Locked-in syndrome …

Douglas J Lanska MD MS MSPH

General Neurology

Updated 05.14.2024
Released 05.19.2004
Expires For CME 05.14.2027

Locked-in syndrome

Author: Douglas J Lanska MD MS MSPH

See Contributor Disclosures

Locked-in syndrome

In This Article

Quick Link

Introduction

Overview

“Locked-in” syndrome describes patients who are awake and conscious but selectively “de-efferented,” with no means of producing speech or moving their facial muscles or limbs. They are aware and perceive normally but are effectively locked in their own bodies, unable to communicate except possibly by blinking or eye movements. Locked-in syndrome typically results from a lesion in the brainstem, classically in the ventral pons. In this article, the author discusses the presentation, etiology, prognosis, diagnostic evaluation, and management of locked-in syndrome. Updates focus on the progress in brain-computer interfaces for communication and functionality of these patients.

Key points

	• Locked-in syndrome is a de-efferented state characterized by quadriplegia and paralysis of the lower cranial nerves.
	• Patients retain consciousness and can classically communicate by vertical eye movements and eye blinking.
	• The most common etiology is atherothrombotic occlusion of the basilar artery resulting in ischemia of the ventral pons.
	• Advances in technology, such as brain-computer interfaces, are allowing for improved communication for patients with locked-in syndrome.

Historical note and terminology

In 1875, French physician Camille Darolles, an intern supervised by François Damaschino (1840-1889), gave the first accurate clinical and pathological report of a complete or total case of locked-in syndrome, which lasted only for a few hours before the patient's death (24; 32; 122). Darolles presented the case at a monthly meeting of the Société Anatomique de Paris chaired by Jean-Martin Charcot (1825-1893).

New York neurologists Fred Plum (1924-2010) and Jerome Posner (1932-) first introduced the term in 1983, and they described the syndrome as “a state in which selective supranuclear motor de-efferentation produces paralysis of all four limbs and the last cranial nerves without interfering with consciousness” (98).

The famous case of Jean-Dominique Bauby (1952-1997) provides a patient’s perspective of locked-in syndrome following a devastating brainstem stroke. Despite being locked in, Bauby “dictated” his memoir to Claude Mendibil by the laborious method of blinking when the correct letter was reached by a person slowly reciting the alphabet over and over again. The book includes vivid depictions of the insensitivity of some healthcare providers toward a severely disabled person (as well as his outspoken reactions to such treatment) (09; 66). Bauby died suddenly 2 days after publication the of his book, The Diving Bell and the Butterfly (09). The book was later adapted for a critically acclaimed film of the same name.

Clinical manifestations

Presentation and course

	• Locked-in syndrome has been categorized into three types: classic, incomplete, and total (or complete).
	• Classic cases have quadriplegia and anarthria with preserved consciousness, vertical eye movements, and blinking. Incomplete cases also possess some voluntary motor movements (typically in the fingers or neck).
	• Total or complete cases have no movements, including that of the eyes or eyelids; patients with this syndrome are particularly likely to be misdiagnosed as comatose or in a persistent vegetative state, even though they are fully conscious.
	• Locked-in syndrome that presents acutely is most often a result of a lesion in the ventral pons that causes bilateral interruption of the corticospinal and corticobulbar tracts.
	• Patients with locked-in syndrome also suffer multiple complications secondary to extended hospitalizations and bedridden states, such as pneumonia, decubiti, urinary incontinence, and urinary infection.

Locked-in syndrome has been categorized into three types: classic, incomplete, and total (or complete) (10; 25). Classic cases have quadriplegia and anarthria with preserved consciousness, vertical eye movements, and blinking. Incomplete cases also possess some voluntary motor movements (typically in the fingers or neck). Total or complete cases have no movements, including that of the eyes or eyelids; patients with this syndrome are particularly likely to be misdiagnosed as comatose or in a persistent vegetative state, even though they are fully conscious (77; 37; 58; 59).

Locked-in syndrome that presents acutely is most often a result of a lesion in the ventral pons that causes bilateral interruption of the corticospinal and corticobulbar tracts. Injury to the corticospinal tracts causes quadriplegia, whereas injury to corticobulbar tracts and exiting cranial nerve fascicles affects the lower cranial nerves, which are essential for control of the facial, pharyngeal, and tongue muscles and, in consequence, for emotional expression, verbal expression (either vocalizations or speech), and swallowing. Preservation of supranuclear oculomotor pathways, due to the sparing of the midbrain tectum, allows the patient with locked-in syndrome to open his or her eyes, blink, and produce vertical eye movements. However, horizontal eye movements may be adversely affected in large ventral pons lesions involving paramedian pontine reticular formation or the abducens nuclei or fascicles (69; 117). Sensation is preserved because of spared sensory pathways, which lie dorsal to the ventral pontine lesion.

This syndrome can also be caused by bilateral mesencephalic lesions involving the cerebral peduncles or by bilateral lesions of the internal capsule or corona radiate (10; 21; 132).

People with acute ventral pontine lesions often remain comatose for days or weeks, supported by artificial respiration before gradually waking up. Despite becoming awake and aware, they remain voiceless and paralyzed. Because of their apparent unresponsiveness, they superficially resemble patients with akinetic mutism or a vegetative state. Consequently, the correct diagnosis is likely often missed or delayed. More often than not, the family rather than a healthcare team member first recognizes the affected patient is aware (67). Even after the patient is recognized as being aware, communication remains difficult and limited, despite coded blinks or eye movements, because of fluctuating vigilance and easy fatigability and because the eye movements themselves may be inconsistent, very small, and easily exhausted (67).

Some survivors with locked-in syndrome report persisting cognitive difficulties, and diverse cognitive impairments have been documented on neuropsychological studies in affected patients (69; 83; 109; 104; 61). Reported impairments in individual cases have variously included mild or moderate difficulties with attention and concentration, processing speed, auditory recognition, verbal learning, oral comprehension of complex sentences, delayed visuospatial memory, mental calculation, problem-solving, and executive skills. In some cases, the observed neuropsychological deficits were attributable to fatigue (answering even a series of simple questions using eye movements can be exhausting for these patients), and others could be related to additional cortical or thalamic structural brain lesions other than the principal ventral pontine lesion.

Emotional lability and pathologic laughter and crying have frequently been described in patients with locked-in syndrome. Pathologic laughter and crying are unrelated to depression and do not ameliorate with pharmacologic treatment but may improve with cognitive behavioral treatment. This emotional lability does not indicate an underlying mood disorder (105).

Respiratory compromise can result from pontine injury, and some patients require ventilator assistance. Subsequent evaluation may reveal intact phrenic nerve function but asymmetric diaphragmatic movement, making these patients good candidates for diaphragmatic pacing. A prolonged wean from the ventilator to pacing may increase their autonomy, reduce complications such as pneumonia, and improve quality of life (30).

Patients with locked-in syndrome also suffer multiple complications secondary to extended hospitalizations and bedridden states, such as pneumonia, decubiti, urinary incontinence, urinary infection, and chronic pain (125; 55; 92; 13). Almost half of the paients with locked-in syndrome report experiencing pain that affects their quality of life, sleep, and cognition (13).

In a survey of attitudes concerning the ethics of life-sustaining treatment in locked-in syndrome in a cohort of medical and nonmedical Chinese participants, the study sample included 1545 respondents, including 180 family members of individuals with locked-in syndrome (130). Most participants (70%), especially neurologists, thought that life-sustaining treatment should not be stopped in individuals with locked-in syndrome. Most respondents (59%) reported wanting to be kept alive if they were in that condition, although older people thought the opposite.

Prognosis and complications

The etiology of the initial insult strongly influences the overall prognosis of the patient with locked-in syndrome, with vascular etiologies generally suffering worse overall functional recoveries and higher mortalities than those with nonvascular causes (54; 114). For example, patients with locked-in syndrome secondary to central pontine myelinolysis have a more favorable prognosis than those with vascular etiologies (47).

Most patients who do not have progressive disorders of the brainstem can ultimately regain some control of finger and toe movements. In a study of 14 patients with locked-in syndrome, significant motor recovery was observed within 3 to 6 months after initiation of early and intensive multidisciplinary rehabilitation; nevertheless, profound impairments persisted over 11 years of follow-up (18; 31). Only a few subjects progressed to the point where they could manipulate an object. None could speak in sentences, and most could not even speak a single word consistently. Although most patients with locked-in syndrome who survive suffer from severe residual impairment, early recovery of eye movements usually indicates a relatively better prognosis (131).

In a study of 100 locked-in patients due to pontine infarcts over 1 year of follow-up, about a quarter (24%) of those with isolated pontine infarcts (n=72) had a "good outcome" (with a score of 3 on the Modified Rankin Scale of Neurological Disability, indicating moderate disability: requiring some help, but able to walk without assistance) (61). Those with pontine infarcts plus multiple ischemic lesions did significantly worse cognitively and overall. Because many patients with locked-in syndrome can show significant improvement, aggressive supportive measures and intense physical, speech, and cognitive therapy are appropriate to facilitate interaction with others and the environment (61).

In a study of 51 patients with vascular locked-in syndrome who remained in the locked-in state for at least 6 weeks, ischemic stroke was the most common etiology (69%) (86). Among the 43 patients with follow-up, (1) 53% emerged from the locked-in state, most within 2 years after onset; (2) 98% achieved some motor improvement; (3) only 7% achieved full motor recovery; and (4) 88% had a persistently high level of dependence. The 3-year survival rate was 87%. Only 9% had an isolated pontine lesion, whereas 80% showed various lesions outside the brainstem. Individuals who emerged from the locked-in state had a significantly lower prevalence of lesions outside the brainstem than those who remained in the locked-in state.

Although the mechanisms of motor recovery in quadriplegic patients with bilateral pontine infarcts remain unclear, potential contributors include perilesional reorganization; in one patient followed with serial diffusion tensor tractography, recovery was apparently mediated by residual portions of the extreme lateral aspects of the corticospinal tracts (64).

There is a high case fatality rate in the first several months following development of locked-in syndrome. In a series of 20 patients with locked-in syndrome (19 were vascular, and one was of unknown etiology), 15 (75%) died in the acute period: five from stroke progression or cardiac arrest and 10 from pulmonary infection or sepsis (85). Intubation was required in all cases during their hospitalization; tracheostomy was required in eight (40%). Another study reported a mortality of 87% among 79 patients with locked-in syndrome during the first 4 months (91).

In contrast, patients with chronic locked-in syndrome (ie, survival for more than 1 year) can have surprisingly long survivals, with 5-, 10-, and 20-year survival rates of 83%, 83%, and 40%, respectively (31). Therefore, once a patient becomes medically stable and survives the acute injury, life expectancy increases to several decades with appropriate medical care (67).

Despite what healthcare professionals, the general public, and even caregivers may think about the quality of life of patients with locked-in syndrome, affected individuals report surprisingly good and meaningful quality of life that stays stable over time (67; 27; 101; 134). Indeed, patients with locked-in syndrome often report normal mental and personal general health despite maximal restriction in physical activities (67). Patients consistently report a higher quality-of-life than is estimated by others, including by their spouses or caregivers (73). When asked to rate their life on a quality scale ranging from the “best time in my life” to the “worst time in my life,” patients with locked-in syndrome did not vary from matched controls (15). In a study of 65 patients with locked-in syndrome, 68% reported never having a suicidal thought, and only 17% reported feelings of depression. Variables associated with unhappiness were dissatisfaction with mobility in the community, with recreational activities, and with the incapacity to deal with life events. Shorter time locked-in, anxiety, and nonrecovery of speech production were also associated with unhappiness. The highest limitations were reported in community reintegration. Quality of life scores did not differ between nonventilated and invasively ventilated patients with locked-in syndrome (102). Even those with “complete” locked-in syndrome reported no difference in quality of life compared to matched controls (103).

Biased clinicians provide less-aggressive medical treatment in patients with locked-in syndrome (73; 74). Although the prompt assessment of decisionality in these patients is challenging, it is nevertheless essential to allow them to participate in decision-making regarding their own care (74). In addition, as eloquently expressed by Laureys and colleagues:

Biased clinicians might provide less aggressive medical treatment and influence the family in inappropriate ways. It is important to stress that only the medically stabilized, informed [locked-in syndrome] patient is competent to consent to or refuse life-sustaining treatment. Patients suffering from [locked-in syndrome] should not be denied the right to die - and to die with dignity - but also, and more importantly, they should not be denied the right to live - and to live with dignity and the best possible revalidation, and pain and symptom management (67).

Nevertheless, complex legal, ethical, and emotional issues are involved in supporting such patients with life-sustaining treatments, such as invasive ventilation, or withdrawing such treatment (40).

Clinical vignette

A 56-year-old, right-handed Caucasian man presented with progressive quadriparesis over a 3-week period. Prior medical history was unremarkable except for the removal of a pigmented skin lesion 6 weeks earlier, although no pathological diagnosis was obtained. On examination, he was breathing independently, his eyes were open, his fundi were without papilledema, and his pupils were equally responsive to light. He did not speak or vocalize. He did not visually track objects but did follow commands to blink or to raise or lower the eyes. Furthermore, he responded appropriately to questions using either vertical eye movements or eye blinking in a binary code. He could not move the mouth or limbs, and examination disclosed spastic quadriplegia with diffuse hyperreflexia. Sleep-wake cycles were linked to a circadian rhythm. Cranial MRI revealed a pontine mass. Emergent posterior fossa excision was performed. Histological diagnosis of the mass was malignant melanoma. In this case, a rapidly expanding pontine mass disrupted motor pathways at the level of the pons with preservation of cortical function, resulting in locked-in syndrome.

Biological basis

	• Locked-in syndrome can potentially be caused by profound bilateral dysfunction of upper or lower motor neuron pathways or the neuromuscular junction.
	• Classically, locked-in syndrome is due to vascular disorders of the basis pontis, usually ischemic but occasionally hemorrhagic (eg, basilar artery thrombosis, hypertensive pontine hemorrhage, etc.).
	• Locked-in syndrome can result from lower motor neuron pathway or neuromuscular junction dysfunction.

Etiology and pathogenesis

Locked-in syndrome can potentially be caused by profound bilateral dysfunction of upper or lower motor neuron pathways or the neuromuscular junction.

Classically, locked-in syndrome is due to vascular disorders of the basis pontis, usually ischemic but occasionally hemorrhagic (eg, basilar artery thrombosis, hypertensive pontine hemorrhage). Damage to the same structures can be caused by demyelinating disorders (eg, central pontine myelinolysis), trauma, structural lesions (eg, abscess, malignancy), transtentorial herniation, and rare other causes (eg, hyperhomocysteinemia due to severe folate deficiency, meningovascular syphilis) (51; 119; 53; 133; 01). Most of these patients have some preserved ability to blink and make vertical eye movements. In some patients with more rostral lesions involving the midbrain, there may be complete bilateral ptosis and external ophthalmoplegia, greatly impeding or obviating the clinical differentiation from coma.

What is often unrecognized is that locked-in syndrome can result from dysfunction of lower motor neuron pathways or the neuromuscular junction. Demyelinating neuropathies (eg, Guillain-Barre syndrome, chronic inflammatory demyelinating polyradiculoneuropathy, and toxic demyelinating neuropathies) can occasionally present fulminantly with the locked-in syndrome (06; 100; 79; 29; 46; 45). Motor neuron disease in the late stage, if supported on a ventilator, progresses into a locked-in state. Amyotrophic lateral sclerosis represents an “overlap” condition in that it results from bilateral dysfunction of both upper and lower motor neuron pathways. Disruption at the neuromuscular junction also can produce a locked-in state (though not often labeled as such); examples include (1) rare instances with myasthenia gravis and (2) toxins that cause either presynaptic (eg, botulinum toxin) or postsynaptic (eg, curare) blockade.

Differential diagnosis

Confusing conditions

Locked-in syndrome versus disorders of consciousness. Confusion of locked-in syndrome with other neurologic disorders that impair consciousness is not infrequent and can lead to mismanagement of afflicted individuals. Therefore, ensuring that patients are given the appropriate diagnosis is critical. One factor that appears to result in misdiagnosis is the confusion in terminology used to describe patients. The terms "apallic syndrome," "akinetic mutism," "coma vigil," "alpha coma," and "neocortical death" should not be used to depict individuals with locked-in syndrome. In addition, the neurologic conditions of coma, persistent vegetative state, and brain death are not synonymous with locked-in syndrome (52).

Unlike individuals who suffer from disorders of consciousness, "locked-in" patients are conscious but cannot communicate (98; 70). Loss of motor control of their facial musculature and extremities prevents these individuals from speaking and interacting with their surroundings. At times, even ocular movements may be lost. Usually, these patients are not aphasic and so can comprehend spoken speech.

The vegetative state is a chronic condition that preserves the ability to maintain blood pressure, respiration, and cardiac function, but not cognitive function. Specifically, the individual has no consciousness of self or the environment. The patient does not possess language function and, therefore, cannot communicate. Voluntary behavior or movements are absent. Facial expressions such as smiling, frowning, and crying can occur. These are not linked to any external stimulus. Sleep-wake cycles are present but do not necessarily reflect a specific circadian rhythm and are not associated with the environment. Although medullary brainstem functions remain intact to support cardiorespiratory functions, the presence of midbrain or pontine reflexes may be variable. Spinal reflex activity also may be present, but bowel and bladder functions are absent.

Coma is a state of unresponsiveness in which the patient remains with eyes closed and is unarousable (98). The patient is not conscious of self or the environment. Blood pressure and respiratory function may be intact, but the patient lacks sleep-wake cycles. The presence of flaccidity and areflexia indicate severe brainstem depression, and this is frequently found in terminal coma or severe sedative intoxication.

Brain death is declared when there is loss of function of the entire cortex and brainstem. A brain-dead individual has no response to noxious stimulation. The pupils are fixed to light stimulation. Corneal blink reflex, doll's eyes, and cold water caloric responses are not present. Brainstem reflexes are absent, with loss of spontaneous respiration. The documentation of apnea is vital to the determination of brain death. The diagnosis of brain death requires the death of the brainstem, whereas the persistent vegetative state preserves brainstem function (135).

Associated or underlying disorders

Etiologies of locked-in syndrome. The most frequent cause of locked-in syndrome in both adults and children is atherothrombotic occlusion of the basilar artery or, less frequently, brainstem hemorrhage.

A few of the most important other causes of locked-in syndrome are trauma, possibly causing basilar artery dissection (most common in younger individuals), transtentorial herniation, primary or secondary malignant infiltration of the basis pontis, and central pontine myelinolysis (85; 51). Although most cases are pathogenic, some cases are from iatrogenic influences such as chiropractic spinal and head manipulations, use of drugs with thrombogenic properties, intrathecal injections of chemotherapeutic agents, regional anesthetic nerve blocks with inadvertent intra-arterial injection of anesthetic agents, and basilar artery dissection as a complication of posterior fossa epidermoid cyst resection (126; 16; 57; 96). Other less common causes of locked-in syndrome include brainstem encephalitis, meningitis with brainstem abscess, polyneuritis (eg, Guillain-Barre syndrome, poliomyelitis, myasthenia gravis, pneumococcal meningitis, Epstein-Barr virus infection, and West Nile viral infection) (33; 76; 62). More unusual cases also exist, including ectatic elongated basilar artery (03), complication of cervical manipulation by a chiropractor (89), unstable atlantooccipital dissociation (28), complication of acute otitis media with inflammatory changes compressing the basilar artery (44), rapidly progressing polymyositis with elevated anti-acetylcholine receptor antibody activity, snake bite (129; 63), medullary infarction following lumbar puncture in a patient with basilar invagination (20), acute thrombosis and subsequent infarction of the basilar artery as a complication of cocaine abuse (02), and acute polyradiculoneuritis in a patient with COVID-19 (94).

Transient locked-in syndrome has been reported in various clinical circumstances, including the following:

	• Guillain-Barre syndrome (62)
	• Perioperative transient ischemic attack associated with cessation of warfarin (68)
	• Ischemic brainstem stroke without (38; 14) or with basilar artery thrombosis (95; 37)
	• Basilar artery vasospasm (65)
	• Posterior fossa subdural hematoma (111)
	• Silent aortic dissection (81)
	• Closed head injury (19; 17)
	• Following uncal herniation (128)
	• Central pontine and extrapontine myelinolysis (123)
	• Postoperative brainstem tension pneumocephalus (11)
	• Following repeated shunt procedures for idiopathic aqueductal stenosis (78)
	• Inadvertent intravertebral artery injection of local anesthetics during stellate ganglion block (34; 126)
	• Snake envenomation (04; 80)

The reversible cases of locked-in syndrome associated with brainstem ischemia represent the fortuitous end of a spectrum of outcomes that depend on the balance of hemodynamic factors and collateralization at the time of the event. Vascular etiologies, head injury, and iatrogenic circumstances seem to be major considerations in cases of transient locked-in syndrome.

Diagnostic workup

	• It is essential to determine whether an unresponsive patient is conscious (ie, to delineate locked-in syndrome from other unresponsive syndromes that affect level of consciousness, such as coma or persistent vegetative state).
	• A discordance between the ability to follow commands to look up or down and the lack of other spontaneous movements or movements to command should immediately suggest the diagnosis of locked-in syndrome.
	• CT or MRI can assist in determining the etiology of locked-in syndrome.
	• EEG findings of well-defined alpha waves and distinct reactivity to sensory stimulation have been used to imply the preservation of cortical function, but such EEG reactivity is inconsistently present in such patients.

First and foremost, it is essential to determine whether an unresponsive patient is conscious—that is, to delineate locked-in syndrome from other unresponsive syndromes that affect level of consciousness, such as coma or persistent vegetative state. Sadly, diagnosis is often long delayed; indeed, diagnosis of locked-in syndrome takes over 2.5 months on average and, in some reported cases, up to 6 years (67).

Careful neurologic examination by an experienced clinician with a high index of suspicion for the possibility of locked-in syndrome is necessary. The examiner should specifically ask the patient to blink and look up and down. A discordance between the performance of these actions, and the lack of other spontaneous movements or movements to command, should immediately suggest the diagnosis of locked-in syndrome. Note, though, that rare cases of total mesencephalic locked-in syndrome may have bilateral ptosis and complete ophthalmoplegia (77; 37). By categorizing cases as affecting upper or lower motor neurons (or both) or the neuromuscular junction and then considering any inciting events, the course (acute, subacute, or chronic), and any associated clinical findings, the differential diagnosis can be rapidly and reliably narrowed.

Many routine clinical tools are not applicable (and, worse, are potentially very misleading) in the setting of locked-in syndrome. For example, although the Glasgow Coma Scale is the “gold standard” for routine assessment of consciousness in acutely unresponsive patients, it relies exclusively on behavioral responses and provides an erroneous measure of consciousness in locked-in patients. Similarly, the Disability Rating Scale also involves basic behavioral functions like eye-opening, communication, and motor response, which cannot be applied to patients with locked-in syndrome.

CT or MRI can assist in determining the etiology of locked-in syndrome. These studies can differentiate between an ischemic infarct, an intracerebral hemorrhage, and a mass lesion involving the brainstem. A CT without contrast is helpful in suspected cases of cerebral hemorrhage. CT within the first 72 hours of onset of intracerebral hemorrhage usually provides greater resolution than MRI. CT angiography or MR angiography can be used to visualize the cerebral vasculature following the exclusion of a cerebral hemorrhage.

None of the other approaches using advanced diagnostic technologies provides a consistently clear and definitive answer to the question of whether an individual patient is locked in.

In the assessment of patients with locked-in syndrome, EEG findings of well-defined alpha waves and distinct reactivity to sensory stimulation have been used to imply the preservation of cortical function (127; 60), but such EEG reactivity is inconsistently present in such patients (43). EEG studies have demonstrated various abnormalities in locked-in syndrome patients, including slowing in the frontal or temporal leads, diffuse slowing, or cortical resting state rhythms, which are thought to imply functional impairment of cortical neuronal synchronization mechanisms in the resting state condition (08; 05). None of these findings are of particular diagnostic or prognostic utility. Transcranial magnetic stimulation has been used in conjunction with EEG to detect the presence of consciousness in states of coma, but although these studies show promise, this is still a research approach (42; 106).

Evoked potentials can provide limited information concerning the functional state of the cerebral cortex and brainstem if communication with the patient is limited or absent, but the findings in patients with locked-in syndrome are highly variable and not particularly critical, either diagnostically or prognostically. Indeed, no pattern of evoked potential abnormality is specific to the locked-in syndrome, with either somatosensory evoked potentials or brainstem auditory evoked potentials (110; 127; 124; 43).

The P300 (P3) event-related potential (ERP) can be recorded in most patients with locked-in syndrome using visual or auditory stimuli under various cognitive “oddball” paradigms (88). In an oddball paradigm, sequences of repetitive stimuli are infrequently interrupted by a deviant stimulus, and the subject’s reaction to this "oddball" stimulus is recorded. Although other electrophysiological techniques can demonstrate normal or abnormal afference of sensory pathways or can suggest indirectly that the cerebral cortex is operative to some degree, early studies suggested that ERPs can provide direct evidence of ongoing cognitive activity (88). A later study recorded the auditory evoked potentials to the patient's own name and to seven other equiprobable first names in 15 brain-damaged patients and found a P3 component in response to the patient’s name in all patients with locked-in syndrome (93). However, they also found this ERP in all minimally conscious patients and in three of five patients in a behaviorally well-documented vegetative state. The authors concluded that a P3 response does not necessarily reflect conscious perception, so its utility in evaluating suspected locked-in syndrome is questionable.

PET and SPECT can assess remaining cortical and brainstem function. Blood flow and metabolic studies can also be used as a diagnostic aid in differentiating individuals in the vegetative state from patients with locked-in syndrome (70) as patients with locked-in syndrome do not usually suffer from significantly depressed cerebral blood flow or metabolism.

Transcranial Doppler can be used to distinguish between locked-in syndrome, persistent vegetative state, and brain death using differences in flow velocities in the middle cerebral and basilar arteries (113).

Functional magnetic resonance imaging has been used to assess consciousness by examining activation differences between blocks of normal speech and reversed speech, making it possible to isolate regions involved in higher-level auditory processing (107; 121).

The development of diffusion tensor imaging has provided a structural evaluation of patients with unresponsive wakefulness and helped to distinguish between patients with locked-in syndrome and minimally conscious patients based on anatomy (12).

Management

	• Decisions for care should focus on the utility of available treatment and management modalities, quality of life, and possible resource constraints.
	• Even if the motor recovery remains very limited, existing eye-controlled, computer-based communication technologies allow affected patients to control aspects of their environment, use a word processor coupled to a speech synthesizer, and access the internet.

Management of locked-in syndrome should be consistent with the desires of the patient. Decisions for care should focus on the utility of available treatment and management modalities, quality of life, and possible resource constraints.

The therapeutic modalities considered for the patient with locked-in syndrome should be directed to resolving the underlying inciting injury whenever possible. For example, thrombolytics or mechanical revascularization may be employed when basilar thrombosis is suspected. Once this has been addressed, intensive and early rehabilitation should be initiated. Particular attention should be directed to maintaining airway function because this may be compromised in quadriplegic patients (108). Intensive nursing care, nutritional support, and an early rehabilitation program that includes physiotherapy, respiratory exercises, and speech training can improve functional recovery in some patients (18).

Management challenges for individuals with locked-in syndrome include blood pressure management and orthostasis, feeding (eg, timing and appropriateness of reinstating oral feeding), ventilation (eg, ventilatory support, decannulation after tracheostomy), bowel and bladder management, eye care, communication, mobility, and independence and autonomy (36). Facilitating mobility required targeted rehabilitation of head, neck, and trunk stability to improve function and proper fit in an appropriate wheelchair (36). Rehabilitation interventions should include a focus on distal motor control (to the extent feasible if not totally locked in) and upright tolerance training. In addition, special consideration should be given to developing workable communication methods through use of augmentative systems to call for help and express needs. Communication systems promote connectivity to family and friends through social media and the internet. Communication, mobility, and connectivity are essential for promoting independence and autonomy and improving quality of life.

Comfort is of the utmost importance, and close attention should be paid to a patient’s pain levels. Even the immobility itself results in considerable discomfort. Patients tend to prefer lying with their arms beside their body rather than in a crucifix position, which was previously advocated (99). Spasticity from injury to the corticospinal tracts can cause pain and discomfort, and it may be ameliorated by oral antispasticity agents or, when necessary, by intrathecal baclofen (97).

Methods of improving communication with patients with locked-in syndrome have had some initial success, and refinements are in development (71). Improved communication improves social inclusion and quality of life for such patients (73; 49; 23).

Even if motor recovery remains limited, existing eye-controlled, computer-based communication technologies allow affected patients to control aspects of their environment, use a word processor coupled to a speech synthesizer, and access the internet (67). Gaze tracking systems are available that move a cursor on a computer screen or perform other motor tasks as directed by the patient’s eye movements. Such systems utilize video-oculography to monitor gaze direction, which is determined by monitoring the “pupil center corneal reflection” using either passive light or active light (infrared light) (115; 41; 82). This approach is used not infrequently in patients with locked-in syndrome and late-stage amyotrophic lateral sclerosis, and training can begin before this technology is absolutely required. Unfortunately, existing eye-writing systems have suffered from slow input rates because they require a pause between input characters to simplify the automatic recognition process. A continuous eye-writing recognition system is in development that achieves a rapid input rate because it accepts characters eye-written continuously without pauses (35).

Brain-computer interfaces have also been developed to allow patients to show nonmotor-dependent signs of awareness and enable communication. Brain-computer interfaces can potentially be utilized for communication and interaction with the environment if voluntary muscle activity is lost or impaired. However, to date, brain-computer interfaces have primarily been used for communication in laboratory research settings (48), with only limited (though promising) application in clinical settings (49). Critical issues must be addressed for brain-computer interfaces to become clinically useful alternative communications systems (48; 84). In a meta-analysis of brain-computer interfaces in amyotrophic lateral sclerosis, the authors concluded, “After 15 years of studies, it is as yet not possible to reliably establish the effectiveness of brain-computer interfaces” (75).

A brain-computer interface provides subjects with a virtual keyboard or mouse, whose keys or cursor are directed by the modulation of brain activity (87). The noninvasive recording of EEG is the most frequently and feasibly used method in brain-computer interface research; invasive recording techniques are also available, though not widely used. Modern brain-computer interfaces determine the intent of the user from a variety of different electrophysiological signals. These signals include slow cortical potentials, P3 potentials, steady-state evoked potentials (SSVEPs), functional near-infrared spectroscopy, and mu or beta rhythms (112). A specific algorithm translates the extracted features into commands representing the user’s intent. These commands can control effectors to select items such as ‘‘yes-no’’ choices or word spelling devices for communication. Visual P3 evoked potentials have been the most robust BCI, enabling accuracy close to 100% in healthy subjects, and P3 paradigms also allow for high accuracy in patients with severe motor paralysis (72). Hybrid models using more than one of these techniques have been developed seeking greater ease and accuracy. Visual, auditory, and tactile brain-computer interfaces are available based on an individual’s functionality (116). There has been more recent promising research on tactile models, suggesting these may be superior to visual and auditory brain-computer interfaces (56; 90). fMRI can also be used to reduce pretraining and does not require external behavior such as eye or finger movements (120). However, functional MRI protocols may fall short in patients with cognitive impairment or dysfunction as they rely on mental imagery, working memory, and sustained attention (26).

Intracortical brain-computer interfaces can decode intended movement from neural activity, transmit to signal processing hardware and software, and not only function as means of communication but also provide a mechanism for which motor function can be imitated. Notable accomplishments include moving a 3-dimensional brain-computer interface-driven robotic arm nonhuman primates and paralyzed humans (22; 50).

Outcomes

Treatment outcomes depend on the etiology of the locked-in syndrome. With acute basilar occlusion, the most common etiology of locked-in syndrome, revascularization reduces mortality from 87% to 39% among those with successful recanalization (118). Age and duration of occlusion are significant factors modifying outcome. Though vessel rupture and fatal bleeding complications are potential risks of treatment, the near-total mortality rate in the absence of intervention most often favors treatment.

References

01: Albert-Brotons DC, Alharkan W, et al. Central pontine myelinolysis and locked-in syndrome associated with tacrolimus after pediatric heart transplantation. Pediatr Transplant 2023;27(3):e14474. PMID 36717958
02: Ali O, Bueno MG, Duong-Pham T, et al. Cocaine as a rare cause of locked-in syndrome: a case report. J Med Case Rep 2019;13(1):337. PMID 31739807
03: Al-Sardar H, Grabau W. Locked-in syndrome caused by basilar artery ectasia. Age Ageing 2002;31(6):481-2. PMID 12446297
04: Azad C, Mahajan V, Jat KR. Locked-in syndrome as a presentation of snakebite. Indian Pediatr 2013;50(7):695-7. PMID 23942434
05: Babiloni C, Pistoia F, Sarà M, et al. Resting state eyes-closed cortical rhythms in patients with locked-in-syndrome: an EEG study. Clin Neurophysiol 2010;121(11):1816-24. PMID 20541461
06: Bakshi N, Maselli RA, Gospe SM Jr, Ellis WG, McDonald C, Mandler RN. Fulminant demyelinating neuropathy mimicking cerebral death. Muscle Nerve 1997;20(12):1595-7. PMID 9390675
07: Barakat MT, Banerjee S, Angelotti T. Anesthetic considerations for patients with locked-in syndrome undergoing endoscopic procedures. Am J Case Rep 2024;25:e942906. PMID 38356258
08: Bassetti C, Mathis J, Hess CW. Multimodal electrophysiological studies including motor evoked potentials in patients with locked-in syndrome: report of six patients. J Neurol Neurosurg Psychiatry 1994;57(11):1403-6. PMID 7964820
09: Bauby JD. The Diving Bell and the Butterfly: A Memoir of Life in Death. New York: Alfred A. Knopf, 1997.**
10: Bauer G, Gerstenbrand F, Rumpl E. Varieties of locked-in syndrome. J Neurol 1979;221(2):77-91. PMID 92545
11: Biyani N, Silbiger A, Ben-Ari J, Constantini S. Postoperative brainstem tension pneumocephalus causing transient locked-in syndrome. Pediatr Neurosurg 2007;43(5):414-7. PMID 17786010
12: Bodart O, Laureys S, Gosseries O. Coma and disorders of consciousness: scientific advances and practical considerations for clinicians. Semin Neurol 2013;33(2):83-90. PMID 23888393
13: Bonin EAC, Delsemme Z, Blandin V, et al. French survey on pain perception and management in patients with locked-in syndrome. Diagnostics (Basel) 2022;12(3):769. PMID 35328322
14: Broomall E, McBride ME, Deal BJ, et al. Posterior circulation ischemia or occlusion in five adults with failing fontan circulation. Ann Thorac Surg 2016;101(6):2315-20. PMID 27016841
15: Bruno MA, Pellas F, Laureys S. Quality of life in locked-in syndrome survivors. In: Vincent JL, editor. Yearbook of intensive care and emergency medicine. Vol. 2008. Berlin Heidelberg: Springer, 2008:881-90.**
16: Cardwell MS. Locked-in syndrome. Tex Med 2013;109(2):e1. PMID 23378122
17: Carrai R, Grippo A, Fossi S, et al. Transient post-traumatic locked-in syndrome: a case report and a literature review. Neurophysiol Clin 2009;39(2):95-100. PMID 19467439
18: Casanova E, Lazzari RE, Lotta S, Mazzucchi A. Locked-in syndrome: improvement in the prognosis after an early intensive multidisciplinary rehabilitation. Arch Phys Med Rehabil 2003;84(6):862-7. PMID 12808539
19: Chang B, Morariu MA. Transient traumatic "locked-in" syndrome. Eur Neurol 1979;18(6):391-4. PMID 546662
20: Chen JA, Driver J, Segar D, Bernstock JD, Gupta S, Gormley W. Medullary infarction leading to locked-in syndrome following lumbar puncture in a patient with basilar invagination. World Neurosurg 2020;137:292-5. PMID 32068170
21: Chia LG. Locked-in syndrome with bilateral ventral midbrain infarcts. Neurology 1991;41(3):445-6. PMID 2006017
22: Collinger JL, Wodinger B, Downey JE, et al. High-performance neuroprosthetic control by an individual with tetraplegia. Lancet 2013;381(9866):557-64. PMID 23253623
23: Corallo F, Bonanno L, Lo Buono V, et al. Augmentative and alternative communication effects on quality of life in patients with locked-in syndrome and their caregivers. J Stroke Cerebrovasc Dis 2017;26(9):1929-33. PMID 28733123
24: Darolles C. Ramolissement de la protuberance: thrombose du tronc basilaire. Le Progres Medicale 1875;3:629-39.
25: Das J, Anosike K, Asuncion RMD. Locked-in syndrome. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing, 2022. PMID 32644452
26: de Jong BM. “Complete motor locked-in” and consequences for the concept of minimally conscious state. J Head Trauma Rehabil 2013;28(2):141-3. PMID 22333679
27: Demertzi A, Jox RJ, Racine E, Laureys S. A European survey on attitudes towards pain and end-of-life issues in locked-in syndrome. Brain Inj 2014;28(9):1209-15. PMID 24911332
28: Desai R, Kinon MD, Loriaux DB, Bagley CA. Traumatic atlanto-occipital dissociation presenting as locked-in syndrome. J Clin Neurosci 2015;22(12):1985-7. PMID 26190221
29: Dilena R, Strazzer S, Esposito S, et al. Locked-in-like fulminant infantile Guillain-Barré syndrome associated with herpes simplex virus 1 infection. Muscle Nerve 2016;53(1):140-3. PMID 26372816
30: DiTommaso C, Berliner J, Cruz D, Wenzel LR. Diaphragmatic pacing and protocol with locked-in syndrome. PM R 2012;4(2):152-3. PMID 22373465
31: Doble JE, Haig AJ, Anderson C, Katz R. Impairment, activity, participation, life satisfaction, and survival in persons with locked-in syndrome for over a decade: follow up on a previously reported cohort. J Head Trauma Rehabil 2003;18(5):435-44. PMID 12973273
32: Dollfus P, Milos PL, Chapuis A, Real P, Orenstein M, Soutter JW. The locked-in syndrome: a review and presentation of two chronic cases. Paraplegia 1990;28(1):5-16. PMID 2152394
33: Doron SI, Dashe JF, Adelman LS, Brown WF, Werner BG, Hadley S. Histopathologically proven poliomyelitis with quadriplegia and loss of brainstem function due to West Nile virus infection. Clin Infect Dis 2003;37(5):74-7. PMID 12942423
34: Dukes RR, Alexander LA. Transient locked-in syndrome after vascular injection during stellate ganglion block. Reg Anesth 1993;18(6):378-80. PMID 8117636
35: Fang F, Shinozaki T. Electrooculography-based continuous eye-writing recognition system for efficient assistive communication systems. PLoS One 2018;13(2):e0192684. PMID 29425248
36: Farr E, Altonji K, Harvey RL. Locked-in wyndrome: practical rehabilitation management. PM R 2021;13(12):1418-28. PMID 33465298
37: Fujimoto Y, Ohnishi Y, Wakayama A, Yoshimine T. Transient total mesencephalic locked-in syndrome after bilateral ptosis due to basilar artery thrombosis. J Stroke Cerebrovasc Dis 2012;21(8):909.e7-8. PMID 22177934
38: Fujiyama K, Motomura M, Shirabe S, et al. Locked-in syndrome and abnormal orientation of the right vertebral artery in a young man. Intern Med 1994;33(8):476-80. PMID 7803914
39: Garcia-Esperon C, López-Cancio E, Martín-Aguilar L, et al. Fluctuating locked-in syndrome as a presentation of a bilateral pontine infarction. Neuroradiol J 2016;29(5):347-9. PMID 27385775
40: Gleeson A, Johnson F. Withdrawal of invasive ventilation in a patient with motor neurone disease and total locked-in syndrome. Pract Neurol 2017;17(5):383-6. PMID 28428229
41: Gneo M, Schmid M, Conforto S, D’Alessio T. A free geometry model-independent neural eye-gaze tracking system. J NeuroEng Rehabil 2012;9:82. PMID 23158726
42: Gosseries O, Thibaut A, Boly M, Rosanova M, Massimini M, Laureys S. Assessing consciousness in coma and related states using transcranial magnetic stimulation combined with electroencephalography. Ann Fr Anesth Reanim 2014;33(2):65-71. PMID 24393302
43: Gutling E, Isenmann S, Wichmann W. Electrophysiology in the locked-in-syndrome. Neurology 1996;46(4):1092-101. PMID 8780098
44: Hantson P, Wittebole X, Rombaux P, Cosnard G. Locked-in syndrome as an unusual complication of acute otitis media. B-ENT 2012;8(2):131-4. PMID 22896933
45: Hass RM, Wijdicks EFM. Locked in from fulminant GBS after lumbar spine surgery. Pract Neurol 2024;24(1):63-5. PMID 37890999
46: Hayashi S, Nagamine S, Makioka K, Kusunoki S, Okamoto K. A case of severe chronic inflammatory demyelinating polyradiculoneuropathy with monoclonal gammopathy of undetermined significance with alternating immunoglobulin class to IgM from IgA. Rinsho Shinkeigaku 2016;56(9):593-9. PMID 27580763
47: Heckmann JG, Dinkel HP. Recovery of locked-in syndrome in central pontine myelinolysis. Am J Case Rep 2013;14:219-20. PMID 23826473
48: Hill K, Kovacs T, Shin S. Critical issues using brain-computer interfaces for augmentative and alternative communication. Arch Phys Med Rehabil 2015;96(3 Suppl):S8-15. PMID 25721552
49: Holz EM, Botrel L, Kaufmann T, Kübler A. Long-term independent brain-computer interface home use improves quality of life of a patient in the locked-in state: a case study. Arch Phys Med Rehabil 2015;96(3 Suppl):S16-26. PMID 25721543
50: Homer ML, Perge JA, Black MJ, Harrison MT, Cash SS, Hochberg LR. Adaptive offset correction for intracortical brain-computer interfaces. IEEE Trans Neural Syst Rehabil Eng 2014;22(2):239-48. PMID 24196868
51: Jang SH, Chang CH, Jung YJ, Seo JP. Locked-in syndrome due to transtentorial herniation and Kernohan notch phenomenon. Am J Phys Med Rehabil 2017;96(4):e77. PMID 28301869
52: Jennett B, Plum F. Persistent vegetative state after brain damage. A syndrome in search of a name. Lancet 1972;1(7753):734-7. PMID 4111204
53: Kartum TA, Baş G, Kemerdere R, Hanci MM. Posttraumatic locked-in syndrome from combined brainstem and upper cervical injury in childhood: a case report. Neurochirurgie 2022;68(6):e104-6. PMID 35644290
54: Katz RT, Haig AJ, Clark BB, DiPaola RJ. Long-term survival, prognosis, and life-care planning for 29 patients with chronic locked-in syndrome. Arch Phys Med Rehabil 1992;73(5):403-8.** PMID 1580764
55: Kaufman DM, Lipton RB. The persistent vegetative state: an analysis of clinical correlates and costs. N Y State J Med 1992;92(9):381-4. PMID 1407797
56: Kaufmann T, Holz EM, Kubler A. Comparison of tactile, auditory, and visual modality for brain-computer interface use: a case study with a patient in the locked-in state. Front Neurosci 2013;7:129.** PMID 23898236
57: Ke JQ, Yin B, Fu FW, et al. A case report of locked-in syndrome due to bilateral vertebral artery dissection after cervical spine manipulation treated by arterial embolectomy. Medicine (Baltimore) 2016;95(5):e2693. PMID 26844510
58: Kohnen RF, Lavrijsen JC, Bor JH, Koopmans RT. The prevalence and characteristics of patients with classic locked-in syndrome in Dutch nursing homes. J Neurol 2013;260(6):1527-34. PMID 23306659
59: Kondziella D. Roald Dahl and the complete locked-in syndrome: "Cold dead body, living brain". J Neurol Sci 2017;379:276-8. PMID 28716259
60: Kotchoubey B, Lotze M. Instrumental methods in the diagnostics of locked-in syndrome. Restor Neurol Neurosci 2013;31(1):25-40. PMID 23168499
61: Kumral E, Dorukoğlu M, Uzunoğlu C, Çetin FE. The clinical and cognitive spectrum of locked-in syndrome: 1-year follow-up of 100 patients. Acta Neurol Belg 2022;122(1):113-21. PMID 33987814
62: Kumta N, Carter A, Schuller P, Evans H, Graffunder A. Locked-in Guillain-Barré syndrome: 'my living nightmare'. Pract Neurol 2022;22(2):126-8. PMID 34716224
63: Kutiyal AS, Malik C, Hyanki G. Locked-in syndrome post snake bite: a rare presentation. Trop Doct 2018;48(1):68-9. PMID 28835176
64: Kwon HG, Jang SH. Motor recovery mechanism in a quadriplegic patient with locked-in syndrome. NeuroRehabilitation 2012;30(2):113-7. PMID 22430576
65: Lacroix G, Couret D, Combaz X, Prunet B, Girard N, Bruder N. Transient locked-in syndrome and basilar artery vasospasm. Neurocrit Care 2012;16(1):145-7. PMID 22131170
66: Lanska DJ. The Diving Bell and the Butterfly, by J-D Bauby (Invited review). Neurology 1998;51:653.
67: Laureys S, Pellas F, Van Eeckhout P, et al. The locked-in syndrome: what is it like to be conscious but paralyzed and voiceless. Prog Brain Res 2005;150:495-511. PMID 16186044
68: Lee SO, Li MJ, Ho HM, Chien CC, Guo SL. Perioperative transient ischemic attack caused by the cessation of warfarin. Acta Anaesthesiol Taiwan 2010;48(4):188-90. PMID 21195993
69: Leon-Carrion J, van Eeckhout P, Dominguez-Morales Mdel R. The locked-in syndrome: a syndrome looking for therapy. Brain Inj 2002;16(7):555-69. PMID 12119075
70: Levy DE, Sidtis JJ, Rottenberg DA, et al. Differences in cerebral blood flow and glucose utilization in vegetative versus locked-in patients. Ann Neurol 1987;22(6):673-82. PMID 3501694
71: Lugo ZR, Bruno MA, Gosseries O, et al. Beyond the gaze: communicating in chronic locked-in syndrome. Brain Inj 2015;29(9):1056-61. PMID 26182228
72: Lule D, Noirhomme Q, Kleih SC, et al. Probing command following in patients with disorders of consciousness using a brain-computer interface. Clin Neurophysiol 2013;124(1):101-6. PMID 22920562
73: Lule D, Zickler C, Häcker S, et al. Life can be worth living in locked-in syndrome. Prog Brain Res 2009;177:339-51. PMID 19818912
74: Maiser S, Kabir A, Sabsevitz D, Peltier W. Locked-in syndrome: case report and discussion of decisional capacity. J Pain Symptom Manage 2016;51(4):789-93. PMID 26674610
75: Marchetti M, Priftis K. Brain-computer interfaces in amyotrophic lateral sclerosis: a metanalysis. Clin Neurophysiol 2015;126(6):1255-63. PMID 25449558
76: Mathais Q, Esnault P, Montcriol A, Gazzola S, Prunet B, Meaudre E. Locked-in syndrome following meningitis with brainstem abscess. Rev Neurol (Paris) 2019;175(1-2):88-9. PMID 30274815
77: Maurri S, Lambruschini P, Barontini F. Total mesencephalic "locked-in" syndrome: a case report and review of the literature. Riv Neurol 1989;59(6):211-6. PMID 2700840
78: McGuire TJ, Hodges DL, Medhat MA, Redford JB. Transient locked-in syndrome and phenobarbital. Arch Phys Med Rehabil 1987;68(9):566-7. PMID 3632327
79: Medici C, Gonzalez G, Cerisola A, Scavone C. Locked-in syndrome in three children with Guillain-Barré syndrome. Pediatr Neurol 2011;45(2):125-8. PMID 21763955
80: Mehta V, Kumar R, Prabhakar R, Sharma CB, Thomas A. Dramatic neuromuscular paralysis following occult snakebites: An awareness for the primary care physician. J Family Med Prim Care 2022;11(1):386-9. PMID 35309641
81: Nadour W, Goldwasser B, Biederman RW, Taffe K. Silent aortic dissection presenting as transient locked-in syndrome. Tex Heart Inst J 2008;35(3):359-61. PMID 18941610
82: Nakazawa A, Nitschke C. Point of gaze estimation through corneal surface reflection in an active illumination environment. In: Fitzgibbon A, Lazebnik S, Perona P, Sato Y, Schmid C, editors. Computer Vision – ECCV 2012. Lecture Notes in Computer Science. Vol 7573. Berlin, Heidelberg: Springer, 2012:159-72.
83: New PW, Thomas SJ. Cognitive impairments in the locked-in syndrome: a case report. Arch Phys Med Rehabil 2005;86(2):338-43. PMID 15706565
84: Nijboer F. Technology transfer of brain-computer interfaces as assistive technology: barriers and opportunities. Ann Phys Rehabil Med 2015;58(1):35-8. PMID 25595535
85: Nikic PM, Jovanović D, Paspalj D, Georgievski-Brkic B, Savic M. Clinical characteristics and outcome in the acute phase of ischemic locked-in syndrome: case series of twenty patients with ischemic LIS. Eur Neurol 2013;69(4):207-12. PMID 23307010
86: Nilsen HW, Martinsen ACT, Johansen I, Kirkevold M, Sunnerhagen KS, Becker F. Demographic, medical, and clinical characteristics of a population-based sample of patients with long-lasting locked-in syndrome. Neurology 2023;101(10):e1025-35. PMID 37442623
87: Oken BS, Orhan U, Roark B, et al. Brain-computer interface with language model-electroencephalography fusion for locked-in syndrome. Neurorehabil Neural Repair 2014;28(4):387-94. PMID 24370570
88: Onofrj M, Thomas A, Paci C, Scesi M, Tombari R. Event related potentials recorded in patients with locked-in syndrome. J Neurol Neurosurg Psychiatry 1997;63(6):759-64. PMID 9416812
89: Orsini GG, Metaxas GE, Legros V. Locked-in syndrome following cervical manipulation by a chiropractor: a case report. J Crit Care Med (Targu Mures) 2019;5(3):107-10. PMID 31431924
90: Ortner R, Lugo Z, Pruckl R, Hintermuller C, Noirhomme Q, Guger C. Performance of a tactile P300 speller for healthy people and severely disabled patients. Conf Proc IEEE Eng Med Biol Soc 2013;2013:2259-62. PMID 24110174
91: Patterson JR, Grabois M. Locked-in syndrome: a review of 139 cases. Stroke 1986;17(4):758-64. PMID 3738962
92: Penders J, Huylenbroeck AA, Everaert K, Van Laere M, Verschraegen GL. Urinary infections in patients with spinal cord injury. Spinal Cord 2003;41(10):549-52. PMID 14504611
93: Perrin F, Schnakers C, Schabus M, et al. Brain response to one’s own name in vegetative state, minimally conscious state, and locked-in syndrome. Arch Neurol 2006;63(4):562-9. PMID 16606770
94: Pfefferkorn T, Dabitz R, von Wernitz-Keibel T, Aufenanger J, Nowak-Machen M, Janssen H. Acute polyradiculoneuritis with locked-in syndrome in a patient with Covid-19. J Neurol 2020;267(7):1883-4. PMID 32399694
95: Phatouros CC, Higashida RT, Malek AM, et al. Endovascular stenting of an acutely thrombosed basilar artery: technical case report and review of the literature. Neurosurgery. 1999;44(3):667-73. PMID 10069607
96: Pikis S, Cohen JE, Margolin E. Basilar artery dissection: a rare complication of posterior fossa epidermoid cyst resection, and evaluation of the possible effects of cerebrospinal fluid drainage on disease progression. J Clin Neurosci 2016;32:141-3. PMID 27344090
97: Pistoia F, Sacco S, Sara M, Franceschini M, Carolei A. Intrathecal baclofen: effects on spasticity, pain, and consciousness in disorders of consciousness and locked-in syndrome. Curr Pain Headache Rep 2015;19(1):466. PMID 25416459
98: Plum F, Posner JB. The diagnosis of stupor and coma. 3rd ed. Philadelphia: FA Davis, 1982.
99: Raab AM, Harvey LA, Baumberger M, Frotzler A. The effect of arm position and bed adjustment on comfort and pressure under the shoulders in people with tetraplegia: a randomized cross-over study. Spinal Cord 2014;52(2):152-6. PMID 24322216
100: Ragazzoni A, Grippo A, Tozzi F, Zaccara G. Event-related potentials in patients with total locked-in state due to fulminant Guillain-Barré syndrome. Int J Psychophysiol 2000;37(1):99-109. PMID 10828378
101: Rousseau MC, Baumstarck K, Alessandrini M, et al. Quality of life in patients with locked-in syndrome: evolution over a 6-year period. Orphanet J Rare Dis 2015;10:88. PMID 26187655
102: Rousseau MC, Pietra S, Blaya J, Catala A. Quality of life of ALS and LIS patients with and without invasive mechanical ventilation. J Neurol 2011;258(10):1801-4. PMID 21461685
103: Rousseau MC, Pietra S, Nadji M, Billette de Villemeur T. Evaluation of quality of life in complete locked-in syndrome patients. J Palliat Med 2013;16(11):1455-8. PMID 24215251
104: Rousseaux M, Castelnot E, Rigaux P, Kozlowski O, Danzé F. Evidence of persisting cognitive impairment in a case series of patients with locked-in syndrome. J Neurol Neurosurg Psychiatry 2009;80(2):166-70. PMID 18948362
105: Sacco S, Sarà M, Pistoia F, Conson M, Albertini G, Carolei A. Management of pathologic laughter and crying in patients with locked-in syndrome: a report of 4 cases. Arch Phys Med Rehabil 2008;89(4):775-8. PMID 18374012
106: Sarasso S, Rosanova M, Casali AG, et al. Quantifying cortical EEG responses to TMS in (Un)consciousness. Clin EEG Neurosci 2014;45(1):40-9. PMID 24403317
107: Schiff ND, Rodriguez-Morena D, Kamal A, et al. fMRI reveals large-scale network activation in minimally conscious patients. Neurology 2005;64(3):514-23. PMID 15699384
108: Schilero GJ, Grimm DR, Bauman WA, Lenner R, Lesser M. Assessment of airway caliber and bronchodilator responsiveness in subjects with spinal cord injury. Chest 2005;127(1):149-55. PMID 15653976
109: Schnakers C, Majerus S, Goldman S, et al. Cognitive function in the locked-in syndrome. J Neurol 2008;255(3):323-30. PMID 18350365
110: Seales DM, Torkelson RD, Shuman RM, Rossiter VS, Spencer JD. Abnormal brainstem auditory evoked potentials and neuropathology in "locked-in" syndrome. Neurology 1981;31(7):893-6. PMID 7195515
111: Sedney CL, Coger BR, Bailes JE. Posterior fossa subdural hematoma resulting in locked-in syndrome: case report. Neurosurgery 2011;69(2):E497-500. PMID 21792146
112: Sellers EW, Ryan DB, Hauser CK. Noninvasive brain-computer interface enables communication after brainstem stroke. Sci Transl Med 2014;6(257):257re7. PMID 25298323
113: Shan G, Yining H, Xia H, Yicheng Z, Bo W, Shunwei L. Transcranial Doppler characteristics in persistent vegetative status, locked-in syndrome and brain death. Chin Med Sci J 1999;14(4):211-4. PMID 12894893
114: Shavelle R, Strauss D, Katz R. Survival of persons with locked-in syndrome. Arch Phys Med Rehabil 2008;89(5):1005. PMID 18452754
115: Sigut J, Sidha SA. Iris center corneal reflection method for gaze tracking using visible light. IEEE Trans Biomed Eng 2011;58(2):411-9. PMID 20952326
116: Silvoni S, Konicar L, Prats-Sedano MA, et al. Tactile event-related potentials in amyotrophic lateral sclerosis (ALS): implications for brain-computer interface. Clin Neurophysiol 2016;127(1):936-45. PMID 26209283
117: Smith E, Delargy M. Locked-in syndrome. BMJ 2005;330(7488):406-9. PMID 15718541
118: Smith WS. Intra-arterial thrombolytic therapy for acute basilar occlusion: pro. Stroke 2007;38(2 Suppl):701-3. PMID 17261720
119: Sonkar SK, Kumar S, Singh NK, Tandon R. Hyperhomocysteinemia induced locked-in syndrome in a young adult due to folic acid deficiency. Nutr Neurosci 2021;24(10):781-3. PMID 31642398
120: Sorger B, Reithler J, Dahmen B, Goebel R. A real-time fMRI-based spelling device immediately enabling robust motor-independent communication. Curr Biol 2012;22(14):1333-8. PMID 22748322
121: Staffen W, Kronbichler M, Aichhorn M, Mair A, Ladurner G. Selective brain activity in response to one’s own name in the persistent vegetative state. J Neurol Neurosurg Pschiatry 2006;77(12):1383-4. PMID 17110753
122: Teive HAG, Ferreira MG, Coutinho L, Camargo CHF, Munhoz RP, Walusinski O. The locked-in syndrome: The early French descriptions. Rev Neurol (Paris) 2022:S0035-3787(22)00643-9. PMID 35902307
123: Thielen N, Merkies ISJ. Reversibel ‘locked-in’ syndroom door centrale pontiene en extrapontiene myelinolyse [Reversible ‘locked in’ syndrome by central pontine and extrapontine myelinolysis]. Tijdschr Neurol Neurochir 2004;105(6):273-8.
124: Towle VL, Maselli R, Bernstein LP, Spire JP. Electrophysiologic studies on locked-in patients: heterogeneity of findings. Electroencephalogr Clin Neurophysiol 1989;73(5):419-26. PMID 2479520
125: Tresch DD, Sims FH, Duthie EH, et al. Clinical characteristics of patients in the persistent vegetative state. Arch Intern Med 1991;151:930-2. PMID 2025140
126: Tuz M, Erodlu F, Dodru H, Uygur K, Yavuz L. Transient locked-in syndrome resulting from stellate ganglion block in the treatment of patients with sudden hearing loss. Acta Anaesthesiol Scand 2003;47:485-7. PMID 12694151
127: Verhagen WI, Huygen PL, Schulte BP. Clinical and electrophysiological study in a patient surviving from locked-in syndrome. Clin Neurol Neurosurg 1986;88(1):57-61. PMID 3709004
128: Wijdicks EF, Miller GM. Transient locked-in syndrome after uncal herniation. Neurology 1999;52(6):1296-7. PMID 10214768
129: Yamaguchi Y, Sakurai Y, Mannen T, Shimizu J. Rapidly progressive polymyositis with elevated antiacetylcholine receptor antibody activity. Intern Med 2000;39:1108-10. PMID 11197802
130: Yan Y, Demertzi A, Xia Y, et al. Ethics of life-sustaining treatment in locked-in syndrome: A Chinese survey. Ann Phys Rehabil Med 2020;63(6):483-7. PMID 31682940
131: Yang CC, Lieberman JS, Hong CZ. Early smooth horizontal eye movement: a favorable prognostic sign in patients with the locked-in syndrome. Arch Phys Med Rehabil 1989;70:230-2. PMID 2923543
132: Ye Q, Xiang T. A clinical characteristic analysis of five cases of rare bilateral cerebral peduncular infarction (BCPI) with the 'Mickey Mouse ears' sign. Brain Inj 2021;35(3):363-367. PMID 33560892
133: Yokota Y, Ishihara M, Ninomiya S, Mitsuke K, Kamei S, Nakajima H. Locked-in syndrome due to meningovascular syphilis: a case report and literature review. Intern Med 2022;61(10):1593-8. PMID 34670896
134: Yoshiki H, Morimoto N, Urayama KY. Understanding the psychological well-being of patients with locked-in syndrome: a scoping review. Cureus 2023;15(1):e34295. PMID 36860234
135: Young B, Blume W, Lynch A. Brain death and the persistent vegetative state: similarities and contrasts. Can J Neurol Sci 1989;16:388-93. PMID 2680003

Contributors

All contributors' financial relationships have been reviewed and mitigated to ensure that this and every other article is free from commercial bias.

Author

Douglas J Lanska MD MS MSPH

Dr. Lanska of the University of Wisconsin School of Medicine and Public Health and the Medical College of Wisconsin has no relevant financial relationships to disclose.
See Profile

Former Authors

Kenneth Maiese MD
Nicole Reams MD

Patient Profile

Age range of presentation: 0 month to 65+ years
Sex preponderance: male=female
Heredity: none
Population groups selectively affected: none selectively affected
Occupation groups selectively affected: none selectively affected

This is an article preview.
Start a Free Account
to access the full version.

Nearly 3,000 illustrations, including video clips of neurologic disorders.
Every article is reviewed by our esteemed Editorial Board for accuracy and currency.
Full spectrum of neurology in 1,200 comprehensive articles.
Listen to MedLink on the go with Audio versions of each article.

Questions or Comment?

MedLink®, LLC

3525 Del Mar Heights Rd, Ste 304
San Diego, CA 92130-2122

Toll Free (U.S. + Canada): 800-452-2400

US Number: +1-619-640-4660

Support: service@medlink.com

Editor: editor@medlink.com

ISSN: 2831-9125

Locked-in syndrome

Associated Disorders

Coma
Confusional state
Delirium
Obtundation
Paralysis
- Persistent vegetative state
- Stupor

Differential Diagnosis

apallic syndrome
akinetic mutism
coma vigil
alpha coma
neocortical death
- coma
- persistent vegetative state
- brain death
- disorders of consciousness
- minimally conscious state

Also Relevant

Basilar artery stroke
Disorders of consciousness
Early myoclonic encephalopathy
Severe closed head injury

Clinical Categories

General Neurology

Patient Handouts

Central pontine myelinolysis

Locked-in syndrome …

Locked-in syndrome

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Confusing conditions

Associated or underlying disorders

Diagnostic workup

Management

Outcomes

Special considerations

Anesthesia

References

Contributors

Author

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview.
Start a Free Account
to access the full version.

Questions or Comment?

Also in This Category

Neurogenetics and genetic and genomic testing

Acute traumatic spinal cord injury

Tumors of the skull base

Toxic and nutritional deficiency optic neuropathies

Third nerve palsy

Nystagmus

Brain death/death by neurologic criteria

Outpatient rehabilitation of chronic neurologic conditions

Locked-in syndrome

Introduction

Overview

Key points

Historical note and terminology

Clinical manifestations

Presentation and course

Prognosis and complications

Clinical vignette

Biological basis

Etiology and pathogenesis

Epidemiology

Prevention

Differential diagnosis

Confusing conditions

Associated or underlying disorders

Diagnostic workup

Management

Outcomes

Special considerations

Anesthesia

References

Contributors

Author

Former Authors

Patient Profile

ICD & OMIM codes

This is an article preview. Start a Free Account to access the full version.

Questions or Comment?

Also in This Category

Neurogenetics and genetic and genomic testing

Acute traumatic spinal cord injury

Tumors of the skull base

Toxic and nutritional deficiency optic neuropathies

Third nerve palsy

Nystagmus

Brain death/death by neurologic criteria

Outpatient rehabilitation of chronic neurologic conditions

This is an article preview.
Start a Free Account
to access the full version.