Journal of Parkinson's Disease - Volume 6, issue 4

Authors: Isaacson, Stuart | Shill, Holly A. | Vernino, Steven | Ziemann, Adam | Rowse, Gerald J.

Article Type: Research Article

Abstract: Background: Neurogenic orthostatic hypotension (nOH) is associated with insufficient norepinephrine release in response to postural change. Objective: The objective of this study was to evaluate the long-term safety and durability of efficacy of the norepinephrine precursor droxidopa in patients with symptomatic nOH. Methods: This multinational study consisted of 3 sequential phases: a 3-month open-label droxidopa treatment phase followed by a 2-week double-blind, placebo-controlled withdrawal phase, and a 9-month open-label extension phase in which all patients received droxidopa. Patients were adults diagnosed with symptomatic nOH associated with Parkinson’s disease, multiple system atrophy, pure autonomic failure, dopamine …β-hydroxylase deficiency, or nondiabetic autonomic neuropathy. Efficacy was evaluated using patient- and investigator-reported questionnaire responses and the orthostatic standing test. Safety was assessed through adverse event (AE) reports and vital signs. Results: A total of 102 patients received treatment with droxidopa. Initial improvements from baseline in patient-reported nOH symptom severity and impact on daily activities, evaluated using the Orthostatic Hypotension Questionnaire, exceeded 50% and were maintained throughout the 12-month study. Decreased nOH severity was also reflected in clinician and patient ratings on the Clinical Global Impression questionnaire. Standing systolic and diastolic blood pressures were increased from baseline throughout the study with droxidopa treatment. The most frequently reported AEs were falls, urinary tract infection, and headache. There was a low incidence (≤2%) of cardiac AEs (eg, first-degree atrioventricular block, supraventricular extrasystoles). Conclusions: Long-term, open-label treatment with droxidopa for up to 12 months was generally well tolerated and provided durable improvements in nOH signs and symptoms. Show more

Keywords: Autonomic nervous system, droxidopa, hypotension, orthostatic, Parkinson disease

DOI: 10.3233/JPD-160860

Citation: Journal of Parkinson's Disease, vol. 6, no. 4, pp. 751-759, 2016

Authors: Beach, Thomas G. | Corbillé, Anne-Gaëlle | Letournel, Franck | Kordower, Jeffrey H. | Kremer, Thomas | Munoz, David G. | Intorcia, Anthony | Hentz, Joseph | Adler, Charles H. | Sue, Lucia I. | Walker, Jessica | Serrano, Geidy | Derkinderen, Pascal

Article Type: Research Article

Abstract: Background: Conflicting results from studies of Lewy-type α−synucleinopathy (LTS) in colonic biopsies of subjects with Parkinson’s disease (PD) prompted a two-part multicenter assessment. The first assessment, now published (Acta Neuropathol Commun 4 : 35, 2016), examined archived colonic biopsies and found that none of the tested methods was adequately sensitive or specific. Objective: As the amount of nervous tissue in typical colonic biopsies may be insufficient, and the clinical diagnosis of PD not completely accurate, the objective of the current study was to use instead full-thickness sections of sigmoid colon from autopsy-proven PD and normal subjects. Methods: …Seven different immunohistochemical (IHC) methods were used, employing five different primary antibodies and four different combinations of epitope exposure and signal development protocols. Specific staining was defined as being restricted to morphological features consistent with neuronal elements. Stained slides from each subject were independently categorized as being positive or negative for LTS, and their density semi-quantitatively graded, by four raters blinded to diagnosis. Results: Agreement and mean diagnostic performance varied markedly between raters. With the two most accurate raters, 5 methods achieved diagnostic accuracies of 70% or greater; one method had 100% accuracy and 100% inter-rater agreement. The submucosa had the highest prevalence of pathological LTS staining, followed by the muscularis and mucosa. Conclusions: The major conclusion of this study is that, when sufficient submucosa and LTS is present, and when specific staining is defined as being consistent with neuronal morphology, adequately-trained raters may reliably distinguish PD colon from control using suitable IHC methods. Show more

Keywords: Lewy body, gastrointestinal tract, diagnosis, pathology, biopsy, enteric nervous system

DOI: 10.3233/JPD-160888

Citation: Journal of Parkinson's Disease, vol. 6, no. 4, pp. 761-770, 2016

Authors: Oh, Yoon-Sang | Choi, Ji Ho | Kwon, Do-Young

Article Type: Research Article

Abstract: Background: Scans without evidence of dopaminergic deficit (SWEDD), a heterogeneous disorder, refers to patients with normal dopamine transporter scan presumed to have Parkinson’s disease (PD). Although clinically hard to discriminate, it is important to differentiate SWEDD from PD in the early stage of disease in practice. Olfactory dysfunction is a sensitive biomarker of neurodegeneration. A considerable number of SWEDD patients show abnormal olfaction. We investigated the olfaction and non-motor symptoms in SWEDD, PD, and healthy controls. A subgroup analysis of SWEDD by olfactory function was also conducted. Methods: This study enrolled 40 SWEDD, 28 PD, and 26 …healthy controls. The Korean version of Sniffin’s stick test II (KVSS II) and the Korean version of non-motor symptoms scale for PD (K-NMSS) were used to evaluate olfaction and non-motor symptoms. Patients with SWEDD were categorized into normal olfaction (SWEDD-N) and olfactory dysfunction (SWEDD-D) subgroups. Results: Overall KVSS II scores of SWEDD group was distinctive when compared to those of PD or controls. K-NMSS scores were increased in PD compared to those in SWEDD or controls. In subgroup analysis, KVSS II scores in SWEDD-D were similar to those in PD. K-NMSS scores in SWEDD-D were also significantly higher than those in SWEDD-N but lower than those in PD. Conclusions: Olfactory dysfunction could be a biomarker to differentiate SWEDD from PD. Non-motor symptoms differed between the two SWEDD subgroups classified by olfaction. These findings suggest that the underlying pathophysiology of SWEDD with normal olfaction and olfactory dysfunction might be different. Show more

Keywords: SWEDD, Parkinson’s disease, olfaction, non-motor symptoms

DOI: 10.3233/JPD-160874

Citation: Journal of Parkinson's Disease, vol. 6, no. 4, pp. 771-778, 2016

Authors: Rabel, Constance | Le Goff, Floriane | Lefaucheur, Romain | Ozel, Gulden | Fetter, Damien | Rouillé, Audrey | Maltête, David

Article Type: Research Article

Abstract: Background: Previous studies found a poor association between parkinsonian patient’s reported subjective improvement after commencing dopaminergic treatment and improvements in objective measures of motor impairment by clinician. Objective: To compare PD patient’s subjective perceived motor improvement after acute levodopa challenge test with objective motor improvement assessed by the clinician using the UPDRS part III. To analyze clinical characteristics, i.e. age, disease duration, cognitive performance or severity of axial features, that may have influenced patient’s perception. Methods: Fifty-seven consecutive PD patients (23 women, 34 men; mean age, 63.4±7.7 years) (Hoehn and Yahr off score, 2.5±0.7; mean …disease duration, 11.4±4.1 years) completed the acute levodopa challenge. The percentage of improvement in motor disability, i.e. objective motor improvement, was determined with respect to the off -drug condition. Results: Bland & Altman visual analysis reveals a high degree of correlation between objective and subjective perceived motor improvement. Both the axial sub-scores in the off- and on- state (respectively, P  = 0.006 and P  = 0.024) and the presence of peak-dose dyskinesia (P  = 0.043) significantly influence the difference between objective and subjective perceived motor improvement. Conclusions: This is the first study reporting on how PD patients assessed their motor improvement after acute levodopa challenge. These findings suggest a strong correlation between objective motor improvement assessed by the clinician using the UPDRS part III and subjective perceived motor improvement reported by the patient. Show more

Keywords: Parkinson’s disease, subjective perception, motor improvement, acute levodopa challenge

DOI: 10.3233/JPD-160906

Citation: Journal of Parkinson's Disease, vol. 6, no. 4, pp. 779-785, 2016

Authors: Fernández-Pajarín, Gustavo | Sesar, Ángel | Ares, Begoña | Castro, Alfonso

Article Type: Research Article

Abstract: Background: There are not many data about the beneficial effect of nocturnal continuous subcutaneous apomorphine infusion (NCSAI) over sleep disturbances in advanced Parkinson’s disease (PD). Objective: Evaluate the effect of the NCSAI in sleeping problems and insomnia due to nocturnal hypokinesia inadvanced PD. Methods: We assessed 17 advanced PD patients with several sleep disturbances measured by SCOPA-SLEEP and PDSS scales. All the patients were on apomorphine infusion during daytime. This therapy was extended to nighttime. We evaluated the patients before the onset and after six weeks with NCSAI. Results: NCSAI allowed highly significant improvements in SCOPA-SLEEP …and PDSS scales (p <0.0001), and daytime somnolence. NCSAI was well tolerated with no major adverse effects were noticed. Conclusion: This study shows and confirms the efficacy of NCSAI on the sleep disturbances related to advanced PD. We provide an easy protocol to start this therapy. Show more

Keywords: Apomorphine infusion, advanced Parkinson’s disease, sleep disturbances, nocturnal hypokinesia

DOI: 10.3233/JPD-160886

Citation: Journal of Parkinson's Disease, vol. 6, no. 4, pp. 787-792, 2016

Authors: Mendes, Alexandre | Gonçalves, Alexandra | Vila-Chã, Nuno | Calejo, Margarida | Moreira, Inês | Fernandes, Joana | Damásio, Joana | Teixeira-Pinto, Armando | Krack, Paul | Lima, António Bastos | Cavaco, Sara

Article Type: Research Article

Abstract: Background: The rate of Parkinson’s disease (PD) progression varies widely between patients. Current knowledge does not allow to accurately predict the evolution of symptoms in a given individual over time. Objectives: To develop regression-based models of PD progression and to explore its predictive value in a three-year follow-up. Methods: At baseline, 300 consecutive PD patients were assessed using the Unified Parkinson’s Disease Rating Scale (UPDRS) - subscales II and III, Hoehn & Yahr (H&Y) and Schwab and England Independence Scale (S&E); and the Freezing of Gait Questionnaire (FOG-Q). UPDRS-III and H&Y were applied in OFF …and ON medication conditions. An axial index was derived from the UPDRS-III. Based on multiple linear regression coefficients, algorithms were developed to adjust test scores to the characteristics of each individual. Sixty-eight patients were reevaluated three years later. Results: In the construction of the models, disease duration, age ≥70, age at disease onset ≥55, tremor as the first symptom alone, and medication description explained between 35% (UPDRS-III in ON) and 57% (axial index in ON) of the variance of test scores. The predictive r2 of the models in a 10-fold cross-validation ranged between 33% (UPDRS-III in ON) and 55% (axial index in ON and S&E in OFF). All measures, except UPDRS-III OFF, H&Y ON, and S&E ON, had moderate/good absolute agreement (intraclass correlation coefficient between 0.60 and 0.72) between baseline and follow-up. Conclusions: A cross-sectional assessment of a PD population allowed the development of models of disease progression, whose predictive value was validated on a three-year longitudinal study. Show more

Keywords: Parkinson disease, disease progression, statistical models, validity of results

DOI: 10.3233/JPD-160877

Citation: Journal of Parkinson's Disease, vol. 6, no. 4, pp. 793-804, 2016

Authors: Hommel, ALAJ | Faber, MJ | Weerkamp, NJ | van Dijk, JG | Bloem, BR | Koopmans, RT

Article Type: Research Article

Abstract: Background: Orthostatic hypotension (OH) in Parkinson’s disease (PD) is a common non-motor sign that can be hard to recognize and treat. OH prevalence and treatment in institutionalized PD-patients remains unknown. Objective: The aim of this study was to explore the prevalence and prescribed treatments of OH in institutionalized patients with PD. Method: A cross-sectional study of nursing homes in the south-east of the Netherlands identified 64 residents with PD (inclusion criteria: MMSE >18). Assessments included blood pressure measurement, both supine and in the upright position (after 1 minute and after 3 minutes of standing), and …2 questions on cardiovascular items including falls of the validated Non-Motor Symptom Scale (NMSS). OH was defined according to the consensus guidelines. OH was considered as ‘probably symptomatic’ if patients had a concomitant frequency score >1 on the selected NMSS items, and ‘probably asymptomatic’ for a frequency score of 0. If OH was not present, but patients had a frequency score >1, OH was considered as ‘possibly symptomatic’. Results: The prevalence of OH was 51.6%, almost equally divided into probably symptomatic and probably asymptomatic cases. Another 20.6% had possibly symptomatic OH. Importantly, only two patients with symptomatic OH had an OH diagnosis noted in their medical records. Five received domperidone, one received fludrocortison and none received midodrine. Conclusion: One half of institutionalized PD patients had OH, of whom half were probably symptomatic. OH was rarely noted in the medical records, suggesting underdiagnosis. Finally, OH was rarely treated, suggesting undertreatment. Show more

Keywords: Parkinson’s disease, nursing home, long-term care, orthostatic hypotension, orthostatic intolerance

DOI: 10.3233/JPD-160853

Citation: Journal of Parkinson's Disease, vol. 6, no. 4, pp. 805-810, 2016

Authors: Tanaka, Yasuhiro | Tsuboi, Takashi | Watanabe, Hirohisa | Kajita, Yasukazu | Nakatsubo, Daisuke | Fujimoto, Yasushi | Ohdake, Reiko | Ito, Mizuki | Atsuta, Naoki | Yamamoto, Masahiko | Wakabayashi, Toshihiko | Katsuno, Masahisa | Sobue, Gen

Article Type: Research Article

Abstract: Background: Voice and speech disorders are one of the most important issues after subthalamic nucleus deep brain stimulation (STN-DBS) in Parkinson’s disease (PD) patients. However, articulation features in this patient population remain unclear. Objective: We studied the articulation features of PD patients with STN-DBS. Methods: Participants were 56 PD patients treated with STN-DBS (STN-DBS group) and 41 patients treated only with medical therapy (medical-therapy-alone group). Articulation function was evaluated with acoustic and auditory-perceptual analyses. The vowel space area (VSA) was calculated using the formant frequency data of three vowels (/a/, /i/, and /u/) from sustained …phonation task. The VSA reportedly reflects the distance of mouth/jaw and tongue movements during speech and phonation. Correlations between acoustic and auditory-perceptual measurements were also assessed. Results: The VSA did not significantly differ between the medical-therapy-alone group and the STN-DBS group in the off-stimulation condition. In the STN-DBS group, the VSA was larger in the on-stimulation condition than in the off-stimulation condition. However, individual analysis showed the VSA changes after stopping stimulation were heterogeneous. In total, 89.8% of the STN-DBS group showed a large VSA size in the on- than in the off-stimulation condition. In contrast, the VSA of the remaining patients in that group was smaller in the on- than the off-stimulation condition. Conclusions: STN-DBS may resolve hypokinesia of the articulation structures, including the mouth/jaw and tongue, and improve maximal vowel articulation. However, in the on-stimulation condition, the VSA was not significantly correlated with speech intelligibility. This may be because STN-DBS potentially affects other speech processes such as voice and/or respiratory process. Show more

Keywords: Parkinson’s disease, deep brain stimulation, speech, dysarthria, speech disorder, acoustic analysis, articulation, speech intelligibility, formant analysis

DOI: 10.3233/JPD-160838

Citation: Journal of Parkinson's Disease, vol. 6, no. 4, pp. 811-819, 2016

Authors: Alzahrani, Hamad | Antonini, Angelo | Venneri, Annalena

Article Type: Research Article

Abstract: Background: Apathy is one of the most common neuropsychiatric symptoms in Parkinson’s disease (PD). Few studies have investigated the cognitive and neuroanatomical correlates of apathy in PD, and those which have done so have not controlled for the presence of other neuropsychiatric comorbidities. Objective: To explore the cognitive and neuroanatomical correlates of apathy in PD at a mild disease stage. Methods: Sixty-five PD patients and 24 healthy controls participated in this study. Patients underwent extensive neuropsychological screening, neuropsychiatric assessment using the Neuropsychiatric Inventory, structural MRI scanning, and neurological examination. Voxel-based independent t -test analyses were …used to assess the differences in grey and white matter volumes between the sample groups with/without apathy/neuropsychiatric symptoms. Results: Patients with apathy had lower grey matter volume in several brain areas including the left insula, left inferior/middle/medial frontal gyrus, right anterior cingulate, and the left superior temporal gyrus. Significant impairments were found in tests assessing executive functions, and a trend-level significant difference was observed in long term memory tests in patients with apathy, when compared with patients without apathy. Conclusions: Apathy was associated with greater levels of atrophy in the frontal and temporal cortex, and anterior cingulate, as well as overall lower level of cognitive performance, particularly in executive function and memory skills. Apathy appears to be associated with cognitive impairments in PD, therefore, treatment of this symptom might mitigate its effects on cognitive performance in this clinical population. Show more

Keywords: Magnetic resonance imaging, executive function, neuropsychiatry, cognitive impairments

DOI: 10.3233/JPD-160809

Citation: Journal of Parkinson's Disease, vol. 6, no. 4, pp. 821-832, 2016

Authors: Nero, Håkan | Benka Wallén, Martin | Franzén, Erika | Conradsson, David | Ståhle, Agneta | Hagströmer, Maria

Article Type: Research Article

Abstract: Background: The desirable effects of physical activity in individuals with Parkinson’s disease are well-known, although according to results from previous studies factors associated with objectively assessed physical activity are not fully investigated. Objective: To investigate demographic, disease-related and mobility-related factors that associate with objectively measured physical activity, in a sample of older adults with mild to moderate Parkinson’s disease. Methods: Demographic, disease-related and mobility-related factors were gathered by interview from a total of 91 older adults with Parkinson’s disease, followed by an evaluation of balance control using the Mini-BESTest. After initial testing, participants wore a …tri-axial accelerometer during a week of free-living. Correlation analysis and multiple linear regression was used to investigate factors associated with total PA, represented by total activity counts, and time in brisk walking. Results: Motor impairment, physical function, body mass index and dyskinesia contributed to the variance of total physical activity, explaining 34 % of the variance, while physical function and balance control were significant factors associated with brisk walking, explaining 22 %. Conclusions: This study identified factors that have not been shown to associate with objectively measured physical activity previously, such as dyskinesia, balance control and self-rated physical function. The findings also demonstrated that associated factors differ, depending on the activity behavior being investigated. However, other factors than those included in this study may also be of importance. Show more

Keywords: Accelerometry, dyskinesias, motor activity, postural control, walking

DOI: 10.3233/JPD-160826

Citation: Journal of Parkinson's Disease, vol. 6, no. 4, pp. 833-840, 2016

Article Type: Other

Citation: Journal of Parkinson's Disease, vol. 6, no. 4, pp. 841-849, 2016