Between-centre differences in care for in-hospital cardiac arrest: a prospective cohort study.

BACKGROUND: Survival after in-hospital cardiac arrest is poor, but current literature shows substantial heterogeneity in reported survival rates. This study aims to evaluate care for patients suffering in-hospital cardiac arrest (IHCA) in the Netherlands by assessing between-hospital heterogeneity in outcomes and to explain this heterogeneity stemming from differences in case-mix or differences in quality of care. METHODS: A prospective multicentre study was conducted comprising 14 centres. All IHCA patients were included. The adjusted variation in structure and process indicators of quality of care and outcomes (in-hospital mortality and cerebral performance category [CPC] scale) was assessed with mixed effects regression with centre as random intercept. Variation was quantified using the median odds ratio (MOR), representing the expected odds ratio for poor outcome between two randomly picked centres. RESULTS: After excluding centres with less than 10 inclusions (2 centres), 701 patients were included of whom, 218 (32%) survived to hospital discharge. The unadjusted and case-mix adjusted MOR for mortality was 1.19 and 1.05, respectively. The unadjusted and adjusted MOR for CPC score was 1.24 and 1.19, respectively. In hospitals where personnel received cardiopulmonary resuscitation (CPR) training twice per year, 183 (64.7%) versus 290 (71.4%) patients died or were in a vegetative state, and 59 (20.8%) versus 68 (16.7%) patients showed full recovery (p < 0.001). CONCLUSION: In the Netherlands, survival after IHCA is relatively high and between-centre differences in outcomes are small. The existing differences in survival are mainly attributable to differences in case-mix. Variation in neurological outcome is less attributable to case-mix.

Minocycline added to subcutaneous interferon ß-1a in multiple sclerosis: randomized RECYCLINE study.

BACKGROUND AND PURPOSE: Combining different therapies may improve disease control in patients with relapsing-remitting multiple sclerosis (RRMS). This study assessed the efficacy and safety of minocycline added to subcutaneous (sc) interferon (IFN) ß-1a therapy. METHODS: This was a double-blind, randomized, placebo-controlled multicentre study. Within 3 months (±1 month) of starting sc IFN ß-1a 44 µg three times weekly, patients with RRMS were randomized to minocycline 100 mg twice daily or placebo, added to sc IFN ß-1a, for 96 weeks. The primary efficacy endpoint was the time to first qualifying relapse. Secondary efficacy endpoints were the annualized relapse rate for qualifying relapses, the number of new/enlarging T2-weighted lesions and change in brain volume [magnetic resonance imaging (MRI) was performed only in a few selected centres]. In addition, a number of tertiary efficacy endpoints were assessed. RESULTS: One hundred and forty-nine patients received minocycline and 155 received placebo; MRI data were available for 23 and 27 patients, respectively. The time to first qualifying relapse did not differ significantly for minocycline versus placebo (hazard ratio 0.85; 95% confidence interval 0.53, 1.35; log-rank = 0.50; P = 0.48). There were no statistically significant differences between the two groups on other efficacy endpoints, although some numerical trends in favour of minocycline were observed. No unexpected adverse events were reported, but more patients discontinued because of adverse events with minocycline versus placebo. CONCLUSION: Minocycline showed no statistically significant beneficial effect when added to sc IFN ß-1a therapy.

[New treatment options in multiple sclerosis and their complications]. / Traitement de tla sclérose en plaques: nouveautés et complications.

A new therapeutic era opened for multiple sclerosis (MS) with the appearance of molecules given p.o. and/or molecules with greater efficiency. Early diagnosis is critical, as the time and the choice of therapeutic intervention. The initiation of treatments must be personalized, including the risks associated with MS and those potentially related to the treatment chosen, answering the question >. Monitoring tools that allow to objectively evaluate: I) MS activity and aggressiveness for each patient and 2) the safety of treatments and their risks of complications, must be further investigated.

[2012: news in neurology]. / Neurologie.

In 2012, intramuscular midazolam appears as effective as intravenous lorezepam for the first line treatment of convulsive status epilepticus. Perampanel, a new anti-epileptic drug, will be soon available. Two oral treatments are now available for stroke prevention in atrial fibrillation setting. The methylphenidate and the Tai Chi could increase the walk capacity of patients suffering from Parkinson disease. A comprehensive cardiac work-up is essential for some congenital myopathy. A new drug against migraine seems free from vasoconstrictive effect. Antioxidants are harmful in Alzheimer disease. Some oral medication will be available for multiple sclerosis.

[Neurology]. / Neurologie.

In 2011, new oral anticoagulants for atrial fibrillation are available and the ABCD3-I score predicting stroke after TIA updates the ABCD2 score. New McDonald criteria allow faster MS diagnosis and the first oral treatment (fingolimod) for MS can be prescribed. A new anti-antiepileptic drug (retigabine) is available and sodium valproate has long term neurological adverse effects after in utero exposure. Among Parkinson disease treatments, deep brain stimulation is extending applications and dopamine agonists with extended release are as efficient and well tolerated as standard forms at long term scale. Monoclonal antibodies and immunosuppressant agents are proposed as good alternatives in the treatment of chronic dysimmune polyneuropathies. Gene therapy for the treatment of genetic myopathies is progressing.

In-depth assessment of health-related quality of life after in-hospital cardiac arrest.

INTRODUCTION: Evidence on physical and psychological well-being of in-hospital cardiac arrest (IHCA) survivors is scarce. The aim of this study is to describe long-term health-related quality of life (HRQoL), functional independence and psychological distress 3 and 12 months post-IHCA. METHODS: A multicenter prospective cohort study in 25 hospitals between January 2017 - May 2018. Adult IHCA survivors were included. HRQoL (EQ-5D-5L, SF-12), psychological distress (HADS, CSI) and functional independence (mRS) were assessed at 3 and 12 months post-IHCA. RESULTS: At 3-month follow-up 136 of 212 survivors responded to the questionnaire and at 12 months 110 of 198 responded. The median (IQR) EQ-utility Index score was 0.77 (0.65-0.87) at 3 months and 0.81 (0.70-0.91) at 12 months. At 3 months, patients reported a median SF-12 (IQR) physical component scale (PCS) of 38.9 (32.8-46.5) and mental component scale (MCS) of 43.5 (34.0-39.7) and at 12 months a PCS of 43.1 (34.6-52.3) and MCS 46.9 (38.5-54.5). DISCUSSION: Using various tools most IHCA survivors report an acceptable HRQoL and a substantial part experiences lower HRQoL compared to population norms. Our data suggest that younger (male) patients and those with poor functional status prior to admission are at highest risk of impaired HRQoL.

Intrathecal delivery of CNTF using encapsulated genetically modified xenogeneic cells in amyotrophic lateral sclerosis patients.

Neuronal growth factors hold promise for providing therapeutic benefits in various neurological disorders. As a means of ensuring adequate central nervous system delivery of growth factors and minimizing significant adverse side effects associated with systemic delivery methods, we have developed an ex vivo gene therapy approach for protein delivery using encapsulated genetically modified xenogeneic cells. Ciliary neurotrophic factor (CNTF) has been shown in various rodent models to reduce the motor neuron cell death similar to that seen in amyotrophic lateral sclerosis (ALS). The initial trials focusing on the systemic administration of CNTF for ALS have been discontinued as a result of major side effects, thus preventing determination of the potential efficacy of the molecule. In order to deliver CNTF directly to the nervous system, we conducted a phase I study in which six ALS patients were implanted with polymer capsules containing genetically engineered baby hamster kidney cells releasing approximately 0.5 microgram of human CNTF per day in vitro. The CNTF-releasing implants were surgically placed within the lumbar intrathecal space. Nanogram levels of CNTF were measured within the patients' cerebrospinal fluid (CSF) for at least 17 weeks post-transplantation, whereas it was undetectable before implantation. Intrathecal delivery of CNTF was not associated with the limiting side effects observed with systemic delivery. These results demonstrate that neurotrophic factors can be continuously delivered within the CSF of humans by an ex vivo gene therapy approach, opening new avenues for the treatment of neurological diseases.

[Therapeutic advances in neurology]. / Neurologie.

This article summarizes the main therapeutic advances of 2010 in the field of neurology. It focuses on aspects that are likely to change the care of patients in clinical practice. Among these, we discuss the new oral treatments that have proved to be effective in multiple sclerosis, the results of two large studies comparing endarterectomy and stenting in carotid stenosis, novel therapeutic approaches for the treatment of non-motor symptoms in Parkinson's disease as well as the results of several pharmacological studies in the field of epilepsy.

A cross-sectional investigation of communication in Do-Not-Resuscitate orders in Dutch hospitals.

BACKGROUND: The decision to attempt or refrain from resuscitation is preferably based on prognostic factors for outcome and subsequently communicated with patients. Both patients and physicians consider good communication important, however little is known about patient involvement in and understanding of cardiopulmonary resuscitation (CPR) directives. AIM: To determine the prevalence of Do Not Resuscitate (DNR)-orders, to describe recollection of CPR-directive conversations and factors associated with patient recollection and understanding. METHODS: This was a two-week nationwide multicentre cross-sectional observational study using a study-specific survey. The study population consisted of patients admitted to non-monitored wards in 13 hospitals. Data were collected from the electronic medical record (EMR) concerning CPR-directive, comorbidity and at-home medication. Patients reported their perception and expectations about CPR-counselling through a questionnaire. RESULTS: A total of 1136 patients completed the questionnaire. Patients' CPR-directives were documented in the EMR as follows: 63.7% full code, 27.5% DNR and in 8.8% no directive was documented. DNR was most often documented for patients >80 years (66.4%) and in patients using >10 medications (45.3%). Overall, 55.8% of patients recalled having had a conversation about their CPR-directive and 48.1% patients reported the same CPR-directive as the EMR. Most patients had a good experience with the CPR-directive conversation in general (66.1%), as well as its timing (84%) and location (94%) specifically. CONCLUSIONS: The average DNR-prevalence is 27.5%. Correct understanding of their CPR-directive is lowest in patients aged ≥80 years and multimorbid patients. CPR-directive counselling should focus more on patient involvement and their correct understanding.

[Neurobehavioral changes occurring during multiple sclerosis]. / Modifications neurocomportementales secondaires à la sclérose en plaques.

Behavioral changes occurring in patients affected by multiple sclerosis (MSI are often neglected by physicians but are actually part of the clinical spectrum of the disease. In addition, they are known to be responsible for a decline in the quality of life of MS patients. Recently, there has been a growing interest to investigate changes in the emotional experience of MS patients and their decision making, showing that the ability to take advantageous decisions was altered in MS. This paper reviews existing data on this topic.

[Therapeutic advances in neurology]. / Neurologie.

The neurology field has been greatly improved in 2008. The therapeutic window of intravenous thrombolysis for acute ischemic stoke is extended to 4 h 30. New studies show that the clinical progression of Parkinson's disease might be slowed by some medication. Deep brain stimulation may be beneficial early in the course of the disease. Tysabri and Fingolimod in multiple sclerosis are discussed. The pharmacopoeia for epilepsy is in constant development with new products recently released in Switzerland. CGRP receptor antagonists are about to be launched as a promising acute migraine treatment. The pharmacological approach in amyotrophic lateral sclerosis patients might be improved according to research results.

Preserved decision making ability in early multiple sclerosis.

BACKGROUND: The purpose of this study was to assess decision making in patients with multiple sclerosis (MS) at the earliest clinically detectable time point of the disease. METHODS: Patients with definite MS (n = 109) or with clinically isolated syndrome (CIS, n = 56), a disease duration of 3 months to 5 years, and no or only minor neurological impairment (Expanded Disability Status Scale [EDSS] score 0-2.5) were compared to 50 healthy controls using the Iowa Gambling Task (IGT). RESULTS: The performance of definite MS, CIS patients, and controls was comparable for the two main outcomes of the IGT (learning index: p = 0.7; total score: p = 0.6). The IGT learning index was influenced by the educational level and the co-occurrence of minor depression. CIS and MS patients developing a relapse during an observation period of 15 months dated from IGT testing demonstrated a lower learning index in the IGT than patients who had no exacerbation (p = 0.02). When controlling for age, gender and education, the difference between relapsing and non-relapsing patients was at the limit of significance (p = 0.06). CONCLUSION: Decision making in a task mimicking real life decisions is generally preserved in early MS patients as compared to controls. A possible consequence of MS relapsing activity in the impairment of decision making ability is also suspected in the early phase of MS.

[Fatigue in neurological disease: different patterns in stroke and multiple sclerosis]. / Dimensions multiples de la fatigue d'origine neurologique: différences entre l'accident vasculaire cérébral et la sclérose en plaques.

INTRODUCTION: Fatigue is a complex, subjective experience, frequent in multiple sclerosis (MS) and stroke patients. The tiredness these patients experience can take on many features depending not only on the cerebral location of the lesions and mood aspects, but also on the pathophysiology of the disease. Thus, it is reasonable to expect that fatigue may have different implications in MS and stroke. The aim of the present work was to compare fatigue syndrome in these two populations. Patients were matched for handicap. MATERIALS AND METHODS: Seventy-nine stroke and 39 MS outpatients were included with the following inclusion criteria: i) patients with possible or relapsing-remitting MS with an Expanded Disability Status Scale (EDSS) score<2.5, disease duration<6 years, and stable medical condition for at least 6 weeks; ii) stroke patients with mild neurological impairment, i.e. scoring<3 at the National Institute of Health Stroke Scale (NIHSS) one year after stroke; iii) absence of functional impairment (Barthel index=100) and similar negligible handicap (Rankin scale<2 for both groups); no or mild cognitive deficit; iv) neither DSMIV criteria of depression, nor significant anxious/depressive symptoms (Hospital Anxiety and Depression scale; HAD; score<8) in both groups. The Fatigue Assessing Instrument (FAI) was used to assess fatigue. RESULTS: Twenty-nine percent of stroke and 46 p. cent of MS patients had a significant score on the FAI (p<0.05). Multiple regression analysis using groups, gender and age as factors showed a group effect in 3 out of 4 subscales: MS patients scored higher than stroke patients mainly for psychic impact (4.86 vs. 3.28), but also for severity (mean 3.86 vs. 2.97) and specificity (4.36 vs. 3.32). Response to rest (5.36 vs. 6.06) only tended to be better in the stroke group. In the subpopulation with significant fatigue scores, psychic impact was more elevated in the MS group. The functional consequence of fatigue in physical, professional and social activities were similar. DISCUSSION: Fatigue was more severe in MS than stroke patients, independently of disability. The most significant factor in the MS group was the psychic impact, reflecting impaired motivation, concentration and irritability, despite the absence of depression. However, subjective consequences of fatigue on work, family and leisure activities were comparable in both groups.

[Neurology]. / Neurologie.

Neurology is a polymorphic discipline, with several subspecialties. In 2006, as in the previous years, a huge amount of scientific work focusing on treatment has been published. However, there has not been a true revolution in any of the current therapeutic strategies; rather, we experienced an improvement in the knowledge about several specific "details". This allows to consider more and more variables when administering a specific treatment, therefore, in each subspecialty a move towards a better patient's care has been made. In this contribution, several specialists analyse and interpret new facts about their respective neurological domain.

[Immunity and neurodegeneration: new concepts in multiple sclerosis]. / Immunité et neurodégénérescence: nouveaux concepts dans la sclérose en plaques.

Multiple sclerosis is an autoimmune demyelinating disease of the central nervous system that leads to a progressive deterioration of the neurological functions. The concept of primary myelin and oligodendrocyte damage with axon sparing (axon-myelin dissociation) has been recently reconsidered with the demonstration that neuro-axonal lesions are an early phenomenon, linked to the inflammatory process, observed outside demyelinated areas, and correlated with the progression of the disease. Neurodegeneration in MS, long considered as a late process following recurrent episodes of demyelination, is now accepted as an early and major trigger of MS pathogenesis on which research should focus in the

[Immunomodulatory/suppressive treatments in neurology]. / Traitements immunomodulateurs/ suppresseurs en neurologie.

Immunomodulatory/suppressive treatments are frequently used in neurological disorders affecting the central and peripheral nervous system. Demyelinating disorders are a good example of a wide application of the various types of existing therapies. Although these therapies are still mostly not disease specific, their combination with more targeted molecules appears most relevant for diseases with multiple pathogenic mechanisms.

Gene therapy for amyotrophic lateral sclerosis (ALS) using a polymer encapsulated xenogenic cell line engineered to secrete hCNTF.

The gene therapy approach presented in this protocol employs a polymer encapsulated, xenogenic, transfected cell line to release human ciliary neurotrophic factor (hCNTF) for the treatment of Amyotrophic Lateral Sclerosis (ALS). A tethered device, containing around 10(6) genetically modified cells surrounded by a semipermeable membrane, is implanted intrathecally; it provides for slow continuous release of hCNTF at a rate of 0.25 to 1.0 micrograms/24 hours. The semipermeable membrane prevents immunologic rejection of the cells and interposes a physical, virally impermeable barrier between cells and host. Moreover, the device and the cells it contains may be retrieved in the event of side effects. A vector containing the human CNTF gene was transfected into a line of baby hamster kidney cells (BHK) with calcium phosphate using a dihydrofolate reductase-based selection vector with a SV40 promoter and contains a HSV-tk killer gene. hCNTF is a potent neurotrophic factor which may have utility for the treatment of ALS. Systemic delivery of hCNTF in humans has been frustrated by peripheral side effects, the molecule's short half life, and its inability to cross the blood-brain barrier. The gene therapy approach described in this protocol is expected to mitigate such difficulties by local intrathecal delivery of a known quantity of continuously-synthesized hCNTF from a retrievable implant.

Immunostaining of motor nerve terminals by IgM M protein with activity against gangliosides GM1 and GD1b from a patient with motor neuron disease.

We demonstrated the binding of an IgM monoclonal protein, obtained from a patient with motor neuron disease, with known antibody activity against gangliosides GM1, GD1b, and asialo GM1, to neuromuscular junctions in guinea pig gastrocnemius muscle, using an indirect immunofluorescence technique. Staining disappeared after delipidation of muscle sections. Denervated muscle sections showed no labeling at the neuromuscular junction after incubation with the patient's serum. This indicates presynaptic binding of the IgM M protein and supports the concept that IgM monoclonal antibody to nerve terminal determinants may underlie a motor neuron disorder.

Monoclonal antibodies that distinguish between normal and denervated human acetylcholine receptor.

Ten monoclonal anti-human acetylcholine receptor (AChR) monoclonal antibodies (m.abs) all exhibited high avidity binding to the human AChR. None was able to inhibit alpha-bungarotoxin (alpha-Butx) binding to the receptor. Five distinct but partially overlapping antibody-binding regions were defined by competition experiments. Four antibodies, which competed with each other for one region on denervated human AChR and also bound to human fetal AChR, failed to bind appreciably to normal human AChR in solution, to normal AChR solubilized from 6 other species, or to human endplates in frozen sections.

Antibody heterogeneity and specificity in myasthenia gravis.

Anti-AChR is heterogeneous within individuals and between individuals. Anti-AChR idiotypes are not shared to any large extent. Ten monoclonal antibodies raised against human AChR: (a) bind to five partially overlapping regions; (b) are not idiotypically identical even within a region; (c) do not all bind to the main immunogenic region; (d) four distinguish between normal and denervated human AChR; (e) can be used to define the antigenic determinants in MG. Antigenic specificities vary in different clinical groups. Antigenic specificities can change during the course of the disease, but some remain relatively constant. Thymus cultures make antibodies with the same specificity as those present in the serum of the individual. All monoclonal antibodies bind to myoid cells of normal and MG thymus. We find no convincing evidence of naturally occurring antiidiotype antibodies in MG sera.