Axial Motor Symptoms Research Articles

White matter changes and the development of motor phenotypes in de novo Parkinson's Disease

BackgroundParkinson's Disease (PD) patients are usually divided into Tremor Dominant (TD) and Postural Instability/Gait Difficulty (PIGD) subtypes. The latter is characterized by axial motor symptoms and worse outcomes, possibly also because of comorbid white matter disease. Therefore, the current study investigated the importance of Age-Related White Matter Changes (ARWMCs) in the development of different PD motor phenotypes. MethodsThe present 4-year longitudinal study recruited 63 de novo PD patients, who underwent MRI at the time of the diagnosis to rate ARWMCs. Motor subtypes (PIGD or TD) were evaluated at baseline visit, and after 2 and 4years. Age, gender, UPDRS part III total score, comorbidities and ARWMC total score were included in a mixed effect logistic regression model for repeated measures. ResultsThe likelihood of being PIGD subtype during the study period was associated with higher ARWMC total score (OR=2.743; 95%CI=1.137–7.802), but not with age (OR=0.967; 95%CI=0.818–1.143), female gender (OR=0.169; 95%CI=0.014–1.970), UPDRS part III total score (OR=1.942; 95%CI=0.888–13.470), and comorbidities (OR=2.979; 95%CI=0.560–15.849). ConclusionMotor dysfunction in PD is apparently multifactorial and, in particular, comorbid white matter disease might concur in the development of axial impairment.

Low-frequency Subthalamic Stimulation in Parkinson's Disease: Long-term Outcome and Predictors.

Parkinson's disease patients undergoing subthalamic nucleus deep brain stimulation (STN DBS) at standard frequency (>100 Hz) often develop gait impairment, postural instability and speech difficulties. Low frequency stimulation (<100 Hz, LFS) can improve such axial symptoms, but there are concerns that improvement may be transient. To identify long-term outcome and predictors of low-frequency subthalamic stimulation in Parkinson's disease. Through a chart review we identified 85 out of 324 STN DBS patients who received a trial of LFS and describe their characteristics and outcome predictors. Patients were switched to LFS (<100 Hz) 3.8 ± 3.3 years after surgery. Most patients (64%) attained a subjective improvement of gait, speech or balance for 2.0 ± 1.9 years. Motor scores improved within the first year after the stimulation change and showed a slower progression over time when compared to patients switched back to high frequency stimulation. UPDRS III axial score on medication before surgery and the y-axis coordinate of the active contact were independent predictors of LFS retention. This report provides evidence that the use of LFS yields an enduring benefit in a considerable percentage of patients who develop axial motor symptoms during conventional stimulation.

Influence of white matter MRI hyper-intensities on acute l-dopa response in patients with Parkinson's disease

ObjectiveTo determine whether brain white matter hyperintensities (WMH) influence l-dopa response in Parkinson's disease (PD) patients. MethodsWe prospectively evaluated 60 PD patients with an acute l-dopa challenge test, and assessed motor performance with the Movement Disorders Society revised Unified Parkinson's Disease Rating Scale (MDS-UPDRS) during “ON” and “OFF” medication states. Magnetic resonance images were examined using a visual semi-quantitative rating scale for quantification and distribution analysis of WMH. l-dopa challenge test response was correlated to extent and location of WMH, to determine a potential association between them. ResultsSubjects with greater deep WMH burden, showed less response to l-dopa on axial motor symptoms (R = −0.35; p < 0.027), when tested with Part III of the MDS-UPDRS before and after acute levodopa challenge. ConclusionsResults suggest WMH may affect response to l-dopa on axial function of PD patients, which could be due to either non-dopaminergic (cortico-basal ganglia) motor pathway disruption, or postsynaptic nigrostriatal pathway involvement.

How well do Parkinson's disease patients turn in bed? Quantitative analysis of nocturnal hypokinesia using multisite wearable inertial sensors

BackgroundNocturnal hypokinesia/akinesia is a distressing symptom in patients with Parkinson's disease (PD). However, it is difficult to accurately monitor these symptoms based on clinical interviews alone. ObjectivesTo quantitatively compare nocturnal movements of PD patients with their spouses by using multisite inertial sensors and to correlate these parameters with disease severity scores. MethodsNocturnal movements in 19 PD couples (mild-moderate stage) were assessed and compared using wearable sensors (limbs and trunk) for one night at their homes. Nocturnal parameters included number, velocity, acceleration, degree, and duration of rolling over, number of getting out of bed, and limb movements. Each activity was compared to sleep diary, and video recording for accuracy. ResultsPD patients significantly had fewer rolling over (p = 0.048), turned with smaller degree (p = 0.007), less velocity (p = 0.011), and acceleration (p < 0.001), but had more episodes of getting out of bed (p = 0.03, nocturia) when compared to their spouses. Moderate and significant correlations were observed between the mean duration of rolling over and the Unified Parkinson's Disease Rating Scale-Axial score, and Nocturnal Akinesia Dystonia and Cramp Score. The number of leg movements (predominant side) significantly correlated with REM behavior disorder single-question screen. Episodes of nocturia correlated with total and bedtime levodopa equivalent dose. Several other correlations were also observed. ConclusionOur study was able to demonstrate quantitatively the presence of nocturnal hypokinesia in PD patients. This problem correlated with daytime axial motor and nonmotor symptoms. Treatment strategy for PD should be based on a comprehensive review of both day- and nighttime symptoms.

Low-Frequency Stimulation of Globus Pallidus Internus for Axial Motor Symptoms of Parkinson's Disease.

Low-Frequency Stimulation of Globus Pallidus Internus for Axial Motor Symptoms of Parkinson's Disease.

P183. Effect of nigral stimulation on gait in Parkinson’s disease

Introduction Freezing of gait is a debilitating symptom of Parkinson’s disease with major impact on quality of life. Interleaved stimulation of the subthalamic nucleus (STN-DBS) and the substantia nigra pars reticulata (SNr) may improve otherwise resistant freezing of gait ( Weiss et al., 2013 ), and SNr stimulation was described to modulate presumably axial motor symptoms ( Chastan et al., 2009 ). Methods We performed combined kinematic and electrophysiological (EMG, EEG) analyses in 6 patients with Parkinson’s disease and STN-DBS (5 male, 63 ± 8 years). 5 of these patients were also available for SNr stimulation (lowest electrode contact of the subthalamic lead reaching SNr). Patients were recorded during walking at self-selected comfortable pace on a straight walkway of nine meters. Patients were measured in three conditions: ‘stimulation off’, ’subthalamic stimulation on’, ’nigral stimulation on’. Gait kinematics were recorded by 3 sensors (both left and right ankle, lumbar position) measuring acceleration, angular velocity, and the direction of the magnetic field in three directions. We calculated the gait cycle time and the peak shank angular velocity during the swing phase (angular velocity maximum during the swing phase). Results Our preliminary analyses show that the gait cycle time was similar in all three conditions. The peak shank angular velocity was faster in both subthalamic and nigral stimulation as compared to ‘stimulation off’. Conclusion Both subthalamic and nigral stimulation modulate the peak shank angular velocity in patients with Parkinson’s disease. Additional measurements and correlations to EMG/ EEG analyses are under preparation and will be presented.

P137. Nigral and subthalamic neurostimulation modulate intermuscular coherence in Parkinson’s disease

Introduction Combined nigral and subthalamic stimulation is under consideration to modulate otherwise resistant axial motor symptoms, namely freezing of gait in idiopathic Parkinson’s disease (PD). The impact of subthalamic or nigral stimulation on neuromuscular motor integration however needs further characterization. Methods We used fully mobile EEG and EMG recordings, wireless kinematic sensors and video documentation to record patients during a gait cycle. Seven patients with deep brain stimulation were examined both during walking and standing after overnight withdrawal of dopaminergic medications. Recordings in different therapeutic conditions were obtained, i.e. ‘stimulation off’ (StimOff), ‘subthalamic stimulation on’ (STNOn), and ‘nigral stimulation on’ (SNrOn). Results The main finding was an increase of intermuscular coherence in the alpha and low beta bands during ‘walking’ in both STNOn and SNrOn. During ‘standing’ there was increased coherence in theta and alpha bands (‘STNOn’) and in the alpha and low beta bands (‘SNrOn’). Discussion Subthalamic and nigral stimulation increase intermuscular beta band coherence. Intermuscular beta band coherence may reflect increased corticospinal motor control from corticospinal beta drives to the spinal motor unit pool (Marsden et al., 2001; Weiss et al., 2012).

Axial disability and deep brain stimulation in patients with Parkinson disease.

Axial motor signs-including gait impairment, postural instability and postural abnormalities-are common and debilitating symptoms in patients with advanced Parkinson disease. Dopamine replacement therapy and physiotherapy provide, at best, partial relief from axial motor symptoms. In carefully selected candidates, deep brain stimulation (DBS) of the subthalamic nucleus or globus pallidus internus is an established treatment for 'appendicular' motor signs (limb tremor, bradykinesia and rigidity). However, the effects of DBS on axial signs are much less clear, presumably because motor control of axial and appendicular functions is mediated by different anatomical-functional pathways. Here, we discuss the successes and failures of DBS in managing axial motor signs. We systematically address a series of common clinical questions associated with the preoperative phase, during which patients presenting with prominent axial signs are considered for DBS implantation surgery, and the postoperative phase, in particular, the management of axial motor signs that newly develop as postoperative complications, either acutely or with a delay. We also address the possible merits of new targets-including the pedunculopontine nucleus area, zona incerta and substantia nigra pars reticulata-to specifically alleviate axial symptoms. Supported by a rapidly growing body of evidence, this practically oriented Review aims to support decision-making in the management of axial symptoms.

Five-Year Outcomes of Bilateral Subthalamic Nucleus Stimulation in Japanese Patients with Parkinson’s Disease

Background: Deep brain stimulation (DBS) of the subthalamic nucleus (STN) is widely performed for medically refractory Parkinson’s disease (PD). Several western studies have examined the long-term outcomes of STN DBS. However, the long-term outcomes in Japanese patients have not been reported. Methods: We studied the long-term outcomes of STN DBS in Japanese patients with PD. Fifty-five consecutive patients treated with bilateral STN DBS were followed for 5 years after surgery. Each patient underwent Unified Parkinson’s Disease Rating Scale assessments preoperatively and 1 and 5 years after surgery. Results: Twelve patients (22%) were lost to follow up within 5 years. Among them, 7 died and 5 became bed ridden because of PD deterioration. In the 43 patients followed for 5 years, STN DBS significantly improved motor function. The cardinal motor symptoms of tremor, rigidity, and bradykinesia in medication-on periods were significantly better than baseline 5 years after DBS. However, axial motor symptoms of speech, gait and postural stability gradually deteriorated and significantly worsened 5 years after DBS. Motor complications, including dyskinesia and motor fluctuations, significantly improved after DBS with a marked reduction in dopaminergic medication. These effects were maintained 5 years after DBS. Frequently, persisting adverse effects included apraxia of eyelid opening and dysarthria. Conclusions: STN DBS significantly improved motor symptoms in patients with advanced PD. These effects were maintained over 5 years in most patients. However, some showed rapid PD progression even after STN DBS. Other treatments for the axial symptoms and disease progression are needed in long-term PD treatment.

Inflammatory mechanisms of fatigue syndrome in Parkinson's disease

To study clinical characteristics of fatigue syndrome in patients with Parkinson's disease (PD) and a role of inflammation in its development. We examined 98 patients with confirmed diagnosis of PD and 18 healthy people. Clinical examination included an analysis of anamnesis and objective somatic symptoms. The unified Parkinson's disease rating scale, The Hoehn and Yahr scale, the Multidimensional Fatigue Inventory (MFI-20) scale, the Modified Fatigue Impact Scale (MFIS), the Hospital Anxiety and Depression Scale (HADS), The Epworth Sleepiness Scale (ESS), Vein's Autonomic Symptoms Questionnaire (VASQ) were used for quantitative assessment. Serum concentrations of IL-6 were measured in 65 patients and 18 controls using ELISA. In PD patients, fatigue assessed with MFI-20 was recorded in 46 (47%) cases and fatigue as assessed with MFIS in 45 (46%) of cases. High frequency and severity of fatigue syndrome were observed. The most prominent components in the structure of fatigue were physical fatigue, reduced motivation and decreased activity. Signs of fatigue increased with disease progression. Correlation between fatigue and axial motor symptoms of PD is of interest. Patients had higher serum IL-6 levels compared to the controls. Concentrations of IL-6 were correlated with fatigue severity and its main components (general and physical fatigue, decreased activity) and with depression level.

Effects of Stochastic Vestibular Galvanic Stimulation and LDOPA on Balance and Motor Symptoms in Patients With Parkinson's Disease.

Balance problems contribute to reduced quality of life in Parkinson's disease (PD) and available treatments are often insufficient for treating axial and postural motor symptoms. To investigate the safety of use and possible effects of stochastic vestibular stimulation (SVS) alone and combined with LDOPA in patients with PD. SVS or sham stimulation was administered to 10 PD patients in a double-blind placebo controlled cross-over pilot study. Motor symptoms and balance were evaluated in a defined off-medication state and after a 200 mg test dose of LDOPA, using UPDRS-III, Posturo-Locomotor-Manual (PLM) movement times (MT), static posturography and force plate measurements of the correcting response to a balance perturbation. Patients did not detect when SVS was active, but SVS increased nausea after LDOPA in two patients. Mixed model analysis demonstrated that SVS improved balance corrections after a backward perturbation and shortened the postural response time. In static posturography there was significant interaction between effects of SVS, medication and proprioceptive input (standing on foam vs. on hard support) and SVS decreased the total sway-path with eyes closed and off medication. As expected, LDOPA improved the UPDRS-III scores and MT. There was an interaction between the effect of SVS and LDOPA on UPDRS-III partly because of reduced UPDRS-III scores with SVS in the off-medication state. Short term use of SVS is safe, improves corrective postural responses and may have a small positive effect on motor symptoms in PD patients off treatment.

Effects of robot assisted gait training in progressive supranuclear palsy (PSP): a preliminary report.

Background and Purpose: Progressive supranuclear palsy (PSP) is a rare neurodegenerative disease clinically characterized by prominent axial extrapyramidal motor symptoms with frequent falls. Over the last years the introduction of robotic technologies to recover lower limb function has been greatly employed in the rehabilitative practice. This observational trial is aimed at investigating the changes in the main spatiotemporal following end-effector robot training in people with PSP.Method: Pilot observational trial.Participants: Five cognitively intact participants with PSP and gait disorders.Interventions: Patients were submitted to a rehabilitative program of robot-assisted walking sessions for 45 min, 5 times a week for 4 weeks.Main outcome measures: The spatiotemporal parameters at the beginning (T0) and at the end of treatment (T1) were recorded by a gait analysis laboratory.Results: Robot training was feasible, acceptable and safe and all participants completed the prescribed training sessions. All patients showed an improvement in the gait spatiotemporal index (Mean velocity, Cadence, Step length, and Step width) (T0 vs. T1).Conclusions: Robot training is a feasible and safe form of rehabilitation for cognitively intact people with PSP. The lack of side effects and the positive results in the gait parameter index in all patients support the recommendation to extend the trials of this treatment. Further investigation regarding the effectiveness of robot training in time is necessary.Trial registration: ClinicalTrials.gov NCT01668407.

Reply: Cognitive declines after deep brain stimulation are likely to be attributable to more than caudate penetration and lead location

Sir, We thank Dr Morishita and colleagues (2014) for their interest and valuable contribution. Many studies report a slight decline in cognitive functioning after subthalamic nucleus (STN) stimulation for Parkinson’s disease (Parsons et al. , 2006; Witt et al. , 2008). The observed neuropsychological sequelae are likely caused by several independent factors: first, there is a patient-inherent risk profile including age, impaired attention, higher antiparkinsonian medication, higher scores on axial motor symptoms and a lower l-DOPA response before surgery (Smeding et al. , 2009; Daniels et al. , 2010). However, these patient-related factors explain only 23% of the variance of postoperative decline (Daniels et al. , 2010). In our study we found penetration of the caudate nucleus to be associated with an increased risk for a decline in global cognitive functioning and working memory abilities (Witt et al. , 2013). Furthermore, we were able to show that an additional factor is the placement of the stimulated electrode contact. We concluded, that besides the well-known inherent risk factors (age and disease progression), the electrodes track and the …

Advanced Parkinson's disease: Clinical characteristics and treatment (part 1)

IntroductionA large percentage of patients with Parkinson's disease (PD) develop motor fluctuations, dyskinesias, and severe non-motor symptoms (NMS) within 3 to 5 years of starting dopaminergic therapy, and these motor complications are refractory to treatment. Several authors refer to this stage of the disease as advanced PD. ObjectiveTo define the clinical manifestations of advanced PD and the risk factors for reaching this stage of the disease. DevelopmentThis consensus document has been prepared by using an exhaustive literature search and by discussion of the contents by an expert group on movement disorders of the Sociedad Española de Neurología (Spanish Neurology Society), coordinated by two of the authors (JK and MRL). ConclusionsSevere motor fluctuations and dyskinesias, axial motor symptoms resistant to levodopa, and cognitive decline are the main signs in the clinical phenotype of advanced PD.

Combined rehabilitation program for postural instability in progressive supranuclear palsy

Progressive supranuclear palsy (PSP) is an atypical parkinsonism clinically characterized by prominent axial extrapyramidal motor symptoms with frequent falls. The clinical response to L-dopa is poor and there is strong need for alternative treatment strategies. We tested the efficacy of a rehabilitative program combining a dynamic antigravity postural system (SPAD) and a vibration sound system (ViSS) on postural instability of 10 patients affected by PSP. The patients underwent SPAD and VISS treatments with a 3 sessions/week schedule for 2 months. Patients were clinically examined at baseline, every week during the 2-months treatment, and at 1 month after the end of treatment for the following parameters: baropodometry static, baropodometry dynamic and stabilometry. PSP rating scale and PD36 quality of life scale were also administered. The combined rehabilitative program produced improvement of all the parameters explored (p = 0.01-0.05) at the end of treatment as compared to baseline. Baropodometric dynamics improvement lasted until the end of follow-up. Our results suggest that a specific rehabilitation program could improve postural instability in PSP patients. A more continuous treatment protocol would allow stabilizations of results.

Enfermedad de Parkinson avanzada. Características clínicas y tratamiento (parte I)

IntroductionA large percentage of patients with Parkinson's disease (PD) develop motor fluctuations, dyskinesias, and severe non-motor symptoms within 3 to 5 years of starting dopaminergic therapy, and these motor complications are refractory to treatment. Several authors refer to this stage of the disease as advanced Parkinson's disease. ObjectiveTo define the clinical manifestations of advanced PD and the risk factors for reaching this stage of the disease. DevelopmentThis consensus document has been prepared by using an exhaustive literature search and by discussion of the contents by an expert group on movement disorders of the Sociedad Española de Neurología (Spanish Neurology Society), coordinated by two of the authors (JK and MRL). ConclusionsSevere motor fluctuations and dyskinesias, axial motor symptoms resistant to levodopa, and cognitive decline are the main signs in the clinical phenotype of advanced PD.

Instability of syllable repetition in Parkinson's disease—Impairment of automated speech performance?

Steady vocal pace performance according to a multi-level syllable repetition paradigm has been previously shown to be compromised in patients in advanced stages of Parkinson's disease (PD) under chronic deep brain stimulation. The aim of the present study was to implement the same syllable repetition test in mildy to moderately affected patients in order to survey if (a) the characteristic pattern of abnormalities can be observed even in early stages of PD and (b) if there are correlations to motor symptoms of PD. Sixty-four patients with PD who were on stable dopaminergic medication and 40 healthy subjects had to repeat a single syllable (/pa/) or a pair of alternating syllables (/pa-ti/) in a self chosen steady pace or in a given pace of 80/min. As main results, PD patients’ pace performance was (1) already irregular in the simple steady syllable repetition task, (2) even more impaired when a given pace had to be kept and (3) showed a further decline when two alternating syllables had to be repeated in a given pace; (4) measures of irregular pace performance showed a correlation to axial motor symptoms. This pattern of impaired vocal pace performance was similar, although less pronounced, to the previously reported findings in advanced PD and therefore might be a characteristic feature of PD. The results could be interpreted as a hint for increasing disruption of automaticity in speech performance with rising complexity of the task which can be found even in early stages of PD and correlate to axial motor symptoms.

Advances in Therapeutic Options for Gait and Balance in Parkinson’s Disease

There is a need to explore non-dopaminergic approaches to treating balance and gait problems in Parkinson's disease (PD). There is emerging evidence on the role of cholinergic denervation of the pedunculopontine nucleus (PPN) thalamus system and falls in PD. Preliminary clinical trial data suggest that the subgroup of PD patients with frequent falls may be suitable candidates for future cholinergic augmentation clinical trials. Recent controlled clinical trials using methylphenidate have been unable to confirm earlier reports of improved gait in PD. Although progressive deterioration of axial motor symptoms occur with deep brain stimulation of the subthalamic nucleus or globus pallidus interna, new preliminary research suggests that other surgical stimulation sites, such as the PPN, may have a potential benefit on gait and balance impairments in PD. Continuing vigorous exercise and physical fitness should be highly encouraged to patients with PD who are at risk of physical deconditioning and fear of falling, but effective antifall physical therapy interventions remain an unmet clinical need.

Deep Brain Stimulation for Movement Disorders – A History of Success and Challenges to Conquer

Deep Brain Stimulation for Movement Disorders – A History of Success and Challenges to Conquer

Acceleration of syllable repetition in Parkinson's disease is more prominent in the left-side dominant patients

BackgroundIn Parkinson's disease (PD), abnormalities of speech rate have been observed in spontaneous speech, reading tasks and syllable repetition tasks. Impaired temporal speech patterns have been contributed to dysfunctional basal ganglia circuits, but little is known about a possible differential role of right and left basal ganglia concerning speech production, although neurodegeneration in PD typically follows an asymmetrical pattern. The aim of our study was to reveal a possible influence of lateralized basal ganglia dysfunction on speech timing in PD. Patients and methods60 patients with PD (30 with predominant symptoms on the left-side PD_L and 30 with predominant symptoms on the right side PD_R) and 40 healthy controls were tested. Participants had to repeat a single syllable in a self chosen steady pace. Additionally, the participants performed a reading task in order to measure speaking rate related to connected speech. ResultsSyllable repetition showed a significant instability in both PD groups as compared to controls. However, the PD_L group performed in a much higher pace with further significant pace acceleration in the course of the syllable repetition task. This pattern showed a further correlation to axial motor symptoms. No correlations were seen between parameters of syllable repetition and the reading task. ConclusionsLateralization of basal ganglia dysfunction in PD seems to differentially impact the stability of spontaneous syllable repetition pace. Our data suggest a crucial role of the right basal ganglia in the maintenance of isochronous speech rhythms at least in patients with additional axial motor symptoms.