Double seronegative neuromyelitis optica spectrum disorder (DN-NMOSD) is a rare autoimmune disease of the central nervous system, typically involving the optic nerve and spinal cord, characterized by negativity for anti-AQP4 and anti-MOG antibodies. A 35-year-old man with optic neuritis and recurrent myelitis, negative for AQP4 and MOG antibodies, was diagnosed with double seronegative NMOSD (DN-NMOSD). Initial treatment with Rituximab led to temporary stability, but relapses in 2021 and 2022 prompted a switch to Satralizumab (anti-IL-6R), achieving two years of clinical and radiological stability. This case underscores the therapeutic potential of anti-IL-6 drugs for DN-NMOSD, especially when anti-CD20 therapies fail. It highlights the heterogeneity of DN-NMOSD and the need for novel biomarkers, such as GFAP, tau, and IL-6, to better understand disease mechanisms and guide targeted treatments. A structured therapeutic approach, starting with anti-CD20 drugs and progressing to anti-IL-6 agents if ineffective, may optimize outcomes in this poorly understood condition.

MOGAD is a demyelinating syndrome with the presence of antibodies against myelin oligodendrocyte glycoprotein, which is, next to multiple sclerosis and the neuromyelitis optica spectrum, one of the manifestations of the demyelinating process, more common in the pediatric population. MOGAD can take a variety of clinical forms: acute disseminated encephalomyelitis (ADEM), retrobulbar optic neuritis, often binocular (ON), transverse myelitis (TM), or NMOSD-like course (neuromyelitis optica spectrum disorders), less often encephalopathy. The course may be monophasic (40-50%) or polyphasic (50-60%), especially with persistently positive anti-MOG antibodies. Very rarely, the first manifestation of the disease, preceding the typical symptoms of MOGAD by 8 to 48 months, is focal seizures with secondary generalization, without typical demyelinating changes on MRI of the head. The paper presents a case of a 17-year-old patient whose first symptoms of MOGAD were focal epileptic seizures in the form of turning the head to the right with the elevation of the left upper limb and salivation. Seizures occurred after surgical excision of a tumor of the right adrenal gland (ganglioneuroblastoma). Then, despite a normal MRI of the head and the exclusion of onconeural antibodies in the serum and cerebrospinal fluid after intravenous treatment, a paraneoplastic syndrome was suspected. After intravenous steroid treatment and immunoglobulins, eight plasmapheresis treatments, and the initiation of antiepileptic treatment, the seizures disappeared, and no other neurological symptoms occurred for nine months. Only subsequent relapses of the disease with typical radiological and clinical picture (ADEM, MDEM, recurrent ON) allowed for proper diagnosis and treatment of the patient both during relapses and by initiating supportive treatment. The patient's case allows us to analyze the multi-phase, clinically diverse course of MOGAD and, above all, indicates the need to expand the diagnosis of epilepsy towards demyelinating diseases: determination of anti-MOG and anti-AQP4 antibodies.

Some patients with neuromyelitis optica spectrum disorder (NMOSD)-like symptoms test negative for anti-aquaporin-4 (anti-AQP4) antibodies. Among them, a subset has antibodies targeting myelin oligodendrocyte glycoprotein (MOG), a condition now termed MOG antibody-associated disease (MOGAD). MOGAD shares features with NMOSD, like optic neuritis and myelitis, but differs in pathophysiology, clinical presentation, imaging findings, and biomarkers. The present study investigated the prevalence of anti-myelin oligodendrocyte glycoprotein (anti-MOG) antibodies in anti-AQP4 seronegative Egyptian patients initially diagnosed with NMOSD and the link between their presence and clinical characteristics and disease-induced disability to gain insights into MOGAD. This pilot cross-sectional study included 40 anti-AQP4 antibody-negative patients initially diagnosed with NMOSD, six children and 34 adults. They were screened for anti-MOG antibodies by the indirect immunofluorescence cell-based assay. Of all included patients, only 7.5% (n = 3) were positive for anti-MOG antibodies and had significantly higher disability scores than seronegative patients (p = 0.021). The presence of anti-MOG antibodies was not significantly associated with age (p = 0.696), gender (p = 0.232), type of relapse (p = 0.488), number of attacks (p = 0.968), family history of consanguinity (p = 0.211), family history of autoimmune disease (p = 0.608), nor with smoking (p = 0.608). Detecting anti-MOG antibodies in anti-AQP4-negative NMOSD patients is essential for accurate diagnosis and personalized treatment, as MOGAD is now recognized as a separate clinical entity.

The coexistence of neuromyelitis optica spectrum disorders (NMOSD) with other autoimmune diseases (AID) has been increasingly reported. The prevalence and significance of this association are not fully understood. This study aimed to compare the clinical and laboratory characteristics in NMOSD patients with and without AID. Retrospective cross-sectional observational study was conducted involving adults meeting NMOSD criteria followed in a neuroimmunology clinic at a tertiary center. Descriptive analysis of clinical/paraclinical/treatment/outcome data collected from the medical records was compared between NMOSD patients with AID (polyautoimmunity) and those without AID. From a cohort of 46 NMOSD patients, 16 (34.8 %) patients, mostly women around 40 years of age, presented with polyautoimmunity: 10 anti-AQP4 positive, 4 anti-MOG positive, and 2 seronegative. Five different organ -specific AID, and six systemic AID were identified in the polyautoimmunity patients group, in addition to 6 cases of multiple autoimmune syndrome. The AID manifestation preceded NMOSD in 10 (62.5 %) patients, with a median interval of 7 years. The NMOSD with polyautoimmunity and NMOSD without AID groups had similar initial clinical manifestations with optic neuritis and/or myelitis being most frequent. Inflammatory CSF, namely elevated proteins, was more common in the polyautoimmunity group (13.0 % in NMOSD vs. 31.3 % in NMOSD+AID, p = 0.003). After a 10±6 years follow-up period, more patients with polyautoimmunity had a relapsing disease (75.0 % in NMOSD vs. 46.7 % in NMOSD+AID, p = 0.012) but no difference in the functional outcome evaluated by the EDSS score was identified. Polyautoimmunity was common in AQP4 positive NMOSD patients leading to a significantly higher risk of disease recorrence. The presence of polyautoimmunity and multiple autoimmune syndrome in NMOSD patients suggests the existence of common susceptibility factors or pathophysiological mechanisms, emphasizing the importance of a multidisciplinary approach to those patients.

In patients with SLE, concurrent NMOSD can manifest with optic neuritis and transverse myelitis. AQP-4 antibody positivity confirms the diagnosis. Prompt treatment is critical to manage the acute symptoms and prevent relapses, as highlighted by a young patient's case with optic neuritis and extensive spinal cord lesions. Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune disorder of the central nervous system that affects the optic nerve and spinal cord. It is associated with autoantibodies against aquaporin-4 (AQP-4) and/or myelin oligodendrocytes glycoproteins. It is diagnosed based on clinical, radiological, and serological criteria, and treated with immunosuppressants in the acute phase. Long-term immunosuppression is essential to prevent potential relapses. In this case report, we present the case of a 19-year-old female patient with systemic lupus erythematosus (SLE), who presented with blurriness and loss of vision in her left eye. Optical coherence tomography was normal, but a gadolinium-enhanced cervico-dorsal MRI showed multiple lesions extending from the brainstem to the C7-T1 junction suggestive of longitudinally extensive transverse myelitis (LETM), the largest of which was a cystic lesion at the cervico-spinal junction. A contrast injection also revealed left optic neuritis. Cerebrospinal fluid analysis showed elevated IgG and red blood cell count, but no oligoclonal bands. The patient tested positive for AQP-4 autoantibodies, confirming the diagnosis of NMOSD. Treatment with intravenous methylprednisolone led to partial improvement, but the patient experienced a relapse with severe neurological symptoms, including tetraplegia and bladder and bowel dysfunction. This case illustrates the importance of considering NMOSD in the differential diagnosis of patients with SLE who present with optic neuritis and/or myelitis, especially when MRI findings are suggestive of LETM. Early diagnosis and adherence to treatment are crucial to prevent further relapses and deleterious sequelae.