Neuroimmunology Reports最新文献

{"title":"DNER-IgG screening of 3290 cerebral spinal fluid samples: Two autoimmune cerebellar ataxia cases without tumors in long-term follow-up","authors":"Xinguang Yang ,&nbsp;Peihao Lin ,&nbsp;Sha Liao ,&nbsp;Lihong Jiang ,&nbsp;Huilu Li ,&nbsp;Lufen Xu ,&nbsp;Jiajia Le ,&nbsp;Chun Lian ,&nbsp;Youming Long","doi":"10.1016/j.nerep.2022.100161","DOIUrl":"https://doi.org/10.1016/j.nerep.2022.100161","url":null,"abstract":"<div><h3>Background</h3><p>This study aimed to retrospectively report the findings of delta/notch-like epidermal growth factor-related receptor (DNER)-immunoglobin G (IgG) in cerebral spinal fluid (CSF) in two cases with cerebellar ataxia.</p></div><div><h3>Methods</h3><p>: CSF samples were collected from 3290 patients with possible autoimmune encephalitis. The immunofluorescence pattern was reviewed using a tissue-based assay.</p></div><div><h3>Results</h3><p>: An immunofluorescence pattern with a specific IgG-binding pattern in the cytoplasm of cerebellar Purkinje cells, as well as a fine-dotted pattern in the molecular layer, was found in two samples (0.06%, 2/3290), each from one patient. DNER-IgG was confirmed by cell-based assays. Both of the patients were male and did not have tumors. This suggests that cerebellar ataxia was the main manifestation. Brain magnetic resonance imaging showed non-specific lesions in both patients. One patient responded well to steroid treatment, but the other patient demonstrated a weak response to treatment. During the two-year follow-up period, both patients were stable, and no tumors developed in either patient.</p></div><div><h3>Conclusion</h3><p>The DNER-IgG antibody is rarely found in patients with possible autoimmune encephalitis, and therefore it is not necessarily associated with tumors.</p></div>","PeriodicalId":100950,"journal":{"name":"Neuroimmunology Reports","volume":"3 ","pages":"Article 100161"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50191176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-CRMP5 optic neuropathy associated with oral squamous cell carcinoma","authors":"Corinne Nulton ,&nbsp;Erin Longbrake ,&nbsp;Rafeed Alkawadri ,&nbsp;Cigdem Isitan Alkawadri","doi":"10.1016/j.nerep.2023.100170","DOIUrl":"https://doi.org/10.1016/j.nerep.2023.100170","url":null,"abstract":"<div><h3>Background</h3><p>Paraneoplastic optic neuropathy is a rare condition typically linked to small-cell lung cancer. This report presents the first known case of such neuropathy associated with squamous-cell carcinoma of the tongue, highlighting the importance of considering atypical etiologies in the differential diagnosis of optic neuropathy.</p></div><div><h3>Design/methods</h3><p>Case Report</p></div><div><h3>Results/case presentation</h3><p>A 64-year-old smoker presented with progressive, bilateral, painless visual loss over a month. An eye exam revealed decreased visual acuity and bilateral optic disk edema. Initial external magnetic resonance imaging (MRI) showed minimal enhancement of the optic nerves, raising concerns for optic neuritis. The patient received five days of high-dose intravenous corticosteroids without improvement. Over the next two months, she progressed to a near-total visual loss. Blood tests revealed non-specific polyclonal antibody elevations, and cerebrospinal fluid (CSF) analysis demonstrated pleocytosis and negative infectious workup. Anti-CRMP-5 IgG antibodies (ab) were identified in CSF and serum. Positron emission tomography (PET) scan showed a small focus of hypermetabolism in the left oral cavity and adjacent cervical lymph node. The biopsy identified squamous cell carcinoma of the tongue. High-dose IV steroids and plasmapheresis resulted in minimal visual improvement only. The patient underwent the surgical removal of the primary tumor, and through four years of follow-up, no other malignancies were discovered.</p></div><div><h3>Conclusions</h3><p>To our knowledge, this is the first case report of anti-CRMP5 paraneoplastic optic neuropathy in the setting of squamous cell carcinoma of the tongue. Paraneoplastic etiologies should be considered in the differential diagnosis of optic neuropathy, particularly in older smoker patients.</p></div>","PeriodicalId":100950,"journal":{"name":"Neuroimmunology Reports","volume":"3 ","pages":"Article 100170"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50191499","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Wearing-off phenomenon in multiple sclerosis patients on ofatumumab: A case series","authors":"Amir Labani ,&nbsp;Daniel Becker","doi":"10.1016/j.nerep.2023.100167","DOIUrl":"https://doi.org/10.1016/j.nerep.2023.100167","url":null,"abstract":"<div><h3>Background</h3><p>Multiple sclerosis (MS) patients receiving the disease modifying therapies (DMT) ocrelizumab and natalizumab occasionally report a transient worsening of MS symptoms prior to receiving their next treatment course. This worsening of symptoms is formally referred to as “end-of-dosing-interval” (EDI) or more commonly referred to as the “crap-gap” within the MS community. The etiology of this process remains poorly understood. To our knowledge, no such report has yet been published on patients receiving ofatumumab. In this report, we describe the cases of 3 MS patients who experienced EDI symptoms while on ofatumumab.</p></div><div><h3>Methods</h3><p>Information presented in this case series was collected as part of routine clinical care.</p></div><div><h3>Conclusion</h3><p>This is the first report of MS patients experiencing EDI symptoms on ofatumumab. Clinical providers need to be aware of this phenomenon to better communicate with their patients as they experience these changes. Its existence seems to expand beyond our traditional DMT options especially as new drugs are coming online.</p></div>","PeriodicalId":100950,"journal":{"name":"Neuroimmunology Reports","volume":"3 ","pages":"Article 100167"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50191503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Neuromyelitis optica spectrum disorder and enterovirus-71 infection: A perplexing neurological constellations","authors":"Abeer Sabry Safan ,&nbsp;Wanis H Ibrahim ,&nbsp;Mahfoud Elbashari ,&nbsp;Gholam Adeli","doi":"10.1016/j.nerep.2023.100168","DOIUrl":"https://doi.org/10.1016/j.nerep.2023.100168","url":null,"abstract":"<div><h3>Background</h3><p>Neuromyelitis Optica Spectrum Disorder is a span of neuro-inflammatory diseases with observed predilection towards causing optic neuritis, longitudinally extensive transverse myelitis, area postrema syndrome, and diencephalon syndrome. Despite the revolutionizing discovery of its biomarker (Aquaporin-4-IgG-antibodies), its pathogenesis and possible para-infectious immunogenic triggers are rarely reported and not fully understood.</p></div><div><h3>Clinical presentation</h3><p>We report a case of Neuromyelitis Optica Spectrum Disorder with positive serum aquaporin-4-IgG-antibodies presenting with severe area postrema syndrome for a month followed by one-week of rapid constellations of extensive brainstem syndrome, transverse myelitis, and left optic neuritis. Magnetic Resonance Imaging of the brain and spine revealed left optic neuritis with multilevel patchy areas of intra-axial high T2- signal of the central and dorsal aspect of the medulla oblongata and cervical-thoracic spinal cord with mild patchy postcontrast enhancement in the lower medulla Interestingly, his illness was preceded by fever and flu-like symptoms and a nasopharyngeal swab polymerase chain reaction was positive for Enterovirus-71. The patient's condition gradually improved with remarkable recovery at nine-week mark. He was treated with plasmapheresis, intravenous pulsed methylprednisolone, an intensive six-week rehabilitation program followed by rituximab.</p></div><div><h3>Conclusions</h3><p>Multiple viral infections have been reported to induce Neuromyelitis Optica Spectrum Disorder. To the best of our knowledge, Enterovirus-71 has never been reported to induce this disorder despite its well-reported association with brainstem syndromes and rhombencephalitis. We postulate that this virus has induced immune-cross reactivity that triggered aquaporin-4-IgG-antibodies in our patient which warrants further research.</p></div>","PeriodicalId":100950,"journal":{"name":"Neuroimmunology Reports","volume":"3 ","pages":"Article 100168"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50191179","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-contactin associated protein like 2 autoimmune encephalitis: A case report and review of the literature","authors":"Sarah J. Inbornone ,&nbsp;Timothy N. Holbrook ,&nbsp;Shyam K. Patel ,&nbsp;Edsel Holden ,&nbsp;James Lamb","doi":"10.1016/j.nerep.2022.100157","DOIUrl":"https://doi.org/10.1016/j.nerep.2022.100157","url":null,"abstract":"<div><h3>Background</h3><p>Autoimmune encephalitis is an insidious neurological disease that can present with an array of neuropsychiatric symptoms. Further classification of autoimmune encephalitis is determined by the presence of unique antibodies such as anti-contactin-associated protein-like-2 (anti-CASPR2). CASPR2 is a voltage gated potassium channel that is found in both the central and peripheral nervous systems and is involved in regulating areas around the nodes of Ranvier. Anti-CASPR2 can also be associated with limbic encephalitis or Morvan syndrome with symptoms ranging from seizures, cerebellar dysfunction, hyper-excitability, dysautonomia, insomnia, neuropathic pain, and weight loss.</p></div><div><h3>Case report</h3><p>A 50-year-old Caucasian female presented to the neurology clinic with a four-month history of acute onset insomnia causing anxiety, poor concentration, memory loss, paranoia, as well as a 13-pound weight loss. She reported a positive antinuclear antibody test two years prior with no established diagnosis. Additionally, a recent thyroid stimulating hormone (TSH) antibody and thyroglobulin antibody screen was found to be negative. Supplementary previous labs determined adrenocorticotropic hormone (ACTH) was within normal limits. She had previously tried a myriad of medications including zolpidem, doxepin, mirtazapine, trazodone, temazepam, eszopiclone, and conjugated estrogen. Constant anxiety forced her to quit both her daily activities and job. Neurologic exam and physical exam revealed no abnormalities. Cerebrospinal fluid analysis (CSF) exhibited an elevated protein of 50.6 mg/dL (normal 15 – 45) and an elevated albumin of 28.1 mg/dL (normal &lt;27.0). A comprehensive autoimmune and paraneoplastic encephalitis panel was performed on serum and CSF, which was positive for CASPR2 (1:10 dilution) antibodies in the serum. The patient was started on a moderate dose of prednisone 20 mg daily for three months and scheduled for monthly infusions of intravenous immunoglobulin (IVIG) 1g/kg body weight for one year. Evaluation of paraneoplastic syndrome by a CT of the chest, abdomen, and pelvis with and without contrast revealed no abnormalities. The patient's insomnia began to improve after initiation of the corticosteroids and was scheduled to continue with the IVIG infusions and prednisone. She reports an improvement with mood and has resumed her job as an exercise instructor as well as daily activities.</p></div><div><h3>Conclusions</h3><p>This case report examines the presentation and workup of a 50-year-old female with a four-month history of acute onset insomnia and mood disturbances. She was seen by primary care, sleep medicine, psychiatry, and endocrinology before arriving at the neurology clinic where we discovered anti-CASPR2 antibodies in her serum, suggestive of autoimmune encephalitis. This case review examines the current literature regarding autoimmune encephalitis with CASPR2 antibodies and attempts to elucida","PeriodicalId":100950,"journal":{"name":"Neuroimmunology Reports","volume":"3 ","pages":"Article 100157"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50191500","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Hemiencephalitic presentation of neurosarcoidosis: A case report","authors":"Kyriakoula Varmpompiti,&nbsp;Simon Philip Heller,&nbsp;Anushka Engineer,&nbsp;Eli Silber","doi":"10.1016/j.nerep.2023.100164","DOIUrl":"https://doi.org/10.1016/j.nerep.2023.100164","url":null,"abstract":"<div><h3>Background</h3><p>Neurosarcoidosis is well recognized as a great imitator, however cerebral neurosarcoidosis is usually characterized by a limited spectrum of radiological features which does not include unilateral encephalitis. Truly unilateral encephalitides have a limited differential diagnosis. Most classically there are the infectious causes, predominantly HSV encephalitis, and the inflammatory causes. Rasmussen's syndrome, more common in children, is reported with presentation in adulthood and anti-MOG antibodies have been reported to cause a unilateral cortical inflammation too. However, most of these present acutely, in contrast to our patient who had a subacute presentation.</p></div><div><h3>Case</h3><p>We present a case of atypical neurosarcoidosis presenting with a hemiencephalitis. A subacute history of clinical and radiological deterioration is seen. Because the clinico-radiological picture was atypical for neurosarcoidosis a brain biopsy was performed which revealed granulomatous inflammation of the cortex without clear involvement of the meninges or vasculitis. Subsequent treatment included steroids, methotrexate and infliximab.</p></div><div><h3>Conclusions</h3><p>In conslusion, neurosarcoidosis is a challenging diagnosis because clinical manifestations and imaging findings can be resembled by several other diseases. This case highlights further variation in it's presentation.</p></div>","PeriodicalId":100950,"journal":{"name":"Neuroimmunology Reports","volume":"3 ","pages":"Article 100164"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50191186","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Anti-IgLON5 disease exacerbated by asymptomatic SARS-CoV-2 infection","authors":"Xiaoyang Li,&nbsp;Timothy Landis,&nbsp;Nikoloz Karazanashvili,&nbsp;Monica M. Diaz","doi":"10.1016/j.nerep.2023.100166","DOIUrl":"https://doi.org/10.1016/j.nerep.2023.100166","url":null,"abstract":"<div><h3>Objective</h3><p>To report a case of anti-IgLON5 disease unmasked by asymptomatic SARS-CoV-2 infection.</p></div><div><h3>Background</h3><p>Anti-IgLON5 disease is a clinically heterogeneous disease that shares features of both neurodegeneration and neuroinflammation. The onset can be insidious, posing diagnostic challenges and often resulting in treatment delay. Infectious trigger was rarely reported in this disease.</p></div><div><h3>Case report</h3><p>A 64-year-old male initially presented with 1-year history of progressive parasomnia and mild cognitive decline that precipitously worsened over the course of 1 month following asymptomatic SARS-CoV-2 infection, resulting in dysphagia, parkinsonism, weight loss and dependence on all activities of daily living. He was found to have high titer (1:3840) of anti-IgLON5 antibody in the serum, confirming the diagnosis of anti-IgLON5 disease.</p></div><div><h3>Conclusion</h3><p>Anti-IgLON5 disease as a potentially reversible cause of neurodegenerative syndrome in patients with atypical features. Timely diagnosis and treatment may improve clinical outcomes. It is also worth noting that symptoms precipitously worsened following SARS-CoV-2 infection. We suspect that a COVID-19-mediated immune activation response exacerbated the underlying autoimmune encephalitis process, unmasking his symptoms.</p></div>","PeriodicalId":100950,"journal":{"name":"Neuroimmunology Reports","volume":"3 ","pages":"Article 100166"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50191498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Case of HLA-B27-associated optic neuritis","authors":"Matar Alexandre ,&nbsp;Ibrikji Sidonie ,&nbsp;Bou Ghannam Alaa","doi":"10.1016/j.nerep.2022.100155","DOIUrl":"https://doi.org/10.1016/j.nerep.2022.100155","url":null,"abstract":"<div><p>We report the case of a young woman who presented with chronic relapsing inflammatory optic neuritis (CRION) in association with HLA-B27 and silent brain lesions. The attacks were refractory to steroids but no further attacks occurred on treatment with mycophenolate mofetil. This is one of the few HLA-B27-associated optic neuritis cases reported in the literature, emphasizing the relation of HLA-B27 and inflammation of the brain and optic nerve, as well as the role mycophenolate mofetil might offer in stabilizing the disease.</p></div>","PeriodicalId":100950,"journal":{"name":"Neuroimmunology Reports","volume":"3 ","pages":"Article 100155"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50191501","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Transient organising pneumonia at the onset of AQP4-antibody neuromyelitis optica spectrum disorder: A case series and literature review","authors":"Jonathan Yexian Lai ,&nbsp;Rui Ya Soh ,&nbsp;Kim Hoong Yap ,&nbsp;Kundan Saripalli ,&nbsp;Gareth Zigui Lim ,&nbsp;Adeline Su Lyn Ng ,&nbsp;Kevin Tan ,&nbsp;Tianrong Yeo","doi":"10.1016/j.nerep.2023.100163","DOIUrl":"https://doi.org/10.1016/j.nerep.2023.100163","url":null,"abstract":"<div><h3>Background</h3><p>Aquaporin-4-antibody Neuromyelitis Optica Spectrum Disorder (AQP4-Ab NMOSD) is an immune-mediated inflammatory central nervous system disease. While AQP4 is widely expressed in other tissues, extra-CNS manifestations are rare, with most cases manifesting as hyperCKemia and myositis. Lung involvement manifesting as organising pneumonia in AQP4-Ab NMOSD has rarely been reported.</p></div><div><h3>Case series</h3><p>We present 3 patients with AQP4-Ab NMOSD who developed organising pneumonia at the onset of neurological disease. All 3 had area postrema syndrome and 2 developed longitudinally extensive transverse myelitis. The lung changes resolved spontaneously in 1 patient and after immunotherapy in the other 2 patients. We also tabulated the published cases to date in order to highlight the pertinent clinical and paraclinical features of this association.</p></div><div><h3>Conclusion</h3><p>The close temporal relationship between organising pneumonia and the onset of AQP4-Ab NMOSD suggests that AQP4-Ab autoimmunity is directly involved in the development of organising pneumonia, presumably from the increased susceptibility to AQP4-Ab induced complement-mediated injury in the peripheral tissues of these individuals in light of the current experimental evidence.</p></div>","PeriodicalId":100950,"journal":{"name":"Neuroimmunology Reports","volume":"3 ","pages":"Article 100163"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50191502","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Headache and papilledema: A case of neurosarcoidosis with cerebrovascular involvement","authors":"Karlo Toljan ,&nbsp;Albert Aboseif ,&nbsp;J. Daniel Bireley ,&nbsp;Brandon Moss","doi":"10.1016/j.nerep.2023.100165","DOIUrl":"https://doi.org/10.1016/j.nerep.2023.100165","url":null,"abstract":"<div><h3>Background</h3><p>Cerebrovascular involvement of neurosarcoidosis is a rare albeit increasingly recognized disorder requiring a multidisciplinary approach to diagnosis and management.</p></div><div><h3>Case description</h3><p>We present a case of systemic sarcoidosis with neurological involvement of brain parenchyma and intracranial vasculature, and discuss a step-wise approach to the diagnostic evaluation.</p></div><div><h3>Conclusion</h3><p>An inflammatory vasculitis should be considered in a patient with confirmed or highly suspected sarcoidosis with ischemic stroke. MR angiography with vessel-wall imaging should be pursued early in the evaluation to support this diagnosis. Cerebrovascular complications of sarcoidosis are often responsive to sarcoid-related immunotherapies.</p></div>","PeriodicalId":100950,"journal":{"name":"Neuroimmunology Reports","volume":"3 ","pages":"Article 100165"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50191497","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}