The challenge of controlling an auditory BCI in the case of severe motor disability.

BACKGROUND: The locked-in syndrome (LIS), due to a lesion in the pons, impedes communication. This situation can also be met after some severe brain injury or in advanced Amyotrophic Lateral Sclerosis (ALS). In the most severe condition, the persons cannot communicate at all because of a complete oculomotor paralysis (Complete LIS or CLIS). This even prevents the detection of consciousness. Some studies suggest that auditory brain-computer interface (BCI) could restore a communication through a « yes-no¼ code. METHODS: We developed an auditory EEG-based interface which makes use of voluntary modulations of attention, to restore a yes-no communication code in non-responding persons. This binary BCI uses repeated speech sounds (alternating "yes" on the right ear and "no" on the left ear) corresponding to either frequent (short) or rare (long) stimuli. Users are instructed to pay attention to the relevant stimuli only. We tested this BCI with 18 healthy subjects, and 7 people with severe motor disability (3 "classical" persons with locked-in syndrome and 4 persons with ALS). RESULTS: We report online BCI performance and offline event-related potential analysis. On average in healthy subjects, online BCI accuracy reached 86% based on 50 questions. Only one out of 18 subjects could not perform above chance level. Ten subjects had an accuracy above 90%. However, most patients could not produce online performance above chance level, except for two people with ALS who obtained 100% accuracy. We report individual event-related potentials and their modulation by attention. In addition to the classical P3b, we observed a signature of sustained attention on responses to frequent sounds, but in healthy subjects and patients with good BCI control only. CONCLUSIONS: Auditory BCI can be very well controlled by healthy subjects, but it is not a guarantee that it can be readily used by the target population of persons in LIS or CLIS. A conclusion that is supported by a few previous findings in BCI and should now trigger research to assess the reasons of such a gap in order to propose new and efficient solutions. CLINICAL TRIAL REGISTRATIONS: No. NCT02567201 (2015) and NCT03233282 (2013).

Transient Locked-in Syndrome after Aneurysmal Subarachnoid Bleeding due to Spasm Hypoxemia?

How to cite this article: Finsterer J. Transient Locked-in Syndrome after Aneurysmal Subarachnoid Bleeding due to Spasm Hypoxemia? Indian J Crit Care Med 2024;28(1):86.

Who gets to decide?: Substitute decision making following severe brain injury with communication impairment.

Purpose: In our prior study (Malhi et al., 2021), we demonstrated that cognitive ability may be masked by communication impairments. We used binary choice (i.e., yes/no) neuropsychological tests to assess cognitive functioning in four patients with severe brain injury and communication impairments. In this study, we aimed to better understand the decision-making process of their substitute decision makers (SDMs). Methods: We interviewed SDMs - two SDMs were supporting patients in the minimally conscious state, one SDM was supporting a patient who had locked-in syndrome and was an augmentative communication user, and the last SDM was supporting a patient who was an alternative communication user. Results: SDMs were performing various roles ranging from making all decisions to simply being the vocal advocate (for the augmentative and alternative communication users). SDMs described heuristics they used to make decisions, and all identified auditory comprehension capabilities as being an important element for decision making. Conclusion: We argue that if mode of communication is established and utilized, and binary choice neuropsychological tests are used to ascertain cognitive functioning, SDMs may more confidently make low/medium stakes decisions based on the present condition and context, rather than solely on past wishes and values before capacity was in question.

Thinking without speaking: Neuropsychological testing with individuals who have communication impairments.

Cognitive ability may be masked by communication impairments. This study aimed to assess cognitive functioning using binary choice (i.e., yes/no) neuropsychological tests in patients with communication impairments. Four participants underwent neuropsychological testing. Two participants were in the minimally conscious state (MCS), one participant had locked-in syndrome and was an alternative communication user, and one participant was an augmentative communication user. There was better performance in all cognitive domains for the augmentative and alternative communication (AAC) users (who performed like the non-communication impaired normative data) compared to the MCS participants. However, using established yes/no communication methods, MCS participants performed above chance on a measure of memory and performance on measures of auditory comprehension was variable. Auditory comprehension appeared to be more influenced by working memory demands for the MCS participants than for the AAC users. For emotional functioning, the AAC users endorsed lower mood compared to the MCS participants. The results support the need to assess cognition, communication, as well as capacity in individuals with communication impairments with the consultation of a neuropsychologist and a speech-language pathologist.

The locked-in syndrome: The early French descriptions.

The classic 1966 description of locked-in syndrome was performed by Plum and Posner. Here, we revisit the world's first case report of this condition, which was presented in 1875 by Camille Darolles, an intern supervised by François Damaschino, at a monthly meeting of the Société Anatomique de Paris chaired by Jean-Martin Charcot. We also review the fascination of classic writers with this syndrome, including Alexandre Dumas, a genius of literature and known admirer of the medical sciences who, in the book "The Count of Monte Cristo" published in 1846, described a character with this condition.

Hyperhomocysteinemia induced locked-in syndrome in a young adult due to folic acid deficiency.

'Locked-in syndrome (LIS)' is a neurological disorder, often missed initially and can have grave consequences. A rare case of LIS caused due to folic acid deficiency-induced hyperhomocysteinemia is being described here. A 16-year-old boy presented with complaints of sudden onset weakness of all the four limbs with loss of voice for one day. All the tendon reflexes were increased, bilateral planters were extensor and sensory system was intact. Patient was conscious and responded to verbal commands by ocular movements in vertical direction. Hence, a diagnosis of LIS was made. Magnetic resonance imaging of the head revealed an acute infarct in ventral pons. Serum homocysteine level was elevated (20.65 µmol/l) and folic acid level was severely low (1.7 nmol/ml). Cause of LIS was found to be hyperhomocysteinemia induced stroke in the pons, related to folic acid deficiency. The patient was managed with antiplatelet agents and folic acid supplementation and was discharged subsequently. Recognition of LIS is important as casual remarks at bedside can severely traumatize an already paralyzed but conscious and awake patient. Folic acid deficiency can lead to hyperhomocysteinemia, which can cause strokes and even LIS. Prevention of hyperhomocysteinemia may possibly prevent such neurological disasters.

The current state of electrocorticography-based brain-computer interfaces.

Brain-computer interfaces (BCIs) provide a way for the brain to interface directly with a computer. Many different brain signals can be used to control a device, varying in ease of recording, reliability, stability, temporal and spatial resolution, and noise. Electrocorticography (ECoG) electrodes provide a highly reliable signal from the human brain surface, and these signals have been used to decode movements, vision, and speech. ECoG-based BCIs are being developed to provide increased options for treatment and assistive devices for patients who have functional limitations. Decoding ECoG signals in real time provides direct feedback to the patient and can be used to control a cursor on a computer or an exoskeleton. In this review, the authors describe the current state of ECoG-based BCIs that are approaching clinical viability for restoring lost communication and motor function in patients with amyotrophic lateral sclerosis or tetraplegia. These studies provide a proof of principle and the possibility that ECoG-based BCI technology may also be useful in the future for assisting in the cortical rehabilitation of patients who have suffered a stroke.

Disorders of consciousness terminology: history, evolution and future directions.

There has been a significant evolution of nomenclature with regards to classification of persons with disorders of consciousness (DoC) over the last 100 years. This paper provides a review of the evolution of this terminology with discussion of the advantages and disadvantages of historical and current terms. Recommendations for how this evolution should continue moving forward in the best interest of patients, their families, society, clinical care, and research will also be addressed. The taxonomy we choose, hopefully by international consensus, has multifaceted implications that go well beyond just a debate on nomenclature.

'Without A Key': A Classroom Case Study.

This case study uses a narrative focused on locked-in syndrome to engage upper-level undergraduate students with functional neuroanatomy, clinical neuroscience, and brain computer interface technology. Students 'diagnose' the etiology of a composite patient's symptoms using behavioral, neurological, neuroimaging, and electrophysiological test results. Students work both in small groups and as a class to develop analytical and communication skills by exploring the underpinnings, symptoms, and outcomes of locked-in syndrome and how behavioral and brain computer interface techniques could be used to improve quality of life in patients. A complete, detailed description of classroom implementation and the case narratives are available from the corresponding author or from cases.at.june@gmail.com.

Stable long-term BCI-enabled communication in ALS and locked-in syndrome using LFP signals.

Restoring communication for people with locked-in syndrome remains a challenging clinical problem without a reliable solution. Recent studies have shown that people with paralysis can use brain-computer interfaces (BCIs) based on intracortical spiking activity to efficiently type messages. However, due to neuronal signal instability, most intracortical BCIs have required frequent calibration and continuous assistance of skilled engineers to maintain performance. Here, an individual with locked-in syndrome due to brain stem stroke and an individual with tetraplegia secondary to amyotrophic lateral sclerosis (ALS) used a simple communication BCI based on intracortical local field potentials (LFPs) for 76 and 138 days, respectively, without recalibration and without significant loss of performance. BCI spelling rates of 3.07 and 6.88 correct characters/minute allowed the participants to type messages and write emails. Our results indicate that people with locked-in syndrome could soon use a slow but reliable LFP-based BCI for everyday communication without ongoing intervention from a technician or caregiver. NEW & NOTEWORTHY This study demonstrates, for the first time, stable repeated use of an intracortical brain-computer interface by people with tetraplegia over up to four and a half months. The approach uses local field potentials (LFPs), signals that may be more stable than neuronal action potentials, to decode participants' commands. Throughout the several months of evaluation, the decoder remained unchanged; thus no technical interventions were required to maintain consistent brain-computer interface operation.

Ethical Considerations in Ending Exploratory Brain-Computer Interface Research Studies in Locked-in Syndrome.

Brain-computer interface (BCI) is a promising technology for restoring communication in individuals with locked-in syndrome (LIS). BCI technology offers a potential tool for individuals with impaired or absent means of effective communication to use brain activity to control an output device such as a computer keyboard. Exploratory studies of BCI devices for communication in people with LIS are underway. Research with individuals with LIS presents not only technological challenges, but ethical challenges as well. Whereas recent attention has been focused on ethical issues that arise at the initiation of studies, such as how to obtain valid consent, relatively little attention has been given to issues at the conclusion of studies. BCI research in LIS highlights one such challenge: How to decide when an exploratory BCI research study should end. In this article, we present the case of an individual with presumed LIS enrolled in an exploratory BCI study. We consider whether two common ethical frameworks for stopping randomized clinical trials-equipoise and nonexploitation-can be usefully applied to elucidating researcher obligations to end exploratory BCI research. We argue that neither framework is a good fit for exploratory BCI research. Instead, we apply recent work on clinician-researcher fiduciary obligations and in turn offer some preliminary recommendations for BCI researchers on how to end exploratory BCI studies.

"Look at my classifier's result": Disentangling unresponsive from (minimally) conscious patients.

Given the fact that clinical bedside examinations can have a high rate of misdiagnosis, machine learning techniques based on neuroimaging and electrophysiological measurements are increasingly being considered for comatose patients and patients with unresponsive wakefulness syndrome, a minimally conscious state or locked-in syndrome. Machine learning techniques have the potential to move from group-level statistical results to personalized predictions in a clinical setting. They have been applied for the purpose of (1) detecting changes in brain activation during functional tasks, equivalent to a behavioral command-following test and (2) estimating signs of consciousness by analyzing measurement data obtained from multiple subjects in resting state. In this review, we provide a comprehensive overview of the literature on both approaches and discuss the translation of present findings to clinical practice. We found that most studies struggle with the difficulty of establishing a reliable behavioral assessment and fluctuations in the patient's levels of arousal. Both these factors affect the training and validation of machine learning methods to a considerable degree. In studies involving more than 50 patients, small to moderate evidence was found for the presence of signs of consciousness or good outcome, where one study even showed strong evidence for good outcome.

Functional integrity in children with anoxic brain injury from drowning.

Drowning is a leading cause of accidental injury and death in young children. Anoxic brain injury (ABI) is a common consequence of drowning and can cause severe neurological morbidity in survivors. Assessment of functional status and prognostication in drowning victims can be extremely challenging, both acutely and chronically. Structural neuroimaging modalities (CT and MRI) have been of limited clinical value. Here, we tested the utility of resting-state functional MRI (rs-fMRI) for assessing brain functional integrity in this population. Eleven children with chronic, spastic quadriplegia due to drowning-induced ABI were investigated. All were comatose immediately after the injury and gradually regained consciousness, but with varying ability to communicate their cognitive state. Eleven neurotypical children matched for age and gender formed the control group. Resting-state fMRI and co-registered T1-weighted anatomical MRI were acquired at night during drug-aided sleep. Network integrity was quantified by independent components analysis (ICA), at both group- and per-subject levels. Functional-status assessments based on in-home observations were provided by families and caregivers. Motor ICNs were grossly compromised in ABI patients both group-wise and individually, concordant with their prominent motor deficits. Striking preservations of perceptual and cognitive ICNs were observed, and the degree of network preservation correlated (ρ = 0.74) with the per-subject functional status assessments. Collectively, our findings indicate that rs-fMRI has promise for assessing brain functional integrity in ABI and, potentially, in other disorders. Furthermore, our observations suggest that the severe motor deficits observed in this population can mask relatively intact perceptual and cognitive capabilities. Hum Brain Mapp 38:4813-4831, 2017. © 2017 Wiley Periodicals, Inc.

Assessment of needs, psychological impact and quality of life in families of patients with locked-in syndrome.

OBJECTIVE: Family needs of patients with acquired brain injuries have been studied for about three decades. In this study, we assessed the needs, the quality of life and the psychological state of relatives of patients with locked-in syndrome (LIS). DESIGN: A survey was carried out using the family needs' questionnaire (FNQ). SUBJECTS AND METHODS: Thirty relatives of patients with LIS fully completed the FNQ. RESULTS: The most important need reported by families corresponded to the need for medical information. The highest percentage of satisfaction (66%) was also observed for this need. Among the needs for information, specifically, the most important for LIS' relatives was to know that the patient's needs and wishes were respected by the professional staff, which were fulfilled in 93% of the sample. The need for emotional support was the least important and had the lowest percentage of satisfaction (55%). The number of met/unmet needs correlated with the quality of life of the families. Most of the relatives reported anxiety feelings and depressive thoughts. CONCLUSIONS: Receiving accurate medical information is the most important need for family of patients with LIS and their quality of life is correlated with the fulfilment of their needs.

Probing consciousness in a sensory-disconnected paralyzed patient.

BACKGROUND: Diagnosis of consciousness can be very challenging in some clinical situations such as severe sensory-motor impairments. CASE STUDY: We report the case study of a patient who presented a total "locked-in syndrome" associated with and a multi-sensory deafferentation (visual, auditory and tactile modalities) following a protuberantial infarction. RESULT: In spite of this severe and extreme disconnection from the external world, we could detect reliable evidence of consciousness using a multivariate analysis of his high-density resting state electroencephalogram. This EEG-based diagnosis was eventually confirmed by the clinical evolution of the patient. CONCLUSION: This approach illustrates the potential importance of functional brain-imaging data to improve diagnosis of consciousness and of cognitive abilities in critical situations in which the behavioral channel is compromised such as deafferented locked-in syndrome.

Reverse Locked-In Syndrome.

BACKGROUND: Basilar artery occlusion can cause locked-in syndrome, which is characterized by quadriplegia, anarthria, and limited communication via eye movements. Here, we describe an uncommon stroke syndrome associated with endovascular recanalization of the top of the basilar artery: "reverse locked-in syndrome." METHODS: We report the case of a patient with atypical neurological deficits caused by acute ischemic stroke of the midbrain tegmentum. We perform neuroanatomic localization of the patient's infarcts by mapping the magnetic resonance imaging (MRI) data onto a brainstem atlas. RESULTS: A 61-year-old man presented with acute coma and quadriplegia due to top of the basilar artery occlusion. He underwent emergent endovascular thrombectomy, with successful recanalization of the basilar artery at 4 h and 43 min post-ictus. The patient regained consciousness and purposeful movement in all four extremities, but the post-procedure neurological examination demonstrated bilateral ptosis with complete pupillary and oculomotor paralysis. MRI revealed infarction of the bilateral oculomotor nuclei in the midbrain tegmentum. At 9-month follow-up, he had anisocoria and dysconjugate gaze, but was living at home and required minimal assistance in performing all activities of daily living. CONCLUSIONS: Since the patient's deficits were the exact opposite of those described in locked-in syndrome, we propose the term "reverse locked-in syndrome" to describe this neurological entity characterized by bilateral ptosis, non-reactive pupils, and ophthalmoplegia with preservation of consciousness and extremity motor function.

Functional MRI for Assessment of the Default Mode Network in Acute Brain Injury.

BACKGROUND: Assessment of the default mode network (DMN) using resting-state functional magnetic resonance imaging (fMRI) may improve assessment of the level of consciousness in chronic brain injury, and therefore, fMRI may also have prognostic value in acute brain injury. However, fMRI is much more challenging in critically ill patients because of cardiovascular vulnerability, intravenous sedation, and artificial ventilation. METHODS: Using resting-state fMRI, we investigated the DMN in a convenience sample of patients with acute brain injury admitted to the intensive care unit. The DMN was classified dichotomously into "normal" and "grossly abnormal." Clinical outcome was assessed at 3 months. RESULTS: Seven patients with acute brain injury (4 females; median age 37 years [range 14-71 years]; 1 traumatic brain injury [TBI]; 6 non-TBI) were investigated by fMRI a median of 15 days after injury (range 5-25 days). Neurological presentation included 2 coma, 1 vegetative state/unresponsive wakefulness syndrome (VS/UWS), 3 minimal conscious state (MCS) minus, and 1 MCS plus. Clinical outcomes at 3 months included 1 death, 1 VS/UWS, 1 MCS plus, and 4 conscious states (CS; 1 modified Rankin Scale 0; 2 mRS 4; 1 mRS 5). Normal DMNs were seen in 4 out of 7 patients (1 MCS plus, 3 CS at follow-up). CONCLUSIONS: It is feasible to assess the DMN by resting-state fMRI in patients with acute brain injury already in the very early period of intensive care unit admission. Although preliminary data, all patients with a preserved DMN regained consciousness levels at follow-up compatible with MCS+ or better.

Locked-in syndrome in a patient with acute obstructive hydrocephalus, caused by large unruptured aneurysm of the basilar artery (BA).

We describe a case of acute obstructive hydrocephalus as a consequence of compression of the brainstem by a large aneurysm of the basilar artery (BA) in a 62-year-old male. After the insertion of the ventriculoperitoneal shunt (VPS), we encountered the "locked-in syndrome" clinical condition. "Locked-in syndrome" is a clinical state characterized by quadriplegia and anarthria with preserved consciousness, most commonly caused by ischemia in the ventral part of pons.

Augmentative and Alternative Communication Effects on Quality of Life in Patients with Locked-in Syndrome and Their Caregivers.

BACKGROUND: The aim of this study was to evaluate the impact of the augmentative and alternative communication system on anxiety and depression performances and the quality of life (QoL) of patients who have the locked-in syndrome (LIS) and that of their caregivers. METHOD: We enrolled 15 patients and their principal caregivers. The assessment consisted of the administration of the employed Short Form-36 Questionnaire for the assessment of QoL, the Hamilton Anxiety Rating Scale (HAM-A) for anxiety, and the Beck Depression Inventory for depression. RESULTS: We compared the clinical test at baseline (T0) and after 3 months (T1) for each group (patients and caregivers). In the patients group, we observed a significant difference in all clinical test scores. In the caregivers group, we observed a significant difference for HAM-A (P = .003), vitality (P < .001), social activity (P < .001), social role functioning (P < .001), and emotional role functioning (P < .001) and no significant differences for other clinical scores. CONCLUSION: The possibility of being able to communicate allows patients with the LIS to recuperate a affective contact with their caregivers, improving global family atmosphere.

Locked Out.

Brain-computer interfaces (BCIs) can enable communication for persons in severe paralysis including locked-in syndrome (LIS); that is, being unable to move or speak while aware. In cases of complete loss of muscle control, termed "complete locked-in syndrome," a BCI may be the only viable solution to restore communication. However, a widespread ignorance regarding quality of life in LIS, current BCIs, and their potential as an assistive technology for persons in LIS, needlessly causes a harmful situation for this cohort. In addition to their medical condition, these persons also face social barriers often perceived as more impairing than their physical condition. Through social exclusion, stigmatization, and frequently being underestimated in their abilities, these persons are being locked out in addition to being locked-in. In this article, we (1) show how persons in LIS are being locked out, including how key issues addressed in the existing literature on ethics, LIS, and BCIs for communication, such as autonomy, quality of life, and advance directives, may reinforce these confinements; (2) show how these practices violate the United Nations Convention on the Rights of Persons with Disabilities, and suggest that we have a moral responsibility to prevent and stop this exclusion; and (3) discuss the role of BCIs for communication as one means to this end and suggest that a novel approach to BCI research is necessary to acknowledge the moral responsibility toward the end users and avoid violating the human rights of persons in LIS.