What is traumatic brain injury-induced locked-in syndrome?

Locked-in Syndrome (LIS), medically known as pseudocoma, is a condition in which patients suffer near-total paralysis, where they are awake and conscious, but unable to produce speech or make limb or facial movements. Despite this profound motor impairment, individuals with LIS remain fully conscious and cognitively intact ¹  

Traumatic Brain Injury (TBI) - an injury to the brain- results from an external mechanical force and is usually classified as a closed or penetrating TBI. ² TBI has been clinically recognised as one possible cause of LIS, with all information below in this review. ³

What is the pathophysiology of LIS? How does it happen?

Locked-In Syndrome occurs when damage to the ventral pons in the brain stem disrupts motor pathways (corticospinal and corticobulbar tracts) - define these terms for the reader? This blocks the connection between the brain and the spinal cord, causing paralysis and loss of speech, while sparing the brain’s consciousness center.⁵

Neurological impairment primarily impacts voluntary movement, but vertical eye movements and blinking are preserved, due to intact neurological pathways controlling cranial nerves III and IV. Sensory and cognitive functions remain unaffected, aiding diagnosis and communication. ⁵

Classification of LIS

• Classic LIS: Defined by paralysis of all 4 limbs and torso, loss of speech (anarthria), preserved vertical eye movement, and intact consciousness
• Incomplete LIS: Includes some additional voluntary movement beyond eye control
• Total LIS: Involves complete paralysis, including eye movements, with preserved consciousness confirmed by neurophysiological testing⁷

TBI and LIS

There are 3 key types of TBI, namely:

• Closed head injury (blunt trauma without skull penetration) 
• Penetrating injury (skull is breached usually by an object) 
• Blast injury is unique to military contexts, caused by explosive forces damaging the brain¹¹ 

These injuries can all lead to haemorrhage in or around the brainstem, elevation in intracranial pressure, which compresses the brainstem, leading to impairment of vital functions or damage to the axons or nerve pathways in the brainstem. ²

Locked-in syndrome (LIS) is a rare consequence of Traumatic Brain Injury (TBI). Although exact incidence rates are difficult to establish due to underreporting and diagnostic challenges, existing data indicate that around 13.6% of LIS cases are associated with TBI. ¹⁰

How is a diagnosis of LIS made?

On average, it takes more than 2 months to diagnose LiS.⁴ The symptoms closely mirror the clinical presentation of the disease itself, including:

• Quadriplegia: Total paralysis of all four limbs
• Anarthria: Loss of the ability to articulate speech
• Consciousness: Patients are awake and aware of their surroundings
• Usual Cognitive Function: Mental faculties, including reasoning and memory, remain unaffected
• Usual Vertical Eye Movements and Blinking: These are often the only means of communication and remain unaffected
• Intact Hearing and Sensory Perception: Patients can hear and feel sensations, but cannot respond due to quadriplegia and anarthria^4,5

Although primarily diagnosed based on clinical evaluation, imaging tools are essential to confirm the diagnosis of LIS and to identify the underlying cause. This is usually a brainstem lesion due to TBI. The main imaging modalities used are:

• MRI - magnetic resonance imaging is the primary tool used and is the gold standard. Can detect haemorrhagic lesions in the brain stem, tumours, or trauma. It also assists in differentiating LIS from disorders of consciousness (vegetative state)^4,5
• CT scan – useful in ruling out structural or haemorrhagic abnormalities. Although it is a rapid method for screening, it may miss changes or infarcts in blood flow to the brain stem⁵
• CT angiography - helps to visualise blood vessels and any blockages, reducing blood flow to the brain stem, known as basilar artery thrombosis⁶

Diagnosis of locked-in syndrome can be difficult, as the condition shares many features with other speechless/paralysis conditions. The below are some differential diagnoses, which are the main conditions considered prior to diagnosis of LIS:

• Coma – patient demonstrates impaired consciousness, and voluntary movement is absent⁵
• Persistent vegetative state - where patients demonstrate eye-opening but have no conscious awareness of themselves or surroundings, they are breathing but lack voluntary facial or body movements⁵
• Akinetic mutism - Eye movements are intact; however, there is a slowness of speech. The patient is conscious with decreased motor response⁵
• Brain death - patient demonstrates impaired consciousness with no voluntary motor movements⁵
• Cervical spinal cord injury - patient demonstrates variable to complete quadriplegia, with voluntary eye and facial movements intact, as well as being conscious and having the ability to speak⁵

During clinical evaluation, a detailed patient history should be obtained when possible to rule out intoxication or drug use, as certain substances—including sedatives, anaesthetics, and toxins—can temporarily mimic a locked-in state.⁵

What does the management of LIS entail?

Management centres on patient stabilisation, determining and treating the underlying condition, and ensuring long-term support and rehabilitation.

Early stages require acute care

• Stabilisation of patient - ABC’s airway, breathing circulation intact, this usually occurs in an ICU department⁷
• Treatment of underlying cause - surgery, steroids, and antibiotics are all appropriate measures, depending on the cause.

Supportive care

• Respiratory support via mechanical ventilation⁷
• Nutritional support via a feeding ‘nasogastric’ tube
• Prevention of complications, including infections, pressure sores or DVT, via physiotherapy and use of anticoagulants/ antibiotics.

Communication tools

LIS means patients are conscious but unable to speak. There are numerous different communication options available for the patient, such as:

• Eye-tracking systems 
• Blinking code systems 
• Assistive communication therapies^4,8,9

Rehabilitation 

• Emphasis on maintaining motor function and improving mobility should be started within one month⁷ 
• Different methods, including physical, occupational and speech therapy⁴

Psychological and social support are also very important in the management of LIS to prevent depression and anxiety.

What is the prognosis for a patient with an LIS diagnosis?

Can a patient recover?

• Recovery is rare and often partial
• Limited motor function may be regained in rare circumstances
• The primary means of communication remains eye movements
• The extent and location of brainstem damage found on MRI correlate with overall recovery potential and prognosis

Are there predictors for the outcome of an LIS patient?

• Early diagnosis improves outcomes
• Early rehabilitation and management improve outcomes       
• If the patient remains conscious and has the ability to perform eye movements, then this is a good prognostic marker
• Patients from a younger cohort usually demonstrate better recovery

What is the expected quality of life (QoL) for a patient with LIS?

• With new technological aids available, like BCIs and AAC, define these briefly for readers. Patient QoL can remain acceptable while also enhancing independence 
• Depression and frustration are common amongst patients, but are manageable through support

What does the future of LIS look like in terms of diagnostics and research needs?

There are many diagnostic challenges in the diagnosis of LIS following a TBI. Patients demonstrating limited movements (eye movements only) can have these symptoms overlooked as LIS, leading to misdiagnosis, and often, early imaging may not detect brain stem damage. 

This demonstrates the need for standardised diagnostic protocols, improved availability of data on LIS incidence and outcomes, along with improvements in the field of analytical biomarkers in early-stage diagnosis and prognosis. 

Further research and development are required to improve the accessibility and usability of communication technologies, including eye-tracking and augmentative and alternative communication (AAC) technologies to allow patients an improved quality of life.^12,13 Functional MRI (fMRI), AI imaging and brain-computer interfaces (BCIS) are all tools which show huge diagnostic potential in the advancement of LIS diagnosis.^12,13

Summary

This review examines Traumatic Brain Injury (TBI) as a relatively uncommon yet important cause of Locked-In Syndrome (LIS). Although the majority of LIS cases stem from vascular events, particularly pontine strokes, TBI is responsible for approximately 13–14%. It usually results from direct injury to the ventral pons, diffuse axonal damage, or trauma to the vertebrobasilar arteries, often due to high-impact or severe head injuries.

Although rare, TBI should be considered a critical cause of LIS, especially in trauma settings. Accurate, early diagnosis and access to rehabilitation technologies are vital for improving outcomes and preserving patient dignity and communication.