OBJECTIVE: The pathogenesis of CM-I is incompletely understood. We describe an association of CM-I and TCS that occurs in a subset of patients with normal size of the PCF. METHODS: The prevalence of TCS was determined in a consecutively accrued cohort of 2987 patients with CM-I and 289 patients with low-lying cerebellar tonsils (LLCT). Findings in 74 children and 244 adults undergoing SFT were reviewed retrospectively. Posterior cranial fossa size and volume were measured using reconstructed 2D computed tomographic scans and MR images. Results were compared to those in 155 age- and sex-matched healthy control individuals and 280 patients with generic CM-I. The relationships of neural and osseus structures at the CCJ and TLJ were investigated morphometrically on MR images. Intraoperative CDU was used to measure anatomical structures and CSF flow in the lumbar theca. RESULTS: Tethered cord syndrome was present in 408 patients with CM-I (14%) and 182 patients with LLCT (63%). In 318 patients undergoing SFT, there were no significant differences in the size or volume of the PCF as compared to healthy control individuals. Morphometric measurements demonstrated elongation of the brain stem (mean, 8.3 mm; P <.001), downward displacement of the medulla (mean, 4.6 mm; P <.001), and normal position of the CMD except in very young patients. Compared to patients with generic CM-I, the FM was significantly enlarged (P <.001). The FT was typically thin and taut (mean transverse diameter, 0.8 mm). After SFT, the cut ends of the FT distracted widely (mean, 41.7 mm) and CSF flow in the lumbar theca increased from a mean of 0.7 cm/s to a mean of 3.7 cm/s (P <.001). Symptoms were improved or resolved in 69 children (93%) and 203 adults (83%) and unchanged in 5 children (7%) and 39 adults (16%) and, worse, in 2 adults (1%) over a follow-up period of 6 to 27 months (mean, 16.1 months +/- 4.6 SD). Magnetic resonance imaging 1 to 18 months after surgery (mean, 5.7 months +/- 3.8 SD) revealed upward migration of the CMD (mean, 5.1 mm, P <.001), ascent of the cerebellar tonsils (mean, 3.8 mm, P <.001), reduction of brain stem length (mean, 3.9 mm, P <.001), and improvement of scoliosis or syringomyelia in some cases. CONCLUSIONS: Chiari malformation type I/TCS appears to be a unique clinical entity that occurs as a continuum with LLCT/TCS and is distinguished from generic CM-I by enlargement of the FM and the absence of a small PCF. Distinctive features include elongation and downward displacement of the hindbrain, normal position of the CMD, tight FT, and reduced CSF flow in the lumbar theca. There is preliminary evidence that SFT can reverse moderate degrees of tonsillar ectopia and is appropriate treatment for cerebellar ptosis after Chiari surgery in this cohort.

Structural cardiovascular alterations in the classical and hypermobile forms of Ehlers-Danlos syndrome(EDS) warrant investigation. We have examined a cohort of 38 patients with hypermobile and classical EDSs using two-dimensional echocardiography. The cohort includes 7 males and 31 females, with an age range from 12-60 years. Altered echocardiographic parameters were seen in the initial cross-sectional data analysis in 24/38 patients. Five of the 38 participants had mildly dilated aortic root (AR) or sinuses of Valsalva (SV), and an additional 7 patients had an abnormal pouching of the SV, although the absolute dimensions did not exceed the normal range. Ten patients had mild mitral, tricuspid, or aortic regurgitation, and only one patient had mitral valve prolapse (MVP). Three patients had low normal systolic function; three had evidence of mildly elevated pulmonary pressures, and two patients had mild concentric left ventricular hypertrophy (LVH). Five patients had evidence of impaired left ventricular relaxation (LVR) based on mitral valve E to A velocity ratio. Interestingly, 26/38 subjects demonstrated a prominent right coronary artery (RCA) easily visualized by trans-thoracic echocardiography, and 10/38 had an elongated cardiac silhouette on the 4-chamber apical views. The "pouching" shape of the SV was more common in hypermobile type than in the classical type of EDS. The study is ongoing and will accrue longitudinal data on 100 subjects with classical and hypermobile EDSs at 2-year intervals. Published 2005 Wiley-Liss, Inc.

OBJECTIVE AND IMPORTANCE: Syringomyelia is generally regarded as a chronic, slowly progressive disorder. We describe a case of acute dilation of the central canal of the spinal cord that presented with rapidly progressive segmental signs. CLINICAL PRESENTATION: A 29-year-old female patient who had previously undergone surgical treatment for a Chiari I malformation, syringomyelia, and hydrocephalus presented with an 8-day history of headaches, progressive paraparesis, and urinary retention. Magnetic resonance imaging scans demonstrated panventricular hydrocephalus in association with a holocord syrinx that extended to the obex. Magnetic resonance imaging scans that had been coincidentally obtained just 3 days before the onset of symptoms had revealed no evidence of hydrocephalus or syringomyelia. INTERVENTION: The patient underwent emergency revision of a failed ventriculoperitoneal shunt. Postoperatively, there was prompt resolution of the syringomyelia, hydrocephalus, and associated neurological deficits. CONCLUSION: Among patients with communicating syringomyelia, the central canal of the spinal cord participates as a "fifth ventricle" and can undergo rapid dilation in association with acute hydrocephalus. Appropriate treatment in such cases involves placement of a ventriculoperitoneal shunt.

OBJECTIVE: We describe an operative technique for Chiari Type I malformation that uses color Doppler ultrasonography as a guide for performing patient-specific posterior fossa decompressions. The technique has been used since 1999 in more than 300 operations. METHODS: On the basis of real-time anatomic and physiological measurements, the following goals of surgery were monitored: 1) adequate decompression of the cervicomedullary junction; 2) creation of a retrocerebellar space of 8 to 10 cm(3) volume; and 3) establishment of optimal cerebrospinal fluid flow between the cranial and spinal compartments. RESULTS: The size of the craniectomy was tailored to conform to the area of cerebellar impaction as demarcated by compressed subarachnoid spaces. A laminectomy was not performed unless the cerebellar tonsils were herniated below C1. Before opening the dura, color Doppler ultrasonography imaging was invaluable in planning operative strategies. A simple duraplasty without additional steps was found to be appropriate treatment in occasional patients with minimal tonsillar herniation (5-8 mm). In all other cases, it was necessary to perform an internal decompression that included lysis of the arachnoid and shrinkage of the cerebellar tonsils to achieve the goals of surgery. Optimal cerebrospinal fluid flow through the foramen magnum in anesthetized, prone patients was found to have the following characteristics: a peak velocity of 3 to 5 cm/s, bidirectional movement, and a waveform exhibiting vascular and respiratory variations. The attainment of surgical goals was confirmed in most patients by postoperative neuroimaging. CONCLUSION: Color Doppler ultrasonography imaging is an important technological advance that permits the neurosurgeon to tailor the steps of Chiari surgery according to patient-specific variables. The success of this technique depends on the mastery of a new and sophisticated monitoring modality.

Congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency is an autosomal recessive disorder and is the most common cause of ambiguous genitalia in the newborn. The genes encoding 21-hydroxylase, CYP21A2, and tenascin-X (TNX), TNXB, are located within the HLA complex, in a region of high gene density termed the RCCX module. The module has multiple pseudogenes as well as tandem repeat sequences that promote misalignment during meiosis leading to complex gene rearrangements, deletions and gene conversion events. CYP21A2 mutations cause CAH, and TNX deficiency has been identified as a cause of hypermobility type Ehlers-Danlos syndrome (EDS). Here we report on a three-generation family with a heterozygous deletion encompassing CYP21A2 and TNXB that initially came to medical attention due to the diagnosis of CAH in the proposita. Southern blotting and PCR-based analysis of the RCCX module revealed a CYP21A2 deletion extending into TNXB in one allele and a CYP21A2 point mutation in the other allele. Family history is notable for joint hypermobility. Additional radiological and clinical investigations showed a quadricuspid aortic valve, single kidney, bicornuate uterus and a bifid uvula in the proposita, and mitral valve prolapse in her mother. These findings further delineate the phenotype of the CAH-TNX contiguous gene deletion syndrome and point to an intersection of connective tissue dysplasias with a common gene-mediated endocrine disorder.(c) 2009 Wiley-Liss, Inc.

OBJECTIVES: There has been debate regarding the safety of performing elective procedures in patients with vascular manifestations associated with Ehlers-Danlos syndrome (EDS). The purpose of this study was to review the surgical management and clinical outcomes of EDS patients undergoing vascular procedures at a tertiary medical center with multimodality expertise in connective tissue disorders. METHODS: All patients with EDS undergoing endovascular and open vascular procedures at a single-institution academic medical center from 1994 to 2009 were retrospectively reviewed. Clinical data were evaluated including patient demographics, length of stay (LOS), and mortality outcomes during hospital course and long-term follow-up. RESULTS: A total of 40 patients with EDS were identified, including individuals diagnosed with classic (n = 15), hypermobility (n = 16), and vascular (n = 9) types of EDS. These patients collectively underwent 45 endovascular and 18 open procedures for vascular disease during the time period, including embolization (n = 37), angioplasty (n = 8), arterial bypass (n = 5), and aortic aneurysm repair (n = 13). All cases were performed electively, except for one (2%) urgent endovascular and one (5%) emergent open procedure. Endovascular procedures were associated with a median LOS (interquartile range [IQR]) of 2 (1 to 3) days with no procedure-related mortality or in-hospital deaths among all EDS types, whereas open vascular procedures had median LOS (IQR) of 6 (5 to 8) days with one (6%) in-hospital death occurring in a vascular EDS patient. Survival free of any complication at 5 years was 85% and 54% following endovascular and open procedures, respectively. CONCLUSIONS: The elective surgical management of vascular disorders in EDS patients using open and endovascular procedures has been associated with good outcomes. Our results suggest that vascular interventions in these EDS patients can be safely performed and should not be withheld until rupture or acute symptoms arise.

BACKGROUND:-Marfan syndrome (MFS) is caused by mutations in the fibrillin-1 gene and dysregulation of transforming growth factor-beta (TGF-beta). Recent evidence suggests that losartan, an angiotensin II type 1 blocker that blunts TGF-beta activation, may be an effective treatment for MFS. We hypothesized that dysregulation of TGF-beta might be mirrored in circulating TGF-beta concentrations. Methods and Results-Serum obtained from MFS mutant mice (Fbn1(C1039G/+)) treated with losartan was analyzed for circulating TGF-beta1 concentrations and compared with those from placebo-treated and wild-type mice. Aortic root size was measured by echocardiography. Data were validated in patients with MFS and healthy individuals. In mice, circulating total TGF-beta1 concentrations increased with age and were elevated in older untreated Fbn1(C1039G/+) mice compared with wild-type mice (P=0.01; n=16; mean+/-SEM, 115+/-8 ng/mL versus n=17; mean+/-SEM, 92+/-4 ng/mL). Losartan-treated Fbn1(C1039G/+) mice had lower total TGF-beta1 concentrations compared with age-matched Fbn1(C1039G/+) mice treated with placebo (P=0.01; n=18; 90+/-5 ng/mL), and circulating total TGF-beta1 levels were indistinguishable from those of age-matched wild-type mice (P=0.8). Correlation was observed between circulating TGF-beta1 levels and aortic root diameters in Fbn1(C1039G/+) and wild-type mice (P=0.002). In humans, circulating total TGF-beta1 concentrations were elevated in patients with MFS compared with control individuals (P<0.0001; n=53; 15+/-1.7 ng/mL versus n=74; 2.5+/-0.4 ng/mL). MFS patients treated with losartan (n=55) or beta-blocker (n=80) showed significantly lower total TGF-beta1 concentrations compared with untreated MFS patients (P</=0.05). Conclusions-Circulating TGF-beta1 concentrations are elevated in MFS and decrease after administration of losartan, beta-blocker therapy, or both and therefore might serve as a prognostic and therapeutic marker in MFS.

OBJECTIVES: To describe a cranioplasty procedure used in conjunction with foramen magnum decompression (FMD) for the treatment of canine caudal occipital malformation syndrome (COMS), and to evaluate the clinical outcome. STUDY DESIGN: Prospective clinical study. ANIMALS: Dogs (n=21) with COMS diagnosed by magnetic resonance imaging (MRI). METHODS: After FMD, titanium screws were placed around the perimeter of the foramen magnum defect and a skull plate fashioned from titanium mesh and polymethylmethacrylate was attached to the back of the skull, using the titanium screws as anchor posts. Follow-up was obtained by direct examination by the authors, telephone interviews with owners and referring veterinarians, and a questionnaire sent to owners of surviving dogs designed to assign objective measures of response to surgical intervention. Surgical success was defined as improvement in >or=1 aspects of clinical dysfunction (e.g. scratching, pain) postoperatively. Owner-assigned pre- and postoperative quality-of-life (QOL) scores (1-5) for surviving dogs were compared using a Wilcoxon's signed rank test for paired data (P<or=.05). RESULTS: No intraoperative complications occurred and postoperative complications were limited to transient worsening of a pre-existing head tilt and ataxia in 1 dog, and the need for oral pain medication for 1-4 weeks in 3 dogs. Seventeen dogs (81%) had clinical improvement after surgery. Although clinical signs resolved in 1 dog, it died after being hit by a car, 5 months after surgery. One dog had no change in clinical signs; this patient's clinical signs were not severe and the owners had opted for surgery primarily to prevent progression of disease. Two dogs were euthanatized; 1 because of no improvement of severe clinical signs, and 1 because of sustained recurrence of apparent head and neck pain 7 months later. One dog required a dorsal laminectomy at a second site (C1/C2 vertebral level), 2 months later. Four dogs has transient "flare-ups" of apparent head/neck pain 2-13 months later; all resolved with transient re-institution of oral analgesic therapy. Further surgery at the FMD was not needed. Based on the returned questionnaires, there was an overall significant improvement in QOL scores. CONCLUSIONS: FMD with cranioplasty was well tolerated, with no intraoperative complications, and minor postoperative complications. Most dogs improved clinically, and none required further surgery at the original FMD site. CLINICAL RELEVANCE: FMD with cranioplasty may be an effective surgical method of treating dogs with COMS and is well tolerated. Based on prior reports of FMD for this disorder, it appears that cranioplasty may reduce the rate of surgical failure caused by formation of compressive scar tissue at the FMD site in the short term. Results of this preliminary study support further evaluation of the cranioplasty procedure in a larger group of dogs over a more extended follow-up period.

Posterior C1-2 fixation with individual screw placement in C-1 and C-2 was performed in three patients presenting with progressive myelopathy caused by retro-odontoid pseudotumor associated with chronic atlantoaxial subluxation. Postoperatively, all patients demonstrated neurological recovery with gradually diminishing pseudotumor. Posterior C1-2 fixation with the cancellous screw and rod system is a safe and reliable method, and can be used to treat retro-odontoid pseudotumor associated with chronic atlantoaxial subluxation.

Joint hypermobility syndrome (JHS) was initially defined as the occurrence of musculoskeletal symptoms in the presence of joint laxity and hypermobility in otherwise healthy individuals. It is now perceived as a commonly overlooked, underdiagnosed, multifaceted, and multisystemic heritable disorder of connective tissue (HDCT), which shares many of the phenotypic features of other HDCTs such as Marfan syndrome and Ehlers-Danlos syndrome. Whereas the additional flexibility can confer benefits in terms of mobility and agility, adverse effects of tissue laxity and fragility can give rise to clinical consequences that resonate far beyond the confines of the musculoskeletal system. There is hardly a clinical specialty to be found that is not touched in one way or another by JHS. Over the past decade, it has become evident that of all the complications that may arise in JHS, chronic pain is arguably the most menacing and difficult to treat.

Microcrystalline arthritis sometimes have atypical localizations and presentations. The crowned dens syndrome, due to hydroxyapatite or calcium pyrophosphate deposits in peri-odontoid ligaments of the atlas, can provoke acute or chronic cervicalgia or misleading presentations such as meningitidis or fever of unknown origin. We present a particularly severe new case requesting urgent surgery, and a literature review to alert clinicians and prevent misdiagnosing this syndrome. Indeed, calcifications may be very discrete or just incidental and prevent a complete diagnostic approach.

The linear dimensions and volume of the posterior fossa, and the length of the supra-occiput and the clivus in children with Chiari I malformations (CMI) were studied. A statistical relationship between patient demographics, radiological features, posterior fossa and occipital bone morphometry in the study and control groups was investigated. The results of 21 pediatric patients was compared to those of a matched control group. The posterior fossa volume (PFV) of an adult CMI group was also studied. Linear measurements were used to calculate the length of the occipital bone, spherical PFV and intracranial volume (ICV) using pre-operative MRI and CT scans. A PFV to ICV ratio was obtained to standardize the comparison. The volumetric measurement in the pediatric study group was also compared to the adult CMI group. The antero-posterior dimension, width, and volume of the posterior fossa and the PFV to ICV ratio in pediatric CMI patients was significantly lower than in the control group (p<0.05). There was no statistical difference in the length of the clivus and the supra-occiput between the two pediatric groups. The difference in the PFV to ICV ratio between pediatric and adult CMI patients was not statistically significant. Thus, the authors provide a simple, yet accurate, and reproducible method of comparison of posterior fossa volume in patients with CMI in different age groups, based on linear measurements. There is no significant difference between the length of the occipital bone at the base of the skull in pediatric CMI patients and the normal pediatric population. Development of the clivus due to late fusion of the sphenoid and occipital synchondroses in the second decade could result in manifestation of the disease in adulthood in CMI patients who were asymptomatic as children.

OBJECTIVE: The pathogenesis of CM-I is incompletely understood. We describe an association of CM-I and TCS that occurs in a subset of patients with normal size of the PCF. METHODS: The prevalence of TCS was determined in a consecutively accrued cohort of 2987 patients with CM-I and 289 patients with low-lying cerebellar tonsils (LLCT). Findings in 74 children and 244 adults undergoing SFT were reviewed retrospectively. Posterior cranial fossa size and volume were measured using reconstructed 2D computed tomographic scans and MR images. Results were compared to those in 155 age- and sex-matched healthy control individuals and 280 patients with generic CM-I. The relationships of neural and osseus structures at the CCJ and TLJ were investigated morphometrically on MR images. Intraoperative CDU was used to measure anatomical structures and CSF flow in the lumbar theca. RESULTS: Tethered cord syndrome was present in 408 patients with CM-I (14%) and 182 patients with LLCT (63%). In 318 patients undergoing SFT, there were no significant differences in the size or volume of the PCF as compared to healthy control individuals. Morphometric measurements demonstrated elongation of the brain stem (mean, 8.3 mm; P <.001), downward displacement of the medulla (mean, 4.6 mm; P <.001), and normal position of the CMD except in very young patients. Compared to patients with generic CM-I, the FM was significantly enlarged (P <.001). The FT was typically thin and taut (mean transverse diameter, 0.8 mm). After SFT, the cut ends of the FT distracted widely (mean, 41.7 mm) and CSF flow in the lumbar theca increased from a mean of 0.7 cm/s to a mean of 3.7 cm/s (P <.001). Symptoms were improved or resolved in 69 children (93%) and 203 adults (83%) and unchanged in 5 children (7%) and 39 adults (16%) and, worse, in 2 adults (1%) over a follow-up period of 6 to 27 months (mean, 16.1 months +/- 4.6 SD). Magnetic resonance imaging 1 to 18 months after surgery (mean, 5.7 months +/- 3.8 SD) revealed upward migration of the CMD (mean, 5.1 mm, P <.001), ascent of the cerebellar tonsils (mean, 3.8 mm, P <.001), reduction of brain stem length (mean, 3.9 mm, P <.001), and improvement of scoliosis or syringomyelia in some cases. CONCLUSIONS: Chiari malformation type I/TCS appears to be a unique clinical entity that occurs as a continuum with LLCT/TCS and is distinguished from generic CM-I by enlargement of the FM and the absence of a small PCF. Distinctive features include elongation and downward displacement of the hindbrain, normal position of the CMD, tight FT, and reduced CSF flow in the lumbar theca. There is preliminary evidence that SFT can reverse moderate degrees of tonsillar ectopia and is appropriate treatment for cerebellar ptosis after Chiari surgery in this cohort.

OBJECTIVES/HYPOTHESIS:: Operative intervention of anterior skull base lesions is challenging. Various endoscopic surgical approaches have been described. The goal of the present study is to perform a radiographic analysis of the endoscopic transnasal approach to the clivus. STUDY DESIGN:: Anatomic study utilizing computed tomography (CT). METHODS:: High-resolution surgical-guidance CT images of the sinuses from 97 patients at a tertiary care medical center between 2002 and 2007 were evaluated. Axial and sagittal images were used to evaluate surgical access to the clivus. Multiple anatomical measurements were obtained and analyzed with imaging and statistical software. RESULTS:: Of the 97 imaging studies, there were 39 males and 58 females. The width of exposure of the clivus without removal of the septum was 2.7 cm (1.9-3.4 cm) and with removal of the bony septum was 3.6 cm (2.6-4.8 cm)(P <.001). No patients had complete exposure of the width of the clivus without the septum removed compared to 56 (58%) patients with the septum removed. Endoscopic exposure of the inferior and superior limits of the clivus was not limited in any images studied. CONCLUSIONS:: The endoscopic transnasal approach to the clivus is a viable option in the treatment of anterior skull base lesions with the preservation of functional anatomy in select patients. A large portion of the population has limited lateral exposure secondary to the eustachian tube and the medial pterygoid plate with an endoscopic transnasal approach. Vertically, this approach allows complete access to the clivus in all patients studied. Laryngoscope, 2009.

The imaging features of four dogs with atlanto-occipital overlapping are described. This malformation appeared to play a role in the development of neck pain, ataxia, variable cerebellar involvement, medullary kinking, and possibly syringomyelia. Using cervical radiographs, three of the four dogs were initially diagnosed with an atlanto-axial malformation. Because this disorder could not account for all clinical signs, magnetic resonance and computed tomography images were also acquired. These provided a more complete evaluation of the craniocervical junction, allowing detection of atlanto-occipital overlapping, medullary kinking, occipital dysplasia, abnormalities of the dens, and syringomyelia in these dogs. Head position during imaging affected the degree of atlanto-occipital overlap. These findings emphasize the need to modify the currently accepted imaging recommendations for dogs with head and neck pain and/or cranial cervical myelopathy. We suggest that the entire craniocervical junction be evaluated, even if atlanto-axial subluxation has already been detected. Moreover, we propose that atlanto-occipital overlapping is a perhaps underrecognized disorder that can influence the clinical signs and therapeutic outcome of dogs with anomalies of the craniocervical junction.

RATIONALE AND OBJECTIVES: To determine whether angled gantry acquisition might be used to image the heart with a shorter scan length and reduced breast exposure during coronary computed tomography angiography. MATERIALS AND METHODS: One hundred consecutive coronary computed tomography angiography examinations of female patients were retrospectively evaluated to define the angle between the long axis of the left heart and the axial imaging plane. The scan length required to image the entire left ventricle along with the coronary arteries was measured for an axial scan plane as well as for a scan plane parallel to the long axis of the left heart. The overlap between these imaging volumes and the lower portion of the breast was measured. RESULTS: The long axis of the left heart varied from 7 degrees to 54 degrees off the axial plane (mean 32 degrees +/- 7 degrees ). The required scan length to include the entire left ventricle and coronary arteries ranged from 8.2 to 12.4 cm (mean, 10.0 +/- 0.9 cm) for the axial scan plane and 5.6-10.1 cm (mean, 7.5 +/- 0.8 cm) for a scan plane parallel to the long axis of the heart (P <.001). cCTA in the axial plane required a 7.4 +/- 1.6 cm overlap with the lower breast, whereas cCTA in the long axis of the heart reduced the overlap to 4.5 +/- 1.8 cm (P <.001). CONCLUSIONS: Using an angled gantry approach, the coronary arteries can be fully imaged in a plane along the long axis of the left heart with a single 10-cm acquisition and with substantial reduction in amount of breast tissue within the irradiated field.

The authors report the case of a 35-year-old man who had polyarthritic affliction with rheumatoid disease. He presented with complaints of quadriparesis that had progressed over the course of 2 years. Investigations revealed telltale evidence of rheumatoid disease of the craniovertebral junction with retroodontoid pannus, basilar invagination, and "fixed" atlantoaxial dislocation. The patient underwent lateral mass reconstruction with distraction of the facets and impaction of a spiked metal spacer and bone graft within the joint. Investigations done in the immediate postoperative phase showed complete disappearance of retroodontoid pannus in addition to reduction of basilar invagination and atlantoaxial dislocation. He had remarkable and sustained relief from symptoms. The authors also review the pathogenesis and treatment of retroodontoid pannus.