Parkinson's Disease Patients In Advanced Stages Research Articles

Evaluating a motor progression connectivity model across Parkinson's disease stages.

Stimulation of a specific site in the dorsolateral subthalamic nucleus (STN) was recently associated with slower motor progression in Parkinson's Disease (PD), based on the deep brain stimulation (DBS) in early-stage PD pilot clinicaltrial. Here, subject-level visualizations are presented of this early-stage PD dataset to further describe the relationship between active contacts and motor progression. This study also evaluates whether stimulation of the sweet spot and connectivity model associated with slower motor progression is alsoassociated with improvements in long-term motor outcomes in patients with advanced-stage PD. Active contacts of the early-stage PD cohort (N = 14) were analyzed alongside the degree of two-year motor progression. Sweet spot and connectivity models derived from the early-stage PD cohort were then used to determine how well they can estimate the variance inlong-term motor outcomes in an independent STN-DBS cohort of advanced-stage PD patients (N = 29). In early-stage PD, proximity of stimulation to the dorsolateral STN wasassociated with slower motor progression. In advanced-stage PD, stimulation proximity to the early PD connectivity model and sweet spot were associated with better long-term motor outcomes (R = 0.60, P < 0.001; R = 0.37, P = 0.046, respectively). Results suggest stimulation of a specific site in the dorsolateral STN isassociated with both slower motor progression and long-term motor improvements in PD.

Adapting to post-COVID19 research in Parkinson's disease: Lessons from a multinational experience

• COVID-19 has significant impact on PD research and education activities. • Country-specific restrictions may pose challenges to PD research and require careful adaptations. • Neurological Symptoms of COVID-19 may overlap with PD.

Disability in Activities of Daily Living andSeverity of Dyskinesias Determine theHandicap of Parkinson's Disease Patients inAdvanced Stage Selected to DBS.

There is scarce data on the level of handicap in Parkinson's disease (PD) and none in advanced stage PD. To assess the handicap in advanced stage PD patients with disabling levodopa-induced motor complications selected to deep brain stimulation (DBS). Data was prospectively recorded during routine evaluation for DBS. Handicap was measured using London Handicap Scale (LHS) (0 = maximal handicap; 1 = no handicap). Disease severity was evaluated using the Hoehn & Yahr scale and the UPDRS/MDS-UPDRS, during off and on after a supra-maximal dose of levodopa. Schwab and England Scale (S&E) was scored in off and on. Dyskinesias were scored using the modified Abnormal Involuntary Movement Scale (mAIMS). Results concern cross-sectional assessment before DBS. 100 PD patients (mean age 61 (±7.6); mean disease duration 12.20 (±4.6) years) were included. Median score of motor MDS-UPDRS was 54 in off and 25 in on. Mean total LHS score was 0.56 (±0.14). Patients were handicapped in several domains with a wide range of severity. Physical Independence and Social Integration were the most affected domains. Determinants of total LHS score were MDS-UPDRS part II off (β= -0.271; p = 0.020), S&E on (β= 0.264; p = 0.005) and off (β= 0.226; p = 0.020), and mAIMS on (β= -0.183; p = 0.042) scores (R2 = 29.6%). We were able to use handicap to measure overall health condition in advanced stage PD. Patients were moderately to highly handicapped and this was strongly determined by disability in ADL and dyskinesias. Change in handicap may be a good patient-centred outcome to assess efficiency of DBS.

Amide proton transfer MR imaging at 3. 0 T of the basal ganglia in Parkinson's disease

Objective To explore the feasibility of amide proton transfer (APT) MR imaging for the detection of basal ganglia abnormalities in patients with Parkinson's disease (PD). Methods Twenty-seven patients with PD and twenty-three age-matched normal control subjects underwent cerebral APT and structural MR imaging. The magnetic resonance ratio asymmetry (MTRasym) values at 3.5 ppm of bilateral globus pallidus, putamen and caudate were measured on APT images. MTRasym (3.5 ppm) values of cerebral structures between PD patients and control subjects were compared with independent-samples t test. Paired-samples t test was used to compare the difference of MTRasym (3.5 ppm) between the side of onset and contralateral side in patients with PD. The difference of MTRasym (3.5 ppm) among normal controls, early-stage PD, and advanced-stage PD patients was assessed with one-way analysis of variance. Results Compared to normal controls, MTRasym (3.5 ppm) values of globus pallidus, putamen and caudate were significantly increased in PD patients ((0.89±0.12)% vs (0.57±0.16)%, (1.05±0.11)% vs (0.82±0.15)%, (1.15±0.13)% vs (0.78±0.19)%; t=3.311, 2.562, 3.277 respectively, all P values <0.05). Significant differences in MTRasym (3.5 ppm) values of these cerebral structures were observed among normal controls, early-stage PD and advanced-stage PD patients. And MTRasym (3.5 ppm) values in globus pallidus, putamen and caudate were significantly higher in early-stage PD patients than normal controls. In PD patients, even not statistically significant, MTRasym (3.5 ppm) values of sides of onset were slightly lower than contralateral sides. Conclusions APT MR imaging can sensitively identify the difference of MTRasym (3.5 ppm) in the basal ganglia between PD patients and normal controls. APT might be a useful tool to evaluate abnormal metabolite in basal ganglia of PD patients. Key words: Parkinson disease; Basal ganglia; Magnetic resonance imaging; Amide proton transfer

Estimulación cerebral profunda del núcleo subtalámico en la enfermedad de Parkinson avanzada: seguimiento de cinco años en un centro portugués

Deep brain stimulation (DBS) of the subthalamic nucleus (STN) in Parkinson's disease (PD) is safe and effective. Most series report stable long-term motor responses. To report the long-term outcome of STN-DBS in advanced stage PD patients at a Portuguese center. Motor status was evaluated before surgery ('off' medication and best 'on'), post-operatively, and at five years ('on' medication and stimulation) using UPDRS part III. Axial symptoms subscores were quantified. Disability was assessed with the modified Rankin Scale (mRS). Development of dementia was assessed at 6 months and five years post-DBS. Of the 183 patients submitted to STN-DBS, 71 had completed 5 years of follow-up. Ten patients were not included: two died (cancer, myocardial infarction), five were lost to follow-up and three had their stimulation systems removed. Motor function improved by 78% and 66% postoperatively and at five years, respectively. There was improvement of axial symptoms postoperatively, with significant worsening at five years (p<0.001). mRS scores improved postoperatively, but declined at five years, although most patients (88.5%) remained ambulatory (mRS<4). One patient (1.6%) and 19 patients (31,2%) were demented at 6 months and 5 years, respectively. Patients who developed dementia were significantly older than non-demented patients (56.5±7.8 vs 63.7±5.9 years-old; p<0.001). In this series STN-DBS proved its efficacy regarding motor symptom improvement even five years after the procedure. Deterioration of axial symptoms and disability, as well as new onset dementia were observed in this period, but the possible role of STN-DBS as a causative factor is yet to be defined.

Palliative Care in Parkinson’s Disease

Palliative care for Parkinson disease (PD) is a new concept in neurodegenerative care. Abundant evidence exists supporting PD as increasing risk of death, most commonly from aspiration pneumonia despite improvements in motor and non-motor symptom management. Palliative care emphasizes an interdisciplinary and holistic approach to symptom management. In the following, the timing for considering palliative care, the communication surrounding this stage of illness, and assessing patients and caregivers will be discussed. Evaluation using the Edmonton Symptom Assessment Scale-PD can help practitioners identify symptoms requiring intervention and track their response to interventions. Adopting palliative care principles will allow neurologists to fulfill the needs of PD patients in advanced stages to the end of life.

Spinal Cord Stimulation for the Treatment of Abnormal Posture and Gait Disorder in Patients With Parkinson's Disease

Patients with advanced Parkinson's disease (PD) often present with axial symptoms, including abnormal posture, postural instability, and gait disorder. Although spinal cord stimulation (SCS) is effective for pain, little is known about the effect of SCS on motor function in PD patients. The present study investigated the effect of SCS on posture and gait in 15 PD patients, 5 men and 10 women aged 63-79 years (mean 71.1 years), with low back pain and leg pain who received SCS. A visual analog scale (VAS) was used for pain evaluation pre- and postoperatively. The Unified Parkinson's Disease Rating Scale, Timed Up and Go tests, and Timed 10-Meter Walk tests were used to evaluate motor function and activities of daily living of patients. Preoperative mean VAS score was 8.9 (range 7.8-10), which showed significant postoperative improvement at 3 months to mean VAS score of 2.0 (range 0-3.3). The improvements in VAS scores persisted at 12 months after surgery with mean VAS score of 2.3 (range 0-4). Posture and postural stability motor subscores were improved at 3 months after SCS, and gait had significantly improved at 3 months and 1 year after surgery. Timed 10-Meter Walk tests also demonstrated that patient gait was significantly improved at 3 months and 12 months after surgery. Most advanced stage PD patients suffer considerable pain that causes abnormal posture and gait disturbance. SCS is expected to lead to both amelioration of pain and improvement of motor function in such patients.

Serum Adiponectin Levels in Advanced-Stage Parkinson's Disease Patients

Patients with advanced Parkinson's disease (PD) experience body weight loss and reductions in the most common cardiovascular risk factors. At present, the pathogenetic mechanisms involved have not been elucidated. Increased serum concentrations of adiponectin, which possesses antiatherogenic and anti-inflammatory properties, are associated with a reduction in cardiovascular risk. The objective of this study was to determine adiponectin serum concentrations in PD patients. Thirty PD patients underwent a full nutritional status assessment, including the determination of adiponectin serum concentrations. Mean ± SD adiponectin concentrations were 9.59 ± 5.9 μg/mL (interquartile range: 5.92–12.9 μg/mL). In PD patients, adiponectin serum levels were similar to those in normal-weight, healthy, young subjects and significantly higher than that in an aged-matched group of morbidly obese subjects. Further studies are warranted to establish the role of adiponectin in the management of PD patients.

Is there a delayed gastric emptying of patients with early-stage, untreated Parkinson’s disease? An analysis using the 13C-acetate breath test

During the pre-symptomatic stage of Parkinson's disease (PD), the idiopathic PD related abnormal synuclein immunostaining is confined to the medulla oblongata and olfactory bulb, according to Braak. In the study of the enteric nervous system of PD, it has reported that Lewy bodies were found in the Auerbach's and Meissner's plexuses. These lesions may cause dysfunction of the gastrointestinal tract (GI) as pre-clinical symptoms of PD. However, because L: -dopa therapy itself may worsen the symptoms of the digestive tract function, it is needed to evaluate the gastrointestinal tract function in patients with early-stage, untreated (de novo) PD. In the present study, using the (13)C-acetate breath test ((13)C-ABT), we investigated gastric emptying in 20 untreated, early-stage PD patients and 40 treated, advanced-stage PD patients, and 20 healthy volunteers. Gastric emptying was examined by the (13)C-ABT [the half emptying time (HET), the peak time of the (13)C% dose-excess curve (T (max))]. The T (max) and HET of gastric emptying as assessed using the (13)C-ABT was significantly delayed in untreated, early-stage PD patients as compared to the controls (P < 0.001). The T (max) and HET of gastric emptying were not significantly delayed in untreated, early-stage PD patients as compared to treated, advanced-stage PD patients. The results demonstrated that delay in gastric emptying did not differ between untreated, early-stage and treated, advanced-stage PD patients. Gastric emptying of untreated, early-stage PD is already delayed. Delayed gastric emptying may be one of markers of the pre-clinical stage of PD.

Two cases of ischemia associated with subthalamic nucleus stimulator implantation for advanced Parkinson's disease

Deep brain stimulation is generally a safe and effective method of alleviating motor impairment in advanced-stage Parkinson's disease patients. However, adverse events of surgery have been noted, such as hemorrhage, infection, seizures, and device failure. In this report, we describe 2 cases of the unusual adverse event of ischemia associated with subthalamic nucleus stimulator implantation. We present the intraoperative neurological symptoms, microelectrode recording data, imaging findings, and other correlated events. In the first case, the clinical effects of ischemia were evident intraoperatively and coincided with silence during microelectrode recording from the ischemic region. In the second case, the timing of the ischemic event could not be determined precisely but also was associated with a difficult mapping. Subcortical ischemia may be an underrecognized event that confounds neurophysiological mapping of deep brain structures and affects clinical outcomes.

Postural reactions to soleus muscle vibration in Parkinson's disease: Scaling deteriorates as disease progresses

Previous research has shown that Parkinson's disease (PD) patients, especially those with postural instability, respond hyperactively to visual, vestibular, and neck proprioceptive sensory manipulation. To determine if this impairment of the sensory information scaling holds true for the lower leg proprioceptive system, we studied postural responses to mechanical vibration (which affects the muscle spindle Ia afferents) applied to the soleus muscles of PD subjects and healthy controls. Early-stage and advanced-stage PD patients as well as age-matched control subjects participated. Each group comprised 11 subjects. Nine pulses of 3-s long vibration were applied randomly to both soleus muscles while subjects kept their eyes closed. Postural responses to these stimuli were measured by static posturography. The effect of dopaminergic medication was established by testing patients in both ON and OFF treatment phases. There was no intergroup difference in the pattern or latencies of responses. However, the amplitudes were significantly larger in advanced PD patients; controls did not differ from early-stage PD patients. Dopaminergic medication had no significant effect on any of the measures. The scaling of postural reactions triggered by lower leg proprioception is disturbed in advanced PD. Neither afferent proprioceptive deficits nor inaccurate timing is involved. This study gives further evidence for the generalized impairment of the scaling of postural responses evoked whenever there is a sudden change of sensory conditions, as occurs with the progression of PD. Such impairment could play a significant role in the pathophysiology of postural instability and falls in PD patients.

Metabolic changes following subthalamotomy for advanced Parkinson's disease.

We studied 6 advanced-stage Parkinson's disease patients with [18F] fluorodeoxyglucose/positron emission tomography before and 3 months after unilateral ablation of the subthalamic nucleus performed with microelectrode mapping. Operative changes in glucose metabolism were assessed by comparing baseline and postoperative scans. We also quantified operative changes in the activity of an abnormal Parkinson's disease-related metabolic network that we had identified in previous [18F] fluorodeoxyglucose/positron emission tomography studies. Following unilateral subthalamic nucleus ablation, a highly significant reduction in glucose utilization was present in the midbrain ipsilateral to the lesion site, most pronounced in the vicinity of the substantia nigra pars reticularis. Significant metabolic reductions were also present in the ipsilateral internal globus pallidus, ventral thalamus, and pons. Operative changes in Parkinson's disease network activity differed significantly for the lesioned and unlesioned hemispheres. In the lesioned hemisphere, network activity declined significantly following surgery, but was unaltered in the contralateral, unlesioned hemisphere. These results suggest that subthalamotomy reduces basal ganglia output through internal globus pallidus/substantia nigra pars reticularis and also influences downstream neural activity in the pons and ventral thalamus. This procedure also reduces the activity of abnormal Parkinson's disease-related metabolic brain networks, suggesting a widespread modulation of motor circuitry.