Long-term clinical and radiological results for fat graft obliteration in subtotal petrosectomy and cochlear implant surgery: a retrospective clinical study.

PURPOSE: The study aimed to evaluate the long-term clinical, radiological, and functional results for subtotal petrosectomy and cochlear implant surgery with closure of the external auditory canal and fat obliteration. METHODS: We retrospectively included all consecutive cases of simultaneous subtotal petrosectomy and cochlear implant surgery performed at a tertiary referral center between 2009 and 2016 using the same surgical technique. All patients underwent postoperative high-resolution computed tomography (HRCT) and annual audiological assessments. A 5-year minimum clinical, radiological, and audiological follow-up was performed. The early and late postoperative results were compared. The main outcome measures were complications, postauricular retraction, fat graft reabsorption, and audiological outcomes. RESULTS: Twenty-nine procedures performed in 23 patients (six bilateral) met the inclusion criteria. The mean age of the patients was 67 ± 13.4 years and mean follow-up duration was 7.5 ± 2 years. At follow-up, postauricular retraction was detected in 24 cases (82.8%), including five cases (17.1%) with subcutaneous protrusion of implant and array. Fat graft volume was significantly reduced at late-HRCT in terms of maximum diameter (2.24 ± 1.0 cm vs 3.69 ± 0.7 cm; p < 0.0005) and surface area (1.88 ± 1.2 vs 4.24 ± 1.6 cm2, p < 0.0005). Six patients had extracochlear electrodes at late-HRCT (3/6 had an increased number of extracochlear electrodes), with a lowering of this group's performance of - 15% (p < 0.005) in the follow-up speech comprehension test. CONCLUSIONS: Subtotal petrosectomy with cochlear implantation is an effective long-term technique in selected cases. Fat grafts showed significant reabsorption at long-term follow-up with reaeration of the middle ear spaces. Prolonged clinical and radiological follow-up is recommended for monitoring implant performances and late complications.

Elevation of brain ADC (apparent diffusion coefficient) in HIV-associated neurocognitive disorders and evolution after treatment: A pilot study.

BACKGROUND: Thirty to 50% of HIV-infected patients develop HIV-Associated Neurocognitive Disorders (HAND) despite virological control. The previously published Neuro+3 study showed their neurocognitive status can be improved by intensifying antiviral therapy. Our study is a part of the Neuro3+ study and aims to study apparent diffusion coefficient (ADC) as a biomarker for neurological improvement. PATIENTS AND METHODS: We prospectively included 31 patients with HAND. They received therapy with better CNS Penetration Effectiveness (CPE) score with two-year follow-up. Cognitive status was assessed at day 0 (D0) and week 96 (W96) using Frascati 3-stage classification and Global Deficit Score (GDS). Brain MRI at D0 and W96 assessed morphological data (white matter hyperintensities, opportunistic infections, ischemic lesions, atrophy) and measured whole brain apparent diffusion coefficient (ADC). We compared their data with a control group of 20 healthy patients with similar ages and sex ratio. RESULTS: After ARV intensification, cognitive status was significantly improved: GDS (n = 1,4 vs 1,0 p = 0.01) and Frascati scale (2HAD/22MND/7ANI vs 1HAD/8MND/17ANI p = 0.001). Mean ADC was significantly higher in patients at inclusion than in controls (0.88 × 10-3 mm2/s ± 0.06 vs 0.81 × 10-3 mm2/s ± 0.04, p = 0.0001). ADC decreased after treatment (0.88 × 10-3 mm2/s ± 0.06 vs 0.85 × 10-3 mm2/s ± 0.06 (p = 0,04). In subgroup analysis, ADC significantly decreased in clinically improved patients (0.89 × 10-3 mm2/s ± 0.07 vs 0.85 × 10-3 mm2/s ± 0.07 (p = 0,03)) and did not significantly change in non-clinically improved patients (0.86 × 10-3 mm2/s ± 0.07 vs 0.84 × 10-3 mm2/s ± 0.07 (p = 0,31)). After treatment, there was no significant difference between patients and controls (0.85 × 10-3 mm2/s ± 0.06 vs 0.81 × 10-3 mm2/s ± 0.04, p = 0.17). CONCLUSION: Whole-brain ADC is a good biomarker of HIV-associated neurocognitive disorders. It is significantly increased in patients with HAND compared with controls and significantly decreases after treatment. It is all the more important to have a quantitative biomarker as conventional imaging does not contribute to the diagnosis.

Central nervous system involvement in Erdheim-Chester disease: An observational cohort study.

OBJECTIVE: CNS involvement in Erdheim-Chester disease (ECD) leads to substantial morbidity and mortality. To assess CNS manifestations in a French cohort of 253 patients with ECD, we determined clinical characteristics and outcomes, including those under targeted therapies. METHODS: This was a retrospective longitudinal study. CNS manifestations were determined by clinical examination and brain or spine MRI. Targeted therapy efficacy was assessed using global assessment from a physician and a radiologist. The study was approved by the ethics committee Comité de Protection des Personnes Ile de France III. RESULTS: Ninety-seven of 253 patients (38%) with ECD had CNS involvement. CNS involvement was significantly associated with a younger age at diagnosis (mean 55.5 years) and at symptom onset (mean 50.5 years), as well as with the presence of the BRAF V600E mutation (in 77% of cases), xanthelasma (34%), and diabetes insipidus (36%). Median survival among patients with CNS involvement was significantly lower than that of patients with ECD without CNS involvement (124 months vs 146 months, p = 0.03). Seventy-four CNS MRIs were centrally reviewed, which showed 3 patterns: tumoral in 66%, pseudo-degenerative in 50%, and vascular in 18%. Targeted therapy (BRAF or MEK inhibitors) was associated with improved symptoms in 43% of patients and MRI improvement in 45%. CONCLUSIONS: CNS manifestations are typically associated with poor prognosis in patients with ECD. Three distinct patterns can be recognized: tumoral, pseudodegenerative, and vascular. CLASSIFICATION OF EVIDENCE: This study provides Class III evidence that targeted therapy leads to clinical or imaging improvement in almost 50% of patients.

ASL perfusion in acute ischemic stroke: The value of CBF in outcome prediction.

OBJECTIVE: The application of novel advanced magnetic resonance imaging (MRI) techniques in clinical practice has significantly improved diagnostic accuracy in early detection of acute ischemic stroke (AIS), additionally allowing outcome prediction. The introduction of arterial spin labeling (ASL) perfusion sequence as a standard in MRI protocols is a significant milestone in neuroradiology. The aim of the present study was to demonstrate the potential of ASL sequence for the detection of absolute (aCBF) and relative (rCBF) cerebral blood flow values for an ischemic area and to examine the correlation of the obtained values with the functional outcome of patients. PATIENTS AND METHODS: The study included 205 patients of both sexes over the age of 18 years, suspected with AIS, who met the inclusion criteria. Brain MRI examination according to the protocol for ischemia with fast three-dimensional pseudocontinuous (3D PCASL) ASL technique was used. Statistical analysis of the collected data was performed with SPSS 15.0. RESULTS: The appearance of the ROC curve indicated good diagnostic characteristics of aCBF in assessing a favorable stroke outcome, demonstrating a high statistical significance (p < 0.001), and high conclusion validity. The value of the rCBF was significantly higher in patients with a favorable outcome compared with patients with a poor outcome (p  < 0.001). The sum of sensitivity and specificity was the highest using aCBF cut-off value of 19.140 mL/100 g/min, and rCBF cut-off of 49.700 of the contralateral side percentage value. CONCLUSION: Our study shows that ASL perfusion sequence allows precise detection of perfusion values and provides a reliable insight into outcome prediction.

Pseudo-continuous arterial spin labelling shows high diagnostic performance in the detection of postoperative residual lesion in hyper-vascularised adult brain tumours.

OBJECTIVES: Our aim was to evaluate the contribution of pseudo-continuous arterial spin labelling (pCASL) in the detection of a postoperative residual lesion in adult brain tumours. METHODS: Seventy-five patients were prospectively included. Following the results of preoperative DSC-PWI assessment, intra-axial lesions, including high-grade gliomas (n = 43) and certain metastases (n = 14), were classified as hyper-vascular (HV+ group, n = 57); other lesions, including low-grade gliomas and certain metastases, were classified as non-hyper-vascular (HV- group, n = 18). To confirm the absence/presence of a residual lesion or disease progression, postoperative MRI including pCASL sequence and follow-up-MRI were performed within 72 h and 1-6 months after the resection, respectively. Two raters evaluated the images. Mean and maximal ASL cerebral blood flow (CBF) values were measured in the perioperative region and normalised to the contralateral tissue. The pCASL-CBF maps and post-contrast T1WI were visually assessed for residual lesion. Quantitative data were analysed with unpaired Student t and Mann-Whitney U tests and the visual diagnostic performance with the McNemar test. RESULTS: In the HV+ group, the mean normalised CBF was 1.97 ± 0.59 and 0.97 ± 0.29 (p < 0.0001, AUC = 0.964, cut-off = 1.27) for patients with or without residual tumours, respectively. The mean normalised CBF was not discriminative for assessing residual tumours in the HV- group (p = 0.454). Visual CBF evaluation allowed 92.98% patients belonging to the HV+ group to be correctly classified (sensitivity 93.02%, specificity 92.86%, p < 0.001). Visual evaluation was correlated with contrast enhancement evaluation and with the mean normalised CBF values (r = 0.505, p < 0.0001 and 0.838, p < 0.0001, respectively). CONCLUSION: Qualitative and quantitative ASL evaluation shows high diagnostic performance in postoperative assessment of hyper-perfused tumours. In this case, postoperative pCASL may be useful, especially if contrast injection cannot be performed or when contrast enhancement is doubtful. KEY POINTS: • Evaluation of postoperative residual lesion in the case of brain tumours is an imaging challenge. • This prospective monocentric study showed that increased normalised cerebral blood flow assessed by pseudo-continuous arterial spin labelling (pCASL) correlates well with the presence of a residual tumour in the case of hyper-vascular tumour diagnosed on preoperative MRI. • Qualitative and quantitative pCASL is an informative sequence for hyper-vascular residual tumour, especially if acquired more than 48 h after brain tumour surgery, when contrast enhancement can give ambiguous results due to blood-brain barrier disruption.

Specificities of arterial spin labeling (ASL) abnormalities in acute seizure.

PURPOSE: Arterial spin labeling (ASL) is a non-invasive tool measuring cerebral blood flow (CBF) and is useful to assess acute neurological deficit. While acute stroke presents as hypoperfused vascular territory, epileptic activity causes cortical hyperperfusion. Other neurological conditions exhibit hyperperfusion, like migraine or secondary "luxury perfusion" in strokes. Our objectives were to evaluate the usefulness and potential specificities of ASL in acute seizure and correlate it with electroencephalogram. MATERIALS AND METHODS: Amongst a cohort of patients with neurological deficit, addressed for suspicion of stroke, we retrospectively reviewed 25 consecutive patients with seizures who underwent magnetic resonance imaging (MRI) with ASL and electroencephalography (EEG). We compared them with a control group of patients with migraine and stroke secondary re-perfusion, exhibiting ASL hyperperfusion. RESULTS: Lateralized cortical hyperperfusion (high relative CBF) was observed in all patients. Good topographic correlation with EEG was found in 18 patients (72%). Eight (32%) had hyperperfusion of ipsilateral pulvinar, 5 (20%) had hyperperfused contralateral cerebellar hemisphere, 16 (64%) presented diffusion abnormalities and 20 (80%) had underlying epileptogenic lesions. Pulvinar hyperperfusion was not observed in the control group, nor were diffusion abnormalities in migrainous patients. Contralateral cerebellar hyperperfusion was observed in two migrainous patient, without associated pulvinar activation, whereas all patients with cerebellar hyperperfusion in the study group had associated pulvinar activation. CONCLUSIONS: Elevated CBF can be observed in the epileptogenic zone, ipsilateral pulvinar and contralateral cerebellum (diaschisis) in seizure. These abnormalities seem specific when compared with other causes of hyperperfusion. Arterial spin labeling can be highly effective in the differential diagnosis of strokes.

Brain MRI features and scoring of leukodystrophy in adult-onset Krabbe disease.

OBJECTIVE: To perform a systematic analysis and scoring of brain MRI white matter hyperintensities (WMH) in adult-onset Krabbe disease. METHODS: We retrospectively collected basic clinical data and the first available brain MRI from patients with confirmed Krabbe disease with first clinical manifestations beyond 10 years of age. Data were obtained from our reference center for lysosomal diseases (n = 6) and from contacted authors of published articles describing patients with adult-onset Krabbe disease (n = 15). T2-weighted fluid-attenuated inversion recovery images of each patient were analyzed and scored using a radiologic score of WMH in a single center. RESULTS: The corticospinal tract was always affected by WMH (100% of patients), however, with some distinctions along the tract: the precentral gyrus (100%), corona radiata (95%), and posterior internal capsule (81%) were highly abnormal, whereas the mesencephalon (57%), pons (52%), and medulla oblongata (5%) were less affected. WMH were also frequently present in the posterior lateral periventricular white matter (95%), optic radiations (86%), postcentral gyrus (71%), medial lemniscus (62%), and corpus callosum, especially in the isthmus (71%), whereas the genu was always normal. A few patients did not have the classical MRI pattern but extensive hyperintensities (n = 3), or patchy distribution of hyperintensities mimicking an acquired etiology (n = 2), or very subtle hyperintensities of the corticospinal tract (n = 1). CONCLUSIONS: We specified the main locations of WMH, which were observed in the earliest stages of the disease and were also present in patients with atypical MRI pattern, highlighting the importance of radiologic features to guide the diagnosis.

Bioactive glass granules for mastoid and epitympanic surgical obliteration: CT and MRI appearance.

PURPOSE: To evaluate the appearance of mastoid and epitympanic obliteration using S53P4 bioactive glass (BG) granules in high-resolution computed tomography (HRCT) and MRI. MATERIALS AND METHODS: Patients undergoing mastoid and epitympanic obliteration between May 2013 and December 2015 were prospectively included in an uncontrolled clinical study. All patients underwent a temporal HRCT scan 1 year after surgery, aimed at evaluating the attenuation, homogeneity, and osseointegration of the BG granules, as well as the ventilation of the middle ear and the volume of the obliterated paratympanic spaces. If a cholesteatoma was found during surgery, additional MRI, including at least pre- and post-contrast T1-weighted, T2-weighted, and axial non-echo-planar diffusion-weighted (DW) sequences, was performed 1 year after surgery, to study the normal signal of the BG granules and the presence of residual cholesteatoma and/or other temporal bone pathologies. RESULTS: Seventy cases were included. On 1-year HRCT, the mean attenuation of the BG granules was 888.34 ± 166.10 HU. The obliteration was found to be mostly homogeneous with partial osseointegration. The appearance of the BG granules having a low-intensity signal in T2-weighted imaging and DW MRI was always different from the appearance of cholesteatoma. A longer follow-up has shown no attenuation or signal modification of the BG granules compared with the 1-year imaging. CONCLUSION: Radiological follow-up of patients operated on with mastoid and epitympanic obliteration using BG granules is effective using both HRCT and MRI. A cholesteatoma and/or other potential complications could easily be detected due to the specific radiological appearance of the BG granules. KEY POINTS: • The appearance of mastoid and epitympanic obliteration by S53P4 bioactive glass (BG) granules on high-resolution computed tomography (HRCT) scans was homogeneous with an attenuation significantly higher than the attenuation of cholesteatoma and lower than mastoid bone attenuation. • The granules have a low-intensity signal on non-echo-planar diffusion-weighted sequences and on T2-weighted images and present contrast enhancement allowing the differential diagnosis with cholesteatoma and effective for the detection of other underlying temporal bone pathologies. • The volume and radiological appearance of the obliteration appear to be stable with time.

Safety and Feasibility of Repeated and Transient Blood-Brain Barrier Disruption by Pulsed Ultrasound in Patients with Recurrent Glioblastoma.

PURPOSE: The blood-brain barrier (BBB) limits the efficacy of drug therapies for glioblastoma (GBM). Preclinical data indicate that low-intensity pulsed ultrasound (LIPU) can transiently disrupt the BBB and increase intracerebral drug concentrations. PATIENTS AND METHODS: A first-in-man, single-arm, single-center trial (NCT02253212) was initiated to investigate the transient disruption of the BBB in patients with recurrent GBM. Patients were implanted with a 1-MHz, 11.5-mm diameter cranial ultrasound device (SonoCloud-1, CarThera). The device was activated monthly to transiently disrupt the BBB before intravenous carboplatin chemotherapy. RESULTS: Between 2014 and 2016, 21 patients were registered for the study and implanted with the SonoCloud-1; 19 patients received at least one sonication. In 65 ultrasound sessions, BBB disruption was visible on T1w MRI for 52 sonications. Treatment-related adverse events observed were transient and manageable: a transient edema at H1 and at D15. No carboplatin-related neurotoxicity was observed. Patients with no or poor BBB disruption (n = 8) visible on MRI had a median progression-free survival (PFS) of 2.73 months, and a median overall survival (OS) of 8.64 months. Patients with clear BBB disruption (n = 11) had a median PFS of 4.11 months, and a median OS of 12.94 months. CONCLUSIONS: SonoCloud-1 treatments were well tolerated and may increase the effectiveness of systemic drug therapies, such as carboplatin, in the brain without inducing neurotoxicity.See related commentary by Sonabend and Stupp, p. 3750.

Blood-brain barrier disruption in humans using an implantable ultrasound device: quantification with MR images and correlation with local acoustic pressure.

OBJECTIVE: One of the goals in this study was to set up a semiautomatic method to estimate blood-brain barrier disruption obtained in patients with glioblastoma by using an implantable, unfocused, ultrasound device. Another goal was to correlate the probability of significant ultrasound-induced signal enhancement (SUISE) with local acoustic pressure in the brain. METHODS: Gd-enhanced MR images acquired before and after ultrasound treatments were analyzed prospectively. The image sets were segmented, normalized, and coregistered to evaluate contrast enhancement. The volume of SUISE was calculated with voxels labeled as gray or white matter, in a cylindrical region of interest, and with enhancement above a given threshold. To validate the method, the resulting volumes of SUISE were compared to qualitative grades previously assigned by 3 clinicians for 40 ultrasound treatments in 15 patients. A parametric study was performed to optimize the algorithm prediction of the qualitative grades. The 3D acoustic field in the brain was estimated from measurements in water combined with simulations accounting for ultrasound attenuation in brain and overlaid on each MR image to correlate local acoustic pressure with the probability of SUISE (defined as enhancement > 10%). RESULTS: The algorithm predicted grade 2 or 3 and grade 3 openings with areas under the receiver operating characteristic curve of 0.831 and 0.995, respectively. The probability of SUISE was correlated with local acoustic pressure (R2 = 0.98) and was 3.33 times higher for gray matter than for white matter. CONCLUSIONS: An algorithm for evaluating blood-brain barrier disruption was validated and can be used for future clinical trials to further understand and quantify this technique in humans.Clinical trial registration no.: NCT02253212 (clinicaltrials.gov).

Neuronal injuries evidenced by transient cortical magnetic resonance enhancement in hemiplegic migraine: A case report.

BACKGROUND: Magnetic resonance imaging abnormalities in hemiplegic migraine have been described previously but were limited to a cortical thickening and biphasic alternation of hypoperfusion and hyperperfusion. Our report reveals possible blood-brain barrier disruption during migraine. CASE: We present the first demonstrated case of regressive diffuse hemispheric cortical enhancement in sporadic hemiplegic migraine, with histological correlation revealing neuronal lesions similar to ischemic lesions. This is probably due to the severity of the attack as indicated by the left hemiplegia and transient altered consciousness in our 43-year-old male patient. CONCLUSION: Cortical contrast enhancement on 3D T1 images may suggest migraine severity and be predictive of neuronal loss.

Muscular MRI-based algorithm to differentiate inherited myopathies presenting with spinal rigidity.

OBJECTIVES: Inherited myopathies are major causes of muscle atrophy and are often characterized by rigid spine syndrome, a clinical feature designating patients with early spinal contractures. We aim to present a decision algorithm based on muscular whole body magnetic resonance imaging (mWB-MRI) as a unique tool to orientate the diagnosis of each inherited myopathy long before the genetically confirmed diagnosis. METHODS: This multicentre retrospective study enrolled 79 patients from referral centres in France, Brazil and Chile. The patients underwent 1.5-T or 3-T mWB-MRI. The protocol comprised STIR and T1 sequences in axial and coronal planes, from head to toe. All images were analyzed manually by multiple raters. Fatty muscle replacement was evaluated on mWB-MRI using both the Mercuri scale and statistical comparison based on the percentage of affected muscle. RESULTS: Between February 2005 and December 2015, 76 patients with genetically confirmed inherited myopathy were included. They were affected by Pompe disease or harbored mutations in RYR1, Collagen VI, LMNA, SEPN1, LAMA2 and MYH7 genes. Each myopathy had a specific pattern of affected muscles recognizable on mWB-MRI. This allowed us to create a novel decision algorithm for patients with rigid spine syndrome by segregating these signs. This algorithm was validated by five external evaluators on a cohort of seven patients with a diagnostic accuracy of 94.3% compared with the genetic diagnosis. CONCLUSION: We provide a novel decision algorithm based on muscle fat replacement graded on mWB-MRI that allows diagnosis and differentiation of inherited myopathies presenting with spinal rigidity. KEY POINTS: • Inherited myopathies are rare, diagnosis is challenging and genetic tests require specialized centres and often take years. • Inherited myopathies are often characterized by spinal rigidity. • Whole body magnetic resonance imaging is a unique tool to orientate the diagnosis of each inherited myopathy presenting with spinal rigidity. • Each inherited myopathy in this study has a specific pattern of affected muscles that orientate diagnosis. • A novel MRI-based algorithm, usable by every radiologist, can help the early diagnosis of these myopathies.

Considerations on the Relevance of Cerebral Fusiform Aneurysms Observed During HIV Infection.

Human immunodeficiency virus (HIV)-associated ectatic cerebral vasculitis (HIV-AECV) is a rare form of vasculitis with diffuse fusiform aneurysms. Its pathophysiology remains poorly understood. Although extensively described in children, it is still incompletely studied in adults. Our objective was to present five adult cases with emphasis on imaging findings and long-term evolution. From 2006 to 2014, we included 5 HIV-infected patients presenting with fusiform cerebral aneurysms. Vessels abnormalities were assessed with brain computed tomography (CT) angiography, magnetic resonance angiography (MRA) and/or digital subtraction angiography (DSA). All patients had MR assessment of the brain. Clinical and biological data were analyzed. Fusiform aneurysms of carotid terminations extending to middle and anterior cerebral arteries were bilateral in three patients and unilateral in one. More distal fusiform aneurysms were observed in four patients and saccular aneurysms in two patients, two patients suffered from ischemic lesions while none experienced hemorrhage. Unlike recent reviews, our study underlines the low hemorrhagic potential of HIV-AECV and long-term follow-up suggests a monophasic evolution under antiretroviral medication.

First Depiction of Flow Voids to Differentiate Pituicytomas from Giant Adenomas.

Pituicytomas are rare low-grade glial lesions of neurohypophysis or adenohypophysis. They are often misdiagnosed as adenomas due to their similar morphology. Previous reports have underlined their nonspecific aspect. In our experience, presence of flow voids on magnetic resonance, which usually indicate hypervascularized tumors with strong arterial supply, may be a useful sign to identify pituicytomas. Unlike adenomas, pituicytomas are highly vascularized tumors. Second, we emphasize the strong enhancement of these tumors when compared with normal hypophysis, which may be another sign of their hypervascularization. Indeed, adenomas, on the opposite side, present less enhancement than normal hypophysis. This observation is corroborated by previous histologic studies that showed adenomas present less vascular density than normal pituitary glands. However, in large tumors, the normal hypophysis can sometimes not be individualized and thus the enhancement gradient between the tumor and normal tissue cannot be properly assessed. Due to their rarity, no previous reports had ever emphasized the specific signs that could allow us to differentiate pituicytomas from adenomas; however, it seems crucial due to the potential hemorrhagic complications of pituicytoma surgery.