Clinical and Experimental Neuroimmunology最新文献

Using proteomic analysis, we identified anti-NAE antibodies (autoantibodies against NH₂-terminal of alpha-enolase) as a diagnostic marker for Hashimoto's encephalopathy (HE). As cases of HE with serum anti-NAE antibodies accumulated, the clinical spectrum of HE with anti-NAE antibodies became expanded. In addition, it is now known that antibodies can be detected in other diseases that differ from conventional HE. We recently reported the detection of anti-NAE antibodies in patients with a clinical diagnosis of multiple system atrophy or corticobasal syndrome. These findings suggest that anti-NAE antibodies indicate an immune mechanism in the pathogenesis of neurodegenerative diseases. We propose a novel disease concept for anti-NAE antibody-associated disorders (NAEAD). The clinical spectrum of NAEAD is not limited to HE but is a broad spectrum that partially shares several autoimmune neurological diseases, including autoimmune acute encephalopathy, autoimmune cerebellar ataxia, and autoimmune psychosis, and even extends to immune-associated neurodegenerative diseases.

We report a rare case of paraneoplastic neurological syndrome with dual seropositivity of anti-aquaporin-4 and myelin oligodendrocyte glycoprotein antibodies in a 40 year-old woman with metastatic triple-negative breast cancer. She received multiple lines of anti-neoplastic treatment, including immunotherapy with pembrolizumab, as well as cytotoxic chemotherapy. Paraneoplastic meningoencephalomyelitis developed 2 years after diagnosis of breast cancer and 1 year after discontinuation of immunotherapy with pembrolizumab. She first developed longitudinally extending transverse myelitis followed by left optic neuritis and meningoencephalitis with new enhancing lesions in the brain and spinal leptomeninges. Cerebrospinal fluid analysis during both episodes showed normal glucose and protein, and elevated white blood cell count. Cytology was negative for malignancy. Cerebrospinal fluid was positive for neuromyelitis optica immunoglobulin G antibody anti-aquaporin-4, and autoimmune myelopathy panel was positive for myelin oligodendrocyte glycoprotein antibody. The patient had significant clinical and radiographic improvement after completion of five cycles of plasmapheresis followed by intravenous immunoglobulin. She did not have recurrence of paraneoplastic syndrome with maintenance rituximab every 6 months and daily low-dose prednisone. She succumbed to progressive systemic metastatic disease 4.5 years after her breast cancer diagnosis. This case shows that these antibodies can occur concurrently and cause clinical features, such as both neuromyelitis optica spectrum disorder and myelin oligodendrocyte glycoprotein antibody disease, in a patient with a singular type of cancer. We highlight the importance of testing for paraneoplastic etiology in cancer patients with radiographic menigoencephalomyelitis or meningitis with atypical symptoms of meningeal carcinomatosis and/or cerebrospinal fluid profile negative for leptomeningeal carcinomatosis.

Autoimmune epilepsy is characterized as a subtype of autoimmune encephalitis, where epileptic seizures serve as the primary or predominant manifestation of the disease. Among patients who are refractory to antiepileptic drug therapy, a part of them experience improved seizure control with immunotherapy. Some of these individuals have been found to possess autoantibodies that target the neuronal surface, intracellular, or extracellular antigens. In 2017, the International League Against Epilepsy (ILAE) proposed a new classification of epilepsy syndromes that, for the first time, recognized “immune” as one of the etiologies of epilepsy. Since early and prompt diagnosis and treatment of autoimmune epilepsy may improve the prognosis, it is crucial to actively consider the utilization of reported diagnostic features and treatment with immunotherapy in the management of patients with refractory epilepsy. We herein provide a review of the literature concerning the clinical features, laboratory findings, pathophysiology, and treatment options associated with this disease.