Relationship between brainstem neurodegeneration and clinical impairment in traumatic spinal cord injury

Abstract

BackgroundBrainstem networks are pivotal in sensory and motor function and in recovery following experimental spinal cord injury (SCI).ObjectiveTo quantify neurodegeneration and its relation to clinical impairment in major brainstem pathways and nuclei in traumatic SCI.MethodsQuantitative MRI data of 30 chronic traumatic SCI patients (15 with tetraplegia and 15 with paraplegia) and 23 controls were acquired. Patients underwent a full neurological examination. We calculated quantitative myelin-sensitive (magnetisation transfer saturation (MT) and longitudinal relaxation rate (R1)) and iron-sensitive (effective transverse relaxation rate (R2*)) maps. We constructed brainstem tissue templates using a multivariate Gaussian mixture model and assessed volume loss, myelin reductions, and iron accumulation across the brainstem pathways (e.g. corticospinal tracts (CSTs) and medial lemniscus), and nuclei (e.g. red nucleus and periaqueductal grey (PAG)). The relationship between structural changes and clinical impairment were assessed using regression analysis.ResultsVolume loss was detected in the CSTs and in the medial lemniscus. Myelin-sensitive MT and R1 were reduced in the PAG, the CSTs, the dorsal medulla and pons. No iron-sensitive changes in R2* were detected. Lower pinprick score related to more myelin reductions in the PAG, whereas lower functional independence was related to more myelin reductions in the vestibular and pontine nuclei.ConclusionNeurodegeneration, indicated by volume loss and myelin reductions, is evident in major brainstem pathways and nuclei following traumatic SCI; the magnitude of these changes relating to clinical impairment. Thus, quantitative MRI protocols offer new targets, which may be used as neuroimaging biomarkers in treatment trials.

Reorganization of the somatosensory pathway after subacute incomplete cervical cord injury

“…The present study showed significant brain functional reorganization in subacute ICCI patients when the right lower extremity was stimulated and all of these regions were closely related to somatosensory function ( Grabher et al, 2017 ; Grodd et al, 2001 ; O'Reilly et al, 2010 ; Salmi et al, 2010 ; Sang et al, 2012 ; Stoodley and Schmahmann, 2009 , Stoodley and Schmahmann, 2010 ). Moreover, a close association was found among the activation intensity of these activated areas.…”

“…Apart from the decrease of activation in the cerebellum, we also found that the activation of the brainstem (the midbrain and right pons) decreased. The brainstem is phylogenetically highly conserved in mammals and plays a pivotal role in the process of sensory signal transmission ( Benarroch, 2012 ; Brooks et al, 2017 ; Grabher et al, 2017 ; Hougaard et al, 2017 ; Liao et al, 2015 ). For instance, Brooks et al (2017) and Grabher et al (2017) found that the brainstem is an important structure for integrating and transmitting sensory signals, and the structural changes caused by SCI were directly related to impaired pinprick sensation ( Grabher et al, 2017 ).…”

“…The brainstem is phylogenetically highly conserved in mammals and plays a pivotal role in the process of sensory signal transmission ( Benarroch, 2012 ; Brooks et al, 2017 ; Grabher et al, 2017 ; Hougaard et al, 2017 ; Liao et al, 2015 ). For instance, Brooks et al (2017) and Grabher et al (2017) found that the brainstem is an important structure for integrating and transmitting sensory signals, and the structural changes caused by SCI were directly related to impaired pinprick sensation ( Grabher et al, 2017 ). As an important part of the brainstem, a few studies have proved that the midbrain is closely related to sensory function ( Cuppini et al, 2018 ; Mylius et al, 2015 ) and is even involved in multisensory integration ( Cuppini et al, 2018 ).…”

“…Therefore, understanding the mechanism of sensory impairment and the potential recovery of sensory function can help us to find a better method of rehabilitation for patients with sensory dysfunction. To date, many studies have shown that the brain reorganization after SCI is the key factor affecting the motor function and rehabilitation of patients ( Grabher et al, 2017 ; Ilvesmäki et al, 2017 ; Villiger et al, 2015 ; Wrigley et al, 2018 ), while the number of studies on somatosensory functions is still relatively small ( Grabher et al, 2015 ; Höller et al, 2017 ; Wrigley et al, 2018 ).…”

Functional MRI Reveals Locomotion-Control Neural Circuits in Human Brainstem

“…The risk of dementia [ 1 ] and falls in the elderly [ 2 ] is related to gait disturbance. Brainstem networks are pivotal in motor/sensory functions including the gait control [ 37 , 38 ]. Clarification on the role of brainstem regions in locomotion control can facilitate developing therapeutic interventions targeting CN and PPN or related neural circuits to improve gait control in the elderly with risks of dementia and falls or in patients with a damaged gait such as those suffering from Parkinson’s disease [ 3 ] and stroke [ 4 ].…”