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NeuroImage. Clinical 2019Abnormal cortical oscillations are markers of Parkinson's Disease (PD). Transcranial alternating current stimulation (tACS) can modulate brain oscillations and possibly... (Randomized Controlled Trial)
Randomized Controlled Trial
Personalized transcranial alternating current stimulation (tACS) and physical therapy to treat motor and cognitive symptoms in Parkinson's disease: A randomized cross-over trial.
Abnormal cortical oscillations are markers of Parkinson's Disease (PD). Transcranial alternating current stimulation (tACS) can modulate brain oscillations and possibly impact on behaviour. Mapping of cortical activity (prevalent oscillatory frequency and topographic scalp distribution) may provide a personalized neurotherapeutic target and guide non-invasive brain stimulation. This is a cross-over, double blinded, randomized trial. Electroencephalogram (EEG) from participants with PD referred to Specialist Clinic, University Hospital, were recorded. TACS frequency and electrode position were individually defined based on statistical comparison of EEG power spectra maps with normative data from our laboratory. Stimulation frequency was set according to the EEG band displaying higher power spectra (with beta excess on EEG map, tACS was set at 4 Hz; with theta excess, tACS was set at 30 Hz). Participants were randomized to tACS or random noise stimulation (RNS), 5 days/week for 2-weeks followed by ad hoc physical therapy. EEG, motor (Unified Parkinson's Disease Rating Scale-motor: UPDRS III), neuropsychological (frontal, executive and memory tests) performance and mood were measured before (T), after (T) and 4-weeks after treatment (T). A linear model with random effects and Wilcoxon test were used to detect differences. Main results include a reduction of beta rhythm in theta-tACS vs. RNS group at T over right sensorimotor area (p = .014) and left parietal area (p = .010) and at T over right sensorimotor area (p = .004) and left frontal area (p = .039). Bradykinesia items improved at T (p = .002) and T (p = .047) compared to T in the tACS group. In the tACS group the Montréal Cognitive Assessment (MoCA) improved at T compared with T (p = .049). Individualized tACS in PD improves motor and cognitive performance. These changes are associated with a reduction of excessive fast EEG oscillations.
Topics: Aged; Aged, 80 and over; Brain Waves; Breathing Exercises; Cognitive Dysfunction; Combined Modality Therapy; Cross-Over Studies; Double-Blind Method; Exercise Therapy; Female; Humans; Hypokinesia; Male; Middle Aged; Outcome Assessment, Health Care; Parkinson Disease; Precision Medicine; Psychomotor Performance; Severity of Illness Index; Transcranial Direct Current Stimulation
PubMed: 30921609
DOI: 10.1016/j.nicl.2019.101768 -
Continuum (Minneapolis, Minn.) Oct 2013The different parkinsonian conditions can be challenging to separate clinically. This review highlights the important clinical features that guide the diagnosis of... (Review)
Review
PURPOSE OF REVIEW
The different parkinsonian conditions can be challenging to separate clinically. This review highlights the important clinical features that guide the diagnosis of Parkinson disease (PD), progressive supranuclear palsy (PSP), multiple system atrophy (MSA), and corticobasal degeneration (CBD). Strategies for treatment and disease management are also discussed.
RECENT FINDINGS
Over the past decade there has been an increasing recognition of the broad clinical presentations of the neurodegenerative forms of parkinsonism. Nonmotor symptoms in these diseases, including psychiatric, cognitive, autonomic, and gastrointestinal dysfunction, appear to have a major impact on quality of life and disability. PSP and CBD are now considered pathologic diagnoses, with several different and varied clinical phenotypes, that overlap and share features with PD and frontotemporal dementia syndromes. PD is distinguished by its excellent response to dopaminergic medications that is maintained over many years, in contrast to the response seen in patients with MSA and PSP. New diagnostic criteria have been proposed for CBD. No new therapeutic interventions have emerged for PSP, MSA, or CBD. Infusional therapies and deep brain stimulation surgery are established therapies for advanced PD.
SUMMARY
The "parkinsonian syndromes" encompass a number of nosologic entities that are grouped together on the basis of their shared clinical features but are separated on the basis of their different pathologies. Overall, the consideration of clinical signs, mode of disease onset, and nature of disease progression are all important to make a timely and definitive diagnosis.
Topics: Aged; Antiparkinson Agents; Deep Brain Stimulation; Diagnosis, Differential; Dopamine Agents; Female; Frontotemporal Dementia; Gait Disorders, Neurologic; Humans; Hypokinesia; Male; Middle Aged; Muscle Rigidity; Neurologic Examination; Parkinsonian Disorders; Prion Diseases; Supranuclear Palsy, Progressive; Tremor
PubMed: 24092286
DOI: 10.1212/01.CON.0000436152.24038.e0 -
Journal of Parkinson's Disease 2023Bradykinesia is the hallmark feature of Parkinson's disease (PD); however, it can manifest in other conditions, including essential tremor (ET), and in healthy elderly...
BACKGROUND
Bradykinesia is the hallmark feature of Parkinson's disease (PD); however, it can manifest in other conditions, including essential tremor (ET), and in healthy elderly individuals.
OBJECTIVE
Here we assessed whether bradykinesia features aid in distinguishing PD, ET, and healthy elderly individuals.
METHODS
We conducted simultaneous video and kinematic recordings of finger tapping in 44 PD patients, 69 ET patients, and 77 healthy elderly individuals. Videos were evaluated blindly by expert neurologists. Kinematic recordings were blindly analyzed. We calculated the inter-raters agreement and compared data among groups. Density plots assessed the overlapping in the distribution of kinematic data. Regression analyses and receiver operating characteristic curves determined how the kinematics influenced the likelihood of belonging to a clinical score category and diagnostic group.
RESULTS
The inter-rater agreement was fair (Fleiss K = 0.32). Rater found the highest clinical scores in PD, and higher scores in ET than healthy elderly individuals (p < 0.001). In regard to kinematic analysis, the groups showed variations in movement velocity, with PD presenting the slowest values and ET displaying less velocity than healthy elderly individuals (all ps < 0.001). Additionally, PD patients showed irregular rhythm and sequence effect. However, kinematic data significantly overlapped. Regression analyses showed that kinematic analysis had high specificity in differentiating between PD and healthy elderly individuals. Nonetheless, accuracy decreased when evaluating subjects with intermediate kinematic values, i.e., ET patients.
CONCLUSION
Despite a considerable degree of overlap, bradykinesia features vary to some extent in PD, ET, and healthy elderly individuals. Our findings have implications for defining bradykinesia and categorizing patients.
Topics: Humans; Aged; Parkinson Disease; Hypokinesia; Essential Tremor; Movement; Biomechanical Phenomena
PubMed: 37522221
DOI: 10.3233/JPD-230119 -
Neuronal Signaling Sep 2023Mutations in the leucine-rich repeat kinase 2 () gene are associated with familial and sporadic forms of Parkinson's disease (PD). Sporadic PD and LRRK2 PD share main... (Review)
Review
Mutations in the leucine-rich repeat kinase 2 () gene are associated with familial and sporadic forms of Parkinson's disease (PD). Sporadic PD and LRRK2 PD share main clinical and neuropathological features, namely hypokinesia, degeneration of nigro-striatal dopamine neurons and α-synuclein aggregates in the form of Lewy bodies. Animals harboring the most common LRRK2 mutations, i.e. p.G2019S and p.R1441C/G, have been generated to replicate the parkinsonian phenotype and investigate the underlying pathogenic mechanisms. Disappointingly, however, LRRK2 rodents did not consistently phenocopy hypokinesia and nigro-striatal degeneration, or showed Lewy body-like aggregates. Instead, LRRK2 rodents manifested non-motor signs and dysregulated transmission at dopaminergic and non-dopaminergic synapses that are reminiscent of behavioral and functional network changes observed in the prodromal phase of the disease. LRRK2 rodents also manifested greater susceptibility to different parkinsonian toxins or stressors when subjected to dual-hit or multiple-hit protocols, confirming LRRK2 mutations as genetic risk factors. In conclusion, LRRK2 rodents represent a unique tool to identify the molecular mechanisms through which LRRK2 modulates the course and clinical presentations of PD and to study the interplay between genetic, intrinsic and environmental protective/risk factors in PD pathogenesis.
PubMed: 37601008
DOI: 10.1042/NS20220040 -
Acta Neurologica Scandinavica Jan 2022The aim of this study was to characterize the associations between sagittal spinopelvic alignment and motor symptoms in patients with Parkinson's disease (PD).
INTRODUCTION
The aim of this study was to characterize the associations between sagittal spinopelvic alignment and motor symptoms in patients with Parkinson's disease (PD).
METHODS
The study included patients with idiopathic PD (aged <80 years and with abnormal posture). All patients underwent whole-spine lateral and coronal radiography. Sagittal spinopelvic alignment was evaluated using nine parameters. Motor symptoms were evaluated using the Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III score-with bradykinesia and axial motor sub-scores. Multivariate analysis was used to analyze associations between motor symptoms and sagittal spinopelvic alignment in PD patients according to sex.
RESULTS
The study subjects were 79 PD patients (39 men, 40 women; median age, 70 years). Clear sex-related differences were noted. In male patients, the MDS-UPDRS part III score correlated significantly with cervical sagittal vertical axis (SVA), and bradykinesia and axial motor scores correlated significantly with SVA, cervical SVA, and T1 slope. In female patients, the MDS-UPDRS part III score correlated significantly with thoracic kyphosis, bradykinesia score correlated significantly with cervical SVA and thoracic kyphosis, and the axial motor score correlated significantly with SVA, cervical SVA, T1 slope, sacral slope, and pelvic tilt.
CONCLUSION
Our results showed clear correlations among various motor symptoms and sagittal global alignment in PD patients and that these correlations are different in female PD patients and their male counterparts.
Topics: Aged; Female; Humans; Kyphosis; Male; Parkinson Disease; Posture; Radiography
PubMed: 34426963
DOI: 10.1111/ane.13521 -
Movement Disorders : Official Journal... Jul 2020The recurrent hemizygous 22q11.2 deletion associated with 22q11.2 deletion syndrome has been identified as a genetic risk factor for early-onset PD. However, little is...
BACKGROUND
The recurrent hemizygous 22q11.2 deletion associated with 22q11.2 deletion syndrome has been identified as a genetic risk factor for early-onset PD. However, little is known about early motor signs in this condition.
OBJECTIVES
We examined the presence, severity and possible factors associated with parkinsonism in adults with 22q11.2 deletion syndrome and without PD.
METHODS
We compared motor signs between 82 adults with 22q11.2 deletion syndrome and 25 healthy controls, using the MDS-UPDRS part III, and three-dimensional motion-tracker technology to quantify components of bradykinesia.
RESULTS
Median MDS-UPDRS part III total and bradykinesia subscores were significantly higher in 22q11.2 deletion syndrome (median age: 26 years; range, 17-65) than in controls (P = 0.000; P = 0.000, respectively). Age was a significant contributor to bradykinesia subscore (B = 0.06; P = 0.01) and to the electronic bradykinesia component, velocity (B = -0.02; P = 0.000); psychotic illness did not significantly impact these analyses. In 22q11.2 deletion syndrome, MDS-UPDRS-defined bradykinesia was present in 18.3%, rigidity in 14.6%, and rest tremor in 12.2%.
CONCLUSIONS
Parkinsonian motor signs appear to be common and age related in 22q11.2 deletion syndrome. Longitudinal studies are needed to investigate possible symptom progression to PD. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.
Topics: Adult; DiGeorge Syndrome; Humans; Hypokinesia; Parkinson Disease; Parkinsonian Disorders; Tremor
PubMed: 32386091
DOI: 10.1002/mds.28080 -
Neurochemical Research Oct 2023Parkinson's disease is a neurodegenerative disease affecting mainly the elderly population. It is characterized by the loss of dopaminergic neurons of the substantia... (Review)
Review
Parkinson's disease is a neurodegenerative disease affecting mainly the elderly population. It is characterized by the loss of dopaminergic neurons of the substantia nigra pars compacta region. Parkinson's disease patients exhibit motor symptoms like tremors, rigidity, bradykinesia/hypokinesia, and non-motor symptoms like depression, cognitive decline, delusion, and pain. Major pathophysiological factors which contribute to neuron loss include excess/misfolded alpha-synuclein aggregates, microglial cell-mediated neuroinflammation, excitotoxicity, oxidative stress, and defective mitochondrial function. Sigma-1 receptors are molecular chaperones located at mitochondria-associated ER membrane. Their activation (by endogenous ligands or agonists) has shown neuroprotective and neurorestorative effects in various diseases. This review discusses the roles of activated Sig-1 receptors in modulating various pathophysiological features of Parkinson's disease like alpha-synuclein aggregates, neuroinflammation, excitotoxicity, and oxidative stress.
Topics: Aged; Humans; Parkinson Disease; alpha-Synuclein; Neurodegenerative Diseases; Neuroinflammatory Diseases; Dopaminergic Neurons; Substantia Nigra; Sigma-1 Receptor
PubMed: 37259012
DOI: 10.1007/s11064-023-03960-6 -
Neurobiology of Disease Oct 2015Bradykinesia is the most important feature contributing to motor difficulties in Parkinson's disease (PD). However, the pathophysiology underlying bradykinesia is not... (Review)
Review
Bradykinesia is the most important feature contributing to motor difficulties in Parkinson's disease (PD). However, the pathophysiology underlying bradykinesia is not fully understood. One important aspect is that PD patients have difficulty in performing learned motor skills automatically, but this problem has been generally overlooked. Here we review motor automaticity associated motor deficits in PD, such as reduced arm swing, decreased stride length, freezing of gait, micrographia and reduced facial expression. Recent neuroimaging studies have revealed some neural mechanisms underlying impaired motor automaticity in PD, including less efficient neural coding of movement, failure to shift automated motor skills to the sensorimotor striatum, instability of the automatic mode within the striatum, and use of attentional control and/or compensatory efforts to execute movements usually performed automatically in healthy people. PD patients lose previously acquired automatic skills due to their impaired sensorimotor striatum, and have difficulty in acquiring new automatic skills or restoring lost motor skills. More investigations on the pathophysiology of motor automaticity, the effect of L-dopa or surgical treatments on automaticity, and the potential role of using measures of automaticity in early diagnosis of PD would be valuable.
Topics: Animals; Basal Ganglia; Humans; Motor Skills; Parkinson Disease
PubMed: 26102020
DOI: 10.1016/j.nbd.2015.06.014 -
Clinical Parkinsonism & Related... 2023The feasibility of measuring bradykinesia and chorea in Huntington's Disease using a wearable sensor system (Parkinson's Kinetigraph: PKG) developed for measuring...
OBJECTIVES
The feasibility of measuring bradykinesia and chorea in Huntington's Disease using a wearable sensor system (Parkinson's Kinetigraph: PKG) developed for measuring bradykinesia and dyskinesia in Parkinson's Disease was assessed.
METHODS
Unified Huntington's Disease Rating Scales (UHDRS) and a PKG were obtained for 25 people with Huntington's Disease. Bradykinesia and Chorea Score were derived from relevant sub-scores of the UHDRS and compared with the PKG's bradykinesia and dyskinesia scores. The PKG's daytime sleepiness score was also used.
RESULTS
There was good correlation between Chorea Scores and the PKG's dyskinesia score (Pearson's ρ = 0.66). Correlation between the Bradykinesia Scores and the PKG's bradykinesia score was also good (Pearson's ρ = 0.51) in cases whose PKG scores were in the normal or bradykinetic range. The PKG's bradykinesia score of 23, which is in the higher range of control subjects, separated participants into those with Independence Score ≥ 80 or < 80 and a Functional Assessment (FAS) score ≥ 18 or < 18. The PKG's daytime sleep score was high in 44 % of participants, whose average time asleep was 21 % compared to 1.6 % in participants with a normal sleep index. Participants with high sleep scores were significantly more likely to have low Independence and TFC scores.
CONCLUSIONS
Measures of bradykinesia and dyskinesia from clinical scales have acceptable correlations with those from the PKG. Continuous monitoring provides information about daytime sleep, which was associated with lower functional status. Further studies and larger sample sizes are required to confirm these findings and the utility of this measure in Huntington's Disease.
PubMed: 36590454
DOI: 10.1016/j.prdoa.2022.100179