Research Article: Diffusion tensor imaging reveals diffuse white matter injuries in locked-in syndrome patients

Date Published: April 10, 2019

Publisher: Public Library of Science

Author(s): Mylene Leonard, Felix Renard, Laura Harsan, Julien Pottecher, Marc Braun, Francis Schneider, Pierre Froehlig, Frederic Blanc, Daniel Roquet, Sophie Achard, Nicolas Meyer, Stephane Kremer, Joseph Najbauer.


Locked-in syndrome (LIS) is a state of quadriplegia and anarthria with preserved consciousness, which is generally triggered by a disruption of specific white matter fiber tracts, following a lesion in the ventral part of the pons. However, the impact of focal lesions on the whole brain white matter microstructure and structural connectivity pathways remains unknown. We used diffusion tensor magnetic resonance imaging (DT-MRI) and tract-based statistics to characterise the whole white matter tracts in seven consecutive LIS patients, with ventral pontine injuries but no significant supratentorial lesions detected with morphological MRI. The imaging was performed in the acute phase of the disease (26 ± 13 days after the accident). DT-MRI-derived metrics were used to quantitatively assess global white matter alterations. All diffusion coefficient Z-scores were decreased for almost all fiber tracts in all LIS patients, with diffuse white matter alterations in both infratentorial and supratentorial areas. A mixture model of two multidimensional Gaussian distributions was fitted to cluster the white matter fiber tracts studied in two groups: the least (group 1) and most injured white matter fiber tracts (group 2). The greatest injuries were revealed along pathways crossing the lesion responsible for the LIS: left and right medial lemniscus (98.4% and 97.9% probability of belonging to group 2, respectively), left and right superior cerebellar peduncles (69.3% and 45.7% probability) and left and right corticospinal tract (20.6% and 46.5% probability). This approach demonstrated globally compromised white matter tracts in the acute phase of LIS, potentially underlying cognitive deficits.

Partial Text

Locked-in syndrome (LIS) was defined by Plum and Posner in 1966 as a condition in which selective supramotor de-efferentiation produces paralysis of all four limbs and the lower cranial nerves without interfering with consciousness [1]. The patients are “locked” in their body, and their only possibility of communicating is to use vertical eye movements and blinking. LIS can be divided into three categories depending on the extent of motor impairment: classical LIS refers to Plum and Posner’s definition of patients with total immobility except for vertical eye movements and blinking; incomplete LIS refers to patients with preserved voluntary movements, other than vertical eye movements and blinking; total LIS refers to patients with total immobility including all eye movements [2].

This study was approved by our Institutionnal Review Board (N° Comité de Protection des Personnes Est IV 08/53, N° Comité de Protection des Personnes Est IV: 08/54). It is registered on the “National agency of Security of Drug and the Health Products” database under the “2008-A00811-54” and “2008-A00694-51” EudraCT identifier.

This study was designed to assess white matter fiber tract integrity using DT-MRI, both at the infratentorial and the supratentorial levels in LIS patients, unravelling the consequences of LIS-specific brain lesions on overall white matter integrity. We showed diffuse compromised supra- and infratentorial white matter fiber tracts in LIS patients. Moreover, we identified three pathways crossing the lesion responsible for LIS in the ventral part of the pons, which showed more injury than the other fiber tracts: the corticospinal tract, the medial lemniscus tract and the superior cerebellar peduncles.

Diffusion tensor magnetic resonance imaging highlighted diffuse supra- and infratentorial white matter fiber tract injuries in consecutive early locked-in syndrome patients. The most injured pathways–the medial lemniscal tracts, corticospinal tracts and superior cerebellar peduncles–cross the ventral part of the pons, the anatomical region responsible for LIS. This finding might contribute to our understanding of cognitive dysfunction in LIS, although the specific pathophysiological mechanisms still remain unknow.