G. A. P. de Kort

New Detected Aneurysms on Follow-Up Screening in Patients With Previously Clipped Intracranial Aneurysms Comparison With DSA or CTA at the Time of SAH

Background and Purpose— Patients with a history of aneurysmal subarachnoid hemorrhage may have aneurysms on screening several years after the hemorrhage. For determining the benefits of follow-up screening, it is important to know whether these aneurysms have developed after the hemorrhage or are visible in retrospect, and if so, whether the size has increased. Methods— Aneurysms were categorized into de novo aneurysms and aneurysms visible in retrospect (already present) with increased or stable size. We studied aneurysm characteristics for these 3 categories: the relation between aneurysm development or enlargement and duration of follow up and the relation between enlargement and initial size of the aneurysm. Results— In 87 of 495 patients (17.6%), aneurysms were detected; for 51 of these patients with 62 aneurysms, the original catheter or computed tomographic angiogram was available for comparison. Of the 62 aneurysms, 19 were de novo and 43 were visible in retrospect, 10 with increased size and 33 with stable size. De novo aneurysms were mainly ≤5 mm (95%) and located at the middle cerebral artery (63%). For aneurysms visible in retrospect, the most frequent location was the posterior communicating artery (21%). There was no relation between the development of de novo aneurysms or enlargement and the duration of follow-up or between enlargement and the initial size of the aneurysm. Conclusions— Of aneurysms detected at screening, one third were de novo and two thirds were missed at the time of the initial hemorrhage. One quarter of initially small aneurysms had enlarged during follow-up.

MR Angiography Follow-Up 5 Years after Coiling: Frequency of New Aneurysms and Enlargement of Untreated Aneurysms

BACKGROUND AND PURPOSE: Patients with intracranial aneurysms are at risk for future development of new aneurysms and growth of additional untreated aneurysms. Because in previous long-term studies duration of follow-up varied widely, the time interval after which screening could be effective remains largely unknown. The purpose of this study was to assess the incidence of de novo aneurysm formation and the growth of additional untreated aneurysms in patients with coiled aneurysms followed up with MR angiography (MRA) after a fixed period of 5 years. MATERIALS AND METHODS: In 65 patients with coiled intracranial aneurysms, high-resolution 3T MRA was performed 5.1 ± 0.2 years after coiling. MRA follow-up imaging was compared with MRA or CT angiography at the time of coiling. Additional aneurysms detected at MRA follow-up were classified as unchanged, grown, de novo, or incomparable with previous imaging. RESULTS: In 13 of 65 patients (20%), 24 additional aneurysms were found. Four aneurysms were incomparable with previous imaging and 2 of these were clipped. Of the remaining 20 additional aneurysms, 1 was de novo, 1 had grown slightly, and 18 were unchanged. The incidence of de novo aneurysm formation after 5 years was 1.54% (95% confidence interval, 0.01–9.0%). For additional aneurysms known at the time of initial coiling and for the 1 de novo aneurysm, no treatment was indicated. CONCLUSIONS: MRA screening 5 years after coiling for detection of de novo aneurysms and growth of additional untreated aneurysms has a low yield in terms of finding aneurysms that need to be treated.

Evaluation of genetic risk loci for intracranial aneurysms in sporadic arteriovenous malformations of the brain

Background In genome-wide association studies (GWAS) five putative risk loci are associated with intracranial aneurysm. As brain arteriovenous malformations (AVM) and intracranial aneurysms are both intracranial vascular diseases and AVMs often have associated aneurysms, we investigated whether these loci are also associated with sporadic brain AVM. Methods We included 506 patients (168 Dutch, 338 American) and 1548 controls, all Caucasians. Controls had been recruited as part of previous GWAS. Dutch patients were genotyped by KASPar assay and US patients by Affymetrix SNP 6.0 array. Associations in each cohort were tested by univariable logistic regression modelling, with subgroup analysis in 205 American cases with aneurysm data. Meta-analysis was performed by a Mantel-Haenszel fixed-effect method. Results In the Dutch cohort none of the single nucleotide polymorphisms (SNPs) were associated with AVMs. In the American cohort, genotyped SNPs near SOX-17 (OR 0.74; 95% CI 0.56–0.98), RBBP8 (OR 0.76; 95% CI 0.62–0.94) and an imputed SNP near CDKN2B-AS1 (OR 0.79; 95% CI 0.64–0.98) were significantly associated with AVM. The association with SNPs near SOX-17 and CDKN2B-AS1 but not RBBP8 were strongest in patients with AVM with associated aneurysms. In the meta-analysis we found no significant associations between allele frequencies and AVM occurrence, but rs9298506, near SOX-17 approached statistical significance (OR 0.77; 95% CI 0.57–1.03, p=0.08). Conclusions Our meta-analysis of two Caucasian cohorts did not show an association between five aneurysm-associated loci and sporadic brain AVM. Possible involvement of SOX-17 and RBBP8, genes involved in cell cycle progression, deserves further investigation.

Predictors of Acute and Persisting Ischemic Brain Lesions in Patients Randomized to Carotid Stenting or Endarterectomy

Background and Purpose— We investigated predictors for acute and persisting periprocedural ischemic brain lesions among patients with symptomatic carotid stenosis randomized to stenting or endarterectomy in the International Carotid Stenting Study. Methods— We assessed acute lesions on diffusion-weighted imaging 1 to 3 days after treatment in 124 stenting and 107 endarterectomy patients and lesions persisting on fluid-attenuated inversion recovery after 1 month in 86 and 75 patients, respectively. Results— Stenting patients had more acute (relative risk, 8.8; 95% confidence interval, 4.4–17.5; P<0.001) and persisting lesions (relative risk, 4.2; 95% confidence interval, 1.6–11.1; P=0.005) than endarterectomy patients. Acute lesion count was associated with age (by trend), male sex, and stroke as the qualifying event in stenting; high systolic blood pressure in endarterectomy; and white matter disease in both groups. The rate of conversion from acute to persisting lesions was lower in the stenting group (relative risk, 0.4; 95% confidence interval, 0.2–0.8; P=0.007), and was only predicted by acute lesion volume. Conclusions— Stenting caused more acute and persisting ischemic brain lesions than endarterectomy. However, the rate of conversion from acute to persisting lesions was lower in the stenting group, most likely attributable to lower acute lesion volumes. Clinical Trial Registration —URL: www.isrctn.org. Unique identifier: ISRCTN25337470.

Lymph node detection by MRI before and after a systematic pelvic lymphadenectomy

OBJECTIVE Pelvic lymphadenectomy is considered the gold standard to diagnose and possibly treat lymphatic metastases in gynaecological cancer patients. The aim of this study is to evaluate whether all presurgical MRI detected lymph nodes were removed during the systematic pelvic lymph node dissection (PLND) in cervical cancer patients. METHODS 21 consecutive cervical cancer patients who were scheduled to undergo a PLND were evaluated by a MRI scan prior to surgery and 6 weeks afterwards. All patients had tumour metastasis negative lymph nodes at histopathological examination. RESULTS On average, 10 pelvic lymph nodes (range 5-17) per patient were detected by presurgical MRI. Postsurgical MRI scans showed that on average 1 (range 0-3) pelvic node per patient was not removed by surgery. In total, 14% of the presurgical MR detected nodes were not removed by surgery (31/225). Approximately half of all lymph nodes that remained after surgery were located in the obturator region. In spite of the remaining nodes, surgery and histopathological examination did detect more nodes than MRI: on average 21 lymph nodes per patient (range 9-59) were removed. Another 2 lymph nodes (range 0-6 per patient) were judged to be newly developed after surgery. CONCLUSION Although surgery was able to remove many more lymph nodes than those detected by presurgical MRI, 14% of presurgical MRI detected lymph nodes were not removed by PLND. The value of MRI prior to surgery for the detection of pathological lymph nodes is a subject of further research.

Mutated PET117 causes complex IV deficiency and is associated with neurodevelopmental regression and medulla oblongata lesions

The genetic basis of the many progressive, multi systemic, mitochondrial diseases that cause a lack of cellular ATP production is heterogeneous, with defects found both in the mitochondrial genome as well as in the nuclear genome. Many different mutations have been found in the genes encoding subunits of the enzyme complexes of the oxidative phosphorylation system. In addition, mutations in genes encoding proteins involved in the assembly of these complexes are known to cause mitochondrial disorders. Here we describe two sisters with a mitochondrial disease characterized by lesions in the medulla oblongata, as demonstrated by brain magnetic resonance imaging, and an isolated complex IV deficiency and reduced levels of individual complex IV subunits. Whole exome sequencing revealed a homozygous nonsense mutation resulting in a premature stop codon in the gene encoding Pet117, a small protein that has previously been predicted to be a complex IV assembly factor. PET117 has not been identified as a mitochondrial disease gene before. Lentiviral complementation of patient fibroblasts with wild-type PET117 restored the complex IV deficiency, proving that the gene defect is responsible for the complex IV deficiency in the patients, and indicating a pivotal role of this protein in the proper functioning of complex IV. Although previous studies had suggested a possible role of this protein in the insertion of copper into complex IV, studies in patient fibroblasts could not confirm this. This case presentation thus implicates mutations in PET117 as a novel cause of mitochondrial disease.

Improved Arterial Visualization in Cerebral CT Perfusion–Derived Arteriograms Compared with Standard CT Angiography: A Visual Assessment Study

BACKGROUND AND PURPOSE: Invasive cerebral DSA has largely been replaced by CTA, which is noninvasive but has a compromised arterial view due to superimposed bone and veins. The purpose of this study was to evaluate whether arterial visualization in CTPa is superior to standard CTA, which would eliminate the need for an additional CTA scan to assess arterial diseases and therefore reduce radiation dose. MATERIALS AND METHODS: In this study, we included 24 patients with subarachnoid hemorrhage for whom CTA and CTP were available. Arterial quality and presence of superimposed veins and bone in CTPa were compared with CTA and scored by 2 radiologists by using a VAS (0%–100%). Average VAS scores were determined and VAS scores per patient were converted to a 10-point NRS. Arterial visualization was considered to be improved when the highest rate (NRS 10, VAS > 90%) was scored for arterial quality, and the lowest rate (NRS 1, VAS < 10%), for the presence of superimposed veins and bone. A sign test with continuity correction was used to test whether the number of cases with these rates was significant. RESULTS: Average VAS scores in the proximal area were 94% (arterial quality), 4% (presence of bone), and 7% (presence of veins). In this area, the sign test showed that a significant number of cases scored NRS 10 for arterial quality (P < .02) and NRS 1 for the presence of superimposed veins and bone (P < .01). CONCLUSIONS: Cerebral CTPa shows improved arterial visualization in the proximal area compared with CTA, with similar arterial quality but no superimposed bone and veins.

Assessment of the preferred plane and sequence in the depiction of mesial temporal sclerosis using magnetic resonance imaging.

RATIONALE AND OBJECTIVES Definition of optimal magnetic resonance (MR) scanning plane and conventional MR sequence for the detection of mesial temporal sclerosis (MTS). METHODS Coronal and axial T2-weighted images and axial T2-weighted images parallel to the long axis of the hippocampus (APLAH) and coronal inversion recovery (IR) images were obtained in patients with medically intractable temporal lobe epilepsy in their phase 1 preoperative evaluation. Thirty-three consecutive MR scans were reviewed by a panel of three radiologists. Twenty-three patients had MR abnormalities consistent with MTS, and ten scans were normal. To assess the best single scanning technique, another group of three radiologists, who were masked to all patient data, individually assessed the different planes and sequences of the 33 studies presented separately in a random fashion. For each plane and sequence, the likelihood (L) ratio for the correct diagnosis was determined separately. RESULTS For all planes considered separately, a likelihood ratio of 4.4 was optimal for the coronal T2-weighted images. The likelihood ratio of APLAH T2 was 2.2; of axial T2, 3.9; of coronal IR, indefinite because of 100% specificity. CONCLUSIONS For the assessment of MTS, coronal T2-weighted images were considered the best single scanning technique.

Vertebral angioplasty for treatment of transient monocular blindness

Sirs: Transient monocular blindness (TMB) is considered an ischemic event in the supply territory of the internal carotid artery (ICA). In most patients, TMB is caused by thromboemboli from the ICA, but a hemodynamic cause may be present in a subgroup of patients with severe carotid artery disease [1–3]. In severe obstructive disease of the ICA, collateral blood flow may be increased to maintain cerebral perfusion pressure within normal limits [4]. The circle of Willis is a major collateral pathway in this respect, but also the ophthalmic artery (OA) can provide collateral blood flow [4, 5]. Such reversed flow in the OA may compromise retinal perfusion, resulting in ocular ischemia. We describe a patient with frequent TMB and reversed OA flow whose symptoms diminished considerably after improvement of collateral flow through the circle of Willis. A 59-year old physician with a history of hypertension presented with recurrent attacks of left-sided TMB for 2 years. The attacks lasted several minutes and occurred at least 2 to 3 times a week. Acetyl salicylic acid, in different doses, did not influence the attacks. Neurological and ophthalmological examination were normal. Magnetic resonance angiography showed no flow in the left ICA. The left posterior communicating artery (PCoA) demonstrated flow that was directed from the posterior to the anterior circulation. Transcranial Doppler sonography showed reversed flow in the left OA. The patient was worried about a future stroke. He was eager to undergo any type of treatment that could positively influence the frequently occurring TMB. Therefore we decided to perform an intra-arterial cerebral angiography. This showed an occlusion of the left ICA. The left middle cerebral artery (MCA) was filled by collateral flow through the left OA and by collateral flow from the vertebrobasilar system through the left PCoA. The left external carotid artery showed no stenosis. On the right side, the ICA had a < 30 % stenosis. There was no cross-filling through the anterior communicating artery (ACoA) towards the left MCA. The left vertebral artery (VA) showed a 70 % stenosis that was located proximal to the posterior inferior cerebellar artery (Fig. 1A). A similar stenosis was present in the right VA. Of the VAs, the left VA was judged to be dominant. With a 4 15 mm balloon (FasStealth®, Boston Scientific), the stenosis in the left VA was redressed in a second session (Fig. 1B). After angioplasty, the filling of the left MCA had improved substantially (Figs. 1C and 1D) due to increased collateral flow through the left PCoA. Apart from a small hematoma at the puncture site in the left groin, no complications occurred. During 4 months of follow-up, the patient experienced only 3 single attacks of vision loss in his left eye. Patients with an ICA occlusion may need collateral flow through the OA to provide sufficient cerebral blood flow. A concordant reduction of collateral flow through the posterior circulation and absence of collateral flow through the ACoA, may make blood supply of the ipsilateral MCA territory more dependant on the OA. In our patient, angioplasty to the VA stenosis resulted in increased filling of the left MCA territory through the left PCoA. We suggest that this has reduced the need of collateral flow through the left OA, thereby improving retinal perfusion and relieving symptoms. Improvement of collateral flow from the posterior to the anterior circulation due to increased flow in the posterior circulation, may also relieve symptoms of cerebral ischemia as shown in patients with ischemic symptoms in the MCA territory [6, 7]. Despite angioplasty, symptoms did not disappear completely in our patient during follow-up. This may indicate that retinal perfusion was still not normal because of the ipsilateral ICA occlusion, although it had been improved by the angioplasty. VA stenosis may be treated by stent placement or angioplasty alone.We generally perform angioplasty first and consider stent placement if angioplasty is unsuccessful. Stent placement in VA stenosis has a number of limitations [8]. For example, accelerated restenosis may be induced.Also, it may be difficult to select a suitable stent that is small enough to be directed to the stenosis and still is strong enough to remain open.Angioplasty has limitations as well. For example, there is an increased risk of VA dissection. However, this seems to occur particularly in angioplasty of lesions at the vertebrobasilar junction rather than in more proximally located VA stenosis [8]. In conclusion, patients with an ICA occlusion who suffer from TMB may have a hemodynamic origin of their ocular complaints. Relief of the OA shunt by improving collateral flow through other pathways should be considered in patients with frequent troublesome TMB. LETTER TO THE EDITORS

EP-1425: Frameless linac based radiosurgery of arteriovenous malformations: geometrical accuracy

(calculated vs. measured) within ±2%. For that tuning task, isocenter dose measurements in a polystyrene phantom were compared to the calculated ones for five IMRS stereotactic plans. Three correction values to the factory DLG value were analyzed: 0.0, -0.25 and -0.5 mm. Accuracy of the M3D software to reproduce the penumbra of stereotactic fields was investigated by comparing the profiles measured in water with the calculated ones for a 1x1 cm MLC-collimated field size. Twelve cranial IMRS plans calculated using the Eclipse were retrospectively recalculated using the Mobius3D software (version 1.3). The same monitor units and calculation voxel sizes (1 mm) were used for both systems. The aperture (complete irradiation area outline) of the modulated beams ranged from 0.9 to 4.4 cm . Differences between both algorithms were evaluated using the 3D gamma tool available in the M3D system. Gamma passing rates for the target and organs at risks (OARs: brainstem, chiasm, optic nerves and normal brain tissue) were compared for 3%/1 mm, 3%/2 mm and 5%/1 mm criteria. Results: 1) Differences (M3D vs. measured) within 1 mm were found for the penumbras of the 1x1 cm field. 2) Dose differences of 2.7% (SD: 1.6%), 1.5% (SD: 1.9%) and 0.4% (SD: 2.0%) were found for the DLG correction values of 0.0, -0.25 and -0.5 mm, respectively. 3) Using the optimal DLG correction (-0.5 mm), the target 3D gamma passing rates were: 94% (73-94%), 97% (80-100%) and 100% (97-100%) for the 3%/1 mm, 3%/2 mm and 5%/1 mm criteria, respectively. 100% rates were obtained for all OARs regardless of the gamma criterium. Conclusions: Great agreement was obtained (within 5% and 1 mm) between IMRS plans calculated by the Eclipse and by the independent dose calculation software M3D. Our findings are restricted to small field sizes down to 1x1 cm . The M3D software may be proposed as an alternative to patientspecific QA based on measurements for IMRS plans.