Focal dermal hypoplasia (goltz-gorlin syndrome): A new case with a novel variant in the PORCN gene (c.1250T>C:p.F417S) and unusual spinal anomaly.

Focal dermal hypoplasia (FDH; Goltz-Gorlin syndrome; OMIM 305600) is a disorder that features involvement of the skin, skeletal system, and eyes. It is caused by loss-of-function mutations in the PORCN gene. We report a young girl with FDH, microphthalmos associated with colobomatous orbital cyst, dural ectasia and cystic malformation of the spinal cord, and a de novo variant in PORCN. This association has not been previously reported, and based on these observations the phenotypic spectrum of FDH might be broader than previously appreciated. It would be prudent to alter the suggested surveillance for this rare disorder. © 2013 Wiley Periodicals, Inc.

Clinical and biochemical profiles suggest fibromuscular dysplasia is a systemic disease with altered TGF-β expression and connective tissue features.

Fibromuscular dysplasia (FMD) is a rare, nonatherosclerotic arterial disease for which the molecular basis is unknown. We comprehensively studied 47 subjects with FMD, including physical examination, spine magnetic resonance imaging, bone densitometry, and brain magnetic resonance angiography. Inflammatory biomarkers in plasma and transforming growth factor β (TGF-β) cytokines in patient-derived dermal fibroblasts were measured by ELISA. Arterial pathology other than medial fibrodysplasia with multifocal stenosis included cerebral aneurysm, found in 12.8% of subjects. Extra-arterial pathology included low bone density (P<0.001); early onset degenerative spine disease (95.7%); increased incidence of Chiari I malformation (6.4%) and dural ectasia (42.6%); and physical examination findings of a mild connective tissue dysplasia (95.7%). Screening for mutations causing known genetically mediated arteriopathies was unrevealing. We found elevated plasma TGF-β1 (P=0.009), TGF-β2 (P=0.004) and additional inflammatory markers, and increased TGF-β1 (P=0.0009) and TGF-β2 (P=0.0001) secretion in dermal fibroblast cell lines from subjects with FMD compared to age- and gender-matched controls. Detailed phenotyping of patients with FMD allowed us to demonstrate that FMD is a systemic disease with alterations in common with the spectrum of genetic syndromes that involve altered TGF-β signaling and offers TGF-β as a marker of FMD.

Delay in the Diagnosis of Cerebral Vein and Dural Sinus Thrombosis Influence on Outcome

Background and Purpose-Diagnostic delay of cerebral vein and dural sinus thrombosis may have an impact on outcome. Methods-In the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT) cohort (624 patients with cerebral vein and dural sinus thrombosis), we analyzed the predictors and the impact on outcome of diagnostic delay. Primary outcome was a modified Rankin Scale score > 2 at the end of follow-up. Secondary outcomes were modified Rankin Scale score 0 to 1 at the end of follow-up, death, and visual deficits (visual acuity or visual field). Results-Median delay was 7 days (interquartile range, 3 to 16). Patients with disturbance of consciousness (P < 0.001) and of mental status (P = 0.042), seizure (< 0.001), and with parenchymal lesions on admission CT/MR (P < 0.001) were diagnosed earlier, whereas men (P = 0.01) and those with isolated intracranial hypertension syndrome (P = 0.04) were diagnosed later. Between patients diagnosed earlier and later than the median delay, no statistically significant differences were found in the primary (P = 0.33) and in secondary outcomes: modified Rankin Scale score 0 to 1 (P = 0.86) or deaths (P = 0.53). Persistent visual deficits were more frequent in patients diagnosed later (P = 0.05). In patients with isolated intracranial hypertension syndrome, modified Rankin Scale score > 2 at the end of follow-up was more frequent in patients diagnosed later (P = 0.02). Conclusions-Diagnostic delay was considerable in this cohort and was associated with an increased risk of visual deficit. In patients with isolated intracranial hypertension syndrome, diagnostic delay was also associated with death or dependency. (Stroke. 2009; 40: 3133-3138.)

Risk Score to Predict the Outcome of Patients with Cerebral Vein and Dural Sinus Thrombosis

Background: Around 15% of patients die or become dependent after cerebral vein and dural sinus thrombosis (CVT). Method: We used the International Study on Cerebral Vein and Dural Sinus Thrombosis (ISCVT) sample (624 patients, with a median follow-up time of 478 days) to develop a Cox proportional hazards regression model to predict outcome, dichotomised by a modified Rankin Scale score > 2. From the model hazard ratios, a risk score was derived and a cut-off point selected. The model and the score were tested in 2 validation samples: (1) the prospective Cerebral Venous Thrombosis Portuguese Collaborative Study Group (VENO-PORT) sample with 91 patients; (2) a sample of 169 consecutive CVT patients admitted to 5 ISCVT centres after the end of the ISCVT recruitment period. Sensitivity, specificity, c statistics and overall efficiency to predict outcome at 6 months were calculated. Results: The model (hazard ratios: malignancy 4.53; coma 4.19; thrombosis of the deep venous system 3.03; mental status disturbance 2.18; male gender 1.60; intracranial haemorrhage 1.42) had overall efficiencies of 85.1, 84.4 and 90.0%, in the derivation sample and validation samples 1 and 2, respectively. Using the risk score (range from 0 to 9) with a cut-off of 6 3 points, overall efficiency was 85.4, 84.4 and 90.1% in the derivation sample and validation samples 1 and 2, respectively. Sensitivity and specificity in the combined samples were 96.1 and 13.6%, respectively. Conclusions: The CVT risk score has a good estimated overall rate of correct classifications in both validation samples, but its specificity is low. It can be used to avoid unnecessary or dangerous interventions in low-risk patients, and may help to identify high-risk CVT patients. Copyright (C) 2009 S. Karger AG, Basel

Ectasie sclérale semi-annulaire pré-équatoriale chez un patient glaucomateux onchocerquien [Semi-annular pre-equatorial scleral ectasia in a patient with glaucoma and onchocerciasis].

We present the case of a glaucomatous young patient with onchocerciasis who developed a bilateral pre-equatorial scleral staphyloma with an important scleral thinness. The pathogenesis of anterior staphyloma is discussed: mechanical stress from very high ocular pressure, ocular onchocerciasis, scleral ischemia. A better understanding of scleral mechanical resistance could explain scleral thinness without any clinical scleritis.

Isolated trochlear nerve palsy secondary to dural carotid-cavernous sinus fistula.

Ophthalmoplegia associated with dural carotid-cavernous sinus fistula typically involves the third, fourth, and sixth cranial nerves. Occasionally, isolated palsy of the oculomotor or abducens nerve is noted. We report a patient with bilateral dural carotid-cavernous sinus fistulas who presented with an isolated trochlear nerve palsy.

Introducing a new MRI classification of lumbar spinal stenosis based on cross-sectional morphology of the dural sac : 37

Introduction: Measures of the degree of lumbar spinal stenosis (LSS) such as antero-posterior diameter of the canal, and dural sac cross sectional area vary, and do not correlate with symptoms or results of surgery. We created a grading system, comprised of seven categories, based on the morphology of the dural sac and its contents as seen on T2 axial images. The categories take into account the ratio of rootlet/ CSF content. Grade A indicates no significant compression, grade D is equivalent to a total myelograhic block. We compared this classification with commonly used criteria of severity of stenosis. Methods: Fifty T2 axial MRI images taken at disc level from 27 symptomatic LSS patients undergoing decompressive surgery were classified twice by two radiologists and three spinal surgeons working at different institutions and countries. Dural sac cross-sectional surface area and AP diameter of the canal were measured both at disc and pedicle level from DICOM images using OsiriX software. Intraand inter-observer reliability were assessed using Cohen's, Fleiss' kappa statistics, and t test. Results: For the morphological grading the average intra-and inter observer kappas were 0.76 and 0.69+, respectively, for physicians working in the study originating country. Combining all observers the kappa values were 0.57 ± 0.19. and 0.44 ± 0.19, respectively. AP diameter and dural sac cross-sectional area measurements showed no statistically significant differences between observers. No correlation between morphological grading and AP diameter or dural sac crosssectional areawas observed in 13 (26%) and 8 cases (16%), respectively. Discussion: The proposed morphological grading relies on the identification of the dural sac and CSF better seen on full MRI series. This was not available to the external observers, which might explain the lower overall kappa values. Since no specific measurement tools are needed the grading suits everyday clinical practice and favours communication of degree of stenosis between practising physicians. The absence of a strict correlation with the dural sac surface suggests that measuring the surface alone might be insufficient in defining LSS as it is essentially a mismatch between the spinal canal and its contents. This grading is now adopted in our unit and further studies concentrating on relation between morphology, clinical symptoms and surgical results are underway.

Decision-making in lumbar spinal stenosis: A survey on the influence of the morphology of the dural sac.

Surgical decision-making in lumbar spinal stenosis involves assessment of clinical parameters and the severity of the radiological stenosis. We suspected that surgeons based surgical decisions more on dural sac cross-sectional area (DSCA) than on the morphology of the dural sac. We carried out a survey among members of three European spine societies. The axial T2-weighted MR images from ten patients with varying degrees of DSCA and morphological grades according to the recently described morphological classification of lumbar spinal stenosis, with DSCA values disclosed in half the assessed images, were used for evaluation. We provided a clinical scenario to accompany the images, which were shown to 142 responding physicians, mainly orthopaedic surgeons but also some neurosurgeons and others directly involved in treating patients with spinal disorders. As the primary outcome we used the number of respondents who would proceed to surgery for a given DSCA or morphological grade. Substantial agreement among the respondents was observed, with severe or extreme stenosis as defined by the morphological grade leading to surgery. This decision was not dependent on the number of years in practice, medical density or specialty. Disclosing the DSCA did not alter operative decision-making. In all, 40 respondents (29%) had prior knowledge of the morphological grading system, but their responses showed no difference from those who had not. This study suggests that the participants were less influenced by DSCA than by the morphological appearance of the dural sac. Classifying lumbar spinal stenosis according to morphology rather than surface measurements appears to be consistent with current clinical practice.

Assessment of a new MRI classification of spinal stenosis based on cross-sectional morphology of the dural sac : FM2

Introduction: Quantitative measures of degree of lumbar spinal stenosis (LSS) such as antero-posterior diameter of the canal or dural sac cross sectional area vary widely and do not correlate with clinical symptoms or results of surgical decompression. In an effort to improve quantification of stenosis we have developed a grading system based on the morphology of the dural sac and its contents as seen on T2 axial images. The grading comprises seven categories ranging form normal to the most severe stenosis and takes into account the ratio of rootlet/CSF content. Material and methods: Fifty T2 axial MRI images taken at disc level from twenty seven symptomatic lumbar spinal stenosis patients who underwent decompressive surgery were classified into seven categories by five observers and reclassified 2 weeks later by the same investigators. Intra- and inter-observer reliability of the classification were assessed using Cohen's and Fleiss' kappa statistics, respectively. Results: Generally, the morphology grading system itself was well adopted by the observers. Its success in application is strongly influenced by the identification of the dural sac. The average intraobserver Cohen's kappa was 0.53 ± 0.2. The inter-observer Fleiss' kappa was 0.38 ± 0.02 in the first rating and 0.3 ± 0.03 in the second rating repeated after two weeks. Discussion: In this attempt, the teaching of the observers was limited to an introduction to the general idea of the morphology grading system and one example MRI image per category. The identification of the dimension of the dural sac may be a difficult issue in absence of complete T1 T2 MRI image series as it was the case here. The similarity of the CSF to possibly present fat on T2 images was the main reason of mismatch in the assignment of the cases to a category. The Fleiss correlation factors of the five observers are fair and the proposed morphology grading system is promising.

Eyes wide shut - unusual two stage repair of pectus excavatum and annuloaortic ectasia in a 37 year old marfan patient: Case report

We report about a 37 year old male patient with a pectus excavatum. The patient was in NYHA functional class III. After performed computed tomography the symptoms were thought to be related to the severity of chest deformation. A Ravitch-procedure had been accomplished in a district hospital in 2009. The crack of a metal bar led to a reevaluation 2010, in which surprisingly the presence of an annuloaortic ectasia (root 73 × 74 mm) in direct neighborhood of the formerly implanted metal-bars was diagnosed. Echocardiography revealed a severe aortic valve regurgitation, the left ventricle was massively dilated presenting a reduced ejection fraction of 45%. A marfan syndrome was suspected and the patient underwent a valve sparing aortic root replacement (David procedure) in our institution with an uneventful postoperative course. A review of the literature in combination with discussion of our case suggests the application of stronger recommendations towards preoperative cardiovascular assessment in patients with pectus excavatum.

Atypical headache following dural puncture in obstetrics.

BACKGROUND: In obstetrics, post-dural puncture headache is a well-recognised complication. Typical symptoms include fronto-temporal or occipital headache, worsening with ambulation and improving in the decubitus position. Occasionally, patients present with non-postural headache, although relatively little is known about this atypical presentation. The purpose of this study was to determine the incidence, associated signs and risk factors for this atypical manifestation of post-dural puncture headache. METHODS: We analysed a series of 27 064 parturients having a neuraxial procedure between January 2001 and December 2010. Using data from electronic anaesthesia patient records, medical charts and a postpartum quality audit, we identified all parturients with atypical post-dural puncture headache. We assessed the incidence and used uni- and multivariate analysis to identify associated risk factors. RESULTS: Amongst 142 parturients with post-dural puncture headache, eight (5.6%, 95% CI 1.7-9.4%) had atypical non-postural headache. Associated symptoms were stiffness and pain in the cervical, thoracic or lumbar vertebral area, visual disturbances and vertigo. Significant risk factors for developing atypical signs were previous migraine, odds ratio 6.1 (95% CI 1.2-28.7), a more cephalad level of needle insertion, odds ratio 17.2 (95% CI 1.4-210.1) and identification of dural puncture by aspiration of cerebrospinal fluid from the epidural catheter, odds ratio 5.5 (95% CI 1.2-24.4). Following multivariate analysis, recognition of dural puncture by aspiration of cerebrospinal fluid from the epidural catheter was the most significant predictor of non-orthostatic postdural puncture headache. CONCLUSION: Anaesthetists should be aware of this atypical clinical presentation, particularly if there is a past history of migraine, a more cephalad level of needle insertion or identification of dural puncture by aspiration of cerebrospinal fluid from the epidural catheter.

Influence of the morphology of the dural sac on surgical decision making in lumbar spinal stenosis

Introduction: Surgical decision making in lumbar spinal stenosis (LSS) takes into account primarily clinical symptoms as well as concordant radiological findings. We hypothesized that a wide variation of operative threshold would be found in particular as far as judgment of severity of radiological stenosis is concerned. Patients and methods: The number of surgeons who would proceed to decompression was studied relative to the perceived severity of radiological stenosis based either on measurements of dural sac cross sectional area (DSCA) or on the recently described morphological grading as seen on axial T2 MRI images. A link to an electronic survey page with a set of ten axial T2 MRI images taken from ten patients with either low back pain or LSS were sent to members of three national or international spine societies. Those 10 images were randomly presented initially and re-shuffled on a second page including this time DSCA measurements in mm2, ranging from 14 to 226 mm2, giving a total of 20 images to appraise. Morphological grades were ranging from grade A to D. Surgeons were asked if they would consider decompression given the radiological appearance of stenosis and that symptoms of neurological claudication were severe in patients who were otherwise fit for surgery. Fisher's exact test was performed following dichotomization of data when appropriate. Results: A total of 142 spine surgeons (113 orthopedic spine surgeons, 29 neurosurgeons) responded from 25 countries. A substantial agreement was observed in operating patients with severe (grade C) or extreme (grade D) stenosis as defined by the morphological grade compared to lesser stenosis (A&B) grades (p<0.0001). Decision to operate was not dependent on number of years in practice, medical density in practicing country or specialty although more neurosurgeons would operate on grade C stenosis (p<0.005). Disclosing the DSCA measurement did not alter the decision to operate. Although 20 surgeons only had prior knowledge of the description of the morphological grading, their responses showed no statistically significant difference with those of the remaining 122 physicians. Conclusions: This study showed that surgeons across borders are less influenced by DSCA in their decision making than by the morphological appearance of the dural sac. Classifying LSS according to morphology rather than surface measurements appears to be consistent with current clinical practice.