RESUMEN
BACKGROUND: Bibrachial amyotrophy associated with an extradural CSF collection and infratentorial superficial siderosis (SS) are rare conditions that may occasionally mimic ALS. Both disorders are assumed to be due to dural tears. CASE PRESENTATION: A 53-year-old man presented with a 7-year history of slowly progressive asymmetric bibrachial amyotrophy. Initially, a diagnosis of atypical motor neuron disease (MND) was made. At re-evaluation 11 years later, upper limb wasting and weakness had further progressed and were accompanied by sensorineural hearing loss. MRI of the brain and spine demonstrated extensive supra- and infratentorial SS (including the surface of the whole spinal cord) as well as a ventral longitudinal intraspinal fluid collection (VLISFC) extending along almost the entire thoracic spine. Osteodegenerative changes were observed at C5-C7 level, with osteophytes protruding posteriorly. The bony spurs at C6-C7 level were hypothesized to have lesioned the dura, causing a CSF leak and thus a VLISFC. Review of the MRI acquired at first evaluation showed that the VLISFC was already present at that time (actually beginning at C7 level), whereas the SS was not. 19 years after the onset of upper limb weakness, the patient additionally developed parkinsonism. Response to levodopa, brain scintigraphy with 123I-ioflupane and brain MRI with nigrosome 1 evaluation were consistent with idiopathic Parkinson's disease (PD). On the latest follow-up 21 years after symptom onset, the VLISFC was unchanged, as were upper arm weakness and wasting. CONCLUSIONS: Based on the long-term follow-up, we could establish that, while the evidence of the VLISFC was concomitant with the clinical presentation of upper limb amyotrophy and weakness, the radiological signs of SS appeared later. This suggests that SS was not per se the cause of the ALS-like clinical picture, but rather a long-term sequela of a dural leak. The latter was instead the causative lesion, giving rise to a VLISFC which compressed the cervical motor roots. Dural tears can actually cause several symptoms, and further studies are needed to elucidate the pathophysiological correlates of "duropathies". Finally, as iron metabolism has been implicated in PD, the co-occurrence of PD with SS deserves further investigation.
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Enfermedad de la Neurona Motora , Siderosis , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de la Neurona Motora/diagnóstico , Enfermedad de la Neurona Motora/complicaciones , Enfermedad de la Neurona Motora/diagnóstico por imagen , Siderosis/complicaciones , Siderosis/diagnóstico , Siderosis/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Diagnóstico Diferencial , Duramadre/diagnóstico por imagen , Duramadre/patologíaRESUMEN
This chapter discusses comprehensive neurophysiological biomarkers utilised in motor neuron disease (MND) and, in particular, its commonest form, amyotrophic lateral sclerosis (ALS). These encompass the conventional techniques including nerve conduction studies (NCS), needle and high-density surface electromyography (EMG) and H-reflex studies as well as novel techniques. In the last two decades, new methods of assessing the loss of motor units in a muscle have been developed, that are more convenient than earlier methods of motor unit number estimation (MUNE),and may use either electrical stimulation (e.g. MScanFit MUNE) or voluntary activation (MUNIX). Electrical impedance myography (EIM) is another novel approach for the evaluation that relies upon the application and measurement of high-frequency, low-intensity electrical current. Nerve excitability techniques (NET) also provide insights into the function of an axon and reflect the changes in resting membrane potential, ion channel dysfunction and the structural integrity of the axon and myelin sheath. Furthermore, imaging ultrasound techniques as well as magnetic resonance imaging are capable of detecting the constituents of morphological changes in the nerve and muscle. The chapter provides a critical description of the ability of each technique to provide neurophysiological insight into the complex pathophysiology of MND/ALS. However, it is important to recognise the strengths and limitations of each approach in order to clarify utility. These neurophysiological biomarkers have demonstrated reliability, specificity and provide additional information to validate and assess lower motor neuron dysfunction. Their use has expanded the knowledge about MND/ALS and enhanced our understanding of the relationship between motor units, axons, reflexes and other neural circuits in relation to clinical features of patients with MND/ALS at different stages of the disease. Taken together, the ultimate goal is to aid early diagnosis, distinguish potential disease mimics, monitor and stage disease progression, quantify response to treatment and develop potential therapeutic interventions.
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Esclerosis Amiotrófica Lateral , Biomarcadores , Electromiografía , Enfermedad de la Neurona Motora , Neuronas Motoras , Conducción Nerviosa , Humanos , Esclerosis Amiotrófica Lateral/fisiopatología , Esclerosis Amiotrófica Lateral/diagnóstico por imagen , Neuronas Motoras/fisiología , Enfermedad de la Neurona Motora/fisiopatología , Enfermedad de la Neurona Motora/diagnóstico por imagen , Enfermedad de la Neurona Motora/diagnóstico , Electromiografía/métodos , Conducción Nerviosa/fisiologíaRESUMEN
BACKGROUND: Motor neuron diseases (MNDs) are progressive neurodegenerative disorders characterized by motor impairment and non-motor symptoms. The involvement of the thalamus in MNDs, especially in conditions such as amyotrophic lateral sclerosis (ALS), and its interaction with frontotemporal dementia (FTD), has garnered increasing research interest. This systematic review analyzed magnetic resonance imaging (MRI) studies that focused on thalamic alterations in MNDs to understand the significance of these changes and their correlation with clinical outcomes. METHODS: Following PRISMA 2020 guidelines, the PubMed and Scopus databases were searched from inception to June 2023 for studies related to MRI findings in the thalamus of patients with MNDs. Eligible studies included adult patients diagnosed with ALS or other forms of MND who underwent brain MRI, with outcomes related to thalamic alterations. Studies were evaluated for risk of bias using the Newcastle-Ottawa scale. RESULTS: A total of 52 studies (including 3009 MND patients and 2181 healthy controls) used various MRI techniques, including volumetric analysis, diffusion tensor imaging, and functional MRI, to measure thalamic volume, connectivity, and other alterations. This review confirmed significant thalamic changes in MNDs, such as atrophy and microstructural degradation, which are associated with disease severity, progression, and functional disability. Thalamic involvement varies across different MND subtypes and is influenced by the presence of cognitive impairment and mutations in genes including chromosome 9 open reading frame 72 (C9orf72). The synthesis of findings across studies indicates that thalamic pathology is a prevalent early biomarker of MNDs that contributes to motor and cognitive deficits. The thalamus is a promising target for monitoring as its dysfunction underpins a variety of clinical symptoms in MNDs. CONCLUSIONS: Thalamic alterations provide valuable insights into the pathophysiology and progression of MNDs. Multimodal MRI techniques are potent tools for detecting dynamic thalamic changes, indicating structural integrity, connectivity disruption, and metabolic activity.
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Imagen por Resonancia Magnética , Enfermedad de la Neurona Motora , Tálamo , Humanos , Tálamo/diagnóstico por imagen , Tálamo/patología , Tálamo/fisiopatología , Enfermedad de la Neurona Motora/diagnóstico por imagen , Enfermedad de la Neurona Motora/patología , Enfermedad de la Neurona Motora/fisiopatología , Esclerosis Amiotrófica Lateral/diagnóstico por imagen , Esclerosis Amiotrófica Lateral/patología , Esclerosis Amiotrófica Lateral/fisiopatologíaRESUMEN
BACKGROUND: Primary lateral sclerosis (PLS) is traditionally solely associated with progressive upper motor neuron dysfunction manifesting in limb spasticity, gait impairment, bulbar symptoms and pseudobulbar affect. Recent studies have described frontotemporal dysfunction in some patients resulting in cognitive manifestations. Cerebellar pathology is much less well characterised despite sporadic reports of cerebellar disease. METHODS: A multi-timepoint, longitudinal neuroimaging study was conducted to characterise the evolution of both intra-cerebellar disease burden and cerebro-cerebellar connectivity. The volumes of deep cerebellar nuclei, cerebellar cortical volumes, cerebro-cerebellar structural and functional connectivity were assessed longitudinally in a cohort of 43 individuals with PLS. RESULTS: Cerebello-frontal, -temporal, -parietal, -occipital and cerebello-thalamic structural disconnection was detected at baseline based on radial diffusivity (RD) and cerebello-frontal decoupling was also evident based on fractional anisotropy (FA) alterations. Functional connectivity changes were also detected in cerebello-frontal, parietal and occipital projections. Volume reductions were identified in the vermis, anterior lobe, posterior lobe, and crura. Among the deep cerebellar nuclei, the dorsal dentate was atrophic. Longitudinal follow-up did not capture statistically significant progressive changes. Significant primary motor cortex atrophy and inter-hemispheric transcallosal degeneration were also captured. CONCLUSIONS: PLS is not only associated with upper motor neuron dysfunction, but cerebellar cortical volume loss and deep cerebellar nuclear atrophy can also be readily detected. In addition to intra-cerebellar disease burden, cerebro-cerebellar connectivity alterations also take place. Our data add to the evolving evidence of widespread neurodegeneration in PLS beyond the primary motor regions. Cerebellar dysfunction in PLS is likely to exacerbate bulbar, gait and dexterity impairment and contribute to pseudobulbar affect.
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Enfermedad de la Neurona Motora , Humanos , Masculino , Persona de Mediana Edad , Femenino , Estudios Longitudinales , Anciano , Enfermedad de la Neurona Motora/diagnóstico por imagen , Enfermedad de la Neurona Motora/patología , Enfermedad de la Neurona Motora/fisiopatología , Cerebelo/patología , Cerebelo/diagnóstico por imagen , Cerebelo/fisiopatología , Adulto , Imagen de Difusión Tensora , Imagen por Resonancia MagnéticaRESUMEN
PURPOSE: Motor neuron disease (MND) causes damage to the upper and lower motor neurons including the motor cranial nerves, the latter resulting in bulbar involvement with atrophy of the tongue muscle. To measure tongue atrophy, an operator independent automatic segmentation of the tongue is crucial. The aim of this study was to apply convolutional neural network (CNN) to MRI data in order to determine the volume of the tongue. METHODS: A single triplanar CNN of U-Net architecture trained on axial, coronal, and sagittal planes was used for the segmentation of the tongue in MRI scans of the head. The 3D volumes were processed slice-wise across the three orientations and the predictions were merged using different voting strategies. This approach was developed using MRI datasets from 20 patients with 'classical' spinal amyotrophic lateral sclerosis (ALS) and 20 healthy controls and, in a pilot study, applied to the tongue volume quantification to 19 controls and 19 ALS patients with the variant progressive bulbar palsy (PBP). RESULTS: Consensus models with softmax averaging and majority voting achieved highest segmentation accuracy and outperformed predictions on single orientations and consensus models with union and unanimous voting. At the group level, reduction in tongue volume was not observed in classical spinal ALS, but was significant in the PBP group, as compared to controls. CONCLUSION: Utilizing single U-Net trained on three orthogonal orientations with consequent merging of respective orientations in an optimized consensus model reduces the number of erroneous detections and improves the segmentation of the tongue. The CNN-based automatic segmentation allows for accurate quantification of the tongue volumes in all subjects. The application to the ALS variant PBP showed significant reduction of the tongue volume in these patients and opens the way for unbiased future longitudinal studies in diseases affecting tongue volume.
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Imagen por Resonancia Magnética , Enfermedad de la Neurona Motora , Redes Neurales de la Computación , Lengua , Humanos , Lengua/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Enfermedad de la Neurona Motora/diagnóstico por imagen , Enfermedad de la Neurona Motora/diagnóstico , Masculino , Femenino , Persona de Mediana Edad , Anciano , Proyectos Piloto , Imagenología Tridimensional/métodos , Esclerosis Amiotrófica Lateral/diagnóstico por imagen , Esclerosis Amiotrófica Lateral/diagnóstico , AdultoRESUMEN
Motor neuron diseases (MND) include two main forms - amyotrophic lateral sclerosis (ALS) and spinal muscular atrophy (SMA). A certain part of these diseases is hereditary, while etiology of sporadic cases remains unknown. Both entities are known to develop because of motoneurons damage. Difference between them lies in the state of the descending pyramidal pathways. The pyramidal pathways in SMA are intact, as brain pyramidal neurons are not affected, thus pathology of SMA is restricted to anterior horns of spinal cord. Meanwhile, most forms of ALS arise due to loss of both cerebral and spinal motoneurons, which, in addition to anterior horn lesion, leads to pyramidal descending pathways damage either in brain or in spinal cord. While pathological distinction between these two entities is clear and definite, the clinical difference remains obscure. We present the case of 41-year old patient with MND, in whom spinal MR tractography has revealed lateral columns to be intact that proves the utility of spinal MR tractography in differential diagnosis between ALS and SMA. Given that ischemic diseases of the spinal cord often occur with a clinical picture of MND, we also examined this patient using spinal MRI angiography, revealing a pronounced narrowing and tortuosity of the spinal arteries, complicated by occlusion of the right twelve intercostal artery.
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Esclerosis Amiotrófica Lateral , Enfermedad de la Neurona Motora , Atrofia Muscular Espinal , Adulto , Humanos , Esclerosis Amiotrófica Lateral/patología , Angiografía por Resonancia Magnética , Enfermedad de la Neurona Motora/diagnóstico por imagen , Neuronas Motoras/patología , Médula Espinal/diagnóstico por imagenRESUMEN
Neuroimaging is a valuable adjunct to the history and examination in the evaluation of motor system disorders. Conventional imaging with computed tomography or magnetic resonance imaging depicts important anatomic information and helps to identify imaging patterns which may support diagnosis of a specific motor disorder. Advanced imaging techniques can provide further detail regarding volume, functional, or metabolic changes occurring in nervous system pathology. This chapter is an overview of the advances in neuroimaging with particular emphasis on both standard and less well-known advanced imaging techniques and findings, such as diffusion tensor imaging or volumetric studies, and their application to specific motor disorders. In addition, it provides reference to emerging imaging biomarkers in motor system disorders such as Parkinson disease, amyotrophic lateral sclerosis, and Huntington disease, and briefly reviews the neuroimaging findings in different causes of myelopathy and peripheral nerve disorders.
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Esclerosis Amiotrófica Lateral , Trastornos Motores , Enfermedad de la Neurona Motora , Humanos , Imagen de Difusión Tensora , Neuroimagen/métodos , Imagen por Resonancia Magnética/métodos , Enfermedad de la Neurona Motora/diagnóstico por imagenRESUMEN
OBJECTIVE: The study aims at comparing the diagnostic accuracy of qualitative and quantitative assessment of the susceptibility in the precentral gyrus in detecting amyotrophic lateral sclerosis (ALS) with predominance of upper motor neuron (UMN) impairment. METHODS: We retrospectively collected clinical and 3T MRI data of 47 ALS patients, of whom 12 with UMN predominance (UMN-ALS). We further enrolled 23 healthy controls (HC) and 15 ALS Mimics (ALS-Mim). The Motor Cortex Susceptibility (MCS) score was qualitatively assessed on the susceptibility-weighted images (SWI) and automatic metrics were extracted from the quantitative susceptibility mapping (QSM) in the precentral gyrus. MCS scores and QSM-based metrics were tested for correlation, and ROC analyses. RESULTS: The correlation of MCS score and susceptibility skewness was significant (Rho = 0.55, p < 0.001). The susceptibility SD showed an AUC of 0.809 with a specificity and positive predictive value of 100% in differentiating ALS and ALS Mim versus HC, significantly higher than MCS (Z = -3.384, p-value = 0.00071). The susceptibility skewness value of -0.017 showed specificity of 92.3% and predictive positive value of 91.7% in differentiating UMN-ALS versus ALS mimics, even if the performance was not significantly better than MCS (Z = 0.81, p = 0.21). CONCLUSION: The MCS and susceptibility skewness of the precentral gyrus show high diagnostic accuracy in differentiating UMN-ALS from ALS-mimics subjects. The quantitative assessment might be preferred being an automatic measure unbiased by the reader. CLINICAL RELEVANCE STATEMENT: The clinical diagnostic evaluation of ALS patients might benefit from the qualitative and/or quantitative assessment of the susceptibility in the precentral gyrus as imaging marker of upper motor neuron predominance. KEY POINTS: ⢠Amyotrophic lateral sclerosis diagnostic work-up lacks biomarkers able to identify upper motor neuron involvement. ⢠Susceptibility-weighted imaging/quantitative susceptibility mapping-based measures showed good diagnostic accuracy in discriminating amyotrophic lateral sclerosis with predominant upper motor neuron impairment from patients with suspected motor neuron disorder. ⢠Susceptibility-weighted imaging/quantitative susceptibility mapping-based assessment of the magnetic susceptibility provides a diagnostic marker for amyotrophic lateral sclerosis with upper motor neuron predominance.
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Esclerosis Amiotrófica Lateral , Corteza Motora , Enfermedad de la Neurona Motora , Humanos , Esclerosis Amiotrófica Lateral/diagnóstico por imagen , Corteza Motora/diagnóstico por imagen , Estudios Retrospectivos , Neuronas Motoras , Enfermedad de la Neurona Motora/diagnóstico por imagen , Imagen por Resonancia Magnética/métodosRESUMEN
INTRODUCTION: Pseudobulbar affect (PBA) is a distressing symptom of a multitude of neurological conditions affecting patients with a rage of neuroinflammatory, neurovascular and neurodegenerative conditions. It manifests in disproportionate emotional responses to minimal or no contextual stimulus. It has considerable quality of life implications and treatment can be challenging. METHODS: A prospective multimodal neuroimaging study was conducted to explore the neuroanatomical underpinnings of PBA in patients with primary lateral sclerosis (PLS). All participants underwent whole genome sequencing and screening for C9orf72 hexanucleotide repeat expansions, a comprehensive neurological assessment, neuropsychological screening (ECAS, HADS, FrSBe) and PBA was evaluated by the emotional lability questionnaire. Structural, diffusivity and functional MRI data were systematically evaluated in whole-brain (WB) data-driven and region of interest (ROI) hypothesis-driven analyses. In ROI analyses, functional and structural corticobulbar connectivity and cerebello-medullary connectivity alterations were evaluated separately. RESULTS: Our data-driven whole-brain analyses revealed associations between PBA and white matter degeneration in descending corticobulbar as well as in commissural tracts. In our hypothesis-driven analyses, PBA was associated with increased right corticobulbar tract RD (p = 0.006) and decreased FA (p = 0.026). The left-hemispheric corticobulbar tract, as well as functional connectivity, showed similar tendencies. While uncorrected p-maps revealed both voxelwise and ROI trends for associations between PBA and cerebellar measures, these did not reach significance to unequivocally support the "cerebellar hypothesis". CONCLUSIONS: Our data confirm associations between cortex-brainstem disconnection and the clinical severity of PBA. While our findings may be disease-specific, they are consistent with the classical cortico-medullary model of pseudobulbar affect.
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Cerebelo , Corteza Cerebral , Llanto , Risa , Modelos Neurológicos , Enfermedad de la Neurona Motora , Tractos Piramidales , Radiología , Anciano , Femenino , Humanos , Masculino , Persona de Mediana Edad , Esclerosis Amiotrófica Lateral/complicaciones , Esclerosis Amiotrófica Lateral/diagnóstico por imagen , Esclerosis Amiotrófica Lateral/patología , Esclerosis Amiotrófica Lateral/fisiopatología , Cerebelo/diagnóstico por imagen , Cerebelo/patología , Cerebelo/fisiopatología , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patología , Corteza Cerebral/fisiopatología , Lóbulo Frontal/diagnóstico por imagen , Lóbulo Frontal/patología , Lóbulo Frontal/fisiopatología , Imagen por Resonancia Magnética , Bulbo Raquídeo/diagnóstico por imagen , Bulbo Raquídeo/patología , Bulbo Raquídeo/fisiopatología , Corteza Motora/diagnóstico por imagen , Corteza Motora/patología , Corteza Motora/fisiopatología , Enfermedad de la Neurona Motora/complicaciones , Enfermedad de la Neurona Motora/diagnóstico por imagen , Enfermedad de la Neurona Motora/patología , Enfermedad de la Neurona Motora/fisiopatología , Tractos Piramidales/diagnóstico por imagen , Tractos Piramidales/patología , Tractos Piramidales/fisiopatología , Calidad de Vida , Lóbulo Temporal/diagnóstico por imagen , Lóbulo Temporal/patología , Lóbulo Temporal/fisiopatologíaRESUMEN
PURPOSE OF REVIEW: Although neuroimaging in motor neuron diseases (MNDs) continues to generate important novel academic insights, the translation of novel radiological protocols into viable biomarkers remains challenging. RECENT FINDINGS: A multitude of technological advances contribute to the success of academic imaging in MND such as the availability of high-field MRI platforms, novel imaging techniques, quantitative spinal cord protocols to whole-brain spectroscopy. International collaborations, protocol harmonization efforts, open-source image analysis suites also fuel developments in the field. Despite the success of academic neuroimaging in MND, the meaningful interpretation of radiological data from single patients and accurate classification into relevant diagnostic, phenotypic and prognostic categories remain challenging. Appraising accruing disease burden over the short follow-up intervals typically used in pharmacological trials is also notoriously difficult. SUMMARY: Although we acknowledge the academic achievements of large descriptive studies, an unmet priority of neuroimaging in MND is the development of robust diagnostic, prognostic and monitoring applications to meet the practical demands of clinical decision-making and pharmacological trials. A paradigm shift from group-level analyses to individual-level data interpretation, accurate single-subject classification and disease-burden tracking is therefore urgently needed to distil raw spatially coded imaging data into practical biomarkers.
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Enfermedad de la Neurona Motora , Humanos , Enfermedad de la Neurona Motora/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Neuroimagen/métodos , Encéfalo , BiomarcadoresRESUMEN
We report a 68-year-old lady who presented with Huntington phenocopy with generalized chorea and was genetically proven to have Spinocerebellar ataxia (SCA)17. MRI Brain demonstrated motor band sign, which is most commonly reported in motor neuron disease. This is the first case of motor band sign with SCA 17 and highlights the widening spectrum of radiological signs in SCA 17.
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Corea , Enfermedad de Huntington , Enfermedad de la Neurona Motora , Ataxias Espinocerebelosas , Femenino , Humanos , Anciano , Enfermedad de Huntington/complicaciones , Enfermedad de Huntington/diagnóstico por imagen , Ataxias Espinocerebelosas/diagnóstico , Corea/diagnóstico por imagen , Corea/etiología , Enfermedad de la Neurona Motora/diagnóstico por imagenRESUMEN
BACKGROUND AND PURPOSE: Primary lateral sclerosis (PLS) is a progressive upper motor neuron disorder associated with considerable clinical disability. Symptoms are typically exclusively linked to primary motor cortex degeneration and the contribution of pre-motor, supplementary motor, cortico-medullary and inter-hemispheric connectivity alterations are less well characterized. METHODS: In a single-centre, prospective, longitudinal neuroimaging study 41 patients with PLS were investigated. Patients underwent standardized neuroimaging, genetic profiling with whole exome sequencing, and comprehensive clinical assessments including upper motor neuron scores, tapping rates, mirror movements, spasticity assessment, cognitive screening and evaluation for pseudobulbar affect. Longitudinal neuroimaging data from 108 healthy controls were used for image interpretation. A standardized imaging protocol was implemented including 3D T1-weighted structural, diffusion tensor imaging and resting-state functional magnetic resonance imaging. Following somatotopic segmentation, cortical thickness analyses, probabilistic tractography, blood oxygenation level dependent signal analyses and brainstem volumetry were conducted to evaluate cortical, brainstem, cortico-medullary and inter-hemispheric connectivity alterations both cross-sectionally and longitudinally. RESULTS: Our data confirm progressive primary motor cortex degeneration, considerable supplementary motor and pre-motor area involvement, progressive brainstem atrophy, cortico-medullary and inter-hemispheric disconnection, and close associations between clinical upper motor neuron scores and somatotopic connectivity indices in PLS. DISCUSSION: Primary lateral sclerosis is associated with relentlessly progressive motor connectome degeneration. Clinical disability in PLS is likely to stem from a combination of intra- and inter-hemispheric connectivity decline and primary, pre- and supplementary motor cortex degeneration. Simple 'bedside' clinical tools, such as tapping rates, are excellent proxies of the integrity of the relevant fibres of the contralateral corticospinal tract.
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Esclerosis Amiotrófica Lateral , Conectoma , Enfermedad de la Neurona Motora , Humanos , Esclerosis Amiotrófica Lateral/genética , Imagen de Difusión Tensora , Estudios Prospectivos , Imagen por Resonancia Magnética/métodos , Enfermedad de la Neurona Motora/diagnóstico por imagenRESUMEN
OBJECTIVE: To investigate whether primary motor cortex (M1) volume measured with an automated approach in MRI reflects upper motor neuron dysfunction and whether it can serve as a potential diagnostic and/or disease-tracking biomarker for amyotrophic lateral sclerosis (ALS). METHODS: In this retrospective study, we enrolled 95 subjects, including 33 possible or laboratory supported probable ALS, 26 probable or definite ALS (Prob/Def), 2 primary lateral sclerosis patients, 8 progressive muscular atrophy patients, 19 normal controls (NC) and 7 ALS patients having a second structural MRI scan. Some subjects also underwent functional MRI. We calculated M1, primary sensory cortex, precuneus volumes, and total gray matter volume (TGMV) with FreeSurfer. The sensorimotor network (SMN) was identified using independent component analysis. RESULTS: The M1/precuneus ratio showed a significant difference between the NC and Prob/Def groups (p < 0.05). The diagnostic accuracy of the M1/precuneus ratio was moderate for distinguishing Prob/Def from NC (cutoff = 1.00, sensitivity = 0.42, specificity = 0.90). Two of eight cases without upper motor neuron dysfunction could be diagnosed with ALS using M1/precuneus ratio as a surrogate marker. A negative correlation between M1/precuneus ratio and functional activity was found in Brodmann area 6 in the SMN in all subjects. TGMV tended to decrease with disease progression (p = 0.04). INTERPRETATION: The M1/precuneus volume ratio, associated with the SMN, may have potential as a surrogate biomarker of upper motor neuron dysfunction in ALS. Furthermore, TGMV may serve as an ALS disease-tracking biomarker.
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Esclerosis Amiotrófica Lateral , Corteza Motora , Enfermedad de la Neurona Motora , Humanos , Esclerosis Amiotrófica Lateral/diagnóstico por imagen , Estudios Retrospectivos , Imagen por Resonancia Magnética , Lóbulo Parietal , Corteza Motora/diagnóstico por imagen , Biomarcadores , Neuronas Motoras , Enfermedad de la Neurona Motora/diagnóstico por imagenRESUMEN
BACKGROUND AND OBJECTIVE: The prevalence and role of the motor band sign (MBS) remain unclear in motor neuron disease. We report the frequency of MBS in amyotrophic lateral sclerosis (ALS) and primary lateral sclerosis (PLS), its correlation with clinical upper motor neuron (UMN) signs, and prognostic value in ALS. METHODS: We conducted a retrospective study of ALS, PLS, and controls with retrievable MRI between 2010 and 2018. We compared the frequencies of MBS across the three groups, and studied correlation between susceptibility-weighted MRI measurements in primary motor cortices and contralateral UMN features. Clinical outcomes were compared between ALS with and without MBS. RESULTS: Thirteen ALS, 5 PLS, and 10 controls were included (median age 60 years, IQR 54-66 years; 14/28 males). MBS was present in 9/13 (69.2%, 95% CI 38.9-89.6%) and 4/5 (80.0%, 95% CI 29.9-99.0%) of ALS and PLS, respectively, and none in controls. 2/13 (15.4%, 95% CI 2.7-46.3%) ALS and 3/5 (60.0%, 95% CI 17.0-92.7%) PLS had MBS in the absence of corticospinal T2/FLAIR hyperintensity sign. Susceptibility measurements in left motor cortices had a significantly positive correlation with contralateral UMN signs in ALS (τb = 0.628, p = 0.03). Similar but nonsignificant trends was observed for right motor cortices in ALS (τb = 0.516, p = 0.07). There were no significant differences in mRS at last follow-up, mortality, or time from symptom onset to last follow-up between ALS patients with and without MBS. CONCLUSIONS: We provide limited evidence that MBS and susceptibility quantification measurements in motor cortices may serve as surrogate markers of UMN involvement in motor neuron disease.
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Esclerosis Amiotrófica Lateral , Enfermedad de la Neurona Motora , Masculino , Humanos , Persona de Mediana Edad , Esclerosis Amiotrófica Lateral/diagnóstico por imagen , Estudios Retrospectivos , Enfermedad de la Neurona Motora/diagnóstico por imagen , Imagen por Resonancia Magnética , Neuronas Motoras/fisiologíaRESUMEN
BACKGROUND AND OBJECTIVES: The C9orf72 expansion is the most common genetic cause of frontotemporal dementia (FTD) and/or motor neuron disease (MND). Corticospinal degeneration has been described in post-mortem neuropathological studies in these patients, especially in those with MND. We used MRI to analyze white matter (WM) volumes in presymptomatic and symptomatic C9orf72 expansion carriers and investigated whether its measure may be helpful in predicting the onset of symptoms. METHODS: We studied 102 presymptomatic C9orf72 mutation carriers, 52 symptomatic carriers: 42 suffering from FTD and 11 from MND, and 75 non-carriers from the Genetic Frontotemporal dementia Initiative (GENFI). All subjects underwent T1-MRI acquisition. We used FreeSurfer to estimate the volume proportion of WM in the brainstem regions (midbrain, pons, and medulla oblongata). We calculated group differences with ANOVA tests and performed linear and non-linear regressions to assess group-by-age interactions. RESULTS: A reduced WM ratio was found in all brainstem subregions in symptomatic carriers compared to both noncarriers and pre-symptomatic carriers. Within symptomatic carriers, MND patients presented a lower ratio in pons and medulla oblongata compared with FTD patients. No differences were found between presymptomatic carriers and non-carriers. Clinical severity was negatively associated with the WM ratio. C9orf72 carriers presented greater age-related WM loss than non-carriers, with MND patients showing significantly more atrophy in pons and medulla oblongata. DISCUSSION: We find consistent brainstem WM loss in C9orf72 symptomatic carriers with differences related to the clinical phenotype supporting the use of brainstem measures as neuroimaging biomarkers for disease tracking.
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Demencia Frontotemporal , Enfermedad de la Neurona Motora , Sustancia Blanca , Humanos , Demencia Frontotemporal/diagnóstico por imagen , Demencia Frontotemporal/genética , Demencia Frontotemporal/patología , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Proteína C9orf72/genética , Enfermedad de la Neurona Motora/diagnóstico por imagen , Enfermedad de la Neurona Motora/genética , Tronco Encefálico/diagnóstico por imagen , Tronco Encefálico/patología , Neuronas Motoras/patología , MutaciónRESUMEN
BACKGROUND: Magnetic resonance imaging (MRI) of the brain and cervical spinal cord is often performed in diagnostic evaluation of suspected motor neuron disease/amyotrophic lateral sclerosis (MND/ALS). Analysis of MRI-derived tissue damage metrics in a common domain facilitates group-level inferences on pathophysiology. This approach was applied to address competing hypotheses of directionality of neurodegeneration, whether anterograde, cranio-caudal dying-forward from precentral gyrus or retrograde, dying-back. METHODS: In this cross-sectional study, MRI was performed on 75 MND patients and 13 healthy controls. Precentral gyral thickness was estimated from volumetric T1-weighted images using FreeSurfer, corticospinal tract fractional anisotropy (FA) from diffusion tensor imaging using FSL, and cross-sectional cervical cord area between C1-C8 levels using Spinal Cord Toolbox. To analyse these multimodal data within a common domain, individual parameter estimates representing tissue damage at each corticospinal tract level were first converted to z-scores, referenced to healthy control norms. Mixed-effects linear regression models were then fitted to these z-scores, with gradients hypothesised to represent directionality of neurodegeneration. RESULTS: At group-level, z-scores did not differ significantly between precentral gyral and intracranial corticospinal tract tissue damage estimates (regression coefficient - 0.24, [95% CI - 0.62, 0.14], p = 0.222), but step-changes were evident between intracranial corticospinal tract and C1 (1.14, [95% CI 0.74, 1.53], p < 0.001), and between C5 and C6 cord levels (0.98, [95% CI 0.58, 1.38], p < 0.001). DISCUSSION: Analysis of brain and cervical spinal MRI data in a common domain enabled investigation of pathophysiological hypotheses in vivo. A cranio-caudal step-change in MND patients was observed, and requires further investigation in larger cohorts.
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Esclerosis Amiotrófica Lateral , Enfermedad de la Neurona Motora , Humanos , Estudios Transversales , Imagen de Difusión Tensora/métodos , Enfermedad de la Neurona Motora/diagnóstico por imagen , Enfermedad de la Neurona Motora/patología , Imagen por Resonancia Magnética/métodos , Esclerosis Amiotrófica Lateral/diagnóstico , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Tractos Piramidales/diagnóstico por imagenRESUMEN
KEY POINTS: ⢠Conventional and advanced MR techniques may aid in the diagnosis of motor neuron disease.⢠Iron-sensitive MR imaging of the primary motor cortex may reveal changes to help differentiate hereditary spastic paraplegia (HSP) from UMM predominant amyotrophic lateral sclerosis (UMN-ALS) and primary lateral sclerosis (PLS).⢠Additional research in this area is necessary.
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Esclerosis Amiotrófica Lateral , Corteza Motora , Enfermedad de la Neurona Motora , Paraplejía Espástica Hereditaria , Humanos , Paraplejía Espástica Hereditaria/diagnóstico por imagen , Corteza Motora/diagnóstico por imagen , Hierro , Enfermedad de la Neurona Motora/diagnóstico por imagen , Esclerosis Amiotrófica Lateral/diagnóstico , Imagen por Resonancia Magnética/métodosRESUMEN
BACKGROUND: Frontotemporal dementia (FTD) is a spectrum of diseases characterised by language, behavioural and motor symptoms. Among the different subcortical regions implicated in the FTD symptomatology, the hypothalamus regulates various bodily functions, including eating behaviours which are commonly present across the FTD spectrum. The pattern of specific hypothalamic involvement across the clinical, pathological, and genetic forms of FTD has yet to be fully investigated, and its possible associations with abnormal eating behaviours have yet to be fully explored. METHODS: Using an automated segmentation tool for volumetric T1-weighted MR images, we measured hypothalamic regional volumes in a cohort of 439 patients with FTD (197 behavioural variant FTD [bvFTD]; 7 FTD with associated motor neurone disease [FTD-MND]; 99 semantic variant primary progressive aphasia [svPPA]; 117 non-fluent variant PPA [nfvPPA]; 19 PPA not otherwise specified [PPA-NOS]) and 118 age-matched controls. We compared volumes across the clinical, genetic (29 MAPT, 32 C9orf72, 23 GRN), and pathological diagnoses (61 tauopathy, 40 TDP-43opathy, 4 FUSopathy). We correlated the volumes with presence of abnormal eating behaviours assessed with the revised version of the Cambridge Behavioural Inventory (CBI-R). RESULTS: On average, FTD patients showed 14% smaller hypothalamic volumes than controls. The groups with the smallest hypothalamic regions were FTD-MND (20%), MAPT (25%) and FUS (33%), with differences mainly localised in the anterior and posterior regions. The inferior tuberal region was only significantly smaller in tauopathies (MAPT and Pick's disease) and in TDP-43 type C compared to controls and was the only regions that did not correlate with eating symptoms. PPA-NOS and nfvPPA were the groups with the least frequent eating behaviours and the least hypothalamic involvement. CONCLUSIONS: Abnormal hypothalamic volumes are present in all the FTD forms, but different hypothalamic regions might play a different role in the development of abnormal eating behavioural and metabolic symptoms. These findings might therefore help in the identification of different underlying pathological mechanisms, suggesting the potential use of hypothalamic imaging biomarkers and the research of potential therapeutic targets within the hypothalamic neuropeptides.
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Demencia Frontotemporal , Enfermedad de la Neurona Motora , Enfermedad de Pick , Demencia Frontotemporal/patología , Humanos , Hipotálamo/diagnóstico por imagen , Hipotálamo/patología , Imagen por Resonancia Magnética , Enfermedad de la Neurona Motora/diagnóstico por imagen , Enfermedad de la Neurona Motora/patología , Enfermedad de Pick/patologíaRESUMEN
INTRODUCTION: Within the core neuroimaging signature of amyotrophic lateral sclerosis (ALS), the corpus callosum (CC) is increasingly recognized as a consistent feature. The aim of this study was to investigate the sensitivity and specificity of the microstructural segmental CC morphology, assessed by diffusion tensor imaging (DTI) and high-resolution T1-weighted (T1w) imaging, in a large cohort of ALS patients including different clinical phenotypes. METHODS: In a single-centre study, 575 patients with ALS (classical phenotype, N = 432; restricted phenotypes primary lateral sclerosis (PLS) N = 55, flail arm syndrome (FAS) N = 45, progressive bulbar palsy (PBP) N = 22, lower motor neuron disease (LMND) N = 21) and 112 healthy controls underwent multiparametric MRI, i.e. volume-rendering T1w scans and DTI. Tract-based fractional anisotropy statistics (TFAS) was applied to callosal tracts of CC areas I-V, identified from DTI data (tract-of-interest (TOI) analysis), and texture analysis was applied to T1w data. In order to further specify the callosal alterations, a support vector machine (SVM) algorithm was used to discriminate between motor neuron disease patients and controls. RESULTS: The analysis of white matter integrity revealed predominantly FA reductions for tracts of the callosal areas I, II, and III (with highest reductions in callosal area III) for all ALS patients and separately for each phenotype when compared to controls; texture analysis demonstrated significant alterations of the parameters entropy and homogeneity for ALS patients and all phenotypes for the CC areas I, II, and III (with again highest reductions in callosal area III) compared to controls. With SVM applied on multiparametric callosal parameters of area III, a separation of all ALS patients including phenotypes from controls with 72% sensitivity and 73% specificity was achieved. These results for callosal area III parameters could be improved by an SVM of six multiparametric callosal parameters of areas I, II, and III, achieving a separation of all ALS patients including phenotypes from controls with 84% sensitivity and 85% specificity. DISCUSSION: The multiparametric MRI texture and DTI analysis demonstrated substantial alterations of the frontal and central CC with most significant alterations in callosal area III (motor segment) in ALS and separately in all investigated phenotypes (PLS, FAS, PBP, LMND) in comparison to controls, while no significant differences were observed between ALS and its phenotypes. The combination of the texture and the DTI parameters in an unbiased SVM-based approach might contribute as a neuroimaging marker for the assessment of the CC in ALS, including subtypes.