Feasibility of changing for a rechargeable constant current neurostimulator in Parkinson's disease.

BACKGROUND: Little is known about outcome and settings adaptations after replacement of constant-voltage non-rechargeable implantable pulse generator (CV-nrIPG) by constant-current rechargeable IPG (CC-rIPG). OBJECTIVE: To determine the feasibility and safety of replacing a CV-nrIPG by a CC-rIPG in Parkinson's disease (PD) and the subsequent outcome. METHODS: A prospective cohort of thirty PD patients, whose CV-nrIPG was replaced by a CC-rIPG in University Hospital of Lyon between January 2017 and December 2018 (rIPG group) and 39 PD patients, who underwent the replacement of a CV-nrIPG by the same device in 2016 (nrIPG group), were enrolled in this study. Three surgeons performed the operations. Duration of hospitalization for the replacement as well as the number of in or outpatient visits during the first 3 months after the surgery were recorded. In the rIPG group, we compared preoperative DBS settings and the theoretical amplitude estimated using Ohm's law to the amplitude used at the end of follow-up. We assessed patients' and clinicians' opinion on the patient global functioning after the replacement using Clinical Global Impression score. RESULTS: Duration of hospitalization (P=0.47) and need for additional hospitalizations (P=0.73) or consultations (P=0.71) to adapt DBS parameters did not differ between the two groups. Neurological condition (CGI score) was considered as unchanged by both patients and neurologists. Final amplitude of stimulation using CC-rIPG was not predicted by Ohm's law in most cases. CONCLUSIONS: Replacing CV-nrIPG by CC-rIPG is safe and well tolerated but require neurological expertise to set the new parameters of stimulation.

The contribution of genetic variants of SLC2A1 gene in T2DM and T2DM-nephropathy: association study and meta-analysis.

An association study was conducted to investigate the relation between 14 variants of glucose transporter 1 gene (SLC2A1) and the risk of type 2 diabetes (T2DM) leading to nephropathy. We also performed a meta-analysis of 11 studies investigating association between diabetic nephropathy (DN) and SLC2A1 variants. The cohort included 197 cases (T2DM with nephropathy), 155 diseased controls (T2DM without nephropathy) and 246 healthy controls. The association of variants with disease progression was tested using generalized odds ratio (ORG). The risk of type 2 diabetes leading to nephropathy was estimated by the OR of additive and co-dominant models. The mode of inheritance was assessed using the degree of dominance index (h-index). We synthesized results of 11 studies examining association between 5 SLC2A1 variants and DN. ORG was used to assess the association between variants and DN using random effects models. Significant results were derived for co-dominant model of rs12407920 [OR = 2.01 (1.17-3.45)], rs841847 [OR = 1.73 (1.17-2.56)] and rs841853 [OR = 1.74 (1.18-2.55)] and for additive model of rs3729548 [OR = 0.52 (0.29-0.90)]. The mode of inheritance for rs12407920, rs841847 and rs841853 was 'dominance of each minor allele' and for rs3729548 'non-dominance'. Frequency of one haplotype (C-G-G-A-T-C-C-T-G-T-C-C-A-G) differed significantly between cases and healthy controls [p = .014]. Regarding meta-analysis, rs841853 contributed to an increased risk of DN [(ORG = 1.43 (1.09-1.88); ORG = 1.58 (1.01-2.48)] between diseased controls versus cases and healthy controls versus cases, respectively. Further studies confirm the association of rs12407920, rs841847, rs841853, as well as rs3729548 and the risk of T2DM leading to nephropathy.

Neurostimulation for Parkinson's disease with early motor complications.

BACKGROUND: Subthalamic stimulation reduces motor disability and improves quality of life in patients with advanced Parkinson's disease who have severe levodopa-induced motor complications. We hypothesized that neurostimulation would be beneficial at an earlier stage of Parkinson's disease. METHODS: In this 2-year trial, we randomly assigned 251 patients with Parkinson's disease and early motor complications (mean age, 52 years; mean duration of disease, 7.5 years) to undergo neurostimulation plus medical therapy or medical therapy alone. The primary end point was quality of life, as assessed with the use of the Parkinson's Disease Questionnaire (PDQ-39) summary index (with scores ranging from 0 to 100 and higher scores indicating worse function). Major secondary outcomes included parkinsonian motor disability, activities of daily living, levodopa-induced motor complications (as assessed with the use of the Unified Parkinson's Disease Rating Scale, parts III, II, and IV, respectively), and time with good mobility and no dyskinesia. RESULTS: For the primary outcome of quality of life, the mean score for the neurostimulation group improved by 7.8 points, and that for the medical-therapy group worsened by 0.2 points (between-group difference in mean change from baseline to 2 years, 8.0 points; P=0.002). Neurostimulation was superior to medical therapy with respect to motor disability (P<0.001), activities of daily living (P<0.001), levodopa-induced motor complications (P<0.001), and time with good mobility and no dyskinesia (P=0.01). Serious adverse events occurred in 54.8% of the patients in the neurostimulation group and in 44.1% of those in the medical-therapy group. Serious adverse events related to surgical implantation or the neurostimulation device occurred in 17.7% of patients. An expert panel confirmed that medical therapy was consistent with practice guidelines for 96.8% of the patients in the neurostimulation group and for 94.5% of those in the medical-therapy group. CONCLUSIONS: Subthalamic stimulation was superior to medical therapy in patients with Parkinson's disease and early motor complications. (Funded by the German Ministry of Research and others; EARLYSTIM ClinicalTrials.gov number, NCT00354133.).

[Anatomical study of muscular latissimus dorsi surface vascularized by the transverse branch of thoraco-dorsal artery]. / Étude anatomique du territoire musculaire du latissimus dorsi vascularisé par la branche transverse de l'artère thoraco-dorsale.

INTRODUCTION: The latissimus dorsi muscle flap is a type V according to Mathes and Nahai. It is vascularized by a proximal main pedicle represented by the thoraco-dorsal pedicle and pedicle distal accessory represented by the dorsal branches of the posterior intercostal arteries. The main thoraco-dorsal pedicle has a descending branch and a transverse branch. This anatomical study clarifies the muscular territory vascularized by the transverse branch of thoraco-dorsal artery for a secondary use after harvesting a thoraco-dorsal artery perforator flap or a muscle-sparing latissimus dorsi flap. MATERIAL AND METHODS: Our study focused on ten dissections latissimus dorsi muscle taken from five fresh cadavers chest, carried out within the University Department of Anatomy. The descending branch of thoraco-dorsal artery was ligated, the transverse branch was cannulated and injected with a mixture of barium sulfate/gelatin. After freezing, a static angiotomodensitometry (3D) of each flap was performed. RESULTS: The average muscular surface vascularized by the transverse branch is measured at 80% (77% minimum value, maximum value 83%) of the complete latissimus dorsi muscle. Intermuscular connections between the two branches of thoraco-dorsal pedicle were shown. CONCLUSION: The use of a ipsilateral latissimus dorsi muscle is a therapeutic option after harvesting a thoraco-dorsal artery perforator flap (TAP) or a muscle-sparing latissimus dorsi flap (MSLD-flap).

Lumbosacral plexus and pudendal nerve magnetic resonance tractography: A systematic review of the clinical applications for pudendal neuralgia.

Diffusion tensor imaging (DTI) is commonly used to establish three-dimensional mapping of white-matter bundles in the supraspinal central nervous system. DTI has also been the subject of many studies on cranial and peripheral nerves. This non-invasive imaging technique enables virtual dissection of nerves in vivo and provides specific measurements of microstructural integrity. Adverse effects on the lumbosacral plexus may be traumatic, compressive, tumoral, or malformative and thus require dedicated treatment. DTI could lead to new perspectives in pudendal neuralgia diagnosis and management. We performed a systematic review of all articles or posters reporting results and protocols for lumbosacral plexus mapping using the DTI technique between January 2011 and December 2023. Twenty-nine articles published were included. Ten studies with a total of 351 participants were able to track the lumbosacral plexus in a physiological context and 19 studies with a total of 402 subjects tracked lumbosacral plexus in a pathological context. Tractography was performed on a 1.5T or 3T MRI system. DTI applied to the lumbosacral plexus and pudendal nerve is feasible but no microstructural normative value has been proposed for the pudendal nerve. The most frequently tracking parameters used in our review are: 3T MRI, b-value of 800 s/mm2, 33 directions, 3 × 3 × 3 mm3, AF threshold of 0.1, minimum fiber length of 10 mm, bending angle of 30°, and 3DT2 TSE anatomical resolution. Increased use of DTI could lead to new perspectives in the management of pudendal neuralgia due to entrapment syndrome, whether at the diagnostic, prognostic, or preoperative planning level. Prospective studies of healthy subjects and patients with the optimal acquisition parameters described above are needed to establish the accuracy of MR tractography for diagnosing pudendal neuralgia and other intrapelvic nerve entrapments.

African horse sickness in The Gambia: circulation of a live-attenuated vaccine-derived strain.

African horse sickness virus serotype 9 (AHSV-9) has been known for some time to be circulating amongst equids in West Africa without causing any clinical disease in indigenous horse populations. Whether this is due to local breeds of horses being resistant to disease or whether the AHSV-9 strains circulating are avirulent is currently unknown. This study shows that the majority (96%) of horses and donkeys sampled across The Gambia were seropositive for AHS, despite most being unvaccinated and having no previous history of showing clinical signs of AHS. Most young horses (<3 years) were seropositive with neutralizing antibodies specific to AHSV-9. Eight young equids (<3 years) were positive for AHSV-9 by serotype-specific RT-PCR and live AHSV-9 was isolated from two of these horses. Sequence analysis revealed the presence of an AHSV-9 strain showing 100% identity to Seg-2 of the AHSV-9 reference strain, indicating that the virus circulating in The Gambia was highly likely to have been derived from a live-attenuated AHSV-9 vaccine strain.

Equine encephalosis virus: evidence for circulation beyond southern Africa.

Prior to the recent outbreak of equine encephalosis in Israel in 2009, equine encephalosis virus (EEV) had only been isolated from equids in South Africa. In this study we show the first evidence for the circulation of EEV beyond South Africa in Ethiopia, Ghana and The Gambia, indicating that EEV is likely to be freely circulating and endemic in East and West Africa. Sequence analysis revealed that the EEV isolate circulating in The Gambia was closely related to an EEV isolate that was isolated from a horse from Israel during the EEV outbreak in 2009, indicating that the two viruses have a common ancestry. Interestingly horses in Morocco tested negative for EEV antibodies indicating that the Sahara desert may be acting as a geographical barrier to the spread to the virus to North African countries. This evidence for EEV circulation in countries in East and West Africa sheds light on how the virus may have reached Israel to cause the recent outbreak in 2009.

Minimally invasive surgery for intradural spinal meningioma: A new standard? A comparative study between minimally invasive and open approaches.

BACKGROUND: Some authors used minimally invasive surgery (MIS) in the treatment of spinal cord tumor, but these studies had a small sample sizes and mixed extra- and intra-medullary tumors, resulting in confounding biases. The objectives of the present study were to evaluate the effectiveness and safety of MIS for spinal meningioma resection in comparison with open surgery (OS). METHODS: Consecutive patients with spinal meningioma who received either MIS or OS were included. Data for extent of resection, functional outcome, postoperative morbidity and recurrence were collected. RESULTS: A total of 48 patients (with 51 spinal meningiomas) were included. Eighteen underwent MIS and 30 OS. Meningioma volume and location did not differ significantly between groups: tumors were predominantly thoracic (n=39, 76.5%) and voluminous (occupying more than 50% of the spinal canal: n=43, 84.3%). In the MIS group, patients were older (mean age: 66.5 vs. 56.4years, P=0.02) and more fragile (mean ASA score: 2.0 vs. 1.6, P=0.06). In the MIS group, the surgical procedure was shorter (mean duration: 2.07 vs. 2.56h, P=0.04), blood loss lower (mean: 252 vs. 456mL, P=0.02), and hospital stay shorter (mean: 6.6 vs. 8.1days). Surgery improved the modified McCormick scale (P<0.0001) irrespective of the surgical technique. MIS led to no significant differences in extent of resection or postoperative morbidity. Mean follow-up was 46.6 months. At last follow-up, 91.7% (n=44) of patients were free of progression; all cases of tumor progression (n=4) occurred in the OS group. CONCLUSIONS: MIS outperformed OS in the management of intradural spinal meningioma, irrespective of location and volume. MIS appears to be particularly suitable for elderly and fragile patients.

Prognostic factors for progression-free survival of the filum terminale ependymomas in adults.

OBJECTIVE: To define the prognostic factors for progression and to determine the impact of the histological grading (according to the World Health Organization) on the progression-free survival (PFS) of filum terminale ependymomas. METHODS: A retrospective chart review of 38 patients with ependymoma of the filum terminale was performed, focusing on demographic data, preoperative symptoms, tumor size, quality of resection, presence of a tumor capsule, and histological grade. RESULTS: Gross total resection (GTR) was achieved in 30 patients (78.9%). Histopathological analysis found 21 (55.3%) myxopapillary grade I ependymoma (MPE), 16 (42.1%) ependymoma grade II (EGII), and 1 (2.6%) ependymoma grade III. There was no significant difference between the mean±SD volume of MPE (5840.5±5244.2mm3) and the one of EGII (7220.3±6305.9mm3, p=0.5). The mean±SD follow-up was 54.1±38.4 months. At last follow-up, 30 (78.9%) patients were free of progression. In multivariate analysis, subtotal resection (p=0.015) and infiltrative tumor (p=0.03) were significantly associated with progression. The PFS was significantly higher in patients with encapsulated tumor than in patients with infiltrative tumor (log-rank p=0.01) and in patients who had a GTR in comparison with those who had an incomplete resection (log-rank p=0.05). There was no difference in PFS between patient with MPE and EGII (p=0.1). CONCLUSION: The progression of ependymoma of the filum terminale highly depends on the quality of resection, and whether the tumor is encapsulated. Except for anaplastic grade, histopathological type does not influence progression.

Functional exploration for neuropathic pain.

Neuropathic pain (NP) may become refractory to conservative medical management, necessitating neurosurgical procedures in carefully selected cases. In this context, the functional neurosurgeon must have suitable knowledge of the disease he or she intends to treat, especially its pathophysiology. This latter factor has been studied thanks to advances in the functional exploration of NP, which will be detailed in this review. The study of the flexion reflex is a useful tool for clinical and pharmacological pain assessment and for exploring the mechanisms of pain at multiple levels. The main use of evoked potentials is to confirm clinical, or detect subclinical, dysfunction in peripheral and central somato-sensory pain pathways. LEP and SEP techniques are especially useful when used in combination, allowing the exploration of both pain and somato-sensory pathways. PET scans and fMRI documented rCBF increases to noxious stimuli. In patients with chronic NP, a decreased resting rCBF is observed in the contralateral thalamus, which may be reversed using analgesic procedures. Abnormal pain evoked by innocuous stimuli (allodynia) has been associated with amplification of the thalamic, insular and SII responses, concomitant to a paradoxical CBF decrease in ACC. Multiple PET studies showed that endogenous opioid secretion is very likely to occur as a reaction to pain. In addition, brain opioid receptors (OR) remain relatively untouched in peripheral NP, while a loss of ORs is most likely to occur in central NP, within the medial nociceptive pathways. PET receptor studies have also proved that antalgic Motor Cortex Stimulation (MCS), indicated in severe refractory NP, induces endogenous opioid secretion in key areas of the endogenous opioid system, which may explain one of the mechanisms of action of this procedure, since the secretion is proportional to the analgesic effect.

Detection of a novel reassortant epizootic hemorrhagic disease virus (EHDV) in the USA containing RNA segments derived from both exotic (EHDV-6) and endemic (EHDV-2) serotypes.

Epizootic hemorrhagic disease virus (EHDV) is a Culicoides-transmitted orbivirus that infects domestic and wild ruminants and is provisionally thought to be distributed throughout Africa, North America, Australia, East Asia and the Middle East. Historically, of the seven proposed serotypes of EHDV, only EHDV-1 and EHDV-2 have been reported from North America. In 2006, EHDV isolates were recovered from moribund or dead white-tailed deer (Odocoileus virginianus) in Indiana and Illinois that could not be identified as either EHDV-1 or EHDV-2 by virus neutralization tests or by serotype-specific RT-PCR. Additional serological and genetic testing identified the isolates as EHDV-6, a serotype that, although originally described from Australia, has recently been recognized as an emerging pathogen of cattle in Morocco, Algeria and Turkey. In 2007 and 2008, EHDV-6 was isolated again from white-tailed deer, this time in Missouri, Kansas and Texas, suggesting that the virus is capable of overwintering and that it may become, or already is, endemic in a geographically widespread region of the USA. Genetic characterization of the virus indicates that it is a reassortant, such that the outer capsid proteins determining serotype specificity (VP2 and VP5) are derived from exotic EHDV-6, whilst the remaining structural and non-structural proteins are apparently obtained from indigenous EHDV-2 (Alberta).

The evolution of two homologues of the core protein VP6 of epizootic haemorrhagic disease virus (EHDV), which correspond to the geographical origin of the virus.

Epizootic haemorrhagic disease virus is a 10-segmented, double-stranded RNA virus. When these ten segments of dsRNA are run on 1% agarose, eastern (Australia, Japan) and western (North America, Africa, Middle-East) strains of the virus can be separated phenotypically based on the migration of genome segments 7-9. In western strains, segments 7-9 are roughly the same size and co-migrate as a single RNA band. In eastern strains, segment 9 is smaller, so while segments 7 and 8 co-migrate, the segment 9 RNA runs faster than its western homologue. Translation experiments demonstrated that these two segment 9 homologues are both functional and produce proteins (VP6) of different sizes-something that has not been reported in any other orbivirus species to date. Sequence analysis suggests that eastern and western versions of segment 9 (VP6) have likely evolved as a response to adaptive selection in different geographical regions via gene duplication and subsequent mutation. These significant findings are considered unusual given the conserved nature of VP6 and its presumed role as the viral helicase. It is not currently known what the biological relevance of each homologue is to the virus.

[Chest compression quality : Can feedback technology help?]. / Thoraxkompressionsqualität : Hilft Feedback-Technologie?

BACKGROUND: The outcome of cardiopulmonary resuscitation (CPR) depends on the quality of chest compressions. Current European Resuscitation Council (ERC) guidelines promote the development of feedback systems. However, no studies presenting satisfactory results of feedback use have been published. METHODS: A total of 60 patients with cardiac arrest (> or =18 years of age) received resuscitation attempts using an automated external defibrillator (AED) with real-time feedback by the ambulance service of the City of Münster. The frequency of chest compressions, no-flow time (NFT) and depth of chest compressions were analyzed for the first three cycles of CPR and compared to the ERC guidelines 2005. RESULTS: Chest compression frequency did not differ significantly from the ideal as set out in the guidelines. Analysis of NFTs showed significantly longer NFT for the first cycle but NFT for the second and third cycles did not differ significantly from the ideal. The target depth of 4-5 cm was achieved in 80% of all chest compressions in the first 3 cycles. CONCLUSION: With the AED real-time feedback technology used in this study standardized performance of chest compressions could be maintained in a professional ambulance service. Implementation of a feedback system requires training of ambulance staff.

Virological, immunological and pathological findings of transplacentally transmitted bluetongue virus serotype 1 in IFNAR1-blocked mice during early and mid gestation.

Transplacental transmission (TPT) of wild-type Indian BTV-1 had never been experimentally proved. This study was first time investigated TPT of Indian BTV-1 (isolated from aborted and stillborn goat fetal spleens). The sequential pathology, virological and immune cell kinetics (CD4+, CD8+ T-lymphocytes and NK cells in spleen and PBMCs), and apoptosis in IFNAR1-blocked pregnant mice during early (infected on 1 GD) and mid (infected on 8 GD) gestation have been studied. There was higher rate of TPT during mid stage (71.43%) than early (57.14%) stage. In early stage reduced implantation sites, early embryonic deaths, abortions, and necro-haemorrhagic lesions had observed. Mid stage, congenital defects and neurological lesions in foetuses like haemorrhages, diffuse cerebral edema, necrotizing encephalitis and decreased bone size (Alizarin red staining) were noticed. BTV-1 antigen was first time demonstrable in cells of mesometrium, decidua of embryos, placenta, uterus, ovary, and brain of foetuses by immunohistochemistry and quantified by real-time qRT-PCR. BTV-inoculated mice were seroconverted by 7 and 5 dpi, and reached peak levels by 15 and 9 dpi in early and mid gestation, respectively. CD4+ and CD8+ cells were significantly decreased (increased ratio) on 7 dpi but subsequently increased on 15 dpi in early gestation. In mid gestation, increased CD8+ cells (decreased ratio) were observed. Apoptotic cells in PBMCs and tissues increased during peak viral load. This first time TPT of wild-type Indian BTV-1 deserves to be reported for implementation of control strategies. This model will be very suitable for further research into mechanisms of TPT, overwintering, and vaccination strategies.

Case series of idiopathic membranous nephropathy with long-term beneficial effects of ACTH peptide 1-24.

BACKGROUND: In patients with idiopathic membranous nephropathy (IMN), immunosuppressive therapy is usually considered when severe nephrotic syndrome or risk for progressive renal failure exist. Recently, several studies showing beneficial effects of synthetic adrenocorticotropic hormone (ACTH) under such circumstances have been published. The objective of the present case series was to evaluate long-term ACTH effects on proteinuria and renal function. METHODS: Four patients with biopsy-proven membranous nephropathy and nephrotic syndrome were enrolled (median age 50 years (range 38 - 61), median GFR 39.5 ml/min (range 20 - 62), median proteinuria 9.6 g/d (range 6.0 - 20.0). Prior immunosuppressive treatment regimens included steroids, cyclosporine A, cyclophosphamide, mycophenolate mofetil or azathioprine. The patients received a synthetic ACTH analogue intramuscularly for a median duration of 8 months (range 3 - 24). ACTH dosage was adjusted according to side effects between 0.25 and 2.25 mg/week. Follow-up lasted between 24 and 82 months after therapy initiation. RESULTS: All 4 patients exhibited partial (n = 2) or complete (n = 2) remissions of their nephrotic syndrome within the first year. After discontinuation of ACTH therapy, proteinuria remained low in 3 of 4 cases, whereas 1 patient exhibited undulating proteinuria. Glomerular function (as assessed by glomerular filtration rate, GFR) was maintained in all patients. Side effects were minor and included weight gain, elevated blood pressure and hyperglycemia. CONCLUSION: In all 4 cases with IMN, ACTH treatment induced a lasting disease remission with relatively few side effects.

[Functional anatomy of the glossopharyngeal, vagus, accessory and hypoglossal cranial nerves]. / Anatomie fonctionnelle des nerfs glossopharyngien, vague, accessoire et hypoglosse.

The glossopharyngeal nerve and the vagus nerve are mixed nerves containing sensory, gustatory, motor and autonomous fibers (parasympathetic). The glossopharyngeal nerve has mainly visceral afferent fibers from the tongue and pharynx, gustatory fibers from the posterior third of the tongue, parasympathetic afferent fibers from carotid sinus and carotid glomus, parasympathetic efferent fibers for the parotid gland and motor fibers for the muscles of the pharynx. The vagus nerve contains mostly visceral afferent fibers from laryngeal, intrathoracic and abdominal organs, parasympathetic efferent fibers for these intrathoracic and abdominal organs and motor fibers to the pharyngeal and laryngeal muscles. The accessory nerve is divided into two branches, different in their origins and their functions: the cranial portion joins the motor fibers of the vagus nerve, to form the recurrent laryngeal nerve, whereas the spinal portion innervates the sternocleidomastoid muscle and the trapezius muscle. Finally, the hypoglossal nerve is the main motor nerve of the tongue.

[Functional anatomy of the cochlear nerve and the central auditory system]. / Anatomie fonctionnelle du nerf cochléaire et du système auditif central.

The auditory pathways are a system of afferent fibers (through the cochlear nerve) and efferent fibers (through the vestibular nerve), which are not limited to a simple information transmitting system but create a veritable integration of the sound stimulus at the different levels, by analyzing its three fundamental elements: frequency (pitch), intensity, and spatial localization of the sound source. From the cochlea to the primary auditory cortex, the auditory fibers are organized anatomically in relation to the characteristic frequency of the sound signal that they transmit (tonotopy). Coding the intensity of the sound signal is based on temporal recruitment (the number of action potentials) and spatial recruitment (the number of inner hair cells recruited near the cell of the frequency that is characteristic of the stimulus). Because of binaural hearing, commissural pathways at each level of the auditory system and integration of the phase shift and the difference in intensity between signals coming from both ears, spatial localization of the sound source is possible. Finally, through the efferent fibers in the vestibular nerve, higher centers exercise control over the activity of the cochlea and adjust the peripheral hearing organ to external sound conditions, thus protecting the auditory system or increasing sensitivity by the attention given to the signal.