A successful combined spinal-epidural anesthesia for cesarean section in a patient with neurofibromatosis type 1-associated dural ectasia.

BACKGROUND: Dural ectasia is a common manifestation of neurofibromatosis type 1. Although there have been reports of unsuccessful spinal anesthesia due to dual ectasia in Marfan syndrome, reports describing similar unsuccessful spinal anesthesia in neurofibromatosis type 1 are lacking. CASE PRESENTATION: A parturient with neurofibromatosis type 1 was scheduled for a repeat cesarean section. During a previous cesarean section, she had experienced a failed spinal anesthesia, which resulted in a conversion to general anesthesia. Preoperative lumbar magnetic resonance imaging revealed dural ectasia, which was speculated to be the cause of the previous spinal anesthesia failure. Therefore, combined spinal-epidural anesthesia was implemented. Because the block level of spinal anesthesia was insufficient as predicted, supplemental administration of epidural anesthesia successfully provided adequate analgesia for the surgery. CONCLUSIONS: Combined spinal-epidural anesthesia can be useful for the management of cesarean sections in patients with neurofibromatosis type 1-associated dural ectasia.

MRI-Derived Dural Sac and Lumbar Vertebrae 3D Volumetry Has Potential for Detection of Marfan Syndrome.

PURPOSE: To assess the feasibility and diagnostic accuracy of MRI-derived 3D volumetry of lower lumbar vertebrae and dural sac segments using shape-based machine learning for the detection of Marfan syndrome (MFS) compared with dural sac diameter ratios (the current clinical standard). MATERIALS AND METHODS: The final study sample was 144 patients being evaluated for MFS from 01/2012 to 12/2016, of whom 81 were non-MFS patients (46 [67%] female, 36 ± 16 years) and 63 were MFS patients (36 [57%] female, 35 ± 11 years) according to the 2010 Revised Ghent Nosology. All patients underwent 1.5T MRI with isotropic 1 × 1 × 1 mm3 3D T2-weighted acquisition of the lumbosacral spine. Segmentation and quantification of vertebral bodies L3-L5 and dural sac segments L3-S1 were performed using a shape-based machine learning algorithm. For comparison with the current clinical standard, anteroposterior diameters of vertebral bodies and dural sac were measured. Ratios between dural sac volume/diameter at the respective level and vertebral body volume/diameter were calculated. RESULTS: Three-dimensional volumetry revealed larger dural sac volumes (p < 0.001) and volume ratios (p < 0.001) at L3-S1 levels in MFS patients compared with non-MFS patients. For the detection of MFS, 3D volumetry achieved higher AUCs at L3-S1 levels (0.743, 0.752, 0.808, and 0.824) compared with dural sac diameter ratios (0.673, 0.707, 0.791, and 0.848); a significant difference was observed only for L3 (p < 0.001). CONCLUSION: MRI-derived 3D volumetry of the lumbosacral dural sac and vertebral bodies is a feasible method for quantifying dural ectasia using shape-based machine learning. Non-inferior diagnostic accuracy was observed compared with dural sac diameter ratio (the current clinical standard for MFS detection).

Surgical management of omega deformity in a patient with neurofibromatosis type 1: a case report.

PURPOSE: To describe the surgical treatment in a patient with a partial omega deformity in the thoracic spine with neurofibromatosis type 1. METHODS: The patient was a 55-year-old man with an omega deformity, which is defined as a curvature in which the end vertebra is positioned at the level of, above, or below the apical vertebra (i.e., a horizontal line bisecting it). We performed halo gravity traction (HGT) for 7 weeks, followed by posterior spinal instrumented nearly equal in situ fusion from T2-L5 with three femoral head allografts and a local bone autograft. We avoided reconstruction of the thoracic anterior spine because of his severe pulmonary dysfunction. RESULTS: HGT improved the % vital capacity from 32.5 to 43.5%, and improved the Cobb angle of the kyphosis from > 180° before traction to 144° after traction. The Cobb angle of kyphosis and scoliosis changed from > 180° preoperatively to 155° and 146°, respectively, postoperatively, and 167° and 156°, respectively, at final follow-up. His postoperative respiratory function deteriorated transiently due to bilateral pleural effusions and compressive atelectasis, which was successfully treated with a frequent change of position and nasal high flow for 1 week. At final follow-up, his pulmonary function improved from 0.86 to 1.04 L in VC, and from 32.5 to 37.9% in %VC. However, there was no overall improvement in preoperative distress following surgery, although his modified Borg scale improved from 3 preoperatively to 0.5 postoperatively. One month after discharge, he felt worsening respiratory distress (SpO2:75%) and was readmitted for pulmonary hypertension for 2 months. He was improved by non-invasive positive pressure ventilation (biphasic positive airway pressure) for 1 week, medication and daily lung physiotherapy. Thereafter, he has been receiving permanent daytime (0.5 L/min) and nighttime (2 L/min) oxygen therapy at home. A solid arthrodesis through the fusion area was confirmed on computed tomography. However, the kyphosis correction loss was 12° (i.e., 155°-167°), while the scoliosis correction loss was 10° (i.e., 146°-156°) at 2 years of recovery. CONCLUSIONS: We suggest that nearly equal in situ fusion is a valid option for preventing further deformity deterioration and avoiding fatal complications.

Quantitative measurement of dural ectasia: associations with clinical and genetic characteristics in Marfan syndrome.

PURPOSE: Dural ectasia (DE) may significantly impact Marfan syndrome (MFS) patients' quality of life due to chronic lower back pain, postural headache and urinary disorders. We aimed to evaluate the association of quantitative measurements of DE, and their evolution over time, with demographic, clinical and genetic characteristics in a cohort of MFS patients. METHODS: We retrospectively included 88 consecutive patients (39% females, mean age 37.1 ± 14.2 years) with genetically confirmed MFS who underwent at least one MRI or CT examination of the lumbosacral spine. Vertebral scalloping (VS) and dural sac ratio (DSR) were calculated from L3 to S3. Likely pathogenic or pathogenic FBN1 variants were categorized as either protein-truncating or in-frame. The latter were further classified according to their impact on the cysteine content of fibrillin-1. RESULTS: Higher values of the systemic score (revised Ghent criteria) were associated with greater DSR at lumbar (p < 0.001) and sacral (p = 0.021) levels. Patients with protein-truncating variants exhibited a greater annual increase in lumbar (p = 0.039) and sacral (p = 0.048) DSR. Mutations affecting fibrillin-1 cysteine content were linked to higher VS (p = 0.009) and DSR (p = 0.038) at S1, along with a faster increase in VS (p = 0.032) and DSR (p = 0.001) in the lumbar region. CONCLUSION: Our study shed further light on the relationship between genotype, dural pathology, and the overall clinical spectrum of MFS. The identification of protein-truncating variants and those impacting cysteine content may therefore suggest closer patient monitoring, in order to address potential complications associated with DE.

Dural ectasia with cauda equina syndrome, a rare case report.

INTRODUCTION AND IMPORTANCE: Dural ectasia, which is often idiopathic, is seen both in patients with neurofibromatosis and Marfan's syndrome. In neurofibromatosis, the ectasia is most often seen in the thoracic region but can occur at any point along the dura. A complication such as cauda equina syndrome is usually rare. CLINICAL PRESENTATION: A 48 year old male complaining of recurrent throbbing headache, for 3 years, 2 years ago he developed progressively lower back pain, associated with numbness and tingling sensation of the lower limbs. A year ago he experienced defecation and urinary incontinence. On further questioning the patient reported to have first degree relative with neurofibromatosis. On examination he has multiple café au laite on the trunk, back and left arm, and plexiform on the left palm, mild right deviation on thoracic region on the back. Lower limb muscle power grade 4/5 bilaterally, sensation was intact. Laboratory work up Full blood counts, electrolytes, renal and liver function tests were normal, MRI of the lumbar spine demonstrate L3/L4 and L4/l5 mild disc bulge with no significant narrowing of the primary canal and no evidence of existing nerve root impingement, increase antero-posterior diameter of dura sac involving L5-S1, with a Dural Sac Diameter of S1 increased compared to that of L4 with mild scalloping of lower lumbar vertebra and pronounced at S1 vertebral body. A diagnosis of cauda equina syndrome and dural ectasia secondary to neurofibromatosis was rendered. Lumbar peritoneal shunting, was reached as a surgical treatment for this patient, but due to inadequate and unavailability of the required shunting equipment, the patient was managed conservatively with anti- inflammatory medications, lumbar CSF tapping, genital hygiene and counselling. 3 months of follow up, the patient was able to walk, with power 5/5 to both lower limbs, however fecal and urine incontinence persisted. DISCUSSION: this case was particularly unusual due to the combination of cauda equina syndrome and dural ectasia, Dural ectasia is seen with various conditions including Marfan syndrome, Ehlers-syndrome, neurofibromatosis 1, Ankylosing spondylitis, trauma, scoliosis or tumors it may also have no clear cause. In most cases patients with dural ectasia are asymptomatic few may present with low back pain, radicular pain in the buttocks or legs and headache and rarely caudal equina syndrome. The management of dura ectasia may be conservative for asymptomatic patient and for a symptomatic patient surgery such as stabilization, marsupialization and lumbar peritoneal shunt. CONCLUSION: Dural ectasia with cauda equina syndrome are rarely complication of neurofibromatosis. Familiarity with its classic imaging and clinical features as described in this case report can help its early detection and management.

Treatment of L5-S1 spondyloptosis with stand-alone anterior lumbar interbody fusion in a patient with neurofibromatosis.

BACKGROUND: Neurofibromatosis type 1 (NF1) is a multisystem disorder that causes multiple tumor formations throughout the nervous system. Common spinal dysplasias seen with NF1, such as dural ectasia (DE), often undergo modulation and predispose these patients to spondylolisthesis, making surgical treatment challenging. CASE DESCRIPTION: A patient with NF1 presented with a 12-year-history of back and left lower extremity radicular pain. Lumbar spine magnetic resonance imaging revealed developmental anomalies with severe DE and associated scalloping of the L4-S1 vertebral bodies and severe L5-S1 Meyerding grade 4 spondylolisthesis. During surgery, post-positioning x-rays demonstrated a grade 5 spondyloptosis. The patient underwent an L5-S1 stand-alone anterior lumbar interbody fusion (ALIF). The final construct was an ALIF cage with one screw into S1, without an anterior plate. By 3-months post-operative, there was complete resolution of preoperative symptoms and at 2 year follow-up the patient was asymptomatic with stable hardware and solid bony fusion. To the authors' knowledge, this is the first report of spondyloptosis treated with a stand-alone ALIF in a patient with NF1 and severe DE.

A Review of Spinal Lesions in Neurofibromatosis Type 1 in a Large Neurofibromatosis Type 1 Center.

BACKGROUND: Spinal lesions are a known manifestation of neurofibromatosis type 1 (NF1). The aim of this retrospective review was to analyze and report the prevalence of spinal lesions on imaging in a large NF1 center. METHODS: The data were collected from a period of 62 months from a cohort of 514 patients. Data were collected from multidisciplinary team meeting reports that included radiologic reports of each patient investigating 20 distinct variables. The prevalence of each of these lesions was calculated, and any statistically significant associations were investigated using the χ2 test. RESULTS: Four-hundred forty-seven patients had classic NF1, and 67 patients had spinal NF1. Many of the patients had spinal abnormalities; 25.7% of these patients were found to have dural ectasia, whereas 44.9% of patients had a spinal deformity. A statistically significant association between dural ectasia and spinal neurofibromatosis was established (P < 0.05). An additional statically significant association was established between dural ectasia and spinal deformity (P < 0.00001). The patients with spinal nerve root tumors were identified, and it was found that 49.8% of patients possessed these tumors, whereas 56.3% of these tumors were intraspinal tumors. The most common region affected was the cervical spine, and the most common spinal level was C2. CONCLUSIONS: This high prevalence of spinal tumours in mobile areas of the spine is possibly the result of a combination of genetic predisposition and repeated microtraumas resulting in tumor formation. This is the largest reported study of spinal lesions in NF1 based on imaging and offers insights into the etiology and relationships between lesions.

Short-Term and Long-Term Complications Associated with Posterior Fossa Decompression for Chiari Malformation.

Surgery is the treatment of choice for symptomatic patients with Chiari anomalies Although the surgical treatment of Chiari anomalies in adults is a straightforward procedure, complications and less than satisfactory outcomes do occur. Understanding these complications is important for correcting the problem as well as preventing the recurrence of similar problems. In this article, the author review the short-term and long-term complications associated with posterior fossa decompression for Chiari malformation.

Management of lateral meningocele syndrome in a child without neurological symptoms and literature review.

PURPOSE: Lateral meningocele syndrome (LMS) is a rare genetic connective tissue disorder which is associated with meningocele-related neurologic dysfunction. Several patients with LMS have been reported. But, guidelines for screening and treatment of LMS have not been established. METHOD AND RESULTS: We review the current knowledge of LMS in the article. Then, we describe a boy for whom a genomic analysis which allowed us to make a diagnosis of LMS and to begin monitoring of his condition for possible neurological complications. CONCLUSION: It would be difficult to make a diagnosis of LMS on the basis of clinical manifestations alone. The natural history of dural ectasia in patients with LMS needs to be better defined to establish surgical indications. Based upon the current literature, ventriculoperitoneal shunting (V-Ps) has been recommended as the first-line surgical treatment option for patients with symptomatic thoracolumbar meningoceles.

Surgical challenges and functional outcomes in dystrophic cervical kyphosis in Neurofibromatosis -1: an institutional experience.

OBJECTIVE: Dystrophic cervical kyphosis secondary to neurofibromatosis 1 (NF1) is rarely reported. The primary objective is to highlight the clinical presentation and surgical outcomes based on clinical and biomechanical parameters. The secondary objective is to highlight the early and late complications of these surgeries. METHODS: The hospital records of six patients operated between 2008 and 2018 were retrospectively reviewed with a minimum follow-up of 24 months. Besides demographics information, radiological findings and operative details, the outcome measures reported were neurological (MJOA score, Nurick scale), pain (VAS score) and operative complications. RESULTS: The mean age of patients was 15.1 years (8-32 years). The average kyphotic vertebra involved-3.6 bodies (range 2-5 bodies) with four patients showing intraspinal anomaly-neurofibromas, dural ectasia. Clinically, patients improved postoperatively with-VAS (pre vs. post-: 6.6 vs. 2.6, p - < 0.05), MJOA score (pre vs. post: 10.3 vs. 13.3, p - < 0.05), Nurick grade (pre vs. post: 3.5 vs. 2.1, p - < 0.05). There was significant deformity correction from 66.8° to 20.7° (p value < 0.031), mean T1 Slope (pre vs. post - 1.8 ± 20.4 to 0.6 ± 12.8, p value - < 0.43). Mean blood loss encountered was 1800 ± 434.6 cc; however, patients with paraspinal neurofibromas reported greater blood loss. Late complications included pseudoarthrosis (1), C5 palsy (1) and junctional kyphosis (1). Vertebral dysplasia and erosions continued in all patients post-operatively. CONCLUSIONS: Antero-posterior approach provides circumferential decompression and better sagittal balance correction. Cervical spine must be screened in all NF-1 patients and followed up regularly to assess for dystrophic changes.

Early diagnosis of lateral meningocele syndrome in an infant without neurological symptoms based on genomic analysis.

Lateral meningocele syndrome is characterized by multiple lateral meningoceles with a distinctive craniofacial appearance, hyperextensibility of the skin, and hypermobility of the joints. The syndrome is caused by heterozygous truncating variants in the last exon, exon 33, of the NOTCH3 gene. Here, we present a 2-year-old girl for whom an early genomic analysis allowed us to recognize the presence of lateral meningoceles and to begin early monitoring of her condition for possible neurological complications. She had a characteristic facial appearance, hyperextensibility of the skin and mobility of the joints, and developmental delays. Given that lateral meningocele syndrome is a rare syndrome, the existence of lateral meningoceles is suspected only when the causative gene is detected by genetic testing. MRI scans are unlikely to be performed in infancy in the absence of neurological symptoms suggestive of meningoceles. No formal guidelines have been established for the neurosurgical indications for lateral meningocele syndrome. Given the features of hyperextensibility of the skin and hypermobility of the joints, lateral meningocele syndrome can be categorized as a connective tissue disease and may be progressive, as with the dural ectasia in Marfan syndrome and Loeys-Dietz syndrome. Watchful monitoring of dural ectasia may be warranted in patients with lateral meningocele syndrome.

The Musculoskeletal Manifestations of Marfan Syndrome: Diagnosis, Impact, and Management.

PURPOSE OF REVIEW: Marfan syndrome (MFS) is an autosomal dominant heritable disorder of fibrillin-1 (FBN1) with predominantly ocular, cardiovascular, and musculoskeletal manifestations that has a population prevalence of approximately 1 in 5-10,000 (Chiu et al. Mayo Clin Proc. 89(1):34-42, 146, Dietz 3, Loeys et al. J Med Genet. 47(7):476-85, 4). RECENT FINDINGS: The vascular complications of MFS still pose the greatest threat, but effective management options, such as regular cardiac monitoring and elective surgical intervention, have reduced the risk of life-threatening cardiovascular events, such as aortic dissection. Although cardiovascular morbidity and mortality remains high, these improvements in cardiovascular management have extended the life expectancy of those with MFS by perhaps 30-50 years from an estimated mean of 32 years in 1972 (Dietz 3, Gott et al. Eur J Cardio-thoracic Surg. 10(3):149-58, 147, Murdoch et al. N Engl J Med. 286(15):804-8, 148). The musculoskeletal manifestations of MFS, which to date have received less attention, can also have a significant impact on the quality of life and are likely to become more important as the age of the Marfan syndrome population increases (Hasan et al. Int J Clin Pract. 61(8):1308-1320, 127). In addition, musculoskeletal manifestations are often critically important in the diagnosis of MFS. Here, we review the main clinically relevant and diagnostically useful musculoskeletal features of MFS, which together contribute to the "systemic features score" (referred to hereafter as systemic score), part of the revised Ghent nosology for MFS. We discuss current treatment strategies and highlight the need for a multidisciplinary approach to diagnosis and management. Finally, we review new pharmacological approaches that may be disease modifying and could help to improve the outcome for individuals with this syndrome.

Multidisciplinary approach for repair of a large ventral thoracic meningocele in neurofibromatosis-1; a systematic review of the literature and case report.

Thoracic meningoceles and dural ectasia are less commonly recognized manifestations of neurofibromatosis 1 (NF1). Rarely, large thoracic meningoceles may become compressive and lead to respiratory compromise secondary to lung compression. Surgical goals aim to increase lung aeration through decreasing the size of the meningocele through shunting, excision or repair of the meningocele, and varying degrees of dural tube reconstruction. There is no agreement on the best approach for large, symptomatic meningoceles. Here, we discuss the case of a 41-year-old woman with NF1 who presented with dyspnea and enlargement of a large, 19 cm thoracic meningocele. A multidisciplinary team of thoracic, plastic, and neurological surgery participated in the operation to excise the meningocele and reconstruct the dural tube without the need for subsequent shunting of spinal fluid. We also systematically review the literature on thoracic meningoceles in NF1 to understand the optimal treatment of this pathology.

Broadening the phenotypic spectrum of Beta3GalT6-associated phenotypes.

Biallelic mutations in B3GALT6, coding for a galactosyltransferase involved in the synthesis of glycosaminoglycans (GAGs), have been associated with various clinical conditions, causing spondyloepimetaphyseal dysplasia with joint laxity type 1 (SEMDJL1 or SEMDJL Beighton type), Al-Gazali syndrome (ALGAZ), and a severe progeroid form of Ehlers-Danlos syndrome (EDSSPD2). In the 2017 Ehlers-Danlos syndrome (EDS) classification, Beta3GalT6-related disorders were grouped in the spondylodysplastic EDSs together with spondylodysplastic EDSs due to B4GALT7 and SLC39A13 mutations. Herein, we describe a patient with a previously unreported homozygous pathogenic B3GALT6 variant resulting in a complex phenotype more severe than spondyloepimetaphyseal dysplasia with joint laxity type 1, and having dural ectasia and aortic dilation as additionally associated features, further broadening the phenotypic spectrum of the Beta3GalT6-related syndromes. We also document the utility of repeating sequencing in patients with uninformative exomes, particularly when performed by using "first generations" enrichment capture methods.

Physiological pseudo-thickened cauda equina associated with dural sac dilatation on magnetic resonance imaging.

OBJECTIVES: In daily clinical practice, the assessment of the thickness of the cauda equina on lumbar spine magnetic resonance imaging is an important parameter. However, its relevance to the size of the dural sac in non-pathological conditions is unknown. To examine the relationship between the size of the dural sac and the apparent thickness of the cauda equina nerve root using lumbar spine magnetic resonance imaging in non-pathological conditions. METHODS: We retrospectively measured the dural sac diameter and vertebral body diameter, counted the apparent number, and calculated total cross-sectional area of the cauda equina, dural sac ratio and the area of one apparent nerve root of cauda equina in 100 cases. Spearman's rank correlation coefficient (ρ) was used. RESULTS: Dural sac ratio and diameter were positively correlated with the area of one apparent nerve root (ρ=0.77, P<0.001; ρ=0.74, P<0.001; respectively) and negatively correlated with the apparent number of cauda equina in a single cross-section (ρ=-0.63, P<0.001; ρ=-0.52, P<0.001; respectively). CONCLUSIONS: A larger dural sac ratio and diameter was associated with an apparently thicker cauda equina and lower visible number. In a larger dural sac, the physiologically clumped and apparently thicker cauda equina should not be misdiagnosed as pathological.

Spontaneous intracranial hypotension secondary to congenital spinal dural ectasia and genetic mosaicism for tetrasomy 10p: illustrative case.

BACKGROUND: Spontaneous intracranial hypotension has historically been a poorly understood pathology that is often unrecognized and undertreated. Even more rarely has it been described in pediatric patients with an otherwise benign past medical history. OBSERVATIONS: Herein the authors describe one of the youngest patients ever reported, a 2-year-old girl who developed severe headaches, nausea, and vomiting and experienced headache relief after lying down. Imaging revealed tonsillar herniation 14 mm below the foramen magnum, presumed to be a Chiari malformation, along with extensive dural cysts starting from thoracic level T2 down to the sacrum. She was found to have streaky skin pigmentary variation starting from the trunk down to her feet. Genetic analysis of skin biopsies revealed mosaicism for an isodicentric marker chromosome (10p15.3-10q11.2 tetrasomy) in 27%-50% of cells. After undergoing a suboccipital and cervical decompression at an outside institution, she continued to be symptomatic. She was referred to the authors' hospital, where she was diagnosed with spontaneous intracranial hypotension. LESSONS: After receiving a series of epidural blood patches, the patient experienced almost complete relief of her symptoms. To the authors' knowledge, this is the first time this chromosomal anomaly has ever been reported in a living child, and this may represent a new genetic association with dural ectasia.

Anterior cervical meningocele with craniovertebral junction instability - A case report and literature review.

Anterior meningocele involves herniation of meninges through an abnormal defect in the anterior vertebral column. The pathogenesis, natural history, and management strategy of anterior cervical meningocele (ACM) are uncertain. We report a case of ACM with high cervical instability in a case of neurofibromatosis 1. Unlike other reported cases, torticollis and instability due to ACM were the major concerns in this case. We aim to discuss the management strategy and surgical nuances of such cases.

Infantile Presentation of Lehman Syndrome with Multiple Lateral Meningoceles, Dural Ectasias, and Herniation of Conus: A Rare Case Report.

Lehman syndrome, or lateral meningocele syndrome, is a rare disorder of skeletal malformation, characterized by facial dysmorphism and multiple lateral meningoceles. We present a case of a 5-month-old girl who presented with macrocephaly, developmental delay, and failure to thrive. A whole spine magnetic resonance imaging was carried out, which showed multiple bilateral well-defined cystic masses within the neural foramina involving the entire spine, predominantly the thoracolumbar regions, with neural foraminal widening and dural ectasia suggestive of multiple lateral meningoceles.