Sarcopenia is a predictor of patient death in acute ischemic stroke.

BACKGROUND: Sarcopenia is proposed as a novel imaging biomarker in several acute conditions regarding outcome and mortality. The aim of the present study was to investigate the prognostic role of the masseter muscles in patients with acute ischemic stroke (AIS). METHODS: Overall, 189 patients with AIS that received mechanical thrombectomy were retrospectively enrolled in this study. Outcome and overall survival after 90 days were analyzed. Transversal surface area and density of the masseter muscles were measured. The diagnostic performance for the estimation of a) favorable modified ranking scale 90 days (mRS 90) outcome and b) death at 90 days was calculated using univariate and multivariate logistic regression analysis, followed by receiver operating characteristics and Odds ratios. RESULTS: The masseter muscle area provided a significant difference between patients who survived and those who died and between patients who had a favorable outcome (mRS 90 < 3) and those who did not. The cutoff for a favorable mRS 90 was found to be 435.8 mm2 for men and 338.8 mm2 for women, the cutoff for the prediction of death 421.3 mm2 for men and 326.6 mm2 for women. Masseter muscle area was the third strongest predictor in both categories after patient age and NIHSS. CONCLUSIONS: Masseter muscle area is an independent predictor of mortality in patients with AIS.

Mechanical thrombectomy using the Nimbus stent-retriever - initial experiences in a single-center observational study.

BACKGROUND: The Nimbus stent-retriever (NSR) was developed for mechanical thrombectomy of wall-adherent thrombi in cerebral arteries. It features a novel geometry with a proximal spiral section and a distal barrel section. The new device is designed to retrieve tough clots with a micro-clamping technique. In the first case series reporting on the NSR, we share our initial experience about the first 12 treated cases. METHODS: In total, 12 patients (5 men, 7 women; mean age 78 years) with occlusion of the internal carotid artery or the middle cerebral artery (M1 or M2 segment) were treated with the NSR, 11 after unsuccessful recanalization attempts with conventional stent-retrievers or aspiration thrombectomy. RESULTS: Retrieving maneuvers with the NSR recovered a thrombus in 7 patients (58%), of which 6 resulted in vessel recanalization mTICI ≥ 2b. Successful recanalization improved the mTICI score by a median of 3 points. In 5 of 7 cases, this required only one thrombectomy maneuver. In 5 cases, no improvement of recanalization could be achieved with the NSR (1-3 attempts). No NSR-related complications occurred in this case series. CONCLUSIONS: In our initial experience, the NSR appeared to be a safe and effective second-line stent-retriever after unsuccessful MT with conventional stent-retrievers or aspiration thrombectomy allowing for mTICI ≥ 2b rescue thrombectomy in ab 50% of cases. No NSR associated complications occurred in our case series.

Therapy results of pericallosal aneurysms: A retrospective unicenter study.

This retrospective study aims to compare treatment results of ruptured and unruptured pericallosal artery aneurysms (PAAs) regarding patient outcome and aneurysm recurrence after endovascular treatment (EVT) and neurosurgical treatment (NT). A total of 67 patients with PAA were admitted to our hospital, 44 patients with subarachnoidal hemorrhage (SAH) due to a ruptured PAA and 23 patients with unruptured PAA. The radiographic features of PAA were collected from pre-treatment digital subtraction angiography. In addition, demographic, clinical and radiographic parameters of all patients were recorded. Outcome was measured based on the modified Rankin scale (mRS) at 6 months after admission (favorable mRS score, 0-2 vs unfavorable mRS score, 3-6). Overall 46 patients underwent EVT and 21 patients NT. Six months after discharge 24 patients with SAH had a favorable outcome (mRS 0-2) and 16 patients an unfavorable outcome (mRS 3-6). Mortality rate of patients with SAH was 9.1% (4/44). Overall aneurysm recurrence was treated in 13 % of patients in the EVT cohort (6/46), whereas patients treated with NT had no recurrence. All patients with unruptured PAA had a favorable outcome. EVT and NT of PAA show comparable good results, although aneurysm recurrence occurs more often after EVT.

Sociodemographic data and APOE-ε4 augmentation for MRI-based detection of amnestic mild cognitive impairment using deep learning systems.

Detection and diagnosis of early and subclinical stages of Alzheimer's Disease (AD) play an essential role in the implementation of intervention and prevention strategies. Neuroimaging techniques predominantly provide insight into anatomic structure changes associated with AD. Deep learning methods have been extensively applied towards creating and evaluating models capable of differentiating between cognitively unimpaired, patients with Mild Cognitive Impairment (MCI) and AD dementia. Several published approaches apply information fusion techniques, providing ways of combining several input sources in the medical domain, which contributes to knowledge of broader and enriched quality. The aim of this paper is to fuse sociodemographic data such as age, marital status, education and gender, and genetic data (presence of an apolipoprotein E (APOE)-ε4 allele) with Magnetic Resonance Imaging (MRI) scans. This enables enriched multi-modal features, that adequately represent the MRI scan visually and is adopted for creating and modeling classification systems capable of detecting amnestic MCI (aMCI). To fully utilize the potential of deep convolutional neural networks, two extra color layers denoting contrast intensified and blurred image adaptations are virtually augmented to each MRI scan, completing the Red-Green-Blue (RGB) color channels. Deep convolutional activation features (DeCAF) are extracted from the average pooling layer of the deep learning system Inception_v3. These features from the fused MRI scans are used as visual representation for the Long Short-Term Memory (LSTM) based Recurrent Neural Network (RNN) classification model. The proposed approach is evaluated on a sub-study containing 120 participants (aMCI = 61 and cognitively unimpaired = 59) of the Heinz Nixdorf Recall (HNR) Study with a baseline model accuracy of 76%. Further evaluation was conducted on the ADNI Phase 1 dataset with 624 participants (aMCI = 397 and cognitively unimpaired = 227) with a baseline model accuracy of 66.27%. Experimental results show that the proposed approach achieves 90% accuracy and 0.90 F1-Score at classification of aMCI vs. cognitively unimpaired participants on the HNR Study dataset, and 77% accuracy and 0.83 F1-Score on the ADNI dataset.

Nusinersen in adults with 5q spinal muscular atrophy: a non-interventional, multicentre, observational cohort study.

BACKGROUND: Nusinersen is approved for the treatment of 5q spinal muscular atrophy of all types and stages in patients of all ages. Although clinical trials have shown improvements in motor function in infants and children treated with the drug, data for adults are scarce. We aimed to assess the safety and efficacy of nusinersen in adults with 5q spinal muscular atrophy. METHODS: We did an observational cohort study at ten academic clinical sites in Germany. Patients with genetically confirmed 5q spinal muscular atrophy (age 16-65 years) with a homozygous deletion of exons 7, 8, or both, or with compound heterozygous mutations were eligible for inclusion and received nusinersen treatment in accordance with the label for a minimum treatment time of 6 months to a follow-up of up to 14 months. The primary outcome was the change in the total Hammersmith Functional Motor Scale Expanded (HFMSE) score, assessed at months 6, 10, and 14, and based on pre-post comparisons. This study is registered with the German Clinical Trials Register (number DRKS00015702). FINDINGS: Between July 13, 2017, and May 1, 2019, 173 patients were screened, of whom 139 (80%) were eligible for data analysis. Of these, 124 (89%) were included in the 6-month analysis, 92 (66%) in the 10-month analysis, and 57 (41%) in the 14-month analysis; patients with missing baseline HFMSE scores were excluded from these analyses. Mean HFMSE scores were significantly increased compared with baseline at 6 months (mean difference 1·73 [95% CI 1·05-2·41], p<0·0001), 10 months (2·58 [1·76-3·39], p<0·0001), and 14 months (3·12 [2·06-4·19], p<0·0001). Clinically meaningful improvements (≥3 points increase) in HFMSE scores were seen in 35 (28%) of 124 patients at 6 months, 33 (35%) of 92 at 10 months, and 23 (40%) of 57 at 14 months. To 14-month follow-up, the most frequent adverse effects among 173 patients were headache (61 [35%] patients), back pain (38 [22%]), and nausea (19 [11%]). No serious adverse events were reported. INTERPRETATION: Despite the limitations of the observational study design and a slow functional decline throughout the natural disease course, our data provide evidence for the safety and efficacy of nusinersen in the treatment of adults with 5q spinal muscular atrophy, with clinically meaningful improvements in motor function in a real-world cohort. FUNDING: None.

18F-FDG-PET/MRI in the diagnostic work-up of limbic encephalitis.

INTRODUCTION: Limbic encephalitis (LE) is an immune-related, sometimes paraneoplastic process of the central nervous system. Initial diagnosis and treatment are based on the clinical presentation as well as antibody profiles and MRI. This study investigated the diagnostic value of integrated 18F-FDG-PET/MRI in the diagnostic work-up of patients with LE for a cerebral and whole-body imaging concept. MATERIAL AND METHODS: Twenty patients with suspected LE were enrolled in this prospective study. All patients underwent a dedicated PET/MRI protocol of the brain as well as the whole-body. Two neuroradiologists, one body radiologist and one nuclear medicine physician performed blinded consensus readings of each corresponding MRI and PET/MRI dataset of the brain and whole-body. Diagnostic confidence was evaluated on a Likert scale. RESULTS: Based on integrated PET/MRI 19 / 20 patients were found to show morphologic and / or metabolic changes indicative of LE, whereas sole MRI enabled correct identification in 16 / 20 patients. Three patients with negative MRI showed metabolic changes of the limbic system or extra-limbic regions, shifting the diagnosis from (negative) MRI to positive for LE in PET/MRI. Whole-body staging revealed suspected lesions in 2/20 patients, identified by MRI and PET, one confirmed as malignant and one false positive. Diagnostic confidence for cerebral and whole-body imaging reached higher scores for PET/MRI (cerebral: 2.7 and whole body: 4.8) compared to MRI alone (cerebral: 2.4 and whole body: 4.5). CONCLUSION: LE diagnosis remains challenging for imaging as it shows only subtle imaging findings in most patients. Nevertheless, based on the simultaneous and combined analysis of morphologic and metabolic data, integrated PET/MRI may enable a dual platform for improved diagnostic confidence and overall detection of LE as well as whole-body imaging for exclusion of paraneoplastic LE.

Clinical Implication of Dosimetry of Computed Tomography- and Fluoroscopy-Guided Intrathecal Therapy With Nusinersen in Adult Patients With Spinal Muscular Atrophy.

Background: Spinal muscular atrophy (SMA) is a genetic disorder that leads to progressive tetraparesis. Nusinersen is the first approved drug for the treatment of SMA and is administered via intrathecal injections. Neuromyopathic scoliosis and spondylodesis can impede lumbar punctures, thus necessitating the use of radiological imaging. Furthermore, dosimetry of this potentially lifelong therapy should be supervised. Methods: Fluoroscopy-assisted or computed tomography (CT)-guided intrathecal injections of nusinersen were performed in adult patients with SMA type 2 and 3. The mean effective dose was compared in patients with and without spondylodesis as well as in those with SMA type 2 and 3. The dosimetry was analyzed in relation to the motor function evaluated with the Revised Upper Limb module (RULM) score and the Hammersmith Functional Motor Scale-Expanded (HFMSE) score. Results: Fifteen patients with SMA type 2 and 3 underwent radiological imaging-assisted intrathecal injections. The mean effective dose per CT-guided injection per patient was 2.59 (±1.67) mSv (n = 12). The mean dose area product (DAP) per fluoroscopy-guided injection per patient was 200.48 (±323.67) µGym2 (n = 3). With increase in the number of injections, the effective dose (r = -0.23) (p < 0.05) and the DAP (r = -0.09) (p > 0.05) decreased. The mean effective dose in 4 patients without spinal fusion (SMA type 2) was 1.39 (±0.51) mSv, whereas that in 8 patients with spondylodesis (SMA type 2 and 3) was 3.21 (±1.73) mSv. The mean effective dose in 5 SMA type 2 patients with spondylodesis was 2.68 (±1.47) mSv (n = 5) and in 3 SMA type 3 patients was 4.00 (±1.82) mSv. Dosimetry did not show significant correlation with the clinical severity of the disease (RULM score: r = -0.045, p > 0.05 and HFMSE score: r = -0.001, p > 0.05). Conclusions: In SMA type 2 and 3 patients undergoing radiological imaging-assisted injections, the effective dose and DAP decreased during therapy with nusinersen. The mean effective dose in patients with spondylodesis was higher than that in patients without spondylodesis. Dosimetry should be monitored carefully in order to detect and prevent unnecessary radiation exposure.

Endovascular treatment of cerebral vasospasm after subarachnoid hemorrhage: More is more.

OBJECTIVE: Delayed cerebral ischemia (DCI) is strongly associated with poor outcome after subarachnoid hemorrhage (SAH). Cerebral vasospasm is a major contributor to DCI and requires special attention. To evaluate the effect of vasospasm management on SAH outcome, we performed a pooled analysis of 2 observational SAH cohorts. MATERIALS: Data from 2 institutional databases with consecutive patients with SAH treated between 2005 and 2012 were pooled. The effect of 2 institutional standards of conservative and endovascular vasospasm treatment (EVT) on the rates of DCI (new cerebral infarcts not visible on the post-treatment imaging) and unfavorable outcome (modified Rankin Scale score >2) at 6 months follow-up was analyzed. RESULTS: The final analysis included 1,057 patients with SAH. There was no difference regarding demographic (age and sex), clinical (Hunt & Hess grades, acute hydrocephalus, treatment modality, and infections), and radiographic (Fisher grades and aneurysm location) characteristics of the populations. However, there was a significant difference in the rate (24.4% [121/495] vs 14.4% [81/562], p < 0.0001) and timing (first treatment on day 6 vs 8.9 after SAH, p < 0.0001) of EVT. The rates of DCI (20.8% vs 29%, p = 0.0001) and unfavorable outcome (44% vs 50.6%, p = 0.04) were lower in the cohort with more frequent and early EVT. Multivariate analysis confirmed independent effect of EVT standard on DCI risk and outcome. CONCLUSIONS: A preventive strategy utilizing frequent and early EVT seems to reduce the risk of DCI in patients with SAH and improve their functional outcome. We recommend prospective evaluation of the value of preventive EVT strategy on SAH. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that for patients with SAH, a frequent and early EVT to treat vasospasm reduces the risk of DCI and improves functional outcome.

Uninterrupted edoxaban vs. vitamin K antagonists for ablation of atrial fibrillation: the ELIMINATE-AF trial.

AIMS: Edoxaban is a direct factor Xa inhibitor approved for stroke prevention in atrial fibrillation (AF). Uninterrupted edoxaban therapy in patients undergoing AF ablation has not been tested. METHODS AND RESULTS: The ELIMINATE-AF trial, a multinational, multicentre, randomized, open-label, parallel-group study, was conducted to assess the safety and efficacy of once-daily edoxaban 60 mg (30 mg in patients indicated for dose reduction) vs. vitamin K antagonists (VKAs) in AF patients undergoing catheter ablation. Patients were randomized 2:1 to edoxaban vs. VKA. The primary endpoint (per-protocol population) was time to first occurrence of all-cause death, stroke, or International Society of Thrombosis and Haemostasis-defined major bleeding during the period from the end of the ablation procedure to end of treatment (90 days). Overall, 632 patients were enrolled, 614 randomized, and 553 received study drug and underwent ablation; 177 subjects underwent brain magnetic resonance imaging to assess silent cerebral infarcts. The primary endpoint (only major bleeds occurred) was observed in 0.3% (1 patient) on edoxaban and 2.0% (2 patients) on VKA [hazard ratio (95% confidence interval): 0.16 (0.02-1.73)]. In the ablation population (modified intent-to-treat population including patients with ablation), the primary endpoint was observed in 2.7% of edoxaban (N = 10) and 1.7% of VKA patients (N = 3) between start of ablation and end of treatment. There were one ischaemic and one haemorrhagic stroke, both in patients on edoxaban. Cerebral microemboli were detected in 13.8% (16) patients who received edoxaban and 9.6% (5) patients in the VKA group (nominal P = 0.62). CONCLUSION: Uninterrupted edoxaban therapy represents an alternative to uninterrupted VKA treatment in patients undergoing AF ablation.

Comparison of L-Methyl-11C-Methionine PET With Magnetic Resonance Spectroscopy in Detecting Newly Diagnosed Glioma.

AIMS: Amino acid PET and magnetic resonance spectroscopy (MRS) are at the forefront of noninvasive imaging techniques used for detection and subtyping of glioma-suspicious lesions. In this pilot study, we compare L-methyl-C-methionine PET and MRS for their ability to predict glioma subtypes. METHODS: Nineteen patients with histologically, confirmed newly diagnosed glioma underwent preoperative L-methyl-C-methionine PET and MRS in 1 diagnostic session. According to the molecular portfolio and histopathologic diagnosis, patients were subdivided in isocitrate dehydrogenase (IDH) wild-type glioblastoma, IDH wild-type grade II/III glioma, IDH-mutant grade II/III glioma without 1p/19q codeletion, and with 1p/19q codeletion subgroups. Maximum tumor-to-brain ratio (TBRmax), creatine, choline, and N-acetyl aspartate peaks were correlated with postoperative histopathologic tumor diagnoses. RESULTS: Maximum tumor-to-brain ratio was highest in glioblastoma patients (4.18) followed by patients with IDH wild-type grade II and III glioma (3.41). The latter TBRmax values were higher compared with those in patients with IDH-mutant grade II/III glioma without 1p/19q codeletion (1.95) and in patients with IDH-mutant 1p/19q codeleted grade II and III glioma (2.79). Magnetic resonance spectroscopy marker distribution showed no clear trend. Receiver operating characteristic analysis revealed TBRmax to be the best performing parameter in identifying IDH status (area under the curve, 0.67) and all spectroscopy markers combined in identifying glioma subgroups (area under the curve, 0.68), respectively. CONCLUSIONS: L-Methyl-C-methionine PET and MRS bear limited potential in glioma subgrouping. L-Methyl-C-methionine PET appears to be superior in differentiating IDH status, whereas MRS is more helpful in glioma subgrouping.

Relative health-related quality of life after treatment of unruptured intracranial aneurysms: long-term outcomes and influencing factors.

Health-related quality of life (HRQOL) is an important clinical outcome parameter. Its analysis is particularly meaningful to patients with minor functional impairment. The main goal of this study was to assess long-term data of HRQOL and their variables for patients undergoing treatment for unruptured intracranial aneurysms (UIAs). Therefore, a cross-sectional study of HRQOL (SF-36 questionnaire) was conducted in patients treated for UIA using a telephone survey assessing numerous medical and sociodemographic variables. A total of 96 patients with a follow up longer than 36 months post-treatment were included. HRQOL results were compared with the German reference population. Uni- and multivariate analyses were performed to detect variables with an impact on outcome. After a mean follow up of 57.75 ± 13.56 months, patients with treated UIAs showed a significant decrease in the mental health domains 'role emotional' and 'social functioning' and the 'mental health component score' (MHCS) compared with the age- and sex-matched reference population. Overall, 47% of the patients showed a clinically and psychosocially relevant decrease compared with the mean MHCS of the reference population. Multivariate analysis suggests that mainly the treatment modality (coiling versus clipping) and additional remaining untreated UIAs negatively impacted mental HRQOL. In conclusion, the partly significant losses in HRQOL identify the necessity for less-wearing treatment strategies and a better prediction of risk of UIA rupture. Our results indicate that certain factors in the guidance and management of patients undergoing endovascular treatment may negatively affect their mental HRQOL. The relevance of additional UIAs remaining untreated on HRQOL is a new finding that should be considered in the counseling of patients with multiple UIAs.

Feasibility of intra-arterial chemotherapy for retinoblastoma: experiences in a large single center cohort study.

PURPOSE: In the last 10 years, intra-arterial chemotherapy (IAC) has been increasingly used in the clinical management of retinoblastoma. It is reported to provide tumor control even in advanced stage disease that might have previously required enucleation. In our clinical experience, there are three conditions that may impair the use of IAC: (1) significant collaterals to meningeal arteries, (2) technical failure of ophthalmic artery catheterization, or (3) retina blood supply from collaterals different to the ophthalmic artery. In the current study, we assessed the rate of IACs that could not be carried out in our institution due to these three reasons. METHODS: All patients admitted for IAC in our hospital were retrospectively assessed by chart review. Non-application rate of IAC was assessed and classified according to the three abovementioned criteria. Complication rate of both finalized and interrupted interventions was recorded. RESULTS: Ninety-eight patients (median age 21.4 months, range 5.3 months-10.5 years) were identified. IAC was performed in 69 (70.4%) patients and interrupted in 12 (12.2%) cases because of meningeal collaterals, in 8 (8.2%) because of technical failure to cannulate the ophthalmic artery, and in 9 (9.2%) because of alternative blood supply of the retina. CONCLUSION: The rather defensive approach that is pursued in our center resulted in an overall non-application rate of IAC around 30%. The relatively high probability of conditions that impair the use of IAC needs to be addressed adequately in the patient conversation prior to the procedure. Our rate of 8% of abstention from IAC due to technical limitations might be reduced by the application of more rigorous therapeutic approaches such as balloon occlusion of the distal internal carotid artery. More research is finally needed to determine if IAC can be safely performed in the presence of meningeal collaterals and via branches of the external carotid artery.

Hybrid 11C-MET PET/MRI Combined With "Machine Learning" in Glioma Diagnosis According to the Revised Glioma WHO Classification 2016.

PURPOSE: With the advent of the revised WHO classification from 2016, molecular features, including isocitrate dehydrogenase (IDH) mutation have become important in glioma subtyping. This pilot trial analyzed the potential for C-methionine (MET) PET/MRI in classifying glioma according to the revised WHO classification using a machine learning model. METHODS: Patients with newly diagnosed WHO grade II-IV glioma underwent preoperative MET-PET/MRI imaging. Patients were retrospectively divided into four groups: IDH wild-type glioblastoma (GBM), IDH wild-type grade II/III glioma (GII/III-IDHwt), IDH mutant grade II/III glioma with codeletion of 1p19q (GII/III-IDHmut1p19qcod) or without 1p19q-codeletion (GII/III-IDHmut1p19qnc). Within each group, the maximum tumor-to-brain-ratio (TBRmax) of MET-uptake was calculated. To gain generalizable implications from our data, we made use of a machine learning algorithm based on a development and validation subcohort. A support vector machine model was fit to the development subcohort and evaluated on the validation subcohort. Receiver operating characteristic (ROC) analysis served as metric to assess model performance. RESULTS: Of a total of 259 patients, 39 patients met the inclusion criteria. TBRmax was highest in the GBM cohort (TBRmax 3.83 ± 1.30) and significantly higher (P = 0.004) compared to GII/III-IDHmut1p19qnc group, where TBRmax was lowest (TBRmax 2.05 ± 0.94). ROC analysis showed poor AUC for glioma subtyping (AUC 0.62) and high AUC of 0.79 for predicting IDH status. In the GII/III-IDHmut1p19qcod group, TBR values were slightly higher than in the IDHmut1p19qnc group. CONCLUSIONS: MET-PET/MRI imaging in pre-operatively classifying glioma entities appears useful for the assessment of IDH status. However, a larger trial is needed prior to translation into the clinical routine.

Post-treatment Antiplatelet Therapy Reduces Risk for Delayed Cerebral Ischemia due to Aneurysmal Subarachnoid Hemorrhage.

BACKGROUND: Delayed cerebral ischemia (DCI) has a strong impact on outcome of patients with aneurysmal subarachnoid hemorrhage (SAH). Positive effect of antiplatelet therapy on DCI rates has been supposed upon smaller SAH series. OBJECTIVE: To analyze the benefit/risk profile of antiplatelet use in SAH patients. METHODS: This retrospective case-control study was based on institutional observational cohort with 994 SAH patients treated between January 2003 and June 2016. The individuals with postcoiling antiplatelet therapy (aspirin with/without clopidogrel) were compared to a control group without antiplatelet therapy. Occurrence of DCI, major/minor bleeding events in the follow-up computed tomography scans, and favorable outcome at 6 mo after SAH (modified Rankin scale < 3) were compared in both groups. RESULTS: Of 580 patients in the final analysis, 329 patients received post-treatment antiplatelet medication. There were no significant differences between the compared groups with regard to basic outcome confounders. Aspirin use was independently associated with reduced DCI risk (P < .001, adjusted odds ratio = 0.41, 95% confidence interval 0.24-0.65) and favorable outcome (P = .02, adjusted odds ratio = 1.78, 95% confidence interval 1.06-2.98). Regarding bleeding complications, aspirin was associated only with minor bleeding events (P = .02 vs P = .51 for major bleeding events). CONCLUSION: Regular administration of aspirin might have a positive impact on DCI risk and outcome of SAH patients, without increasing the risk for clinically relevant bleeding events. In our SAH cohort, dual antiplatelet therapy showed no additional benefit on DCI risk, but increased the likelihood of major bleeding events.

Feasibility and safety of intrathecal treatment with nusinersen in adult patients with spinal muscular atrophy.

BACKGROUND: Nusinersen is an intrathecally administered antisense oligonucleotide (ASO) and the first approved drug for the treatment of spinal muscular atrophy (SMA). However, progressive neuromyopathic scoliosis and the presence of spondylodesis can impede lumbar punctures in SMA patients. Our aim was to assess the feasibility and safety of the treatment in adults with SMA. METHODS: For the intrathecal administration of nusinersen, we performed conventional, fluoroscopy-assisted and computer tomography (CT)-guided lumbar punctures in adult patients with type 2 and type 3 SMA. We documented any reported adverse events and performed blood tests. RESULTS: We treated a total of 28 adult SMA patients (9 patients with SMA type 2 and 19 patients with SMA type 3) aged between 18-61 years with nusinersen. The mean Revised Upper Limb Module (RULM) score at baseline in SMA type 2 and SMA type 3 patients was 9.9 ± 4.6 and 29.5 ± 8.5, respectively. The mean Hammersmith Functional Motor Scale Expanded (HFMSE) score at baseline was 3.1 ± 2.5 and 31.2 ± 18.1, respectively. Half of the SMA type 3 patients were ambulatory at treatment onset. In total, we performed 122 lumbar punctures with 120 successful intrathecal administrations of nusinersen. Lumbar punctures were well tolerated, and no serious adverse events occurred. CONCLUSIONS: Our data demonstrate the feasibility and tolerability of intrathecal treatment with nusinersen in adults with SMA type 2 and type 3. However, treatment can be medically and logistically challenging, particularly in patients with SMA type 2 and in patients with spondylodesis.

Liponeurocytoma: Systematic Review of a Rare Entity.

OBJECTIVE: Liponeurocytoma is a rare benign tumor of the central nervous system, which develops mainly in adult patients within the posterior fossa. The World Health Organization has categorized this entity in its last classification of 2016 as a benign grade II tumor. Histopathologic characteristics contain neuronal and variable astrocytic differentiation with foci of lipomatous distinction. Only a few case reports and case series have been reported and the knowledge of this tumor is limited. General treatment guidelines do not exist. The aim of this study was to analyze the literature to create treatment guidelines. METHODS: PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines were followed to search existing online databases between January 1, 1978 and May 15, 2018. RESULTS: A systematic review of the literature found 73 patients (40 female, 33 male) with liponeurocytoma, in 59 of whom (80.8%) the disease occurred in the posterior fossa. The Ki-67/MIB-1 proliferation index was described in 58 patients, showing a mean value of 3.73% ± 4.01%. Follow-up was performed in 49 patients, with a median length of 52.02 ± 50.52 months, showing tumor recurrence in 14 patients (28.57%). Tumor recurrence was observed in only 1 patient (1/12, 8.33%) after adjuvant radiotherapy, whereas tumor recurrence was seen in 13/29 patients (44.83%) who did not receive adjuvant radiotherapy. CONCLUSIONS: Liponeurocytomas are rare benign tumors, occurring mainly in the cerebellum. The therapy of choice is surgery. Postoperative radiotherapy seems to decrease the risk of tumor recurrence and should be offered to the patient.

Stent-assisted treatment of ruptured intracranial aneurysms in the acute phase: A single center experience.

INTRODUCTION: The purpose of this study was to analyze the results of patients with ruptured aneurysms who were treated with a specific microstent in the acute phase of subarachnoid hemorrhage. METHODS: Data from patients with acutely-ruptured intracranial aneurysm treated with the Neuroform stent in the period between 2003 and 2016 were retrospectively assessed, addressing aneurysm occlusion and clinical outcome with a focus on periprocedural complications. RESULTS: Twenty-nine consecutive patients with ruptured intracranial aneurysms were included in the analysis. Periprocedural hemorrhagic complications were stated in six patients, leading to death in four. Thromboembolic complications were observed in seven patients, among whom only one affected the clinical outcome with death due to basilar thrombosis. Immediate complete occlusion and occlusion with residual neck was achieved in 79.3% of cases. CONCLUSION: Stent-assisted coiling of acutely-ruptured aneurysms achieves good immediate aneurysm occlusion. Rates of intra- and periprocedural adverse events observed in this series were significant, but did not translate to corresponding morbidity and mortality in all cases. The retrospective analysis did not allow assessing the overall risks of endovascular therapy with stent use in ruptured and complex aneurysm when compared to the overall risks with other alternative options.

Diagnostic impact of integrated 18F-FDG PET/MRI in cerebral staging of patients with non-small cell lung cancer.

Background Integrated positron emission tomography/magnetic resonance imaging (PET/MRI) systems are increasingly being available and used for staging examinations. Brain metastases (BM) are frequent in patients with non-small cell lung cancer (NSCLC) and decisive for treatment strategy. Purpose To assess the diagnostic value of integrated 18F-2-fluoro-2-deoxy-D glucose (18F-FDG) PET/MRI in initial staging in patients with NSCLC for BM in comparison to MRI alone. Material and Methods Eighty-three patients were prospectively enrolled for an integrated 18F-FDG PET/MRI examination. The 3 T MRI protocol included a fluid-attenuated inversion-recovery sequence (FLAIR) and a contrast-enhanced three-dimensional magnetization prepared rapid acquisition GRE sequence (MPRAGE). Two neuroradiologists evaluated the datasets in consensus regarding: (i) present lesions; (ii) size of lesions; and (iii) number of lesions detected in MRI alone, compared to the PET component when reading the 18F-FDG PET/MRI. Results Based on MRI alone, BM were detected in 15 out of the 83 patients, comprising a total of 39 metastases. Based on PET alone, six patients out of the 83 patients were rated positive for metastatic disease, revealing a total of 15 metastases. PET detected no additional BM. The size of the BM correlated positively with sensitivity of detection in PET. Conclusion The sensitivity of PET in detection of BM depends on their size. 18F-FDG PET/MRI does not lead to an improvement in diagnostic accuracy in cerebral staging of NSCLC patients, as MRI alone remains the gold standard.

Of Bubbles and Layers: Which Cerebral Cavernous Malformations are Most Difficult to Dissect From Surrounding Eloquent Brain Tissue?

BACKGROUND: Cerebral cavernous malformations (CCM) may lead to repetitive intracerebral hemorrhage. In selected cases, a surgical resection is indicated. OBJECTIVE: To identify magnetic resonance imaging (MRI) features of CCM that correlate with the difficulty of dissection and postoperative outcome. METHODS: This study prospectively analyzed pre- and postoperative MRI features, intraoperative findings (surgical questionnaire), and postoperative outcome of 41 patients with eloquent CCM. Based on the results of the surgeon's questionnaire and postoperative MRI findings, all surgical procedures were dichotomized in a "difficult" (group A) or "not difficult" (group B) lesion dissection. Based on the correlation of preoperative MRI features with groups A and B, a 3-tiered classification was established and tested for sensitivity and specificity. RESULTS: In 22 patients, dissection of the lesion was rated difficult. This was significantly correlated with amount of postoperative diffusion restriction on MRI ( P = .001) and postoperative outcome ( P = .05). Various preoperative MRI features were tested for correlation and combined in a 3-tiered classification. Receiver operating characteristics revealed excellent and good results for predicting difficulty of dissection for the different classification types. CONCLUSION: We provide a meticulous analysis and new classification of preoperative MRI features that seem to be involved in the microsurgical resection of CCM.

Making use of longitudinal information in pattern recognition.

Longitudinal designs are widely used in medical studies as a means of observing within-subject changes over time in groups of subjects, thereby aiming to improve sensitivity for detecting disease effects. Paralleling an increased use of such studies in neuroimaging has been the adoption of pattern recognition algorithms for making individualized predictions of disease. However, at present few pattern recognition methods exist to make full use of neuroimaging data that have been collected longitudinally, with most methods relying instead on cross-sectional style analysis. This article presents a principal component analysis-based feature construction method that uses longitudinal high-dimensional data to improve predictive performance of pattern recognition algorithms. The method can be applied to data from a wide range of longitudinal study designs and permits an arbitrary number of time-points per subject. We apply the method to two longitudinal datasets, one containing subjects with mild cognitive impairment along with healthy controls, the other with early dementia subjects and healthy controls. Across both datasets, we show improvements in predictive accuracy relative to cross-sectional classifiers for discriminating disease subjects from healthy controls on the basis of whole-brain structural magnetic resonance image-based voxels. In addition, we can transfer longitudinal information from one set of subjects to make disease predictions in another set of subjects. The proposed method is simple and, as a feature construction method, flexible with respect to the choice of classifier and image registration algorithm. Hum Brain Mapp 37:4385-4404, 2016. © 2016 Wiley Periodicals, Inc.