Locked-In Syndrome

What Causes Locked-In Syndrome?

LIS is caused by damage to the part of the brain that sends nerve impulses to the rest of the body. This damage is usually caused by a stroke, but it can also result from other sources of damage, including:

• Infections
• Brain tumors
• Amyotrophic lateral sclerosis (ALS)
• Guillain-Barre syndrome
• Demyelination (loss of a protective fatty layer around nerve cells in the brain)
• Brain injuries
• Exposure to toxins
• Substance abuse

Some factors put an individual at increased risk of having a stroke. Ischemic and hemorrhagic strokes have some risk factors in common, and some are unique to each type of stroke.

Risk factors for an ischemic stroke

• Age 40 or over
• Heart disease
• High blood pressure (hypertension)
• Smoking
• Diabetes
• High blood cholesterol levels
• Illegal drug use
• Recent childbirth
• Previous mini-stroke or transient ischemic attack (TIA)
• Inactive lifestyle and lack of exercise
• Obesity
• Current or past history of blood clots
• Family history of cardiac disease and/or stroke

Risk factors for hemorrhagic stroke

• High blood pressure (hypertension)
• Heavy alcohol use
• Advanced age
• Illegal drug use (primarily cocaine and “crystal meth”)
• Smoking
• Anticoagulant medications
• Bleeding disorders
• Deformities in blood vessels
• Aneurysm (a weakening in the lining of the blood vessel)

Is Locked-In Syndrome Hereditary?

There is no known direct genetic component to LIS, but some of the conditions that cause LIS may have an inherited risk. Scientists have not yet found a definitive genetic link to stroke, the most common cause of LIS. However, many of the underlying conditions causing strokes may be inherited or more common in people with a family history of the conditions.

People at risk for a stroke often have a family history of:

• High blood pressure
• High levels of cholesterol, especially “bad” cholesterol or LDL
• High triglyceride values
• Inherited bleeding disorders
• Sickle cell disease
• Blockage in the neck or brain arteries
• An arteriovenous malformation (AVM), a tangle of abnormal blood vessels in the brain

How Is Locked-In Syndrome Detected?

LIS typically develops without warning, but when a stroke is the potential underlying cause, there may be warning signs. FAST emergency treatment of the stroke may decrease the likelihood of complications such as LIS.

Brief episodes of numbness, weakness, or vision loss are urgent warning signs of a stroke. A transient ischemic attack (TIA)—a “mini-stroke”—often precedes a more serious cardiovascular event.

The acronym FAST is a reminder to take symptoms seriously. Each letter in the word stands for one of the things to watch for if a stroke is suspected:

Face: Sudden weakness or drooping of the face and/or visual problems

Arm: Sudden weakness or numbness of one or both arms

Speech: Difficulty speaking and/or slurred speech

Time: Time saves the brain. The sooner treatment begins, the better the chances are for recovery. Dial 9-1-1 to call an ambulance right away.

How Is Locked-In Syndrome Diagnosed?

LIS can be difficult to diagnose because it is not always apparent that the patient is alert and mentally intact despite their inability to communicate. Tests of reflexes are likely to be negative, possibly leading doctors to believe that the patient is unconscious.

The following tests can be used to diagnose LIS:

• Tests of eye movements to determine if the patient is alert and/or able to communicate
• Computed tomography (CT) and/or magnetic resonance imaging (MRI) scans to look for damage to the part of the brain associated with LIS
• Lumbar puncture or spinal tap to look for evidence of infections or autoimmune disorders 
• Cerebral angiography to map blood flow in the brain
• Blood tests to look for low sodium levels, a potential sign of demyelination
• Electroencephalogram (EEG) to measure the brain’s electrical activity. This test can show whether the patient is conscious and experiencing normal sleep-wake cycles
• Electromyography to measure muscle function 

PLEASE CONSULT A PHYSICIAN FOR MORE INFORMATION.

How Is Locked-In Syndrome Treated?

There is no specific treatment for LIS. Care for someone with the condition usually focuses on treating the underlying cause and providing supportive care to prevent complications.

A stroke is a medical emergency that requires immediate medical attention. The faster someone reaches the hospital after the stroke begins, the better the chances of recovery.

Ischemic stroke

When a blood clot blocks an artery, doctors try to restore blood flow to the brain as soon as possible. Treatment procedures for an ischemic stroke include:

• Clot-retrieval devices can be used up to 24 hours after symptoms begin. Minimally invasive procedures offer new hope for acute stroke patients with blood clots in the brain’s blood vessels. Doctors insert a spaghetti-thin tube (catheter) into an artery in the groin and move it up through the body to an artery in the brain. The doctor then threads the clot-retrieval device up through the catheter, snags the clot, and removes it.
• Clot-busting (thrombolytic) drugs can be delivered directly to the blockage to dissolve the blockage. The most common drug is tissue plasminogen activator (tPA). Drugs to dissolve a clot must be given as soon as possible after the onset of symptoms. At most, the window of time for clot-busting drug delivery is 4-1/2 hours.

Hemorrhagic stroke

Early treatment of a “bleeding” stroke can repair bleeding blood vessels. Weakened blood vessels are at greater risk of developing aneurysms that can burst and lead to a bleeding stroke.

• Aneurysms can be repaired by placing a surgical clip or coil to stop the bleeding.
• A tiny metal mesh tube (stent) can be placed in the blood vessel.
• Medications are used to lower the pressure within the skull.
• Patients may be connected to a mechanical ventilator to help them breathe.
• Surgery may be needed to prevent a hemorrhage from happening again.

Supportive Treatments

Treatment to prevent complications of LIS can include:

• Breathing assistance
• Feeding assistance
• Therapies to prevent infections, respiratory diseases, and bed sores
• Physical therapy
• Communication training (possibly using assistive technologies)

How Does Locked-In Syndrome Progress?

The long-term outlook for people with LIS depends on the type and severity of the underlying cause. For example, LIS caused by relatively minor strokes may be temporary, with symptoms resolving as the patient recovers. People with treatable conditions such as Guillain-Barre syndrome may recover some movement abilities by treating the underlying disorder.

People with long-term LIS are vulnerable to complications such as:

• Respiratory infections
• Pressure ulcers (bed sores)
• Limb contractures
• Malnutrition

Many people with LIS can maintain communication with those around them, often using assistive technologies, and a happy, fulfilling life is possible for someone with the condition.

How Is Locked-In Syndrome Prevented?

There is no known way to prevent LIS. Taking steps to prevent strokes is the best strategy to decrease your risk of LIS.

If you have high blood pressure, high cholesterol, or other conditions that increase the risk of stroke, it is vital that you follow your doctor’s instructions for the treatment of the condition(s).

• Take blood pressure medication as prescribed by your doctor.
• Control cholesterol levels with statin medications.
• Take anticoagulant drug therapy to prevent dangerous clotting.
• Make heart-healthy lifestyle changes, like eating a diet low in animal fat, losing weight, exercising, and quitting smoking.
• Treat type 2 diabetes. The disease more than doubles the risk of stroke.
• Drink only moderately. Excessive alcohol consumption dramatically increases the risk of having a stroke, particularly in women.
• Follow a healthy sleep routine. Sleep disorders are associated with an increased risk of stroke.

Locked-In Syndrome Caregiver Tips

Tips to help a loved one with LIS:

• Create a safe, comfortable environment for your loved one.
• Encourage communication with your loved one as much as possible. Find a doctor specializing in rehabilitation, and advocate for your loved one’s continued treatment and rehabilitation.
• Understand the difficulty of accepting disability and brain injury, and be prepared for frustration.

Locked-In Syndrome Brain Science

LIS results from damage to a part of the brain called the pons. The pons is a collection of nerve fibers at the base of the skull. It is part of the brain stem and connects the upper part of the brain to the lowest part of the brain stem (the medulla oblongata) and the spinal cord. The pons is a critical junction, and damage to this area, which may be caused by a stroke or other neurological condition, can disrupt most nerve signals normally passed from the brain to the rest of the body.

The pons is also the place where several cranial nerves converge. These nerves connect the face, eyes, and ears directly to the brain and are responsible for facial movement and sensory input. The preservation of some of these nerve connections despite other damage to the pons may allow some people with LIS to hear, see, and move their eyes.

Locked-In Syndrome Research

Title: Brain-Computer Interface Implant for Severe Communication Disability

Stage: Recruiting

Principal investigator: Nathan Crone, MD 

Johns Hopkins University

Baltimore, MD

Locked-In Syndrome (LIS) is a devastating condition in which a person has lost the ability to communicate due to motor impairment while being mentally intact. For people affected by this severe communication impairment, Brain-Computer Interfaces (BCI) may be the only solution that allows these people to start a conversation, ask questions, or request assistance (i.e., self-initiated communication). To date, spelling was accomplished at a rate of 2-3 letters per minute with a predecessor device (the Medtronic Activa PC+S). To improve BCI performance, the current protocol will use the Medtronic Summit System, which offers a rechargeable battery and enhanced signal quality relative to Activa PC+S. Using signals from the motor hand/arm and/or motor mouth/face area, the investigators will investigate different avenues to improve the speed of communication using the Summit System. The primary objective is to evaluate the safety of the Summit System when used to chronically record subdural electrocorticographic (ECoG) signals in a BCI for use by patients with LIS in patients’ homes. The secondary objective will be to evaluate the efficacy of the Summit System as a long-term source of ECoG signals for a BCI capable of allowing participants to control alternative and augmentative communication software in patients’ homes.

Title: iBCI Optimization for Veterans With Paralysis

Stage: Not Yet Recruiting

Principal investigator: John D. Simeral, PhD 

Providence VA Medical Center

Providence, RI

VA research has been advancing a high-performance brain-computer interface (BCI) to improve independence for Veterans and others living with tetraplegia or the inability to speak resulting from amyotrophic lateral sclerosis, spinal cord injury, or stroke. In this project, the investigators enhance deep-learning neural network decoders and multi-state gesture decoding for increased accuracy and reliability. They deploy them on a battery-powered mobile BCI device for independent use of computers and touch-enabled mobile devices at home. The accuracy and usability of the mobile iBCI will be evaluated with participants already enrolled separately in the investigational clinical trial of the BrainGate neural interface.

This project builds on a custom, mobile neural signal processing device with exceptional processing and low power characteristics, developed through previous VA RR&D-funded research. This project takes advantage of the unique and exceptional processing system, previously developed and validated, to create and quantify advanced neural decoding algorithms that show promise (in preclinical studies) for improving the accuracy and reliability of neural decoding – but are likely too computationally demanding to be viable on existing real-time BCI systems. Decoding methods include magnitude kinematic decoding with recursive neural networks and high-dimensional discrete gesture decoding. Computational methods to be evaluated include latent space methods and stable manifolds to improve day-to-day reliability of high performance and high-dimensional orthogonalization approaches to improve the independence of kinematic and gesture decoding.

Title: Optimizing BCI-FIT: Brain-Computer Interface – Functional Implementation Toolkit (BCI-FIT)

Stage: Recruiting

Principal investigator: Melanie Fried-Oken, PhD 

Oregon Health and Science University

Portland, OR

This project adds to non-invasive BCIs for communication for adults with severe speech and physical impairments due to neurodegenerative diseases. Researchers will optimize & adapt BCI signal acquisition, signal processing, natural language processing, & clinical implementation. BCI-FIT relies on active inference and transfer learning to customize a completely adaptive intent estimation classifier to each user’s multi-modality signals simultaneously. 3 specific aims are: 1. develop & evaluate methods for online & robust adaptation of multi-modal signal models to infer user intent; 2. develop & evaluate methods for efficient user intent inference through active querying; and 3. integrate partner & environment-supported language interaction & letter/word supplementation as input modality. The same 4 dependent variables are measured in each SA: typing speed, typing accuracy, information transfer rate (ITR), & user experience (UX) feedback. Four alternating-treatments single case experimental research designs will test hypotheses about optimizing user performance and technology performance for each aim. Tasks include copy-spelling with BCI-FIT to explore the effects of multi-modal access method configurations (SA1.3a), adaptive signal modeling (SA1.3b), & active querying (SA2.2), and story retelling to examine the effects of language model enhancements. Five people with SSPI will be recruited for each study. Control participants will be recruited for experiments in SA2.2 and SA3.4. Study hypotheses are: (SA1.3a) A customized BCI-FIT configuration based on multi-modal input will improve typing accuracy on a copy-spelling task compared to the standard P300 matrix speller. (SA1.3b) Adaptive signal modeling will allow people with SSPI to type accurately during a copy-spelling task with BCI-FIT without training a new model before each use. (SA2.2) Either of the two methods of adaptive querying will improve BCI-FIT typing accuracy for users with mediocre AUC scores. (SA3.4) Language model enhancements, including a combination of partner and environmental input and word completion during typing, will improve typing performance with BCI-FIT, as measured by ITR during a story-retell task. Optimized recommendations for a multi-modal BCI for each end user will be established, based on an innovative combination of clinical expertise, user feedback, customized multi-modal sensor fusion, and reinforcement learning.