Association between craniovertebral junction abnormalities and syringomyelia in patients with chiari malformation type-1

Objectives:To assess the correlation between craniovertebral junction (CVJ) abnormalities and syringomyelia in patients with Chiari malformation type-1 (CM1).Methods:This was a retrospective study including patients with CM1. Identification of cases was done by searching a radiology database at a university hospital from 2012 to 2017. Patients were divided into 2 groups based on whether CVJ abnormalities were present (CVJ+) or absent (CVJ-). The patients’ demographic and clinical data were reviewed. All magnetic resonance imaging studies were examined by a certified neuroradiologist.Results:Sixty-four consecutive patients with CM1 were included. The mean age was 24±17 years; 59% were females. The CVJ+ group had more female patients (p = 0.012). The most frequent CVJ abnormality was platybasia (71%), followed by short clivus (44%) and cervical kyphosis (33%). The CVJ abnormalities were more in Syringomyelia cases (p = 0.045). However, the results were not significant when hydrocephalus cases were excluded.Conclusion:Among CM1 patients, CVJ abnormalities were found more in patients with syringomyelia. Future studies with larger sample size are required to further study the correlation between CVJ abnormalities and both syringomyelia and hydrocephalus in CM1 patients.

Chiari malformation type-1 (CM1) was first described in 1891 by Austrian pathologist Hans Chiari.1,2 The CM1 is defined as caudal displacement of the cerebellar tonsils below the foramen magnum by 5 mm or more.3,4 This definition is merely a radiological definition. In the literature, the degree of cerebellar tonsil displacement varies from 3 mm to 5 mm.4 CM1 affects approximately 1% of the population and may involve a spectrum of neurologic involvement.2 Syringomyelia is reported in 25% of CM1 cases and may cause irreversible damage to the spinal cord with subsequent neurological deficits.5The pathophysiology of syringomyelia development in patients with CM1 has been extensively studied.6-9 Majority of publications indicated a block to the cerebrospinal fluid (CSF) circulation at the level of the craniovertebral junction (CVJ).8,9 Subsequently, the cerebrospinal fluid (CSF) accumulates and forms syringomyelia.8,9 The source of the CSF forming the syringomyelia can be from the fourth ventricle, the subarachnoid space (SAS), or from an extracellular source.8,9 From the 1950s to the 1970s, syringomyelia was believed to result from a difference in CSF pressure between the fourth ventricle and the central canal of the spinal canal.7 Theories to explain this mechanism include James Gardner’s water-hammer theory, Bernard Williams’ cranio-spinal pressure dissociation theory, and Ball and Dayan’s theory of tonsillar obstruction to the CSF pathway.10-12 In the 1990s, Oldfield believed that the mechanism of the development of syringomyelia involved abnormal CSF flow at the level of the foramen magnum.6,7 The descent of the cerebellar tonsils with each cardiac cycle produces a pressure wave in the spinal SAS, and thereby compresses the spinal cord from the outside and propagates a syrinx.7,9Several intradural and extradural factors have been implicated in the pathophysiology of CM1. Among the intradural factors identified during surgery for CM1, the presence of an arachnoid membrane obstructing the foramen of Magendie (i.e., an arachnoid veil) was significantly more frequent in patients with an associated syringomyelia.6 Other studies have examined whether the degree of tonsillar descent below foramen magnum in the CM1 patients is a contributing factor to the development of syringomyelia; however, the impact of tonsillar descent is controversial.6,9,13 Some studies have reported that the rate of syringomyelia increases as the degree of tonsillar herniation increases.6,9 As a possible explanation for syringomyelia development, other studies14,15 have addressed crowding of the SAS at the foramen magnum caused by tonsillar decent. In a study by Doruk et al15, the measured cervicomedullary compression ratio, defined as the ratio of the area occupied by the cerebellar tonsils to the area of the foramen magnum, was significantly correlated with the development of syringomyelia. This ratio could reflect the severity of blockage of the SAS at the CVJ and further supports the previously described mechanisms of syringomyelia development.9Extradural abnormalities at the CVJ are associated with CM1.15 Such pathologies include a small posterior cranial fossa, platybasia, basilar invagination, and short clivus.3,6,8,9 Several studies have examined the presence of CVJ abnormities in CM1 patients with and without syringomyelia.13,16-21 However, the presence of associated syringomyelia within the context of CM1 with and without CVJ abnormalities was inadequately highlighted. For instance, in one study,13 syringomyelia existed in 64% of CM1 patients with a short clivus, compared to 36% of CM1 patients without a short clivus. In order to further understand the relationship between the presence of one or more CVJ abnormalities and syringomyelia in CM1, the current study was conducted. Such knowledge will likely enhance the understanding of CVJ relationship with CM1 and may aid in the management of syringomyelia in such patients.     

Pulmonary delivery of polyplexes for combined PAI-1 gene silencing and CXCR4 inhibition to treat lung fibrosis

This report describes the development of polyplexes based on CXCR4-inhibiting poly(ethylenimine) derivative (PEI-C) for pulmonary delivery of siRNA to silence plasminogen activator inhibitor-1 (siPAI-1) as a new combination treatment of pulmonary fibrosis (PF). Safety and delivery efficacy of the PEI-C/siPAI-1 polyplexes was investigated in vitro in primary lung fibroblasts isolated from mice with bleomycin-induced PF. Biodistribution analysis following intratracheal administration of fluorescently labeled polyplexes showed prolonged retention in the lungs. Treatment of mice with bleomycin-induced PF using the PEI-C/siPAI-1 polyplexes resulted in a significant down-regulation of the PAI-1 expression and decreased collagen deposition in the lung. The results of this study provide first evidence of the potential benefits of combined inhibition of CXCR4 and PAI-1 in the pulmonary treatment of PF.     

Assessing the complications and effectiveness of open carpal tunnel release in a tertiary care centre in a developing country

INTRODUCTION

Open surgical release for carpal tunnel syndrome is not devoid of complications and its quantitative assessment with the Boston questionnaire in a developing country had not been conducted, where, lack of facilities and surgical technique can influence the outcome.

PRESENTATION OF CASE

This was a prospective study in which all cases of carpal tunnel syndrome undergoing open release between June 2007 and June 2012 and who returned for follow up were included. Each patient was requested to fill out the Boston questionnaire twice both pre and post op at 3 months. All complications were recorded as well as bio-data of patients and co morbidities. Follow up was at 2 weeks and at 3 months. Those reporting complications at 3 months were further followed up until 6 months. 373 patients were included in the study. Twenty four patients developed complications. Of these, 12 experienced pain resulting from reflex sympathetic dystrophy. Three patients developed wound dehiscence, 2 cases acquired infections, 4 patients developed immediate post-operative haemorrhage and in 3 patients there was late recurrence of median nerve compression. The symptom severity score pre-operatively was 3.30 (±0.60) and it improved to 1.65 (±0.75) post-operatively indicating a significant change (p < 0.0001). The preoperative functional status score was 2.58 (±0.75) and post-op it became 1.60 (±0.80) again implying a good improvement with an effect size of 1.3.

DISCUSSION

All of the complications produced were well managed. The complication incidence was low. The open release procedure produced good improvement in hand function and in decreasing the symptom severity.

CONCLUSION

Conducting open release for carpal tunnel syndrome in a tertiary referral centre in a developing country offers a good outcome.     

The oblique plane deformity in slipped capital femoral epiphysis

Background

Slipped capital femoral epiphysis (SCFE) is commonly treated with in situ pinning. However, a severe slip may not be suitable for in situ pinning because the required screw trajectory is such that it risks perforating the posterior cortex and damaging the remaining blood supply to the capital epiphysis. In such cases, an anteriorly placed screw may also cause impingement. It is also possible to underestimate the severity of the slip using conventional radiographs. The aim of this study was to describe and evaluate a novel method for calculating the true deformity in SCFE and to assess the interobserver and intraobserver reliability of this technique.

Methods

We selected 20 patients with varying severity of SCFE who presented to our institution. Cross-sectional imaging [either axial computed tomography (CT) scans or magnetic resonance imaging (MRI) scans] and anteroposterior (AP) pelvis radiographs were assessed by four reviewers with varying levels of experience on two occasions. The degree of slip on the axial image and on the AP pelvis radiographs were measured and, from this, the oblique plane deformity was calculated using the method as popularised by Paley. The intraclass correlation coefficient (ICC) was calculated to determine the interobserver and intraobserver reliabilities between and amongst the raters.

Results

The interobserver reliability for the calculated oblique plane deformity in SCFE ICC was 0.947 [95 % confidence interval (CI) 0.90–0.98] and the intraobserver reliability for the calculated oblique plane deformity of individual raters ranged from 0.81 to 0.94. The deformity in the oblique plane was always greater than the deformity measured in the axial or the coronal plane alone.

Conclusion

This method for calculating the true deformity in SCFE has excellent interobserver and intraobserver reliability and can be used to guide treatment options. This technique is a reliable and reproducible method for assessing the degree of deformity in SCFE. It may help orthopaedic surgeons with varying degrees of experience to identify which hips are suitable for in situ pinning and those which require surgical dislocation and anatomical reduction, given that plain radiographs in a single plane will underestimate the true deformity in the oblique plane.

Level of evidence

Level II diagnostic study.     

Ameliorative effects of rutin against cisplatin-induced reproductive toxicity in male rats

Background

Cisplatin (CP) or cis-diammine dichloroplatinum (II) is a platinum based standard antineoplastic drug which is used against variety of solid tumors and neoplasms. The present study aimed to evaluate the shielding effects of rutin against CP induced testicular toxicity in rats.

Methods

28 male rats were divided into four groups. First group was given saline orally while second group received intra-peritoneal (i.p) injection of cisplatin (7 mg/kg) on day first and received saline for next 13 days. Third group received i.p injection of cisplatin at day one and treated with rutin (75 mg/kg) orally for next 13 days. Fourth group was treated with rutin orally for 13 days. Animals were sacrificed on 14th day and reproductive organs were analyzed for various parameters.

Results

Cisplatin treatment resulted in a significant decrease in daily sperm production, decrease in head length and % DNA in head, reduction of epithelial cell height, tubular diameter, reduction of the number of spermatogonia, spermatocytes and spermatids, increase in the thiobarbituric acid reactive substances (TBARS) and oxidative stress in testicular tissues, and change of the intra-testicular testosterone concentrations. Rutin co-treatment resulted in reversing cisplatin effect on DNA damage, sperm count, histological and biochemical parameters.

Conclusion

These results indicated that rutin co-treatment could ameliorate cisplatin-induced reproductive toxicity in male rats.

     

Immune molecular profiling of whole blood drawn from a non‐human primate cardiac xenograft model treated with anti‐CD154 monoclonal antibodies

Most studies of xenografts have been carried out with complex immunosuppressive regimens to prevent immune rejection; however, such treatments may be fatal owing to unknown causes. Here, we performed immune molecular profiling following anti‐CD 154 monoclonal antibody (mA b) treatment in heterotopic abdominal cardiac xenografts from α‐1,3‐galactosyltransferase‐knockout pigs into cynomolgus monkeys to elucidate the mechanisms mediating the undesirable fatal side effects of immunosuppressive agents. Blood samples were collected from healthy monkeys as control and then at 2 days after xenograft transplantation and just before humane euthanasia; 94 genes related to the immune system were analyzed. The basic immunosuppressive regimen included cobra venom factor, anti‐thymocyte globulin, and rituximab, with and without anti‐CD 154 mA bs. The maintenance therapy was followed with tacrolimus, MMF , and methylprednisolone. The number of upregulated genes was initially decreased on Day 2 (?/+ anti‐CD 154 mA b, 22/13) and then increased before euthanasia in recipients treated with anti‐CD 154 mA bs (?/+ anti‐CD 154 mA b, 30/37). The number of downregulated genes was not affected by anti‐CD 154 mA b treatment. Additionally, the number of upregulated genes increased over time for both groups. Interestingly, treatment with anti‐CD 154 mA bs upregulated coagulation inducers (CCL 2/IL 6 ) before euthanasia. In conclusion, immunosuppressive regimens used for cardiac xenografting affected upregulation of 6 inflammation genes (CXCL 10, MPO , MYD 88, NLRP 3, TNF α, and TLR 1) and downregulation of 8 genes (CCR 4 , CCR 6 , CD 40 , CXCR 3 , FOXP 3 , GATA 3 , STAT 4 , and TBX21 ).