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OBJECTIVE: Primary angiitis of the central nervous system (PACNS) is a rare vasculitis restricted to the brain, spinal cord, and leptomeninges. This study aimed to describe the imaging characteristics of patients with small vessel PACNS (SV-PACNS) using 7 T magnetic resonance imaging (MRI). METHODS: This ongoing prospective observational cohort study included patients who met the Calabrese and Mallek criteria and underwent 7 T MRI scan. The MRI protocol includes T1-weighted magnetization-prepared rapid gradient echo imaging, T2 star weighted imaging, and susceptibility-weighted imaging. Two experienced readers independently reviewed the neuroimages. Clinical data were extracted from the electronic patient records. The findings were then applied to a cohort of patients with large vessel central nervous system (CNS) vasculitis. RESULTS: We included 21 patients with SV-PACNS from December 2021 to November 2023. Of these, 12 (57.14%) had cerebral cortical microhemorrhages with atrophy. The pattern with microhemorrhages was described in detail based on the gradient echo sequence, leading to the identification of what we have termed the "coral-like sign." The onset age of patients with coral-like sign (33.83 ± 9.93 years) appeared younger than that of patients without coral-like sign (42.11 ± 14.18 years) (P = 0.131). Furthermore, the cerebral lesions in patients with cortical microhemorrhagic SV-PACNS showed greater propensity toward bilateral lesions (P = 0.03). The coral-like sign was not observed in patients with large vessel CNS vasculitis. INTERPRETATION: The key characteristics of the coral-like sign represent cerebral cortical diffuse microhemorrhages with atrophy, which may be an important MRI pattern of SV-PACNS. ANN NEUROL 2024;96:194-203.
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Imagen por Resonancia Magnética , Vasculitis del Sistema Nervioso Central , Humanos , Masculino , Femenino , Vasculitis del Sistema Nervioso Central/diagnóstico por imagen , Vasculitis del Sistema Nervioso Central/patología , Vasculitis del Sistema Nervioso Central/complicaciones , Adulto , Persona de Mediana Edad , Estudios Prospectivos , Hemorragia Cerebral/diagnóstico por imagen , Hemorragia Cerebral/patología , Adulto Joven , Corteza Cerebral/diagnóstico por imagen , Corteza Cerebral/patología , Estudios de Cohortes , AdolescenteRESUMEN
Gray matter (GM) atrophies were observed in multiple sclerosis, neuromyelitis optica spectrum disorders (both anti-aquaporin-4 antibody-positive [AQP4+], and -negative [AQP4-] subtypes NMOSD), and myelin oligodendrocyte glycoprotein antibody-associated disease (MOGAD). Revealing the pathogenesis of brain atrophy in these disorders would help their differential diagnosis and guide therapeutic strategies. To determine the neurobiological underpinnings of GM atrophies in multiple sclerosis, AQP4+ NMOSD, AQP4- NMOSD, and MOGAD, we conducted a virtual histology analysis that links T1-weighted image derived GM atrophy and gene expression using a multicenter cohort of 324 patients with multiple sclerosis, 197 patients with AQP4+ NMOSD, 75 patients with AQP4- NMOSD, 47 patients with MOGAD, and 2,169 healthy controls (HCs). First, interregional GM atrophy profiles across the cortical and subcortical regions were determined by Cohen's d between patients with multiple sclerosis, AQP4+ NMOSD, AQP4- NMOSD, MOGAD and HCs. Then, the GM atrophy profiles were spatially correlated with the gene expressions extracted from the Allen Human Brain Atlas, respectively. Finally, we explored the virtual histology of clinical feature relevant GM atrophy by subgroup analysis that stratified by physical disability, disease duration, number of relapses, lesion burden, and cognitive function. Multiple sclerosis showed severe widespread GM atrophy pattern, mainly involving subcortical nuclei and brainstem. AQP4+ NMOSD showed obvious widespread GM atrophy pattern, predominately located in occipital cortex as well as cerebellum. AQP4- NMOSD showed mild widespread GM atrophy pattern, mainly located in frontal and parietal cortices. MOGAD showed GM atrophy mainly involving the frontal and temporal cortices. High expression of genes specific to microglia, astrocytes, oligodendrocytes, and endothelial cells in multiple sclerosis, S1 pyramidal cells in AQP4+ NMOSD, as well as S1 and CA1 pyramidal cells in MOGAD had spatial correlations with GM atrophy profiles were observed, while no atrophy profile related gene expression was found in AQP4- NMOSD. Virtual histology of clinical feature relevant GM atrophy mainly pointed to the shared neuronal and endothelial cells among the four neuroinflammatory diseases. The unique underlying virtual histology patterns were microglia, astrocytes, and oligodendrocytes for multiple sclerosis; astrocytes for AQP4+ NMOSD; and oligodendrocytes for MOGAD. Neuronal and endothelial cells were shared potential targets across these neuroinflammatory diseases. These findings might help their differential diagnosis and optimal therapeutic strategies.
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BACKGROUND: Although trigeminal nerve involvement is a characteristic of multiple sclerosis (MS), its prevalence across studies varies greatly due to MRI resolution and cohort selection bias. The mechanism behind the site specificity of trigeminal nerve injury is still unclear. We aim to determine the prevalence of trigeminal nerve involvement in patients with MS in a consecutive 7T brain MRI cohort. METHODS: This observational cohort originates from an ongoing China National Registry of Neuro-Inflammatory Diseases. Inclusion criteria were the following: age 18 years or older, diagnosis of MS according to the 2017 McDonald criteria and no clinical relapse within the preceding 3 months. Each participant underwent 7T MAGNETOM Terra scanner (Siemens, Erlangen, Germany), using a 32-channel phased array coil at Beijing Tiantan Hospital. T1-weighted magnetisation-prepared rapid acquisition gradient echoes, fluid-attenuated inversion recovery (FLAIR) and fluid and white matter suppression images were used to identify lesions. FLAIR* and T2* weighted images were used to identify central vein sign (CVS) within the trigeminal lesions. RESULTS: 120 patients underwent 7T MRI scans between December 2021 and May 2023. 19/120 (15.8%) patients had a total of 45 trigeminal lesions, of which 11/19 (57.9%) were bilateral. The linear lesions extended along the trigeminal nerve, from the root entry zone (REZ) (57.8%, 26/45) to the pontine-medullary nucleus (42.2%, 19/45). 26.9% (7/26) of the lesions in REZ showed a typical central venous sign. CONCLUSION: In this 7T MRI cohort, the prevalence of trigeminal nerve involvement was 15.8%. Characteristic CVS was detected in 26.9% of lesions in REZ. This suggests an inflammatory demyelination mechanism of trigeminal nerve involvement in MS.
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Imagen por Resonancia Magnética , Esclerosis Múltiple , Nervio Trigémino , Humanos , Masculino , Femenino , Adulto , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/patología , Persona de Mediana Edad , Nervio Trigémino/diagnóstico por imagen , Nervio Trigémino/patología , Estudios de Cohortes , Enfermedades del Nervio Trigémino/diagnóstico por imagen , Adulto JovenRESUMEN
BACKGROUND AND PURPOSE: This study aimed to investigate the clinical efficacy and safety of telitacicept in patients with generalized myasthenia gravis (gMG) who tested positive for acetylcholine receptor antibodies or muscle-specific kinase antibodies and were receiving standard-of-care therapy. METHODS: Patients meeting the eligibility criteria were randomly assigned to receive telitacicept subcutaneously once a week for 24 weeks in addition to standard-of-care treatment. The primary efficacy endpoint was the mean change in the quantitative myasthenia gravis (QMG) score from baseline to week 24. Secondary efficacy endpoints included mean change in QMG score from baseline to week 12 and gMG clinical absolute score from baseline to week 24. Additionally, safety, tolerability and pharmacodynamics were assessed. RESULTS: Twenty-nine of the 41 patients screened were randomly selected and enrolled. The mean (± standard deviation [SD]) reduction in QMG score from baseline to week 24 was 7.7 (± 5.34) and 9.6 (± 4.29) in the 160 mg and 240 mg groups, respectively. At week 12, mean reductions in QMG scores for these two groups were 5.8 (± 5.85) and 9.5 (± 5.03), respectively, indicating rapid clinical improvement. Safety analysis revealed no adverse events leading to discontinuation or mortalities. All patients showed consistent reductions in serum immunoglobulin (Ig) A, IgG and IgM levels throughout the study. CONCLUSION: Telitacicept demonstrated safety, good tolerability and reduced clinical severity throughout the study period. Further validation of the clinical efficacy of telitacicept in gMG will be conducted in an upcoming phase 3 clinical trial.
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Miastenia Gravis , Humanos , Miastenia Gravis/tratamiento farmacológico , Femenino , Masculino , Persona de Mediana Edad , Adulto , Anciano , Resultado del Tratamiento , Receptores Colinérgicos/inmunologíaRESUMEN
BACKGROUND: Recognizing the predictors of poor short-term prognosis after first-line immunotherapy in patients with anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis is essential for individualized treatment strategy. The objective of this study was to ascertain the factors that forecast short-term prognosis in patients with anti-NMDAR encephalitis, develop a prognostic prediction model, and authenticate its efficacy in an external validation cohort. Further, all patients were followed-up long-term to assess the factors of long-term outcome and relapses. METHODS: A prospective enrollment of patients diagnosed with anti-NMDAR encephalitis was conducted across five clinical centers in China from June 2014 to Mar 2022. The enrolled patients were divided into the derivation and validation sets based on enrollment time. The short-term prognostic model was visualized using a nomogram. Further, all patients were followed-up long-term to assess the factors of long-term outcome. RESULTS: This study found that poor short-term prognosis was a risk factor for poor long-term outcome (6-month prognosis, OR 29.792, 95%CI 6.507-136.398, p < 0.001; 12-month prognosis, OR 15.756, 95%CI 3.384-73.075, p < 0.001; 24-month prognosis, OR 5.500, 95%CI 1.045-28.955, p = 0.044). Abnormal behavior or cognitive dysfunction (OR 8.57, 95%CI 1.48-49.79, p = 0.017), consciousness impairment (OR19.32, 95%CI 3.03-123.09, p = 0.002), autonomic dysfunction or central hypoventilation (OR 5.66, 95%CI 1.25-25.75, p = 0.025), CSF pleocytosis (OR 4.33, 95%CI 1.48-12.65, p = 0.007), abnormal EEG (OR 5.48, 95% CI 1.09-27.54, p = 0.039) were independent predictors for a poor short-term prognosis after first-line immunotherapy. A nomogram that incorporated those factors showed good discrimination and calibration abilities. The area under the curve (AUC) for the prognostic model were 0.866 (95%CI: 0.798-0.934) with a sensitivity of 0.761 and specificity of 0.869. CONCLUSION: We established and validated a prognostic model that can provide individual prediction of short-term prognosis after first-line immunotherapy for patients with anti-NMDAR encephalitis. This practical prognostic model may help neurologists to predict the short-term prognosis early and potentially assist in adjusting appropriate treatment timely.
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Encefalitis Antirreceptor N-Metil-D-Aspartato , Humanos , Encefalitis Antirreceptor N-Metil-D-Aspartato/diagnóstico , Masculino , Femenino , Pronóstico , Adulto , China/epidemiología , Adulto Joven , Adolescente , Estudios Prospectivos , Niño , Persona de Mediana Edad , Nomogramas , Estudios de Seguimiento , Pueblos del Este de AsiaRESUMEN
OBJECTIVES: Malnutrition is prevalent in geriatric patients and associated with poor prognosis. This study aimed to evaluate the incremental prognostic value of different nutritional assessment tools in patients (90 years and older) with multimorbidity in China. METHODS: Patients aged ≥90 years with multimorbidity from the Geriatric Research Center in Nanjing Jinling Hospital from January 1, 2008 to December 31, 2018 were analyzed. Patients were followed until December 31,2022. The nutrition status was assessed according to the mini nutritional assessment (MNA), the geriatric nutritional risk index (GNRI), and the prognostic nutritional index score (PNI), respectively. The outcome was all-cause death. Kaplan-Meier method was used to draw the survival curve, and univariate and multivariate Cox proportional risk regression analysis was used to explore the influencing factors of all-cause death in the patients. RESULTS: 160 participants aged 90(90,91) years were included. During a median follow-up of 5.41(3.12-7.64) years, 106(66.25 %) patients died. Deceased patients had lower MNA [20.75(16.75,23.00) vs. 26.00(24.00,26.00); p < 0.001], lower GNRI [96.21±8.75 vs. 100.94±6.80; p = 0.001] and lower PNI [46.16(40.77,49.57) vs. 47.75(45.36,51.53); p = 0.010] than did survivors. According to MNA, GNRI, and PNI score, 93(58.1 %), 72(45.0 %) and 41(25.6 %) of participants were at risk of malnutrition. Multivariate analysis revealed that malnutrition was independently associated with increased risk for mortality by MNA score (adjusted hazard ratio [HR] 2.502, 95 % confidence interval [CI] 1.561-4.009, p<0.001), GNRI score (adjusted HR 1.650, 95 % CI, 1.117-2.438, p = 0.012), and PNI score (adjusted HR 2.894, 95 % CI, 1.891-4.431, p<0.001). Furthermore, the inclusion of malnutrition indicators in the survival prediction model significantly improved the predictive power of mortality. CONCLUSION: The risk of malnutrition, as assessed by MNA, GNRI and PNI, in long-lived patients with multimorbidity is a strong independent predictor of mortality and adds significant prognostic information to the survival models.
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BACKGROUND: Anti-NMDA receptor (NMDAR) encephalitis is an autoimmune disease characterized by complex neuropsychiatric syndrome and cerebrospinal fluid (CSF) NMDAR antibodies. Triggering receptor expressed on myeloid cells 2 (TREM2) has been reported to be associated with inflammation of the central nervous system (CNS). Matrix metalloproteinase-9 (MMP9) and cluster of differentiation (CD44) were measured to evaluate bloodâbrain barrier (BBB) permeability in anti-NMDAR encephalitis. The roles of microglial activation and BBB disruption in anti-NMDAR encephalitis are not well known. FINDINGS: In this work, we detected increased expression levels of CSF sTREM2, CSF and serum CD44, and serum MMP9 in anti-NMDAR encephalitis patients compared with controls. CSF sTREM2 levels were positively related to both CSF CD44 levels (r = 0.702, p < 0.0001) and serum MMP9 levels (r = 0.428, p = 0.021). In addition, CSF sTREM2 levels were related to clinical parameters (modified Rankin Scale scores, r = 0.422, p = 0.023, and Glasgow Coma Scale scores, r = - 0.401, p = 0.031). CONCLUSION: Increased sTREM2 levels in CSF as well as increased CD44 and MMP9 in serum and CSF reflected activation of microglia and disruption of the BBB in anti-NMDAR encephalitis, expanding the understanding of neuroinflammation in this disease. The factors mentioned above may have potential as novel targets for intervention or novel diagnostic biomarkers.
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Encefalitis Antirreceptor N-Metil-D-Aspartato , Barrera Hematoencefálica , Humanos , Metaloproteinasa 9 de la Matriz , Microglía , BiomarcadoresRESUMEN
BACKGROUND: The cerebellum plays key roles in the pathology of multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD), but the way in which these conditions affect how the cerebellum communicates with the rest of the brain (its connectome) and associated genetic correlates remains largely unknown. METHODS: Combining multimodal MRI data from 208 MS patients, 200 NMOSD patients and 228 healthy controls and brain-wide transcriptional data, this study characterized convergent and divergent alterations in within-cerebellar and cerebello-cerebral morphological and functional connectivity in MS and NMOSD, and further explored the association between the connectivity alterations and gene expression profiles. RESULTS: Despite numerous common alterations in the two conditions, diagnosis-specific increases in cerebellar morphological connectivity were found in MS within the cerebellar secondary motor module, and in NMOSD between cerebellar primary motor module and cerebral motor- and sensory-related areas. Both diseases also exhibited decreased functional connectivity between cerebellar motor modules and cerebral association cortices with MS-specific decreases within cerebellar secondary motor module and NMOSD-specific decreases between cerebellar motor modules and cerebral limbic and default-mode regions. Transcriptional data explained > 37.5% variance of the cerebellar functional alterations in MS with the most correlated genes enriched in signaling and ion transport-related processes and preferentially located in excitatory and inhibitory neurons. For NMOSD, similar results were found but with the most correlated genes also preferentially located in astrocytes and microglia. Finally, we showed that cerebellar connectivity can help distinguish the three groups from each other with morphological connectivity as predominant features for differentiating the patients from controls while functional connectivity for discriminating the two diseases. CONCLUSIONS: We demonstrate convergent and divergent cerebellar connectome alterations and associated transcriptomic signatures between MS and NMOSD, providing insight into shared and unique neurobiological mechanisms underlying these two diseases.
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Conectoma , Esclerosis Múltiple , Neuromielitis Óptica , Humanos , Esclerosis Múltiple/diagnóstico por imagen , Esclerosis Múltiple/genética , Neuromielitis Óptica/diagnóstico por imagen , Neuromielitis Óptica/genética , Neuromielitis Óptica/patología , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Imagen por Resonancia Magnética , Cerebelo/diagnóstico por imagen , Cerebelo/patologíaRESUMEN
Varicella-zoster virus (VZV) infection may cause vascular inflammatory changes leading to an increased risk of stroke. Previous studies have focused on the risk of stroke and less on changes in stroke risk and prognosis. We aimed to explore the changing patterns of stroke risk and stroke prognosis after VZV infection. This study is a systematic review and meta-analysis. We searched PubMed, Embase, and the Cochrane Library for studies on stroke after VZV infection between January 1, 2000, and October 5, 2022. Relative risks were combined for the same study subgroups using a fixed-effects model and pooled across studies using a random-effects model. 27 studies met the requirements, including 17 herpes zoster (HZ) studies and ten chickenpox studies. There was an increased risk of stroke after HZ, and this risk decreased over time: relative risk 1.80 (95% CI 1.42-2.29) within 14 days, 1.61 (95% CI 1.43-1.81) within 30 days, 1.45 (95% CI 1.33-1.58) within 90 days, 1.32 (95% CI 1.25-1.39) within 180 days, 1.27 (95% CI 1.15-1.40) at one year and 1.19 (95% CI 0.90-1.59) after one year, with the same trend in the stroke subtype. The risk of stroke after herpes zoster ophthalmicus was higher, with a maximum relative risk of 2.26 (95% CI 1.35-3.78). The risk of stroke after HZ was higher in patients aged around 40 years: relative risk 2.53 (95% CI 1.59-4.02), and similar in men and women. Also, after pooling studies of post-chickenpox stroke, we found that the middle cerebral artery and its branches were most frequently involved (78.2%), with a better prognosis in most patients (83.1%) and less frequent vascular persistence progression (8.9%). In conclusion, the risk of stroke increases after VZV infection, decreasing over time. Post-infection vascular inflammatory changes often occur in the middle cerebral artery and its branches, with a better prognosis in most patients and less frequent persistent progression.
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Varicela , Herpes Zóster , Accidente Cerebrovascular , Masculino , Humanos , Femenino , Anciano , Herpesvirus Humano 3 , Varicela/complicaciones , Herpes Zóster/complicaciones , Riesgo , InflamaciónRESUMEN
BACKGROUND: Hypertrophic olivary degeneration (HOD), a rare form of transsynaptic degeneration, is secondary to dentato-rubro-olivary pathway injuries in some cases. We describe a unique case of an HOD patient who presented with palatal myoclonus secondary to Wernekinck commissure syndrome caused by a rare bilateral "heart-shaped" infarct lesion in the midbrain. CASE PRESENTATION: A 49-year-old man presented with progressive gait instability in the past 7 months. The patient had a history of posterior circulation ischemic stroke presenting with diplopia, slurred speech, and difficulty in swallowing and walking 3 years prior to admission. The symptoms improved after treatment. The feeling of imbalance appeared and was aggravated gradually in the past 7 months. Neurological examination demonstrated dysarthria, horizontal nystagmus, bilateral cerebellar ataxia, and 2-3 Hz rhythmic contractions of the soft palate and upper larynx. Magnetic resonance imaging (MRI) of the brain performed 3 years prior to this admission showed an acute midline lesion in the midbrain exhibiting a remarkable "heart appearance" on diffusion weighted imaging. MRI after this admission revealed T2 and FLAIR hyperintensity with hypertrophy of the bilateral inferior olivary nucleus. We considered a diagnosis of HOD resulting from a midbrain heart-shaped infarction, which caused Wernekinck commissure syndrome 3 years prior to admission and later HOD. Adamantanamine and B vitamins were administered for neurotrophic treatment. Rehabilitation training was also performed. One year later, the symptoms of this patient were neither improved nor aggravated. CONCLUSION: This case report suggests that patients with a history of midbrain injury, especially Wernekinck commissure injury, should be alert to the possibility of delayed bilateral HOD when new symptoms occur or original symptoms are aggravated.
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Ataxia Cerebelosa , Mioclonía , Masculino , Humanos , Persona de Mediana Edad , Mioclonía/complicaciones , Núcleo Olivar/patología , Mesencéfalo/patología , Hipertrofia/patología , Imagen por Resonancia Magnética/métodos , SíndromeRESUMEN
BACKGROUND: Hippocampal involvement may differ between multiple sclerosis (MS) and neuromyelitis optica spectrum disorder (NMOSD). OBJECTIVE: To investigate the morphometric, diffusion and functional alterations in hippocampus in MS and NMOSD and the clinical significance. METHODS: A total of 752 participants including 236 MS, 236 NMOSD and 280 healthy controls (HC) were included in this retrospective multi-center study. The hippocampus and subfield volumes, fractional anisotropy (FA) and mean diffusivity (MD), amplitude of low frequency fluctuation (ALFF) and degree centrality (DC) were analyzed, and their associations with clinical variables were investigated. RESULTS: The hippocampus showed significantly lower volume, FA and greater MD in MS compared to NMOSD and HC (p < 0.05), while no abnormal ALFF or DC was identified in any group. Hippocampal subfields were affected in both diseases, though subiculum, presubiculum and fimbria showed significantly lower volume only in MS (p < 0.05). Significant correlations between diffusion alterations, several subfield volumes and clinical variables were observed in both diseases, especially in MS (R = -0.444 to 0.498, p < 0.05). FA and MD showed fair discriminative power between MS and HC, NMOSD and HC (AUC > 0.7). CONCLUSIONS: Hippocampal atrophy and diffusion abnormalities were identified in MS and NMOSD, partly explaining how clinical disability and cognitive impairment are differentially affected.
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Esclerosis Múltiple , Neuromielitis Óptica , Hipocampo/diagnóstico por imagen , Humanos , Imagen por Resonancia Magnética , Esclerosis Múltiple/diagnóstico por imagen , Neuromielitis Óptica/diagnóstico por imagen , Estudios RetrospectivosRESUMEN
BACKGROUND: Antibodies against myelin-oligodendrocyte-glycoprotein (MOG-Abs) associated disease (MOGAD) has been recognized as a disease entity. Optic neuritis (ON) is the most common symptom in MOGAD. To demonstrate the differences in retinal microvascular characteristics between patients with MOGAD-ON and aquaporin-4 antibody (AQP4-Ab) positive ON. METHODS: In a prospective study, optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA) were used to measure retinal and microvascular parameters. RESULTS: Twenty-six MOGAD-ON eyes, 40 AQP4-ON eyes, and 60 control eyes were included in the study. The thickness of RNFL and GCC in MOGAD-ON eyes was significantly lower than that of HC (p < 0.001, respectively), but comparable to AQP4-ON eyes. The vessel density in retina capillary plexus (RCP) was reduced significantly in MOGAD-ON than that in AQP4-ON (p < 0.05, respectively). The visual accuracy was positively correlated with vessel density of superficial RCP in MOG-ON (p = 0.001) and positively correlated with the thickness of the inner retina layer in AQP4-ON (p < 0.001). CONCLUSION: The retinal neuro-axonal damages between MOGAD-ON and AQP4-ON were comparable. Unlike AQP4-ON eyes, microvascular densities were significantly reduced in MOGAD-ON and were positively correlated with the deterioration of visual acuity in MOGAD-ON. TRIAL REGISTRATION: Clinical and Imaging Patterns of Neuroinflammation Diseases in China (CLUE, NCT: 04106830).
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Neuromielitis Óptica , Neuritis Óptica , Enfermedades de la Retina , Acuaporina 4 , Autoanticuerpos , Humanos , Glicoproteína Mielina-Oligodendrócito , Estudios Prospectivos , Retina , Tomografía de Coherencia ÓpticaRESUMEN
INTRODUCTION: Neuromyelitis optica spectrum disorders (NMOSD) is a rare inflammatory demyelinating disease of the central nervous system. NMOSD pathogenesis is mainly mediated by antibodies directed against aquaporin4 (AQP4 antibody). Immunoadsorption (IA) could specifically remove pathogenic antibody to alleviate the disease. Until now, prospective studies concerning the efficacy of IA on NMOSD are scarce. This study aims to prospectively evaluate the efficacy and safety of IA in the treatment of NMOSD. PATIENTS AND METHODS: We included patients with AQP4 antibody-positive NMOSD who were hospitalized from September 2019 to September 2020, with no significant improvement in symptoms after 1 week of high-dose intravenous steroid therapy. Tryptophan IA therapy was initiated with five sessions on alternate days. Expanded Disability Status Scale (EDSS), visual acuity, and laboratory values were measured before and after IA, with a follow-up of 6 months. Spinal magnetic resonance imaging (MRI) characteristics were collected. Related side effects were recorded. RESULTS: Seven patients were enrolled in the present study. After five IA, the patients' EDSS decreased from 5.71 ± 2.04 to 4.64 ± 2.29, P = .006. The visual acuity of the three visually impaired patients was improved. AQP4-IgG decreased significantly from 80.00 (interquartile range [IQR], 21.00-80.00) (U/mL) to 9.72 (IQR, 5.21-55.57) (U/mL) (P = .018). MRI of the spinal cord showed the scope of the myelopathy was narrowed and no significant enhancement was observed on postcontrast T1-weighted image at 90 days after treatment. Only one patient had transient hypotension. CONCLUSIONS: Tryptophan IA therapy effectively and safely improved neurological function and visual acuity, and reduced the AQP4 antibody concentration in patients with NMOSD.
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Neuromielitis Óptica , Acuaporina 4 , Autoanticuerpos , Humanos , Imagen por Resonancia Magnética , Neuromielitis Óptica/terapia , Estudios Prospectivos , TriptófanoRESUMEN
BACKGROUND: Brain structural alterations and their clinical significance of myelin oligodendrocyte glycoprotein antibody disease (MOGAD) have not been determined. METHODS: We recruited 35 MOGAD, 38 aquaporin 4 antibody positive neuromyelitis optica spectrum diseases (AQP4+ NMOSD), 37 multiple sclerosis (MS) and 60 healthy controls (HC) who underwent multimodal brain MRI from two centres. Brain lesions, volumes of the whole brain parenchyma, cortical and subcortical grey matter (GM), brainstem, cerebellum and cerebral white matter (WM) and diffusion measures (fractional anisotropy, FA and mean diffusivity, MD) were compared among the groups. Associations between the MRI measurements and the clinical variables were assessed by partial correlations. Logistic regression was performed to differentiate MOGAD from AQP4+ NMOSD and MS. RESULTS: In MOGAD, 19 (54%) patients had lesions on MRI, with cortical/juxtacortical (68%) as the most common location. MOGAD and MS showed lower cortical and subcortical GM volumes than HC, while AQP4+ NMOSD only demonstrated a decreased cortical GM volume. MS demonstrated a lower cerebellar volume, a lower FA and an increased MD than MOGAD and HC. The subcortical GM volume was negatively correlated with Expanded Disability Status Scale in MOGAD (R=-0.51; p=0.004). A combination of MRI and clinical measures could achieve an accuracy of 85% and 93% for the classification of MOGAD versus AQP4+ NMOSD and MOGAD versus MS, respectively. CONCLUSION: MOGAD demonstrated cortical and subcortical atrophy without severe WM rarefaction. The subcortical GM volume correlated with clinical disability and a combination of MRI and clinical measures could separate MOGAD from AQP4+ NMOSD and MS.
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Autoanticuerpos , Encéfalo/diagnóstico por imagen , Esclerosis Múltiple/diagnóstico por imagen , Glicoproteína Mielina-Oligodendrócito/inmunología , Neuromielitis Óptica/diagnóstico por imagen , Adulto , Acuaporina 4/inmunología , Femenino , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Esclerosis Múltiple/inmunología , Neuromielitis Óptica/inmunología , Adulto JovenRESUMEN
BACKGROUND: The impact of myelin oligodendrocyte glycoprotein antibody disease (MOGAD) on brain structure and function is unknown. OBJECTIVES: The aim of this study was to study the multimodal brain MRI alterations in MOGAD and to investigate their clinical significance. METHODS: A total of 17 MOGAD, 20 aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorders (AQP4 + NMOSD), and 28 healthy controls (HC) were prospectively recruited. Voxel-wise gray matter (GM) volume, fractional anisotropy (FA), mean diffusivity (MD), and degree centrality (DC) were compared between groups. Clinical associations and differential diagnosis were determined using partial correlation and stepwise logistic regression. RESULTS: In comparison with HC, MOGAD had GM atrophy in frontal and temporal lobe, insula, thalamus, and hippocampus, and WM fiber disruption in optic radiation and anterior/posterior corona radiata; DC decreased in cerebellum and increased in temporal lobe. Compared to AQP4 + NMOSD, MOGAD presented lower GM volume in postcentral gyrus and decreased DC in cerebellum. Hippocampus/parahippocampus atrophy associated with Expanded Disability Status Scale (R = -0.55, p = 0.04) and California Verbal Learning Test (R = 0.62, p = 0.031). The differentiation of MOGAD from AQP4 + NMOSD achieved an accuracy of 95% using FA in splenium of corpus callosum and DC in occipital gyrus. CONCLUSION: Distinct structural and functional alterations were identified in MOGAD. Hippocampus/parahippocampus atrophy associated with clinical disability and cognitive impairment.
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Acuaporina 4 , Neuromielitis Óptica , Encéfalo/diagnóstico por imagen , Sustancia Gris/diagnóstico por imagen , Humanos , Glicoproteína Mielina-Oligodendrócito , Neuromielitis Óptica/diagnóstico por imagenRESUMEN
BACKGROUND: Glucocorticoid (GC) is the first-line therapy in acute attacks of multiple sclerosis (MS), but its efficacy is individually variable and may be associated with glucocorticoid receptor (GR) gene. OBJECTIVE: To establish the association between GR gene sequence and clinical GC sensitivity in Chinese MS patients. And to investigate the expression differences of serum GRα and FK506 binding protein 5 (FKBP5) in GC responders and non-responders. MATERIALS AND METHODS: Coding exons 2-9 of the GR gene from 97 MS patients were sequenced. We performed ELISA to detect serum GRα and FKBP5 before the GC impulse therapy in patients with different GC sensitivities (according to the EDSS changes before and after the GC medication). RESULTS: Seven new mutations were located in exon 2, but the presence or absence of mutations was not associated with the response to GC therapy (P = 0.416). The GC-sensitive patients had higher GRα (P = 0.011) but lower FKBP5 (P = 0.025) levels in the serum. CONCLUSIONS: The GR mutations detected in our study were not associated with the response to GC in Chinese MS patients. Higher GRα and lower FKBP5 levels in the serum might predict the response to GC, which may provide potential therapeutic target for GC-resistant patients with acute MS attack.
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Glucocorticoides , Esclerosis Múltiple , China , Glucocorticoides/uso terapéutico , Humanos , Esclerosis Múltiple/tratamiento farmacológico , Esclerosis Múltiple/genética , Mutación , Receptores de Glucocorticoides/genéticaRESUMEN
BACKGROUND: Sarcopenia is a decrease in skeletal muscle mass, physical performance, and muscle strength in older people. In this study, we aimed to explore the correlation between comorbidity and skeletal muscle mass and physical performance in older people. METHODS: This retrospective study included 168 subjects. Their medical history, physical function, computed tomography (CT) chest scans, and blood tests for nutrition were evaluated. The patients were divided into two groups: (1) a low muscle mass group and (2) a normal muscle mass group. Multivariate analysis of variance was used to compare multiple sets of mean vectors. RESULTS: Overall, 72.02% of the subjects had a low skeletal muscle index (SMI) and low gait speed. The patients with low skeletal muscle mass and physical performance were older, had more serious comorbidities, and had longer average hospitalization periods and lower albumin and hemoglobin levels. Subjects with a high Charlson comorbidity index (CCI) were more likely to be in the sarcopenic group than in the non-sarcopenic group. In addition, there was a linear correlation between the CCI and SMI (r = - 0.549, P < 0.05), and between the CCI and gait speed (r = - 0.614, P < 0.05). The area under the curve (AUC) value for low skeletal muscle mass with the CCI was 0.879. CONCLUSIONS: We identified an independent association between comorbidity and skeletal muscle mass/physical performance by researching the correlation between the CCI and SMI/gait speed. Our results suggested that the CCI score may have important clinical diagnostic value for sarcopenia.
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Fuerza Muscular/fisiología , Músculo Esquelético/fisiopatología , Sarcopenia/epidemiología , Velocidad al Caminar/fisiología , Anciano , Anciano de 80 o más Años , Comorbilidad , Femenino , Humanos , Masculino , Músculo Esquelético/diagnóstico por imagen , Rendimiento Físico Funcional , Estudios Retrospectivos , Sarcopenia/diagnóstico , Tomografía Computarizada por Rayos XRESUMEN
The two most common surgical interventions for spontaneous intracerebral hemorrhage in the basal ganglia of patients more than 65 years old are either minimally invasive puncture and drainage or craniotomy. This study aimed to compare the curative effects of these two procedures in such patients. A retrospective study of patients older than years with spontaneous intracerebral hemorrhage was conducted between January 2012 and December 2015. Of the 86 patients, 47 received minimally invasive puncture and drainage and 39 underwent craniotomy. One year after surgery no statistically significant difference was observed between the two groups with respect to: evacuation rate of the hematoma five days after the operation, volume of residual hematoma, occurrence of rebleeding, development of infectious meningitis, length of hospitalization, fatality, or Glasgow Outcome Scale and Barthel Index scores. However, the amount of blood loss during the procedure (P < 0.001), total cost of hospitalization (P = 0.004), and incidence of epilepsy (P = 0.045) were significantly higher for the craniotomy group than the minimally invasive puncture and drainage group. It was found that, in patients older than 65 years with basal ganglia hemorrhage, minimally invasive puncture and drainage is less invasive, more cost efficient and induces less bleeding during surgery than craniotomy.
Asunto(s)
Hemorragia de los Ganglios Basales/cirugía , Craneotomía/métodos , Paracentesis/métodos , Anciano , Anciano de 80 o más Años , Craneotomía/normas , Femenino , Humanos , Masculino , Procedimientos Quirúrgicos Mínimamente Invasivos/métodos , Procedimientos Quirúrgicos Mínimamente Invasivos/normas , Paracentesis/normas , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
A novel and efficient protocol for the construction of trifluoroethyl pyrazolines has been developed by cascade cyclization/trifluoromethylation reaction of ß,γ-unsaturated hydrazones. This strategy uses cheap and commercially available trichloroisocyanuric acid as promoter and TMSCF3 as the trifluoromethylating reagent, which make the trifluoromethylating process much cheaper. A wide range of substrates can be applied in this process to afford the trifluoroethyl pyrazolines in good yield.
RESUMEN
OBJECTIVE: We investigated the contribution of several cytokines in the pathogenesis of first-onset neuromyelitis optica spectrum disorder (NMOSD) and determined the differences between aquaporin 4 immunoglobulin G (AQP4-IgG)-positive and AQP4-IgG-negative subtypes. METHODS: We enrolled 18 NMOSD (10 AQP4-IgG-positive and 8 AQP4-IgG-negative) and 8 multiple sclerosis (MS) patients, whose serum and cerebrospinal fluid (CSF) samples were collected during the acute phase of the first onset before immunotherapy. Fifteen patients with other noninflammatory neurological diseases (OND) were also included. The serum and CSF levels of interleukin (IL)-6, IL-10, IL-17, IL-21, IL-23, transforming growth factor (TGF)-ß1 and the CSF levels of 3 biomarkers of axonal loss and astrocytic damage were measured using the human cytokine multiplex assay or ELISA. RESULTS: Serum levels of IL-10 and TGF-ß1 and CSF levels of IL-6, IL-10, and TGF-ß1 were significantly increased in first-onset NMOSD compared to in OND patients. In a subgroup analysis, the CSF levels of IL-6, neurofilament light protein (NFL), S100B, and glial fibrillary acidic protein (GFAP) were significantly more elevated in the AQP4-IgG-positive patients than in the AQP4-IgG-negative NMOSD patients. Correlations were found between the CSF cytokines and tissue damage biomarkers and the clinical findings in NMOSD patients. Notably, the CSF IL-6 level had the strongest correlation with the tissue damage biomarkers and it also correlated with CSF white blood cell (WBC) count. CONCLUSIONS: IL-6 plays a role in the pathogenetic process of NMOSD, especially in the AQP4-IgG-positive subtype. Distinct pathogenesis exists between AQP4-IgG-positive and AQP4-IgG-negative NMOSD in the initial phase of the disease.