Diagnostic and prognostic significance of miR-486-5p in patients who underwent minimally invasive surgery for lumbar spinal stenosis.

BACKGROUND: This study aimed to investigate the expression and clinical value of microRNA miR-486-5p in diagnosing lumbar spinal stenosis (LSS) patients and predicting the clinical outcomes after minimally invasive spinal surgery (MISS) in LSS patients, and the correlation of miR-486-5p with inflammatory responses in LSS patients. METHODS: This study included 52 LSS patients, 46 patients with lumbar intervertebral disk herniation (LDH) and 42 healthy controls. Reverse transcription quantitative PCR was used to detect miR-486-5p expression. The ability of miR-486-5p to discriminate between different groups was evaluated by receiver-operating characteristic analysis. The visual analogue scale (VAS), Oswestry Disability Index (ODI) and Japanese Orthopaedic Association (JOA) scores at 6 months postoperatively were used to reflect the clinical outcomes of LSS patients. Enzyme-linked immunosorbent assay was used to measure the levels of inflammatory factor [interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α)]. The correlation of miR-486-5p with continuous variables in LSS patients was evaluated by the Pearson correlation coefficient. RESULTS: Expression of serum miR-486-5p was upregulated in LSS patients and had high diagnostic value to screen LSS patients. In addition, serum miR-486-5p could predict the 6-month clinical outcomes after MISS therapy in LSS patients. Moreover, serum miR-486-5p was found to be positively correlated with the levels of IL-1ß and TNF-α in patients with LSS. CONCLUSION: miR-486-5p, increased in LSS patients, can function as an indicator to diagnose LSS and a predictive indicator for the clinical outcomes after MISS therapy in LSS patients. In addition, miR-486-5p may regulate LSS progression by modulating inflammatory responses.

Surgically Treated Degenerative Lumbar Spine Diseases in Twins.

BACKGROUND: There is growing evidence to suggest a potential genetic component underlying the development and progression of lumbar spine diseases. However, the heritability and the concordance rates for the phenotypes requiring surgery for the common spine diseases lumbar spinal stenosis (LSS) and lumbar disc herniation (LDH) are unknown. The aim of this study was to determine the heritability and the concordance rates for LSS and LDH requiring surgery by studying monozygotic (MZ) and dizygotic (DZ) twin pairs. METHODS: Patients between 18 and 85 years of age who underwent surgery for LSS or LDH between 1996 and 2022 were identified in the national Swedish spine registry (LSS: 45,110 patients; LDH: 39,272 patients), and matched with the Swedish Twin Registry to identify MZ and DZ twins. Pairwise and probandwise concordance rates, heritability estimates, and MZ/DZ concordance ratios were calculated. RESULTS: We identified 414 twin pairs (92 MZ and 322 DZ pairs) of whom 1 or both twins underwent surgery for LSS. The corresponding number for LDH was 387 twin pairs (118 MZ and 269 DZ pairs). The probandwise concordance rate for LSS requiring surgery was 0.25 (26 of 105) (95% confidence interval [CI], 0.14 to 0.34) for MZ twins and 0.04 (12 of 328) (95% CI, 0.01 to 0.07) for DZ twins. The corresponding values for LDH requiring surgery were 0.03 (4 of 120) (95% CI, 0 to 0.08) and 0.01 (4 of 271) (95% CI, 0 to 0.04), respectively. The probandwise MZ/DZ concordance ratio was 6.8 (95% CI, 2.9 to 21.5) for LSS and 2.3 (95% CI, 0 to 8.9) for LDH. The heritability was significantly higher in LSS compared with LDH (0.64 [95% CI, 0.50 to 0.74] versus 0.19 [95% CI, 0.08 to 0.35]). CONCLUSIONS: Our findings suggest that genetic factors may play an important role in the risk of developing LSS requiring surgery, whereas heredity seems to be of less importance in LDH requiring surgery. LEVEL OF EVIDENCE: Prognostic Level III . See Instructions for Authors for a complete description of levels of evidence.

Molecular and Genetic Mechanisms of Spinal Stenosis Formation: Systematic Review.

Spinal stenosis (SS) is a multifactorial polyetiological condition characterized by the narrowing of the spinal canal. This condition is a common source of pain among people over 50 years old. We perform a systematic review of molecular and genetic mechanisms that cause SS. The five main mechanisms of SS were found to be ossification of the posterior longitudinal ligament (OPLL), hypertrophy and ossification of the ligamentum flavum (HLF/OLF), facet joint (FJ) osteoarthritis, herniation of the intervertebral disc (IVD), and achondroplasia. FJ osteoarthritis, OPLL, and HLF/OLFLF/OLF have all been associated with an over-abundance of transforming growth factor beta and genes related to this phenomenon. OPLL has also been associated with increased bone morphogenetic protein 2. FJ osteoarthritis is additionally associated with Wnt/ß-catenin signaling and genes. IVD herniation is associated with collagen type I alpha 1 and 2 gene mutations and subsequent protein dysregulation. Finally, achondroplasia is associated with fibroblast growth factor receptor 3 gene mutations and fibroblast growth factor signaling. Although most publications lack data on a direct relationship between the mutation and SS formation, it is clear that genetics has a direct impact on the formation of any pathology, including SS. Further studies are necessary to understand the genetic and molecular changes associated with SS.

Association between spinal stenosis and wild-type ATTR amyloidosis.

Age-related cardiac amyloidosis results from deposits of wild-type tranthyretin amyloid (ATTRwt) in cardiac tissue. ATTR may play a role in carpal tunnel syndrome (CTS) and in spinal stenosis (SS), indicating or presaging systemic amyloidosis. We investigated consecutive patients undergoing surgery for SS for ATTR deposition in the resected ligamentum flavum (LF) and concomitant risk of cardiac amyloidosis. Each surgical specimen (LF) was stained with Congo red, and if positive, the amyloid deposits were typed by mass spectrometry. Patients with positive specimens underwent standard of care evaluation with fat pad aspirates, serum and urine protein electrophoresis with immunofixation, free light-chain assay, TTR gene sequencing and technetium 99 m-pyrophosphate-scintigraphy. In 2018-2019, 324 patients underwent surgery for SS and 43 patients (13%) had ATTR in the LF with wild-type TTR gene sequences. Two cases of ATTRwt cardiac amyloidosis were diagnosed and received treatment. In this large series, ATTRwt was identified in 13% of the patients undergoing laminectomy for SS. Patients with amyloid in the ligamentum flavum were older and had a higher prevalence of CTS, suggesting a systemic form of ATTR amyloidosis involving connective tissue. Further prospective study of patients with SS at risk for systemic amyloidosis is warranted.

Circular RNA Expression Profile in Patients with Lumbar Spinal Stenosis Associated with Hypertrophied Ligamentum Flavum.

STUDY DESIGN: Sequencing and experimental analysis of the expression profile of circular RNAs (circRNAs) in hypertrophic ligamentum flavum (LFH). OBJECTIVES: The aim of this study was to identify differentially expressed circRNAs between LFH and nonhypertrophic ligamentum flavum tissues from lumbar spinal stenosis (LSS) patients. SUMMARY OF BACKGROUND DATA: Hypertrophy of the ligamentum flavum (LF) can cause LSS. circRNAs are important in various diseases. However, no circRNA expression patterns related to LF hypertrophy have been reported. METHODS: A total of 33 patients with LSS participated in this study. LF tissue samples were obtained when patients underwent decompressive laminectomy during surgery. The expression profile of circRNAs was analyzed by transcriptome high-throughput sequencing and validated with quantitative real-time polymerase chain reaction (PCR). Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses were performed for the differentially expressed circRNA-associated genes and related pathways. The connections between circRNAs and microRNAs were explored using Cytoscape. The role of hsa_circ_0052318 on LF cell fibrosis was assessed by analyzing the expression of collagen I and collagen III. RESULTS: The results showed that 2439 circRNAs of 4025 were differentially expressed between the LFH and nonhypertrophic ligamentum flavum tissues, including 1276 upregulated and 1163 downregulated circRNAs. The Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analyses revealed that these differentially expressed circRNAs functioned in biological processes, cellular components, and molecular functions. Autophagy and mammalian target of rapamycin were the top two signaling pathways affected by these circRNAs. Five circRNAs (hsa_circ_0021604, hsa_circ_0025489, hsa_circ_0002599, hsa_circ_0052318, and hsa_circ_0003609) were confirmed by quantitative real-time PCR. The network indicated a strong relationship between circRNAs and miRNAs. Furthermore, hsa_circ_0052318 overexpression decreased mRNA and protein expression of collagen I and III in LF cells from LFH tissues. CONCLUSION: This study identified circRNA expression profiles characteristic of hypertrophied LF in LSS patients, and demonstrated that hsa_circ_0052318 may play an important role in the pathogenesis of LF hypertrophy.Level of Evidence: N/A.

ADAM10 promotes the proliferation of ligamentum flavum cells by activating the PI3K/AKT pathway.

Ligamentum flavum hypertrophy (LFH) is an important cause of spinal canal stenosis and posterior longitudinal ligament ossification. Although a number of studies have focused on the mechanisms responsible for LFH, the cellular mechanisms remain poorly understood. The aim of the present study was to investigate the roles of differentially expressed genes (DEGs) in LFH, elucidate the mechanisms responsible for LFH and provide a potential therapeutic target for further studies. The GSE113212 dataset was downloaded from the Gene Expression Omnibus (GEO) database. The microarray data were analyzed and DEGs were obtained. Bioinformatics methods, such as Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment and protein­protein interaction (PPI) network analyses were used to obtain the key genes and signaling pathways. In addition, cells derived from hypertrophied ligamentum flavum were cultured, and the key genes and signaling pathways in ligamentum cells were identified through in vitro cell biology and molecular biology experiments. A total of 2,123 genes were screened as DEGs. Among these DEGs, 1,384 genes were upregulated and 739 genes were downregulated. The KEGG pathway analysis revealed that the DEGs were mainly enriched in the PI3K/AKT signaling pathway, and the PPI network analysis screened A disintegrin and metalloproteinase 10 (ADAM10) as a key gene. In vitro experimental verification revealed that ADAM10 promoted the proliferation of ligamentum flavum cells and led to the hypertrophy of the ligamentum by activating the PI3K/AKT pathway. On the whole, the in vitro experimental results suggested that ADAM10 promoted the proliferation of ligamentum flavum cells by activating the PI3K/AKT pathway, which may represent a pathogenic mechanism of LFH. The findings of the present study may provide a basis and direction for further studies on the cellular mechanisms of LFH and present a potential novel therapeutic target and clinical approach.

Two GWAS-identified variants are associated with lumbar spinal stenosis and Gasdermin-C expression in Chinese population.

The aim of this study is to investigate the expression levels of genome-wide association studies (GWAS)-identified variants near Gasdermin-C (GSDMC) and its association with lumbar disc degeneration (LDD) in a Chinese population. In accordance with previously reported findings, our study involved the top 4 variants; rs6651255, rs7833174, rs4130415, and rs7816342. A total of 800 participants, 400 LDD patients and 400 controls were involved in the study. The LDD patients were divided into two mutually exclusive subgroups: subgroup 1: lumbar disc herniation; subgroup 2: lumbar spinal stenosis. Genotyping were performed using TaqMan assay, and Enzyme-Linked Immunosorbent Assay (ELISA) used to measure the plasma GSDMC levels, while quantitative reverse-transcription (qRT)-PCR and immunohistochemistry (IHC) were used to evaluate the GSDMC expression levels. Among the studied variants, there were no statistically significant differences in allelic and genotypic frequencies between LDD patients and their controls (all P > 0.05). However, the subgroup analysis revealed a significant association between rs6651255 and rs7833174 in patients with lumbar spinal stenosis (subgroup 2). Furthermore, the max-statistic test revealed that the inheritance models of two variants of lumbar spinal stenosis were represented by the recessive model. The plasma and mRNA expression levels of GSDMC were significantly higher in patients with lumbar spinal stenosis compared with the control group (P < 0.05). Furthermore, the CC genotypes of rs6651255 and rs7833174 were significantly associated with increased plasma expression levels of GSDMC in patients with lumbar spinal stenosis (P < 0.01). Two GWAS-identified variants (rs6651255 and rs7833174) near GSDMC were associated with a predisposition to lumbar spinal stenosis. GSDMC protein and mRNA expression levels may have prognostic qualities as biomarkers for the existence, occurrence or development of lumbar spinal stenosis.

MiR-21 promotes fibrosis and hypertrophy of ligamentum flavum in lumbar spinal canal stenosis by activating IL-6 expression.

The molecular mechanism underlying the fibrosis of ligamentum flavum(LF) in patients with lumbar spinal canal stenosis(LSCS) remains unknown. MicroRNAs are reported to play important roles in regulating fibrosis in different organs. The present study aimed to identify fibrosis related miR-21 expression profile and investigate the pathological process of miR-21 in the fibrosis of LF hypertrophy and associated regulatory mechanisms. 15 patients with LSCS underwent surgical treatment were enrolled in this study. For the control group, 11 patients with lumbar disc herniation(LDH) was included. The LF thickness was measured on MRI. LF samples were obtained during the surgery. Fibrosis score was assessed by Masson's trichrome staining. The expression of miR-21 in LF tissues were determined by RT-PCR. Correlation among LF thickness, fibrosis score, and miR-21 expression was analyzed. In addition, Lentiviral vectors for miR-21 mimic were constructed and transfected into LF cells to examine the role of miR-21 in LF fibrosis. Types I and III collagen were used as indicators of fibrosis. IL-6 expression in LF cells after transfection was investigated by RT-PCR and ELISA. Patients in two groups showed similar outcomes regarding age, gender, level of LF tissue. The thickness and fibrosis score of LF in the LSCS group were significantly greater than those in LDH group (all P < 0.05). Similarly, the expression of miR-21 in LSCS group was substantially higher than that in LDH group(P < 0.05). Furthermore, the miR-21 expression exhibited positive correlations with the LF thickness (r = 0.595, P < 0.05) and fibrosis score (r = 0.608, P < 0.05). Of note, miR-21 over-expression increased the expression levels of collagen I and III (P < 0.05). Also, IL-6 expression and secretion in LF cells was elevated after transfection of miR-21 mimic. MiR-21 is a fibrosis-associated miRNA and promotes inflammation in LF tissue by activating IL-6 expression, leading to LF fibrosis and hypertrophy.

Expression of the JAK/STAT signaling pathway in the ligamentum flavum of patients with lumbar spinal canal stenosis.

BACKGROUND: Ligamentum flavum (LF) hypertrophy is an important cause of lumbar spinal canal stenosis (LSS), one of the most common spinal disorders in the elderly. Although many cytokines are reported to be associated with LF hypertrophy, the intracellular signaling system is rarely discussed. The purpose of this study was to identify the JAK/STAT signaling pathway and to examine the role of the JAK/STAT systems in the hypertrophied LF. METHODS: The LF of 10 LSS patients was analyzed and the expression of JAK1, STAT3, phosphorylated (p)-STAT3, and actin was examined by Western blot analysis. The expression of p-STAT3 was also examined by immunostaining and its positive cell ratio was compared between LSS and non-LSS samples. We measured the thickness of the LF on magnetic resonance images and studied the relationship between its thickness and the expression of p-STAT3. RESULTS: JAK1, STAT3, and p-STAT3 were detected in almost all samples by Western blot analysis. Immunoreactivity against p-STAT3 was observed mainly in endothelial- and fibroblast-like cells. The expression of p-STAT3 was significantly higher in LSS than non-LSS samples; it was significantly stronger on the dorsal than the dural side of the LF and positively correlated with the thickness of the LF on the dorsal side. CONCLUSIONS: The JAK/STAT signaling pathway is positively correlated with the thickness of the LF. Our findings suggest that JAK1 and STAT3 molecules are involved in and regulate LF hypertrophy.

Minimally Invasive Surgical Management of Thoracic Ossification of the Ligamentum Flavum Associated with X-linked Hypophosphatemia.

BACKGROUND: X-linked hypophosphatemia (XLH) is the most common inherited form of renal phosphate wasting and inherited rickets. Patients have hyperplasia of fibrochondrocytes in tendons and ligaments, causing the structures to thicken and calcify. Thickening of the lamina, hypertrophy of facet joints, and calcification of spinal ligaments are sequelae of this condition and can result in central or foraminal stenosis that compresses nerve roots or the spinal cord. We present a case of XLH with calcification of the ligamentum flavum in which the patient was operated on using minimally invasive posterior decompression. CASE DESCRIPTION: A 49-year-old man with a history of XLH presented to our emergency department with symptomatic myelopathy from multilevel thoracic stenosis. Radiographically, the calcified ligamentum flavum appeared to be the cause of the stenosis at various levels. The patient underwent a posterior decompression at the levels of compression, T4-T5, T8-T9, T9-T10, and T11-T12, via a minimally invasive spine surgery approach. Intraoperatively, the ligamentum flavum appeared to be both calcified and the source of spinal compression. Postoperatively, the patient experienced neurologic and radiographic improvement. CONCLUSION: Patients with a history of XLH and multilevel symptomatic spine stenosis can be treated successfully and safely with a minimally invasive posterior decompression.

A genealogical and clinical study of the phenotypical variation within the Swedish transthyretin His88Arg (p. His108Arg) amyloidosis family.

UNLABELLED: In 2005 we reported the first case of transthyretin His88Arg (p. His108Arg) amyloidosis, a mutation characterised by cardiomyopathy. Six additional gene carriers of whom five have clinical symptoms of disease have now been identified in Sweden, and we have been able to identify a possible founder and to characterise the Swedish phenotype of the transthyretin (TTR) His88Arg mutation. Genealogical studies of church records were used to identify the individuals with the disease and their families. Routine clinical investigations of neurological and heart manifestation of the disease were utilised. We found that genealogically all seven individuals were related and originated from the same region in Sweden. Amyloid deposits were demonstrated in biopsies and the TTR His88Arg mutation was identified in all patients. Patients had a late onset disease (≥ 50 years of age) and all exhibited a severe amyloid cardiomyopathy. A pronounced peripheral axonal neuropathy was with certainty demonstrated in one patient only, who also was operated for a magnetic resonance confirmed spinal stenosis, however, without any effect on his neurological symptoms. Five of the patients had carpal tunnel syndrome. The first reported case is now deceased from cardiac failure. One patient has had a sequential heart and liver transplantation. One gene carrier had no symptoms or findings of disease on latest evaluation at the age of 44. IN CONCLUSION: the Swedish TTRHis88Arg patients all have a common Swedish founder. Cardiomyopathy with heart failure, as well as carpal tunnel syndrome and spinal stenosis were early signs of disease; but peripheral neuropathy was present in one patient before symptoms of cardiomyopathy so the phenotypical presentation of this mutation is variable.

Isolated cervical spinal canal stenosis at C-1 in the pediatric population and in Williams syndrome.

OBJECT: Isolated cervical canal stenosis at the level of the atlas (C-1) is a rare cause of cervical myelopathy in the pediatric population. It has been associated with several genetic disorders including spondyloepiphysial dysplasia congenita, Down syndrome, and Klippel-Feil syndrome. The purpose of this study is to highlight the authors' experience with 4 additional pediatric cases, review the literature, and report a new association of this disease with Williams syndrome. METHODS: The medical records and radiological imaging studies of 4 patients treated at Texas Children's Hospital for symptomatic hypoplasia of the atlas were retrospectively reviewed. Pertinent patient demographic data, clinical presentation, imaging findings, and outcomes after surgery were recorded. A thorough literature review was performed, allowing the authors to compare and contrast their 4 cases to surgical cases already published in the literature. RESULTS: There were 11 boys and 1 girl in the aggregate series. The average age of the patients was 7 years (range 13 months-14 years), and the duration of symptoms prior to presentation was 6 months (range 0-36 months). The mean sagittal diameter of the spinal canal at the level of the atlas measured from the posterior aspect of the dens to the anterior aspect of the arch of C-1 was 11.9 mm (range 8.3-16 mm) in the aggregate series. In 2 new pediatric patients with hypoplasia of the atlas the disease was associated with Williams syndrome, which has not been previously described. Patients in the aggregate series were followed for an average of 18 months (range 3-50 months). Laminectomy of C-1 provided neurological improvement in all patients who presented. CONCLUSIONS: Isolated cervical spinal canal stenosis at the level of the atlas is a rare cause of cervical myelopathy. The authors hope that this report will prompt clinicians to consider it when searching for the origin of signs and symptoms of cervical myelopathy, especially in children.

Type IX collagen neo-deposition in degenerative discs of surgical patients whether genotyped plus or minus for COL9 risk alleles.

STUDY DESIGN: Immunohistochemical analysis of type IX collagen in disc tissue from spinal fusion patients. OBJECTIVE: To determine if collagen IX can be detected in adult disc tissue removed at spinal fusion surgery from patients either with or without degeneration-associated tryptophan single nucleotide polymorphisms (SNPs) and whether the distribution is associated either with severity of degeneration or incidence of a collagen IX SNP genotype. SUMMARY OF BACKGROUND DATA: Genetic factors are strongly associated with risk of development and/or progression of disc degeneration. Two SNPs that introduce tryptophan polymorphisms in COL9A2 and COL9A3 are independently linked to an increased risk of lumbar disc disease. Although tryptophan variants are associated with accelerated degeneration, it is not known if collagen IX can be detected in adult disc tissue. METHODS: We selected age-matched disc samples from five clinical groups: fracture with Trp(-) (six cases), herniation (six cases), degeneration (five cases), spondylolisthesis with Trp(-) (eight cases), and spondylolisthesis/herniation/fracture with Trp(+) (six cases of Trp3 allele and one case of Trp2 allele). Using hematoxylin and eosin staining and immunohistochemical staining (collagens IX and IIA), 78 sections from 32 patients were analyzed. Selected disc tissues were assayed biochemically for collagen IX. RESULTS: Focal deposition of collagen IX was observed in regions of adult human disc tissue from spines showing degenerative changes in patients whether or not they were positive for a tryptophan SNP. However, in nondegenerative control disc tissue from fracture cases, little or no collagen IX was detected. The latter finding was confirmed by direct biochemical analyses for collagen IX in pooled samples of normal adult human annulus fibrosus or nucleus pulposus. CONCLUSION: During growth and maturation of the disc, collagen IX is presumably removed completely during matrix remodeling so that the protein is absent from normal adult annulus and nucleus but can reappear at sites of degeneration presumably as part of a repair response to mechanical injury.

Neurosurgical implications of achondroplasia.

OBJECT: Achondroplasia is the most common form of human short-limbed dwarfism. The pediatric neurosurgeon is frequently required to treat children with achondroplasia who have hydrocephalus, cervicomedullary compression (CMD), and spinal canal stenosis. Accordingly, the authors have reviewed the experience of neurosurgery in children with achondroplasia at The Hospital for Sick Children. METHODS: The medical records and neurosurgery database at The Hospital for Sick Children were searched to identify all children with achondroplasia who underwent at least 1 neurosurgical procedure between 1956 and the present. RESULTS: Twenty-nine children with achondroplasia underwent 85 surgical procedures: 52 for CSF diversion in 12 patients, 20 for CMD in 18 patients, 8 for spinal disorders in 4 patients, and 5 for miscellaneous purposes in 4 patients. The CSF shunts were placed almost exclusively before 1990 and were associated with a significant number of complications. Patients undergoing CMD did very well, with only 1 patient failing to improve clinically. CONCLUSIONS: This review provides a historical perspective on the evolution of treatment of pediatric patients with achondroplasia. The use of CSF diversion procedures, formerly fraught with complications, is now rare following the realization of the natural history of CSF space enlargement in these patients. Cervicomedullary compression is more commonly recognized due to better imaging. Central apnea is now better detected by routine sleep studies. Spine surgery, although rare, requires evaluation of both spinal stenosis and instability. These patients are best evaluated by a multidisciplinary team.

The association of lumbar spondylolisthesis with collagen IX tryptophan alleles.

Two collagen type IX gene polymorphisms that introduce a tryptophan residue into the protein's triple-helical domain have been linked to an increased risk of lumbar disc disease. To determine whether a particular subset of symptomatic lumbar disease is specifically associated with these polymorphisms, we performed a prospective case-control study of 107 patients who underwent surgery of the lumbar spine. Patients were assigned to one of five clinical categories (fracture, disc degeneration, disc herniation, spinal stenosis without spondylolisthesis and spinal stenosis with spondylolisthesis) based on history, imaging results, and findings during surgery. Of the 11 tryptophan-positive patients, eight had spinal stenosis with spondylolisthesis and three had disc herniation. The presence of the tryptophan allele was significantly associated with African-American or Asian designation for race (odds ratio 4.61, 95% CI 0.63 to 25.35) and with the diagnosis of spinal stenosis with spondylolisthesis (odds ratio 6.81, 95% CI 1.47 to 41.95). Our findings indicate that tryptophan polymorphisms predispose carriers to the development of symptomatic spinal stenosis associated with spondylolisthesis which requires surgery.

Brachyolmia and spinal stenosis.

Brachyolmia is a rare short-trunk short stature skeletal dysplasia characterized by generalized platyspondyly without significant epiphyseal or metaphyseal changes in the long bones. This group of skeletal dysplasia is heterogeneous and four types have been differentiated on the basis of radiological and genetic findings. We report on two siblings with Hobaek-type brachyolmia complicated by spinal stenosis. This combination has never been reported in the literature and suggests further genetic heterogeneity within brachyolmia.

Cervical spinal cord compression attributable to a calcified intervertebral disc in a patient with X-linked hypophosphatemic rickets: case report and review of the literature.

OBJECTIVE AND IMPORTANCE: X-linked hypophosphatemic rickets is a common inherited phosphate-wasting disorder, but it is a rare cause of spinal cord compression. We present the first reported case of a calcified intervertebral disc causing spinal canal stenosis in X-linked hypophosphatemic rickets. CLINICAL PRESENTATION: A 44-year-old woman presented with paresthesia of her left arm and a loss of grip in both hands. Magnetic resonance imaging revealed a calcified intervertebral disc, as well as a posterior osteophytic bar causing marked cervical cord compression at C6/C7. INTERVENTION: An anterior cervical discectomy at C6/C7 and fusion with autologous bone graft were performed. The patient then exhibited significant improvement. CONCLUSION: A review of the 16 published cases demonstrates that thickening of the vertebral laminae, facet joint hypertrophy, and ossification of the intervertebral discs, posterior longitudinal ligament, and/or ligamentum flavum contribute to spinal canal stenosis in X-linked hypophosphatemic rickets. Those changes are caused by the disease itself and are unlikely to be related to long-term vitamin D treatment. Eleven of 16 patients were reported to have experienced favorable outcomes after surgery.

Acromesomelic dysplasia associated with mild lumbar spine stenosis.

A rare case of acromesomelic dysplasia is reported. The radiological findings were consistent with shortness of all tubular bones, especially those of the forearms. There was also evidence of mild lumbar spine stenosis.

Foramen magnum decompression for cervicomedullary encroachment in craniometaphyseal dysplasia: case report.

OBJECTIVE AND IMPORTANCE: Foramen magnum encroachment has been cited as a potential cause for the premature demise of patients afflicted with craniometaphyseal dysplasia (CMD). To our knowledge, the association of Chiari malformation and syringomyelia with CMD has not been previously reported. We describe our evaluation and surgical treatment of a patient presenting with CMD, foramen magnum stenosis, Chiari I malformation, and syringomyelia. CLINICAL PRESENTATION: A 15-year-old female patient with CMD presented with severe headaches and progressive myelopathy. Evaluation by computed tomography and magnetic resonance imaging revealed mild ventriculomegaly, cervicomedullary compression secondary to Chiari I malformation and foramen magnum stenosis, and C3-T10 syringomyelia. INTERVENTION: Foramen magnum decompression was performed via suboccipital craniectomy, C1-C2 laminectomy, and dural augmentation. Dysplastic bone was revealed to be extremely thick and mineralized. Removal required lengthy and extensive drilling. The postoperative course was complicated by prolonged intubation secondary to airway obstruction and a perforated duodenal ulcer. Airway obstruction was attributed to severe nasopharyngeal bony dysplasia and soft tissue edema. The use of steroids in the treatment of airway edema and delayed enteral feeding was thought to contribute to ulcer development. Nevertheless, neurological symptoms improved dramatically. CONCLUSION: Foramen magnum decompression can be used to treat life-threatening cervicomedullary compression in patients with CMD. However, caution should be used because surgical intervention may be associated with a higher incidence of complications because of lengthy procedures and the spectrum of craniofacial impairments in patients with CMD.