Multi-approach comparative study of EEG patterns associated with the most common forms of dementia.

Electroencephalography's (EEG) sensitivity in discriminating dementia syndromes remains unclear. This study aimed to investigate EEG markers in patients with major cognitive disorders. The studied population included 4 groups of patients: Alzheimer's disease with associated vascular lesions, Alzheimer's disease without vascular lesions (AD-V), Lewy body disease and vascular dementia (VaD); and completed by a control group composed by cognitively unimpaired patients. EEGs were analysed quantitatively using spectral analysis, functional connectivity and micro-states. By comparison to the controls, expected slowing and alterations of functional connectivity were detected in patients with dementia. Among these patients, an overall increase in power in the alpha band was observed in the VaD group, mainly when compared to the 2 AD groups, while the Alzheimer's disease without vascular lesions group exhibited increased power in the beta-2 band and higher functional connectivity in the same frequency band. Micro-state analyses revealed differences in temporal dynamics for the VaD group. A number of EEG modifications reported as markers of some syndromes were found, but others were not reproduced.

The contribution of executive control dysfunction to freezing of gait in Parkinson's disease.

OBJECTIVE: An executive dysfunction is supposed to contribute to freezing of gait (FoG) in Parkinson's disease. We aimed to investigate at a behavioral and cortical levels whether an attentional load (particularly, a conflicting situation) can specifically impact preparation and execution phases of step initiation in parkinsonian patients with FoG. METHODS: Fifteen patients with FoG, 16 without and 15 controls performed an adapted version of the Attention Network Test, with step initiation as response instead of the standard manual keypress. Kinetic and kinematic features of gait initiation as well as high-resolution electroencephalography were recorded during the task. RESULTS: Patients with FoG presented an impaired executive control. Step execution time was longer in parkinsonian patients. However, the executive control effect on step execution time was not different between all groups. Compared to patients, controls showed a shorter step initiation-locked alpha desynchronization, and an earlier, more intense and shorter beta desynchronization over the sensorimotor cortex. Even though controls were faster, the induced alpha and beta activity associated with the effect of executive control didn't differ between patients and controls. CONCLUSIONS: Tasks of conflict resolution lead to a comparable alteration of step initiation and its underlying brain activity in all groups. Links between executive control, gait initiation and FoG seem more complex than expected. SIGNIFICANCE: This study questions the cognitive hypothesis in the pathophysiology of freezing of gait. Executive dysfunction is associated with FoG but is not the main causal mechanism since the interaction between attention and motor preparation didn't provoke FoG.

Pain and Parkinson's disease: Current mechanism and management updates.

The aim of this comprehensive review was to provide an overview of pain in Parkinson's disease (PD) by identifying different clinical features and potential mechanisms, and presenting some data on the evaluation and management of pain in PD. PD is a multifocal degenerative and progressive disease, which could affect the pain process at multiple levels. Pain in PD has a multifactorial aetiology, with a dynamic process based on pain intensity, complexity of symptoms, pain pathophysiology and presence of comorbidities. In fact, pain in PD responds to the concept of multimorphic pain, which can evolve, in relation to the different factors, whether they are linked to disease and its management. Understanding the underlying mechanisms will help in guiding of treatment choices. Providing scientific support useful for clinicians and health professionals involved in management of PD, the aim of this review was to bringing practical suggestions and clinical perspectives on the development of a multimodal approach guided by a multidisciplinary clinical intervention through a combination of pharmacological and rehabilitative approaches, to manage pain to improve the quality of life on individuals with PD.

The frontostriatal subtype of mild cognitive impairment in Parkinson's disease, but not the posterior cortical one, is associated with specific EEG alterations.

BACKGROUND: The 'dual syndrome' hypothesis states that two cognitive subtypes can be distinguished in mild cognitive impairment in Parkinson's disease (PD-MCI): a frontostriatal one, characterized by attentional and/or executive deficits, and a posterior cortical one, characterized by visuospatial, memory and/or language deficits. The latter type has been associated with a higher risk of earlier development of PD dementia. The functional bases of these subtypes remain partly unknown. OBJECTIVE: To identify EEG modifications associated with PD-MCI subtypes. METHODS: 75 non-demented PD patients underwent a comprehensive neuropsychological assessment and a high-density EEG. They were classified as having normal cognition (PD-NC; n = 37), PD-MCI with a frontostriatal subtype (PD-FS; n = 11) or PD-MCI with a posterior cortical subtype (PD-PC; n = 27). Two EEG analyses were performed: (a) spectral powers quantification and (b) functional connectivity analysis. RESULTS: PD-FS patients displayed spectral and functional EEG alterations, namely (a) higher powers in the theta and delta bands, (b) lower powers in the beta2 band and (c) lower functional connectivity in the beta2 band compared to PD-NC and PD-PC patients. These alterations were mainly located in the frontal, limbic and parietal regions. There were no significant differences between PD-NC and PD-PC. CONCLUSION: EEG alterations previously reported in PD-MCI may only concern the frontostriatal subtype, and not the posterior-cortical subtype. This provides evidence for the dual syndrome hypothesis and emphasizes the importance of identifying PD-MCI subtypes. It also shows the promising potential of EEG to discriminate between PD-MCI subtypes.

Factors impacting performance on the 6-minute walk test by people with late-onset Pompe disease.

INTRODUCTION/AIMS: Pompe disease is a progressive myopathy that combines motor, respiratory, and cardiac impairments. The 6-min walk test is the gold standard for assessing disease severity at the motor level. The objective of this study was to better determine the parameters that influence the total distance covered in patients with Pompe disease. METHODS: We performed a retrospective review of 15 patients with late-onset Pompe disease who were followed regularly at a single referral center. Logistic regression was used to investigate the links between motor, respiratory and cardiac variables and 6-min walk test performance. RESULTS: When considering baseline clinical and demographic variables, a seven-step backward elimination regression analysis yielded a model with two predictors (age and the use of an assistive device) that explained 85.5% of the variance. When considering the cardiorespiratory variables monitored during gait, a three-step backward elimination regression analysis showed that two predictors (heart rate recovery and the baseline partial pressure of carbon dioxide) explained 42.2% of the variance. DISCUSSION: Our results highlighted the importance of respiratory and cardiac adaptation during exercise (along with motor ability) during the 6-min walk test in patients with Pompe disease. Further studies of larger cohorts are necessary to validate the model, which might enable investigators to determine whether intra-individual fluctuations in 6-min walk test performance are related to physiological parameters and/or to other variables such as the patient's level of motivation during the test.

Functional networks underlying freezing of gait: a resting-state electroencephalographic study.

INTRODUCTION: The pathophysiology of freezing of gait in people with Parkinson's disease (PD) remains unclear, despite its association with motor, cognitive, limbic and sensory-perceptual impairments. Resting-state electroencephalography (EEG) may provide functional information for a better understanding of freezing of gait by studying spectral power and connectivity between brain regions in different frequency bands. METHODS: High-resolution EEG was recorded in 36 patients with PD (18 freezers, 18 non-freezers), and 18 healthy controls during a 5-min resting-state protocol with eyes open, followed by a basic spectral analysis in the sensor space and a more advanced analysis of functional connectivity at the source level. RESULTS: Freezers showed a diffusely higher theta-band relative spectral power than controls. This increased power was correlated with a deficit in executive control. Concerning resting-state functional connectivity, connectivity strength within a left fronto-parietal network appeared to be higher in freezers than in controls in the theta band, and to be correlated with freezing severity and a history of falls. CONCLUSION: We have shown that spectral power and connectivity analyses of resting-state EEG provide useful and complementary information to better understand freezing of gait in PD. The higher connectivity strength seen within the left ventral attention network in freezers is in keeping with an excessive guidance of behavior by external cues, due to executive dysfunction, and spectral analysis also found changes in freezers that was closely correlated with executive control deficits. This exaggerated influence of the external environment might result in behavioral consequences that contribute to freezing of gait episodes. These findings should be further investigated with a longitudinal study.

EEG-based functional connectivity and executive control in patients with Parkinson's disease and freezing of gait.

OBJECTIVE: To explore changes over time in the network specificities underpinning a visual attentional task in patients with Parkinson's disease and freezing of gait (the PD + FoG group), patients with Parkinson's disease but no FoG (PD-FoG), and healthy controls (HCs). METHODS: High-resolution electroencephalography (EEG) data were acquired for 15 PD + FoG patients, 14 PD-FoG patients, and 18 HCs performing the Attention Network Test. After source localization, functional connectivity was assessed and compared by applying the dynamic phase-locking value method. RESULTS: The PD + FoG patients showed an impairment in executive control. Furthermore, the PD + FoG patients showed abnormally high theta band connectivity (relative to HCs, and 400 to 600 ms after target presentation) in a network connecting the orbitofrontal and occipitotemporal regions. CONCLUSIONS: In PD + FoG, the greater functional connectivity between the visual network and the regions to which executive function has been attributed might indicate greater reliance on environmental features when seeking to overcome the impairment in executive control. SIGNIFICANCE: FoG in PD involves cognitive, attentional and executive dysfunctions. Our observation of abnormally high connectivity in PD + FoG patients argues in favor of the interference model of FoG.

Anxiety in Parkinson's disease: A resting-state high density EEG study.

OBJECTIVE: To identify markers of Parkinson's disease (PD) related anxiety, using high density electroencephalography (hd-EEG). METHODS: 108 patients participated in the study. They were divided into two groups: with and without clinically relevant anxiety, according to their score on the Parkinson Anxiety Scale. Resting-state hd-EEG was recorded. Spectral and functional connectivity characteristics were compared between the two groups. RESULTS: Thirty-three patients (31%) had significant anxiety symptoms. In the spectral analysis, relative power in the alpha1 frequency band in the right prefrontal cortex was lower in patients with anxiety than without. Functional connectivity analysis showed a stronger connectivity between the left insula and several regions of the right prefrontal cortex in patients with anxiety than in those without. CONCLUSION: This study shows the pivotal role of the insula and frontal cortex in the pathophysiology of anxiety in PD and extends the results of previous studies using magnetic resonance imaging or positron emission tomography imaging.

Repetitive transcranial magnetic stimulation for patients with functional paralysis: a randomized controlled study.

BACKGROUND AND PURPOSE: Repetitive transcranial magnetic stimulation (rTMS) has been proposed to treat functional neurological disorders. Here, the aim was to assess the efficacy of rTMS to treat functional paralysis in a controlled randomized trial. METHODS: Patients received two sessions of active or sham 0.25 Hz rTMS (60 stimuli each), with a 1-day interval, applied over the motor cortex contralateral to the paralysis. The primary outcome was the number of patients with an increase in motor score between baseline and after the second rTMS session, rated by two investigators blinded to the treatment allocation. Secondary outcomes were changes in global and fine motor scores between groups after rTMS, and the occurrence of adverse events. RESULTS: Sixty-two patients (46 female; mean [SD] age, 35.2 [13.9] years) were enrolled and randomized. Thirteen out of 32 (41%) and 11/30 (37%) patients had increased motor strength after active or sham rTMS, respectively (p = 0.80). Changes in both global and fine motor scores after rTMS relative to baseline were also not significantly different between treatment groups (median difference in the global motor score 0.62 [0.83] and 0.37 [0.61], and in the fine motor scores 0.12 [0.18] and 0.08 [0.11], in active and sham rTMS groups, respectively; p = 0.14). Six serious adverse events, consisting of three cephalalgia in the active group and two cephalalgia and one asthenia in the sham group, were observed. CONCLUSIONS: Two sessions of sham or active low frequency rTMS were effective to improve functional paralysis, suggesting a placebo effect of this non-invasive brain stimulation technique.

Neurophysiological recordings improve the accuracy of the evaluation of the outcome in perinatal hypoxic ischemic encephalopathy.

OBJECTIVES: Our objective was to evaluate the potential additional value of electroencephalogram (EEG) and evoked potentials in neonates with hypoxic-ischemic encephalopathy to predict their disability at 1 and 2 years old. METHODS: 30 full-term infants after perinatal asphyxia who underwent therapeutic hypothermia were evaluated at 1 year and 2 years for disability using International Classification of Functioning, Disability and Health classification. Scores for EEG, sensory evoked potentials and brainstem auditory evoked potentials were evaluated after withdrawal of therapeutic hypothermia that lasted 72 h. A regression approach was investigated to build models allowing to distinguish neonates according to their disability at 1 and 2 years. Two models were built, the first by considering the clinical data and EEG before and after therapeutic hypothermia and the second by incorporating evoked potentials recording. RESULTS: Adding EEG and evoked potentials data after rewarming improved dramatically the accuracy of the model considering outcome at 1 and 2 years. INTERPRETATION: We propose to record systematically EEG and evoked potentials following rewarming to predict the outcome of neonates with hypoxic ischemic encephalopathy. Combination of altered evoked potentials with no improvement of EEG after rewarming appeared to be a robust criterion for a poor outcome.

Role of the peripheral nervous system for an appropriate postural preparation during gait initiation in patients with a chronic inflammatory demyelinating polyneuropathy: A pilot study.

BACKGROUND: Gait initiation is an automatized motor program that is preceded by anticipatory postural adjustments (APAs). During attentional tasks, these APAs can be modulated, producing multiple APAs. However, the role of the peripheral nervous system in the regulation of these APAs is unknown. RESEARCH QUESTION: The objective of our study was to investigate whether APAs are also regulated by peripheral nervous afferents. METHODS: We assessed 21 patients suffering from chronic inflammatory demyelinating neuropathy and 20 healthy controls. Participants initiated gait with the right or left leg either freely (in the standard condition) or according to a visual trigger (i.e., the select condition). Kinetic and kinematic parameters of APAs and step initiation were recorded. RESULTS: The select condition was related to a higher rate of multiple APAs compared to the standard condition, and was more attention-consuming in both groups. The group with a neuropathy showed longer APAs than the control group, associated with a longer time to recover from multiple APAs. Consequently, the step execution time was delayed in patients with a peripheral neuropathy. SIGNIFICANCE: The impairment of the peripheral nervous system is therefore responsible for an alteration of the mechanisms underlying the recovery from multiple APAs during gait initiation. Our results are in favor of a role of proprioceptive afferents in the early peripheral regulation of motor errors. Further study on gait initiation in peripheral nervous disease could be helpful to better explore sensory-motor coupling in tasks requiring balance control.

Assessing the upper motor neuron in amyotrophic lateral sclerosis using the triple stimulation technique: A multicenter prospective study.

OBJECTIVE: To evaluate the relevance of transcranial magnetic stimulation (TMS) using triple stimulation technique (TST) to assess corticospinal function in amyotrophic lateral sclerosis (ALS) in a large-scale multicenter study. METHODS: Six ALS centers performed TST and conventional TMS in upper limbs in 98 ALS patients during their first visit to the center. Clinical evaluation of patients included the revised ALS Functional Rating Scale (ALSFRS-R) and upper motor neuron (UMN) score. RESULTS: TST amplitude ratio was decreased in 62% of patients whereas conventional TMS amplitude ratio was decreased in 25% of patients and central motor conduction time was increased in 16% of patients. TST amplitude ratio was correlated with ALSFRS-R and UMN score. TST amplitude ratio results were not different between the centers. CONCLUSIONS: TST is a TMS technique applicable in daily clinical practice in ALS centers for the detection of UMN dysfunction, more sensitive than conventional TMS and related to the clinical condition of the patients. SIGNIFICANCE: This multicenter study shows that TST can be a routine clinical tool to evaluate UMN dysfunction at the diagnostic assessment of ALS patients.

Optimization of postural control in precise gaze shifts and laser pointing.

Young adults are known to reduce their postural sway to perform precise visual search and laser pointing tasks. We tested if young adults could reduce even more postural and/or center of pressure sway to succeed in both tasks simultaneously. The methodology is novel because published pointing tasks usually require continuously looking at the pointed target and not exploring an image while pointing elsewhere at the same time. Twenty-five healthy young adults (23.2 ± 2.5 years) performed six visual tasks. In the free-viewing task, participants randomly explored images with no goal. In two visual search tasks, participants searched to locate objects (easy search task) or graphical details (hard search task). Participants additionally pointed a laser beam into a central circle (2°) or pointed the laser turned off. Postural sway and center of pressure sway were reduced complementarily - in various variables - to perform the visual search and pointing tasks. Unexpectedly, the pointing task influenced more strongly postural sway and center of pressure sway than the search tasks. Overall, the participants adopted a functional strategy in stabilizing their posture to succeed in the pointing task and also to fully explore images. Therefore, it is possible to inverse the strength of effects found in the literature (usually stronger for the search task) in modulating the experimental methodology. In search tasks more than in free-viewing tasks, participants mostly rotated their eyes and head, and not their full body, to stabilize their posture. These results could have implications for shooting activities, video console games and rehabilitation most particularly.

Parkinson's disease-related changes in the behavioural synergy between eye movements and postural movements.

Patients with Parkinson's disease (PD patients) have been shown to exhibit abnormally low levels of synergy in their posture control. The goal of this study was to determine how synergic interactions between vision and posture are affected in PD patients. These synergic interactions were expected to be impaired because PD affects the basal ganglia, which are involved in the modulation of both types of movement. Twenty patients (mean age: 60) on levodopa and 20 age-matched-controls (mean age: 61) performed a precise visual task (searching for targets in an image) and an unprecise control task (randomly looking at an image) in which images were projected onto a large panoramic display. Lower back, upper back, head and eye movements were recorded simultaneously. To test behavioural synergies, Pearson correlations between eye and postural movements were analysed. The relationships between eye movements and upper and lower back movements were impaired in the patients. The age-matched controls did not show any significant correlations between eye and postural movements. Overall, our results showed that the PD patients failed to adjust and control their postural stability for success in the visual task. The impaired synergy between eye and postural movements was not related to clinical variables-probably because our patients had early-stage PD. Our results showed that impairments in synergy can occur very early in PD. Hence, the analysis of this synergy might provide a better understanding of postural instability, visual task performance in the upright stance, and perhaps the risk of falls in PD patients.

Neurophysiological findings and their prognostic value in critical COVID-19 patients: An observational study.

OBJECTIVE: To describe EEG patterns of critical Coronavirus Disease 2019 (COVID-19) patients with suspicion of encephalopathy and test their association with clinical outcome. METHODS: EEG after discontinuation of sedation in all patients, and somesthesic evoked potentials and brainstem auditive evoked potentials when EEG did not show reactivity, were performed. Clinical outcome was assessed at day 7 and 14 after neurophysiological explorations. RESULTS: 33 patients were included for analysis. We found slowed background activity in 85% of cases, unreactive activity in 42% of cases, low-voltage activity in 21% of cases and rhythmic or periodic delta waves in 61% of cases. EEG epileptic events were never recorded. Clinical outcome at day 14 was associated with unreactive background activity and tended to be associated with rhythmic or periodic delta waves and with low-voltage activity. Results of multimodal evoked potentials were in favor of a preservation of central nervous system somatosensory and auditory functions. CONCLUSIONS: Among critical COVID-19 patients with abnormal arousal at discontinuation of sedation, EEG patterns consistent with encephalopathy are found and are predictive for short term clinical outcome. SIGNIFICANCE: The abnormal EEG with presence of periodic discharges and lack of reactivity could be related to encephalopathy linked to COVID-19.

Do kinematic gait parameters help to discriminate between fallers and non-fallers with Parkinson's disease?

OBJECTIVE: Although a number of clinical factors have been linked to falls in Parkinson's disease (PD), the diagnostic value of gait parameters remains subject to debate. The objective of this retrospective study was to determine to what extent the combination of gait parameters with clinical characteristics can distinguish between fallers and non-fallers. METHODS: Using a video motion system, we recorded gait in 174 patients with PD. The patients' clinical characteristics (including motor status, cognitive status, disease duration, dopaminergic treatment and any history of falls or freezing of gait) were noted. The considered kinematic gait parameters included indices of gait bradykinesia and hypokinesia, asymmetry, variability, and foot clearance. After a parameters selection using an ANCOVA analysis, support vector machine algorithm was used to build classification models for distinguishing between fallers and non-fallers. Two models were built, the first included clinical data only while the second incorporated the selected gait parameters. RESULTS: The "clinical-only" model had an accuracy of 94% for distinguishing between fallers and non-fallers. The model incorporating additional gait parameters including stride time and foot clearance performed even better, with an accuracy of up to 97%. CONCLUSION: Although fallers differed significantly from non-fallers with regard to disease duration, motor impairment or dopaminergic treatment, the addition of gait parameters such as foot clearance or stride time to clinical variables increased the model's discriminant power. SIGNIFICANCE: This predictive model now needs to be validated in prospective cohorts.

Quantitative approach to early neonatal EEG visual analysis in hypoxic-ischemic encephalopathy severity: Bridging the gap between eyes and machine.

OBJECTIVES: To identify relevant quantitative parameters for early classification of neonatal hypoxic-ischemic encephalopathy (HIE) severity from conventional EEGs. METHODS: Ninety EEGs, recorded in full-term infants within 6 h of life after perinatal hypoxia, were visually classified according to the French EEG classification into three groups of increasing HIE severity. Physiologically significant EEG features (signal amplitude, continuity and frequency content) were automatically quantified using different parameters. The EEG parameters selection was based on their ability to reproduce the visual EEG classification. Post hoc analysis based on clinical outcome was performed. RESULTS: Six EEG parameters were selected, with overall EEG classification performances between 61% and 70%. All parameters differed significantly between group 3 (severe) and groups 1 (normal-mildly abnormal) and 2 (moderate) EEGs (p < 0.001). Amplitude and discontinuity parameters were different between the 3 groups (p < 0.01) and were also the best predictors of clinical outcome. Conversely, pH and lactate did not differ between groups. DISCUSSION: This study provides quantitative EEG parameters that are complementary to visual analysis as early markers of neonatal HIE severity. These parameters could be combined in a multiparametric algorithm to improve their classification performance. The absence of relationship between pH lactate and HIE severity reinforces the central role of early neonatal EEG.

Initial center of pressure position prior to anticipatory postural adjustments during gait initiation in people with Parkinson's disease with freezing of gait.

INTRODUCTION: Freezing of gait (FOG) in Parkinson's disease (PD) is associated with an altered posture during quiet stance as well as an impaired preparation and execution of the gait initiation process. We aimed to investigate whether an altered initial posture impacts anticipatory postural adjustments (APAs) and first-step execution during gait initiation in people with PD with FOG (PD + FOG). METHODS: Twenty-seven PD+FOG, 30 PD patients without FOG and 27 age-matched healthy controls performed self-generated gait initiation. Initial mean center of pressure (COP) position prior to APA onset, characteristics of APAs and features of first-step execution were investigated. RESULTS: Contrarily to controls, PD patients showed a COP that was initially positioned more towards the stance leg (p = 0.007). Moreover, significantly smaller backward COP shift, longer duration of swing-foot unloading phase, and lower first-step length and velocity characterized PD+FOG compared to controls. While size and duration of backward COP shift during APA and lateral COP shift during the unloading phase were main predictors of first-step length and velocity in all groups, the medio-lateral shift of the initial COP position in PD+FOG was a main predictor of first-step execution (ß = -0.191, p = 0.001 for velocity). CONCLUSION: In PD+FOG, the more the COP was initially positioned towards the stance foot, the slower and shorter the first step. The initial medio-lateral COP position may be a compensatory strategy to address postural instability of PD+FOG. A specific training regarding postural control prior to gait preparation and execution could improve functional mobility in PD+FOG.