**Background:** Locked-in syndrome (LiS), first described by Plum and Posner in 1972, is a rare condition where patients are quadriplegic but retain cognitive abilities, with only vertical eye and eyelid movements preserved. Subcategorizations by Bauer et al. (1979) include classical, incomplete, and complete LiS, and the Salzburg Coma Group introduced locked-in plus syndrome (LiPS) for patients with additional consciousness disturbances. The most common cause is infarction or hemorrhage in the vertebrobasilar artery territory, often affecting the ventral pons. Incidence and prevalence are poorly defined; a 1986 study reported a mean age of onset of 52 years (range 16–90) with a male predominance (85:52), and a mortality rate of 60% (majority within 4 months). A newer study reports 75% mortality in the acute phase. Life expectancy has improved, with some patients living decades. This review aims to provide an up-to-date overview of LiS, focusing on anatomy, pathophysiology, treatments, quality of life, ethics, and new developments.
**Methods:** A literature search was conducted in MEDLINE/PubMed in 2022 using the title or MeSH term 'locked-in syndrome', yielding 441 results (265 case reports) from 1971 to 2022. Titles and abstracts were screened for relevance, and essential citations were pursued. Literature on special topics (e.g., brainstem anatomy) was searched separately.
**Key Results:** The corticospinal and corticobulbar tracts in the ventral pons are damaged, causing quadriplegia and anarthria, while eye movements are spared due to separate brainstem control centers (PPRF for horizontal, mesencephalic structures for vertical). Complete LiS involves additional mesencephalic damage, while incomplete LiS spares some movements. LiPS results from lesions extending into the mesencephalon, thalamus, or dorsal brainstem (ascending reticular activating system). Differential diagnoses include unresponsive wakefulness syndrome (UWS), minimally conscious state (MCS), cognitive motor dissociation (CMD), and akinetic mutism. Misdiagnosis is common; a 2002 study found it takes over 2 months to diagnose LiS, and only in 25% of cases is the physician the first to realize consciousness. Treatment emphasizes early, interdisciplinary rehabilitation (physical, speech, occupational therapy), psychological support, and communication aids. Brain-computer interfaces (BCIs) are important; 63% of patients in one survey used high-tech assistive devices. Quality of life surveys show 72% of chronic LiS patients report happiness, and only 7% express a wish for euthanasia. However, 24% of medical professionals in a European survey thought treatment could be withdrawn, and 9% denied LiS patients can feel pain. A French survey found half of LiS patients experience pain, and half do not communicate it.
**Clinical Implications:** LiS is not a disorder of consciousness, and patients can have a high quality of life. Early, aggressive rehabilitation and establishment of communication are essential. Misconceptions among healthcare professionals (e.g., denying pain perception or capacity to express desires) must be corrected. Ethical care requires respecting patient autonomy, dignity, and right to life, while avoiding prejudiced end-of-life decisions. Investment in BCI research and user-centered design is needed to enable communication and societal participation. Diagnostic delays must be reduced through standardized protocols including functional tests (fMRI, EEG).