Progressive multifocal leukoencephalopathy in a patient with occult hypogammaglobulinemia experiencing bilateral visual impairment.

INTRODUCTION: Progressive multifocal leukoencephalopathy (PML) is a rare, lethal, demyelinating disease classically seen in profoundly immunosuppressed individuals. It is caused by intracerebral infection by John Cunningham polyomavirus (JCV). We report a rare case of PML in a man with presumed immunocompetence at presentation experiencing bilateral painless visual impairment. CASE DESCRIPTION: A 60-year-old man with a 3-week history of bilateral painless visual impairment attended our ophthalmology department. Unusually, he navigated around the room well and was able to read 4 of 13 Ishihara test plates in spite of a best-corrected visual acuity of counting fingers at 1 m bilaterally. Slit lamp examination, routine blood tests and optical coherence tomography (OCT) of the maculae and discs were unremarkable. Diffuse hyperintense white matter lesions on T2-weighted magnetic resonance imaging of the brain and detection of JCV within the parietal lobe tissue obtained by biopsy confirmed PML. Additional investigations identified an underlying hypogammaglobulinaemia, which may have initiated PML. He received intravenous immunoglobulin but passed away 2 months after diagnosis. CONCLUSIONS: To our knowledge this case is one of only a handful worldwide to describe PML developing in a patient with presumed immunocompetence at presentation - there was no previous history of recurrent, chronic, or atypical infections. There has only been one other report of visual symptoms presenting as the primary complaint. The case illustrates the importance of ruling out organic, central nervous system pathology in patients presenting with visual loss and normal objective visual function tests such as slit lamp examination and OCT.

Glycyrrhizin Blocks the Detrimental Effects of HMGB1 on Cortical Neurogenesis After Traumatic Neuronal Injury.

Despite medical advances, neurological recovery after severe traumatic brain injury (TBI) remains poor. Elevated levels of high mobility group box protein-1 (HMGB1) are associated with poor outcomes; likely via interaction with receptors for advanced-glycation-end-products (RAGE). We examined the hypothesis that HMGB1 post-TBI is anti-neurogenic and whether this is pharmacologically reversible. Post-natal rat cortical mixed neuro-glial cell cultures were subjected to needle-scratch injury and examined for HMGB1-activation/neuroinflammation. HMGB1-related genes/networks were examined using genome-wide RNA-seq studies in cortical perilesional tissue samples from adult mice. Post-natal rat cortical neural stem/progenitor cell cultures were generated to quantify effects of injury-condition medium (ICM) on neurogenesis with/without RAGE antagonist glycyrrhizin. Needle-injury upregulated TNF-α/NOS-2 mRNA-expressions at 6 h, increased proportions of activated microglia, and caused neuronal loss at 24 h. Transcriptome analysis revealed activation of HMGB1 pathway genes/canonical pathways in vivo at 24 h. A 50% increase in HMGB1 protein expression, and nuclear-to-cytoplasmic translocation of HMGB1 in neurons and microglia at 24 h post-injury was demonstrated in vitro. ICM reduced total numbers/proportions of neuronal cells, but reversed by 0.5 µM glycyrrhizin. HMGB1 is activated following in vivo post mechanical injury, and glycyrrhizin alleviates detrimental effects of ICM on cortical neurogenesis. Our findings highlight glycyrrhizin as a potential therapeutic agent post-TBI.

C-reactive protein kinetics post elective cranial surgery. A prospective observational study.

Introduction: Post cranial surgery readmission, largely caused by surgical site infection (SSI), is a marker of patient-care quality requiring comprehensive discharge planning. Currently, discharge assessment is based on clinical recovery and basic laboratory tests, including C-reactive protein (CRP). Although CRP kinetics have been examined postoperatively in a handful of papers, the validity of CRP as a standalone test to predict SSI is yet to be explored.Methods: A prospective observational study was performed on adult patients undergoing elective cranial surgery over a 3-month period. Laboratory data; CRP, white cell count (WCC), neutrophil cell count (NCC), and clinical data were assessed pre and post-operatively and were evaluated as predictors for safe discharge. Readmission rates within 1 month were recorded.Results: In this study, 68 patients were included. About 8.6% were readmitted due to SSI. A postoperativepeak in CRP was seen on day 2 with a value of 57 in the non-readmitted group, and 115 in the readmitted group. CRP dropped gradually to normal levels by day 5 in the non-readmitted group. A secondary CRP rise at day 5 was noted in the readmitted group with a sensitivity, specificity, and negative predictive value of 71%, 90%, and 96%, respectively. Interestingly, our ROC analysis indicates that a CRP value of less than 65 predicts safe discharge with a sensitivity of 86%, specificity of 89% and negative predictive value of 98% of safe discharge (area under the curve, AUC: 0.782). No significant difference in other inflammatory markers was found between both groups.Conclusions: CRP increases postoperatively for 4-5 d which could be a physiological response to surgery, however, prolonged elevation or a secondary increase in CRP may indicate an ongoing infection. Our data validate the potential use of CRP levels to predict SSI. A multicentre study is warranted to investigate the role of CRP in predicting SSI.