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Study Design This study is a case series of 48 patients. Objectives This study’s primary objective was to provide a clinical description of a group of individuals with a working diagnosis of idiopathic spinal cord herniation (ISCH). The secondary objectives were to appreciate the natural history of these patients and describe their clinical evolution with conservative or surgical management. Setting The study was carried out at l’Hôpital de l’Enfant-Jésus, CHU de Québec (Québec, Canada), a tertiary care university hospital. Methods This case series study is based on routinely collected data. Forty-eight (48) cases were identified as having an ISCH on MR imaging, between 2009 and 2019. Their medical files have been searched retrospectively. Patient characteristics were described according to their asymptomatic or symptomatic status. Results The mean age of patients at the time of diagnosis was 52.5 years. Most of the patients identified were asymptomatic (69%) and followed clinically. The main neurologic presentation for the symptomatic group was Brown-Séquard-like syndrome. 20% of the symptomatic patients were rapidly treated surgically after consultation with the neurosurgeon. The mean follow-up duration was 56 months for asymptomatic patients and 51 months for symptomatic patients. Most of our patients (41 out of 45) were considered stable or unchanged at follow-up. There was no neurological progression in all asymptomatic patients. Conclusions Our study shows that ISCH and its variants are not always symptomatic and may be a fortuitous finding. As the natural history may be non-progressive, it is probably appropriate to treat some cases expectantly.

Cervical sagittal alignment is correlated with myelopathy severity and used by spinal surgeons for surgical planification. Magnetic resonance imaging (MRI) is the gold standard for the evaluation of cervical myelopathy but may not be for the assessment of cervical sagittal balance compared to X-rays. The objective of this study was to assess the correlation of cervical alignment between supine MRI and standing radiographs in patients with cervical spondylotic myelopathy (CSM). Cobb, Jackson and Harrison methods were used to measure cervical sagittal alignment on supine MRI and standing radiographs of CSM adults. Cervical alignment was divided based on Cobb angle values on lordotic (> 4°), kyphotic (

OBJECTIVEChronic subdural hematoma (CSDH) is a common neurosurgical condition that can result in significant morbidity. The incidence of epileptic events associated with CSDH reported in the literature varies considerably and could potentially increase morbidity and mortality rates. The effectiveness of antiepileptic prophylaxis for this indication remains unclear. The primary objective of this study was to assess the relevance of anticonvulsant prophylaxis in reducing seizure events in patients with CSDH.METHODSAll consecutive cases of CSDH from January 1, 2005, to May 30, 2014, at the Hôpital de l’Enfant-Jésus in Quebec City were retrospectively reviewed. Sociodemographic data, antiepileptic prophylaxis use, incidence of ictal events, and clinical and radiological outcome data were collected. Univariate analyses were done to measure the effect of antiepileptic prophylaxis on ictal events and to identify potential confounding factors. Multivariate logistic regression was performed to evaluate factors associated with epileptic events.RESULTSAntiepileptic prophylaxis was administered in 28% of the patients, and seizures occurred in 11%. Univariate analyses showed an increase in the incidence of ictal events in patients receiving prophylaxis (OR 5.92). Four factors were identified as being associated with seizures: septations inside the hematoma, membranectomy, antiepileptic prophylaxis, and a new deficit postoperatively. Antiepileptic prophylaxis was not associated with seizures in multivariate analyses.CONCLUSIONSAntiepileptic prophylaxis does not seem to be effective in preventing seizures in patients with CSDH. However, due to the design of this study, it is difficult to conclude definitively about the usefulness of this prophylactic therapy that is widely prescribed for this condition.

OBJECTIVES Tonic spinal cord stimulation (SCS) is currently used to treat neuropathic pain. With this type of stimulation, an implantable pulse generator generates electrical paresthesias in the affected area through 1 or more epidural leads. The goal of this study was to evaluate the impact of tonic SCS on the sensory perception of chronic pain patients using quantitative sensory testing (QST). MATERIALS AND METHODS Forty-eight patients (mean age: 57 y) with chronic leg pain due to failed back surgery syndrome or complex regional pain syndrome treated with SCS were recruited from 3 research centers. Test procedures included 2 sessions (stimulation On or Off), with measures of detection thresholds for heat, touch, vibration, and of pain thresholds for cold, heat, pressure, the assessment of dynamic mechanical allodynia, and temporal pain summation. Three different areas were examined: the most painful area of the most painful limb covered with SCS-induced paresthesias (target area), the contralateral limb, and the ipsilateral upper limb. Wilcoxon signed-rank tests were used to compare the mean difference between On and Off for each QST parameter at each area tested. P-values

Background Circulating interleukin-6 (IL-6) improves outcome prediction for second primary cancer (SPC) in head and neck cancer (HNC) patients. This study aimed to identify factors associated with IL-6 serum levels in HNC patients. Methods This study was conducted as part of a phase III chemoprevention trial. IL-6 was measured using chemiluminescent immunometric assay on pretreatment serum sample obtained from 527 stage I-II HNC patients. Patients’ lifestyle habits, sociodemographic, medical and tumor characteristics were evaluated before radiation therapy (RT). Factors independently associated with IL-6 levels before RT were identified using multiple linear regression. Results The median IL-6 serum level was 3.1 ng/L. In the multivariate analysis, eight factors were significantly associated (p

Introdução: A distonia pode ser definida como um distúrbio neurológico com a presença de movimentos involuntários com contrações espasmódicas. A estimulação cerebral profunda (DBS) é considerada altamente efetiva em pacientes criteriosamente selecionados e avaliados. A maior efetividade da ECP é demonstrada principalmente nos casos de refratariedade do tratamento clínico e farmacológico na distonia cervical. Objetivo: realizar uma revisão de literatura comprando os resultados da Estimulação Cerebral Profunda no Globo Pálido Interno (GPi), analisando os resultados obtidos no tratamento da distonia focal e segmentar. Métodos: Foram pesquisados no banco de dados do MEDLINE artigos descrevendo DBS para distonia por meio de palavras-chave. Resultados: Foram identificados 308 artigos que envolvem estudos no tratamento de distonia com DBS no GPi. Após aplicar os filtros na base de dados “MEDLINE”, 48 artigos foram excluídos, restando 260 artigos elegíveis. Posteriormente, realizou-se uma revisão minuciosa dos artigos publicados na plataforma em questão. Conclusões: Aponta-se que pacientes com distonia primária são mais beneficiados pelo DBS quando eletrodos são inseridos na porção ventromedial do GPi com taxas de efeitos adversos aceitáveis. Um melhor prognóstico desses pacientes depende de um acompanhamento interdisciplinar individualizado no período pré e pós-operatório.

Introduction: The spinal cord stimulation (SCS) has been described as a valuable neuromodulating procedure in the management of chronic and medically untreated neuropathic pain. Although, many studies have discussed the use of this technique, a question still remains regarding its efficacy in different medical conditions with different etiology in the long term. The aim of this paper is to discuss the risks, complications, cost-effectiveness and results of SCS in patients affected by chronic neuropathic pain based on the comprehensive literature review. Methods: Bibliographic search of references from 1950 to 2016 using the databases MEDLINE, LILACS, SciELO, PubMed, and applied language as selection criteria, choosing preferably recent articles written in Portuguese, Spanish or English. Results: Based on literature review, SCS is a safe, reversible, adjustable and nondestructive surgical procedure demonstrating a significant effect in the reduction of pain intensity and improvement in quality of life in these patients. Furthermore, in spite of the initial high cost to its application, SCS has been associated with lower rates of complications and high rates of cost-effectiveness when compared to standard therapies. Conclusion: Although used in medical conditions with different etiology, the procedure is still an effective and a cost-effective approach to neuropathic pain, mainly in patients affected by failed back pain syndrome (FBSS) and complex regional pain syndrome (CRPS).

Background Defined as a headache lasting at least 15 days per month, chronic headache is reported by 3% of the general population, and a substantial proportion of them are refractory to current therapies. Occipital nerve stimulation (ONS) is a treatment option, but is still considered as a last resort treatment especially because of its invasive nature and the cost associated. Some reviews reported a limited efficacy of ONS for the treatment of migraines, with a high risk of complications. However, results reporting its efficacy and safety on other headache disorders are unclear. The aim of this review is to assess the efficacy and safety of ONS in regards to non-migrainous chronic headaches. Methods We will conduct a systematic review and meta-analysis of studies evaluating the use of ONS in comparison to sham stimulation or the best available treatment in patients with chronic headache. MEDLINE, CINHAL, EMBASE, PsycINFO, ECRI Institute Library, WIKISTIM, the Cochrane Library databases, and clinical trial registries will be searched for eligible studies. The review will include adult patients diagnosed with chronic headache excluding migraine. Two independent reviewers will process to the screening of studies according to titles, abstracts, and then full texts. The primary outcome is the overall reduction of head pain severity. The secondary outcomes are rates of reduction in the severity of head pain, headache frequency, and duration, use of medication, impairment, quality of life, healthcare utilization, return to work, and adverse events. Extracted data will include patients’ and procedure characteristics, details on comparative treatment or sham, and clinical outcomes. The risk of bias of the studies will be also independently assessed using the Cochrane risk of bias tools. Discussion This systematic review will allow us to better evaluate the potential role of ONS for the treatment of patients with chronic headache that are refractory to less invasive therapies. It will help to determine the degree of safety of ONS. Moreover, it will help to design and conduct future randomized controlled trials focused on patients who may better respond to such treatment. Systematic review registration PROSPERO CRD42019121623 Electronic supplementary material The online version of this article (10.1186/s13643-019-1101-x) contains supplementary material, which is available to authorized users.

OBJECTIVES: Even if spinal cord stimulation (SCS) is widely used and effective in treating intractable chronic neuropathic pain conditions, little is known about its possible impacts on sensory perception. Quantitative sensory testing (QST) is a useful tool to assess this issue. The aim of this study was to review the impact of tonic SCS on somatosensory perception quantified by QST in chronic pain patients.MATERIALS AND METHODS: Relevant articles and abstracts were searched in all languages from CINAHL, Cochrane, Embase, MEDLINE, and Web of Knowledge data bases. Data were extracted and included studies were assessed for risk of bias.RESULTS: Out of 5610 records, 15 peer-reviewed articles were eligible and included. The results are heterogeneous due to inadequate comparability among studies for populations (a total of 224 patients diagnosed with more than 13 chronic pain conditions), QST parameters (22 measured with 25 different devices) and experimental procedures (study design, comparator, evaluation time, and area tested). The wide variety of studies, designs, populations, and measures included in this review did not lead to strong evidence on how conventional ("tonic") SCS affects sensory processing in patients with chronic pain.CONCLUSIONS: The data available tend to suggest that conventional SCS does not interfere with perception of external stimuli. New studies that follow a standardized procedure and consider the possible influence of sensory profile, after-effect bias, and confounding factors are required to confirm this observation. Moreover, the impact on sensory perception of other SCS modalities and alternative electrical neuromodulation therapies could also be explored.

Objective Procedure-related rupture is one of the most feared complications in treating patients with cerebral aneurysm. The primary aim of this study was to estimate the effect of aneurysm size on procedure-related rupture. We also estimated its effect on peri-procedural thromboembolic events. Methods This observational study was conducted using routinely-collected health data on patients admitted for subarachnoid hemorrhage and treated with aneurysm coil occlusion in the CHU de Quebec — Enfant-Jesus hospital from January 1st, 2000 until sample size was reached. Patients were identified from the Discharge Abstract Database using the Canadian Classification of Health codes. Assessment of complications was blind to aneurysm size. Logistic regression models were performed to test associations between aneurysm size and procedure-related rupture or peri-procedural thromboembolic events, and between both procedure-related rupture and thromboembolic events and patients' outcomes. Results This study included 532 aneurysms treated with coil occlusion in 505 patients. Procedure-related rupture occurred in 34 patients (6.7%) and thromboembolic events in 53 (10.5%) patients. Aneurysms of 2 to 3 mm inclusively were not more significantly associated with procedure-related rupture or thromboembolic events than those larger than 3 mm (OR 1.02, 95% CI: 0.9–1.16, p = 0.78 and OR 1.06, 95% CI: 0.96–1.17, p = 0.3, respectively). However, procedure-related rupture had a significant effect on patient mortality (OR 3.86, 95% CI: 1.42–10.53, p Conclusions Very small aneurysm size should not preclude aneurysm coil occlusion. Every measure should be taken to prevent procedure-related rupture as it is strongly associated with higher mortality.

We report a severe adverse event occurring in the course of a cohort study (ISRCTN13784335) aimed at measuring the efficacy and safety of venous stenting in the treatment of patients with medically refractory idiopathic intracranial hypertension (IIH). The patient was a 41-year-old woman who was not overweight, who presented with severe headache, grade 1 bilateral papilledema and transient tinnitus, refractory to medical treatment. Right transverse sinus stenting was successfully performed. Following surgery, the patient’s state of consciousness decreased acutely with rapid and progressive loss of brainstem reflex. CT scan revealed acute cerebellar and intraventricular hemorrhage with obstructive hydrocephalus. Angioscan revealed normal venous sinus patency and cerebral MRI showed acute mesencephalic ischemia. Mechanical impairment of cerebellar venous drainage by the stent or venous perforation with the large guidewire used in this technique are two logical ways to explain the cerebellar hemorrhage seen in our patient. The risk of such a complication could probably be reduced using alternative tools and technique. However, given the low level of evidence around the safety of transverse sinus stenting in IIH, its formal assessment in clinical trials is required.

Background: Current opinions regarding the use of dexamethasone in the treatment of chronic subdural hematomas (CSDH) are only based on observational studies. Moreover, the use of corticosteroids in asymptomatic or minimally symptomatic patient with this condition remains controversial. Here, we present data from a prospective randomized pilot study of CSDH patients treated with dexamethasone or placebo. Methods: Twenty patients with imaging-confirmed CSDH were recruited from a single center and randomized to receive dexamethasone (12 mg/day for 3 weeks followed by tapering) or placebo as a conservative treatment. Patients were followed for 6 months and the rate of success of conservative treatment with dexamethasone versus placebo was measured. Parameters such as hematoma thickness and clinical changes were also compared before and after treatment with chi-square tests. Adverse events and complications were documented. Results: During the 6-month follow-up, one of ten patients treated with corticosteroids had to undergo surgical drainage and three of ten patients were treated surgically after placebo treatment. At the end of the study, all remaining patients had complete radiological resolution. No significant differences were observed in terms of hematoma thickness profile and impression of change; however, patients experienced more severe side effects when treated with steroids as compared with placebo. Dexamethasone contributed to many serious adverse events. Conclusions: Given the small sample size, these preliminary results have not shown a clear beneficial effect of dexamethasone against placebo in our patients. However, the number of secondary effects reported was much greater for corticosteroids, and dexamethasone treatment was responsible for significant complications.

Glioblastoma is a very aggressive astrocytic tumor and most patients have 1-year survival time after diagnosis. A promising therapeutic strategy is the local delivery of the herpes simplex virus thymidine kinase gene in the tumor bed followed by ganciclovir treatment. The presence of functional gap junctions is highly relevant for the success of suicide gene therapy. Connexins are expressed in practically all tissues and form gap junctions that allow intercellular communication. Connexin 43 (Cx43) is the major connexin member being expressed in astrocytes but its status in glioblastoma is not well defined. We have investigated by immunofluorescence the presence of Cx43 in 74 human glioblastoma samples; its expression was detected in 77% of the samples analyzed. We report here that glioblastoma is a heterogenous disease as regards Cx43 expression with presentations, in which Cx43 expression is unaltered, reduced or totally lost. A predominant Cx43 cytoplasmic localization was observed in four out of eight primary glioblastoma cultures that we have established. This aberrant localization reduced gap junctionnal intercellular communication by 50 to 75% as compared with primary cell cultures displaying gap junctional plaques. However, the bystander effect evaluated after lentiviral delivery of the herpes simplex virus thymidine kinase gene and ganciclovir treatment was detected in all Cx43-positive primary cell cultures, and it was independant of the Cx43 localization. These findings may have important clinical implications for the design of anticancer cytotoxic therapies that rely on the gap junction-mediated bystander effect for their success.

Background Retroviral vectors derived from the Moloney murine leukemia virus (MLV) are widely used in gene therapy. Pseudotyping of these vectors with the cat RD114 retrovirus envelope increases their potential for delivering genes into human hematopoietic cells. In the present study, we have further investigated the potential of the RD114 retrovirus in gene therapy. We describe and characterize an alternative retroviral packaging system derived from the RD114 retrovirus. Methods RD114-derived recombinant retroviruses were produced transiently by transfection of 293T cells, and viral titers were assessed on TE671 cells by measuring the percentage of infected green fluorescent protein (GFP) positive cells by fluorescence-activated cell sorter (FACS) analysis. Purified human hematopoietic cells (lymphocytes and CD34+ cells) were activated and transduced on retronectin-coated plates. Two days later, the percentage of GFP positive cells was evaluated by FACS analysis. Results We demonstrate that RD114 viral particles could package MLV transfer vectors, and that, in addition to its natural envelope, RD114 cores could be efficiently pseudotyped by the Gibbon ape leukemia, the MLV-amphotropic and the vesicular stomatitis virus G protein envelopes. Furthermore, we found that RD114 viral particles were highly efficient to transduce human lymphocytes and CD34+ cells. Conclusions This is the first demonstration that replication-defective RD114 viral particles can be generated and used for efficient gene delivery into human hematopoietic cells. We conclude that RD114-derived vectors could be useful in the field of gene therapy. Copyright © 2009 John Wiley & Sons, Ltd.

Herpes simplex virus thymidine kinase (TK) gene transfer followed by ganciclovir (GCV) administration is an approach investigated for glioblastoma treatment. The bystander effect (BE) enhances the cytotoxic effect of this strategy by allowing the diffusion of phosphorylated GCV from TK-expressing cells toward neighboring TK negative cells. This transfer of toxic metabolites is mainly mediated via gap junctions that are composed of connexins. Downregulation and/or cytoplasmic localization of connexins are common in tumors, and should be detrimental to the success of the TK/GCV strategy. In this study, we investigated the level of expression, the localization and the functionality of connexin43 (Cx43) in three glioblastoma cell lines. We showed that Cx43 was predominantly located in lysosomes and late endosomes, with only few gap junctions present at the cell surface. Surprisingly, the gap-junctional intercellular communication (GJIC) and the BE capacity were preserved, and in two of the cell lines analyzed, it was at least twice as high as compared to a control HeLa transfectant that expresses high levels of Cx43 at the cell membrane. Experiments performed in the presence of alpha-glycyrrhetinic acid or small interfering RNA confirmed that Cx43 was responsible for the GJIC and the BE. Our results indicate for the first time that the very limited numbers of gap junctions present in glioblastoma cells are highly functional. We thus conclude that the TK/GCV strategy is still a valuable therapeutic option to be developed for the treatment of glioblastoma patients.

BACKGROUND: Metastatic brain tumors are a common complication of systemic cancers. Good performance status, absence of extracranial metastases, age < 65 years and control of the primary tumor are the strongest predictors of survival. Controversy exists regarding best adjuvant treatment for patients. Therefore, careful evaluation of patient features and tumor characteristics must be considered when determining treatment modality. OBJECTIVES: The aim of the study was to assess the treatment management and clinical features of metastatic brain neoplasms following a neurosurgical procedure and evaluate factors conditioning survival. METHODS: Between January 1st 2009 and January 1st 2013, medical files of patients who underwent a surgical procedure for metastatic brain tumors at Hopital de l'Enfant-Jesus in Quebec City were reviewed. Data on patient features, primary and metastatic neoplasm characteristics, procedure and survival were recorded. Wilcoxon rank sum test, Kruskal-Wallis test and Cox proportional-hazards regression for survival data were used to assess the impact of treatments and patient characteristics on survival. Efficacy of whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS) and combined treatment in terms of patient survival were also evaluated. RESULTS: One hundred and twenty six patient files were reviewed and 109 were included for analysis. The mean survival time for patients was 537.9 days. Age below 65 years (p = 0.08) was a protective factor. WBRT combined with SRS (p < 0.0001), the use of WBRT alone (p = 0.002) or SRS alone (p = 0.004) all significantly improved survival. SRS, when compared to WBRT alone or to combined WBRT and SRS treatment, did not show significant difference in survival. CONCLUSION: Survival in our population is influenced by age and the use of adjuvant treatment. The choice of treatment modality after surgery remains somewhat controversial and our results support the need for further studies to compare WBRT and SRS.

Psychosurgery, such as anterior capsulotomy, is a therapeutic option for treatment-resistant obsessive-compulsive disorder (OCD). In this paper, we present a prospective, long-term follow-up study aimed at evaluating both the efficacy and the safety of anterior capsulotomy for the treatment of severe, refractory OCD.Twenty-four patients were surgically treated in our centre between 1997 and 2009, 19 of whom were included in this study. Patients were assessed at 3, 6, 12, and 24 months and last follow-up (mean of 7 years) was carried out by phone. OCD symptom severity was evaluated using the Yale-Brown Obsessive Compulsive Scale (Y-BOCS). A patient with an improvement rate of over 35% in the Y-BOCS score was considered a responder, while a patient with a 25% improvement was considered a partial responder.With a mean improvement of 31% in the Y-BOCS score at long-term follow-up, 36.8% of the patients responded fully to the procedure and 10.5% were considered partial responders, for an overall response rate of 47.3% of patients. At the end of the study, 3/19 patients had recovered (Y-BOCS score8) and 3/19 were in remission (Y-BOCS score16). No cases of mortality were reported and the overall adverse event rate was 57.9%. Only 2 patients had permanent surgical complications.Anterior capsulotomy is an effective and safe technique for the treatment of severe refractory OCD in patients who have no other alternative to improve their symptoms.

Background Solid tumors are often poorly vascularized, with cells that can be 100 μm away from blood vessels. These distant cells get less oxygen and nutrients and are exposed to lower doses of chemotherapeutic agents. As gap junctions allow the passage of small molecules between cells, we tested the possibility that the chemotherapeutic agent gemcitabine can diffuse through gap junctions in solid tumors. Results We first showed with a dye transfer assay that the glioblastoma and the osteosarcoma cells used in this study have functional gap junctions. These cells were genetically engineered to express the herpes simplex virus thymidine kinase (TK), and induced a "bystander effect" as demonstrated by the killing of TK-negative cells in presence of the nucleoside analogue ganciclovir (GCV). The ability of gemcitabine to induce a similar bystander effect was then tested by mixing cells treated with 3 μM gemcitabine for 24 hours with untreated cells at different ratios. In all cell lines tested, bystander cells were killed with ratios containing as low as 5% treated cells, and this toxic effect was reduced in presence of α-glycyrrhetinic acid (AGA), a specific gap junction inhibitor. We also showed that a 2- or a 24-hour gemcitabine treatment was more efficient to inhibit the growth of spheroids with functional gap junctions as compared to the same treatment made in presence of AGA. Finally, after a 24-hour gemcitabine treatment, the cell viability in spheroids was reduced by 92% as opposed to 51% in presence of AGA. Conclusion These results indicate that gemcitabine-mediated toxicity can diffuse through gap junctions, and they suggest that gemcitabine treatment could be more efficient for treating solid tumors that display gap junctions. The presence of these cellular channels could be used to predict the responsiveness to this nucleoside analogue therapy.