[Show abstract][Hide abstract] ABSTRACT: Parkinson’s disease (PD) and essential tremor (ET) are the two most common movement disorders but the rate of misdiagnosis rate in these disorders is high due to similar characteristics of tremor. The purpose of the study is to present: (a) a solution to identify PD and ET patients by using the novel measurement of tremor signal variations while performing the resting task, (b) the improvement of the differentiation of PD from ET patients can be obtained by using the ratio of the novel measurement while performing two specific tasks.
35 PD and 22 ET patients were asked to participate in the study. They were asked to wear a 6-axis inertial sensor on his/her index finger of the tremor dominant hand and perform three tasks including kinetic, postural and resting tasks. Each task required 10 s to complete. The angular rate signal measured during the performance of these tasks was band-pass filtered and transformed into a two-dimensional representation. The ratio of the ellipse area covering 95 % of this two-dimensional representation of different tasks was investigated and the two best tasks were selected for the purpose of differentiation.
The ellipse area of two-dimensional representation of the resting task of PD and ET subjects are statistically significantly different (p < 0.05). Furthermore, the fluctuation ratio, defined as a ratio of the ellipse area of two-dimensional representation of resting to kinetic tremor, of PD subjects were statistically significantly higher than ET subjects in all axes (p = 0.0014, 0.0011 and 0.0001 for x, y and z-axis, respectively). The validation shows that the proposed method provides 100 % sensitivity, specificity and accuracy of the discrimination in the 5 subjects in the validation group. While the method would have to be validated with a larger number of subjects, these preliminary results show the feasibility of the approach.
This study provides the novel measurement of tremor variation in time domain termed ‘temporal fluctuation’. The temporal fluctuation of the resting task can be used to discriminate PD from ET subjects. The ratio of the temporal fluctuation of the resting task to the kinetic task improves the reliability of the discrimination. While the method is powerful, it is also simple so it could be applied on low resource platforms such as smart phones and watches which are commonly equipped with inertial sensors.
Full-text · Article · Dec 2015 · BioMedical Engineering OnLine
[Show abstract][Hide abstract] ABSTRACT: Background:
Nocturnal hypokinesia/akinesia is a distressing symptom in patients with Parkinson's disease (PD). However, it is difficult to accurately monitor these symptoms based on clinical interviews alone.
To quantitatively compare nocturnal movements of PD patients with their spouses by using multisite inertial sensors and to correlate these parameters with disease severity scores.
Nocturnal movements in 19 PD couples (mild-moderate stage) were assessed and compared using wearable sensors (limbs and trunk) for one night at their homes. Nocturnal parameters included number, velocity, acceleration, degree, and duration of rolling over, number of getting out of bed, and limb movements. Each activity was compared to sleep diary, and video recording for accuracy.
PD patients significantly had fewer rolling over (p = 0.048), turned with smaller degree (p = 0.007), less velocity (p = 0.011), and acceleration (p < 0.001), but had more episodes of getting out of bed (p = 0.03, nocturia) when compared to their spouses. Moderate and significant correlations were observed between the mean duration of rolling over and the Unified Parkinson's Disease Rating Scale-Axial score, and Nocturnal Akinesia Dystonia and Cramp Score. The number of leg movements (predominant side) significantly correlated with REM behavior disorder single-question screen. Episodes of nocturia correlated with total and bedtime levodopa equivalent dose. Several other correlations were also observed.
Our study was able to demonstrate quantitatively the presence of nocturnal hypokinesia in PD patients. This problem correlated with daytime axial motor and nonmotor symptoms. Treatment strategy for PD should be based on a comprehensive review of both day- and nighttime symptoms.
No preview · Article · Nov 2015 · Parkinsonism & Related Disorders
[Show abstract][Hide abstract] ABSTRACT: The formation of neutralizing antibodies (NAbs) directed specifically against the active neurotoxin part of the botulinum neurotoxin (BoNT) complex is often cited as a major cause of secondary non-responsiveness (SnR) to treatment. This systematic and meta-analytic review evaluates the frequency of NAbs among patients treated with BoNT therapy for any clinical indication. A comprehensive database search strategy was designed to retrieve relevant clinical data from the published literature up to April 2013. All English-language publications that analyzed NAbs prevalence in more than ten patients were included, regardless of BoNT formulation, assay method, and study design. For the meta-analysis, patients were divided into three categories: secondary non-response (SnR) patients, clinically responding patients and all patients, independently of BoNT responsiveness. The meta-analysis included 61 studies reporting data for 8525 patients; 4972 dystonic patients, 1170 patients with spasticity, 294 patients with urologic indications, 396 patient with hyperhidrosis, 1659 patients with glabellar line, and 34 patients with hypersalivation. Among the "all patients" group NAbs frequency was 20 % for dystonia, 5.9 % for spasticity, and 2.7 % for urologic patients and 1.1 % for other conditions. The prevalence of NAbs was lower (3.5 %) among clinically responding patients and higher in 53.5 % SnR patients. About a half of patients with SnR do not have NAbs. NAbs was high among patients treated with RIMA but it was not associated with clinical non-responsiveness. Meta-analysis of the frequency of NAbs and SnR are limited by the heterogeneity of study design and reported outcomes. Indeed the analysis of several factors that can influence the development of NAbs, i.e., MHC of patients, frequency and site of injection, injection technique, cumulative dose, and toxin denaturation, was not specifically evaluated due to the paucity and heterogeneity of data. The identification of all these missing data should be taken into account in order to improve the methodology of future studies.
No preview · Article · Oct 2015 · Neurotoxicity Research
[Show abstract][Hide abstract] ABSTRACT: Most Parkinson's disease patients will receive levodopa therapy, and of these, the majority will develop some levodopa-induced complications. For many patients, the first complication to develop is the decline in the duration of therapeutic benefit of each levodopa dose, a phenomenon commonly termed 'wearing-off'. There is already extensive literature documenting the epidemiology and management of wearing-off in Parkinson's disease patients of western descent. However, data derived from these studies might not always apply to patients of Asian descent due to genetic variations, differences in co-morbidities or non-availability of certain drugs. This review summarizes the current literature regarding the epidemiology of wearing-off in Asian (including Arab) patients and discusses the management issues in the context of drug availability in Asia.
No preview · Article · Sep 2015 · Expert Review of Neurotherapeutics
[Show abstract][Hide abstract] ABSTRACT: Background:
About 50 % of Thai patients with adult-onset spinocerebellar ataxia (SCA) was Machado-Joseph disease (MJD), SCA1, SCA2 and SCA6. The author investigated further on less common SCAs in the patients without any known mutations.
DNA samples of 82 index patients who were genetically excluded MJD, SCA1, SCA2, SCA6, SCA7 and dentatorubro-pallidoluysian atrophy (DRPLA) were examined. Analysis of SCA8, SCA10, SCA12, SCA17 and SCA19 genes were comprehensively performed. Normal range of trinucleotide repeat expansion sizes of TATA-box-binding protein gene (TBP) were also determined in 374 control subjects.
Eight patients carried ≥42 CAG/CAA repeat allele in the TBP consistent with SCA17. The pathological repeat alleles ranged from 42 to 57 repeats. All patients had significant degree of cognitive dysfunction. Other non-ataxic phenotypes comprised of parkinsonism, chorea, dystonia and myoclonus. A sporadic patient carried a heterozygous 41-repeat allele developed chronic progressive cerebellar degeneration commenced at the age of 28 years. Whilst, 2 % of the control subjects (8/374) carried the 41-repeat allele. Five of the carriers were re-examined, and revealed that four of them had parkinsonism and/or cognitive impairment without cerebellar signs. Analysis of other types of SCAs was all negative.
This is the first study of SCA8, SCA10, SCA12, SCA17 and SCA19 in Thais. SCA17 appears to be an important cause of ataxia in Thailand. Although, the pathological cut-off point of the TBP repeat allele remains unclear, the finding suggests that the 41-repeat may be a pathological allele resulting late-onset or mild phenotype. Apart from ataxia, cognitive impairment and parkinsonism may be clinical presentations in these carriers.
[Show abstract][Hide abstract] ABSTRACT: Treatment of dystonias is generally symptomatic. To produce sufficient therapy effects, therefore, frequently a multimodal and interdisciplinary therapeutic approach becomes necessary, combining botulinum toxin therapy, deep brain stimulation, oral antidystonic drugs, adjuvant drugs and rehabilitation therapy including physiotherapy, occupational therapy, re-training, speech therapy, psychotherapy and sociotherapy. This review presents the recommendations of the IAB-Interdisciplinary Working Group for Movement Disorders Special Task Force on Interdisciplinary Treatment of Dystonia. It reviews the different therapeutic modalities and outlines a strategy to adapt them to the dystonia localisation and severity of the individual patient. Hints to emerging and future therapies will be given.
[Show abstract][Hide abstract] ABSTRACT: Background:
As the pathophysiology of tremor in Parkinson disease (PD) involves a complex interaction between central and peripheral mechanisms, we propose that modulation of peripheral reflex mechanism by electrical muscle stimulation (EMS) may improve tremor temporarily.
To determine the efficacy of EMS as a treatment for drug resistant tremor in PD patients.
This study was a single-blinded, quasi-experimental study involving 34 PD patients with classic resting tremor as confirmed by tremor analysis. The EMS was given at 50Hz over the abductor pollicis brevis and interrosseus muscles for 10s with identified tremor parameters before and during stimulation as primary outcomes.
Compared to before stimulation, we observed a significant reduction in the root mean square (RMS) of the angular velocity (p<0.001) and peak magnitude (p<0.001) of resting tremor while tremor frequency (p=0.126) and dispersion (p=0.284) remained unchanged during stimulation. The UPDRS tremor score decreased from 10.59 (SD=1.74) before stimulation to 8.85 (SD=2.19) during stimulation (p<0.001). The average percentage of improvement of the peak magnitude and RMS angular velocity was 49.57% (SD=38.89) and 43.81% (SD=33.15) respectively. 70.6% and 61.8% of patients experienced at least 30% tremor attenuation as calculated from the peak magnitude and RMS angular velocity respectively.
Our study demonstrated the efficacy of EMS in temporarily improving resting tremor in medically intractable PD patients. Although tremor severity decreased, they were not completely eliminated and continued with a similar frequency, thus demonstrating the role of peripheral reflex mechanism in the modulation of tremor, but not as a generator. EMS should be further explored as a possible therapeutic intervention for tremor in PD.
No preview · Article · Sep 2015 · Journal of the neurological sciences
[Show abstract][Hide abstract] ABSTRACT: The manifestations of nocturnal movements in Parkinson's disease (PD) are protean, with major disabilities related to nocturnal hypokinesia. While it can be assessed by clinical interviews and screening instruments, these are often inaccurate and prone to recall bias. In light of advances in sensor technology, we explored the use of sensors in the study of nocturnal hypokinesia, by performing a systematic review of the professional literature on this topic. Evidence suggests that nocturnal hypokinesia exists even in patients in the early stages, and PD patients turned significantly less and with much slower speed and acceleration than controls, partly related to low nocturnal dopamine level. We conducted another systematic review to evaluate the evidence of the efficacy of dopaminergic agents in the treatment of nocturnal hypokinesia. Several lines of evidence support the use of long-acting drugs or by continuous administration of short-acting agents to control symptoms. Sensor parameters could be considered as one of the important objective outcomes in future clinical trials investigating potential drugs to treat nocturnal hypokinesia. Physicians should be aware of this technology as it can aid the clinical assessment of nocturnal hypokinesia and enhance the quality of patient care. In addition, the use of sensors currently is being considered for various aspects of research on early diagnosis, treatment, and rehabilitation of PD patients.
No preview · Article · Sep 2015 · Parkinsonism & Related Disorders
[Show abstract][Hide abstract] ABSTRACT: "Home" is where one has a sense of belonging and feels secure, but it can also be a risky place for people with Parkinson's disease (PD). PD patients need assistance making adjustments to their physical environment to maintain appropriate care and provide a safe environment. This relationship is called the "person-environmental fit" (P-E fit). While most PD patients remain in their own homes, little is known about the specific challenges that PD patients and their caregivers encounter in the routine activities of daily living. The aim of our study was to identify the existing evidence on the issue of housing environmental adaptation in PD by performing a systematic review with a proposal of development strategies to integrate a multidisciplinary team into a home environmental research. MEDLINE, and life science journals were searched by querying appropriate key words, but revealed very few publications in this area. However, early evidence suggested that PD patients do not enjoy an adequate P-E fit in their own homes and face more functional limitations compared to matched controls. We concluded that we need to develop research-based evaluation strategies that can provide us with a theoretical and conceptual basis as well as tools for analysis of the P-E fit for PD patients and caregivers. We recommend that individual members of the multidisciplinary team including patients, caregivers, physicians, rehabilitation specialists, and social workers use a team approach to identify the key indicators and solutions for the development of PD-specific solutions for improving the P-E fit.
Full-text · Article · Aug 2015 · Parkinsonism & Related Disorders
[Show abstract][Hide abstract] ABSTRACT: The clinical utility of long-term oral levodopa therapy in Parkinson disease (PD) is often limited by the emergence of motor complications. Over time, many patients with PD experience regular and/or unpredictable "off" periods, despite taking optimized oral medication regimens, with a major negative impact on their ability to undertake routine activities of daily living and consequently on their overall quality of life. One established approach for treating patients experiencing off periods and controlling motor fluctuations refractory to conventional oral drug therapy is the subcutaneous administration of the dopaminergic agonist apomorphine. This article outlines how the pharmacokinetic properties of apomorphine underpin its efficacy for the treatment of PD and provides practical guidance for the 3 main approaches in which it is used: subcutaneous intermittent apomorphine injection as a "rescue" therapy for off states, subcutaneous continuous apomorphine infusion for PD patients with intractable motor fluctuations as an alternative to other dopaminergic treatment, and in the apomorphine response (or challenge) test for assessment of dopamine-induced motor response in patients thought to have PD, or in establishing the optimal tolerated dose of apomorphine in patients already known to have PD. Also discussed is the management of potential adverse events with subcutaneous administration of apomorphine, the majority of which are mild and easily managed in practice. The importance of a multidisciplinary PD team in the optimal management of PD patients is now recognized, in particular the role of the specialist PD nurse.
No preview · Article · May 2015 · Clinical neuropharmacology
[Show abstract][Hide abstract] ABSTRACT: The development of secondary non-response (SNR) to botulinum neurotoxin type-A (BoNT-A) is considered a key issue in the management of cervical dystonia (CD). This case-controlled study was performed to systematically identify factors influencing SNR during BoNT-A therapy.Methods
This was a retrospective, international, non-interventional study of CD patients. Patients with SNR were matched with up to three responder patients (control) on the basis of duration of therapy and number of injection cycles. Factors influencing the development of SNR were screened using a univariate logistic regression model and confirmed using a multivariate conditional logistic regression model.Results216 patients were enrolled, and 201 (SNR=52; responder=149) were matched and subdivided into blocks (doublets, triplets or quadruplets). At baseline, a significantly higher proportion of SNR patients had received previous or concomitant therapies (p=0.038) and surgery for CD (p=0.007) compared with controls. Although disease severity at onset was similar between groups, a significantly higher proportion of SNR patients experienced severe CD at the time of SNR compared with controls at the last documented visit. Multivariate analyses identified five factors that were significantly associated in predicting SNR (odds ratio [OR]>1 indicated higher chances for being SNR): previous surgical procedure for CD (OR 9.8, p=0.013), previous BoNT-A related severe adverse event (AE) (OR 5.6 p=0.027), physical therapy (OR 4.6, p=0.028), neuroleptic use (OR 3.3, p=0.019) and average BoNT-A dose (OR 2.7, p=0.010).Conclusions
These findings suggest that SNR may not reflect true pharmacological resistance to BoNT-A therapy, but may be related to underlying disease severity.
No preview · Article · Nov 2014 · Parkinsonism & Related Disorders
[Show abstract][Hide abstract] ABSTRACT: To determine the prevalence and predictors of sexual dysfunction (SD) in Parkinson's disease (PD) patients.Background
Assessments of SD in the professional literature is limited. Understanding the predictors of SD can help physicians focus on this problem in vulnerable patients.MethodA total of 60 PD patients and 60 controls answered the Arizona Sexual Experiences Scale-Thai Version (ASEX-Thai) and the Hamilton Depression Rating Scale (HAMD) questionnaires, and were asked on 3 additional sets of questions about premature ejaculation (PE), dyspareunia, and hypersexual disorders.ResultThe prevalence of SD in PD patients and controls was 81.6% and 48.3% respectively (p < 0.05). PD patients had lower BMI, lower uric acid level, higher HAMD score and had sexual intercourse (SI) less frequently. SD correlated with greater disease severity and depression. The most distressing problem in male patients was PE (51.4%) and orgasmic dissatisfaction (76%) for female patients. Logistic regression analysis found 3 factors were related to SD: no SI in the past month (p < 0.001), postural instability (PI) (p = 0.028), and HAMD item 14 (p = 0.021), predicting SD with the OR of 12.2, 5.5, and 5.0 respectively.ConclusionsSD in PD is common and usually occurs with depression. Absence of SI in the past month, PI, and loss of libido are predictors of SD in PD. A simple and quick screening of SD can be routinely performed by inquiring patients about the frequency of SI and the examination of the pull test. Detailed assessment of sexual functioning and depression may guide physicians in proper management.
No preview · Article · Nov 2014 · Parkinsonism & Related Disorders