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.

Myasthenia gravis (MG) is a disease that causes muscle weakness and fatigue due to an abnormality in the neuromuscular junction, which prevents the transmission of information. In the 1970s, it became clear that MG was caused by an autoimmune mechanism, and treatments began to be developed. Most studies on the pathophysiology and treatment of MG have been conducted in adults. However, even in terms of acetylcholine receptor antibodies, which are related to MG pathophysiology, adults and children differ significantly. Moreover, epidemiological studies around the world have revealed significant differences in the prevalence of MG between East Asia, Europe, and the United States. Treatment methods also differ slightly across countries, depending on the differences in pathophysiology and medical practices that have been developed in each region of the world. Japanese pediatric neurologists have revealed a pathophysiology unique to children and differences in treatment methods for childhood MG. However, few studies have systematically reported these findings. Therefore, this article reviews the current basic concepts related to the pathophysiology and treatment of childhood MG in Japan.

Central nervous system (CNS) vasculitis is an uncommon inflammatory disease that affects the brain and spinal cord. It might present with headache, focal neurological deficits, seizures and encephalopathy. CNS vasculitis might be triggered by systemic vasculitides, connective tissue diseases, malignancies and infectious agents, including severe acute respiratory syndrome coronavirus 2. Diagnosis requires a combination of clinical presentation, serological and cerebral spinal fluid analysis, radiological findings (magnetic resonance imaging and conventional angiography), and brain biopsy. In the lack of randomized prospective studies, the treatment approach is based on retrospective cohort studies, anecdotal reports and therapeutic approaches derived from other vasculitides. In this report, we present a case of a 55-year-old man who presented with hemiparesthesia 39 days after coronavirus disease 2019 (COVID-19) infection. During the disease course, the patient developed right-sided hemiparesis and was referred to our center. Conventional angiogram suggested CNS vasculitis. After an extensive work-up, systemic vasculitis was excluded. Despite having been treated with pulse steroid and cyclophosphamide, the patient experienced relapses. As we administered intravenous immunoglobulin and rituximab, remission was achieved both in clinical and radiological aspects. In this study, we present the first case of treatment-refractory CNS vasculitis associated with COVID-19, which was treated successfully with intravenous immunoglobulin and rituximab. Second, we report a review of COVID-19-related CNS vasculitis articles and applied treatment strategies published in English. To elucidate the mechanism of COVID-19-related CNS vasculitis, further research is needed.