Paraneoplastic Neuromyelitis Optica Spectrum Disorder Associated with Atypical Thymic Carcinoid: A Case Report.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune inflammatory disease, occasionally accompanied by malignant tumors. Immunosuppressive therapy is the mainstay treatment for idiopathic NMOSD; no guidelines have been published for paraneoplastic NMOSD because it is rarely reported in the literature. We report a rare case of a 67-year-old man with paraneoplastic NMOSD associated with thymic carcinoid whose cells expressed aquaporin-4 antibody. After surgical resection, the patient's symptoms improved, and serum aquaporin-4 autoantibody turned negative. We believe that radiographic examination for mediastinal tumors in patients with NMOSD is necessary because thymic epithelial tumors could have a role in the pathogenesis of paraneoplastic NMOSD. After mediastinal tumor has been detected, they should be surgically resected to improve neurological symptoms.

Autologous hematopoietic stem cell transplantation in neuromyelitis optica: a registry study of the EBMT Autoimmune Diseases Working Party.

BACKGROUND: Neuromyelitis optica (NMO) is an inflammatory autoimmune disorder of the central nervous system, hallmarked by pathogenic anti-aquaporin 4 antibodies. NMO prognosis is worse compared with multiple sclerosis. OBJECTIVE: The European Group for Blood and Marrow Transplantation (EBMT) Autoimmune Diseases Working Party (ADWP) conducted a retrospective survey to analyze disease outcome following autologous stem cell transplantation (ASCT). METHODS: This retrospective multicenter study assessed the efficacy and safety of ASCT in 16 patients suffering from refractory NMO reported to the EBMT registry between 2001 and 2011. RESULTS: Fifteen patients were successfully mobilized with cyclophosphamide (Cy) and G-CSF, one with G-CSF alone. All patients received an unmanipulated autologous peripheral blood stem cell graft, after conditioning with BEAM plus anti-thymocyte globulin (ATG, n = 9 patients), thiotepa-Cy (n = 3) or Cy (200 mg/kg) plus ATG (n = 4). After a median follow-up of 47 months, three of 16 cases were progression and treatment free, while in the remaining 13 patients further treatments were administered for disability progression or relapse after ASCT. Altogether, relapse-free survival at three and five years was 31% and 10%, respectively, while progression-free survival remained 48% at three and five years. CONCLUSIONS: In these NMO patients, highly resistant to conventional treatment, ASCT allows for temporary control of the disease, despite a tendency to progress or relapse in the long term.

[Neuromyelitis optica following thymectomy with severe spinal cord atrophy after frequent relapses for 30 years].

A 60-year-old woman had frequent relapses of neuromyelitis optica (NMO) for 30 years despite receiving steroid and azathioprine therapy. She developed MGFA Class IIIb type of myasthenia gravis (MG) at the age of 23, and thymectomy resulted in complete remission of MG. The initial symptoms of NMO, including headache, high fever, retrobulbar optic neuritis, and neurogenic bladder, appeared at the age of 30. Two years later, paraplegia also developed. Although she received oral administration of steroids or azathioprine and intravenous steroid pulse therapy for treatment of NMO for over 30 years, she experienced frequent relapses. The examination at the ages of 58 and 60 years showed that anti-aquaporin-4 antibody was absent. Intravenous immunoglobulin therapy administered in January and June 2009 was effective, and she had 2 years of remission of NMO attack. Spinal MRI after frequent NMO attacks for 30 years revealed an extended spinal cord atrophy involving the lower cervical region and the entire thoracic region. We describe and discuss the prognosis of NMO and the effectiveness of therapies in an NMO patient who underwent thymectomy for MG.

Human umbilical cord mesenchymal stem cell therapy on neuromyelitis optica.

Stem cell transplantation is a promising therapy for neuromyelitis optica (NMO). Among stem cell varieties, human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) possess many advantages, add a differential potential into neural cells, secrete a set of trophic factors and cytokines, regulate immunological function, and have therapeutic potential for neurological diseases. In this study, hUC-MSCs transplantation was used to treat five NMO patients with follow-up for 18 months including evaluation of Expanded Disability Status Scale (EDSS) levels, clinical course, magnetic resonance imaging (MRI) characteristics, adverse events, and so on. Among the five cases, four showed therapeutic improvement after hUC-MSCs treatment. Both symptoms and signs improved and relapse frequencies were reduced. MRI characteristics also showed decreased volume and severity of lesions, while few adverse events occurred. The results suggest that hUC-MSCs transplantation appear safe and might be effective for NMO treatment in the near future. In addition, according to flow cytometry assay (FACS) results, B cells of blood were inhibited while T cells increased after treatment, indicating an immune-related mechanism.

A preliminary result of treatment of neuromyelitis optica with autologous peripheral hematopoietic stem cell transplantation.

Autologous peripheral hematopoietic stem cell transplantation (APHSCT) was performed to treat a patient with neuromyelitis optica. We observed that the patient achieved clinical remission after APHSCT during 12 months of follow-up. The patient improved on the expanded disability status scale neurologic assessment and the Scripps neurologic rating scale worksheet scores on follow-up examination compared with baseline. The MRI abnormalities on T1WI and T2WI improved. The postpartum maternal blood helper T (CD3+CD4+ T cell) and the CD4+/CD8+ ratio were decreased, and the cytotoxic T (CD3+CD8+ T) cell increased. This shows that APHSCT in this patient with neuromyelitis optica appears to reduce the frequency of attacks with improvement in disability. However, a larger study with more patients and a longer follow-up would be required to assess the encouraging preliminary results.

A 10-year old girl with neck pain.

Neuromyelitis optica (NMO), (Devic's disease), is a relatively uncommon autoimmune disease predominantly involving the spinal cord and optic nerves. We present a 10 year-old female with intermittent neck pain, progressive right upper and bilateral lower extremity weakness. MR imaging and intraoperative findings were strongly suggestive of a neoplastic process. However, pathologic examination showed an inflammatory demyelinating lesion and serological studies were positive for NMO-IgG. The patient improved dramatically following resection of the compressive "pseudotumor", with resolution of her preoperative deficits. This case underscores the diverse clinical presentation of neuromyelitis optica and the importance of maintaining a broad differential diagnosis in pediatric lesions resembling neoplasms.

Neuromyelitis optica in patients with myasthenia gravis who underwent thymectomy.

BACKGROUND: Myasthenia gravis (MG) and neuromyelitis optica (NMO, also known as Devic disease) are rare autoimmune disorders, with upper-limit prevalence estimates in the general population of 15 per 100,000 and 5 per 100,000, respectively. To our knowledge, an association between these diseases has not been previously reported. OBJECTIVES: To describe 4 patients with MG who developed NMO after thymectomy and to analyze possible causes of apparent increased prevalence of NMO among patients with MG. DESIGN: Case series. PATIENTS: Four patients with MG who underwent thymectomy. INTERVENTIONS: None. RESULTS: The prevalence of MG within the published cohort of patients with NMO is more than 150 times higher than that in the general population. CONCLUSION: Dysregulation of B-cell autoimmunity in myasthenia, possibly exacerbated by loss of control over autoreactive cells as a result of thymectomy, may predispose patients to the development of NMO.