Pulsed-field gradient nuclear magnetic resonance measurements (PFG NMR) for diffusion ordered spectroscopy (DOSY) mapping.

While NMR is the most used analytical method for determining the molecular structure of isolated chemical entities, small compounds as well as macromolecules, its capability of analysing complex mixtures is less known. The advent of Diffusion Ordered SpectroscopY (DOSY) NMR has made diffusion experiments popular, enabling diffusion coefficients to be routinely measured and used to characterize chemical systems in solution. Indeed, since the translational diffusion coefficients of molecular species reflect their effective sizes and shapes, DOSY NMR allows the separation of the chemical entities present in multicomponent systems and, as in all diffusion NMR experiments, provides information on their intermolecular interactions as well as on their size and shape. The main aim of this review is to present an overview of the DOSY NMR mapping and its applications. The paper starts with a brief introduction to pulsed-field gradient (PFG) NMR and then focuses on the methodological procedures that can be used to perform good diffusion data acquisition and to obtain good-quality DOSY maps. The second part describes, through selected literature examples, different applications of DOSY NMR to demonstrate the potential of the method for (i) unravelling the components of complex matrices comprising pharmaceuticals, dietary supplements, foods and beverages, and biological extracts, and (ii) probing intermolecular interactions and evaluating association constants between different hosts and guests, as well as estimating the sizes and molecular weights of molecular species.

Management and outcome of cerebral venous thrombosis after head trauma: A case series.

Cerebral venous thrombosis (CVT) is an underdiagnosed complication of head trauma. To date, initiation of anticoagulation is still a matter of debate because of the risk of worsening traumatic hemorrhage. This report describes a case series of five patients admitted for head injury complicated by CVT. The main associated radiological signs were skull fractures crossing the venous sinus and adjacent traumatic hematoma. In four patients, anticoagulation was introduced within 48-72h of CVT diagnosis, with no subsequent hemorrhagic complications. The present report and data from the literature raise the question of systematic additional venoscans when confronted by associated radiological features of post-traumatic CVT. The safety of anticoagulation in selected patients is also discussed.

Pituitary metastasis: is there still a place for neurosurgical treatment?

Pituitary metastases are uncommon, ranging from 1 to 5 % of all metastases. Between 10 and 30 % of pituitary lesions are symptomatic responsible for diabetes insipidus, visual field defect or cranial nerve palsy. Primary sites are lung or breast in two-thirds of cases. There is no current reference concerning treatment of such lesions. Overall survival is poor and depends on primary site. Although the role of surgery is currently limited, discussion is warranted in several indications for diagnostic or symptomatic purposes. We report two cases of symptomatic pituitary metastases in a context of breast cancer and review the litterature concerning the role of surgery and other treatment modalities.

Metastasis of the choroid plexuses: A systematic review of the literature and case illustration.

BACKGROUND: Choroid plexus (CP) metastases are an extremely rare condition accounting for less than 1% of brain metastases. Due to its scarcity, little is known about this pathology and its management. Herein, we propose a review of the current literature to help its diagnosis and management. METHODS: Through a literature review based on PubMed/MEDLINE database, we reviewed 94 cases of intraventricular metastasis of solid cancer in 28 full-text articles in English from 1980 to 2010. We have reported epidemiological, clinical, radiological, histological data, as well as management strategies and outcomes. A case report of fourth ventricular pulmonary metastasis illustrates this review. RESULTS: Intraventricular metastases are most often reported in patients in their 6th decade. The clinical presentation is marked by acute hydrocephalus, more rarely lesional bleeding. Three-quarters of intraventricular metastases develop in lateral ventricle, then respectively in the fourth and third ventricles. Kidney cancer accounts for 45% of the cases. The treatment modalities are surgical removal in case of a single lesion and adjuvant radiotherapy and chemotherapy depending on the primary cancer. The prognosis remains poor due to dissemination via the cerebrospinal fluid. CONCLUSION: Multiple choroid plexus metastasis is a rare diagnosis, affecting patients with a specific clinical presentation and a misleading radiological appearance. There is no standard of care for the management of these lesions and surgical approach can be challenging.

Ruptured dural arteriovenous fistula and sinus venous thrombosis following surgical resection of a vestibular schwannoma: Case report and review of the literature.

Dural arteriovenous fistula (DAVF) is a rare vascular malformation. Strong evidence suggests that the development of DAVF in adults is acquired and multifactorial. The link between cerebral venous thrombosis and DAVF is probably explained by dynamic changes in the venous drainage pattern. We report the case of a 34-year-old man admitted to the emergency department for seizure and headaches. The patient had a medical history of right vestibular schwannoma resection 9 months earlier, complicated by untreated asymptomatic sigmoid sinus thrombosis. At admission, CT scan revealed a spontaneous temporal intracerebral hemorrhage associated with ventricular hemorrhage due to the rupture of a DAVF diagnosed by complementary CT angiography. External ventricular drainage was performed in emergency, followed by endovascular exclusion of the DAVF. Good neurological outcome was achieved, with complete exclusion of the vascular malformation. This clinical case underlines the absence of guidelines on the use of anticoagulation drugs to treat postoperative venous sinus thrombosis and to potentially prevent DAVF as a late complication following cerebellopontine angle surgery.

Massive non-aneurysmal subarachnoid hemorrhage after cervical carotid angioplasty and stenting: A case report and review of the literature.

INTRODUCTION: Carotid angioplasty and stenting (CAS) of the cervical segment is a safe and effective procedure for the treatment of carotid artery disease. In rare cases, this procedure causes intracranial hemorrhage (ICH), which is described most often as an ipsilateral intra-parenchymal hematoma. This ICH is the result of a cerebral hyperperfusion syndrome (CHS). Isolated subarachnoid hemorrhage may occur exceptionally, with only 9 cases that have been reported in the literature. OBSERVATION: We reported a case of a 71-year-old man who presented a massive non-aneurysmal subarachnoid hemorrhage one hour after angioplasty and stenting of the cervical segment of the left internal carotid artery. Medical and surgical management included external ventricular drain placement. Rebleeding occurred two days later, worsening the patient's clinical condition. Finally, the patient died 2 weeks later. COMMENTS: This rare presentation of ICH following CAS allows us to discuss the risk factors, complications and management of CHS.

[Identification of factors associated with performance in objective structured clinical examination in Rouen medical school]. / Identification des facteurs associés à la réussite aux examens cliniques objectifs et structurés dans la faculté de médecine de Rouen.

CONTEXT: Objective structured clinical examination (OSCE) became a national exam at the end of medical studies in France. The aim of this study was to identify the predictive factors for success at OSCEs. METHODS: Aurvey query after the OSCEs was completed by fifth-year medicine students at Rouen Uuniversity.. Data on continuous variables were compared using the Mann-Whitney test. Data on quantitative variables were compared using the Spearman's correlation. RESULTS: Two hundred and thirty-nine students, i.e., 98.7 % of the students, responded to the query. The median (IQR 25-75) OSCE score was 13.6/20 (12.5-14.2). Students' personal factors significantly associated with a higher OSCE performance were female sex (median score of 13.7 versus 13.4; P=0.03) and good health during the clerkship (median score of 13.6 versus 12.6; P=0.02). A higher OSCE performance was associated with an increased number (≥6)  of medicine clerkships (median score of 13.8 versus 13.3; P=0.02) and a decreased number (<3) of surgery clerkships (median score of 13.7 versus 12.9; P=0.009). There was no correlation between the OSCE score and medical school performance (Spearman's correlation, r=0.24). CONCLUSION: Homogenization of student's clerkships, assistance to students with health problems seem to be teaching approaches to promote success at OSCEs.

pH optimization for a reliable quantification of brain tumor cell and tissue extracts with (1)H NMR: focus on choline-containing compounds and taurine.

The aim of this study was to define the optimal pH for (1)H nuclear magnetic resonance (NMR) spectroscopy analysis of perchloric acid or methanol-chloroform-water extracts from brain tumor cells and tissues. The systematic study of the proton chemical shift variations as a function of pH of 13 brain metabolites in model solutions demonstrated that recording (1)H NMR spectra at pH 10 allowed resolving resonances that are overlapped at pH 7, especially in the 3.2-3.3 ppm choline-containing-compounds region. (1)H NMR analysis of extracts at pH 7 or 10 showed that quantitative measurements of lactate, alanine, glutamate, glutamine (Gln), creatine + phosphocreatine and myo-inositol (m-Ino) can be readily performed at both pHs. The concentrations of glycerophosphocholine, phosphocholine and choline that are crucial metabolites for tumor brain malignancy grading were accurately measured at pH 10 only. Indeed, the resonances of their trimethylammonium moieties are cleared of any overlapping signal, especially those of taurine (Tau) and phosphoethanolamine. The four non-ionizable Tau protons resonating as a singlet in a non-congested spectral region permits an easier and more accurate quantitation of this apoptosis marker at pH 10 than at pH 7 where the triplet at 3.43 ppm can be overlapped with the signals of glucose or have an intensity too low to be measured. Glycine concentration was determined indirectly at both pHs after subtracting the contribution of the overlapped signals of m-Ino at pH 7 or Gln at pH 10.

Counterfeit drugs: analytical techniques for their identification.

In recent years, the number of counterfeit drugs has increased dramatically, including not only "lifestyle" products but also vital medicines. Besides the threat to public health, the financial and reputational damage to pharmaceutical companies is substantial. The lack of robust information on the prevalence of fake drugs is an obstacle in the fight against drug counterfeiting. It is generally accepted that approximately 10% of drugs worldwide could be counterfeit, but it is also well known that this number covers very different situations depending on the country, the places where the drugs are purchased, and the definition of what constitutes a counterfeit drug. The chemical analysis of drugs suspected to be fake is a crucial step as counterfeiters are becoming increasingly sophisticated, rendering visual inspection insufficient to distinguish the genuine products from the counterfeit ones. This article critically reviews the recent analytical methods employed to control the quality of drug formulations, using as an example artemisinin derivatives, medicines particularly targeted by counterfeiters. Indeed, a broad panel of techniques have been reported for their analysis, ranging from simple and cheap in-field ones (colorimetry and thin-layer chromatography) to more advanced laboratory methods (mass spectrometry, nuclear magnetic resonance, and vibrational spectroscopies) through chromatographic methods, which remain the most widely used. The conclusion section of the article highlights the questions to be posed before selecting the most appropriate analytical approach.

Analysis of hydrophilic and lipophilic choline compounds in radioresistant and radiosensitive glioblastoma cell lines by HILIC-ESI-MS/MS.

A new method based on hydrophilic interaction chromatography-electrospray ionisation-tandem mass spectrometry (HILIC-ESI-MS/MS) coupled to the use of a stable isotope labelled substrate was developed to study the metabolism of choline (Cho) compounds in two human glioblastoma multiform (GBM) cell lines with different responses to ionising radiation. Analysis was performed in the positive ion mode using multiple reaction monitoring. This fast, sensitive and selective method enabled the profiling of both hydrophilic and lipophilic Cho-containing compounds, to analyse specifically different phosphatidylcholine (PtdCho) molecular species, and to measure simultaneously native and labelled Cho metabolites. Radioresistant (SF763) and radiosensitive (SF767) cells were incubated for 8 h with d(9)-Cho. Higher native Cho and phosphocholine (PCho) concentrations and higher uptake of d(9)-Cho and formation of d(9)-PCho were found in the radioresistant cell line. The similar low concentrations of native cytidine 5'-diphosphocholine (CDP-Cho) and d(9)-CDP-Cho in both cell lines show that CDP-Cho is the limiting metabolite in the two models. The turnovers (percentage of each d(9)-Cho compound in its respective pool, i.e. native + labelled) were lower in radioresistant cells for all Cho compounds, suggesting a global PtdCho metabolism more active in radiosensitive cells that could be related to their higher proliferation rate.

Case report: Mini-invasive surgery assisted by Da Vinci® robot for a recurrent paravertebral schwannoma.

BACKGROUND AND OBJECTIVES: More and more surgeons are changing their surgical procedures by using mini-invasive technology with the aim of reducing morbidity. Robotized technology for the surgery of narrow spinal space, for the resection of intervertebral foramen tumor, is a valuable option that should be considered. The authors report the case of a patient who underwent robotic surgery for the treatment of a paravertebral schwannoma and show the benefits of this approach. CASE REPORT: A 53-year-old man was treated, in 1995, via an open right latero-thoracic approach for a T8-T9 thoracic schwannoma with a complete resection. Twenty years later, the patient complained of recurrent T8-T9 thoracic pain with unilateral radicular irradiation related to a recurrent schwannoma with a right foraminal extension. Using robotic technology (Da Vinci®), a complete resection was achieved and confirmed by a postoperative MRI. The patient, who was free of neurological symptoms, discharged the hospital at day 2. COMMENTS: Robot-assisted surgery by Da Vinci® robot is a very useful approach for the treatment of spinal paravertebral schwannoma. Thanks to multi-directional arms and 3D vision, this technology is safe and effective about quality of resection. The use of mini-invasive technology should be routinely discussed for lesions in that specific location.

Practice of stereoelectroencephalography (sEEG) in drug-resistant epilepsy: Retrospective series with surgery and thermocoagulation outcomes.

OBJECTIVE: The aim of this study was to determine the success rate of sEEG in locating the epileptogenic zone (EZ) in patients with pharmaco-resistant epilepsy. Secondary objectives were to analyze sEEG-related morbidity and outcomes for post-sEEG thermocoagulation and cortical resection. METHODS: Data were collected on 49 sEEGs from 46 consecutive patients between 2010 and 2018. Following sEEG, either resective or palliative surgery with vagus nerve stimulation was performed. In 8 patients, EZ thermocoagulation was performed before EEG leads were withdrawn. Outcomes were collected based on the Engel and ILAE outcome scales. RESULTS: sEEG was contributive in 45 of 49 recordings, with a success rate of 92% in locating the EZ. Minor complications, such as transient neurologic deficit and electrode implantation failures, occurred in 6%. One major complication occurred, with death due to atypical late hematoma. Thermocoagulation was performed in 8 patients and stopped or significantly reduced seizure frequency in 7 (88%). Outcome of surgical resection (n=33) was good, with 20 (61%) seizure-free patients and 32 (97%) with definite improvement. CONCLUSIONS: Our findings suggest that sEEG is an effective technique for EZ location in patients with drug-resistant epilepsy. sEEG was contributive in up to 92% of patients, allowing thermocoagulation and/or surgical resection that resulted in seizure-freedom in two-thirds and seizure-reduction in one-third of cases. This study highlights the need for strict selection of implantation candidates, with strong initial hypothesis as to EZ location.

Blood loss and perioperative transfusions related to surgery for spinal tumors. Relevance of tranexamic acid.

INTRODUCTION: Tranexamic acid (TXA) has been shown to reduce bleeding. Patients with spinal tumors are fragile and acute anemia may be harmful. Tumor excision surgery is reputed to be hemorrhagic and treatment may increase thromboembolic complications. The aim of this study was to compare blood loss with or without perioperative TXA injection. The transfusion-related and postoperative complications were documents. METHOD: This retrospective analysis of prospectively collected data involved 83 patients with spinal tumors who underwent decompressive surgery associated with bone fixation. Tranexamic acid was used arbitrarily in 36 of them, while the other 47 did not receive TXA. The overall, intraoperative and postoperative blood loss was recorded. Blood loss was reported relative to the number of fixed levels and the number of levels decompressed by laminectomy. Transfusions were quantified in number of red blood cell packets and erythrocyte volume. Postoperative complications were documented. RESULTS: Epidemiological and morphological data were similar between groups. There were no significant differences between the two groups in the overall, intraoperative, and postoperative blood loss. A significant reduction in postoperative bleeding was found in the TXA group when the volume was related to the number of decompressed levels. A significant reduction (P<0.05) in the volume of transfused blood was identified in the treated group. No predictor of blood loss was identified, and no additional complications occurred. CONCLUSION: The efficacy of TXA appears to be moderate during spinal tumor surgery since it does not lead to a reduction in perioperative bleeding. However, a significant reduction in transfusion volume was found without an increase in complications.

Sudden paraplegia due to spontaneous bleeding in a thoracic epidural angiolipoma and literature review.

BACKGROUND: Spinal angiolipomas are rare epidural tumours that are usually revealed by chronic symptoms of medullar irritation. We report a case of acute paraplegia caused by spontaneous bleeding revealing a thoracic angiolipoma. CASE DESCRIPTION: A 17-year-old male patient with no previous medical history was admitted for acute onset of paraplegia with bladder retention and loss of sensation in the lower limbs, preceded by dorsal pain during the three previous days. MRI showed an enhanced T1-weighted image of a T7-T12 epidural lesion. The T1-weighted isosignal and the T2-weighted hyposignal suggested haemorrhagic complications. Due to a mass effect on the spinal cord, an emergency laminectomy was performed. Histopathological examination of the lesion revealed an angiolipoma with spontaneous bleeding. Clinical outcome was favourable after two months. CONCLUSION: This case is one of the first to be reported, although the clinical presentation is similar to that of other rare reported cases of paraplegia due to spinal compression by tumoural bleeding.

Cervical pedicular agenesis: Case report and a review of the literature.

Cervical pedicular agenesis, an unusual disorder, is a rare clinical and radiological finding, which can lead to misdiagnosis, moreover in a traumatic situation. The authors report the case of a young woman with a C3 right congenital absence of the cervical pedicle. A systematic review of literature found more than 70 reported cases. In patients with congenital agenesis of the cervical pedicle, the two most common levels of this congenital absence are C6 and C5. The three radiological findings were: the false appearance of an enlarged ipsilateral neural foramen due to the absent pedicle; a dysplastic, dorsally displaced ipsilateral articular pillar and lamina; and a dysplastic ipsilateral transverse process. These pedicle ageneses are a stable congenital anomaly.

Untreated unruptured aneurysm: Natural history at long-term.

BACKGROUND AND OBJECTIVES: Although the diagnosis of unruptured intracranial aneurysm (IA) has become more frequent, its natural history and management still remain controversial. A better comprehension of its evolution could optimize our therapeutic strategies. The aim of our study was to evaluate, in a cohort of patients with untreated unruptured IA based on the proposition of multidisciplinary staff meetings, the proportion of bleeding, death and cardiovascular events during a long-term prospective follow-up. PATIENTS AND METHODS: This longitudinal study concerned a series of patients with unruptured IA collected over a period of 8 years (2006-2014) identified from a prospectively collected database including all patients with unruptured IA discussed during multidisciplinary staff meetings in the neurosurgery department at Rouen University Hospital. Clinical endpoints were the rupture rate, incidence of death or occurrence of noticeable pathological event defined by any event leading to death, admission to the intensive care unit or challenging the vital prognosis. RESULTS: After a mean follow-up delay of 46.9±18.7 months, the IA remained stable in 73 patients (98.6%) out of 74. The rate of rupture per aneurysm year of follow-up was 0.3%, the rate of cardiovascular events was 2.1% and the death rate was 2.8% per year of follow-up. DISCUSSION: In this study, we emphasize the important incidence of adverse events in these patients, which has to be taken into account before proposing a prophylactic IA exclusion. The low incidence of IA rupture confirmed the decision of conservative treatment made during a multidisciplinary staff meeting.

Growth of giant intracranial aneurysms: An aneurysmal wall disorder?

The enlargement of giant intracranial aneurysms (IA) can be observed in 30 % of cases resulting in a neurological deficit and epilepsy due to its mass effect. This growth process could be due to a morphological disorder of the IA wall. The authors report on 2 cases of giant IA growth responsible for intracranial hypertension. The treatment of these giant IA required a microsurgical excision combined with a series of cerebral revascularization procedures. The role of vasa vasorum on the inflammatory granuloma outside the vessel, which induced the enlargement, is discussed. These cases illustrate the abluminal vasculopathy as the main involvement of this unfavourable natural history.