A link between inflammation and metastasis: serum amyloid A1 and A3 induce metastasis, and are targets of metastasis-inducing S100A4.

S100A4 is implicated in metastasis and chronic inflammation, but its function remains uncertain. Here we establish an S100A4-dependent link between inflammation and metastatic tumor progression. We found that the acute-phase response proteins serum amyloid A (SAA) 1 and SAA3 are transcriptional targets of S100A4 via Toll-like receptor 4 (TLR4)/nuclear factor-κB signaling. SAA proteins stimulated the transcription of RANTES (regulated upon activation normal T-cell expressed and presumably secreted), G-CSF (granulocyte-colony-stimulating factor) and MMP2 (matrix metalloproteinase 2), MMP3, MMP9 and MMP13. We have also shown for the first time that SAA stimulate their own transcription as well as that of proinflammatory S100A8 and S100A9 proteins. Moreover, they strongly enhanced tumor cell adhesion to fibronectin, and stimulated migration and invasion of human and mouse tumor cells. Intravenously injected S100A4 protein induced expression of SAA proteins and cytokines in an organ-specific manner. In a breast cancer animal model, ectopic expression of SAA1 or SAA3 in tumor cells potently promoted widespread metastasis formation accompanied by a massive infiltration of immune cells. Furthermore, coordinate expression of S100A4 and SAA in tumor samples from colorectal carcinoma patients significantly correlated with reduced overall survival. These data show that SAA proteins are effectors for the metastasis-promoting functions of S100A4, and serve as a link between inflammation and tumor progression.

Fatigue, sleepiness, and physical activity in patients with multiple sclerosis.

Fatigue is a frequent and disabling symptom in patients with multiple sclerosis (MS). The objective of the study was to compare fatigue and sleepiness in MS, and their relationship to physical activity. Eighty patients with MS rated the extent of experienced fatigue (Fatigue Severity Scale, FSS) and sleepiness (Epworth Sleepiness Scale, ESS). The relationship between the scales was analysed for the scales as a whole and for single items. The clinical status of the patients was measured with the Extended Disability Status Scale (EDSS). In addition, physical activity was recorded continuously for 1 week by wrist actigraphy. The mean scores of fatigue and sleepiness were significantly correlated (FSS vs. ESS r=0.42). Single item analysis suggests that fatigue and sleepiness converge for situations that demand self-paced activation, while they differ for situations in which external cues contribute to the level of activation. While fatigue correlated significantly with age (r=0.40), disease severity (EDSS, r=0.38), and disease duration (r=0.25), this was not the case for sleepiness. Single patient analysis showed a larger scatter of sleepiness scores in fatigued patients (FSS>4) than in non-fatigued patients. Probably, there is a subgroup of MS patients with sleep disturbances that rate high on ESS and FSS. The amount of physical activity, which was measured actigraphically, decreased with disease severity (EDSS) while it did not correlate with fatigue or sleepiness.

Accuracy of non-invasive ICP assessment can be increased by an initial individual calibration.

OBJECTIVE: In a formerly introduced mathematical model, intracranial pressure (ICP) could be non-invasively assessed using cerebral blood flow velocity (FV) and arterial blood pressure (ABP). The current study attempts to check whether the accuracy of the non-invasive ICP assessment (nICP) improves after an initial individual calibration by implanted ICP probes. METHODS: Thirteen patients with brain lesions (35-77 years, mean: 58 +/- 13 years) were studied. FV, ABP and ICP signals were recorded at days 1, 2, 4 and 7. nICP was calculated and compared to ICP. In the first recording of each patient the (invasively assessed) ICP signal was used to calibrate the nICP calculation procedure, while the follow-up recordings were used for its validation. FINDINGS: In 11 patients 22 follow-up recordings were performed. The mean deviation between ICP and the original nICP (+/- SD) was 8.3 +/- 7.9 mmHg. Using the calibrated method this deviation was reduced to 6.7 +/- 6.7 mmHg (P < 0.005). CONCLUSIONS: Initial individual calibration of nICP assessment method significantly improves the accuracy of nICP estimation on subsequent days. This hybrid method of ICP assessment may be used in intensive care units in patients with initially implanted ICP probes. After removal of the probes, ICP monitoring can be continued using the calibrated nICP assessment procedure.

Fuzzy pattern classification of hemodynamic data can be used to determine noninvasive intracranial pressure.

OBJECTIVE: The authors previously introduced a method in which intracranial pressure (ICP) was estimated using parameters (TCD characteristics) derived from cerebral blood flow velocity (FV) and arterial blood pressure (ABP). Some results suggested that this model might be influenced by the patient's state of cerebral autoregulation and other clinical parameters. Hence, it was the aim of the present study to improve the method by modifying the previously used global procedure in certain subgroups of patients. METHODS: In 103 traumatic brain injured patients (3-76 years, mean: 31 +/- 16 years) signal data of FV, ABP and ICP were used to generate samples of TCD characteristics together with time corresponding ICP. Fuzzy Pattern Classification was used to identify cluster subsets (classes) of the sample space. On each class a local estimator of ICP was defined. This approach provides a non-invasive assessment of ICP (nICP) as follows: Using FV and ABP the TCD characteristics were computed and related to the matching classes. nICP was calculated as a weighted sum of local ICP estimations. RESULTS: ICP A and B waves and long-term trends could be visibly assessed. The median absolute difference between ICP and nICP was 5.7 mmHg. CONCLUSIONS: The class structure of the model facilitates nICP assessment in heterogeneous patient groups and supports a stepwise extension of the target patient group without affecting the former validity.

[Arthroscopically assisted refixation for avulsion fracture of the intercondylar eminence with Fiber-Wire cerclage]. / Arthroskopisch gestützte Refixation von Ausrissen der Eminentia intercondylica über Fiber-Wire-Cerclagen.

Avulsion fracture of the intercondylar eminence is a rare knee injury. It is found either isolated or connected to other bone or intra-articular injuries. Arthroscopically assisted treatment is nowadays the most common procedure. The refixation of the fragment is technically sophisticated and usually requires a longer period of immobilization. In two patients we used a suture cerclage with extreme tensile strength (Fiber-Wire, Arthrex Inc.) placed through a tibial guide. Using this procedure we combined the advantages of easy implantation, sufficient retention, and thereby the possibility of forced follow-up treatment. The present results are promising.

Prognostic relevance of pathological sympathetic activation after acute thromboembolic stroke.

OBJECTIVE: To evaluate the prognostic impact of early pathologic sympathetic activation after stroke. METHODS: The authors examined 112 consecutive patients (mean age, 69 years; 60 men) with their first brain infarction. A pathologic sympathetic activation was presumed if the initial norepinephrine level exceeds 300 pg/mL. In addition, involvement of the insular cortex, nighttime blood pressure changes, and several cardiovascular risk factors were determined. One-year outcome measures were mortality rate, cardiovascular and cerebrovascular events, and activities of daily living (Barthel index and Rankin score). RESULTS: Norepinephrine levels greater than 300 pg/mL, nighttime blood pressure increases, and insular involvement were associated with a lower Barthel index (p < 0.005) at the 1-year follow-up. By stepwise logistic regression analysis, insular infarction, serum norepinephrine concentration, right-sided infarction, and nighttime blood pressure increase were significant and independent predictors of an unfavorable functional outcome. Cox regression analysis showed a higher rate of cardiovascular and cerebrovascular events (hazard ratio, 2.9; 95% CI, 1.07; 6.83; p < 0.04) in patients with initially increased norepinephrine concentrations. CONCLUSIONS: The involvement of the insular cortex, the occurrence of a pathologic nighttime blood pressure increase, and an initially increased serum norepinephrine concentration are independent predictors of poor long-term outcome.

The metastasis-associated Mts1(S100A4) protein could act as an angiogenic factor.

The involvement of Mts1(S100A4), a small Ca(2+)-binding protein in tumor progression and metastasis had been demonstrated. However, the mechanism by which mts1(S100A4) promoted metastasis had not been identified. Here we demonstrated that Mts1(S100A4) had significant stimulatory effect on the angiogenesis. We detected high incidence of hemangiomas--benign tumors of vascular origin in aged transgenic mice ubiquitously expressing the mts1(S100A4) gene. Furthermore, the serum level of the Mts1(S100A4) protein increased with ageing. Tumors developed in Mts1-transgenic mice revealed an enhanced vascular density. We showed that an oligomeric, but not a dimeric form of the Mts1(S100A4) protein was capable of enhancing the endothelial cell motility in vitro and stimulate the corneal neovascularization in vivo. An oligomeric fraction of the protein was detected in the conditioned media as well as in human serum. The data obtained allowed us to conclude that mts1(S100A4) might induce tumor progression via stimulation of angiogenesis.

Cerebral blood flow velocity in untreated panic disorder patients: a transcranial Doppler ultrasonography study.

BACKGROUND: The aim of this study was to compare resting cerebral blood flow velocity values of unmedicated patients in the acute phase of panic disorder with resting values of healthy control subjects. METHODS: Nineteen unmedicated panic disorder patients were assessed for degree of anxiety using the Hamilton Anxiety Scale. The patients and 20 healthy age-matched control subjects were then insonated at rest using transcranial Doppler ultrasonography (TCD). For TCD, the anterior, the middle, and the posterior cerebral arteries were insonated bilaterally in all patients. RESULTS: Compared with healthy age-matched control subjects, acute unmedicated panic disorder patients showed a significant increase in cerebral blood flow velocity, bilaterally in the middle and the anterior cerebral artery, and unilaterally in the left posterior cerebral artery. Cerebral blood flow velocity in the right middle cerebral artery correlated positively to the item "Fear" on the Hamilton Anxiety Scale, whereas pulsatility index in the posterior cerebral artery bilaterally and in the left middle cerebral artery correlated negatively to the item "Mood." CONCLUSIONS: Transcranial Doppler ultrasonography agrees well with validated psychometric methods. If follow-up studies confirm our findings, TCD could allow an objective assessment of the mental state of panic disorder patients and reliably discriminate panic disorder patients from normal control subjects.

Enhanced progression of early carotid atherosclerosis is related to Chlamydia pneumoniae (Taiwan acute respiratory) seropositivity.

BACKGROUND: Chlamydia pneumoniae (Cp) infection has been associated with atherosclerosis and has been proposed as a possible additional cardiovascular risk factor. However, the relationship between Cp seropositivity and the progression of early carotid atherosclerosis is not unequivocally clarified. METHODS AND RESULTS: We evaluated the association between serological detection of Cp IgG and/or IgA antibodies and the progression of the intima-media thickness (IMT) of the common carotid artery using duplex ultrasonography in a prospective study with a follow-up of 3 years in 272 consecutive patients with cerebrovascular disease. Cp-seropositive patients showed a significantly enhanced progression of the IMT even after adjustment for other cardiovascular risk factors (0.12 mm/y [95% CI 0.11 to 0.14] versus 0.07 mm/y [0.05 to 0.09]; P:<0.005). Patients with increased C-reactive protein (>/=0.5 mg/dL) and Cp seropositivity showed the most pronounced IMT progression. Multivariate regression analysis revealed Cp seropositivity to be an independent risk factor for progression of early carotid atherosclerosis. Cox proportional-hazard regression analysis demonstrated a significantly increased rate of cerebrovascular and cardiovascular events in patients with Cp seropositivity, particularly in patients with increased C-reactive protein levels. CONCLUSIONS: Our data support the importance of chronic inflammation and infection for the early stages of atherosclerotic development.

Disturbance of venous flow patterns in patients with transient global amnesia.

Transient global amnesia (TGA) is an inability to form new memories. The pathophysiology and cause of TGA have not been defined. We examined the changes of internal jugular venous flow patterns in 21 patients with TGA and 21 age-matched and sex-matched controls using duplex ultrasonography during two Valsalva manoeuvres (blocking venous return through the superior vena cava). During both manoeuvres a retrograde flow component was seen significantly more frequently in the TGA group than in the controls. Ten patients reported Valsalva-like activities preceding TGA. In these patients a retrograde flow component took place more frequently than in those who did not report preceding Valsalva-like activities. Our results lend support to the hypothesis that TGA may be attributable to venous congestion, and consequent venous ischaemia to bilateral diencephalic or hippocampal structures.

Extent of cerebral white matter lesions is related to changes of circadian blood pressure rhythmicity.

OBJECTIVE: To evaluate the relationship between circadian blood pressure patterns and the extent of cerebral white matter lesions (WML). DESIGN: Case-control study. PARTICIPANTS: A total of 227 healthy subjects older than 55 years were investigated. Extent and occurrence of WML were evaluated using a computer-supported image analysis system. Circadian blood pressure variation was defined as the average percentage change of nighttime blood pressure compared with the daily blood pressure values. RESULTS: Subjects with WML were significantly older and showed more often a history of hypertension, elevated average systolic daily blood pressure, a reduced systolic circadian blood pressure variation, and an increased incidence of pathological nighttime blood pressure increases. A significant correlation was found between systolic circadian blood pressure variation and the extent of WML. A multiple regression analysis revealed that this parameter was best correlated with the extent of WML. CONCLUSION: In addition to the absolute level of blood pressure, systolic circadian blood pressure variation and in particular a systolic nighttime blood pressure increase may play an important role in the pathogenesis of WML.

Relationship between circadian blood pressure patterns and progression of early carotid atherosclerosis: A 3-year follow-up study.

BACKGROUND: Arterial hypertension is a major risk factor for cardiovascular damage. The results of several studies suggest that target organ damage is greater in hypertensive persons with high blood pressure variability. METHODS AND RESULTS: During 3.3 years of follow-up, we studied the relationship between circadian blood pressure changes and the progression of early carotid atherosclerosis in 286 patients aged >55 years. Blood pressure patterns were evaluated with a long-term blood pressure monitor, and the extent of atherosclerosis was measured as the intima-media wall thickness (IMT) of the common carotid artery. Patients were subdivided according to blood pressure variability. The progression of IMT was significantly greater in the patients with increased systolic blood pressure variability (0.11 mm/y [95% CI 0.09 to 0.14] versus 0.05 mm/y [0.03 to 0.08]; P:<0.005) even after adjustment for other risk factors. Multivariate regression analysis revealed the daytime systolic blood pressure variability to be the best predictor for the progression of IMT. Raised daytime systolic blood pressure variability (>15 mm Hg) is associated with an increased relative risk of the development of early atherosclerosis (3.9 [1.4 to 11.1]; P:<0.01) and of cardiovascular events (1.87 [1.08 to 3.20]; P:<0.01). CONCLUSIONS: The daytime systolic blood pressure variability is a strong predictor of early carotid atherosclerosis progression and is useful to define the risk-benefit ratio of therapeutic approaches.

Amino-terminal domain of classic cadherins determines the specificity of the adhesive interactions.

Classic cadherins are transmembrane receptors involved in cell type-specific calcium-dependent intercellular adhesion. The specificity of adhesion is mediated by homophilic interactions between cadherins extending from opposing cell surfaces. In addition, classic cadherins can self-associate forming lateral dimers. Whereas it is widely excepted that lateral dimerization of cadherins is critical for adhesion, details of this process are not known. Yet, no evidence for physical association between different classic cadherins in cells expressing complex cadherin patterns has been reported. To study lateral and adhesive intercadherin interactions, we examined interactions between two classic cadherins, E- and P-cadherins, in epithelial A-431 cells co-producing both proteins. We showed that these cells exhibited heterocomplexes consisting of laterally assembled E- and P-cadherins. These complexes were formed by a mechanism involving Trp(156) of E-cadherin. Removal of calcium ions from the culture medium triggered a novel Trp(156)-independent type of lateral E-cadherin-P-cadherin association. Notably, an antiparallel (adhesive) mode of interaction between these cadherins was negligible. The specificity of adhesive interaction was localized to the amino-terminal (EC1) domain of both cadherins. Thus, EC1 domain of classic cadherins exposes two determinants responsible for nonspecific lateral and cadherin type-specific adhesive dimerization.

Evaluation of a method for noninvasive intracranial pressure assessment during infusion studies in patients with hydrocephalus.

OBJECT: A mathematical model previously introduced by the authors allowed noninvasive intracranial pressure (nICP) assessment. In the present study the authors investigated this model as an aid in predicting the time course of raised ICP during infusion tests in patients with hydrocephalus and its suitability for estimating the resistance to outflow of cerebrospinal fluid (Rcsf). METHODS: Twenty-one patients with hydrocephalus were studied. The nICP was calculated from the arterial blood pressure (ABP) waveform by using a linear signal transformation, which was dynamically modified by the relationship between ABP and cerebral blood flow velocity. This model was verified by comparison of nICP with "real" ICP measured during lumbar infusion tests. In all simulations, parallel increases in real ICP and nICP were evident. The simulated Rcsf was computed using nICP and then compared with Rcsf computed from real ICP. The mean absolute error between real and simulated Rcsf was 4.1 +/- 2.2 mm Hg minute/ml. By the construction of simulations specific to different subtypes of hydrocephalus arising from various causes, the mean error decreased to 2.7 +/- 1.7 mm Hg minute/ml, whereas the correlation between real and simulated Rcsf increased from R = 0.73 to R = 0.89 (p < 0.001). CONCLUSIONS: The validity of the mathematical model was confirmed in this study. The creation of type-specific simulations resulted in substantial improvements in the accuracy of ICP assessment. Improvement strategies could be important because of a potential clinical benefit from this method.

Removal of calcium ions triggers a novel type of intercadherin interaction.

Depletion of Ca(2+) ions from epithelial cell cultures has been shown to result in the rapid destruction of intercellular junctions. To understand the mechanism of this effect we have examined how removal of calcium ions from the culture medium of A-431 epithelial cells affects complexes incorporating the cell-cell adhesive receptors, E-cadherin, desmoglein or desmocollin. Sedimentation and biochemical analysis demonstrated that calcium removal triggers a rapid formation of a novel type of complex formed via direct lateral E-cadherin-desmoglein, E-cadherin-desmocollin and desmoglein-desmocollin dimerization of the extracellular cadherin regions. Replacement of Trp(156) and Val(157) of E-cadherin, that has been shown to abolish lateral and adhesive E-cadherin homodimerization in standard cultures, did not influence the formation of these 'calcium-sensitive' complexes. Furthermore, experiments with this mutant revealed that EGTA induced lateral Trp(156)/Val(157)-independent homodimerization of E-cadherin. Deletion mutagenesis of E-cadherin showed that these complexes are mediated by at least two extracellular cadherin domains, EC3 and EC4. Notably, protein kinase inhibitor H-7 which confers EGTA-independence of the adhesive E-cadherin complexes does not block this association. We propose that this novel type of intercadherin interaction is involved in the assembly of adherens junctions and their disassembly in low-calcium medium.

Cerebral vasodilatation causing acute intracranial hypertension: a method for noninvasive assessment.

Deep spontaneous vasodilatatory events are frequently recorded in various cerebral diseases, causing dramatic increases (A-waves) in intracranial pressure (ICP) and subsequently provoking ischemic brain insults. The relationship between fluctuations in CBF, ICP, and arterial blood pressure (ABP) is influenced by properties of cerebrovascular control mechanisms and the cerebrospinal pressure-volume compensation. The goal of this study was to construct a mathematical model of this relationship and to assess its ability to predict the occurrence and time course of A-waves. A group of 17 severely head-injured patients were included in the study. In our model ICP was derived from the ABP waveform using a linear signal transformation. The transformation was modified during the simulation by a relationship between ABP and flow velocity, i.e., by the characterization of the cerebrovascular bed. In this way the ICP could be calculated from the ABP waveform. This model was verified by comparison of simulated and directly measured ICP during A-waves recorded in seven of the patients. In all simulations, plateau elevations of ICP were well replicated. The mean absolute error between real and simulated ICP was 8.3 +/- 5.4 mm Hg at the baseline and 7.9 +/- 4.3 mm Hg at the top of plateau waves. The correlation coefficient between real and simulated increase in ICP was R = 0.98; P < .001. Similarly, correlation between real and simulated increase in pulse amplitude of ICP was highly significant (R = 0.94; P < .001). The mathematical model of the relationship between ABP, flow velocity, and ICP is of potential clinical use for the noninvasive detection of A-waves in patients in whom invasive ICP assessment is not conducted.

Methodological parameters influence the detection of right-to-left shunts by contrast transcranial Doppler ultrasonography.

BACKGROUND AND PURPOSE: Contrast transcranial Doppler ultrasonography is a new method to detect intracardiac right-to-left shunts, such as the patent foramen ovale. However, the methodology of the procedure varies considerably among investigators. This study was undertaken to assess the influence of methodological parameters on the results of the contrast transcranial Doppler examination in the detection of right-to-left shunts. METHODS: A total of 72 patients (mean age, 58.2+/-14.7 years) had a contrast transcranial Doppler ultrasonography examination. To study the influence of methodological factors, patients with evidence of a right-to-left shunt underwent repeated examinations with modified procedures. Parameters under investigation were the timing of the Valsalva maneuver, the dose of the contrast medium, and the patient's posture during the examination. RESULTS: The median contrast signal count was 58.5 and 48.0 (P<0.001) and the median latency of the first intracranially detected contrast signal was 12.5 and 8.5 seconds (P=0.05) when the Valsalva maneuver was performed 5 and 0 seconds after the start of the injection, respectively. Reducing the contrast medium dose from 10 to 5, 2.5, and 1.2 mL resulted in a decline of the median signal count from 54.5 to 28.5, 20.5, and 12.0 (P<0.01), respectively, while the latency of the first contrast signal increased from 13.3 to 14.0, 14.6, and 15.0 seconds (P<0.05). The sitting position also produced a lower signal count than the supine position (P<0.02). CONCLUSIONS: This study demonstrates that several essential methodological parameters influence the results of the contrast transcranial Doppler ultrasonography examination. Therefore, it is necessary to standardize the procedure to permit comparable quantitative assessments of the shunt volume. The findings of the present study suggest that 10 mL of contrast medium be injected with the patient in the supine position and that the Valsalva maneuver be performed 5 seconds after the start of the injection.

A method for a simulation of continuous intracranial pressure curves.

The study introduces a method to simulate continuously an intracranial pressure (ICP) wave form. In a system analysis approach the intracranial compartment was viewed as a black box with arterial blood pressure (ABP) as an input signal and ICP as an output. A weight function was used to transform the ABP curve into the ICP curve. The output ICP waveform was generated using a weight function derived from the transcranial Doppler blood flow velocity (FV) and ABP curves. In order to establish the relationship between TCD characteristics and weight functions simultaneous recordings of FV, ABP, and ICP curves of a defined group of patients were used. A linear function between the TCD characteristics and the weight functions was obtained by calculating a series of multiple regression analyses. Given examples demonstrate the procedure's capabilities in predicting the mean ICP, the pulse and respiratory waveform modulations, and the trends of ICP changes.

Cerebral blood flow velocity in acute schizophrenic patients. A transcranial Doppler ultrasonography study.

BACKGROUND AND PURPOSE: The aim of this study was to determine whether acutely psychotic first-episode schizophrenics show an increased cerebral blood flow velocity and whether this condition is reversible on psychopathological improvement. METHODS: In the first of two examinations, transcranial Doppler ultrasonography and assessment with the Positive and Negative Syndrome Scale (PANSS) were performed on 28 acutely psychotic, neuroleptically naive, first-episode schizophrenics. In the second examination, the same patients were assessed psychometrically (PANSS) as well as with Doppler ultrasonography after psychopathological improvement. RESULTS: Acutely psychotic first-episode schizophrenics showed a significant increase of the mean velocity on both sides in the middle and anterior cerebral arteries and in the right posterior cerebral artery. Blood flow showed significant correlations with productive psychotic symptoms. After psychopathological improvement there was a bilateral normalization of the mean velocity in the middle, anterior, and posterior cerebral arteries. CONCLUSIONS: Acutely psychotic first-episode schizophrenics show a significantly increased bilateral cerebral blood flow velocity, which normalizes on psychopathological improvement. There were significant correlations of cerebral blood flow velocity with psychopathology.

Changes of circadian blood pressure patterns are associated with the occurence of lucunar infarction.

BACKGROUND: The occurrence of lacunar infarction is closely related to arterial hypertension. However, there is only limited and partly controversial knowledge regarding the possible pathogenetic role of circadian blood pressure changes. OBJECTIVE: To evaluate the relationship between circadian blood pressure rhythm, occurrence, and extent of lacunar infarction. METHODS: We analyzed circadian blood pressure patterns, other cardiovascular risk factors, and occurrence of lacunar infarction in 118 hospitalized patients older than 55 years. Noninvasive 24-hour blood pressure measurements and magnetic resonance or computed tomographic brain imaging were performed in 61 patients with lacunar infarction and in 57 control patients. Daytime blood pressure variability was defined as the within-subject SD of all systolic and diastolic blood pressure readings during the daytime measurement period. Circadian blood pressure variation was defined as the average percentage change of nighttime blood pressure values compared with the daytime blood pressure values. RESULTS: Patients with lacunar infarction were significantly older and showed more often a history of arterial hypertension, elevated average daytime blood pressure values, an increased systolic daytime blood pressure variability, and a reduced circadian blood pressure variation due to an increased incidence of a pathologic nighttime blood pressure increase. No significant correlation was found between these parameters and the number of lacunae. A logistic regression analysis revealed that a reduced systolic circadian blood pressure variation, age, systolic average daytime blood pressure, and a history of arterial hypertension were best correlated with the occurrence of lacunar infarction. CONCLUSION: Reduced nighttime decline in systolic blood pressure may be an important risk factor for the development of lacunar infarction in addition to the absolute level of blood pressure and age.