NEUROSYPHILIS - THE WHITE MATTER DISINTEGRATION? - TWO CASE REPORTS

Background: There is evidence for neurosyphilis being associated with the central nervous system vasculitis involving medium and small vessels. As the hemispheric white matter is the major target of these vascular alterations the white matter axonal and myelination disruption may be observed employing measure for the rate of water molecule diffusion. High apparent diffusion coefficient (ADC) correspond to unimpeded water diffusion and indicating white matter disintegration. Case reports: In a retrospective study exploringcentral nervous system magnetic resonance (MR) images of two subjects presenting with neurosyphilis the ADC values were found to be increased as related to normal values being accompanied with normal appearing white matter of hemispheres Conclusions: Applying ADC analysis to evaluate the brain in patients with neurosyphilis may reveal undetectable changes and explain the scale of abnormalities that occur in CNS. The increased mean ADC valuesin the normal appearing white matter of the hemispheres may correlate with neuropsychoatric symptomatology in syphilis

Predictive role of NKCD56bright cells in monitoring the progression of chronic lymphocytic leukemia during treatment

Introduction. Standard treatment for chronic lymphocytic leukemia (CLL) has experienced a dramatic change over the last few years. Until recently, CLL was treated using chemoimmunotherapy (CIT) with anti-CD20 monoclonal antibodies. Even though novel agents such as BTKi (Bruton Tyrosine Kinase inhibitor) and BCL2 inhibitors are the standard of care in most therapeutic settings, CIT still has its place in CLL treatment. Interestingly, little is known about its effects on the immune system of patients with CLL. Contrary to the reduction of the number of CLL cells during CIT administration, little attention has been paid to the cellular microenvironment, the evaluation of which during treatment may provide additional information about the course of the disease and prognosis and therefore was set as the aim of this study.Material and methods. Flow cytometry was used to evaluate the phenotypes of different populations and subpopulations of lymphocytes in the peripheral blood (PB) of 20 patients with CLL before, during, and after CIT.Results. During the CIT with R-FC (Rituximab, Fludarabine, and Cyclophosphamide) and R-B (Rituximab, Bendamustine) regimens, the sizes of the assessed populations and subpopulations of lymphocytes were dramatically reduced. Twenty-eight days after the first course of treatment, the exponential decrease of CLL cells was observed, and their number had declined to the median level of 10% of the numbers observed before the treatment. T cells, NK cells, NKCD56dim, NKT-like, and NKT-like CD56dim also decreased exponentially. After the second treatment course, a decline in the numbers of T, NK, NKCD56dim, NKT-like, and NKT-like CD56dim cells was observed, which were stable until the sixth treatment course. However, the number of NKT-like CD56bright cells decreased to the third course of treatment and then increased. The number of CLL cells in peripheral blood correlated with the number of NKCD56bright cells, influencing the treatment response.Conclusions. Upon CIT, the reduction of CLL cells is accompanied by shifts in immune cell populations, T, NK, and NKT-like cells. Monitoring changes of those cell populations in the peripheral blood may serve as an important predictive and prognostic indicator

NEUROSYPHILIS - THE WHITE MATTER DISINTEGRATION? - TWO CASE REPORTS

Background: There is evidence for neurosyphilis being associated with the central nervous system vasculitis involving medium and small vessels. As the hemispheric white matter is the major target of these vascular alterations the white matter axonal and myelination disruption may be observed employing measure for the rate of water molecule diffusion. High apparent diffusion coefficient (ADC) correspond to unimpeded water diffusion and indicating white matter disintegration. Case reports: In a retrospective study exploringcentral nervous system magnetic resonance (MR) images of two subjects presenting with neurosyphilis the ADC values were found to be increased as related to normal values being accompanied with normal appearing white matter of hemispheres Conclusions: Applying ADC analysis to evaluate the brain in patients with neurosyphilis may reveal undetectable changes and explain the scale of abnormalities that occur in CNS. The increased mean ADC valuesin the normal appearing white matter of the hemispheres may correlate with neuropsychoatric symptomatology in syphilis

Synaptic UNC13A protein variant causes increased neurotransmission and dyskinetic movement disorder

Munc13 proteins are essential regulators of neurotransmitter release at nerve cell synapses. They mediate the priming step that renders synaptic vesicles fusion-competent, and their genetic elimination causes a complete block of synaptic transmission. Here we have described a patient displaying a disorder characterized by a dyskinetic movement disorder, developmental delay, and autism. Using whole-exome sequencing, we have shown that this condition is associated with a rare, de novo Pro814Leu variant in the major human Munc13 paralog UNC13A (also known as Munc13-1). Electrophysiological studies in murine neuronal cultures and functional analyses in Caenorhabditis elegans revealed that the UNC13A variant causes a distinct dominant gain of function that is characterized by increased fusion propensity of synaptic vesicles, which leads to increased initial synaptic vesicle release probability and abnormal short-term synaptic plasticity. Our study underscores the critical importance of fine-tuned presynaptic control in normal brain function. Further, it adds the neuronal Munc13 proteins and the synaptic vesicle priming process that they control to the known etiological mechanisms of psychiatric and neurological synaptopathies