Insights from a Multicenter Study on Adult H3 K27M-Mutated Glioma: Surgical Resection's Limited Influence on Overall Survival, ATRX as Molecular Prognosticator.

BACKGROUND: H3 K27M-mutated gliomas were first described as a new grade 4 entity in the 2016 WHO classification. Current studies have focused on its typical appearance in children and young adults, increasing the need to better understand the prognostic factors and impact of surgery on adults. Here, we report a multicentric study of this entity in adults. METHODS: We included molecularly confirmed H3 K27M-mutated glioma cases in patients >18 years diagnosed between 2016 and 2022. Clinical, radiological, and surgical features were analyzed. Univariate and multivariate analyses were performed to identify prognostic factors. RESULTS: Among 70 patients with a mean age of 36.1 years, the median overall survival (OS) was 13.6 + 14 months. Gross-total resection was achieved in 14.3% of patients, whereas 30% had a subtotal resection and 54.3% a biopsy.Tumors located in telencephalon/diencephalon/myelencephalon were associated with a poorer OS, while a location in the mesencephalon/metencephalon showed a significantly longer OS (8.7 vs. 25.0 months, p=0.007). Preoperative Karnofsky Performance Score (KPS) < 80 showed a reduced OS (4.2 vs. 18 months, p=0.02). Furthermore, ATRX loss, found in 25.7%, was independently associated with an increased OS (31 vs. 8.3 months, p=0.0029). Notably, patients undergoing resection showed no survival benefit over biopsy (12 vs. 11 months, p=0.4006). CONCLUSION: The present study describes surgical features of H3 K27M-mutated glioma in adulthood in a large multicentric study. Our data reveal that ATRX status, location and KPS significantly impact OS in H3 K27M-mutated glioma. Importantly, our dataset indicates that resection does not offer a survival advantage over biopsy.

Patterns, predictors and prognostic relevance of high-grade hematotoxicity after temozolomide or temozolomide-lomustine in the CeTeG/NOA-09 trial.

PURPOSE: In the randomized phase III trial CeTeG/NOA-09, temozolomide (TMZ)/lomustine (CCNU) combination therapy was superior to TMZ in newly diagnosed MGMT methylated glioblastoma, albeit reporting more frequent hematotoxicity. Here, we analyze high grade hematotoxicity and its prognostic relevance in the trial population. METHODS: Descriptive and comparative analysis of hematotoxicity adverse events ≥ grade 3 (HAE) according to the Common Terminology of Clinical Adverse Events, version 4.0 was performed. The association of HAE with survival was assessed in a landmark analysis. Logistic regression analysis was performed to predict HAE during the concomitant phase of chemotherapy. RESULTS: HAE occurred in 36.4% and 28.6% of patients under CCNU/TMZ and TMZ treatment, respectively. The median onset of the first HAE was during concomitant chemotherapy (i.e. first CCNU/TMZ course or daily TMZ therapy), and 42.9% of patients with HAE receiving further courses experienced repeat HAE. Median HAE duration was similar between treatment arms (CCNU/TMZ 11.5; TMZ 13 days). Chemotherapy was more often discontinued due to HAE in CCNU/TMZ than in TMZ (19.7 vs. 6.3%, p = 0.036). The occurrence of HAE was not associated with survival differences (p = 0.76). Regression analysis confirmed older age (OR 1.08) and female sex (OR 2.47), but not treatment arm, as predictors of HAE. CONCLUSION: Older age and female sex are associated with higher incidence of HAE. Although occurrence of HAE was not associated with shorter survival, reliable prediction of patients at risk might be beneficial to allow optimal management of therapy and allocation of supportive measures. TRIAL REGISTRATION: NCT01149109.

Invasiveness of decompression surgery affects modeled lumbar spine kinetics in patients with degenerative spondylolisthesis.

Introduction: The surgical treatment of degenerative spondylolisthesis with accompanying spinal stenosis focuses mainly on decompression of the spinal canal with or without additional fusion by means of a dorsal spondylodesis. Currently, one main decision criterion for additional fusion is the presence of instability in flexion and extension X-rays. In cases of mild and stable spondylolisthesis, the optimal treatment remains a subject of ongoing debate. There exist different opinions on whether performing a fusion directly together with decompression has a potential benefit for patients or constitutes overtreatment. As X-ray images do not provide any information about internal biomechanical forces, computer simulation of individual patients might be a tool to gain a set of new decision criteria for those cases. Methods: To evaluate the biomechanical effects resulting from different decompression techniques, we developed a lumbar spine model using forward dynamic-based multibody simulation (FD_MBS). Preoperative CT data of 15 patients with degenerative spondylolisthesis at the level L4/L5 who underwent spinal decompression were identified retrospectively. Based on the segmented vertebrae, 15 individualized models were built. To establish a reference for comparison, we simulated a standardized flexion movement (intact) for each model. Subsequently, we performed virtual unilateral and bilateral interlaminar fenestration (uILF, bILF) and laminectomy (LAM) by removing the respective ligaments in each model. Afterward, the standardized flexion movement was simulated again for each case and decompression method, allowing us to compare the outcomes with the reference. This comprehensive approach enables us to assess the biomechanical implications of different surgical approaches and gain valuable insights into their effects on lumbar spine functionality. Results: Our findings reveal significant changes in the biomechanics of vertebrae and intervertebral discs (IVDs) as a result of different decompression techniques. As the invasiveness of decompression increases, the moment transmitted on the vertebrae significantly rises, following the sequence intact ➝ uILF ➝ bILF ➝ LAM. Conversely, we observed a reduction in anterior-posterior shear forces within the IVDs at the levels L3/L4 and L4/L5 following LAM. Conclusion: Our findings showed that it was feasible to forecast lumbar spine kinematics after three distinct decompression methods, which might be helpful in future clinical applications.

[Excisional surgery of orbital tumors]. / Exzisionale Chirurgie orbitaler Tumoren.

The indications for orbital tumor surgery are an incisional biopsy to confirm the diagnosis or in malignant operable tumors a complete excision or a debulking to avoid complications in large invasively infiltrating tumors. In the case of benign tumors, the indications for surgery depend mostly on the clinical symptoms and cosmetic esthetic disfigurement. In the present article the preoperative examinations as well as surgical access approaches to different orbital regions, endoscopic procedures and methods of intraoperative navigation are presented. Magnetic resonance imaging is the instrument of choice, whereby in many cases computed tomography (CT) adds further information. Depending on the indications, diffusion-weighted sequences, CT angiography and digital subtraction angiography (DSA, catheter angiography) are added to the preoperative diagnostics. For space-occupying lesions located anterior to the bulbar equator, an anterior orbitotomy can be performed transconjunctivally or transpalpebrally. A lateral orbitotomy is used to reach lateral, laterocranial, and lateroinferior orbital segments, whereas transcranial approaches are suitable for processes located far posterior and for those with retro-orbital intracranial extension as well as for processes in the optic foramen/superior orbital fissure. The indications for an endonasal access approach are processes medial to the bulb or optic nerve and up to the orbital apex. A transantral access can be chosen for caudal, mediolateral, and medioinferior space-occupying lesions. Modern orbital surgery is complemented by endoscopic procedures and intraoperative navigation. Orbital tumors belong to the interdisciplinary relevant diseases. Therefore, an optimal management takes place at specialized multidisciplinary centers.

Tentorial Incision vs. Retraction of the Tentorial Edge during the Subtemporal Approach: Anatomical Comparison in Cadaveric Dissections and Retrospective Clinical Case Series.

Objective The aim of this study was to compare tentorial incision (group A) versus retraction and tack up suture (group B) of the tentorial edge during the subtemporal approach for surgery in the high basilar region. Design 24 cadaveric dissections and 4 clinical cases of aneurysms of the high basilar region are presented. Assessment included visibility and operability afforded by either tentorial incision creating a dural flap (group A) or retraction of the tentorial edge and tethering with a suture (group B). Four patients, two with superior cerebellar artery aneurysms and two with proximal posterior cerebral artery aneurysms were treated with each approach. Results In the quantitative evaluations, we found no significant difference in the exposure of the posterior cerebral, superior cerebellar, and perforant arteries as well as surgical working area provided by either approach. However, tentorial incision allowed a significantly greater exposure of the basilar artery and the fourth cranial nerve (both p < 0.001). Concerning operability, tentorial incision provided no objective advantage for direct clipping of the high basilar region (groups A vs. B, p > 0.05). Subjectively, clipping of the high basilar segment was feasible using tentorial tethering only. Conclusion Retraction of the free edge of the tentorium downward by tethering with a suture is simple and fast method for exposure of aneurysms in the high basilar region when the pathology does not require a proximal control. In our data the rather more invasive and time consuming tentorial incision provided an additional objectified advantage only for placement of a proximal temporary clip.

[Surgical treatment of adult spinal deformities]. / Operative Behandlung adulter spinaler Deformitäten.

BACKGROUND: Adult spinal deformity (ASD) is mostly a progressive disease which usually leads to chronic pain. Due to increased prevalence in older people many patients suffer from comorbidities, which make conservative and surgical treatment even more complex. OBJECTIVE: This article provides an overview on the current conservative and surgical treatment options. MATERIAL AND METHODS: An extensive literature search was carried out via Medline plus an additional evaluation of the authors' personal experiences was performed. RESULTS: The current conservative and surgical treatments are outlined and potential risk factors and predictors which may lead to inferior clinical outcome are discussed. CONCLUSION: Patients for whom even conservative treatment leads to success should be identified earlier and better. The surgical treatment ranges from minimally invasive decompression to multilevel fusions. Complications in large corrective interventions can be substantial but if the indications are correctly assessed, such complex surgical treatment has excellent clinical results in terms of pain and quality of life.

[Operative treatment of degenerative diseases of the lumbar spine]. / Operative Versorgung degenerativer Erkrankungen der Lendenwirbelsäule.

BACKGROUND: Degenerative diseases of the lumbar spine and associated lower back pain represent a major epidemiological and health-related economic challenge. A distinction is made between specific and unspecific lower back pain. In specific lower back pain lumbar disc herniation and spinal canal stenosis with or without associated segment instability are among the most frequent pathologies. Diverse conservative and operative strategies for treatment of these diseases are available. OBJECTIVES: The aim of this article is to present an overview of current data and an evidence-based assessment of the possible forms of treatment. MATERIAL AND METHODS: An extensive literature search was carried out via Medline plus an additional evaluation of the authors' personal experiences. RESULTS: Conservative and surgical treatment represent efficient treatment options for degenerative diseases of the lumbar spine. Surgical treatment of lumbar disc herniation shows slight advantages compared to conservative treatment consisting of faster recovery of neurological deficits and a faster restitution of pain control. Surgical decompression is superior to conservative measures for the treatment of spinal canal stenosis and degenerative spondylolisthesis. In this scenario conservative treatment represents an important supporting measure for surgical treatment in order to improve the mobility of patients and the outcome of surgical treatment. CONCLUSION: The treatment of specific lower back pain due to degenerative lumbar pathologies represents an interdisciplinary challenge, requiring both conservative and surgical treatment strategies in a synergistic treatment concept in order to achieve the best results for patients.

[Operative treatment of the degenerative cervical spine]. / Operative Versorgung der degenerativen Halswirbelsäule.

BACKGROUND: Degenerative alterations of the cervical spine often entail disc herniations and stenoses of the spinal canal and/or neural foramen. Mediolateral or lateral compression of nerve roots causes cervical radiculopathy, which is an indication for surgery in cases of significant motor deficits or refractory pain. Median canal encroachment may result in compression of the spinal cord and cervical myelopathy. Its natural history is typically characterized by episodic deterioration, so that surgical decompression is indicated in cases of clear myelopathic signs. OBJECTIVE: The aim of the present article is to outline the operative options for patients with cervical radiculopathy and myelopathy. Furthermore, we describe the operative complications and the outcome in these patients. MATERIAL AND METHODS: For this manuscript a systematic PubMed search was carried out, the papers were systematically analyzed for the best evidence and this was combined with the authors' experience. RESULTS AND CONCLUSION: Depending on the cervical pathology, the most prevalent surgical options for radiculopathy include anterior cervical discectomy and fusion (ACDF), cervical arthroplasty or posterior cervical foraminotomy. Cervical myelopathy may be decompressed by ACDF, corpectomy or posterior approaches like laminectomy plus instrumented fusion or laminoplasty. The outcome depends on the cervical pathology and the type of operation. Overall, in long-term follow-up studies the results of all surgical techniques on the cervical spine are generally considered to be very good, although specific patient characteristics are more suited for a particular approach.

Reliability of Semi-Automated Segmentations in Glioblastoma.

PURPOSE: In glioblastoma, quantitative volumetric measurements of contrast-enhancing or fluid-attenuated inversion recovery (FLAIR) hyperintense tumor compartments are needed for an objective assessment of therapy response. The aim of this study was to evaluate the reliability of a semi-automated, region-growing segmentation tool for determining tumor volume in patients with glioblastoma among different users of the software. METHODS: A total of 320 segmentations of tumor-associated FLAIR changes and contrast-enhancing tumor tissue were performed by different raters (neuroradiologists, medical students, and volunteers). All patients underwent high-resolution magnetic resonance imaging including a 3D-FLAIR and a 3D-MPRage sequence. Segmentations were done using a semi-automated, region-growing segmentation tool. Intra- and inter-rater-reliability were addressed by intra-class-correlation (ICC). Root-mean-square error (RMSE) was used to determine the precision error. Dice score was calculated to measure the overlap between segmentations. RESULTS: Semi-automated segmentation showed a high ICC (> 0.985) for all groups indicating an excellent intra- and inter-rater-reliability. Significant smaller precision errors and higher Dice scores were observed for FLAIR segmentations compared with segmentations of contrast-enhancement. Single rater segmentations showed the lowest RMSE for FLAIR of 3.3 % (MPRage: 8.2 %). Both, single raters and neuroradiologists had the lowest precision error for longitudinal evaluation of FLAIR changes. CONCLUSIONS: Semi-automated volumetry of glioblastoma was reliably performed by all groups of raters, even without neuroradiologic expertise. Interestingly, segmentations of tumor-associated FLAIR changes were more reliable than segmentations of contrast enhancement. In longitudinal evaluations, an experienced rater can detect progressive FLAIR changes of less than 15 % reliably in a quantitative way which could help to detect progressive disease earlier.

New aspects on the efficacy of high-dose intravenous immunoglobulins in patients with autoimmune thrombocytopenia.

BACKGROUND AND OBJECTIVES: The clinical significance of autoimmune thrombocytopenia (ITP) is reflected by bleeding and/or an increased bleeding risk due to low platelet counts. In most cases, treatment with high-dose (1-2 g/kg body weight) intravenous immunoglobulin has been demonstrated to result in an increase in platelet counts after one day of treatment. Until now, there is little information on the true beginning of therapy effect in patients treated with high-dose intravenous immunoglobulin. In this study, we focused on the kinetic of platelet counts and cessation of bleeding within the first 24 h of treatment. MATERIALS AND METHODS: Nineteen patients with chronic ITP were treated with high-dose intravenous immunoglobulin due to clinically relevant bleeding and/or for increased bleeding risk. RESULTS: Although the response was variable in treated patients, cessation of bleeding was observed within 12 h in all such affected patients (n = 7), even in patients with platelet counts that were not increased (n = 3). Furthermore, platelet counts were observed to increase already within 1 h in 10 (53%) patients and within 8 h in 12 (63%) patients. CONCLUSIONS: From a clinical perspective, the onset of therapeutic effects of intravenous immunoglobulin in patients with ITP may occur at an earlier stage and be superior to that previously expected. Failure to measure an increase in platelets in the circulation of 'non-responders' may be explained by an increased consumption of platelets due to recognizable or unrecognizable bleeding in such affected patients.

COXIBRAIN: results of the prospective, randomised, phase II/III study for the selective COX-2 inhibition in chronic subdural haematoma patients.

BACKGROUND: Chronic subdural haematomas (cSDHs) have shown an increasing incidence in an ageing population over the last 20 years, while unacceptable recurrence rates of up to 30 % persist. The recurrence rate of cSDH seems to be related to the excessive neoangiogenesis in the parietal membrane, which is mediated via vascular endothelial growth factor (VEGF). This is found to be elevated in the haematoma fluid and is dependent on eicosanoid/prostaglandin and thromboxane synthesis via cyclo-oxygenase-2 (COX-2). With this investigator-initiated trial (IIT) it was thought to diminish the recurrence rate of operated-on cSDHs by administering a selective COX-2 inhibitor (Celecoxib) over 4 weeks' time postoperatively in comparison to a control group. METHOD: The thesis of risk reduction of cSDH recurrence in COX-2-inhibited patients was to be determined in a prospective, randomised, two-armed, open phase-II/III study with inclusion of 180 patients over a 2-year time period in four German university hospitals. The treated- and untreated-patient data were to be analysed by Fisher's exact test (significance level of alpha, 0.05 [two-sided]). RESULTS: After screening of 246 patients from January 2009 to April 2010, the study had to be terminated prematurely as only 23 patients (9.3 %) could be enrolled because of on-going non-steroid anti-rheumatic (NSAR) drug treatment or contraindication to Celecoxib medication. In the study population, 13 patients were treated in the control group (six women, seven men; average age 66.8 years; one adverse event (AE)/serious adverse event (SAE) needing one re-operation because of progressive cSDH (7.7 %); ten patients were treated in the treatment group (one woman, nine men; average age 64.7 years; five AEs/SAEs needing two re-operations because of one progressive cSDH and one wound infection [20 %]). Significance levels are obsolete because of insufficient patient numbers. CONCLUSIONS: The theoretical advantage of COX-2 inhibition in the recurrent cSDH could not be transferred into the treatment of German cSDH patients as 66.6 % of the patients showed strict contraindications for Celecoxib. Furthermore, 55 % of the patients were already treated with some kind of COX-2 inhibition and, nevertheless, developed cSDH. Thus, although conceptually appealing, an anti-angiogenic therapy with COX-2 inhibitors for cSDH could not be realised in this patient population due to the high prevalence of comorbidities excluding the administration of COX2 inhibitors.

Novel Metal Artifact Reduction Techniques with Use of Slice-Encoding Metal Artifact Correction and View-Angle Tilting MR Imaging for Improved Visualization of Brain Tissue near Intracranial Aneurysm Clips.

PURPOSE: The MR image quality after intracranial aneurysm clipping is often impaired because of artifacts induced by metal implants. The purpose of the present study was to evaluate the benefit of a new WARP sequence with slice-encoding metal artifact correction (SEMAC) and view-angle tilting (VAT) MR imaging as novel artifact reduction techniques. MATERIALS AND METHODS: A new WARP TSE (a work-in-progress software package provided by Siemens Healthcare) sequence was implemented for cranial applications based on a turbo spin echo (TSE) sequence. T1- and T2-weighted images with standard and WARP TSE sequences were acquired from 6 patients with 11 clipping sites, and the images were compared based on artifact size and general image quality. RESULTS: T2- and T1-weighted WARP TSE sequences resulted in a highly significant reduction of metal artifacts compared with standard sequences (T2w- WARP TSE: 89.8 ± 1.4 %; T1w- WARP TSE: 84.9 ± 2.9 %; p < 0.001) without a substantial loss of image quality. CONCLUSION: The use of a new WARP TSE sequence after aneurysm clipping is highly beneficial for increasing the diagnostic MR image quality due to a striking reduction of metal artifacts.

Intraoperative mapping and monitoring in supratentorial tumor surgery.

With the increasing strive for complete resections of supratentorial low or high-grade gliomas, the necessity for intraoperative electrical stimulation methods to map and monitor functional important cortical or subcortical brain areas increased. While many brain functions can be assessed during awake surgery using electrical stimulation, motor function as well as visual function can be mapped and monitored in the asleep patient, as well. Several different methods reviewed in this article are available which lead to an improved functional outcome while increasing the extent of tumor resection and thereby potentially the oncological outcome of the patient.

Prediction of glioma recurrence using dynamic ¹8F-fluoroethyltyrosine PET.

BACKGROUND AND PURPOSE: Inter- and intratumor heterogeneity and the variable course of disease in patients with glioma motivate the investigation of new prognostic factors to optimize individual treatment. Here we explore the usefulness of standard static and more sophisticated dynamic (18)F-fluoroethyltyrosine-PET imaging for the assessment of patient prognosis. MATERIALS AND METHODS: Thirty-four consecutive patients with untreated, first-diagnosed, histologically proved glioma were included in this retrospective study. All patients underwent dynamic PET scans before surgery (± standard treatment) and were followed up clinically and by MR imaging. Static and dynamic tumor-to-background ratio, TTP, and slope-to-peak were obtained and correlated with progression-free survival. RESULTS: Twenty of 34 patients experienced progression, with a median progression-free survival of 28.0 ± 11.1 months. Dynamic TTP was highly prognostic for recurrent disease, showing a strong correlation with progression-free survival (hazard ratio, 6.050; 95% CI, 2.11-17.37; P < .001). Most interesting, this correlation also proved significant in the subgroup of low-grade glioma (hazard ratio, 5.347; 95% CI, 1.05-27.20; P = .044), but not when using established static imaging parameters, such as maximum tumor-to-background ratio and mean tumor-to-background ratio. In the high-grade glioma subgroup, both dynamic and static parameters correlated with progression-free survival. The best results were achieved by defining ROIs around "hot spots" in earlier timeframes, underlining the concept of intratumor heterogeneity. CONCLUSIONS: (18)F-fluoroethyltyrosine-PET can predict recurrence in patients with glioma, with dynamic analysis showing advantages over static imaging, especially in the low-grade subgroup.

Long-term follow-up of standard microdiscectomy versus minimal access surgery for lumbar disc herniations.

BACKGROUND: Surgery of lumbar disc herniations is one of the most common neurosurgical procedures. New surgical approaches and techniques are constantly evolving. We present our long-term follow-up results comparing standard open microdiscectomy (SOMD) and minimal access microdiscectomy (MAMD) for single-level lumbar disc herniations. METHODS: Patients were randomized in two groups receiving either MAMD or SOMD. Physical and mental health and pain relief were assessed (ODI, SF-36 questionnaire, VAS leg and back pain). In addition, all patients received MR imaging for morphological evaluation of postoperative peridural scar tissue formation. RESULTS: Of the 60 initial patients (SOMD: 30 pts, MAMD: 30 pts), 38 were available for long-term follow-up. Mean follow-up time was 33 months. Long-term follow-up revealed significant postoperative pain relief in both groups. Good to excellent results concerning physical and mental health and pain relief were achieved in both groups. Significantly less peridural scar tissue formation was observed in the MAMD patients, but without clinical impact. CONCLUSION: MAMD is a feasible alternative to the standard open approach. Both groups show significant and long-lasting pain relief and good to excellent results regarding health-related quality of life. Congruent to our short-term results, we observed slightly but not statistically significant better clinical results in the MAMD group when compared to the SOMD group.

Treatment of infections of the spine.

Spinal infection may involve the vertebrae, the intervertebral discs, and the adjacent intraspinal and paraspinal soft tissues. It often starts with subtle and insidious clinical signs and symptoms and may development to a debilitating and even life threatening disease. Spinal infections occur with increasing incidence and are nowadays a disease of everyday's practice for physicians treating spinal disorders. Traditionally, conservative treatment consisting of antibiosis and immobilisation is considered the first tier therapy. However, due to a considerably high rate of vertebral column instability or neurological impairment caused by the infected tissue, comprehensive experience with surgical measures have been acquired over the last decades. Thanks to tremendous improvements of surgical implants and techniques, surgical treatment has already begun to challenge conservative treatment to eventually become the first tier therapy for spinal infections in the future. This review seeks to give an overview of epidemiology, pathogenesis, diagnostic evaluation, and current nonsurgical and surgical therapy of spinal infections on the basis of the existing literature, which consists largely of retrospectively acquired data of single-centre experience with sample sizes of less than 100 patients treated with individually defined indications and treatment algorithms, and followed with various outcome parameters.

Murine abortion is associated with enhanced hyaluronan expression and abnormal localization at the fetomaternal interface.

The remodelling of the endometrial architecture is fundamental to create a suitable environment for the establishment of pregnancy. During this process, substantial alterations in the composition of maternal extracellular matrix play an important role by providing a prosperous medium for implantation as well as modulating trophoblast invasion leading to the formation of a functional placental unit. Hyaluronan is a conspicuous component of the extracellular matrix, particularly in remodelling tissues undergoing regeneration and repair. During gestation, changes in HA deposition and distribution indicate that this molecule may participate in preparation of the endometrial stroma for reception and implantation of the embryo. However, little is known about the role of hyaluronan at the fetomaternal interface, specially regarding its influence in pregnancy outcome. In the present study we show increased decidual hyaluronan levels in spontaneous abortion compared with normal pregnancy mice on gestation day 7.5. Both in normal and pathologic pregnancies, high molecular size hyaluronan was found at the fetomaternal unit. However, hyaluronan metabolism (which results from the activity of hyaluronan synthases and hyaluronidases) seems to be altered in spontaneous abortion as shown by a decrease in Hyal-3 expression as well as by differences in hyaluronan molecular size spectrum. This alteration in hyaluronan metabolism in spontaneous abortion could explain its increased concentration observed in decidua and the abnormal distribution of hyaluronan around the embryo implantation crypt. Thus, increased decidual hyaluronan levels resulting from abnormal deposition and turn over may contribute to the pathogenesis of pregnancy failure.