What is Locked-in Syndrome?
Locked-in syndrome (LIS) is a severe condition that causes full-body paralysis, difficulty swallowing and talking, and loss of all body sensations due to damage in the part of the brain that connects to the spinal cord, usually at the front. Despite these challenges, people with LIS are usually still able to think clearly, move their eyes up and down, blink, and hear. Diagnosing this condition can be difficult as it can be mistaken for other conditions that limit movement and responsiveness, like being completely still and silent, or being in a coma. Often, it’s the family members who first notice that the person is having trouble moving.
There are three main types of locked-in syndrome. The classic type is when a person can’t move at all but can still move their eyes up and down, blink, and stay conscious – meaning they’re aware of what’s happening around them. The incomplete type is just like the classic type, but the person can still move a bit. The complete type is when a person is paralyzed, can’t move their eyes at all, but can still think and process information, which is checked by using an EEG, a test that looks for changes in brain activity. For the classic and incomplete types, whether the person is still conscious is usually checked by seeing if they can blink or move their eyes in response to questions. An EEG is used for those in the complete form to check brain activity, sleep and wake cycles, and attention.
For immediate care, CT or MRI scans of the brain can help doctors figure out what caused the condition and treat it earlier. Doctors also often check the person’s movement, sensation, and reflexes to rule out other possible causes and guess how quickly the person might recover. Because locked-in syndrome is rare, there’s still a lot of discussion about the best way to treat it and help people recover. However, more and more studies are finding that traditional supportive care and rehabilitation can be effective.
What Causes Locked-in Syndrome?
Locked-in syndrome is a condition that happens when there’s damage to specific parts of the brain known as the ventral pons and midbrain. This can result from things like vascular issues, traumas, masses or growths, infections, and disorders that cause loss of protective nerve tissue (demyelination).
Vascular issues – things to do with blood vessels – is the most common cause. This usually happens due to a stroke, either from bleeding in the brain (hemorrhagic stroke) or a blockage cutting off the blood supply to part of the brain (ischemic stroke). A study looked at cases of locked-in syndrome and found that 105 out of 139 were caused by vascular issues, with many of these patients having high blood pressure history.
Head injuries are the second most common cause of locked-in syndrome. This can result from either blunt or sharp trauma that leads to damage or blockage of the blood supply in the brain.
In some cases, things like various types of tumors or growths in the brain can cause locked-in syndrome. It’s also reported that infections, though rare, can lead to locked-in syndrome – for example, an infection causing a brain abscess or severe meningitis.
Another cause of locked-in syndrome can be from demyelination – the loss of the protective tissue around nerves. This commonly occurs due to rapid correction of low sodium levels in the body (hyponatremia) but can also happen in severe cases of diseases like multiple sclerosis (MS), Guillain-Barre syndrome, and amyotrophic lateral sclerosis (ALS).
Risk Factors and Frequency for Locked-in Syndrome
Locked-in syndrome typically begins between the ages of 30 to 50 and tends to occur slightly more in males than females. In a study called ALIS, it was found that both genders were nearly equally affected by the condition, with 51.2% of men and 48.1% of women diagnosed. The ages in this study ranged from 22 to 77, with the average age being around 46.79 years. Other studies have similar findings, with more males typically affected and average ages ranging from 33 to 45 years. Many people with locked-in syndrome caused by vascular conditions also have other health problems such as high blood pressure, hardening of the arteries, and diabetes.
- Locked-in syndrome generally arises between the ages of 30 to 50.
- This condition is slightly more prevalent in males.
- In the ALIS study, both men and women were nearly equally affected: 51.2% of diagnosed cases were men and 48.1% were women.
- The ages in the ALIS study varied from 22 to 77 with an average age of about 46.79 years.
- Other studies showed similar results, with the average ages varying from 33 to 45 years.
- Many patients with locked-in syndrome due to vascular causes also have high blood pressure, hardening of the arteries, and diabetes.
Signs and Symptoms of Locked-in Syndrome
The Locked-in syndrome is a medical condition that can present various symptoms. Symptoms generally fall into three categories depending on the severity, as identified by Bauer in 1979, named classical, incomplete, and total immobility. The condition disrupts the neuronal pathways in the ventral brainstem, leading to a loss of certain functions and retention of others.
- Lost functions can include:
- Paralysis of the voluntary muscles of the limbs and torso
- An inability to speak or swallow
- Difficulty with voluntary breathing, dizziness, and vertigo
- Retained functions can include:
- Maintaining consciousness, understanding language, and awareness
- Ability to hear
- Vertical eye movement and the ability to blink
To understand the condition better, it’s crucial to talk to family members and evaluate how the symptoms started, and whether they have intensified or evolved over time. Sudden onset of symptoms could suggest conditions like strokes, trauma, or metabolic demyelination, whereas a more gradual onset could indicate infections, pontine contusions, or Guillain-Barre syndrome. Chronic and recurring symptoms could suggest an autoimmune demyelinating condition. Additionally, if there are symptoms like fever, chills, malaise, headache, neck stiffness, and sensitivity to light, it could imply an infection like meningitis or an abscess. It’s important to know about any severe accidents to rule out trauma.
Physical examination results can vary depending on whether the causative agent primarily affects the brainstem or the entire central nervous system. Exams can reveal horizontal eye movement impairment, involvement of cranial nerves, and hearing preservation. Patients could respond to verbal communication by moving their eyes vertically, indicating the preserved functioning of cranial nerve 8.
Tests for motor strength, sensory deficits, and reflexes help to locate the site of the lesion and track progress or improvements. Locked-in syndrome may present with bilateral weakness and sensory deficits. Total paralysis is observed in nearly all patients, whereas sensations like proprioception, light touch, temperature, and pain may significantly decrease or vanish completely.
Brainstem strokes or large brainstem lesions may first put a patient into a comatose state before transitioning into a locked-in state. It often takes weeks from the onset of the inciting event to correctly diagnose locked-in syndrome. Assessing alertness, limb movements and reflexes can help in early recognition of the condition and reducing the diagnosis time.
Finally, patients recovering from a comatose state need careful attention. Checking for visual tracking, eye movements, and eye blinking responses are vital. Family members often first notice minor improvements, so it’s important to gather any bedside information from them to not miss subtle improvements.
Testing for Locked-in Syndrome
To diagnose locked-in syndrome, a condition where a person is conscious and can think and reason, but cannot move or talk, doctors usually rely on brain imaging tests. These include CT scans or MRI, which can provide detailed pictures of the brain. Sometimes, doctors may use CT or MR angiography, a special type of imaging that can show blood vessels, to look for the cause of the condition, such as a stroke or tear in an artery. By adding a contrast medium, a special dye, the doctors can better see anything abnormal, like a tumor, infection pocket, or areas of the brain affected by diseases that damage the protective covering of nerve fibers.
In situations where brain scans don’t show a mass or blood vessel abnormality, doctors may decide to examine the cerebrospinal fluid (fluid around your brain and spinal cord). This analysis can help find an infection or an autoimmune disease, where your body’s immune system attacks healthy cells. The doctors may look at the type and number of cells in the fluid and test it for protein and glucose levels, and send it for cultures to check if there’s an infection present.
If other nerve diseases like ALS (Amyotrophic lateral sclerosis, a condition that affects nerve cells in the brain and spinal cord) or GBS (Guillain-Barré Syndrome, a condition in which the body’s immune system attacks your nerves) are suspected, the doctors may use electromyography and nerve conduction studies. These tests measure the electrical activity of muscles and speed of nerve signals.
An EEG (Electroencephalography) may also be used to study brain activity, sleep patterns, and attention levels. For patients who cannot speak, the doctors may use infrared eye movement sensors or computer-modulated voice prosthetics to assess language comprehension and orientation.
Blood tests, like metabolic panels, may also be used to discern abnormal levels of sodium, which could indicate a possible damage to the protective covering of nerve fibers in the brain. History of rapid sodium correction (change in sodium levels) may also be a clue to this type of damage. Certain deficiencies like low sodium, phosphate, and magnesium, or decreased blood sugar levels, can cause coma-like states similar to locked-in syndrome. Doctors may also order a complete blood count to check for signs of infection, which can sometimes be an underlying cause of coma.
Treatment Options for Locked-in Syndrome
The first step to healing locked-in syndrome is to remove or stop what’s causing it. When someone first shows signs of locked-in syndrome, doctors will make sure the person can breathe, has enough oxygen in their body, and that their heart is working normally, all while monitoring their heart rate, blood pressure, and sometimes changes in blood pressure when standing up.
Next, doctors focus on treating what caused the problem in the first place. If it’s a stroke, they’ll follow the usual stroke treatment, which could include breaking up clots in the blood vessels. This technique has helped someone recover almost entirely from locked-in syndrome due to blood vessel blockage.
If a tumor or similar growth is behind the syndrome, it needs to be removed. If it’s an infection or abscess, antibiotics can often do the trick.
Treating locked-in syndrome caused by diseases that destroy the protective covering of nerve cells (like central pontine myelinolysis) typically involves a variety of approaches – things like bringing sodium levels back to normal, carefully and constantly checking on the patient’s breathing situation. Inflammatory neuropathies might be approached similarly, with treatments such as immune protein IV infusions, blood plasma exchange, and monitored breathing assistance. Doctors may treat flare-ups of multiple sclerosis with high doses of steroids, and long-term treatment may involve medication to modify the disease’s progression and lab-made antibodies. The treatment for locked-in syndrome due to ALS usually involves the help of certain medications which can extend the patient’s lifespan.
For the longer-term, therapy is used to improve movement months after the syndrome starts. This phase will focus mainly on physical, respiratory, and speech therapy to improve patients’ communication skills. Chest exercises that help with breathing and changing positions regularly can also help maintain good heart and lung function. Other types of tech, like eye movement sensors that connect to a computer or computer-based voice devices, can also be useful in gradually improving speech. Books that track thoughts and activities can be beneficial to monitor cognitive recovery.
What else can Locked-in Syndrome be?
Diagnosing the locked-in syndrome is often challenging because it shares many symptoms with other conditions where the patient can’t speak. These conditions include coma, persistent vegetative state, akinetic mutism, and catatonic states.
Here are some conditions that are considered when diagnosing the locked-in syndrome:
- Persistent Vegetative State: Patients have eye opening but do not recognize themselves or their surroundings, their language understanding is not intact, there are no voluntary facial or body movements, but they can breathe on their own.
- Akinetic mutism: Patients have consciousness, reduced motor response (without paralysis), and intact brainstem reflexes. They have eye movements, slow speech, and very little spontaneous speech.
- Coma: Patients have impaired consciousness, no voluntary motor movements. Their ability to breathe may or may not be intact and brainstem reflexes may or may not be preserved.
- Brain death: Patients have impaired consciousness, can’t move voluntarily, can’t breathe on their own and do not have brainstem reflexes.
- Catatonia: Often seen in people with a history of mental health problems. They have preserved consciousness and brainstem reflexes, often accompanied by rigidity, mute state, echoing what others say, and inappropriate posturing.
- Cervical spinal cord injury: Their motor function in their face is retained, they have intact eye movements, consciousness, orientation, and language. However, their respiratory function may vary.
In medical examinations, doctors use radiography and early physical checks to identify the parts of the brain that are damaged. A loss of facial expressions, difficulty swallowing, lack of neck movement and tone, and absence of the gag reflex point to damage at the front structures of the midbrain or pons.
An often-used method to rule out other causes includes checking the patient’s consciousness, alertness, and communication capabilities. They also see if there is a cervical cord injury through observation of respiration and check of muscles above the spinal cord. Lastly, they do tests to rule out akinetic mutism. If all three tests come back negative, there’s a high chance that the patient may have a locked-in syndrome.
Also, in complex conditions like the locked-in syndrome, doctors must get a detailed history to rule out the chance of intoxication. They check for depressive drugs, anesthetics, and poisons that may temporarily cause the locked-in state. One such drug is Curare, which is known to cause complete paralysis and breathing failure, thus mimicking a form of locked-in syndrome. Quick patient stabilization and thorough history checks can exclude less common causes of the locked-in syndrome and assist with quicker management.
What to expect with Locked-in Syndrome
Survival rates and recovery times from locked-in syndrome can differ greatly. This is largely due to what initially caused the condition. Unfortunately, many people who are affected by this diagnosis do not survive, especially in the early stages. In historical studies, it’s been estimated that within five and ten years of diagnosis, 84% and 31% of patients respectively, do not survive.
A survey by Patterson and Grabois on 139 cases of Locked-in syndrome showed an overall mortality rate of 60%. When the cause of locked-in syndrome was due to a blood vessel related issues, the mortality rate jumped to 67% of 105 patients. If the cause was unrelated to blood vessels, the survival rate improved with 41% (14 of 34 patients) not surviving. Many patients that survived remained in a somewhat paralyzed state with minimal improvement in their physical abilities.
Patients were grouped into five categories, based on their recovery a few months after their symptoms started:
No recovery: patients who showed no signs of regaining any physical movement.
Minimum recovery: patients who regained some ability to move voluntarily, but still needed to rely on others to take care of them.
Moderate recovery: patients who regained enough movement to perform some everyday tasks on their own.
Full recovery: patients who could perform all of their daily tasks on their own, even though they might have minor lasting neurological issues.
No neurological deficit: patients who reported no ongoing neurological problems.
The study showed that more patients whose condition was not due to a blood vessel issue had a moderate to full recovery. Out of 34 patients in this group, 18 regained some ability to move. Additionally, the study found that 12 of these 18 patients fully recovered their movement abilities within the first six months.
However, for patients whose locked-in syndrome was caused by a blood vessel issue, just 29 out of 105 patients showed any kind of recovery. Of the patients who survived past the initial four months, 13 of 16 showed signs of moderate to full recovery, while only 2 fully recovered.
Possible Complications When Diagnosed with Locked-in Syndrome
Locked-in syndrome can lead to serious health issues even after initial improvement. One of the most significant concerns is a high death rate. Also, many survivors experience full or partial paralysis.
According to one study, out of 29 cases studied, 18 patients survived. However, only a few of these survivors could return to their homes. The majority had to stay in a hospital or nursing homes indefinitely. It should be noted that most of these patients required help with everyday tasks, and only a few could live independently or work part-time.
Furthermore, the study showed that most survivors could not communicate effectively without using devices or computers.
Surviving patients also face numerous health complications because of the length of their hospital stay and the number of procedures they undergo while in the hospital. These complications include:
- Multiple infections from the hospital setting
- Pneumonia because of long-term use of a breathing tube
- Urinary tract infections from using a catheter
- Blood clots in deep veins and bedsores due to prolonged bed rest
Another study states that only 42% of the recovered patients could swallow normally, and half of these patients had breathing trouble. Moreover, most patients had control issues over their bladder and bowel movements in the long term.
