Αρχειοθήκη ιστολογίου

Αλέξανδρος Γ. Σφακιανάκης
ΩτοΡινοΛαρυγγολόγος
Αναπαύσεως 5
Άγιος Νικόλαος Κρήτη 72100
2841026182
6032607174

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

Anatomical Site Differences of Sodium Laurylsulphate Induced Irritation: randomised controlled trial

Summary

Background

Sodium laurylsulphate (SLS) induced contact dermatitis is a commonly used model for testing effects of different topical formulations. Volar forearms are preferred testing site by the guidelines, but other anatomical locations were used in previous research, especially upper back, as the clinically used site for testing different antigens.

Objectives

Aim of the present study was to investigate existence of anatomical variations of skin response to irritation and its' effects on response to treatment.

Methods

Irritation was induced with SLS on symmetrical sites on both forearms and sides of upper back with additional sites exposed to water as controls. Half of the sites were treated with emollient cream while the other half were left untreated. Irritation was assessed using bioengineering methods and clinical scoring.

Results

Upper back skin showed higher reactivity to irritants with stronger barrier disruption (measured by Tewameter, 80·2±18·3 vs 48·0±24·2 gm−2h−1), more pronounced erythema (measured by Mexameter, 186·5±88·4 vs 92·1±58·2 AU) and dryness (measured by Corneometer, ‐28·6±14·5 vs 2·7±16·9 AU). Skin recovery rates were also influenced by anatomical location with the upper back showing faster recovery (316·7±223·1 vs 156·2±198·5). Treatment didn't lead to improvement in measured parameters, regardless of anatomical location.

Conclusion

Skins' reaction to irritant and recovery were dependant on anatomical location. Location where testing was conducted should always be reported as treatments tested across different locations could not be directly compared to each other.

This article is protected by copyright. All rights reserved.



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Identification of small peptides and glycinamide that inhibit melanin synthesis using a positional scanning synthetic peptide combinatorial library

Summary

Background

Antimelanogenic peptides are potentially useful to treat hyperpigmentation, but many peptides have limited application because of high cost and/or low activity.

Objectives

To identify small and potent peptide inhibitors of cellular melanin synthesis useful for cosmetic and medical applications.

Methods

A positional scanning synthetic tetrapeptide combinatorial library was used for screening of potentially active peptides. Antimelanogenic activities of the peptide pools and individual peptides were evaluated in B16‐F10 melanoma cells and human epidermal melanocytes (HEMs) treated with alpha‐melanocyte‐stimulating hormone (α‐MSH).

Results

The predicted active tetrapeptide sequences were R‐(F/L)‐(C/W)‐(G/R)‐NH2. Of the individual tetrapeptides tested, D3 (RFWG‐NH2) and D5 (RLWG‐NH2) exhibited high antimelanogenic activities. Tetrapeptide D9 (FRWG‐NH2) with a sequence identical to that of a portion of α‐MSH also showed antimelanogenic activity. Of the tripeptides tested, E5 (FWG‐NH2), E6 (LWG‐NH2), and E7 (RWG‐NH2) were relatively more active. Dipeptide F1 (WG‐NH2) and monopeptide G1 (G‐NH2, glycinamide) retained activity, but G2 (Ac‐G‐NH2) and G3 (glycine) did not. The antimelanogenic activities of peptides D3, E5, F1, and G1 were verified in α‐MSH‐stimulated HEMs. Commercially available G‐NH2·HCl suppressed the phosphorylation levels of cAMP‐responsive element binding protein, protein levels of microphthalmia‐associated transcription factor and tyrosinase, L‐tyrosine hydroxylase activity of tyrosinase, and the melanin levels in stimulated cells.

Conclusions

Small peptides, including glycinamide and tryptophanyl glycinamide, are potent antimelanogenic agents with potential value for the treatment of skin hyperpigmentation.

This article is protected by copyright. All rights reserved.



http://bit.ly/2QNhX38

Validation and Reliability of a Disease‐Specific Quality of Life Measure in Patients with Cutaneous Lupus Erythematosus: CLEQoL

Abstract

Background

Cutaneous lupus erythematosus (CLE) is a potentially disfiguring, chronic autoimmune disease with extremely variable skin manifestations, negatively affecting quality of life (QoL) of patients. Patient‐reported outcome (PRO) measures used in assessing QoL in CLE patients have been either generic or developed without input from patients with CLE.

Objectives

To demonstrate the reliability and validity of a disease‐specific QoL measure for CLE – the cutaneous lupus erythematosus quality of life (CLEQoL).

Methods

A total of 101 patients with a clinical diagnosis of CLE were recruited, and each patient was asked to complete the CLEQoL. Internal consistency was used as a measure of reliability. Validity was measured in two ways – structural validity via exploratory factor analysis and convergent validity via Spearman correlations between CLEQoL and the Short Form 36 (SF‐36). Patient demographic and disease characteristics were collected. Data was analyzed using SPSS and significance was set to p<0·05.

Results

The average age of our CLE patients was 48±13 with discoid lupus (n=72, 71·3%) being the most predominant CLE subtype. Patients were mostly female (n=88, 87·1%) and African‐American/Black (n=59, 58·4%). Internal consistency ranged from 0·67 to 0·97. A total of five domains, functioning, emotions, symptoms, body image/cosmetic effects and photosensitivity, were extracted with a total explained variance of 71·06%. CLEQoL‐related domains correlated with SF‐36 domains (r ranging from ‐0·39 to ‐0·65).

Conclusion

The CLEQoL was found to be a valid and reliable PRO measure for assessing QoL in patients with CLE. Demonstrating that the CLEQoL has strong psychometric properties is an important step towards the development of a disease‐specific PRO measure that future clinical trials can use.

This article is protected by copyright. All rights reserved.



http://bit.ly/2VLmZ45

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

New Aspect of Liver IL-17+γδ T Cells

Publication date: March 2019

Source: Molecular Immunology, Volume 107

Author(s): Chen Xi, Zhenghu Jia, Wu Xiaoli, Zhao Na, Weifeng He, Jianlei Hao

Abstract

Liver is a critical organ where comprehensive immune regulation or defense occurs. γδ T cells in liver represent indispensable population and are found to be regulating a variety of diseases including autoimmunity, cancer, fibrosis, and infections. IL-17+ γδ T cells in liver is a functional subset which has been found to have pro-inflammatory effect or anti-infection ability. However, how their function is activated or maintained, isn't well understood. Microbiota in the intestine provide continual source of metabolites to the liver, through at least the portal vein. The interaction between intestinal microbiota and liver γδ T cells has not been well studied. Li et al found that lipid antigen derived from intestinal microbiota was presented by hepatocyte CD1d, and activated liver-resident γδ T cells and maintained the IL-17 production. Moreover, microbiota promoted NAFLD through IL-17+ γδ T cells. Thus, new aspect of IL-17+ γδ T cells in the liver was characterized.



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Clinical outcomes and management of facial nerve in patients with parotid gland cancer and pretreatment facial weakness

Publication date: February 2019

Source: Oral Oncology, Volume 89

Author(s): Woori Park, Jongwon Park, Song I. Park, Hackjung Kim, Hyunsik Bae, Junhun Cho, Hojeong Won, Minsu Park, Han-Sin Jeong

Abstract
Objectives

In parotid gland cancer (PGC), it is not clear whether facial weakness always reflects tumor invasion of the facial nerve (FN) requiring nerve resection. The aims of this study were to evaluate oncological and functional outcomes in patients with PGC and pre-treatment facial weakness, and to analyze local tumor invasion of the FN.

Materials and methods

The clinical outcomes of patients (n = 45) with PGC and pretreatment facial weakness were retrospectively analyzed. Patients had undergone 1 of 4 types of treatments: complete tumor resection, FN sacrifice with or without FN reconstruction, tumor resection with FN preservation and primary non-surgical treatments. Pathologic specimens in patients with nerve resection patients (n = 26) were reviewed to identify FN invasion by the tumor.

Results

Patients with PGC and facial weakness had poor clinical outcomes (44.0%, 3Y progression-free survival), and 86.7% of tumors were high-grade. In these subjects, regional or distant metastasis was an independent prognostic factor for survival. Recovery from facial weakness was suboptimal in patients with FN graft. In cases with nerve resection, 26.9% had intra-neural tumor invasion, 42.3% had perineural invasion, and 30.8% had no neural invasion in the FN.

Conclusion

Facial weakness did not always indicate tumor invasion of the FN in PGC. Thus, the decision regarding FN resection can reasonably be further based on intraoperative findings. In cases with incomplete facial weakness and safe separation of the FN from the tumor, FN preservation offers the best functional outcomes, without compromising oncological outcomes.

Graphical abstract

Graphical abstract for this article



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Transcranial Direct Current Stimulation (tDCS) and trigeminal pain: a pre‐clinical study

Abstract

Objective

Our objective was to evaluate the tDCS effect on facial allodynia induced by chronic constriction of the infraorbital nerve (CCI‐ION) and on the brainstem levels of TNF‐α, NGF, IL‐10 and, serum LDH in rats.

Methods

Rats were exposed to the CCI‐ION model. Facial allodynia was assessed by Von Frey filaments test at baseline, 3, 7, 10 and 14 days post‐surgery and24h and 7 days after the bimodal tDCS sessions for 20 min/day/8 days.

Results

CCI‐ION induced a significant decrease in the mechanical threshold 14 days after surgery. This effect was reversed by tDCS treatment, with the mechanical threshold returning to basal levels at 24h after the end of the treatment and it persisted for 7 days after the end of the treatment. tDCS also decreased LDH serum levels compared to those in the control group. There was an interaction between pain and treatment with respect to brainstem levels of NGF, TNF‐α, and IL‐10.

Conclusion

CCI‐ION model was effective in establishing trigeminal neuropathic pain on 14 days after surgery, and tDCS reduced allodynia and LDH serum levels and promoted alterations in NGF, TNF‐α, and IL‐10 brainstem levels. Thus, we suggest that tDCS may be a potential therapy in the trigeminal pain treatment.

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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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