Ischemic Vascular Lesions Research Articles

Heparin-Mediated Extracorporeal Low-Density Lipoprotein Precipitation Apheresis for Treating Peripheral Arterial Disease in Patients with Chronic Kidney Disease.

Patients with chronic kidney disease (CKD), particularly those with end-stage renal disease (ESRD), have a high prevalence of cardiovascular disease and peripheral arterial disease (PAD). Medical treatment is mainly based on risk factor management, and the surgical approach remains the gold standard treatment in specific conditions. Heparin-mediated extracorporeal low-density lipoprotein precipitation (H.E.L.P.) apheresis is effective in reducing circulating lipoprotein, fibrinogen, inflammatory mediators and procoagulant factors, thereby reducing cardiovascular risk in patients with familial hypercholesterolemia and hypertriglyceridemia. These activities may be effective in reducing symptoms and ischemic vascular lesions even in patients with severe PAD. We reported the application of a treatment protocol with H.E.L.P. apheresis in an ESRD patient with severe PAD without clinical improvement after severe revascularization who was not suitable for further surgical approaches, despite normal LDL cholesterol and lipoprotein (a). The H.E.L.P. protocol was characterized by an intensive first phase with weekly treatments followed by a single session every 10-15 days for 6 months of treatment. The overall clinical condition, foot lesions and walking distance improved significantly after the first 2 months of treatment, and foot amputation was avoided. Here, we review the main pathogenetic mechanisms through which LDL apheresis improves microcirculation and clinical outcomes. Its wider application may represent an optimal therapeutic option for patients unresponsive to standard treatment.

Perilesional and contralesional brain activations related to associative encoding of unfamiliar face-names pairs in adults with left chronic stroke with or without ischemic infarct on left inferior frontal gyrus

The study of an Ischemic stroke infarction allows verifying how the lesion produces alterations in the neuronal networks resulting in cognitive deficits. It also allows the verification of adaptive and maladaptive cerebral reorganization related to the injury. In our previous fMRI study, we found that patients without ischemic vascular lesions in left inferior frontal gyrus showed an efficient compensation mechanism during the associative encoding of face name pairs, by the increased activation of ventrolateral and dorsolateral areas of contralesional hemisphere associated with better memory performance. While patients with ischemic vascular lesions on left inferior frontal gyrus (IFG) demonstrated worse memory performance and no signs of compensation mechanism. The present study explores more of these findings by analyzing perilesional and contralesional activations related to unfamiliar face name associative encoding in adults with chronic ischemic stroke, with or without left IFG lesion, compared to healthy controls. The main results showed that stroke survivors without lesions in IFG demonstrated increased activation in perilesional and contralesional prefrontal regions associated with better associative memory recognition, which are indicative of adaptive compensatory mechanisms. However, they also showed a negative correlation between the activation of right anterior prefrontal and inferior parietal regions and the associative memory performance, which may indicate the presence of maladaptive interhemispheric disinhibition. On the other hand, stroke survivors with IFG lesions demonstrated negative correlations in activations of the ipsilesional inferior parietal cortex and positive correlations in activations of the left middle frontal gyrus and left precentral cortex, which demonstrate the simultaneous occurrence of adaptive and maladaptive brain reorganization mechanisms in this group. However, the increase in perilesional prefrontal regions, associated with bilateral activation of the hippocampus and amygdala, was not enough to compensate for the inefficiency of associative memory performance. Finally, the differences in activation observed in stroke survivors reflect their clinical heterogeneity and demonstrate that adaptive or maladaptive compensatory mechanisms can coexist in the same group of patients. Furthermore, they reinforce the importance of the left IFG in the associative encoding of unfamiliar face name pairs and may suggest a deficit in associative memory related to injury in this region.

Anatomical basis of a safe mini-invasive technique for lengthening of the anterior gastrocnemius aponeurosis

BackgroundThe surgical procedure itself of lengthening the gastrocnemius muscle aponeurosis is performed to treat multiple musculoskeletal, neurological and metabolical pathologies related to a gastro-soleus unit contracture such as plantar fasciitis, Achilles tendinopathy, metatarsalgia, cerebral palsy, or diabetic foot ulcerations. Therefore, the aim of our research was to prove the effectiveness and safety of a new ultrasound-guided surgery-technique for the lengthening of the anterior gastrocnemius muscle aponeurosis, the “GIAR”- technique: the gastrocnemius-intramuscular aponeurosis release.Methods and resultsAn ultrasound-guided surgical GIAR on ten fresh-frozen specimens (10 donors, 8 male, 2 females, 5 left and 5 right) was performed. Exclusion criteria of the donated bodies to science were BMI above 35 (impaired ultrasound echogenicity), signs of traumas in the ankle and crural region, a history of ankle or foot ischemic vascular disorder, surgery or space-occupying mass lesions. The surgical procedures were performed by two podiatric surgeons with more than 6 years of experience in ultrasound-guided procedures. The anterior gastrocnemius muscle aponeurosis was entirely transected in 10 over 10 specimens, with a mean portal length of 2 mm (± 1 mm). The mean gain at the ankle joint ROM after the GIAR was 7.9° (± 1.1°). No damages of important anatomical structures could be found.ConclusionResults of this study indicate that our novel ultrasound-guided surgery for the lengthening of the anterior gastrocnemius muscle aponeurosis (GIAR) might be an effective and safe procedure.

Resting state functional connectivity and neural correlates of face-name encoding in patients with ischemic vascular lesions with and without the involvement of the left inferior frontal gyrus

Face-name association is a relevant ability for social interactions and involves the ventral and dorsolateral prefrontal cortices, particularly in the left hemisphere, bilateral hippocampal, fusiform gyrus and occipital regions. Previous studies demonstrated the primary role of the hippocampus for this ability in healthy subjects. However, no study has examined the participation of the left inferior frontal area, specially the left inferior frontal gyrus (LIFG) in patients with ischemic vascular lesions. In the present study we addressed this issue and investigated the neural correlates and resting state functional connectivity of face-name memory encoding in ischemic patients with LIFG or without lesions in the left IFG (nLIFG) and healthy controls (HC) using fMRI. The main results showed that the nLIFG group demonstrated efficient compensation related to encoding and performance on face-name learning and recognition memory task, in addition to similar brain areas activated during task performance compared to healthy controls. Some of these areas were more activated in nLIFG group, indicating a compensation mechanism. In contrast, the LIFG group showed worse behavior performance, and no signs of an efficient compensation mechanism. Functional connectivity analysis suggested that the left IFG region seems to be important for maintaining the connectivity of the right fusiform gyrus or, perhaps, lesion in this area is associated to maladaptive reorganization. Our findings highlight the relevant role of the left IFG in face-name learning and encoding, possibly as a primary region in addition to the bilateral hippocampal formation and fusiform gyrus.

Prosopagnosia as unusual presentation of semantic dementia: a case study

Object: Semantic dementia is one of the main clinical variants of frontotemporal dementia and it is characterized by severe loss of conceptual knowledge with relative preservation of other cortical abilities.Methods: We described a case of a patient affected by right temporal variant of frontotemporal lobar degeneration, characterized by prosopagnosia as an unusual disease onset.Results: The neuropsychological evaluation showed a progressive deficit in face recognition and a slow decline in language in the absence of behavioral alterations. Magnetic resonance imaging showed diffuse vascular ischemic lesions, cortical atrophy in bilateral temporal lobes, and a marked bilateral decrease hippocampal volume, mainly involving the right side.Conclusions: Our findings suggest that prosopagnosia could be a predictive marker of atypical semantic dementia onset.

Thromboinflammation in Stroke Brain Damage.

The main goal of ischemic stroke treatment is rapid recanalization of the occluded blood vessel to limit brain injury and to salvage threatened cerebral tissue. To achieve early vessel recanalization, thrombolysis using recombinant tissue-type plasminogen activator is currently the only approved pharmacological intervention. Only recently, endovascular therapy has made its way into the clinic extending the therapeutic time-window and increasing reperfusion rates. However, despite fast restoration of blood vessel patency, progressive stroke still develops in many patients, which has led to the concept of reperfusion injury. During the past decades, many studies have been addressing the mechanisms underlying ischemic stroke damage and cerebral reperfusion injury, but the picture remains far from complete.1 It has become clear that both thrombotic and inflammatory pathways are important pathophysiologic contributors to ischemic brain damage. At ischemic vascular lesions, blood platelets adhere and become activated, increasing the risk of secondary thrombotic events.2 At the same time, cerebral ischemia elicits a strong inflammatory response involving upregulation of cell adhesion molecules and cytokines as well as adhesion, activation, and transmigration of several subsets of leukocytes.3 Interestingly, emerging insights indicate an important link between these thrombotic and inflammatory pathways in stroke, which led to the concept of thromboinflammation in stroke pathology. In this review, we focus on recently discovered thromboinflammatory pathways of ischemic stroke and discuss the clinical potential of targeting thromboinflammation as a novel treatment strategy in stroke management. An overview of the key components is given in Tables I to III in the online-only Data Supplement. Collagen, von Willebrand factor (vWF), and platelet glycoprotein (GP) Ib together form an important axis that is crucial for initial platelet adhesion at sites of vascular injury.4 On exposure of the subendothelial matrix, platelets are able to adhere to exposed collagen via their collagen receptors GP …

Cerebral Microbleeds Are Associated with the Progression of Ischemic Vascular Lesions

Background: Despite their different appearance on imaging, hemorrhagic and ischemic vascular lesions frequently co-occur in the brain and are hypothesized to progress concurrently. Although silent hemorrhagic and ischemic vascular brain lesions are highly prevalent in the general population, the concomitant progression of these lesions has only been studied to a limited extent in this population. We therefore aimed to investigate whether pre-existing and incident cerebral microbleeds (CMBs) are related to the progression of ischemic lesions in the general population. Methods: In the prospective population-based Rotterdam Scan Study, 803 individuals aged ≥60 years underwent magnetic resonance imaging at baseline and after an average interval of 3.4 years. The presence of microbleeds and lacunes was visually rated by trained research physicians, and white matter lesions (WMLs) were automatically segmented at both time points. Logistic regression was used to investigate the association of microbleeds with incident lacunes, and linear regression was used to investigate the relation between microbleeds and progression of WML volume. All analyses were adjusted for age, sex and the time interval between baseline and follow-up scanning. The analyses were repeated after additional adjustments for cardiovascular risk factors: blood pressures; total and high-density lipoprotein cholesterol; smoking; diabetes mellitus; lipid lowering, antihypertensive and antiplatelet medications, and apolipoprotein E ε4. The analyses involving WMLs were also adjusted for intracranial volume. Results: We found that pre-existing microbleeds in any location of the brain were related to a higher incidence of lacunes (odds ratio [OR] adjusted for age, sex and scan interval: 4.67; 95% confidence interval [CI]: 1.84-11.85). Pre-existing microbleeds were not related to progression of WML volume (mean difference in WML volume increase: -0.03; 95% CI: -0.15 to 0.09). Additional adjustments for cardiovascular risk factors did not change the results considerably. Incident microbleeds in any location of the brain were associated with a higher incidence of lacunes (OR: 9.18; 95% CI: 3.61-23.35), whereas only incident microbleeds located in cortico-subcortical regions were related to progression of WML volume (mean difference in WML volume increase: 0.41; 95% CI: 0.21-0.62). Again, adjustments for cardiovascular risk factors did not change the results significantly. Conclusions: Our findings suggest that in the general population, CMBs serve as a predictor of ischemic brain lesions and may represent an imaging marker of active vasculopathy. These results support the hypothesis of a common underlying pathway in the development of ischemic and hemorrhagic brain lesions.

Inhibition of serotonin reuptake by antidepressants and cerebral microbleeds in the general population.

Serotonin reuptake inhibiting antidepressants decrease platelet aggregation. This may cause an increased risk of intracerebral hemorrhage. However, the risk of subclinical microbleeds, which are highly prevalent in middle-aged and elderly people, is unknown. We studied whether serotonin reuptake inhibiting antidepressants increase the frequency of cerebral microbleeds and secondarily whether they lower the presence of ischemic vascular damage. Within the population-based Rotterdam Study, information on antidepressant use was obtained from continuously monitored pharmacy records. Brain MRI was available in 4945 participants (55% women, mean age 64 years) between 2005 and 2011. We categorized antidepressants based on affinity for the serotonin transporter: high, intermediate, or low. Microbleeds (presence and location) and ischemic lesions (lacunes, white matter lesions) were rated on MRI. Logistic and linear regression, adjusted for age, sex, depressive symptoms, and cardiovascular risk were used to study the association of antidepressants with microbleeds and ischemic vascular lesions. Antidepressant use with strong serotonin reuptake inhibition was not associated with microbleed presence (odds ratio compared with nonuse, 1.03; confidence interval, 0.75-1.39) irrespective of microbleed location in the brain. Exclusion of antithrombotic users or persons with cortical infarcts did not change our results. Furthermore, serotonin reuptake inhibition was not related to ischemic vascular brain damage. In the general population, use of serotonin reuptake inhibiting antidepressants is not related to presence of cerebral microbleeds. This strengthens the idea that the platelet inhibitor effects of antidepressant drugs with affinity for serotonin are minimal and further supports the safety of selective serotonin reuptake inhibitors for nongastrointestinal bleedings.

Pre-Existing and Incident Cerebral Microbleeds Are Associated with Progression of Ischemic Vascular Lesions (S62.006)

Pre-Existing and Incident Cerebral Microbleeds Are Associated with Progression of Ischemic Vascular Lesions (S62.006)

Simultaneous Direct Cortical Motor Evoked Potential Monitoring and Subcortical Mapping for Motor Pathway Preservation During Brain Tumor Surgery

The warning-sign hierarchy between quantitative subcortical motor mapping and continuous motor evoked potential monitoring during resection of supratentorial brain tumors: clinical article.Seidel K, Beck J, Steiglitz L, Schucht P, Raabe A.J Neurosurg 2013; 118:287-296. Mapping and monitoring are believed to provide an early warning sign to determine when to stop tumor removal to avoid mechanical damage to the corticospinal tract (CST). The objective of this study was to systematically compare subcortical monopolar stimulation thresholds (1-20 mA) with direct cortical stimulation (DCS)-motor evoked potential (MEP) monitoring signal abnormalities and to correlate both with new postoperative motor deficits. The authors sought to define a mapping threshold and DCS-MEP monitoring signal changes indicating a minimal safe distance from the CST. A consecutive cohort of 100 patients underwent tumor surgery adjacent to the CST while simultaneous subcortical motor mapping and DCS-MEP monitoring were used. Evaluation was performed regarding the lowest subcortical mapping threshold (monopolar stimulation, train of 5 stimuli, interstimulus interval 4.0 milliseconds, pulse duration 500 microseconds) and signal changes in DCS-MEPs (same parameters, 4 contact strip electrode). Motor function was assessed 1 day after the surgery, at discharge, and at 3 months postoperatively. The lowest individual motor thresholds (MTs) were as follows (MT in mA, number of patients): >20 mA, n = 12; 11 to 20 mA, n = 13; 6 to 10 mA, n = 20; 4 to 5 mA, n = 30; and 1 to 3 mA, n = 25. Direct cortical stimulation showed stable signals in 70 patients, unspecific changes in 18, irreversible alterations in 8, and irreversible loss in 4 patients. At 3 months, 5 patients had a postoperative new or worsened motor deficit (lowest mapping MT 20 mA, 13 mA, 6 mA, 3 mA, and 1 mA). In all 5 patients, DCS-MEP monitoring alterations were documented (2 sudden irreversible threshold increases and 3 sudden irreversible MEP losses). Of these 5 patients, 2 had vascular ischemic lesions (MT 20 mA, 13 mA) and 3 had mechanical CST damage (MT: 1 mA, 3 mA, and 6 mA; in the latter 2 cases, the resection continued after mapping and severe DCS-MEP alterations occurred thereafter). In 80% of patients with a mapping MT of 1 to 3 mA and in 75% of patients with a mapping MT of 1 mA, DCS-MEPs were stable or showed unspecific reversible changes, and none had a permanent motor worsening at 3 months. In contrast, 25% of patients with irreversible DCS-MEP changes and 75% of patients with irreversible DCS-MEP loss had permanent motor deficits. Mapping should primarily guide tumor resection adjacent to the CST. Direct cortical stimulation-motor evoked potential is a useful predictor of deficits, but its value as a warning sign is limited because signal alterations were reversible in only approximately 60% of the present cases and irreversibility is a post hoc definition. The true safe mapping MT is lower than previously thought. The authors postulate a mapping MT of 1 mA or less where irreversible DCS-MEP changes and motor deficits regularly occur. Therefore, they recommend stopping tumor resection at an MT of 2 mA at the latest. The limited spatial and temporal coverage of contemporary mapping may increase error and may contribute to false, higher MTs.

Effects of genetically modified adipose stromal cells implantation in rabbits with experimental peripheral vascular disease

Purpose: Adipose Stromal Cells (ASCs) have been shown to display reparative and regenerative potential in diverse tissues, including skeletal muscle, mainly due to the paracrine effect of secreted angiogenic factors. On the other hand, we have demonstrated that gene transfection with a plasmid encoding human Vascular Endothelial Growth Factor (pVEGF165) promotes angio-arteriogenesis and affords protection against ischemic muscle lesions in rabbits with hind limb ischemia. We therefore hipothesised that in this animal model ASCs genetically modified to overexpress VEGF165 would exert greater anti-ischemic effect than non-modified ASCs. Methods: Rabbit ASCs were isolated, identified, cultured and transfected with pVEGF165. Rabbits with extirpation of the superficial femoral artery and ligature of the deep femoral artery of the left hind limb were randomized to receive 10 local intramuscular injections of 10 million (total amount) allogeneic modified ASCs (ASC-VEGF group, n=10), non-modified ASCs (ASC group, n=10) or PBS (placebo group, n=10). Prior to surgery, and at 1 and 30 days after treatment, Peak Systolic flow Velocity (PSV) was measured by Doppler echo in both hind limbs. At 30 days post-treatment vascular density of both hind limbs was assessed by angiography, and after euthanasia (sodium thiopental overdose followed by potassium chloride) tissue samples from the adductor, gastrocnemius and quadriceps muscles were harvested for assessment of ischemic muscle lesions. Investigators involved in data collection and analysis were blinded to the animals' study groups. Results: PSV increased in the ASC-VEGF group (pre-treatment: 11.1±3.3, post-treatment: 23.4±19 cm/sec; p<0.05, mean ± SD, 2-way ANOVA-Bonferroni), but not in the ASC (from 11±4.7 to 16±10.7 cm/sec, p=NS) or placebo (from 10.1± to 17±10.9 cm/sec p=NS) groups. In the angiography, only the ACS-VEGF group showed greater vascular density than the placebo group (5.6±1.1 vs. 4.5±0.6 vessels/cm2; p<0.04). Ischemic vascular lesions were present in 20% of the harvested samples in ASC-VEGF group, 33% in ASC group, and 73% in placebo group (p<0.05 vs. ASC-VEGF and ASC, Fisher's exact test). Conclusions: In rabbits with experimental peripheral vascular disease, the local injection of ASCs overexpressing human VEGF165 improves vascularisation and hemodinamics of the affected limb more than non-modified ASCs. However, both treatments afford protection against ischemic muscle lesions to a similar extent.

Fixing Hearts and Protecting Minds

Ischemic heart disease is a significant cause of mortality and morbidity in Western populations. Consistent with this, coronary artery bypass graft (CABG) surgery remains one of the most frequently performed major surgeries. Improved survival rates mean that our research focus now extends beyond surgical technique to include quality of postoperative outcome. Postoperative cognitive dysfunction (POCD) has emerged as one of the most challenging and hotly debated issues, with increasing impetus to answer the unresolved question: does fixing the heart come at a cost to the brain? CABG surgery is associated with neurological events including stroke in 1.6%1 and delirium in 5.8%2 of patients. Beyond these severe and marked alterations to neurological function, there has been a widely held belief that CABG surgery is associated with POCD, which may presage a decline toward dementia. Research has been influenced by the 1995 Consensus Statement3 into the study of POCD in patients undergoing CABG surgery. Although the methods of investigation set forth by the Consensus Statement achieved widespread acknowledgment, its specific recommendations have not always been followed.4 Despite significant methodological issues, it seems that the balance of interpretation has historically been in favor of CABG surgery as a cause of significant POCD. More recently, however, a review of a series of publications from a well-controlled longitudinal cohort study conducted at Johns Hopkins5 and a meta-analysis6 suggested that cognition is in fact stable or may even show some improvement after CABG surgery in the majority of patients, at least within the first year (Figures 1 and 2). There is little doubt that POCD affects some patients in the short term, but the pathophysiological mechanisms underlying this and the influence on longer-term cognitive function remain uncertain. For research to progress, we require a paradigmatic shift in our focus from …

Pathology and pathogenesis of vascular cognitive impairment-a critical update.

Vascular cognitive impairment (VCI) [vascular cognitive disorder (VCD), vascular dementia] describes a continuum of cognitive disorders ranging from mild cognitive impairment (MCI) to dementia, in which vascular brain injury involving regions important for memory, cognition and behavior plays an important role. Clinical diagnostic criteria show moderate sensitivity (ca 50%) and variable specificity (range 64–98%). In Western clinical series, VaD is suggested in 8–10% of cognitively impaired elderly subjects. Its prevalence in autopsy series varies from 0.03 to 58%, with means of 8 to 15% (in Japan 22–35%). Major types of sporadic VaD are multi-infarct encephalopathy, small vessel and strategic infarct type dementias, subcortical arteriosclerotic leukoencephalopathy (SAE) (Binswanger), multilacunar state, mixed cortico-subcortical type, granular cortical atrophy (rare), postischemic encephalopathy, and a mixture of cerebrovascular lesions (CVLs). They result from systemic, cardiac and local large or small vessel disease (SVD); their pathogenesis is multifactorial. Hereditary forms of VaD caused by gene mutations are rare. Cognitive decline is commonly associated with widespread small ischemic vascular lesions involving subcortical brain areas (basal ganglia and hemispheral white matter). The lesions affect neuronal networks involved in cognition, memory, and behavior (thalamo-cortical, striato-subfrontal, cortico-subcortical, limbic systems). CVLs often coexist with Alzheimer-type lesions and other pathologies; 25–80% of elderly demented show mixed pathologies. The lesion pattern of “pure” VaD differs from that in mixed dementia (AD + CVLs) suggesting different pathogenesis of both phenotypes. Minor CVLs, except for severe amyloid angiopathy, appear not essential for cognitive impairment in full-blown AD, while both mild AD-type pathology and SVD may interact synergistically in promoting dementia. However, in a large percentage of non-demented elderly individuals, both AD-related and vascular brain pathologies have been reported. Despite recent suggestions for staging and grading CVLs in specific brain areas, due to the high variability of CVLs associated with cognitive impairment, no validated neuropathological criteria are currently available for VaD and mixed dementia. Further clinico-pathological studies and harmonization of neuropathological procedures are needed to validate the diagnostic criteria for VaD and mixed dementia in order to clarify the impact of CVLs and other coexistent pathologies on cognitive impairment as a basis for further successful therapeutic options.

The warning-sign hierarchy between quantitative subcortical motor mapping and continuous motor evoked potential monitoring during resection of supratentorial brain tumors

Mapping and monitoring are believed to provide an early warning sign to determine when to stop tumor removal to avoid mechanical damage to the corticospinal tract (CST). The objective of this study was to systematically compare subcortical monopolar stimulation thresholds (1-20 mA) with direct cortical stimulation (DCS)-motor evoked potential (MEP) monitoring signal abnormalities and to correlate both with new postoperative motor deficits. The authors sought to define a mapping threshold and DCS-MEP monitoring signal changes indicating a minimal safe distance from the CST. A consecutive cohort of 100 patients underwent tumor surgery adjacent to the CST while simultaneous subcortical motor mapping and DCS-MEP monitoring was used. Evaluation was done regarding the lowest subcortical mapping threshold (monopolar stimulation, train of 5 stimuli, interstimulus interval 4.0 msec, pulse duration 500 μsec) and signal changes in DCS-MEPs (same parameters, 4 contact strip electrode). Motor function was assessed 1 day after surgery, at discharge, and at 3 months postoperatively. The lowest individual motor thresholds (MTs) were as follows (MT in mA, number of patients): > 20 mA, n = 12; 11-20 mA, n = 13; 6-10 mA, n = 20; 4-5 mA, n = 30; and 1-3 mA, n = 25. Direct cortical stimulation showed stable signals in 70 patients, unspecific changes in 18, irreversible alterations in 8, and irreversible loss in 4 patients. At 3 months, 5 patients had a postoperative new or worsened motor deficit (lowest mapping MT 20 mA, 13 mA, 6 mA, 3 mA, and 1 mA). In all 5 patients DCS-MEP monitoring alterations were documented (2 sudden irreversible threshold increases and 3 sudden irreversible MEP losses). Of these 5 patients, 2 had vascular ischemic lesions (MT 20 mA, 13 mA) and 3 had mechanical CST damage (MT 1 mA, 3 mA, and 6 mA; in the latter 2 cases the resection continued after mapping and severe DCS-MEP alterations occurred thereafter). In 80% of patients with a mapping MT of 1-3 mA and in 75% of patients with a mapping MT of 1 mA, DCS-MEPs were stable or showed unspecific reversible changes, and none had a permanent motor worsening at 3 months. In contrast, 25% of patients with irreversible DCS-MEP changes and 75% of patients with irreversible DCS-MEP loss had permanent motor deficits. Mapping should primarily guide tumor resection adjacent to the CST. DCS-MEP is a useful predictor of deficits, but its value as a warning sign is limited because signal alterations were reversible in only approximately 60% of the present cases and irreversibility is a post hoc definition. The true safe mapping MT is lower than previously thought. The authors postulate a mapping MT of 1 mA or less where irreversible DCS-MEP changes and motor deficits regularly occur. Therefore, they recommend stopping tumor resection at an MT of 2 mA at the latest. The limited spatial and temporal coverage of contemporary mapping may increase error and may contribute to false, higher MTs.

Vascular lesions associated with bicruciate and knee dislocation ligamentous injury

The incidence of associated vascular lesions in biligamentous cruciate injuries of the knee ranges from 16 to 64%, with a mean rate of 30%. Treatment of ischemic vascular lesions associated with ligaments injury is well established, comprising emergency arterial vascular repair, most of the times combined to external fixation. In the absence of clinical symptoms of vascular lesion, some authors recommend systematically performing arteriography, while others advocate selectively prescribing this examination in doubtful clinical situations. The present study analyzed data extracted from the prospective series of the 2008 SOFCOT Symposium (dedicated to management of bicruciate knee lesions) and from an analysis of the literature, with emphasis on developing a diagnostic strategy for vascular lesions associated with bicruciate lesions. This multicenter prospective study included all patients treated in the reference centers for dislocation or bicruciate lesion of the knee between January 2007 and January 2008. All patients underwent early objective vascular imaging. Sixty-seven patients were included. Mean dislocation reduction time was 2 hrs 45 min (max, 21 hrs). There were nine vascular lesions (12%). Absence of vascular lesion could be confirmed in 58 of the 59 patients exhibiting presence of peripheral pulses at initial examination. In one case, a vascular lesion was found on early imaging, but with no clinical consequence. In all eight cases with associated clinical pulse abnormality, complementary vascular check-up confirmed the presence of a vascular lesion. Angioscan induced no error of vascular assessment in this series, with no false positives or false negatives. One patient underwent amputation for critical ischemia. Three patients had vascular surgical treatment, two not undergoing secondary ligament surgery. Four of the five patients whose vascular lesion was conservatively managed by simple observation were able to undergo the scheduled treatment for their ligament lesions. At initial examination, it is essential to look for the peripheral pulse. In case of ischemic syndrome, the priority is a revascularization procedure associated to intraoperative arteriography. In case of abnormal pulse without obvious ischemia, emergency imaging (usually arteriogram or angioscan) is essential. Where there is no initial clinical vascular abnormality, good practice is less clearly cut. Initially, present pulses are found in a mean 30% (17-55%) of cases of popliteal artery lesion, according to the series. Different authors draw diverging conclusions from this fact. For some, the absence of frank abnormality on clinical examination is sufficient to exclude not any possible anatomic vascular lesion but any vascular lesion requiring surgery. However, even without pulse abnormality, we consider systematic imaging to be justified, partly by the difficulty of ensuring strict monitoring, and partly by the decompensation risk of clinically asymptomatic intimal lesions during the ligament surgery under consideration in most cases. Although many authors cling to the dogma of late emergency arteriography, recent reports argue against this attitude. Angio-MRI has good diagnostic value, but in practice is difficult to obtain in emergency. We would rather advocate angioscanning, which is easily available in emergency and does not incur the risk of local complication associated with arteriography.

Association of White Matter Lesions and Lacunar Infarcts With Executive Functioning: The SMART-MR Study

The authors investigated the association of white matter lesions and lacunar infarcts with cognitive performance and whether brain atrophy mediates these associations. Within the Second Manifestations of Arterial Disease-Magnetic Resonance study (2001-2005, the Netherlands), cross-sectional analyses of 522 patients were performed (mean age, 57 years (standard deviation, 10); 76% male). Brain segmentation was used to quantify volumes of brain tissue, cerebrospinal fluid, and white matter lesions. Infarcts were rated visually. Brain volume, ventricular volume, and gray matter volume were divided by intracranial volume to obtain indicators of brain atrophy. Neuropsychological tests assessing executive functioning and memory were performed, and scores were transformed into z scores. The authors used linear regression analyses, adjusted for age, sex, education, intelligence, and vascular risk factors, to investigate the association of white matter lesions and number of lacunar infarcts with cognitive performance. A 1-standard-deviation higher volume of white matter lesions (beta = -0.12, 95% confidence interval: -0.20, -0.04) and the presence of >or=2 lacunar infarcts (beta = -0.48, 95% confidence interval: -0.87, -0.09) were associated with worse executive functioning. These associations remained after adjusting for brain atrophy. Both were not associated with worse memory. Results suggest that subcortical ischemic vascular lesions are associated with decreased executive functioning, but not with memory functioning, independent of brain atrophy.

Progressive "Vascular" Corticobasal Syndrome Due to Bilateral Ischemic Hemispheric Lesions

We report a patient that presented with the corticobasal syndrome (CBS), including progressive dementia, asymmetric parkinsonism associated with constructional and ideomotor apraxia, action myoclonus and focal hand dystonia. Magnetic resonance imaging of the brain revealed extensive ischemic lesions in both fronto-temporo-parieto-occipital lobes and steno-occlusion of the middle cerebral arteries, bilaterally. This case illustrates that extensive cortical vascular-ischemic lesions may present with symptoms mimicking the corticobasal syndrome.

Autoimmune disorders: nail signs and therapeutic approaches

Systemic sclerosis (scleroderma, SSc) is an autoimmune disease that targets small and medium-sized arteries and arterioles in the involved tissues, resulting in a fibrotic vasculopathy and tissue fibrosis. Several prominent nail and periungual changes are apparent in scleroderma. Examination of the nail fold capillaries can reveal the nature and extent of microvascular pathology in patients with collagen vascular disease and Raynaud's phenomenon. Among the complications stemming from Raynaud's phenomenon can be painful ischemic digital ulcers. This can be managed, and potentially prevented, through pharmacologic and nonpharmacologic means. Whereas oral calcium channel blockers remain the most convenient therapy, oral endothelin receptor antagonists and intravenous prostaglandins may be important therapeutic advances for ischemic digital vascular lesions.

P2-245: White matter changes associated with dementia development in patients with subcortical ischemic white matter lesions: A diffusion tensor image study

Diffusion tensor MRI (DTI) is a new technique that may provide a better index of white matter damage in central nervous system. Both discrete lacunar infarcts and leukoaraiosis are important mechanisms in developing dementia in patients with subcortical ischemic vascular lesions. But the location and severity of white matter changes associated with development of dementia has not been established yet. We investigate the difference of location and severity of white matter damage in patients with subcortical ischemic vascular lesions with and without dementia. Eleven demented patients(age: 74.80 yrs, MMSE: 22.10) who fulfill the criteria of Erkinjuntti's subcortical ischemic vascular dementia (SIVD) criteria, ten patients (age: 67.50 yrs, MMSE: 26.63) with subcortical vascular cognitive impairment no dementia (SVCIND) and twelve healthy volunteers(age: 70.64 yrs, MMSE: 28.73) were recruited. They underwent DTI, neuropsychological assessment and clinical interview. Fractional anisotropy (FA) and mean diffusivity (MD) were measured in temporal, frontal, parietal and occipital white matter regions as well as in the corpus callosum (genu, body and splenium), cingulate white matter(anterior and posterior), internal capsule(anterior and posterior limb), superior and inferior longitudinal fasciculus, centrum semiovale, hippocampus, and anterior thalamus. SVCIND and SIVD patients showed lower FA and higher MD values in the both frontal, occipital, right anterior thalamus, centrum semiovale, superior longitudinal fasciculus and in both hippocampi than the control group. Compared to SVCIND patients, SIVD patients had decreased FA values and increased MD values in both frontal areas and decreased MD in left superior longitudinal fasciculus. The findings support the white matter damage and disruption in the frontal region and superior association fiber is important for the cognitive dysfunctions associated with dementia development in patients with subcortical ischemic lesions. This study was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea(A050079).

IC-P-005: White matter changes associated with dementia development in patients with subcortical ischemic white matter lesions: A diffusion tensor image study

Diffusion tensor MRI (DTI) is a new technique that may provide a better index of white matter damage in central nervous system. Both discrete lacunar infarcts and leukoaraiosis are important mechanisms in developing dementia in patients with subcortical ischemic vascular lesions. But the location and severity of white matter changes associated with development of dementia has not been established yet. We investigate the difference of location and severity of white matter damage in patients with subcortical ischemic vascular lesions with and without dementia. Eleven demented patients (age: 74.80 yrs, MMSE: 22.10) who fulfill the criteria of Erkinjuntti's subcortical ischemic vascular dementia (SIVD) criteria, ten patients (age: 67.50 yrs, MMSE: 26.63) with subcortical vascular cognitive impairment with no dementia (SVCIND) and twelve healthy volunteers (age: 70.64 yrs, MMSE: 28.73) were recruited. They underwent DTI, neuropsychological assessment and clinical interview. Fractional anisotropy (FA) and mean diffusivity (MD) were measured in temporal, frontal, parietal and occipital white matter regions as well as in the corpus callosum (genu, body and splenium), cingulate white matter (anterior and posterior), internal capsule (anterior and posterior limb), superior and inferior longitudinal fasciculus, centrum semiovale, hippocampus, and anterior thalamus. SVCIND and SIVD patients showed lower FA and higher MD values in the both frontal, occipital, right anterior thalamus, centrum semiovale, superior longitudinal fasciculus and in both hippocampi than the control group. Compared to SVCIND patients, SIVD patients had decreased FA values and increased MD values in both frontal areas and decreased MD in left superior longitudinal fasciculus. The findings support the white matter damage and disruption in the frontal region and superior association fiber is important for the cognitive dysfunctions associated with dementia development in patients with subcortical ischemic lesions. This study was supported by a grant of the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (A050079).