Spinal Defects Research Articles

A Rare Case of Oeis Complex

OEIS complex is a rare and complex anomaly of the genitourinary and intestinal tract. It includes Omphalocele, Exstrophy of cloaca, Imperforate anus and Spinal defects. Cloacal exstrophy is considered the most severe ventral abdominal wall defect. The defect occurs due to failure of convergence of mesodermal migrations and inability of development of urorectal septum during embryonic life. The failure of these two events to occur manifests as exstrophy of bladder and bowel. Diagnosis is primarily based on the presenting features. Management requires initial resuscitation and stabilization followed by either single staged closure or multi-stage procedures by multi-disciplinary surgical team. We are reporting a case of classical case of OEIS complex managed successfully at our center.

Spinal reconstruction for osteomyelitis with free vascularized fibular grafts using intra‐abdominal recipient vessels: A series of three cases

Reconstruction of bony defects in the surgical management of vertebral osteomyelitis is a challenging endeavor. Our objective is to report the use of intra-abdominal vessels as the recipient vessels for microanastomosis of vascularized bone graft and the use of a spinal cage for fixation. Three patients failed conservative treatment for vertebral osteomyelitis and suffered pathologic fracture. Their treatment consisted of staged posterior irrigation and debridement with segmental fixation, followed by a thoracoabdominal approach multiple-level corpectomy. Reconstruction was performed with a free vascularized fibular graft placed within a custom, expandable cage. The vascularized fibular graft was anastomosed to an intra-abdominal recipient vessel. All patients improved clinically with no neurologic deficits noted. All showed evidence of successful fusion. Free vascularized bone grafts continue to be an excellent option for multi-level spinal defects related to osteomyelitis. Intra-abdominal recipient vessels are appropriate recipient vessels, as their diameter, length, and accessibility allow vascularized bone graft reconstruction of vertebral column defects of the thoracolumbar region. These vessels are also easily accessible and the anastomoses can be performed in the superficial operating incision.

Experimental models of spinal open neural tube defect and Chiari type II malformation

Experimental animal models are essential for investigation of the pathoembryogenesis, pathophysiology, and management strategy of spinal open neural tube defect (ONTD) and its associated anomalies including Chiari type II malformation. Genetic, chemical/nutrient, and surgical models have been widely used for a variety of purposes. The aim of this article is to review the representative animal models of spinal ONTD and associated Chiari type II malformation with respect to their advantages and disadvantages. Among them, the surgical model was described in detail because it is familiar to neurosurgeons and it is used for evaluations of prenatal repair of spinal ONTDs. The surgical model also has advantages because it allows quantitative analysis of the lesions. A description of our previous studies on spinal ONTDs using a chick surgical model is presented as an example.

Idiopathic scoliosis: An overview for school and paediatric nurses

Scoliosis is a medical condition in which a spinal defect is characterized by an abnormal curvature of various degrees, in an S or C shape (Kaushik et al, 2008). Individuals with family members diagnosed with scoliosis have a 20% chance of being diagnosed as well. This article looks at the potential physical and psychological impact of a scoliosis diagnosis. It aims to provide paediatric and school nurses with an overview of the condition, including its history, aetiology, symptoms, screening and diagnosis, common myths, and treatment.

Intracranial Translucency and Spinal Cord Defects: Early Prenatal Diagnosis of Diastematomyelia

Journal of Ultrasound in MedicineVolume 32, Issue 9 p. 1676-1677 Clinical Letters Intracranial Translucency and Spinal Cord Defects: Early Prenatal Diagnosis of Diastematomyelia Makarios Eleftheriades MD, Makarios Eleftheriades MD Second Department of Obstetrics and Gynecology, Aretaieion Hospital, University of Athens, Athens, GreeceSearch for more papers by this authorCharalambos Grigoriadis MD, Charalambos Grigoriadis MD Second Department of Obstetrics and Gynecology, Aretaieion Hospital, University of Athens, Athens, GreeceSearch for more papers by this authorAlexander Sotiriadis MD, Alexander Sotiriadis MD Second Department of Obstetrics and Gynecology, Aretaieion Hospital, University of Athens, Athens, GreeceSearch for more papers by this authorDemetrios Botsis MD, Demetrios Botsis MD Second Department of Obstetrics and Gynecology, Aretaieion Hospital, University of Athens, Athens, GreeceSearch for more papers by this authorAnastasia Konstantinidou MD, Anastasia Konstantinidou MD Department of Pathology, Laikon Hospital, University of Athens, Athens, GreeceSearch for more papers by this authorAthena P. Souka MD, Athena P. Souka MD Third Department of Obstetrics and Gynecology, Attikon Hospital, University of Athens, Athens, GreeceSearch for more papers by this author Makarios Eleftheriades MD, Makarios Eleftheriades MD Second Department of Obstetrics and Gynecology, Aretaieion Hospital, University of Athens, Athens, GreeceSearch for more papers by this authorCharalambos Grigoriadis MD, Charalambos Grigoriadis MD Second Department of Obstetrics and Gynecology, Aretaieion Hospital, University of Athens, Athens, GreeceSearch for more papers by this authorAlexander Sotiriadis MD, Alexander Sotiriadis MD Second Department of Obstetrics and Gynecology, Aretaieion Hospital, University of Athens, Athens, GreeceSearch for more papers by this authorDemetrios Botsis MD, Demetrios Botsis MD Second Department of Obstetrics and Gynecology, Aretaieion Hospital, University of Athens, Athens, GreeceSearch for more papers by this authorAnastasia Konstantinidou MD, Anastasia Konstantinidou MD Department of Pathology, Laikon Hospital, University of Athens, Athens, GreeceSearch for more papers by this authorAthena P. Souka MD, Athena P. Souka MD Third Department of Obstetrics and Gynecology, Attikon Hospital, University of Athens, Athens, GreeceSearch for more papers by this author First published: 01 September 2013 https://doi.org/10.7863/ultra.32.9.1676Citations: 5Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article.Citing Literature Volume32, Issue9September 2013Pages 1676-1677 RelatedInformation

Myelomeningocele: the management of the associated hydrocephalus

The pathogenesis of the hydrocephalus associated with myelomeningocele (MMC) has been the subject of an extensive number of studies. The contemporary reduction of the incidence of the Chiari II malformation and of the associated active hydrocephalus after closure of the spinal defect in utero is in line with previous studies suggesting a prominent role of the posterior cranial fossa abnormalities, where even the increased venous pressure might be at least mostly a consequence of the constriction of the posterior cranial fossa structures. Pure absorptive abnormalities however coexist, the main ones documented to be abnormal cisternal spaces and peculiar cerebrospinal fluid chemical features. We reviewed the pertinent literature concerning the pathogenesis and management of the hydrocephalus associated to MMC. We also reviewed our personal experience in managing the hydrocephalus in such patients through an endoscopic third ventriculostomy. The literature review demonstrated an overall reduction in more recent series of children with MMC needing to be treated for the associated hydrocephalus postnatally, questioning the role of the prenatal care of the disease in this context. Less severe conditions and a more conservative neurosurgical attitude have certainly contributed to the reduction of the reported active postnatal hydrocephalus rate. Long-term cognitive evaluation of the children with MMC that we managed with an endoscopic third ventriculocisternostomy (ETV) as primary as well as secondary procedure did not demonstrate significant differences in the outcome compared with non-complicated extrathecally shunted children, favouring ETV as a valuable option in this subset of patients.

Clinical Manifestations of Goldenhar Syndrome

Goldenhar syndrome is a congenital disorder with diverse clinical presentation. This case series describes variousclinical manifestations of Goldenhar Syndrome. Materials and Methods: 11 patients at least two of the described features of Goldenharsyndrome were randomly included in the study to form a case series. Clinical data of all these subjects was documented, described inpercentages and analyzed. Results: Out of the 11 patients studied, 6 were females and 5 males. Mean age was 7.3 years (ranging from 1year to 23 years). 7 (63.6%) patients had a limbal dermoid, 6 (54.5%) patient had mandibular hypoplasia, whereas only 3(27.3%)presented with hemifacial microsomia. Spinal defects and polydactyly were present in (36.4%) patients each. There was one patient (9%)who had both microphthalmia and lid coloboma in addition to limbal dermoid. Similarly, renal defect (atrophic kidney), cleft upper lip andpalate and CNS defect (7th nerve palsy) were present in one patient (9%) each. None of our patients had either cardiac or GIT defect.Conclusions: In our study we were able to document the variable manifestations of Goldenhar syndrome with their frequencies. Thisknowledge base will help us in planning treatment and assistance strategies or these patients.

Index of Suspicion in the Nursery

A 37-week female infant is born via cesarean delivery due to preeclampsia to a 26-year-old G1 mother. All maternal serologic test results are within normal limits. The pregnancy was complicated by maternal primary generalized epilepsy treated with valproic acid (VPA) and supplemented with folic acid, mild thrombocytopenia attributed to VPA therapy, and increased maternal serum α-fetoprotein level at 17 weeks. Antenatal ultrasound reveals a lumbosacral myelomeningocele and Chiari II malformation. After birth, the infant is noted to have a midline sacral defect and is positioned side-lying. She has mild respiratory distress that improves with continuous positive airway pressure. Apgar scores are 7 and 8 at 1 and 5 minutes, respectively. She is transitioned to a high-humidity nasal cannula and transported to the NICU for further management. On physical examination, the patient’s birthweight is 2.79 kg (25th percentile), length is 51 cm (90th percentile), and head circumference is 29.5 cm (<3rd percentile). She has close-set eyes, a prominent glabella, and epicanthal folds. Her ears are normal in size and position. Her anterior fontanelle is slightly full, with sagittal sutures splayed 1 cm. Her palate is intact, with gag and suck present. Her heart has a regular rate and rhythm with no murmur appreciated. Pulses and perfusion are normal, and breath sounds are clear with moderate aeration. Her abdomen is soft, nontender, and nondistended, with no hepatosplenomegaly. She has spontaneous movement bilaterally at her hips, knees, and ankles. Her spinal defect is located over the lumbosacral area and is 2 cm × 1 cm, with moist reddish-purplish tissue. A 1-cm rim of hemangiomatous tissue is present at the superior and lateral aspects of the lesion. The patient has normal Tanner 1 female genitalia. Anus is patent with anal wink reflex present. She has long thumbs bilaterally with low-set, inverted, and widely spaced …

Spinal bone defects in neurofibromatosis type I with dural ectasia: stress fractures or dysplastic? A case series

Neurofibromatosis type I (NF1) is a multisystem neurocutaneous disorder with varied musculoskeletal manifestations. Dural ectasia is a known association, whilst pedicular anomalies have been described, although not as frequently as other skeletal manifestations. However, reports of pedicular and other spinal clefts or fractures in combination with dural ectasia in NF1 are scarce. We aimed to identify osseous defects in the posterior elements of NF1 patients with dural ectasia. Images of patients with NF1 and back pain were reviewed for osseous defects in the posterior elements. Four patients were identified with NF1, back pain, dural ectasia and bone defects. The imaging appearances of the defects are illustrated. Defects in the spinal posterior elements of patients with NF1, back pain and dural ectasia may be dysplastic, stress fractures or, most probably, multifactorial in origin. Computed tomography demonstrates these defects most clearly.

Cloacal exstrophy with extensive Chiari II malformation: case report and review of the literature

Cloacal exstrophy is a rare condition characterized by a defect in the abdominal wall with extrusion of malformed abdominal contents. The normal separation of the genitourinary and gastrointestinal systems does not occur. While patients with cloacal exstrophy have a high incidence of spinal defects, cranial defects are rare. Chiari malformation has been rarely reported in children with cloacal exstrophy, although the embryogenesis is unknown. In this report, the authors describe a child with cloacal exstrophy and a large myelocystocele. The child also had an extensive Chiari II malformation. We review the relevant embryology and suggest a possible mechanism for Chiari formation in this patient.

Dorsolateraler Zugang und interkorporelle Spondylodese bei Spondylodiszitis der Brust- und Lendenwirbelsäule (TLIF-Technik)

SURGICAL GOAL: Resolve infection and achieve primary stability of instrumentation and permanent fusion of the affected spinal segment by means of debridement of the focus of infection. Defect-filling using autologous/allograft bone or a spacer, as well as immobilization by means of dorsal instrumentation. Acute and chronic thoracolumbar spondylodiscitis. Purely epidural abscesses requiring only decompression (fenestration). Defects whose size make a ventral approach necessary. Classic dorsal approach to the thoracolumbar spine. Pedicle placed using screws depending on the size of the spinal defect for mono-, bi-, or multisegmental spinal fusion. Exposure performed at the level of the infected spinal disc or vertebral body on the more strongly affected side. Focus of infection removed. Depending on the degree of infection, defect filling is carried out using autologous bone or cancellous allograft, followed by rod assembly. Back brace-free follow-up treatment, physiotherapy and back training. Antibiotic administration until inflammation values fall within the normal range, or for at least 14 days. Successful fusion of affected segments, including resolution of infection, is reported in over 90% of cases described in the literature. The revision rate among our mostly multimorbid patient group with an average age of 66 years was 16%. Of 39 of the 114 (34%) patients with preoperative neurological deficits, 26 (66%) demonstrated postoperative regression. Nine patients (23%) showed no improvement, whilst exacerbation of existing neurological deficits was seen in four patients (11%). Staphylococcus was the major pathogen in 34% of cases.

Eps8 controls dendritic spine density and synaptic plasticity through its actin-capping activity

Actin-based remodelling underlies spine structural changes occurring during synaptic plasticity, the process that constantly reshapes the circuitry of the adult brain in response to external stimuli, leading to learning and memory formation. A positive correlation exists between spine shape and synaptic strength and, consistently, abnormalities in spine number and morphology have been described in a number of neurological disorders. In the present study, we demonstrate that the actin-regulating protein, Eps8, is recruited to the spine head during chemically induced long-term potentiation in culture and that inhibition of its actin-capping activity impairs spine enlargement and plasticity. Accordingly, mice lacking Eps8 display immature spines, which are unable to undergo potentiation, and are impaired in cognitive functions. Additionally, we found that reduction in the levels of Eps8 occurs in brains of patients affected by autism compared to controls. Our data reveal the key role of Eps8 actin-capping activity in spine morphogenesis and plasticity and indicate that reductions in actin-capping proteins may characterize forms of intellectual disabilities associated with spine defects.

Yunis-Varón Syndrome Is Caused by Mutations in FIG4, Encoding a Phosphoinositide Phosphatase

Yunis-Varón syndrome (YVS) is an autosomal-recessive disorder with cleidocranial dysplasia, digital anomalies, and severe neurological involvement. Enlarged vacuoles are found in neurons, muscle, and cartilage. By whole-exome sequencing, we identified frameshift and missense mutations of FIG4 in affected individuals from three unrelated families. FIG4 encodes a phosphoinositide phosphatase required for regulation of PI(3,5)P(2) levels, and thus endosomal trafficking and autophagy. In a functional assay, both missense substitutions failed to correct the vacuolar phenotype of Fig4-null mouse fibroblasts. Homozygous Fig4-null mice exhibit features of YVS, including neurodegeneration and enlarged vacuoles in neurons. We demonstrate that Fig4-null mice also have small skeletons with reduced trabecular bone volume and cortical thickness and that cultured osteoblasts accumulate large vacuoles. Our findings demonstrate that homozygosity or compound heterozygosity for null mutations of FIG4 is responsible for YVS, the most severe known human phenotype caused by defective phosphoinositide metabolism. In contrast, in Charcot-Marie-Tooth disease type 4J (also caused by FIG4 mutations), one of the FIG4 alleles is hypomorphic and disease is limited to the peripheral nervous system. This genotype-phenotype correlation demonstrates that absence of FIG4 activity leads to central nervous system dysfunction and extensive skeletal anomalies. Our results describe a role for PI(3,5)P(2) signaling in skeletal development and maintenance.

The adhesion-GPCR BAI1 regulates synaptogenesis by controlling the recruitment of the Par3/Tiam1 polarity complex to synaptic sites.

Excitatory synapses are polarized structures that primarily reside on dendritic spines in the brain. The small GTPase Rac1 regulates the development and plasticity of synapses and spines by modulating actin dynamics. By restricting the Rac1-guanine nucleotide exchange factor Tiam1 to spines, the polarity protein Par3 promotes synapse development by spatially controlling Rac1 activation. However, the mechanism for recruiting Par3 to spines is unknown. Here, we identify brain-specific angiogenesis inhibitor 1 (BAI1) as a synaptic adhesion GPCR that is required for spinogenesis and synaptogenesis in mice and rats. We show that BAI1 interacts with Par3/Tiam1 and recruits these proteins to synaptic sites. BAI1 knockdown results in Par3/Tiam1 mislocalization and loss of activated Rac1 and filamentous actin from spines. Interestingly, BAI1 also mediates Rac-dependent engulfment in professional phagocytes through its interaction with a different Rac1-guanine nucleotide exchange factor module, ELMO/DOCK180. However, this interaction is dispensable for BAI1's role in synapse development because a BAI1 mutant that cannot interact with ELMO/DOCK180 rescues spine defects in BAI1-knockdown neurons, whereas a mutant that cannot interact with Par3/Tiam1 rescues neither spine defects nor Par3 localization. Further, overexpression of Tiam1 rescues BAI1 knockdown spine phenotypes. These results indicate that BAI1 plays an important role in synaptogenesis that is mechanistically distinct from its role in phagocytosis. Furthermore, our results provide the first example of a cell surface receptor that targets members of the PAR polarity complex to synapses.

Abstract 352: Murine model of chordoma: Sonic Hedgehog promoter-driven Cre activation of Brachyury (T) expression induces spinal disk abnormalities and perinatal lethal developmental defects.

Abstract Introduction: Chordoma is a rare malignancy arising in the axial skeleton from notochord remnants. The T-box transcription factor, Brachyury (T), is associated with familial chordoma, is expressed in over 90% of chordomas, and is a driver of cell growth in cultured chordoma cells. Suppression of T expression or function in vitro results in down-regulation of cell growth pathways and reduction in matrix formation. To further understand the mechanisms of T's oncogenic properties, we sought to generate a murine model of constitutive, notochord-directed T expression. Methods: To produce elevated expression of T in the notochord-derived (ND) cells, we generated a murine transgenic animal in which a cassette (T/GFP) containing the β-actin promoter, a transcriptional stop sequence flanked by LoxP sites (FS), the murine T cDNA, an intragenic ribosomal entry sequence and a GFP cDNA was homologously recombined into the ROSA26 locus. We termed these animals FS-T/GFP mice. FS-T/GFP mice were mated to mice with Cre expression regulated by the developmentally-timed and tissue-specific control of the Sonic Hedgehog promoter (Shh-Cre mice). Results: Excision of the FS sequence by Cre was confirmed to result in constitutive expression of T and GFP in 293 cells prior to transgenic creation, and subsequently in cultured fibroblasts from ear punches of the transgenic animals. Mice containing homozygous FS-T/GFP at ROSA26 were healthy with no apparent physiologic or developmental defects and with the expected Mendelian ratios of sex and genotype. A cross of FS-T/GFP with Shh-Cre mice resulted in T/Cre pups that died perinatally with grossly evident heart, lung and kidney defects. In addition, these animals showed incomplete fusion of the vertebral bodies, and dysmorphic spinal disks. Elevated T protein levels and GFP co-expression in disk cells was demonstrated by immunofluorescent detection in tissue sections. Summary: Constitutive expression of T in ND lineage cells results in alteration of the morphology of intervertebral disks possibly indicative of a proliferative effect of Brachyury on ND cells. Expression of T in “off-target” tissues that express Sonic Hedgehog likely results in perinatal death. Citation Format: David A. Alcorta, Jennifer A. Maier, Brian D. Harfe, Michael J. Kelley. Murine model of chordoma: Sonic Hedgehog promoter-driven Cre activation of Brachyury (T) expression induces spinal disk abnormalities and perinatal lethal developmental defects. [abstract]. In: Proceedings of the 104th Annual Meeting of the American Association for Cancer Research; 2013 Apr 6-10; Washington, DC. Philadelphia (PA): AACR; Cancer Res 2013;73(8 Suppl):Abstract nr 352. doi:10.1158/1538-7445.AM2013-352 Note: This abstract was not presented at the AACR Annual Meeting 2013 because the presenter was unable to attend.

Fixing Dendritic Spines in Fragile X

Inhibition of PAK, a protein that regulates the actin cytoskeleton, rescues the dendritic spine defect and behavioral abnormalities in a mouse model of fragile X syndrome.

Morphometric study of the T6 vertebra and its three ossification centers in the human fetus

PurposeKnowledge on the normative growth of the spine is critical in the prenatal detection of its abnormalities. We aimed to study the size of T6 vertebra in human fetuses with the crown-rump length of 115–265 mm.Materials and methodsUsing the methods of computed tomography (Biograph mCT), digital image analysis (Osirix 3.9) and statistics, the normative growth of the T6 vertebral body and the three ossification centers of T6 vertebra in 55 spontaneously aborted human fetuses (27 males, 28 females) aged 17–30 weeks were studied.ResultsNeither male–female nor right–left significant differences were found. The height, transverse, and sagittal diameters of the T6 vertebral body followed natural logarithmic functions as y = −4.972 + 2.732 × ln(age) ± 0.253 (R 2 = 0.72), y = −14.862 + 6.426 × ln(age) ± 0.456 (R 2 = 0.82), and y = −10.990 + 4.982 × ln(age) ± 0.278 (R 2 = 0.89), respectively. Its cross-sectional area (CSA) rose proportionately as y = −19.909 + 1.664 × age ± 2.033 (R 2 = 0.89), whereas its volumetric growth followed the four-degree polynomial function y = 19.158 + 0.0002 × age4 ± 7.942 (R 2 = 0.93). The T6 body ossification center grew logarithmically in both transverse and sagittal diameters as y = −14.784 + 6.115 × ln(age) ± 0.458 (R 2 = 0.81) and y = −12.065 + 5.019 × ln(age) ± 0.315 (R 2 = 0.87), and proportionately in both CSA and volume like y = −15.591 + 1.200 × age ± 1.470 (R 2 = 0.90) and y = −22.120 + 1.663 × age ± 1.869 (R 2 = 0.91), respectively. The ossification center-to-vertebral body volume ratio was gradually decreasing with age. On the right and left, the neural ossification centers revealed the following models: y = −15.188 + 6.332 × ln(age) ± 0.629 (R 2 = 0.72) and y = −15.991 + 6.600 × ln(age) ± 0.629 (R 2 = 0.74) for length, y = −6.716 + 2.814 × ln(age) ± 0.362 (R 2 = 0.61) and y = −7.058 + 2.976 × ln(age) ± 0.323 (R 2 = 0.67) for width, y = −5.665 + 0.591 × age ± 1.251 (R 2 = 0.86) and y = −11.281 + 0.853 × age ± 1.653 (R 2 = 0.78) for CSA, and y = −9.279 + 0.849 × age ± 2.302 (R 2 = 0.65) and y = −16.117 + 1.155 × age ± 1.832 (R 2 = 0.84) for volume, respectively.ConclusionsNeither sex nor laterality differences are found in the morphometric parameters of evolving T6 vertebra and its three ossification centers. The growth dynamics of the T6 vertebral body follow logarithmically for its height, and both sagittal and transverse diameters, linearly for its CSA, and four-degree polynomially for its volume. The three ossification centers of T6 vertebra increase logarithmically in both transverse and sagittal diameters, and linearly in both CSA and volume. The age-specific reference intervals for evolving T6 vertebra present the normative values of potential relevance in the diagnosis of congenital spinal defects.

473 UROLOGIC OUTCOMES AFTER PRIMARY TETHERED CORD RELEASE IN CHILDREN WITH OCCULT SPINAL DYSRAPHISM (OSD): A 10 YEAR SINGLE INSTITUTION REVIEW

You have accessJournal of UrologyPediatrics: Neuropathic Bladder/Reconstruction1 Apr 2013473 UROLOGIC OUTCOMES AFTER PRIMARY TETHERED CORD RELEASE IN CHILDREN WITH OCCULT SPINAL DYSRAPHISM (OSD): A 10 YEAR SINGLE INSTITUTION REVIEW Niki Kanaroglou, Elias Wehbi, Joseph M Gleason, Reva Matta, Joao Pippi Salle, James Drake, Sumit Dave, Armando Lorenzo, and Walid Farhat Niki KanaroglouNiki Kanaroglou Toronto, Canada More articles by this author , Elias WehbiElias Wehbi Toronto, Canada More articles by this author , Joseph M GleasonJoseph M Gleason Toronto, Canada More articles by this author , Reva MattaReva Matta Beirut, Lebanon More articles by this author , Joao Pippi SalleJoao Pippi Salle Toronto, Canada More articles by this author , James DrakeJames Drake Toronto, Canada More articles by this author , Sumit DaveSumit Dave London, Canada More articles by this author , Armando LorenzoArmando Lorenzo Toronto, Canada More articles by this author , and Walid FarhatWalid Farhat Toronto, Canada More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2013.02.1865AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES OSD varies from a clear anatomic abnormality to equivocal MRI pathology in the presence of clinical symptoms. Urologic symptoms (Ux) are sometimes the only indication for neurosurgical intervention but the benefit of this is still unclear. Herein, we describe the urologic outcomes of tethered cord release in children with OSD. METHODS Records of patients aged 0-18 years undergoing primary tethered cord release for OSD at our institution were reviewed (2000-2010). Patients with open spinal defects, lipomyelomeningoceles, secondary tethering, spinal trauma and tumors were excluded. MRI pathology, indications for surgery and the presence of lumbar cutaneous stigmata (CS) were correlated with Ux before and after surgery. Ux included subjective urinary symptoms (eg. frequency, urgency), incontinence, constipation, urinary infections and need for intermittent catheterization. Clinical history, renal ultrasonography and urodynamics (UDS) were assessed. RESULTS 216 patients underwent untethering and 55 met inclusion criteria, with median follow up of 4.7 years (IQR 2.0–6.7). 58%(32/55) had no CS and, as expected, their median age at surgery than those with CS (9.3 vs 2.4 years, p<0.01). The indication for surgery was Ux alone in 46%(25/55) and primarily neurologic (Nx) in 38%(21/55) with CS present in 24%(6/25) and 62%(13/21), respectively. 16%(9/55) had no clinical symptoms but an abnormal MRI ordered due to CS (dermal sinus in 55%, 5/9). Median age at surgery for the Ux, Nx and no-symptom groups were 9.29, 8.65 and 1.21 years, respectively (ANOVA p<0.0001). In the Ux group, mean age at surgery with and without CS was 9 and 7.7 years (p=0.5). Fatty filum was the most common MRI diagnosis both overall (32/55, 58%), and in Ux patients (12/25, 64%). Early and late urologic outcomes for any symptomatic patient in Ux and Nx groups are shown in Table 1. Only subjective urinary symptoms showed a significant improvement. 21 patients with pre and postoperative ultrasounds had no clear improvement in hydronephrosis at last follow up. In the 13 patients with pre and postoperative UDS, detrusor overactivity was the only parameter that significantly improved at median follow up of 15.4 months (10 vs 3 patients, p<0.01). CONCLUSIONS Though Ux may be a common indication for neurosurgical intervention, in our series only subjective urinary symptoms and detrusor overactivity improved after surgery. These findings may help families establish realistic expectations about potential benefits of cord detethering for urologic findings in children with OSD. Table 1. Urologic Outcomes Preoperatively and at 3 and 12 Month Follow Up (N=46) Preoperative Early Follow Up Late Follow Up P value⁎ Subjective Urinary Symptoms 30 26 16 < 0.01 Urinary Incontinence 26 22 18 > 0.25 Constipation 19 15 17 > 0.69 Urinary Tract Infection 9 7 4 > 0.33 Clean Intermittent Catheterization 4 8 5 > 0.42 ⁎ Chi-Squared © 2013 by American Urological Association Education and Research, Inc.FiguresReferencesRelatedDetails Volume 189Issue 4SApril 2013Page: e194 Advertisement Copyright & Permissions© 2013 by American Urological Association Education and Research, Inc.MetricsAuthor Information Niki Kanaroglou Toronto, Canada More articles by this author Elias Wehbi Toronto, Canada More articles by this author Joseph M Gleason Toronto, Canada More articles by this author Reva Matta Beirut, Lebanon More articles by this author Joao Pippi Salle Toronto, Canada More articles by this author James Drake Toronto, Canada More articles by this author Sumit Dave London, Canada More articles by this author Armando Lorenzo Toronto, Canada More articles by this author Walid Farhat Toronto, Canada More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Rescue of fragile X syndrome phenotypes in Fmr1 KO mice by the small-molecule PAK inhibitor FRAX486

Fragile X syndrome (FXS) is the most common inherited form of autism and intellectual disability and is caused by the silencing of a single gene, fragile X mental retardation 1 (Fmr1). The Fmr1 KO mouse displays phenotypes similar to symptoms in the human condition--including hyperactivity, repetitive behaviors, and seizures--as well as analogous abnormalities in the density of dendritic spines. Here we take a hypothesis-driven, mechanism-based approach to the search for an effective therapy for FXS. We hypothesize that a treatment that rescues the dendritic spine defect in Fmr1 KO mice may also ameliorate autism-like behavioral symptoms. Thus, we targeted a protein that regulates spines through modulation of actin cytoskeleton dynamics: p21-activated kinase (PAK). Our results demonstrate that a potent small molecule inhibitor of group I PAKs reverses dendritic spine phenotypes in Fmr1 KO mice. Moreover, this PAK inhibitor--which we call FRAX486--also rescues seizures and behavioral abnormalities such as hyperactivity and repetitive movements, thereby supporting the hypothesis that a drug treatment that reverses the spine abnormalities can also treat neurological and behavioral symptoms. Finally, a single administration of FRAX486 is sufficient to rescue all of these phenotypes in adult Fmr1 KO mice, demonstrating the potential for rapid, postdiagnostic therapy in adults with FXS.

Spinal Reconstruction with Free Vascularised Bone Grafts; Approaches and Selection of Acceptor Vessels

The use of free vascularised bone grafts is an infrequently performed surgical technique for the reconstruction of spinal defects. This field of surgery brings many challenges concerning the choice of free vascularised bone graft, planning of the operative procedure and selection of recipient vessels. This study aims to report our experience with free vascularised bone grafts, with special emphasis on the surgical approach and the selection of recipient vessels. Over a period of 17 years (1994-2011), we used these grafts for anterior spinal reconstruction in 30 patients. In 28 patients, a free vascularised fibular graft was used, and in two cases a free vascularised iliac crest graft was used. The spinal segments reconstructed involved the cervical or cervicothoracic spine (6 cases), the thoracic spine (11 cases) and the thoracolumbar and lumbosacral spine (13 cases). Revascularisation of the free vascularised bone graft proved to be technically feasible in 30 patients, but failed in one fibular graft due to difficulties with recipient vessels in the lumbar region. Technical challenges were met with respect to the choice of the recipient vessel at various anatomical sites. Availability of acceptor vessels was highly de-pendant of the type of surgery (resection or stabilisation) and the selected surgical approach. Based on these findings, a preferred approach is given for each region. The use of free vascularised bone grafts is a valuable technique for the reconstruction of complex spinal disorders. Successful execution requires microvascular expertise with respect to graft harvesting and appropriate choice of recipient vessels. Adequate preoperative planning in a multidisciplinary setting and adherence to the basic principles for spinal reconstruction are required.