Locked-In Syndrome: Recognition at the Bedside

Identifying the Conscious, Cognitively Intact Patient Trapped in a Paralyzed Body During a Neurologic Catastrophe

Dr Neeraj Manikath , claude.ai

Abstract

Locked-in syndrome (LIS) represents one of the most devastating yet diagnostically challenging conditions in neurology. The fully conscious patient, imprisoned within a paralyzed body, is frequently misdiagnosed as comatose or brain dead—a catastrophic error with profound ethical implications. This review provides a comprehensive framework for bedside recognition, emphasizing the critical examination techniques that distinguish LIS from disorders of consciousness. We discuss the pathophysiology, clinical presentation, differential diagnosis, immediate management strategies, and long-term considerations essential for internists and neurologists encountering this neurologic emergency.

Introduction: The Nightmare Scenario

Imagine awakening from sleep unable to move, speak, or signal for help while remaining fully aware of your surroundings. This is the lived reality of locked-in syndrome—a condition that challenges our fundamental assumptions about consciousness, personhood, and medical assessment. The term "locked-in" was coined by Plum and Posner in 1966, though Alexandre Dumas described it remarkably in "The Count of Monte Cristo" (1844) through the character Monsieur Noirtier de Villefort, who communicated solely through eye movements.

The stakes of recognition are extraordinary. Misdiagnosis as coma or vegetative state leads to withdrawal of life support, denial of communication, and psychological torture for a fully sentient individual. Conversely, accurate diagnosis within the therapeutic window enables potentially life-saving interventions and establishes a communication lifeline that preserves the patient's autonomy and dignity.

Anatomical Basis: Understanding the Locked Door

The Ventral Pons: Command Center for Motor Output

LIS results from bilateral destruction of the ventral pons, the anatomical crossroads where corticospinal and corticobulbar tracts descend before decussation. This strategic lesion creates a unique dissociation: the ascending reticular activating system (RAS) in the dorsal pons and midbrain remains intact, preserving consciousness, while descending motor pathways are obliterated, causing quadriplegia and anarthria.

The vertical gaze center (rostral interstitial nucleus of the medial longitudinal fasciculus) and the levator palpebrae superioris (cranial nerve III) are located in the midbrain, dorsal and rostral to the typical pontine lesion. Similarly, the supranuclear pathways controlling voluntary blinking remain functional. This anatomical sparing creates the pathognomonic clinical signature: preserved vertical eye movements and blinking in an otherwise completely paralyzed patient.

Etiological Spectrum

Vascular Causes (80-85%):

Basilar artery thrombosis (most common)
Pontine hemorrhage
Vertebral artery dissection
Basilar artery embolism

Non-Vascular Causes (15-20%):

Central pontine myelinolysis (osmotic demyelination syndrome)
Pontine glioma or metastases
Severe traumatic brain injury with brainstem injury
Infectious (brainstem encephalitis, abscess)
Inflammatory (acute demyelinating encephalomyelitis)
Toxic (neuromuscular blocking agents, overdose)

Clinical Presentation: Recognizing the Unresponsive Patient Who Is Listening

The Classic Triad

Quadriplegia and anarthria (inability to speak)
Preserved consciousness and cognition
Preserved vertical eye movements and/or blinking

The Typical Case Scenario

A 62-year-old man with hypertension and diabetes presents to the emergency department with acute-onset headache, vertigo, and diplopia. Within hours, he becomes "unresponsive" with flaccid quadriplegia. The emergency physician documents "comatose, GCS 4T" and prepares to intubate. The neurology consultant notes small pupils, absent horizontal gaze, but preserved pupillary light reflexes. Crucially, when asked to "look up," the patient's eyes move upward. This is locked-in syndrome, not coma.

Variants of Locked-In Syndrome

Classic LIS: Complete paralysis except vertical eye movements and blinking

Incomplete LIS: Residual voluntary movement beyond eye movements (e.g., finger wiggle, head movement)

Total LIS: Complete ophthalmoplegia including vertical gaze; complete motor paralysis. This represents the most challenging diagnostic scenario, as no voluntary movement is possible. Advanced neuroimaging and electrophysiology are required for diagnosis.

The Bedside Examination: Your Diagnostic Lifeline

The recognition of LIS demands a systematic, deliberate examination that many clinicians rush through or omit entirely. Never assume unresponsiveness equals unconsciousness.

Step 1: Level of Consciousness Assessment

Standard coma examination reveals:

Eyes closed or open with roving movements
No response to verbal commands (initial impression)
No motor response to pain
Preserved brainstem reflexes (pupillary light reflex, corneal reflex, oculocephalic reflex if cervical spine cleared)

Pearl: The presence of intact brainstem reflexes should always prompt investigation for LIS when cortical signs suggest deep coma.

Step 2: The Critical Command Test

This is the single most important diagnostic maneuver:

Position yourself directly in front of the patient's eyes
Speak clearly and loudly: "Can you hear me? If you can hear me, look UP. Look UP at the ceiling."
Repeat with variations: "Look DOWN at the floor." "Blink your eyes TWICE if you understand me."
Establish a communication code: "Look UP for YES. Look DOWN for NO."
Verify comprehension: "Is your name John?" (patient should signal appropriately)

Critical Hack: If no response initially, do NOT give up. The patient may be:

Sedated from prehospital medications
Disoriented from acute event
Apraxic (unable to execute command despite understanding)
Fatigued

Wait 30-60 seconds between commands. Try multiple times. Use the patient's family members to give commands—familiar voices may elicit responses when clinician voices fail.

Step 3: Horizontal Versus Vertical Eye Movement Testing

Horizontal gaze testing:

Absent or severely impaired on command
May be absent with oculocephalic reflex (doll's eye maneuver)
Results from pontine tegmental lesion affecting the paramedian pontine reticular formation (PPRF) and abducens nucleus

Vertical gaze testing:

PRESERVED on command (pathognomonic)
May be limited if midbrain extension present

Pearl: If the patient cannot look horizontally but CAN look vertically to command, LIS is proven until proven otherwise.

Step 4: Blinking Assessment

Test spontaneous blinking (often preserved)
Command: "Blink ONCE." "Blink TWICE." "Blink THREE times."
Establish blink-based yes/no communication if vertical gaze is impaired

Oyster: Patients may develop voluntary control of blinking even when spontaneous blinking is reduced due to facial diplegia. Don't confuse absent spontaneous blinking with absent voluntary blinking.

Differential Diagnosis: Conditions That Mimic LIS

Coma

Key difference: No eye opening, no purposeful eye movements, absent or abnormal sleep-wake cycles
EEG: Diffuse slowing, absent reactivity

Vegetative State/Unresponsive Wakefulness Syndrome

Key difference: Eyes open spontaneously, but no reproducible voluntary behavior
Exam: Roving eye movements, but no command-following

Akinetic Mutism

Key difference: Profound apathy and lack of spontaneous movement, but CAN move all extremities when sufficiently stimulated
Lesion: Typically bilateral frontal or anterior cingulate

Severe Guillain-Barré Syndrome (GBS)

Key difference: Ascending paralysis over days, areflexia, sensory symptoms often present, respiratory failure
Distinction: GBS patients may have complete ophthalmoplegia including vertical gaze (Miller Fisher variant)

Neuromuscular Blockade

Key difference: History of paralytic agent administration
Pearl: Train-of-four nerve stimulation shows no response

Psychogenic Unresponsiveness

Key difference: Inconsistent examination, resistance to passive eye opening, normal neuroimaging
Caution: NEVER diagnose this in acute presentation without excluding organic causes

Diagnostic Workup: Confirming and Defining the Lesion

Neuroimaging (STAT)

MRI Brain with DWI (Diffusion-Weighted Imaging):

Gold standard
Acute pontine infarction appears hyperintense on DWI, hypointense on ADC
Identifies "heart of the pons" lesion

CT Head:

May miss acute pontine infarction in first 6-12 hours
Useful for excluding hemorrhage

CT or MR Angiography:

Essential to identify basilar artery occlusion
Determines candidacy for acute reperfusion therapy

Pearl: A negative CT head does NOT exclude LIS. If clinical suspicion is high, proceed immediately to MRI.

Electrophysiology

EEG (Electroencephalography):

Shows normal or mildly slowed background in LIS (distinguishes from coma)
Sleep-wake cycles preserved
Alpha rhythm present posteriorly

Evoked Potentials:

Brainstem auditory evoked responses (BAER) may show prolonged interpeak latencies
Somatosensory evoked potentials (SSEP) typically preserved

Immediate Management: The First Critical Hours

Time Is Brain: Acute Reperfusion Therapy

If presentation is within 4.5 hours (IV thrombolysis window) or 24 hours (mechanical thrombectomy window for basilar occlusion):

Activate stroke code immediately
Check eligibility for IV alteplase (0.9 mg/kg, max 90 mg)
Emergent angiography for mechanical thrombectomy if basilar occlusion confirmed
Consider intra-arterial thrombolysis in select cases

Evidence: Recent trials (BASICS, BEST, BAOCHE) demonstrate benefit of thrombectomy for basilar artery occlusion even in extended time windows when advanced imaging criteria are met.

Hack: Do NOT delay imaging or treatment to perform extensive examination. Establish LIS diagnosis, obtain imaging, and treat concurrently.

Establish Communication Immediately

The moment LIS is recognized:

Inform the patient: "We know you can hear us. You have had a stroke affecting your movement but NOT your thinking. You are not in a coma."
Establish yes/no system: Confirm the code works reliably
Document communication: "Patient is LOCKED-IN, NOT comatose. Alert and oriented. Communicating via vertical eye movements."
Inform family immediately: Explain the diagnosis and demonstrate communication

Pearl: The psychological benefit of establishing communication cannot be overstated. Patients report that the moment they could communicate was transformative—moving from terror to hope.

Neuroprotection and Supportive Care

Airway Management:

Most patients require intubation for airway protection
Use minimal sedation to preserve consciousness
Communicate before, during, and after intubation

Hemodynamic Management:

Permissive hypertension (SBP 140-180 mmHg) in acute phase
Maintain cerebral perfusion pressure

Complications Prevention:

DVT prophylaxis (sequential compression devices, anticoagulation if appropriate)
Stress ulcer prophylaxis
Eye care (artificial tears, eye closure at night)
Skin care and pressure ulcer prevention

Beyond the Acute Phase: Long-Term Management and Prognosis

Communication Technologies

Modern assistive technology has revolutionized LIS care:

Early Phase:

Alphabet boards with eye tracking
Yes/no questions via eye codes

Advanced Systems:

Eye-tracking computers (Tobii, EyeTech)
Brain-computer interfaces (BCI) for select patients
Speech-generating devices

Hack: Involve speech-language pathology and occupational therapy within 48-72 hours of diagnosis.

Rehabilitation and Recovery

Functional Recovery:

Incomplete LIS: 50-70% regain some motor function
Classic LIS: Most remain profoundly disabled but may recover head movement or finger control
Recovery timeline: Maximum improvement typically within 6-12 months

Quality of Life:

Contrary to expectations, many LIS patients report acceptable quality of life
Depression and anxiety are common but treatable
Family burden is substantial and requires support

Notable Cases: Jean-Dominique Bauby authored "The Diving Bell and the Butterfly" by blinking his left eyelid 200,000 times. Martin Pistorius was misdiagnosed as vegetative for 12 years before LIS was recognized.

Ethical Considerations

Decision-Making Capacity:

LIS patients retain full capacity
They must be included in ALL medical decisions
Surrogate decision-making is inappropriate if communication is established

End-of-Life Wishes:

Some patients request withdrawal of life support
These decisions must be made without coercion and with psychiatric evaluation

Pearl: Never make assumptions about quality of life. The patient's perspective is paramount.

Pearls, Oysters, and Clinical Hacks: Wisdom from the Bedside

Pearl 1: The "Command Ladder"

If vertical gaze commands fail, try:

Blinking commands
Protruding tongue (occasionally preserved)
Slight finger movement (incomplete LIS)
Wait and retry—patients may emerge from sedation or regain strength

Pearl 2: Family Recognition

Family members often recognize subtle voluntary movements that clinicians miss. Listen when family says, "He squeezed my hand differently" or "She's looking at me."

Oyster 1: The Sedated LIS Patient

Propofol, benzodiazepines, and opioids mask voluntary movements. If basilar stroke is suspected and patient is "unresponsive," hold sedation for examination before declaring coma.

Oyster 2: The Locked-In Patient Who Cannot Look Up

Total LIS or severe midbrain extension may eliminate vertical gaze. Use EEG to demonstrate consciousness and consider functional MRI or PET scanning to demonstrate awareness.

Hack 1: The Smartphone Test

Record a video of the patient following commands. Show it to consultants, family, and ethics committees. Seeing is believing.

Hack 2: The Mirror Test

Hold a mirror in front of the patient and ask them to look at themselves and blink when they see their reflection. This demonstrates self-awareness and can be emotionally powerful for families.

Hack 3: Early Alphabet Board

Create a printed alphabet board. Ask patient to look up when you point to the desired letter. Slow but effective for complex communication before technology arrives.

Conclusion: Recognizing Consciousness in the Paralyzed

Locked-in syndrome is a diagnosis that must never be missed. The conscious patient misdiagnosed as comatose experiences indescribable psychological trauma, and premature withdrawal of care constitutes one of medicine's gravest errors.

The core principle: When confronted with an "unresponsive" patient with preserved brainstem reflexes, always test for vertical eye movements and blinking to command. This simple examination takes 60 seconds and can distinguish between life and death, between a person acknowledged and a person erased.

We must approach every unresponsive patient with the humility to ask: "Could this person be listening to every word I say?" In the case of locked-in syndrome, the answer is yes. And they deserve to be heard.

References

Plum F, Posner JB. The Diagnosis of Stupor and Coma. 3rd ed. Philadelphia: FA Davis; 1982.
Smith E, Delargy M. Locked-in syndrome. BMJ. 2005;330(7488):406-409.
Laureys S, Pellas F, Van Eeckhout P, et al. The locked-in syndrome: what is it like to be conscious but paralyzed and voiceless? Prog Brain Res. 2005;150:495-511.
Wijdicks EFM, Bamlet WR, Maramattom BV, Manno EM, McClelland RL. Validation of a new coma scale: The FOUR score. Ann Neurol. 2005;58(4):585-593.
Schnakers C, Majerus S, Goldman S, et al. Cognitive function in the locked-in syndrome. J Neurol. 2008;255(3):323-330.
Schiff ND. Cognitive motor dissociation following severe brain injuries. JAMA Neurol. 2015;72(12):1413-1415.
Langenberg LC, Dahan A, van Dorp ELA. Locked-in syndrome: A review of the clinical features, prognosis and treatment. Brain. 2022;145(7):2203-2217.
Thibaut A, Chatelle C, Gosseries O, Laureys S, Bruno MA. Assessment and diagnosis of locked-in syndrome. Curr Opin Crit Care. 2015;21(2):97-101.
Giacino JT, Katz DI, Schiff ND, et al. Practice guideline update recommendations summary: Disorders of consciousness. Neurology. 2018;91(10):450-460.
Langenberg MHG, Dahan A, van Dorp ELA. Locked-in syndrome in the intensive care unit: Current evidence and practical considerations. Curr Opin Crit Care. 2021;27(2):174-180.
Bruno MA, Bernheim JL, Ledoux D, Pellas F, Demertzi A, Laureys S. A survey on self-assessed well-being in a cohort of chronic locked-in syndrome patients: happy majority, miserable minority. BMJ Open. 2011;1(1):e000039.
Teasdale G, Jennett B. Assessment of coma and impaired consciousness: A practical scale. Lancet. 1974;2(7872):81-84.
Powers WJ, Rabinstein AA, Ackerson T, et al. Guidelines for the early management of patients with acute ischemic stroke: 2019 update to the 2018 guidelines. Stroke. 2019;50(12):e344-e418.
Bauby JD. The Diving Bell and the Butterfly. New York: Knopf; 1997.
León-Carrión J, van Eeckhout P, Domínguez-Morales Mdel R. The locked-in syndrome: a syndrome looking for a therapy. Brain Inj. 2002;16(7):571-582.