[Diagnostic capabilities of spinal MR angiography and spinal MR tractography in a patient with motor neuron disease]. / Diagnosticheskie vozmozhnosti spinal'noi MR-angiografii i spinal'noi MRT-traktografii u bol'nogo s bolezn'yu dvigatel'nogo neirona.

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.

Amyotrophic lateral sclerosis with upper motor neuron predominance: diagnostic accuracy of qualitative and quantitative susceptibility metrics in the precentral gyrus.

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.

Advances in the neuroimaging of motor disorders.

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.

Promises and pitfalls of imaging-based biomarkers in motor neuron diseases.

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.

Not a benign motor neuron disease: longitudinal imaging captures relentless motor connectome disintegration in primary lateral sclerosis.

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.

Motor band sign in a Huntington disease phenocopy.

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.

M1/precuneus ratio as a surrogate marker of upper motor neuron sign in ALS.

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.

Motor Band Sign in Motor Neuron Disease: A Marker for Upper Motor Neuron Involvement.

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.

Loss of brainstem white matter predicts onset and motor neuron symptoms in C9orf72 expansion carriers: a GENFI study.

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.

Analysis of brain and spinal MRI measures in a common domain to investigate directional neurodegeneration in motor neuron disease.

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.

Editorial Comment: Iron-sensitive MR imaging of the primary motor cortex to differentiate hereditary spastic paraplegia from other motor neuron diseases.

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.

Segmental alterations of the corpus callosum in motor neuron disease: A DTI and texture analysis in 575 patients.

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.

In vivo hypothalamic regional volumetry across the frontotemporal dementia spectrum.

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.

Neurometabolic Alterations in Motor Neuron Disease: Insights from Magnetic Resonance Spectroscopy.

Magnetic resonance spectroscopy (MRS) has contributed important academic insights in motor neuron diseases (MNDs), particularly in amyotrophic lateral sclerosis (ALS). Over the past three decades momentous methodological advances took place, including the emergence of high-field magnetic resonance imaging (MRI) platforms, multi-voxel techniques, whole-brain protocols, novel head-coil designs, and a multitude of open-source imaging suites. Technological advances in MRS are complemented by important conceptual developments in MND, such as the recognition of the importance of extra-motor brain regions, multi-timepoint longitudinal study designs, assessment of asymptomatic mutation carriers, description of genotype-associated signatures, and the gradual characterisation of non-ALS MND phenotypes. We have conducted a systematic review of published MRS studies in MND to identify important emerging research trends, key lessons from pioneering studies, and stereotyped shortcomings. We also sought to highlight notable gaps in the current literature so that research priorities for future studies can be outlined. While MRS remains relatively underutilised in MND compared to other structural, diffusivity and functional imaging modalities, our review suggests that MRS can not only advance our academic understanding of MND biology, but has a multitude of practical benefits for clinical and pharmaceutical trial applications.

Iron-sensitive MR imaging of the primary motor cortex to differentiate hereditary spastic paraplegia from other motor neuron diseases.

OBJECTIVES: Hereditary spastic paraplegia (HSP) is a group of genetic neurodegenerative diseases characterised by upper motor neuron (UMN) impairment of the lower limbs. The differential diagnosis with primary lateral sclerosis (PLS) and amyotrophic lateral sclerosis (ALS) can be challenging. As microglial iron accumulation was reported in the primary motor cortex (PMC) of ALS cases, here we assessed the radiological appearance of the PMC in a cohort of HSP patients using iron-sensitive MR imaging and compared the PMC findings among HSP, PLS, and ALS patients. METHODS: We included 3-T MRI scans of 23 HSP patients, 7 PLS patients with lower limb onset, 8 ALS patients with lower limb and prevalent UMN onset (UMN-ALS), and 84 ALS patients with any other clinical picture. The PMC was visually rated on 3D T2*-weighted images as having normal signal intensity, mild hypointensity, or marked hypointensity, and differences in the frequency distribution of signal intensity among the diseases were investigated. RESULTS: The marked hypointensity in the PMC was visible in 3/22 HSP patients (14%), 7/7 PLS patients (100%), 6/8 UMN-ALS patients (75%), and 35/84 ALS patients (42%). The frequency distribution of normal signal intensity, mild hypointensity, and marked hypointensity in HSP patients was different than that in PLS, UMN-ALS, and ALS patients (p < 0.01 in all cases). CONCLUSIONS: Iron-sensitive imaging of the PMC could provide useful information in the diagnostic work - up of adult patients with a lower limb onset UMN syndrome, as the cortical hypointensity often seen in PLS and ALS cases is apparently rare in HSP patients. KEY POINTS: • The T2* signal intensity of the primary motor cortex was investigated in patients with HSP, PLS with lower limb onset, and ALS with lower limb and prevalent UMN onset (UMN-ALS) using a clinical 3-T MRI sequence. • Most HSP patients had normal signal intensity in the primary motor cortex (86%); on the contrary, all the PLS and the majority of UMN-ALS patients (75%) had marked cortical hypointensity. • The T2*-weighted imaging of the primary motor cortex could provide useful information in the differential diagnosis of sporadic adult-onset UMN syndromes.

Corneal confocal microscopy in the evaluation of immune-related motor neuron disease syndrome.

BACKGROUND: To investigate the sensitivity and specificity of corneal confocal microscopy (CCM) in the diagnosis of immune-related motor neuron disease syndrome and evaluation of the response to immunosuppressive therapy. METHODS: Seventy-two patients with clinical manifestations of motor neuron disease (MND) were analysed. According to whether they had concomitant rheumatic immune disease or rheumatic immune antibody abnormalities, they were divided into an MND group (33 patients) and an immune-related MND syndrome group (39 patients). Another 10 healthy adults were selected as the control group. All individuals were examined by CCM. RESULTS: For Langerhans cell(LC) density, the area under the receiver operating characteristic(ROC)curve was 0.8, the best cut-off was 67.7 cells/mm2, the sensitivity was 79.5%, and the specificity was 72.7%. For inferior whorl length (IWL), the area under the ROC curve was 0.674, the best cut-off was 17.41 mm/mm2, the sensitivity was 69.2%, and the specificity was 66.7%. After immunosuppressive therapy in 5 patients with immune-related MND syndrome, the LCD was significantly reduced (P < 0.05), and there was no statistically significant change in the IWL (P > 0.05). CONCLUSION: The LC density and IWL are ideal for distinguishing MND from immune-related MND syndrome. The LC density reflects the immunotherapy response sensitively.