Locked-in syndrome (ORPHA:2406)
A rare neurologic disease characterized by severe paralysis of the limbs and the oral structures causing the person to be completely dependent on help in all activities of daily living and communication, while having preserved cognition. Most commonly, the term locked-in syndrome (LIS) is used when the condition is caused by acquired brain injury (as in this text), but sometimes also when referring to the advanced stage of certain neurodegenerative disorders.
Epidemiology
LIS is a very rare condition. No prevalence studies have been published. A study published in 1986 identified 139 cases in the literature. A recent (2023) national population-based study from Norway reported 16 cases living with LIS in a population of approximately 5.425 million (1 out of 339,000 individuals).
Clinical description
LIS can be classified into 3 categories: classic, where patients are quadriplegic and anarthric with preserved consciousness and upper eyelid and vertical eye movements; incomplete, where patients have limited voluntary movements in addition to vertical eye movements; total, where patients show complete immobility including eye movements.
Etiology
The most common cause of LIS is vascular lesions; trauma, infection, myelinolysis, polyneuropathy and demyelination are rare etiologies.
Diagnostic methods
Diagnosis is based on clinical features. The presence of cognitive abilities and willingness to communicate is frequently noticed by patient's relatives or caregivers. Eye movement response to verbal commands should systematically be searched for in apparent vegetative state cases. Unambiguous but limited signs of consciousness (voluntary eye movements or blinking), fluctuations of vigilance and cognitive or sensory deficits lead to diagnostic difficulties. A normal and reactive EEG rhythm should alert the physician but is not sufficient to disentangle LIS from unconscious patients. Brain imaging (ideally MRI) usually shows isolated lesions of the ventral portion of the pons or midbrain, but cerebral lesions outside the brain stem might occur in as much as 80% of the cases.
Differential diagnosis
Differential diagnoses include coma, vegetative state/unresponsive wakefulness and minimally conscious states.
Management and treatment
Initial management is based on respiratory assistance, gastrostomy and prevention of any immobility, dysphagia and incontinence complications. It is important to establish a mode of communication; eye movements are preferred rather than blinking. As the individual is completely dependent on help, one needs to assure the patient feels safe. Rehabilitation should start in the acute phase and be continued throughout the subacute stage. Cornerstones are chest physiotherapy, recovery of independent swallowing and continence, and motor rehabilitation. Motor progress should be accurately monitored as even small movements might be used for interaction by switches etc. Often, communication methods can be gradually refined as a number of technical solutions are available. Brain-computer interfaces (BCI) are of growing help to provide more direct and spontaneous ways of communication.
Prognosis
In the acute phase, patients may rarely experience a transient LIS, while some patients do not survive. Further prognosis varies. Usually some motor improvement occurs. Almost 9 out of 10 patients who are ''locked in'' for at least 6 weeks remain highly dependent on help while 1 in 20 experiences complete motor recovery. Young age at onset and early intensive rehabilitation are probably favorable prognostic factors. LIS caused by a non-vascular brain injury seems to have better motor recovery.

                            Last update: 
                            February 2024


                            - Expert reviewer(s): 
                            Dr Frank BECKER