A sleep stage estimation algorithm based on cardiorespiratory signals derived from a suprasternal pressure sensor.

Automatic estimation of sleep structure is an important aspect in moving sleep monitoring from clinical laboratories to people's homes. However, the transition to more portable systems should not happen at the expense of important physiological signals, such as respiration. Here, we propose the use of cardiorespiratory signals obtained by a suprasternal pressure (SSP) sensor to estimate sleep stages. The sensor is already used for diagnosis of sleep-disordered breathing (SDB) conditions, but besides respiratory effort it can detect cardiac vibrations transmitted through the trachea. We collected the SSP sensor signal in 100 adults (57 male) undergoing clinical polysomnography for suspected sleep disorders, including sleep apnea syndrome, insomnia, and movement disorders. Here, we separate respiratory effort and cardiac activity related signals, then input these into a neural network trained to estimate sleep stages. Using the original mixed signal the results show a moderate agreement with manual scoring, with a Cohen's kappa of 0.53 in Wake/N1-N2/N3/rapid eye movement sleep discrimination and 0.62 in Wake/Sleep. We demonstrate that decoupling the two signals and using the cardiac signal to estimate the instantaneous heart rate improves the process considerably, reaching an agreement of 0.63 and 0.71. Our proposed method achieves high accuracy, specificity, and sensitivity across different sleep staging tasks. We also compare the total sleep time calculated with our method against manual scoring, with an average error of -1.83 min but a relatively large confidence interval of ±55 min. Compact systems that employ the SSP sensor information-rich signal may enable new ways of clinical assessments, such as night-to-night variability in obstructive sleep apnea and other sleep disorders.

Multimodal nocturnal seizure detection in children with epilepsy: A prospective, multicenter, long-term, in-home trial.

OBJECTIVE: There is a pressing need for reliable automated seizure detection in epilepsy care. Performance evidence on ambulatory non-electroencephalography-based seizure detection devices is low, and evidence on their effect on caregiver's stress, sleep, and quality of life (QoL) is still lacking. We aimed to determine the performance of NightWatch, a wearable nocturnal seizure detection device, in children with epilepsy in the family home setting and to assess its impact on caregiver burden. METHODS: We conducted a phase 4, multicenter, prospective, video-controlled, in-home NightWatch implementation study (NCT03909984). We included children aged 4-16 years, with ≥1 weekly nocturnal major motor seizure, living at home. We compared a 2-month baseline period with a 2-month NightWatch intervention. The primary outcome was the detection performance of NightWatch for major motor seizures (focal to bilateral or generalized tonic-clonic [TC] seizures, focal to bilateral or generalized tonic seizures lasting >30 s, hyperkinetic seizures, and a remainder category of focal to bilateral or generalized clonic seizures and "TC-like" seizures). Secondary outcomes included caregivers' stress (Caregiver Strain Index [CSI]), sleep (Pittsburgh Quality of Sleep Index), and QoL (EuroQol five-dimension five-level scale). RESULTS: We included 53 children (55% male, mean age = 9.7 ± 3.6 years, 68% learning disability) and analyzed 2310 nights (28 173 h), including 552 major motor seizures. Nineteen participants did not experience any episode of interest during the trial. The median detection sensitivity per participant was 100% (range = 46%-100%), and the median individual false alarm rate was .04 per hour (range = 0-.53). Caregiver's stress decreased significantly (mean total CSI score = 8.0 vs. 7.1, p = .032), whereas caregiver's sleep and QoL did not change significantly during the trial. SIGNIFICANCE: The NightWatch system demonstrated high sensitivity for detecting nocturnal major motor seizures in children in a family home setting and reduced caregiver stress.

Singular Value Decomposition for Removal of Cardiac Interference from Trunk Electromyogram.

A new algorithm based on singular value decomposition (SVD) to remove cardiac contamination from trunk electromyography (EMG) is proposed. Its performance is compared to currently available algorithms at different signal-to-noise ratios (SNRs). The algorithm is applied on individual channels. An experimental calibration curve to adjust the number of SVD components to the SNR (0-20 dB) is proposed. A synthetic dataset is generated by the combination of electrocardiography (ECG) and EMG to establish a ground truth reference for validation. The performance is compared with state-of-the-art algorithms: gating, high-pass filtering, template subtraction (TS), and independent component analysis (ICA). Its applicability on real data is investigated in an illustrative diaphragm EMG of a patient with sleep apnea. The SVD-based algorithm outperforms existing methods in reconstructing trunk EMG. It is superior to the others in the time (relative mean squared error < 15%) and frequency (shift in mean frequency < 1 Hz) domains. Its feasibility is proven on diaphragm EMG, which shows a better agreement with the respiratory cycle (correlation coefficient = 0.81, p-value < 0.01) compared with TS and ICA. Its application on real data is promising to non-obtrusively estimate respiratory effort for sleep-related breathing disorders. The algorithm is not limited to the need for additional reference ECG, increasing its applicability in clinical practice.

Comparative Review of the Algorithms for Removal of Electrocardiographic Interference from Trunk Electromyography.

Surface electromyogram (EMG) is a noninvasive measure of muscle electrical activity and has been widely used in a variety of applications. When recorded from the trunk, surface EMG can be contaminated by the cardiac electrical activity, i.e., the electrocardiogram (ECG). ECG may distort the desired EMG signal, complicating the extraction of reliable information from the trunk EMG. Several methods are available for ECG removal from the trunk EMG, but a comparative assessment of the performance of these methods is lacking, limiting the possibility of selecting a suitable method for specific applications. The aim of the present study is therefore to review and compare the performance of different ECG removal methods from the trunk EMG. To this end, a synthetic dataset was generated by combining in vivo EMG signals recorded on the biceps brachii and healthy or dysrhythmia ECG data from the Physionet database with a predefined signal-to-noise ratio. Gating, high-pass filtering, template subtraction, wavelet transform, adaptive filtering, and blind source separation were implemented for ECG removal. A robust measure of Kurtosis, i.e., KR2 and two EMG features, the average rectified value (ARV), and mean frequency (MF), were then calculated from the processed EMG signals and compared with the EMG before mixing. Our results indicate template subtraction to produce the lowest root mean square error in both ARV and MF, providing useful insight for the selection of a suitable ECG removal method.

Quantitative muscle ultrasound and quadriceps strength in patients with post-polio syndrome.

INTRODUCTION: We investigated whether muscle ultrasound can distinguish muscles affected by post-polio syndrome (PPS) from healthy muscles and whether severity of ultrasound abnormalities is associated with muscle strength. METHODS: Echo intensity, muscle thickness, and isometric strength of the quadriceps muscles were measured in 48 patients with PPS and 12 healthy controls. RESULTS: Patients with PPS had significantly higher echo intensity and lower muscle thickness than healthy controls. In patients, both echo intensity and muscle thickness were associated independently with muscle strength. A combined measure of echo intensity and muscle thickness was more strongly related to muscle strength than either parameter alone. CONCLUSIONS: Quantitative ultrasound distinguishes healthy muscles from those affected by PPS, and measures of muscle quality and quantity are associated with muscle strength. Hence, ultrasound could be a useful tool for assessing disease severity and monitoring changes resulting from disease progression or clinical intervention in patients with PPS.

Quantitative validation of the suprasternal pressure signal to assess respiratory effort during sleep.

Objective.Intra-esophageal pressure (Pes) measurement is the recommended gold standard to quantify respiratory effort during sleep, but used to limited extent in clinical practice due to multiple practical drawbacks. Respiratory inductance plethysmography belts (RIP) in conjunction with oronasal airflow are the accepted substitute in polysomnographic systems (PSG) thanks to a better usability, although they are partial views on tidal volume and flow rather than true respiratory effort and are often used without calibration. In their place, the pressure variations measured non-invasively at the suprasternal notch (SSP) may provide a better measure of effort. However, this type of sensor has been validated only for respiratory events in the context of obstructive sleep apnea syndrome (OSA). We aim to provide an extensive verification of the suprasternal pressure signal against RIP belts and Pes, covering both normal breathing and respiratory events.Approach.We simultaneously acquired suprasternal (207) and esophageal pressure (20) signals along with RIP belts during a clinical PSG of 207 participants. In each signal, we detected breaths with a custom algorithm, and evaluated the SSP in terms of detection quality, breathing rate estimation, and similarity of breathing patterns against RIP and Pes. Additionally, we examined how the SSP signal may diverge from RIP and Pes in presence of respiratory events scored by a sleep technician.Main results.The SSP signal proved to be a reliable substitute for both esophageal pressure (Pes) and respiratory inductance plethysmography (RIP) in terms of breath detection, with sensitivity and positive predictive value exceeding 75%, and low error in breathing rate estimation. The SSP was also consistent with Pes (correlation of 0.72, similarity 80.8%) in patterns of increasing pressure amplitude that are common in OSA.Significance.This work provides a quantitative analysis of suprasternal pressure sensors for respiratory effort measurements.

Quantitative facial muscle ultrasound: feasibility and reproducibility.

INTRODUCTION: In this study we describe a protocol for quantitative ultrasound of facial muscles (procerus, zygomaticus major, levator labii superior, depressor anguli oris, mentalis, orbicularis oris pars labialis, orbicularis oris pars marginalis). METHODS: Muscle thickness (MT) and echo intensity (EI) were measured in 12 healthy subjects and a myotonic dystrophy type 1 patient. RESULTS: MTs ranged from 0.15 to 0.30 mm, except for the procerus muscle (0.06 mm). EIs ranged from 1 to 34, except for the procerus muscle. MT reproducibility was fair for the orbicularis oris pars labialis, excellent for the procerus and levator labii, and good for the other muscles. The myotonic dystrophy type 1 patient showed high EIs, outside the range in healthy subjects in 6 of the 7 muscles. MT was lower than the range seen in healthy subjects in 4 muscles. CONCLUSION: Quantitative muscle ultrasound of the facial muscles is feasible and shows moderate to excellent reproducibility.

The Use of Respiratory Effort Improves an ECG-Based Deep Learning Algorithm to Assess Sleep-Disordered Breathing.

BACKGROUND: Sleep apnea is a prevalent sleep-disordered breathing (SDB) condition that affects a large population worldwide. Research has demonstrated the potential of using electrocardiographic (ECG) signals (heart rate and ECG-derived respiration, EDR) to detect SDB. However, EDR may be a suboptimal replacement for respiration signals. METHODS: We evaluated a previously described ECG-based deep learning algorithm in an independent dataset including 198 patients and compared performance for SDB event detection using thoracic respiratory effort versus EDR. We also evaluated the algorithm in terms of apnea-hypopnea index (AHI) estimation performance, and SDB severity classification based on the estimated AHI. RESULTS: Using respiratory effort instead of EDR, we achieved an improved performance in SDB event detection (F1 score = 0.708), AHI estimation (Spearman's correlation = 0.922), and SDB severity classification (Cohen's kappa of 0.62 was obtained based on AHI). CONCLUSION: Respiratory effort is superior to EDR to assess SDB. Using respiratory effort and ECG, the previously described algorithm achieves good performance in a new dataset from an independent laboratory confirming its adequacy for this task.

Extraction of cardiac-related signals from a suprasternal pressure sensor during sleep.

Objective.The accurate detection of respiratory effort during polysomnography is a critical element in the diagnosis of sleep-disordered breathing conditions such as sleep apnea. Unfortunately, the sensors currently used to estimate respiratory effort are either indirect and ignore upper airway dynamics or are too obtrusive for patients. One promising alternative is the suprasternal notch pressure (SSP) sensor: a small element placed on the skin in the notch above the sternum within an airtight capsule that detects pressure swings in the trachea. Besides providing information on respiratory effort, the sensor is sensitive to small cardiac oscillations caused by pressure perturbations in the carotid arteries or the trachea. While current clinical research considers these as redundant noise, they may contain physiologically relevant information.Approach.We propose a method to separate the signal generated by cardiac activity from the one caused by breathing activity. Using only information available from the SSP sensor, we estimate the heart rate and track its variations, then use a set of tuned filters to process the original signal in the frequency domain and reconstruct the cardiac signal. We also include an overview of the technical and physiological factors that may affect the quality of heart rate estimation. The output of our method is then used as a reference to remove the cardiac signal from the original SSP pressure signal, to also optimize the assessment of respiratory activity. We provide a qualitative comparison against methods based on filters with fixed frequency cutoffs.Main results.In comparison with electrocardiography (ECG)-derived heart rate, we achieve an agreement error of 0.06 ± 5.09 bpm, with minimal bias drift across the measurement range, and only 6.36% of the estimates larger than 10 bpm.Significance.Together with qualitative improvements in the characterization of respiratory effort, this opens the development of novel portable clinical devices for the detection and assessment of sleep disordered breathing.

A Potential Multimodal Test for Clinical Assessment of Visual Attention in Neurological Disorders.

Attention is an important aspect of human brain function and often affected in neurological disorders. Objective assessment of attention may assist in patient care, both for diagnostics and prognostication. We present a compact test using a combination of a choice reaction time task, eye-tracking and EEG for assessment of visual attention in the clinic. The system quantifies reaction time, parameters of eye movements (i.e. saccade metrics and fixations) and event related potentials (ERPs) in a single and fast (15 min) experimental design. We present pilot data from controls, patients with mild traumatic brain injury and epilepsy, to illustrate its potential use in assessing attention in neurological patients. Reaction times and eye metrics such as fixation duration, saccade duration and latency show significant differences (p < .05) between neurological patients and controls. Late ERP components (200-800 ms) can be detected in the central line channels for all subjects, but no significant group differences could be found in the peak latencies and mean amplitudes. Our system has potential to assess key features of visual attention in the clinic. Pilot data show significant differences in reaction times and eye metrics between controls and patients, illustrating its promising use for diagnostics and prognostication.

Decoding executed and imagined grasping movements from distributed non-motor brain areas using a Riemannian decoder.

Using brain activity directly as input for assistive tool control can circumventmuscular dysfunction and increase functional independence for physically impaired people. The motor cortex is commonly targeted for recordings, while growing evidence shows that there exists decodable movement-related neural activity outside of the motor cortex. Several decoding studies demonstrated significant decoding from distributed areas separately. Here, we combine information from all recorded non-motor brain areas and decode executed and imagined movements using a Riemannian decoder. We recorded neural activity from 8 epilepsy patients implanted with stereotactic-electroencephalographic electrodes (sEEG), while they performed an executed and imagined grasping tasks. Before decoding, we excluded all contacts in or adjacent to the central sulcus. The decoder extracts a low-dimensional representation of varying number of components, and classified move/no-move using a minimum-distance-to-geometric-mean Riemannian classifier. We show that executed and imagined movements can be decoded from distributed non-motor brain areas using a Riemannian decoder, reaching an area under the receiver operator characteristic of 0.83 ± 0.11. Furthermore, we highlight the distributedness of the movement-related neural activity, as no single brain area is the main driver of performance. Our decoding results demonstrate a first application of a Riemannian decoder on sEEG data and show that it is able to decode from distributed brain-wide recordings outside of the motor cortex. This brief report highlights the perspective to explore motor-related neural activity beyond the motor cortex, as many areas contain decodable information.

Towards hippocampal navigation for brain-computer interfaces.

Automatic wheelchairs directly controlled by brain activity could provide autonomy to severely paralyzed individuals. Current approaches mostly rely on non-invasive measures of brain activity and translate individual commands into wheelchair movements. For example, an imagined movement of the right hand would steer the wheelchair to the right. No research has investigated decoding higher-order cognitive processes to accomplish wheelchair control. We envision an invasive neural prosthetic that could provide input for wheelchair control by decoding navigational intent from hippocampal signals. Navigation has been extensively investigated in hippocampal recordings, but not for the development of neural prostheses. Here we show that it is possible to train a decoder to classify virtual-movement speeds from hippocampal signals recorded during a virtual-navigation task. These results represent the first step toward exploring the feasibility of an invasive hippocampal BCI for wheelchair control.

Contactless Camera-Based Sleep Staging: The HealthBed Study.

Polysomnography (PSG) remains the gold standard for sleep monitoring but is obtrusive in nature. Advances in camera sensor technology and data analysis techniques enable contactless monitoring of heart rate variability (HRV). In turn, this may allow remote assessment of sleep stages, as different HRV metrics indirectly reflect the expression of sleep stages. We evaluated a camera-based remote photoplethysmography (PPG) setup to perform automated classification of sleep stages in near darkness. Based on the contactless measurement of pulse rate variability, we use a previously developed HRV-based algorithm for 3 and 4-class sleep stage classification. Performance was evaluated on data of 46 healthy participants obtained from simultaneous overnight recording of PSG and camera-based remote PPG. To validate the results and for benchmarking purposes, the same algorithm was used to classify sleep stages based on the corresponding ECG data. Compared to manually scored PSG, the remote PPG-based algorithm achieved moderate agreement on both 3 class (Wake-N1/N2/N3-REM) and 4 class (Wake-N1/N2-N3-REM) classification, with average κ of 0.58 and 0.49 and accuracy of 81% and 68%, respectively. This is in range with other performance metrics reported on sensing technologies for wearable sleep staging, showing the potential of video-based non-contact sleep staging.

Pitfalls in EEG Analysis in Patients With Nonconvulsive Status Epilepticus: A Preliminary Study.

Objective: Electroencephalography (EEG) interpretations through visual (by human raters) and automated (by computer technology) analysis were still not reliable for the diagnosis of nonconvulsive status epilepticus (NCSE). This study aimed to identify typical pitfalls in the EEG analysis and make suggestions as to how those pitfalls might be avoided. Methods: We analyzed the EEG recordings of individuals who had clinically confirmed or suspected NCSE. Epileptiform EEG activity during seizures (ictal discharges) was visually analyzed by 2 independent raters. We investigated whether unreliable EEG visual interpretations quantified by low interrater agreement can be predicted by the characteristics of ictal discharges and individuals' clinical data. In addition, the EEG recordings were automatically analyzed by in-house algorithms. To further explore the causes of unreliable EEG interpretations, 2 epileptologists analyzed EEG patterns most likely misinterpreted as ictal discharges based on the differences between the EEG interpretations through the visual and automated analysis. Results: Short ictal discharges with a gradual onset (developing over 3 s in length) were liable to be misinterpreted. An extra 2 min of ictal discharges contributed to an increase in the kappa statistics of >0.1. Other problems were the misinterpretation of abnormal background activity (slow-wave activities, other abnormal brain activity, and the ictal-like movement artifacts), continuous interictal discharges, and continuous short ictal discharges. Conclusion: A longer duration criterion for NCSE-EEGs than 10 s that is commonly used in NCSE working criteria is recommended. Using knowledge of historical EEGs, individualized algorithms, and context-dependent alarm thresholds may also avoid the pitfalls.

Neurophysiological signatures reflect differences in visual attention during absence seizures.

OBJECTIVE: Absences affect visual attention and eye movements variably. Here, we explore whether the dissimilarity of these symptoms during absences is reflected in differences in electroencephalographic (EEG) features, functional connectivity, and activation of the frontal eye field. METHODS: Pediatric patients with absences performed a computerized choice reaction time task, with simultaneous recording of EEG and eye-tracking. We quantified visual attention and eye movements with reaction times, response correctness, and EEG features. Finally, we studied brain networks involved in the generation and propagation of seizures. RESULTS: Ten pediatric patients had absences during the measurement. Five patients had preserved eye movements (preserved group) and five patients showed disrupted eye movements (unpreserved group) during seizures. Source reconstruction showed a stronger involvement of the right frontal eye field during absences in the unpreserved group than in the preserved group (dipole fraction 1.02% and 0.34%, respectively, p < 0.05). Graph analysis revealed different connection fractions of specific channels. CONCLUSIONS: The impairment of visual attention varies among patients with absences and is associated with differences in EEG features, network activation, and involvement of the right frontal eye field. SIGNIFICANCE: Assessing the visual attention of patients with absences can be usefully employed in clinical practice for tailored advice to the individual patient.

Dataset of Speech Production in intracranial.Electroencephalography.

Speech production is an intricate process involving a large number of muscles and cognitive processes. The neural processes underlying speech production are not completely understood. As speech is a uniquely human ability, it can not be investigated in animal models. High-fidelity human data can only be obtained in clinical settings and is therefore not easily available to all researchers. Here, we provide a dataset of 10 participants reading out individual words while we measured intracranial EEG from a total of 1103 electrodes. The data, with its high temporal resolution and coverage of a large variety of cortical and sub-cortical brain regions, can help in understanding the speech production process better. Simultaneously, the data can be used to test speech decoding and synthesis approaches from neural data to develop speech Brain-Computer Interfaces and speech neuroprostheses.

Clinical Utility of Eye Tracking in Assessing Distractibility in Children with Neurological Disorders or ADHD: A Cross-Sectional Study.

This study aims to investigate distractibility quantified by recording and analyzing eye movements during task-irrelevant distraction in children with and without ADHD and in children with and without neurological disorders. Gaze behavior data and press latencies of 141 participants aged 6−17 that were collected during a computerized distraction paradigm with task-irrelevant stimuli (IDistrack) were analyzed. Children using attention-regulating medication were excluded from participation. Data were analyzed for subgroups that were formed based on the presence of neurological disorders and the presence of ADHD separately. Participants with ADHD and participants with neurological disorders spent less time fixating on the target stimuli compared to their peers without ADHD (p = 0.025) or their peers without neurological disorders (p < 0.001). Participants with and without ADHD had equal press latencies (p = 0.79). Participants with neurological disorders had a greater press latency compared to their typically developing peers (p < 0.001). Target fixation duration shows a significant association with parent-reported attention problems (r = −0.39, p < 0.001). We conclude that eye tracking during a distraction task reveals potentially valid clinical information that may contribute to the assessment of dysfunctional attentional processes. Further research on the validity and reliability of this paradigm is recommended.

Camera-Based Vital Signs Monitoring During Sleep - A Proof of Concept Study.

Polysomnography (PSG) is the current gold standard for the diagnosis of sleep disorders. However, this multi-parametric sleep monitoring tool also has some drawbacks, e.g. it limits the patient's mobility during the night and it requires the patient to come to a specialized sleep clinic or hospital to attach the sensors. Unobtrusive techniques for the detection of sleep disorders such as sleep apnea are therefore gaining increasing interest. Remote photoplethysmography using video is a technique which enables contactless detection of hemodynamic information. Promising results in near-infrared have been reported for the monitoring of sleep-relevant physiological parameters pulse rate, respiration and blood oxygen saturation. In this study we validate a contactless monitoring system on eight patients with a high likelihood of relevant obstructive sleep apnea, which are enrolled for a sleep study at a specialized sleep center. The dataset includes 46.5 hours of video recordings, full polysomnography and metadata. The camera can detect pulse and respiratory rate within 2 beats/breaths per minute accuracy 92% and 91% of the time, respectively. Estimated blood oxygen values are within 4 percentage points of the finger-oximeter 89% of the time. These results demonstrate the potential of a camera as a convenient diagnostic tool for sleep apnea, and sleep disorders in general.

It is All in the Wrist: Wearable Sleep Staging in a Clinical Population versus Reference Polysomnography.

PURPOSE: There is great interest in unobtrusive long-term sleep measurements using wearable devices based on reflective photoplethysmography (PPG). Unfortunately, consumer devices are not validated in patient populations and therefore not suitable for clinical use. Several sleep staging algorithms have been developed and validated based on ECG-signals. However, translation from these techniques to data derived by wearable PPG is not trivial, and requires the differences between sensing modalities to be integrated in the algorithm, or having the model trained directly with data obtained with the target sensor. Either way, validation of PPG-based sleep staging algorithms requires a large dataset containing both gold standard measurements and PPG-sensor in the applicable clinical population. Here, we take these important steps towards unobtrusive, long-term sleep monitoring. METHODS: We developed and trained an algorithm based on wrist-worn PPG and accelerometry. The method was validated against reference polysomnography in an independent clinical population comprising 244 adults and 48 children (age: 3 to 82 years) with a wide variety of sleep disorders. RESULTS: The classifier achieved substantial agreement on four-class sleep staging with an average Cohen's kappa of 0.62 and accuracy of 76.4%. For children/adolescents, it achieved even higher agreement with an average kappa of 0.66 and accuracy of 77.9%. Performance was significantly higher in non-REM parasomnias (kappa = 0.69, accuracy = 80.1%) and significantly lower in REM parasomnias (kappa = 0.55, accuracy = 72.3%). A weak correlation was found between age and kappa (ρ = -0.30, p<0.001) and age and accuracy (ρ = -0.22, p<0.001). CONCLUSION: This study shows the feasibility of automatic wearable sleep staging in patients with a broad variety of sleep disorders and a wide age range. Results demonstrate the potential for ambulatory long-term monitoring of clinical populations, which may improve diagnosis, estimation of severity and follow up in both sleep medicine and research.

Monitoring disease progression using high-density motor unit number estimation in amyotrophic lateral sclerosis.

In amyotrophic lateral sclerosis (ALS), progressive motor neuron loss causes severe weakness. Functional measurements tend to underestimate the underlying pathology because of collateral reinnervation. A more direct marker of lower motor neuron loss is of significant importance. We evaluated high-density motor unit number estimation (MUNE), as compared with the ALS Functional Rating Scale (ALSFRS) and maximal compound muscle action potential (CMAP) amplitude, for monitoring and classifying disease progression. MUNE showed good reproducibility (intraclass correlation coefficient = 0.86). MUNE showed a significantly greater decrease than the ALSFRS, the Medical Research Council (MRC) scale, and CMAP amplitude. Patients could be stratified into groups with rapidly or slowly progressive disease based on a decrement in MUNE at 4 months from baseline; ALSFRS score at 8 months was significantly lower in the rapidly progressive group. MUNE was sensitive to motor neuron loss early in the disease course when compared to other clinical measures. Stratification of patients based on a decrease in MUNE seems feasible.