Serial Magnetic Resonance Imaging Scans Research Articles

A randomised crossover trial of tezacaftor-ivacaftor for gut dysfunction in cystic fibrosis with magnetic resonance imaging (MRI) outcomes: a pilot study.

Background People with cystic fibrosis (CF) can experience recurrent chest infections, pancreatic exocrine insufficiency and gastrointestinal symptoms. New cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs improve lung function but gastrointestinal effects are unclear. We aimed to see if a CFTR modulator (tezacaftor-ivacaftor,TEZ/IVA) improves gastrointestinal outcomes in CF. Methods We conducted a randomised, double-blind, placebo-controlled, two-period crossover trial (2019-2020) at Nottingham University Hospitals. The effects of TEZ/IVA on gut physiology were measured using MRI. Participants were randomly assigned to treatment sequences AB or BA (A:TEZ/IVA, B:placebo, each 28 days), with a 28-day washout period. Participants had serial MRI scans at baseline and after 19-23 days of each treatment. Due to the COVID-19 pandemic, a protocol amendment allowed for observer-blind comparisons prior to and during TEZ/IVA. In such cases, participants were not blind to the treatment but researchers remained blind. The primary outcome was oro-caecal transit time (OCTT). Secondary outcomes included MRI metrics, symptoms and stool biomarkers. Results We randomised 13 participants. Before the COVID-19 pandemic 8 participants completed the full protocol and 1 dropped out. The remaining 4 participants followed the amended protocol. There were no significant differences between placebo and TEZ/IVA for OCTT (TEZ/IVA >360minutes [225,>360] vs. placebo 330minutes [285,>360], p=0.8) or secondary outcomes. There were no adverse events. Conclusions Our data contribute to a research gap in the extra-pulmonary effects of CFTR modulators. We found no effect after TEZ/IVA on MRI metrics of gut function, GI symptoms or stool calprotectin. Effects might be detectable with larger studies, longer treatment or more effective CFTR modulators. ClinicalTrials.gov registration NCT04006873 (02/07/2019)

Novel TLR7 hemizygous variant in post-COVID-19 neurological deterioration: a case report with literature review

The neurological complications of coronavirus disease 2019 (COVID-19) can range from simple tremors and dystonia to features of encephalopathy. Toll-like receptor 7 (TLR7) belongs to a family of innate immune receptors responsible for viral RNA detection (such as SARS-CoV-2) and immune response initiation. TLR7 loss of function variants have been previously reported as genetic risk factors for severe COVID-19 infection in young patients with no comorbidities. In this case, we report a pediatric patient who developed severe long-term neurological deterioration following his COVID-19 infection. Presenting first to the clinic with episodic dystonia and finger spasticity, the patient’s condition rapidly deteriorated with a significant drop in the Glasgow Coma Scale (GCS). Despite improvement following initial treatment with rituximab and intravenous immunoglobulin, the patient’s symptoms relapsed, and GCS further dropped to 3/15. Serial brain magnetic resonance imaging scans revealed diffuse parenchymal atrophy, ventricular enlargement, and spinal cord thickening. Autoimmune investigations were negative but clinical whole genome sequencing prioritized four gene variants, the most significant of which was a novel frameshift null variant of the X chromosomal TLR7 gene (c.1386_1389dup, p.[His464Ilefs*7]). This case illustrates a role for TLR7 in long-term COVID-19 complications and highlights that TLR7 deficiency in the future may be addressed as a therapeutic measure.

A randomised crossover trial of tezacaftor-ivacaftor for gut dysfunction in cystic fibrosis with magnetic resonance imaging (MRI) outcomes.

Background People with cystic fibrosis (CF) can experience recurrent chest infections, pancreatic exocrine insufficiency and gastrointestinal symptoms. New cystic fibrosis transmembrane conductance regulator (CFTR) modulator drugs improve lung function but gastrointestinal effects are unclear. We aimed to see if a CFTR modulator (tezacaftor-ivacaftor,TEZ/IVA) improves gastrointestinal outcomes in CF. Methods We conducted a randomised, double-blind, placebo-controlled, two-period crossover trial (2019-2020) at Nottingham University Hospitals. The effects of TEZ/IVA on gut physiology were measured using MRI. Participants were randomly assigned to treatment sequences AB or BA (A:TEZ/IVA, B:placebo, each 28 days), with a 28-day washout period. Participants had serial MRI scans at baseline and after 19-23 days of each treatment. Due to the COVID-19 pandemic, a protocol amendment allowed for observer-blind comparisons prior to and during TEZ/IVA. In such cases, participants were not blind to the treatment but researchers remained blind. The primary outcome was oro-caecal transit time (OCTT). Secondary outcomes included MRI metrics, symptoms and stool biomarkers. Results We randomised 13 participants. Before the COVID-19 pandemic 8 participants completed the full protocol and 1 dropped out. The remaining 4 participants followed the amended protocol. There were no significant differences between placebo and TEZ/IVA for OCTT (TEZ/IVA >360minutes [225,>360] vs. placebo 330minutes [285,>360], p=0.8) or secondary outcomes. There were no adverse events. Conclusions Our data contribute to a research gap in the extra-pulmonary effects of CFTR modulators. We found no effect after TEZ/IVA on MRI metrics of gut function, GI symptoms or stool calprotectin. Effects might be detectable with larger studies, longer treatment or more effective CFTR modulators. ClinicalTrials.gov registration NCT04006873 (02/07/2019)

Longitudinal trajectories of basal forebrain volume in normal aging and Alzheimer’s disease

Dysfunction of the cholinergic basal forebrain (BF) system and amyloid-β (Aβ) deposition are early pathological features in Alzheimer’s disease (AD). However, their association in early AD is not well-established. This study investigated the nature and magnitude of volume loss in the BF, over an extended period, in 516 older adults who completed Aβ-PET and serial magnetic resonance imaging scans. Individuals were grouped at baseline according to the presence of cognitive impairment (CU, CI) and Aβ status (Aβ−, Aβ+). Longitudinal volumetric changes in the BF and hippocampus were assessed across groups. The results indicated that high Aβ levels correlated with faster volume loss in the BF and hippocampus, and the effect of Aβ varied within BF subregions. Compared to CU Aβ+ individuals, Aβ-related loss among CI Aβ+ adults was much greater in the predominantly cholinergic subregion of Ch4p, whereas no difference was observed for the Ch1/Ch2 region. The findings support early and substantial vulnerability of the BF and further reveal distinctive degeneration of BF subregions during early AD.

Characterization of Brain Volume Changes in Aging Individuals With Normal Cognition Using Serial Magnetic Resonance Imaging

Characterizing longitudinal patterns of regional brain volume changes in a population with normal cognition at the individual level could improve understanding of the brain aging process and may aid in the prevention of age-related neurodegenerative diseases. To investigate age-related trajectories of the volumes and volume change rates of brain structures in participants without dementia. This cohort study was conducted from November 1, 2006, to April 30, 2021, at a single academic health-checkup center among 653 individuals who participated in a health screening program with more than 10 years of serial visits. Serial magnetic resonance imaging, Mini-Mental State Examination, health checkup. Volumes and volume change rates across brain tissue types and regions. The study sample included 653 healthy control individuals (mean [SD] age at baseline, 55.1 [9.3] years; median age, 55 years [IQR, 47-62 years]; 447 men [69%]), who were followed up annually for up to 15 years (mean [SD], 11.5 [1.8] years; mean [SD] number of scans, 12.1 [1.9]; total visits, 7915). Each brain structure showed characteristic age-dependent volume and atrophy change rates. In particular, the cortical gray matter showed a consistent pattern of volume loss in each brain lobe with aging. The white matter showed an age-related decrease in volume and an accelerated atrophy rate (regression coefficient, -0.016 [95% CI, -0.012 to -0.011]; P < .001). An accelerated age-related volume increase in the cerebrospinal fluid-filled spaces, particularly in the inferior lateral ventricle and the Sylvian fissure, was also observed (ventricle regression coefficient, 0.042 [95% CI, 0.037-0.047]; P < .001; sulcus regression coefficient, 0.021 [95% CI, 0.018-0.023]; P < .001). The temporal lobe atrophy rate accelerated from approximately 70 years of age, preceded by acceleration of atrophy in the hippocampus and amygdala. In this cohort study of adults without dementia, age-dependent brain structure volumes and volume change rates in various brain structures were characterized using serial magnetic resonance imaging scans. These findings clarified the normal distributions in the aging brain, which are essential for understanding the process of age-related neurodegenerative diseases.

Effects of anesthesia exposure on postnatal maturation of white matter in rhesus monkeys.

There is increasing concern about the potential effects of anesthesia exposure on the developing brain. The effects of relatively brief anesthesia exposures used repeatedly to acquire serial magnetic resonance imaging scans could be examined prospectively in rhesus macaques. We analyzed magnetic resonance diffusion tensor imaging (DTI) of 32 rhesus macaques (14 females, 18 males) aged 2weeks to 36 months to assess postnatal white matter (WM) maturation. We investigated the longitudinal relationships between each DTI property and anesthesia exposure, taking age, sex, and weight of the monkeys into consideration. Quantification of anesthesia exposure was normalized to account for variation in exposures. Segmented linear regression with two knots provided the best model for quantifying WM DTI properties across brain development as well as the summative effect of anesthesia exposure. The resulting model revealed statistically significant age and anesthesia effects in most WM tracts. Our analysis indicated there were major effects on WM associated with low levels of anesthesia even when repeated as few as three times. Fractional anisotropy values were reduced across several WM tracts in the brain, indicating that anesthesia exposure may delay WM maturation, and highlight the potential clinical concerns with even a few exposures in young children.

Persistence of Human Immunodeficiency Virus-Associated Cerebral Toxoplasmosis Lesions in Successfully Treated Patients Receiving Combination Antiretroviral Therapy.

Toxoplasmic encephalitis (TE) is a life-threatening complication of people with human immunodeficiency virus (PWH) with severe immunodeficiency, especially those with a CD4+ T-cell count <100 cells/µL. Following a clinical response to anti-Toxoplasma therapy, and immune reconstitution after initiation of combination antiretroviral therapy (ART), anti-Toxoplasma therapy can be discontinued with a low risk of relapse. To better understand the evolution of magnetic resonance imaging (MRI)-defined TE lesions in PWH receiving ART, we undertook a retrospective study of PWH initially seen at the National Institutes of Health between 2001 and 2012, who had at least 2 serial MRI scans. Lesion size and change over time were calculated and correlated with clinical parameters. Among 24 PWH with TE and serial MRI scans, only 4 had complete clearance of lesions at the last MRI (follow-up, 0.09-5.8 years). Of 10 PWH off all anti-Toxoplasma therapy (median, 3.2 years after TE diagnosis), 6 had persistent MRI enhancement. In contrast, all 5 PWH seen in a pre-ART era study who were followed for >6 months had complete clearance of lesions. TE lesion area at diagnosis was associated with the absolute change in area (P < .0001). Contrast enhancement can persist even when TE has been successfully treated and anti-Toxoplasma therapy has been stopped, highlighting the need to consider diagnostic alternatives in successfully treated patients with immune reconstitution presenting with new neurologic symptoms.

Comparing Linear and Volumetric Tumor Measurements During Observation of Growing Sporadic Vestibular Schwannomas.

To assess the correlation between linear and volumetric changes in vestibular schwannomas (VS). Retrospective imaging review was performed on patients diagnosed with sporadic VS from 2000 to 2019 who demonstrated linear growth on observation with serial magnetic resonance imaging (MRI). Two large tertiary care centers. Changes in diameter on serial MRI scans, measured by 1995 American Academy of Otolaryngology-Head and Neck Surgeryguidelines, were compared to changes in volume, calculated by segmentation. Ninety-two patients had VS confined to the internal auditory canal (IAC) with 236 MRIs analyzed, and 108 patients had VS involving the cerebellopontine angle (CPA) with 193 MRIs analyzed. The Spearman rank correlation coefficients between changes in diameter and volume for IAC and CPA tumors were 0.43 (p < .001) and 0.65 (p < .001), respectively. Linear diameter increases of 1 to <2 mm corresponded to a median volume change of 32% (interquartile range [IQR]: 6%-86%) for IAC tumors, compared to 23% (IQR: 13%-40%) for CPA tumors. Linear diameter increases of 2 to <3 mm (ie, the minimum linear diameter change classically considered "true growth") corresponded to a median volume change of 42% (IQR: 23%-100%) and 47% (IQR: 26%-69%) for IAC and CPA tumors, respectively. Changes in linear diameter significantly correlated with changes in volume for IAC and CPA tumors, although diameter changes that did not meet the definition of linear growth (<2 mm) had corresponding median volume changes in excess of 20% for both IAC and CPA tumors.

Radiologic Characteristics of Spinal Hemangioblastomas in von Hippel Lindau Disease as Guidance in Clinical Interventions

Hemangioblastomas in the central nervous system are the most common manifestation of von Hippel-Lindau (VHL) disease. Because the growth rate of hemangioblastomas is unpredictable, regular follow-up is mandatory, focusing on clinical symptoms and imaging of the central nervous system. However, clinical symptoms may be subtle and nonspecific, and data about the relationship between the radiologic findings and clinical symptoms are sparse. This study aims to evaluate if and how findings of magnetic resonance imaging (MRI) regarding spinal hemangioblastomas are associated with symptoms of VHL disease, with special attention to peritumoral edema and spinal cysts. Serial spinal MRI scans of 43 genetically or clinically established VHL patients with at least 2 years of follow-up were reevaluated to examine the volume, growth rate, and location of spinal hemangioblastomas and the presence, size, and growth rate of peritumoral edema and cysts. Findings were compared with clinical symptoms using the Fisher exact test. We observed a total of 77 spinal hemangioblastomas in 28 patients. Eight of the 28 patients showed peritumoral edema and spinal cysts, and 1 patient showed peritumoral edema without cyst formation; 6 of these 9 patients showed clinical symptoms. Both peritumoral edema and spinal cysts were associated with clinical symptoms (P= 0.023 and P= 0.011, respectively). The presence of peritumoral edema and/or spinal cysts shown on MRI in VHL patients with spinal hemangioblastomas is associated with symptoms in more than half of the patients and may alert the clinician to intensify clinical and radiologic surveillance.

Chronological Progression and Management of Syringobulbia Caused by Spinal Hemangioblastoma: A Case Series and Review of the Literature

Syringomyelia often accompanies spinal hemangioblastoma (SHB). It often shows progression to the medulla oblongata, dubbed as "syringobulbia", which presents critical symptoms such as dysphagia and respiratory compromise. Appropriate management of chronological syringomyelia progression toward syringobulbia is not set in stone. This study aims to unravel the clinical and chronological behavior of syringobulbia and its management. A single-institution case series study of 5 patients operated for SHB with syringobulbia was conducted. Serial preoperative magnetic resonance imaging scans were analyzed in further details, especially focusing on the chronological progression of syringomyelia. A literature review was performed to describe clinical/imaging characteristics. Chronological imaging analyses revealed that despite the relatively steady progression of syringomyelia over years, it accelerated when developing syringobulbia. Intramedullary signal change ("presyringomyelia") was observed in the area where syringomyeliasubsequently occurred. Literature review yielded another 15 cases of SHB with syringobulbia, totaling 20 cases. Bulbar dysfunction was seen in 4 cases (20%). Gross total resection was performed in all cases except 1, which underwent just syringotomy. Rapid postoperativesymptom improvement was observed in all cases, as well as immediate imaging resolution of syringomyelia. The symptoms associated with syringobulbia often become life-threatening. Notably, its resolution may be near-synchronous to surgical resection of the spinal lesion. The speed of progression of syringomyelia is usually steady, but it may accelerate when extending to syringobulbia. Regular imaging follow-up is thus highly recommended to determine the best timing of intervention when presyringomyelia and syringomyelia are ascending toward the medulla oblongata.

IgG kappa multiple myeloma with isolated central nervous system relapse.

A 76-year-old male presented with acute renal failure and cast nephropathy was diagnosed with IgG kappa multiple myeloma (MM). His paraprotein was 40 g/L, kappa-free light chain level was 17,058 mg/L, kappa: lambda light chain ratio was 1445. An automated full blood count showed hemoglobin 90 g/L, white blood cells 2.96 × 109/L, neutrophil 1.7 × 109/L, and platelet 179 × 109/L. Bone marrow trephine sample was hypercellular with nearly 100% plasma cells, which were positive for CD138, CD56, and cyclin D1, and showed kappa light chain restriction. Fluorescence in situ hybridization analysis with dual color/dual probes for immunoglobulin heavy chain (IGH) and MYC genes (Cytocell) and whole genome screening using 8 × 60K oligonucleotide arrays (Agilent) performed on the CD138 enriched cells (CD138 microbeads Miltenyi Biotech) from the liquid bone marrow sample showed no evidence of IGH rearrangement, MYC rearrangement, 1q gain, 1p loss, 17p loss, or any clinically significant imbalance. He was treated with eight cycles of bortezomib, cyclophosphamide, and dexamethasone (VCD) to very good partial response. He relapsed 30 months after diagnosis with paraprotein of 36 g/L, kappa light chains of 10,000 mg/L, and creatinine of 498 μmol/L. He was treated with eight cycles of bortezomib, thalidomide, and dexamethasone (VTD) to paraprotein undetectable and kappa light chain 29 mg/L. Seven months post completion of VTD (4 years after myeloma diagnosis), he presented with abnormal gait, falls, and a left-sided facial droop. His paraprotein was 2 g/L and serum-free kappa light chain was 81 mg/L. Magnetic resonance imaging (MRI) head and whole spine showed multifocal diseases in spinal canal and intracranially, involving the cranial nerves most prominent the fifth, seventh, eighth, and hypoglossal nerve on the left, anterior surface of the inferior pons medulla (Figure 1A). There were multiple lesions in the cervical spine as well as in the thoracic spine (Figure 1B). Computerized tomography (CT) chest abdomen pelvis did not show the evidence of other new diseases. Plasma cells were detected in cerebral spinal fluid (CSF) (Figure 1C, May–Grünwald–Giemsa stain x100 objective). He was treated with pomalidomide and dexamethasone. Weekly cytarabine intrathecal (IT) treatment was given until the clearance of plasma cells from CSF samples for three times. Four months later, he achieved the complete remission on MRI head and whole spine with undetectable paraprotein and normal light chain ratio. Serial MRI scans confirmed ongoing remission. A year later, he relapsed again with worsening mobility and reappearance of myeloma cells in CSF. By flow cytometry, these cells were positive for CD138, CD38, CD56, CD117, and negative for CD19. MRI head showed leptomeningeal disease with a new 2.2 cm frontal lobe lesion. His paraprotein remained undetectable and kappa light chain remained at below 100 mg/L. He continued systemic pomalidomide and dexamethasone chemotherapy and received palliative whole brain radiotherapy 20 Gy in 5 fractions for symptom control. His disease continued progressing and he passed away 3 months later (5.5 years after myeloma diagnosis). Here, we reported a myeloma patient with isolated CNS relapse, who achieved 1 year of remission with combination of intrathecal chemotherapy and systemic pomalidomide and dexamethasone treatment, but sadly passed away 4 months after second CNS relapse. CNS MM is a rare form of extramedullary disease, but carries a very poor prognosis. The optimal approach to treatment of CNS MM is not currently known. The current approach includes systemic therapy with agents known to cross the blood brain barrier, intrathecal therapy, and CNS irradiation. Innovative approach to treatment is urgently needed. The authors received no specific funding for this work. Ke Xu and Lucy Kamuriwo wrote the manuscript. Ke Xu, Lucy Kamuriwo, Claire Anderson and Parag Jasani critically revised the final version of the manuscript. The authors declare they have no conflicts of interest. No written or verbal consent obtained from patient. Patient has passed away.

Determinants and Temporal Dynamics of Cerebral Small Vessel Disease: 14-Year Follow-Up

Background:The aim of this study is to investigate the temporal dynamics of small vessel disease (SVD) and the effect of vascular risk factors and baseline SVD burden on progression of SVD with 4 neuroimaging assessments over 14 years in patients with SVD.Methods:Five hundred three patients with sporadic SVD (50–85 years) from the ongoing prospective cohort study (RUN DMC [Radboud University Nijmegen Diffusion Tensor and Magnetic Resonance Cohort]) underwent baseline assessment in 2006 and follow-up in 2011, 2015, and 2020. Vascular risk factors and magnetic resonance imaging markers of SVD were evaluated. Linear mixed-effects model and negative binomial regression model were used to examine the determinants of temporal dynamics of SVD markers.Results:A total of 382 SVD patients (mean [SD] 64.1 [8.4]; 219 men and 163 women) who underwent at least 2 serial brain magnetic resonance imaging scans were included, with mean (SD) follow-up of 11.15 (3.32) years. We found a highly variable temporal course of SVD. Mean (SD) WMH progression rate was 0.6 (0.74) mL/y (range, 0.02–4.73 mL/y) and 13.6% of patients had incident lacunes (1.03%/y) over the 14-year follow-up. About 4% showed net WMH regression over 14 years, whereas 38 out of 361 (10.5%), 5 out of 296 (2%), and 61 out of 231 (26%) patients showed WMH regression for the intervals 2006 to 2011, 2011 to 2015, and 2015 to 2020, respectively. Of these, 29 (76%), 5 (100%), and 57 (93%) showed overall progression across the 14-year follow-up, and the net overall WMH change between first and last scan considering all participants was a net average WMH progression over the 14-year period. Older age was a strong predictor for faster WMH progression and incident lacunes. Patients with mild baseline WMH rarely progressed to severe WMH. In addition, both baseline burden of SVD lesions and vascular risk factors independently and synergistically predicted WMH progression, whereas only baseline SVD burden predicted incident lacunes over the 14-year follow-up.Conclusions:SVD shows pronounced progression over time, but mild WMH rarely progresses to clinically severe WMH. WMH regression is noteworthy during some magnetic resonance imaging intervals, although it could be overall compensated by progression over the long follow-up.

Longitudinal Tau Positron Emission Tomography in Dementia with Lewy Bodies.

ABSTRACTBackground and ObjectivePatients with dementia with Lewy bodies (DLB) may have overlapping Alzheimer's disease pathology. We investigated the longitudinal rate of tau accumulation and its association with neurodegeneration and clinical disease progression in DLB.MethodsConsecutive patients with probable DLB (n = 22) from the Mayo Clinic Alzheimer's Disease Research Center and age‐matched and sex‐matched cognitively unimpaired controls (CU; n = 22) with serial magnetic resonance imaging and flortaucipir positron emission tomography scans within an average of 1.6 years were included. Regional annualized rates of flortaucipir uptake standardized uptake value ratios (SUVr) were calculated. Regional annualized rates of cortical volume change were measured with the Tensor Based Morphometry–Syn algorithm.ResultsThe annual increase of flortaucipir SUVr was greater in the middle and superior occipital, fusiform, and inferior parietal cortices in DLB (mean: 0.017, 0.019, 0.019, and 0.015, respectively) compared with the CU (mean: −0.006, −0.009, −0.003, and − 0.005, respectively; P < 0.05). In patients with DLB (but not the CU), a longitudinal increase in flortaucipir SUVr was associated with longitudinal cortical atrophy rates in the lateral occipital and inferior temporoparietal cortices, hippocampus, and the temporal pole as well as a concurrent decline on Mini‐Mental State Examination and Clinical Dementia Rating–Sum of Boxes in the lateral occipital and the fusiform cortices.ConclusionsTau accumulation was faster in DLB compared with the CU, with increased accumulation rates in the lateral occipital and temporoparietal cortices. These increased rates of tau accumulation were associated with neurodegeneration and faster disease progression in DLB. Tau may be a potential treatment target in a subset of patients with DLB. © 2022 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society

Stability of Two Cross-Linked Hyaluronic Acid Gels for the Treatment of Temporal Fossa Volume Loss: A Preliminary Study Using MRI and Visual Observations

Introduction: Hyaluronic Acid (HA) gels are a commonly used option for correcting facial volume loss. Over the past 2 years, we have been testing the clinical results of two HA gels, without lidocaine, made by the same manufacturer using the patented “Inter- Penetrating NetworkLike” (IPN-Like) cross-linking technology. The aim of this work was to evaluate if there is a difference in the tissue stability and associated clinical outcomes between these two gels. Material and methods: A 67 and 75 years old Caucasian women, from our private aesthetic center, agreed to be injected with the different HA volumiser gel, one in each of their temporal fossae. The Stylage® XL and XXL HA gels (LABORATOIRES VIVACY, Archamps, France) were used for this study. The gels have different concentrations and levels of cross-linking, but have the same indications for correcting facial volume loss resulting from the ageing process. Clinical outcomes included assessing the degree of pain experienced by participants during and after injection using a Visual Analog Scale (VAS). Aesthetic improvement was evaluated using the Merz Analogic Scale® (MAS)® and Global Aesthetic Improvement Scale (GAIS) scales completed by patients and independent experts at different pre-set time-points using photographs taken from the front, profile and three-quarter left and right angles. Moreover, Serial magnetic Resonance Imaging (MRI) scans were used to assess the tissue behavior of the gels immediately after injection and then 6 monthly for 2 years. Results: Both gels led to an improvement in the patients’ clinical outcomes. This improvement persisted over time. The MRI scans showed that, at Day 0, the injected gel was spherical in shape and became elongated by 6 months. This appearance did not change throughout the follow-up period. The scans showed little resorption at 24 months. Conclusion: Despite the relatively advanced age of the two patients and the small quantities of gel injected, the IPN-Like cross-linked hyaluronic acid volumiser gels had a satisfactory sustainable clinical effect as assessed by patients and experts. There was a slight advantage in favor of the gel with the lower HA concentration but higher level of cross-linking (Stylage® XXL). Given the observed persistent effect of the gels in our preliminary observation, it is now important to conduct a larger study with longer follow- up.

Association of Metformin With Volumetric Tumor Growth of Sporadic Vestibular Schwannomas.

Recent research demonstrates a potential association between metformin use and reduced sporadic vestibular schwannoma (VS) growth in patients undergoing conservative observation. The current study was designed to elucidate the effect of metformin on tumor growth in sporadic VS using volumetric analyses. Retrospective cohort. Tertiary referral center. Patients with sporadic VS who elected initial conservative treatment with at least two serial magnetic resonance imaging (MRI) scans were included. Metformin use among patients with observed sporadic VS. Tumor growth, defined as an increase in volume of at least 20% from the initial MRI. A total of 361 patients were evaluated. Thirty-four patients (9%) had a diagnosis of diabetes at baseline. Nineteen patients (5%) were taking metformin at the time of the initial MRI. Metformin use was not significantly associated with a reduced risk of volumetric tumor growth in a univariable analysis in all patients undergoing observation for VS (hazard ratio [HR] 0.75; 95% confidence intervals [CI] 0.40-1.42; p = 0.38) or within the diabetic subset (HR 0.79; 95% CI 0.34-1.83; p = 0.58). Additionally, diabetes status, insulin dependence, hemoglobin A1c value, and metformin dose were not significantly associated with volumetric tumor growth. Despite promising initial results in several previous studies, our data suggest that metformin use does not significantly reduce the risk of volumetric tumor growth in sporadic VS.

Silent New Brain MRI Lesions in Children with MOG-Antibody Associated Disease.

Anti-myelin oligodendrocyte glycoprotein immunoglobulin G (MOG-IgG) antibodies are associated clinically with either a monophasic or relapsing disease course. We investigated the frequency and clinical importance of acquired asymptomatic brain magnetic resonance imaging (MRI) lesions in a prospective incident cohort of 74 MOG-IgG positive children with serial MRI scans over a median of 5 years from presentation. Silent new lesions were detected in 14% of MOG-IgG positive participants, most commonly within the first months post-onset, with a positive predictive value for clinically relapsing disease of only 20%. Detection of asymptomatic lesions alone need not prompt initiation of chronic immunotherapy. ANN NEUROL 2021;89:408-413.

Investigating the Chronology of Meniscus Root Tears: Do Medial Meniscus Posterior Root Tears Cause Extrusion or the Other Way Around?

Background:Meniscus root tears are increasingly being recognized. Meniscal extrusion has previously been associated with medial root tears; however, the relationship between secondary meniscal restraints, such as the meniscotibial (MT) ligament, extrusion, and root tears has yet to be formally evaluated.Purpose:To better understand the association between MT ligament competence, medial meniscal extrusion, and medial meniscus posterior root tears (MMPRTs) as well as to determine the progression of meniscal extrusion over time.Study Design:Case series; Level of evidence, 4.Methods:Serial magnetic resonance imaging (MRI) scans were reviewed for patients who showed evidence of medial meniscal extrusion and MMPRTs on at least 1 of ≥2 available MRI scans. All patients were symptomatic at the time of diagnosis. All MRI scans were analyzed independently by 2 board-certified musculoskeletal radiologists. MT ligament disruption, medial meniscal extrusion, and MMPRTs were recorded for each MRI scan. The time between MRI scans, presence of insufficiency fractures, and Outerbridge classification for the medial femur and tibia were also evaluated.Results:Overall, 27 knees in 26 patients were included in this study, with a total of 63 MRI scans analyzed (21 knees with 2 MRI scans, 3 with 3 MRI scans, and 3 with 4 MRI scans). All patients demonstrated clear medial meniscal extrusion and MT ligament disruption before the subsequent development of MMPRTs (P < .001). Mean extrusion at the time of initial MRI was 3.3 ± 1.1 mm and increased significantly to 5.5 ± 1.8 mm at the time of first imaging with an identified MMPRT (P < .001). The mean time between initial MRI and the first identification of an MMPRT on later MRI was 1.7 ± 1.6 years.Conclusion:In a sample of 27 symptomatic knees with serial MRI scans both before and after an MMPRT diagnosis, all patients demonstrated MT ligament disruption and associated meniscal extrusion before the development of subsequent medial meniscus root tears. These findings suggest that MT ligament disruption and medial meniscal extrusion represent early and predisposing events contributing to MMPRTs. Therefore, this provides a possible explanation of why meniscal extrusion is not corrected with medial meniscus root repair.

Spectrum of neuroimaging findings post-proton beam therapy in a large pediatric cohort.

Proton beam therapy (PBT) is now well established for the treatment of certain pediatric brain tumors. The intrinsic properties of PBT are known to reduce long-term negative effects of photon radiotherapy (PRT). To better understand the intracranial effects of PBT, we analyzed the longitudinal imaging changes in a cohort of children with brain tumors treated by PBT with clinical and radiotherapy dose correlations. Retrospective imaging review of 46 patients from our hospital with brain tumors treated by PBT. The imaging findings were correlated with clinical and dose parameters. Imaging changes were assessed by reviewing serial magnetic resonance imaging (MRI) scans following PBT over a follow-up period ranging from 1 month to 7 years. Imaging changes were observed in 23 patients undergoing PBT and categorized as pseudoprogression (10 patients, 43%), white matter changes (6 patients, 23%), parenchymal atrophy (6 patients, 23%), and cerebral large vessel arteriopathy (5 patients, 25%). Three patients had more than one type of imaging change. Clinical symptoms attributable to PBT were observed in 13 (28%) patients. In accordance with published literature, we found evidence of varied intracranial imaging changes in pediatric brain tumor patients treated with PBT. There was a higher incidence (10%) of large vessel cerebral arteriopathy in our cohort than previously described in the literature. Twenty-eight percent of patients had clinical sequelae as a result of these changes, particularly in the large vessel arteriopathy subgroup, arguing the need for angiographic and perfusion surveillance to pre-empt any morbidities and offer potential neuro-protection.

Extrusions do not affect degenerative morphologic changes in lateral meniscus allografts during midterm follow-ups.

To investigate degenerative morphological changes in meniscus allograft after lateral meniscus allograft transplantation (MAT) based on extrusions. Ninety-one patients who underwent lateral MAT were divided into extruded and non-extruded groups. Serial magnetic resonance imaging scans obtained 6weeks, 1year, and at the last follow-up (midterm, 3-7years) post-surgery were evaluated retrospectively. Degenerative morphological changes at each time point in each group were compared using the postoperative meniscal width, thickness, and intrameniscal signal intensity (IMSI) at the anterior horn, mid-body, and posterior horn. The Lysholm scores and meniscal tears based on graft extrusion were also investigated. The mean age was 33.7 ± 11.1years (64 men and 27 women). Fifty-three (58%) and 38 knees (42%) were classified into the non-extruded and extruded groups, respectively. The overall meniscal width of the mid-body decreased from 9.6 ± 1.3 to 6.5 ± 1.2mm (p < 0.01), and IMSI of mid-body was increased from 1.2 ± 0.1 to 1.7 ± 0.1 (p < 0.01) during midterm follow-ups. No significant differences were observed between the meniscal width, thickness, and IMSI at the anterior horn (n.s.), mid-body (n.s.), and posterior horn (n.s.) of the two groups during the midterm follow-ups. The incidence of meniscus tears and Lysholm scores did not differ significantly between the groups during midterm follow-ups. The overall meniscus width of mid-body decreased while the relative IMSI of mid-body increased during midterm follow-ups after lateral MAT. Meniscal allograft extrusions did not influence postoperative changes in meniscus width, thickness, and relative intrameniscal signal intensity. Level III.

Magnetic Resonance Imaging Study of the Pericranial Flap and Its Local Effects Following Endoscopic Craniofacial Resection.

To describe the magnetic resonance imaging (MRI) characteristics of the pericranial flap, changes in the pericranial flap thickness over time, presence of frontal sinus opacification, and presence of frontal lobe herniation into the nasal cavity. Retrospective case series. Seventeen consecutive endoscopic craniofacial resections with pericranial flap reconstruction performed at a tertiary hospital from 2010 to 2019 were reviewed. Sixty-eight serial MRI scans were evaluated. All pericranial flaps consistently featured a homogenous appearance on T1-weighted sequence and enhanced with contrast. On T2-weighted sequence, the skull base reconstruction demonstrated four layers of alternating hypo- and hyperintensity, which corresponded with the inlay synthetic graft or neodura (hypointense), loose areolar tissue (hyperintense), fibrous pericranium (hypointense), and nasal mucosa or granulation tissue (hyperintense). The mean pericranial flap thickness was 9.9 mm. In thicker flaps, the loose areolar layer contributed the bulk of the thickness. Of 13 patients who underwent three or more serial MRI scans, 11 flaps (84.6%) were stable and two (15.4%) had >50% reduction in their original thickness over time. Thirteen of 17 (76.5%) patients had frontal sinus opacification on follow-up. None developed frontal sinus mucoceles or frontal lobe herniation. The pericranial flap has a distinctive MRI appearance, especially on T2-weighted sequence. The thickness of the flap remains relatively stable over time for most patients even following radiotherapy. It is a sturdy flap that is able to support the frontal lobe. Frontal sinus obstruction is common, although complications from this appear to be rare. 4 Laryngoscope, 131:E90-E97, 2021.