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  • 1
    Online Resource
    Online Resource
    AI is a viable alternative to high throughput screening: a 318-target study
    Springer Science and Business Media LLC ; 2024
    In:  Scientific Reports Vol. 14, No. 1 ( 2024-04-02)
    Details
    In: Scientific Reports, Springer Science and Business Media LLC, Vol. 14, No. 1 ( 2024-04-02)
    Abstract: High throughput screening (HTS) is routinely used to identify bioactive small molecules. This requires physical compounds, which limits coverage of accessible chemical space. Computational approaches combined with vast on-demand chemical libraries can access far greater chemical space, provided that the predictive accuracy is sufficient to identify useful molecules. Through the largest and most diverse virtual HTS campaign reported to date, comprising 318 individual projects, we demonstrate that our AtomNet® convolutional neural network successfully finds novel hits across every major therapeutic area and protein class. We address historical limitations of computational screening by demonstrating success for target proteins without known binders, high-quality X-ray crystal structures, or manual cherry-picking of compounds. We show that the molecules selected by the AtomNet® model are novel drug-like scaffolds rather than minor modifications to known bioactive compounds. Our empirical results suggest that computational methods can substantially replace HTS as the first step of small-molecule drug discovery.
    Type of Medium: Online Resource
    ISSN: 2045-2322
    URL: Article
    DOI: 10.1038/s41598-024-54655-z
    Language: English
    Publisher: Springer Science and Business Media LLC
    Publication Date: 2024
    detail.hit.zdb_id: 2615211-3
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  • 2
    Online Resource
    Online Resource
    Skull Fracture Healing in Children Up to 36 Months - A Cohort Analysis
    Elsevier BV ; 2023
    In:  Current Problems in Diagnostic Radiology Vol. 52, No. 4 ( 2023-07), p. 253-256
    Details
    In: Current Problems in Diagnostic Radiology, Elsevier BV, Vol. 52, No. 4 ( 2023-07), p. 253-256
    Type of Medium: Online Resource
    ISSN: 0363-0188
    URL: Article
    DOI: 10.1067/j.cpradiol.2022.11.008
    Language: English
    Publisher: Elsevier BV
    Publication Date: 2023
    detail.hit.zdb_id: 198954-6
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  • 3
    Online Resource
    Online Resource
    Dural augmentation approaches and complication rates after posterior fossa decompression for Chiari I malformation and syringomyelia: a Park-Reeves Syringomyelia Research Consortium study
    Journal of Neurosurgery Publishing Group (JNSPG) ; 2021
    In:  Journal of Neurosurgery: Pediatrics Vol. 27, No. 4 ( 2021-04), p. 459-468
    Details
    In: Journal of Neurosurgery: Pediatrics, Journal of Neurosurgery Publishing Group (JNSPG), Vol. 27, No. 4 ( 2021-04), p. 459-468
    Abstract: Posterior fossa decompression with duraplasty (PFDD) is commonly performed for Chiari I malformation (CM-I) with syringomyelia (SM). However, complication rates associated with various dural graft types are not well established. The objective of this study was to elucidate complication rates within 6 months of surgery among autograft and commonly used nonautologous grafts for pediatric patients who underwent PFDD for CM-I/SM. METHODS The Park-Reeves Syringomyelia Research Consortium database was queried for pediatric patients who had undergone PFDD for CM-I with SM. All patients had tonsillar ectopia ≥ 5 mm, syrinx diameter ≥ 3 mm, and ≥ 6 months of postoperative follow-up after PFDD. Complications (e.g., pseudomeningocele, CSF leak, meningitis, and hydrocephalus) and postoperative changes in syrinx size, headaches, and neck pain were compared for autograft versus nonautologous graft. RESULTS A total of 781 PFDD cases were analyzed (359 autograft, 422 nonautologous graft). Nonautologous grafts included bovine pericardium (n = 63), bovine collagen (n = 225), synthetic (n = 99), and human cadaveric allograft (n = 35). Autograft (103/359, 28.7%) had a similar overall complication rate compared to nonautologous graft (143/422, 33.9%) (p = 0.12). However, nonautologous graft was associated with significantly higher rates of pseudomeningocele (p = 0.04) and meningitis (p 〈 0.001). The higher rate of meningitis was influenced particularly by the higher rate of chemical meningitis (p = 0.002) versus infectious meningitis (p = 0.132). Among 4 types of nonautologous grafts, there were differences in complication rates (p = 0.02), including chemical meningitis (p = 0.01) and postoperative nausea/vomiting (p = 0.03). Allograft demonstrated the lowest complication rates overall (14.3%) and yielded significantly fewer complications compared to bovine collagen (p = 0.02) and synthetic (p = 0.003) grafts. Synthetic graft yielded higher complication rates than autograft (p = 0.01). Autograft and nonautologous graft resulted in equal improvements in syrinx size (p 〈 0.0001). No differences were found for postoperative changes in headaches or neck pain. CONCLUSIONS In the largest multicenter cohort to date, complication rates for dural autograft and nonautologous graft are similar after PFDD for CM-I/SM, although nonautologous graft results in higher rates of pseudomeningocele and meningitis. Rates of meningitis differ among nonautologous graft types. Autograft and nonautologous graft are equivalent for reducing syrinx size, headaches, and neck pain.
    Type of Medium: Online Resource
    ISSN: 1933-0707 , 1933-0715
    URL: Article
    DOI: 10.3171/2020.8.PEDS2087
    RVK:
    XA 55270.2
    Language: Unknown
    Publisher: Journal of Neurosurgery Publishing Group (JNSPG)
    Publication Date: 2021
    detail.hit.zdb_id: 2403990-1
    detail.hit.zdb_id: 2403985-8
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  • 4
    Online Resource
    Online Resource
    Complications and outcomes of posterior fossa decompression with duraplasty versus without duraplasty for pediatric patients with Chiari malformation type I and syringomyelia: a study from the Park-Reeves Syringomyelia Research Consortium
    Journal of Neurosurgery Publishing Group (JNSPG) ; 2022
    In:  Journal of Neurosurgery: Pediatrics Vol. 30, No. 1 ( 2022-07-01), p. 39-51
    Details
    In: Journal of Neurosurgery: Pediatrics, Journal of Neurosurgery Publishing Group (JNSPG), Vol. 30, No. 1 ( 2022-07-01), p. 39-51
    Abstract: The aim of this study was to determine differences in complications and outcomes between posterior fossa decompression with duraplasty (PFDD) and without duraplasty (PFD) for the treatment of pediatric Chiari malformation type I (CM1) and syringomyelia (SM). METHODS The authors used retrospective and prospective components of the Park-Reeves Syringomyelia Research Consortium database to identify pediatric patients with CM1-SM who received PFD or PFDD and had at least 1 year of follow-up data. Preoperative, treatment, and postoperative characteristics were recorded and compared between groups. RESULTS A total of 692 patients met the inclusion criteria for this database study. PFD was performed in 117 (16.9%) and PFDD in 575 (83.1%) patients. The mean age at surgery was 9.86 years, and the mean follow-up time was 2.73 years. There were no significant differences in presenting signs or symptoms between groups, although the preoperative syrinx size was smaller in the PFD group. The PFD group had a shorter mean operating room time (p 〈 0.0001), fewer patients with 〉 50 mL of blood loss (p = 0.04), and shorter hospital stays (p = 0.0001). There were 4 intraoperative complications, all within the PFDD group (0.7%, p 〉 0.99). Patients undergoing PFDD had a 6-month complication rate of 24.3%, compared with 13.7% in the PFD group (p = 0.01). There were no differences between groups for postoperative complications beyond 6 months (p = 0.33). PFD patients were more likely to require revision surgery (17.9% vs 8.3%, p = 0.002). PFDD was associated with greater improvements in headaches (89.6% vs 80.8%, p = 0.04) and back pain (86.5% vs 59.1%, p = 0.01). There were no differences between groups for improvement in neurological examination findings. PFDD was associated with greater reduction in anteroposterior syrinx size (43.7% vs 26.9%, p = 0.0001) and syrinx length (18.9% vs 5.6%, p = 0.04) compared with PFD. CONCLUSIONS PFD was associated with reduced operative time and blood loss, shorter hospital stays, and fewer postoperative complications within 6 months. However, PFDD was associated with better symptom improvement and reduction in syrinx size and lower rates of revision decompression. The two surgeries have low intraoperative complication rates and comparable complication rates beyond 6 months.
    Type of Medium: Online Resource
    ISSN: 1933-0707 , 1933-0715
    URL: Article
    DOI: 10.3171/2022.2.PEDS21446
    RVK:
    XA 55270.2
    Language: Unknown
    Publisher: Journal of Neurosurgery Publishing Group (JNSPG)
    Publication Date: 2022
    detail.hit.zdb_id: 2403990-1
    detail.hit.zdb_id: 2403985-8
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  • 5
    Online Resource
    Online Resource
    The role of occipital condyle and atlas anomalies on occipital cervical fusion outcomes in Chiari malformation type I with syringomyelia: a study from the Park-Reeves Syringomyelia Research Consortium
    Journal of Neurosurgery Publishing Group (JNSPG) ; 2024
    In:  Journal of Neurosurgery: Pediatrics ( 2024-04-01), p. 1-9
    Details
    In: Journal of Neurosurgery: Pediatrics, Journal of Neurosurgery Publishing Group (JNSPG), ( 2024-04-01), p. 1-9
    Abstract: Congenital anomalies of the atlanto-occipital articulation may be present in patients with Chiari malformation type I (CM-I). However, it is unclear how these anomalies affect the biomechanical stability of the craniovertebral junction (CVJ) and whether they are associated with an increased incidence of occipitocervical fusion (OCF) following posterior fossa decompression (PFD). The objective of this study was to determine the prevalence of condylar hypoplasia and atlas anomalies in children with CM-I and syringomyelia. The authors also investigated the predictive contribution of these anomalies to the occurrence of OCF following PFD (PFD+OCF). METHODS The authors analyzed the prevalence of condylar hypoplasia and atlas arch anomalies for patients in the Park-Reeves Syringomyelia Research Consortium database who underwent PFD+OCF. Condylar hypoplasia was defined by an atlanto-occipital joint axis angle (AOJAA) ≥ 130°. Atlas assimilation and arch anomalies were identified on presurgical radiographic imaging. This PFD+OCF cohort was compared with a control cohort of patients who underwent PFD alone. The control group was matched to the PFD+OCF cohort according to age, sex, and duration of symptoms at a 2:1 ratio. RESULTS Clinical features and radiographic atlanto-occipital joint parameters were compared between 19 patients in the PFD+OCF cohort and 38 patients in the PFD-only cohort. Demographic data were not significantly different between cohorts (p 〉 0.05). The mean AOJAA was significantly higher in the PFD+OCF group than in the PFD group (144° ± 12° vs 127° ± 6°, p 〈 0.0001). In the PFD+OCF group, atlas assimilation and atlas arch anomalies were identified in 10 (53%) and 5 (26%) patients, respectively. These anomalies were absent (n = 0) in the PFD group (p 〈 0.001). Multivariate regression analysis identified the following 3 CVJ radiographic variables that were predictive of OCF occurrence after PFD: AOJAA ≥ 130° (p = 0.01), clivoaxial angle 〈 125° (p = 0.02), and occipital condyle–C2 sagittal vertical alignment (C–C2SVA) ≥ 5 mm (p = 0.01). A predictive model based on these 3 factors accurately predicted OCF following PFD (C-statistic 0.95). CONCLUSIONS The authors’ results indicate that the occipital condyle–atlas joint complex might affect the biomechanical integrity of the CVJ in children with CM-I and syringomyelia. They describe the role of the AOJAA metric as an independent predictive factor for occurrence of OCF following PFD. Preoperative identification of these skeletal abnormalities may be used to guide surgical planning and treatment of patients with complex CM-I and coexistent osseous pathology.
    Type of Medium: Online Resource
    ISSN: 1933-0707 , 1933-0715
    URL: Article
    DOI: 10.3171/2024.1.PEDS23229
    RVK:
    XA 55270.2
    Language: Unknown
    Publisher: Journal of Neurosurgery Publishing Group (JNSPG)
    Publication Date: 2024
    detail.hit.zdb_id: 2403990-1
    detail.hit.zdb_id: 2403985-8
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  • 6
    Online Resource
    Online Resource
    Occipital-Cervical Fusion and Ventral Decompression in the Surgical Management of Chiari-1 Malformation and Syringomyelia: Analysis of Data From the Park-Reeves Syringomyelia Research Consortium
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Neurosurgery Vol. 88, No. 2 ( 2021-02), p. 332-341
    Details
    In: Neurosurgery, Ovid Technologies (Wolters Kluwer Health), Vol. 88, No. 2 ( 2021-02), p. 332-341
    Abstract: Occipital-cervical fusion (OCF) and ventral decompression (VD) may be used in the treatment of pediatric Chiari-1 malformation (CM-1) with syringomyelia (SM) as adjuncts to posterior fossa decompression (PFD) for complex craniovertebral junction pathology. OBJECTIVE To examine factors influencing the use of OCF and OCF/VD in a multicenter cohort of pediatric CM-1 and SM subjects treated with PFD. METHODS The Park-Reeves Syringomyelia Research Consortium registry was used to examine 637 subjects with cerebellar tonsillar ectopia ≥ 5 mm, syrinx diameter ≥ 3 mm, and at least 1 yr of follow-up after their index PFD. Comparisons were made between subjects who received PFD alone and those with PFD + OCF or PFD + OCF/VD. RESULTS All 637 patients underwent PFD, 505 (79.2%) with and 132 (20.8%) without duraplasty. A total of 12 subjects went on to have OCF at some point in their management (PFD + OCF), whereas 4 had OCF and VD (PFD + OCF/VD). Of those with complete data, a history of platybasia (3/10, P  = .011), Klippel-Feil (2/10, P  = .015), and basilar invagination (3/12, P   〈  .001) were increased within the OCF group, whereas only basilar invagination (1/4, P   〈  .001) was increased in the OCF/VD group. Clivo-axial angle (CXA) was significantly lower for both OCF (128.8 ± 15.3°, P  = .008) and OCF/VD (115.0 ± 11.6°, P  = .025) groups when compared to PFD-only group (145.3 ± 12.7°). pB-C2 did not differ among groups. CONCLUSION Although PFD alone is adequate for treating the vast majority of CM-1/SM patients, OCF or OCF/VD may be occasionally utilized. Cranial base and spine pathologies and CXA may provide insight into the need for OCF and/or OCF/VD.
    Type of Medium: Online Resource
    ISSN: 0148-396X , 1524-4040
    URL: Article
    DOI: 10.1093/neuros/nyaa460
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 135446-2
    detail.hit.zdb_id: 1491894-8
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  • 7
    Online Resource
    Online Resource
    Radiological and clinical predictors of scoliosis in patients with Chiari malformation type I and spinal cord syrinx from the Park-Reeves Syringomyelia Research Consortium
    Journal of Neurosurgery Publishing Group (JNSPG) ; 2019
    In:  Journal of Neurosurgery: Pediatrics Vol. 24, No. 5 ( 2019-11), p. 520-527
    Details
    In: Journal of Neurosurgery: Pediatrics, Journal of Neurosurgery Publishing Group (JNSPG), Vol. 24, No. 5 ( 2019-11), p. 520-527
    Abstract: Scoliosis is frequently a presenting sign of Chiari malformation type I (CM-I) with syrinx. The authors’ goal was to define scoliosis in this population and describe how radiological characteristics of CM-I and syrinx relate to the presence and severity of scoliosis. METHODS A large multicenter retrospective and prospective registry of pediatric patients with CM-I (tonsils ≥ 5 mm below the foramen magnum) and syrinx (≥ 3 mm in axial width) was reviewed for clinical and radiological characteristics of CM-I, syrinx, and scoliosis (coronal curve ≥ 10°). RESULTS Based on available imaging of patients with CM-I and syrinx, 260 of 825 patients (31%) had a clear diagnosis of scoliosis based on radiographs or coronal MRI. Forty-nine patients (5.9%) did not have scoliosis, and in 516 (63%) patients, a clear determination of the presence or absence of scoliosis could not be made. Comparison of patients with and those without a definite scoliosis diagnosis indicated that scoliosis was associated with wider syrinxes (8.7 vs 6.3 mm, OR 1.25, p 〈 0.001), longer syrinxes (10.3 vs 6.2 levels, OR 1.18, p 〈 0.001), syrinxes with their rostral extent located in the cervical spine (94% vs 80%, OR 3.91, p = 0.001), and holocord syrinxes (50% vs 16%, OR 5.61, p 〈 0.001). Multivariable regression analysis revealed syrinx length and the presence of holocord syrinx to be independent predictors of scoliosis in this patient cohort. Scoliosis was not associated with sex, age at CM-I diagnosis, tonsil position, pB–C2 distance (measured perpendicular distance from the ventral dura to a line drawn from the basion to the posterior-inferior aspect of C2), clivoaxial angle, or frontal-occipital horn ratio. Average curve magnitude was 29.9°, and 37.7% of patients had a left thoracic curve. Older age at CM-I or syrinx diagnosis (p 〈 0.0001) was associated with greater curve magnitude whereas there was no association between syrinx dimensions and curve magnitude. CONCLUSIONS Syrinx characteristics, but not tonsil position, were related to the presence of scoliosis in patients with CM-I, and there was an independent association of syrinx length and holocord syrinx with scoliosis. Further study is needed to evaluate the nature of the relationship between syrinx and scoliosis in patients with CM-I.
    Type of Medium: Online Resource
    ISSN: 1933-0707 , 1933-0715
    URL: Article
    DOI: 10.3171/2019.5.PEDS18527
    RVK:
    XA 55270.2
    Language: Unknown
    Publisher: Journal of Neurosurgery Publishing Group (JNSPG)
    Publication Date: 2019
    detail.hit.zdb_id: 2403990-1
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  • 8
    Online Resource
    Online Resource
    Socioeconomic and demographic factors in the diagnosis and treatment of Chiari malformation type I and syringomyelia
    Journal of Neurosurgery Publishing Group (JNSPG) ; 2022
    In:  Journal of Neurosurgery: Pediatrics Vol. 29, No. 3 ( 2022-03-01), p. 288-297
    Details
    In: Journal of Neurosurgery: Pediatrics, Journal of Neurosurgery Publishing Group (JNSPG), Vol. 29, No. 3 ( 2022-03-01), p. 288-297
    Abstract: The goal of this study was to assess the social determinants that influence access and outcomes for pediatric neurosurgical care for patients with Chiari malformation type I (CM-I) and syringomyelia (SM). METHODS The authors used retro- and prospective components of the Park-Reeves Syringomyelia Research Consortium database to identify pediatric patients with CM-I and SM who received surgical treatment and had at least 1 year of follow-up data. Race, ethnicity, and insurance status were used as comparators for preoperative, treatment, and postoperative characteristics and outcomes. RESULTS A total of 637 patients met inclusion criteria, and race or ethnicity data were available for 603 (94.7%) patients. A total of 463 (76.8%) were non-Hispanic White (NHW) and 140 (23.2%) were non-White. The non-White patients were older at diagnosis (p = 0.002) and were more likely to have an individualized education plan (p 〈 0.01). More non-White than NHW patients presented with cerebellar and cranial nerve deficits (i.e., gait ataxia [p = 0.028], nystagmus [p = 0.002] , dysconjugate gaze [p = 0.03], hearing loss [p = 0.003] , gait instability [p = 0.003], tremor [p = 0.021] , or dysmetria [p 〈 0.001]). Non-White patients had higher rates of skull malformation (p = 0.004), platybasia (p = 0.002), and basilar invagination (p = 0.036). Non-White patients were more likely to be treated at low-volume centers than at high-volume centers (38.7% vs 15.2%; p 〈 0.01). Non-White patients were older at the time of surgery (p = 0.001) and had longer operative times (p 〈 0.001), higher estimated blood loss (p 〈 0.001), and a longer hospital stay (p = 0.04). There were no major group differences in terms of treatments performed or complications. The majority of subjects used private insurance (440, 71.5%), whereas 175 (28.5%) were using Medicaid or self-pay. Private insurance was used in 42.2% of non-White patients compared to 79.8% of NHW patients (p 〈 0.01). There were no major differences in presentation, treatment, or outcome between insurance groups. In multivariate modeling, non-White patients were more likely to present at an older age after controlling for sex and insurance status (p 〈 0.01). Non-White and male patients had a longer duration of symptoms before reaching diagnosis (p = 0.033 and 0.004, respectively). CONCLUSIONS Socioeconomic and demographic factors appear to influence the presentation and management of patients with CM-I and SM. Race is associated with age and timing of diagnosis as well as operating room time, estimated blood loss, and length of hospital stay. This exploration of socioeconomic and demographic barriers to care will be useful in understanding how to improve access to pediatric neurosurgical care for patients with CM-I and SM.
    Type of Medium: Online Resource
    ISSN: 1933-0707 , 1933-0715
    URL: Article
    DOI: 10.3171/2021.9.PEDS2185
    RVK:
    XA 55270.2
    Language: Unknown
    Publisher: Journal of Neurosurgery Publishing Group (JNSPG)
    Publication Date: 2022
    detail.hit.zdb_id: 2403990-1
    detail.hit.zdb_id: 2403985-8
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  • 9
    Online Resource
    Online Resource
    Occipital-Cervical Fusion and Ventral Decompression in the Surgical Management of Chiari-1 Malformation and Syringomyelia: Analysis of Data From the Park-Reeves Syringomyelia Research Consortium
    Ovid Technologies (Wolters Kluwer Health) ; 2021
    In:  Neurosurgery Vol. 89, No. Supplement_2 ( 2021-11-18), p. S89-S89
    Details
    In: Neurosurgery, Ovid Technologies (Wolters Kluwer Health), Vol. 89, No. Supplement_2 ( 2021-11-18), p. S89-S89
    Type of Medium: Online Resource
    ISSN: 0148-396X , 1524-4040
    URL: Article
    DOI: 10.1093/neuros/nyaa460_S089
    RVK:
    XA 10000
    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2021
    detail.hit.zdb_id: 135446-2
    detail.hit.zdb_id: 1491894-8
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  • 10
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    Institutional experience with 500 cases of surgically treated pediatric Chiari malformation Type I : Clinical article
    Journal of Neurosurgery Publishing Group (JNSPG) ; 2011
    In:  Journal of Neurosurgery: Pediatrics Vol. 7, No. 3 ( 2011-03), p. 248-256
    Details
    In: Journal of Neurosurgery: Pediatrics, Journal of Neurosurgery Publishing Group (JNSPG), Vol. 7, No. 3 ( 2011-03), p. 248-256
    Abstract: The diagnosis and treatment of Chiari malformation Type I (CM-I) has evolved over the last few decades. The authors present their surgical experience of over 2 decades of treating children with this form of hindbrain herniation. Methods The authors conducted a retrospective review of their institutional experience with the surgical treatment of the pediatric CM-I from 1989 to 2010. Results The 2 most common presentations were headache/neck pain (40%) and scoliosis (18%). Common associated diagnoses included neurofibromatosis Type 1 (5%) and idiopathic growth hormone deficiency (4.2%). Spine anomalies included scoliosis (18%), retroversion of the odontoid process (24%), Klippel-Feil anomaly (3%), and atlantooccipital fusion (8%). Approximately 3% of patients had a known family member with CM-I. Hydrocephalus was present in 48 patients (9.6%). Syringomyelia was present in 285 patients (57%), and at operation, 12% of patients with syringomyelia were found to have an arachnoid veil occluding the fourth ventricular outlet. Fifteen patients (3%) have undergone reoperation for continued symptoms or persistent large syringomyelia. The most likely symptoms and signs to resolve following surgery were Valsalva-induced headache and syringomyelia. The average hospital stay and “return to school” time were 3 and 12 days, respectively. The follow-up for this group ranged from 2 months to 15 years (mean 5 years). Complications occurred in 2.4% of cases; there was no mortality. No patient required acute return to the operating room, and no blood transfusions were performed. Conclusions The authors believe this to be the largest reported series of surgically treated pediatric CM-I patients and hope that their experience will be of use to others who treat this surgical entity.
    Type of Medium: Online Resource
    ISSN: 1933-0707 , 1933-0715
    URL: Article
    DOI: 10.3171/2010.12.PEDS10379
    RVK:
    XA 55270.2
    Language: Unknown
    Publisher: Journal of Neurosurgery Publishing Group (JNSPG)
    Publication Date: 2011
    detail.hit.zdb_id: 2403990-1
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