Background:Neuromyelitis optica spectrum disorders (NMOSDs) are degenerative diseases frequently associated with severe recurrences and high risk of progressive disability. In this report, we describe an unusual case of a patient with the coexistence between NMOSD and mixed connective tissue disease (MCTD). Case Description:A 58-year-old Caucasian man was admitted to the Emergency Department (ED) with low back pain and walking inability. He had an unsteady gait, paraesthesia of the lower limbs and pain in the left lumbar area of the spine. He previously manifested repeated episodes of Raynaud's phenomenon. The neurological examination revealed pyramidal signs with asymmetric and progressive paraparesis associated with hypoesthesia and bladder dysfunction. A spine magnetic resonance imaging (MRI) revealed the presence of a long extensive cervico-dorsal myelitis. Among laboratory analyses, serum immunometric examinations came back positive for anti-RNP (272 U/mL) and anti-SSA (20 U/mL) antibodies, whereas a recombinant immunofluorescence assay revealed the presence of immunoglobulin G (IgG) antibodies against AQP4. Consequently, he was treated with high-doses of corticosteroids, with progressive resolution of symptoms. To date, his last cervico-dorsal spine MRI showed negative results. Conclusions:Only a few anecdotal cases of the coexistence between NMOSD and MCTD have so far been described, and many clinical aspects of this association are not yet fully known. Missed diagnosis of rheumatologic or neurologic diseases may lead to treatment delay and, potentially, irreversible disability. Closer collaboration between neurologists and rheumatologists is needed for the early diagnosis of both diseases.

Background: Several results support the hypothesis that a group of pathologies falling within the Neuromyelitis Optica Spectrum Disorders (NMOSD) diagnostic criteria may coexist with Connective Tissue Diseases (CTD) in patients with a high susceptibility to autoimmune conditions. However, the relationship between NMOSD and rheumatologic diseases deserves further investigations to clarify all clinical aspects of this coexistence. We designed a systematic review and a proportional meta-analysis to estimate the association between CTD and MNOSD, with the aim of helping to plan the best strategy to achieve the most significant public health benefit for these conditions. Methods: We conducted a systematic review of the literature published until February 2023, searching in four databases: PubMed, Web of Science, EmBase, and OVID. Then, we conducted a random-effects proportional meta-analysis and assessed the risk of bias of the included studies using the Joanna Briggs Institute checklist. Results: The literature search yielded an overall result of 3176 publications (272 from PubMed, 880 from Web of Science, 634 from EmBase and 1390 from OVID). Of these, 29 were included in this systematic review. Analyzing studies that recruited unselected patients with Systemic Lupus Erythematosus (SLE) and Sjogren Syndrome (SjS), the pooled percentages of NMOSD overlapping were 0.6% (95% Confidence Interval [95% CI]: 0.1%–1.4%,) and 6.5% (95% CI: 4.7–8.6), respectively. Studies enrolling rheumatologic patients with nervous system symptoms involvement reported higher percentage of NMOSD (i.e., among SjS patients, a pooled percentage of 26.5%, 95% CI: 5.5–54.6%, was found). Similarly, recruiting patients with NMOSD, we found pooled percentages of SjS or SLE respectively of 7.0% and 3.5%. Conclusions: Our research found that the coexistence of these two disorders was more frequent in female rheumatologic patients with a SjS diagnosis with neurological manifestations and in neurologic patients for whom a SjS diagnosis was suspected. Similarly, NMOSD are less frequently found in SLE and very rarely incident in Mixed Connective Tissue Disease (MCTD) patients. These considerations should be taken into account in clinical experience of rheumatologists and neurologists, since early diagnosis of both conditions may influence the timing of immunosuppressive therapy and the prevention of systemic disabilities.

BACKGROUND:The anti-SOX-1 antibodies have been mainly associated with Lambert-Eaton Myasthenic Syndrome (LETMS) and Small-Cell Lung Cancer (SCLC). In this report, we describe the interesting case of a patient with serum anti-SOX-1 antibodies and Crohn's Disease (CD) with ensuing neurological symptoms.CASE PRESENTATION:A Caucasian 67-year-old female was admitted to the Emergency Department with seizures, vertigo, emesis, nausea, postural instability and recurrent falls, over a period of 10 days. She had been affected by Crohn's Disease since 1991. A CT scan failed to detect any ischemic or haemorrhagic lesion. A brain MRI revealed signs of leukoencephalopathy. Western blot analysis of her serum revealed a high titre of the onconeural antibody anti-SOX1, consistent with a neurological, cerebellar type, paraneoplastic syndrome. In spite of multiple efforts to unmask a possible underlying malignancy, no neoplastic lesion cropped up during hospitalization. Her clinical conditions progressively deteriorated, up to respiratory failure; a few days later she died, due to ensuing septic shock and Multiple Organ Failure.CONCLUSIONS:Our experience may usher and reveal a new role of anti-neural antibodies, so far reckoned an early indicator of associated malignancy, suggesting that neurological syndromes associated with such antibodies may complicate also chronic Gastrointestinal (GI) diseases. As of now, testing for anti-neuronal antibodies appeared unnecessary within the diagnostic assessment of gastroenterological disorders, which may lead to overlooking incident neurologic autoimmune diseases. Further exploration of such research hypothesis in clinical grounds appears intriguing.