Brainstem pathology in amyotrophic lateral sclerosis and primary lateral sclerosis: A longitudinal neuroimaging study
| Autor: | Russell L. McLaughlin, Mark A. Doherty, Rangariroyashe H. Chipika, Jennifer C. Hengeveld, Alice Vajda, Colette Donaghy, Siobhan Hutchinson, Eoin Finegan, Peter Bede, Stacey Li Hi Shing, Orla Hardiman |
|---|---|
| Rok vydání: | 2019 |
| Předmět: |
FSL
FMRIB Software Library Male Pathology PBA pseudobulbar affect SOD1 superoxide dismutase 1 0302 clinical medicine Pons TIV total intracranial volume Longitudinal Studies Prospective Studies FA fractional anisotropy CST corticospinal tract TE echo time T1W T1-weighted imaging PLS primary lateral sclerosis Regular Article ALS amyotrophic lateral sclerosis Myo myoinositol FWE familywise error Neurology FOV field-of-view SBMA spinal and bulbar muscular atrophy / Kennedy's disease LMN lower motor neuron Longitudinal study medicine.medical_specialty FDR false discovery rate ANCOVA analysis of covariance PMC primary motor cortex SC spinal cord TFCE threshold-free cluster enhancement lcsh:Computer applications to medicine. Medical informatics MR magnetic resonance 03 medical and health sciences NODDI Neurite orientation dispersion and density imaging QBI q-ball imaging Humans CNN cranial nerve nuclei WM white matter Aged HARDI high angular resolution diffusion imaging HSP hereditary spastic paraplegia Amyotrophic Lateral Sclerosis T2 Timepoint 2 GM grey matter medicine.disease TBSS tract-based spatial statistics nervous system DTI diffusion tensor imaging Neurology (clinical) NAA N-acetylaspartate 030217 neurology & neurosurgery M mean FTD frontotemporal dementia Internal capsule C9orf72 chromosome 9 open reading frame 72 lcsh:RC346-429 Cr creatine‐phosphocreatine Primary lateral sclerosis Mesencephalon TI inversion time CN cranial nerve Gray Matter Amyotrophic lateral sclerosis pTDP-43 phosphorylated 43 kDa TAR DNA-binding protein Primary Lateral Sclerosis MEM mixed-effect model 05 social sciences MND motor neuron disease Middle Aged Medulla HC healthy control MNI152 Montreal Neurological Institute 152 standard space Magnetic Resonance Imaging White Matter RD radial diffusivity TR repetition time medicine.anatomical_structure ALS T2 ALS cohort at the second timepoint RE repeat expansion PCL pathological crying and laughing lcsh:R858-859.7 Female Brainstem AD axial diffusivity BG basal ganglia BRS brainstem Cognitive Neuroscience EPI echo-planar imaging Neuroimaging Grey matter 050105 experimental psychology Atrophy IR-SPGR Inversion Recovery prepared Spoiled Gradient Recalled echo medicine 0501 psychology and cognitive sciences Radiology Nuclear Medicine and imaging Motor neuron disease lcsh:Neurology. Diseases of the nervous system MD mean diffusivity business.industry T1 Timepoint 1 UMN upper motor neuron MRS magnetic resonance spectroscopy MB midbrain ALS T1 ALS cohort at the first timepoint SD standard deviation business Brain Stem |
| Zdroj: | NeuroImage: Clinical, Vol 24, Iss, Pp-(2019) NeuroImage : Clinical |
| ISSN: | 2213-1582 |
| DOI: | 10.1016/j.nicl.2019.102054 |
| Popis: | Highlights • Computational neuroimaging captures focal brainstem pathology in motor neuron diseases in contrast to both healthy- and disease controls. • ALS patients exhibit progressive medulla oblongata, pontine and mesencephalic volume loss over time. • Brainstem atrophy in ALS and PLS is dominated by medulla oblongata volume reductions. • Vertex analyses of ALS patients reveal flattening of the medullary pyramids bilaterally. • Morphometric analyses in ALS detect density reductions in the mesencephalic crura consistent with corticospinal tract degeneration. Background Brainstem pathology is a hallmark feature of ALS, yet most imaging studies focus on cortical grey matter alterations and internal capsule white matter pathology. Brainstem imaging in ALS provides a unique opportunity to appraise descending motor tract degeneration and bulbar lower motor neuron involvement. Methods A prospective longitudinal imaging study has been undertaken with 100 patients with ALS, 33 patients with PLS, 30 patients with FTD and 100 healthy controls. Volumetric, vertex and morphometric analyses were conducted correcting for demographic factors to characterise disease-specific patterns of brainstem pathology. Using a Bayesian segmentation algorithm, the brainstem was segmented into the medulla, pons and mesencephalon to measure regional volume reductions, shape analyses were performed to ascertain the atrophy profile of each study group and region-of-interest morphometry was used to evaluate focal density alterations. Results ALS and PLS patients exhibit considerable brainstem atrophy compared to both disease- and healthy controls. Volume reductions in ALS and PLS are dominated by medulla oblongata pathology, but pontine atrophy can also be detected. In ALS, vertex analyses confirm the flattening of the medullary pyramids bilaterally in comparison to healthy controls and widespread pontine shape deformations in contrast to PLS. The ALS cohort exhibit bilateral density reductions in the mesencephalic crura in contrast to healthy controls, central pontine atrophy compared to disease controls, peri-aqueduct mesencephalic and posterior pontine changes in comparison to PLS patients. Conclus ions: Computational brainstem imaging captures the degeneration of both white and grey matter components in ALS. Our longitudinal data indicate progressive brainstem atrophy over time, underlining the biomarker potential of quantitative brainstem measures in ALS. At a time when a multitude of clinical trials are underway worldwide, there is an unprecedented need for accurate biomarkers to monitor disease progression and detect response to therapy. Brainstem imaging is a promising addition to candidate biomarkers of ALS and PLS. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|