Κυριακή, 13 Ιανουαρίου 2019

Allergic contact dermatitis from topical ophthalmic medications

Allergic contact dermatitis from topical ophthalmic medications: keep an eye on it!
Liesbeth Gilissen  Lana Dedecker  Toon Hulshagen  An Goossens
First published: 10 January 2019 https://doi.org/10.1111/cod.13209
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/cod.13209.
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Abstract
Background
Allergic contact dermatitis (ACD) from topical ophthalmic medications is often overlooked.

Objectives
To study the demographic characteristics, lesion locations, and associated medical conditions of the patients with ACD from ophthalmic drugs, and to identify the most common allergenic culprits, as well as trends in frequencies over the years.

Methods
From January 1990 until December 2016, 16 065 patients were investigated in our clinic; all patients with a positive patch‐test reaction to eye medication or its ingredient(s) having caused ACD were studied. For each allergen identified, the number of positive test results compared with the total number of those in the total population, as well as trends across three periods, namely 1990‐1998, 1999‐2007, and 2008‐2016 were studied.

Results
118 patients (0.7%) presented with positive patch‐test results to ingredients of, and/or topical ophthalmic medications. Aminoglycoside antibiotics, followed by corticosteroids, as pharmacologically active ingredients, as well as wool alcohols, thiomersal and benzalkonium chloride, as excipients were the most frequent culprits. Particularly chloramphenicol showed a decreasing trend in positive reactions over time, whereas reactions tobramycin were increasing.

Conclusion
ACD from eye medication is mainly due to active principles, but other excipient ingredients, beside the products "as is", should be tested as well.
https://onlinelibrary.wiley.com/doi/10.1111/cod.13209

The combination of lanolin alcohol and Amerchol L101 is effective in patch testing for diagnosing lanolin contact allergy

Diagnosing lanolin contact allergy with lanolin alcohol and Amerchol L101
Jannet Knijp  Derk P. Bruynzeel  Thomas Rustemeyer
First published: 09 January 2019 https://doi.org/10.1111/cod.13210
This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi: 10.1111/cod.13210.
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Summary
Background
The prevalence of lanolin contact allergy in dermatitis patients varies from 1.2% to 6.9%. Different lanolin derivatives are used in patch testing.

Objectives
To determine which combination of lanolin derivatives is most effective in patch testing for diagnosing lanolin contact allergy.

Methods
A retrospective analysis of patients patch tested between 2016 and 2017 was performed. Patients were eligible if tested with lanolin alcohol 30% pet., Amerchol L101 50% pet. and a supplementary series containing other lanolin derivatives. Lanolin alcohol and Amerchol L101 were tested in duplicate.

Results
Out of 594 patients, 28.6% (95% confidence interval [CI]: 25.1%‐32.3%) had a positive patch test reaction to at least one lanolin derivative. Reactions were common to lanolin alcohol (14.7%, 95% CI: 11.3%‐18.2%) and Amerchol L101 (15.0%, 95% CI: 11.5%‐18.5%) in the routinely tested series. Reactions to other test preparations were significantly less frequent (P < 0.05). The addition of Amerchol L101 to lanolin alcohol significantly increased the number of positive cases (odds ratio 1.79, P < 0.001).

Conclusions
The combination of lanolin alcohol and Amerchol L101 is effective in patch testing for diagnosing lanolin contact allergy. Routinely testing with other lanolin derivatives may not be worthwhile as it detects only few additional patients.
https://onlinelibrary.wiley.com/doi/10.1111/cod.13210

Impaired antimicrobial response and mucosal protection induced by ibuprofen


Impaired antimicrobial response and mucosal protection induced by ibuprofen in the immature human intestine
Emanuela Ferretti, Eric Tremblay, Marie-Pierre Thibault, Sepideh Fallah, David Grynspan, Karolina M. Burghardt, Marcos Bettolli, Corentin Babakissa, Emile Levy & Jean-François Beaulieu 
Pediatric Researchvolume 84, pages813–820 (2018) | Download Citation

Abstract
Background
The use of nonsteroidal anti-inflammatory drugs (NSAIDs) such as indomethacin (INDO) and ibuprofen (IBU) has been shown to be an effective therapy for the closure of patent ductus arteriosus (PDA). However, this treatment has been associated with an increased risk of developing enteropathies in neonates. Whether the use of IBU is safer than INDO for the immature intestine remains to be elucidated.

Methods
The direct impact of IBU on the human immature intestinal transcriptome was investigated using serum-free organ culture. Differentially expressed genes were analyzed with Ingenuity Pathway Analysis software and compared with those previously reported with INDO. Validation of differentially expressed genes was confirmed by qPCR.

Results
We identified several biological processes that were significantly modulated by IBU at similar levels to what had previously been observed with INDO, while the expression of genes involved in "antimicrobial response" and "mucus production" was significantly decreased exclusively by IBU in the immature intestine.

Conclusions
Our findings indicate that IBU has a harmful influence on the immature intestine. In addition to exerting many of the INDO observed deleterious effects, IBU alters pathways regulating microbial colonization and intestinal epithelial defense.
https://www.nature.com/articles/s41390-018-0201-y

Pediatric sinonasal rhabdomyosarcoma (RMS)


Clinicopathologic traits and prognostic factors associated with pediatric sinonasal rhabdomyosarcoma
Sana H. Siddiqui BA  Emaad Siddiqui BS  Rich D. Bavier BA  Nirali M. Patel BA  Suat Kiliç MD Soly Baredes MD, FACS  Wayne D. Hsueh MD  Jean Anderson Eloy MD, FACS, FARS
First published: 10 January 2019 https://doi.org/10.1002/alr.22267
Potential conflict of interest: None provided.
Presented orally at the 64th Annual Meeting of the American Rhinologic Society, Atlanta, GA, October 5‐6, 2018.
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Abstract
Background
Pediatric sinonasal rhabdomyosarcoma (RMS) is an aggressive and rare malignancy. This is the first multi‐institutional study on the prognostic factors associated with outcomes in this population.

Methods
The National Cancer Database was queried for the period from 2004 to 2013 for all cases of malignant sinonasal RMS in the pediatric population. The impact of patients' demographics, tumor characteristics, and Intergroup Rhabdomyosarcoma Study Group (IRSG) staging on survival was assessed using chi‐square test, Fisher's exact test, Kaplan‐Meier test, and Cox regression analyses.

Results
A total of 157 cases of pediatric sinonasal RMS were identified. Mean age at diagnosis was 9.38 years and male patients comprised 48.4% of the cohort. The nasal cavity (31.8%) and maxillary sinus (30.6%) were the most common primary sites. Alveolar was the most common histology (49.7%), followed by embryonal type (32.5%). The majority of patients received solely chemoradiation (52.9%), followed by surgery with adjuvant chemoradiation (30.6%). Five‐year overall survival (OS) was 55.2% (±4.5%). Metastatic disease was associated with a poorer 5‐year OS rate (24.4% vs 61.5%; p = 0.010). Maxillary sinus site was associated with an improved survival (71.8% vs 47.6%; p = 0.009). On multivariate analysis, chemoradiation with or without surgery was an additional prognostic factor. Although IRSG clinical stages did not correlate with survival, high‐risk patients in the IRSG clinical risk groups were associated with poorer survival on multivariate analysis (hazard ratio [HR], 2.005; 95% confidence interval, 1.007‐3.993; p = 0.048).

Conclusion
To date, this is the largest study on pediatric sinonasal RMS. IRSG clinical risk groups may be useful in stratifying high‐risk patients with poor prognosis.
https://onlinelibrary.wiley.com/doi/10.1002/alr.22267

Formation of papillary mucosa folds and enhancement of epithelial barrier in odontogenic sinusitis


Formation of papillary mucosa folds and enhancement of epithelial barrier in odontogenic sinusitis
Yuan Zhang MD, PhD  Feng Lan MD, PhD  Ying Li BS  Chengshuo Wang MD, PhD  Luo Zhang MD, PhD
First published: 08 January 2019 https://doi.org/10.1002/alr.22277
Funding sources for the study: National Key R&D Program of China (2016YFC20160905200); the National Natural Science Foundation of China (81570895, 81420108009, 81400444, 81470678, and 81630023); Changjiang Scholars and Innovative Research Team (IRT13082); Special Fund of Capital Health Development (2011‐1017‐06, 2011‐1017‐02); Special Fund of Sanitation Elite Reconstruction of Beijing (2009‐2‐007); Beijing Health Bureau Program for High Level Talents (2011‐3‐043); Beijing Municipal Administration of Hospitals' Mission Plan (SML20150203); Capital Citizenry Health Program (z161100000116062).
Potential conflict of interest: None provided.
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Abstract
Background
Odontogenic sinusitis (OS) presents more satisfactory therapeutic effect after endoscopic surgery compared with chronic rhinosinusitis (CRS) of other origin. The aim of the present study was to investigate the clinical characteristics, morphological features, and epithelial barrier function of sinus mucosa of OS and discuss the possible relationship with good prognosis.

Methods
A total of 25 subjects with OS, 7 CRS without nasal polyps (CRSsNP), 10 CRS with nasal polyps (CRSwNP), and 9 control subjects were recruited. The biopsy specimens were stained with hematoxylin and eosin for general observation of cytomorphologic features. Epithelial tight junctions (TJs) protein claudin‐4 expression was determined to evaluate the epithelial barrier integrity by using immunofluorescence and Image‐Pro Plus software analysis. The representative cytokine profiles regarding T helper 1 (Th1) (interferon [IFN]‐γ), Th2 (interleukin [IL]‐5), and Th17 (IL‐17) were examined by reverse transcription–polymerase chain reaction (RT‐PCR).

Results
Extensively small papillary protrusions could be seen in the maxillary sinus mucosa of OS patients under nasal endoscopy, similar to the morphological behavior, which also presented as papillary folds in the surface of the epithelium. The epithelium in OS kept an increased claudin‐4 expression compared with that seen in CRSsNP, CRSwNP, and control subjects. The inflammatory pattern analysis demonstrated that OS belonged to the lymphocyte and plasma cell‐dominant cellular phenotypes, whereas IL‐17 was dominant compared with IFN‐γ as well as IL‐5.

Conclusion
The odontogenic infections might induce the formation of papillary mucosa folds and enhance the epithelial TJ barrier function. OS exhibited as lymphocyte and plasma cell–dominant cellular phenotypes and Th17 cytokine profiles.
https://onlinelibrary.wiley.com/doi/10.1002/alr.22277

Broncho‐Vaxom(R) (OM‐85 BV) soluble components stimulate sinonasal innate immunity


Broncho‐Vaxom® (OM‐85 BV) soluble components stimulate sinonasal innate immunity
Vasiliki Triantafillou BS  Alan D. Workman MD  Neil N. Patel BA, BS  Ivy W. Maina BA Charles C. L. Tong MD  Edward C. Kuan MD, MBA  David W. Kennedy MD  … See all authors
First published: 07 January 2019 https://doi.org/10.1002/alr.22276
Funding sources for the study: National Institutes of Health (National Institute on Deafness and Other Communication Disorders [NIDCD] R01DC013588 to N.A.C.); Veterans Affairs Merit Review (CX001617 to N.A.C.).
Potential conflict of interest: None provided.
Presented orally at the ARS Meeting at the annual Combined Otolaryngology Spring Meetings (COSM) on April 18‐22, 2018, National Harbor, MD.
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Abstract
Background
Broncho‐Vaxom® (OM‐85 BV) is an extract of infectious respiratory bacteria that is used as an immunostimulant outside of the United States for the prevention and treatment of bronchitis and rhinosinusitis. Prior studies have shown that use of OM‐85 BV is associated with reduction in frequency of respiratory infection and decreased duration of antibiotic usage. However, the effects of OM‐85 BV on respiratory mucosal innate immunity are unknown.

Methods
Human sinonasal epithelial cells were grown at an air‐liquid interface (ALI). Ciliary beat frequency (CBF) and nitric oxide (NO) production in response to stimulation with OM‐85 BV was measured in vitro. Pharmacologic inhibitors of bitter taste receptor (T2R) signaling were used to determine if this pathway was taste‐receptor–mediated.

Results
Apical application of OM‐85 BV resulted in an NO‐mediated increase in CBF (p < 0.05) and increased NO production (p < 0.0001) when compared to saline‐stimulated control cultures. ALI pretreatment with taste receptor pathway inhibitors blocked OM‐85 BV–induced increases in NO.

Conclusion
OM‐85 BV has ciliostimulatory and immunogenic properties that may be partially responsible for its observed efficacy as a respiratory therapeutic. These responses were NO‐dependent and consistent with T2R activation. Further work is necessary to elucidate specific component‐receptor signaling relationships.
https://onlinelibrary.wiley.com/doi/10.1002/alr.22276

Phenotypic spectrum of NDE1‐related disorders: from microlissencephaly to microhydranencephaly

Biallelic variants in the NDE1 gene have been shown to occur in extreme microcephaly. Most of the patients displayed microlissencephaly but one with microhydranencephaly. We report on three sibs in which the brain MRI and CT scans demonstrated variable degree of reduced volume of cerebral hemispheres and ventriculomegaly. Further, they had agenesis of corpus callosum, cerebellar, and brainstem hypoplasia. Fetal ultrasound at 32 weeks' gestation of the third sib revealed severe micrencephaly with extensive hydranencephaly and an anomaly consistent with non cleaved (fused) thalami. Because of the fused thalami, the STIL gene was targeted initially but showed negative results. His postnatal MRI showed that the cerebral hemispheres are markedly reduced in size (with no definite frontal, parietal, or occipital lobes) and replaced by a large sac filled with CSF. An intact falx cerebri was identified. This extensive hydarencephaly led us to consider the NDE1 and to identify a novel homozygous nonsense variant (c.54G>A, p.W18*). The variability of the degree of brain malformations and the apparent fusion of the thalami were illusive and delayed the recognition of the genetic etiology. Our results provide the first antenatal description of this rare syndrome. Further, we expand the genetic architecture and the neuroradiologic phenotype of NDE1‐related disorders.



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Refining the Primrose syndrome phenotype: A study of five patients with ZBTB20 de novo variants and a review of the literature

Abstract

Primrose syndrome is a rare autosomal dominant condition caused by heterozygous missense variants within ZBTB20. Through an exome sequencing approach (as part of the Deciphering Developmental Disorders [DDD] study) we have identified five unrelated individuals with previously unreported, de novo ZBTB20 pathogenic missense variants. All five missense variants targeted the C2H2 zinc finger domains. This genotype‐up approach has allowed further refinement of the Primrose syndrome phenotype. Major characteristics (>90% individuals) include an intellectual disability (most frequently in the moderate range), a recognizable facial appearance and brain MRI abnormalities, particularly abnormalities of the corpus callosum. Other frequent clinical associations (in 50–90% individuals) include sensorineural hearing loss (83%), hypotonia (78%), cryptorchidism in males (75%), macrocephaly (72%), behavioral issues (56%), and dysplastic/hypoplastic nails (57%). Based upon these clinical data we discuss our current management of patients with Primrose syndrome.



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Abnormal bone mineral content and density in people with tetrasomy 18p

Tetrasomy 18p is a rare chromosomal abnormality, resulting from an additional iso‐chromosome composed of two copies of the short arm. It is characterized by craniofacial abnormalities, neuromuscular dysfunction, and developmental delay. The Chromosome 18 Clinical Research Center has established the largest cohort of individuals with this rare genetic condition. Here, we describe a case series of 21 individuals with tetrasomy 18p who have a previously unreported clinical finding: low bone mineral density. Most individuals met criteria for osteopenia despite being relatively young (mean age of 21 years). Clinicians providing care to individuals affected by Tetrasomy 18p should be aware of their increased risk for decreased bone density and pathological fractures.



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The incidence of anxiety symptoms in boys with 47,XXY (Klinefelter syndrome) and the possible impact of timing of diagnosis and hormonal replacement therapy

47,XXY (Klinefelter syndrome) is the most common X and Y chromosomal variation (1:660 males). The incidence of anxiety disorders and the impact of hormonal replacement therapy (HRT) is not well understood. Child Behavior Checklist and Screen for Childhood Anxiety Related Emotional Disorders were completed by parents of 80 boys with 47,XXY. Forty received HRT prior to 10 years of age while 40 did not. HRT (22.5%) received early hormonal treatment prior to 18 months. About 32.5% received hormone booster treatment between 5 and 10 years. The remaining 42.5% received both. There were fewer reported social (p = .015), thought (p = .012), and affective problems (p = .048) in treated boys when compared to untreated. Boys with both treatments demonstrated fewer symptoms on anxious/depressed scale (p = .001) compared to those with early treatment only. Within the treated group, prenatally diagnosed showed fewer indications of anxiety problems (p = .02) than their postnatal counterparts. This comparative, cross‐sectional study expands previous findings on the possible positive effect of HRT in boys with 47,XXY. Anxiety disorders appear to be a penetrant aspect of the 47,XXY phenotype. Further investigation is warranted to explore the relationship between biological treatment and individual responses to HRT to develop more personalized and precise medicine.



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Solid tumor screening recommendations in trisomy 18

The purpose of this study was to determine whether trisomy 18 patients are at an increased risk of tumor development and require formal tumor screening recommendations. A literature search of trisomy 18 patients with reports of tumors or malignancies, and compilation of all previously reported as well as new unreported cases was performed. 67 patients with trisomy 18 were found to have documented malignancies. 44 patients had hepatoblastomas, 21 patients had Wilms tumors, one patient had a functional neurogenic neoplasia, and one patient had Hodgkins lymphoma. The increasing numbers of reported malignancies in patients with trisomy 18 supports the indication for an early screening process. Specific screening recommendations are outlined consisting of imaging exams and laboratory values performed at specific intervals.



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High 222Rn concentrations and dynamics in Shawan Cave, southwest China

Publication date: April 2019

Source: Journal of Environmental Radioactivity, Volumes 199–200

Author(s): Yanwei Wang, Weijun Luo, Guangneng Zeng, Yang Wang, Hanling Yang, Meifang Wang, Lin Zhang, Xianli Cai, Jia Chen, Anyun Cheng, Shijie Wang

Abstract

Cave 222Rn has been a major health issue and subject of scientific debate for decades. While the basics of natural ventilation physics are well understood, it is difficult to make blind predictions of 222Rn concentrations in a given cave due to the complexity of cave systems. In-situ continuous observation is necessary to improve our ability to quantify radiation dose exposure and reduce radiation hazard to cave users, and trace the air exchange patterns occurring in caves. In this study, continuous monitoring using a RAD7 radon detector revealed high 222Rn concentrations and large fluctuations in 222Rn concentration in a small karst cave in southwest China, Shawan Cave. From August 2016 to July 2017, the average annual concentration was 47,419 Bqm−3 and ranged between 3720 and 123,000 Bqm−3, with lower values during summer than other seasons. Taking Shawan Cave as a case study, we suggest a framework to evaluate the potential dose exposure, allowing cave users to minimize risk of exposure to hazardous levels of 222Rn. Furthermore, we comparing results from this study with other studies in 35 caves worldwide, and conclude that there are three patterns of seasonal 222Rn variation. They were classified into five types of ventilation mode based on diversity of cave locations, geometry and connectivity of bed rock fracture networks, together with temperature differences between outside atmosphere and cave air.



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Cervical spondylotic myelopathy


Natural history, prevalence, and pathophysiology of cervical spondylotic myelopathy Highly accessed article p. 5
Gomatam Raghavan Vijay Kumar, Dibyendu Kumar Ray, Rupant Kumar Das
DOI:10.4103/isj.isj_48_18  
This study is a narrative review performed to summarize the current knowledge about the epidemiology, natural history and pathogenesis of cervical spondylotic myelopathy (CSM). A comprehensive search was undertaken to look at all available articles between January 1, 1956 to May 1, 2018, on PubMed and the Cochrane Collaboration Library. The natural history of CSM is variable. The main determinants of the clinical course of CSM are the extent of neurological impairment, age, cervical instability, abnormalities of cord conduction, canal diameter, congenitally stenotic spinal canal and the extent of involvement and tract disruption on diffusion tensor imaging (DTI) imaging. There is little data on the true incidence and prevalence of CSM across the globe and none from India. The pathoanatomic basis of CSM is cord compression, either dynamic or static. The biological events that are thought to play a significant role in the development of CSM are ischemia, derangement of the blood-spinal cord barrier, chronic neuronal inflammation, and apoptosis. Emerging knowledge about the molecular biology holds promise for potential intervention, both for prevention and for cure, of this common and debilitating condition.

Degenerative cervical myeloradiculopathy

Clinical spectrum and importance of evaluation systems in degenerative cervical myeloradiculopathy p. 13
Ganesh Swaminathan, Vetrivel Muralidharan, Baylis Vivek Joseph
DOI:10.4103/isj.isj_61_18  
Degenerative cervical myelopathy includes facet joint arthropathy and/or intervertebral disc prolapse, as well as aberration (hypertrophy, calcification, or ossification) in the ligamentum flavum, and/or posterior longitudinal ligament. Cervical spondylotic myelopathy and ossification of posterior longitudinal ligament are two major conditions under this spectrum. Patients with degenerative changes of the cervical spine can present with wide spectrum of symptoms and signs ranging from axial neck pain, radiculopathy or myelopathy. A combination of history, physical examination, and provocative tests such as Spurling's sign, shoulder abduction test, neck distraction test, Valsalva maneuver, Elvey's upper limb tension/brachial plexus tension test increase the likelihood of diagnosis of cervical radiculopathy. Myelopathy can manifest in the early stage as subtle changes in the upper limb dexterity or mild walking difficulty and in late stage with severe spasticity and flexor spasms. Clinicians are increasingly using quantitative or semi-quantitative scales of neurological impairment. However, there is no gold standard evaluation systems that can reliably assess disease severity.

Cervical spondylotic myelopathy

Anterior surgical options for cervical spondylotic myelopathy p. 33
Andrei Fernandes Joaquim, John Alex Sielatycki, K Daniel Riew
DOI:10.4103/isj.isj_39_18  
Cervical spondylotic myelopathy (CSM) is one of the most common among causes of spinal cord dysfunction worldwide. In this article, we provide a broad narrative review of the options to treat CSM from an anterior approach to the cervical spine. Anterior procedures are effective and safe, especially for one or two level disease (although can be used up to 7-8 levels). This approach can be used in patients with lordotic, neutral, or kyphotic cervical spine alignment and provide excellent access for direct neural decompression. The most common adverse effects of anterior cervical operations are dysphagia and dysphonia, but fortunately, these are mild and transient in the majority of cases. Severe complications, such as vertebral arterial injury, spinal cord injury or airway compromise, are rare but must be taken into consideration, especially when additional risk factors are present (multilevel procedures, revision surgeries, older, and infirm patients). The primary anterior cervical procedures for treating CSM are anterior cervical discectomy and fusion (ACDF), anterior cervical corpectomy and fusion (ACCF), oblique cervical corpectomy, and cervical disc arthroplasty. A combination (hybrid) of ACDF and ACCF is also utilized as an option to allow for wide decompression, deformity correction, and provide more surface area of exposed, and bleeding cancellous bone. More recently, the senior author (KDR) has utilized a hemi-corpectomy and fusion hybrid technique which will be described in this text. Advantages and disadvantages of each of these options are discussed in detail, as well as the need for posterior instrumentation supplementation in selected patients; such as those with concomitant cervical deformity, poor bone quality, or those at risk for pseudarthrosis following multilevel arthrodeses. The management of patients with cervical spinal cord compression without myelopathy or with mild symptoms is also discussed.

Spondylotic cervical myelopathy

Posterior surgical options for spondylotic cervical myelopathy p. 42
Shankar Acharya, Nikhil Jain
DOI:10.4103/isj.isj_57_18  
Cervical spondylotic myelopathy (CSM) is a common presentation in the middle-aged to elderly population. The cause of myelopathy is multifactorial, and cervical spondylosis is the most common cause. This review looks into the treatment options, timing of the surgery, and the advantages and disadvantages of the various posterior approaches for multilevel spondylotic myelopathy. CSM is a disabling disorder that should be addressed in its early phases. There are limited surgical options available, and each procedure has its advantages and disadvantages. Since the neurological and functional outcomes are the same for all well-performed decompressions, the choice of surgical approach depends on various other factors. Posterior approaches are good for multilevel disease as they make the surgery simpler, shorter and with reduced complications in comparison to multilevel anterior surgeries.

Ossification of the posterior longitudinal ligament

: Etiology, prevalence, progression, and surgical strategies p. 52
Yoshiharu Kawaguchi
DOI:10.4103/isj.isj_41_18  
Ossification of the posterior longitudinal ligament (OPLL) is characterized by replacement of the ligamentous tissue by ectopic new bone formation. OPLL often causes narrowing of the spinal canal and has been recognized as a cause of cervical myelopathy and/or radiculopathy. Although a clear inheritance of OPLL has not been identified, there is a strong genetic background for OPLL. A recent genome-wide association study using all Japan cohort reported that there were 6 susceptible loci for OPLL. In addition, there were several studies to seek the biomarkers of OPLL. OPLL is frequently found in the cervical spine. However, 53.4% had OPLL not only in the cervical spine, but also in other spinal regions in patients with cervical OPLL. Further, 65.2% with cervical OPLL had ossification of the ligamentum flavum (OLF) especially at the levels of the thoracic and the lumbar spine. There is no effective conservative treatment. Surgical decompression is considered in patients with severe and/or progressive myelopathy. Early surgical decompression of the spinal cord is recommended in patients with apparent myelopathy. Operative methods are divided into two procedures, anterior decompressive surgery and posterior decompressive surgery. The choice of the surgical procedure is determined according to several factors, such as local pathology of OPLL and spinal alignment.

The median labio-mandibulo-glossotomy approach to the upper cervical spine

: A personal series and tips and pearlsp. 92
K Venugopal Menon, Hood Al Saqri, Renjit Kumar, Maruti Kambali
DOI:10.4103/isj.isj_8_18  
Background: Wide exposure to the anterior part of the upper cervical spine is difficult due to anatomical constraints. The Labio-Mandibulo-Glossotomy (LMG) approach is considered a difficult approach with high morbidity. The objective of this study is to describe the authors experience with the approach and it's outcomes in six cases and offer tips and pearls to the surgical access. Methods: This is a retrospective review of a small series of six cases that were operated for upper cervical lesions by the LMG approach. Two had mandible fractures that needed fixation and in the others osteotomy of the mandible was performed. The patients were followed up for minimum two years or death (in malignancy). We specifically looked for cosmetic or functional problems related to osteotomy, glossotomy, and, hospital and ICU stay duration. Surgical access is described in detail. Results: The hospital stay was similar to other major spine trauma or tumour surgeries at our center (median 14 days) and mean ICU stay 2.8 days. There were no long-term issues related to the access. Several tips and tricks are offered to minimize intra and post-operative problems. Conclusions: The LMG approach, though apparently formidable, is quite a safe and simple procedure with few residual complications.

Spine

EDITORIALS 

Publish or perish Highly accessed articlep. 1
Anil K Jain, Manish Chadha
DOI:10.4103/isj.isj_74_18  
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Symposium on cervical spondylo-myelopathyp. 4
T Ajoy Prasad Shetty, Ankur Nanda
DOI:10.4103/isj.isj_71_18  
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SYMPOSIUM - CERVICAL SPONDYLOMYELOPATHYTop

Natural history, prevalence, and pathophysiology of cervical spondylotic myelopathy Highly accessed articlep. 5
Gomatam Raghavan Vijay Kumar, Dibyendu Kumar Ray, Rupant Kumar Das
DOI:10.4103/isj.isj_48_18  
This study is a narrative review performed to summarize the current knowledge about the epidemiology, natural history and pathogenesis of cervical spondylotic myelopathy (CSM). A comprehensive search was undertaken to look at all available articles between January 1, 1956 to May 1, 2018, on PubMed and the Cochrane Collaboration Library. The natural history of CSM is variable. The main determinants of the clinical course of CSM are the extent of neurological impairment, age, cervical instability, abnormalities of cord conduction, canal diameter, congenitally stenotic spinal canal and the extent of involvement and tract disruption on diffusion tensor imaging (DTI) imaging. There is little data on the true incidence and prevalence of CSM across the globe and none from India. The pathoanatomic basis of CSM is cord compression, either dynamic or static. The biological events that are thought to play a significant role in the development of CSM are ischemia, derangement of the blood-spinal cord barrier, chronic neuronal inflammation, and apoptosis. Emerging knowledge about the molecular biology holds promise for potential intervention, both for prevention and for cure, of this common and debilitating condition.
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Clinical spectrum and importance of evaluation systems in degenerative cervical myeloradiculopathyp. 13
Ganesh Swaminathan, Vetrivel Muralidharan, Baylis Vivek Joseph
DOI:10.4103/isj.isj_61_18  
Degenerative cervical myelopathy includes facet joint arthropathy and/or intervertebral disc prolapse, as well as aberration (hypertrophy, calcification, or ossification) in the ligamentum flavum, and/or posterior longitudinal ligament. Cervical spondylotic myelopathy and ossification of posterior longitudinal ligament are two major conditions under this spectrum. Patients with degenerative changes of the cervical spine can present with wide spectrum of symptoms and signs ranging from axial neck pain, radiculopathy or myelopathy. A combination of history, physical examination, and provocative tests such as Spurling's sign, shoulder abduction test, neck distraction test, Valsalva maneuver, Elvey's upper limb tension/brachial plexus tension test increase the likelihood of diagnosis of cervical radiculopathy. Myelopathy can manifest in the early stage as subtle changes in the upper limb dexterity or mild walking difficulty and in late stage with severe spasticity and flexor spasms. Clinicians are increasingly using quantitative or semi-quantitative scales of neurological impairment. However, there is no gold standard evaluation systems that can reliably assess disease severity.
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Imaging in cervical myelopathyp. 20
Rajavelu Rajesh, Shanmuganathan Rajasekaran, Sri Vijayanand
DOI:10.4103/isj.isj_63_18  
This is a narrative review. The objective of this study is to provide an overview on the imaging modalities and their utilization in cervical myelopathy (CM). Using PubMed, studies published on the "imaging modalities in CM," "cervical spondylotic myelopathy (CSM) imaging," "computed tomography (CT) and magnetic resonance imaging (MRI) in CM," "imaging in ossified posterior longitudinal ligament (OPLL)," "dural ossification in OPLL," "diffusion tensor imaging (DTI) in CSM," and "dynamic MRI, functional MRI, and magnetic resonance spectroscopy (MRS) in CSM" were evaluated. The review addresses the evaluation of CM with various imaging modalities ranging from radiographs, CT, and MRI to advanced imaging techniques such as DTI and MRS. Each investigation contributes specific detail to the disease process in a different dimension. Specific parameters for CSM and OPLL, and their influence on outcome are discussed. Imaging in CM plays an important role in analyzing the cause of myelopathy, defining the level of the lesion, parameters to assess the time of intervention and to predict the outcome.
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Anterior surgical options for cervical spondylotic myelopathyp. 33
Andrei Fernandes Joaquim, John Alex Sielatycki, K Daniel Riew
DOI:10.4103/isj.isj_39_18  
Cervical spondylotic myelopathy (CSM) is one of the most common among causes of spinal cord dysfunction worldwide. In this article, we provide a broad narrative review of the options to treat CSM from an anterior approach to the cervical spine. Anterior procedures are effective and safe, especially for one or two level disease (although can be used up to 7-8 levels). This approach can be used in patients with lordotic, neutral, or kyphotic cervical spine alignment and provide excellent access for direct neural decompression. The most common adverse effects of anterior cervical operations are dysphagia and dysphonia, but fortunately, these are mild and transient in the majority of cases. Severe complications, such as vertebral arterial injury, spinal cord injury or airway compromise, are rare but must be taken into consideration, especially when additional risk factors are present (multilevel procedures, revision surgeries, older, and infirm patients). The primary anterior cervical procedures for treating CSM are anterior cervical discectomy and fusion (ACDF), anterior cervical corpectomy and fusion (ACCF), oblique cervical corpectomy, and cervical disc arthroplasty. A combination (hybrid) of ACDF and ACCF is also utilized as an option to allow for wide decompression, deformity correction, and provide more surface area of exposed, and bleeding cancellous bone. More recently, the senior author (KDR) has utilized a hemi-corpectomy and fusion hybrid technique which will be described in this text. Advantages and disadvantages of each of these options are discussed in detail, as well as the need for posterior instrumentation supplementation in selected patients; such as those with concomitant cervical deformity, poor bone quality, or those at risk for pseudarthrosis following multilevel arthrodeses. The management of patients with cervical spinal cord compression without myelopathy or with mild symptoms is also discussed.
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Posterior surgical options for spondylotic cervical myelopathyp. 42
Shankar Acharya, Nikhil Jain
DOI:10.4103/isj.isj_57_18  
Cervical spondylotic myelopathy (CSM) is a common presentation in the middle-aged to elderly population. The cause of myelopathy is multifactorial, and cervical spondylosis is the most common cause. This review looks into the treatment options, timing of the surgery, and the advantages and disadvantages of the various posterior approaches for multilevel spondylotic myelopathy. CSM is a disabling disorder that should be addressed in its early phases. There are limited surgical options available, and each procedure has its advantages and disadvantages. Since the neurological and functional outcomes are the same for all well-performed decompressions, the choice of surgical approach depends on various other factors. Posterior approaches are good for multilevel disease as they make the surgery simpler, shorter and with reduced complications in comparison to multilevel anterior surgeries.
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Ossification of the posterior longitudinal ligament: Etiology, prevalence, progression, and surgical strategiesp. 52
Yoshiharu Kawaguchi
DOI:10.4103/isj.isj_41_18  
Ossification of the posterior longitudinal ligament (OPLL) is characterized by replacement of the ligamentous tissue by ectopic new bone formation. OPLL often causes narrowing of the spinal canal and has been recognized as a cause of cervical myelopathy and/or radiculopathy. Although a clear inheritance of OPLL has not been identified, there is a strong genetic background for OPLL. A recent genome-wide association study using all Japan cohort reported that there were 6 susceptible loci for OPLL. In addition, there were several studies to seek the biomarkers of OPLL. OPLL is frequently found in the cervical spine. However, 53.4% had OPLL not only in the cervical spine, but also in other spinal regions in patients with cervical OPLL. Further, 65.2% with cervical OPLL had ossification of the ligamentum flavum (OLF) especially at the levels of the thoracic and the lumbar spine. There is no effective conservative treatment. Surgical decompression is considered in patients with severe and/or progressive myelopathy. Early surgical decompression of the spinal cord is recommended in patients with apparent myelopathy. Operative methods are divided into two procedures, anterior decompressive surgery and posterior decompressive surgery. The choice of the surgical procedure is determined according to several factors, such as local pathology of OPLL and spinal alignment.
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Clinical predictors of complications and outcomes in degenerative cervical myeloradiculopathyp. 59
Jamie R F Wilson, Fan Jiang, Michael G Fehlings
DOI:10.4103/isj.isj_60_18  
Degenerative cervical myelopathy (DCM) is the leading cause of adult spinal cord dysfunction worldwide, and surgical decompression remains the mainstay treatment to arrest the progression of neurological deterioration. A number of clinical factors can predict and influence the outcomes of surgery, including patient demographics, baseline myelopathy severity, duration of symptoms, imaging characteristics, and types of surgical approach. Understanding the influence and relationship of these factors on surgical outcomes allows the treating clinician the ability to provide the patient with realistic expectations when discussing surgical intervention for DCM.
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The spine clinics – Cervical spondylotic myelopathy – Clinical scenariosp. 68
Ankur Nanda, KR Renjith, Abhinandan Mallepally, C S Vishnu Prasath, Ajoy P Shetty
DOI:10.4103/isj.isj_67_18  
This section of the symposium deals with different case scenarios related to cervical spondylotic myelopathy (CSM) which in our daily clinical practice not only act as diagnostic challenges but also test our decision-making abilities. These cases have been handled by different experts and hence help the readers in providing a wider perspective to the problem of cervical myelopathy and its management. This section ends with comments by the authors on key takeaway points from each case scenario, and some literature supported recommendations for the management of CSM.
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REVIEW ARTICLETop

Cell-based treatment strategies for intervertebral disc degeneration: An overview on potentials and shortcomingsp. 81
Prasanthi Sampara, Rajkiran Reddy Banala, Satish Kumar Vemurit, AV Gurava Reddy, G P V Subbaiah
DOI:10.4103/isj.isj_21_17  
The intervertebral discs (IVDs) are the cushioning pads of fibrocartilage, which are immeasurably vital for the uprightness of vertebral column and for its function. IVD provides flexibility, tensile strength to the spine, and also cope up with varied types of biomechanical stresses. IVD degeneration (IVDD) is one of the musculoskeletal disorders mostly seen in older population, and it is the foremost cause of low back pain and consequences of IVDD are disc herniation, spinal stenosis, and degenerative lumbar scoliosis. Yet the therapeutic options are restricted and the treatments given remain unsatisfactory putting more economical burden on world's population. IVDD is considered as a multifactorial disorder, due to the involvement of factors such as genetic inheritance, alterations in cellular composition, and anabolic and catabolic reactions, which could initiate degenerative process in the IVD. However, our conception on IVD genesis and the etiopathology of IVDD have given us an opportunity for exploring and formulate appropriate therapies to tackle IVDD. The cell therapy gives scope for sustained matrix synthesis, controlled inflammation, and prevention of osteophyte formation in IVD. The present review focuses on the existing issues related to current therapeutic approaches and about latest evidence on cell therapy-based regeneration of IVD and maintaining the microenvironment of cellular matrix which holds a promise for future therapeutic applications.
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ORIGINAL ARTICLESTop

The median labio-mandibulo-glossotomy approach to the upper cervical spine: A personal series and tips and pearlsp. 92
K Venugopal Menon, Hood Al Saqri, Renjit Kumar, Maruti Kambali
DOI:10.4103/isj.isj_8_18  
Background: Wide exposure to the anterior part of the upper cervical spine is difficult due to anatomical constraints. The Labio-Mandibulo-Glossotomy (LMG) approach is considered a difficult approach with high morbidity. The objective of this study is to describe the authors experience with the approach and it's outcomes in six cases and offer tips and pearls to the surgical access. Methods: This is a retrospective review of a small series of six cases that were operated for upper cervical lesions by the LMG approach. Two had mandible fractures that needed fixation and in the others osteotomy of the mandible was performed. The patients were followed up for minimum two years or death (in malignancy). We specifically looked for cosmetic or functional problems related to osteotomy, glossotomy, and, hospital and ICU stay duration. Surgical access is described in detail. Results: The hospital stay was similar to other major spine trauma or tumour surgeries at our center (median 14 days) and mean ICU stay 2.8 days. There were no long-term issues related to the access. Several tips and tricks are offered to minimize intra and post-operative problems. Conclusions: The LMG approach, though apparently formidable, is quite a safe and simple procedure with few residual complications.
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CASE REPORTSTop

A novel surgical technique for hydatid cyst involving cervicothoracic anterior epidural spacep. 99
Bharat R Dave, Degulmadi Devanand, Ganesh Deshmukh
DOI:10.4103/isj.isj_17_18  
Spinal hydatid cyst comprises <1% of the total cases of hydatid disease. There is very little literature on the involvement of anterior epidural space by hydatid cyst and its management. This report presents a unique presentation of spinal hydatidosis in cervicothoracic anterior epidural space and a novel technique in surgical management.
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Sacral chordoma with degenerative spondylolisthesis and upper lumbar disc herniationp. 102
Shakti A Goel, Hitesh N Modi, Yatin J Desai, Bhavin Patel
DOI:10.4103/isj.isj_24_17  
Sacral chordoma is a rare condition requiring multidisciplinary approach for management. Here, we report a 72-year-old male patient who was diagnosed with sacral chordoma with L2–L3 disc herniation and L5–S1 degenerative spondylolisthesis and L1 body fracture. The patient was first managed by discectomy L2–L3 with D12–L3 decompression and fixation. Sacral chordoma excision was done 10 months later. The chordoma was excised by anterior laparoscopic resection and mobilization of tissues from the tumor followed by posterior sacrectomy with L5–S1 decompression and extension of fixation in a single stage. Proline mesh was used to support the colon posteriorly. This was further complicated by proximal junction fracture due to fall which was further managed by proximal extension of the rod-screw construct. The patient became symptom free without any radiotherapy or chemotherapy and is able to walk independently, two years following the primary surgery without recurrence of tumor.
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Lumbar disc herniation in ochronosisp. 108
Subbiah Jayakumar, Sathish Devadoss, Annamalai Devadoss
DOI:10.4103/isj.isj_40_18  
Alkaptonuria is a rare metabolic, autosomal recessive disorder caused by the deficiency of homogentisic acid oxidase and it is characterized by bluish-black discoloration of cartilages, skin (Ochronosis), degenerative changes in the articular, extra-articular cartilages, intervertebral disc, other tissues causing pain in the joints and spinal column. Although intervertebral disc degeneration is common in these patients, those presenting with symptoms severe enough to warrant surgery are rare. Only a few patients have been treated surgically. We present a case of alkaptonuria presenting with radiculopathy and lumbar disc herniation. The case presented demonstrates that although lumbar disc herniation is rare in alkaptonuria, it should be sought in such patients and surgical treatment yields good functional outcome.
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