BackgroundImpulse control disorders/other compulsive behaviours (‘ICD behaviours’) occur in Parkinson’s disease (PD), but prospective studies are scarce, and prevalence and clinical characteristics ...of patients are insufficiently defined.ObjectivesTo assess the presence of ICD behaviours over a 2-year period, and evaluate patients’ clinical characteristics.MethodsA prospective, non-interventional, multicentre study (ICARUS (Impulse Control disorders And the association of neuRopsychiatric symptoms, cognition and qUality of life in ParkinSon disease); SP0990) in treated Italian PD outpatients. Study visits: baseline, year 1, year 2. Surrogate primary variable: presence of ICD behaviours and five ICD subtypes assessed by modified Minnesota Impulsive Disorder Interview (mMIDI).Results1069/1095 (97.6%) patients comprised the Full Analysis Set. Point prevalence of ICD behaviours (mMIDI; primary analysis) was stable across visits: 28.6% (306/1069) at baseline, 29.3% (292/995) at year 1, 26.5% (245/925) at year 2. The most prevalent subtype was compulsive eating, followed by punding, compulsive sexual behaviour, gambling and buying disorder. Patients who were ICD positive at baseline were more likely to be male, younger, younger at PD onset, have longer disease duration, more severe non-motor symptoms (including mood and sexual function), depressive symptoms, sleep impairment and poorer PD-related quality of life. However, they did not differ from the ICD-negative patients in their severity of PD functional disability, motor performance and cognitive function.ConclusionsPrevalence of ICD behaviours was relatively stable across the 2-year observational period. ICD-positive patients had more severe depression, poorer sleep quality and reduced quality of life.
Alterations in blood-brain barrier permeability have been proposed to represent a relevant factor contributing to Parkinson's disease progression. However, few studies have addressed this issue in ...patients at different stages of disease.
Albumin was measured in cerebrospinal fluid and serum samples obtained from 73 non-demented subjects with idiopathic Parkinson's disease and 47 age-matched control subjects. The albumin ratio (AR) was calculated to assess blood-cerebrospinal fluid and blood-brain barrier function. The group of patients with Parkinson's disease included 46 subjects with Hoehn-Yahr staging between 1 and 2 and 27, with a score ranging from 2.5 to 4.
Statistically significant differences in albumin ratio were found between patients with advanced disease, and both early-stage and unaffected groups. Conversely, early-phase patients did not differ from healthy subjects. Additionally, dopaminergic treatment seems to exert a possible effect on AR values.
Our study demonstrates that possible dysfunction of the blood-cerebrospinal fluid barrier, blood-brain barrier, or both, characterize Parkinson's disease progression. The associations between clinical scores, treatments and biochemical findings suggest a progressive impairment of barrier integrity during the course of the disease.
The peduncolopontine nucleus modulates locomotor activity and dysfunction in this nucleus may be responsible for the gait and postural impairments seen in Parkinson's disease and other movement ...disorders. We report the first surgical exploration and implantation of deep brain stimulating electrodes of the peduncolopontine nucleus area in two Parkinson's disease patients to examine the safety and the potential benefit of chronic electrical stimulation at this site. Under local anesthesia, the peduncolopontine nucleus was approached from a coronal burr hole using a trajectory that was 78-80 degrees and 62-64 degrees on the coronal and sagittal planes. Microrecordings helped to identify neurons in peduncolopontine nucleus and the adjacent substantia nigra pars reticulata. Chronic deep brain stimulating electrodes were implanted within the peduncolopontine nucleus in a manner similar to that practiced with deep brain stimulating surgery at other targets. Peduncolopontine nucleus neurons were characterized by small and broad multiunits (230 muV, 2.5 ms, 14.6 Hz). Caudal to this area, neurons firing at higher frequency, approximately 70 Hz, characteristic of nigral neuronal discharges, were encountered, followed by 2 mm of cells similar to those recorded in the dorsal peduncolopontine nucleus area. After deep brain stimulating electrodes implantation, acute intraoperative stimulation (up to 3 V) was performed with two stimulation frequencies in each session. Stimulation at 80 Hz has little discernable effect. On the other hand, stimulation at 10 Hz fostered a subjective feeling of 'well-being' and a time-locked amelioration of the clinical scores. These findings demonstrate that the stereotactic approach of peduncolopontine nucleus is safe. The target may reliably be identified by microrecordings. Low-frequency stimulation may produce acute improvements in motor function.
Highlights • Sleep disturbances are frequently encountered non-motor symptoms in Parkinson's Disease (PD). • The impact of dopaminergic therapies on sleep impairment in PD remains controversial. • ...Rotigotine improved sleep fragmentation by increasing sleep efficiency in PD patients. • Rotigotine induced the increase of REM sleep in PD patients. • The benefit of rotigotine on sleep may be related to its pharmacodynamic profile.
Objective
The spectrum of clinical symptom changes during the course of Parkinson disease (PD). Levodopa therapy, while offering remarkable control of classical motor symptoms, causes abnormal ...involuntary movements as the disease progresses. This levodopa‐induced dyskinesia (LID) has been associated with abnormal cortical plasticity. Because slow wave activity (SWA) of nonrapid eye movement (NREM) sleep underlies adjustment of cortical excitability, we sought to elucidate the relationship between this physiological process and LID.
Methods
Thirty‐six patients at different stages of PD underwent whole‐night video polysomnography–high‐density electroencephalography (vPSG‐hdEEG), preceded by 1 week of actigraphy. To represent the broad spectrum of the disease, patients were divided into 3 groups by disease stage—(1) de novo (n = 9), (2) advanced (n = 13), and (3) dyskinetic (DYS; n = 14)—were compared to an age‐matched control group (n = 12). The SWA‐NREM content of the vPSG‐hdEEG was then temporally divided into 10 equal parts, from T1 to T10, and power and source analyses were performed. T2‐T3‐T4 were considered early sleep and were compared to T7‐T8‐T9, representing late sleep.
Results
We found that all groups, except the DYS group, manifested a clear‐cut SWA decrease between early and late sleep.
Interpretation
Our data demonstrate a strong pathophysiological association between sleep and PD. Given that SWA may be a surrogate for synaptic strength, our data suggest that DYS patients do not have adequate synaptic downscaling. Further analysis is needed to determine the effect of drugs that can enhance cortical SWA in LID. Ann Neurol 2018;84:905–917
Sleep disorders are frequent non-motor symptoms in Parkinson disease (PD), probably due to multifactorial pathogeneses including disease progression, dopaminergic drugs, or concomitant illness. In ...recent years, the pedunculopontine tegmental (PPTg) nucleus has been considered a surgical target for deep brain stimulation (DBS) in advanced PD patients. As it is involved in controlling the sleep-wake cycle, we investigated the long-lasting effects of PPTg-DBS on the sleep of five PD patients implanted in both the PPTg and the subthalamic nucleus (STN) by rating two subjective clinical scales for sleep: the Parkinson's Disease Sleep Scale (PDSS), and the Epworth Sleepiness Scale (ESS).
Sleep scales were administered a week before surgery (T0), three months after DBS (T1), and one year later (T2). In this study, STN-DBS was kept constantly in ON, and three different patterns of PPTg-DBS were investigated: STN-ON (PPTg switched off); PPTg-ON (PPTg stimulated 24 h/day); PPTg-cycle (PPTg stimulated only at night).
In post-surgery follow-up, PD patients reported a marked improvement of sleep quality in all DBS conditions. In particular, stimulation of the PPTg nucleus produced not only a remarkable long-term improvement of nighttime sleep, but unlike STN-DBS, also produced significant amelioration of daytime sleepiness.
Our study suggests that PPTg-DBS plays an important role in reorganizing regular sleep in PD patients.
To evaluate outcomes and prognostic factors in patients with acute ischemic stroke caused by tandem internal carotid artery/middle cerebral artery occlusion undergoing endovascular treatment.
...Characteristics of consecutive patients with tandem occlusion (TO) were extracted from a prospective registry. Collateral vessel quality on pretreatment computed tomographic (CT) angiography was evaluated on a 4-point grading scale, and patients were dichotomized as having poor or good collateral flow. Outcome measures included successful reperfusion according to Thrombolysis In Cerebral Infarction score, good outcome at 3 months defined as a modified Rankin scale score ≤ 2, symptomatic intracranial hemorrhage (ICH; sICH), and mortality.
A total of 72 patients with TO (mean age, 65.6 y ± 12.8) were treated. Intravenous thrombolysis was performed in 54.1% of patients, and a carotid stent was inserted in 48.6%. Successful reperfusion was achieved in 64% of patients, and a good outcome was achieved in 32%. sICH occurred in 12.5% of patients, and the overall mortality rate was 32%. Univariate analysis demonstrated that good outcome was associated with good collateral flow (P = .0001), successful reperfusion (P = .001), and lower rate of any ICH (P = .02) and sICH (P = .04). On multivariate analysis, good collateral flow (odds ratio OR, 0.18; 95% confidence interval CI, 0.04-0.75; P = .01) and age (OR, 1.08; 95% CI, 1.01-1.15; P = .01) were the only predictors of good outcome. The use of more than one device for thrombectomy was the only predictor of sICH (OR, 10.74; 95% CI, 1.37-84.13; P = .02).
Endovascular treatment for TO resulted in good outcomes. Collateral flow and age were independent predictors of good clinical outcomes at 3 months.
Neurodegenerative diseases are disabling conditions continuously increasing due to aging of population. A disease modifying therapy that slows or stops disease progression is therefore a major unmet ...medical need. Unfortunately, research for effective treatments is hampered by lack of knowledge on the pathologic processes underpinning these diseases and of reliable biomarkers. Clinical trials are difficult, as they require large populations that need to be followed for very long periods to capture possible effects on disease progression. These difficulties produce frequent failures and waste of human and economic resources. Since research has to continue in this area, until comprehensive knowledge of basic pathologic processes is obtained, alternative study designs can be considered to identify disease modifiers and to reduce costs of clinical studies.
Abstract Background Cerebellar repetitive transcranial magnetic stimulation may be effective in reducing peak-dose levodopa induced dyskinesia in Parkinson’s disease patients. It was proposed that ...the antidyskinetic effect could be due to modulation of cerebello-thalamo-cortical pathways. However the neural basis for these clinical effects have not yet been demonstrated. Methods We investigated the effects of repeated sessions of cerebellar continuous theta burst stimulation in Parkinson’s disease patients with levodopa induced dyskinesia on brain metabolism by means of positron emission tomography scan with fluorodeoxyglucose (18 F-FDG) to characterize the specific cerebral network activated by cerebellar stimulation in these patients. Results We found that five days of bilateral cerebellar continuous theta burst stimulation (cTBS) were effective in reducing levodopa induced dyskinesia. Clinical changes were paralleled by a reduction of18 F-FDG metabolism in the cerebellum as revealed by positron emission tomography imaging. We found a global decrease in the metabolism of the bilateral cerebellar hemispheres, and a significant decrease in18 F-FDG uptake in correspondence of bilateral dentate nucleus. Conclusions Our study demonstrates the antidyskinetic effect of cerebellar cTBS in Parkinson’s disease patients with levodopa induced dyskinesia, is paralleled by modulation of the activity of the pathways connecting the cerebellar cortex with the deep cerebellar nuclei, confirming the hypothesis that the motor cerebellar circuit is involved in the generations of levodopa induced dyskinesia.
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