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Locked-in syndrome (LIS) is a neurological condition characterized by the presence of sustained eye opening, quadriplegia or quadriparesis, anarthria, preserved cognitive functioning and a primary code of communication that uses vertical eye movements or blinking.
ORPHA:2406Classification level: Disorder
- Cerebromedullospinal disconnection
- Prevalence: <1 / 1 000 000
- Inheritance: Not applicable
- Age of onset: All ages
- ICD-10: G83.8
- OMIM: -
- UMLS: C0023944
- MeSH: -
- GARD: 6919
- MedDRA: 10024792
Prevalence is unknown but LIS is a very rare condition. By 2009, 33 cases had been published.
LIS may occur at any age but pediatric cases are rare. A two-phase course may be observed: an initial acute phase of variable duration, characterized by anarthria, respiratory impairment, frequent unconscious or comatose state and total paralysis, followed by a chronic phase during which respiratory function, swallowing ability and consciousness are totally or partially restored. LIS can be classified into 3 categories: in the classic form patients are quadriplegic and anarthric with preserved consciousness and upper eyelid and vertical eye movements; in the incomplete form, patients still have limited voluntary movements other than vertical eye movements, most frequently of fingers, toes and head; in the total form, patients show complete immobility including eye movements but have preserved consciousness. In any category, patients may rarely experience a transient LIS, characterized by neurological improvement that may even be complete. Overall, sensation and cognitive skills are preserved, even if visual difficulties occur (blurring, diplopia, impaired accomodation). Emotional lability is reported with pathologic crying or laughing.
The most common causes of LIS are vascular or traumatic (brain stem lesions, vertebral or basilar artery damage or occlusion, or compression of the cerebral peduncles from tentorial herniation). Rarer causes are mesencephalic lesion, subarachnoid hemorrhage, vascular spasm of the basilar artery, brain stem tumor, central pontine myelinolysis, encephalitis (see this term), pontine abscess, drug toxicity, vaccine reaction and prolonged hypoglycemia.
Diagnosis is based on clinical features. Willingness to communicate is frequently noticed by patient's relatives or caregivers and 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 in the acute phase and additional cognitive or sensory deficits (deafness or dysacusia) lead to diagnostic difficulties. A normal and reactive EEG rhythm should alert the physician but is not sufficient to disentangle LIS from post-comatose unconscious patients. Functional neuroimaging such as positron emission tomography (PET) shows normal metabolic activity, i.e. higher than in vegetative state. Brain imaging (ideally MRI) shows isolated lesions (bilateral infarction, hemorrhage or tumor) of the ventral portion of the pons or midbrain.
Differential diagnosis includes coma, vegetative state/unresponsive wakefulness or minimally conscious states.
Management and treatment
Initial management is based on respiratory assistance, gastrostomy and prevention of any immobility, dysphagia and incontinence complications. In the chronic phase, rehabilitation relies on chest physiotherapy, recovery of independent swallowing and continence, and development of fingers, head and neck motricity. Eye-based communication codes must be established very early with the patient. Brain-computer interfaces (BCI) are of growing help to provide more direct and spontaneous ways of communication.
Prognosis is poor as some patients do not survive the acute phase, or experience very limited recovery. Young age at onset and early intensive rehabilitation are favorable prognostic factors. LIS caused by a non-vascular brain injury seems to have better motor recovery. Life expectancy is severely reduced.