Krystyna Mitosek-Szewczyk

Symptomatology and pathogenesis of different types of pain in multiple sclerosis

Multiple sclerosis (MS) is a progressive disease of the central nervous system. It is characterized by disseminated foci of demyelination, which are responsible for the diverse clinical picture of MS. Pain is a frequent but underestimated symptom of multiple sclerosis. It is estimated to affect 29-86% of MS patients in various stages of the disease and severely influences rehabilitation and quality of life. The pain experienced by MS patients is generally caused by nervous system damage during the course of the disease process and can usually be characterized as central neuropathic pain (less frequently as peripheral or nociceptive pain). The most frequent symptoms include dysesthetic extremity pain, painful tonic spasms, Lhermittes sign, trigeminal neuralgia, headaches and low back pain. This paper discusses the probable mechanisms behind the development of pain in MS, the prevalence, classification, types of pain, as well as the most effective treatment methods.

Impact of cladribine therapy on changes in circulating dendritic cell subsets, T cells and B cells in patients with multiple sclerosis

BACKGROUND Cladribine causes sustained reduction in peripheral T and B cell populations while sparing other immune cells. We determined two populations of dendritic cells (DCs): namely CD1c(+)/CD19(-) (myeloid DCs) and CD303(+)/CD123(+) (plasmacytoid DCs), CD19(+) B lymphocytes, CD3(+) T lymphocytes and CD4(+) or CD8(+) subpopulations in patients with multiple sclerosis after cladribine therapy. METHODS We examined 50 patients with secondary progressive multiple sclerosis (SP MS) according to McDonalds et al.s criteria, 2001 [15]. Blood samples were collected before the initiation of cladribine therapy and after 1st, 2nd, 3th, 4th and 5th courses of treatment. DC subsets, T and B cells were analyzed by flow cytometry. RESULTS During cladribine treatment the myeloid DCs CD1c(+)/CD19(-) did not change (p=0.73175), and the plasmacytoid DCs CD303(+)/CD123(+) significantly increased (p=0.00034) which resulted in significant changes in the ratio of myeloid DCs to plasmacytoid DCs (p=0.00273). During therapy, B lymphocyte CD19(+) significantly decreased (p=0.00005) and significant changes in CD4(+) cells (p=0.00191), changes in CD8(+) cells (p=0.05760) and significant changes in CD3(+) (p=0.01822) were found. CONCLUSIONS We noticed significant trend to increase the CD303(+) circulating the dendritic cells. This population produces large amounts of IFN-alfa. We found significant and rapid decrease in B cells and CD4(+) Th cells. Our results suggest two possible ways of beneficial cladribine influence on immune system in MS. Induction of IFN-alfa producing cells and their predominance over BDCA-1(+) DCs, which are associated with cytotoxic response. Additionally, cladribine could influence two populations of lymphocytes: B cells and Th lymphocytes responsible for induction of immune response against myelin antigens.

B-type natriuretic peptide as a marker of subclinical heart injury during mitoxantrone therapy in MS patients—Preliminary study

The aim of this study was to evaluate the plasma level changes of B-type natriuretic peptide (BNP), biochemical marker of heart failure, and echocardiographic parameters during mitoxantrone treatment in 22 multiple sclerosis (MS) patients (8 males, 14 females, mean age 37.1+/-6.6). Mitoxantrone (after mean cumulative dose of 58.0+/-7.0 mg/m(2)) did not alter left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), posterior wall thickness (PWT) and left ventricular end-diastolic volume (LVEDV). However, mean plasma level of BNP raised from 14.53+/-3.29 pg/ml at the baseline to 16.79+/-3.05 pg/ml and 18.83+/-4.90 pg/ml (P<0.01) after mean mitoxantrone dose of 30.7+/-5.9 mg/m(2) and 58.0+/-7.0 mg/m(2), respectively. These results strongly suggest subclinical myocardial dysfunction in mitoxantrone-treated group. We assume, that low-cost, repeated BNP measurements may be a good alternative for detection of early subtle myocardial injury in MS patients during routine mitoxantrone therapy.