Philipp Gölitz

Hereditary myopathy with early respiratory failure: occurrence in various populations

Objective Several families with characteristic features of hereditary myopathy with early respiratory failure (HMERF) have remained without genetic cause. This international study was initiated to clarify epidemiology and the genetic underlying cause in these families, and to characterise the phenotype in our large cohort. Methods DNA samples of all currently known families with HMERF without molecular genetic cause were obtained from 12 families in seven different countries. Clinical, histopathological and muscle imaging data were collected and five biopsy samples made available for further immunohistochemical studies. Genotyping, exome sequencing and Sanger sequencing were used to identify and confirm sequence variations. Results All patients with clinical diagnosis of HMERF were genetically solved by five different titin mutations identified. One mutation has been reported while four are novel, all located exclusively in the FN3 119 domain (A150) of A-band titin. One of the new mutations showed semirecessive inheritance pattern with subclinical myopathy in the heterozygous parents. Typical clinical features were respiratory failure at mid-adulthood in an ambulant patient with very variable degree of muscle weakness. Cytoplasmic bodies were retrospectively observed in all muscle biopsy samples and these were reactive for myofibrillar proteins but not for titin. Conclusions We report an extensive collection of families with HMERF with five different mutations in exon 343 of TTN, which establishes this exon as the primary target for molecular diagnosis of HMERF. Our relatively large number of new families and mutations directly implies that HMERF is not extremely rare, not restricted to Northern Europe and should be considered in undetermined myogenic respiratory failure.

Optimized angiographic computed tomography with intravenous contrast injection: an alternative to conventional angiography in the follow-up of clipped aneurysms?

OBJECT The purpose of this study was to evaluate the diagnostic accuracy of an optimized angiographic CT (ACT) program with intravenous contrast agent injection (ivACT) in the assessment of potential aneurysm remnants after neurosurgical clipping compared with conventional digital subtraction angiography (DSA). METHODS The authors report on 14 patients with 19 surgically clipped cerebral aneurysms who were scheduled to undergo angiographic follow-up. For each patient, the authors performed ivACT with dual rotational acquisition and conventional angiography including a 3D rotational run. The ivACT and 3D DSA data were reconstructed with different imaging modes, including a newly implemented subtraction mode with motion correction. Thereafter, the data sets were merged by the dual-volume technique, and freely rotatable 3D images were obtained for further analysis. Observed aneurysm remnants were electronically measured and classified for each modality by 2 experienced neuroradiologists. RESULTS Digital subtraction angiography and ivACT both provided high-quality images without motion artifacts. Artifact disturbances from the aneurysm clips led to a compromised, but still sufficient, image quality in 1 case. The ivACT assessed all aneurysm remnants as true-positive up to a minimal size of 2.6×2.4 mm in accordance with the DSA findings. There was a tendency for ivACT to overestimate the size of the aneurysm remnants. All cases without aneurysm remnants on DSA were scored correctly as true-negative by ivACT. CONCLUSIONS By using an optimized image acquisition protocol as well as enhanced postprocessing algorithms, the noninvasive ivACT seems to achieve results comparable to those of conventional angiography in the follow-up of clipped cerebral aneurysms. The authors have shown that ivACT can provide reliable diagnostic information about potential aneurysm remnants after neurosurgical clipping with high sensitivity and specificity, sufficient for clinical decision making, at least for aneurysms in the anterior circulation located distal to the internal carotid artery. These preliminary results may be a promising step to replace conventional angiography by a noninvasive imaging technique in selected cases after aneurysm clipping.

Intravenous flat detector CT angiography for non-invasive visualisation of intracranial flow diverter: technical feasibility.

ObjectiveTo demonstrate the feasibility of intravenous Flat Detector CT Angiography (FD-CTA) for visualisation of intracranial Flow Diverting Devices. Flow Diverting Devices are used increasingly for treatment of intracranial aneurysms. A close follow up is necessary because it becomes obvious that a significant proportion of aneurysms treated with these devices remain patent. A minimally invasive method is highly desirable.MethodsIn two patients treated with flow diverters a Flat Detector CT (FD-CT) with intravenous contrast medium application was performed. Post-processing was performed using commercially available software.ResultsIn both patients the lumen of the device and the lumen of the aneurysm could be clearly evaluated. Some beam hardening artefacts due to the marker wires of the device were obvious.ConclusionFlat Detector CT with intravenous contrast material application to evaluate flow-diverting devices seems to be feasible. Further studies are necessary to perform comparative evaluation of FD-CTA with angiography and other techniques like MRA or conventional CT angiography.

Flat-Panel Computed Tomography (DYNA-CT) in Neuroradiology. From High-Resolution Imaging of Implants to One-Stop-Shopping for Acute Stroke.

Originally aimed at improving standard radiography by providing higher absorption efficiency and a wider dynamic range, flat-panel detector technology has meanwhile got widely accepted in the neuroradiological community. Especially flat-panel detector computed tomography (FD-CT) using rotational C-arm mounted flat-panel detector technology is capable of volumetric imaging with a high spatial resolution. By providing CT-like images of the brain within the angio suite, FD-CT is able to rapidly visualize hemorrhage and may thus improve complication management without the need of patient transfer. As “Angiographic CT” FD-CT may be helpful during many diagnostic and neurointerventional procedures and for noninvasive monitoring and follow-up. In addition, spinal interventions and high-resolution imaging of the temporal bone might also benefit from FD-CT. Finally, using novel dynamic perfusion and angiographic protocols, FD-CT may provide functional information on brain perfusion and vasculature with the potential to replace standard imaging in selected acute stroke patients.Originally aimed at improving standard radiography by providing higher absorption efficiency and a wider dynamic range, flat-panel detector technology has meanwhile got widely accepted in the neuroradiological community. Especially flat-panel detector computed tomography (FD-CT) using rotational C-arm mounted flat-panel detector technology is capable of volumetric imaging with a high spatial resolution. By providing CT-like images of the brain within the angio suite, FD-CT is able to rapidly visualize hemorrhage and may thus improve complication management without the need of patient transfer. As “Angiographic CT” FD-CT may be helpful during many diagnostic and neurointerventional procedures and for noninvasive monitoring and follow-up. In addition, spinal interventions and high-resolution imaging of the temporal bone might also benefit from FD-CT. Finally, using novel dynamic perfusion and angiographic protocols, FD-CT may provide functional information on brain perfusion and vasculature with the potential to replace standard imaging in selected acute stroke patients.

Clinical/perfusion CT CBV mismatch as prognostic factor in intraarterial thrombectomy in acute anterior circulation stroke.

OBJECTIVE Contradictory results were reported for the outcome after endovascular recanalization (ERT) in acute anterior circulation ischemic stroke. We assessed whether a clinical/perfusion CT cerebral blood volume (CBV) mismatch concept (CPM) can identify patients who will benefit from reperfusion therapy. METHODS Imaging and clinical data of 58 consecutive ERT cases with acute anterior circulation stroke (ICA, M1, proximal M2) undergoing intraarterial thrombectomy within 4.5h after symptom onset were analyzed retrospectively. CPM was defined as NIHSS≥8 and PCT CBV ASPECTS≥7. Minor CBV lesion was defined as PCT CBV ASPECTS≥7. RESULTS All baseline characteristics other than blood glucose did not differ between the paired groups. Revascularization was achieved in 87.9% of all patients without significant difference between the paired groups. Favorable clinical outcome after 3 months (mRS≤2) resulted in 29.3% of all patients, in contrast to 47.4% of the CPM positive and 52.2% of the minor CBV lesion groups. CONCLUSION CPM can identify patients who will benefit from reperfusion therapy in acute anterior circulation ischemic stroke.

Contrast-enhanced angiographic computed tomography for detection of aneurysm remnants after clipping: a comparison with digital subtraction angiography in 112 clipped aneurysms.

BACKGROUND For preclusion of remnants after aneurysm clipping, a reliable, noninvasive imaging technique is desirable. OBJECTIVE To evaluate the reliability of optimized angiographic computed tomography with intravenous contrast agent injection (ivACT) in detecting remnants after aneurysmal clipping compared with digital subtraction angiography (DSA), the gold standard. METHODS We included 84 patients with 112 clipped cerebral aneurysms of the anterior circulation. For treatment, 116 clips of cobalt and 57 clips of titanium alloy were used. In each patient, we performed an ivACT with dual rotational acquisition and a DSA. Data from ivACT were postprocessed with a dual-volume technique with newly implemented reconstructions modes. Aneurysm remnants were measured, classified, and correlated with DSA by 2 raters. RESULTS In total, 12 remnants were revealed by DSA, meaning a prevalence of 11%. IvACT demonstrated a sensitivity of 75% to 92% and a specificity of 99% in detecting remnants up to a minimal size of 0.7 × 0.3 mm. Classification of remnants by ivACT was identical to that by DSA, and assessment of size showed a significant correlation with DSA (P < .001). No significant differences between cobalt and titanium alloy were revealed concerning artifacts. CONCLUSION Optimized ivACT with enhanced postprocessing demonstrated high sensitivity and specificity in detecting remnants after aneurysm clipping in the anterior circulation. Classification and assessment of remnant size and detection of relevant parent artery stenosis showed high accuracy of ivACT compared with DSA. Our results indicate that ivACT might become a noninvasive alternative to DSA for postsurgical control.

Optimized Flat-Detector CT in Stroke Imaging: Ready for First-Line Use?

Background: Using flat-detector CT (FD-CT) for stroke imaging has the advantage that both diagnostic imaging and endovascular therapy can be performed directly within the Angio Suite without any patient transfer and time delay. Thus, stroke management could be speeded up significantly, and patient outcome might be improved. But as precondition for using FD-CT as primary imaging modality, a reliable exclusion of intracranial hemorrhage (ICH) has to be possible. This study aimed to investigate whether optimized native FD-CT, using a newly implemented reconstruction algorithm, may reliably detect ICH in stroke patients. Additionally, the potential to identify ischemic changes was evaluated. Methods: Cranial FD-CT scans were obtained in 102 patients presenting with acute ischemic stroke (n = 32), ICH (n = 45) or transient ischemic attack (n = 25). All scans were reconstructed with a newly implemented half-scan cone-beam algorithm. Two experienced neuroradiologists, unaware of clinical findings, evaluated independently the FD-CTs screening for hemorrhage or ischemic signs. The findings were correlated to CT, and rater and inter-rater agreement was assessed. Results: FD-CT demonstrated high sensitivity (95-100%) and specificity (100%) in detecting intracerebral and intraventricular hemorrhage (IVH). Overall, interobserver agreement (κ = 0.92) was almost perfect and rater agreement to CT highly significant (r = 0.81). One infratentorial ICH and 10 or 11 of 22 subarachnoid hemorrhages (SAHs) were missed of whom 7 were perimesencephalic. The sensitivity for detecting acute ischemic signs was poor in blinded readings (0 or 25%, respectively). Conclusions: Optimized FD-CT, using a newly implemented reconstruction algorithm, turned out as a reliable tool for detecting supratentorial ICH and IVH. However, detection of infratentorial ICH and perimesencephalic SAH is limited. The potential of FD-CT in detecting ischemic changes is poor in blinded readings. Thus, plain FD-CT seems insufficient as a standalone modality in acute stroke, but within a multimodal imaging approach primarily using the FD technology, native FD-CT seems capable to exclude reliably supratentorial hemorrhage. Currently, FD-CT imaging seems not yet ready for wide adoption, replacing regular CT, and should be reserved for selected patients. Furthermore, prospective evaluations are necessary to validate this approach in the clinical setting.

Intraprocedural angiographic CT as a valuable tool in the course of endovascular treatment of direct sinus cavernous fistulas.

This investigation aimed to demonstrate the potential of intraprocedural angiographic CT in monitoring complex endovascular coil embolization of direct carotid cavernous fistulas. Angiographic CT was performed as a dual rotational 5 s run with intraarterial contrast medium injection in two patients during endovascular coil embolization of direct carotid cavernous fistulas. Intraprocedural angiographic CT was considered helpful if conventional 2D series were not conclusive concerning coil position or if a precise delineation of the parent artery was impossible due to a complex anatomy or overlying coil material. During postprocessing multiplanar reformatted and dual volume images of angiographic CT were reconstructed. Angiographic CT turned out to be superior in the intraprocedural visualization of accidental coil migration into the parent artery where conventional 2D-DSA series failed to reliably detect coil protrusion. The delineation of coil protrusion by angiographic CT allowed immediate correct coil repositioning to prevent parent artery compromising. Angiographic CT can function as a valuable intraprocedurally feasible tool during complex coil embolizations of direct carotid cavernous fistulas. It allows the precise visualization of the cerebral vasculature and any accidental coil protrusion can be determined accurately in cases where conventional 2D-DSA series are unclear or compromised. Thus angiographic CT might contribute substantially to reduce procedural complications and to increase safety in the management of endovascular treatment of direct carotid cavernous fistulas.

Clinical and radiological outcome after mechanical thrombectomy in acute ischemic stroke: What matters?

Objective Recent studies have shown the efficacy of mechanical thrombectomy in acute ischemic stroke. We sought to identify prognostic parameters for clinical and radiological outcome after mechanical thrombectomy. Methods In 34 patients (age 72 ± 13 years, 64.7% women) with acute occlusion of the distal ICA and/or M1 segment who were treated with mechanical thrombectomy, the Spearman correlation was performed to assess potential prognostic outcome parameters (age, NIHSS, ASPECT, thrombus length (TL), clot burden score (CBS), relative filling time delay (rFTD), time to recanalization (TTR) and TICI score). The modified Rankin scale (mRS) and the Alberta Stroke Program Early CT (ASPECT) score were used for clinical and radiological outcome, respectively. Receiver operating characteristic (ROC) analysis was performed to assess parameters predicting favorable clinical (ΔmRS ≤ 2) and radiological outcome (ΔASPECT ≤ 2). Results Variables associated with favorable clinical outcome included NIHSS, TL, TTR and TICI score (p ≤ 0.01) with NIHSS ≤ 15 (p = 0.001, area under the curve (AUC) 0.87), TL ≤ 2 cm (p = 0.017, AUC 0.75), TTR ≤ 231 min (p = 0.001 AUC 0.88) and TICI ≥ 2b (p = 0.050, AUC 0.70). Shorter TTR and higher TICI scores were associated with favorable radiological outcome (p < 0.001) with TTR ≤ 224 min (p = 0.023, AUC 0.77) and TICI ≥ 2b (p = 0.000, AUC 0.86). Conclusion Fast and complete recanalization is essential to achieve a favorable radiological and functional outcome after mechanical thrombectomy in acute ischemic stroke. Age, CBS and collateral supply play a subordinate role.

Flat-detector computed tomography evaluation in an experimental animal aneurysm model after endovascular treatment: A pilot study.

We compared flat-detector computed tomography angiography (FD-CTA) to multislice computed tomography (MS-CTA) and digital subtracted angiography (DSA) for the visualization of experimental aneurysms treated with stents, coils or a combination of both. In 20 rabbits, aneurysms were created using the rabbit elastase aneurysm model. Seven aneurysms were treated with coils, seven with coils and stents, and six with self-expandable stents alone. Imaging was performed by DSA, MS-CTA and FD-CTA immediately after treatment. Multiplanar reconstruction (MPR) was performed and two experienced reviewers compared aneurysm/coil package size, aneurysm occlusion, stent diameters and artifacts for each modality. In aneurysms treated with stents alone, the visualization of the aneurysms was identical in all three imaging modalities. Residual aneurysm perfusion was present in two cases and visible in DSA and FD-CTA but not in MS-CTA. The diameter of coil-packages was overestimated in MS-CT by 56% and only by 16% in FD-CTA compared to DSA (p < 0.05). The diameter of stents was identical for DSA and FD-CTA and was significantly overestimated in MS-CTA (p < 0.05). Beam/metal hardening artifacts impaired image quality more severely in MS-CTA compared to FD-CTA. MS-CTA is impaired by blooming and beam/metal hardening artifacts in the visualization of implanted devices. There was no significant difference between measurements made with noninvasive FD-CTA compared to gold standard of DSA after stenting and after coiling/stent-assisted coiling of aneurysms. FD-CTA may be considered as a non-invasive alternative to the gold standard 2D DSA in selected patients that require follow up imaging after stenting.