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Locked In Syndrome

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NORD is very grateful to Steven Laureys, MD, PhD, Coma Science Group, University Hospital of Liege, Belgium, for assistance in the preparation of this report.

Synonyms of Locked In Syndrome

Disorder Subdivisions

General Discussion

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.

Symptoms

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. In some cases, 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.

Causes

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).

Affected Populations

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 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.

Related Disorders

Symptoms of the following disorders can be similar to those of locked-in syndrome. Comparisons may be useful for a differential diagnosis.

Locked-in syndrome is also called pseudo-coma because affected individuals are conscious but make little body movement - like unconscious "eyes-closed" coma patients or unconscious "eye-open" vegetative state patients.

Akinetic mutism is a rare neurological condition in which an affected individual does not move (akinetic) or talk (mute) despite being awake. Individuals with akinetic mutism have normal sleep/wake cycles, but (when awake) lie still and unresponsive, neither moving nor talking. Akinetic mutism is a form of minimally conscious state often due to vascular or traumatic damage in the midline frontal grey matter.

A variety of conditions can cause symptoms or a clinical picture that is similar to locked-in syndrome. These disorders or conditions include Guillain-Barre syndrome, myasthenia gravis, poliomyelitis, polyneuritis or bilateral brainstem tumors. As said, locked-in syndrome can be mistaken for a vegetative state that may occur secondary to trauma or a variety of different conditions, especially if affected individuals have visual or hearing loss making the diagnosis more difficult.

Standard Therapies

Diagnosis
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 examples, 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.

Often affected individuals in the beginning may need an artificial aid for breathing and will have a tracheotomy (a tube going in the airway via a small hole in the throat).

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 givers 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 (T A O I N S H R D L C U M W F G E Y P B V K J X Q 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 cases 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.

Investigational Therapies

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

For information about clinical trials sponsored by private sources, contact:
www.centerwatch.com

Organizations related to Locked In Syndrome

References

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
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. http://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.

Schnakers C, Majerus S, Goldman S, et al. Cognitive function in the locked-in syndrome. J Neurol. 2008;255:323-330. http://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. http://www.coma.ulg.ac.be/papers/LIS/2005_PBR_vol150_495_511.pdf

FROM THE INTERNET
National Institute of Neurological Disorders and Stoke. Locked-In Syndrome Information Page. February 13, 2007. Available at: http://www.ninds.nih.gov/disorders/lockedinsyndrome/lockedinsyndrome.htm Accessed On: April 12, 2010.

Orphanet encyclopedia. Locked-In Syndrome. December 2003. Available at: http://www.orpha.net Accessed on: April 12, 2010.

Maiese K. Locked-in Syndrome. The Merck Manual Online Medical Library. January 2008. Available at: http://www.merck.com/mmpe/sec16/ch212/ch212c.html Accessed on: April 12, 2010.

Coma Science Group. Locked-in Syndrome. Available at: http://www.coma.ulg.ac.be/inform/locked_in_syndrome.html

Report last updated: 2010/08/12 00:00:00 GMT+0