Diffuse large B-cell lymphoma: the history, current view and new perspectives.

The basic principles of lymphoma classification(s) in general have been widely evolving in a course of decades of years wiht the use of contemporary resources and recent cutting edges in hematooncology on a clinical, morphological and molecular level bring new possibilities not only in improvements of diagnostic and prognostic algorithms and also bear new opportunities in so called targeted and tailored strategies of lymphoma therapy. The pathogenesis and biologic behavior of lymphoproliferations and even lymphomas should be studied in a context of lymphocytic and (neoplastic) lymphoid stage and chronologic development. In a current more complex insight into lymphoproliferations we would like to describe huge heterogeneity of diffuse large B-cell lymphoma in relationship to mandatory WHO classification since 2008 and the next development of knowledge in this field with potential new influence on an advancement of both classification and therapy.

Gender impact on electrophysiological activity of the brain.

Gender is presumed to be one of the factors causing interindividual variability in the brain's electrophysiological parameters. Our aim was to characterize the role of gender in visual evoked potentials (VEPs), event-related potentials (ERPs), visual mismatch negativity (vMMN) and the spectral characteristics of the EEG. We examined 42 healthy volunteers (21 women and 21 men, aged 20-29 years). We measured VEPs in response to pattern-reversal and motion-onset stimulation, ERPs in an oddball paradigm and vMMN in response to a combination of motion directions presented in the visual periphery. P100 peak latency for 40' reversal VEPs was significantly shorter in women than in men as determined using a non-parametric Wilcoxon signed-rank test. In addition, women showed higher relative EEG spectral power in the alpha band (p=0.023) and lower power in the theta band (p=0.004). Our results in this small but homogeneous group of subjects confirm previously reported gender influences on pattern-reversal VEPs and the EEG frequency spectrum. Gender should be taken into consideration in establishing norms on these measures. We found no statistically significant differences between women and men for any of the other stimuli presented.

Pattern and motion-related visual-evoked potentials in neuroborreliosis: follow-up study.

Visual-evoked potentials (VEPs) were used for objective testing of visual functions during treatment courses of Lyme neuroborreliosis (LNB) in adult patients in the Czech Republic. In 30 LNB patients with originally delayed VEP latencies, pattern-reversal (R-VEP) and motion onset (M-VEP) VEPs were repeatedly examined within 1 to 8 years. Six patients had Lyme optic neuritis (ON), five of them displayed prolonged latencies in both R-VEPs and M-VEPs, and one had only abnormal R-VEPs. The VEP recovery to normal latency values was in three of them. In the group of 24 LNB patients without ON, 14 patients displayed prolonged latencies only to motion stimuli, and 10 patients had abnormal latencies in both R-VEPs and M-VEPs. During the follow-up period, 7 patients displayed shortening to normal latencies. In 5 patients, VEPs latencies improved only partially, and in the remaining 12 patients, VEPs did not improve at all. This study provides objective evidence that in LNB, most of the patients without clinically manifesting ON display optic pathway involvement-predominantly magnocellular system/dorsal stream function changes. In patients with ON, however, mainly the parvocellular system is affected. About half of the patients without ON improved with a relatively long-time course of latency shortening.

Role of latency jittering correction in motion-onset VEP amplitude decay during prolonged visual stimulation.

Visual evoked potentials to motion-onset stimulation (M-VEPs) gradually attenuate in amplitude during examination. The observed decline in averaged responses can be caused by decreases in single response magnitudes and/or increased variability in a response delays, that is, latency jittering. To illuminate the origins of the suppression of M-VEPs during stimuli repetition, we used correlation technique to estimate an upper bound of possible latency jittering of single sweeps and we evaluated the effect of its correction on the amplitudes of three M-VEP dominant peaks P1, N2 and P3. During prolonged visual motion stimulation, the variability of corrective latency shifts in the occipital region increased (r = 0.35: 0.44) and the number of single responses corresponding to the average curve declined in occipital and parietal derivations (r = -0.48: -0.62). While the P1 peak amplitude did not exhibit any time-specific behaviour, the N2 amplitude exhibited a significant decay of 29.4% that was partially reduced to 16.6% in the central occipital derivation by the latency jitter and non-correspondence corrections. The strongest attenuation (32.7%) was observed in the P3 amplitude and was less sensitive to the corrections, dropping only to 27.9%. The main part of the response suppression to repeated motion stimulation was caused by amplitude drop and represents non-stationary process that likely correspond to a fatigue model. The rise of variability in latency jitter correction and the reduction in single responses correlated with the M-VEP were significant factors associated with prolonged motion stimulation. The relation of these parameters to a hypothetical veridical response is ambiguous and can be caused by a time shift of the response or by a change of signal-to-noise ratio. Using selective averaging and latency jitter correction, the effect of response suppression was partially removed.

Determining the extent and stage of disease in patients with newly diagnosed non-Hodgkin's lymphoma using 18F-FDG-PET/CT.

Positron emission tomography (PET) using 2-[fluorine-18]-fluoro-2-deoxy-D-glucose (18F-FDG) combined with computed tomography (CT) represents a three-dimensional imaging method suitable for staging in patients with non-Hodgkin's lymphomas (NHLs). The aim of our prospective multicenter study was to assess the value of initial PET/CT as compared with CT and PET alone for determining the stage and extent of the disease. A total of 122 patients with newly diagnosed NHL were examined using PET/CT. Four patients with resected lymphoma lesion and negative PET/CT were therefore excluded from the study. Of the remaining 118 cases, a total of 117 (99%) were described as 18F-FDG-avid. When compared with PET/CT, CT and PET showed very good sensitivity of lymph node imaging (97% and 100%, respectively); the specificity, however, was significantly lower (66.7% and 94.4%, respectively; p=0.0001). When detecting organ lesions, the sensitivity of CT and PET was lower than that of PET/CT (92.5% and 96.3%, respectively; p=0.0001); specificity was significantly decreased in CT and a little lower in PET (59.5% and 91.9%; p=0.0001). When compared with CT alone, PET/CT changed staging of the disease in 11 patients (9%) and was able to detect a total of 82 discrepancies in 67 of the 117 patients (57%). In conclusion, PET/CT is a new standard in imaging the involvement of lymph nodes and extranodal organs in NHL patients regardless of their histopathological types. Both sensitivity and specificity of the examination are higher than those of CT as well as PET alone.

Visual evoked potentials to pattern, motion and cognitive stimuli in Alzheimer's disease.

The aim of our study was to verify reported visual dysfunctions of patients with Alzheimer disease with the use of several variants of VEPs and visual ERPs and to learn whether these methods can be useful in diagnostics of AD. We tested 15 patients (6 women and 9 men, aged from 58 to 87) with mild to moderate Alzheimer disease (12-23 points of Mini Mental State Examination) and 15 age, gender and education level matched controls. The examination consisted of VEPs to pattern-reversal and motion-onset stimulation (to translational and radial movement) and of visual ERPs recorded during an odd-ball test. The subjects were instructed to signalize target stimuli by pressing of a button, which enabled to evaluate also the reaction time. While pattern-reversal VEPs were comparable in patients and controls, there were significantly smaller N2 peak amplitudes of motion-onset VEPs in patients with AD (in particular in radial moving stimuli outside the central 20 deg of the visual field), which suggests a dysfunction of the motion-processing (magnocellular) system or the dorsal cortical stream. ERPs, having significantly longer latencies in patients than in controls, distinguished well both groups. However, the individual AD diagnostics based on ERPs seems to be limited by rather high inter-individual variability of the ERP latencies. The ERPs might, however, be useful in disease progress and therapy effect estimation. Electrophysiological parameters did not correlate with neuropsychological ADAS cog test (Alzheimer Disease Assessment Scale--cognitive part).

High-dose therapy and autologous stem cell transplantation in patients with diffuse large B-cell lymphoma in first complete or partial remission.

Improved survival has been observed in poor-risk diffuse large B-cell lymphoma (DLBCL) patients treated with high-dose therapy (HDT) followed by autologous stem cell transplantation (ASCT) in first complete remission. Retrospective studies have suggested that HDT with ASCT can improve survival also in partial responders but some doubts about the advantage of intensive therapy in such patients still remain. We evaluated retrospectively the results of HDT and ASCT in 55 patients with confirmed DLBCL treated between May 1999 and July 2006. Thirty-six patients (65%) showed partial remission (PR) and 19 patients (35%) reached complete remission (CR) after induction treatment with (44%) or without (56%) concomitant rituximab (R) immunotherapy. After HDT and ASCT, 69% of patients fulfilled the criteria of CR, 22% had unconfirmed CR (CRu), 7% remained in PR and 1 patient (2%) relapsed. Twenty patients in PR after the induction treatment reached CR after ASCT, 12 other PR patients achieved CRu. The 5-year event-free survival (EFS) of the 55 transplanted patients was 76% (95% confidence interval /CI/, 63% to 89%) and the 5-year overall survival (OS) was 85% (95% CI, 73% to 97%). The EFS and OS rates differed significantly only between patients younger than 40 years and older groups (p=0.022 and p=0.046, respectively). On univariate analysis of prognostic factors, EFS and OS were not affected by any of the following: age, sex, stage, subtype of DLBCL, initial lactate dehydrogenase, beta-2-microglobulin and serum thymidine kinase levels, International Prognostic Index (IPI) and age-adjusted IPI scores, induction treatment with or without rituximab and type of primary therapeutic response (CR vs PR). These results show that first-line HDT and ASCT for adults up to the age of 65 years with poor-risk DLBCL is a feasible and effective treatment option even in the era of R-chemotherapy in CR as well as for patients in PR.

Motion-onset VEPs: characteristics, methods, and diagnostic use.

This review article summarises the research on the motion-onset visual evoked potentials (VEPs) and important motion stimulus parameters which have been clarified. For activation of the visual motion processing system and evocation of the motion-onset specific N2 peak (with latency of 160-200ms) from the extra-striate temporo-occipital and/or parietal cortex, the following stimulus parameters can be recently recommended: low luminance (

Motion-onset VEPs reflect long maturation and early aging of visual motion-processing system.

Pattern-reversal and motion-onset visual evoked potentials (VEPs) were simultaneously tested in a group of 70 healthy subjects between the ages of 6-60 years to verify suspected differences in maturation and aging dynamics of the pattern and motion processing subsystems of the visual pathway. The motion-onset VEPs displayed dramatic configuration development and shortening of latencies up to 18 years of age (correl. coeff. -0.85; p < 0.001) and systematic prolongation from about 20 years of age (correl. coeff. 0.70; p < 0.001). This confirms long-lasting maturation of the magnocellular system and/or motion processing cortex and their early age related changes. Less significant changes of pattern-reversal VEPs in the tested age range can be interpreted as a sign of early maturation of the parvocellular system and its enhanced functional endurance in the elderly.

Visual mismatch negativity elicited by magnocellular system activation.

The processing of visual motion was tested by means of event related potentials recording (ERP) using a paradigm designed to produce a visual mismatch negativity effect. The stimuli were unattended and presented in the peripheral visual field (outside the central 15 degrees). The standard stimulus consisted of an up/down motion sequence, whilst the deviant stimulus of a down/up motion sequence. Significant ERP differences between the standard and deviant conditions were found in 8 out of 10 adult subjects already in 80 ms and prevailingly in interval 145-260 ms from the initial stimulus presentation. The results demonstrate that the magnocellular information undergoes processing capable of detecting differences in the sequence of unattended peripheral motion stimuli.

Visual evoked potentials and event related potentials in congenitally deaf subjects.

The purpose was to test parameters of visual evoked potentials (VEPs) and of event-related potentials (ERPs) in deaf subjects to verify visual and cognitive CNS functions in a handicapped group of the population. Three types of visual stimuli (with dominating parvocellular or magnocellular system activation or with cognitive tasks) were used in the study. Six deaf persons (4 women, 2 men, mean age 17 years) and 6 persons with normal hearing (sex- and age-matched) were included in this pilot study. In all types of stimulation, latencies and amplitudes of main VEPs and ERPs components were evaluated. No significant latency differences were found. However, significantly reduced amplitudes were found in the occipital area for responses to motion and cognitive stimuli which might be interpreted as a part of functional reorganization of the extrastriate and cognitive cortical areas of deaf subjects.

Influence of physiological changes of glycaemia on VEPs and visual ERPs.

Since hypoglycemia is known to influence cognitive functions, we checked whether the physiological changes in glycemia (after fasting or exertion) can explain the rather high intra-individual variability of event-related potentials (ERPs). Besides the ERPs to "change in coherence of a moving pattern" with reaction time (RT) recording, binocular pattern reversal VEPs and motion-onset VEPs (to linear and radial motion) were also examined in 14 healthy subjects prior to and after 24-h fasting that decreased glycemia from 5.3 to 3.9 mmol/l on the average. We only found one significant change in the latencies and amplitudes of VEPs and ERPs (with no change of RT). The N160 peak in the motion-onset VEPs to radial (expansive) motion (EM-VEPs) showed a larger amplitude at lower glycemia. For evaluation of the exertion influence, we tested glycemia prior to and after 90 min long exercise -- bicycle ergometry with the load set to 2 W/kg in women and 2.5 W/kg in men (average age-related values for W170/kg index). The changes of glycemia to exertion were, however, less distinct than those to fasting. We conclude that in healthy subjects the glycemia decrease due to 24-h fasting or intensive time-limited exercise never reaches the critical value to change the VEP, ERPs and RTs.

Effect of stimulus localisation on motion-onset VEP.

Reliable motion-onset visual evoked potentials (result of the dorsal stream activation) were recorded to motion stimuli with the temporal frequency of five cycles per seconds in 20 different locations with eccentricity up to 42 degrees to periphery of the visual field. Amplitudes and latencies of the positive-negative-positive (P1-N1-P2; 84-144-208 ms) complex were evaluated in occipital (OZ and two derivations 5 cm to the left and right from OZ) and central region (CZ) in 10 subjects. We observed: (1) Shortening of the N1 latency toward periphery of the visual field. (2) The N1 amplitude maximum and latency minimum moved from occipital into central region (CZ derivation) as stimulus moved from centre toward periphery of visual field. (3) The P1 and N1 peaks displayed significantly greater amplitudes and shorter latencies when the lower part of the visual field was stimulated. (4) The N1 peak changed lateralisation of its maximum amplitude in dependence on the eccentricity. Up to 17 degrees, it corresponds to striate projection of the "optic radiation" whilst more in periphery, there was paradoxical lateralisation of higher amplitude and shorter latency. The retinotopic dependence shows that the motion response includes position information and that the motion-onset VEPs are not generated solely in the higher extrastriate areas (MT or MST).

Visual event-related potentials to moving stimuli: normative data.

Visual cognitive responses (P300) to moving stimuli were tested in 36 subjects with the aim to find the normal range of P300 parameters. Concomitantly, the circadian intra-individual variability of the P300 was studied in a subgroup of 6 subjects. Visual stimuli consisted of either coherent (frequent stimulus) or non-coherent motion (random stimulus). The oddball paradigm was applied for recording cognitive responses. P300 to rare stimuli had an average latency of 447.3 +/- 46.6 ms and amplitude of 12.9 +/- 6.0 microV. The average reaction time was in the range from 322 to 611 ms and there was no correlation between the reaction time and P300 latency. We did not find any significant circadian changes of the P300 parameters in the 6 subjects tested four times during the same day. Cognitive (event-related) responses (P300) displayed distinctly greater inter-individual variability (S.D. of 50 ms) when compared with pattern-reversal and motion-onset VEPs (S.D. of 6.0 ms and 14 ms, respectively). For this reason, the clinical use of P300 elicited by this kind of visual stimuli seems to be rather restricted and the evaluation of its intra-individual changes is preferable.

Electrophysiological testing of dyslexia.

We enlarged our previous study (Kubová Z. et al. Physiol Res 1995;44:87-89) giving an evidence about magnocellular pathway involvement (delayed motion-onset visual evoked potentials (M-VEPs)) in 70% of dyslexic children. In the new group presented here, only 48% of 25 dyslexics displayed prolonged latencies of cortical responses to motion stimuli. However, there was no correlation of this defect with the used quantification of the reading skills (reading quotients). No significant EEG frequency spectrum changes were found. 10 subjects from the former group, who were re-examined 4 years after the previous study at the mean age of 14 years, exhibited significant shortening of the M-VEP latencies compared to the original values. Also in control subjects a distinct improvement in magnocellular pathway function was proved (in M-VEP re-examination after 4 years). These results document rather late maturation of the magnocellular pathway, which is evident mainly in dyslexic children. In both groups of dyslexics an effect of colour in moving stimuli was also tested to verify the reported effect of light wavelengths onto the magnocellular pathway function. However, no latency differences among grey, green, pink, yellow and blue stimuli were observed.

The development of hemispheric asymmetry in human motion VEPs.

In six healthy adults we examined the sources underlying P1 and N2 of the motion VEP. For this purpose was acquired, in addition to the VEP, MRI images and patterns of regional cerebral blood flow with SPECT for three of the subjects. With the same motion stimulus we also examined the spatial distribution of N2 in children. In both adults and children left and right half-field responses were compared. It was found that N2 is generated by extrastriate activity and that motion stimuli are not equivalently processed in the two cerebral hemispheres. In adults, N2 dominates in one hemisphere irrespective of the visual half-field used for stimulation whereas children show an ipsilateral maximum for N2 upon half-field presentation.

Simple and powerful visual stimulus generator.

We describe a cheap, simple, portable and efficient approach to visual stimulation for neurophysiology which does not need any special hardware equipment. The method based on an animation technique uses the FLI autodesk animator format. This form of the animation is replayed by a special program ('player') providing synchronisation pulses toward recording system via parallel port. The 'player is running on an IBM compatible personal computer under MS-DOS operation system and stimulus is displayed on a VGA computer monitor. Various stimuli created with this technique for visual evoked potentials (VEPs) are presented.

Cognitive evoked potentials related to visual perception of motion in human subjects.

A method was tested for simultaneous recordings of evoked potentials from the secondary visual cortex (mediotemporal) and from the brain cognitive areas (fronto-central). Visual moving stimulations with cognitive tasks seem to be suitable for combined examination of visual motion perception and cognitive processes based on the magnocellular system activity. This arrangement enhances the analysis of visual information processing and evaluation of central nervous system functions.

Visual evoked potential evidence for magnocellular system deficit in dyslexia.

Some recent studies on dyslexia have suggested a selective abnormality in the magnocellular visual pathway. To verify this hypothesis, we investigated motion-onset visual evoked potentials (VEPs) (predominantly testing the magnocellular system) as well as pattern-reversal VEPs (presumably testing the parvocellular system) in 20 dyslexics and 16 controls (both groups with a mean age of 10.0 years). Although the latencies and amplitudes of the main positive peak of pattern-reversal VEPs did not differ between the dyslexic and control group, the motion specific negative peak of motion-onset VEPs was significantly delayed (p < 0.001) in dyslexics. Our results confirm a selective magnocellular pathway disorder in dyslexics and indicate that the motion-onset VEPs might serve as an objective method for early diagnosis of dyslexia.

Motion-onset visual evoked potentials improve the diagnosis of glaucoma.

Chronic glaucoma has been shown preferentially to damage larger retinal cells and optic nerve fibres that provide the input to the magnocellular visual pathway. We compared the motion-onset visual evoked potentials (primarily the magnocellular system) with those to standard pattern reversal in 20 patients with bilateral chronic glaucoma. For motion-onset visual evoked potentials, the pattern (isolated 40' checks of 10% contrast) moved in four cardinal directions (varied randomly from trial to trial) at a velocity of 10 deg/s for 20 ms, with an interstimulus interval of 1 s. In pattern-reversal stimulation, the checkerboard reversed at a rate of 2 reversals per second. In 60% of the eyes investigated, the results of both types of visual evoked potentials correlated, showing either normal (27.5%) or increased (32.5%) latencies. In the remaining 40% of the eyes, the normal pattern-reversal visual evoked potential latencies were accompanied by prolonged motion-onset visual evoked potentials. The high occurrence of delayed motion-onset visual evoked potentials in our patients confirms the primary magnocellular loss in chronic glaucoma and suggests that the motion-onset VEPs are suitable for detection of glaucomatous changes.