Showing papers in "Nature Reviews Neurology in 2005"

Brain stimulation for epilepsy.

Abstract: It is estimated that epilepsy affects up to 1% of the world's population, and although many patients derive considerable benefits from antiepileptic drugs or resective surgery, new therapeutic approaches are still needed In this Viewpoint, William Theodore assesses the potential of techniques that involve direct or indirect electrical stimulation of the epileptic focus

Technology insight: visualizing peripheral nerve injury using MRI.

Abstract: Currently, the evaluation of peripheral nerve disorders depends on clinical examination, supplemented by electrophysiological studies. These approaches provide general information on the distribution and classification of nerve lesions-for example, axonal versus demyelinative-but nerve biopsies are still required to obtain morphological and pathophysiological details. In this article, we review recent progress in the imaging of peripheral nerve injury by magnetic resonance (MR) neurography. Axonal nerve injury leads to Wallerian degeneration, resulting in a hyperintense nerve signal on T2-weighted MR images of the distal nerve segment. This signal is lost following successful regeneration. Concomitant denervation-induced signal alterations in muscles can further help us to determine whether nerve trunks or roots are affected. These signal changes are caused by various combinations of nonspecific tissue alterations, however, and are not related to particular pathoanatomical findings, such as inflammation, demyelination or axonal injury. New experimental MR contrast agents, such as gadofluorine M and superparamagnetic iron oxide particles, allow visualization of the dynamics of peripheral nerve injury and repair. Further clinical development of these MR contrast agents should allow these functional aspects of nerve injury and repair to be assessed in humans, thereby aiding the differential diagnosis of peripheral nerve disorders.

Harlequin syndrome - one face of many etiologies

Abstract: Background A 55-year-old woman presented to hospital with a 3-month history of asymmetric facial flushing of the skin during exertion, and an 18-month history of left-sided ptosis and miosis. Detailed medical history analysis revealed that a palpable node measuring 0.8 × 1.2 × 1.2 cm (volume 1.1 ml) had been discovered 2 years previously, within the left lobe of an otherwise uncomplicated goiter that had been successfully managed for 20 years. Otherwise, the patient was healthy. Investigations Neurological examination, autonomic testing, duplex ultrasonography, scintigraphy and MRI. Diagnosis Harlequin syndrome following a lesion of the preganglionic sympathetic efferents, caused by neurovascular compression of the sympathetic chain between the stellate and superior cervical ganglion brought about by an elongated inferior thyroid artery. Management Explanation of pathophysiology and benign nature of the condition.

Drug Insight: temozolomide as a treatment for malignant glioma--impact of a recent trial.

Abstract: Despite advances in surgery, radiotherapy and chemotherapy, the median survival for patients with glioblastoma—the most common primary brain tumor in adults—has changed little in 40 years. A recent trial, however, has shown that administration of the DNA methylating agent temozolamide during and after radiotherapy can prolong survival in patients with newly diagnosed glioblastomas.

Drug insight: using monoclonal antibodies to treat multiple sclerosis.

Abstract: Multiple sclerosis (MS) is an immunopathological, presumably autoimmune, disease of the CNS. Several immunomodulatory treatments, including various preparations of interferon-beta, glatiramer acetate and mitoxantrone, have been approved for MS therapy. Because these agents are only partially effective, the search for better therapies continues. Therapeutic monoclonal antibodies (mAbs), a class of biotechnological agents, allow the precise targeting of molecules involved in pathological processes. Therapeutic mAbs have shown much promise in the treatment of many disorders, including inflammatory and putative autoimmune diseases such as MS. These agents have intrinsic limitations, however, such as induction of neutralizing 'anti-antibodies', systemic inflammatory reactions and severe adverse effects, some of which remain to be explained. Most notably, natalizumab (Tysabri), a mAb against alpha4 integrin, was very effective in suppressing MS activity, but had to be withdrawn from the market because several treated patients developed progressive multifocal leukoencephalopathy. This article reviews the state of development of various therapeutic mAbs for MS treatment.

Drug Insight: using statins to treat neuroinflammatory disease.

Abstract: Statins, a family of 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors, are used primarily to reduce atherogenesis and cardiovascular morbidity Surprisingly, they have also been shown to have immunomodulatory properties that might be of benefit for the treatment of autoimmune disorders Statins can prevent and even reverse ongoing paralysis in experimental autoimmune encephalomyelitis--the mouse model for multiple sclerosis--and on the basis of these findings, statins are now being tested in patients with multiple sclerosis in clinical trials

Ganglioside complexes: new autoantibody targets in Guillain-Barré syndromes.

Abstract: Autoantibodies against nerve glycosphingolipid antigens have been shown to have a central role in Guillain–Barre syndrome pathogenesis. Until recently, research has focused on antibody reactivity to highly purified single species of gangliosides, but new findings highlight the importance of analyzing antibody reactivity to ganglioside complexes.

Technology Insight: imaging amyloid plaques in the living brain with positron emission tomography and MRI.

Abstract: Alois Alzheimer first imaged amyloid plaques in 1906 by examining dead tissue under the microscope, but their clinical significance has remained undetermined. Now, nearly a century later, investigators are beginning to image amyloid plaques in living brains using both positron emission tomography and MRI. In this article, we review the studies that report on these recent technical advances, and discuss their potential importance in clarifying the diagnostic and pathogenic relevance of amyloid plaques to Alzheimer's disease.

The value of metabolic imaging in diagnosis and resection of cerebral gliomas

Abstract: Currently, there is considerable scientific interest in modes of imaging that rely on the metabolic characteristics of tissues. Metabolic imaging is emerging as a promising diagnostic tool for the evaluation of cerebral gliomas, although it remains to be seen whether treatment decisions based on this approach will produce significant improvements in outcome.

A case of late-onset chorea.

Abstract: Background A 75-year-old woman with rheumatoid arthritis presented with a 4-year history of chorea to a hospital movement disorder clinic. The involuntary movements were initially mild, affecting only the right side of the body, but gradually worsened and became bilateral. There was no relevant family history. Medications included hormone replacement therapy (HRT), diclofenac sodium, vitamin D, folic acid, methotrexate and zopiclone. On examination, bilateral choreiform movements were seen, affecting the face and limbs, with the right side more severely affected than the left. Investigations Neuropsychological testing, laboratory blood and DNA testing, echocardiogram, MRI of the brain, and brain perfusion single-photon emission computed tomography (SPECT) scanning. Diagnosis HRT-related chorea, possibly caused by a predisposition secondary to rheumatoid arthritis and small-vessel ischemic disease, or subclinical childhood rheumatic fever. Management Discontinuation of HRT.

Is amyloid-β-peptide immunization clinically effective in patients with Alzheimer's disease?

Abstract: Is amyloid-β-peptide immunization clinically effective in patients with Alzheimer's disease?

Lumbar total disc replacement compared with spinal fusion: treatment choice and evaluation of outcome.

Abstract: Spinal fusion is the conventional surgical option for treating degenerative disc disease, but it can decrease the spine's overall range of motion, thereby increasing stress on adjacent discs and accelerating their degeneration. Artificial disc replacement should allow motion to be retained at the operative level, and the results of initial trials have been encouraging, but randomized studies are still needed to assess the long-term outcome of this procedure.

Can vaccinating older adults against varicella zoster virus prevent herpes zoster and postherpetic neuralgia

Abstract: Can vaccinating older adults against varicella zoster virus prevent herpes zoster and postherpetic neuralgia?

Can rofecoxib delay a diagnosis of Alzheimer's disease in patients with mild cognitive impairment?

Abstract: Original article Thal LJ et al. (2005) A randomized, double-blind, study of rofecoxib in patients with mild cognitive impairment. Neuropsychopharmacology 30: 1204–1215 PubMed Clinical studies have failed to show convincing effects of nonsteroidal anti-inflammatory drugs (NSAIDs)—including the selective cyclo-oxygenase 2 (COX2) inhibitor rofecoxib—on the progression of Alzheimer's disease (AD).

Prenatal exposure to antiepileptic drugs|[mdash]|risk factor for autism spectrum disorder

Abstract: Left-hemispheric and right-hemispheric strokes have different characteristic symptoms; for instance, left-hemispheric stroke can cause aphasia, whereas right-hemispheric stroke is associated with neglect. The symptoms of right-hemispheric stroke can be difficult to recognize, raising concerns about the adequacy of clinical management in this patient group. A recent German study has examined the impact of such symptom differences on patient treatment, particularly with regard to admission to hospital. Foerch and colleagues carried out statistical analysis of data from 20,097 stroke patients (mean age 70 years) who had received inpatient care for their condition—patients had sustained a transient ischemic attack, a cerebral infarction or an intracerebral hemorrhage. The data included information on stroke side and localization, stroke severity and cause, vascular risk factors, and time between the onset of symptoms and admission to hospital. Overall, 11,328 patients were diagnosed with a left-sided stroke, and 8,769 with a rightsided stroke (P <0.0001). Fifty-eight percent of patients who received thrombolytic treatment had suffered a left-hemispheric stroke, and a larger proportion of left-hemispheric than righthemispheric stroke patients received treatment within 3 hours. Overall, more patients were admitted to hospital with left-hemispheric than with right-hemispheric stroke, yet there is no evidence that left-hemispheric stroke occurs more frequently in the general population. The findings of this study indicate that the poorer recognition of symptoms associated with right-hemispheric stroke, in particular during the first few hours after an event, leads to an inequality in the medical treatment and management of patients with left-hemispheric and right-hemispheric stroke. Christine Kyme

Understanding risk factors for childhood stroke: a feasibility study

Abstract: endovascular coiling was associated with the lowest risk of death or dependency at 1 year. The International Subarachnoid Aneurysm Trial (ISAT) included 2,143 patients at 42 neurosurgical centers. All patients had sub arachnoid hemorrhage due to intracranial aneurysm and were randomized to endovascular detachablecoil treatment (n = 1,073) or neurosurgical clipping (n = 1,070). In 2002, an interim analysis showed that patients treated with endo vascular coiling were more likely to achieve independent survival at 1 year; the latest results confirm these findings and provide information on subgroup analyses and secondary outcomes. After the first procedure, the endovascular group showed a highly significant reduction in seizures when compared with the neurosurgery group (relative risk 0.52; 95% CI 0.37–0.74). During the first year after treatment, death or dependency was reported in 23.5% of patients randomized to endovascular coiling, compared with 30.9% of those in the neurosurgical clipping group. This corresponded to an absolute risk reduction of 7.4% (95% CI 3.6–11.2%; P = 0.0001) in the endovascular treatment group. Although follow-up continues, the data available thus far suggest that the survival bene fit might persist for up to 7 years. Ruth Kirby

How severe is chronic pain in multiple sclerosis

Abstract: DESIGN AND INTERVENTION In this prospective study, 99 communitydwelling patients with confirmed MS (mean age 41.5 years, mean disease duration 10.8 years) completed self-administered questionnaires. The SF-36 was used to assess HRQOL, and the HADS to assess mental health. The clinician-rated EDSS was used to measure physical disability. Pain severity was measured using the SF-36 bodily pain subscale and the VAS from the Short-Form McGill Pain Questionnaire. Pain was classified as chronic if it had been constant or nearly constant during the previous month. Pain that possessed a burning or sharp quality and had no underlying structural basis was classified as neurogenic (caused directly by MS); all other pain was classified as non-neurogenic.

Is simvastatin cost-effective for reducing the risk of vascular events?

Abstract: DESIGN AND INTERVENTION Data from an average of 5 years’ follow-up of the Medical Research Council/British Heart Foundation Heart Protection Study (HPS) were used for the economic analyses. People (n = 20,536) aged 40–80 years who had nonfasting blood total cholesterol concentrations of ≥3.5 mmol/l, and a history of cerebrovascular disease, coronary disease, other occlusive arterial disease, diabetes mellitus, or treated hypertension (in males aged ≥65 years), were randomly allocated to receive simvastatin 40 mg daily or placebo. All serious adverse events were included in the cost analyses. The daily cost of simvastatin was UK£1.06 per patient (adjusted accordingly for non-study statin). Costs of statin and hospitalizations for vascular events were compared using INTENTION-TO-TREAT ANALYSIS. Net absolute costs of treatment and estimates of costeffectiveness were calculated for subgroups defined by variables such as prior disease, age, sex and plasma cholesterol levels, and for five multivariate risk subgroups that were Is simvastatin cost-effective for reducing the risk of vascular events?

Not just another journal

Abstract: Welcome to Nature Clinical Practice Neurology. I am delighted that Nature, one of the premier publishers in biomedical research and medicine, has chosen neurology as one of the many clinical subspecialties covered by the Nature Clinical Practice series. This journal will complement and complete Nature’s already authoritative presence in basic neuroscience, represented by Nature Neuroscience and Nature Reviews Neuroscience. The Nature Clinical Practice journals are an innovative approach by Nature to address the disparity between the wealth of neurological knowledge and the diminishing time that is available for practitioners to incorporate that knowledge into their practices. As neurologists, we recognize that understanding the nervous system is set to be one of the greatest intellectual and research challenges of the next few decades, comparable to the challenge of molecular biology over the past 30 years. We see the excitement that is experienced by students as they learn how the brain works and what goes wrong in disease, as reflected in the popularity of brain science majors on undergraduate campuses. The brain also features prominently in lay science shows on television. In addition, neurologists are in the best position to understand the stake that society holds in improving the prevention and treatment of neuro logical disease in an aging population. The shrinkage in the amount of time that we are able to devote to learning, combined with increased demands on our time from administrative activities, are worldwide issues in the field of neurology, and the increasing sub specialization of the field compounds the challenge of keeping abreast of current knowledge. How will this journal help? This journal has several innovative approaches and unique editorial content. Nature Clinical Practice Neurology is an allreview journal with an international scope. Its principal aim is to present—in a succinct and accessible format—information that is relevant to practice or practice enhancement. The content will be timely, putting the newest data into a clinical context. We will make a point of dealing with prevalent diseases that are not well served by other neurology journals but are important in practice. The journal will tackle issues such as the neurological effects of exercise, the neurology of diabetes, spine disease, infectious diseases (including AIDS), aging and pain. The journal will provide basic science information that truly enhances practice. For example, many heritable central and peripheral nervous system ‘dying back’ axonal degenerations have recently been shown to reflect defects in the axonal transport systems. Understanding the basic science and pathophysiology behind such phenomena will make consultations with patients with these conditions more satisfying. I intend to make such presentations truly authoritative by combining expert opinions from basic scientists and clinicians in the authorship of review articles. Finally, the journal will touch on the political and economic issues that affect neurology practice. For example, why is there a worldwide shortage of human gamma globulin for infusion? What determines when procedures such as cerebrovascular stenting move out of the experimental domain to become procedures that are paid for by health insurance, and how does the policy for making such decisions differ around the world? In the past, I have resisted invitations to edit new or existing journals. I am excited about this undertaking, about the enthusiastic response of the Advisory Board, and by the opportunity to work with the superb Nature staff. This will not be ‘just another journal’. Not just another journal

Nocturnal back pain: useful diagnostic indicator of serious spinal pathology?

Abstract: Abciximab could have beneficial effects on neurological status and size of ischemic lesions in patients with ischemic stroke, an MRI-guided trial has shown. Abciximab is a glycoprotein IIb/IIIa receptor antagonist previously shown to induce thrombo lysis and restore vessel patency in patients with acute coronary syndromes who receive coronary stents. Mitsias and colleagues recruited 29 patients with supratentorial stroke to take part in a single-center, open-label trial. Trial participants received abciximab therapy within 3–24 h of stroke onset. Following treatment, patients were monitored for bleeding and changes in hemoglobin levels, hematocrit and platelet count. Neurological deterioration was also measured at regular intervals using the NATIONAL INSTITUTES OF HEALTH STROKE SCALE (NIHSS). Posttreatment primary outcome measures were changes in NIHSS scores at 48–72 hours and ischemic lesion size on diffusion-weighted imaging at 24-hour follow-up. NIHSS scores decreased for most patients after abciximab therapy, indicating that their neurol ogical status had improved. Furthermore, there was a reduction in the size of ischemic lesions in 27% of patients. No treatment-related deaths, symptomatic intracranial hemorrhages or major systemic hemorrhages were observed. Despite the small number of patients and uncontrolled nature of this study, the authors conclude that abciximab is relatively safe when used to treat patients with ischemic stroke within a 3–24-hour window, and that the drug could attenuate both neurological deterioration and ischemic lesion growth. Claire Braybrook

Is buccal midazolam more effective than rectal diazepam for treating seizures in children

Abstract: Oswestry Disability Index questionnaire, and the VISUAL ANALOG SCALE for pain (scale 0–100). Overall clinical success in each patient was determined by four criteria: no neuro logical deterioration from preoperative status, no major complications, no failure of the device, and ≥25% improvement in Oswestry Disability Index score at 24 months compared with the preoperative score. Overall clinical success at 24 months was significantly higher for patients who received the artificial disc than for controls (P = 0.0004), as was patient satisfaction (P = 0.0011). The authors conclude that the CHARITÉ® artificial disc provides a safe and effective alternative to the established surgical treatment for DDD, and state that it is associated with economic benefits such as a lower rate of reoperation. Christine Kyme

Does Doppler detection of asymptomatic embolization predict stroke risk in symptomatic carotid artery stenosis

Abstract: Does Doppler detection of asymptomatic embolization predict stroke risk in symptomatic carotid artery stenosis?

Can tacrolimus replace ciclosporin and prednisone to treat myasthenia gravis

Abstract: BACKGROUND The immunosuppressive agents ciclosporin and prednisone are both established treatments for the autoimmune neuromuscular disease myasthenia gravis, but their longterm use can result in serious side effects. Furthermore, some patients are refractory to these medications. The MACROLIDE immunosuppressant tacrolimus, which acts by inhibiting T-lymphocyte activation, has been reported to treat myasthenia gravis successfully; however, the long-term results of tacrolimus treatment in myasthenia gravis patients who are dependent on ciclosporin and prednisone remain to be determined.

Stroke severity—an important predictor of post-stroke epilepsy

Abstract: Oswestry Disability Index questionnaire, and the VISUAL ANALOG SCALE for pain (scale 0–100). Overall clinical success in each patient was determined by four criteria: no neuro logical deterioration from preoperative status, no major complications, no failure of the device, and ≥25% improvement in Oswestry Disability Index score at 24 months compared with the preoperative score. Overall clinical success at 24 months was significantly higher for patients who received the artificial disc than for controls (P = 0.0004), as was patient satisfaction (P = 0.0011). The authors conclude that the CHARITÉ® artificial disc provides a safe and effective alternative to the established surgical treatment for DDD, and state that it is associated with economic benefits such as a lower rate of reoperation. Christine Kyme

Neuroblastic tumors and the epigenome

Abstract: lymphoblastic leukemia. A study into the ability of AMN107 to inhibit the TEL-PDGFRβ and FIP1L1-PDGRFα fusion kinases, associated with chronic myelomonocytic leukemia and hypereosinophilic syndrome, respectively, has shown that the molecule could have potential as an effective treatment for these diseases. In vitro, AMN107 was shown to inhibit the proliferation of murine hematopoietic Ba/F3 cells transformed with both TEL-PDGFRβ and FIP1L1-PDGRFα. It also inhibited phosphorylation of tyrosine residues in these fusion kinases and activation of their downstream signaling targets. An imatinib-resistant TELPDGFRβ mutant corresponding to the T3151 in BCR-ABL, known to be a clinically relevant mutation that confers imatinib resistance, was sensitive to AMN107. The analogous FIP1L1PDGRFα mutant, however, was resistant to the drug. In a murine bone marrow transplant model, AM107 effectively treated myeloproliferative disease associated with TEL-PDGFRβ and FIP1L1-PDGRFα, increasing survival and disease latency and reducing disease severity as assessed by fluorescence-activated cellsorting analysis and histopathology. These results suggest that AMN107 could potentially serve as an effective therapy in myeloproliferative disease caused by TELPDGFRβ and FIP1L1-PDGRFα. The authors suggest that it might also have potential in other malignancies caused by activated versions of these kinases or related tyrosine kinases, such as KIT. Carol Lovegrove

Encouraging clinical potential for Lorenzo's oil

Abstract: at 0, 30, 60, 90, 120 and 180 min after glucose loading. The plasma glucose response and total insulin secretion were calculated, and insulin sensitivity was assessed using various formulae, including ISI-stumvoll and OGIS-180 indexes. Although basal glucose and insulin concentrations were relatively similar for patients and controls, glucose concentrations at 90, 120 and 180 min were significantly higher in migraine patients than in controls. When insulin sensitivity was compared between the two groups, ISI-stumvoll and OGIS-180 indexes showed a significant alteration in migraine patients compared with controls. OGIS-180 was found to be significantly lower in migraine-without-aura patients than in controls. The authors suggest that these results might guide the development of new therapies for migraine patients. Lowering insulin resistance with aerobic exercise could reduce vascular complications, and insulin-sensitizing drugs might, in time, provide a prophylactic migraine therapy. Christine Kyme

Can point-of-care platelet-function tests be used to screen for aspirin responsiveness after TIA and stroke?

Abstract: Can point-of-care platelet-function tests be used to screen for aspirin responsiveness after TIA and stroke?