bluuebunny/crossref_metadata_2025 huggingface dataset:
An introduction to the European Terrestrial Ecosystem Modelling Activity
Authors: Sykes Martin T. , Prentice I. Colin , Smith Benjamin , Cramer Wolfgang , Venevsky Sergey
Published: March 2003

The objective of the European Terrestrial Ecosystem Modelling Activity (ETEMA) was to address some of the major challenges in developing generalized models to examine responses of natural and seminatural ecosystems to environmental change at the regional to European scale. The approach described herein was to break down the totality of ecosystem functioning into its key components, each with its characteristic spatial and temporal scales. A conceptual framework was developed describing the configuration of these components as modules within a generalized simulation model. The framework describes the key inputs, outputs and state variables, their spatial and temporal contexts, and information flows between modules. The ‘backbone’ of the model is a system of nested timing loops corresponding to the disparate time scales at which different ecosystem processes occur. The framework is a theoretical construct into which ecosystem models at levels of complexity ranging from the very general to the highly detailed can be mapped, and thus provides a guide for development of models for novel, particularly regional‐scale, applications. A number of subsystem studies of the major components of ecosystem functioning, i.e. modules of the conceptual framework, are briefly introduced herein. The general aim of the subsystem studies was to identify the key alternative formulations (as opposed to minor variants) and test these against observational data. The various subsystem studies concern planetary boundary layer–ecosystem interactions, ecosystem CO2 and H2O fluxes, vegetation physiology and phenology, biogeography and vegetation dynamics, detritus and SOM dynamics, soil moisture and human and natural disturbances and, as individual papers, they complete this special ETEMA issue.
Geographical distributions of spiny pocket mice in South America: insights from predictive models
Authors: Anderson Robert P. , Gómez‐Laverde Marcela , Peterson A. Townsend
Published: March 2003

Aim Predictive models of species’ distributions use occurrence records and environmental data to produce a model of the species’ requirements and a map of its potential distribution. To determine regions of suitable environmental conditions and assess biogeographical questions regarding their ranges, we modelled the potential geographical distributions of two spiny pocket mice (Rodentia: Heteromyidae) in north‐western South America.

Location North‐western South America.

Methods We used the Genetic Algorithm for Rule‐Set Prediction (GARP), environmental data from GIS maps and georeferenced collection localities from a recent systematic review of Heteromys australis and H. anomalus to produce the models.

Results GARP models indicate the potential presence of H. australis throughout mesic montane regions of north‐western South America, as well as in some lowland regions of moderately high precipitation. In contrast, H. anomalus is predicted to occur primarily in drier areas of the Caribbean coast and rain‐shadowed valleys of the Andes.

Conclusions The models support the disjunct status of the population of H. australis in the Cordillera de Mérida, but predict a continuous distribution between known populations of H. anomalus in the upper Magdalena Valley and the Caribbean coast. Regions of suitable environmental conditions exist disjunct from known distributional areas for both species, suggesting possible historical restrictions to their ranges. This technique holds wide application to other study systems.
Are Alaskan trees found in locally more favourable sites in marginal areas?
Authors: Lennon Jack J. , Kunin William E. , Corne Simon , Carver Steve , Van Hees Willem W. S.
Published: March 2003

Aim Species generally become rarer and more patchily distributed as the margins of their ranges are approached. We predicted that in such marginal sites, tree species would tend to occur where some key environmental factors are at particularly favourable levels, compensating in part for the low overall suitability of marginal sites.

Location The article considers the spatial distributions of trees in Southeast Alaska (the Alaskan ‘panhandle’).

Methods We quantified range marginality using spatial distributions of eight tree species across more than one thousand surveyed sites in Southeast Alaska. For each species we derived a site core/margin index using a three‐dimensional trend surface generated from logistic regression on site coordinates. For each species, the relationships between the environmental factors slope, aspect and site marginality were then compared for occupied and unoccupied sets of sites.

Results We found that site slope is important for more Alaskan tree species than aspect. Three out of eight had a significant core/margin by occupied/unoccupied interaction, tending to be present in significantly shallower‐sloped (more favourable) sites in the marginal areas than the simple core/margin trend predicted. For site aspect, one species had a significant interaction, selecting potentially more favourable northerly aspects in marginal areas. A finer‐scale analysis based on the same data came to the same overall conclusions.

Conclusions There is evidence that several tree species in Alaska tend to occur in especially favourable sites in marginal areas. In these marginal areas, these species amplify habitat preferences shown in core areas.
Interspecific abundance–occupancy relationships of British mammals and birds: is it possible to explain the residual variation?
Authors: Holt Alison R. , Gaston Kevin J.
Published: March 2003

AimThe majority of studies concerning positive interspecific abundance–occupancy relationships have used broad‐scale and microcosm data to test the occurrence and correlates of the relationship to determine which of the proposed mechanisms give rise to it. It has been argued recently that studying the residual variation about abundance–occupancy relationships is a more logical analysis and may yield faster progress in identifying the relative roles of the mechanisms. However, to date this approach has been largely unsuccessful. Here we test if fundamental species traits such as the status (native and introduced), habitat and trophic group of mammal and bird species may explain any of the residual variation about their respective abundance–occupancy relationships.

LocationThe study used British mammal and bird species.

MethodsWe tested if species traits explained any of the variation about abundance–occupancy relationships using linear regression techniques both treating species as independent data points for analysis and controlling for phylogenetic association.

ResultsNone of the species traits could explain any residual variation about the positive interspecific abundance–occupancy relationships of British mammals and birds. This applied both when treating species as independent data points and after controlling for phylogenetic association.

ConclusionsGiven the lack of explanatory power of the species traits here and in other studies using this approach it seems that the variation about positive interspecific abundance–occupancy relationships is not explicable in a simple fashion. Predicting the likely influence of traits that are independent of phylogeny is also problematic. Therefore, the general utility of this approach and its future role in understanding the mechanisms causing positive interspecific abundance–occupancy relationships is doubtful.
Do placentation issues bias twin studies?
Authors: Phillips David
Published: March 2003

Because monozygous twins are almost genetically identical whereas dizygous twins are genetically no more similar than siblings, greater similarity between members of a monozygotic twin pair than between a dizygotic pair is usually taken as evidence that the condition or trait being studied has a genetic contribution. However, besides greater similarity of genes, monozygous pairs may share more similar environments than do dizygotic pairs. This environmental sharing may occur in fetal life where close placental relationships lead to more similar fetal environments. It may also occur postnatally. If the twins are of the same sex and look alike, the parents may dress, feed and in other ways treat the twins more similarly. Whereas the effects of a more similar postnatal environment have been explored by comparisons of twins raised together or separately, remarkably little is known about the influence of prenatal exposures.
Uses of twins in studying the genetics of complex traits
Authors: Spector Tim D. , MacGregor Alex J. , Snieder Harold
Published: March 2003

Twins provide a useful and powerful tool for identifying genes, by acting as ideally matched sib‐pairs, but are also uniquely placed to measure the extent of their action, their expression and the nature of their interaction with the environment. Classical twin studies have provided insight into the relative genetic and environmental contribution to characteristics and diseases in human populations. The search for a more detailed understanding of genetic mechanisms through linkage and association has, however, traditionally been regarded as the province of other family designs. The last few years have seen a resurgence of interest in twin research following an increasing awareness that the study of twins can also provide an important contribution to localizing and understanding the function of specific genes.1 In this brief overview, we focus on these newer developments that are currently being applied in the search to uncover the genetic basis of disease.
Fine‐scale mapping of disease loci
Authors: Whittaker J. C. , Morris A. P. , Balding D. J.
Published: March 2003

We review the issues involved in the fine‐scale mapping of disease loci via allelic association. We argue that it is vital to properly account for uncertainty about the genealogy of the disease locus and founding haplotypes at the surrounding markers: we sketch how this might be done in a Bayesian framework using Markov chain Monte Carlo tecniques, and show that this works well for the much analysed data on the location of the Δ508 mutation for cystic fibrosis.
The use of Mx for association and linkage analysis
Authors: Neale Michael C.
Published: March 2003

Evidence for genetic linkage, obtained from a correlation between phenotypic similarity and genetic similarity at a specific chromosomal location typically yields a broad genomic region in which a candidate locus might be found. Evidence for association is usually gathered from case control studies and is subject to false positives from phenomena such as population stratification. Data from relatives may be used to distinguish population stratification from genuine allelic effects in an association context. Of special interest is joint linkage and association which may be used for fine mapping because evidence for linkage will be reduced in the presence of evidence for association. This article describes the implementation of these methods using Mx, in both path diagram and script formats, and discusses a number of possible extensions to the model.
Challenges for genetic analysis in the 21st century: localizing and characterizing genes for common complex diseases and their quantitative risk factors
Authors: Almasy L. , Blangero J.
Published: March 2003

The optimal study design and method of analysis for genetic studies of complex traits have received much attention of late. Most previous works on this topic have assumed that investigators will study a single focal disease trait. In this paper, we approach the question of study design from the perspective of the inherently multivariate study which includes a variety of quantitative risk factors as well as one or more common complex disease traits. We conclude that a sample of randomly ascertained extended pedigrees provides both analytical power and flexibility, permitting profitable investigation of numerous traits using both linkage and linkage‐disequilibrium based methods.
A new approach to prioritizing marine fish and shellfish populations for conservation
Authors: Nielsen Einar Eg , Kenchington Ellen
Published: March 2003

There has been increasing awareness of the vulnerability of marine organisms to population extirpation and species extinction. While very few documented cases of species extinction exist in the marine environment, it is anticipated that managers will face the dilemma of prioritizing populations of marine fish and shellfish for protection in the near future. Current prioritization procedures have been developed from salmonid models with the intent of applying them to all marine organisms, and in some cases to freshwater and terrestrial taxa. In this review we provide evidence for the relevance of such a process for marine species and further suggest five broad categories of marine organisms that have distinctive traits influencing their genetic structure. The current prioritization models have been adapted to account for each of these species groups. Emphasis is placed on ‘Classical Marine Species’ which represent the opposite end of the continuum from the salmon model, displaying high within‐population genetic variance. From this category, three cod (Gadus morhua) stocks were selected to evaluate a revised scheme developed specifically for ‘Classical Marine Species’ that includes performance measures such as (i) reduction in number of spawning populations; (ii) reduction of Ne : Nc (ratio of effective to census population size); (iii) changes in life‐history traits; (iv) critical density for spawning success; and (v) patchy vs. continuous distribution pattern. When the salmonid scheme was applied, the cod examples were allocated low values, indicating that they were not under threat. However, when the revised scheme was applied, all three cod stocks were allocated high values, indicating that the revised scheme was more reflective of the particular life‐history traits of this category of organisms.
Co‐management without involvement: the plight of fishing communities
Authors: Schreiber Dorothee K
Published: March 2003

This paper discusses the role of fishing communities in the stewardship of their adjacent fish resources, and the benefits associated with community participation in co‐management. Contrary to the view of most fisheries management agencies, local communities are able to design institutions that can successfully restore equity and limit access to the fishery. The dismissal of local concerns may be at the root of biological and social crises in fisheries, and the privatization of common fishing rights world‐wide through individual transferable quotas (ITQs) is contributing to these problems. Community involvement that is embedded into a network of management at larger spatial scales would allow fishing communities to regain some control over their livelihoods. Meaningful co‐management arrangements must go beyond consultation by redirecting the flow of social and economic benefits from the fishery back into communities. Unless geographically defined communities are allowed to share power and responsibility with government fisheries managers, both fish stocks and fishing as a way of life are in danger of vanishing.
Petrarch’s Principle: how protected human‐made reefs can help the reconstruction of fisheries and marine ecosystems
Authors: Pitcher Tony J. , Seaman Jr William
Published: March 2003

Petrarch’s Principle, named here, is to know things unseen, yet to ignore things seen. We apply the principle to the debate over the appropriate role and utility of human‐made reefs (HMRs) in fishery and ecosystem management by reviewing four linked issues that were discussed at the recent 7th International Conference on Artificial Reefs and Related Aquatic Habitats. First, deploying protected HMRs can help to mitigate the depletion of fishery stocks through overharvest and habitat degradation. Secondly, to achieve this objective effectively, it is essential that HMRs are protected as no‐take areas, and that, thirdly, HMRs are large, well‐planned, evaluated and monitored. Finally, ecosystem modelling and adaptive management responses are necessary to forecast and manage the benefits of HMRs. Moreover, uncertainty about the resolution of the well‐rehearsed attraction/production debate may be resolved by ensuring that HMRs are managed as protected no‐take areas. And to ensure an unbiased attitude that will aid the clarification of consequences, costs and benefits, we propose a change in terminology, from artificial reefs to human‐made reefs.
An introduction to species concepts and speciation of fishes
Authors: Ruffing Renea A , Kocovsky Patrick M , Stauffer Jay R
Published: March 2003

More than 22 different species concepts have been proposed. The concepts in general reflect the philosophical outlook, particular expertise, and the groups on which the authors are working. The full‐length papers in this special issue dedicated to species concepts relative to fishes are based on presentations by the authors at the 2001 annual meeting of the American Society of Ichthyologists and Herpetologists at University Park, Pennsylvania, USA and generated much discussion on the topic of what constitutes a species.
Long‐term effect of a single dose of flunarizine in Huntington's disease
Authors: Belfiore G. , Di Maiob L. , Napolitano G. , Cella S. , Filla A. , De Michele G. , Campanella G.
Published: March 2003

We report a preliminary pilot study on the clinical efficacy of flunarizine (FNZ), a calcium‐entry blocker that causes extrapyramidal side‐effects, in 10 patients with Huntington's disease (HD). FNZ (20 mg) administered by the sublingual route resulted in a decrease in choreic movements and improved dexterity in performing several tests. These effects lasted for at least 7 days after a single dose. Therefore, FNZ seems to exert the same effect as a long‐acting neuroleptic agent in our HD patients.
Memory and depression in Parkinson's disease
Authors: Boller F. , Marcie P. , Starkstein S. , Traykov L.
Published: March 2003

Disorders of learning and memory are a frequent finding in nondemented Parkinson disease (PD) patients. It is not clear to what extent depression, present in at least half the cases of PD, contributes to these disorders. This paper investigates the possible influence of depression on tests of episodic memory in patients with Parkinson's disease (PD). We studied three groups of 11 subjects each (controls, non‐depressed PD, mildly to moderately depressed PD). Neuropsychological tests included tests of short and long‐term memory in verbal and non‐verbal modalities. The two groups of PD patients performed significantly worse than controls on the memory tests, but there were no differences between the depressed and non‐depressed PD patients. This lack of influence of depression on neuropsychological performance is compatible with Starkstein's view that cognitive imnpairment is only found beyond a given threshold of depression severity.
Neurological complications to vaccination against Japanese encephalitis
Authors: Plesner Anne‐Marie , Arlien‐Søborg Peter , Herning Margrethe
Published: March 2003

Japanese encephalitis (JE) vaccine has been used for childhood immunization programmes in Asia since the 1960s. Also, travellers from other parts of the world have been vaccinated before travelling to Asian countries. Some JE vaccines are produced from infected mouse brains and contain small amounts of myelin basic protein. Neurological side effects in larger vaccine trials in Asia have been reported in 1–2.3 per million vaccinees. Statens Serum Institut is the only distributor of JE vaccine in Denmark, delivering 384 000 doses from 1983–96. In 1996, evaluation of initial symptoms and findings in 10 adult travellers from Denmark, who developed moderate‐severe neurological symptoms within a few weeks of JE vaccination, was performed as well as follow‐up magnetic resonance imaging (MRI) and clinical neurological examination. Three patients initially had symptoms varying from severe encephalitis‐like illness to paraesthesia, double vision or parkinsonian gait disturbance. MRI showed severe atrophy of the corpus callosum with altered signal intensity indicating gliosis in one patient, another patient had several hyperintense spots located periventricularly in the white matter, while a third patient had spots with increased signals in the pons, the right substantia nigra and the occipital region. Acute disseminated encephalomyelitis (ADEM) is a possible explanation for these MRI changes, although multiple sclerosis is an alternative diagnosis in one or two of the patients. Another three patients had long‐lasting headache, concentration difficulty or intellectual reduction. One man had afebrile convulsions, another gait instability and depression and one parkinsonism. A woman developed myelitis. If these findings are due to JE vaccination the frequency of neurological reactions to the vaccine is considerably higher than previously reported and in the future any minor neurological complaints occurring shortly after vaccination should lead to neurological examination and acute MRI scan should be considered.
Cerebellar agenesis: a case report with clinical and MR imaging findings and a review of the literature
Authors: Velioǧlu Sibel K. , Kuzeyli Kayhan , Özmenoǧlu Mehmet
Published: March 2003

We describe the clinical and MRI findings in a 22‐year‐old male patient with absence of the cerebellum, an extremely rare anomaly. Clinical features included ataxia of limbs, gait and stance, cerebellar oculomotor signs. MRI evaluation showed minute remnants of cerebellar tissue corresponding to the anterior quadrangular lobules. Nine previous cases of total or subtotal cerebellar agenesis have been reported, including Combettes's first report in 1831. We report an additional case and provide MRI of this unusual anomaly detected during life. Diagnosis in this case was made on the basis of MR findings. To our knowledge, this is the fifth report of this disorder being diagnosed in a living patient.
The Milan Overall Dementia Assessment and the Mini‐Mental State Examination compared: an epidemiological investigation of dementia
Authors: Cossa Federico M. , Sala Sergio Della , Musicco Massimo , Spinnler Hans , Ubezio Maria C.
Published: March 2003

We assessed the validity of two screening tests [the Mini‐Mental State Examination (MMSE) and the Milan Overall Dementia Assessment or (MODA)] in a population study on the prevalence of Alzheimer's disease, carried out in a small town in the north of Italy. A random sample of 1000 subjects aged 60 years or over entered the study. Subjects who scored below the cut‐off points on MODA or on MMSE, or both, were further investigated with neuropsychological, laboratory and instrumental tests to ascertain a final diagnosis, which was considered as the gold standard. Our findings show that MODA has a higher sensitivity than MMSE in detecting subjects affected by dementing illnesses, while MMSE shows a higher specificity. MODA seems to be preferable to MMSE as a screening test for studies where a very high sensitivity is required.
Hereditary sensory neuropathy with deafness and dementia: a clinical and neuroimaging study
Authors: Hojo Kaori , Imamura Toru , Takanashi Mayako , Ishii Kazunari , Sasaki Masahiro , Imura Shigeaki , Ozono Reiko , Takatsuki Yoko , Takauchi Shigeru , Mori Etsuro
Published: March 2003

We describe three sibling patients with autosomal dominantly inherited sensory neuropathy, sensorineural hearing loss and dementia. The features of cognitive‐behavioral deficits in the patients, including executive dysfunction, apathy, indifference and inattention, were consistent with a frontal lobe dysfunction. Magnetic resonance imaging showed a diffuse brain atrophy. A fluorodeoxyglucose positron emission tomography in one patient and a single photon emission computed tomography in another demonstrated a glucose hypometabolism or a hypoperfusion in the medial frontal and thalamic regions. Primary frontal involvement or frontal dysfunction secondary to thalamic lesions may contribute to the nature of dementia in these patients.
Bilateral sphenoid wing metastases of prostate cancer presenting with extensive brain edema
Authors: Lindsberg Perttu J. , Tatlisumak Turgut , Tienari Jukka , Brander Antti
Published: March 2003

A 76‐year‐old man insidiously developed diffuse neurological symptoms: cognitive decline, dysphagia, dysphasia and mental disturbance. Computed tomography of the cranium revealed widespread bilateral brain edema and symmetrical bilateral sphenoid wing hyperostosis. Adjacent to the hyperostosis that resembled skull base meningeomas, two separate parenchymatous temporal lobe lesions enhancing with contrast medium were observed. The patient had earlier been diagnosed to have prostatic carcinoma. Dexamethason therapy resulted in discontinuation of the neurological symptoms. The diagnosis of metastased adenocarcinoma of the prostate was confirmed histologically on autopsy after a sudden death from pneumonia. Intracranial metastases of prostate cancer may have a predilection site at the sphenoid wing, and can mimic a skull base meningeoma. Intracranial spread of prostatic adenocarcinoma should be considered in elderly men as a treatable cause of gradual neurological deterioration, especially if cranial malignancy or hyperostosis is found.
Total innervation of the extensor digitorum brevis by the accessory deep peroneal nerve
Authors: Murad Hatem , Neal Peggy , Katirji Bashar
Published: March 2003

We deseribe a patient with complete (100%) innervation of the extensor digitorum brevis muscle by the accessory deep peroneal nerve, which resulted in an erroneous diagnosis of peroneal mononeuropathy.
A novel mutation in the GTP cyclohydrolase I gene associated with a broad range of clinical presentations in a family with autosomal dominant dopa‐responsive dystonia
Authors: Markova Elena D. , Slominsky Pyotr A. , Illarioshkin Sergei N. , Miklina Natalya I. , Popova Svetlana N. , Limborska Svetlana A. , Ivanova‐Smolenskaya Irina A.
Published: March 2003

We examined a large family of Ashkenazi Jewish origin with autosomal dominant dopa‐responsive dystonia (DRD). Mutation analysis of the GTP cyclohydrolase I gene revealed in affected members a novel point mutation (a C/A change in exon 1) resulting in a threonine‐to‐lysine substitution at residue 94. The mutation was characterized by variable expressivity and was associated with either a ‘classical’ DRD phenotype or various atypical phenotypes, such as subtle transitory equinovarus postures of the feet or isolated hand tremor. This observation demonstrates the significance of the molecular testing in establishing the clinical diagnosis of DRD.
Progressive multifocal leukoencephalopathy: simultaneous detection of JCV DNA and anti‐JCV antibodies in the cerebrospinal fluid
Authors: Guillaume B. , Sindic C. J. M. , Weber T.
Published: March 2003

We report on a case of biopsy‐proven progressive multifocal leukoencephalopathy (PML) in a patient without obvious immunodeficiency. Analysis of the cerebrospinal fluid revealed the simultaneous presence of JC virus DNA and of locally produced, anti‐JC virus antibodies. The intrathecal humoral immune response increased throughout the course of the disease, whereas the detection of the JC genome became ultimately negative in spite of the continuous extension of the lesions with fatal outcome.
Alcohol with xylocaine for treatment of eyelid dystonia
Authors: Mubaidin A. F.
Published: March 2003

Eyelid dystonia represents a form of idiopathic torsion dystonia, and it is considered as a rare disorder. Although botulinum toxin injections into the eyelids and eyebrows are considered by many neurologists as the treatment of choice for this, its cost limit its use in our community. A study was conducted at the King Hussein Medical Center between January 1995 and January 1998 using 1–2 ml of 0.5% xylocaine added to 99.5% ethanol in one‐tenth of the volume of xylocaine, made injectable into the eyelids and eyebrows muscles in patients with blepharospasm. The treatment was aimed at reducing muscle spindle afferent activity. Twenty‐one patients were given this modality of treatment in at least 8–12 separate sessions, with two weeks elapsing between any two sessions . Mild to moderate improvement was observed in 47.6% of our patients. The average latency from the time of the injection to the onset of improvement was 30–60 min and the average duration of improvement was 5–7 days. The commonest encountered side‐effect was bruising at the site of injection that resolved spontaneously in less than 5 days. It is obvious that the usefulness of this treatment is limited by the substantially shorter duration of benefit, thus it cannot be considered as an alternative to Botox treatment. It may be useful to investigate whether a higher alcohol concentration is more effective.
Increased numbers of mononuclear cells from blood and CSF expressing interferon‐gamma mRNA in multiple sclerosis are from both the CD4+ and the CD8+ subsets
Authors: Wallström E. , Khademi M. , Andersson M. , Olsson T.
Published: March 2003

Activated, cytokine‐producing lymphocytes may regulate central nervous system (CNS) inflammation in multiple sclerosis (MS). We utilize a novel combination of in situ hybridization (ISH) and immunocytochemical staining of peripheral blood lymphocytes (PBLs) to identify spontaneously interferon‐gamma (IFNγ) mRNA expressing cells as CD4+ or CD8+. A major proportion of the IFNγ mRNA expressing lymphocytes belonged to the CD4+ lineage, which concords with the cellular composition of MS brain lesions, findings in experimental models and the HLA class II haplotype association in MS. There were also significantly more CD8+ IFNγ mRNA expressing lymphocytes in the MS patients compared with healthy controls, further suggesting the contribution of activated cells from this lineage in the inflammatory response in MS. Both CD4+ and CD8+ IFNγ mRNA expressing cells were enriched in the cerebrospinal fluid (CSF) as compared with the peripheral blood of the MS patients. Combined with emerging genetic data on HLA class I influences, our data argues for a joint role of activated CD8+ and CD4+ cells in the pathogenesis of MS.
Multimedia education in headache: the European Neurological Network
Authors: Russell M. B. , Dremstrup Nielsen K. , Rasmussen C. , Schoenen J. , Paiva T.
Published: March 2003

The European Neurological Network is a European Economic Community supported project. The purpose of the project was to develop a multimedia educational tool for general practitioners in order to improve their management of sleep disorders, epilepsy and headache. The project involves approximately one hundred engineers and physicians from Belgium, Denmark, England, Finland, France, Germany, Italy, Portugal and Spain. This paper concerns the multimedia educational tool on headache. The system consists of five different modules, i.e. classification, clinical data, headache tutorial, diagnostic headache diary and nomenclature. It is possible to move between the modules both vertically and horizontally. The headache classification of the International Headache Society is provided in full text as a work of reference. This classification is used world wide and has been adopted by International Classification of Diseases 10 Neurological Adaptation (ICD‐10 NA) and the World Health Organisation. The clinical data concentrate on migraine and tension‐type headache, the two most common headache disorders, but data on familial hemiplegic migraine, cluster headache, drug‐induced headache and secondary headaches are also available. The headache tutorial consists of case records that the user can test their diagnostic abilities on. The diagnostic headache diary is an expert system on headache diagnostics. It can be filled in during a consultation in order to provide the headache diagnosis or it can be printed and used by the headache patient to record headache attacks and medicine consumption. The nomenclature module provides an explanation of words and expressions used in the system.
Effect of diabetes on some primitive reflexes
Authors: Volpe G. , Della Rocca G. , Brescia Morra V. , Belfiore G. , Coppola G. , Campanella G. , Orefice G.
Published: March 2003

Primitive reflexes (PRs) are present in newborns; they disappear as the brain matures and increase in frequency in healthy elderly individuals . Primitive reflexes are more frequent in some neurological disorders than in age‐matched controls. The aim of this study was to investigate the effect of diabetes on some PRs. We examined three PRs (glabellar tap, snout and palmomental reflexes) in 376 subjects: 111 normal age‐matched controls, 60 patients with cerebrovascular disease (CVD) and 205 patients with type 2 diabetes mellitus. The latter patients were divided into three groups: (1) diabetics without neurological complications (D); (2) diabetics with cerebrovascular disease (D‐CVD); and (3) diabetics with polyneuropathy (D‐PN). The frequency of PRs was increased in CVD, unchanged in D‐CVD (except palmomental) and greatly reduced in D and D‐PN. It is possible that the vascular lesions in perforating arteries of the pons in diabetic subjects, previously studied in some pathological reports, can account for the reduced occurrence of primitive reflex responses.
How to succeed in using dopamine agonists in Parkinson’s disease
Authors: Shulman L. M.
Published: March 2003

Dopamine receptor agonists are assuming increased importance in the treatment of both early and advanced symptoms of Parkinson's disease (PD). However, tolerability of these drugs can be a problem. Identifying patients who are at increased risk of adverse effects is central to using dopamine agonists in PD. The newer agonists, pramipexole and ropinirole, are generally adequate without levodopa for early symptoms and carry the hope for a more acceptable profile of long‐term side‐effects. In the patient with advanced disease, all four dopamine agonists significantly augment the response to levodopa, which reduces the problems of motor fluctuations and drug related dyskinesia. Understanding the common pitfalls when prescribing these drugs will facilitate their safety and efficacy.
Referral and care for acute ischemic stroke in a Japanese tertiary emergency hospital
Authors: Yoneda Y. , Mori E. , Uehara T. , Yamada O. , Tabuchi M.
Published: March 2003

To examine the current emergency referral and care for acute stroke at a Japanese tertiary emergency hospital with a 24‐h stroke team and care unit, we surveyed the presentations of patients with acute ischemic stroke or transient ischemic attack (TIA) seen within 7 days of onset. Delay from symptom onset to arrival at our hospital, from arrival to initial diagnostic brain computed tomography (CT), and the type of anti‐thrombotic treatments were evaluated. During the 18‐month period, there were 254 ischemic events in 244 patients; 239 (94%) had an ischemic stroke and 15 (6%) TIA. Eighty‐two (32%) events presented within 3 h of onset, and 102 (40%) and 179 (70%) within the first 6 and 24 h, respectively. The median delay from hospital arrival to CT was 32 min, ranging 10 min to 22 h. Two hundred (79%) events underwent CT within 1 h of arrival (n=172) or at the referral hospitals before transfer (n=28). Direct ambulance transportation and more severe neurological deficits were independent predictors both for early arrival and short in‐hospital delay to CT. Anti‐thrombotic therapies including anticoagulant and/or antiplatelet medications were given in 237 (93%) episodes. Two (1%) patients received thrombolysis, although 18 (7%) patients fulfilled the National Institute of Neurological Disorders and Stroke guidelines for intravenous thrombolysis with tissue plasminogen activator. As in western communities, our pre‐hospital emergency referral systems for acute stroke require substantial improvements including the wider use of ambulance calling. Although our in‐hospital stroke management is functioning relatively well, further efforts are necessary in reducing the diagnostic delay.
Hospitalization of patients with neurological disorders and estimation of the need of beds and of the related costs in Austria’s non‐profit hospitals
Authors: Lampl C. , Klingler D. , Deisenhammer E. , Hagenbichler E. , Neuner L. , Pesec B.
Published: March 2003

In 1997, 273 722 hospitalizations as a result of neurological disorders, including the related operated cases, were reported in Austria’s non‐profit hospitals (80% of all hospitals). They represent 14.12% of all 1.9 million in‐patient treatments. The individual disease groups, e.g. cerebrovascular disorders (59 269 admissions or 3.06%), multiple sclerosis (3920 admissions or 0.2%) and all other groups are detailed. We estimated the cost resulting from these diseases which amounted to 11.88% of all hospital costs. We were also able to estimate that 5549 beds are required for in‐patient treatment in the area of neurology, assuming an average duration of treatment of 8 days (Austrian mean value for neurological disorders). This is equivalent to one bed per 1367 inhabitants or 11.31% of all beds for in‐patient treatment in non‐profit hospitals in Austria. Obviously at present the majority of neurological patients are treated in non‐neurological departments. A major increase in resources to neurology is necessary if patients are to receive the benefit of specialized diagnosis and treatment. These further resources not only cover the increase of neurological beds in hospitals but also financial, personal resources and in consequence increased capacity for neurological education, training and research.
Heightened intrathecal release of soluble CD137 in patients with multiple sclerosis
Authors: Sharief M. K.
Published: March 2003

Human CD137 (ILA/4‐1BB), a member of the tumour necrosis factor (TNF) receptor family, regulates the activation and proliferation of immune cells, and may induce apoptosis (programmed cell death) of activated lymphocytes. A soluble form of CD137 (sCD137) released by activated lymphocytes may interfere with the activities of the membrane‐bound CD137. This study reports the detection of significantly high intrathecal and systemic levels of sCD137 in patients with clinically active multiple sclerosis (MS) when compared with corresponding levels from patients with clinically stable MS or those with inflammatory and non‐inflammatory neurological disorders, or from healthy individuals. Intrathecal concentrations of sCD137 in patients with active MS correlate with the intrathecal release of the soluble death receptor protein Fas, but not with the release of interleukin‐2, TNF or the synthesis of immunoglobulins G and M. Results presented here suggest that heightened release of sCD137 is a feature of clinically active MS.
Homozygous Machado–Joseph disease presenting as REM sleep behaviour disorder and prominent psychiatric symptoms
Authors: Fukutake T. , Shinotoh H. , Nishino H. , Ichikawa Y. , Goto J. , Kanazawa I. , Hattori T.
Published: March 2003

A male patient carrying the homozygous gene for Machado–Joseph disease (MJD) presented at age 43 with sleep disturbances and psychiatric symptoms followed by ataxic speech and gait. A polysomnogram (PSG) showed decreased rates of sleep time and stage rapid eye movement (REM) and an increased rate of ‘stage 1‐REM with tonic EMG’ (Tachibana et al., 1975); all compatible with REM sleep behaviour disorder (RBD). Molecular gene analysis at age 59 showed that the CAG repeat units in the MJD gene were 60 and 60, smaller than the reported lengths for homozygous MJD patients (63–70 and 66–72). In addition to sleep disturbances, in particular RBD, psychiatric symptoms may be important clinical features in both heterozygous and homozygous MJD.
Dissection and atherosclerosis of carotid arteries in the young: role of the apolipoprotein E polymorphism
Authors: Orlandi G. , Fanucchi S. , Mancuso M. , Gelli A. , Rocchi A. , Siciliano G. , Murri L.
Published: March 2003

Twenty‐seven young (<50 years old) patients with spontaneous carotid artery dissection in 11 cases and carotid atherosclerosis in 16 cases were evaluated to determine the apolipoprotein E polymorphism. At the DNA analysis the ɛ3/ɛ3 genotype was observed in all patients with dissection, in 13 of 16 (81.2%) patients with atherosclerosis and in 27 of 30 (90%) controls. Three of 16 (18.8%) patients with atherosclerosis and 3 of 30 (10%) controls presented with the ɛ4/ɛ3 genotype, and this difference was not statistically significant. Moreover, observation of the ɛ4/ɛ3 genotype was not significantly higher in patients with atherosclerosis compared with those with dissection. No homozygote ɛ4/ɛ4, ɛ2/ɛ2 or heterozygote ɛ2 genotype was observed. No correlation was found between the presence of the ɛ4/ɛ3 genotype and vascular risk factors. Therefore, the ɛ4 allele seems to be involved in carotid premature atherosclerosis development whereas it may appear to be protective for artery dissection occurrence. A larger sample size is needed to support this suggestion.
Depletion of Vβ5.2/5.3 T cells with a humanized antibody in patients with multiple sclerosis
Authors: Olsson T. , Edenius C. , Ferm M. , Samuelson P. , Torrång A. , Wallström E. , Khademi M. , Andersson M. , Årfors L.
Published: March 2003

A potentially pathogenic expansion of T cells expressing T cell receptor (TCR) Vβ5.2/5.3 has been demonstrated in patients with multiple sclerosis (MS). A humanized antibody (ATM‐027) directed against these T cells has been developed to further investigate the role of this subpopulation of T cells in MS. The pharmacokinetics/dynamics and safety of ATM‐027 (0.3–300 mg intravenously over 30 min) were investigated in 14 patients with MS. The effect of treatment on cytokine expression and autoreactivity to peptides of myelin basic protein (MBP) was also studied. ATM‐027 was well tolerated and raised no safety concerns. Clearance of the antibody was low and elimination half‐life was approximately 3 weeks. The majority of the target Vβ5.2/5.3 expressing T cells were depleted for at least 18 months. The small remaining fraction of target cells showed a marked decrease in their TCR expression, which was recovered within 8 months. The numbers of peripheral blood mononuclear cells (PBMCs) with spontaneous expression of IFN‐γ was decreased at 72 h and 8 weeks after treatment, whilst no clear effects on TNF‐α, IL‐4, IL‐10, TGF‐β expression were observed. There was also a significant decrease in the number of PBMCs producing IFN‐γ in response to MBP peptide 80–102. We conclude that long‐term depletion of T cells expressing defined Vβ subgroups in MS patients is feasible using selective immunotherapy. The selective depletion of Vβ5.2/5.3 expressing T cells in this study resulted in a decrease in potentially disease promoting anti‐MBP reactivity and pro‐inflammatory cytokine production.
Therapeutical considerations in patients with intracranial venous angiomas
Authors: Buhl R. , Hempelmann R. G. , Stark A. M. , Mehdorn H. M.
Published: March 2003

The clinical presentation of intracranial venous angiomas are usually headache, seizures or dizziness. Very often these anomalies are found incidentally on magnetic resonance imaging (MRI). We reviewed 35 patients, which were examined in our department between 1994 and 2000. Only one patient became symptomatic with an intracranial haematoma, which was removed surgically. In three patients an associated cavernous angioma was found, which was removed successfully with preservation of the coexisting venous angioma. There is no indication in operating a venous angioma because the risk of postoperative deterioration caused by venous infarction is high. When removing cavernous angiomas the associated venous angioma has to be preserved.
Cognitive functions after transient topographical amnesia
Authors: Stracciari A. , Lorusso S. , Ponti A. Delli , Mattarozzi K. , Tempestini A.
Published: March 2003

Twelve consecutive patients having previously experienced one or more episodes of isolated transient topographical amnesia (TTA) underwent neuropsychological examination 6–12 months after the last episode to detect signs of global cognitive decline and to assess, in particular, cognitive functions deemed critical for topographical orientation. The test scores were compared with those of 12 normal subjects matched for age, sex, educational level and place of residence. Both patients and controls showed normal performances in all tasks. The comparison between the two groups revealed a significantly lower performance of the patient group in a task of geographical orientation, namely `Map of Italy'. We conclude that isolated episodes of TTA in the elderly per se do not represent a sign of mental deterioration, but can be associated with frailty on survey components of spatial orientation. It remains to be explained whether this feature is a pre‐existing condition favouring the occurrence of the episodes of topographical amnesia or represents a sequela.
Intravenous immunoglobulin G for the treatment of relapsing–remitting multiple sclerosis: a meta‐analysis
Authors: Sorensen P. S. , Fazekas F. , Lee M.
Published: March 2003

Intravenous immunoglobulin (IVIG) has several effects on the immune system that could have a beneficial influence on disease processes in multiple sclerosis (MS). Four double‐blind trials in relapsing–remitting MS have demonstrated that IVIG may reduce the relapse rate, progression and the number of gadolinium‐enhancing lesions. However, these trials were smaller than the pivotal trials of interferon‐β and glatiramer acetate, and therefore, we performed a meta‐analysis of the four trials in order to provide an overall assessment of the benefits of IVIG in relapsing–remitting multiple sclerosis in comparison with other drugs currently available for treatment of disease activity in MS. The meta‐analysis showed a significant beneficial effect on the annual relapse rate (effect size −0.5; P = 0.00003), on the proportion of relapse‐free patients (0.29 difference; P = 2.1 × 10−8), change in Expanded Disability Status Scale (EDSS) score (effect size: 0.25; P = 0.04), and a trend towards a reduction in the proportion of patients who deteriorated (P = 0.03). Each single study in the meta‐analysis had its weaknesses, but all studies were positive regarding their primary end‐point, and the results yield concordant evidence for reduction of relapse rate and progression. The ideal dosage of IVIG for treating MS needs still to be determined. In conclusion, IVIG may be a valuable alternative for treatment of relapsing–remitting MS, but can presently not be considered as a first‐line treatment. IVIG could be considered in patients who do not tolerate or are unwilling to take the approved injectable medications, but additional studies are needed to establish the role of IVIG in the management of multiple sclerosis.