Introduction

Locked-In Syndrome (LIS) is a neurological medical condition where a person experiences total paralysis except for some eye movements. The individual still has preserved cognition, consciousness, blinking and hearing but cannot move their limbs, torso, head, neck or throat, and also cannot feel these parts of their body. 

LIS occurs due to damage to a particular part of the brain stem, called the anterior pons, mesencephalon or thalamus. It can be caused by trauma, vascular problems, demyelination, masses or infection. In this article, we will look into the vascular problem that can cause LIS. 

The vascular problem we will be discussing in this article is basilar artery thrombosis, a major cause of LIS. The basilar artery is one of the most important blood vessels in the human body, and it provides blood (and therefore oxygen) to various parts of the brain. Therefore, a thrombosis, while very rare, is a catastrophic event. 

Basilar artery thrombosis can lead to LIS by blocking the brain’s network of blood vessels (circle of Willis), leading to a stroke. The basilar artery’s main function is to supply the cerebellum, brainstem, thalamus, occipital, and medial temporal lobes of the brain with oxygen-rich blood. So, when the basilar artery is damaged, these parts of the brain cannot function. Basilar artery thrombosis must be treated as quickly as possible because the prognosis is usually poor, with a high mortality rate. 

Anatomy and physiology overview

The brainstem and pons

The brainstem is part of the brain that connects the main part of the brain to the spinal cord. It is made up of three parts (in descending order): the midbrain, the pons and the medulla oblongata. It is in charge of breathing, consciousness, heart rate, and sleep. There are also about 10 out of 12 cranial nerves arising from the brainstem. These parts of the brain have something called nuclei and tracts. Think of the nuclei as buildings where specific jobs are done, and tracts as roads or highways where information is passed on. The brainstem is an important part of the network because it forms part of motor pathways (corticospinal and corticobulbar tracts). The pons, the middle part of the brain stem, has a groove on its front portion for the artery known as the basilar artery.

Role of the basilar artery

The basilar artery is a vital blood vessel that provides blood supply to the posterior part of the brain and the circle of Willis. It supplies blood to the brainstem, cerebellum, and parts of the occipital lobes. It is formed by joining the vertebral arteries and gives off many branches. LIS syndrome can sometimes be referred to as damage to the vertebrobasilar arteries. Damage to the basilar artery causes many problems because normal bodily functions are affected.

Pathogenesis

A thrombosis is a clot that is formed in a blood vessel or inside your heart. This stops blood from flowing freely. The artery can be occluded in the basilar artery due to atherosclerotic conditions, embolism or dissection. Atherosclerosis is the formation of plaque in the arteries, thereby narrowing them. It happens due to certain diseases like hypertension, hyperlipidemia, smoking, obesity, diabetes, and coronary artery disease. Embolism is the formation of an embolus/clot that starts somewhere else and gets stuck in certain arteries, like the basilar artery. Meanwhile, arteries are made up of three layers, and an artery dissection occurs when there is a tear in the inner wall of an artery, allowing blood to get in between the other layers. Any of these methods will damage the basilar artery, causing an infarction (death of tissue due to a lack of blood supply) in the ventral pons. This will disrupt the motor pathways (roads or highways) known as tracts we talked about, causing quadriplegia.

Also, the brain has different systems and teams to ensure that it runs smoothly. This article covers three systems particular to LIS: RAS, PPRF and MLF. The reticular activating system (RAS) is a system in the brain that controls consciousness. The brainstem forms part of this system. In LIS, it is spared because it affects only the front part of the pons, and RAS uses the back part of the pons. This is also the reason why certain nerves controlling eye movements like vertical gaze and blinking are unaffected: although the paramedian pontine reticular formation (PPRF), which controls horizontal eye movement and saccades, is damaged, the MLF (medial longitudinal fasciculus), which controls vertical eye movement, is not. 

Clinical presentation

LIS is known as ‘locked in syndrome’ because the individual is essentially locked inside their body and cannot move. 

Patients who are likely to experience LIS may present with:

• Sudden onset of symptoms are dizziness, double vision, dysarthria, loss of consciousness
• When it progresses to LIS, there is rapid development of complete paralysis of the limbs and torso, but preserved awareness, hearing and certain eye movements

Diagnosis

Clinical assessment

In order to conclude that a person has LIS, a physician may look at the following: 

• Eye movement in an otherwise unresponsive patient: tests for impairment of the horizontal eye movement and sparing of the vertical eye movements and blinking. Eye reflexes are also tested
• Sensory deficits: on both sides of the face, bilateral peripheral facial paralysis, absence of a gag reflex, weak tongue movements, and neck weakness
• Hearing: can be tested using vertical eye movement to get “yes” or “no” responses
• Testing of limb motor strength: sensory deficits like sensitivity to touch and pain, and reflexes to ascertain the site of the lesion is the basilar artery

All of this will be done occasionally to monitor progress or improvement.

Imaging studies

• MRI: detects pontine infarction
• CT Angiography: identifies basilar artery occlusion

EEG or functional MRI

• Confirms consciousness

Prognosis

• Short-term outlook
  • High risk of early death without rapid intervention
• Long-term prognosis
  • Generally poor motor recovery
  • Some can learn to communicate using eye movements or assistive devices
• Factors affecting prognosis
  • Speed of diagnosis and treatment
  • Age, overall health, and cause of thrombosis
• Quality of life
  • LIS may come with possible emotional distress, but preserved cognitive abilities
  • The quality of life may not be the same as before the incident, so there is a low potential for a full recovery of motor skills 
  • It is important to have multidisciplinary support between all medical staff and the family. There must be physical modifications made to support patients and provide emotional support to provide the highest quality of life possible

Treatment and management

Acute management

• The first thing to be done in an instance of locked-in syndrome is securing a clear airway by mechanical ventilation, maintaining adequate oxygen saturation levels, and ensuring the patient is stable from a circulatory point of view, using heart rate, blood pressure, and sometimes orthostatic hypotension
• Thrombolysis or thrombectomy if within the treatment window. Thrombolysis involves medicinally dissolving the clot whilst thrombectomy is the surgical removal of the clot. It should be noted that a thrombectomy is usually more invasive, thus thrombolysis is preferred. The size of the clot and the timeframe of the incident will determine which treatment is used

Supportive care

• Continued mechanical ventilation, management of nutrition, incontinence, pain, vision and prevention of complications
• Psychological and psychiatric support

Rehabilitation

Rehabilitation should begin about a month after the onset of symptoms for best outcomes and should include:

• Communication training
• Physical therapy to prevent muscle wasting
• Speech and occupational therapy
• Teaching the use of assistive devices like infrared eye movement sensors or computer-modulated voice devices
• Physiotherapy and psychological support

Summary

Locked-in syndrome is a medical condition that can be caused by various factors, but most commonly by damage to the basilar artery, which supplies the front part of the pons in the brainstem. When damaged, insufficient oxygen is delivered to the brain, causing the tissues to die. Therefore, LIS has a very poor prognosis, and high mortality rate when left untreated. Early symptom recognition and intervention is vital to provide the best outcome for patients. Ongoing research on LIS is crucial to understanding how to manage, and possibly reverse some of the damage caused by the syndrome, and also help patients adapt to normal living.