Severe Parkinson's Disease Research Articles

Construct validity of the 9-Hole Peg Test and Purdue Pegboard Test in people with mild to moderately severe Parkinson’s disease

ObjectivesTo evaluate the construct validity of two dexterity measures, the 9-Hole Peg Test (9HPT) and Purdue Pegboard Test (PPT) in people with Parkinson’s disease (PD). DesignCross-sectional observational study. SettingTesting was conducted at the university or in participants’ homes. ParticipantsThirty community dwelling people with mild to moderately severe PD and no major upper limb comorbidities or cognitive impairments. InterventionsPegboard tests were administered in the ‘on’ and ‘end-of-dose’ phases of participants’ PD medication cycles. Participants rated hand function with two self-report questionnaires – the Manual Ability Measure-36 (MAM-36) and a subset of upper limb items from the MDS-UPDRS. To explore construct validity, we compared ‘on’ phase pegboard scores with normative values for unimpaired men and women and investigated relationships between pegboard scores and hand function questionnaires. ResultsIn the ‘on’ phase, pegboard scores were poorer than normative values. Differences in individual subtest scores ranged between 10 and 41%. Correlations between self-reported hand function and pegboard scores were weak to moderately strong in the ‘on’ phase (r=0.21–0.51), and weak at ‘end-of-dose’ (r=0.13–0.22). Higher correlation coefficients were observed between hand function and PPT subtest scores than with hand function and 9HPT scores. Most participants reported difficulty with daily hand tasks. ConclusionsWe found evidence for construct validity supporting the use of the 9HPT and PPT to evaluate people with mild to moderately severe PD when ‘on’, but not at the ‘end-of-dose’. Results also suggest that the PPT may be more sensitive to PD-related changes in dexterity than the 9HPT.

Epidural Spinal Cord Stimulation Improves Motor Function in Rats With Chemically Induced Parkinsonism

Background. Epidural stimulation of the spinal cord can reorganize and change the excitability of the neural circuitry to facilitate stepping in rats with a complete spinal cord injury. Parkinson’s disease results in abnormal supraspinal signals from the brain to the spinal cord that affect the functional capacity of the spinal networks. Objective. The objective was to determine whether epidural stimulation (electrical enabling motor control, eEmc) of the lumbosacral spinal cord can reorganize the spinal networks to facilitate hindlimb stepping of rats with parkinsonism. Methods. A unilateral 6-OHDA (6-hydroxydopamine) lesion of the nigrostriatal pathway was used to induce parkinsonism. Sham rats (N = 4) were injected in the same region with 0.1% of ascorbic acid. Stimulation electrodes were implanted epidurally at the L2 and S1 (N = 5) or L2 (N = 5) spinal levels. Results. The 6-OHDA rats showed severe parkinsonism in cylinder and adjusting step tests and were unable to initiate stepping when placed in a running wheel and dragged their toes on the affected side during treadmill stepping. During eEmc, the 6-OHDA rats initiated stepping in the running wheel and demonstrated improved stepping quality. Conclusion. Stepping was facilitated in rats with parkinsonism with spinal cord stimulation. The underlying assumption is that the normal functional capacity of spinal networks is affected by supraspinal pathology associated with Parkinson’s disease, which either generates insufficient or abnormal descending input to spinal networks and that eEmc can appropriately modulate spinal and supraspinal networks to improve the motor deficits.

Faecal Transplantation, Pro- and Prebiotics in Parkinson's Disease; Hope or Hype?

Faecal microbiome transplantation (FMT) is an attractive technique, because the administration is relatively simple and in general has a mild adverse effect pattern. Moreover, FMT consists of a broad mixture, which could be beneficial, because at this moment it is not known what type of changes in the microbiome are needed. However, except from a few cases no clinical data in Parkinson’s disease (PD) is available yet. There is some indication that FMT might be beneficial in severe constipated PD patients, but the clinical data to support this are very scarce. So, actually there are no good data in the public domain to support FMT at this moment in PD patients. FMT at this moment is a black box with too many unanswered questions, also with respect to safety concerns. Only the administration of species of Lactobacillus and Bifidobacterium over a time period of four to twelve weeks has repeatedly proven to be effective in treating constipation in PD. Also, no solid clinical data are available about the possible effects of probiotic treatment on motor symptoms or progression of PD. Therefore, also probiotic treatments in PD should wait until better clinical data become available, in order to select the right target populations and to have good estimates of the clinical effects to be expected.

Apomorphine induced immune hemolytic anemia

Drug‐induced immune hemolytic anemia (DIIHA) is not a frequent complication yet has threatening consequences. Managing patients with parkinsonism, L-Dopa was first described as a drug which directly cause DIHA. Very few confirmed cases have been reported for the same adverse effect of other dopaminergic drugs such as apomorphine and cabergoline. Hereby, We Describe a patient with severe parkinsonism for whom Apomorphine was started as the last choice since he was resistant to high dose L-Dopa. He developed pallor and jaundice and further work up revealed DIHA at very early stages of administration of the drug at Intensive Care Unit. The drug was withdrawn for the prevention of serious adverse effects. Strong clinical suspicion is required to detect this rare complication. proper immunohematological test and prompt management is warranted

The Association of Iron and the Pathologies of Parkinson's Diseases in MPTP/MPP+-Induced Neuronal Degeneration in Non-human Primates and in Cell Culture.

Despite much efforts in the last few decades, the mechanism of degeneration of dopamine (DA) neurons in the substantia nigra (SN) in Parkinson’s disease (PD) remains unclear. This represents a major knowledge gap in idiopathic and genetic forms of PD. Among various possible key factors postulated, iron metabolism has been widely suggested to be involved with fueling oxidative stress, a known factor in the pathogenesis of PD. However, the correlation between iron and DA neuron loss, specifically in the SN, has not been described in experimental animal models with great detail, with most studies utilizing rodents and, rarely, non-human primates. In the present study, aiming to gain further evidence of a pathological role of iron in PD, we have examined the correlation of iron with DA neuron loss in a non-human primate model of PD induced by MPTP. We report a significant iron accumulation accompanied by both DA degeneration in the SN and motor deficits in the monkey that displayed the most severe PD pathology and behavioral deficits. The other two monkeys subjected to MPTP displayed less severe PD pathologies and motor deficits, however, their SN iron levels were significantly lower than controls. These findings suggest that high iron may indicate and contribute to heightened MPP+-induced PD pathology in late or severe stages of PD, while depressed levels of iron may signal an early stage of disease. Similarly, using a cell culture preparation, we have found that high doses of ferric ammonium citrate (FAC), a factor known to enhance iron accumulation, increased MPP+-induced cell death in U251 and SH-SY5Y cells, and even in control cells. However, at low dose FAC restored or increased the viability of U251 and SH-SY5Y cells in the absence or presence of MPP+. These observations imply that high levels of iron likely contribute to or heighten MPP+ toxicity in the later stages of PD. While we report reduced iron levels in the earlier stages of MPTP induced PD, the significance of these changes remains to be determined.

Severe parkinsonism under treatment with antipsychotic drugs.

The aim of the study was to assess rates of severe parkinsonism related to different antipsychotic drugs (APDs) using data from an observational pharmacovigilance programme in German-speaking countries-Arzneimittelsicherheit in der Psychiatrie (AMSP). Data on APD utilization and reports of severe APD-induced parkinsonism were collected in 99 psychiatric hospitals in Austria, Germany and Switzerland during the period 2001-2016. Of 340,099 patients under surveillance, 245,958 patients were treated with APDs for the main indications of schizophrenic disorders, depression, mania and organic mental disorders. A total of 200 events of severe APD-induced parkinsonism were identified (0.08%). First-generation low-potency APDs were significantly less often implicated (0.02%) than second-generation APDs (0.07%) and first-generation high-potency APDs (0.16%). Among the second-generation APDs, amisulpride and risperidone ranked highest. The phenothiazines were associated with significantly lower rates of severe parkinsonism (0.02%) than those of the butyrophenones (0.11%) and thioxanthenes (0.12%). In 71 cases (35.5%), more than 1 drug was considered responsible for the induction of severe parkinsonism. In 44 patients (22.0%), the symptoms were extremely severe, leading to complete immobility and/or massive complications such as pneumonia and severe injuries due to falls. Higher age (> 60years) was associated with significantly higher rates of severe parkinsonism, as were the diagnoses of schizophrenic disorder or mania. The large number of patients included in the present survey allows for the comparison of severe parkinsonism rates related to different APD classes and single APDs. The first-generation low-potency APDs had significantly reduced risk of severe parkinsonism compared not only to high potency but also to second-generation APDs.

Postural Abnormalities in Parkinson's Disease: An Epidemiological and Clinical Multicenter Study.

The overall frequency of postural abnormalities (PA) in Parkinson's disease (PD) is unknown. We evaluated the overall prevalence of PA and assessed the association with demographic and clinical variables. For this multicenter, cross-sectional study, consecutive PD outpatients attending 7 tertiary Italian centers were enrolled. Patients were evaluated and compared for the presence of isolated PA such as camptocormia, Pisa syndrome, and anterocollis and for combined forms (ie, camptocormia + Pisa syndrome) together with demographic and clinical variables. Of the total 811 PD patients enrolled, 174 (21.5%; 95% confidence interval [CI], 18.6%-24.3%) presented PA, 144 of which had isolated PA and 30 had combined PA. The prevalence of camptocormia was 11.2% (95% CI, 9%-13.3%), Pisa syndrome 8% (95% CI, 6.2%-9.9%), and anterocollis 6.5% (95% CI, 4.9%-8.3%). Patients with PA were more often male and older with longer disease duration, more advanced disease stage, more severe PD symptoms, a bradykinetic/rigid phenotype, and poorer quality of life. They were initially treated with levodopa, and more likely to be treated with a combination of levodopa and dopamine agonist, took a higher daily levodopa equivalent daily dose, and had more comorbidities. Falls and back pain were more frequent in PD patients with PA than in those without PA. Multiple logistic regression models confirmed an association between PA and male gender, older age, Hoehn and Yahr stage, and total Unified Parkinson's Disease Rating Scale score. PA are frequent and disabling complications in PD, especially in the advanced disease stages.

Effects of utterance rate and length on the spatiotemporal index in Parkinson’s disease

Purpose: To characterise labial articulatory pattern variability using the spatiotemporal index (STI) in speakers with idiopathic Parkinson’s disease (PD) across different speaking rates and syllable-sentence conditions compared to age- and sex-matched healthy controls.Method: Ten speakers with mild–severe idiopathic PD and 10 controls produced “pa” and the Rainbow Passage at slow, typical and fast speech rates. Upper lip and lower lip kinematics were digitised during a motion capture system. Data were analysed using linear mixed modelling.Result: Regardless of the participant group, a high STI value was observed in the fast speech rate for the “pa” syllable condition, particularly for movements of the lower lip. As utterance rate increased, the control group showed the highest variability, followed by PD OFF and PD ON conditions. Syllable “pa” showed a greater STI value compared to both the first and second utterance of Rainbow Passage.Conclusion: PD manifests sufficient residual capacity to achieve near-normal motor compensation to preserve the consistency of lower lip movements during speech production. The lack of a significant difference in lip STI values between ON-OFF medication states suggests that dopaminergic treatment does not influence stability of speech for individuals with mild-moderate stage PD.

Quantitative analysis of macular retinal thickness and volume in patients with different degrees of Parkinson’s disease

Objective To observe the macular retinal thickness and volume in patients with different degrees of Parkinson's disease (PD). Methods Thirty eyes of 30 patients with primary PD and 20 eyes of 20 healthy subjects (control group) in Xuanwu Hospital of Capital Medical University from October 2016 to October 2017 were enrolled in this study. There were 17 males and 13 females, with the mean age of 63.2±6.4 years and disease course of 3.9±2.4 years. The patients were divided into mild to moderate PD group (15 eyes of 15 patients) and severe PD group (15 eyes of 15 patients). The macular area was automatically divided into 3 concentric circles by software, which were foveal area with a diameter of 1 mm (inner ring), middle ring of 1 to 3 mm, and outer ring of 3 to 6 mm. The middle and outer ring were divided into 4 quadrants by 2 radiations, respectively. The changes of retinal thickness and macular volume of the macular center and its surrounding quadrants were analyzed. SPSS 16.0 software was used for statistical analysis. One-way ANOVA were used to analyze all data. Results Compared with the control group, the retinal thickness and volume in macular center and each quadrant of the mild to moderate PD group and severe PD group were reduced. Compared with the mild to moderate PD group, the retinal thickness and volume in macular center and each quadrant of the severe PD group were reduced. The differences of retinal thickness and macular volume among 3 groups were significant(F=5.794, 5.221, 5.586, 5.302, 5.926, 5.319, 5.404, 5.261, 5.603; P=0.001, 0.007, 0.003, 0.005, 0.000, 0.004,0.004, 0.006, 0.002). In inner ring of the mild to moderate PD group and the severe PD group, the retinal thickness and macular volume in the upper and the nasal were the largest, the inferior was followed, and the temporal was the smallest. In outer ring of the mild to moderate PD group and the severe PD group, the retinal thickness and macular volume in the nasal was the largest, the upper was the second, the temporal and the inferior were the smallest. Conclusions The retinal thickness and volume of the macular central fovea and its surrounding areas in PD patients are significantly thinner than that in the healthy subjects. And with the increase of the severity of PD, the macular structure changes obviously, showing macular center and its surrounding macular degeneration thin, macular volume reduced. Key words: Parkinson disease; Macula lutea/pathology; Retina/physiopathology; Tomography, optical coherence/utilization

ParkinSong: A Controlled Trial of Singing-Based Therapy for Parkinson’s Disease

Background. Communication impairment is one of the most common symptoms of Parkinson’s disease (PD), significantly affecting quality of life. Singing shares many of the neural networks and structural mechanisms used during speech and, thus, has potential for therapeutic application to address speech disorders. Objective. To explore the effects of an interdisciplinary singing-based therapeutic intervention (ParkinSong) on voice and communication in people with PD. Methods. A controlled trial compared the effects of the ParkinSong intervention with an active control condition at 2 dosage levels (weekly vs monthly) over 3 months, on voice, speech, respiratory strength, and voice-related quality-of-life outcomes for 75 people living with PD. The interdisciplinary ParkinSong model comprised high-effort vocal and respiratory tasks, speech exercises, group singing, and social communication opportunities. Results. ParkinSong intervention participants demonstrated significant improvements in vocal intensity (P = .018), maximum expiratory pressure (P = .032), and voice-related quality of life (P = .043) in comparison to controls. Weekly ParkinSong participants increased vocal intensity more than monthly participants (P = .011). Vocal intensity declined in nontreatment control groups. No statistical differences between groups on maximum phonation length or maximum inspiratory pressure were observed at 3 months. Conclusions. ParkinSong is an engaging intervention with the potential to increase loudness and respiratory function in people with mild to moderately severe PD.

Management of Dysphagia in Patients with Parkinson's Disease and Related Disorders.

Various methods of rehabilitation for dysphagia have been suggested through the experience of treating stroke patients. Although most of these patients recover their swallowing function in a short period, dysphagia in Parkinson's disease (PD) and Parkinson-related disorder (PRD) degenerates with disease progression. Muscle rigidity and bradykinesia are recognized as causes of swallowing dysfunction, and it is difficult to easily apply the strategies for stroke to the rehabilitation of dysphagia in PD patients. Disease severity, weight loss, drooling, and dementia are important clinical predictors. Silent aspiration is a pathognomonic sign that may lead to aspiration pneumonia. Severe PD patients need routine video fluoroscopy or video endoscopy to adjust their food and liquid consistency. Patients with PRD experience rapid progression of swallowing dysfunction. Nutrition combined with nasogastric tube feeding or percutaneous endoscopic gastrostomy feeding should be considered owing to the increased risk of aspiration and difficulty administrating oral nutrition.

Feasible Classified Models for Parkinson Disease from 99mTc-TRODAT-1 SPECT Imaging.

The neuroimaging techniques such as dopaminergic imaging using Single Photon Emission Computed Tomography (SPECT) with 99mTc-TRODAT-1 have been employed to detect the stages of Parkinson’s disease (PD). In this retrospective study, a total of 202 99mTc-TRODAT-1 SPECT imaging were collected. All of the PD patient cases were separated into mild (HYS Stage 1 to Stage 3) and severe (HYS Stage 4 and Stage 5) PD, according to the Hoehn and Yahr Scale (HYS) standard. A three-dimensional method was used to estimate six features of activity distribution and striatal activity volume in the images. These features were skewness, kurtosis, Cyhelsky’s skewness coefficient, Pearson’s median skewness, dopamine transporter activity volume, and dopamine transporter activity maximum. Finally, the data were modeled using logistic regression (LR) and support vector machine (SVM) for PD classification. The results showed that SVM classifier method produced a higher accuracy than LR. The sensitivity, specificity, PPV, NPV, accuracy, and AUC with SVM method were 0.82, 1.00, 0.84, 0.67, 0.83, and 0.85, respectively. Additionally, the Kappa value was shown to reach 0.68. This claimed that the SVM-based model could provide further reference for PD stage classification in medical diagnosis. In the future, more healthy cases will be expected to clarify the false positive rate in this classification model.

Freezing of gait before the introduction of levodopa

Freezing of gait (FOG) occurs in over half of patients with advanced Parkinson's disease. It is characterised by sudden, brief episodes of inability to produce effective forward stepping that typically occur upon gait initiation or during turning while walking. FOG can be subdivided into three clinically distinguishable phenotypes. The two most common forms, which can be seen both when patients are ‘on’ or ‘off’ their dopaminergic medication, are shuffling forward with very small steps and trembling in place without effective forward motion. The third and most severe, but also least common, form of FOG is complete akinesia. FOG is associated with increased disease severity and with prolonged levodopa treatment (although the latter could also be explained by greater disease severity). FOG is generally responsive to dopaminergic medication, and episodes are therefore more frequent and of longer duration when dopaminergic medication has worn off. Paradoxically, our general impression is that FOG is nowadays more common than before the introduction of levodopa. In a brief report published in 2011, Pedro J Garcia-Ruiz also reached this conclusion, but he did not perform a systematic assessment of all resources. MPTP-induced parkinsonism: an historical case seriesIn 1982, seven young adults developed severe and irreversible parkinsonism shortly after they injected themselves with a new synthetic heroin.1 Sample analyses revealed that this synthetic heroin consisted of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP),2 a potent neurotoxin targeting neurons within the substantia nigra.3 Full-Text PDF Freezing of gait: a practical approach to managementFreezing of gait is a common and disabling symptom in patients with parkinsonism, characterised by sudden and brief episodes of inability to produce effective forward stepping. These episodes typically occur during gait initiation or turning. Treatment is important because freezing of gait is a major risk factor for falls in parkinsonism, and a source of disability to patients. Various treatment approaches exist, including pharmacological and surgical options, as well as physiotherapy and occupational therapy, but evidence is inconclusive for many approaches, and clear treatment protocols are not available. Full-Text PDF Freezing of gait and levodopaIn their Historical Insight, Peter Koehler and colleagues1 propose that freezing of gait (FOG) in patients with advanced Parkinson's disease is the result of chronic long-term levodopa use. Furthermore, they notice that, if FOG was present in the pre-levodopa era, it expressed itself as akinetic, not as the shuffling and trembling subtypes seen mostly nowadays. Therefore, they conclude that the high-frequency oscillatory features of FOG are probably induced by levodopa. Although we appreciate this thought-provoking hypothesis, we would like to present some observations that refute it. Full-Text PDF

Long-term outcomes of deep brain stimulation in severe Parkinson’s disease utilizing UPDRS III and modified Hoehn and Yahr as a severity scale

ObjectivesDeep brain stimulation (DBS) is the surgical treatment of choice for moderate to severe Parkinson’s Disease (PD). However, few studies have assessed its efficacy in severe PD as defined by the modified Hoehn and Yahr scale (HY). This study evaluates long-term and medication outcomes of DBS in severe PD. Patients and methodsWe retrospectively collected the data of 15 patients from 2008 to 2014 with severe PD treated with DBS. Retrospective assessment with the modified Hoehn and Yahr scale and motor subset of the Unified Parkinson’s Disease Rating Scale (UPDRS III) were used to objectively track severity and motor function improvement, respectively. Levodopa equivalence daily doses (LEDD), number of anti-PD medications and number of daily medication doses were used to measure improvements in medication burden. Data was evaluated using univariate analyses, one sample paired t-test, two sample paired t-test, and Wilcoxon signed-rank test. ResultsThe mean post-operative follow-up was 44.63 months, average age at diagnosis and the average age at time of DBS was 51.3 years and 61.5 years, respectively, and the time from diagnosis to treatment was 13.2 years. Significant decreases were seen in UPDRS III scores (pre-op = 44.533; post-op = 26.13; p = 0.0094), LEDD (pre-op = 1679.34 mg; post-op = 837.48 mg; p = 0.0049), and number of daily doses (pre-op = 21.266; post-op 12.2; p = 0.0046). No significant decrease was seen in the number of anti-PD medications (pre-op = 3.8; post-op = 3.2; p = 0.16). ConclusionFollowing DBS, severe PD patients demonstrated significant improvements in motor function and medication burden during long-term follow-up. We believe our results prove that DBS is efficacious in the management of severe PD, and that further research should follow to expand DBS criteria to include severe disease.

Comparative Effectiveness of mHealth-Supported Exercise Compared With Exercise Alone for People With Parkinson Disease: Randomized Controlled Pilot Study

Declining physical activity commonly occurs in people with Parkinson disease (PD) and contributes to reduced functional capacity and quality of life. The purpose of this study was to explore the preliminary effectiveness, safety, and acceptability of a mobile health (mHealth)-mediated exercise program designed to promote sustained physical activity in people with PD. This was a 12-month single-blind (assessor), pilot, comparative-effectiveness, randomized controlled study. An mHealth-mediated exercise program (walking with a pedometer plus engagement in planned exercise supported by a mobile health application) was compared over 1 year with an active control condition (walking with a pedometer and exercise only). There were 51 participants in a community setting with mild-to-moderately severe (Hoehn and Yahr stages 1-3) idiopathic PD. Daily steps and moderate-intensity minutes were measured using a step activity monitor for 1 week at baseline and again at 12 months. Secondary outcomes included the 6-Minute Walk Test, Parkinson Disease Questionnaire 39 mobility domain, safety, acceptability, and adherence. Both groups increased daily steps, moderate-intensity minutes, and 6-Minute Walk Test, with no statistically significant between-group differences observed. In the less active subgroup, changes in daily steps and moderate-intensity minutes were clinically meaningful. An improvement in the Parkinson Disease Questionnaire 39 mobility score favored mHealth in the overall comparison and was statistically and clinically meaningful in the less active subgroup. The limitation of the current study was the small sample size. Both groups improved physical activity compared with expected activity decline over 1 year. The addition of the mHealth app to the exercise intervention appeared to differentially benefit the more sedentary participants. Further study in a larger group of people with low activity at baseline is needed.

Cortical thinning across Parkinson's disease stages and clinical correlates

BackgroundImaging studies have revealed cortical thinning and subcortical atrophy occurring in Parkinson's disease (PD); however, the topographical distribution and clinical associations related to advancing stages of PD remains unclear. ObjectiveWe aimed to investigate the topographical distribution of cortical and subcortical morphometric changes, and their clinical associations, related to increasing disease severity. MethodsIn this cross-sectional imaging study, T1-weighted structural magnetic resonance imaging data for 80 non-demented PD patients and 30 age-matched healthy controls were analysed using FreeSurfer software suite to derive morphometric changes using whole-brain vertex-wise analysis, and surface-based (cortical) and volume-based (subcortical) parcellation maps. PD patients were divided into three groups of mild (n = 27), moderate (n = 27), and severe (n = 26) PD based disease duration and Hoehn and Yahr and Unified Parkinson's Disease Rating Scale Part-III motor severity scores. ResultsWhole-brain vertex-wise analysis revealed cortical thinning in the orbitofrontal cortex in early PD (P = .011), and in the superior frontal (P = .002), caudal middle frontal gyrus (P = .001) and inferior parietal cortex (P = .006) in moderate PD. Severe PD patients showed additional cortical thinning in temporal and occipital cortices (P < .005). Subcortical volume loss was detected in the thalamus (P = .012) and hippocampus (P = .032) in moderate PD, which extended to the caudate (P = .012), putamen (P = .042) and amygdala (P = .008) in severe PD. Increasing disease duration and motor severity scores, correlated with cortical thinning in frontal, temporal, parietal and occipital cortices, and subcortical volumetric loss in the thalamus, caudate, putamen, amygdala and hippocampus. Lower global cognitive status, measured with MMSE, correlated with cortical thinning in temporal, parietal, frontal and cingulate cortices, and with volumetric loss in the hippocampus (r = 0.31; P = .009); suggesting subclinical pathogenic changes occur prior to the onset of cognitive impairment. ConclusionIn conclusion, in more severe disease stages PD patients exhibit progressive cortical thinning and subcortical volume loss which could have relevance to the development of cognitive impairment.

Charcot spinal arthropathy presenting as adjacent segment disease after lumbar spinal fusion surgery in Parkinson’s disease: A case report

Charcot spinal arthropathy (CSA) is a rare spinal disorder presenting neuropathic osteoarthropathy of facet joints leading to progressive destruction. After L4-5 PLIF, a 63-year-old woman with Parkinson’s disease (PD) underwent L3-4 and L5-S1 PLIF for primary adjacent segment disease caused by degenerative change, which was found as facet joint osteophytes and a vacuum disc phenomenon with endplate sclerosis. However, her postural disorder from PD deteriorated, and strong opioid analgesics were administered for severe recurring low back pain. Anterior subluxation at L2-3 occurred because of destructive secondary adjacent segment disease, which was found as destruction of the endplate and the facet without degenerative change, and formation of paravertebral osteophytes and fluid collection in the intervertebral space. The appearance on imaging met that for neuroarthropathic change, which was previously reported as CSA. L2-3 PLIF following extension of posterior fusion to T10 was additionally performed, and the postoperative course was uneventful with symptomatic improvement. In this case, the important finding was in the different appearance of the disease between adjacent segments on imaging. It is possible that deterioration of PD and administration of the analgesics inhibited deep pain sensation, and concentration of mechanical stress in the proximal adjacent segment by the long lever arm because of extension of the fusion level resulted in neuroarthropathic change of the facets in the secondary adjacent segments. The pathophysiology of association of CSA and PD remains unknown. However, we recommend vigilance for destructive neuroarthropathic facet change as CSA after spinal surgery in patients with severe PD.

The transition between turning and sitting in patients with Parkinson's disease: A wearable device detects an unexpected sequence of events

BackgroundWhen older adults turn to sit, about 80% of the subjects complete the turn before starting to sit i.e., a distinct-strategy, while in about 20%, part of the turning and sitting take place concurrently, i.e., an overlapping-strategy. A prolonged duration of the separation between tasks in the distinct-strategy (D-interval) and a prolonged duration of the overlap interval in overlapping-strategy (O-interval) are related to worse motor symptoms and poorer cognition. In the present study, we evaluated what strategy is employed by patients with Parkinson’s disease (PD) when they transition from turning to sitting. Methods96 participants with PD performed turn to sit as part of the Timed Up and Go test, both with and without medications, while wearing a body-fixed sensor. We quantified the turn-to-sit transition and determined which strategy (distinct or overlapping) was employed. We then stratified the cases and used regression models adjusted for age, gender, height, and weight to examine the associations of the D-interval or O-interval with parkinsonian features and cognition. ResultsMost patients (66%) employed the overlapping-strategy, both off and on anti-parkinsonian medications. Longer O-intervals were associated with longer duration of PD, more severe PD motor symptoms, a higher postural-instability-gait-disturbance (PIGD) score, and worse freezing of gait. Longer D-intervals were not associated with disease duration or PD motor symptoms. Neither the D- nor O-intervals were related to cognitive function. Individuals who employed the overlapping-strategy had more severe postural instability (i.e., higher PIGD scores), as compared to those who used the distinct-strategy. SignificanceIn contrast to older adults without PD, most patients with PD utilize the overlapping strategy. Poorer postural and gait control are associated with the strategy choice and with the duration of concurrent performance of turning and sitting. Additional work is needed to further explicate the mechanisms underlying these strategies and their clinical implications.

Global, regional, and national burden of Parkinson's disease, 1990–2016: a systematic analysis for the Global Burden of Disease Study 2016

SummaryBackgroundNeurological disorders are now the leading source of disability globally, and ageing is increasing the burden of neurodegenerative disorders, including Parkinson's disease. We aimed to determine the global burden of Parkinson's disease between 1990 and 2016 to identify trends and to enable appropriate public health, medical, and scientific responses.MethodsThrough a systematic analysis of epidemiological studies, we estimated global, regional, and country-specific prevalence and years of life lived with disability for Parkinson's disease from 1990 to 2016. We estimated the proportion of mild, moderate, and severe Parkinson's disease on the basis of studies that used the Hoehn and Yahr scale and assigned disability weights to each level. We jointly modelled prevalence and excess mortality risk in a natural history model to derive estimates of deaths due to Parkinson's disease. Death counts were multiplied by values from the Global Burden of Disease study's standard life expectancy to compute years of life lost. Disability-adjusted life-years (DALYs) were computed as the sum of years lived with disability and years of life lost. We also analysed results based on the Socio-demographic Index, a compound measure of income per capita, education, and fertility.FindingsIn 2016, 6·1 million (95% uncertainty interval [UI] 5·0–7·3) individuals had Parkinson's disease globally, compared with 2·5 million (2·0–3·0) in 1990. This increase was not solely due to increasing numbers of older people, because age-standardised prevalence rates increased by 21·7% (95% UI 18·1–25·3) over the same period (compared with an increase of 74·3%, 95% UI 69·2–79·6, for crude prevalence rates). Parkinson's disease caused 3·2 million (95% UI 2·6–4·0) DALYs and 211 296 deaths (95% UI 167 771–265 160) in 2016. The male-to-female ratios of age-standardised prevalence rates were similar in 2016 (1·40, 95% UI 1·36–1·43) and 1990 (1·37, 1·34–1·40). From 1990 to 2016, age-standardised prevalence, DALY rates, and death rates increased for all global burden of disease regions except for southern Latin America, eastern Europe, and Oceania. In addition, age-standardised DALY rates generally increased across the Socio-demographic Index.InterpretationOver the past generation, the global burden of Parkinson's disease has more than doubled as a result of increasing numbers of older people, with potential contributions from longer disease duration and environmental factors. Demographic and potentially other factors are poised to increase the future burden of Parkinson's disease substantially.FundingBill & Melinda Gates Foundation.

Can aripiprazole cause Parkinsonism? Two cases with aripiprazole-induced Parkinsonism

Can aripiprazole cause Parkinsonism? Two cases with aripiprazole-induced Parkinsonism The association between aripiprazole and Parkinsonism has not been well demonstrated. Our patients’ present complaints started several weeks after the initiation of aripiprazole only. We present two female cases who developed extrapyramidal syndrome (EPS) after administration of aripiprazole. Neither of them had ever used any antipsychotic agent except aripiprazole and the EPS disappeared within less than a week after administration of an anticholinergic drug. The severe Parkinsonism in our cases is associated with aripiprazole. Our report emphasizes the need for careful monitoring for the development of Parkinsonian features in patients treated with aripiprazole.