Recurrent attacks of optic neuritis and myelitis are the hallmarks of both neuromyelitis optica (NMO) and multiple sclerosis (MS). NMO immunoglobulin G (NMO-IgG), which recognizes astrocytic ...aquaporin-4 (AQP4) water channels, is a specific serum autoantibody that distinguishes NMO from MS. The pathogenic role of the anti-AQP4 antibody (AQP4-Ab, NMO-IgG) in NMO has been speculated based on several studies in vitro. The aim of this study was to demonstrate the pathogenicity of AQP4-Ab in vivo. We obtained IgG from patients who underwent therapeutic plasmapheresis, and developed an animal model by passive transfer of IgG to rats. The active lesions of the rats exhibited pathological characteristics strikingly similar to those of NMO, marked by astrocytic loss and perivascular deposition of immunoglobulin and complements. These findings provide the first evidence of the pathogenicity of AQP4-Ab in vivo and support the therapeutic efficacy of eliminating the antibodies by plasmapheresis.
Purpose
The word “fixel” refers to the specific fiber population within each voxel, and fixel-based analysis (FBA) is a recently developed technique that facilitates fiber tract-specific statistical ...analysis. The aim of the paper is to apply FBA to detect impaired fibers for corticobasal syndrome (CBS) especially in regions that contain multiple crossed fibers.
Methods
FBA was performed in cohorts of participants clinically diagnosed with CBS (
n
= 10) and Parkinson’s disease (
n
= 15) or in healthy controls (
n
= 9). The parameters of the diffusion weighted image were echo time, 83 ms; time, 8123.6 ms; flip angle, 90°; section thickness, 2 mm;
b
= 1000 s/mm
2
; and 32 axes. Diffusion tensor analysis was conducted using tract-based spatial statistics (TBSS), and white matter volume was estimated via voxel-based morphometry.
Results
A comparison of PD or HC to CBS revealed a significant difference in the dentatorubrothalamic tract of the brainstem in FBA in addition to the affected regions in voxel-based morphometry and TBSS (family-wise error-corrected
p
< 0.05). Reduction of the white matter fibers crossing the brainstem could not be detected via microstructural changes identified using TBSS, but it was detected using FBA.
Conclusion
FBA has some advantages in determining the distribution of corticobasal syndrome lesions.
Neuromyelitis optica (NMO) is an inflammatory demyelinating disease of the central nervous system (CNS). Anti-aquaporin-4 antibody (AQP4-Ab) is a highly specific serum autoantibody that is detected ...in patients with NMO. Several lines of evidence indicate that AQP4-Ab not only serves as a disease marker but also plays a pivotal role in the pathogenesis of NMO. Although the pathogenicity of AQP4-Ab in vivo has recently been demonstrated, the presence of CNS antigen-specific T cells is recognized as a prerequisite for the antibody to exert pathogenic effects. Thus, it remains unclear whether AQP4-Ab is the primary cause of the disease or a disease-modifying factor in NMO. Here we report that pre-treatment with complete Freund’s adjuvant (CFA) alone is sufficient for AQP4-Ab to induce astrocytic damage in vivo. Our results show the primary pathogenic role of AQP4-Ab in the absence of CNS antigen-specific T cells, and suggest that danger signals provided by nonspecific inflammation can be a trigger for those who harbor the autoantibody to develop NMO.
Abstract Recent studies have suggested that the elevation of intracellular chloride contributes to excitotoxic cell death in motor neuron and can be related to the pathogenesis of amyotrophic lateral ...sclerosis (ALS). We investigated whether chloride levels in cerebrospinal fluid (CSF) and serum were lower in ALS patients than in control patients with other neurological diseases (OND). We also examined the relationship between chloride levels and clinical ALS phenotypes. We measured chloride levels (CSF and serum) in 27 ALS patients and 33 age- and gender-matched OND controls admitted to our hospital for diagnosis. The CSF chloride levels were lower in ALS patients (117 range 102–130 mmol/L) than in OND controls (126 range 114–134 mmol/L) ( P < 0.0001). However, no significant difference was found in their serum chloride levels ( P > 0.05). There was no significant difference in CSF chloride levels among the sub-groups of ALS patients classified according to their age, gender, duration of illness, clinical state and type of onset ( P > 0.05). CSF chloride levels already significantly decreased in ALS patients at the time of diagnosis. We conclude that the elevation of intracellular chloride would cause the reduction of chloride in CSF and be related to the pathogenesis of ALS.
The concept of neural reorganization after brain damage is already well established, and many previous studies have successfully reported the translocation of the neural activation in the ...motor-related cortices during motor tasks using functional imaging modalities. Several primate and human studies have suggested the formation of newly reorganized tracts in the ipsilesional or contralesional hemisphere, but the mechanism for the formation of these tracts is still largely unknown.
Three acute stroke patients who presented with abrupt deterioration of their right-sided hemiparesis due to the infarcts following a recurrent stroke in the originally unaffected hemisphere were studied using magnetic resonance imaging (MRI), MR angiography and single-photon emission CT. The relationship between the neurological symptom on admission and the precise location of the new infarct was carefully investigated from the perspective of reorganization.
Diffusion-weighted MRI showed a new subcortical infarct in the right hemisphere contralateral to the initial stroke in all patients. These new lesions involved the thalamus, globus pallidus or corona radiata, sparing the area of the internal capsule. T2-weighed MRI on admission showed an old infarct in the left middle cerebral artery territory, which had caused the original right-sided hemiparesis.
It is proposed that the 'extrapyramidal' motor pathway in the unaffected hemisphere is associated with poststroke neural reorganization.
