Trapped Within

 Imagine you hear someone talking to your loved ones, “I’m sorry…. their chance of survival is small”. What is this? What's going on? ‘Maybe this is a dream’, you start to think to yourself as you try to wake yourself up. You are unsuccessful in waking up, and you still see complete darkness. You start to hear a doctor talk to your family about ending life support. You are conscious, afraid, your heart is racing, and to make matters worse, you realize you cannot move or speak. “How can I tell them that I am still here and alive?” you say to yourself in your head. This is merely a glimpse of what locked-in syndrome may feel like. If you have ever experienced or heard of sleep paralysis, where you are conscious, but unable to move your body, except your eyes, then you can begin to appreciate what individuals living with locked-in syndrome experience continuously. Instead of your experience lasting for a few minutes, like sleep paralysis, locked-in syndrome could be something you are trapped in for the rest of your life. This article examines the world of locked-in syndrome, its etiologies, types of locked-in syndrome, and what diagnosis/treatment looks like.

What is locked-in syndrome?

Locked-in syndrome (LIS), also known as pseudocoma, is a rare neurological disorder in which all voluntary muscles are completely paralyzed, except the muscles that control the movements of the eyes [6]. Patients appear unconscious and unable to breathe independently, but they are fully conscious and cognitive. However, patients do not have the ability to communicate verbally or physically. From patient to patient, symptoms and functions can differ, as there are three types of locked-in: classic, incomplete, and total form. So how does locked-in happen? Damage to a part of the brain stem known as pons can result in this disorder. The pons is crucial for supporting automatic functions, such as our heart rate, breathing and motor functions. Though researchers have found which part of the brain is responsible for locked-in syndrome, they are still seeking to understand how other conditions can lead to this neurological disorder.

What are the etiologies of locked-in syndrome?

The most common cause of locked-in syndrome is a bilateral ventral lesion to the pons. A bilateral ventral lesion is when there is damage to the underside and both sides of the pons. In some rarer cases, there have been findings of mesencephalic lesion, which has also led to this disorder [5].  The mesencephalic part of the brain, another section of the brain stem, known as the midbrain. The midbrain helps us regulate our motor movements, process visual and auditory information, and maintain consciousness. This preservation of consciousness seen in LIS is due to a structure unaffected by these ventral lesions known as the reticular formation. The reticular formation is responsible for a few different functions such as consciousness and sleep. Damage to the pons or the midbrain can be caused by other conditions, such as pontine hemorrhages, where blood is released from a broken blood vessel [9]. Other commonly encountered conditions include traumatic brain injuries [3], brain stem tumors [4], encephalitis; inflammation of brain tissue [1], tissue loss, pontine strokes, etc. In addition to strokes, some acute strokes in severe COVID patients have resulted in locked-in syndrome[2]. Undoubtedly, there are many conditions that lead to locked-in syndrome, and new conditions researchers found to have some indirect effects. Depending on the severity of certain conditions, different types of locked-in can be identified and improved in some cases.

What are the types of locked-in syndrome?

When it comes to locked-in syndrome, there are three categories: classic, incomplete, and total. To know which category a patient belongs to, they are evaluated on the basis of their abilities and impairments. Despite the differences between the three categories, patients that have any form of locked-in syndrome are fully conscious and aware of their surroundings. The classic form involves full paralysis of all four limbs and the inability to communicate verbally, while retaining vertical eye movements. Incomplete is similar to the classic form, but a small amount of motor function is observed in the face, body or eyes. Lastly, total locked-in is the most severe form patients can present in. Total form is classified as total body paralysis, including loss of eye movements [7]. Due to paralysis in all forms of locked-in syndrome, the respiratory muscles that control breathing are also paralyzed. In cases where these muscles are paralyzed, a ventilator is needed to help with breathing. Locked-in syndrome can be difficult to diagnose, as many health care providers are unfamiliar with it. For example, the total form is most difficult to diagnose because it presents as a comma or death. Brain imaging technology has become extremely helpful in diagnosing this syndrome by revealing patients’ consciousness through retained brain function. 

How is it diagnosed and treated?

When it comes to diagnosing LIS, it can be extremely difficult to. The presentation of paralysis, the inability to speak, breathe independently.can overlap with other conditions that present similarly such as akinetic mutism, a cervical spinal injury, and is even mistaken as coma or vegetative state. Coma patients can even transition from a coma state to a locked-in state. Studies report that locked-in syndrome can take an average of 2.5 months to be diagnosed. While for some people it took 4-6 years before providers realized they were conscious [5]. Without thorough and the right testing, such as assessing voluntary eye movements in patients who appear unconscious, LIS can be missed and misdiagnosed. Doctors can carry out neurological tests, such as EEG (electroencephalography recordings) to evaluate consciousness. EEG's can show reactivity to conditions outside the patient's body. In a review of eight patients with LIS, seven showed normal or minimally slow activity of surrounding conditions in an EEG test [5]. Other brain imaging include structural brain imaging such as MRI, which can show damaged areas of the brain. Positron Emission Tomography (PET) scans can also be used in the work up for LIS. 

Distressingly, there is no treatment or cure for locked-in syndrome. Early findings in autopsies have shown that long-term survival is rare without the recovery of neurological functions [8]. Early rehabilitation and care can help reduce mortality for patients. Rehabilitation tends to focus on smaller motor functions, as significant recovery of motor movements is rare. Improving motor function can help the patient use a type of communication device if needed, such as a computerized voice synthesizer, like the physicist Stephen Hawking used. Patients who are nonverbal have also used eye tracking communication, Augmentative and Alternative Communication devices (AAC). These devices emit infrared light that is reflected back by the pupils and detected by the camera on the device. Then it is processed to determine the location of their eyesight and fixation. While these technologies can be helpful for the time being, most individuals never fully recover from the effects of locked-in syndrome. 

As debilitating as this condition can be, it does not stop individuals from being productive members of their families and society. There have been reports that a LIS patient was a lawyer who communicated through morse code with eye blinks, emails and faxes. Another person living with locked-in was teaching third graders through an electronic voice device [5]. As individuals living with locked-in syndrome can still be productive, there are others who are never able to live the life they once had. This necessitates further research into neurological disorders and other conditions that can lead to locked-in syndrome in hope of. Finding ways to treat and prevent anyone from being trapped within their bodies.

References:

[1]. Acharya, V.Z., Talwar, D. and Elliott, S.P. (2001) Enteroviral encephalitis leading to a locked-in state. J. Child Neurol., 16: 864–866.

[2]. Avula, A., Gill, A., Nassar, R., Nalleballe, K., Siddamreddy, S., & Chalhoub, M. (2020). Locked-In with COVID-19. Journal of clinical neuroscience : official journal of the Neurosurgical Society of Australasia, 79, 80–83. https://doi.org/10.1016/j.jocn.2020.07.014

[3].  Golubovic, V., Muhvic, D. and Golubovic, S. (2004) Posttrau- matic locked-in syndrome with an unusual three day delay in the appearance. Coll. Antropol., 28: 923–926.

[4]. Keane,   J.R.   (1986)   Locked-in   syndrome   after   head   and   neck trauma.  Neurology,  36:  80–82.

[5]. Laureys, S., Pellas, F., Van Eeckhout, P., Ghorbel, S., Schnakers, C., Perrin, F., Berré, J., Faymonville, M. E., Pantke, K. H., Damas, F., Lamy, M., Moonen, G., & Goldman, S. (2005). The locked-in syndrome : what is it like to be conscious but paralyzed and voiceless?. Progress in brain research, 150, 495–511. https://doi.org/10.1016/S0079-6123(05)50034-7 

[6]. 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.

[7]. M Das J, Anosike K, Asuncion RMD. Locked-in Syndrome. [Updated 2021 Jul 30]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2021 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK559026/

 [8]. Smith, E., & Delargy, M. (2005, February 17). Locked-in Syndrome. Shibboleth authentication request. https://www-bmj-com.libproxy.temple.edu/content/330/7488/406. 

 [9]. Patterson, J. R., & Grabois, M. (1986). Locked-in syndrome: a review of 139 cases. Stroke, 17(4), 758–764. https://doi.org/10.1161/01.str.17.4.758