8 research outputs found
FXTAS presenting with cervical dystonia as the initial symptom: Considering FXTAS in the clinical evaluation of cervical dystonia
No full textFXTAS (Fragile X-associated tremor/ataxia syndrome) is characterized by typical clinical features, including tremor, cerebellar ataxia, parkinsonism, and the middle cerebellar peduncle (MCP) sign, which appears as T2 hyperintensity in the MCP on MRI. FXTAS is almost never considered in the context of cervical dystonia. However, this case demonstrates that FXTAS can initially present with cervical dystonia.A 59-year-old man presented with cervical dystonia, characterized by right lateral flexion, and sensory trick. His initial symptom was cervical tilt at age 54. At age 55, the patient developed an unsteady gait. The patient was unable to perform a tandem gait and stand up from a crouch, suggesting trunk ataxia, and exhibited lateral gaze nystagmus, which was indicative of a cerebellar disorder. MRI revealed MCP sign. Genetic testing confirmed FXTAS, revealing 90 CGG repeats in the FMR 1 (Fragile X Mental Retardation 1) gene.Notably, a pre-symptomatic MRI, incidentally acquired at the age of 52, retrospectively revealed the presence of the MCP sign. This suggests that, even when FXTAS initially presents as cervical dystonia, the MCP sign can remain a reliable diagnostic feature for early detection.This case highlights that early FXTAS may mimic idiopathic cervical dystonia and that considering FXTAS during the clinical evaluation of cervical dystonia can enable early diagnosis
Mimic of transient ischemic attack by anemia-induced asterixis: A novel differential diagnosis of stroke with critical pitfalls
No full textMimic of transient ischemic attack by anemia-induced asterixis: A novel differential diagnosis of stroke with critical pitfalls
No full textTable_2_Case Report: Anti-mGluR5 antibody-negative Ophelia syndrome with failed lymph node biopsy due to steroid therapy.xlsx
No full textOphelia syndrome is paraneoplastic limbic encephalitis (PLE) with Hodgkin lymphoma. Some Ophelia syndrome patients have been reported as testing positive for anti-metabotropic glutamate receptor 5 (mGluR5) antibodies. However, we experienced a case of anti-mGluR5 antibody-negative Ophelia syndrome. The type of onset, neurological symptoms, and imaging as well as electroencephalographic findings were like previous reports except for a normal cell count in cerebrospinal fluid (CSF). Unfortunately, a lymph node biopsy failed and could not diagnose the patient before death because steroid treatment for limbic encephalitis had shrunk lymph nodes. We believe it is essential to accumulate cases of this syndrome and clarify the association between PLE and Hodgkin lymphoma so chemotherapy can be initiated even if malignant lymphoma cannot be pathologically proven or when antibodies cannot be measured or are negative.</p
Remission of idiopathic retroperitoneal fibrosis by ofatumumab as a disease-modifying therapy for multiple sclerosis
No full textTable_1_Case Report: Anti-mGluR5 antibody-negative Ophelia syndrome with failed lymph node biopsy due to steroid therapy.xlsx
No full textOphelia syndrome is paraneoplastic limbic encephalitis (PLE) with Hodgkin lymphoma. Some Ophelia syndrome patients have been reported as testing positive for anti-metabotropic glutamate receptor 5 (mGluR5) antibodies. However, we experienced a case of anti-mGluR5 antibody-negative Ophelia syndrome. The type of onset, neurological symptoms, and imaging as well as electroencephalographic findings were like previous reports except for a normal cell count in cerebrospinal fluid (CSF). Unfortunately, a lymph node biopsy failed and could not diagnose the patient before death because steroid treatment for limbic encephalitis had shrunk lymph nodes. We believe it is essential to accumulate cases of this syndrome and clarify the association between PLE and Hodgkin lymphoma so chemotherapy can be initiated even if malignant lymphoma cannot be pathologically proven or when antibodies cannot be measured or are negative.</p
CANOMAD mimicking anti-MAG/SGPG neuropathy: A case highlighting the diagnostic specificity of ophthalmoplegia and cold agglutination
No full textAnti-myelin-associated glycoprotein/sulfated glucuronyl paragloboside (MAG/SGPG) neuropathy is a major differential diagnosis for sensory ataxic neuropathy with IgM κ type M proteinemia. Alternatively and less commonly, an important differential diagnosis for chronic sensory ataxic neuropathy with IgM κ type M proteinemia is chronic ataxic neuropathy with ophthalmoplegia, M proteinemia, cold agglutinins, and disialosyl antibodies (CANOMAD), which has been reported to respond to therapies such as intravenous immunoglobulin (IVIg). Confusingly, this case tested positive for anti-SGPG antibodies despite CANOMAD.A 68-year-old man had sensory ataxia, IgM κ type M protein, prolongation of distal latency without conduction block, and was positive for anti-SGPG IgM antibodies, which could be the misdiagnosis of anti-MAG/SGPG neuropathy. However, the patient had ptosis, binocular diplopia, cold agglutination, and anti-GQ1b IgM antibodies, fulfilling all the key features of CANOMAD. Consistently, IVIg therapy improved both clinical symptoms and electrophysiological findings. After that, anti-MAG antibody testing returned negative results.Here, we report a case of CANOMAD with the presence of misleading anti-SGPG antibodies, revealing the risk of misdiagnosis because of reliance on anti-SGPG antibodies in the diagnosis of sensory ataxic neuropathy. The present case also emphasized that ocular symptoms (ptosis, binocular diplopia), and cold agglutination were more specific keys to the initial diagnosis of CANOMAD. The accurate diagnosis of CANOMAD may benefit patients by enabling appropriate treatment selection
Translational research in rheumatoid arthritis: Exploiting melanocortin receptors
No full textThe copyright of this thesis rests with the author and no quotation from it or information derived from it may be published without the prior written consent of the authorRheumatoid arthritis (RA) is a chronic inflammatory disease affecting 1% of the population. The aetiology of rheumatoid arthritis is unknown, although there are multiple postulated theories. In 1950, Philip Hench won the Nobel prize for treating patients with rheumatoid arthritis with cortisone. He also treated 6 patients with adrenocorticotropic hormone (ACTH) with good results. ACTH is a melanocortin. The melanocortin system describes the five melanocortin receptors, their ligands, agonists and antagonists and the accessory proteins. The aim of this study was to explore the melanocortin receptors in rheumatoid arthritis synovium.
Methods
HA-tagged stable cell lines were created for MC1R, MC3R and MC5R. Multiple antibodies were tested for their utility using Western Blot, immunohistochemistry and flow cytometry. Samples of synovium from 28 patients with RA were tested using RTPCR for the presence of MC1R and MC3R. Gene expression was correlated with clinical characteristics, cytokine (RTPCR) expression and immunohistochemical score.
Results
The stable cell lines expressed MC1R, MC3R and MC5R respectively. Of the antibodies tested none were found to be of utility in detecting MC1R or MC3R .The MC1R RQ values in rheumatoid synovium appear to split into two groups, high and low. The medians of the two groups are significantly different (p=0.0005). There is almost a 5 cycle, or 64 fold, difference in gene expression between the medians of the two groups (1.59 v 6.23). Of note no MC3R positive samples were CD138 high (i.e. no MC3R positive samples had a significant plasma cell infiltrate) (p=0.006). Categorical analysis using Fishers Exact test revealed an association between MC1R high samples and CD68 lining high scores, (i.e. MC1R high samples also had a high macrophage score in the lining of the sample) (p=0.02). MC1R low samples were associated with not being on combination therapy,
15
this did not quite reach significance (p=0.07). Linear regression analysis confirmed these associations for MC1R. PCA analysis did not show any grouping of samples according to any of the variables tested, likely due to sample size.
Conclusion
MC1R and MC3R are found in human synovium. Current commercial antibodies are not of utility in detecting MC1R or MC3R. Synovial samples can be split into high and low MC1R gene expression groups. MC3R was either present or absent. High expression of MC1R was associated with a high macrophage score and MC3R expression was associated with a low plasma cell score. MC1R and MC3R expression in RA synovium could be used as biomarkers of disease state or severity as well as a target for therapy
