CCL3 as Possible Negative Prognostic Factor in Chronic Lymphocytic Leukemia.

INTRODUCTION: Both microenvironmental signals from surrounding cells and changes in the genome of leukemic cells play essential role in the development of chronic lymphocytic leukemia. Nurse-like cells (NLCs) are one of the important elements of the microenvironment of CLL cells. The key role in the interactions of leukemic cells with NLCs is played by chemokines, which may interfere with the programmed cell death process in the leukemic lymphocytes. The aim of our study was analysis of selected microenvironmental factors having a potential impact on the leukemic cells survival, as well as their association with clinical, cytogenetic, and molecular parameters. For this study, we selected three types of molecules which can modulate microenvironment: chemokines IL-8 and CCL3 (which are classically secreted to extracellular matrix), soluble forms of adhesion molecules JAG1 and CD163, and secreted form of endogenous protein BIRC5. We assessed their expression in the serum of CLL patients as well as in medium of long-term NLCs cultures. METHODS: Long-term cell culture was prepared from mononuclear cells derived from the blood of 34 patients with CLL. Number of NLCs cells was evaluated, under a light inverted microscope. The concentration of IL-8, CCL3, sBIRC5, sCD163, and sJAG1 in culture medium and serum was assessed by enzyme-linked immunosorbent assays. RESULTS: There were significant differences in the concentration of IL-8, sBIRC5, CCL3, sCD163, and sJAG1 between the patient's blood serum and the culture medium. The concentrations of IL-8, CCL3, and JAG1 were higher in the culture medium, which confirmed the role of the microenvironment in the production of these proteins. In addition, the concentration of CCL3 chemokine in both patient's blood serum and in the culture medium correlated with the number of NLCs and with known prognostic factors in the course of CLL, e.g., Rai stage, WBC, expression of ZAP-70, CD38, and CD5/19. CONCLUSION: The microenvironment of CLL cells, which includes NLCs, plays an important role in the pathogenesis of CLL. The CCL3 chemokine seems to be a good factor representing microenvironment of CLL cells. Chronic lymphocytic leukemia is a complex and very heterogeneous disease; therefore, its progress should be considered both in the context of genetic changes and the interaction with microenvironmental cells.

Susac syndrome as a multidisciplinary diagnostic challenge.

INTRODUCTION: Susac syndrome (SuS) is a disease manifested as the clinical triad of encephalopathy, branch retinal artery occlusion, and loss of sensory neural hearing. CASE REPORT: The case is presented of a 28-year-old patient hospitalized due to visual impairment of the left eye, and whose hearing and neuropsychiatric disorders had appeared two years earlier. Magnetic resonance imaging demonstrated lesions located in the white matter and along the corpus callosum. An audiogram showed bilateral sensory neural hearing loss. Fluorescein angiography examination revealed branch retinal artery occlusion of the left eye. Based on the clinical picture and results of tests, the diagnosis of SuS was made. Despite the use of steroid and immunosuppression therapy the disease progressed. CONCLUSIONS: The prognosis for SuS depends on the early diagnosis and implementation of treatment. It should be underlined that in case of hearing loss or encephalopathy of unknown cause, SuS should always be excluded.

Targeting pain in the long-term treatment of cervical dystonia with botulinum toxin A.

AIMS: Cervical pain is one of the most common non-motor symptoms of cervical dystonia (CD) and affects from 54.6% to 88.9% of patients. To date, minority of studies investigated the relevance of pain in a long-term botulinum toxin (BoNT) therapy of CD. The aim of the study was to define an impact of cervical pain on the disease severity and disability, as well as to assess antinociceptive BoNT efficacy in a long-term treatment of CD. MATERIALS AND METHODS: In this case-control study, CD patients who received stable doses of BoNT for at least 3 years were assessed with the use of validated scales. Participants were divided into two groups depending on the occurrence of CD-related pain. RESULTS: We examined 50 participants who received a mean of 24 injection cycles (6-51) of BoNT during a mean treatment period of 10.3 years (3.0-23.5). Participants with cervical pain (68.0%) were characterized by higher scores in all scales used in this study: TWSTRS severity (p = 0.030), disability (p < 0.001), total (p < 0.001) and TSUI score (p = 0.046). Pain reduction following BoNT injection lasted longer than muscle relaxation in 85.3% of patients. Pain improvement between first and last BoNT injection cycle was reported by 76.5% of patients with CD-related pain. CONCLUSIONS: The presence of cervical pain in CD may increase the severity of muscular symptoms and disease-related disability. BoNT has a noticeable antinociceptive effect in the long-term treatment of CD.

Cervical dystonia: factors deteriorating patient satisfaction of long-term treatment with botulinum toxin.

OBJECTIVES: Botulinum toxin (BoNT) is an effective first-line treatment for cervical dystonia (CD). Despite generally good therapeutic efficacy, approximately 20-40% of CD patients do not achieve acceptable relief of the dystonic symptoms. The aim of this study was to identify factors of low patient satisfaction of long-term BoNT therapy for CD. METHODS: In this case-control study CD patients treated with BoNT intramuscular injections for up to 24 years were assessed by two independent assessors in three validated scales: TWSTRS, Tsui and VAS for pain measurement. Data on received BoNT doses and treatment duration were obtained from medical history. All of participants rated their long-term treatment satisfaction compared to the therapy onset on a 0-3 scale. RESULTS: Study was completed by 58 participants who were treated with BoNT for 9.0 ± 6.3 years and received a median of 19 injection cycles. None/low therapy satisfaction was reported by 20.7% of participants. Compared to moderate/good treatment satisfaction, CD patients with none/low BoNT efficacy had increased incidence of cervical pain (p =.018), enhanced mean VAS score for pain (p =.037) and had higher coexistence of oromandibular dystonia (p =.018). In addition, worse treatment satisfaction correlated with shorter time intervals between treatment cycles, enhanced scores of Tsui total, TWSTRS total, as well as TWSTRS subscales: severity, disability and pain. CONCLUSION: Cervical pain and coexistence of oromandibular dystonia deteriorated long-term treatment satisfaction in CD patients. Higher scores of Tsui and TWSTRS subscales were correlated with worse subjective BoNT treatment response.

Biomarkers in Multiple Sclerosis: a review of diagnostic and prognostic factors.

INTRODUCTION: Multiple Sclerosis (MS) is a chronic, demyelinating disease of the central nervous system which affects mostly young people. Because it leads to disability and cognitive impairment, it is crucial to recognise MS at an early stage. STATE OF THE ART: Magnetic resonance imaging is the golden standard in MS diagnosis. However, it is not an infallible diagnostic tool, especially at the stage of clinically isolated syndrome. The incorporation of oligoclonal bands in the diagnostic process of MS is a step towards the extension of diagnostic methods. Recently, a lot of research has been carried out on potential biomarkers in blood serum and cerebrospinal fluid that may be useful in the diagnosis of MS. CLINICAL IMPLICATIONS: This article summarises current knowledge on the use of new prognostic factors such as neurofilament light chain, chitinase 3-like 1 and 2, heat shock proteins, and tubulins in MS. FUTURE DIRECTIONS: Despite numerous studies on the use of biomarkers in the diagnosis of MS, more extensive research is needed to determine the clinical usefulness of these molecules and to develop diagnostic tests applicable in everyday practice. This in turn may result in earlier MS detection, faster implementation of treatment, and better therapeutic effects.

Non-traumatic cervical artery dissection and ischemic stroke: A narrative review of recent research.

Cervical artery dissection (CAD) is a leading cause of ischaemic stroke (IS) in young and middle-aged adults. Despite well characterized clinical presentation, the diagnosis of CAD can be quite challenging due to a wide variety of symptoms ranging from minor neck pain to severe neurological symptoms. Invasive diagnostic procedures such as DSA are nowadays being replaced by the sensitive and CAD-specific sequences of MR. The most recent studies confirmed the overall efficacy of antiplatelet and anticoagulant therapies for CAD patients is equivalent, although patients should be qualified for concrete treatment on the basis of recently characterized clinical features. The use of NOAC in CAD-related IS prevention cannot yet be recommended due to the lack of evidences from randomized controlled trials. Endovascular therapies should be considered as the treatment of CAD, especially in the cases of large occlusion or antithrombotic treatment failure. Further research is needed to evaluate the efficacy of new imaging modalities and treatment options. This review summarize the last 5-year development of the diagnosis and treatment for CAD as a causative factor for IS.

Pain in cervical dystonia and the antinociceptive effects of botulinum toxin: what is currently known?

Pain is the most common and disabling non-motor symptom in cervical dystonia (CD). Up to 88.9% of patients report pain at some point in the course of the disease. It is still a matter of debate whether CD-related pain originates only from prolonged muscle contraction. Recent data suggest that the alterations of transmission and processing of nociceptive stimuli play a crucial role in pain development. Botulinum toxin (BT) is the first-line therapy for CD. Despite fully elucidated muscle relaxant action, the antinociceptive effect of BT remains unclear and probably exceeds a simple decompression of the nerve fibers due to the reduction in muscle tone. The proposed mechanisms of the antinociceptive action of BT include inhibition of pain mediator release, inhibition of membrane sodium channels, retrograde axonal transport and impact on the other pain pathways. This article summarizes the current knowledge about the antinociceptive properties of BT and the clinical analgesic efficacy in the treatment of CD patients.