Cervical Spinal Cord Atrophy can be Accurately Quantified Using Head Images

Background Spinal cord atrophy provides a clinically relevant metric for monitoring MS. However, the spinal cord is imaged far less frequently than brain due to artefacts and acquisition time, whereas MRI of the brain is routinely performed. Objective To validate spinal cord cross-sectional area measurements from routine 3DT1 whole-brain MRI versus those from dedicated cord MRI in healthy controls and people with MS. Methods We calculated cross-sectional area at C1 and C2/3 using T2*-weighted spinal cord images and 3DT1 brain images, for 28 healthy controls and 73 people with MS. Correlations for both groups were assessed between: (1) C1 and C2/3 using cord images; (2) C1 from brain and C1 from cord; and (3) C1 from brain and C2/3 from cord. Results and Conclusion C1 and C2/3 from cord were strongly correlated in controls ( r = 0.94, p<0.0001) and MS ( r = 0.85, p<0.0001). There was strong agreement between C1 from brain and C2/3 from cord in controls ( r = 0.84, p<0.0001) and MS ( r = 0.81, p<0.0001). This supports the use of C1 cross-sectional area calculated from brain imaging as a surrogate for the traditional C2/3 cross-sectional area measure for spinal cord atrophy.

Constrictive Myelopathy in An Old Giant Dog

In pugs, West Highland white terriers and other small breeds, congenital or acquired malformations/deviations of the spine are commonly reported, resulting, amongst other complications, in chronic meningeal compression and fibrosis, and interference with cerebrospinal fluid flow into the sub-arachnoid space. This leads to constrictive myelopathy (CM) which involves the constriction and consequent reduced diameter of the spinal cord accompanied by parenchymal damage (mostly gliosis). A11-year-old giant mixed breed male dog presented with ataxia in the hindlimbs, paresis, reduced proprioception, and normal reflexes. Neurolocalization was to the thoracolumbar spinal cord (T3-L3). Myelographic computed tomography and magnetic resonance imaging (MRI) of this tract showed spondylosis, multiple disc protrusions with mild cord compression, and reduced spinal cord diameter. Genetic test for SOD1 mutations performed to evaluate predisposition to degenerative myelopathy negative results; although poorly compressive, the symptoms were attributed to multiple disc protrusions, leading to spinal cord atrophy. The dog underwent physiotherapy and 23 months later, was more ataxic and paretic however still ambulatory; repeated MRI confirmed the previous findings, however, the onset of concomitant megacolon and a chronic kidney failure, induced the owner to euthanasia. Histopathological assessment indicated diffused remodeling of the meninges with progressive constriction of the spinal cord of concomitant megacolon and a chronic kidney failure, induced the owner to euthanasia. Histopathological assessment indicated diffused remodeling of the meninges with progressive constriction of the spinal cord. Altered distribution of the mechanical forces among the meningeal layers with stiffening of the ventral pachymeninges, probably caused by the disc protrusions, was considered the most likely trigger. To our knowledge, this is the first case reporting clinical, MRI and histological findings resembling an acquired constrictive myelopathy in a large-breed dog.

Normalizing automatic spinal cord cross-sectional area measures

Spinal cord cross-sectional area (CSA) is a relevant biomarker to assess spinal cord atrophy in various neurodegenerative diseases. However, the considerable inter-subject variability among healthy participants currently limits its usage. Previous studies explored factors contributing to the variability, yet the normalization models were based on a relatively limited number of participants (typically < 300 participants), required manual intervention, and were not implemented in an open-access comprehensive analysis pipeline. Another limitation is related to the imprecise prediction of the spinal levels when using vertebral levels as a reference; a question never addressed before in the search for a normalization method. In this study we implemented a method to measure CSA automatically from a spatial reference based on the central nervous system (the pontomedullary junction, PMJ), we investigated various factors to explain variability, and we developed normalization strategies on a large cohort (N=804). Cervical spinal cord CSA was computed on T1w MRI scans for 804 participants from the UK Biobank database. In addition to computing cross-sectional at the C2-C3 vertebral disc, it was also measured at 64 mm caudal from the PMJ. The effect of various biological, demographic and anatomical factors was explored by computing Pearson's correlation coefficients. A stepwise linear regression found significant predictors; the coefficients of the best fit model were used to normalize CSA. The correlation between CSA measured at C2-C3 and using the PMJ was y = 0.98x + 1.78 (R2 = 0.97). The best normalization model included thalamus volume, brain volume, sex and interaction between brain volume and sex. With this model, the coefficient of variation went down from 10.09% (without normalization) to 8.59%, a reduction of 14.85%. In this study we identified factors explaining inter-subject variability of spinal cord CSA over a large cohort of participants, and developed a normalization model to reduce the variability. We implemented an approach, based on the PMJ, to measure CSA to overcome limitations associated with the vertebral reference. This approach warrants further validation, especially in longitudinal cohorts. The PMJ-based method and normalization models are readily available in the Spinal Cord Toolbox.

Potential markers for sample size estimations in hereditary spastic paraplegia type 5

Background Aim to identify potential biomarkers to assess therapeutic efficacy for hereditary spastic paraplegias type 5 (SPG5) by investigating the clinical, cerebrospinal fluid (CSF) and magnetic resonance imaging (MRI) features. Methods We performed a cross-sectional study to compare SPG5 patients with age- and sex-matched healthy controls who underwent conventional and quantitative MRI techniques of spinal cord (C1-T9) and brain. SPG5 patients also underwent assessment for clinical status and CSF biomarkers (27-hydroxycholesterol, neurofilament light). We identified a set of markers with standardized effect sizes (|t|> 0.5) to estimate sample sizes for disease progression (disease duration > 14 years vs. ≤ 14 years). Results Seventeen genetically confirmed SPG5 patients (11 men, 6 women; age range, 13–49 years; median disease duration, 14 years) were enrolled. Compared to healthy controls, the total spinal cord area (SCA) of SPG5 patients was reduced particularly at the thoracic levels (cervical levels: 12–27%; thoracic levels 41–60%). Patients did not show significant alterations of brain signal abnormalities or atrophy relative to controls. A total of 10 surrogate markers were selected and a minimum sample size was achieved with the measurement of SCA on T9 (n = 22) much less that what would be required if using clinical disability assessment (n = 124). Conclusions SPG5 patients showed distinct MRI features of spinal cord atrophy without significant brain alterations. Our finding supports the measurements of spinal cord on T9 level as potential endpoint for SPG5 clinical trials. Trial registration ClinicalTrials.gov, NCT04006418. Registered 05 July 2019, https://clinicaltrials.gov/ct2/show/NCT04006418?term=NCT04006418&draw=2&rank=1.