(2001). "[Multiple Sclerosis. Consensus Conference Organized by the French Federation for Neurology. 7-8 June 2001]." Rev Neurol (Paris) 157(8-9 Pt 2): 902-1192.

(2001). "[Consensus Conference on Multiple Sclerosis, Paris, 7 and 8 June 2001. Organized by the French Federation of Neurology with participation of l'ANAES. Recommendations of the Jury]." Rev Neurol (Paris) 157(8-9 Pt 2): 1184-92.

(2001). "[Guidelines of the consensus conference on multiple sclerosis]." Rev Neurol (Paris) 157(6-7): 713-21.

(2001). "Glatiramer acetate for multiple sclerosis." Drug Ther Bull 39(6): 41-3.
Glatiramer acetate (Copaxone-Teva) was first marketed in the UK last year as a treatment for reducing the "frequency of relapses in ambulatory patients with relapsing-remitting multiple sclerosis characterised by at least one clinical relapse over the preceding two-year period". Here, we assess the place of this drug.

(2001). "[Escalating immunomodulatory therapy of multiple sclerosis. 1st supplement: December 2000]." Nervenarzt 72(2): 150-7.
New clinical studies in multiple sclerosis provided data on the treatment of clinical isolated syndromes and secondary progressive forms which may have important implications for the optimal care of MS patients. The MSTKG critically evaluated the available data again and provides evidence-based recommendations for the application of immunoprophylactic therapies. Initiation of treatment after the first relapse may be indicated if there is clear evidence from MRI for subclinical dissemination of disease. Recent trials indicate that efficacy of therapy with IFN--is more likely with superimposed bouts or other indicators of inflammatory disease activity than without them in secondary progressive MS. If immunoprophylactic treatment is initiated with a provisional diagnosis of MS, confirmation of MS is essential. In long-term treated patients secondary treatment failure should be identified by follow-up examinations and other treatment options discussed.

Adam, P., L. Taborsky, et al. (2001). "Cerebrospinal fluid." Adv Clin Chem 36: 1-62.

Adorini, L. (2001). "Selective immunointervention in autoimmune diseases: lessons from multiple sclerosis." J Chemother 13(3): 219-34.
Activation of peripheral T cells by foreign and self antigens is under stringent control by different mechanisms, both thymic and peripheral. Control of T cell reactivity is accomplished by three major types of mechanisms: 1) deletion, the physical elimination of T cells specific for a given antigen, 2) anergy, the functional incapacity of T cells to respond to antigen, 3) suppression, the inhibition of T cell function by a regulatory (suppressor) cell. Their failure may lead to autoimmune diseases. The progress in understanding T cell activation, inactivation and modulation is being translated into strategies able to induce selective immunosuppression to treat different pathological situations, notably autoimmune diseases, allergies, and allograft rejection. The medical need for selective immunosuppression is very high, as the available immunosuppressive drugs are substantially inadequate because of limited efficacy, modest selectivity, and considerable toxicity. Key attack points for selective immunointervention have been identified: modulation of antigen recognition, co-stimulation blockade, induction of regulatory cells, deviation to non-pathogenic or protective responses, neutralization of proinflammatory cytokines, induction or administration of anti-inflammatory cytokines, and modulation of leukocyte trafficking. All these forms of immunointervention have been successfully used to prevent and sometimes treat experimental autoimmune diseases. Based on these results, expectations have been raised for exploiting the same strategies to inhibit the activation of human autoreactive T cells. In this overview, we will examine recent advances towards immunointervention in multiple sclerosis (MS) as a paradigm for successes and failures of current immunotherapeutic approaches in human autoimmune diseases.

Ahlbom, I. C., E. Cardis, et al. (2001). "Review of the epidemiologic literature on EMF and Health." Environ Health Perspect 109 Suppl 6: 911-33.
Exposures to extremely low-frequency electric and magnetic fields (EMF) emanating from the generation, transmission, and use of electricity are a ubiquitous part of modern life. Concern about potential adverse health effects was initially brought to prominence by an epidemiologic report two decades ago from Denver on childhood cancer. We reviewed the now voluminous epidemiologic literature on EMF and risks of chronic disease and conclude the following: a) The quality of epidemiologic studies on this topic has improved over time and several of the recent studies on childhood leukemia and on cancer associated with occupational exposure are close to the limit of what can realistically be achieved in terms of size of study and methodological rigor. b) Exposure assessment is a particular difficulty of EMF epidemiology, in several respects: i) The exposure is imperceptible, ubiquitous, has multiple sources, and can vary greatly over time and short distances. ii) The exposure period of relevance is before the date at which measurements can realistically be obtained and of unknown duration and induction period. iii) The appropriate exposure metric is not known and there are no biological data from which to impute it. c) In the absence of experimental evidence and given the methodological uncertainties in the epidemiologic literature, there is no chronic disease for which an etiological relation to EMF can be regarded as established. d) There has been a large body of high quality data for childhood cancer, and also for adult leukemia and brain tumor in relation to occupational exposure. Among all the outcomes evaluated in epidemiologic studies of EMF, childhood leukemia in relation to postnatal exposures above 0.4 microT is the one for which there is most evidence of an association. The relative risk has been estimated at 2.0 (95% confidence limit: 1.27-3.13) in a large pooled analysis. This is unlikely to be due to chance but, may be, in part, due to bias. This is difficult to interpret in the absence of a known mechanism or reproducible experimental support. In the large pooled analysis only 0.8% of all children were exposed above 0.4 microT. Further studies need to be designed to test specific hypotheses such as aspects of selection bias or exposure. On the basis of epidemiologic findings, evidence shows an association of amyotrophic lateral sclerosis with occupational EMF exposure although confounding is a potential explanation. Breast cancer, cardiovascular disease, and suicide and depression remain unresolved.

Allt, G. and J. G. Lawrenson (2001). "Pericytes: cell biology and pathology." Cells Tissues Organs 169(1): 1-11.
Pericytes are perivascular cells with multifunctional activities which are now being elucidated. The functional interaction of pericytes with endothelial cells (EC) is now being established, using current molecular and cytochemical techniques. The detailed morphology of the pericyte has been well described. Pericytes extend long cytoplasmic processes over the surface of the EC, the two cells making interdigitating contacts. At points of contact, communicating gap junctions, tight junctions and adhesion plaques are present. Pericytes appear to show both structural and functional heterogeneity. The coverage of EC by pericytes varies considerably between different microvessel types and the location of pericytes on the microvessel is not random but appears to be functionally determined. Interaction between pericytes and EC is important for the maturation, remodelling and maintenance of the vascular system via the secretion of growth factors or modulation of the extracellular matrix. There is also evidence that pericytes are involved in the transport across the blood-brain barrier and the regulation of vascular permeability. The long-standing view that pericytes are the microvessel equivalent of larger vessel smooth muscle cells and are contractile is being reassessed using current methods. An important role for pericytes in pathology, and neuropathology in particular, has been indicated in hypertension, diabetic retinopathy, Alzheimer's disease, multiple sclerosis and CNS tumour formation.

Althaus, H. H., K. Mursch, et al. (2001). "Differential response of mature TrkA/p75(NTR) expressing human and pig oligodendrocytes: aging, does it matter?" Microsc Res Tech 52(6): 689-99.
A differential morphological response of mature oligodendrocytes (OL) isolated from human and pig brains to the phorbol ester 12-O-tetradecanoylphorbol-13-acetate (TPA) and to the nerve growth factor (NGF) was observed. In both cases, OL regenerate their processes; however, the rate and the extension of the process formation of human OL were behind that of pig OL. Presumably, the advanced age of the human tissue in these experiments might have contributed to this decrease in process formation, an effect that was already observed for rat OL [Yong et al. (1991) J Neurosci Res 29:87-99]. The less effectivity of NGF via TrkA, which was immunocytochemically shown in human OL, and of TPA via the protein kinase C (PKC) pathway, may have its common focus on the mitogen-activated protein kinase (MAPK) cascade. In this context, it was noted that only a few studies on aging of mature OL are available. It is conceivable that age-related changes in the properties of OL could be an important factor for their cellular responsiveness during longer lasting demyelinating diseases such as multiple sclerosis. Hence, this review would like to provide a basis for future investigations on the aging of mature OL. The data presently available suggest a preliminary classification of mature OL into three categories.

Arnold, A. C. and A. G. Lee (2001). "Systemic disease and neuro-ophthalmology: annual update 2000 (Part I)." J Neuroophthalmol 21(1): 46-61.

Autret, A., B. Lucas, et al. (2001). "Sleep and brain lesions: a critical review of the literature and additional new cases." Neurophysiol Clin 31(6): 356-75.
We present a comprehensive review of sleep studies performed in patients with brain lesions complemented by 16 additional personal selected cases and by discussion of the corresponding animal data. The reader is cautioned about the risk of establishing an erroneous correlation between abnormal sleep and a given disorder due to the important inter and intra variability of sleep parameters among individuals. Salient points are stressed: the high frequency of post-stroke sleep breathing disorders is becoming increasingly recognised and may, in the near future, change the way this condition is managed. Meso-diencephalic bilateral infarcts induce a variable degree of damage to both waking and non-REM sleep networks producing and abnormal waking and sometimes a stage 1 hypersomnia reduced by modafinil or bromocriptine, which can be considered as a syndrome of cathecholaminergic deficiency. Central pontine lesions induce REM and non-REM sleep insomnia with bilateral lateral gaze paralysis. Bulbar stroke leads to frequent sleep breathing disorders. Polysomnography can help define the extent of involvement of various degenerative diseases. Fragmented sleep in Parkinson's disease may be preceded by REM sleep behavioural disorders. Multiple system atrophies are characterised by important sleep disorganization. Sleep waking disorganization and a specific ocular REM pattern are often seen in supra-nuclear ophtalmoplegia. In Alzheimer patients, sleep perturbations parallel the mental deterioration and are possibly related to cholinergic deficiency. Fronto-temporal dementia may be associated with an important decrease in REM sleep. Few narcoleptic syndromes are reported to be associated with a tumour of the third ventricle or a multiple sclerosis or to follow a brain trauma; all these cases raise the question whether this is a simple coincidence, a revelation of a latent narcolepsy or, as in non-DR16/DQ5 patients, a genuine symptomatic narcolepsy. Trypanosomiasis and the abnormal prion protein precociously after sleep patterns. Polysomnography is a precious tool for evaluating brain function provided it is realised under optimal conditions in stable patients and interpreted with caution. Several unpublished cases are presented: one case of pseudohypersomnia due to a bilateral thalamic infarct and corrected by modafinil, four probable late-onset autosomal recessive cerebellar ataxias without sleep pattern anomalies, six cases of fronto-temporal dementia with strong reduction in total sleep time and REMS percentage on the first polysomnographic night, one case of periodic hypersomnia associated with a Rathke's cleft cyst and four cases of suspected symptomatic narcolepsy with a DR16-DQ5 haplotype, three of which were post-traumatic without MRI anomalies, and one associated with multiple sclerosis exhibiting pontine hyper signals on MRI.

Bajetto, A., R. Bonavia, et al. (2001). "Chemokines and their receptors in the central nervous system." Front Neuroendocrinol 22(3): 147-84.
Chemokines are a family of proteins associated with the trafficking of leukocytes in physiological immune surveillance and inflammatory cell recruitment in host defence. They are classified into four classes based on the positions of key cystiene residues: C, CC, CXC, and CX3C. Chemokines act through both specific and shared receptors that all belong to the superfamily of G-protein-coupled receptors. Besides their well-established role in the immune system, several recent reports have demonstrated that these proteins also play a role in the central nervous system (CNS). In the CNS, chemokines are constitutively expressed by microglial cells, astrocytes, and neurons, and their expression can be increased after induction with inflammatory mediators. Constitutive expression of chemokines and chemokine receptors has been observed in both developing and adult brains, and the role played by these proteins in the normal brain is the object of intense study by many research groups. Chemokines are involved in brain development and in the maintenance of normal brain homeostasis; these proteins play a role in the migration, differentiation, and proliferation of glial and neuronal cells. The chemokine stromal cell-derived factor 1 and its receptor, CXCR4, are essential for life during development, and this ligand-receptor pair has been shown to have a fundamental role in neuron migration during cerebellar formation. Chemokine and chemokine receptor expression can be increased by inflammatory mediators, and this has in turn been associated with several acute and chronic inflammatory conditions. In the CNS, chemokines play an essential role in neuroinflammation as mediators of leukocyte infiltration. Their overexpression has been implicated in different neurological disorders, such as multiple sclerosis, trauma, stroke, Alzheimer's disease, tumor progression, and acquired immunodeficiency syndrome-associated dementia. An emerging area of interest for chemokine action is represented by the communication between the neuroendocrine and the immune system. Chemokines have hormone-like actions, specifically regulating the key host physiopathological responses of fever and appetite. It is now evident that chemokines and their receptors represent a plurifunctional family of proteins whose actions on the CNS are not restricted to neuroinflammation. These molecules constitute crucial regulators of cellular communication in physiological and developmental processes.

Balcer, L. J. (2001). "Clinical outcome measures for research in multiple sclerosis." J Neuroophthalmol 21(4): 296-301.
The development of new and more sensitive clinical outcome measures for research in multiple sclerosis (MS) has been fueled by the development of effective therapies. As such, active arm comparison studies that require more sensitive clinical outcome measures are now commonplace. The Kurtzke Expanded Disability Status Scale (EDSS), the most widely used measure of neurologic impairment in MS, is particularly designed for classifying patients with respect to disease severity but has been criticized for its noninterval scaling, emphasis on ambulation status, relatively reduced sensitivity in the mid and upper ranges of scores, and absence of adequate cognitive and visual components. In response to perceived difficulties with the EDSS, the National Multiple Sclerosis Society Clinical Outcomes Assessment Task Force has developed the Multiple Sclerosis Functional Composite (MSFC). The MSFC includes three components that yield objective and quantitative results: 1) the timed 25-ft walk, 2) the nine-hole peg test, and 3) the 3-second paced auditory serial addition test. This scale has the advantages of continuous scoring with a composite Z score, standardized protocols, and high degrees of reliability and validity. Candidate visual function outcome measures for the MSFC, including the low-contrast Sloan letter chart, are currently under investigation. In addition to measures of neurologic impairment, health-related quality of life (HRQOL) measures have gained increasing importance as clinical trial outcome measures. The MS Quality of Life Inventory, a disease-specific HRQOL measure, has been developed to capture self-reported neurologic dysfunction and the impact of MS upon activities of daily living. MS clinical trials of the future, particularly active-arm comparison studies, will require more sensitive clinical outcome measures such as the MSFC. Measures of visual function and HRQOL should also be incorporated to capture the broad scope of neurologic impairment and disability in MS populations.

Balcer, L. J. (2001). "Evidence-based neuro-ophthalmology: advances in treatment." Curr Opin Ophthalmol 12(6): 387-92.
This review presents highlights and updates from of the most significant clinical trials in neuro-ophthalmology to date, the Optic Neuritis Treatment Trial, the Controlled High-Risk Avonex Multiple Sclerosis Prevention Study, and the Ischemic Optic Neuropathy Decompression Trial. The quality of evidence for treatment efficacy from these trials and other recent investigations of giant cell arteritis and idiopathic intracranial hypertension is classified herein according to published criteria based on sample size and study design.

Bauer, J., H. Rauschka, et al. (2001). "Inflammation in the nervous system: the human perspective." Glia 36(2): 235-43.
Many basic aspects of brain inflammation, recently disclosed in experimental models, are reflected in the pathology of human inflammatory brain diseases. Examples include the key role of T lymphocytes in immune surveillance and in the regulation of the inflammatory response, the essential contributions of adhesion molecules, proinflammatory cytokines, chemokines, and proteases in the recruitment of inflammatory cells into the nervous tissue, the modulating effect of glia cells on the inflammatory process and the termination of T-cell-mediated inflammation by apoptotic cell death. Despite this progress in our understanding of the pathogenesis of brain inflammation, there are still major unresolved questions. Because of technical constraints, most of our knowledge on central nervous system inflammation so far relates to the role of a specific T-cell subset, the so-called T-helper-1 cells. Other T-cell subsets, in particular cytotoxic class I MHC-restricted T lymphocytes, however, appear to be of major importance in human disease. Furthermore, the detailed mechanisms, which are responsible for the profound differences in the patterns of tissue damage in different human inflammatory brain diseases, such as multiple sclerosis or various forms of virus encephalitis, are largely unresolved. We discuss the open questions to be addressed in the future, which, when answered, may help to design novel therapeutic strategies.

Benn, T., C. Halfpenny, et al. (2001). "Glial cells as targets for cytotoxic immune mediators." Glia 36(2): 200-11.
Oligodendrocytes and Schwann cells are the glia principally responsible for the synthesis and maintenance of myelin. Damage may occur to these cells in a number of conditions, but perhaps the most studied are the idiopathic inflammatory demyelinating diseases, multiple sclerosis in the CNS, and Guillain-Barre syndrome and its variants in the peripheral nervous system (PNS). This article explores the effects on these cells of cytotoxic immunological and inflammatory mediators: similarities are revealed, of which perhaps the most important is the sensitivity of both Schwann cells and oligodendrocytes to many such agents. This area of research is, however, characterised and complicated by numerous and often very substantial inter-observer discrepancies. Marked variability in cell culture techniques, and in assays of cell damage and death, provide artifactual explanations for some of this variability; true inter-species differences also contribute. Not the least important conclusion centres on the limited capacity of in vitro studies to reveal disease mechanisms: cell culture findings merely illustrate possibilities which must then be tested ex vivo using human tissue samples affected by the relevant disease.

Benoist, C. and D. Mathis (2001). "Autoimmunity provoked by infection: how good is the case for T cell epitope mimicry?" Nat Immunol 2(9): 797-801.
Autoimmune diseases remain one of the mysteries that perplex immunologists. What makes the immune system, which has evolved to protect an organism from foreign invaders, turn on the organism itself? A popular answer to this question involves the lymphoid network's primordial function: autoimmunity is a by-product of the immune response to microbial infection. For decades there have been tantalizing associations between infectious agents and autoimmunity: beta-hemolytic streptococci and rheumatic fever; B3 Coxsackieviruses and myocarditis; Trypanosoma cruzi and Chagas' disease; diverse viruses and multiple sclerosis; Borrelia burgdorfii and Lyme arthritis; and B4 Coxsackievirus, cytomegalovirus or rubella and type 1 diabetes, to name the most frequently cited examples. In addition, animal models have provided direct evidence that infection with a particular microbe can incite a particular autoimmune disease. Nonetheless, many of the associations appear less than convincing and, even for those that seem to be on solid footing, there is no real understanding of the underlying mechanism(s).

Bjartmar, C. and B. D. Trapp (2001). "Axonal and neuronal degeneration in multiple sclerosis: mechanisms and functional consequences." Curr Opin Neurol 14(3): 271-8.
Renewed interest in axonal injury in multiple sclerosis has significantly shifted the focus of research into this disease toward neurodegeneration. During the past year magnetic resonance and morphologic studies have continued to confirm and extend the concept that axonal transection begins at disease onset, and that cumulative axonal loss provides the pathologic substrate for the progressive disability that most long-term MS patients experience. Although inflammation and chronic demyelination are probable causes of axonal transection, little is known about the molecular mechanisms that are involved. The view that MS can also be considered an inflammatory neurodegenerative disease has important clinical implications for therapeutic approaches, monitoring of patients, and future treatment strategies.

Bougher, D. J. (2001). "Reinventing the government role in pharmacotherapy." Can J Clin Pharmacol 8 Suppl A: 45A-47A.
Governments face enormous challenges in managing escalating expenditures under their prescription drug plans while providing access to new, cost effective therapies. Strategies to address cost pressures must be considered carefully, however, to ensure the achievement of optimum health outcomes. Alberta has adopted an inclusive approach in addressing utilization and cost issues through a variety of advisory processes and initiatives supported by the Minister of Health and Wellness. The Expert Committee on Drug Evaluation and Therapeutics advises the Minister on Alberta's government-sponsored drug programs and related policy matters. The Alberta Management Committee on Drug Utilization, co-chaired by the Alberta Medical Association and the Pharmacists Association of Alberta, is mandated to oversee the implementation of a number of drug utilization initiatives. The Pharmaceutical Information Network is the cornerstone project of Alberta Wellnet, supported by a unique multistakeholder task force that includes physicians, pharmacists, representatives from health regions and government. Recent successful program launches in Alberta include a palliative drug program, trial prescription program and the multiple sclerosis drug program. Successes in Alberta reinforce the importance of government's role in achieving optimum pharmacotherapy. This role can only be undertaken in collaboration with key stakeholders.

Brassat, D. (2001). "[Therapeutic indications targeting etiology. (With the exception of primary progressive forms)]." Rev Neurol (Paris) 157(8-9 Pt 2): 1014-28.
On the subject of the treatment of Multiple Sclerosis, JM Charcot stated in 1877 that "the time has not yet come when such a subject can be seriously considered". Fortunately such point of view is no more up to date. This chapter will review the available treatment for relapsing-remitting and secondary progressive Multiple Sclerosis. The immunosuppressive drugs and steroids have been used for many years. Immunomodulation appeared more recently. A review of the evidence on the use of those drugs will be performed.

Brecher, L. S. and T. C. Cymet (2001). "A practical approach to fibromyalgia." J Am Osteopath Assoc 101(4 Suppl Pt 2): S12-7.
The term fibromyalgia refers to a collection of symptoms with no clear physiologic cause, but the symptoms together constitute a clearly recognizable and distinct pathologic entity. The diagnosis is made through the examiner's clinical observations. The differential diagnosis must include other somatic syndromes as well as disease entities, including hepatitis, hypothyroidism, diabetes mellitus, electrolyte imbalance, multiple sclerosis, and cancer. Diagnostic criteria serve as guidelines for diagnosis, not as absolute requirements. Treatment of fibromyalgia, which is an ongoing process, remains individualized, relying on a good physician-patient relationship. It is goal-oriented, directed at helping patients get restorative sleep, alleviating the somatic pains, keeping patients productive, and regulating schedules. It can be achieved through a goal-oriented agreement between patient and provider. Because fibromyalgia is chronic and may affect all areas of an individual's functioning, the physician needs to also evaluate the social support systems of patients with fibromyalgia. The approach to treatment should integrate patient education as well as non-pharmacologic and pharmacologic modalities. To keep patients well educated and involved in their healthcare, physicians should provide patients with adequate sources for reliable information.

Bright, J. J. and S. Sriram (2001). "Immunotherapy of inflammatory demyelinating diseases of the central nervous system." Immunol Res 23(2-3): 245-52.
Inflammatory demyelinating diseases comprise a heterogeneous group of disorders that affect the peripheral and central nervous system. Multiple sclerosis (MS) is the most common disease affecting the CNS white matter. Close similarities between MS and the animal model of the disease, experimental allergic encephalitis (EAE), have suggested that MS might be an autoimmune disease, which is triggered by an infectious agent. Our laboratory has directed its effort in identifying and designing therapies that interfere with key signaling pathways that mediate CNS inflammation in experimental allergic encephalitis. These have included naturally occurring cytokines such as TGFbeta and synthetic small molecules, lysofyline and tyrphostin, which inhibit the inflammatory response and prevent the development of EAE.

Brochet, B. (2001). "[Therapeutic indications for acute episodes of multiple sclerosis]." Rev Neurol (Paris) 157(8-9 Pt 2): 988-95.
The natural history of multiple sclerosis (MS) exacerbations is characterized by a poor outcome in about 70 p. cent of cases. By contrast, the outcome of a first episode of acute optic neuritis (ON) is usually good. However the disability associated with MS bouts and ON requires the use of a specific treatment. Nine randomized controlled clinical trials against placebo performed exclusively for MS exacerbations or acute ON were identified. Corticosteroids or ACTH produced a significant improvement in disability or vision at 30 days and shortened the duration of exacerbations. Longer follow-up clinical trials performed in MS exacerbation were not able to clearly demonstrate a significant effect. In acute ON clinical trials the long term visual outcome was not significantly different after steroid treatment than after placebo but this outcome is usually good. There is some evidence that high doses of intravenous methylprednisolone delay the occurrence of the next relapse, and have a dose-dependent effect on the rate of new lesion formation. There is no convincing evidence of the effectiveness of oral steroids in MS exacerbations but this treatment is associated with an increase relapse rate in ON. Side effects with intravenous methylprednisolone are less severe than with oral mega doses or ACTH.

Brody, J. A. and M. D. Grant (2001). "Age-associated diseases and conditions: implications for decreasing late life morbidity." Aging (Milano) 13(2): 64-7.
We discuss two types of age-associated diseases; aging-dependent such as Alzheimer's disease and congestive heart failure which increase logarithmically with age, versus age-dependent such as multiple sclerosis and amyotrophic lateral sclerosis which occur at proscribed ages, and then occurrence of new cases ceases or diminishes with further aging. Prevention strategies with both types emphasize postponement or delay of onset. The non-fatal aging-dependent diseases and conditions are an accumulating burden as we age, and increase overall morbidity in late years. These include Alzheimer's disease and other dementias, Parkinson's disease, loss of vision and hearing, incontinence, osteoporosis and hip fracture, osteoarthritis and depression. With mortality postponed, we will be living for many years at old and vulnerable ages. Life's quality will be reasonable for most. Still, increasing the chance that all will experience this desirable outcome requires pursuing the means to delay the onset of the physical and social events which we categorize as the non-fatal aging-dependent diseases and conditions. We must recognize that each added year occurs at the tip of an exponential curve where risk is maximal.

Caserta, M. T., D. J. Mock, et al. (2001). "Human herpesvirus 6." Clin Infect Dis 33(6): 829-33.
The development of techniques for the culture of lymphoid cells and the isolation of viruses that infect these cells led to the discovery of human herpesvirus (HHV) 6 in 1986. At the time, HHV-6 was the first new human herpesvirus to be discovered in roughly a quarter of a century, and its isolation marked the beginning of an era of discovery in herpesvirology, with the identification of HHV-7 and HHV-8 (Kaposi's sarcoma-associated herpesvirus) during the following decade. Like most human herpesviruses, HHV-6 is ubiquitous and capable of establishing a lifelong, latent infection of its host. HHV-6 is particularly efficient at infecting infants and young children, and primary infection with the virus is associated with roseola infantum (exanthem subitum) and, most commonly, an undifferentiated febrile illness. Viral reactivation in the immunocompromised host has been linked to a variety of diseases, including encephalitis, and HHV-6 has been tentatively associated with multiple sclerosis. This article discusses the major properties of HHV-6, its association with human disease, and the pathobiological significance of viral reactivation.

Chen, R. T., R. Pless, et al. (2001). "Epidemiology of autoimmune reactions induced by vaccination." J Autoimmun 16(3): 309-18.
In order for vaccinations to 'work', the immune system must be stimulated. The concern that immunizations may lead to the development of autoimmune disease (AID) has been questioned. Since AID occur in the absence of immunizations, it is unlikely that immunizations are a major cause of AID. Epidemiological studies are needed, however, to assess whether immunizations may increase the risk in some susceptible individuals. This paper discusses the evidence for and against vaccination as a risk factor for AID. Evidence for immunizations leading to AID come from several sources including animal studies, single and multiple case reports, and ecologic association. However more rigorous investigation has failed to confirm most of the allegations. Unfortunately the question remains difficult to address because for most AIDs, there is limited knowledge of the etiology, background incidence and other risk factors for their development. This information is necessary, in the absence of experimental evidence derived from controlled studies, for any sort of adequate causality assessment using the limited data that are available. Several illustrative examples are discussed to highlight what is known and what remains to be explored, and the type of epidemiological evidence that would be required to better address the issues. Examples include the possible association of immunization and multiple sclerosis (and other demyelinating diseases), type 1 diabetes mellitus, Guillain-Barre Syndrome, idiopathic thrombocytopenic purpura, and rheumatoid arthritis.

Chilton, P. M., Y. Huang, et al. (2001). "Bone marrow cell graft engineering: from bench to bedside." Leuk Lymphoma 41(1-2): 19-34.
Bone marrow transplantation (BMT) has the potential to treat hemoglobinopathies (sickle cell and thalassemia) autoimmunity (diabetes, lupus, multiple sclerosis, rheumatoid arthritis, Crohn's colitis) and enzyme deficiency states. Graft versus host disease (GVHD) is a major complication and limitation to the therapeutic application of BMT. There have been many clinical trials and experimental animal models that have attempted to control GVHD through the engineering of the donor bone marrow cells (BMC). Historically, several methods have demonstrated effectiveness in controlling GVHD; however they were also associated with a marked increase in the rate of graft failure. Highly purified hematopoietic stem cells (HSC) engraft quite readily in genetically-matched recipients while they do not engraft as easily in MHC-disparate recipients. The numbers of HSC must be increased 100-200 fold in order to overcome the allogeneic barrier. We were the first to phenotypically and to functionally characterize a novel cell in the bone marrow that enables engraftment of highly purified HSC in allogeneic recipients. The discovery of graft facilitating cell populations has resulted in the restoration of the engraftment-potential of purified HSC between genetically-disparate individuals. The addition of facilitating cells (FC) to T cell-depleted BMC grafts results in allogeneic engraftment without GVHD or graft failure. New strategies of BMC engineering that retain FC and HSC but avoid GVHD have allowed successful engraftment in mismatched and older recipients. These techniques have expanded the therapeutic potential of BMT to virtually every candidate as well as to non-malignant diseases in which the morbidity associated with conventional BMT could not be accepted. This article reviews the transition of the FC technology from bench to bedside and discuss the potentially broad-reaching applications of BMT and mixed chimerism.

Comi, G., L. Leocani, et al. (2001). "Physiopathology and treatment of fatigue in multiple sclerosis." J Neurol 248(3): 174-9.
Fatigue is a common symptom of patients with multiple sclerosis (MS). It is reported by about one-third of patients, and for many fatigue is the most disabling symptom. Fatigue may be associated with motor disturbances and/or mood disorders, which makes it very difficult to determine whether the fatigue is an aspect of these features or a result per se of the disease. Although peripheral mechanisms have some role in the pathogenesis of fatigue, in MS there are clear indications that the more important role is played by "central" abnormalities. Neurophysiological studies have shown that fatigue does not depend on involvement of the pyramidal tracts and implicate impairment of volitional drive of the descending motor pathways as a physiopathological mechanism. Metabolic abnormalities of the frontal cortex and basal ganglia revealed by positron-emission tomography and correlations between fatigue and magnetic resonance imaging lesion burden support this hypothesis. Some recent studies also suggest that pro-inflammatory cytokines contribute to the sense of tiredness. No specific treatments are available. Management strategies include medications, exercise, and behavioural therapy; in most cases a combined approach is appropriate.

Conti, P. and M. DiGioacchino (2001). "MCP-1 and RANTES are mediators of acute and chronic inflammation." Allergy Asthma Proc 22(3): 133-7.
Regulation of leukocyte migration and activation by chemokines are recognized as potentially important functions in the induction of acute and chronic inflammatory reactions. Regulated upon activation normal T cell expressed and presumably secreted (RANTES), monocyte chemotactic protein-1 (MCP-1), and related molecules constitute the C-C class of the beta chemokine supergene family with inflammatory properties. Here we report that in experimental studies RANTES and MCP-1 provoke mast cell activation and increase histidine decarboxylase mRNA expression in a dose-dependent manner. Moreover, injections of RANTES and MCP-1 in the rat skin cause mast cell, eosinophil, and macrophage recruitment, and prostaglandin E2 (PGE2) generation. In a chronic inflammatory model MCP-1 was found to mediate the recruitment of mononuclear cells in calcified granulomas. In addition, MCP-1 mediated parasitic infections caused by Trichinella spiralis. In accordance with other studies, RANTES and MCP-1 were found to play an important role in the lung allergic inflammation, lung leukocyte infiltration, bronchial hyperresponsiveness, and the recruitment of eosinophils in the pathogenesis of asthma. Here for the first time we propose a new mechanism of pulmonary airway inflammation where RANTES and MCP-1 are deeply involved. We also studied the apparent role played by RANTES in the pathogenesis of relapsing-remitting multiple sclerosis enhancing the inflammatory response within the nervous system.

Correale, J. and E. Cristiano (2001). "[Current concepts on the use of some immunomodulatory drugs in the treatment of multiple sclerosis]." Medicina (B Aires) 61(4): 470-80.
Biotechnological research and a better understanding of the immunopathogenesis of multiple sclerosis (MS) have recently led to major breakthroughs in treatment. Different drugs that modify the disease process such as interferon beta 1a, interferon beta 1b and glatiramer acetate are now available. Decisions about initiation of therapy and choice of agent should be individualised based on the severity and activity of the disease, concomitant illnesses, adverse effects of the drugs, lifestyle issues, and patient preferences. These different drugs were tested in different clinical trials that used different designs, patient populations, endpoints and statistical analysis. Therefore, simple comparisons between them are hazardous. In this article, the pivotal clinical trials of beta interferons and glatiramer acetate in the treatment of MS are reviewed, and recommendations for their appropriate use are provided. Several ongoing and planned clinical trials in various stages of disease will help to define further the role of these agents in the treatment of multiple sclerosis.

Couture, R., M. Harrisson, et al. (2001). "Kinin receptors in pain and inflammation." Eur J Pharmacol 429(1-3): 161-76.
Kinins are among the most potent autacoids involved in inflammatory, vascular and pain processes. These short-lived peptides, including bradykinin, kallidin and T-kinin, are generated during tissue injury and noxious stimulation. However, emerging evidence also suggests that kinins are stored in neuronal elements of the central nervous system (CNS) where they are thought to play a role as neuromediators in various cerebral functions, particularly in the control of nociceptive information. Kinins exert their biological effects through the activation of two transmembrane G-protein-coupled receptors, denoted bradykinin B(1) and B(2). Whereas the B(2) receptor is constitutive and activated by the parent molecules, the B(1) receptor is generally underexpressed in normal tissues and is activated by kinins deprived of the C-terminal Arg (des-Arg(9)-kinins). The induction and increased expression of B(1) receptor occur following tissue injury or after treatment with bacterial endotoxins or cytokines such as interleukin-1 beta and tumor necrosis factor-alpha. This review summarizes the most recent data from various animal models which convey support for a role of B(2) receptors in the acute phase of the inflammatory and pain response, and for a role of B(1) receptors in the chronic phase of the response. The B(1) receptor may exert a strategic role in inflammatory diseases with an immune component (diabetes, asthma, rheumatoid arthritis and multiple sclerosis). New information is provided regarding the role of sensory mechanisms subserving spinal hyperalgesia and intrapleural neutrophil migration that occur upon B(1) receptor activation in streptozotocin-treated rats, a model of insulin-dependent diabetes mellitus in which the B(1) receptor seems to be rapidly overexpressed. Although it is widely accepted that the blockade of kinin receptors with specific antagonists could be of benefit in the treatment of somatic and visceral inflammation and pain, recent molecular and functional evidence suggests that the activation of B(1) receptors with an agonist may afford a novel therapeutic approach in the CNS inflammatory demyelinating disorder encountered in multiple sclerosis by reducing immune cell infiltration (T-lymphocytes) into the brain. Hence, the B(1) receptor may exert either a protective or detrimental effect depending on the inflammatory disease. This dual function of the B(1) receptor deserves to be investigated further.

Couvreur, G. (2001). "[Evaluation of follow-up and evolution of multiple sclerosis]." Rev Neurol (Paris) 157(8-9 Pt 2): 1143-51.
The aim of this paper is to review the quantitative methods used for assessing neurological status in multiple sclerosis patients. The Expanded Disability Status Scale (EDSS) is the most wide used. Its psychometric properties, validity, and inter- and intra-rater reliability are modest and responsiveness is weak. Similar results are obtained with the other scales used. The recently developed Multiple Sclerosis Functional Composite (MSFC) scale for clinical trials satisfies this requirement, but is not suitable for individual evaluation. There is no scale in French for assessment of cognitive disturbances and only one, the SEP-90, for quality of life. Brain and spinal cord abnormalities with conventional magnetic resonance imaging parameters (T1, T2-weighted and gadolinium enhanced images) have a weak relationship with disability. New magnetic resonance techniques (magnetic resonance spectroscopy and magnetized transfer imaging) would be more sensitive and should be further investigated.

Crawley, F., I. Saddeh, et al. (2001). "Acute pulmonary oedema: presenting symptom of multiple sclerosis." Mult Scler 7(1): 71-2.
Acute pulmonary oedema and headache are both common. The former is usually cardiogenic in origin. Severe headache of sudden onset in a young person may be suggestive of subarachnoid headache. We describe a 24-year-old man who presented with headache and pulmonary oedema, finally ascribed to multiple sclerosis. This is the first report of neurogenic pulmonary oedema as the first symptom of multiple sclerosis. We review the neuroanatomical basis and experimental evidence for neurogenic pulmonary oedema.

Cross, A. H., J. L. Trotter, et al. (2001). "B cells and antibodies in CNS demyelinating disease." J Neuroimmunol 112(1-2): 1-14.
There is much evidence to implicate B cells, plasma cells, and their products in the pathogenesis of MS. Despite unequivocal evidence that the animal model for MS, EAE, is initiated by myelin-specific T cells, there is accumulating evidence of a role for B cells, plasma cells, and their products in EAE pathogenesis. The role(s) played by B cells, plasma cells, and antibodies in CNS inflammatory demyelinating diseases are likely to be multifactorial and complex, involving distinct and perhaps opposing roles for B cells versus antibody.

Dammann, O., H. Hagberg, et al. (2001). "Is periventricular leukomalacia an axonopathy as well as an oligopathy?" Pediatr Res 49(4): 453-7.
Periventricular leukomalacia is a white matter disorder, the neonatal cranial ultrasound images of which predict long-term developmental limitations among preterm infants. The vulnerability of oligodendrocytes has led to the hypothesis that oligodendrocytes suffer the primary damage, with axonal damage occurring as a consequence. In this article, we discuss the differential role of oligodendrocytes and axons in this disorder's etiology, offering analogies from the multiple sclerosis and hydrocephalus literature. We conclude that it is too early to view periventricular leukomalacia exclusively as a consequence of oligodendrocyte damage and/or maldevelopment.

Davidson, A. and B. Diamond (2001). "Autoimmune diseases." N Engl J Med 345(5): 340-50.

Davies, N. M., J. Longstreth, et al. (2001). "Misoprostol therapeutics revisited." Pharmacotherapy 21(1): 60-73.
Misoprostol, a prostaglandin E1 analog, is a racemate of four stereoisomers. On administration it rapidly de-esterifies to its active form, misoprostolic acid. Misoprostolic acid is 85% albumin bound and has a half-life of approximately 30 minutes. It is excreted in urine as inactive metabolites. No significant drug interactions have been reported. Besides its gastrointestinal protective and uterotonic activities, misoprostol regulates various immunologic cascades. It inhibits platelet-activating factor and leukocyte adherence, and modulates adhesion molecule expression. It protects against gut irradiation injury, experimental gastric cancer, enteropathy, and constipation. It improves nutrient absorption in cystic fibrosis. Misoprostol has utility in acetaminophen and ethanol hepatotoxicity, hepatitis, and fibrosis. It is effective in asthmatics and aspirin-sensitive asthmatic and allergic patients. It lowers cholesterol and severity of peripheral vascular diseases, prolongs survival of cardiac and kidney transplantation, synergizes cyclosporine, and protects against cyclosporine-induced renal damage. It works against drug-induced renal damage, interstitial cystitis, lupus nephritis, and hepatorenal syndrome. It is useful in periodontal disease and dental repair. Misoprostol enhances glycosoaminoglycan synthesis in cartilage after injury. It prevents ultraviolet-induced cataracts and reduces intraocular pressure in glaucoma and ocular hypertension. It synergizes antiinflammatory and analgesic effects of diclofenac or colchicine and has been administered to treat trigeminal neuralgic pain. It reduces chemotherapy-induced hair loss and recovery time from burn injury, and is effective in treating sepsis, multiple sclerosis, and pancreatitis.

Davis, K. M. and J. Y. Wu (2001). "Role of glutamatergic and GABAergic systems in alcoholism." J Biomed Sci 8(1): 7-19.
The pharmacological effects of ethanol are complex and widespread without a well-defined target. Since glutamatergic and GABAergic innervation are both dense and diffuse and account for more than 80% of the neuronal circuitry in the human brain, alterations in glutamatergic and GABAergic function could affect the function of all neurotransmitter systems. Here, we review recent progress in glutamatergic and GABAergic systems with a special focus on their roles in alcohol dependence and alcohol withdrawal-induced seizures. In particular, NMDA-receptors appear to play a central role in alcohol dependence and alcohol-induced neurological disorders. Hence, NMDA receptor antagonists may have multiple functions in treating alcoholism and other addictions and they may become important therapeutics for numerous disorders including epilepsy, Parkinson's disease, amyotrophic lateral sclerosis, Huntington's chorea, anxiety, neurotoxicity, ischemic stroke, and chronic pain. One of the new family of NMDA receptor antagonists, such as DETC-MESO, which regulate the redox site of NMDA receptors, may prove to be the drug of choice for treating alcoholism as well as many neurological diseases.

De Broe, S., F. Christopher, et al. (2001). "The role of specialist nurses in multiple sclerosis: a rapid and systematic review." Health Technol Assess 5(17): 1-47.
BACKGROUND: Multiple sclerosis (MS) is a disease of the central nervous system. The cause is unknown. There are about 80-160 people with MS per 100,000 population, with twice as many women affected as men. The management of individuals with MS includes treatment of acute relapses and chronic symptoms. The care of MS patients is provided by various healthcare professionals, such as general practitioners (GPs), neurologists, physiotherapists, occupational therapists and nurses. Some MS patients have access to an MS specialist nurse, although this provision varies geographically. OBJECTIVES: The aim of this report is to assess the effectiveness and relative cost-effectiveness of MS specialist nurses in improving care and outcomes for patients with MS. METHODS: A systematic review of the literature, involving a range of databases, was performed. Full details are described in the main report. RESULTS: Only one study was identified that tried to evaluate the benefit of MS specialist nurses. The study concluded that MS patients and their carers found the MS specialist nurse to be helpful, particularly in improving their knowledge of MS, ability to cope, mood and confidence about the future. GPs also reported finding the nurse to be helpful with their MS patients, and 40% of the GPs stated they would purchase the services of an MS specialist nurse if their practices became fundholding. However, there were considerable methodological weaknesses inherent in the study design, and it was unclear whether the results of the study could be extrapolated to other settings or to other MS patient groups. RESULTS - ONGOING RESEARCH: There are two ongoing research studies regarding MS specialist nurses. One of these studies involves the provision of MS nurses to several areas, but also has two control populations to allow evaluation of the health benefits of the nurses to MS patients and their carers. This study will help to fill the evidence gap. RESULTS - COSTS: The costs of providing MS specialist nurses consist of their yearly salary (usually NHS grade G), as well as additional costs for travelling, administration, computer and telephone use, a pension scheme, National Insurance and study leave. The MS Society of Great Britain and Northern Ireland allows a generous total yearly cost to the employer of 40,000 pounds. CONCLUSIONS: The present evidence does not make it possible to comment with any certainty on the value of specialist nurses in MS. The best evidence available to the authors is specialist opinion from neurologists and nurses, and comments from patients with MS; this opinion supports the provision of MS specialist nurses. CONCLUSIONS - RECOMMENDATIONS FOR RESEARCH: Further research is needed before it will be feasible to make firm recommendations on the value of MS specialist nurses relative to other possible uses of funds.

De Groot, C. J. and M. N. Woodroofe (2001). "The role of chemokines and chemokine receptors in CNS inflammation." Prog Brain Res 132: 533-44.

Deluca, H. F. and M. T. Cantorna (2001). "Vitamin D: its role and uses in immunology." Faseb J 15(14): 2579-85.
In recent years there has been an effort to understand possible noncalcemic roles of vitamin D, including its role in the immune system and, in particular, on T cell-medicated immunity. Vitamin D receptor is found in significant concentrations in the T lymphocyte and macrophage populations. However, its highest concentration is in the immature immune cells of the thymus and the mature CD-8 T lymphocytes. The significant role of vitamin D compounds as selective immunosuppressants is illustrated by their ability to either prevent or markedly suppress animal models of autoimmune disease. Results show that 1,25-dihydroxyvitamin D3 can either prevent or markedly suppress experimental autoimmune encephalomyelitis, rheumatoid arthritis, systemic lupus erythematosus, type I diabetes, and inflammatory bowel disease. In almost every case, the action of the vitamin D hormone requires that the animals be maintained on a normal or high calcium diet. Possible mechanisms of suppression of these autoimmune disorders by the vitamin D hormone have been presented. The vitamin D hormone stimulates transforming growth factor TGFbeta-1 and interleukin 4 (IL-4) production, which in turn may suppress inflammatory T cell activity. In support of this, the vitamin D hormone is unable to suppress a murine model of the human disease multiple sclerosis in IL-4-deficient mice. The results suggest an important role for vitamin D in autoimmune disorders and provide a fertile and interesting area of research that may yield important new therapies.

Derfuss, T., R. Hohlfeld, et al. (2001). "[Multiple sclerosis. Chlamydia hypothesis in debate]." Nervenarzt 72(10): 820-3.
Recently, an association between multiple sclerosis and Chlamydia pneumoniae infection has been suggested. Because standardized PCR protocols are lacking, a series of studies could not clarify whether C. pneumoniae is present in brain tissue and CSF of MS patients. Therefore, other studies focused on the humoral immune response against C. pneumoniae: 24% of MS patients, but only 5% of the control patients showed intrathecally produced antibodies against C. pneumoniae. If an infection with C. pneumoniae was involved in the pathogenesis of MS, one would expect that, in analogy to other infections of the CNS, the oligoclonal bands in the CSF of MS patients would recognize the responsible agent. However, the results we obtained by affinity-mediated immunoblots showed that the oligoclonal bands in the CSF of MS patients are not directed against Chlamydia antigen. In contrast to this, we found that the immunoglobulins in the CSF of neuroborreliosis patients reacted strongly against Borrelia antigen in the affinity-mediated immunoblots. In light of these results we assume that the intrathecal immunoglobulin production against C. pneumoniae is part of a polyspecific immune response. Thus, it is not likely that C. pneumoniae is causally linked to the pathogenesis of multiple sclerosis.

Dimitri, D. (2001). "[Electrophysiological diagnostic criteria of multiple sclerosis]." Rev Neurol (Paris) 157(8-9 Pt 2): 981-6.
Visual and somatosensory evoked potentials are useful to identify patients at increased risk for developing Multiple sclerosis (MS). However Magnetic Resonance Imaging (MRI) is more sensitive and predictive. More studies are needed to determine the optimal sequence of evoked potentials and MRI that best predict the development of MS especially in monosymptomatic manifestations and in primary progressive MS.

Dimitri, D. (2001). "[Biological diagnostic criteria in multiple sclerosis]." Rev Neurol (Paris) 157(8-9 Pt 2): 968-73.
The clinical diagnosis of multiple sclerosis (MS) can be supported by the analysis of the cerebrospinal fluid (CSF) by the detection of an inflammatory reaction in central nervous system. The most sensitive method for the detection of oligoclonal IgG bands is isoelectric focusing. However magnetic resonance imaging (MRI) is more sensitive and predictive. Nevertheless CSF study is useful in monosymptomatic manifestation when MRI is normal, and primordial in primary progressive MS diagnosis. More studies are needed to determine the optimal sequence of CSF study, MRI and evoked potentials in the diagnosis of different presentation of MS.

Dimitri, D. (2001). "[Diagnostic criteria of multiple sclerosis with reference to different clinical forms]." Rev Neurol (Paris) 157(8-9 Pt 2): 914-28.
This paper reviews the validity of clinical diagnostic criteria and clinical course classification. Validation based on the pathological verification is not available. MS diagnosis remains clinical based on the objective demonstration of dissemination of lesions suggestive of MS in both time and space. Also clinical features are not specific and sensitive enough. MRI is primordial. MRI diagnosis criteria are discussed. Clinical course classification is difficult in regard to the extreme heterogeneity of the disease. Classical distinction between recurrent and progressive forms is reviewed from natural history studies and recent MRI and pathological findings. Recent studies focus on presentation including monosymptomatic disease and primary progressive forms.

Dorries, R. (2001). "The role of T-cell-mediated mechanisms in virus infections of the nervous system." Curr Top Microbiol Immunol 253: 219-45.
T lymphocytes play a decisive role in the course and clinical outcome of viral CNS infection. Summarizing the information presented in this review, the following sequence of events might occur during acute virus infection: After invasion of the host and a few initial rounds of replication, the virus reaches the CNS in most cases by hematogeneous spread. After passage through the BBB, CNS cells are infected and replication of virus in brain cells causes activation of the surrounding microglia population. Moreover, local production of IFN-alpha/beta induces expression of MHC antigens on CNS cells, and microglial cells start to phagocytose cellular debris, which accumulates as a result of virus-induced cytopathogenic effects. Upon phagocytosis, microglia becomes more activated; they up-regulate MHC molecules, acquire antigen presentation capabilities and secrete chemokines. This will initiate up-regulation of adhesion molecules on adjacent endothelial cells of the BBB. Transmigration of activated T lymphocytes through the BBB is followed by interaction with APC, presenting the appropriate peptides in the context of MHC antigens. It appears that CD8+ T lymphocytes are amongst the first mononuclear cells to arrive at the infected tissue. Without a doubt, their induction and attraction is deeply influenced by natural killer cells, which, after virus infection, secrete IFN-gamma, a cytokine that stimulates CD8+ T cells and diverts the immune response to a TH1-type CD4+ T cell-dominated response. Following the CD8+ T lymphocytes, tissue-penetrating, TH1 CD4+ T cells contact local APC. This results in a tremendous up-regulation of MHC molecules and secretion of more chemotactic and toxic substances. Consequently an increasing number of inflammatory cells, including macrophages/microglia and finally antibody-secreting plasma cells, are attracted to the site of virus infection. All trapped cells are mainly terminally differentiated cells that are going to enter apoptosis during or shortly after exerting their effector functions. The clinical consequences and the influence of the effector phase on the further course of the infection depends on the balance and fine-tuning of the contributing lymphoid cell populations. Generally, any delay in the recruitment of effector lymphocytes to the tissue or an unbalanced combination of lymphocyte subsets allows the virus to spread in the CNS, which in turn will cause severe immune-mediated tissue effects as well as disease. If either too late or partially deficient, the immune system response may contribute to a lethal outcome or cause autosensitization to brain-specific antigens by epitope spreading to the antigen-presenting system in peripheral lymphoid tissue. This could form the basis for subsequent booster reactions of autosensitized CD4+ T cells--a process that finally will end in an inflammatory autoimmune reaction, which in humans we call multiple sclerosis. In contrast, a rapid and specific local response in the brain tissue will result in efficient limitation of viral spread and thereby a subclinical immune system-mediated termination of the infection. After clearance of virus-infected cells, downsizing of the local response probably occurs via self-elimination of the contributing T cell populations and/or by so far unidentified signal pathways. However, much of this is highly speculative, and more data have to be collected to make decisive conclusions regarding this matter. Several strategies have been developed by viruses to escape T cell-mediated eradication, including interference with the MHC class I presentation pathway of the host cell or "hiding" in cells which lack MHC class I expression. This may result in life-long persistence of the virus in the brain, a state which probably is actively controlled by T lymphocytes. Under severe immunosuppression, however, reactivation of viral replication can occur, which is a lethal threat to the host.

Dupel-Pottier, C. (2001). "[Diagnostic criteria of multiple sclerosis in neuroimaging]." Rev Neurol (Paris) 157(8-9 Pt 2): 949-62.
To date, there is no biological test available with enough confidence to make alone a diagnosis of Multiple Sclerosis (MS). MS diagnosis criteria are then an association of clinical and para clinical criteria that allow an objective demonstration of dissemination of lesions in both time and space. Adapted MRI criteria from Barkhof have a good sensitivity and the best specificity to evaluate MS. 3 of 4 criteria are necessary: 1 gadolinium enhancing lesion or 9 T2 hyper intense lesions; at least 1 infratentorial lesion; at least 1 juxtacortical lesion; at least four periventricular lesions; NB: 1 spinal cord lesion can substitute for 1 brain lesion. News methods as spectroscopy, magnetization transfer, diffusion MRI and functional MRI complete results of conventional MRI and give new informations about physiopathology of MS demyelinating lesions.

Dupel-Pottier, C. (2001). "[Diagnostic criteria of borderline forms of multiple sclerosis]." Rev Neurol (Paris) 157(8-9 Pt 2): 935-43.
Border forms of multiple sclerosis (MS) can be separated in two groups: either they are variants of MS or they are distinct from MS but they share several characteristics with MS thus representing for some of them a continuum with MS. All these entities are central nervous system demyelinating diseases. Here we describe, for the first group, MS in childhood, MS in elderly subjects, Balo's concentric sclerosis, Schilder's myelinoclastic diffuse sclerosis and MS simulating a mass lesion, and for the second group, acute disseminated encephalomyelitis and Devic's neuromyelitis optica.

Eggenberger, E. R. (2001). "Inflammatory optic neuropathies." Ophthalmol Clin North Am 14(1): 73-82.
Inflammatory optic neuropathies are common in clinical practice. Monosymptomatic optic neuritis has important implications for the development of multiple sclerosis. In the patient presenting with monosymptomatic optic neuritis, MR imaging provides critical prognostic information concerning the development of MS. The ONTT provided valuable information regarding the natural history and therapy of optic neuritis. Oral prednisone alone is contraindicated in the treatment of optic neuritis because of its association with increased recurrence rate of optic neuritis. Intravenous methylprednisolone remains a viable treatment option to slightly increase the rate of recovery and provide a degree of short-term protection against the subsequent development of MS. Other inflammatory optic neuropathies include sarcoidosis, neuroretinitis, and Devic's disease with each possessing distinct clinical characteristics and treatment approaches.

Enbom, M. (2001). "Multiple sclerosis and Kaposi's sarcoma--chronic diseases associated with new human herpesviruses?" Scand J Infect Dis 33(9): 648-58.
Two diseases that for many years have been suspected to be of viral origin are multiple sclerosis (MS) and Kaposi's sarcoma (KS). With the use of a new technique called representational difference analysis both these diseases have recently been associated with new lymphotropic herpesviruses, i.e. human herpesviruses (HHV) 6 and 8. HHV-6 is a ubiquitous virus and the etiological agent of exanthema subitum. Viral neuroinvasion occurs frequently in primary HHV-6 infection, and meningitis, encephalitis and demyelination have been described as rare complications. A relation with MS has been suggested for HHV-6, as the virus has been detected in MS plaques in the brain. Data from different studies are, however, conflicting and a definitive role for HHV-6 in MS pathogenesis has not been established. HHV-8 is believed to be the causative agent of KS, and is also associated with some rare hematological malignancies. The viral genome contains several potential oncogenes that are believed to have been picked up from the human genome during evolution. The role of HHV-8 in healthy, immunocompetent individuals is however uncertain. In conclusion, the full spectrum of human diseases associated with these new viruses is not yet understood, and rapid developments in molecular biology will continue to shed new light on the interactions between herpesviruses and their hosts.

Enbom, M. (2001). "Human herpesvirus 6 in the pathogenesis of multiple sclerosis." Apmis 109(6): 401-11.
Multiple sclerosis (MS) is one of the most common disabling neurological diseases affecting young adults. It is a chronic disease characterised by inflammation and demyelination. The aetiology of MS is still unknown, but involvement of viruses has been suspected for many years. Recently much interest has focused on human herpesvirus 6 (HHV-6), since the virus has been detected in MS plaques in the brain and patients with MS have been shown to have an aberrant immune response to HHV-6. Results from different studies are, however, conflicting and in the light of the long list of previous claims to have found the viral aetiology of MS it is necessary to interpret the HHV-6 findings with great caution. Possible mechanisms for virally induced demyelination and autoimmunity are discussed in this review, and the evidence for and against a role for HHV-6 in MS is summarised.

Engelhardt, B., K. Wolburg-Buchholz, et al. (2001). "Involvement of the choroid plexus in central nervous system inflammation." Microsc Res Tech 52(1): 112-29.
During inflammatory conditions in the central nervous system (CNS), immune cells immigrate into the CNS and can be detected in the CNS parenchyma and in the cerebrospinal fluid (CSF). The most comprehensively investigated model for CNS inflammation is experimental autoimmune encephalomyelitis (EAE), which is considered the prototype model for the human disease multiple sclerosis (MS). In EAE autoagressive CD4(+), T cells gain access to the CNS and initiate the molecular and cellular events leading to edema, inflammation, and demyelination in the CNS. The endothelial blood-brain barrier (BBB) has been considered the obvious place of entry for the circulating immune cells into the CNS. A role of the choroid plexus in the pathogenesis of EAE or MS, i.e., as an alternative entry site for circulating lymphocytes directly into the CSF, has not been seriously considered before. However, during EAE, we observed massive ultrastructural changes within the choroid plexus, which are different from changes observed during hypoxia. Using immunohistochemistry and in situ hybridization, we observed expression of VCAM-1 and ICAM-1 in the choroid plexus and demonstrated their upregulation and also de novo expression of MAdCAM-1 during EAE. Ultrastructural studies revealed polar localization of ICAM-1, VCAM-1, and MAdCAM-1 on the apical surface of choroid plexus epithelial cells and their complete absence on the fenestrated endothelial cells within the choroid plexus parenchyme. Furthermore, ICAM-1, VCAM-1, and MAdCAM-1 expressed in choroid plexus epithelium mediated binding of lymphocytes via their known ligands. In vitro, choroid plexus epithelial cells can be induced to express ICAM-1, VCAM-1, MAdCAM-1, and, additionally, MHC class I and II molecules on their surface. Taken together, our observations imply a previously unappreciated function of the choroid plexus in the immunosurveillance of the CNS.

Evseev, V. A., T. V. Davydova, et al. (2001). "Dysregulation in neuroimmunopathology and perspectives of immunotherapy." Bull Exp Biol Med 131(4): 305-8.
Dysregulation of neuroimmune connections is a primary or secondary pathogenic factor of some CNS diseases. Autoimmune aggression is typical of multiple sclerosis, Alzheimer's disease, and epilepsy, while dysregulation characterized by enhanced production of autoantibodies to neurotransmitters and activation of cell factors is characteristic of alcoholism and drug abuse. In experimental models of alcoholism and drug addiction, protective effects of antiserotonin antibodies are mediated by immune cells stimulated by these antibodies. These effects can be used in the therapy of various forms of neuroimmunopathology by the method of adoptive immunotherapy.

Evtushenko, S. K. and I. N. Derevianko (2001). "[Magnetic resonance imaging in the diagnosis of multiple sclerosis]." Zh Nevrol Psikhiatr Im S S Korsakova 101(4): 61-4.

Fehder, W. P. and S. D. Douglas (2001). "Interactions between the nervous and immune systems." Semin Clin Neuropsychiatry 6(4): 229-40.
Substantial morphologic and functional evidence exists that supports the reciprocal interactions that occur between the nervous and immune systems. The nervous and immune systems have been increasingly found to use a common chemical language in the form of neuropeptides, cytokines, and hormones. Sophisticated immunologic techniques such as the identification and detection of immune cell surface markers enable researchers to determine the origin and activity of diverse cells in the blood and central nervous system. These techniques have elucidated the activity of immune cells in the central nervous system (CNS) that was previously thought to be privileged from immune surveillance in the presence of an intact blood brain barrier. Immune cells in the CNS play a central role in several degenerative diseases such as Alzheimer's disease, Huntington's disease, Multiple sclerosis, AIDS dementia complex, and nerve destruction associated with trauma. Immune cells also play a role in demyelinating peripheral nerve disorders. Cytokines and neuropeptides secreted by peripheral immune cells have profound effects on behavior that is mediated by the CNS. The close integration between immune and nervous system responses is being increasingly recognized in physiologic and pathologic conditions.

Filippi, M. (2001). "Linking structural, metabolic and functional changes in multiple sclerosis." Eur J Neurol 8(4): 291-7.
In patients with multiple sclerosis (MS), conventional magnetic resonance imaging (MRI) has markedly improved our ability to detect the macroscopic abnormalities of the brain and spinal cord. New quantitative magnetic resonance (MR) approaches with increased sensitivity to subtle normal-appearing white matter (NAWM) and grey matter changes and increased specificity to the heterogeneous pathological substrates of MS may give information complementary to conventional MRI. Magnetization transfer imaging (MTI) and diffusion-weighted imaging (DWI) have the potential to provide important information on the structural changes occurring within and outside T2-visible lesions. Magnetic resonance spectroscopy (MRS) adds information on the biochemical nature of such changes. Functional MRI might quantify the efficiency of brain plasticity in response to MS injury and improve our understanding of the link between structural damage and clinical manifestations. The present review summarizes how the application of these MR techniques to the study of MS is dramatically changing our understanding of how MS causes irreversible neurological deficits.

Filippi, M. and M. Inglese (2001). "Overview of diffusion-weighted magnetic resonance studies in multiple sclerosis." J Neurol Sci 186 Suppl 1: S37-43.
Diffusion-weighted magnetic resonance imaging (DW-MRI) provides a unique form of MR contrast that enables the diffusional motion of water molecules to be quantitatively measured. As a consequence, DW-MRI provides information about the size, shape, integrity, and orientation of brain structures. Pathological processes able to alter tissue integrity by removing or modifying some of the structural barriers that normally restrict water molecular motion in biological tissues cause changes in water diffusion characteristics, which can be measured in-vivo using DW-MRI. Although DW-MRI has been shown to be of great clinical utility in the assessment of patients with cerebral ischemia, it is also increasingly being used to quantify in-vivo the extent and severity of multiple sclerosis (MS) pathology. The pathological elements of MS have the potential to alter the permeability or geometry of structural barriers to water molecular motion in the brain, optic nerve and spinal cord. The present review outlines the major contributions given by DW-MRI for the quantification of MS-related damage and for the understanding of MS pathophysiology.

Filippi, M. (2001). "Multiple sclerosis: a white matter disease with associated gray matter damage." J Neurol Sci 185(1): 3-4.

Finiels, H., D. Strubel, et al. (2001). "[Deglutition disorders in the elderly. Epidemiological aspects]." Presse Med 30(33): 1623-34.
THE PREVALENCE: The exact prevalence of deglutition disorders in the elderly is not known. It appears frequent in very old patients and in those suffering from polypathological symptoms, affecting 50% of the populations in long-term care units. THE EFFECTS OF AGING: Physiological aging alters various parameters of swallowing, however it seems that these modifications related to age have little effect on healthy subjects. However, they may increase vulnerability in those presenting with intercurrent pathologies. CONCOMITANT DISORDERS: Other than the decrease in efficient mastication and the existence of xerostomia, frequently observed contributing factors, many diseases may be responsible for dysphagia in the elderly. Neurological disorders, particularly cerebral vascular diseases, central nervous system degenerative disorders and neuro-motor diseases predominate. In the aging, muscular disorders and after effects of various diseases can set-in. Modifications in oropharyngeal anatomy generally results from cancerous lesions of the aero-digestive junction, but also, occasionally from extrinsic compression that does not necessarily reflect a neoplastic etiology. Zenker's diverticulitis represents a cause of dysphagia specific to the elderly. Problems in swallowing of iatrogenic origin are also frequent, following cervical radiotherapy or after oropharyngeal surgery, during tracheal intubation or when using feeding tubes and also during various medical treatments. UNDERRATED CONSEQUENCES: Dysphagia leads to multiple morbid after effects, primarily alteration in quality of life, dehydration, undernutrition, asphyxia and congestion and recurrent infections of the respiratory tract. The responsibility of deglutition disorders in the occurrence of these complications is difficult to assess in weak elderly subjects because of the frequent concomitance with multiple deficiencies and incapacities.

Fischer, C., N. Andre-Obadia, et al. (2001). "[Diagnostic criteria of multiple sclerosis: electrophysiological criteria]." Rev Neurol (Paris) 157(8-9 Pt 2): 974-80.
We have made a review on the use of evoked potentials in multiple sclerosis (MS) for the past 30 years, in the diagnosis of MS, to disclose subclinical lesions or to assess atypical symptoms. Yet the role of evoked potentials in evaluation of multiple sclerosis has been changed since MRI is now widely and easily used for the diagnosis of MS. Evoked potentials are useful when symptoms are atypical without any objective impairment and when symptoms have already recovered at the time of clinical examination. Visual evoked potentials and somatosensory evoked potentials are widely used thanks to their diagnostic value and their ability to disclose spatial dissemination of multiple sclerosis. Evoked potentials have to be recorded in validated technical conditions such as to ensure reliability of data and have to be interpreted in reference to a population of healthy people recorded in the same conditions and in the same age range as MS patients.

Flammer, J., M. Pache, et al. (2001). "Vasospasm, its role in the pathogenesis of diseases with particular reference to the eye." Prog Retin Eye Res 20(3): 319-49.
Vasospasm can have many different causes and can occur in a variety of diseases, including infectious, autoimmune, and ophthalmic diseases, as well as in otherwise healthy subjects. We distinguish between the primary vasospastic syndrome and secondary vasospasm. The term "vasospastic syndrome" summarizes the symptoms of patients having such a diathesis as responding with spasm to stimuli like cold or emotional stress. Secondary vasospasm can occur in a number of autoimmune diseases, such as multiple sclerosis, lupus erythematosus, antiphospholipid syndrome, rheumatoid polyarthritis, giant cell arteritis, Behcet's disease, Buerger's disease and preeclampsia, and also in infectious diseases such as AIDS. Other potential causes for vasospasm are hemorrhages, homocysteinemia, head injury, acute intermittent porphyria, sickle cell disease, anorexia nervosa, Susac syndrome, mitochondriopathies, tumors, colitis ulcerosa, Crohn's disease, arteriosclerosis and drugs. Patients with primary vasospastic syndrome tend to suffer from cold hands, low blood pressure, and even migraine and silent myocardial ischemia. Valuable diagnostic tools for vasospastic diathesis are nailfold capillary microscopy and angiography, but probably the best indicator is an increased plasma level of endothelin-1. The eye is frequently involved in the vasospastic syndrome, and ocular manifestations of vasospasm include alteration of conjunctival vessels, corneal edema, retinal arterial and venous occlusions, choroidal ischemia, amaurosis fugax, AION, and glaucoma. Since the clinical impact of vascular dysregulation has only really been appreciated in the last few years, there has been little research in the according therapeutic field. The role of calcium channel blockers, magnesium, endothelin and glutamate antagonists, and gene therapy are discussed.

Fontaine, B. (2001). "[Borderline forms of multiple sclerosis]." Rev Neurol (Paris) 157(8-9 Pt 2): 929-34.
Multiple sclerosis (MS) has been described for more than a century, but its cause remains unknown and no simple diagnostic marker is available. Therefore, it is not surprising that numerous articles were written on closely related diseases, borderline forms of multiple sclerosis. Different forms have been distinguished: a clinical form of MS (Devic's neuromyelitis optica), pathological forms (Balo, Schilder, Maburg), forms associated with MS (peripheral neuropathy, autoantibodies) and closely related disorders (acute disseminated encephalomyelitis).

Francis, D. A. (2001). "Glatiramer acetate (Copaxone)." Int J Clin Pract 55(6): 394-8.
Glatiramer acetate (Copaxone) is a novel preparation of synthetic peptides composed of four amino acids. Laboratory studies have shown that it prevents, or modifies, experimental allergic encephalomyelitis, the animal model for multiple sclerosis (MS), in several mammalian species. Its mode of action has not been fully elucidated but it is known to induce suppresser T-cells, known to be deficient in MS, and competitively inhibits the effect of CNS myelin antigens, thought to be important in the pathogenesis of MS, through MHC blockade. Controlled clinical trials have shown it to improve the natural history of MS by reducing both the relapse rate and the resultant disability. GA shows similar efficacy to interferon-beta (IFN-beta) but with fewer systemic side-effects and appears to be better tolerated by patients. It has thus justified its place in the new era of disease-modifying treatments for MS. While the evidence suggests GA should be considered as first-line therapy in selected patients, its differing mechanism of action also gives patients and doctors the option of an alternative agent when the efficacy of IFN-beta is waning or side-effects predominate.

Franklin, R. J., G. L. Hinks, et al. (2001). "What roles do growth factors play in CNS remyelination?" Prog Brain Res 132: 185-93.

Freeman, J. A. (2001). "Improving mobility and functional independence in persons with multiple sclerosis." J Neurol 248(4): 255-9.
Persons with multiple sclerosis (MS) commonly experience restrictions in mobility and everyday functional activities. A wide range of factors including physical, psychological, environmental and economic issues may contribute to these difficulties. This is particularly the case as the disease evolves, and the impairments and disabilities become more numerous, inter-related and hence more complex. Effective management of these complex problems requires assessment and intervention from a variety of different perspectives by using a coordinated, goal-oriented, multi-disciplinary management approach. Crucially, it requires management to be considered from a long-term perspective rather than as a fragmented series of isolated "quick-fixes".

Frohman, E. M., N. L. Monson, et al. (2001). "Autonomic regulation of neuroimmunological responses: implications for multiple sclerosis." J Clin Immunol 21(2): 61-73.
The expression of neural regulatory molecules by immune cells that infiltrate the nervous system upon injury may be a mechanism for cross regulation between the nervous system and the immune system. Several lines of evidence implicate nerve growth factor signaling through its receptors as a potential source of communication between the two systems. The expression of beta-adrenergic receptors and sympathetic innervation of lymphoid organs represents another example of communication between the immune and the nervous system. In this review, we discuss mechanisms of how factors in common between the nervous system and the immune system may result in regulatory circuits which are important in both healthy and diseased states. These studies may have relevance for a number of inflammatory conditions in humans, including multiple sclerosis.

Fuhr, P. and L. Kappos (2001). "Evoked potentials for evaluation of multiple sclerosis." Clin Neurophysiol 112(12): 2185-9.
The role of evoked potentials (EP) in the assessment of multiple sclerosis (MS) has changed over the last decade. This is largely due to progress in imaging techniques. But while MRI has a greater diagnostic sensitivity, EP remain a useful diagnostic tool in many clinical situations. Moreover, recent studies demonstrate the utility of EP for monitoring and predicting the course of the disease in patient groups, although not yet in individuals. For these purposes, EP show better results than conventional MRI. In the near future, new developments in electrophysiology, immunology and imaging may allow to differentiate between different subtypes of MS early in the course, and consequently to tailor therapeutic measures more precisely to the individual patients.

Fujinami, R. S. (2001). "Can virus infections trigger autoimmune disease?" J Autoimmun 16(3): 229-34.

Gebicke-Haerter, P. J., O. Spleiss, et al. (2001). "Microglial chemokines and chemokine receptors." Prog Brain Res 132: 525-32.

Gebicke-Haerter, P. J. (2001). "Microglia in neurodegeneration: molecular aspects." Microsc Res Tech 54(1): 47-58.
Inflammatory events in the CNS are associated with injuries as well as with well-known chronic degenerative diseases, such as Multiple Sclerosis, Parkinson's, or Alzheimer's disease. Compared to inflammation in peripheral tissues, inflammation in brain appears to follow distinct pathways and time-courses, which likely has to do with a relatively strong immunosuppression in that organ. For this reason, it is of great importance to get insights into the molecular mechanism governing immune reactions in brain tissue. This task is hard to achieve in vivo, but can be approached by studying the major cell type responsible for brain inflammation, the microglia, in culture. Since these cells are the only professional antigen-presenting cells resident in brain parenchyma, molecular mechanisms of antigen presentation are being discussed first. After covering the expression and regulation of anti- and proinflammatory cytokines, induction and regulation of two key enzymes and their products-COX-2 and iNOS-are summarized. Possibly, pivotal molecular targets for drug therapies of brain disorders will be discovered in intracellular signaling pathways leading to activation of transcription factors. Finally, the impact of growth factors, of neurotrophins in particular, is highlighted. It is concluded that the presently available data on the molecular level is far from being statisfying, but that only from better insights into molecular events will we obtain the information required for more specific therapies.

Gerard, C. and B. J. Rollins (2001). "Chemokines and disease." Nat Immunol 2(2): 108-15.
We examine here several diseases that are associated with inappropriate activation of the chemokine network. Detailed comment has been restricted to pathological states for which there are compelling data either from clinical observations or animal models. These include cardiovascular disease, allergic inflammatory disease, transplantation, neuroinflammation, cancer and HIV-associated disease. Discussion focuses on therapeutic directions in which the rapidly evolving chemokine field appears to be headed.

Girard, S., E. Bruckert, et al. (2001). "[Endocrine disease in adrenoleukodystrophy]." Ann Med Interne (Paris) 152(1): 15-26.
X-linked adrenoleukodysrophy is the most frequent genetic disorder affecting central and peripheral nervous system myelin. One of the biochemical abnormalities is the accumulation of very long chain fatty acids (VLCFA) in tissues and body fluids subsequent to defective catabolism in the peroxysomes. The principal characteristic of the disease is an association between a neurological disorder and an endocrine disorder: primary adrenal insufficiency and testicular failure. Clinical manifestations are variable. There are two main forms, one affecting boys between the age of 5 and 10 years with severe rapidly fatal cerebral involvement, and the other affecting young adults between the age of 20 and 30 years with degeneration of the anterior and posterior long spinal cord tracts, similar to the disorders observed in multiple sclerosis. About 20% of the heterozygous women may develop a syndrome which resembles adrenomyeloneuropathy, rarely adrenal insufficiency. Adrenal insufficiency is present in 85% of the childhood cerebral forms and in about 70% of the adult forms. It may occur before, after or at the same time as the neurological disease but is not correlated with the severity of the neurological disorder. Careful screening is required to avoid missing subclinical forms. Adrenoleukodystrophy should be envisaged in young boys with primary adrenal insufficiency, accounting for about 30% of the cases of primary adrenal insufficiency in children under 3 years of age and about 13% of those in adults. Experience with dietary therapy (low-VLCFA diet and supplementation with unsaturated fatty acids such as glyceryl trioleate (GTO) and glyceryl trierucate (GTE), commonly called Lorenzo's oil) has not demonstrated any clinical improvement in the cerebral forms. Bone marrow transplantation is recommended for children who show early evidence of cerebral involvement. Gene therapy is a promising perspective. Lovastatin and 4-phenlbutyrate have recently been shown to normalize plasma VLCFA levels. Their therapeutic efficacy must be assessed in a randomized trial.

Go, J. L., P. E. Kim, et al. (2001). "The trigeminal nerve." Semin Ultrasound CT MR 22(6): 502-20.
The trigeminal nerve is the largest of the cranial nerves, serving as a major conduit for sensory information from the head and neck and primarily providing motor innervation to the muscles of mastication. An understanding of the pathologic processes that may involve this nerve requires a detailed knowledge of its origin within the brain stem as well as its course intracranially. This article describes the neuroanatomy of the nerve and divides it into its various segments to provide a differential diagnosis of common and some uncommon pathologic processes.

Godessart, N. and S. L. Kunkel (2001). "Chemokines in autoimmune disease." Curr Opin Immunol 13(6): 670-5.
Growing evidence indicates that structural cells play a crucial role in the chronic inflammation of autoimmunity by their recruitment of chemokine-dependent cells. Members of the two functional classes of chemokines, inflammatory and homeostatic, seem to be involved in lymphocyte recruitment and survival, and in establishing ectopic lymphoid structures in the target organs of autoimmune diseases. Results from animal models suggest that chemokines are reasonable therapeutic targets in autoimmunity.

Gold, R., F. Buttgereit, et al. (2001). "Mechanism of action of glucocorticosteroid hormones: possible implications for therapy of neuroimmunological disorders." J Neuroimmunol 117(1-2): 1-8.
Glucocorticosteroids are the most potent immunosuppressive and antiinflammatory drugs. Over the six decades that have passed since their discovery, a variety of genomic effector mechanisms of steroid hormones has been described which are mediated by the cytosolic steroid receptor. Recent evidence supports a direct effect of glucocorticosteroids on cellular membranes that occurs at higher hormone concentrations, termed nongenomic effects. These imply a qualitatively distinct mode of steroid action leading to cellular apoptosis. In this review, we discuss in vitro and in vivo data on nongenomic effects of glucocorticosteroids and their possible implications for the therapy of human neuroimmunological diseases.

Gomariz, R. P., C. Martinez, et al. (2001). "Immunology of VIP: a review and therapeutical perspectives." Curr Pharm Des 7(2): 89-111.
Vasoactive intestinal peptide (VIP) is a neuropeptide with a broad distribution in the body that exerts very important pleiotropic functions in several systems. The present work reviews the immunology of VIP. Being daring, this neuropeptide could be included in the group of cytokines since it is produced and secreted by different immunocompetent cells in response to various immune signals, plays a broad spectrum of immunological functions, and exerts them, in a paracrine and/or autocrine way, through three different specific receptors. Although VIP has been classically considered as an immunodepressant agent, and its main described role has been as an anti-inflammatory factor, several evidences suggest that a better way to see this peptide is as a modulator of the homeostasis of the immune system. In the last decade, the pharmacology of VIP has spectacularly grown, and VIP itself, as well as more stable VIP-derived agents, have been used or proposed as efficient therapeutical treatments of several disorders, specially inflammatory and autoimmune diseases, such as septic shock, rheumatoid arthritis, multiple sclerosis, Crohn's disease and autoimmune diabetes. A broad field of perspectives is actually open, and further investigations will help us to definitively understand the immunology of this very important peptide.

Grauer, O., M. Offenhausser, et al. (2001). "[Glucocorticosteroid therapy in optic neuritis and multiple sclerosis. Evidence from clinical studies and practical recommendations]." Nervenarzt 72(8): 577-89.
High-dose intravenous glucocorticosteroids (GS) are the treatment of choice for acute relapses in patients with multiple sclerosis. We review the evidence from published trials on GS treatment in MS. Several controlled clinical trials have proven the efficacy of high-dose GS in accelerating the recovery from acute attacks. With serial MRI recordings, a reduction in the number of enhancing lesions has been observed after high-dose GS treatment. Definitive long-term effects of GS on disease evolution could not been demonstrated. There is now evidence that ultra-high doses of GS might be superior in comparison to standard pulse treatment regarding relapse rate and disease progression. In experimental autoimmune encephalomyelitis (EAE), an animal model for some features of MS, doses of up to 50 mg/kg methylprednisolone markedly augmented T cell apoptosis in situ, leading to a faster clearance of inflammatory infiltrates. Apoptosis in peripheral blood leukocytes could also be detected after i.v. GS treatment in MS patients. In a recent MRI study, ultra-high doses of GS were significantly more effective in reducing contrast-enhancing lesions and in maintaining blood-brain barrier integrity after a clinical relapse. Further clinical trials are necessary to study the long-term effects of ultra-high doses of GS on disease progression and disability.

Green, A. J., A. W. Bollen, et al. (2001). "Multiple sclerosis and oligodendroglioma." Mult Scler 7(4): 269-73.
Two cases of multiple sclerosis (MS) and oligodendroglioma are reviewed, increasing the total number of reported cases to II. In this series, the clinical onset of MS preceded the discovery of the tumor by a mean of 15 years. No distinguishing features of oligodendroglioma were characteristic of MS-associated cases. However, there was an overrepresentation of benign MS. Although this could result from biased ascertainment, other possibilities, including effective remyelination mediated by mitotically active oligodendrocytes, or secretion of immunosuppressive cytokines by the tumor tissue, cannot be excluded. It is likely that the coexistence of MS and oligodendroglioma is due to chance alone, nonetheless the possibility that glioma derived factors can moderate the disease course in MS is deserving of further study.

Grimaud, J., N. Pageot, et al. (2001). "[Parallels between clinical aspects and MRI in multiple sclerosis]." Rev Neurol (Paris) 157(8-9 Pt 1): 884-90.

Grimaud, J., M. Hermier, et al. (2001). "[What can be expected from brain MRI in early-stage multiple sclerosis?]." Rev Neurol (Paris) 157(1): 13-9.

Gulick, E. E. (2001). "Emotional distress and activities of daily living functioning in persons with multiple sclerosis." Nurs Res 50(3): 147-54.
BACKGROUND: Emotional distress is higher in persons with multiple sclerosis (MS) than in other chronic illnesses. Not known is whether personal attributes of the person with MS and/or the presence of social support will function as mediating and/or moderating variables between emotional distress and adaptation to the illness. OBJECTIVES: Determine if personal attributes and social support function as mediating and/or moderating variables between emotional distress and ADL functioning in persons with MS. METHODS: Secondary analyses of data obtained from 686 persons with MS through self-report measures of emotional distress, personal attributes, social support, and ADL functioning was conducted. Separate mediation and moderation models were tested using stepwise and hierarchical multiple regression. Demographic variables of education, age, and length of MS illness, were controlled in all analyses. RESULTS: Personal attributes and social support functioned as mediator variables between emotional distress and ADL functioning. Additionally, personal attributes and not social support functioned as a moderator. Significant main effects were shown for social support and emotional distress in the moderator model. CONCLUSION: Personal attributes and social support mediated the effects of emotional distress by decreasing its impact on ADL functioning. Personal attributes, as a moderator variable, demonstrated that higher levels were associated with low levels of emotional stress and moderate or lower levels of personal attributes were associated with increased emotional distress suggesting that personal attributes may intervene between emotional distress and ADL functioning by attenuating or preventing a stress appraisal response.

Gusev, E. I., A. N. Boiko, et al. (2001). "[Clinical genetics of multiple sclerosis]." Zh Nevrol Psikhiatr Im S S Korsakova 101(9): 61-8.

Guzman, M., C. Sanchez, et al. (2001). "Control of the cell survival/death decision by cannabinoids." J Mol Med 78(11): 613-25.
Cannabinoids, the active components of Cannabis sativa (marijuana), and their derivatives produce a wide spectrum of central and peripheral effects, some of which may have clinical application. The discovery of specific cannabinoid receptors and a family of endogenous ligands of those receptors has attracted much attention to cannabinoids in recent years. One of the most exciting and promising areas of current cannabinoid research is the ability of these compounds to control the cell survival/death decision. Thus cannabinoids may induce proliferation, growth arrest, or apoptosis in a number of cells, including neurons, lymphocytes, and various transformed neural and nonneural cells. The variation in drug effects may depend on experimental factors such as drug concentration, timing of drug delivery, and type of cell examined. Regarding the central nervous system, most of the experimental evidence indicates that cannabinoids may protect neurons from toxic insults such as glutamaergic overstimulation, ischemia and oxidative damage. In contrast, cannabinoids induce apoptosis of glioma cells in culture and regression of malignant gliomas in vivo. Breast and prostate cancer cells are also sensitive to cannabinoid-induced antiproliferation. Regarding the immune system, low doses of cannabinoids may enhance cell proliferation, whereas high doses of cannabinoids usually induce growth arrest or apoptosis. The neuroprotective effect of cannabinoids may have potential clinical relevance for the treatment of neurodegenerative disorders such as multiple sclerosis, Parkinson's disease, and ischemia/stroke, whereas their growth-inhibiting action on transformed cells might be useful for the management of malignant brain tumors. Ongoing investigation is in search for cannabinoid-based therapeutic strategies devoid of nondesired psychotropic effects.

Haase, C. G. (2001). "[Devics neuromyelitis optica. Disease or variants of multiple sclerosis?]." Nervenarzt 72(10): 750-4.
Neuromyelitis optica (NMO, or Devic's syndrome) is a rare syndrome characterized by the combination of acute or subacute optic neuritis and transverse myelitis. This strict confinement of lesions together with immunologic parameters such as frequent absence of oligoclonal banding despite increased signs of CSF inflammation suggest that NMO is distinct from multiple sclerosis (MS). Magnetic resonance imaging (MRI) data support NMO and MS as separate entities due to lesion distribution and signal characteristics. This is further supported by epidemiological and genetic evidence associating HLA-DRB1*1501 with disseminated "western" MS in contrast to NMO associated with DRB1*802, DPB1 501, and DPA1 202, the "Asian" type. Most findings suggest a heterogeneous pathogenesis of NMO and, in spite of the distinct localization, rather unspecific immune reactions seem to be involved. As to the frequent relapses of NMO, therapeutic options besides prednisolone are difficult to assess and favor long-term immune suppression or modulation.

Hanley, K., T. O'Dowd, et al. (2001). "A systematic review of vertigo in primary care." Br J Gen Pract 51(469): 666-71.
The symptom of vertigo is usually managed in primary care without further referral. This review examines the evidence on which general practitioners can base clinical diagnosis and management of this relatively common complaint. Research in this area has in the main been from secondary and tertiary centres and has been of variable quality. Indications are that the conditions that present in general practice are most likely to be benign positional vertigo, acute vestibular neuronitis, and Meniere's disease; however, vascular incidents and neurological causes, such as multiple sclerosis, must be kept in mind. An important practice point is that vestibular sedatives are not recommended on a prolonged basis for any type of vertigo. There is a need for basic epidemiological and clinical management research of vertigo in general practice.

Happle, R. (2001). "[Segmental type 2 manifestation of autosome dominant skin diseases. Development of a new formal genetic concept]." Hautarzt 52(4): 283-7.
The prevailing theory says that mosaic forms of autosomal dominant skin diseases originate from postzygotic new mutations. This theory is no longer generally valid. According to a new rule of dichotomy, we can distinguish two types of segmental manifestations. The type 1 reflects heterozygosity for a postzygotic new mutation, whereas the type 2 results from loss of the corresponding wildtype allele occurring in a heterozygous embryo and reflects either homozygosity or hemizygosity for the underlying mutation, giving rise to rather pronounced segmental lesions that are superimposed on the ordinary nonsegmental phenotype. Autosomal dominant skin diseases exemplifying the concept of type 2 segmental manifestation so far include neurofibromatosis 1, tuberous sclerosis, cutaneous leiomyomatosis, glomangiomatosis, Buschke-Ollendorff syndrome, multiple syringomas, multiple trichoepitheliomas, multiple basaloid follicular hamartomas, multiple nevoid basal cell carcinomas, Darier disease, Hailey-Hailey disease, epidermolytic hyperkeratosis of Brocq, KID syndrome, disseminated superficial actinic porokeratosis and autosomal dominant dyskeratosis congenita. A strikingly high frequency of type 2 segmental involvement has been documented in cutaneous leiomyomatosis, glomangiomatosis and disseminated superficial actinic porokeratosis. It should be noted that there is so far no molecular proof for the proposed rule of dichotomy that has been developed from clinical dermatology. According to present knowledge, however, it is very likely that molecular analysis will confirm the described concept that can explain some so far enigmatic features as observed in autosomal dominant genodermatoses.

Haring, J. and S. Perlman (2001). "Mouse hepatitis virus." Curr Opin Microbiol 4(4): 462-6.
Inoculation of mice with most neurotropic strains of the coronavirus mouse hepatitis virus results in an immune response-mediated demyelinating disease that serves as an excellent animal model for the human disease multiple sclerosis. Recent work has shown that either virus-specific CD4(+) or CD8(+) T cells are able to mediate demyelination and also that the antibody response is crucial for clearing infectious virus. Another exciting advance is the development of recombinant coronaviruses, which, for the first time, will allow genetic manipulation of the entire viral genome.

Hartung, H. P. and R. I. Grossman (2001). "ADEM: distinct disease or part of the MS spectrum?" Neurology 56(10): 1257-60.

Hedlund, G., H. Link, et al. (2001). "Effects of Linomide on immune cells and cytokines inhibit autoimmune pathologies of the central and peripheral nervous system." Int Immunopharmacol 1(6): 1123-30.
Linomide (roquinimex, LS 2616) is a quinoline-3-carboxamide with pleiotropic immune modulating capacity and it has therapeutic effects in several experimental animal models of autoimmune diseases. Linomide has been evaluated in clinical trials for multiple sclerosis, and was indeed shown to have disease inhibitory effects. However, due to unexpected side effects recorded in patients treated with Linomide, premature termination of clinical trials was required. The basic mechanism(s) of action of Linomide in inducing beneficial effects in autoimmune diseases is still elusive. Some experimental evidence indicates that Linomide influences the regulation of the cytokine profile, resulting in the inhibition of autoimmune and inflammation pathologies. This review focuses on Linomide applied in models for autoimmune and inflammation pathologies of the central and the peripheral nervous system, and summarises its very encouraging disease inhibitory effects and their potential pharmacological basis. The beneficial effects recorded with Linomide in both experimental and clinical trials emphasise the possible value of substances with Linomide-like activity for clinical use in autoimmune and inflammation pathologies in the near future.

Hodgkinson, S. J. (2001). "Should all patients with an initial diagnosis of multiple sclerosis be treated with beta interferon?" J Clin Neurosci 8(4): 378-9.

Hohlfeld, R. and H. Wekerle (2001). "Immunological update on multiple sclerosis." Curr Opin Neurol 14(3): 299-304.
The present review of the recent literature focuses on antigen-specific immune reactions in multiple sclerosis. New techniques have allowed precise quantitative analysis of the antigen-receptor repertoire of infiltrating T cells in the multiple sclerosis brain. Novel candidate autoantigens, including B-cell autoantigens, have been identified. 'Humanized' animal models allow the functional characterization of human immune molecules in vivo. Finally, several therapeutic trials have recently assessed the clinical benefit of selective immunotherapies.

Hohlfeld, R. (2001). "[Interferon therapy of multiple sclerosis. A question of the correct dose?]." Nervenarzt 72(2): 67-8.

Horowski, R., C. S. Sturzebecher, et al. (2001). "Neutralizing antibodies (NABS) and interferon beta-1b therapy of multiple sclerosis." Funct Neurol 16(2): 117-28.

Horsfield, M. A. (2001). "Using diffusion-weighted MRI in multicenter clinical trials for multiple sclerosis." J Neurol Sci 186 Suppl 1: S51-4.
This paper reviews the current state of knowledge about the use of diffusion-weighted MRI in the field of multiple sclerosis (MS) research. The contribution that diffusion-weighted imaging has made to our understanding of MS is critically appraised, and pointers are given to the sort of work that needs to be done before diffusion-weighted MRI could be recommended for inclusion in a clinical trial. The types of procedures that would be needed for quality assurance of diffusion data, and the data collection schemes that would lead to reliable data, are then reviewed. The quantitative nature of diffusion MRI makes it an attractive proposition for inclusion in clinical trials for MS therapeutic agents, but without further validation work with clinical correlates cannot be recommended at present.

Huang, Z., Y. Ducharme, et al. (2001). "The next generation of PDE4 inhibitors." Curr Opin Chem Biol 5(4): 432-8.
A number of highly potent PDE4 inhibitors are being developed for the treatment of asthma, chronic obstructive pulmonary disease, rheumatoid arthritis, multiple sclerosis and Crohn's disease. Cilomilast (Ariflo, SB 207499, SmithKline Beecham), the most advanced member of the class in Phase III clinical trials, was reported to have a limited therapeutic window. Other inhibitors with improved profiles in preclinical models are entering into (or are in) clinical trials. The recent developments in understanding PDE4 catalysis, inhibitor binding and their emetic response should facilitate the design of the next generation of PDE4 inhibitors.

Huber, J. D., R. D. Egleton, et al. (2001). "Molecular physiology and pathophysiology of tight junctions in the blood-brain barrier." Trends Neurosci 24(12): 719-25.
Disruption of the tight junctions (TJs) of the blood-brain barrier (BBB) is a hallmark of many CNS pathologies, including stroke, HIV encephalitis, Alzheimer's disease, multiple sclerosis and bacterial meningitis. Furthermore, systemic-derived inflammation has recently been shown to cause BBB tight junctional disruption and increased paracellular permeability. The BBB is capable of rapid modulation in response to physiological stimuli at the cytoskeletal level, which enables it to protect the brain parenchyma and maintain a homeostatic environment. By allowing the "loosening" of TJs and an increase in paracellular permeability, the BBB is able to "bend without breaking"; thereby, maintaining structural integrity.

Huizinga, T. W., S. C. Steens, et al. (2001). "Imaging modalities in central nervous system systemic lupus erythematosus." Curr Opin Rheumatol 13(5): 383-8.
Within the past few years, a clearly defined case definition system for central nervous system systemic lupus erythematosus (CNS-SLE) has been established. This has allowed cross-study comparisons of patients fulfilling the specific case definitions. New imaging techniques used on the subgroup of CNS-SLE patients that did not have any evidence for infarctions suggest that in these patients symptoms are associated with a diffuse process in the brain. Most likely this process leads to axonal damage and demyelination, ultimately leading to cerebral atrophy. With respect to the diagnostic work-up of SLE patients with neuropsychiatric symptoms, it has become clear that cranial magnetic resonance imaging is the technique of choice. Preliminary studies using quantitative magnetic resonance imaging techniques suggest that patients with neuropsychiatric symptoms caused by active CNS-SLE can be differentiated from patients with the same symptoms caused by residual disease.

Huoponen, K. (2001). "Leber hereditary optic neuropathy: clinical and molecular genetic findings." Neurogenetics 3(3): 119-25.
Leber hereditary optic neuropathy (LHON) is a maternally inherited disease characterized by acute or subacute painless central visual loss usually in young adults, predominantly in males. Except for optic atrophy, LHON patients are usually otherwise healthy. Occasionally, LHON is associated with neurological, cardiac, and skeletal changes. The clinical course of LHON has several stages. Peripapillary microangiopathy is present from the beginning. Microangiopathy disappears as the disease progresses towards the end stages. Simultaneously, the retinal nerve fiber layer fades from view, first papillomacular nerve fiber bundles, and months later, the whole nerve fiber layer becomes atrophic. At the end stage the centrocecal scotoma is large and absolute. Loss of vision is usually permanent, but spontaneous recovery can occur. Despite a few attempts, no effective treatment to prevent or halt LHON has been found. Several mitochondrial DNA (mtDNA) mutations are associated with LHON, but the pathogenic processes leading to optic nerve atrophy are largely unknown. About 15% of the families are heteroplasmic, i.e., both mutant and wild type mtDNA coexist within an individual. The level of heteroplasmy between different tissues can vary markedly. mtDNA mutations are not sufficient to cause visual loss in LHON, since not all individuals harboring a pathogenic LHON mutation express the disease. There are additional genetic and/or environmental precipitating factors, but thus far they are unknown.

Hutt, N., M. Kopferschmitt-Kubler, et al. (2001). "Anaphylactic reactions after therapeutic injection of mistletoe (Viscum album L.)." Allergol Immunopathol (Madr) 29(5): 201-3.
Mistletoe (Viscum album) is a plant that is semiparasitic of several trees: apple, oak, pine trees, etc. Because of the probable cytolytic action of one of the leaf's most abundant composites, in some countries mistletoe is used as a complementary medicine. Although only a few adverse reactions have been noted (cephalea, fever), cases of anaphylactic shock have been described. We present three cases of severe reaction after injection of mistletoe extract. Two of the patients had cancer. The third, whose brother had cancer, used the plant for preventive purposes. We discuss the danger of possible severe reactions due to the use of products employed in so-called alternative therapies.

Iglesias, A., J. Bauer, et al. (2001). "T- and B-cell responses to myelin oligodendrocyte glycoprotein in experimental autoimmune encephalomyelitis and multiple sclerosis." Glia 36(2): 220-34.
The identification of myelin oligodendrocyte glycoprotein (MOG) as a target for autoantibody-mediated demyelination in experimental autoimmune encephalomyelitis (EAE) resulted in the re-evaluation of the role of B cell responses to myelin autoantigens in the immunopathogenesis of multiple sclerosis. MOG is a central nervous system specific myelin glycoprotein that is expressed preferentially on the outermost surface of the myelin sheath. Although MOG is only a minor component of CNS myelin it is highly immunogenic, inducing severe EAE in both rodents and primates. In rat and marmoset models of MOG-induced EAE demyelination is antibody-dependent and reproduces the immunopathology seen in many cases of MS. In contrast, in mice inflammation in the CNS can result in demyelination in the absence of a MOG-specific B cell response, although if present this will enhance disease severity and demyelination. Clinical studies indicate that autoimmune responses to MOG are enhanced in many CNS diseases and implicate MOG-specific B cell responses in the immunopathogenesis of multiple sclerosis. This review provides a summary of our current understanding of MOG as a target autoantigen in EAE and MS, and addresses the crucial question as to how immune tolerance to MOG may be maintained in the healthy individual.

Imam, S. Z., J. el-Yazal, et al. (2001). "Methamphetamine-induced dopaminergic neurotoxicity: role of peroxynitrite and neuroprotective role of antioxidants and peroxynitrite decomposition catalysts." Ann N Y Acad Sci 939: 366-80.
Oxidative stress, reactive oxygen (ROS), and nitrogen (RNS) species have been known to be involved in a multitude of neurodegenerative disorders such as Parkinson's disease (PD), Alzheimer's disease (AD), and amyotrophic lateral sclerosis (ALS). Both ROS and RNS have very short half-lives, thereby making their identification very difficult as a specific cause of neurodegeneration. Recently, we have developed a high performance liquid chromatography/electrochemical detection (HPLC/EC) method to identify 3-nitrotyrosine (3-NT), an in vitro and in vivo biomarker of peroxynitrite production, in cell cultures and brain to evaluate if an agent-driven neurotoxicity is produced by the generation of peroxynitrite. We show that a single or multiple injections of methamphetamine (METH) produced a significant increase in the formation of 3-NT in the striatum. This formation of 3-NT correlated with the striatal dopamine depletion caused by METH administration. We also show that PC12 cells treated with METH has significantly increased formation of 3-NT and dopamine depletion. Furthermore, we report that pretreatment with antioxidants such as selenium and melatonin can completely protect against the formation of 3-NT and depletion of striatal dopamine. We also report that pretreatment with peroxynitrite decomposition catalysts such as 5, 10,15,20-tetrakis(N-methyl-4'-pyridyl)porphyrinato iron III (FeTMPyP) and 5, 10, 15, 20-tetrakis (2,4,6-trimethyl-3,5-sulfonatophenyl) porphinato iron III (FETPPS) significantly protect against METH-induced 3-NT formation and striatal dopamine depletion. We used two different approaches, pharmacological manipulation and transgenic animal models, in order to further investigate the role of peroxynitrite. We show that a selective neuronal nitric oxide synthase (nNOS) inhibitor, 7-nitroindazole (7-NI), significantly protect against the formation of 3-NT as well as striatal dopamine depletion. Similar results were observed with nNOS knockout and copper zinc superoxide dismutase (CuZnSOD)-overexpressed transgenic mice models. Finally, using the protein data bank crystal structure of tyrosine hydroxylase, we postulate the possible nitration of specific tyrosine moiety in the enzyme that can be responsible for dopaminergic neurotoxicity. Together, these data clearly support the hypothesis that the reactive nitrogen species, peroxynitrite, plays a major role in METH-induced dopaminergic neurotoxicity and that selective antioxidants and peroxynitrite decomposition catalysts can protect against METH-induced neurotoxicity. These antioxidants and decomposition catalysts may have therapeutic potential in the treatment of psychostimulant addictions.

Itoyama, Y. (2001). "[Etiology and treatment of multiple sclerosis]." Nippon Naika Gakkai Zasshi 90(9): 1827-32.

Ivanhoe, C. B., A. H. Tilton, et al. (2001). "Intrathecal baclofen therapy for spastic hypertonia." Phys Med Rehabil Clin N Am 12(4): 923-38, viii-ix.
Intrathecal baclofen is perhaps the most effective treatment for significant spasticity regardless of the origin. For appropriately selected patients, it can provide qualitative and quantitative improvements in quality of life. This article discusses the practical aspects and patient selection, trial, implant, and ongoing management of patients with intrathecal baclofen pump therapy.

Jefferson, T. and H. Heijbel (2001). "Demyelinating disease and hepatitis B vaccination: is there a link?" Drug Saf 24(4): 249-54.
The recent decision by the French government to compensate 3 recipients of hepatitis B vaccine preceding the onset of multiple sclerosis presumes a possible causal link and brings into question the use of current rules of causality assessment. Available evidence does not support a causal link or is equivocal but the accuracy of current methods of vaccine surveillance should be urgently improved. Larger and longer randomised trials, updated summaries of evidence, linked databases, prospective vaccination registers, bar-coding of vaccines and standardisation of adverse event definitions are possible measures to address current problems.

Joffroy, A., M. Levivier, et al. (2001). "Trigeminal neuralgia. Pathophysiology and treatment." Acta Neurol Belg 101(1): 20-5.
Trigeminal neuralgia is a very peculiar disease. The pain, also known as "tic douloureux", is paroxystic and very severe. It can be triggered by a light cutaneous stimulus on a very localized spot on the face (the so-called "trigger zone"). The patient can sometimes benefit from long remissions without any treatment. With the exception of multiple sclerosis and of uncommon cases of posterior fossa tumours or other lesions impinging on the trigeminal nerve, ganglion or root, trigeminal neuralgia is considered as "idiopathic". Some