts were identified, of which four were included for analysis. Targeted clinical applications included neurological disorders. The studies compared ONA to ABO dose conversion ratios of 1:2.5 (n = 1), 1:3 (n = 2), and 1:4 (n = 2). One study compared both 1:3 and 1:4 ratios. An ONA:ABO conversion factor of 1:2.5 was associated with similar efficacy and side effects. An ONA:ABO ratio of 1:3 provided similar or higher efficacy, but an increased rate of adverse effects, and an ONA:ABO ratio of 1:4 was associated with higher efficacy, but with an excessive rate of intolerable side effects. Conclusion A dose conversion ratio of ONA to ABO between 1:2.5 and 1:3.0 provides comparable safety and efficacy for therapeutic movement disorders chemodenervation procedures.