scholarly journals Unsuspected involvement of spinal cord in Alzheimer Disease

2019 ◽  
Author(s):  
Roberta Maria Lorenzi ◽  
Fulvia Palesi ◽  
Gloria Castellazzi ◽  
Paolo Vitali ◽  
Nicoletta Anzalone ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Alzheimer Disease ◽  
Sensorimotor Control ◽  
Cognitive Domain ◽  
Imaging Biomarker ◽  
Cervical Cord ◽  
Spinal Cord Atrophy ◽  
Cross Sectional ◽  
Brain Volumes

AbstractObjectiveBrain atrophy is an established biomarker for dementia, yet spinal cord involvement has not been investigated to date. As the spinal cord is relaying sensorimotor control signals from the cortex to the peripheral nervous system and viceversa, it is indeed a very interesting question to assess whether it is affected by atrophy in a disease that is known for its involvement of cognitive domains first and foremost, with motor symptoms being clinically assessed too. We therefore hypothesize that Alzheimer Disease severe atrophy can affect the spinal cord too and that spinal cord atrophy is indeed an important in vivo imaging biomarker contributing to understanding neurodegeneration associated with dementia.Methods3DT1 images of 31 Alzheimer’s disease (AD) and 35 healthy control (HC) subjects were processed to calculate volumes of brain structures and cross-sectional area (CSA) and volume (CSV) of the cervical cord (per vertebra as well as the C2-C3 pair (CSA23 and CSV23)). Correlated features (ρ>0.7) were removed, and best subset identified for patients’ classification with the Random Forest algorithm. General linear model regression was used to find significant differences between groups (p<=0.05). Linear regression was implemented to assess the explained variance of the Mini Mental State Examination (MMSE) score as dependent variable with best features as predictors.ResultsSpinal cord features were significantly reduced in AD, independently of brain volumes. Patients classification reached 76% accuracy when including CSA23 together with volumes of hippocampi, left amygdala, white and grey matter, with 74% sensitivity and 78% specificity. CSA23 alone explained 13% of MMSE variance.DiscussionOur findings reveal that C2-C3 spinal cord atrophy contributes to discriminate AD from HC, together with more established features. Results show that CSA23, calculated form the same 3DT1 scan as all other brain volumes (including right and left hippocampi), has a considerable weight in classification tasks warranting further investigations. Together with recent studies revealing that AD atrophy is spread beyond the temporal lobes, our result adds the spinal cord to a number of unsuspected regions involved in the disease. Interestingly, spinal cord atrophy explains also cognitive scores, which could significantly impact how we model sensorimotor control in degenerative diseases with a primary cognitive domain involvement. Prospective studies should be purposely designed to understand the mechanisms of atrophy and the role of the spinal cord in AD.

Atrophy and structural variability of the upper cervical cord in early multiple sclerosis

2014 ◽  
Vol 21 (7) ◽  
pp. 875-884 ◽  
Author(s):  
Viola Biberacher ◽  
Christine C Boucard ◽  
Paul Schmidt ◽  
Christina Engl ◽  
Dorothea Buck ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Brain Magnetic Resonance Imaging ◽  
Cervical Cord ◽  
Focal Lesions ◽  
Spinal Cord Atrophy ◽  
Cross Sectional ◽  
Structural Variability ◽  
Upper Cervical ◽  
In Cis

Background: Despite agreement about spinal cord atrophy in progressive forms of multiple sclerosis (MS), data on clinically isolated syndrome (CIS) and relapsing–remitting MS (RRMS) are conflicting. Objective: To determine the onset of spinal cord atrophy in the disease course of MS. Methods: Structural brain magnetic resonance imaging (MRI) was acquired from 267 patients with CIS (85) or RRMS (182) and 64 healthy controls (HCs). The upper cervical cord cross-sectional area (UCCA) was determined at the level of C2/C3 by a segmentation tool and adjusted for focal MS lesions. The coefficient of variation (CV) was calculated from all measurements between C2/C3 and 13 mm above as a measure of structural variability. Results: Compared to HCs (76.1±6.9 mm2), UCCA was significantly reduced in CIS patients (73.5±5.8 mm2, p=0.018) and RRMS patients (72.4±7.0 mm2, p<0.001). Structural variability was higher in patients than in HCs, particularly but not exclusively in case of focal lesions (mean CV HCs/patients without/with lesions: 2.13%/2.55%/3.32%, all p-values<0.007). UCCA and CV correlated with Expanded Disability Status Scale (EDSS) scores ( r =−0.131/0.192, p=0.044/<0.001) and disease duration ( r=−0.134/0.300, p=0.039/< 0.001). CV additionally correlated with hand and arm function ( r=0.180, p=0.014). Conclusion: In MS, cervical cord atrophy already occurs in CIS. In early stages, structural variability may be a more meaningful marker of spinal cord pathology than atrophy.

The role of cerebellar abnormalities in neuromyelitis optica – a comparison with multiple sclerosis and healthy controls

2014 ◽  
Vol 21 (6) ◽  
pp. 757-766 ◽  
Author(s):  
Katrin Weier ◽  
Arman Eshaghi ◽  
Stefano Magon ◽  
Michaela Andelova ◽  
Ernst-Wilhelm Radue ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Neuromyelitis Optica ◽  
Brain Magnetic Resonance Imaging ◽  
Cervical Cord ◽  
Healthy Controls ◽  
Brain Volumes ◽  
Secondary Degeneration ◽  
Cerebellar Volume ◽  
And Gender

Background: In relapsing–remitting multiple sclerosis (RRMS), the cerebellum is a known predilection site for atrophy. Neuromyelitis optica (NMO) is characterized by extensive lesions in the spinal cord and optic nerve; however, cerebellar involvement has been less studied. Secondary degeneration of the spinocerebellar tract could impact the cerebellum in NMO. Objective: We aimed to investigate whether spinal cord and cerebellar volume measures differ between patients with NMO and RRMS. Methods: Volumetric analyses of the cerebellum (TCV), the upper cervical cord (UCV) as well as the whole brain (NBV) of age- and gender-matched patients with NMO ( n=30; 56% AQP4 +ve) and RRMS ( n=25) were performed on 3T brain magnetic resonance imaging (MRI) and compared with 34 healthy controls (HC). Results: UCV was significantly reduced in NMO patients (6.3 cm3) as compared with HC (6.7 cm3), while patients with MS had reduced brain volumes compared with HC (NBV=1482 cm3; p<0.001; TCV=188 cm3; p=0.042), but UCV close to normal values. Patients with RRMS and NMO differed in NBV ( p=0.001; lower in RRMS) and by trend (towards reduction in RRMS) in cerebellar volume ( p=0.06). Conclusions: While atrophy seems to be diffuse in MS patients, a rather focussed pattern with predominant involvement of the UCV was observed in NMO patients.

scholarly journals Axonal Damage in Multiple Sclerosis Patients with High versus Low Expanded Disability Status Scale Score

2004 ◽  
Vol 31 (2) ◽  
pp. 225-228 ◽  
Author(s):  
Steven D. Brass ◽  
Sridar Narayanan ◽  
Jack P. Antel ◽  
Yves Lapierre ◽  
Louis Collins ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Magnetic Resonance ◽  
Disease Process ◽  
Resonance Spectroscopy ◽  
Lesion Volume ◽  
Spinal Cord Atrophy ◽  
Neuronal Marker ◽  
Multiple Sclerosis Patients

AbstractBackground:The pathophysiological basis for differences in disability in patients with multiple sclerosis is unclear.Methods:We used magnetic resonance imaging to examine whether differences in disability in cohorts of multiple sclerosis patients with similar T2-weighted lesion volume and disease duration were associated with a more destructive disease process in the more disabled patients.Results:The benign and severely disabled groups had similar brain atrophy metrics and similar decreases of the neuronal marker, N-acetylaspartate, in the normal appearing white matter of the cerebrum on magnetic resonance spectroscopy examination in vivo. The severely disabled cohort had more spinal cord atrophy.Conclusion:The dissociation of spinal cord atrophy and cerebral atrophy between these two groups suggests that the difference between the more benign and more disabled groups cannot be explained by a more aggressive pathological process that is affecting the entire neuroaxis in a homogeneous fashion.

scholarly journals Quantitative Gradient Echo MRI Identifies Dark Matter as a New Imaging Biomarker of Neurodegeneration that Precedes Tissue Atrophy in Early Alzheimer Disease

2021 ◽  
Author(s):  
Satya V.V.N. Kothapalli ◽  
Tammie L. Benzinger ◽  
Andrew. J. Aschenbrenner ◽  
Richard. J. Perrin ◽  
Charles. F. Hildebolt ◽  
...  
Keyword(s):  
Dark Matter ◽  
Alzheimer Disease ◽  
Amyloid Β ◽  
Neuronal Loss ◽  
Imaging Biomarker ◽  
Control Group ◽  
Histopathological Study ◽  
In Vivo Evaluation ◽  
Preclinical Ad

AbstractBackgroundCurrently, brain tissue atrophy serves as in vivo MRI biomarker of neurodegeneration in Alzheimer Disease (AD). However, postmortem histopathological studies show that neuronal loss in AD exceeds volumetric loss of tissue and that loss of memory in AD begins when neurons and synapses are lost. Therefore, in vivo detection of neuronal loss prior to detectable atrophy in MRI is essential for early AD diagnosis.ObjectiveTo apply a recently developed quantitative Gradient Recalled Echo (qGRE) MRI technique for in vivo evaluation of neuronal loss in human hippocampus.MethodsSeventy participants were recruited from the Knight Alzheimer Disease Research Center, representing three groups: Healthy controls [Clinical Dementia Rating® (CDR®)=0, amyloid β (Aβ)-negative), n=34]; Preclinical AD (CDR=0, Aβ-positive, n=19); and mild AD (CDR=0.5 or 1, Aβ-positive, n=17).ResultsIn hippocampal tissue, qGRE identified two types of regions: one, practically devoid of neurons, we designate as “Dark Matter”, the other, with relatively preserved neurons - “Viable Tissue”. Data showed a greater loss of neurons than defined by atrophy in the mild AD group compared with the healthy control group - neuronal loss ranged between 31% and 43% while volume loss ranged only between 10% and 19%. The concept of Dark Matter was confirmed with histopathological study of one participant who underwent in vivo qGRE 14 months prior to expiration.Conclusionin vivo qGRE method identifies neuronal loss that is associated with impaired AD-related cognition but is not recognized by MRI measurements of tissue atrophy, therefore providing new biomarkers for early AD detection.

scholarly journals Advances in spinal cord imaging in multiple sclerosis

2019 ◽  
Vol 12 ◽  
pp. 175628641984059 ◽  
Author(s):  
Marcello Moccia ◽  
Serena Ruggieri ◽  
Antonio Ianniello ◽  
Ahmed Toosy ◽  
Carlo Pozzilli ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Imaging Techniques ◽  
Quantitative Imaging ◽  
Automated Analysis ◽  
Spinal Cord Atrophy ◽  
Recent Developments ◽  
Magnetic Resonance Imaging Mri ◽  
Spinal Cord Imaging

The spinal cord is frequently affected in multiple sclerosis (MS), causing motor, sensory and autonomic dysfunction. A number of pathological abnormalities, including demyelination and neuroaxonal loss, occur in the MS spinal cord and are studied in vivo with magnetic resonance imaging (MRI). The aim of this review is to summarise and discuss recent advances in spinal cord MRI. Advances in conventional spinal cord MRI include improved identification of MS lesions, recommended spinal cord MRI protocols, enhanced recognition of MRI lesion characteristics that allow MS to be distinguished from other myelopathies, evidence for the role of spinal cord lesions in predicting prognosis and monitoring disease course, and novel post-processing methods to obtain lesion probability maps. The rate of spinal cord atrophy is greater than that of brain atrophy (−1.78% versus −0.5% per year), and reflects neuroaxonal loss in an eloquent site of the central nervous system, suggesting that it can become an important outcome measure in clinical trials, especially in progressive MS. Recent developments allow the calculation of spinal cord atrophy from brain volumetric scans and evaluation of its progression over time with registration-based techniques. Fully automated analysis methods, including segmentation of grey matter and intramedullary lesions, will facilitate the use of spinal cord atrophy in trial designs and observational studies. Advances in quantitative imaging techniques to evaluate neuroaxonal integrity, myelin content, metabolic changes, and functional connectivity, have provided new insights into the mechanisms of damage in MS. Future directions of research and the possible impact of 7T scanners on spinal cord imaging will be discussed.

Topographic specificity of corticospinal connections formed in explant coculture

Development ◽  
1994 ◽  
Vol 120 (7) ◽  
pp. 1937-1947 ◽  
Author(s):  
R.Z. Kuang ◽  
M. Merline ◽  
K. Kalil
Keyword(s):  
Spinal Cord ◽  
Sensorimotor Cortex ◽  
Target Selection ◽  
Cervical Cord ◽  
Target Tissue ◽  
Early Postnatal Development ◽  
Axon Collaterals ◽  
Visual Cortical

The corticospinal pathway connects layer V pyramidal neurons in discrete regions of the sensorimotor cortex to topographically matching targets in the spinal cord. In rodents initial pathway errors occur transiently during early postnatal development, such that visual cortical axons project inappropriately into the corticospinal tract. Nevertheless, only sensorimotor axons form corticospinal connections, which are topographically ordered in hamsters from the earliest stages of innervation. Previous work in vivo suggests that pathfinding is carried out by primary cortical axons whereas target innervation occurs by extension of axon collaterals at appropriate locations. In vitro studies have provided evidence that chemotropic factors may selectively attract extension of neurites into specific targets. To investigate the basis for corticospinal target selection during development, we have used an in vitro explant coculture system. Sensorimotor and visual cortical explants from newborn hamsters were presented with inappropriate targets from olfactory bulb and cerebellum and targets from the cervical (forelimb) and lumbar (hindlimb) enlargements of the early postnatal spinal cord. Under in vitro conditions, corticospinal target selection was highly specific and remarkably similar to corticospinal connectivity in vivo. Visual and sensorimotor cortical neurites extended nonselectively into the white matter of the spinal cord. However, only neurites from the sensorimotor cortex were able to extend into and arborize within the spinal gray. In the majority of cases, these connections were topographically appropriate, matching forelimb cortex to cervical cord and hindlimb cortex to lumbar cord. However, we found no evidence that chemotropic attraction was responsible for selection of appropriate targets by cortical neurites or that spinal target tissue promoted extension of cortical axon collaterals within the collagen matrix. These results suggest that the ability of cortical neurites to recognize correct spinal targets and form terminal arbors may require direct axon target interaction.

scholarly journals Grey matter involvement by focal cervical spinal cord lesions is associated with progressive multiple sclerosis

2015 ◽  
Vol 22 (7) ◽  
pp. 910-920 ◽  
Author(s):  
Hugh Kearney ◽  
Katherine A Miszkiel ◽  
Marios C Yiannakas ◽  
Daniel R Altmann ◽  
Olga Ciccarelli ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Spinal Cord ◽  
Grey Matter ◽  
Cervical Spinal Cord ◽  
Spinal Cord Lesion ◽  
Cervical Cord ◽  
Focal Lesions ◽  
Lateral Column ◽  
Cord Lesion

Background: The in vivo relationship of spinal cord lesion features with clinical course and function in multiple sclerosis (MS) is poorly defined. Objective: The objective of this paper is to investigate the associations of spinal cord lesion features on MRI with MS subgroup and disability. Methods: We recruited 120 people: 25 clinically isolated syndrome, 35 relapsing–remitting (RR), 30 secondary progressive (SP), and 30 primary progressive (PP) MS. Disability was measured using the Expanded Disability Status Scale. We performed 3T axial cervical cord MRI, using 3D-fast-field-echo and phase-sensitive-inversion-recovery sequences. Both focal lesions and diffuse abnormalities were recorded. Focal lesions were classified according to the number of white matter (WM) columns involved and whether they extended to grey matter (GM). Results: The proportion of patients with focal lesions involving at least two WM columns and extending to GM was higher in SPMS than in RRMS ( p = 0.03) and PPMS ( p = 0.015). Diffuse abnormalities were more common in both PPMS and SPMS, compared with RRMS (OR 6.1 ( p = 0.002) and 5.7 ( p = 0.003), respectively). The number of lesions per patient involving both the lateral column and extending to GM was independently associated with disability ( p < 0.001). Conclusions: More extensive focal cord lesions, extension of lesions to GM, and diffuse abnormalities are associated with progressive MS and disability.

scholarly journals Association of asymptomatic spinal cord lesions and atrophy with disability 5 years after a clinically isolated syndrome

2016 ◽  
Vol 23 (5) ◽  
pp. 665-674 ◽  
Author(s):  
WJ Brownlee ◽  
DR Altmann ◽  
P Alves Da Mota ◽  
JK Swanton ◽  
KA Miszkiel ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Brain Atrophy ◽  
Brain Magnetic Resonance Imaging ◽  
Clinically Isolated Syndrome ◽  
Cervical Cord ◽  
Spinal Cord Lesions ◽  
Spinal Cord Atrophy ◽  
Lesion Number ◽  
Cord Lesion

Background: Spinal cord pathology is an important substrate for long-term disability in multiple sclerosis (MS). Objective: To investigate longitudinal changes in spinal cord lesions and atrophy in patients with a non-spinal clinically isolated syndrome (CIS), and how they relate to the development of disability. Methods: In all, 131 patients with a non-spinal CIS had brain and spinal cord imaging at the time of CIS and approximately 5 years later (median: 5.2 years, range: 3.0–7.9 years). Brain magnetic resonance imaging (MRI) measures consisted of T2-hyperintense and T1-hypointense lesion loads plus brain atrophy. Spinal cord MRI measures consisted of lesion number and the upper cervical cord cross-sectional area (UCCA). Disability was measured using the Expanded Disability Status Scale (EDSS). Multiple linear regression was used to identify independent predictors of disability after 5 years. Results: During follow-up, 93 (71%) patients were diagnosed with MS. Baseline spinal cord lesion number, change in cord lesion number and change in UCCA were independently associated with EDSS ( R2 = 0.53) at follow-up. Including brain T2 lesion load and brain atrophy only modestly increased the predictive power of the model ( R2 = 0.64). Conclusion: Asymptomatic spinal cord lesions and spinal cord atrophy contribute to the development of MS-related disability over the first 5 years after a non-spinal CIS.

scholarly journals Quantification of Cervical Cord Cross-Sectional Area: Which Acquisition, Vertebra Level, and Analysis Software? A Multicenter Repeatability Study on a Traveling Healthy Volunteer

2021 ◽  
Vol 12 ◽  
Author(s):  
Carsten Lukas ◽  
Barbara Bellenberg ◽  
Ferran Prados ◽  
Paola Valsasina ◽  
Katrin Parmar ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Healthy Volunteer ◽  
Brain Mri ◽  
Cross Sectional Area ◽  
Image Resolution ◽  
Cervical Cord ◽  
Surface Model ◽  
Sectional Area ◽  
Cross Sectional ◽  
Brain Images

Background: Considerable spinal cord (SC) atrophy occurs in multiple sclerosis (MS). While MRI-based techniques for SC cross-sectional area (CSA) quantification have improved over time, there is no common agreement on whether to measure at single vertebral levels or across larger regions and whether upper SC CSA can be reliably measured from brain images.Aim: To compare in a multicenter setting three CSA measurement methods in terms of repeatability at different anatomical levels. To analyze the agreement between measurements performed on the cervical cord and on brain MRI.Method: One healthy volunteer was scanned three times on the same day in six sites (three scanner vendors) using a 3T MRI protocol including sagittal 3D T1-weighted imaging of the brain (covering the upper cervical cord) and of the SC. Images were analyzed using two semiautomated methods [NeuroQLab (NQL) and the Active Surface Model (ASM)] and the fully automated Spinal Cord Toolbox (SCT) on different vertebral levels (C1–C2; C2/3) on SC and brain images and the entire cervical cord (C1–C7) on SC images only.Results: CSA estimates were significantly smaller using SCT compared to NQL and ASM (p &lt; 0.001), regardless of the cord level. Inter-scanner repeatability was best in C1–C7: coefficients of variation for NQL, ASM, and SCT: 0.4, 0.6, and 1.0%, respectively. CSAs estimated in brain MRI were slightly lower than in SC MRI (all p ≤ 0.006 at the C1–C2 level). Despite protocol harmonization between the centers with regard to image resolution and use of high-contrast 3D T1-weighted sequences, the variability of CSA was partly scanner dependent probably due to differences in scanner geometry, coil design, and details of the MRI parameter settings.Conclusion: For CSA quantification, dedicated isotropic SC MRI should be acquired, which yielded best repeatability in the entire cervical cord. In the upper part of the cervical cord, use of brain MRI scans entailed only a minor loss of CSA repeatability compared to SC MRI. Due to systematic differences between scanners and the CSA quantification software, both should be kept constant within a study. The MRI dataset of this study is available publicly to test new analysis approaches.

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