Spezifität der anerkannten MRT-Kriterien für Multiple Sklerose bei der Differentialdiagnose

Die Diagnose der Multiplen Sklerose (MS) ist eine klinische Diagnose (65), die jedoch mit einer Zahl von paraklinischen Methoden erhärtet wird. Mit Einführung der MRT in die klinische bildgebende Diagnostik hat die MRT sehr schnell eine Schlüsselposition innerhalb der diagnostischen paraklinischen Methoden bei Patienten mit Verdacht auf MS erreicht. Die MRT ist die sensitivste Methode, pathologische Veränderungen in der weißen Substanz des Gehirns mit einer hohen örtlichen Auflösung darzustellen. Allerdings trifft dies auch auf ein breites Spektrum neurologischer Erkrankungen und Syndrome zu, weitgehend unabhängig von der zugrunde liegenden Pathologie; daher ist die hohe Sensitivität mit einer geringen Spezifität verbunden. Es wurden erhebliche Anstrengungen unternommen, möglichst verlässliche Kriterien für die MRT-Diagnostik für MS aufzustellen. (5, 25, 62) Die aktuell anerkannten MRT-Kriterien nach Barkhof et al. (5) wurden anhand eines präselektionierten Patientenkollektivs erstellt, bei welchem die Verdachtsdiagnose MS gestellt wurde. Auf der Grundlage der MRT-Untersuchungen wurden dann die Kriterien bestimmt, die am besten geeignet waren, eine Voraussage über die Entwicklung von möglicher MS zu klinisch sicherer MS zu treffen. Barkhof konnte mit diesen Kriterien eine Spezifität von 78%, eine Treffgenauigkeit von 80% und einen positiven Vorhersagewert von 75% erreichen (5). In dieser Studie wurde untersucht, wie verlässlich diese Kriterien bei der Differentialdiagnose in einem weniger selektierten Patientengut mit verschieden neurologischen Krankheitsbildern sind, die jedoch im MRT einer MS ähnlich sein können. So wurden Sensitivität, Spezifität und Treffsicherheit der Barkhof-Kriterien in unserem Patientenkollektiv untersucht. Das zweite Ziel dieser Studie war, zusätzliche MRT-Kriterien ergänzend auf das gleiche Kollektiv anzuwenden, und zu überprüfen, ob sich dadurch die Zahl der nach den Barkhof-Kriterien diagnostisch falsch klassifizierten Patienten vermindern und damit die differentialdiagnostische Sicherheit verbessern lässt. Die zusätzlichen Kriterien bestanden aus dem Magnetisierungstransferverhältnis des Zerebrums, des gemessenen Gesamtläsions-volumens T2-hyperintenser zerebraler Läsionen und dem Nachweis von T2 hyperintensen Läsionen in der MRT des Zervikalmarks im Hinblick auf deren Anzahl und Ausdehnung. Zwei Patientengruppen und eine Kontrollgruppe gesunder Probanden wurden in die Studie eingeschlossen. Die Kontrollgruppe war erforderlich, um einen Normalwert für die Beurteilung des Magnetisierungstransferverhältnisses zu erstellen. Die Analyse der Patientengruppen erfolgte retrospektiv. Die erste Gruppe setzte sich aus 64 Patienten zusammen, die an MS erkrankt waren. Die zweite Gruppe bestand aus 81 Patienten mit anderen Erkrankungen, die wie bei der MS ebenfalls zu Veränderungen der weißen Substanz des zentralen Nervensystems führen können. Die Gruppe untergliederte sich in Patienten mit systemischen Immunerkrankungen (SID; n=44), mit zerebral autosomal dominanter Arteriopathie mit subkortikalen Infarkten und Leukoencephalopathie (CADASIL; n=22) und Patienten mit Migräne (n=15). Die Kontrollgruppe bestand aus 20 gesunden Probanden. Von allen Patienten lagen eine kranielle MRT mit PD/T2-gewichteten Doppelechosequenzen und eine MRT des Halsmarks mit einer fast-STIR Sequenz vor. Die Magnetisierungstransfersequenzen des Gehirns wurden erst nach Abschluss der Untersuchungen der CADASIL-Patienten nachträglich dem Protokoll hinzugefügt und lagen daher bei Abschluss der Studie für diese Patientenuntergruppe nicht vor. Die Anzahl und Lokalisation der hyperintensen Läsionen in den T2-gewichteten Sequenzen des Gehirns und die Anzahl und Ausdehnung der Zervikalmarkläsionen wurden erfaßt. Die Sequenzen der kraniellen MRT wurden nachverarbeitet, um das komplette Läsionsvolumen des Zerebrums (TLV-total lesion volume) quantitativ zu erfassen, und um Histogramme des Magnetisationstransferverhältnisses (MTR – magnetisation transfer ratio) zu erstellen. Aufgrund des retrospektiven Charakters der Studie wurden die zusätzlichen Kriterien nur auf die nach den Barkhof-Kriterien falsch diagnostizierten Patienten angewandt, es wurde daher auch keine Analyse bezüglich Spezifität und Treffsicherheit durchgeführt. Pathologische Veränderungen in den T2-gewichteten MRT-Schichten des Hirns fanden sich bei allen MS-Patienten und bei 61,7% der Patienten mit anderen Erkrankungen. Hyperintense Läsionen des Zervikalmarks wurden nur bei MS-Patienten gefunden (84,4%). Kein Patient der zweiten Gruppe (0%) wies pathologische Veränderungen im Halsmark auf. Die statistische Auswertung der zusätzlichen potentiellen Kriterien definierte die Grenzwerte, die am besten geeignet sind, um MS von anderen Erkrankungen zu unterscheiden: 1. ein Gesamtläsionsvolumen über 1,83 ml 2. ein Magnetisierungstransferverhältnis des Gehirns kleiner als 40,2% und 3. der Nachweis von Halsmark-Läsionen. Anhand der anerkannten Barkhof-Kriterien wurden 108 von 145 Patienten richtig klassifiziert, diese zeigten somit eine Treffgenauigkeit von 74,5 %. Eine “falsch-negative“ Diagnose fand sich bei 13 Patienten. 2 Patienten mit systemischen Lupus Erythematodes mit neurologischer Symptomatik (NSLE) und 22 Patienten mit CADASIL wurden „falsch-positiv“ klassifiziert“. Wurden die Barkhof-Kriterien um das TLV mit einem Grenzwert größer als 1,83 ml ergänzt, konnten 9 „falsch-negative“ Patienten noch korrekt klassifiziert werden. Eine richtige Klassifizierung von 10 weiteren MS-Patienten und allen NSLE-, bzw. CADASIL-Patienten konnte aufgrund des Nachweises bzw. des Nichtvorhandenseins von Zervikalmarkläsionen durchgeführt werden. Zwei MS-Patienten mit negativen Barkhof-Kriterien und ohne Zervikalmarkläsionen im MRT konnten auf Grund des Hirn-MTR-Wertes richtig als MS-krank bestimmt werden. Letztendlich konnte nur ein Patient mit den verwendeten Kriterien nicht richtig diagnostiziert werden. Diese Daten rechtfertigen einen vermehrten Einsatz der zervikalen MRT als zusätzlichen differentialdiagnostischen Parameter bei Patienten mit Verdacht auf eine Erkrankung mit MS. Auch die Berechnung des Magnetisierungstransferverhältnisses ermöglichte eine verbesserte Differentialdiagnose. Die Berechnung des T2-Läsionsvolumens ist mit erheblichem Aufwand verbunden und hat zu keiner wesentlich verbesserten diagnostischen Sicherheit beigetragen

Serial stereotactic biopsy of brainstem lesions in adults improves diagnostic accuracy compared with MRI only.

Objective: The aim of the current prospective study was to analyse the validity of MRI based diagnosis of brainstem gliomas which was verified by stereotactic biopsy and follow-up evaluation as well as to assess prognostic factors and risk profile. Methods: Between 1998 and 2007, all consecutive adult patients with radiologically suspected brainstem glioma were included. The MRI based diagnosis of the lesions was made independently by an experienced neuroradiologist. Histopathological evaluation was performed in all patients from paraffin embedded specimens obtained by multimodal image guided stereotactic serial biopsy technique. Histopathological results were compared with prior radiological assessment. Length of survival was estimated with the Kaplan–Meier method and prognostic factors were calculated using the Cox model. Results: 46 adult patients were included. Histological evaluation revealed pilocytic astrocytoma (n=2), WHO grade II glioma (n=14), malignant glioma (n=12), metastasis (n=7), lymphoma (n=5), cavernoma (n=1), inflammatory disease (n=2) or no tumour/ gliosis (n=3). Perioperative morbidity was 2.5% (n=1). There was no permanent morbidity and no mortality. All patients with ‘‘no tumour’’ or ‘‘inflammatory disease’’ survived. Patients with low grade glioma and malignant glioma showed a 1 year survival rate of 75% and 25%, respectively; the 1 year survival rate for patients with lymphoma or metastasis was 30%. In the subgroup with a verified brainstem glioma, negative predictors for length of survival were higher tumour grade (p=0.002) and Karnofsky performance score (70 (p=0.004). Conclusion: Intra-axial brainstem lesions with a radiological pattern of glioma represent a very heterogeneous tumour group with completely different outcomes. Radiological features alone are not reliable for diagnostic classification. Stereotactic biopsy is a safe method to obtain a valid tissue diagnosis, which is indispensible for treatment decision

Post procedure headache in patients treated for neurovascular arteriovenous malformations and aneurysms using endovascular therapy

BACKGROUND: Though endovascular therapy (EVT) is increasingly applied in the treatment of intracranial vascular lesions, little is known about the effect of EVT on post-procedure headache. We aimed to investigate the prevalence of headache in patients who have undergone EVT for cerebral arteriovenous malformations (AVMs) and aneurysms. METHODS: A total of 324 patients underwent EVT treatment for aneurysms and AVMs at the Danish National Hospital from January 2012 to December 2014. We applied strict exclusion criteria in order to minimize the effect of other factors on headache occurrence, e.g., craniotomy. Eligible subjects were phone-interviewed using a purpose-developed semi-structured questionnaire. Headaches were classified according to ICHD-III beta criteria. RESULTS: The 59 patients underwent treatment of aneurysms (n = 43), cranial dural fistulas (n = 11), and AVMs (n = 5). There was a significant increase in overall headache (p = 0.017) and tension-type headache (TTH) (p = 0.012) within the first 3 months after EVT compared to 1 month before EVT. However, at interview time (median 2.5 years post-EVT), the increase in overall headache, migraine, and tension-type headache was not statistically significant. A minority of patients experienced headaches for the first time within 3 months of their EVT (migraine 4, TTH 10). At interview time, 50 % of these new headaches still persisted. CONCLUSION: Our results suggest a temporary increase in headache in the first 3 months after EVT, which normalizes over time. Clinicians may use this knowledge to better inform their patients of functional outcomes after their EVT procedure

Endovascular thrombectomy and post-procedural headache

BACKGROUND: We investigated the prevalence of post-procedural headache in patients who have undergone thrombectomy for ischemic stroke, and correlated history of migraine with risk of peri-procedural complications. A total of 314 patients underwent thrombectomy at the Danish National Hospital from January 2012 to December 2014. Eligible subjects were phone-interviewed using a purpose-developed semi-structured questionnaire according to the International Classification of Headache Disorders 3, beta version criteria. FINDINGS: Among 96 eligible subjects, there was a significant decrease in migraine (p = 0.022) within the first 3 months after EVT compared to 1 year before treatment, which was further evident at interview time (on average 1.6 years after EVT, p = 0.013). A minority of patients experienced headaches for the first time within 3 months of their EVT (migraine 2, TTH 9), which persisted at interview time for subjects with migraine. Out of 12 subjects with peri-procedural complications, 2 had a history of migraine with aura. CONCLUSION: Thrombectomy leads to a significant decrease in previously known migraine, and new onset of headache in a small subset of patients. A history of migraine does not appear to predispose to peri-procedural complications. ELECTRONIC SUPPLEMENTARY MATERIAL: The online version of this article (doi:10.1186/s10194-017-0719-0) contains supplementary material, which is available to authorized users

Mechanisms of Cognitive Impairment in Cerebral Small Vessel Disease: Multimodal MRI Results from the St George's Cognition and Neuroimaging in Stroke (SCANS) Study.

Cerebral small vessel disease (SVD) is a common cause of vascular cognitive impairment. A number of disease features can be assessed on MRI including lacunar infarcts, T2 lesion volume, brain atrophy, and cerebral microbleeds. In addition, diffusion tensor imaging (DTI) is sensitive to disruption of white matter ultrastructure, and recently it has been suggested that additional information on the pattern of damage may be obtained from axial diffusivity, a proposed marker of axonal damage, and radial diffusivity, an indicator of demyelination. We determined the contribution of these whole brain MRI markers to cognitive impairment in SVD. Consecutive patients with lacunar stroke and confluent leukoaraiosis were recruited into the ongoing SCANS study of cognitive impairment in SVD (n = 115), and underwent neuropsychological assessment and multimodal MRI. SVD subjects displayed poor performance on tests of executive function and processing speed. In the SVD group brain volume was lower, white matter hyperintensity volume higher and all diffusion characteristics differed significantly from control subjects (n = 50). On multi-predictor analysis independent predictors of executive function in SVD were lacunar infarct count and diffusivity of normal appearing white matter on DTI. Independent predictors of processing speed were lacunar infarct count and brain atrophy. Radial diffusivity was a stronger DTI predictor than axial diffusivity, suggesting ischaemic demyelination, seen neuropathologically in SVD, may be an important predictor of cognitive impairment in SVD. Our study provides information on the mechanism of cognitive impairment in SVD

Application of Diffusion Tensor Imaging Parameters to Detect Change in Longitudinal Studies in Cerebral Small Vessel Disease.

Cerebral small vessel disease (SVD) is the major cause of vascular cognitive impairment, resulting in significant disability and reduced quality of life. Cognitive tests have been shown to be insensitive to change in longitudinal studies and, therefore, sensitive surrogate markers are needed to monitor disease progression and assess treatment effects in clinical trials. Diffusion tensor imaging (DTI) is thought to offer great potential in this regard. Sensitivity of the various parameters that can be derived from DTI is however unknown. We aimed to evaluate the differential sensitivity of DTI markers to detect SVD progression, and to estimate sample sizes required to assess therapeutic interventions aimed at halting decline based on DTI data. We investigated 99 patients with symptomatic SVD, defined as clinical lacunar syndrome with MRI confirmation of a corresponding infarct as well as confluent white matter hyperintensities over a 3 year follow-up period. We evaluated change in DTI histogram parameters using linear mixed effect models and calculated sample size estimates. Over a three-year follow-up period we observed a decline in fractional anisotropy and increase in diffusivity in white matter tissue and most parameters changed significantly. Mean diffusivity peak height was the most sensitive marker for SVD progression as it had the smallest sample size estimate. This suggests disease progression can be monitored sensitively using DTI histogram analysis and confirms DTI's potential as surrogate marker for SVD

Endoscopic Resection of Sinonasal Hemangiopericytoma following Preoperative Embolisation: A Case Report and Literature Review

Objectives. Hemangiopericytoma is a rare tumor entity deriving from pericytes. Less than 5% of hemangiopericytoma occur in the nasal cavity and are characterised by a rather benign nature with low tendency of metastasis. However, as the recurrence rate in the literature ranges from 9.5% to 50%—depending on the length of followup—a radical surgical resection is considered as the gold-standard treatment. Only a few years ago, a wide external approach, usually via lateral rhinotomy or Caldwell-Luc, was performed. Endoscopic techniques were regarded as appropriate for small low-vascularised tumors only. Methods. We present the case of a 64-year-old patient with an extended sinonasal hemangiopericytoma, who was successfully treated by an endoscopic controlled endonasal tumor resection after embolisation with Onyx. Further, to support the new treatment option, we review the literature concerning all features of sinonasal hemangiopericytomas and their therapeutical management. Results/Conclusion. Onyx, which has not been described in the context of hemangiopericytoma yet, is a very effective embolic agent for a preoperative embolisation of sinonasal hemangiopericytoma allowing a safe endoscopic surgery

Abstract Number ‐ 33: Patients Treated with The Pipeline Shield Flow Diverter Enrolled Within the INSPIRE Study: Primary analysis

Introduction The INSPIRE study collects post‐market data on multiple devices from more than 40 centers world‐wide. One of these devices is the PipelineTM Flex flow diverter with Shield TechnologyTM (Pipeline Shield) for the treatment of intracranial aneurysms. The Shield surface modification is designed to enhance endothelization of the device with low thromboembolic risks. We analyze the efficacy and safety outcomes after Pipeline Shield therapy at the 1‐year follow‐up in a large prospective study. Methods INSPIRE is a prospective, multicenter, single arm study. Patients are followed for 1‐year post‐procedure and results are adjudicated by an independent Clinical Events Committee and Imaging Core Laboratory. All patients were treated per their hospital’s standard of care. The primary safety endpoint was neurological death or major stroke in the treated vascular area. The primary efficacy endpoint was complete aneurysm occlusion without significant parent artery stenosis (>50%) or retreatment. For this analysis, the last‐available observation was carried forward to overcome differences between centers’ imaging schedules. Results A total of 537 patients were enrolled, with 504 patients with 488 aneurysms included in the analysis (mean age 53.8±12.2, 77.0% [388/504] female). The majority of aneurysms were located in the ICA (74.2%, 362/488). Of the remaining aneurysms, 16.0% (78/488) were in the anterior circulation and 9.8% (48/488) were in the posterior circulation. The majority of aneurysms were saccular (89.3% [436/488]). A total of 47.1% of aneurysms were small ( = 25 mm, 25/488). Adjunctive devices were used in 20.9% (102/488) of cases, including balloon (42.2% [19/43]), coil (63.7%, [65/102]), stent (5.9% [6/102]), or flow diverter (9.8% [10/102]). At 1‐year post‐procedure, complete occlusion (Raymond Roy Class I) was achieved in 74.9% (326/435) aneurysms. The primary safety endpoint occurred in 2.2% (11/504) patients. The primary endpoint was achieved in 73.2% (290/396) cases; reasons for primary endpoint failure included residual neck (5.8% [23/396]), residual aneurysm (19.4% [77/396]), stenosis >50% (1.0% [4/396]), and re‐treatment (1.5% [6/396]). Among ICA aneurysms, complete occlusion was achieved in 78.1% (249/319). The primary safety endpoint occurred in 2.0% (7/356) patients. The primary endpoint was achieved in 77.1% (225/292) cases; reasons for primary endpoint failure among ICA aneurysms included residual neck (5.5% [16/292]), residual aneurysm (16.4% [48/292]), stenosis >50% (0.7% [2/292]), and re‐treatment (1.4% [67/292]). Conclusions INSPIRE data suggests good rates of complete occlusion, efficacy, and safety among a large cohort of patients with aneurysms in a variety of challenging locations and sizes treated with the Pipeline Shield device, with adjudication by CEC and Imaging Core Lab ensuring high quality of these data