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Last updated:
March 07, 2018
Years published: 1988, 1989, 1997, 2000, 2010, 2018
NORD gratefully acknowledges Francesca Pistoia, MD, PhD, Neurologist and Assistant Professor of Neurorehabilitation, University of L’Aquila, Italy, and Steven Laureys, MD, PhD, Coma Science Group, University Hospital of Liege, Belgium, for assistance in the preparation of this report.
Summary
Locked-in syndrome is a rare neurological disorder in which there is complete paralysis of all voluntary muscles except for the ones that control the movements of the eyes. Individuals with locked-in syndrome are conscious and awake, but have no ability to produce movements (outside of eye movement) or to speak (aphonia). Cognitive function is usually unaffected. Communication is possible through eye movements or blinking. Locked-in syndrome is caused by damaged to the pons, a part of the brainstem that contains nerve fibers that relay information to other areas of the brain.
Introduction
The first description of the locked-in syndrome can be found in The Count of Monte Cristo authored by Alexandre Dumas. To describe a patient with a locked-in syndrome, the author used the following words:
‘Sight and hearing were the only senses remaining…. It was only, however, by means of one of these senses that he could reveal the thoughts and feelings that still occupied his mind, and the look by which he gave expression to his inner life was like the distant gleam of a candle which a traveler sees by night across some desert place, and knows that a living being dwells beyond the silence and obscurity. In his eyes, shaded by thick black lashes, was concentrated, as it often happens with an organ which is used to the exclusion of the others, all the activity, address, force, and intelligence which were formerly diffused over his whole body; and so although the movement of the arm, the sound of the voice, and the agility of the body, were wanting, the speaking eye sufficed for all’.
In this way, he brilliantly highlighted the potential that these patients have to maintain a meaningful life despite their extreme disability.
Individuals with locked-in syndrome classically cannot consciously or voluntarily chew, swallow, breathe, speak, or produce any movements other than those involving the eyes or eyelids. Some affected individuals can move their eyes up and down (vertically), but not side-to-side (horizontally). Affected individuals are bedridden and completely reliant on caregivers. Despite physical paralysis, cognitive function is unaffected.
Individuals with locked-in syndrome are fully alert and aware of their environment. They can hear, see and have preserved sleep-wake cycles. Affected individuals can communicate through purposeful movements of their eyes or blinking or both. They can comprehend people talking or reading to them.
Individuals with locked-in syndrome often initially are comatose before gradually regaining consciousness, but remain paralyzed and unable to speak.
Clinical forms
The locked-in syndrome may be classified in three different clinical forms, according to the traditional classification of Bauer. This classification is based on the amount of motor outputs, which are preserved in the patients. It talks about a pure form when the patient loses the control of all body movements with the exception of blinking and vertical eye movements; an incomplete form when some voluntary movements other than eye movements are preserved and a total form when a complete loss of motor function occurs. The last condition is particularly dramatic as the patients are completely unable to interact with the environment and to express their needs and thoughts.
Quality of life
Although the locked-in syndrome appears as the most dramatic form of motor disability one can imagine, some scientific reports indicate that the quality of life of patients is not so poor as expected. A recent survey investigated the self-reported quality of life of chronic patients with locked-in syndrome and concluded that many patients have a happy and meaningful life, especially when proper social services help patients to have a normal role at home as well as in the community.
Additional symptoms under investigation
Patients with locked-in syndrome are traditionally considered cognitively intact as all the cerebral structures with the exception of the ventral portion of the pons of the brain are apparently preserved. However, recent evidence suggests that the patients can develop some non-motor symptoms including motor imagery defects, pathological laughter and crying, and difficulties in the recognition of some facial expressions. The interruption of the cortico-ponto-cerebellar pathways, by means of the the same lesion causing the locked-in syndrome, may be responsible for the appearance of these clinical manifestations. However, these symptoms are not detected in all affected individuals and are currently under further investigation. The recognition of motor imagery defects deserves special attention because these symptoms, whenever present, may interfere with the success of rehabilitation strategies.
Locked-in syndrome is most often caused by damage to a specific part of the brainstem known as the pons. The pons contains important neuronal pathways between the cerebrum, spinal cord and cerebellum. In locked-in syndrome there is an interruption of all the motor fibers running from grey matter in the brain via the spinal cord to the body’s muscles and also damage to the centers in the brainstem important for facial control and speaking.
Damage to the pons most often results from tissue loss due to lack of blood flow (infarct) or bleeding (hemorrhage) – less frequently it can be caused by trauma. An infarct can be caused by several different conditions such as a blood clot (thrombosis) or stroke. Additional conditions that can cause locked-in syndrome include infection in certain portions of the brain, tumors, loss of the protective insulation (myelin) that surrounds nerve cells (myelinolysis), inflammation of the nerves (polymyositis), and certain disorders such as amyotrophic lateral sclerosis (ALS).
Locked-in syndrome is a rare neurological disorder that affects males and females in equal numbers. Locked-in syndrome can affect individuals of all ages including children, but most often is seen in adults who are more at risk for brain stroke and bleeding. Because cases of locked-in syndrome may go unrecognized or misdiagnosed, it is difficult to determine the actual number of individuals who have had the disorder in the general population.
A diagnosis of locked-in syndrome is usually made clinically. A variety of tests may be performed to rule out other conditions. Such tests include magnetic resonance imaging (MRI), which shows the damage to the pons, and magnetic resonance angiography, which can show the blood clot in the arteries of the brainstem. These tests can also rule out damage elsewhere in the brain.
An electroencephalogram (EEG), a test that measures the electrical activity of the brain, may reveal normal brain activity and sleep-wake cycles in individuals with locked-in syndrome.
Evoked potentials, tests that average the EEG signal in response to stimulation (pain or auditory or visual), permit a look at the damaged responses in the brainstem and the preserved responses in the brain.
Electromyography and nerve conduction study can be used to rule out damage to the muscles and nerves.
An MRI uses a magnetic field and radio waves to produce cross-sectional images of particular organs and bodily tissues such as the brain. MR angiography uses a magnetic field and radio waves to produce cross-sectional images of blood vessels inside the body.
An electromyography is a test that records electrical activity in the skeletal (voluntary) muscles at rest and during muscle contraction.
Nerve conduction study determines the ability of specific nerves to relay nerve impulses to the muscles.
Treatment
Treatment should first be aimed at the underlying cause of the disorder. For example, reversal of a basilar artery blood clot (thrombosis) with intraarterial thrombolytic therapy may be attempted up to six hours after symptoms onset. Tumors may be treated with intravenous steroids or radiation.
Affected individuals often need an artificial aid for breathing and will have a tracheotomy (a tube going in the airway via a small hole in the throat) in the beginning.
Feeding and drinking will not be possible via the mouth (it may cause respiratory infection by running into the lungs rather than stomach) and hence will need to be assured via a small tube inserted in the stomach called gastrostomy.
It is important to establish an eye-coded communication as soon as possible. Healthcare providers and family and friends should try to find out what is the easiest code for the affected individual and consequently all use the same code. This can be ‘look up’ for ‘yes’ and ‘look down’ for no or whatever is the easiest movement for the specific case. Communication is then limited to closed yes-no questions and can next be replaced by eye-coded letter spellers such as saying the alphabet and having the affected individual look down to choose her or his letter. There are many variations on this way of communication presenting the letters in frequency of use in the English language (. . . . . . . . . . . . . . . . . . . . . . . . . Z) or using letter boards with different columns and lines for vowels and consonants for example.
Next, treatment should be aimed at the early rehabilitation of the small voluntary movements that remain or recover (often in a finger or foot or swallowing and sound production). Rehabilitation and various supportive therapies are very beneficial and should be started as early as possible even if it needs to be stressed that recovery of near-normal motor control, speaking, swallowing and walking are extremely unusual.
Devices to aid in communication and other assistive technologies have proven beneficial as well as allowing individuals to become active members of society. Infrared eye tracking devices now permit affected individuals to use a computer with artificial voice, control their environment, surf on the internet and send email. In rare cases, some individuals have recovered limited motor abilities, however, in most people such recovery does not occur. Those who recover some motor control in hand or head (as will over half of the patients) can use this to communicate with a computer and sometimes control their wheelchair.
Recent studies and articles in the medical literature have noted that despite significant motor disability affected individuals can retain a good quality of life. In addition, quality of life is unrelated to the degree of physical impairment. With advances in care and assistive technologies, individuals with locked-in syndrome can become productive members of society.
Stem cell therapy has no proven benefit for individuals with locked-in syndrome and can be harmful. It should not be proposed except in case of research protocols where participants don’t pay for the treatment.
Information on current clinical trials is posted on the Internet at www.clinicaltrials.gov. All studies receiving U.S. Government funding, and some supported by private industry, are posted on this government web site.
For information about clinical trials being conducted at the NIH Clinical Center in Bethesda, MD, contact the NIH Patient Recruitment Office:
Tollfree: (800) 411-1222
TTY: (866) 411-1010
Email: prpl@cc.nih.gov
Some current clinical trials also are posted on the following page on the NORD website:
https://rarediseases.org/living-with-a-rare-disease/find-clinical-trials/
For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com
For information about clinical trials conducted in Europe, contact:
https://www.clinicaltrialsregister.eu/
TEXTBOOKS
Sahoo S, Pearl PL. Locked-In Syndrome. NORD Guide to Rare Disorders. Lippincott Williams & Wilkins. Philadelphia, PA. 2003:554.
Lyon G, Adams RD, Kolodny EH. Eds. Neurology of Hereditary Metabolic Diseases in Childhood. 2nd ed. McGraw-Hill Companies. New York, NY; 1996:347-348
JOURNAL ARTICLES
Bruno MA, Bernheim JL, Ledoux D, Pellas F, Demertzi A, Laureys S. A survey on self-assessed well-being in a cohort of chronic locked-in syndrome patients: happy majority, miserable minority. BMJ Open 2011;1:e000039.
Babiloni C, Pistoia F, Sarà M, Vecchio F, Buffo P, Conson M, Onorati P, Albertini G, Rossini PM. Resting state eyes-closed cortical rhythms in patients with locked-in-syndrome: An EEG study. Clin Neurophysiol 2010;121:1816-24.
Conson M, Pistoia F, Sarà M, Grossi D, Trojano L. Recognition and mental manipulation of body parts dissociate in locked-in syndrome. Brain Cogn 2010;73:189-93.
Pistoia F, Conson M, Trojano L, Grossi D, Ponari M, Colonnese C, Pistoia ML, Carducci F, Sarà M. Impaired conscious recognition of negative facial expressions in patients with locked-in syndrome. J Neurosci 2010;30:7838-44.
Lule D, Zickler C, Hacker S, et al. Life can be worth living in locked-in syndrome. Prog Brain Res. 2009;177:339-351.
Bruno MA, Schnakers C, Damas F, et al. Locked-in syndrome in children: report of five cases and review of the literature. Pediatr Neruol. 2009;41:237-246. https://www.coma.ulg.ac.be/papers/LIS/Bruno_LIS_PediatricNeurology_2009.pdf
Bruno MA, Pellas F, Schnakers C, et al. Blink and you live: the locked-in syndrome. Rev Neurol (Paris). 2008;164:322-335.
Conson M, Sacco S, Sarà M, Pistoia F, Grossi D, Trojano L. Selective motor imagery defect in patients with locked-in syndrome. Neuropsychologia 2008;46:2622-2628.
Schnakers C, Majerus S, Goldman S, et al. Cognitive function in the locked-in syndrome. J Neurol. 2008;255:323-330. https://www.coma.ulg.ac.be/papers/LIS/schnakers_JNeurol08.pdf
Smith E, Delargy M. Locked-in syndrome. BMJ. 2005;330:406-409.
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. https://www.coma.ulg.ac.be/papers/LIS/2005_PBR_vol150_495_511.pdf
Bauer, G., Gerstenbrand, F., Rumpl, E. Varieties of the locked-in syndrome. J Neurol 1979;221:77-91.
INTERNET
National Institute of Neurological Disorders and Stoke. Locked-In Syndrome Information Page. May 25, 2017. Available at: https://www.ninds.nih.gov/Disorders/All-Disorders/Locked-Syndrome-Information-Page Accessed March 5, 2018.
Orphanet encyclopedia. Locked-In Syndrome. December 2012. Available at: https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=GB&Expert=2406 Accessed March 5, 2018.
Maiese K. Locked-in Syndrome. The Merck Manual Online Medical Library. Dec. 2017. Available at: https://www.merck.com/mmpe/sec16/ch212/ch212c.html Accessed March 5, 2018.
Coma Science Group. Locked-in Syndrome. Available at: https://www.coma.ulg.ac.be/inform/locked_in_syndrome.html Accessed March 5, 2018.
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