Mikolaj Pawlak

Clinical study on CXCL13, CCL17, CCL20 and IL-17 as immune cell migration navigators in relapsing−remitting multiple sclerosis patients

BACKGROUND There has been a growing evidence for the role of chemokines in the pathology of multiple sclerosis. Recently, there has been great emphasis placed on humoral immunity and the T(H)-17 response, which has not yet been thoroughly described in MS. The aim of this study was to investigate the role of specific chemokines involved in B-cell migration (CXCL13) and in the T(H)-17 immune response (IL-17, CCL17, CCL20). METHODS Using ELISA, the chosen chemokine concentrations were measured in the serum and cerebrospinal fluid of relapsing-remitting MS patients with both active and stable disease, and the relapse prediction rate was calculated. RESULTS We found that the CSF concentrations of CXCL13 in patients with RRMS both, during relapse and remission, were significantly higher than in controls. CCL17 and CCL20 were not detected in CSF in either of the groups, whereas serum CCL20 level was significantly higher in remission than during relapse. Intravenous methylprednisolone treatment of patients with relapse did not influence serum CXCL13 and CCL20 levels. However, it did lower CCL17 and IL-17 concentrations. CONCLUSIONS CXCL13 is an important mediator in MS that is strongly linked to the neuroinflammatory activity of the disease. However, more studies are needed for elucidating the roles of CCL17, CCL20 and IL-17 in MS pathology.

Basal Ganglia Volumes: MR-Derived Reference Ranges and Lateralization Indices for Children and Young Adults.

Previous studies indicate rightward asymmetry of the caudate nucleus (CN) volume and leftward asymmetry of the putamen (PN) and globus pallidus (GP). This study aimed to estimate reference ranges for basal ganglia asymmetry in a large cohort of healthy individuals (n= 949), aged seven to 21 years. MRI images of 949 (320 female, mean age 12.6 +/− 3.3, range 7–21) healthy individuals were reviewed. Volumetric measurements of the basal ganglia were obtained using automated segmentation (FreeSurfer). We computed two lateralization indices: (L-R)/(L+R) (LI) and right/left ratio (RLR). Tolerance interval estimates were used to calculate reference ranges. Rightward asymmetry of the CN and leftward asymmetry of the PN and GP were confirmed. PN and GP volume decreased with age, but CN volume did not. The lateralization index decreased with age for PN, but not for CN and GP. RLR increased with age for PN and not for CN or GP. Females were associated with smaller volume, but not with either LI or RLR difference. Reference ranges obtained in this study provide useful resources for power analysis and a reference group for future studies using basal ganglia asymmetry indices.

Genetic Programming with Alternative Search Drivers for Detection of Retinal Blood Vessels

A classification task is a test-based problem, with examples corresponding to tests. A correct classification is equivalent to passing a test, while incorrect to failing it. This applies also to classifying pixels in an image, viz. image segmentation. A natural performance indicator in such a setting is the accuracy of classification, i.e., the fraction of passed tests. When solving a classification tasks with genetic programming, it is thus common to employ this indicator as a fitness function. However, recent developments in GP as well as some earlier work suggest that the quality of evolved solutions may benefit from using other search drivers to guide the traversal of the space of programs. In this study, we systematically verify the usefulness of selected alternative search drivers in the problem of detection of blood vessels in ophthalmology imaging.

Anti-leukemic treatment-induced neurotoxicity in long-term survivors of childhood acute lymphoblastic leukemia: impact of reduced central nervous system radiotherapy and intermediate- to high-dose methotrexate

Abstract The aim of the study was to evaluate the long-term neurodevelopmental consequences of currently applied acute lymphoblastic leukemia (ALL) therapy containing chemotherapy alone or combined with 12 Gy radiotherapy. Seventy-nine children aged 6.3–21.7 years diagnosed with ALL and treated according to ALL IC-BFM 2002 have been studied. The control group consisted of 23 children newly diagnosed with ALL. We assessed subcortical gray matter volume using automatic MRI segmentation and cognitive performance to identify differences between three therapeutic schemes and patients prior to treatment. Irradiated patients had smaller selected subcortical volumes than those treated with chemotherapy alone and than the controls, while the chemotherapy group had similar volumes as the control one. In neurocognitive assessment, irradiated children performed worse in major domains than the control group. There were no significant results for patients after high dose chemotherapy without radiotherapy. There was a significant relationship between full scale IQ together with verbal learning and volumes of hippocampus, amygdala, and pallidum. In all children treated for ALL, both decreased volume of selected subcortical structures and cognitive impairment were observed, especially in children who were irradiated.

Cerebellar Volume in Children With Attention-Deficit Hyperactivity Disorder (ADHD): Replication Study

Attention Deficit Hyperactivity Disorder (ADHD) is associated with altered cerebellar volume and cerebellum is associated with cognitive performance. However there are mixed results regarding the cerebellar volume in young patients with ADHD. To clarify the size and direction of this effect, we conducted the analysis on the large public database of brain images. The aim of this study was to confirm that cerebellar volume in ADHD is smaller than in control subjects in currently the largest publicly available cohort of ADHD subjects.We applied cross-sectional case control study design by comparing 286 ADHD patients (61 female) with age and gender matched control subjects. Volumetric measurements of cerebellum were obtained using automated segmentation with FreeSurfer 5.1. Statistical analysis was performed in R-CRAN statistical environment. Patients with ADHD had significantly smaller total cerebellar volumes (134.5±17.11cm3 vs.138.90±15.32 cm3). The effect was present in both females and males (males 136.9±14.37 cm3 vs. 141.20±14.75 cm3; females 125.7±12.34 cm3 vs. 131.20±15.03 cm3). Age was positively and significantly associated with the cerebellar volumes. These results indicate either delayed or disrupted cerebellar development possibly contributing to ADHD pathophysiology.

Serum sPECAM-1 and sVCAM-1 levels are associated with conversion to multiple sclerosis in patients with optic neuritis

Platelet-Endothelial-Cell-Adhesion-Molecule-1 (PECAM-1) and Human-Vascular-CAM-1 (VCAM-1) are adhesion molecules involved in leukocyte-endothelial interaction. In our study serum levels of sPECAM-1 and sVCAM-1 were measured (ELISA) in twenty-nine patients during their first monosymptomatic optic neuritis (ON) episode. Anti-aquaporin-4-antibodies (AQP4-IgG) were detected with the cell-based assay. Patients were followed for seven years, during which 16/24 AQP4-IgG (-) patients developed MS and 2/5 AQP4-IgG (+) patients developed NMO. Patients who developed MS had significantly lower sPECAM-1 and sVCAM-1 than those who did not. Serum sPECAM-1 and sVCAM-1 may turn out to be useful biomarkers correlated with the risk of progression to MS after first ON incident.

Subcortical gray matter atrophy is associated with cognitive deficit in multiple sclerosis but not in systemic lupus erythematosus patients

Cognitive impairment is a significant clinical problem both in multiple sclerosis (MS) and systemic lupus erythematosus (SLE) patients. In MS cognitive dysfunction has been associated with brain atrophy and total demyelinating lesion volume. In SLE cognitive impairment is much less understood, and its link to structural brain damage remains to be established. The aim of this study was to identify the relationship between subcortical gray matter volume and cognitive impairment in MS and SLE. We recruited 37 MS and 38 SLE patients matched by age, disease duration and educational level. Patients underwent magnetic resonance imaging (MRI) and a battery of psychometric tests. Severity of cognitive impairment was similar in both cohorts despite larger white matter lesion load in MS patients. Psychometric scores were associated with global and subcortical gray matter atrophy measures and lesion load in MS, but not in SLE. In SLE, the lack of a relationship between cognitive impairment and structural damage, defined either as atrophy or white matter lesions, indicates a different causal mechanism of cognitive deficit.

Unique Neural Characteristics of Atypical Lateralization of Language in Healthy Individuals

Using functional magnetic resonance imaging (fMRI) in 63 healthy participants, including left-handed and ambidextrous individuals, we tested how atypical lateralization of language—i. e., bilateral or right hemispheric language representation—differs from the typical left-hemisphere dominance. Although regardless of their handedness, all 11 participants from the atypical group engaged classical language centers, i.e., Brocas and Wernickes areas, the right-hemisphere components of the default mode network (DMN), including the angular gyrus and middle temporal gyrus, were also critically involved during the verbal fluency task. Importantly, activity in these regions could not be explained in terms of mirroring the typical language pattern because left-hemisphere dominant individuals did not exhibit similar significant signal modulations. Moreover, when spatial extent of language-related activity across whole brain was considered, the bilateral language organization entailed more diffuse functional processing. Finally, we detected significant differences between the typical and atypical group in the resting-state connectivity at the global and local level. These findings suggest that the atypical lateralization of language has unique features, and is not a simple mirror image of the typical left hemispheric language representation.

Disentangling the neural bases of action intentions: evidence from fMRI studies.

The way we interact with manipulable objects varies substantially depending on the goal of the intended action. Surprisingly, very little is known about the neural underpinnings of planning disparate actions and interactions taken with tools, e.g., whether or not the praxis representation network (PRN) of the left cerebral hemisphere is involved in each case. To address this issue, in a series of functional magnetic resonance imaging (fMRI) studies involving both event-related and block-design paradigms, brain activity was measured while twenty (20) right-handed participants - using either their right or left hands - processed images of tools with the following intentions: (1) to subsequently use them according to their functions, (2) to pass them to a different person, (3) to simply move the tool in front of them with the back of their hands, or (4) to move the tool by grasping and putting the object aside. Counter to the hypothesis that PRN would be involved more in, or would mediate primarily, intentions related to the planning of the actual use of tools, we report convincing evidence showing that the crucial nodes of this network - the left supramarginal and middle frontal gyri - are engaged significantly more in preparation for actions that are not use related. This is the case both at the hand-dependent, i.e. separately for the right and left hand, as well as at hand-independent level of analyses. These findings shed a new light on how different goals and/or contexts influence the perception of object affordances, and to what extent they modulate the fMRI activity within the parieto-frontal action networks and beyond them. Meeting abstract presented at VSS 2015.

Who Should Care for Stroke Patients

To the Editor: We read the discussion on the management of stroke in the November 2003 issue of Stroke with great interest. In general we agree with Prof Caplan’s point of view1 and disagree with Prof Lees’s suggestion of establishing a stroke subspecialty.2 It is not clear to us whether the background for such a subspecialty would be in neurology, internal medicine, or emergency medicine. The fact that every neurological patient needs holistic care is widely accepted. The problem is how to deliver it. Neurology is probably the most interdisciplinary field of current medicine and, as such, requires close collaboration with other specialties. Prof Lees states that “stroke is neurological but the cause is vascular.” Most conditions of the nervous system have some “nonneurological” causes: inflammatory, genetic, degenerative, infectious, etc. Should we then focus on causes only, rather than consider the clinical picture as a whole? In this discussion we are faced with 2 problems: (1) the structure and “philosophy” of medical education and (2) the administrative and financial needs of different health systems. Changes are necessary, but in what direction? …