Journal of Parkinson's Disease - Volume 6, issue 3

Authors: Barnish, Maxwell S. | Whibley, Daniel | Horton, Simon M.C. | Butterfint, Zoe R. | Deane, Katherine H.O.

Article Type: Research Article

Abstract: Background: Communication is fundamental to human interaction and the development and maintenance of human relationships and is frequently affected in Parkinson’s disease (PD). However, research and clinical practice have both tended to focus on impairment rather than participation aspects of communicative deficit in PD. In contrast, people with PD have reported that it is these participation aspects of communication that are of greatest concern to them rather than physical speech impairment. Objective: To systematically review the existing body of evidence regarding the association between cognitive status and/or intelligibility and everyday communication in PD. Methods: Five …online databases were systematically searched in May 2015 (Medline Ovid, EMBASE, AMED, PsycINFO and CINAHL) and supplementary searches were also conducted. Two reviewers independently evaluated retrieved records for inclusion and then performed data extraction and quality assessment using standardised forms. Articles were eligible for inclusion if they were English-language original peer-reviewed research articles, book chapters or doctoral theses investigating the associations between at least one of cognitive status and level of intelligibility impairment and an everyday communication outcome in human participants with PD. Results: 4816 unique records were identified through database searches with 16 additional records identified through supplementary searches. 41 articles were suitable for full-text screening and 15 articles (12 studies) met the eligibility criteria. 10 studies assessed the role of cognitive status and 9 found that participants with greater cognitive impairment had greater everyday communication difficulties. 4 studies assessed the role of intelligibility and all found that participants with greater intelligibility impairment had greater everyday communication difficulties, although effects were often weak and not consistent. Conclusions: Both cognitive status and intelligibility may be associated with everyday communicative outcomes in PD. The contribution of intelligibility to everyday communication appears to be of small magnitude, suggesting that other factors beyond predominantly motor-driven impairment-level changes in intelligibility may play an important role in everyday communication difficulties in PD. Show more

Keywords: Parkinson disease, cognition disorders, speech disorders, communication, social participation, international classification of functioning, disability and health, review, systematic

DOI: 10.3233/JPD-150757

Citation: Journal of Parkinson's Disease, vol. 6, no. 3, pp. 453-462, 2016

Authors: Baille, Guillaume | De Jesus, Anna Maria | Perez, Thierry | Devos, David | Dujardin, Kathy | Charley, Christelle Monaca | Defebvre, Luc | Moreau, Caroline

Article Type: Review Article

Abstract: In contrast to some other neurodegenerative diseases, little is known about ventilatory dysfunction in Parkinson’s disease (PD). To assess the spectrum of ventilation disorders in PD, we searched for and reviewed studies of dyspnea, lung volumes, respiratory muscle function, sleep breathing disorders and the response to hypoxemia in PD. Among the studies, we identified some limitations: (i) small study populations (mainly composed of patients with advanced PD), (ii) the absence of long-term follow-up and (iii) the absence of functional evaluations under “off-drug” conditions. Although there are many reports of abnormal spirometry data in PD (mainly related to impairment of the …inspiratory muscles), little is known about hypoventilation in PD. We conclude that ventilatory dysfunction in PD has been poorly studied and little is known about its frequency and clinical relevance. Hence, there is a need to characterize the different phenotypes of ventilation disorders in PD, study their relationships with disease progression and assess their prognostic value. Show more

Keywords: Parkinson’s disease, pathophysiology, ventilatory function, review

DOI: 10.3233/JPD-160804

Citation: Journal of Parkinson's Disease, vol. 6, no. 3, pp. 463-471, 2016

Authors: Barnish, Jean | Atkinson, Rachel A. | Barran, Susannah M. | Barnish, Maxwell S.

Article Type: Research Article

Abstract: Background: There is evidence that participation in performing arts brings psychosocial benefits in the general population and in recent years there has been substantial interest in the potential therapeutic benefit of performing arts, including singing, for people with chronic medical conditions including those of neurological aetiology. Objective: To systematically review the existing body of evidence regarding the potential benefit of singing on clinical outcomes of people with PD. Methods: Seven online bibliographic databases were systematically searched in January 2016 and supplementary searches were conducted. Full-text original peer-reviewed scientific papers that investigated the potential benefit of …singing on at least one of speech, functional communication, cognitive status, motor function and quality of life in human participants with PD were eligible for inclusion. Results: 449 unique records were identified, 25 full-text articles were screened and seven studies included in the review. All seven studies assessed the impact of singing on speech, five found partial evidence of benefit and two found no evidence of benefit. One study assessed each of functional communication and quality of life and no significant benefit was found. No included study assessed the impact of singing on motor function or cognitive status. Conclusions: Singing may benefit the speech of people with PD, although evidence is not unequivocal. Further research is required to assess wider benefits including on functional communication, cognitive status, motor function and quality of life. Substantial methodological limitations were identified in the existing literature. Recommendations are made for advancing the state of the literature. Show more

Keywords: Parkinson disease, rehabilitation, singing, speech therapy, music therapy, review, systematic

DOI: 10.3233/JPD-160837

Citation: Journal of Parkinson's Disease, vol. 6, no. 3, pp. 473-484, 2016

Authors: Margraf, N.G. | Wrede, A. | Deuschl, G. | Schulz-Schaeffer, W.J.

Article Type: Review Article

Abstract: Camptocormia is a disabling pathological, non-fixed, forward bending of the trunk. The clinical definition using only the bending angle is insufficient; it should include the subjectively perceived inability to stand upright, occurrence of back pain, typical individual complaints, and need for walking aids and compensatory signs (e.g. back-swept wing sign). Due to the heterogeneous etiologies of camptocormia a broad diagnostic approach is necessary. Camptocormia is most frequently encountered in movement disorders (PD and dystonia) and muscles diseases (myositis and myopathy, mainly facio-scapulo-humeral muscular dystrophy (FSHD)). The main diagnostic aim is to discover the etiology by looking for signs of the …underlying disease in the neurological examination, EMG, muscle MRI and possibly biopsy. PD and probably myositic camptocormia can be divided into an acute and a chronic stage according to the duration of camptocormia and the findings in the short time inversion recovery (STIR) and T1 sequences of paravertebral muscle MRI. There is no established treatment of camptocormia resulting from any etiology. Case series suggest that deep brain stimulation (DBS) of the subthalamic nucleus (STN-DBS) is effective in the acute but not the chronic stage of PD camptocormia. In chronic stages with degenerated muscles, treatment options are limited to orthoses, walking aids, physiotherapy and pain therapy. In acute myositic camptocormia an escalation strategy with different immunosuppressive drugs is recommended. In dystonic camptocormia, as in dystonia in general, case reports have shown botulinum toxin and DBS of the globus pallidus internus (GPi-DBS) to be effective. Camptocormia in connection with primary myopathies should be treated according to the underlying illness. Show more

Keywords: Camptocormia, bent spine syndrome, stooped posture, postural abnormality, back pain

DOI: 10.3233/JPD-160836

Citation: Journal of Parkinson's Disease, vol. 6, no. 3, pp. 485-501, 2016

Authors: Pagan, Fernando | Hebron, Michaeline | Valadez, Ellen H. | Torres-Yaghi, Yasar | Huang, Xu | Mills, Reversa R. | Wilmarth, Barbara M. | Howard, Hellen | Dunn, Connell | Carlson, Alexis | Lawler, Abigail | Rogers, Sean L. | Falconer, Ramsey A. | Ahn, Jaeil | Li, Zhaoxia | Moussa, Charbel

Article Type: Research Article

Abstract: Background : We evaluated the effects of low doses of the tyrosine kinase Abelson (Abl) inhibitor Nilotinib, on safety and pharmacokinetics in Parkinson’s disease dementia or dementia with Lewy bodies. Objectives : The primary outcomes of this study were safety and tolerability; pharmacokinetics and target engagement were secondary, while clinical outcomes were exploratory. Methods : Twelve subjects were randomized into 150 mg (n  = 5) or 300 mg (n  = 7) groups and received Nilotinib orally every day for 24 weeks. Results : This study shows that 150 mg and 300 mg doses of Nilotinib appear to be safe and tolerated in subjects …with advanced Parkinson’s disease. Nilotinib is detectable in the cerebrospinal fluid (CSF) and seems to engage the target Abl. Motor and cognitive outcomes suggest a possible beneficial effect on clinical outcomes. The CSF levels of homovanillic acid are significantly increased between baseline and 24 weeks of treatment. Exploratory CSF biomarkers were measured. Conclusions : This small proof-of-concept study lacks a placebo group and participants were not homogenous, resulting in baseline differences between and within groups. This limits the interpretations of the biomarker and clinical data, and any conclusions should be drawn cautiously. Nonetheless, the collective observations suggest that it is warranted to evaluate the safety and efficacy of Nilotinib in larger randomized, double-blind, placebo-controlled trials. Show more

Keywords: Parkinson, Lewy bodies, Nilotinib, synuclein, dopamine, homovanillic acid, tau

DOI: 10.3233/JPD-160867

Citation: Journal of Parkinson's Disease, vol. 6, no. 3, pp. 503-517, 2016

Authors: Wyse, Richard K. | Brundin, Patrik | Sherer, Todd B.

Article Type: Article Commentary

Abstract: We discuss a report in the current issue on clinical and biochemical findings from a safety trial using the cAbl tyrosine kinase inhibitor Nilotinib (150 mg or 300 mg given daily for 24 weeks) in a small group of patients with either advanced Parkinson’s disease or Dementia with Lewy Bodies. Despite some side effects (one serious), the authors claim that Nilotinib, which is normally used at much higher doses for treating leukemia, is safe and tolerated. Furthermore, they report a possible benefit on motor and cognitive outcomes. We debate the safety of Nilotinib and the reported efficacy signals. We emphasize that due …to the small sample size, and lack of a control group, it is impossible to rule out a placebo effect. We briefly discuss a range of aspects surrounding the current and possible future use of this cAbl inhibitor in patients with alpha-synucleinopathy, and what must now be done to obtain definitive information about its safety and efficacy in this population of patients. Show more

Keywords: Drug repositioning, neuroprotection, Nilotinib

DOI: 10.3233/JPD-160904

Citation: Journal of Parkinson's Disease, vol. 6, no. 3, pp. 519-522, 2016

Authors: He, Lu | Lee, Eun-Young | Sterling, Nicholas W. | Kong, Lan | Lewis, Mechelle M. | Du, Guangwei | Eslinger, Paul J. | Huang, Xuemei

Article Type: Research Article

Abstract: Background: The impact of motor- and non-motor symptoms on health-related quality of life (HRQOL) in Parkinson’s disease (PD) has received increasing attention. Objectives: To address this, the study explored a large cohort of patients enrolled in the PD Biomarker Program. Methods: The PD Questionnaire-39 (PDQ-39) measured HRQOL, whereas the Unified PD Rating Scale (UPDRS) assessed motor and non-motor symptoms. Determinants of HRQOL in PD patients were identified by stepwise linear regression analysis. The relationship between the PDQ-39 and UPDRS subscale scores then was explored through structural equation modeling. Results: The mean disease duration …was 6.8 years and the mean PDQ-39 summary index (PDQ-39SI) was 18.4. UPDRS-I (non-motor function) and UPDRS-II (motor questionnaire) scores demonstrated the strongest correlations with PDQ-39SI (r Ϡ 0.4, P  < 0.05), whereas UPDRS-III (motor exam) and UPDRS-IV (motor complications) scores were correlated moderately with PDQ-39SI (0.3 < r < 0.4, P  < 0.05). Multiple linear stepwise regression analyses showed that age (β= –0.13, P  < 0.001), education (β= –0.07, P  = 0.008), UPDRS-I (β= 0.32, P  = 0.000), and UPDRS-II (β= 0.44, P  < 0.001) significantly contributed to HRQOL, and cumulatively accounted for 69.1% of the PDQ-39SI variance. UPDRS-II score was the primary predictor of PDQ-39SI, accounting for 57.3% of the variance, whereas UPDRS-I score accounted for 7.5%. UPDRS-III and -IV and other factors measured did not survive stepwise regression. Structural equation modeling confirmed the association of UPDRS-II (β= 0.67, P  < 0.001) and UPDRS-I (β= 0.35, P  < 0.001) with the PDQ-39SI. Conclusion: Both motor and non-motor function scores impacted significantly HRQOL in PD. UPDRS-III, however, has limited contributions to HRQOL although it is used as a main outcome in many clinical trials. Show more

Keywords: Parkinson’s disease, quality of life, motor symptoms, non-motor symptoms, structural equation modeling, Unified Parkinson’s disease rating scales, structure, review

DOI: 10.3233/JPD-160851

Citation: Journal of Parkinson's Disease, vol. 6, no. 3, pp. 523-532, 2016

Authors: Nijhuis, Frouke A.P. | van Heek, Jolien | Bloem, Bastiaan R. | Post, Bart | Faber, Marjan J.

Article Type: Research Article

Abstract: Background: In advanced Parkinson’s disease (PD), neurologists and patients face a complex decision for an advanced therapy. When choosing a treatment, the best available evidence should be combined with the professional’s expertise and the patient’s preferences. Objective: The objective of this study was to explore current decision-making in advanced PD. Methods: We conducted focus group discussions and individual interviews with patients (N  = 20) who had received deep brain stimulation, Levodopa-Carbidopa intestinal gel, or subcutaneous apomorphine infusion, and with their caregivers (N  = 16). Furthermore, we conducted semi-structured interviews with neurologists (N  = 7) and PD nurse specialists …(N  = 3) to include the perspectives of all key players in this decision-making process. Data were analyzed by two researchers using a qualitative thematic analysis approach. Results: Four themes representing current experiences with the decision-making process were identified: 1) information and information needs, 2) factors influencing treatment choice and individual decision strategies, 3) decision-making roles, and 4) barriers and facilitators to shared decision-making (SDM). Patient preferences were taken into account, however patients were not always provided with adequate information. The professional’s expertise influenced the decision-making process in both positive and negative ways. Although professionals and patients considered SDM essential for the decision of an advanced treatment, they mentioned several barriers for the implementation in current practice. Conclusions: In this study we found several factors explaining why in current practice, evidence-based decision-making in advanced PD is not optimal. An important first step would be to develop objective information on all treatment options. Show more

Keywords: Parkinson’s disease, evidence-based medicine, shared decision-making, qualitative research

DOI: 10.3233/JPD-160816

Citation: Journal of Parkinson's Disease, vol. 6, no. 3, pp. 533-543, 2016

Authors: Gu, Quanquan | Zhang, Huan | Xuan, Min | Luo, Wei | Huang, Peiyu | Xia, Shunren | Zhang, Minming

Article Type: Research Article

Abstract: Background: Patients with the postural instability and gait difficulty subtype (PIGD) of Parkinson’s disease (PD) are a refractory challenge in clinical practice. Despite previous attempts that have been made at studying subtype-specific brain alterations across PD population, conclusive neuroimaging biomarkers on patients with the PIGD subtype are still lacking. Machine learning-based classifications are a promising tool for differential diagnosis that effectively integrate complex and multivariate data. Objective: Our present study aimed to introduce the machine learning-based automatic classification for the first time to distinguish patients with the PIGD subtype from those with the non-PIGD subtype of PD …at the individual level. Methods: Fifty-two PD patients and forty-five normal controls (NCs) were recruited and underwent multi-modal MRI scans including a set of resting-state functional, 3D T1-weighted and diffusion tensor imaging sequences. By comparing the PD patients with the NCs, features that were not conducive to the subtype-specific classification were ruled out from massive brain features. We applied a support vector machine classifier with the recursive feature elimination method to multi-modal MRI data for selecting features with the best discriminating power, and evaluated the proposed classifier with the leave-one-out cross-validation. Results: Using this classifier, we obtained satisfactory diagnostic rates (accuracy = 92.31%, specificity = 96.97%, sensitivity = 84.21% and AUCmax  = 0.9585). The diagnostic agreement evaluated by the Kappa test showed an almost perfect agreement with the existing clinical categorization (Kappa value = 0.83). Conclusions: With these favorable results, our findings suggested the machine learning-based classification as an alternative technique to classifying clinical subtypes in PD. Show more

Keywords: Parkinson’s disease, functional neuroimaging, diagnosis, machine learning, support vector machines

DOI: 10.3233/JPD-150729

Citation: Journal of Parkinson's Disease, vol. 6, no. 3, pp. 545-556, 2016

Authors: Sterling, N.W. | Lewis, M.M. | Du, G. | Huang, X.

Article Type: Review Article

Abstract: Parkinson’s disease (PD) is a progressive age-related neurodegenerative disorder. Although the pathological hallmark of PD is dopaminergic cell death in the substantia nigra pars compacta, widespread neurodegenerative changes occur throughout the brain as disease progresses. Postmortem studies, for example, have demonstrated the presence of Lewy pathology, apoptosis, and loss of neurotransmitters and interneurons in both cortical and subcortical regions of PD patients. Many in vivo structural imaging studies have attempted to gauge PD-related pathology, particularly in gray matter, with the hope of identifying an imaging biomarker. Reports of brain atrophy in PD, however, have been inconsistent, most likely due …to differences in the studied populations (i.e. different disease stages and/or clinical subtypes), experimental designs (i.e. cross-sectional vs. longitudinal), and image analysis methodologies (i.e. automatic vs. manual segmentation). This review attempts to summarize the current state of gray matter structural imaging research in PD in relationship to disease progression, reconciling some of the differences in reported results, and to identify challenges and future avenues. Show more

Keywords: Parkinson’s disease, MRI, structure, review

DOI: 10.3233/JPD-160824

Citation: Journal of Parkinson's Disease, vol. 6, no. 3, pp. 557-567, 2016