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:
categories:
Small molecules
cell therapies
2025-05-23 | When the Body Fails but the Mind Remains: Understanding 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.
2012-07-20 | Motor recovery mechanism in a quadriplegic patient with locked-in syndrome.
Locked-in syndrome (LIS) is a rare neurologic condition caused by bilateral pontine lesions. Quadriplegia is one of the most serious clinical manifestations in patients with LIS. However, little is known about the motor recovery mechanism of quadriplegia in patients with LIS. In the current study, we present with a quadriplegic patient with bilateral pontine infarcts, whose motor function appeared to be reorganized into the peri-infarct areas of the infarcted pons, as demonstrated by diffusion tensor tractography (DTT). A 60-year-old was diagnosed as LIS due to bilateral pontine infarcts 6 years ago. The patient presented with complete paralysis of all four extremities at onset. After slow motor recovery, the patient was able to move all joint muscles against gravity and demonstrated some fine motor activity at the time of DTT scanning (6 years after onset). Results of DTTs for the corticospinal tract (CST) in both hemispheres showed that the CSTs originated from the primary motor cortex, descended along the known CST pathway, and passed through lateral areas of infarcts in the pons. Therefore, motor function of the four extremities of this patient appears to have been recovered by the CST, which passed through the lateral areas to the pontine infarcts.
1980-08-01 | Hyperbaric Chamber Treatment for 'Locked-in' Syndrome
The "locked-in" syndrome described by Plum and Posner is characterized by quadriplegia and bulbar and facial paralysis.1Pathologic findings are those of infarction of the ventral pons bilaterally, usually due to thrombotic or embolic occlusion of the basilar artery.2-3We describe a patient in whom the locked-in syndrome developed after operation to establish an aortocoronary bypass and who subsequently recovered completely with hyperbaric oxygenation. It is likely that air embolization was the cause of the locked-in syndrome in this patient. A 54-year-old man with a history of two myocardial infarctions and hypertension was hospitalized with crushing substernal chest pain. Coronary angiography revealed severe coronary atherosclerosis. On two occasions during aortocoronary bypass surgery, the surgeon noted small air bubbles in the grafts, and evacuation was attempted by aspiration through a 25-gauge needle. Each time the air bubbles were observed, cardiac action deteriorated, and on the
proteins
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.
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.
2025-04-01 | An Introduction to Locked-in-Syndrome: Diagnosis, Care, and Outcomes
The chapter deals with an uncommon neurological disorder called Locked-In Syndrome (LIS), characterized by total body paralysis with preserved consciousness. Diagnosis of LIS is rather challenging and often protracted, due to its similarity to disorders of consciousness. Once properly diagnosed, rehabilitation is important for establishing a better prognosis and offering the patients with LIS a chance for an improved outcome. This chapter emphasizes the need for early and intense motor therapy, cognitive support, and emotional support to improve functionality and reduce mortality. Despite physical limitations of a serious nature, many LIS patients report a quite high quality of life, often adapting to their situation over time. However, psychological and emotional burdens remain high for both patients and caregivers. Unmet needs, particularly about the emotional support of caregivers, must be addressed with the purpose of overall improvement of the well-being of such patients. Finally, the chapter addresses ethical considerations pertinent to end-of-life decisions in LIS, where respect for patient autonomy is considered paramount, factoring in relevant cultural contexts. Integrating advances in technology, rehabilitative care, and ethical frameworks, this chapter gives further insight into how management and care for individuals with LIS are evolving.
2024-11-13 | From locked-in syndrome to recovery: thrombolysis success in bilateral pontine infarction with 'heart appearance' sign.
Locked-in syndrome (LIS) is a severe neurological condition characterised by tetraplegia and anarthria, with preserved consciousness and vertical eye movements. It often results from bilateral pontine infarctions, which sometimes demonstrate a characteristic 'heart appearance' sign on MRI. We report a case of a mid-60s female with acute onset LIS and dyspnoea. Clinical examination suggested a pontine infarction, later confirmed by an MRI scan revealing a characteristic 'heart appearance' on axial diffusion-weighted imaging sequence. As the patient presented within the thrombolysis time window and had no contraindications, alteplase was administered. The patient demonstrated an exceptional neurological improvement within 10 days of hospitalisation, transitioning from tetraplegia and anarthria to moving all four limbs against gravity and mild dysarthria. She was subsequently discharged to a rehabilitation centre. This case underscores the efficacy of timely thrombolysis in severe pontine strokes and highlights the diagnostic significance of MRI findings in such cases.
2011-05-12 | Locked in and out: a case of emerging basilar artery obstruction secondary to vertebral artery dissection thrombolysed with intravenous rt-PA
The authors present a case in which intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) potentially saved a young man from locked-in syndrome or life threatening consequences. The patient presented with acute stroke secondary to vertebral artery dissection and was treated with intravenous rt-PA. There were no post thrombolysis complications and the patient left hospital with mild neurological symptoms. Our report suggests that in cases of acute posterior circulation stroke due to arterial dissection, treatment with intravenous thrombolysis is safe, practicable and effective.
small molecules
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.
2025-11-01 | 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.
2024-09-01 | Infection related ischemic stroke presenting as partial locked-in syndrome
Ischemic stroke in young adults have a multiplicity of possible causes making it a diagnostic challenge. Inflammatory and infectious diseases must be considered, alongside the most common etiologies and risk factors. We present a case of a 34-year-old male, with no known vascular risk factors, admitted to a stroke unit with partial locked-in syndrome characterized by quadriplegia and anarthria but with sustained horizontal bilateral gaze, with imaging study showing a pontine acute ischemic lesion. Diagnostic workup revealed a positive serum serology for HIV and Treponema pallidum. Even though cerebrospinal fluid showed negative Treponema pallidum serology, both meningovascular syphilis and HIV vasculopathy were considered potential and/or cumulative causative agents. The patient showed dramatic neurologic improvement after penicillin and antiretroviral treatment were started, as well as intensive physical therapy, being able to ambulate at hospital discharge. The importance of this report rests not only on the rarity of Partial locked-in syndrome and the above-mentioned stroke etiologies but is also an example of the rehabilitation potential of younger adults.
2024-07-19 | Locked-In Syndrome: A Rare Manifestation of Neuropsychiatric Lupus.
Neuropsychiatric systemic lupus erythematosus (SLE) is a rare condition that has a multitude of mechanisms resulting in the emergence of variable clinical presentations. We describe a peculiar case of a 33-year-old female with a history of SLE presented with two weeks of fever, headache, and vomiting. On admission, she became obtunded and was emergently intubated. Initial lumbar puncture revealed pleocytosis (46% neutrophils, 320 corrected nucleated cells/μL), elevated protein (244 mg/dL; normal, 15-40 mg/dL), normal glucose (63 mg/dL), and negative cultures. Empiric acyclovir, ampicillin, ceftriaxone, and vancomycin were initiated without clinical improvement. Neurological examination was notable for limited ability to follow commands, vertical nystagmus, horizontal gaze palsy, diffuse hyperreflexia, and quadriparesis. Electroencephalogram (EEG) was consistent with diffuse encephalopathy. Brain magnetic resonance imaging demonstrated restricted diffusion and contrast enhancement in the posterior and central pons with edema. A cerebral angiogram showed no signs of vasculitis. Treatment with intravenous (IV) methylprednisolone 1 g and IV immunoglobulin 2 g/kg was initiated for five days. Despite these interventions, no discernible clinical improvement was observed, prompting the commencement of 500 mg/m2 cyclophosphamide and daily maintenance of IV methylprednisolone at 2 mg/kg. A repeat MRI three weeks later revealed a marked reduction in the size of the lesion involving the pons. The patient also improved clinically over the month with successful extubation, complete return in mental capabilities, and the ability to ambulate short distances with assistance.
gene therapies
2025-04-01 | For a Better Life
Born into a very modest family, leaving his native Portugal at the age of 13, Julio hoped to find a simpler and more peaceful life in France than what he could have hoped for in his modest village. He began school, then work, earning a living and enjoying his youth. But, with no warning, just before his 22nd birthday, he was devastated by a Cerebral Vascular Accident which left him completely paralysed and mute: Locked-in Syndrome. What followed was a long and tedious fight for the most autonomous LIFE possible. Despite the doctors’ pessimism, with the help of many wonderful people, Julio now lives autonomously in his own apartment. He tells us the stages, the ups and downs that he went through as well as his doubts, hopes, sorrows and joys.
cell therapies
2025-05-23 | When the Body Fails but the Mind Remains: Understanding 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.
2012-07-20 | Motor recovery mechanism in a quadriplegic patient with locked-in syndrome.
Locked-in syndrome (LIS) is a rare neurologic condition caused by bilateral pontine lesions. Quadriplegia is one of the most serious clinical manifestations in patients with LIS. However, little is known about the motor recovery mechanism of quadriplegia in patients with LIS. In the current study, we present with a quadriplegic patient with bilateral pontine infarcts, whose motor function appeared to be reorganized into the peri-infarct areas of the infarcted pons, as demonstrated by diffusion tensor tractography (DTT). A 60-year-old was diagnosed as LIS due to bilateral pontine infarcts 6 years ago. The patient presented with complete paralysis of all four extremities at onset. After slow motor recovery, the patient was able to move all joint muscles against gravity and demonstrated some fine motor activity at the time of DTT scanning (6 years after onset). Results of DTTs for the corticospinal tract (CST) in both hemispheres showed that the CSTs originated from the primary motor cortex, descended along the known CST pathway, and passed through lateral areas of infarcts in the pons. Therefore, motor function of the four extremities of this patient appears to have been recovered by the CST, which passed through the lateral areas to the pontine infarcts.
1980-08-01 | Hyperbaric Chamber Treatment for 'Locked-in' Syndrome
The "locked-in" syndrome described by Plum and Posner is characterized by quadriplegia and bulbar and facial paralysis.1Pathologic findings are those of infarction of the ventral pons bilaterally, usually due to thrombotic or embolic occlusion of the basilar artery.2-3We describe a patient in whom the locked-in syndrome developed after operation to establish an aortocoronary bypass and who subsequently recovered completely with hyperbaric oxygenation. It is likely that air embolization was the cause of the locked-in syndrome in this patient. A 54-year-old man with a history of two myocardial infarctions and hypertension was hospitalized with crushing substernal chest pain. Coronary angiography revealed severe coronary atherosclerosis. On two occasions during aortocoronary bypass surgery, the surgeon noted small air bubbles in the grafts, and evacuation was attempted by aspiration through a 25-gauge needle. Each time the air bubbles were observed, cardiac action deteriorated, and on the
proteins
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.
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.
2025-04-01 | An Introduction to Locked-in-Syndrome: Diagnosis, Care, and Outcomes
The chapter deals with an uncommon neurological disorder called Locked-In Syndrome (LIS), characterized by total body paralysis with preserved consciousness. Diagnosis of LIS is rather challenging and often protracted, due to its similarity to disorders of consciousness. Once properly diagnosed, rehabilitation is important for establishing a better prognosis and offering the patients with LIS a chance for an improved outcome. This chapter emphasizes the need for early and intense motor therapy, cognitive support, and emotional support to improve functionality and reduce mortality. Despite physical limitations of a serious nature, many LIS patients report a quite high quality of life, often adapting to their situation over time. However, psychological and emotional burdens remain high for both patients and caregivers. Unmet needs, particularly about the emotional support of caregivers, must be addressed with the purpose of overall improvement of the well-being of such patients. Finally, the chapter addresses ethical considerations pertinent to end-of-life decisions in LIS, where respect for patient autonomy is considered paramount, factoring in relevant cultural contexts. Integrating advances in technology, rehabilitative care, and ethical frameworks, this chapter gives further insight into how management and care for individuals with LIS are evolving.
2024-11-13 | From locked-in syndrome to recovery: thrombolysis success in bilateral pontine infarction with 'heart appearance' sign.
Locked-in syndrome (LIS) is a severe neurological condition characterised by tetraplegia and anarthria, with preserved consciousness and vertical eye movements. It often results from bilateral pontine infarctions, which sometimes demonstrate a characteristic 'heart appearance' sign on MRI. We report a case of a mid-60s female with acute onset LIS and dyspnoea. Clinical examination suggested a pontine infarction, later confirmed by an MRI scan revealing a characteristic 'heart appearance' on axial diffusion-weighted imaging sequence. As the patient presented within the thrombolysis time window and had no contraindications, alteplase was administered. The patient demonstrated an exceptional neurological improvement within 10 days of hospitalisation, transitioning from tetraplegia and anarthria to moving all four limbs against gravity and mild dysarthria. She was subsequently discharged to a rehabilitation centre. This case underscores the efficacy of timely thrombolysis in severe pontine strokes and highlights the diagnostic significance of MRI findings in such cases.
2011-05-12 | Locked in and out: a case of emerging basilar artery obstruction secondary to vertebral artery dissection thrombolysed with intravenous rt-PA
The authors present a case in which intravenous thrombolysis with recombinant tissue plasminogen activator (rt-PA) potentially saved a young man from locked-in syndrome or life threatening consequences. The patient presented with acute stroke secondary to vertebral artery dissection and was treated with intravenous rt-PA. There were no post thrombolysis complications and the patient left hospital with mild neurological symptoms. Our report suggests that in cases of acute posterior circulation stroke due to arterial dissection, treatment with intravenous thrombolysis is safe, practicable and effective.
small molecules
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.
2025-11-01 | 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.
2024-09-01 | Infection related ischemic stroke presenting as partial locked-in syndrome
Ischemic stroke in young adults have a multiplicity of possible causes making it a diagnostic challenge. Inflammatory and infectious diseases must be considered, alongside the most common etiologies and risk factors. We present a case of a 34-year-old male, with no known vascular risk factors, admitted to a stroke unit with partial locked-in syndrome characterized by quadriplegia and anarthria but with sustained horizontal bilateral gaze, with imaging study showing a pontine acute ischemic lesion. Diagnostic workup revealed a positive serum serology for HIV and Treponema pallidum. Even though cerebrospinal fluid showed negative Treponema pallidum serology, both meningovascular syphilis and HIV vasculopathy were considered potential and/or cumulative causative agents. The patient showed dramatic neurologic improvement after penicillin and antiretroviral treatment were started, as well as intensive physical therapy, being able to ambulate at hospital discharge. The importance of this report rests not only on the rarity of Partial locked-in syndrome and the above-mentioned stroke etiologies but is also an example of the rehabilitation potential of younger adults.
2024-07-19 | Locked-In Syndrome: A Rare Manifestation of Neuropsychiatric Lupus.
Neuropsychiatric systemic lupus erythematosus (SLE) is a rare condition that has a multitude of mechanisms resulting in the emergence of variable clinical presentations. We describe a peculiar case of a 33-year-old female with a history of SLE presented with two weeks of fever, headache, and vomiting. On admission, she became obtunded and was emergently intubated. Initial lumbar puncture revealed pleocytosis (46% neutrophils, 320 corrected nucleated cells/μL), elevated protein (244 mg/dL; normal, 15-40 mg/dL), normal glucose (63 mg/dL), and negative cultures. Empiric acyclovir, ampicillin, ceftriaxone, and vancomycin were initiated without clinical improvement. Neurological examination was notable for limited ability to follow commands, vertical nystagmus, horizontal gaze palsy, diffuse hyperreflexia, and quadriparesis. Electroencephalogram (EEG) was consistent with diffuse encephalopathy. Brain magnetic resonance imaging demonstrated restricted diffusion and contrast enhancement in the posterior and central pons with edema. A cerebral angiogram showed no signs of vasculitis. Treatment with intravenous (IV) methylprednisolone 1 g and IV immunoglobulin 2 g/kg was initiated for five days. Despite these interventions, no discernible clinical improvement was observed, prompting the commencement of 500 mg/m2 cyclophosphamide and daily maintenance of IV methylprednisolone at 2 mg/kg. A repeat MRI three weeks later revealed a marked reduction in the size of the lesion involving the pons. The patient also improved clinically over the month with successful extubation, complete return in mental capabilities, and the ability to ambulate short distances with assistance.
gene therapies
2025-04-01 | For a Better Life
Born into a very modest family, leaving his native Portugal at the age of 13, Julio hoped to find a simpler and more peaceful life in France than what he could have hoped for in his modest village. He began school, then work, earning a living and enjoying his youth. But, with no warning, just before his 22nd birthday, he was devastated by a Cerebral Vascular Accident which left him completely paralysed and mute: Locked-in Syndrome. What followed was a long and tedious fight for the most autonomous LIFE possible. Despite the doctors’ pessimism, with the help of many wonderful people, Julio now lives autonomously in his own apartment. He tells us the stages, the ups and downs that he went through as well as his doubts, hopes, sorrows and joys.
Access all drug discovery papers and probability of success in trials forecasts:
Access all drug discovery papers and probability of success in trials forecasts:
Drug Discovery Landscape
0 orphan drug designations.
0 orphan drug designations.
Let's accelerate rare disease drug discovery
Let's accelerate drug discovery
Get access to Explority AI’s forecasts to outperform average preclinical success rates. Whether you’re expanding your R&D pipeline, evaluating a partnership, or simply have a question — we’d love to hear from you.