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.).

The use of ultrasound in France: a point of view from experienced regional anesthesiologists.

A cross-sectional survey study on French practice in ultrasound-guided regional anesthesia was carried out. A questionnaire (demographic data, assessment of the likely benefits of ultrasonography, and its use in daily practice: blocks and hygiene) was emailed to all members of the French-speaking association of anesthesiologists involved in regional anesthesia. The questionnaire was filled out and returned by 634 experienced anesthesiologists. An ultrasound machine was available in 94% of cases. Ultrasound-guided regional anesthesia has become the gold standard technique for three-quarters of responders. Axillary, interscalene, popliteal sciatic and femoral nerve blocks were performed by more than 90% of responders, most frequently under ultrasound supervision. Conversely, ultrasound guidance was rarely used for spinal or deep nerve blocks. A specific sterile sheath was used in only 43% of cases. The present study confirms that ultrasound guidance has gained in popularity for many superficial, but not deep, regional anesthesia procedures in France.

The echogenicity of nerve blockade needles.

We performed a prospective, randomised study to evaluate the echogenicity of 11 regional block needles when inserted into a gel phantom at 45° in the ultrasound plane. Two hundred anaesthetists viewed in random sequence recordings of each needle as it was advanced into the phantom. Participants scored the needle for echogenicity on a scale of 0-10 and categorised the needle as 'hyperechoic' or 'standard'. The mean (95% CI) echogenicity score was 1.7 (1.4-2.0) units higher for three needles marketed as 'hyperechoic' compared with standard needles marketed by the same companies, p < 0.001. The odds ratios (95% CI) that an anaesthetist would categorise a needle as hyperechoic were: 5.3 (3.6-8.0) if the needle was marketed as hyperechoic, p < 0.001; and 1.7 (1.1-2.6) if regional anaesthetic experience was ≥ 1 year compared with < 1 year, p = 0.025.

Comparison of esCCO and transthoracic echocardiography for non-invasive measurement of cardiac output intensive care.

BACKGROUND: The esCCO monitor (ECG- estimated Continuous Cardiac Output, Nihon Kohden(®)) is a new non-invasive tool for estimating cardiac output (CO). It derives CO from the pulse wave transit time (PWTT) estimated by the ECG and the plethysmographic wave. An initial calibration is needed to refine the relation linking pulse pressure (measured by arterial pressure cuff) to PWTT. To assess the accuracy and reliability of the esCCO system, we performed an analysis of agreement of CO values obtained by transthoracic echocardiography (TTE). METHODS: Thirty-eight intensive care unit patients were prospectively included. CO was determined simultaneously using esCCO (CO(esCCO)) and TTE (CO(TTE)) as our reference method. RESULTS: A total of 103 paired readings from 38 patients were collected. The correlation coefficient between CO(esCCO) and CO(TTE) was 0.61 (P<0.001). The Bland and Altman analysis corrected for repeated measures showed a bias of -1.6 litre min(-1) and limits of agreement from -4.7 to +1.5 litre min(-1), with a percentage error (2 sd/mean CO) of 49%. The correlation for CO changes was significant (R=0.63, P<0.001), but the concordance rate was poor (73%). Polar plot analysis showed an angular bias of -9° with radial limits of agreement from -54° to +36°. The bias appeared to correlate with systemic vascular resistance (R=-0.45, P<0.001). CONCLUSIONS: In critically ill patients, the performance of the esCCO monitor was not clinically acceptable, and this monitor cannot be recommended in this setting. Moreover, the esCCO failed to trend CO data reliably.

[The role of radiotherapy to the primary tumor and metastases in patients with oligometastatic prostate cancer]. / Place de la radiothérapie de la tumeur primitive et/ou des métastases du cancer de la prostate oligométastatique.

Oligometastatic prostate cancer is among the most studied oligometastatic cancers in the literature. However few prospective studies have assessed stereotactic body radiotherapy (SBRT) for prostate cancer oligometastases. Two randomised phase II trials show a progression-free survival benefit compared with observation. Prospective registry data show very good local control and low toxicity too. Inclusion in ongoing trials should be strongly encouraged to define the role of SBRT in addition to systemic therapy. Radiation therapy to the primary tumour has been studied in randomised trials and provides an overall survival benefit in patients with low metastatic burden. The benefit is inversely correlated with the number of bone lesions using conventional imaging, up to three metastases. Radiotherapy to the primary tumour is recommended by the learned societies for patients with low metastatic burden. Its role in combination with second generation anti androgen therapy needs to be clarified.

Temporal analysis of regional anaesthesia-induced sensorimotor dysfunction: a model for understanding phantom limb.

BACKGROUND: The peripheral deafferentation induced by regional anaesthesia (RA) results in misperception of size-shape (S) and posture (P) of the anesthetized limb. During RA, most patients seem to describe motionless 'phantom limbs' fixed in stereotyped illusory positions, suggesting that RA could unmask stable postural patterns. The question of whether movement illusions exist or not after anaesthesia needs a prospective study. This study aimed to describe the phenomenology of RA-induced kinesthetic illusions (K illusions). METHODS: We examined prospectively the body image alteration during infraclavicular blocks in 20 patients. Multimodal sensory testing (pinprick, heat-cold, pallesthesia, and arthrokinesia) and assessment of motor function were performed every 5 min for 60 min after administration of the local anaesthetics. Meanwhile, patients described phantom limb sensations (S, P, and K illusions). RESULTS: We individualized the occurrence of K illusions [44 (8) min] with respect to S illusions [7 (3) min; P<0.005] and P illusions [22 (4) min; P<0.001]. A close relationship between the onset of K illusions and proprioceptive impairment (arthrokinesia: r=0.92, P<0.001; pallesthesia: r=0.89, P<0001) and abolishment of motor activity (r=0.83, P<0.001) was identified. Finally, a principal component analysis showed that S and P illusions were essentially related to the proprioceptive impairment. CONCLUSIONS: This study analyses for the first time the temporal evolution of sensorimotor dysfunction and the onset of K illusions during RA. Our results suggest the involvement of an alteration of proprioception and motor functions in the origin of this phenomenon. These data agree with the motor awareness theory.

Functional outcome 1 year after aneurysmal subarachnoid hemorrhage due to ruptured intracranial aneurysm in elderly patients.

BACKGROUND: Population aging raises questions about extending treatment indications in elderly patients with aneurysmal subarachnoid hemorrhage (aSAH). We therefore assessed functional status 1 year after treatment. METHODS: This study involved 310 patients, aged over 70 years, with ruptured brain aneurysm, enrolled between 2008 and 2014 in a prospective multicentre trial (FASHE study: NCT00692744) but considered unsuitable for randomisation and therefore analysed in the observational arms of the study: endovascular occlusion (EV), microsurgical exclusion (MS) and conservative treatment. The aims were to assess independence, cognition, autonomy and quality of life (QOL) at 1 year post-treatment, using questionnaires (MMSE, ADLI, IADL, EORTC-QLQ-C30) filled in by independent nurses after discharge. RESULTS: The 310 patients received the following treatments: 208 underwent EV (67.1%), 54 MS (17.4%) and 48 were conservatively managed (15.5%). At 1 year, independence rates for patients admitted with good clinical status (WFNS I-III) were, according to the aneurysm exclusion procedure (EV, MS or conservative), 58.9%, 50% and 12.1% respectively. MMSE score was pathological in 26 of the 112 EV patients (23.2%), 10 of the 25 MS patients (40%) and 4 of the 9 patients treated conservatively (44%), without any statistically significant difference [Pearson's Chi2 test, F ratio=4.29; P=0.11]. Regarding QoL, overall score was similar between the EV and MS cohorts, but significantly lower with conservative treatment. CONCLUSION: Elderly patients in good clinical condition with aSAH should be treated regardless of associated comorbidities. Curative treatment (EV or MS) reduced mortality without increasing dependence, in comparison with conservative treatment.

[Medical and economic reflections on Restore and Itrel neurostimulation systems for neuropathic pain treatment]. / Réflexion sur l'intérêt médicoéconomique des boîtiers de neurostimulation Restore et Itrel dans le traitement des douleurs neuropathiques chroniques.

In 2007, four patients where implanted with the Restore neurostimulation system for intractable chronic leg pain at the Poitiers Hospital. The potential for improving the patients' quality of life and medical-economic concerns motivated this choice for these highly selected patients. In this paper, we propose brief clinical case reports and discuss the reasons for choosing this new rechargeable system, even though it was initially more expensive than the standard neurostimulation system (Itrel 3). All patients receiving implants declared that they were very satisfied with the quality of stimulation provided by Restore and noted a significant improvement in their quality of life. If this solution becomes advantageous from an economic point of view, clinical data should lend support to the utility of this technological innovation for patients who have hitherto been in treatment failure.

Prognostic molecular markers with no impact on decision-making: the paradox of gliomas based on a prospective study.

This study assessed the prognostic value of several markers involved in gliomagenesis, and compared it with that of other clinical and imaging markers already used. Four-hundred and sixteen adult patients with newly diagnosed glioma were included over a 3-year period and tumour suppressor genes, oncogenes, MGMT and hTERT expressions, losses of heterozygosity, as well as relevant clinical and imaging information were recorded. This prospective study was based on all adult gliomas. Analyses were performed on patient groups selected according to World Health Organization histoprognostic criteria and on the entire cohort. The endpoint was overall survival, estimated by the Kaplan-Meier method. Univariate analysis was followed by multivariate analysis according to a Cox model. p14(ARF), p16(INK4A) and PTEN expressions, and 10p 10q23, 10q26 and 13q LOH for the entire cohort, hTERT expression for high-grade tumours, EGFR for glioblastomas, 10q26 LOH for grade III tumours and anaplastic oligodendrogliomas were found to be correlated with overall survival on univariate analysis and age and grade on multivariate analysis only. This study confirms the prognostic value of several markers. However, the scattering of the values explained by tumour heterogeneity prevents their use in individual decision-making.

High-amylose sodium carboxymethyl starch matrices for oral, sustained drug-release: formulation aspects and in vitro drug-release evaluation.

High-amylose sodium carboxymethyl starch (HASCA), produced by spray-drying (SD), was previously shown to have interesting properties as a promising pharmaceutical sustained drug-release tablet excipient for direct compression, including ease of manufacture and high crushing strength. This study describes the effects of some important formulation parameters, such as compression force (CF), tablet weight (TW), drug-loading and electrolyte particle size, on acetaminophen-release performances from sustained drug-release matrix tablets based on HASCA. An interesting linear relationship between TW and release time was observed for a typical formulation of the system consisting of 40% (w/w) acetaminophen as model drug and 27.5% NaCl as model electrolyte dry-mixed with HASCA. Application of the Peppas and Sahlin model gave a better understanding of the mechanisms involved in drug-release from the HASCA matrix system, which is mainly controlled by surface gel layer formation. Indeed, augmenting TW increased the contribution of the diffusion mechanism. CFs ranging from 1 to 2.5 tonnes/cm(2) had no significant influence on the release properties of tablets weighing 400 or 600 mg. NaCl particle size did not affect the acetaminophen-release profile. Finally, these results prove that the new SD process developed for HASCA manufacture is suitable for obtaining similar-quality HASCA in terms of release and compression performances.

A randomized controlled study assessing outcome, cognition, autonomy and quality of life in over 70-year-old patients after aneurysmal subarachnoid hemorrhage.

BACKGROUND: Current aging of the population with good physiological status and the increasing incidence of subarachnoid hemorrhage (SAH) in elderly patients has enhanced the benefit of treatment in terms of independence and long-term quality of life (QoL). METHODS: From November 1, 2008 to October 30, 2012, 351 patients aged 70 years or older with aneurysmal SAH underwent adapted treatment: endovascular coiling (EV) for 228 (65%) patients, microsurgical clipping (MS) for 75 (29.3%) or conservative treatment for 48 (13.7%). Forty-one of these were randomized to EV (n=20) or to MS (n=21). The objectives were to determine the proportion of patients with modified Rankin Scale score≤2 (independence) at 1 year, and, secondarily, to compare cognitive function on the Mini-Mental State Examination (MMSE), autonomy on the Activities of Daily Living Index (ADLI) and Instrumental Activities of Daily Living scale (IADL), and QoL, in the prospective and randomized arms, at 1 year. RESULTS: At 1 year, with 1 loss to follow-up in the EV arm, 11 patients (55%) were independent after EV occlusion and 8 (38.1%) after MS exclusion, without significant difference (P=0.29). Mortality was higher after MS during the first 2 postoperative months, and thereafter the difference between MS and EV ceased to be significant. Cognitive function and autonomy scores were similar in both arms. CONCLUSION: In elderly patients treated for aneurysmal SAH, approximately 50% were independent at 1 year, with conserved cognition and autonomy. EV and MS are valid procedures in this population, with similar results at 1 year in terms of independence, cognition, autonomy, and QoL.

High-amylose carboxymethyl starch matrices for oral sustained drug-release: in vitro and in vivo evaluation.

High-amylose corn starch, that contains 70% of amylose chains and 30% of amylopectin, has been used to obtain substituted amylose (SA) polymers. Tablets have been prepared by direct compression, i.e. dry mixing of drug and SA, followed by compression, which is the easiest way to manufacture an oral dosage form. Until now, their controlled-release properties have been assessed only by an in vitro dissolution test. Amylose-based polymers are normally subject to biodegradation by alpha-amylase enzymes present in the gastrointestinal tract, but matrix systems show no significant degradation of tablets by alpha-amylase in vitro. High-amylose sodium carboxymethyl starch (HASCA) is an interesting excipient for sustained drug-release in solid oral dosage forms. In addition to the easy manufacture of tablets by direct compression, the results show that in vitro drug-release from an optimized HASCA formulation is not affected by either acidic pH value or acidic medium residence time. In addition, a compressed blend of HASCA with an optimized quantity of sodium chloride provides a pharmaceutical sustained-release tablet with improved integrity for oral administration. In vivo studies demonstrate extended drug absorption, showing that the matrix tablets do not disintegrate immediately. Nevertheless, acetaminophen does not seem to be the most appropriate drug for this type of formulation.

Diagnostic strategy for growth hormone deficiency: relevance of IGF-1 determination as a screening test.

BACKGROUND: Adult growth hormone (GH) deficiency must be diagnosed before prescribing therapeutic recombinant human GH. We studied the clinical relevance of a diagnostic strategy for growth hormone deficiency (GHD) using IGF-1 determination as a first step. METHODS: In 2000 and 2001, we tested 142 adult patients with hypothalamo-pituitary disorders for somatotropic function using Insulin Tolerance Test (ITT), the reference test for the diagnosis of GHD, with concomitant Insulin-like growth factor-1 (IGF-1) determination, a marker of somatotropic function. Patients were classified as GHD (peak GH concentration<3 ng/ml with the ITT) or normal. SETTING: Monocenter prospective study in a tertiary referral center. RESULTS: GHD was diagnosed in 61 subjects. Using a ROC curve, a threshold IGF-1 concentration of 175 ng/ml yielded a negative predictive value of 89+/-5%. A diagnostic strategy with IGF-1 determination as the first step followed by ITT for patients with an IGF-1 concentration below 175 ng/ml missed five of the 61 GHD patients, avoided 46/142 ITT and reduced the cost of diagnosis by 15%. CONCLUSION: We propose the use of a strategy consisting of IGF-1 determination followed, if below 175 ng/ml by confirmatory ITT to diagnose GHD in adults.

Operating environment for awake brain surgery - Choice of tests.

INTRODUCTION: The indication for awake brain surgery depends on a prerequisite, i.e. recognition that the brain area concerned is truly eloquent, and identification of one or more functions that must be preserved. These functions are determined preoperatively in collaboration with the patient, and neuropsychological tests considered to be the most relevant are performed in the operating room according to each team's technical preferences. OPERATING ENVIRONMENT: The neurosurgeon must choose transfer equipment considered to be relevant. Although a minimal technological environment is an option, a surgical team with great human wealth is essential, composed of specialized personnel with complementary skills. CHOICE AND IMPLEMENTATION OF INTRAOPERATIVE TESTS: The choice of intraoperative tests, which can be relatively simple for certain primary functions, can be much more difficult for high-level cognitive functions. No consensus has been reached concerning these tests, which must therefore be selected on an individual basis. Intraoperative testing must be based on preoperative multidisciplinary decisions made jointly by the neurosurgeon, neurologist, speech therapist and neuropsychologist. CONCLUSIONS: Numerous operating tools and technology transfers are available for neurosurgical teams performing awake brain surgery but none - or very few - of them constitutes a mandatory prerequisite. In contrast, the transition from the concept of eloquent brain area to that of brain functions that must be preserved requires highly skilled multidisciplinary human resources. This goal will be more likely achieved in centers highly specialized in functional oncological neurosurgery.

[Emergency surgery of a large ruptured arteriovenous malformation previously treated by several embolization procedures]. / Intervention en urgence après rupture d'une malformation arterio-veineuse intracérébrale complexe embolisée à plusieurs reprises.

A 56-year-old patient with a giant parieto-occipital left-sided arteriovenous malformation (AVM) revealed by seizure was treated by four embolization procedures. Stereotactic radiosurgery was scheduled for the residual nidus but significant intracranial hemorrhage occurred and surgical excision had to be performed. The immediate post-operative status was precarious, but the final outcome was successful. Therapeutic indications are discussed. A multidisciplinary approach for judicious patient selection is surely the key to safe overall management of AVMs.

[Gene MGMT and oligodendrogliomas. Fundamental data and short review of the literature]. / Gène MGMT et oligodendrogliomes. Données fondamentales et brève revue de la littérature.

MGMT (O6 methyl guanine methyl transferase) is a gene involved in DNA repair. Its mechanism of action is to remove alkyl groups created by alkylating chemotherapy and therefore induces chemoresistances. Recent studies show that this gene expression seems to be related to the promoter's methylation, which could predict a possible chemosensitivity. The study of MGMT could be of some therapeutic and prognostic interest. Few series of oligodendrogliomas have been published and their results appear to be controversial. This is probably due to both tumour heterogeneity and multiple parameters associated with chemosensitivity. To date, it thus appears difficult to choose the adjuvant treatment according to the sole status of MGMT.

Epidemiology, genetic, natural history and clinical presentation of giant cerebral aneurysms.

Giant cerebral aneurysms represent 5% of intracranial aneurysms, and become symptomatic between 40 and 70 years with a female predominance. In the paediatric population, the giant aneurysm rate is higher than in the adult population. Classified as saccular, fusiform and serpentine, the natural history of giant cerebral aneurysms is characterized by thrombosis, growth and rupture. The pathogenesis of these giant aneurysms is influenced by a number of risk factors, including genetic variables. Genome-wide association studies have identified some chromosomes highlighting candidate genes. Although these giant aneurysms can occur at the same locations as their smaller counterparts, a predilection for the cavernous location has been observed. Giant aneurysms present with symptoms caused by a mass effect depending on their location or by rupture; ischemic manifestations rarely reveal the aneurysm. If the initial clinical descriptions have been back up by imagery, the clinical context with a pertinent analysis of the risk factors remain the cornerstone for the management decisions of these lesions. Five year cumulative rupture rates for patients with giant aneurysm were 40% for those located on the anterior part of circle of Willis and 50% for those on the posterior part. The poor outcome of untreated patients justifies the therapeutic risks.

A novel, objective, quantitative method of evaluation of the back pain component using comparative computerized multi-parametric tactile mapping before/after spinal cord stimulation and database analysis: the "Neuro-Pain't" software.

INTRODUCTION: One of the major challenges of neurostimulation is actually to address the back pain component in patients suffering from refractory chronic back and leg pain. Facing a tremendous expansion of neurostimulation techniques and available devices, implanters and patients can still remain confused as they need to select the right tool for the right indication. To be able to evaluate and compare objectively patient outcomes, depending on therapeutical strategies, it appears essential to develop a rational and quantitative approach to pain assessment for those who undergo neurostimulation implantation. OBJECTIVES, MATERIAL AND METHODS: We developed a touch screen interface, in Poitiers University Hospital and N(3)Lab, called the "Neuro-Pain'T", to detect, record and quantify the painful area surface and intensity changes in an implanted patient within time. The second aim of this software is to analyse the link between a paraesthesia coverage generated by a type of neurostimulation and a potential analgesic effect, measured by pain surface reduction, pain intensity reduction within the painful surface and local change in pain characteristics distribution. The third aim of Neuro-Pain'T is to correlate these clinical parameters to global patient data and functional outcome analysis, via a network database (Neuro-Database), to be able to provide a concise but objective approach of the neurostimulation efficacy, summarized by an index called "RFG Index". RESULTS AND DISCUSSION: This software has been used in more than 190 patients since 2012, leading us to define three clinical parameters grouped as a clinical component of the RFG Index, which might be helpful to assess neurostimulation efficacy and compare implanted devices. CONCLUSION: The Neuro-Pain'T is an original software designed to objectively and quantitatively characterize reduction of a painful area in a given individual, in terms of intensity, surface and pain typology, in response to a treatment strategy or implantation of an analgesic device. Because pain is a physical sensation, which integrates a psychological dimension, its assessment justifies the use of multidimensional and global evaluation scales. However, in the context of neurostimulation and comparative clinical trials designed to test the technical efficacy of a given device, a simple, objective and quantitative evaluation tool could help to guide tomorrow's treatment options by transforming personal convictions into a more robust scientific rationale based on data collection and data mining techniques.