Quantitative MRI of rostral spinal cord and brain regions is predictive of functional recovery in acute spinal cord injury.

Objective: To reveal the immediate extent of trauma-induced neurodegenerative changes rostral to the level of lesion and determine the predictive clinical value of quantitative MRI (qMRI) following acute spinal cord injury (SCI). Methods: Twenty-four acute SCI patients and 23 healthy controls underwent a high-resolution T1-weighted protocol. Eighteen of those patients and 20 of controls additionally underwent a multi-parameter mapping (MPM) MRI protocol sensitive to the content of tissue structure, including myelin and iron. Patients were examined clinically at baseline, 2, 6, 12, and 24 months post-SCI. We assessed volume and microstructural changes in the spinal cord and brain using T1-weighted MRI, magnetization transfer (MT), longitudinal relaxation rate (R1), and effective transverse relaxation rate (R2*) maps. Regression analysis determined associations between acute qMRI parameters and recovery. Results: At baseline, cord area and its anterior-posterior width were decreased in patients, whereas MT, R1, and R2* parameters remained unchanged in the cord. Within the cerebellum, volume decrease was paralleled by increases of MT and R2* parameters. Early grey matter changes were observed within the primary motor cortex and limbic system. Importantly, early volume and microstructural changes of the cord and cerebellum predicted functional recovery following injury. Conclusions: Neurodegenerative changes rostral to the level of lesion occur early in SCI, with varying temporal and spatial dynamics. Early qMRI markers of spinal cord and cerebellum are predictive of functional recovery. These neuroimaging biomarkers may supplement clinical assessments and provide insights into the potential of therapeutic interventions to enhance neural plasticity.

Changes in auditory feedback connections determine the severity of speech processing deficits after stroke.

We compared brain structure and function in two subgroups of 21 stroke patients with either moderate or severe chronic speech comprehension impairment. Both groups had damage to the supratemporal plane; however, the severe group suffered greater damage to two unimodal auditory areas: primary auditory cortex and the planum temporale. The effects of this damage were investigated using fMRI while patients listened to speech and speech-like sounds. Pronounced changes in connectivity were found in both groups in undamaged parts of the auditory hierarchy. Compared to controls, moderate patients had significantly stronger feedback connections from planum temporale to primary auditory cortex bilaterally, while in severe patients this connection was significantly weaker in the undamaged right hemisphere. This suggests that predictive feedback mechanisms compensate in moderately affected patients but not in severely affected patients. The key pathomechanism in humans with persistent speech comprehension impairments may be impaired feedback connectivity to unimodal auditory areas.

Normal-appearing brain t1 relaxation time predicts disability in early primary progressive multiple sclerosis.

OBJECTIVE: To investigate whether patients with early primary progressive multiple sclerosis show changes in T1 relaxation time (T1-RT) in normal-appearing white matter (NAWM) and normal-appearing gray matter (NAGM) during 2 years and whether T1-RT at baseline predicts disability. METHODS: Twenty-one patients and 12 control subjects were studied at baseline and after 2 years. Expanded Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC) scores were assessed. T1 relaxation time histograms of NAWM and NAGM were obtained in all subjects, and mean, peak height, and peak location of the histograms were measured. Paired t tests were used to compare baseline and 2-year histogram values in patients and control subjects. To investigate whether T1-RT predicted clinical changes, multiple linear regression analysis was used. RESULTS: Patients showed increases in NAWM and NAGM T1-RT mean and peak location during follow-up, and significant decreases in NAWM and NAGM peak height. Baseline NAWM T1-RT mean values and peak height predicted disability at 2 years, as measured with the Multiple Sclerosis Functional Composite score. CONCLUSION: T1 relaxometry is a good marker of disease progression and has prognostic potential in primary progressive multiple sclerosis.

Functional-anatomical validation and individual variation of diffusion tractography-based segmentation of the human thalamus.

Parcellation of the human thalamus based on cortical connectivity information inferred from non-invasive diffusion-weighted images identifies sub-regions that we have proposed correspond to nuclei. Here we test the functional and anatomical validity of this proposal by comparing data from diffusion tractography, cytoarchitecture and functional imaging. We acquired diffusion imaging data in eleven healthy subjects and performed probabilistic tractography from voxels within the thalamus. Cortical connectivity information was used to divide the thalamus into sub-regions with highest probability of connectivity to distinct cortical areas. The relative volumes of these connectivity-defined sub-regions correlate well with volumetric predictions based on a histological atlas. Previously reported centres of functional activation within the thalamus during motor or executive tasks co-localize within atlas regions showing high probabilities of connection to motor or prefrontal cortices, respectively. This work provides a powerful validation of quantitative grey matter segmentation using diffusion tractography in humans. Co-registering thalamic sub-regions from 11 healthy individuals characterizes inter-individual variation in segmentation and results in a population-based atlas of the human thalamus that can be used to assign likely anatomical labels to thalamic locations in standard brain space. This provides a tool for specific localization of functional activations or lesions to putative thalamic nuclei.

Integrated care pathways: disease-specific or process-specific?

BACKGROUND/AIM: conventional teaching on integrated care pathways (ICP) suggests that they have to be specific both to a particular setting and to a specific diagnosis. We wished to explore the potential for a generic process-based care pathway. STUDY DESIGN: we evaluated three different, disease-specific ICPs in use on a neurological rehabilitation unit to identify prompts common to and differing between them. Variance types and goal outcomes in all three diagnostic groups were compared. RESULTS: 93% of prompts on the care pathway were common to all three diagnostic groups. The prompts that differed were unique to each diagnostic group and provided important guidelines about management. CONCLUSION: in neurorehabilitation, where the process of multidisciplinary care is well defined, it is possible to develop a process-based ICP. Process-based ICPs may not be unique to rehabilitation but may also be relevant to other settings in which patients with differing diagnoses share similar needs.

The therapeutic potential of cannabis.

Research of the cannabinoid system has many similarities with that of the opioid system. In both instances, studies into drug-producing plants led to the discovery of an endogenous control system with a central role in neurobiology. Few compounds have had as much positive press from patients as those of the cannabinoid system. While these claims are investigated in disorders such as multiple sclerosis spasticity and pain, basic research is discovering interesting members of this family of compounds that have previously unknown qualities, the most notable of which is the capacity for neuroprotection. Large randomised clinical trials of the better known compounds are in progress. Even if the results of these studies are not as positive as many expect them to be, that we are only just beginning to appreciate the huge therapeutic potential of this family of compounds is clear.

Cannabinoids inhibit neurodegeneration in models of multiple sclerosis.

Multiple sclerosis is increasingly being recognized as a neurodegenerative disease that is triggered by inflammatory attack of the CNS. As yet there is no satisfactory treatment. Using experimental allergic encephalo myelitis (EAE), an animal model of multiple sclerosis, we demonstrate that the cannabinoid system is neuroprotective during EAE. Mice deficient in the cannabinoid receptor CB1 tolerate inflammatory and excitotoxic insults poorly and develop substantial neurodegeneration following immune attack in EAE. In addition, exogenous CB1 agonists can provide significant neuroprotection from the consequences of inflammatory CNS disease in an experimental allergic uveitis model. Therefore, in addition to symptom management, cannabis may also slow the neurodegenerative processes that ultimately lead to chronic disability in multiple sclerosis and probably other diseases.