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The use of diffusion tensor imaging (DTI) has seen significant development over the last two decades, in particular with the development of the tractography of association tracts for preoperative planning of surgery. However, projection tracts are difficult to differentiate from one another and tractography studies have failed to reconstruct these ascending/descending pathways from/to the spinal cord. The present study proposes an atlas of regions of interest (ROIs) designed specifically for projection tracts tractography. Forty-nine healthy subjects were included in this prospective study. Brain DTI was acquired using the same 3 T MRI scanner, with 32 diffusion directions. Distortions were corrected using the FSL software package. ROIs were drawn using the anterior commissure (AC)-posterior commissure (PC) line on the following landmarks: the pyramid for the corticospinal tract, the medio-caudal part of the red nucleus for the rubrospinal tract, the pontine reticular nucleus for corticoreticular tract, the superior and inferior cerebellar peduncles for, respectively, the anterior and posterior spinocerebellar tract, the gracilis and cuneatus nucleus for the dorsal columns, and the ventro-posterolateral nucleus for the spinothalamic tract. Fiber tracking was performed using a deterministic algorithm using DSI Studio software. ROI coordinates, according to AC-PC line, were given for each tract. Tractography was obtained for each tract, allowing tridimensional rendering and comparison of tracking metrics between tracts. The present study reports the accurate design of specific ROIs for tractography of each projection tract. This could be a useful tool in order to differentiate projection tracts at the spinal cord level.
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The frequency of corticospinal tract (CST) T2/FLAIR hyperintensity in disorders with neuroglial antibodies is unclear. Herein, we retrospectively reviewed brain MRIs of 101 LGI1-antibody encephalitis patients, and observed CST hyperintensity in 30/101 (30%). It was mostly bilateral (93%), not associated with upper motor neuron signs/symptoms (7%), and frequently decreased over time (39%). In a systematic review including patients with other neuroglial antibodies, CST hyperintensity was reported in 110 with neuromyelitis optica (94%), myelin oligodendrocyte glycoprotein-associated disease (2%), Ma2-antibody (3%) and GAD65-antibody paraneoplastic neurological syndrome (1%). CST hyperintensity is not an infrequent finding in LGI1-Ab encephalitis and other disorders with neuroglial antibodies.
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Autoanticorpos , Encefalite , Peptídeos e Proteínas de Sinalização Intracelular , Tratos Piramidais , Humanos , Autoanticorpos/imunologia , Autoanticorpos/sangue , Feminino , Pessoa de Meia-Idade , Masculino , Estudos Retrospectivos , Idoso , Adulto , Encefalite/imunologia , Encefalite/diagnóstico por imagem , Tratos Piramidais/diagnóstico por imagem , Tratos Piramidais/patologia , Tratos Piramidais/imunologia , Peptídeos e Proteínas de Sinalização Intracelular/imunologia , Imageamento por Ressonância Magnética , Adulto Jovem , Neuroglia/patologia , Neuroglia/imunologia , Adolescente , Idoso de 80 Anos ou mais , Doenças do Sistema Nervoso Central/imunologia , Doenças do Sistema Nervoso Central/diagnóstico por imagemRESUMO
Differentiating neoplastic from non-neoplastic spinal cord pathologies may be challenging due to overlapping clinical and radiological features. Spinal cord tumors, which comprise only 2-4% of central nervous system tumors, are rarer than non-tumoral myelopathies of inflammatory, vascular, or infectious origins. The risk of neurological deterioration and the high rate of false negatives or misdiagnoses associated with spinal cord biopsies require a cautious approach. Facing a spinal cord lesion, prioritizing more common non-surgical myelopathies in differential diagnoses is essential. A comprehensive radiological diagnostic approach is mandatory to identify spinal cord tumor mimics. The diagnostic process involves a multi-step approach: detecting lesions primarily using MRI techniques, precise localization of lesions, assessing lesion signal intensity characteristics, and searching for potentially associated anomalies at spinal cord and cerebral MRI. This review aims to delineate the radiological diagnostic approach for spinal cord lesions that may mimic tumors and briefly highlight the primary pathologies behind these lesions.
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OBJECTIVE: Central pontine myelinolysis (CPM) is a rare demyelinating disease that affects the pons and which can cause extreme disabilities such as locked-in syndrome (LIS) in the initial phase. The aim of the study was to describe the evolution over a 12-month period of two patients with CPM causing an initial LIS. METHOD: We retrospectively report the unexpected clinical outcome of these two patients in relation with the anatomical damages documented by brain MRI, associated with diffusion tensor imaging and reconstruction of corticospinal tracts in tractography. The following clinical parameters systematically assessed at 3, 6, 9, and 12 months: muscle testing on 12 key muscles (Medical Research Council), prehension metrics (box and block test and purdue pegboard), and independence for acts of daily living (functional independence measure). RESULTS: Both patients showed a progressive recovery beginning between 2 and 3 months after the onset of symptoms, leading to almost complete autonomy at 12 months (FIM > 110), with motor strength greater than 4/5 in all joint segments (MRC > 50/60). On brain MRI with tractography, CST appeared partially preserved at pons level. INTERPRETATION: The possibility of a near-complete functional recovery at 12 months is important to consider given the ethical issues at stake and the discussions about limiting care that may take place initially. It seems to be the consequence of reversible myelin damage combined with partially preserved neurons. Development of collateral pathways or resolution of conduction block may explain this recovery. MRI comprising DTI and tractography could play a key role in the prognosis of motor recovery.
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Síndrome do Encarceramento , Mielinólise Central da Ponte , Humanos , Mielinólise Central da Ponte/diagnóstico por imagem , Mielinólise Central da Ponte/etiologia , Imagem de Tensor de Difusão , Estudos Retrospectivos , Tratos Piramidais/diagnóstico por imagemRESUMO
BACKGROUND: Blood-barrier (BBB) breakdown and active inflammation are hallmarks of relapsing multiple sclerosis (RMS), but the molecular events contributing to the development of new lesions are not well explored. Leaky endothelial junctions are associated with increased production of endothelial-derived extracellular microvesicles (EVs) and result in the entry of circulating immune cells into the brain. MRI with intravenous gadolinium (Gd) can visualize acute blood-barrier disruption as the initial event of the evolution of new lesions. METHODS: Here, weekly MRI with Gd was combined with proteomics, multiplex immunoassay, and endothelial stress-optimized EV array to identify early markers related to BBB disruption. Five patients with RMS with no disease-modifying treatment were monitored weekly using high-resolution 3T MRI scanning with intravenous gadolinium (Gd) for 8 weeks. Patients were then divided into three groups (low, medium, or high MRI activity) defined by the number of new, total, and maximally enhancing Gd-enhancing lesions and the number of new FLAIR lesions. Plasma samples taken at each MRI were analyzed for protein biomarkers of inflammation by quantitative proteomics, and cytokines using multiplex immunoassays. EVs were characterized with an optimized endothelial stress EV array based on exosome surface protein markers for the detection of soluble secreted EVs. RESULTS: Proteomics analysis of plasma yielded quantitative information on 208 proteins at each patient time point (n = 40). We observed the highest number of unique dysregulated proteins (DEPs) and the highest functional enrichment in the low vs. high MRI activity comparison. Complement activation and complement/coagulation cascade were also strongly overrepresented in the low vs. high MRI activity comparison. Activation of the alternative complement pathway, pathways of blood coagulation, extracellular matrix organization, and the regulation of TLR and IGF transport were unique for the low vs. high MRI activity comparison as well, with these pathways being overrepresented in the patient with high MRI activity. Principal component analysis indicated the individuality of plasma profiles in patients. IL-17 was upregulated at all time points during 8 weeks in patients with high vs. low MRI activity. Hierarchical clustering of soluble markers in the plasma indicated that all four MRI outcomes clustered together with IL-17, IL-12p70, and IL-1ß. MRI outcomes also showed clustering with EV markers CD62E/P, MIC A/B, ICAM-1, and CD42A. The combined cluster of these cytokines, EV markers, and MRI outcomes clustered also with IL-12p40 and IL-7. All four MRI outcomes correlated positively with levels of IL-17 (p < 0.001, respectively), and EV-ICAM-1 (p < 0.0003, respectively). IL-1ß levels positively correlated with the number of new Gd-enhancing lesions (p < 0.01), new FLAIR lesions (p < 0.001), and total number of Gd-enhancing lesions (p < 0.05). IL-6 levels positively correlated with the number of new FLAIR lesions (p < 0.05). Random Forests and linear mixed models identified IL-17, CCL17/TARC, CCL3/MIP-1α, and TNF-α as composite biomarkers predicting new lesion evolution. CONCLUSIONS: Combination of serial frequent MRI with proteome, neuroinflammation markers, and protein array data of EVs enabled assessment of temporal changes in inflammation and endothelial dysfunction in RMS related to the evolution of new and enhancing lesions. Particularly, the Th17 pathway and IL-1ß clustered and correlated with new lesions and Gd enhancement, indicating their importance in BBB disruption and initiating acute brain inflammation in MS. In addition to the Th17 pathway, abundant protein changes between MRI activity groups suggested the role of EVs and the coagulation system along with innate immune responses including acute phase proteins, complement components, and neutrophil degranulation.
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Because the spinal cord contains a rich concentration of longitudinal and transversal fibers in a very small area, intramedullary surgery could result in a high likelihood of morbidity. In this video, the authors demonstrate the microsurgical technique and surgical skills used to perform excision of an intramedullary ependyma. The authors also present tools (electrophysiology and neuroimaging) that are useful for surgical decision-making and planning, and thus are used intraoperatively, that allow safer and more effective resection of an intramedullary tumor.
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BACKGROUND: Pseudocystic inflammatory demyelinating lesions (PIDLs) are poorly described in MS and might represent a diagnostic challenge. OBJECTIVES: We described the clinical, radiological, pathological, and follow-up characteristics of 13 PIDL in 9 MS patients. METHODS: We constituted a single-center retrospective case series of PIDLs in MS, defined on MRI as expansive cyst-like lesions, with a fluid-signal content, and a diameter of 1 cm or more. RESULTS: PIDL often occurred at first event (56%), were often asymptomatic (69%), and encircled by a hypo-T2 diffusion-restricted rim and a thin ring-like gadolinium enhancement (100%) on magnetic resonance imaging (MRI). Associated typical MS lesions were constant. Biopsies from two PIDLs displayed classical features of active MS, except for unusual edema. CONCLUSION: PIDLs are clinically unremarkable and associated with a good outcome. Their easily recognizable MRI features could help avoid biopsy.
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Esclerose Múltipla , Humanos , Esclerose Múltipla/diagnóstico por imagem , Meios de Contraste , Gadolínio , Estudos Retrospectivos , BiópsiaRESUMO
Introduction: We report a very unique clinical presentation of a patient who complained, after a left parietal brain damage, about feeling tactile stimulations on his right upper limb without being able to localize them. Methods: Using a single case study approach, we report three experiments relying on several custom-made tasks to explore the different levels of somatosensory information processing, ranging from somato-sensation to somato-representation. Results: Our results showed a preserved ability to localize tactile stimuli applied on the right upper limb when using pointing responses while the ability to localize was less efficient when having to name the stimulated part (akin Numbsense). When the stimuli were applied on more distal locations (i.e., on the hand and on fingers), the number of correct responses decreased significantly independently of the modality of response. Finally, when visually presented with a stimulus delivered on the hand of an examiner in synchrony with the stimulation on the hidden hand of the patient, responses were largely influenced by the visual information available. Altogether, the convergence of these different customized tasks revealed an absence of autotopagnosia for motor responses for the right upper limb, associated with altered abilities to discriminate stimulus applied on distal and restricted/closer zones in the hand. Discussion: The somato-representation of our patient seemed to significantly rely on visual information, leading to striking deficits to localize tactile stimuli when vision and somesthesic afferences are discordant. This case report offers a clinical illustration of pathological imbalance between vision and somesthesia. Implications of these troubles in somato-representation on higher cognitive level processes are discussed.
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Today's medicine strives to be personalized, preventive, predictive and participatory. This implies to have access to multimodal data to better characterize patients groups and to combine clinical and imaging data with high-quality biological samples. Collecting such data is one of the objectives of the Observatoire français de la sclérose en plaques (OFSEP), the French MS registry. On December 2022, the OFSEP biocollection includes 4,888 patients with scientific characteristics and about 90,000 samples. Thanks to its richness, this biocollection open for the scientific community, contributes to address unmet needs in MS through identification of multiomics determinants of MS activity, progression and secondary effects.
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Esclerose Múltipla , Humanos , Sistema de RegistrosRESUMO
The lack of interpretability of deep learning reduces understanding of what happens when a network does not work as expected and hinders its use in critical fields like medicine, which require transparency of decisions. For example, a healthy vs pathological classification model should rely on radiological signs and not on some training dataset biases. Several post-hoc models have been proposed to explain the decision of a trained network. However, they are very seldom used to enforce interpretability during training and none in accordance with the classification. In this paper, we propose a new weakly supervised method for both interpretable healthy vs pathological classification and anomaly detection. A new loss function is added to a standard classification model to constrain each voxel of healthy images to drive the network decision towards the healthy class according to gradient-based attributions. This constraint reveals pathological structures for patient images, allowing their unsupervised segmentation. Moreover, we advocate both theoretically and experimentally, that constrained training with the simple Gradient attribution is similar to constraints with the heavier Expected Gradient, consequently reducing the computational cost. We also propose a combination of attributions during the constrained training making the model robust to the attribution choice at inference. Our proposition was evaluated on two brain pathologies: tumors and multiple sclerosis. This new constraint provides a more relevant classification, with a more pathology-driven decision. For anomaly detection, the proposed method outperforms state-of-the-art especially on difficult multiple sclerosis lesions segmentation task with a 15 points Dice improvement.
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Esclerose Múltipla , Humanos , Esclerose Múltipla/diagnóstico por imagem , Processamento de Imagem Assistida por ComputadorRESUMO
White matter hyperintensities (WMH), frequently seen in older adults, are usually considered vascular lesions, and participate in the vascular contribution to cognitive impairment and dementia. However, emerging evidence highlights the heterogeneity of WMH pathophysiology, suggesting that non-vascular mechanisms could also be involved, notably in Alzheimer's disease (AD). This led to the alternative hypothesis that in AD, part of WMH may be secondary to AD-related processes. The current perspective brings together the arguments from different fields of research, including neuropathology, neuroimaging and fluid biomarkers, and genetics, in favor of this alternative hypothesis. Possible underlying mechanisms leading to AD-related WMH, such as AD-related neurodegeneration or neuroinflammation, are discussed, as well as implications for diagnostic criteria and management of AD. We finally discuss ways to test this hypothesis and remaining challenges. Acknowledging the heterogeneity of WMH and the existence of AD-related WMH may improve personalized diagnosis and care of patients.
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Doença de Alzheimer , Disfunção Cognitiva , Substância Branca , Humanos , Idoso , Doença de Alzheimer/patologia , Substância Branca/diagnóstico por imagem , Substância Branca/patologia , Imageamento por Ressonância Magnética/métodos , Disfunção Cognitiva/patologia , NeuroimagemRESUMO
INTRODUCTION: Implementation of Lung cancer screening (LCS) programs is challenging. The ILYAD study objectives is to evaluate communication methods to improve participation rate among the Lyon University Hospital employees. In this first part of the study, we aimed to determinate the number of eligible individuals among our population of employees. METHOD: In November 2020, we conducted a questionnaire based cross sectional survey among the Lyon University Hospital employees (N = 26,954). We evaluated the PLCO m2012 risk prediction model and the eligibility criteria recommended by French guidelines. We assessed the proportion of eligible individuals among the responders and calculated the total eligible individuals in our hospital. RESULTS: Overall, 4,526 questionnaires were available for analysis. 16.0% were current smokers, and 28.2% were former smokers. Among the 50-75yo ever-smoker employees, 27% were eligible according to the French guidelines, 2.7% of all eversmokers according to a PLCO m2012 score ≥ 1.51%, and thus, 3.8% of the surveyed population were eligible to the combined criteria. The factors associated with higher eligibility among 50-75yo ever-smokers were educational level, feeling symptoms related to tobacco smoking, personal history of COPD and family history of lung cancer. Using the French guidelines criteria only, we estimated the total number of eligible individuals in the hospital at 838. CONCLUSION: In this study, we determined a theoretical number of eligible employees to LCS in our institution and the factors associated to eligibility. Secondly, we will propose LCS to all eligible employees of Lyon University Hospital with incremented information actions.
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Detecção Precoce de Câncer , Neoplasias Pulmonares , Humanos , Estudos Transversais , Detecção Precoce de Câncer/métodos , Programas de Rastreamento/métodos , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/epidemiologia , Hospitais UniversitáriosRESUMO
BACKGROUND AND PURPOSE: Cerebral hypoperfusion has been reported in patients with COVID-19 and neurological manifestations in small cohorts. We aimed to systematically assess changes in cerebral perfusion in a cohort of 59 of these patients, with or without abnormalities on morphological MRI sequences. METHODS: Patients with biologically-confirmed COVID-19 and neurological manifestations undergoing a brain MRI with technically adequate arterial spin labeling (ASL) perfusion were included in this retrospective multicenter study. ASL maps were jointly reviewed by two readers blinded to clinical data. They assessed abnormal perfusion in four regions of interest in each brain hemisphere: frontal lobe, parietal lobe, posterior temporal lobe, and temporal pole extended to the amygdalo-hippocampal complex. RESULTS: Fifty-nine patients (44 men (75%), mean age 61.2 years) were included. Most patients had a severe COVID-19, 57 (97%) needed oxygen therapy and 43 (73%) were hospitalized in intensive care unit at the time of MRI. Morphological brain MRI was abnormal in 44 (75%) patients. ASL perfusion was abnormal in 53 (90%) patients, and particularly in all patients with normal morphological MRI. Hypoperfusion occurred in 48 (81%) patients, mostly in temporal poles (52 (44%)) and frontal lobes (40 (34%)). Hyperperfusion occurred in 9 (15%) patients and was closely associated with post-contrast FLAIR leptomeningeal enhancement (100% [66.4%-100%] of hyperperfusion with enhancement versus 28.6% [16.6%-43.2%] without, p = 0.002). Studied clinical parameters (especially sedation) and other morphological MRI anomalies had no significant impact on perfusion anomalies. CONCLUSION: Brain ASL perfusion showed hypoperfusion in more than 80% of patients with severe COVID-19, with or without visible lesion on conventional MRI abnormalities.
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COVID-19 , Masculino , Humanos , Pessoa de Meia-Idade , Marcadores de Spin , COVID-19/complicações , Imageamento por Ressonância Magnética , Perfusão , Circulação CerebrovascularRESUMO
OBJECTIVES: To determine whether diffusion-weighted imaging (DWI) can help to distinguish early stage autoimmune (AI) and herpes simplex virus (HSV) encephalitides. METHODS: This case-control study included patients from a multi-center cohort of AI encephalitides whose initial MRI including DWI was performed within ten days after symptoms onset. They were compared with patients with HSV encephalitis enrolled prospectively in a single-center from June, 2020 to December, 2020. The final diagnosis of AI encephalitis required a positive autoantibody assay, and that of HSV encephalitis required a positive HSV polymerase chain reaction based on cerebrospinal fluid. Brain MRI were evaluated for restricted diffusion, fluid-inversion recovery (FLAIR) abnormalities, lesion topography, hemorrhagic changes, and contrast enhancement. RESULTS: Forty-nine patients were included of which, 19 (38.8%) had AI encephalitis. Twenty-seven patients (55.1%) were males and the median age was 46.0 years (interquartile range (IQR):[22.0; 65.0]). Brain MRI were performed after a median of 4 days (IQR:[2.0; 7.0]) of symptom onset and time between symptom onset and MRI was not significantly different (pâ¯=â¯0.60). Twenty-six patients had restricted diffusion lesions in the medial temporal lobe, including 25/30 in the HSV encephalitis group (p < 0.001). FLAIR abnormalities were observed in 36 patients, including 29/30 in the HSV encephalitis group (p < 0.001). Lesion topography, hemorrhagic changes, and contrast enhancement did not differ significantly between the two groups. CONCLUSION: Our results suggest that restricted diffusion lesions in the medial temporal lobe are a hallmark of HSV encephalitis and may help distinguish it from early-stage AI encephalitis.
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Encefalite por Herpes Simples , Masculino , Humanos , Pessoa de Meia-Idade , Feminino , Encefalite por Herpes Simples/diagnóstico por imagem , Encefalite por Herpes Simples/líquido cefalorraquidiano , Estudos de Casos e Controles , Imagem de Difusão por Ressonância Magnética/métodos , Imageamento por Ressonância Magnética/métodosRESUMO
Despite recent improvements in diffusion-weighted imaging, spinal cord tractography is not used in routine clinical practice because of difficulties in reconstructing tractograms, with a pertinent tri-dimensional-rendering, in a long post-processing time. We propose a new full tractography approach to the cervical spinal cord without extensive manual filtering or multiple regions of interest seeding that could help neurosurgeons manage various spinal cord disorders. Four healthy volunteers and two patients with either cervical intramedullary tumors or spinal cord injuries were included. Diffusion-weighted images of the cervical spinal cord were acquired using a Philips 3 Tesla machine, 32 diffusion directions, 1,000 s/mm2 b-value, 2 × 2 × 2 mm voxel size, reduced field-of-view (ZOOM), with two opposing phase-encoding directions. Distortion corrections were then achieved using the FSL software package, and tracking of the full cervical spinal cord was performed using the DSI Studio software (quantitative anisotropy-based deterministic algorithm). A unique region of avoidance was used to exclude everything that is not of the nervous system. Fiber tracking parameters used adaptative fractional anisotropy from 0.015 to 0.045, fiber length from 10 to 1,000 mm, and angular threshold of 90°. In all participants, a full cervical cord tractography was performed from the medulla to the C7 spine level. On a ventral view, the junction between the medulla and spinal cord was identified with its pyramidal bulging, and by an invagination corresponding to the median ventral sulcus. On a dorsal view, the fourth ventricle-superior, middle, and inferior cerebellar peduncles-was seen, as well as its floor and the obex; and gracile and cuneate tracts were recognized on each side of the dorsal median sulcus. In the case of the intramedullary tumor or spinal cord injury, the spinal tracts were seen to be displaced, and this helped to adjust the neurosurgical strategy. This new full tractography approach simplifies the tractography pipeline and provides a reliable 3D-rendering of the spinal cord that could help to adjust the neurosurgical strategy.
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BACKGROUND AND OBJECTIVES: There is no report on the long-term outcomes of ataxia with antibodies against Delta and Notch-like epidermal growth factor-related (DNER). We aimed to describe the clinical-immunologic features and long-term outcomes of patients with anti-DNER antibodies. METHODS: Patients tested positive for anti-DNER antibodies between 2000 and 2020 were identified retrospectively. In those with available samples, immunoglobulin G (IgG) subclass analysis, longitudinal cerebellum volumetry, human leukocyte antigen isotyping, and CSF proteomic analysis were performed. Rodent brain membrane fractionation and organotypic cerebellar slices were used to study DNER cell-surface expression and human IgG binding to the Purkinje cell surface. RESULTS: Twenty-eight patients were included (median age, 52 years, range 19-81): 23 of 28 (82.1%) were male and 23 of 28 (82.1%) had a hematologic malignancy. Most patients (27/28, 96.4%) had cerebellar ataxia; 16 of 28 (57.1%) had noncerebellar symptoms (cognitive impairment, neuropathy, and/or seizures), and 27 of 28 (96.4%) became moderately to severely disabled. Half of the patients (50%) improved, and 32.1% (9/28) had no or slight disability at the last visit (median, 26 months; range, 3-238). Good outcome significantly associated with younger age, milder clinical presentations, and less decrease of cerebellar gray matter volumes at follow-up. No human leukocyte antigen association was identified. Inflammation-related proteins were overexpressed in the patients' CSF. In the rodent brain, DNER was enriched in plasma membrane fractions. Patients' anti-DNER antibodies were predominantly IgG1/3 and bound live Purkinje cells in vitro. DISCUSSION: DNER ataxia is a treatable condition in which nearly a third of patients have a favorable outcome. DNER antibodies bind to the surface of Purkinje cells and are therefore potentially pathogenic, supporting the use of B-cell-targeting treatments.