Time is myelin: early cortical myelin repair prevents atrophy and clinical progression in multiple sclerosis.

Cortical myelin loss and repair in multiple sclerosis (MS) have been explored in neuropathological studies, but the impact of these processes on neurodegeneration and the irreversible clinical progression of the disease remains unknown. Here, we evaluated in vivo cortical demyelination and remyelination in a large cohort of people with all clinical phenotypes of MS followed up for 5 years using magnetization transfer imaging (MTI), a technique that has been shown to be sensitive to myelin content changes in the cortex. We investigated 140 people with MS (37 clinically isolated syndrome, 71 relapsing-MS, 32 progressive-MS), who were clinically assessed at baseline and after 5 years and, along with 84 healthy controls, underwent a 3 T-MRI protocol including MTI at baseline and after 1 year. Changes in cortical volume over the radiological follow-up were computed with a Jacobian integration method. Magnetization transfer ratio was employed to calculate for each patient an index of cortical demyelination at baseline and of dynamic cortical demyelination and remyelination over the follow-up period. The three indices of cortical myelin content change were heterogeneous across patients but did not significantly differ across clinical phenotypes or treatment groups. Cortical remyelination, which tended to fail in the regions closer to CSF (-11%, P < 0.001), was extensive in half of the cohort and occurred independently of age, disease duration and clinical phenotype. Higher indices of cortical dynamic demyelination (ß = 0.23, P = 0.024) and lower indices of cortical remyelination (ß = -0.18, P = 0.03) were significantly associated with greater cortical atrophy after 1 year, independently of age and MS phenotype. While the extent of cortical demyelination predicted a higher probability of clinical progression after 5 years in the entire cohort [odds ratio (OR) = 1.2; P = 0.043], the impact of cortical remyelination in reducing the risk of accumulating clinical disability after 5 years was significant only in the subgroup of patients with shorter disease duration and limited extent of demyelination in cortical regions (OR = 0.86, P = 0.015, area under the curve = 0.93). In this subgroup, a 30% increase in cortical remyelination nearly halved the risk of clinical progression at 5 years, independently of clinical relapses. Overall, our results highlight the critical role of cortical myelin dynamics in the cascade of events leading to neurodegeneration and to the subsequent accumulation of irreversible disability in MS. Our findings suggest that early-stage myelin repair compensating for cortical myelin loss has the potential to prevent neuro-axonal loss and its long-term irreversible clinical consequences in people with MS.

Positron Emission Tomography with [18 F]-DPA-714 Unveils a Smoldering Component in Most Multiple Sclerosis Lesions which Drives Disease Progression.

OBJECTIVE: To determine the prognostic value of persisting neuroinflammation in multiple sclerosis (MS) lesions, we developed a 18 kDa-translocator-protein-positron emission tomography (PET) -based classification of each lesion according to innate immune cell content and localization. We assessed the respective predictive value of lesion phenotype and diffuse inflammation on atrophy and disability progression over 2 years. METHODS: Thirty-six people with MS (disease duration 9 ± 6 years; 12 with relapsing-remitting, 13 with secondary-progressive, and 11 with primary-progressive) and 19 healthy controls (HCs) underwent a dynamic [18 F]-DPA-714-PET. At baseline and after 2 years, the patients also underwent a magnetic resonance imaging (MRI) and neurological examination. Based on a threshold of significant inflammation defined by a comparison of [18 F]-DPA-714 binding between patients with MS and HCs, white matter lesions were classified as homogeneously active (active center), rim-active (inactive center and active periphery), or nonactive. Longitudinal cortical atrophy was measured using Jacobian integration. RESULTS: Patients with MS had higher innate inflammation in normal-appearing white matter (NAWM) and cortex than HCs (respective standardized effect size = 1.15, 0.89, p = 0.003 and < 0.001). Out of 1,335 non-gadolinium-enhancing lesions, 53% were classified as homogeneously-active (median = 17 per patient with MS), 6% rim-active (median = 1 per patient with MS), and 41% non-active (median = 14 per patient with MS). The number of homogenously-active lesions was the strongest predictor of longitudinal changes, associating with cortical atrophy (ß = 0.49, p = 0.023) and Expanded Disability Status Scale (EDSS) changes (ß = 0.35, p = 0.023) over 2 years. NAWM and cortical binding were not associated to volumetric and clinical changes. INTERPRETATION: The [18 F]-DPA-714-PET revealed that an unexpectedly high proportion of MS lesions have a smoldering component, which predicts atrophy and clinical progression. This suggests that following the acute phase, most lesions develop a chronic inflammatory component, promoting neurodegeneration and clinical progression. ANN NEUROL 2023;94:366-383.

Periventricular remyelination failure in multiple sclerosis: a substrate for neurodegeneration.

In multiple sclerosis, spontaneous remyelination is generally incomplete and heterogeneous across patients. A high heterogeneity in remyelination may also exist across lesions within the same individual, suggesting the presence of local factors interfering with myelin regeneration. In this study we explored in vivo the regional distribution of myelin repair and investigated its relationship with neurodegeneration. We first took advantage of the myelin binding property of the amyloid radiotracer 11C-PiB to conduct a longitudinal 11C-PiB PET study in an original cohort of 19 participants with a relapsing-remitting form of multiple sclerosis, followed-up over a period of 1-4 months. We then replicated our results on an independent cohort of 40 people with multiple sclerosis followed-up over 1 year with magnetization transfer imaging, an MRI metrics sensitive to myelin content. For each imaging method, voxel-wise maps of myelin content changes were generated according to modality-specific thresholds. We demonstrated a selective failure of remyelination in periventricular white matter lesions of people with multiple sclerosis in both cohorts. In both the original and the replication cohort, we estimated that the probability of demyelinated voxels to remyelinate over the follow-up increased significantly as a function of the distance from ventricular CSF. Enlarged choroid plexus, a recently discovered biomarker linked to neuroinflammation, was found to be associated with the periventricular failure of remyelination in the two cohorts (r = -0.79, P = 0.0018; r = -0.40, P = 0.045, respectively), suggesting a role of the brain-CSF barrier in affecting myelin repair in surrounding tissues. In both cohorts, the failure of remyelination in periventricular white matter lesions was associated with lower thalamic volume (r = 0.86, P < 0.0001; r = 0.33; P = 0.069, respectively), an imaging marker of neurodegeneration. Interestingly, we also showed an association between the periventricular failure of remyelination and regional cortical atrophy that was mediated by the number of cortex-derived tracts passing through periventricular white matter lesions, especially in patients at the relapsing-remitting stage. Our findings demonstrate that lesion proximity to ventricles is associated with a failure of myelin repair and support the hypothesis that a selective periventricular remyelination failure in combination with the large number of tracts connecting periventricular lesions with cortical areas is a key mechanism contributing to cortical damage in multiple sclerosis.

Clinically relevant profiles of myelin content changes in patients with multiple sclerosis: A multimodal and multicompartment imaging study.

OBJECTIVE: To investigate the clinical relevance of individual profiles of cortical and white matter lesion myelin content changes combining magnetisation transfer imaging (MTI) and 11C-PiB-positron emission tomography (PET) in patients with multiple sclerosis (MS). METHODS: MTI and [11C]PiB-PET acquired in 19 patients with MS followed up over 2-4 months and in seven healthy controls (HCs), were employed to generate individual maps of cortical and white matter (WM) lesion myelin content changes, respectively. These maps were used to calculate individual indices of demyelination and remyelination, and to investigate their association with clinical scores. RESULTS: Cortical remyelination ranged between 1% and 5% of the total cortical volume (17%-45% of the cortical volume demyelinated at baseline). WM lesion remyelination ranged between 8% and 22% of the lesional volume. An extensive cortical remyelination was associated with a shorter disease duration (rho = -0.63, p = 0.01) and, in combination with WM lesion remyelination, explained 68%-70% of the variance of clinical scores (p < 0.01). CONCLUSION: Our multimodal and multicompartment approach allows us to explore single-patient cortical and WM lesion demyelination and remyelination, and to generate clinically relevant indices of myelin repair. These indices may be used as outcome measures in clinical trials, thus increasing the chance to identify successful promyelinating treatments in patients with MS.

Spontaneous remyelination in lesions protects the integrity of surrounding tissues over time in multiple sclerosis.

BACKGROUND AND PURPOSE: Lesion remyelination preserves axonal integrity in animal models of multiple sclerosis (MS), but an in vivo demonstration of its protective effect on surrounding tissues in humans is lacking. METHODS: Nineteen persons with MS were enrolled in a cohort study and underwent two positron emission tomography (PET)/magnetic resonance imaging (MRI) scans 1-4 months apart. Voxelwise maps of Pittsburgh compound B distribution volume ratio, reflecting myelin content, were used to calculate an index of baseline demyelination, and of dynamic demyelination and remyelination over the follow-up in 549 single white matter lesions. Changes in fractional anisotropy and mean diffusivity, reflecting microstructural damage, were calculated in the proximal and distal 3-mm-thick rings surrounding each lesion, and used to classify perilesional microstructure as "preserved" or "worsening" over the follow-up. Mixed-effect linear models and logistic regressions were employed to investigate whether PET-derived lesional indices were associated with changes in MRI metrics in perilesions, and to identify which of them best predicted the microstructural evolution of perilesions over time. RESULTS: A higher index of remyelination, and a lower index of baseline and dynamic demyelination in lesions were associated with a less severe microstructural deterioration of the corresponding proximal and distal perilesions over time (p-value range: <0.001-0.012), but the index of remyelination was the best predicting variable of perilesional fate. For every extra 1% of remyelination within each lesion, the probability of the corresponding perilesional microstructure remaining preserved over time increased by 39% (odds ratio = 6.62, 95% confidence interval = 2.16-20.32, p < 0.001). CONCLUSIONS: Intralesional remyelination is associated with the microstructural preservation of surrounding tissues, possibly preventing neuroaxonal damage resulting from Wallerian degeneration.

Social Profiloplasty: A Practical Assessment and Injection Guide.

The trend of aesthetic medical procedures continues growing every year since decades all over the globe, especially considering minimal invasive treatments since the results are immediate and the downtime minimal. Hence, treatments with hyaluronic acid fillers have become extremely popular and routinely used in common practice. However, numerous areas of treatment were identified and described in the last years clinical training and consciousness of possibly complication remain still under represented. In the following article, we present four key treatment areas for optimal overall facial rejuvenation of what the authors define the social profile. Of each area an assessment, anatomical considerations, danger zones, and the preferred personal technique of the authors are described.

Early red nucleus atrophy in relapse-onset multiple sclerosis.

No study has investigated red nucleus (RN) atrophy in multiple sclerosis (MS) despite cerebellum and its connections are elective sites of MS-related pathology. In this study, we explore RN atrophy in early MS phases and its association with cerebellar damage (focal lesions and atrophy) and physical disability. Thirty-seven relapse-onset MS (RMS) patients having mean age of 35.6 ± 8.5 (18-56) years and mean disease duration of 1.1 ± 1.5 (0-5) years, and 36 age- and sex-matched healthy controls (HC) were studied. Cerebellar and RN lesions and volumes were analyzed on 3 T-MRI images. RMS did not differ from HC in cerebellar lobe volumes but significantly differed in both right (107.84 ± 13.95 mm3 vs. 99.37 ± 11.53 mm3 , p = .019) and left (109.71 ± 14.94 mm3 vs. 100.47 ± 15.78 mm3 , p = .020) RN volumes. Cerebellar white matter lesion volume (WMLV) inversely correlated with both right and left RN volumes (r = -.333, p = .004 and r = -.298, p = .010, respectively), while no correlation was detected between RN volumes and mean cortical thickness, cerebellar gray matter lesion volume, and supratentorial WMLV (right RN: r = -.147, p = .216; left RN: r = -.153, p = .196). Right, but not left, RN volume inversely correlated with midbrain WMLV (r = -.310, p = .008), while no correlation was observed between whole brainstem WMLV and either RN volumes (right RN: r = -.164, p = .164; left RN: r = -.64, p = .588). Finally, left RN volume correlated with vermis VIIb (r = .297, p = .011) and right interposed nucleus (r = .249, p = .034) volumes. We observed RN atrophy in early RMS, likely resulting from anterograde axonal degeneration starting in cerebellar and midbrain WML. RN atrophy seems a promising marker of neurodegeneration and/or cerebellar damage in RMS.

Hyperdiluted calcium hydroxylapatite for the treatment of skin laxity of the neck.

Despite being a common concern, there are very few minimally invasive treatments targeting neck skin laxity (NSL) reported in the literature. To assess the efficacy of hyperdiluted calcium hydroxyapatite (hy-CaHA) for the treatment of NSL, according to the NSL scale, and to estimate safety. Twenty patients showing NSL were treated with hy-CaHA 1:2. To evaluate the efficacy of hy-CaHA treatment for NSL, pictures of treated subjects were collected before and 3 months after treatment and graded according to the NSL scale, and T-student's test was applied to estimate differences. Hy-CaHA for the neck was effective according to the previously unreported NSL scale (p < 0.001) and safe. There were no major adverse events reported. This study supports the efficacy (according to the NSL scale) and safety of hy-CaHA (1:2) for NSL. Our results also highlight the utility of the newly developed NSL scale, being a useful tool to evaluate the level of NSL before treatment and to measure the outcome.

Temporomandibular Joint Arthrocentesis and Microfragmented Adipose Tissue Injection for the Treatment of Internal Derangement and Osteoarthritis: A Randomized Clinical Trial.

PURPOSE: Internal derangement and osteoarthritis are the most common degenerative temporomandibular joint diseases and initial treatment for such conditions relies on arthrocentesis. Microfragmentation of adipose tissue has been proven in orthopedic literature to represent a more effective method to preserve stem cells, but no application has ever been reported in the temporomandibular joint. The purpose of this randomized clinical trial is to compare standard treatment conducted by injecting hyaluronic acid after the procedure to the new treatment relying upon microfragmented adipose tissue injection using the Lipogems technology. MATERIALS AND METHODS: A randomized clinical trial was designed enrolling 20 patients in the control group receiving the standard treatment and 20 patients in the experimental group receiving microfragmented adipose tissue obtained through the Lipogems technology after arthrocentesis. Two main outcomes were defined, pain (visual analogic scale) and function (maximum interincisal opening). Both were measured in the immediate preoperative time, and 10 days, 1 month, and 6 months after the procedure. RESULTS: In both groups, pain reduction and mouth opening significantly improved compared with the preoperative situation (P = .001). At 6-month follow-up, there was an almost statistically significant reduction of pain compared with preoperative visual analogic scale (P = .0546) and a statistically significant improvement of mouth opening (P = .0327). Overall, statistical analyses showed that the experimental group had a statistically significant superiority in the success rate of the procedure compared with the control group (P = .018). CONCLUSIONS: Preliminary results of this clinical trial show that the injection of microfragmented adipose tissue can significantly improve outcomes of pain and function compared with the standard treatment and encourage to pursue research on this topic. Further studies with a longer follow-up time are needed to evaluate the clinical stability of the achieved improvement in pain and function.

Nonsurgical Redefinition of the Chin and Jawline of Younger Adults With a Hyaluronic Acid Filler: Results Evaluated With a Grid System Approach.

BACKGROUND: Aesthetic treatment of the lower face is increasingly in demand, particularly owing to age-related changes in appearance. VYC-25L is a novel hyaluronic acid filler with high G' and high cohesivity, specifically designed for sculpting and contouring of the chin and jaw. OBJECTIVES: The aim of this study was to assess the use of a grid traced onto the chin and jaw for guiding treatment with VYC-25L. METHODS: This was a retrospective, single-center analysis of data from adult patients undergoing treatment of the lower third of the face with VYC-25L. A grid system of horizontal and vertical lines was used to systematize the process of treatment planning and performance. RESULTS: Thirty subjects were enrolled (53.3% female; mean [standard deviation] age, 34.4 [2.8] years). The mean quantity of VYC-25L used was 4.0 [0.8] mL. Based on the 5-point Global Aesthetic Improvement Scale, 29 patients (96.7%) rated their appearance at 20 days posttreatment as "much improved" or "very much improved." The only complications recorded were early transient soft-tissue edema (n = 14; 46.7%) and bruising (n = 6; 20.0%). There were no cases of infection, paresthesia, asymmetry, hematoma, necrosis, or skin discoloration. CONCLUSIONS: Treatment of the chin and jawline with VYC-25L, with injection locations determined by a standardized grid-based approach, appears to be effective and safe with high rates of patient satisfaction. Injection of this filler offers a potentially high-impact approach for patients across a variety of biological and economic circumstances.

Selective Cerebellar Atrophy Associates with Depression and Fatigue in the Early Phases of Relapse-Onset Multiple Sclerosis.

Cerebellar dysfunctions have been associated to depressive disorders and cognitive impairment in neurodegenerative diseases. The objective is to analyze the associations between cerebellar atrophy, depression, and fatigue in the early phases of relapse-onset multiple sclerosis (RRMS). Sixty-one RRMS patients and 50 healthy controls (HC) were enrolled and clinically evaluated by means of expanded disability status scale (EDSS), Rao's brief repeatable battery of neuropsychological tests (BRB-NT), Delis-Kaplan executive function system sorting test, beck depression inventory II (BDI-II), and fatigue severity scale (FSS). The relationships between MRI variables and clinical scores were assessed. Depressed RRMS (dRRMS) had significantly lower Vermis Crus I volume compared with not depressed RRMS (ndRRMS) (p = 0.009). Vermis Crus I volume was lower in dRRMS suffering from fatigue than in ndRRMS without fatigue (p = 0.01). The hierarchical regression models which included demographic and clinical data (age, sex, and disease duration, FSS or BDI-II) and cerebellar volumes disclosed that cerebellar lobule right V atrophy explained an increase of 4% of the variability in FSS (p = 0.25) and Vermis Crus I atrophy explained an increase of 6% of variability in BDI-II (p = 0.049). Since clinical onset, atrophy of specific cerebellar lobules associates with important clinical aspects of RRMS. Cerebellar pathology may be one of the determinants of fatigue and depression that contribute to worsen disability in RRMS.

Piezosurgery: Ten Years' Experience of Percutaneous Osteotomies in Rhinoplasty.

PURPOSE: The possibility to obtain precise osteotomies without major soft tissue damage represents a key point in modern approaches to rhinoplasty. In 2007, the authors first described their ultrasonic approach for percutaneous nasal bone osteotomies with minimal periosteal detachment. In this article, they retrospectively analyze the results of their piezo-surgical rhinoplasty technique through their 10-year experience and describe new perspectives of this technique. PATIENTS AND METHODS: A series of 183 patients was retrospectively evaluated. Surgical technique was based on piezoelectric external nasal osteotomies, performed percutaneously, without periosteal detachment. For the last patients, the piezoelectric instrument also was tracked with a navigator (piezo-navigated approach). Data on surgery, hospitalization, ecchymosis, edema, and postoperative complications were evaluated. RESULTS: Of the 183 patients, 168 (91.8%) showed grade 0 or 1 edema. Grade 2 edema was noticed in only 15 of 183 patients (8.2%). In 6 of the 183 procedures (3.3%), postoperative complications potentially related to the piezoelectric osteotomy system occurred. CONCLUSION: The piezoelectric external approach can be considered a safe and reliable technique. Preliminary data suggest the possibility of using surgical planning and navigation in positioning the osteotomies in selected subsets of patients.

Volumetric Analysis of Fat Injection by Computerized Tomography in Orthognathic Surgery: Preliminary Report on a Novel Volumetric Analysis Process for the Quantification of Aesthetic Results.

BACKGROUND: Integrated approaches to orthognathic surgery should include accurate volumetric evaluation of the skull and soft tissues. In patients with dentofacial deformities, the most frequent aesthetic deficits are attributable to an underdevelopment of hard and soft tissues. Traditional osteotomic procedures often fail to guarantee a stability of soft tissues over time. For this reason, in selecting a surgical strategy, the surgeon should consider not only traditional osteotomies, but also soft-tissue improving procedures, such as lipofilling. Preoperative surgical planning systems, such as the Virtual surgical planning (VSP) protocol, are based mainly on skeletal movement prediction. Quantitative estimation of soft-tissue modifications is not part of common clinical practice. Most commonly, the evaluation of soft-tissue modifications after orthognathic procedures is instead performed by clinical qualitative means.The purpose of this study was to describe a novel computed tomography (CT)-based volumetric analysis process for the quantification of injected autologous adipose tissue in patients who have undergone simultaneous orthognathic and lipofilling procedures. METHODS: This was a retrospective review of consecutive patients who underwent combined orthognathic surgery and lipofilling from June 2016 to May 2017 for malocclusion with functional and aesthetic impairments. Preoperative planning included clinical evaluation and virtual osteotomy planning according to the VSP protocol. The volume of fat to be injected was estimated clinically by comparing virtual renderings with preoperative clinical photographs. The surgical technique involved Le Fort I and sagittal split mandibular osteotomies, combined with autologous fat injection in the malar and perioral regions. Postoperative evaluation was performed with a novel imaging process based on CT image segmentation to quantify the exact volume of injected fat. Skeletal stability was also evaluated at 3 months. RESULTS: Sixteen patients were enrolled in the study, all females, with a mean age of 24.5 years (range, 18-36 years). The mean difference between the fat tissue injected and that quantified postoperatively was 6.01 cm. All patients had clinically satisfactory facial convexity, with complete restoration of the cheekbone contour, at 3 months. CONCLUSION: This study introduces a novel CT-image based technique to quantitatively assess the contribution of injected fat to the postoperative soft-tissue volume increase after combined orthognathic surgery with autologous lipofilling. In the future, this CT-based volumetric analysis technique could be the gold standard for evaluating facial lipofilling outcomes, and for assessing clinical aesthetic outcomes based on the injected volume of fat.

MRI-detectable cortical lesions in the cerebellum and their clinical relevance in multiple sclerosis.

BACKGROUND: The demonstration of cortical lesions (CL) in the cerebellum by magnetic resonance imaging (MRI) is hampered by technical and anatomical constraints. OBJECTIVE: To investigate the occurrence of cerebellar CL and their correlation with cerebellar-related disability by combining Double Inversion Recovery (DIR) and Phase Sensitive Inversion Recovery (PSIR) MRI images in multiple sclerosis (MS) patients. MATERIAL AND METHODS: 40 MS patients (10 CIS/eRRMS, 24 RRMS, 6 SPMS), having a wide range of disability and disease duration, were enrolled. DIR and PSIR images were obtained with a 3T-MRI. RESULTS: Cerebellar white matter lesions (WML) and/or CL were observed in 33/40 patients (82.5%) among which 14/40 had only CL. CL were demonstrated in 26/40 patients by DIR and in 31/40 by PSIR, and their number increased from CIS/eRRMS to SPMS. PSIR disclosed a significantly higher number of CL compared to DIR (RRMS: p=0.0008; SPMS: p=0.002). CL number correlates with the cerebellar Expanded Disability Status Score (EDSS) score (r=0.72, p<0.0001). No correlation was observed between supra-tentorial and cerebellar CL. CONCLUSIONS: CL are detected by PSIR in the cerebellum of the majority of MS patients, are more than WML, increase with disease progression and strongly correlate with the cerebellar EDSS. Thus, the observation of CL in the cerebellum of MS at clinical onset might be useful for prognostic and therapeutic aims.

Computer guided maxillo-malar piezoelectric osteotomies for midface augmentation.

PURPOSE: Despite maxillo-malar osteotomies having been discarded in the most recent literature, in the setting of orthognathic surgery they provide several advantages for middle third augmentation. This paper reintroduces maxillo-malar osteotomies as an effective method to increase volume of midfacial region in combination with contemporary technology, including piezosurgery, virtual surgical planning, and navigation. MATERIAL AND METHODS: Eighteen patients with midface hypoplasia were included in this study and underwent orthognathic surgery with maxillo-malar osteotomies. All patients underwent the same workflow: virtual design of maxillo-malar osteotomies, surgery with navigation-assisted piezoelectric osteotomies, and computerized morphometric analysis. RESULTS: Simulated maxillo-malar osteotomies were successfully replicated in the operating room, as shown by accuracy evaluation performed using three-dimensional analysis. In long-term follow-up period, no permanent complications were assessed. Superimposition between postoperative and preoperative CBCTs revealed that the soft tissue area influenced by the underlying skeletal movement was comparable for all cases. CONCLUSIONS: Virtual surgical planning, navigation, and piezosurgery are today indispensable tools to perform maxillo-malar osteotomies safely and accurately. We suggest incorporating such osteotomies in the surgeon's armamentarium for patients with severe midfacial hypoplasia as they offer an integrated solution to restore functionality and aesthetics.

Pneumomediastinum, pneumothorax and subcutaneous emphysema after tracheostomy closure. When less is more.

Pneumomediastinum is a threatening complication that might occur after tight surgical closure of tracheostomy is performed. Physiopathology of this condition is based on several factors, including direct trauma to the tracheal wall caused by surgical maneuvers or insufficient closure of soft tissue layers which do not seal air leakage. In this paper we explore this phenomenon by reporting the case of one patient undergoing surgical closure of tracheostomy after two weeks, who later developed subcutaneous emphysema followed by pneumomediastinum. Physiopatology is analyzed and management strategies for this condition are suggested based on our experience.

Imaging Characteristics of Choroid Plexuses in Presymptomatic Multiple Sclerosis: A Retrospective Study.

BACKGROUND AND OBJECTIVES: Recent imaging studies have suggested a possible involvement of the choroid plexus (CP) in multiple sclerosis (MS). Here, we investigated whether CP changes are already detectable at the earliest stage of MS, preceding symptom onset. METHODS: This study is a retrospective analysis of 27 patients with presymptomatic MS, 97 patients with clinically definite MS (CDMS), and 53 healthy controls (HCs) who underwent a cross-sectional 3T-MRI acquisition; of which, 22 MS, 19 HCs, and 1 presymptomatic MS (evaluated 8 months before conversion to CDMS) also underwent translocator protein (TSPO) 18F-DPA-714 PET and were included in the analysis. CPs were manually segmented on 3D T1-weighted images for volumetric analysis. CP 18F-DPA-714 uptake, reflecting inflammation, was calculated as the average standardized uptake value (SUV). Multivariable regressions adjusted for age, sex, and ventricular and brain volume were fitted to test CP volume differences between presymptomatic patients and MS or HCs. For the presymptomatic case who also had 18F-DPA-714 PET, CP SUV differences with MS and HCs were assessed through Crawford-Howell tests. To provide further insight into the interpretation of 18F-DPA-714-PET uptake at the CP level, a postmortem analysis of CPs in MS vs HCs was performed to characterize the cellular localization of TSPO expression. RESULTS: Compared with HCs, patients with presymptomatic MS had 32% larger CPs (ß = 0.38, p = 0.001), which were not dissimilar to MS CPs (p = 0.69). Moreover, in the baseline scan of the presymptomatic case who later on developed MS, TSPO PET showed 33% greater CP inflammation vs HCs (p = 0.04), although no differences in 18F-DPA-714 uptake were found in parenchymal regions vs controls. CP postmortem analysis identified a population of CD163+ mononuclear phagocytes expressing TSPO in MS, possibly contributing to the increased 18F-DPA-714 uptake. DISCUSSION: We identified an imaging signature in CPs at the presymptomatic MS stage using MRI; in addition, we found an increased CP inflammation with PET in a single presymptomatic patient. These findings suggest a role of CP imaging as an early biomarker and argue for the involvement of the blood-CSF barrier dysfunction in disease development. TRIAL REGISTRATION INFORMATION: APHP-20210727144630, EudraCT-Number: 2008-004174-40; ClinicalTrials.gov: NCT02305264, NCT01651520, and NCT02319382.

All-in-one surgical guide: A new method for cranial vault resection and reconstruction.

INTRODUCTION: Great precision is required for craniofacial surgery, and computer-aided design (CAD) methods may be used to plan surgery before it is performed. In this study, three-dimensional (3D)-printed cutting guides are used to match computer models with surgical procedures. We describe a novel method of computer-aided surgery for autologous cranioplasty that includes a new strategy for generating and using cutting guides. These guides may be used not only for osteotomies, but also for many other steps in the surgical procedure. MATERIALS AND METHODS: Preoperatively, anatomical data were imported into a CAD package and used for virtual surgical planning (VSP). Cutting guides were designed after considering how to integrate all the surgical steps. Models of the microplates and micro-screws were also made. Surgical guides were exported and printed, and preoperative simulations using a replica of the patient's skull established the sequence of steps. The accuracy of the procedure was evaluated postoperatively using computed tomography (CT) scans. RESULTS: In every patient examined, the all-in-one surgical-guide system was able to automate the many steps in the procedure and dramatically decreased the duration of surgery. The experimental guide enhanced every phase of surgery, including excising the lesion, and harvesting, positioning, and fixing the graft. In each step, precision was enhanced and the outcome corresponded with the VSP. CONCLUSIONS: The few previous reports on cutting guides used in cranioplasty generally describe the use of separate guides for dismantling and reconstruction. The ability to perform more surgical sequences using a single tool can improve surgical accuracy. Clearly there is no single perfect surgical guide; however, effective surgical-design strategies should be used to build the best approach to each procedure.

Enlarged Virchow Robin spaces associate with cognitive decline in multiple sclerosis.

The clinical significance of Virchow Robin spaces (VRS) in inflammatory brain disorders, especially in multiple sclerosis (MS), is still undefined. We analysed enlarged VRS (eVRS) by means of phase sensitive inversion recovery (PSIR) MRI sequence and investigated their association with inflammation or brain atrophy, and to clinical or physical disability. Forty-three MS patients (21 clinically isolated syndrome suggestive of MS [CIS], 15 RRMS, 7 progressive [PMS]) and 10 healthy controls (HC) were studied. 3DT1, 3DFLAIR and 2DPSIR images were obtained with a 3T MRI scanner. eVRS number and volume were calculated by manual segmentation (ITK-SNAP). Freesurfer was used to assess brain parenchymal fraction (BPF). All patients underwent clinical (EDSS) and cognitive (Rao's BRB and DKEFS) evaluation. eVRS number and volume resulted significantly higher on 2D-PSIR compared to both 3D-T1 (p<0.001) and 3D-FLAIR (p<0.001) and were significantly increased in CIS compared to HC (p<0.05), in PMS and RRMS compared to CIS (p<0.001) and in male versus female patients (p<0.05). eVRS volume increased significantly with disease duration (r = 0.6) but did not correlate with EDSS. eVRS significantly correlated with SPARTd (r = -0.47) and DKEFSfs (r = -0.46), especially when RRMS and PMS were merged in a single group (r = 0.89, p = 0.002 and r = 0.66, p = 0.009 respectively), while no correlation was found with BPF (r = 0.3), gadolinium-enhancing lesions (r = 0.2) and WMT2 lesion volume (r = 0.2). 2DPSIR allowed the detection of an impressive higher number of eVRS compared to 3DT1 and 3DFLAIR. eVRS associate with SPARTd and DKEFSfs failure in relapse-onset MS, suggesting they may contribute to cognitive decline in MS.

The Parallel Analysis of Phase Sensitive Inversion Recovery (PSIR) and Double Inversion Recovery (DIR) Images Significantly Improves the Detection of Cortical Lesions in Multiple Sclerosis (MS) since Clinical Onset.

BACKGROUND: Double inversion recovery (DIR) detects only a minority (<20%) of cortical lesions (CL) in multiple sclerosis (MS). Phase-sensitive inversion recovery (PSIR) was suggested to be substantially superior to DIR in the detection of cortical lesions (CL). These two sequences might be complementary. OBJECTIVES: To analyze CL frequency and type in MS patients having different disease duration and disability, including patients at clinical onset, and to discern more correctly the artifacts, by combining DIR and PSIR images. PATIENTS AND METHODS: 40 patients were enrolled in the study: 10 clinically isolated syndrome/early relapsing remitting MS (CIS/eRRMS), 24 relapsing remitting MS (RRMS), 6 secondary progressive MS (SPMS). DIR and PSIR images were jointly used to classify lesions as purely intracortical (IC), leukocortical (LC) and juxtacortical (JC). RESULTS: PSIR disclosed CL in 100% of the patients and was capable of identifying more than four times lesions (455.5%, p<0.00001), especially IC (mean numbers: 36.5 in CIS/eRRMS, 45.0 in RRMS and 52.3 in SPMS) and LC (mean numbers: 10.9 in CIS/eRRMS, 20.1 in RRMS and 25.3 in SPMS), compared to DIR (p<0.00001). CL number was significantly higher in SPMS compared to RRMS (p<0.0001). Artifacts were more accurately identified by comparing the two sequences. CONCLUSIONS: Our study confirms the higher ability of PSIR in disclosing and classifying CL. The presence of CL in all CIS patients further points out the relevance of cortical pathology in MS. Whether the parallel analysis of DIR and PSIR images may be useful for diagnostic purposes, especially when a diagnosis of MS is suspected but not confirmed by routine MRI, needs to be evaluated in larger patient series. The analysis of the cortex by DIR and PSIR may also allow a better stratification of the patients for prognostic and counseling purposes, as well as for their inclusion in clinical studies.