The intrathecal chemotherapy with methotrexate and cytarabine arabinoside is used for the treatment and prophylaxis of the primary central nervous system lymphoma. The therapy may induce neurotoxicity including the cauda equina syndrome. We report a case of a 58-year-old man with the diffuse large B-cell lymphoma, who developed the cauda equina syndrome after the administration of intrathecal methotrexate and cytarabine arabinoside, as diagnosed by the electrodiagnostic, urodynamic, and radiologic approaches.
Cauda Equina ; Central Nervous System ; Cytarabine ; Humans ; Injections, Spinal ; Lymphoma ; Lymphoma, B-Cell ; Methotrexate ; Polyradiculopathy ; Urodynamics

OBJECTIVE: To investigate the clinical characteristics of dysphagic elderly Korean patients diagnosed with aspiration pneumonia as well as to examine the necessity of performing a videofluoroscopic swallowing study (VFSS) in order to confirm the presence of dysphagia in such patients. METHOD: The medical records of dysphagic elderly Korean subjects diagnosed with aspiration pneumonia were retrospectively reviewed for demographic and clinical characteristics as well as for VFSS findings. RESULTS: In total, medical records of 105 elderly patients (81 men and 24 women) were reviewed in this study. Of the 105 patients, 82.9% (n=87) were admitted via the emergency department, and 41.0% (n=43) were confined to a bed. Eighty percent (n=84) of the 105 patients were diagnosed with brain disorders, and 68.6% (n=72) involved more than one systemic disease, such as diabetes mellitus, cancers, chronic cardiopulmonary disorders, chronic renal disorders, and chronic liver disorders. Only 66.7% (n=70) of the 105 patients underwent VFSS, all of which showed abnormal findings during the oral or pharyngeal phase, or both. CONCLUSION: In this study, among 105 dysphagic elderly patients with aspiration pneumonia, only 66.7% (n=70) underwent VFSS in order to confirm the presence of dysphagia. As observed in this study, the evaluation of dysphagia is essential in order to consider elderly patients with aspiration pneumonia, particularly in patients with poor functional status, brain disorders, or more than one systemic disease. A greater awareness of dysphagia in the elderly, as well as the diagnostic procedures thereof, particularly VFSS, is needed among medical professionals in Korea.
Aged ; Brain Diseases ; Deglutition ; Deglutition Disorders ; Diabetes Mellitus ; Emergencies ; Humans ; Korea ; Liver ; Male ; Medical Records ; Pneumonia, Aspiration ; Retrospective Studies

OBJECTIVE: To examine the usefulness of the Scale for the Assessment and Rating of Ataxia (SARA) in ataxic stroke patients. METHOD: This was a retrospective study of 54 patients following their first ataxic stroke. The data used in the analysis comprised ambulation status on admission and scores on the SARA, the Korean version of the Modified Barthel Index (K-MBI) and the Berg Balance Scale (BBS). The subjects were divided into four groups by gait status and into five groups by level of dependency in activities of daily living (ADLs) based on their K-MBI scores. Data were subjected to a ROC curve analysis to obtain cutoff values on the SARA for individual gait status and levels of activity dependency. The correlations between the SARA, K-MBI and BBS scores were also computed. RESULTS: There was significant correlation between the SARA and the K-MBI scores (p<0.001), and this correlation (r=-0.792) was higher than that found between the BBS and the K-MBI scores (r=0.710). The SARA scores of upper extremity ataxia categories were significantly related to the K-MBI scores of upper extremity related function (p<0.001). The SARA scores were also significantly correlated negatively with ambulation status (p<0.001) and positively with ADL dependency (p<0.001). In the ROC analysis, patients with less than 5.5 points on the SARA had minimal dependency in ADL, while those with more than 23 points showed total dependency. CONCLUSION: SARA corresponds well with gait status and ADL dependency in ataxic stroke patients and is considered to be a useful functional measure in that patient group.
Activities of Daily Living ; Ataxia ; Dependency (Psychology) ; Gait ; Humans ; Retrospective Studies ; ROC Curve ; Stroke ; Upper Extremity ; Walking

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease that is frequently linked to microtubule abnormalities and mitochondrial trafficking defects. Whole exome sequencing (WES) of patient-parent trios has proven to be an efficient strategy for identifying rare de novo genetic variants responsible for sporadic ALS (sALS). Using a trio-WES approach, we identified a de novo RAPGEF2 variant (c.4069G>A, p.E1357K) in a patient with early-onset sALS. To assess the pathogenic effects of this variant, we have used patient-derived skin fibroblasts and motor neuron-specific overexpression of the RAPGEF2-E1357K mutant protein in Drosophila. Patient fibroblasts display reduced microtubule stability and defective microtubule network morphology. The intracellular distribution, ultrastructure, and function of mitochondria are also impaired in patient cells. Overexpression of the RAPGEF2 mutant in Drosophila motor neurons reduces the stability of axonal microtubules and disrupts the distribution of mitochondria to distal axons and neuromuscular junction (NMJ) synapses. We also show that the recruitment of the pro-apoptotic protein BCL2-associated X (BAX) to mitochondria is significantly increased in patient fibroblasts compared with control cells. Finally, increasing microtubule stability through pharmacological inhibition of histone deacetylase 6 (HDAC6) rescues defects in the intracellular distribution of mitochondria and BAX. Overall, our data suggest that the RAPGEF2 variant identified in this study can drive ALS-related pathogenic effects through microtubule dysregulation.
Amyotrophic Lateral Sclerosis* ; Axons* ; Drosophila ; Exome ; Fibroblasts ; Histone Deacetylases ; Humans ; Microtubules* ; Mitochondria* ; Motor Neurons ; Mutant Proteins ; Mutation, Missense ; Neurodegenerative Diseases ; Neuromuscular Junction ; Skin ; Synapses

The tyramide signal amplification (TSA) technique, based on the ability of HRP to catalyze the deposition of tyramide onto the surrounding proteins, has been proved to detect scarce tissue antigens. In this study we applied this technique to a biochip platform and an immunocytochemistry at the electron microscopic level. First, in the optical fluorescence sensing, the signal was amplified by Dako Envision(TM) (goat anti-mouse immunoglobulins IgG conjugated to peroxidase labelled-dextran polymer) and tyramide-Cy3, which was then compared to the non-amplified control using goat antimouse IgG-Cy3 conjugate instead. The result showed that the tyramide method produced a more sensitive signal than the control method. Secondly, in the pre-embedding immunocytochemistry, we investigated to see whether it is possible to label proteins within a organelle in the cell using the TSA method. The signal was amplified by a primary antibody, a biotinylated secondary antibody, streptavidin-HRP, biotinyl-tyramide, and streptavidinnanogold followed by silver enhancement and gold toning. Then, this protocol was compared to the non-amplified or simple protocol that does not include the steps of streptavidin-HRP and biotinyl-tyramide. With the TSA protocol, the labeling for a membrane bound antigen (gp100) that is known to be exclusively localized to melanosomes in melanocyte, was tested in a melanoma cell line (G361) and found to be highly sensitive and more enhanced than with the simple protocol. Moreover, the gold particles were well localized to the subcellular structures or melanosomes both in the TSA and simple protocols, which indicates that resolution of the signals remains high. Control experiment with omission of the primary antibody demonstrated that background levels or nonspecific bindings are negligible. This result showed that the TSA method can be successfully applied to label the intra-organelle protein that is known to be labeled only in the specific fixation condition with the optimal permeability.
Cell Line ; Fluorescence ; Goats ; Immunoglobulin G ; Immunoglobulins ; Immunohistochemistry ; Melanocytes ; Melanoma ; Melanosomes ; Membranes ; Microscopy, Immunoelectron* ; Organelles* ; Permeability ; Peroxidase ; Protein Array Analysis ; Silver