Sleep Disturbances in Autoimmune Neurological Diseases.

PURPOSE OF REVIEW: To summarize the current evidence on the associations between autoimmune neurological diseases (e.g., multiple sclerosis, myasthenia gravis) and sleep disturbances (e.g., insomnia, parasomnias), as well as to review the main characteristics of sleep disorders with an immune-related pathophysiology (e.g., narcolepsy, anti-IgLON5 disease). RECENT FINDINGS: An immune-mediated damage of the areas in the central nervous system that control sleep and wake functions (e.g., hypothalamus, brainstem) can lead to sleep disorders and sleep symptoms. Sleep disturbances are the reason to seek for medical attention in certain neuroimmunological conditions (e.g., narcolepsy, anti-IgLON5 disease) where sleep-related alterations are the main clinical feature. The assessment of sleep-related symptomatology and disorders should be included in the routine evaluation of patients with autoimmune neurological diseases. Clinicians should be aware of the typical clinical presentation of certain neuroimmunological disorders mainly affecting sleep.

Neuromyelitis Optica Spectrum Disorder.

Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune condition characterized by recurrent episodes of optic neuritis (ON) and transverse myelitis. This case report aims to highlight the importance of considering atypical presentations of NMOSD when confronted with MRI-detected Wernicke's encephalopathy. The primary target in NMOSD is the aquaporin-4 (AQP4) protein, predominantly located on astrocyte surfaces. Antibodies binding to AQP4 can lead to astrocyte dysfunction and damage, contributing to NMOSD's distinctive pathology. The associated immune response and inflammation can cause secondary harm to various components of the central nervous system, including oligodendrocytes and neuronal axons. This inflammatory process results in perivascular demyelination and axonal injury, further aggravating neurological deficits in NMOSD. In this case, we present a 39-year-old female with no prior medical or surgical history who sought medical attention due to a three-week history of progressive eyelid heaviness and somnolence. NMOSD is an autoimmune condition primarily targeting the AQP4 protein, resulting in recurrent ON and transverse myelitis. The patient was initially misdiagnosed with myasthenia gravis due to somnolence and ptosis. Due to concerns about myasthenia gravis due to diffuse fatigue and bilateral ptosis, the patient was initially treated with intravenous immunoglobulin (IVIG) and admitted to the neurology service. On the first day of her hospitalization, MRI with and without contrast revealed extensive, non-enhancing T2-weighted-fluid-attenuated inversion recovery (T2-FLAIR) hyperintensities surrounding the third ventricle and affecting the periaqueductal grey, medial thalami, and mammillary bodies. There was also an interval increase in T2-FLAIR hyperintensity within the right medial temporal lobe, extending more posteriorly and inferiorly, abutting the temporal horn. Subsequent CSF encephalitis panel results showed positive West Nile virus (WNV) IgG but negative WNV IgM, and AQP4 antibodies were positive. Given the high specificity of AQP4 antibodies, the patient was diagnosed with neuromyelitis optica (NMO) encephalitis. This case underscores the importance of considering atypical presentations of NMO when confronted with MRI-detected Wernicke's encephalopathy. Since our patient primarily displayed somnolence and eye-related symptoms, neither NMO nor Wernicke's encephalopathy were initially considered in the differential diagnosis. Furthermore, despite MRI findings suggestive of Wernicke's encephalopathy, it was considered less likely due to the absence of thiamine deficiency and consistent denials by family members regarding alcohol use, gastrointestinal issues, or inadequate oral intake. This case underscores the importance of considering NMOSD in patients with atypical symptoms, even when initial presentations suggest other conditions. Timely diagnosis is crucial to prevent mismanagement and improve patient outcomes. Clinicians should maintain a high level of suspicion for NMOSD, especially when MRI findings do not align with the initial diagnosis, as early recognition and treatment can significantly impact patient care and prognosis.

Effect of different initial rituximab regimens on B cell depletion in children with autoimmune neurological diseases.

BACKGROUND: Rituximab (RTX) is a promising B-cell-depleting monoclonal antibody used to treat several autoimmune neurological diseases in children. The RTX administration regimen relies on the reconstitution of B cells in the peripheral blood. OBJECTIVE: The objective of this study was to investigate the effect of different initial RTX regimens on B cell depletion. METHODS: This single-center retrospective analysis included children with autoimmune neurological diseases who received RTX; Group 1 received two infusions of 375 mg/m2 RTX, while Group 2 received four infusions of the same dose. We examined the evolution of B cells at regular intervals in patients. The time required for B cell reconstitution, risk factors, and the effect on immunoglobulin (Ig) and T cells were studied. RESULTS: A total of 113 patients with the first course of rituximab were included. Median time required for B cell reconstitution was 147.7 [130.1-165.2] and 181.9 [165.2-198.6] days in Group 1 and 2 respectively (p = 0.008). Ig production was affected by RTX, which reduced IgG, IgA and IgM serum concentrations, yet within the normal level. There was significant difference in the decline of IgG between the two groups. Absolute cell counts for T cells did not change over time after treatment, and the variation trend was similar in the two groups. CONCLUSION: The initial regimen of RTX impacts time required for B cell reconstitution. There was an increased time to B cell reconstitution with four standard infusions of RTX when compared with two standard infusions. Furthermore, as the prolonged B cell depletion leads to decreased antibody production, regular measurements of serum Ig concentrations after RTX treatment and follow-up should be performed regularly.

CD8(+) T Cell-Mediated Neuronal Dysfunction and Degeneration in Limbic Encephalitis.

Autoimmune inflammation of the limbic gray matter structures of the human brain has recently been identified as major cause of mesial temporal lobe epilepsy with interictal temporal epileptiform activity and slowing of the electroencephalogram, progressive memory disturbances, as well as a variety of other behavioral, emotional, and cognitive changes. Magnetic resonance imaging exhibits volume and signal changes of the amygdala and hippocampus, and specific anti-neuronal antibodies binding to either intracellular or plasma membrane neuronal antigens can be detected in serum and cerebrospinal fluid. While effects of plasma cell-derived antibodies on neuronal function and integrity are increasingly becoming characterized, potentially contributing effects of T cell-mediated immune mechanisms remain poorly understood. CD8(+) T cells are known to directly interact with major histocompatibility complex class I-expressing neurons in an antigen-specific manner. Here, we summarize current knowledge on how such direct CD8(+) T cell-neuron interactions may impact neuronal excitability, plasticity, and integrity on a single cell and network level and provide an overview on methods to further corroborate the in vivo relevance of these mechanisms mainly obtained from in vitro studies.