Background and ObjectivesPatients with classic locked-in syndrome (LIS), typically caused by ventral pontine stroke, present with quadriplegia, mutism, intact consciousness, and communication skills limited to vertical gazing and/or blinking. Clinical presentations and definitions ofLISdiffer, especially regarding incomplete LIS. In our study, we explored the functional diversity of LIS, its outcomes, and the complexity of its course, along with variations in the location of lesions and their potential significance for outcomes.MethodsA national cohort of patients with vascular LIS who remained in the LIS state for at least 6 weeks according to a functional definition ofLISwas studied. Demographic, medical, and follow-up data, collected between 2012 and 2022, were obtained from the quality register of the Norwegian National Unit for Rehabilitation of Locked-In Syndrome. Outcomes in verbal communication, motor function, and dependency were evaluated according to criteria for being in or not in the LIS state. Modified Rankin Scale and LIS Motor Recovery Scale were applied. Descriptive analysis was performed. The relationship between lesion location and functional outcome was investigated.ResultsThe sample included 51 patients (median age: 55.7 years, 36 males), 43 of whom had follow-up data. Ischemic stroke was the most common etiology (n= 35). Twenty-three patients had emerged from the LIS state, mostly within 2 years after onset. All but one patient achieved some motor improvement, whereas only three achieved full motor recovery, and 88% had a persistently high level of dependence. The 3-year survival rate was 87%. Five patients had an isolated pontine lesion, whereas 80% showed various lesions outside the brain stem. Patients who emerged from the LIS state had a significantly lower prevalence of lesions outside the brain stem than patients who remained in the LIS state did.DiscussionInvestigating an unselected population-based sample of patients with vascular LIS offers important insights into LIS’s functional diversity. Although most patients remained severely disabled, even small improvements in function can substantially increase the potential for activity and participation. Additional lesions outside the brain stem seem to be common in long-lasting LIS and might be prognostic for remaining in the LIS state.