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BACKGROUND: The endovascular treatment of intracranial aneurysms can be hampered by the tortuosity of extracranial vessels. Percutaneous or surgical vessel puncture can resolve the problem of inaccessibility. OBJECTIVE: We describe rerouting of a kinked vertebral artery (VA) to restore transfemoral endovascular access to an aneurysm. CASE REPORT: A 63-year-old woman presented with progressive hemiparesis. Magnetic resonance imaging demonstrated a left fusiform vertebrobasilar aneurysm with mass effect on the brainstem. The patient was found to have a dominant left VA on angiography with a severe kink in its V1 segment. Tight loops of this segment prevented catheter progression past V1 during endovascular treatment. INTERVENTION: The left VA was rerouted from its subclavian origin to the C5 transverse foramen through a combined lateral and supraclavicular approach. Release of the VA off the C6 transverse process and C6 and C7 cranial nerve roots permitted unfolding of the VA. The excess length of the VA, initially present between the subclavian artery and the C6 transverse process, was spread over a longer distance. The tight angles present preoperatively were converted into a harmonious curvature. The rerouted VA was attached to surrounding soft tissue to maintain its position. The patient's postoperative course was uneventful. Endovascular treatment of the aneurysm was performed 15 days later. CONCLUSION: The VA rerouting technique can be used successfully in patients in whom tight loops in the VA prevent endovascular access to intracranial vessels., Journal Article, SCOPUS: ar.j, info:eu-repo/semantics/published

BACKGROUND: The endovascular treatment of intracranial aneurysms can be hampered by the tortuosity of extracranial vessels. Percutaneous or surgical vessel puncture can resolve the problem of inaccessibility. OBJECTIVE: We describe rerouting of a kinked vertebral artery (VA) to restore transfemoral endovascular access to an aneurysm. CASE REPORT: A 63-year-old woman presented with progressive hemiparesis. Magnetic resonance imaging demonstrated a left fusiform vertebrobasilar aneurysm with mass effect on the brainstem. The patient was found to have a dominant left VA on angiography with a severe kink in its V1 segment. Tight loops of this segment prevented catheter progression past V1 during endovascular treatment. INTERVENTION: The left VA was rerouted from its subclavian origin to the C5 transverse foramen through a combined lateral and supraclavicular approach. Release of the VA off the C6 transverse process and C6 and C7 cranial nerve roots permitted unfolding of the VA. The excess length of the VA, initially present between the subclavian artery and the C6 transverse process, was spread over a longer distance. The tight angles present preoperatively were converted into a harmonious curvature. The rerouted VA was attached to surrounding soft tissue to maintain its position. The patient's postoperative course was uneventful. Endovascular treatment of the aneurysm was performed 15 days later. CONCLUSION: The VA rerouting technique can be used successfully in patients in whom tight loops in the VA prevent endovascular access to intracranial vessels., Journal Article, SCOPUS: ar.j, info:eu-repo/semantics/published

INTRODUCTION: Aneurysms of the proximal segment of the anterior cerebral artery (A1A) are rare and challenging to treat. No information is available regarding their management by endovascular approach. The aim of this study was to report our experience with endovascular treatment (EVT) of A1As. PATIENTS AND METHODS: A retrospective review of our prospectively maintained database identified all A1As treated in our institution. The clinical charts, procedural data, and angiographic results were reviewed. RESULTS: From April 2004 to August 2008, eight patients were identified and presented with an unruptured A1A. All aneurysms but one were <3 mm in diameter and two aneurysms had a perforator at the neck. Surgery was performed in two patients with an aneurysm <2 mm. Six patients were treated by selective embolization including five patients with balloon-assisted coiling (BAC) and/or via a retrograde approach from the contralateral side through the anterior communicating artery. These adjunctive techniques were used to safely catheterize the sac or to protect a branch at the neck. All patients showed an excellent clinical outcome. A complete aneurysm occlusion was obtained in all but one patient. Follow-up imaging in four patients showed stable results. CONCLUSION: EVT of A1As is feasible and associated with good clinical and anatomical results. Because of their location, small size, and close relationship with perforators, EVT frequently requires the use of BAC and/or a retrograde approach. Our results suggest that EVT is an alternative therapeutic option to surgical clipping if the aneurysm size is compatible with selective embolization., Clinical Trial, Journal Article, info:eu-repo/semantics/published

INTRODUCTION: Stent-assisted coiling (SAC) is an alternative to surgical clipping for the treatment of wide-necked intracranial aneurysms (IA). However, little information is available concerning the long-term results of this treatment. The aim of this study was to report the long-term clinical and anatomical findings in 32 patients with 34 wide-necked IA treated by SAC. METHODS: A retrospective review of our prospectively maintained database identified all patients followed up for wide-necked IA treated by SAC. The clinical charts, procedural data, and angiographic results were reviewed. RESULTS: Thirty-two patients with 34 IA were identified including 25 asymptomatic patients, four with cranial nerve palsies, two with a subarachnoid hemorrhage, and one with transient ischemic attacks. Mean aneurysm size was 10.2 mm (range 3.5 to 26 mm). Embolization was successful in all patients and no procedure-related neurological morbidity or mortality was observed. Immediate anatomical results included nine complete occlusions (26.5%), two neck remnants (6%), and 23 incomplete occlusions (67.5%). Mean imaging follow-up of 20 months showed 18 further thrombosis (53%) and 16 stable results (47%). Finally, 27 aneurysms were completely occluded (79%), three had a neck remnant (9%), and four were incompletely occluded (12%). Asymptomatic and nonsignificant in-stent stenosis occurred in seven patients (22%). CONCLUSIONS: SAC is safe and effective for the treatment of wide-necked IA. Despite unsatisfying immediate aneurysm occlusion, the adjunctive effect of the stent is stabilizing or significantly improving long-term anatomical results., Journal Article, info:eu-repo/semantics/published

INTRODUCTION: Endovascular treatment (EVT) of anterior choroidal artery aneurysms (AChAA) may be challenging because of the close relationship with the parent artery. The aim of this study was to report our experience with EVT of AChAA. METHODS: A retrospective review of our prospectively maintained database identified all AChAA treated by embolization. The clinical charts, procedural data and angiographic results were reviewed. RESULTS: From April 2004-August 2008, 11 patients were identified. Five patients presented with a subarachnoid hemorrhage (SAH) and six patients were asymptomatic. Aneurysms size varied from two to 13 mm (mean size=3.6 mm) and nine had an unfavourable neck/sac ratio (>or=0.7). The anterior choroidal artery was arising from the sac (n=6) or from the neck (n=5). Endovascular treatment consisted of balloon-assisted coiling (n=8), coiling (n=2) and stent-assisted coiling (n=1). No procedural complication occurred and all patients had an excellent outcome except one patient who died because of severe vasospasm 8 days after an uneventful EVT. Immediate angiographic control showed six complete occlusions, one neck remnant and four incomplete occlusions. Follow-up controls (mean=18 months) were obtained in eight patients and showed five stable occlusions and three further thrombosis achieving complete occlusion. CONCLUSION: EVT of AChAA is associated with very good clinical and long-term anatomical results. Because of their small size, unfavourable neck/sac ratio and close relationship with the parent artery, EVT frequently requires the use of adjunctive techniques such as balloon or stent-assisted coiling., Journal Article, info:eu-repo/semantics/published

INTRODUCTION: Stent-assisted coiling (SAC) is an alternative to surgical clipping for the treatment of wide-necked intracranial aneurysms (IA). However, little information is available concerning the long-term results of this treatment. The aim of this study was to report the long-term clinical and anatomical findings in 32 patients with 34 wide-necked IA treated by SAC. METHODS: A retrospective review of our prospectively maintained database identified all patients followed up for wide-necked IA treated by SAC. The clinical charts, procedural data, and angiographic results were reviewed. RESULTS: Thirty-two patients with 34 IA were identified including 25 asymptomatic patients, four with cranial nerve palsies, two with a subarachnoid hemorrhage, and one with transient ischemic attacks. Mean aneurysm size was 10.2 mm (range 3.5 to 26 mm). Embolization was successful in all patients and no procedure-related neurological morbidity or mortality was observed. Immediate anatomical results included nine complete occlusions (26.5%), two neck remnants (6%), and 23 incomplete occlusions (67.5%). Mean imaging follow-up of 20 months showed 18 further thrombosis (53%) and 16 stable results (47%). Finally, 27 aneurysms were completely occluded (79%), three had a neck remnant (9%), and four were incompletely occluded (12%). Asymptomatic and nonsignificant in-stent stenosis occurred in seven patients (22%). CONCLUSIONS: SAC is safe and effective for the treatment of wide-necked IA. Despite unsatisfying immediate aneurysm occlusion, the adjunctive effect of the stent is stabilizing or significantly improving long-term anatomical results., Journal Article, info:eu-repo/semantics/published

INTRODUCTION: Endovascular treatment (EVT) of anterior choroidal artery aneurysms (AChAA) may be challenging because of the close relationship with the parent artery. The aim of this study was to report our experience with EVT of AChAA. METHODS: A retrospective review of our prospectively maintained database identified all AChAA treated by embolization. The clinical charts, procedural data and angiographic results were reviewed. RESULTS: From April 2004-August 2008, 11 patients were identified. Five patients presented with a subarachnoid hemorrhage (SAH) and six patients were asymptomatic. Aneurysms size varied from two to 13 mm (mean size=3.6 mm) and nine had an unfavourable neck/sac ratio (>or=0.7). The anterior choroidal artery was arising from the sac (n=6) or from the neck (n=5). Endovascular treatment consisted of balloon-assisted coiling (n=8), coiling (n=2) and stent-assisted coiling (n=1). No procedural complication occurred and all patients had an excellent outcome except one patient who died because of severe vasospasm 8 days after an uneventful EVT. Immediate angiographic control showed six complete occlusions, one neck remnant and four incomplete occlusions. Follow-up controls (mean=18 months) were obtained in eight patients and showed five stable occlusions and three further thrombosis achieving complete occlusion. CONCLUSION: EVT of AChAA is associated with very good clinical and long-term anatomical results. Because of their small size, unfavourable neck/sac ratio and close relationship with the parent artery, EVT frequently requires the use of adjunctive techniques such as balloon or stent-assisted coiling., Journal Article, info:eu-repo/semantics/published

INTRODUCTION: Aneurysms of the proximal segment of the anterior cerebral artery (A1A) are rare and challenging to treat. No information is available regarding their management by endovascular approach. The aim of this study was to report our experience with endovascular treatment (EVT) of A1As. PATIENTS AND METHODS: A retrospective review of our prospectively maintained database identified all A1As treated in our institution. The clinical charts, procedural data, and angiographic results were reviewed. RESULTS: From April 2004 to August 2008, eight patients were identified and presented with an unruptured A1A. All aneurysms but one were <3 mm in diameter and two aneurysms had a perforator at the neck. Surgery was performed in two patients with an aneurysm <2 mm. Six patients were treated by selective embolization including five patients with balloon-assisted coiling (BAC) and/or via a retrograde approach from the contralateral side through the anterior communicating artery. These adjunctive techniques were used to safely catheterize the sac or to protect a branch at the neck. All patients showed an excellent clinical outcome. A complete aneurysm occlusion was obtained in all but one patient. Follow-up imaging in four patients showed stable results. CONCLUSION: EVT of A1As is feasible and associated with good clinical and anatomical results. Because of their location, small size, and close relationship with perforators, EVT frequently requires the use of BAC and/or a retrograde approach. Our results suggest that EVT is an alternative therapeutic option to surgical clipping if the aneurysm size is compatible with selective embolization., Clinical Trial, Journal Article, info:eu-repo/semantics/published

info:eu-repo/semantics/nonPublished

Niemann-pick type C (NPC) disease is characterized by endosomal and lysosomal accumulation of lipids, impaired tubulovesicular trafficking, and neurodegeneration leading to premature death. Current treatment options are limited to mainly symptomatic treatments. Thus, new and efficient drug targets are needed, and therefore we performed a Gene Set Enrichment Analysis (GSEA) on NPC and healthy fibroblasts to identify globally affected pathways in NPC that could serve as targets for later drug discovery programs. Cell lines were characterized by analyzing cellular concentrations of cholesterol, its precursors and metabolites, as well as cellular plant sterol levels. Gene expression analyses were performed with Sentrix Human-8 Expression BeadChips, analyzing 23,000 transcripts. Pathway analysis of the expression data was performed using the GSEA method. Twenty-seven upregulated and 33 downregulated pathways emerged as globally affected in the GSEA analysis. These pathways included, for example, mitochondrial pathway, caspase cascade, as well as prostaglandin and leukotriene metabolism. Based on the present results and earlier published data, anti-inflammatory and antiapoptotic treatment could be beneficial in NPC., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

Sterol regulatory element-binding proteins (SREBPs) are transcription factors governing transcription of genes related to cholesterol and fatty acid metabolism. To become active, SREBPs must undergo a proteolytic cleavage to allow an active NH(2)-terminal segment to translocate into the nucleus. SKI-1/S1P is the first protease in the proteolytic activation cascade of SREBPs. SREBP inhibition may be useful, for example, in the treatment of liver steatosis caused by homocysteine-induced lipid synthesis. Accordingly, we overexpressed inhibitory prodomains (proSKI) of SKI-1/S1P in HepG2 cells to block SREBP activation to evaluate the potential of SKI-1/S1P in controlling cellular cholesterol synthesis. SKI-1/S1P inhibition resulted in reduced cholesterol synthesis and mRNA levels of the rate-limiting enzymes, HMG-CoA reductase and squalene epoxidase, in the cholesterol synthetic pathway. The inhibitory effect was maintained in the presence of homocysteine-induced endoplasmic reticulum stress. A gene set enrichment analysis was performed to elucidate other metabolic effects caused by SKI-1/S1P inhibition. SKI-1/S1P inhibition was observed to affect a number of other metabolic pathways, including glycolysis and citric acid cycle. These results demonstrate that inhibition of SREBPs decreases cholesterol synthesis in HepG2 cells both in the absence and presence of homocysteine. SKI-1/S1P inhibition may cause widespread changes in other key metabolic pathways., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

info:eu-repo/semantics/nonPublished

Sterol regulatory element-binding proteins (SREBPs) are transcription factors governing transcription of genes related to cholesterol and fatty acid metabolism. To become active, SREBPs must undergo a proteolytic cleavage to allow an active NH(2)-terminal segment to translocate into the nucleus. SKI-1/S1P is the first protease in the proteolytic activation cascade of SREBPs. SREBP inhibition may be useful, for example, in the treatment of liver steatosis caused by homocysteine-induced lipid synthesis. Accordingly, we overexpressed inhibitory prodomains (proSKI) of SKI-1/S1P in HepG2 cells to block SREBP activation to evaluate the potential of SKI-1/S1P in controlling cellular cholesterol synthesis. SKI-1/S1P inhibition resulted in reduced cholesterol synthesis and mRNA levels of the rate-limiting enzymes, HMG-CoA reductase and squalene epoxidase, in the cholesterol synthetic pathway. The inhibitory effect was maintained in the presence of homocysteine-induced endoplasmic reticulum stress. A gene set enrichment analysis was performed to elucidate other metabolic effects caused by SKI-1/S1P inhibition. SKI-1/S1P inhibition was observed to affect a number of other metabolic pathways, including glycolysis and citric acid cycle. These results demonstrate that inhibition of SREBPs decreases cholesterol synthesis in HepG2 cells both in the absence and presence of homocysteine. SKI-1/S1P inhibition may cause widespread changes in other key metabolic pathways., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published

Niemann-pick type C (NPC) disease is characterized by endosomal and lysosomal accumulation of lipids, impaired tubulovesicular trafficking, and neurodegeneration leading to premature death. Current treatment options are limited to mainly symptomatic treatments. Thus, new and efficient drug targets are needed, and therefore we performed a Gene Set Enrichment Analysis (GSEA) on NPC and healthy fibroblasts to identify globally affected pathways in NPC that could serve as targets for later drug discovery programs. Cell lines were characterized by analyzing cellular concentrations of cholesterol, its precursors and metabolites, as well as cellular plant sterol levels. Gene expression analyses were performed with Sentrix Human-8 Expression BeadChips, analyzing 23,000 transcripts. Pathway analysis of the expression data was performed using the GSEA method. Twenty-seven upregulated and 33 downregulated pathways emerged as globally affected in the GSEA analysis. These pathways included, for example, mitochondrial pathway, caspase cascade, as well as prostaglandin and leukotriene metabolism. Based on the present results and earlier published data, anti-inflammatory and antiapoptotic treatment could be beneficial in NPC., Journal Article, Research Support, Non-U.S. Gov't, info:eu-repo/semantics/published