7/5/23, 12:06 PM Locked-in syndrome - UpToDate Official reprint from UpToDate www.uptodate.com 2023 UpToDate, Inc. and/or its affiliates. All Rights Reserved. Locked-in syndrome : Louis R Caplan, MD : Jos Biller, MD, FACP, FAAN, FAHA, Glenn A Tung, MD, FACR : Janet L Wilterdink, MD All topics are updated as new evidence becomes available and our peer review process is complete. Literature review current through: Jun 2023. This topic last updated: Sep 20, 2021. INTRODUCTION The locked-in syndrome is a catastrophic condition caused most often by ischemic stroke or hemorrhage, affecting the corticospinal, corticopontine, and corticobulbar tracts in the brainstem. Because consciousness and higher cortical functions are spared, patients can sometimes communicate through eye movements. Alexandre Dumas provided one of the earliest descriptions of the locked-in syndrome in "The Count of Monte Cristo" by vividly depicting a character who was "a corpse with living eyes." Following a stroke, Monsignor Noirtier de Villefort could only communicate by raising, closing, or winking his eyes [1]. Issues related to the locked-in syndrome will be reviewed here. Conditions superficially similar to the locked-in syndrome, such as coma, minimally conscious state, and persistent vegetative state, are discussed separately. (See "Stupor and coma in adults".) DEFINITION AND ANATOMY In 1966, Plum and Posner coined the term "locked-in" to describe the state of quadriplegia and anarthria (speechlessness due to severe dysarthria) with preserved consciousness [2]. Synonymous with locked-in syndrome are "de-efferented state," "pseudocoma," and "coma vigilante." There are two requisites for the diagnosis of locked-in syndrome: https://www.uptodate.com/contents/locked-in-syndrome/print 1/20 7/5/23, 12:06 PM Locked-in syndrome - UpToDate Retained alertness and cognitive abilities Paralysis of the limbs and oral structures such that the individual cannot signal with the limbs or speak The important neuronal tracts that are disrupted in patients with locked-in syndrome course from the cortex toward the bulbar motor neurons and spinal cord by traveling through the brainstem. Limb movements are mediated by the tracts to the spinal cord neurons that travel in the basal and ventral portions of the brainstem; these include the cerebral peduncles in the midbrain, the base of the pons, and the medullary pyramids. Bilateral lesions of these structures cause a loss of voluntary limb movement accompanied by exaggerated deep tendon reflexes, limb spasticity, and extensor plantar reflexes (Babinski signs). Motor function of the mouth, pharynx, and jaws is mediated by the corticobulbar fibers that travel in the dorsal portion of the midbrain and pons near the tegmental-basal junction and synapse with the motor neurons located in the ambiguous (cranial nerves IX, X, XI), trigeminal (cranial nerve V), and facial (cranial nerve VII) nuclei. Bilateral lesions involving these fibers cause a loss of voluntary mouth and tongue movement as well as loss of speech and swallow. The structures within the brainstem that control eye movements and consciousness are located in the dorsal portion of the tegmentum in the midbrain and pons near the midline. The eye movement nuclei (cranial nerves III, IV, VI) and connecting pathways that relate to eye movements (the medial longitudinal fasciculi [MLF] and the so-called pontine lateral gaze center in the paramedian pontine reticular formation [PPRF]) are symmetrically represented in the medial tegmentum on each side of the midline. Bilateral lesions that involve these structures cause a loss of horizontal eye movements. When the lesions involve only one side, some horizontal eye movement is preserved. The medial and lateral reticular formation subserves consciousness and the control of respiratory, cardiac, and vasomotor functions, respectively. The portion of the reticular activating system that relates to consciousness is located in the paramedian tegmentum, while cardiovascular and respiratory-related structures are located more laterally in the tegmentum of the pons and medulla oblongata. Lesions must involve the medial tegmentum bilaterally to cause coma. Automatic respirations and cardiovascular functions are not affected if the brainstem tegmental lesions are paramedial, and lateral tegmental structures are spared. (See "Stupor and coma in adults".) ETIOLOGY https://www.uptodate.com/contents/locked-in-syndrome/print 2/20 7/5/23, 12:06 PM Locked-in syndrome - UpToDate The most common cause of locked-in syndrome is ischemic or hemorrhagic stroke, accounting for 38 of 44 cases in a review from France [3]. Ischemic infarction of the ventral pons is usually due to basilar artery embolism or thrombosis ( picture 1) [4]. The most vulnerable territory is the paramedian base of the pons. Because the tegmentum has generous collateral supply that courses from the lateral aspect, the lateral and medial tegmentum are often spared. Midbrain infarction or traumatic injury of the bilateral cerebral peduncles causing the locked-in syndrome has also been reported [5-7]. A second cause of stroke-induced locked-in syndrome is pontine hemorrhage, which is most often related to hypertension but can also result from vascular malformations. Hypertensive pontine hemorrhages typically begin at the tegmentobasal junction and usually cause coma, loss of horizontal gaze, quadriplegia, and eventually death. A residual locked-in state is rare. Additional causes of the locked-in syndrome include trauma [3,7], pontine abscess [8], brainstem tumors [9,10], central pontine myelinolysis [11-13], toxins, heroin abuse [14], and others [15]. CLINICAL FEATURES Bilateral ventral pontine damage causes quadriplegia and inability to speak or swallow, but consciousness is preserved. Because the supranuclear ocular motor pathways lie more dorsally, patients with locked-in syndrome can move their eyes. Thus, voluntary blinking and vertical eye movements remain intact, but the patient cannot otherwise move muscles in the limbs, trunk, or face. Sparing of the reticular formation allows for normal wakefulness, but sleep-wake cycles may be abnormal depending on the extent of damage to the intricate sleep pathways in the brainstem. Various abnormalities have been identified in both rapid eye movement (REM) and non-REM sleep [15]. Tegmental lesions In some patients, the initial dysfunction (most often ischemia) also extends to the tegmentum of the pons on one or both sides. Bilateral lesions affecting the paramedian tegmentum result in coma and loss of horizontal eye movements. Vertical eye movements, which are controlled in the rostral portion of the brainstem, are preserved. Sometimes, the eyes bob downward spontaneously or when the head is rolled from side to side in the "doll's eyes" maneuver. With unilateral pontine tegmental lesions, consciousness is preserved. In such cases, the eye movement abnormality may consist of one of the following types: https://www.uptodate.com/contents/locked-in-syndrome/print 3/20 7/5/23, 12:06 PM Locked-in syndrome - UpToDate Loss of horizontal conjugate gaze to the side of the lesion. An internuclear ophthalmoplegia (INO) manifested by abnormalities of gaze to the opposite side that are due to loss of adduction of the ipsilateral eye along with nystagmus of the abducting eye. As an example, a lesion of the left medial longitudinal fasciculus (MLF) would result in loss of rightward movement of the left eye and nystagmus of the right eye during attempted gaze to the right side. (See "Internuclear ophthalmoparesis".) A combination of the lateral gaze and internuclear deficits referred to as a "one-and-a-half" syndrome. If gaze to each side is tallied as one, the only gaze remaining is abduction of one eye (ie, only one-half of the usual two movements). As an example, a lesion of the left pontine tegmentum affecting both the paramedian pontine reticular formation (PPRF) and the MLF would result in the only residual movement being abduction of the right eye on right lateral gaze. Other Many patients with the locked-in syndrome retain some other voluntary movements beside vertical eye motion such as horizontal gaze, facial expression, limb, head, or tongue movements [15]. Patients with the locked-in syndrome may have various different involuntary motor phenomena including ocular bobbing, crying, trismus, oral automatisms, groaning, facial grimacing, yawning, palatal myoclonus, sighing, coughing, bruxism, and laughing [15]. Some have involuntary limb movements that resemble seizures, especially when they first become weak [16]. These movements can be periodic limb-stiffening, shivering, and dystonic postures. Respiration is often affected in the locked-in syndrome when the lateral tegmentum of the pons or medulla is involved. Patients may require assistance in ventilation and pulmonary toilet. The lips, tongue, and soft palate are all thoroughly weakened as to prevent coordination of breathing, voluntary vocalization, or swallowing. DIAGNOSIS In order to establish the diagnosis of the locked-in syndrome, it is imperative to demonstrate preservation of consciousness, alertness, and cognitive function in a patient with paralysis of the limbs and oral structures. Observation and examination of eye movements during bedside interaction is the key to making this determination, since patients with the locked-in syndrome cannot respond to questions by speaking or moving the limbs. The diagnosis can easily be missed if voluntary vertical eye movements are not examined with great care in patients who seem unresponsive [17]. https://www.uptodate.com/contents/locked-in-syndrome/print 4/20 7/5/23, 12:06 PM Locked-in syndrome - UpToDate Vertical eye movements should be reexamined in otherwise unresponsive patients if brain magnetic resonance imaging (MRI) shows a lesion in the ventral pons [17]. In addition, eye movements should be reexamined over time, as some patients may emerge from coma into a locked-in state after a variable delay. Hearing may recover before eye-opening [18]. Some investigators have noted that patients with the locked-in syndrome tire quickly when using vertical eye movements to communicate [17]. In addition, patients with the locked-in syndrome may have a severely limited attention span in the first weeks or months after onset of the locked-in syndrome [17]. Because of the inherent difficulty in diagnosing the locked-in syndrome, the diagnosis is often delayed. In a review of 44 cases from France, the mean time to diagnosis of the locked-in syndrome was 79 days after onset [3]. The neurologic examination should begin by determining whether the patient is awake, opens eyes to voice, blinks to command, and can move the limbs. The paralyzed patient with the locked-in syndrome will be able to respond to complex linguistic requests with vertical eye movements and blinking but cannot move the limbs or speak. Neuroimaging Infarction and other structural lesions of the brainstem including tumor, abscess, and demyelination are best visualized on MRI because computed tomography (CT) of the posterior fossa may be compromised by beam-hardening artifact ( image 1). Diffusion- weighted MRI is very sensitive for acute ischemic infarction. Noncontrast CT and both T2*-weighted gradient echo and susceptibility-weighted MRI are sensitive for the detection of brainstem hemorrhage ( image 2). Both CT and magnetic resonance angiography can identify the location and severity of large- and medium-size vessel occlusions in the extracranial arteries of the neck and intracranial circulation. Steno-occlusive disease of short and long circumferential basilar artery branches that supply the pons is often too small to be detected on these examinations. Other tests Electroencephalography (EEG) reactivity is not a reliable measure of consciousness in patients with the locked-in syndrome as reactivity can be absent in some cases [19]. However, the presence of alpha coma does help to distinguish diffuse cerebral injuries such as the persistent vegetative state from the locked-in syndrome. In addition, a normal EEG in a patient who seems unresponsive suggests either the locked-in syndrome or psychogenic coma, so it can be helpful. Somatosensory evoked potentials have variable patterns and thus show no specific characteristics in the locked-in syndrome [19]. Brainstem auditory evoked potentials are normal https://www.uptodate.com/contents/locked-in-syndrome/print 5/20 7/5/23, 12:06 PM Locked-in syndrome - UpToDate when brainstem lesions do not involve auditory pathways, as can be the case in the locked-in syndrome. A lumbar puncture is warranted to consider inflammatory and infectious causes such as encephalitis if MRI does not reveal a structural cause in patients with possible locked-in syndrome. Differential diagnosis When immobile patients do not respond to queries or directions, the differential diagnosis includes the locked-in syndrome, coma, persistent vegetative state, akinetic mutism, catatonia, and psychogenic unresponsiveness ( table 1). Is the patient not responding because of paralysis with retained consciousness (the locked-in syndrome), reduced consciousness and awareness (stupor or coma), wakefulness without awareness (persistent vegetative state), or a psychiatric disorder (catatonia or psychogenic unresponsiveness)? (See "Stupor and coma in adults".) The essential criteria to make a diagnosis of the locked-in syndrome are paralysis with intact awareness and cognitive function. Comatose patients do not open or move the eyes, respond to voice or noxious stimuli, or move the limbs. The patient with the locked-in syndrome uses vertical eye movements and blinking to follow complex linguistic requests. Since control of eye movements rests in the medial tegmentum of the brainstem, examination of eye movement function is an important key to differential diagnosis. What is the position of the eyes at rest? An ocular skew may indicate damage to the brainstem. Are there spontaneous roving eye movements? This finding is often caused by bilateral cerebral hemisphere disease due to bilateral strokes or metabolic or toxic disorders. Is there bobbing of the eyes downward? This finding suggests a pontine lesion. Can the patient open the eyes and look up and down? Preserved vertical eye movements indicate intact midbrain function. Are doll's eyes movements in the horizontal and vertical positions preserved? In coma due to brainstem lesions, horizontal eye movements are lost and vertical eye movements are often spared. In akinetic mutism, patients lack drive and motivation to move and speak spontaneously. Maintenance of body posture is a distinguishing feature of catatonia. https://www.uptodate.com/contents/locked-in-syndrome/print 6/20 7/5/23, 12:06 PM Locked-in syndrome - UpToDate Amyotrophic lateral sclerosis (ALS) is another central cause of the locked-in syndrome in which oculomotor function is spared, but ALS causes gradual weakness and does not present acutely. (See "Clinical features of amyotrophic lateral sclerosis and other forms of motor neuron disease".) Purely peripheral conditions that may have clinical features similar to the locked-in syndrome include severe polyneuropathy, such as acute inflammatory demyelinating polyradiculoneuropathy (AIDP; also known as Guillain-Barr syndrome); neuromuscular disorders, such as myasthenia gravis and critical illness neuropathy/myopathy; and pharmacologic neuromuscular blockade. (See "Guillain-Barr syndrome in adults: Pathogenesis, clinical features, and diagnosis" and "Clinical manifestations of myasthenia gravis" and "Neuromuscular weakness related to critical illness".) While these neuromuscular disorders may cause profound diffuse limb weakness, it is rare for any of them to cause complete bulbar and limb paralysis. Either speech or some limb motion is typically spared, permitting communication or signaling. The past history and gradual development of paralysis almost always allows identification of a peripheral neuromuscular problem. Toxic-metabolic encephalopathies and the presence of sedative, analgesic, or psychotropic drugs must all be considered and ruled out when the patient is unresponsive and imaging does not support a structural cause. (See "Diagnosis of delirium and confusional states" and "Stupor and coma in adults".) PROGNOSIS Although early literature suggested that the locked-in syndrome was an irreversible condition leading to death shortly after onset [20], accumulating evidence suggests that a substantial proportion regain some function over time, and a minority have a good functional recovery. However, most survivors of the locked-in syndrome remain chronically locked-in or severely impaired. Case studies described patients who recovered from the locked-in syndrome anywhere from 30 minutes to several weeks after onset. In these cases, the causes of the locked-in syndrome were brainstem ischemia, encephalitis, and trauma [21]. One report described four patients with the locked-in syndrome due to presumed basilar artery occlusion who made substantial functional gains over several months while receiving supportive therapy and rehabilitation [22]. These patients recovered to independence in at least some activities of daily living; they regained https://www.uptodate.com/contents/locked-in-syndrome/print 7/20 7/5/23, 12:06 PM Locked-in syndrome - UpToDate bowel and bladder control, could eat by mouth, and regained functional, although dysarthric, speech. Few large-scale studies have evaluated the extent of recovery and mortality of patients with the locked-in syndrome. In the largest published review of 139 cases, the mortality rate was 60 percent, and most of the deaths (87 percent) occurred within the first four months [15]. The most common causes of death were pneumonia, pulmonary embolism, extension of brainstem lesions, and sepsis. Patients with the locked-in syndrome due to nonvascular etiologies (eg, trauma) had lower mortalities and faster and more complete recoveries compared with patients with the locked-in syndrome due to vascular causes, mainly pontine infarction. However, functional recovery was generally good in those patients with a vascular etiology who survived beyond four months. The most extensive longitudinal evidence comes from a cohort of 27 patients with the locked-in syndrome who were locked-in for over a year; the first report from this cohort was an observational study published in 1987 [23]. Mean survival was 4.9 years and ranged from 1.2 to 12.8 years by study completion. The majority of the survivors were at home, while some lived in nursing homes or acute care hospitals. Eleven patients never moved their limbs or head, six had minor movements, and 10 could trigger a switch, point, or type. Seven patients could use an electric wheelchair. Many patients in this series achieved bowel and bladder continence [23]. All except for seven ate food by mouth. Eight patients (29 percent) could consistently answer questions appropriately but had learning difficulties. Some of those patients had extrapontine hemorrhages or traumatic injury. Sixteen patients (59 percent) recovered the ability to cry involuntarily or speak words and sentences. All except for three patients communicated with gestures, limb movements, a letter board, or electronic equipment. Almost all of the patients in this series developed typical complications of chronic assisted care including urinary tract infections, pneumonia, pressure sores, gastrointestinal bleeding, and deep venous thrombosis [23]. Many of these medical problems were attributed to indwelling urinary catheters, gastrostomy tubes, and tracheostomies, although there were insufficient patient numbers to ascertain a statistical association between medical complications and these devices. In a subsequent report published in 1992 by the same investigators, who added two further patients, survival ranged from 2 to 18 years [24]. A telephone survey published in 2003 found that from the original cohort of 29 patients, 16 had died in the interim. Overall survival rates at https://www.uptodate.com/contents/locked-in-syndrome/print 8/20 7/5/23, 12:06 PM Locked-in syndrome - UpToDate 10 and 20 years were 83 and 40 percent, respectively [25]. This is one of the few studies to date showing that some patients with the locked-in syndrome survive for a decade or more. In another study, among 11 patients with the locked-in syndrome followed anywhere from 7 months to 10 years, four (36 percent) achieved good functional outcomes [26]. All of the patients could manipulate a digital switch, and some used electric wheelchairs and computers for communication. Recovery tended to progress distally and spread proximally along the axial musculature. Quality of life There is limited information on the quality of life or emotional state of patients with the locked-in syndrome. A psychological analysis of seven long-term survivors found that their quality of life was worse than cancer patients but better than the terminally ill; all scored in the range of a depressive illness, and four had contemplated suicide. All, however, wanted life-sustaining treatments including antibiotics for pneumonia [27]. In a retrospective survey cited above involving 13 survivors with the locked-in syndrome (from an initial cohort of 29) or their caregivers, satisfaction with life was expressed by seven patients, occasional depression was reported for five patients, euthanasia was never considered by seven, euthanasia was considered but refused by six, and a wish to die was expressed by one patient [25]. None had do not resuscitate (DNR) directives. A subsequent case-control study compared 19 patients with the locked-in syndrome and 20 age-matched healthy control subjects [28]. There was no significant difference between the locked-in syndrome group and healthy controls on scores assessing overall quality of life and mental health. However, the locked-in syndrome group had significantly lower scores on measures of physical function, as might be expected. In addition, the locked-in syndrome group had a significantly higher frequency of depressive symptoms. These studies underscore the need to screen for the development of and to address possible treatment for depression and suicidal ideation in patients with the locked-in syndrome. TREATMENT While there are no proven medical therapies that promote recovery from the locked-in syndrome, care should be centralized and coordinated in a specialized rehabilitation center experienced in the locked-in syndrome. Multimodal therapy with physical and speech therapy https://www.uptodate.com/contents/locked-in-syndrome/print 9/20 7/5/23, 12:06 PM Locked-in syndrome - UpToDate and assistive devices to facilitate interaction may improve outcome. Supportive and preventive measures are of paramount importance for patients with the locked-in syndrome. Patients with the locked-in syndrome are fully conscious and should be encouraged to participate in decisions affecting their care at all stages of treatment. Immediate therapies The acute stage of treatment for the locked-in syndrome focuses on securing and maintaining an airway and ensuring adequate oxygenation. Primary attention should be paid to rapidly identifying the vascular cause of the locked-in syndrome. For patients with the locked-in syndrome due to acute ischemic stroke (within 48 hours from onset or most recent deterioration) with persistent vascular occlusion, revascularization is appropriate. This recommendation is made because of the poor functional prognosis of brainstem stroke associated with the locked-in syndrome. The utility of intravenous thrombolysis and endovascular treatments for posterior circulation stroke are discussed separately. (See "Approach to reperfusion therapy for acute ischemic stroke", section on 'Posterior circulation stroke'.) The use of antithrombotic therapy for vertebral and basilar artery dissection is reviewed separately. (See "Cerebral and cervical artery dissection: Treatment and prognosis".) Nonvascular causes should be managed according to specific etiologies (eg, antibiotics for infection, steroids for inflammatory lesions, radiation/chemotherapy for brainstem tumors). Subacute and chronic therapies Given that many patients can achieve some meaningful recovery, we suggest aggressive supportive measures; intense physical, speech, respiratory, and swallowing therapy; and assisted devices to facilitate interaction with others and the environment [17]. Although data are limited, support for aggressive rehabilitation therapy comes from a case series published in 2003 that evaluated the recovery patterns of 14 patients with the locked-in syndrome who underwent intensive, multidisciplinary rehabilitation within a mean of one month of symptom onset [29]. The following observations were made: Partial or full independence in activities of daily living within three to six months of onset was achieved by three patients (21 percent) Complete swallowing ability recovered in six (43 percent) Verbal communication recovered despite dysarthria and dysphonia in four (28 percent) Ability to use a device by hand, finger, or head movement was achieved in six (43 percent) https://www.uptodate.com/contents/locked-in-syndrome/print 10/20 7/5/23, 12:06 PM Locked-in syndrome - UpToDate Tracheostomy removal was achieved by six patients (43 percent) Finally, all but four patients returned home. Unless patients themselves express wishes not to be sustained, we discourage attitudes of medical nihilism towards the locked-in syndrome [30,31]. After hospitalization, care should be centralized and coordinated in a specialized rehabilitation center experienced in the locked-in syndrome. Care should include identifying and treating reversible medical conditions such as infections and electrolyte abnormalities, inquiring about and treating pain, and preventing immobility, contractures, corneal abrasions, and decubitus ulcers. The locked-in syndrome poses high risks for respiratory complications, and patients need to be monitored closely for difficulties handling secretions or needs for ventilatory assistance. Accordingly, we favor chest physiotherapy, deep breathing exercises [29], and chest mobilization to facilitate bronchial secretions. Vigorous medical management may allow for the formation of collateral circulation and recovery of damaged neural pathways. Modification of vascular risk factors is imperative to reduce the risk of subsequent strokes and other vascular events. (See "Overview of secondary prevention of ischemic stroke".) Planning with family and friends is necessary to design long-term care. Communication For basic communication, a combination of eyelid-blinking and vertical eye movements can be used to establish a yes/no code. A variety of electronic devices are available to facilitate communication, including computers, printers, synthetic voice machines triggered by sensitive switches, and head or eye gaze sensors [32]. Such communication devices have allowed patients to e-mail, use the internet, read daily news, write stories, compose music, and shop online [32]. Whatever form of communication is used, the method should be posted at the bedside. SUMMARY AND RECOMMENDATIONS Definition The locked-in syndrome is a rare catastrophic condition characterized by limb paralysis and loss of speech with retained consciousness, alertness, and cognition. (See 'Definition and anatomy' above.) Neuroanatomy and causes The locked-in syndrome is caused by destructive bilateral brainstem lesions affecting the corticospinal, corticopontine, and corticobulbar tracts. The https://www.uptodate.com/contents/locked-in-syndrome/print 11/20 7/5/23, 12:06 PM Locked-in syndrome - UpToDate most common cause is ischemic infarction of the ventral pons. (See 'Etiology' above.) Clinical features Quadriplegia and inability to speak or swallow with retained cognition are the hallmarks of the locked-in syndrome. Respiration is often affected. Because the supranuclear ocular motor pathways are spared, patients can move their eyes and blink. Many patients with LIS also retain some other voluntary movements such as horizontal gaze, facial expression, and limb, head, or tongue movements. In addition, patients with the locked-in syndrome may have involuntary ocular, oral, or limb movements. (See 'Clinical features' above.) Diagnosis In a patient with quadriplegia who cannot speak, demonstration of preserved consciousness requires close observation and examination of eye movements during bedside interaction. This is the key to making the diagnosis of the locked-in syndrome. (See 'Diagnosis' above.) Differential diagnosis The differential diagnosis of the locked-in syndrome includes coma, persistent vegetative state, akinetic mutism, catatonia, and psychogenic unresponsiveness. (See 'Differential diagnosis' above.) Management The acute stage of treatment for the locked-in syndrome focuses on securing and maintaining an airway, ensuring adequate oxygenation, and rapidly identifying and treating vascular causes. (See 'Immediate therapies' above.) For patients with the locked-in syndrome due to acute ischemic stroke caused by vertebral or basilar artery embolism or thrombosis with persistent vascular occlusion, reperfusion therapy is advised. Specific recommendations are provided separately. (See "Approach to reperfusion therapy for acute ischemic stroke", section on 'Posterior circulation stroke'.) Prognosis Most survivors of the locked-in syndrome remain chronically locked-in or severely impaired. However, many regain some motor function over time, and a minority have a good functional recovery. Aggressive multidisciplinary rehabilitation measures are appropriate for patients with the locked-in syndrome who indicate a desire for such therapy. Ideally, such therapy should begin within one month of onset and include intense physical, speech, and respiratory therapy. (See 'Subacute and chronic therapies' above.) Long-term supportive care Supportive care for the locked-in syndrome should include identifying and treating reversible medical conditions such as infections and electrolyte https://www.uptodate.com/contents/locked-in-syndrome/print 12/20 7/5/23, 12:06 PM Locked-in syndrome - UpToDate abnormalities, inquiring about and treating patients' pain, and preventing immobility, contractures, corneal abrasions, and decubitus ulcers. (See 'Subacute and chronic therapies' above.) ACKNOWLEDGMENT The UpToDate editorial staff acknowledges Sean Savitz, MD, who contributed to an earlier version of this topic review. Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Dumas A. The Count of Monte Cristo, Wordworth Editions, London 1997. 2. Plum F, Posner JB. The Diagnosis of Stupor and Coma, FA Davis, Philadelphia 1966. 3. Le n-Carri n J, van Eeckhout P, Dom nguez-Morales Mdel R, P rez-Santamar a FJ. The locked-in syndrome: a syndrome looking for a therapy. Brain Inj 2002; 16:571. 4. Bruno MA, Schnakers C, Damas F, et al. Locked-in syndrome in children: report of five cases and review of the literature. Pediatr Neurol 2009; 41:237. 5. Karp JS, Hurtig HI. "Locked-in" state with bilateral midbrain infarcts. Arch Neurol 1974; 30:176. 6. Zakaria T, Flaherty ML. Locked-in syndrome resulting from bilateral cerebral peduncle infarctions. Neurology 2006; 67:1889. 7. Carrai R, Grippo A, Fossi S, et al. Transient post-traumatic locked-in syndrome: a case report and a literature review. Neurophysiol Clin 2009; 39:95. 8. Murphy MJ, Brenton DW, Aschenbrener CA, Van Gilder JC. Locked-in syndrome caused by a solitary pontine abscess. J Neurol Neurosurg Psychiatry 1979; 42:1062. 9. Cherington M, Stears J, Hodges J. Locked-in syndrome caused by a tumor. Neurology 1976; 26:180. 10. Inci S, Ozgen T. Locked-in syndrome due to metastatic pontomedullary tumor case report. Neurol Med Chir (Tokyo) 2003; 43:497. 11. Pirzada NA, Ali II. Central pontine myelinolysis. Mayo Clin Proc 2001; 76:559. 12. Heckmann JG, Dinkel HP. Recovery of locked-in syndrome in central pontine myelinolysis. Am J Case Rep 2013; 14:219. https://www.uptodate.com/contents/locked-in-syndrome/print 13/20 7/5/23, 12:06 PM Locked-in syndrome - UpToDate 13. Sohn MK, Nam JH. Locked-in Syndrome due to Central Pontine Myelinolysis: Case Report. Ann Rehabil Med 2014; 38:702. 14. Hall JH 3rd, Karp HR. Acute progressive ventral pontine disease in heroin abuse. Neurology 1973; 23:6. 15. Patterson JR, Grabois M. Locked-in syndrome: a review of 139 cases. Stroke 1986; 17:758. 16. Ropper AH. 'Convulsions' in basilar artery occlusion. Neurology 1988; 38:1500. 17. Smith E, Delargy M. Locked-in syndrome. BMJ 2005; 330:406. 18. Chisholm N, Gillett G. The patient's journey: living with locked-in syndrome. BMJ 2005; 331:94. 19. G tling E, Isenmann S, Wichmann W. Electrophysiology in the locked-in-syndrome. Neurology 1996; 46:1092. 20. Bauer G, Gerstenbrand F, Rumpl E. Varieties of the locked-in syndrome. J Neurol 1979; 221:77. 21. Khurana RK, Genut AA, Yannakakis GD. Locked-in syndrome with recovery. Ann Neurol 1980; 8:439. 22. McCusker EA, Rudick RA, Honch GW, Griggs RC. Recovery from the 'locked-in' syndrome. Arch Neurol 1982; 39:145. 23. Haig AJ, Katz RT, Sahgal V. Mortality and complications of the locked-in syndrome. Arch Phys Med Rehabil 1987; 68:24. 24. 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; 73:403. 25. 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; 18:435. 26. Richard I, P reon Y, Guiheneu P, et al. Persistence of distal motor control in the locked in syndrome. Review of 11 patients. Paraplegia 1995; 33:640. 27. Anderson C, Dillon C, Burns R. Life-sustaining treatment and locked-in syndrome. Lancet 1993; 342:867. 28. 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; 16:1455. 29. 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; 84:862. https://www.uptodate.com/contents/locked-in-syndrome/print 14/20 7/5/23, 12:06 PM Locked-in syndrome - UpToDate 30. Thiel A, Schmidt H, Prange H, Nau R. [Treatment of patients with thromboses of the basilar artery and locked-in syndrome. An ethical dilemma]. Nervenarzt 1997; 68:653. 31. 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. 32. S derholm S, Meinander M, Alaranta H. Augmentative and alternative communication methods in locked-in syndrome. J Rehabil Med 2001; 33:235. Topic 1099 Version 20.0 https://www.uptodate.com/contents/locked-in-syndrome/print 15/20 7/5/23, 12:06 PM Locked-in syndrome - UpToDate GRAPHICS Basilar artery thrombosis Postmortem photograph of the ventral surface of the brainstem showing a dilated, thrombosed basilar artery. The thrombus extends into the anterior inferior cerebellar artery on the right. The two vertebral arteries that join to form the basilar are seen at the bottom of the photograph. Graphic 56754 Version 2.0 https://www.uptodate.com/contents/locked-in-syndrome/print 16/20 7/5/23, 12:06 PM Locked-in syndrome - UpToDate Central pontine myelinolysis Fifty-year-old individual with alcohol use disorder was treated for hyponatremia and developed decreased consciousness and de-efferented state (ie, patient was not able to speak or move face or limbs) secondary to osmotic demyelination syndrome. Sagittal T1-weighted (A) and transverse axial T2-weighted (B) MRIs demonstrate abnormal signal intensity in basis pontis consistent with central pontine myelinolysis. MRI: magnetic resonance imaging. Courtesy of Glenn A Tung, MD, FACR. Graphic 132737 Version 2.0 https://www.uptodate.com/contents/locked-in-syndrome/print 17/20 7/5/23, 12:06 PM Locked-in syndrome - UpToDate Hypertensive pontine hemorrhage Thirty-six-year-old with locked-in syndrome from hypertensive pontine hemorrhage. Noncontrast CT (A), T2* weighted gradient echo (B), and magnified susceptibility-weighted MRI (C) demonstrate acute upper pontine hematoma. CT: computed tomography; MRI: magnetic resonance imaging. Courtesy of Glenn A Tung, MD, FACR. Graphic 132738 Version 2.0 https://www.uptodate.com/contents/locked-in-syndrome/print 18/20 7/5/23, 12:06 PM Locked-in syndrome - UpToDate Differential diagnosis of locked-in syndrome Distinguishing clinical features Anatomical lesion Locked-in Quadriplegia with preserved vertical Pontine base syndrome eye movements and consciousness Coma Unresponsive to stimuli, does not follow commands Bilateral cerebral or upper brain stem Akinetic mutism No spontaneity or motivation Bifrontal, deep gray matter, upper brain stem Catatonia Maintenance of body posture No CNS lesions Persistent vegetative state No higher cortical functions, does not follow commands, retained Diffuse cerebral hemisphere cardiovascular and respiratory functions CNS: central nervous system. Graphic 65484 Version 3.0 https://www.uptodate.com/contents/locked-in-syndrome/print 19/20 7/5/23, 12:06 PM Locked-in syndrome - UpToDate Contributor Disclosures Louis R Caplan, MD No relevant financial relationship(s) with ineligible companies to disclose. Jos Biller, MD, FACP, FAAN, FAHA No relevant financial relationship(s) with ineligible companies to disclose. Glenn A Tung, MD, FACR No relevant financial relationship(s) with ineligible companies to disclose. Janet L Wilterdink, MD No relevant financial relationship(s) with ineligible companies to disclose. Contributor disclosures are reviewed for conflicts of interest by the editorial group. When found, these are addressed by vetting through a multi-level review process, and through requirements for references to be provided to support the content. Appropriately referenced content is required of all authors and must conform to UpToDate standards of evidence. Conflict of interest policy https://www.uptodate.com/contents/locked-in-syndrome/print 20/20