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.

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.

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.

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.

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.

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.

Leukoencephalopathia, demyelinating peripheral neuropathy and dural ectasia explained by a not formerly described de novo mutation in the SAMD9L gene, ends 27 years of investigations - a case report.

BACKGROUND: Missense mutations in SAMD9L gene is associated with ataxia-pancytopenia syndrome (ATXPC), OMIM#159550. Common clinical features in these patients include neurological and hematological symptoms. The phenotype and age of onset is variable. CASE PRESENTATION: In this case report whole exome sequencing (WES) revealed a not previously reported de novo variant c.2686 T > G, p.(Phe896Val) in SAMD9L in a patient with widespread findings of slow developing pathology in the peripheral and central nervous system. The clinical picture was dominated by neurological symptoms, unlike previously described cases, and in addition dural ectasias and multiple cysts in the brain was observed using magnetic resonance imaging. CONCLUSIONS: This case underscores the effect of variable expressivity, i.e. different mutations in the same gene can cause different phenotypes.

The association of spinal deformity with dural ectasia in neurofibromatosis type 1.

Objective: To establish the prevalence of dural ectasia in patients with complex neurofibromatosis type-1 (NF-1) and its association with spinal deformities that manifest alongside.Methods: Analysis of the neuroradiological notes from 24 months of multidisciplinary team meetings for patients with complex NF-1 (equating to 378 patients). Review of the MRI scans of all patients with dural ectasia with each scan graded using a novel grading system.Results: A total of 38 of the 378 patients were found to have dural ectasia (10.05%). The median age of these 38 patients was 36 years ranging from 18 to 64. The male: female ratio was 16:22. In all, 90.9% of patients with a 'major' form of dural ectasia had a concurrent spinal deformity present compared to 18.18% of patients with a minor form.Conclusions: The more severe the dural ectasia, the greater the likelihood a concurrent deformity with NF-1. The vertebral bodies and pedicles are more commonly involved than the posterior elements.

Coexistence of cervical vertebral scalloping, pedicle deficiencies and dural ectasia in type I neurofibromatosis.

Neurofibromatosis type 1 (NF-1; also known as Von Recklinghausen's disease) is a common autosomal dominant disease that occurs in the general population at the rate of 1 in 3000. Many NF-1 patients present with spinal malformations. A 54-year-old female patient was admitted to the Outpatient Clinic of Dermatology with gradually increasing swelling and spots on the body that had been present for a long period of time. Cervical vertebral scalloping, pedicle deficiencies and dural ectasia (DE) were also detected. She was diagnosed with NF-1. NF-1 is routinely seen in dermatology practice. Coexistence of NF-1 with vertebral scalloping, pedicle deficiencies and DE rarely occurs. Our case is the second reported instance in the literature of NF-1 with a spinal anomaly in the cervical region, and the first reported instance of the coexistence of NF-1 with cervical vertebral scalloping, pedicle deficiencies and DE.

Truncating mutations in the last exon of NOTCH3 cause lateral meningocele syndrome.

Lateral meningocele syndrome (LMS, OMIM%130720), also known as Lehman syndrome, is a very rare skeletal disorder with facial anomalies, hypotonia and meningocele-related neurologic dysfunction. The characteristic lateral meningoceles represent the severe end of the dural ectasia spectrum and are typically most severe in the lower spine. Facial features of LMS include hypertelorism and telecanthus, high arched eyebrows, ptosis, midfacial hypoplasia, micrognathia, high and narrow palate, low-set ears and a hypotonic appearance. Hyperextensibility, hernias and scoliosis reflect a connective tissue abnormality, and aortic dilation, a high-pitched nasal voice, wormian bones and osteolysis may be present. Lateral meningocele syndrome has phenotypic overlap with Hajdu-Cheney syndrome. We performed exome resequencing in five unrelated individuals with LMS and identified heterozygous truncating NOTCH3 mutations. In an additional unrelated individual Sanger sequencing revealed a deleterious variant in the same exon 33. In total, five novel de novo NOTCH3 mutations were identified in six unrelated patients. One had a 26 bp deletion (c.6461_6486del, p.G2154fsTer78), two carried the same single base pair insertion (c.6692_93insC, p.P2231fsTer11), and three individuals had a nonsense point mutation at c.6247A > T (pK2083*), c.6663C > G (p.Y2221*) or c.6732C > A, (p.Y2244*). All mutations cluster into the last coding exon, resulting in premature termination of the protein and truncation of the negative regulatory proline-glutamate-serine-threonine rich PEST domain. Our results suggest that mutant mRNA products escape nonsense mediated decay. The truncated NOTCH3 may cause gain-of-function through decreased clearance of the active intracellular product, resembling NOTCH2 mutations in the clinically related Hajdu-Cheney syndrome and contrasting the NOTCH3 missense mutations causing CADASIL.

Dural ectasia in Loeys-Dietz syndrome: comprehensive study of 30 patients with a TGFBR1 or TGFBR2 mutation.

The purpose of this study was to assess the frequency, severity, and clinical associations of dural ectasia (DE) in Loeys-Dietz syndrome (LDS). Database analysis of three German metropolitan regions identified 30 patients with LDS and TGFBR1 mutation in 6 and a TGFBR2 mutation in 24 individuals (17 men; mean age: 31 ± 19 years), as well as 60 age and sex-matched control patients with Marfan syndrome carrying a FBN1 mutation. DE was present in 22 patients with LDS (73%), and it related to skeletal score points (p = 0.008), non-skeletal score points (p < 0.001), and to the presence of ≥7 systemic score points (p = 0.010). Similarly, the severity of DE was related to body height (p = 0.010) and non-skeletal score points (p = 0.004). Frequency (p = 0.131) and severity of DE (p = 0.567) was similar in LDS and Marfan syndrome. DE is a manifestation of LDS that occurs with similar frequency and severity as in Marfan syndrome. Severity of DE may serve as a marker of the overall connective tissue disease severity. LDS may be considered in patients 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.

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).

Idiopathic Inflammatory Neuroretinitis Simulating Optic Nerve Sheath Dural Ectasia.

We report a case of a 32-year-old female patient who presented with decreased vision on both eyes and headache. In fundus examination, both eyes had elevation of the optic disc and star shaped hard exudates in the macula. Magnetic resonance imaging was completely normal except the saccular dilatation of bilateral optic nerve sheath. The patient was treated with oral steroids following high-dose intravenous methylprednisolone. She displayed good anatomical and functional results during the follow-up. This case raises the possibility that optic nerve sheath enlargement, probably induced by an idiopathic inflammatory optic neuritis, may simulate dural ectasia of the optic nerve sheath.

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.