Assessment of Fitbit Charge 4 for sleep stage and heart rate monitoring against polysomnography and during home monitoring in Huntington's disease.

STUDY OBJECTIVES: Wearable devices, monitoring sleep stages and heart rate (HR), bring the potential for longitudinal sleep monitoring in patients with neurodegenerative diseases. Sleep quality reduces with disease progression in Huntington's disease (HD). However, the involuntary movements characteristic of HD may affect the accuracy of wrist-worn devices. This study compares sleep stage and heart rate data from the Fitbit Charge 4 (FB) against polysomnography (PSG) in participants with HD. METHODS: Ten participants with manifest HD wore a FB during overnight hospital-based PSG, and for nine of these participants continued to wear the FB for seven nights at home. Sleep stages (30s epochs) and minute-by-minute HR were extracted and compared against PSG data. RESULTS: FB-estimated total sleep and wake times, and sleep stage times were in good agreement with PSG, with intra-class correlations 0.79-0.96. However, poor agreement was observed for Wake After Sleep Onset, and the number of awakenings. FB detected wake with 68.6±15.5% sensitivity and 93.7±2.5% specificity, rapid eye movement (REM) sleep with high sensitivity and specificity (78.7±31.9%, 95.6±2.3%), and deep sleep with lower sensitivity but high specificity (56.4±28.8%, 95.0±4.8%). FB HR was strongly correlated with PSG, and the mean absolute error between FB and PSG HR data was 1.16 ± 0.42 bpm. At home, longer sleep and shorter wake times were observed compared to hospital data, while percentage sleep stage times were consistent with hospital data. CONCLUSIONS: Results suggest the potential for long-term monitoring of sleep patterns using wrist-worn wearable devices as part of symptom management in HD.

Direct subthalamic nucleus stimulation influences speech and voice quality in Parkinson's disease patients.

BACKGROUND: DBS of the subthalamic nucleus (STN) considerably ameliorates cardinal motor symptoms in PD. Reported STN-DBS effects on secondary dysarthric (speech) and dysphonic symptoms (voice), as originating from vocal tract motor dysfunctions, are however inconsistent with rather deleterious outcomes based on post-surgical assessments. OBJECTIVE: To parametrically and intra-operatively investigate the effects of deep brain stimulation (DBS) on perceptual and acoustic speech and voice quality in Parkinson's disease (PD) patients. METHODS: We performed an assessment of instantaneous intra-operative speech and voice quality changes in PD patients (n = 38) elicited by direct STN stimulations with variations of central stimulation features (depth, laterality, and intensity), separately for each hemisphere. RESULTS: First, perceptual assessments across several raters revealed that certain speech and voice symptoms could be improved with STN-DBS, but this seems largely restricted to right STN-DBS. Second, computer-based acoustic analyses of speech and voice features revealed that both left and right STN-DBS could improve dysarthric speech symptoms, but only right STN-DBS can considerably improve dysphonic symptoms, with left STN-DBS being restricted to only affect voice intensity features. Third, several subareas according to stimulation depth and laterality could be identified in the motoric STN proper and close to the associative STN with optimal (and partly suboptimal) stimulation outcomes. Fourth, low-to-medium stimulation intensities showed the most optimal and balanced effects compared to high intensities. CONCLUSIONS: STN-DBS can considerably improve both speech and voice quality based on a carefully arranged stimulation regimen along central stimulation features.

NASCarD (Nanopore Adaptive Sampling with Carrier DNA): A Rapid, PCR-Free Method for SARS-CoV-2 Whole-Genome Sequencing in Clinical Samples.

Whole-genome sequencing (WGS) represents the main technology for SARS-CoV-2 lineage characterization in diagnostic laboratories worldwide. The rapid, near-full-length sequencing of the viral genome is commonly enabled by high-throughput sequencing of PCR amplicons derived from cDNA molecules. Here, we present a new approach called NASCarD (Nanopore Adaptive Sampling with Carrier DNA), which allows a low amount of nucleic acids to be sequenced while selectively enriching for sequences of interest, hence limiting the production of non-target sequences. Using COVID-19 positive samples available during the omicron wave, we demonstrate how the method may lead to >99% genome completeness of the SARS-CoV-2 genome sequences within 7 h of sequencing at a competitive cost. The new approach may have applications beyond SARS-CoV-2 sequencing for other DNA or RNA pathogens in clinical samples.

Role of sleep in neurodegeneration: the consensus report of the 5th Think Tank World Sleep Forum.

Sleep abnormalities may represent an independent risk factor for neurodegeneration. An international expert group convened in 2021 to discuss the state-of-the-science in this domain. The present article summarizes the presentations and discussions concerning the importance of a strategy for studying sleep- and circadian-related interventions for early detection and prevention of neurodegenerative diseases. An international expert group considered the current state of knowledge based on the most relevant publications in the previous 5 years; discussed the current challenges in the field of relationships among sleep, sleep disorders, and neurodegeneration; and identified future priorities. Sleep efficiency and slow wave activity during non-rapid eye movement (NREM) sleep are decreased in cognitively normal middle-aged and older adults with Alzheimer's disease (AD) pathology. Sleep deprivation increases amyloid-ß (Aß) concentrations in the interstitial fluid of experimental animal models and in cerebrospinal fluid in humans, while increased sleep decreases Aß. Obstructive sleep apnea (OSA) is a risk factor for dementia. Studies indicate that positive airway pressure (PAP) treatment should be started in patients with mild cognitive impairment or AD and comorbid OSA. Identification of other measures of nocturnal hypoxia and sleep fragmentation could better clarify the role of OSA as a risk factor for neurodegeneration. Concerning REM sleep behavior disorder (RBD), it will be crucial to identify the subset of RBD patients who will convert to a specific neurodegenerative disorder. Circadian sleep-wake rhythm disorders (CSWRD) are strong predictors of caregiver stress and institutionalization, but the absence of recommendations or consensus statements must be considered. Future priorities include to develop and validate existing and novel comprehensive assessments of CSWRD in patients with/at risk for dementia. Strategies for studying sleep-circadian-related interventions for early detection/prevention of neurodegenerative diseases are required. CSWRD evaluation may help to identify additional biomarkers for phenotyping and personalizing treatment of neurodegeneration.

The role of leucine and isoleucine in tuning the hydropathy of class A GPCRs.

Leucine and Isoleucine are two amino acids that differ only by the positioning of one methyl group. This small difference can have important consequences in α-helices, as the ß-branching of Ile results in helix destabilization. We set out to investigate whether there are general trends for the occurrences of Leu and Ile residues in the structures and sequences of class A GPCRs (G protein-coupled receptors). GPCRs are integral membrane proteins in which α-helices span the plasma membrane seven times and which play a crucial role in signal transmission. We found that Leu side chains are generally more exposed at the protein surface than Ile side chains. We explored whether this difference might be attributed to different functions of the two amino acids and tested if Leu tunes the hydrophobicity of the transmembrane domain based on the Wimley-White whole-residue hydrophobicity scales. Leu content decreases the variation in hydropathy between receptors and correlates with the non-Leu receptor hydropathy. Both measures indicate that hydropathy is tuned by Leu. To test this idea further, we generated protein sequences with random amino acid compositions using a simple numerical model, in which hydropathy was tuned by adjusting the number of Leu residues. The model was able to replicate the observations made with class A GPCR sequences. We speculate that the hydropathy of transmembrane domains of class A GPCRs is tuned by Leu (and to some lesser degree by Lys and Val) to facilitate correct insertion into membranes and/or to stably anchor the receptors within membranes.

The risk of developing motor complications with Levodopa immediate versus dual release upon treatment initiation in Parkinson's disease.

Introduction: Motor complications (MCs) compromise therapy in many patients suffering from Parkinson's Disease. By achieving more physiologic stimulation of dopamine-receptors, the continuous dopamine stimulation hypothesis suggests that longer-acting levodopa formulations may improve outcome. The aim of this study was to compare the duration until onset of MCs and motor disease progression in patients during their treatment initiation with either an immediate (IR) or a combined rapid- and sustained-release (i.e. dual-release; DR) levodopa formulation. Methods: Using a sample of 69 patients, we applied time-varying survival regression analyses and linear mixed effect models to analyze the data. The latter involved preprocessing of the data to temporally align the response and predictors, including analyzing the extent of visit irregularity and potential predictors of visit intensity. Results: This retrospective study suggests that levodopa-benserazide DR is not superior to levodopa-benserazide IR in affecting duration until MCs and disease progression. Conversely, using DR levodopa-benserazide, similar disease progression was achieved with lower and more constant doses. Conclusions: The effects of DR levodopa-benserazide might not be strong enough to delay onset of MCs. The development of more powerful levodopa formulations remains a pressing clinical need.

Impact of target depth on safety and efficacy outcomes in MR-guided focused ultrasound thalamotomy for tremor patients.

OBJECTIVE: Target depth, defined by the z-coordinate in the dorsoventral axis relative to the anterior commissure-posterior commissure axial plane of the MR-guided focused ultrasound (MRgFUS) lesion, is considered to be critical for tremor improvement and the occurrence of side effects such as gait impairment. However, although different z-coordinates are used in the literature, there are no comparative studies available with information on optimal lesion placement. This study aimed to compare two different MRgFUS lesion targets (z = +2 mm vs z = 0 mm) regarding efficacy and safety outcomes. METHODS: The authors conducted a retrospective analysis of 52 patients with pharmacoresistant tremor disorders who received unilateral MRgFUS thalamotomy in the ventral intermediate nucleus for the first time between 2017 and 2022 by one neurosurgeon, with two different z-coordinates, either z = +2 mm (+2-mm group; n = 17) or z = 0 mm (0-mm group; n = 35), but otherwise identical parameters. Standardized video-recorded assessments of efficacy (including the Washington Heights-Inwood Genetic Study of Essential Tremor scale) and safety (using a standardized grading system) outcomes at baseline and at 6 months posttreatment were reviewed and compared. Moreover, overall patient satisfaction was extracted as documented by the examiner at 6 months. RESULTS: Based on a multiple logistic regression analysis, the authors found that a more dorsal target with a z-coordinate of +2 mm as compared with 0 mm was associated with a higher incidence of any persistent side effect at 6 months (p = 0.02). Most consistently, sensory disturbances, although mild and nondisturbing in most cases, occurred more frequently in the +2-mm group (35% vs 11%, p = 0.007), while no significant differences were found for gait impairment (29% vs 35%) and arm ataxia (24% vs 11%). On the other hand, average tremor suppression was similar (63.6% vs 60.2%) between the groups. Here, higher efficacy was associated with a higher side effect burden in the 0-mm group but not in the +2-mm group. Despite the occurrence of side effects, general patient satisfaction was high (87% would undergo MRgFUS again) as most patients valued tremor suppression more. CONCLUSIONS: A more ventral MRgFUS target of z = 0 mm seems to be associated with a more favorable safety and a comparable efficacy profile as compared with a more dorsal target of z = +2 mm, but prospective studies are warranted.

Side-chain dynamics of the α1B -adrenergic receptor determined by NMR via methyl relaxation.

G protein-coupled receptors (GPCRs) are medically important membrane proteins that sample inactive, intermediate, and active conformational states characterized by relatively slow interconversions (~µs-ms). On a faster timescale (~ps-ns), the conformational landscape of GPCRs is governed by the rapid dynamics of amino acid side chains. Such dynamics are essential for protein functions such as ligand recognition and allostery. Unfortunately, technical challenges have almost entirely precluded the study of side-chain dynamics for GPCRs. Here, we investigate the rapid side-chain dynamics of a thermostabilized α1B -adrenergic receptor (α1B -AR) as probed by methyl relaxation. We determined order parameters for Ile, Leu, and Val methyl groups in the presence of inverse agonists that bind orthosterically (prazosin, tamsulosin) or allosterically (conopeptide ρ-TIA). Despite the differences in the ligands, the receptor's overall side-chain dynamics are very similar, including those of the apo form. However, ρ-TIA increases the flexibility of Ile1764×56 and possibly of Ile2145×49 , adjacent to Pro2155×50 of the highly conserved P5×50 I3×40 F6×44 motif crucial for receptor activation, suggesting differences in the mechanisms for orthosteric and allosteric receptor inactivation. Overall, increased Ile side-chain rigidity was found for residues closer to the center of the membrane bilayer, correlating with denser packing and lower protein surface exposure. In contrast to two microbial membrane proteins, in α1B -AR Leu exhibited higher flexibility than Ile side chains on average, correlating with the presence of Leu in less densely packed areas and with higher protein-surface exposure than Ile. Our findings demonstrate the feasibility of studying receptor-wide side-chain dynamics in GPCRs to gain functional insights.

Evolution of Cd2+ and Cu+ binding in Helix pomatia metallothioneins.

Metallothioneins (MTs) are small proteins present in all kingdoms of life. Their high cysteine content enables them to bind metal ions, such as Zn2+, Cd2+, and Cu+, providing means for detoxification and metal homeostasis. Three MT isoforms with distinct metal binding preferences are present in the Roman Snail Helix pomatia. Here, we use nuclear magnetic resonance (NMR) to follow the evolution of Cd2+ and Cu+ binding from the reconstructed ancestral Stylommatophora MT to the three H. pomatia MT (HpMT) isoforms. Information obtained from [15N,1H]-HSQC spectra and T2 relaxation times are combined to describe the conformational stability of the MT-metal complexes. A well-behaved MT-metal complex adopts a unique structure and does not undergo additional conformational exchange. The ancestor to all three HpMTs forms conformationally stable Cd2+ complexes and closely resembles the Cd2+-specific HpCdMT isoform, suggesting a role in Cd2+ detoxification for the ancestral protein. All Cu+-MT complexes, including the Cu+-specific HpCuMT isoform, undergo a considerable amount of conformational exchange. The unspecific HpCd/CuMT and the Cu+-specific HpCuMT isoforms form Cu+ complexes with comparable characteristics. It is possible to follow how Cd2+ and Cu+ binding changed throughout evolution. Interestingly, Cu+ binding improved independently in the lineages leading to the unspecific and the Cu+-specific HpMT isoforms. C-terminal domains are generally less capable of coordinating the non-cognate metal ion than N-terminal domains, indicating a higher level of specialization of the C-domain. Our findings provide new insights into snail MT evolution, helping to understand the interplay between biological function and structural features toward a comprehensive understanding of metal preference.

Visualizing alpha-synuclein and iron deposition in M83 mouse model of Parkinson's disease in vivo.

Background: Abnormal alpha-synuclein and iron accumulation in the brain play an important role in Parkinson's disease (PD). Herein, we aim at visualizing alpha-synuclein inclusions and iron deposition in the brains of M83 (A53T) mouse models of PD in vivo. Methods: Fluorescently labelled pyrimidoindole-derivative THK-565 was characterized by using recombinant fibrils and brains from 10-11 months old M83 mice, which subsequently underwent in vivo concurrent wide-field fluorescence and volumetric multispectral optoacoustic tomography (vMSOT) imaging. The in vivo results were verified against structural and susceptibility weighted imaging (SWI) magnetic resonance imaging (MRI) at 9.4 Tesla and scanning transmission X-ray microscopy (STXM) of perfused brains. Brain slice immunofluorescence and Prussian blue staining were further performed to validate the detection of alpha-synuclein inclusions and iron deposition in the brain, respectively. Results: THK-565 showed increased fluorescence upon binding to recombinant alpha-synuclein fibrils and alpha-synuclein inclusions in post-mortem brain slices from patients with Parkinson's disease and M83 mice. i.v. administration of THK-565 in M83 mice showed higher cerebral retention at 20 and 40 minutes post-injection by wide-field fluorescence compared to non-transgenic littermate mice, in congruence with the vMSOT findings. SWI/phase images and Prussian blue indicated the accumulation of iron deposits in the brains of M83 mice, presumably in the Fe3+ form, as evinced by the STXM results. Conclusion: We demonstrated in vivo mapping of alpha-synuclein by means of non-invasive epifluorescence and vMSOT imaging assisted with a targeted THK-565 label and SWI/STXM identification of iron deposits in M83 mouse brains ex vivo.

How reliable is a simplified MSLT nap termination protocol?

OBJECTIVE: According to current practical guidelines, naps of the Mean Sleep Latency Test (MSLT) must be terminated 15 min after sleep onset, which requires ad hoc scoring. For clinical convenience, some sleep clinics use a simplified protocol with fixed nap lengths of 20min. Its diagnostic accuracy remains unknown. METHODS: A subset of MSLT naps of 56 narcolepsy type 1 (NT1), 98 Parkinson's disease (PD), 117 sleep disordered breathing (SDB), 22 insufficient sleep syndrome (ISS) patients, and 24 patients with idiopathic hypersomnia (IH), originally performed according to the simplified protocol, were retrospectively adjusted to standard protocol (nap termination 15min after sleep onset or after 20min when no sleep occurs). This was feasible in 60% of MSLT naps; in this subset, we compared sensitivity and specificity of both MSLT protocols for identification of patients with and without NT1. RESULTS: Sensitivity of classical MSLT criteria for NT1, i.e. mean sleep latency ≤8.0min and ≥2 sleep onset rapid eye movement periods (SOREMPs), did not differ between protocols (95%). Specificity, however, was slightly lower (88.1% vs. 89.7%) in the simplified nap termination protocol, with 3 SDB patients and 1 ISS patient having false-positive MSLT findings in the simplified but not in the standard protocol. CONCLUSIONS: The use of a simplified MSLT protocol with fixed nap duration had no impact on MSLT sensitivity for NT1, but the longer sleep periods in the simplified protocol increased the likelihood of REM sleep occurrence particularly in non-NT1 conditions, resulting in a slightly lower MSLT specificity compared to the standard protocol.

Worsening of Parkinson's Disease After Termination of COVID-19 Quarantine Cannot Be Reversed Despite Resumption of Physiotherapy.

In a retrospective analysis, we recently reported findings on the detrimental motor effects of interrupted physiotherapy following the COVID-19 pandemic in parkinsonian patients. Using an extended follow-up period, we investigated the beneficial effect of reinstated physiotherapy on patients' disease severity and reversal of interruption-induced motor deterioration. Compared to before the COVID-19 outbreak, we observed persistence of motor disease worsening despite full resumption of state-of-the-art physical therapy suggesting that motor deterioration after discontinuation of physical therapy could not be compensated for. Therefore, and considering possible future crises, establishing means to safeguard continuation of physical therapy and to foster remote provision of care should be major goals.

Functional network dynamics between the anterior thalamus and the cortex in deep brain stimulation for epilepsy.

Owing to its unique connectivity profile with cortical brain regions, and its suggested role in the subcortical propagation of seizures, the anterior nucleus of the thalamus (ANT) has been proposed as a key deep brain stimulation (DBS) target in drug-resistant epilepsy. However, the spatio-temporal interaction dynamics of this brain structure, and the functional mechanisms underlying ANT DBS in epilepsy remain unknown. Here, we study how the ANT interacts with the neocortex in vivo in humans and provide a detailed neurofunctional characterization of mechanisms underlying the effectiveness of ANT DBS, aiming at defining intraoperative neural biomarkers of responsiveness to therapy, assessed at 6 months post-implantation as the reduction in seizure frequency. A cohort of 15 patients with drug-resistant epilepsy (n = 6 males, age = 41.6 ± 13.79 years) underwent bilateral ANT DBS implantation. Using intraoperative cortical and ANT simultaneous electrophysiological recordings, we found that the ANT is characterized by high amplitude θ (4-8 Hz) oscillations, mostly in its superior part. The strongest functional connectivity between the ANT and the scalp EEG was also found in the θ band in ipsilateral centro-frontal regions. Upon intraoperative stimulation in the ANT, we found a decrease in higher EEG frequencies (20-70 Hz) and a generalized increase in scalp-to-scalp connectivity. Crucially, we observed that responders to ANT DBS treatment were characterized by higher EEG θ oscillations, higher θ power in the ANT, and stronger ANT-to-scalp θ connectivity, highlighting the crucial role of θ oscillations in the dynamical network characterization of these structures. Our study provides a comprehensive characterization of the interaction dynamic between the ANT and the cortex, delivering crucial information to optimize and predict clinical DBS response in patients with drug-resistant epilepsy.

Deep brain stimulation of the anterior nucleus of the thalamus increases slow wave activity in non-rapid eye movement sleep.

OBJECTIVE: Previous studies suggest that intermittent deep brain stimulation (DBS) of the anterior nucleus of the thalamus (ANT) affects physiological sleep architecture. Here, we investigated the impact of continuous ANT DBS on sleep in epilepsy patients in a multicenter crossover study in 10 patients. METHODS: We assessed sleep stage distribution, delta power, delta energy, and total sleep time in standardized 10/20 polysomnographic investigations before and 12 months after DBS lead implantation. RESULTS: In contrast to previous studies, we found no disruption of sleep architecture or alterations of sleep stage distribution under active ANT DBS (p = .76). On the contrary, we observed more consolidated and deeper slow wave sleep (SWS) under continuous high-frequency DBS as compared to baseline sleep prior to DBS lead implantation. In particular, biomarkers of deep sleep (delta power and delta energy) showed a significant increase post-DBS as compared to baseline (36.67 ± 13.68 µV2 /Hz and 799.86 ± 407.56 µV2 *s, p < .001). Furthermore, the observed increase in delta power was related to the location of the active stimulation contact within the ANT; we found higher delta power and higher delta energy in patients with active stimulation in more superior contacts as compared to inferior ANT stimulation. We also observed significantly fewer nocturnal electroencephalographic discharges in DBS ON condition. In conclusion, our findings suggest that continuous ANT DBS in the most cranial part of the target region leads to more consolidated SWS. SIGNIFICANCE: From a clinical perspective, these findings suggest that patients with sleep disruption under cyclic ANT DBS could benefit from an adaptation of stimulation parameters to more superior contacts and continuous mode stimulation.

Association of Mortality and Risk of Epilepsy With Type of Acute Symptomatic Seizure After Ischemic Stroke and an Updated Prognostic Model.

Importance: Acute symptomatic seizures occurring within 7 days after ischemic stroke may be associated with an increased mortality and risk of epilepsy. It is unknown whether the type of acute symptomatic seizure influences this risk. Objective: To compare mortality and risk of epilepsy following different types of acute symptomatic seizures. Design, Setting, and Participants: This cohort study analyzed data acquired from 2002 to 2019 from 9 tertiary referral centers. The derivation cohort included adults from 7 cohorts and 2 case-control studies with neuroimaging-confirmed ischemic stroke and without a history of seizures. Replication in 3 separate cohorts included adults with acute symptomatic status epilepticus after neuroimaging-confirmed ischemic stroke. The final data analysis was performed in July 2022. Exposures: Type of acute symptomatic seizure. Main Outcomes and Measures: All-cause mortality and epilepsy (at least 1 unprovoked seizure presenting >7 days after stroke). Results: A total of 4552 adults were included in the derivation cohort (2547 male participants [56%]; 2005 female [44%]; median age, 73 years [IQR, 62-81]). Acute symptomatic seizures occurred in 226 individuals (5%), of whom 8 (0.2%) presented with status epilepticus. In patients with acute symptomatic status epilepticus, 10-year mortality was 79% compared with 30% in those with short acute symptomatic seizures and 11% in those without seizures. The 10-year risk of epilepsy in stroke survivors with acute symptomatic status epilepticus was 81%, compared with 40% in survivors with short acute symptomatic seizures and 13% in survivors without seizures. In a replication cohort of 39 individuals with acute symptomatic status epilepticus after ischemic stroke (24 female; median age, 78 years), the 10-year risk of mortality and epilepsy was 76% and 88%, respectively. We updated a previously described prognostic model (SeLECT 2.0) with the type of acute symptomatic seizures as a covariate. SeLECT 2.0 successfully captured cases at high risk of poststroke epilepsy. Conclusions and Relevance: In this study, individuals with stroke and acute symptomatic seizures presenting as status epilepticus had a higher mortality and risk of epilepsy compared with those with short acute symptomatic seizures or no seizures. The SeLECT 2.0 prognostic model adequately reflected the risk of epilepsy in high-risk cases and may inform decisions on the continuation of antiseizure medication treatment and the methods and frequency of follow-up.

Sleep spindle and slow wave activity in Parkinson disease with excessive daytime sleepiness.

STUDY OBJECTIVES: Excessive daytime sleepiness (EDS) is a common and devastating symptom in Parkinson disease (PD), but surprisingly most studies showed that EDS is independent from nocturnal sleep disturbance measured with polysomnography. Quantitative electroencephalography (EEG) may reveal additional insights by measuring the EEG hallmarks of non-rapid eye movement (NREM) sleep, namely slow waves and spindles. Here, we tested the hypothesis that EDS in PD is associated with nocturnal sleep disturbance revealed by quantitative NREM sleep EEG markers. METHODS: Patients with PD (n = 130) underwent polysomnography followed by spectral analysis to calculate spindle frequency activity, slow-wave activity (SWA), and overnight SWA decline, which reflects the dissipation of homeostatic sleep pressure. We used the Epworth Sleepiness Scale (ESS) to assess subjective daytime sleepiness and define EDS (ESS > 10). All examinations were part of an evaluation for deep brain stimulation. RESULTS: Patients with EDS (n = 46) showed reduced overnight decline of SWA (p = 0.036) and reduced spindle frequency activity (p = 0.032) compared with patients without EDS. Likewise, more severe daytime sleepiness was associated with reduced SWA decline (ß= -0.24 p = 0.008) and reduced spindle frequency activity (ß= -0.42, p < 0.001) across all patients. Reduced SWA decline, but not daytime sleepiness, was associated with poor sleep quality and continuity at polysomnography. CONCLUSIONS: Our data suggest that daytime sleepiness in PD patients is associated with sleep disturbance revealed by quantitative EEG, namely reduced overnight SWA decline and reduced spindle frequency activity. These findings could indicate that poor sleep quality, with incomplete dissipation of homeostatic sleep pressure, may contribute to EDS in PD.

Triggers for freezing of gait in individuals with Parkinson's disease: a systematic review.

Background: Freezing of Gait (FOG) is a motor symptom frequently observed in advanced Parkinson's disease. However, due to its paroxysmal nature and diverse presentation, assessing FOG in a clinical setting can be challenging. Before FOG can be fully investigated, it is critical that a reliable experimental setting is established in which FOG can be evoked in a standardized manner, but the efficacy of various gait tasks and triggers for eliciting FOG remains unclear. Objectives: This study aimed to conduct a systematic review of the existing literature and evaluate the available evidence for the relationship between specific motor tasks, triggers, and FOG episodes in individuals with Parkinson's disease (PwPD). Methods: We conducted a literature search on four online databases (PubMed, Web of Science, EMBASE, and Cochrane Library) using the keywords "Parkinson's disease," "Freezing of Gait", "triggers" and "tasks". A total of 128 articles met the inclusion criteria and were included in our analysis. Results: The review found that a wide range of gait tasks were employed in studies assessing FOG among PD patients. However, three tasks (turning, dual tasking, and straight walking) emerged as the most frequently used. Turning (28%) appears to be the most effective trigger for eliciting FOG in PwPD, followed by walking through a doorway (14%) and dual tasking (10%). Conclusion: This review thereby supports the utilisation of turning, especially a 360-degree turn, as a reliable trigger for FOG in PwPD. This finding could be beneficial to clinicians conducting clinical evaluations and researchers aiming to assess FOG in a laboratory environment.