RESUMEN
The following case describes a constellation of progressive cognitive and motor deficits in a 73-year-old man with cirrhosis and history of early-stage hepatocellular carcinoma confined to his liver. He had deficits in calculation, language, and writing, as well as subtle right-sided weakness. Magnetic resonance imaging (MRI) of the brain demonstrated non-enhancing white matter lesions without mass effect in the bilateral parietal and left occipitotemporal regions, correlating with neurologic exam findings. The patient's basic blood and cerebrospinal fluid (CSF) studies were within normal limits. Our differential included inflammatory and demyelinating conditions, hepatic encephalopathy, posterior reversible encephalopathy syndrome, progressive multifocal leukoencephalopathy (PML), and central nervous system (CNS) tumors. He did not improve with an empiric course of high-dose steroids or adequate hepatic encephalopathy treatment. A repeat lumbar puncture sent for additional CSF studies revealed a positive John Cunningham (JC) virus PCR test, confirming diagnosis of PML. Although the patient did not have any known overt immunosuppressive condition or treatment, the patient's cirrhosis and age placed him at higher risk for developing JC virus CNS reactivation. In a published case series of patients with PML and no classic immunosuppressive condition that includes several patients with concomitant cirrhosis, prognosis is much worse compared to those with known, reversible causes of immunosuppression.
RESUMEN
Vitamin B12 deficiency is commonly associated with dementia in patients over the age of 65 years; however, it can affect people of all ages. Recognizing the clinical sequelae of subacute combined degeneration is essential for the timely diagnosis and treatment of vitamin B12 deficiency. In this report, we describe a case of a young man presenting with several months of neuropathy, depression, and abdominal symptoms. His initial vitamin B12 levels were within normal limits, but an elevated methylmalonic acid level and subacute combined degeneration of his spine on MRI confirmed the diagnosis of vitamin B12 deficiency. The patient later tested positive for autoantibodies associated with pernicious anemia. His symptoms improved with intramuscular injections of cyanocobalamin. This case highlights the importance of recognizing vitamin B12 deficiency in patients of all age groups even in the setting of apparently "normal" B12 levels.
RESUMEN
Previous work from our group has shown that Cd38-/- mice develop a milder pristane-induced lupus disease than WT or Art2-/- counterparts, demonstrating a new role for CD38 in promoting aberrant inflammation and lupus-like autoimmunity via a Transient Receptor Potential Melastatin 2 (TRPM2)-dependent apoptosis-driven mechanism. In this study we asked whether CD38 may play a role in the expression and function of regulatory B cells (IL-10-producing B cells or B10 cells). In pristane-treated mice the frequency of spleen CD19âºCD1dhiCD5⺠B cells, which are highly enriched in B10 cells, was significantly increased in Cd38-/- splenocytes compared to WT, while the frequency of peritoneal plasmacytoid dendritic cells (pDCs), which are major type I Interferon (IFN) producers, was greatly diminished. The low proportion of pDCs correlated with lower amounts of IFN-α in the peritoneal lavage fluids of the Cd38-/- mice than of WT and Art2-/- mice. Functional ex vivo assays showed increased frequencies of IL-10-producing B cells in Cd38-/- splenocytes than in WT upon stimulation with an agonist anti-CD40 mAb. Overall these results strongly suggest that Cd38-/- mice are better suited than WT mice to generate and expand regulatory B10 cells following the appropriate stimulation.