Locked-in Syndrome Research Articles

Brain–computer interfaces: a new horizon in communication for locked-in syndrome

We here delve into the intricate and evolving concepts of brain death and consciousness, particularly at the end of life. We examine the historical and technological advancements that have influenced our understanding of death, such as mechanical ventilation and resuscitation techniques. These developments have challenged traditional definitions of death, leading to the concept of brain death, defined as the irreversible loss of all brain functions, including the brainstem. We emphasize that consciousness exists on a continuum, ranging from full alertness to deep coma and complete cessation of brain activity. It explores various disorders of consciousness, including coma, vegetative state, minimally conscious state, and locked-in syndrome, each with distinct characteristics and levels of awareness. Neuroimaging techniques, such as EEG, fMRI, and DTI, are highlighted for their crucial role in diagnosing and understanding disorders of consciousness. These techniques help to detect covert consciousness, assess brain activity, and predict recovery potential. The phenomenon of the “wave of death,” which includes a paradoxical surge in brain activity at the point of death, is also discussed. We address the challenges in defining and understanding both death and consciousness, calling for biologically grounded, ethically defensible, and culturally sensitive definitions. We advocate for standardized neuroimaging protocols, longitudinal studies, and the integration of artificial intelligence to improve diagnosis and treatment. In conclusion, the document underscores the importance of an integrated, evidence-based approach to understanding the gray zones between life and death, recognizing that consciousness and death are dynamic processes with both biological and experiential dimensions.

Patients with locked-in syndrome (LIS) pose unique ethical challenges for decision making, given the complexities of communication. However, some of these patients may retain the ability to participate in decisions regarding their care, including whether to continue life-sustaining treatment or pursue comfort care only. Following a deidentified case, this article has 2 central aims. First, it examines the ethical foundations of decision making and the complexities of capacity assessments for this patient population. Second, it offers a practical guide for neurologists to use when making such evaluations. This guide facilitates a way of communicating with patients with LIS so that clinicians may more systematically assess the patient's capacity to make their own consequential medical decisions.

The social life of locked-in syndrome (LIS) patients is significantly impacted by their difficulties to communicate. Consequently, researchers have started to explore how to decode intended speech from neural signals directly recorded from the cortex. The first studies in the late 2000s reported modest decoding accuracies. However, thanks to fast advances in machine learning, the most recent studies have reached decoding accuracies high enough to be optimistic about the clinical benefit of neural speech decoders in the near future. We first discuss the selection criteria for implanting a neural speech decoder in LIS patients, emphasizing the advantages and disadvantages associated with conditions such as brainstem stroke and amyotrophic lateral sclerosis. We examine the key design considerations for neural speech decoders, demonstrating how successful implantation requires careful optimization of multiple interrelated factors including language representation, cortical recording areas, neural features, training paradigms, and decoding algorithms. We then discuss current approaches and provide arguments for potential improvements in decoder design and implementation. Finally, we explore the crucial question of who should learn to use the neural speech decoder-the patient, the machine, or both. In conclusion, while neural speech decoders present promising avenues for improving communication for LIS patients, interdisciplinary efforts spanning neurorehabilitation, neuroscience, neuroengineering, and ethics are imperative to design future clinical trials.

Research indicates that locked-in syndrome (LIS) patients retain both consciousness and cognitive functions, despite their inability to perform voluntary muscle movements or communicate. Brain-Computer Interfaces (BCIs) provide a means for these patients to communicate, which is crucial, as the ability to interact with their environment has been shown to significantly enhance their wellbeing and quality of life. This paper presents an innovative approach to analyzing electroencephalogram (EEG) data from four LIS patients to assess their consciousness levels, referred to as normalized consciousness levels (NCL) in this study. It consists of extracting different features based on frequency, complexity, and connectivity measures to maximize the probability of correctly determining the patients' actual states given the inexistence of ground truth. The consciousness levels derived from this approach aim to improve our understanding of the patients' condition, which is vital in order to build effective communication systems. Despite considerable inter-patient variability, the findings indicate that the approach is effective in detecting neural markers of consciousness and in differentiating between states across the majority of patients. By accurately assessing consciousness, this research aims to improve diagnosis in addition to determining the optimal time to initiate communication with these non-communicative patients. It is important to note that consciousness is a complex and difficult concept to define. In this study, the term “consciousness level” does not refer to a medical definition. Instead, it represents a scale of NCL values ranging from 0 to 1 representing the likelihood of the patient being fully conscious (1) or not (0).

Intracortical brain-computer interfaces (iBCIs) for decoding intended speech have provided individuals with ALS and severe dysarthria an intuitive method for high-throughput communication. These advances have been demonstrated in individuals who are still able to vocalize and move speech articulators. Here, we decoded intended speech from an individual with longstanding anarthria, locked-in syndrome, and ventilator dependence due to advanced symptoms of ALS. We found that phonemes, words, and higher-order language units could be decoded well above chance. While sentence decoding accuracy was below that of demonstrations in participants with dysarthria, we are able to attain an extensive characterization of the neural signals underlying speech in a person with locked-in syndrome and through our results identify several directions for future improvement. These include closed-loop speech imagery training and decoding linguistic (rather than phonemic) units from neural signals in middle precentral gyrus. Overall, these results demonstrate that speech decoding from motor cortex may be feasible in people with anarthria and ventilator dependence. For individuals with longstanding anarthria, a purely phoneme-based decoding approach may lack the accuracy necessary to support independent use as a primary means of communication; however, additional linguistic information embedded within neural signals may provide a route to augment the performance of speech decoders.

This article functions as a companion to The BrainStem Stroke Atlas Part 1. Here we present an overview of the most prevalent brainstem stroke syndromes and use a color-coded atlas overlay to illustrate classic infarct patterns on MRI. These include lateral medullary syndrome (Wallenberg syndrome), medial medullary syndrome (Déjerine syndrome), Babinski-Nageotte syndrome, hemi-medullary syndrome (Reinhold syndrome), facial colliculus syndrome, cochlear and vestibular infarcts, medial pontine infarcts, and Foville syndrome, lateral pontine syndrome (Marie Foix syndrome), Locked-in syndrome, medial midbrain infarct (Claude and Benedikt syndrome), ventrolateral midbrain infarcts (Weber syndrome), and isolated medial longitudinal fasciculus infarcts. We provide insight into the clinical presentation of posterior circulation infarcts, including helpful localizing signs such as crossed sensory and crossed motor deficits.Learning Objectives: To describe the clinical presentation of classic brainstem stroke syndromes; apply an illustrated neuroanatomy atlas of the brainstem to case-based examples of brainstem infarcts; and interpret imaging findings of brainstem infarcts with greater anatomic specificity.

Modern palliative care requires innovative solutions to maintain communication and cognitive functions in patients with severe speech and motor impairments. The aim of the study is to analyze the possibilities of using digital neurotechnologies in palliative practice and determine the role of nurses in their implementation. A systematic review of international and Russian experience in using eye-tracking technologies, neurointerfaces and EEG monitoring was conducted.The systems Tobii Dynavox, EyeControl, GazeSpeak, Neurable, Emotiv and domestic developments iTracker and CEREBRO are considered. The results show that eye-tracking systems improve communication in patients with ALS and locked-in syndrome, neurofeedback helps reduce anxiety, and portable EEG monitoring allows objective assessment of consciousness state. The nurse plays a key role in training patients, interpreting data and coordinating the interdisciplinary team. Implementation of digital neurotechnologies requires special training of nursing staff and adaptation of palliative care infrastructure

Locked-in Syndrome (LIS) poses significant challenges for individuals experiencing complete paralysis, who must rely solely on eye and head movements and hearing to communicate. The main issue arises from the urgent need for a customized communication solution due to the severe limitations LIS patients encounter in interacting with their surroundings. This difficulty extends beyond physical constraints, greatly impacting their overall quality of life and psychological well-being. To address this complex challenge, we have developed an innovative approach that integrates advanced eye-tracking technology, Natural Language Processing (NLP) and Artificial Intelligence (AI). This holistic solution not only restores communication capabilities but also provides crucial support for the mental health and psychological well-being of LIS patients, offering a ray of hope for a better future. Beyond addressing communication challenges, our proposal also focuses on improving the mental health of LIS patients through interactive communication either with surrounding people or AI bots. Our solution, named “ParaEyes” utilizes webcam-detected eye movements to navigate the communication interface, employing real-time video image processing using Python. Additionally, users can engage with various AI bots, including ChatGPT, YouTube Bot and ParaEyes Visual Bot, based on their preferences. ParaEyes achieves a notably 2X faster average setup time and on average 10% higher accuracy compared to the open-source alternatives. This approach enhances communication skills and mental health support while also being inspired by ChatGPT’s robust measures to safeguard user data and ensure user privacy through tailored interactions and responsive functionalities.

Humans intensifying interactions with natural systems due to population growth and escalating energy, land and resources use, are accelerating a deep erosion of ecological functions and values upon which socioeconomic systems and human wellbeing depend (Rockström et al. 2023). This erosion is compounded by an ever tighter global interconnection of crises spanning multiple sociopolitical, technological and environmental domains, in what has been termed a polycrisis (Søgaard Jørgensen et al. 2023). The latter encompasses the nexus among human health, biodiversity, climate change, water availability and quality, food (in)security, and inequalities (IPBES 2024). A burgeoning field of research, the nexus polycrisis posits a rather existential question: are humans locked-in in an undesirable trajectory increasingly difficult to escape from? But more importantly, how can humans leverage their collective-action potential to prevent systemic risks and shift to more sustainable pathways at local and global scales? Indeed, the widespread policy consensus is no longer why or whether sustainability pathways are required, but how to trigger, operationalize and accelerate them with urgency and justice (UNEP 2021, UNEP 2021,IPCC 2023 ,IPBES 2024). In this presentation, we describe the methodological approach and preliminary results of a research initiative dealing with sustainability pathways in the European agrifood sector. The agrifood sector is exemplary of locked-in undesirable trajectories, with implications for the nexus polycrisis and across key production-consumption value chains (Lamine and Marsden 2023). Historically, agrifood technological innovation and high specialization have come at the cost of environmental degradation at multiple spatial scales, ultimately compromising the sustainability of land productivity and food production, and hence human wellbeing (IPBES 2024). This is likely due to a long-term process of post-war stabilization through the convergence of innovations, and technocratic strategies and policies at different levels of the agrifood system (e.g., production, processing, consumption), which generated the system’s “resistance to change” and lock-in at present (Conti et al. 2021, Williams et al. 2023). Using several cases of agrifood systems in 8 LTSER Platforms, our research focuses on two interrelated knowledge and data gaps. First, governance and politics are inherently implicated in any effort to foster sustainability pathways (Méndez et al. 2023). However, understanding the role of governance in fostering sustainability pathways remain underdeveloped in the literature, in particular around the more specific causal mechanisms underlying undesirable trajectories that become stuck in costly-to-escape social-ecological traps, in particular locked-in states (Lambert-Peck et al. 2024). Thus, we engage methodologically with the effect and feedback dynamics of different governance structures on locked-in social-ecological states. Second, policy mixes for tackling systemic lock-ins and transformative changes require a strong coordination to achieve the necessary directionality and coherence across policy areas affecting multiple socio-economic interests, environmental domains and cultural value systems. In turn, evidence-based coordination mechanisms and policy mixes require long-term research and monitoring programs based on harmonised sets of variables, in order to achieve meaningful understanding of policy impact over time (Pacheco-Romero et al. 2020). Here, we contribute to develop representative, efficient and feasible European long-term monitoring programs, with a focus on eLTER RI Standardised Observation system. Our particular focus is on the development of eLTER RI’s approach and protocol for the long-term monitoring of social-ecological governance in LTSER platforms, in coordination with other key protocols such as those focused on ecosystem services and land-use change. The role of standardised biophysical data and variables is also explored. We aim at revealing their potential to understand the role of key processes like ecological suppression in producing system-level social-ecological lock-ins that can propagate and cumulate across scales and induce systemic risks at biosphere level. We hope that this research may inform the study of social-ecological lock-ins in a more comparative and applicable way beyond agrifood systems and LTSER Platforms. We also hope that it can support transdisciplinary research processes in their efforts to explore and support co-produced solutions for collectively learning how to navigate away from and out undesirable trajectories of development in a safe and equitable way. At policy level, we aim at highlighting the potential of eLTER RI for informing multi-level policies and governance modes in their role to prevent local and global situations prone to systemic risks derived from lock-in phenomena (e.g., through the development of early warning systems to detect signs of lock-in at multiple scales). Finally, we show how this research is informing the foundation for a collaborative space aimed at mutual-learning and knowledge exchange between the LTSER Platforms network and the nascent network of Soil Health Living Labs under the Soil Mission.

A Case Report : Communication Training Utilizing Eye-Tracking Device in a Patient with Locked-in Syndrome

Locked-in syndrome (LIS) is an uncommon but devastating condition in which patients lose nearly all voluntary motor control—typically all four limbs and speech—yet remain fully conscious and can usually move their eyes vertically. It most often follows a brain-stem insult, classically a basilar-artery stroke. Because patients appear unresponsive, LIS is frequently mistaken for coma or a vegetative state; accurate diagnosis therefore hinges on high clinical suspicion backed by neuroimaging and electrophysiologic testing. There is no disease-modifying therapy, so management centers on rapid identification, meticulous critical-care support, and early, intensive rehabilitation. Communication aids—ranging from low-tech eye-blink codes to sophisticated eye-tracking devices and brain-computer interfaces—are vital for preserving autonomy and quality of life. Prognosis is generally guarded, but outcomes vary with the lesion’s cause, the degree of brain-stem damage, and the timeliness and breadth of rehabilitation. Current investigations into neuroplasticity, stem-cell approaches, and next-generation interfaces are beginning to offer cautious optimism for better long-term function. Throughout care, clinicians must balance medical advances with ethical considerations, ensuring respect for patient wishes, robust psychosocial support, and thoughtful end-of-life planning.

Visual imagery (VI) is a mental process in which an individual generates and sustains a mental image of an object without physically seeing it. Recent advancements in assistive technology have enabled the utilization of VI mental tasks as a control paradigm to design brain–computer interfaces (BCIs) capable of generating numerous control signals. This, in turn, enables the design of control systems to assist individuals with locked-in syndrome in communicating and interacting with their environment. This paper presents an electroencephalogram (EEG) dataset captured from 30 healthy native Arabic-speaking subjects (12 females and 18 males; mean age: 20.8 years; age range: 19–23) while they visually imagined the 28 letters of the Arabic alphabet. Each subject conducted 10 trials per letter, resulting in 280 trials per participant and a total of 8400 trials for the entire dataset. The EEG signals were recorded using the EMOTIV Epoc X wireless EEG headset (San Francisco, CA, USA), which is equipped with 14 data electrodes and two reference electrodes arranged according to the 10–20 international system, with a sampling rate of 256 Hz. To the best of our knowledge, this is the first EEG dataset that focuses on visually imagined Arabic letters.

Individuals with mobility impairments, including those affected by conditions such as Locked-in Syndrome (LIS), ALS, or stroke, face significant challenges in communication due to the loss of voluntary muscle control. This research presents an advanced eye- tracking system that enables individuals with restricted mobility to communicate using eye blinks. The proposed system leverages computer vision, artificial intelligence, and machine learning techniques to detect and interpret eye movements, converting them into textual communication. By integrating Haar cascades and adaptive language modeling, the system ensures precise detection and real-time processing, even on low-end devices. Additionally, the study highlights challenges such as accuracy, affordability, and accessibility while proposing solutions to improve usability. The research aims to empower individuals with mobility impairments, enhancing their independence and fostering social inclusion through assistive technology. Index Terms-Eye Tracking, Communication, Assistive Technology, Machine Learning, Mobility Impairment, Human-Computer Interaction.

Paralyzed people lack the ability to control muscle function in one or more muscle groups. The condition can be caused by stroke, ALS, multiple sclerosis, and many other diseases. Locked in Syndrome (LIS) is a form of paralysis where patients have lost control of nearly all voluntary muscles. These people are unable to control any part of their body, besides eye movement and blinking. Due to their condition, these people are unable to talk, text, and communicate in general. Even though people that have LIS are cognitively aware, their thoughts and ideas are locked inside of them. These people depend on eye blinks to communicate. They rely on nurses and caretakers to interpret and decode their blinking. Whenever LIS patients do not have a person to read their eye blinks available, they have no means of self-expression. Our project Blink to Text offers a form of independence to paralyzed people. The software platform converts eye blinks to text. Every feature of the software can be controlled by eye movement. Thus, the software can be independently operated by paralyzed people. The software can be run on any low-end computer. The software uses computer vision and Haar cascades to detect eye blinking and convert the motion into text. The program uses language modelling to predict the next words that the user might blink. INDEX TERMS: Eye-tracking, Deep learning, human machine interface.

ABSTRACT : Paralyzed people lack the ability to control muscle function in one or more muscle groups. The condition can be caused by stroke, ALS, multiple sclerosis, and many other diseases. Locked in Syndrome (LIS) is a form of paralysis where patients have lost control of nearly all voluntary muscles. These people are unable to control any part of their body, besides eye movement and blinking. Due to their condition, these people are unable to talk, text, and communicate in general. Even though people that have LIS are cognitively aware, their thoughts and ideas are locked inside of them. These people depend on eye blinks to communicate. They rely on nurses and caretakers to interpret and decode their blinking. Whenever LIS patients do not have a person to read their eye blinks available, they have no means of self-expression. Our project Blink to Text offers a form of independence to paralyzed people. The software platform converts eye blinks to text. Every feature of the software can be controlled by eye movement. Thus, the software can be independently operated by paralyzed people. The software can be run on any low end computer. The software uses computer vision and Haar cascades to detect eye blinking and convert the motion into text. The program uses language modelling to predict the next words that the user might blink. INDEX TERMS: Eye-tracking, Deep learning, human machine interface.

When Normonatremia Isn't Safe: Late Onser Osmotic Demyelination Causing Locked-In Syndrome in Alcoholic Cirrhosis with Wernicke's

First-in-Man Report of Acute Intra-Arterial Allogeneic Mesenchymal Stem Cell Therapy in Two Patients with Locked-In Syndrome Post-Thrombectomy: (P3-14.007)

Abstract Background/Aims We report a case series of four patients who presented to a single centre within a 9 month period in 2023/2024, with posterior circulation strokes (POCS) soon after starting treatment for giant cell arteritis (GCA). Previous studies indicate that POCS incidence in GCA ranges from 9% to 30%, significantly higher than anterior circulation strokes. Despite adherence to British Society for Rheumatology (BSR) guidelines, these patients experienced severe cerebrovascular events. This case series, along with findings from existing literature, prompted a reassessment of stroke risk factors and prevention strategies in GCA patients. Methods We collected patient data including demographics, cerebrovascular risk, steroid regimens, inflammatory markers (ESR, CRP), stroke types, treatment details, and clinical outcomes. All patients received high-dose prednisolone therapy in line with BSR guidelines. To contextualize our findings, we reviewed existing case series and literature discussing GCA-related strokes and their management. Results The cohort comprised four patients (three males, one female) aged between 56 and 80 years. All had extensive POCS. Three patients were smokers with cardiovascular risk factors, including hypertension and dyslipidemia, mirroring risk profiles in other reports of GCA-related strokes. Strokes occurred within 1 to 9 days of initiating steroid therapy. Clinical outcomes were poor: two patients developed locked-in syndrome, and all died; three between 9 and 15 days and one 135 days after the stroke. None were on anti-platelet therapy i.e., aspirin or clopidogrel. One was on a statin and antihypertensives. 3/4 patients had an average atherosclerotic cardiovascular disease risk of 21.87%, one was excluded given >75 years old. These findings are consistent with other case series. Elevated inflammatory markers, combined with pre-existing cardiovascular risks may exacerbate stroke severity and outcomes, even with steroid therapy. The data and literature suggest that current guidelines may be insufficient for preventing strokes in certain GCA patients. Conclusion This case series emphasizes the cerebrovascular risks associated with GCA, particularly in the vertebrobasilar system, despite guideline-directed therapy. There is currently no literature to measure risk in this cohort as conventional cardiovascular risk scoring will underestimate the risk given that GCA is an acute pro-inflammatory condition. Additional imaging like vertebral artery ultrasound/computed tomography angiography may identify posterior circulation involvement. These patients could potentially be targeted with more aggressive thrombotic reduction measures, for example-dual anti-platelet therapy for 14-21 days, prophylactic low molecular weight heparin, and high dose statin. More intensive immunosuppressant regimes may also be appropriate for those at extreme risk. Given the significant morbidity and mortality seen in GCA-related strokes, future research should focus on early identification of high-risk patients and exploring therapeutic interventions that may reduce cerebrovascular events in this vulnerable population. Disclosure F.A. Khan: None. Z.M. Iftikhar: None. A. Gani: None. B. Thompson: Honoraria; I have received honoraria / travel support from Abbvie, Chugai, Janssen, Lilly, Novartis and UCB. Grants/research support; (Grants) Novartis have funded a post-CCT ultrasound fellowship in Newcastle / Northumbria.

Introduction Locked-in syndrome (LIS) is a complex neurological condition characterised by paralysis of all four limbs and anarthria. Persons with LIS may communicate via eye blinks/low technology Augmentative and Alternative Communication devices (low tech AAC devices) or may use high technology Augmentative and Alternative Communication devices (high tech AAC devices). Our three objectives were: (1) to describe the distribution of communication modalities used by persons with LIS, (2) to describe the satisfaction of persons with LIS with their communication modality and social participation, and (3) to compare the characteristics and social participation among high tech AAC devices users versus low tech AAC devices or eye blinking users. Methods The questionnaires were sent by e-mail to persons with LIS. Data collected were communication modality, examination of communication ability, satisfaction with the communication modality and contribution of the communication modality to social participation. Results Of the 53 participants, their mean age was 52years, 43% used low tech AAC devices, 43% used high tech AAC devices and 13% communicated via eye blinking. Communication ability was examined in only half the participants. Participants' satisfaction with their communication modality in terms of ergonomics, rapidity, adaptability and functionality were 80, 67, 36 and 47% respectively. Participants who used high tech AAC devices had significantly better e-mail and social network access, could more often initiate conversations and had longer communication durations. Conclusion The communication abilities of persons with LIS should be examined as quickly as possible and repeated regularly. High tech AAC devices should be rapidly and systematically proposed.