RARE DISEASE
Locked-in syndrome
Locked-in syndrome
Locked-in syndrome
Synonyms: LIS, Pseudocoma
Synonyms: LIS, Pseudocoma
Synonyms: LIS, Pseudocoma
Drug discovery
0
drugs
With orphan designations
Overview
Locked-in syndrome (LiS) is a rare neurological disorder marked by complete quadriplegia, cranial nerve paralysis, and anarthria, with preserved consciousness and vertical eye movements. Typically caused by pontine strokes (ischemic or hemorrhagic), it results from damage to corticospinal/corticobulbar tracts. Diagnosis relies on clinical assessment of eye-based communication and neuroimaging (MRI/CT). Management focuses on supportive care, communication aids, and preventing complications like pneumonia or contractures. Cognitive function remains intact, enabling patient autonomy in decision-making [1][6][9][11].
Burden
Mortality: 30% mortality rate; median survival 1.9 years for deceased patients [4][12].
Disability: 88% require full-time care ≥2 years post-onset; only 3% achieve full motor recovery [12][14].
Psychosocial impact: High rates of depression, communication barriers, and caregiver dependency [4][8][18].
Therapies
Acute care: Tracheostomy, gastrostomy, and respiratory therapy [3][18].
Rehabilitation: Physical/occupational therapy to preserve motor function; speech therapy for eye-based communication codes [1][8][13].
Technology: Eye-tracking devices, brain-computer interfaces, and adaptive switches to restore interaction [1][3][9].
Categories: rare neurological diseases
Research Papers
415 drug discovery papers about Locked-in syndrome, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
415 drug discovery papers about Locked-in syndrome, with 1 first-in-class emerging drug candidates forecasted to outperform the average preclinical success rate. Recent publications:
2026-06-09 | Post-infectious CNS Vasculitis Presenting With Stroke, New Onset Status Epilepticus, and Reversible Locked-in Syndrome (P2-19.009)
To describe a rare case of post-infectious CNS vasculitis presenting as acute ischemic stroke, new-onset status epilepticus, and locked-in syndrome which showed remarkable recovery after immunomodulatory therapy.
2026-06-09 | Transcranial Direct Current Stimulation as an Adjunct Intervention to Acute Neurorehabilitation in Locked-in Syndrome: A Case Report (P4-14.012)
To describe the feasibility, safety, and outcomes of intensive, team-based neurorehabilitation incorporating transcranial direct current stimulation (tDCS) in acute locked-in syndrome (LIS).
2026-03-28 | Brainstem control of sleep, wakefulness, alertness, and consciousness.
The brainstem is crucial for maintaining wakefulness, sleep regulation, and consciousness. It orchestrates alertness through the ascending reticular activating system, integrating sensory information and projecting to the cortex. Consciousness emerges from intricate interactions involving the brainstem, though the brainstem alone does not generate consciousness. Clinical syndromes resulting from brainstem lesions highlight distinctions between wakefulness, alertness, and consciousness. Disorders such as sleep paralysis, parasomnias, vegetative state, minimally conscious state, coma, and locked-in syndrome illustrate how brainstem dysfunction affects consciousness and behavior. Unique states like lucid dreaming and hypnagogia further demonstrate brainstem contributions, revealing a distinct form of internally directed consciousness ("consciousness II"). Understanding these phenomena provides insights into the brainstem's essential role in the complex neural network underlying human consciousness and cognitive function.
2025-12-10 | The Dissociation Structure of Consciousness: A Refutation of Foundational Theories and an Experimental Roadmap for the "How" Problem
Neuroscience remains blocked at the "How" Barrier due to a fundamental conceptual error: the conflationof Wakefulness (Activation) with Subjective Experience (Content), treating consciousness as an indivisibleunitary entity. The field has failed to progress by ignoring clinical evidence that consciousness is adissociable structure.This document rigorously proposes the Consciousness Dissociation Structure into two independent andanatomically separable components: Activation (Thalamic-Brainstem Axis) and Content (Cortical). Basedon the irrefutable survival hierarchy and clinical data (PVS, Locked-in Syndrome), this structure refutes themethodological failures of IIT and the descriptive incompleteness of GWT.We propose the BrainEx Principle as the unique and necessary methodology to causally isolate and testthis Dissociation mechanism. The success of this experimental roadmap initiates a clinical revolution,enabling the restoration of consciousness in non-responsive states (coma) and targeted treatments forASD, Depression, and memory diseases, by modulating the content-generating mechanism.Most crucially, this research provides the essential and original architecture for the development of trueArtificial General Intelligence (AGI), ending the scientific debate on mind-body dualism and ushering in theAge of Causality in neuroscience.
2025-11-01 | Abstract 305: Cyclical nightmare, Recurrent basilar occlusion culminating in locked‐in syndrome
Background Basilar artery occlusion (BAO) is a rare but devastating cause of stroke, representing only 1% of cases but with mortality rates up to 95% if untreated. Diagnosis is often delayed due to nonspecific symptoms, which may range from dizziness to quadriplegia. Management remains challenging; recent trials support endovascular treatment (EVT), though with risks of complications and hemorrhage. Data on recurrent BAO resistant to multimodal therapies are especially limited. We present a patient with recurrent BAO and complete recovery between events, whose final episode resulted in locked‐in syndrome. Case: A 68‐year‐old man presented with sudden left arm and leg ataxia, right facial droop, and mild dysarthria (NIHSS 4). Initial CT was negative, and IV thrombolysis was administered. Hours later, symptoms worsened (NIHSS 17) and CTA revealed basilar occlusion. Mechanical thrombectomy (TICI 3c) was performed, followed by dual antiplatelet therapy. MRI showed a small left pontine infarct. Stroke workup was unrevealing, and he was discharged on dual antiplatelets and statin, returning to work without deficits. Outpatient CTA demonstrated improvement in basilar stenosis. Platelet testing revealed aspirin non‐responsiveness, so he remained on clopidogrel monotherapy. Three months later, he re‐presented with dysarthria, severe ataxia, and left‐sided weakness (NIHSS 6). CTA showed persistent basilar occlusion with progression. IV thrombolysis was given, but no EVT was pursued. MRI revealed right pontine and multifocal left pontine infarcts. Cilostazol was added, and he was discharged NIHSS 0, with mRS 2 on follow‐up. Four months later, he presented with generalized weakness, dysarthria, and gait impairment (NIHSS 5). CTA showed near‐occlusive basilar stenosis. IV thrombolysis was administered, but NIHSS rapidly worsened to 13, with plegia, dysconjugate gaze, and obtundation. EVT was not attempted due to chronicity and near‐total occlusion. MRI demonstrated bilateral pontine infarction with hemorrhage. He became locked‐in, with only vertical gaze and blinking. During hospitalization, extensive deep vein thromboses were discovered in both lower and upper extremities, and he was transitioned to long‐term anticoagulation. Discussion Basilar occlusions can be devastating as they are associated with locked‐in syndrome. Current studies have shown a benefit of thrombectomy in BAOs, but the best management remains uncertain, especially in relation to recurrent thrombosis when both medical and surgical avenues have been exhausted. This case highlights the difficulty of treating BA stenosis in that, even after successful recanalization, BAO can recur despite maximal medical therapy with multiple platelet inhibition strategies. It questions the efficacy of antiplatelet strategies alone for preventing recurrent basilar artery occlusion and may suggest that other strategies (anticoagulation or a combination of antiplatelet with anticoagulation) may be needed to prevent BAO.
2026-06-09 | Post-infectious CNS Vasculitis Presenting With Stroke, New Onset Status Epilepticus, and Reversible Locked-in Syndrome (P2-19.009)
To describe a rare case of post-infectious CNS vasculitis presenting as acute ischemic stroke, new-onset status epilepticus, and locked-in syndrome which showed remarkable recovery after immunomodulatory therapy.
2026-06-09 | Transcranial Direct Current Stimulation as an Adjunct Intervention to Acute Neurorehabilitation in Locked-in Syndrome: A Case Report (P4-14.012)
To describe the feasibility, safety, and outcomes of intensive, team-based neurorehabilitation incorporating transcranial direct current stimulation (tDCS) in acute locked-in syndrome (LIS).
2026-03-28 | Brainstem control of sleep, wakefulness, alertness, and consciousness.
The brainstem is crucial for maintaining wakefulness, sleep regulation, and consciousness. It orchestrates alertness through the ascending reticular activating system, integrating sensory information and projecting to the cortex. Consciousness emerges from intricate interactions involving the brainstem, though the brainstem alone does not generate consciousness. Clinical syndromes resulting from brainstem lesions highlight distinctions between wakefulness, alertness, and consciousness. Disorders such as sleep paralysis, parasomnias, vegetative state, minimally conscious state, coma, and locked-in syndrome illustrate how brainstem dysfunction affects consciousness and behavior. Unique states like lucid dreaming and hypnagogia further demonstrate brainstem contributions, revealing a distinct form of internally directed consciousness ("consciousness II"). Understanding these phenomena provides insights into the brainstem's essential role in the complex neural network underlying human consciousness and cognitive function.
2025-12-10 | The Dissociation Structure of Consciousness: A Refutation of Foundational Theories and an Experimental Roadmap for the "How" Problem
Neuroscience remains blocked at the "How" Barrier due to a fundamental conceptual error: the conflationof Wakefulness (Activation) with Subjective Experience (Content), treating consciousness as an indivisibleunitary entity. The field has failed to progress by ignoring clinical evidence that consciousness is adissociable structure.This document rigorously proposes the Consciousness Dissociation Structure into two independent andanatomically separable components: Activation (Thalamic-Brainstem Axis) and Content (Cortical). Basedon the irrefutable survival hierarchy and clinical data (PVS, Locked-in Syndrome), this structure refutes themethodological failures of IIT and the descriptive incompleteness of GWT.We propose the BrainEx Principle as the unique and necessary methodology to causally isolate and testthis Dissociation mechanism. The success of this experimental roadmap initiates a clinical revolution,enabling the restoration of consciousness in non-responsive states (coma) and targeted treatments forASD, Depression, and memory diseases, by modulating the content-generating mechanism.Most crucially, this research provides the essential and original architecture for the development of trueArtificial General Intelligence (AGI), ending the scientific debate on mind-body dualism and ushering in theAge of Causality in neuroscience.
2025-11-01 | Abstract 305: Cyclical nightmare, Recurrent basilar occlusion culminating in locked‐in syndrome
Background Basilar artery occlusion (BAO) is a rare but devastating cause of stroke, representing only 1% of cases but with mortality rates up to 95% if untreated. Diagnosis is often delayed due to nonspecific symptoms, which may range from dizziness to quadriplegia. Management remains challenging; recent trials support endovascular treatment (EVT), though with risks of complications and hemorrhage. Data on recurrent BAO resistant to multimodal therapies are especially limited. We present a patient with recurrent BAO and complete recovery between events, whose final episode resulted in locked‐in syndrome. Case: A 68‐year‐old man presented with sudden left arm and leg ataxia, right facial droop, and mild dysarthria (NIHSS 4). Initial CT was negative, and IV thrombolysis was administered. Hours later, symptoms worsened (NIHSS 17) and CTA revealed basilar occlusion. Mechanical thrombectomy (TICI 3c) was performed, followed by dual antiplatelet therapy. MRI showed a small left pontine infarct. Stroke workup was unrevealing, and he was discharged on dual antiplatelets and statin, returning to work without deficits. Outpatient CTA demonstrated improvement in basilar stenosis. Platelet testing revealed aspirin non‐responsiveness, so he remained on clopidogrel monotherapy. Three months later, he re‐presented with dysarthria, severe ataxia, and left‐sided weakness (NIHSS 6). CTA showed persistent basilar occlusion with progression. IV thrombolysis was given, but no EVT was pursued. MRI revealed right pontine and multifocal left pontine infarcts. Cilostazol was added, and he was discharged NIHSS 0, with mRS 2 on follow‐up. Four months later, he presented with generalized weakness, dysarthria, and gait impairment (NIHSS 5). CTA showed near‐occlusive basilar stenosis. IV thrombolysis was administered, but NIHSS rapidly worsened to 13, with plegia, dysconjugate gaze, and obtundation. EVT was not attempted due to chronicity and near‐total occlusion. MRI demonstrated bilateral pontine infarction with hemorrhage. He became locked‐in, with only vertical gaze and blinking. During hospitalization, extensive deep vein thromboses were discovered in both lower and upper extremities, and he was transitioned to long‐term anticoagulation. Discussion Basilar occlusions can be devastating as they are associated with locked‐in syndrome. Current studies have shown a benefit of thrombectomy in BAOs, but the best management remains uncertain, especially in relation to recurrent thrombosis when both medical and surgical avenues have been exhausted. This case highlights the difficulty of treating BA stenosis in that, even after successful recanalization, BAO can recur despite maximal medical therapy with multiple platelet inhibition strategies. It questions the efficacy of antiplatelet strategies alone for preventing recurrent basilar artery occlusion and may suggest that other strategies (anticoagulation or a combination of antiplatelet with anticoagulation) may be needed to prevent BAO.
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