浙医二院神经内科

专家名录

张宝荣

姓　　名：张宝荣
职　　称：教授/主任医师
门诊时间：周一下午，周三上午
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丁美萍

姓　　名：丁美萍
职　　称：教授/主任医师
门诊时间：周二上午,周五上午
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程源深

姓　　名：程源深
职　　称：教授/主任医师
门诊时间：周一下午,周三上午
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俞玉信

姓　　名：俞玉信
职　　称：主任医师
门诊时间：周一上午,周四上午
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英文文献摘要08-09

2008

Therapeutic Advances in Neurological Disorders, Vol. 1, No. 2, 99-114 (2008)

Review: Progress in the treatment of myasthenia gravis

Ralf Gold

Department of Neurology at St. Josef Hospital Ruhr University Bochum Germany, ralf.gold@ruhr-uni-bochum.de

Reinhard Hohlfeld

Institute of Clinical Neuroimmunology Klinikum Großhadern University of Munich Germany

Klaus V. Toyka

Department of Neurology and Clinical Research Group for Neuroimmunology, University of Würzburg Germany

Substantial therapeutic progress has been made in myastheniagravis (MG) even before the era of molecular medicine. Herewe characterize modern treatment algorithms that are adaptedto disease severity and introduce the principle of escalatingtreatment strategies for MG. In very mild cases and in someocular forms of MG, treatment with acetylcholinesterase inhibitorsmay be sufficient, at least temporarily, but commonly some kindof immunologically active treatment is needed. In generalizedMG, a wide array of immunosuppressive treatments has been establishedthrough observational studies, some prospective, but most ofthem have never been tested in a double-blind, prospective andrandomized trial. Within the immunologically active drugs, glucocorticosteroids(GCS) and the immunosuppressive drug azathioprine (Aza) havebeen studied the longest. Aza is still the standard base-linetreatment, in particular in cases where high doses of GCS wouldbe needed to maintain remission. If Aza is not tolerated, severalalternatives are available including cyclosporine A (Cic A),mycophenolate mofetil, cyclophosphamide, and methotrexate, allof them off-label in most western countries. Tacrolimus is underinvestigation. More severe cases may profit from drug combinationsin which compounds with more rapidly acting drugs (GCS, CicA) are combined with others showing a more delayed action (Aza).All such combination therapies need to be supervised by an experiencedneuroimmunological center because of potentially serious adversereactions. Serial measurements of anti-acetylcholine receptorantibodies, once these are elevated, is a useful adjunct formonitoring long-term treatment success and may help in weaningfrom higher to lower doses or to single drugs rather than combinations.For very severe and treatment-resistant cases, co-treatmentwith intravenous immunoglobulins or different modalities ofplasmapheresis may be considered on the short term while thehumanized monoclonal anti-CD 20 antibody (rituximab) is a candidatefor the long term. In highly refractory cases also immuno-ablationvia high-dose cyclophosphamide, followed by hematologic trophicfactors such as G-CSF, has been tried successfully. Future developmentsmay include other immunologically active monoclonal antibodies(e.g., anti-CD 52, Campath-1). Up to 10% of patients with MGare associated with a malignant thymoma, often referred to asparaneoplastic MG, as detected by CT scan or MRI, and thesepatients require thymomectomy and sometimes postsurgical chemotherapyand radiation treatment. In nonthymoma patients with generalisedMG, including older children and adults up to the 5th decade,a complete transsternal thymectomy is recommended based on availableopen trials and expert opinion, preferentially during the firstyear of disease. Endoscopic surgery may also be effective. Beforesurgery, pretreatment with immunosuppressive medication or plasmapheresisis usually recommended to ameliorate MG and subsequently reduceperioperative morbidity and mortality which is now near zeroin experienced centers. Myasthenic crisis is the life-threateningexacerbation of MG and is best treated by plasmapheresis, mostlycombined with immunoadsorption techniques. Intravenous immunoglobulinsare a reasonable alternative, but a shortage in supplies andhigh prices limit its use.

Key Words: immunosuppression , immunoglobulins , plasmapheresis , immuno-adsorption , acetylcholine receptor , muscle specific kinase , thymoma

THE LACENT Neurology

Volume 7, Issue 10, October 2008, Pages 939-950

Lancet Neurol 2008; 7: 939–50

Department of Neurology(P A van Doorn PhD, L Ruts MD,B C Jacobs PhD) and

Department of Immunology(B C Jacobs), Erasmus Medical Centre, Rotterdam,Netherlands

Correspondence to:Pieter A van Doorn, Erasmus MC,Department of Neurology,

Gravendijkwal 230, 3015CE Rotterdam, Netherlands

p.a.vandoorn@erasmusmc.nl

Clinical features, pathogenesis, and treatment of Guillain-Barré syndrome

Pieter A van Doorn PhD^a , Liselotte Ruts MD^a and Bart C Jacobs PhD^a

^aDepartment of Neurology, Erasmus Medical Centre, Rotterdam, Netherlands

^bDepartment of Immunology, Erasmus Medical Centre, Rotterdam, Netherlands

Summary

Guillain-Barré syndrome (GBS) is an important cause of acute neuromuscular paralysis. Molecular mimicry and a cross-reactive immune response play a crucial part in its pathogenesis, at least in those cases with a preceding Campylobacter jejuni infection and with antibodies to gangliosides. The type of preceding infection and patient-related host factors seem to determine the form and severity of the disease. Intravenous immunoglobulin (IVIg) and plasma exchange are effective treatments in GBS; mainly for practical reasons, IVIg is the preferred treatment. Whether mildly affected patients or patients with Miller Fisher syndrome also benefit from IVIg is unclear. Despite medical treatment, GBS often remains a severe disease; 3–10% of patients die and 20% are still unable to walk after 6 months. In addition, many patients have pain and fatigue that can persist for months or years. Advances in prognostic modelling have resulted in the development of a new and simple prognostic outcome scale that might also help to guide new treatment options, particularly in patients with GBS who have a poor prognosis.

(Stroke. 2009;40:994.)2009 American Heart Association, Inc.

Guidelines for the Management of Aneurysmal Subarachnoid Hemorrhage

A Statement for Healthcare Professionals From a Special Writing Group of the Stroke Council, American Heart Association

Joshua B. Bederson, MD, Chair; E. Sander Connolly, Jr, MD, FAHA, Vice-Chair; H. Hunt Batjer, MD; Ralph G. Dacey, MD, FAHA; Jacques E. Dion, MD, FRCPC; Michael N. Diringer, MD, FAHA; John E. Duldner, Jr, MD, MS; Robert E. Harbaugh, MD, FAHA; Aman B. Patel, MD Robert H. Rosenwasser, MD, FAHA

Key Words: AHA Scientific Statements • aneurysm • angiography • cerebrovascular disorders • hemorrhage • stroke • surgery • vasospasm

Annals of Emergency Medicine
Volume 52, Issue 2, August 2008, Pages S27-S39

Transient Ischemic Attack Update

Transient Ischemic Attack: Risk Stratification and Treatment

Brett Cucchiara MD^a and Michael Ross MD^b

^aDepartment of Neurology, University of Pennsylvania, Philadelphia, PA

^bDepartment of Emergency Medicine, Emory University, Atlanta, GA.

A major challenge facing the physician evaluating patients with transient ischemic attack is determining which patients are at highest short-term risk of stroke. A number of stratification schemes have been recently developed incorporating easily obtainable clinical information about the individual patient. Further, emerging data suggest a role for brain and vascular imaging in risk stratification. Many aspects of acute management of transient ischemic attack, such as which patients should be hospitalized and choice of acute antithrombotic therapy, remain controversial because of a lack of evidence from controlled trials. For longer-term prevention, there is much firmer evidence from multiple large randomized trials, and these data are reviewed in this article.

THE LANCET Neurology

Volume 8, Issue 1, January 2009, Pages 10-12

Epilepsy: seizures, syndromes, and survival

Emilio Perucca^a and Torbjörn Tomson^b

^aClinical Trial Centre, Institute of Neurology IRCCS C Mondino Foundation, Pavia and Clinical Pharmacology Unit, Department of Internal Medicine and Therapeutics, University of Pavia, Pavia, Italy

^bDepartment of Clinical Neuroscience, Karolinska Institute, Stockholm, Sweden

Article Outline

References

The commentary on epilepsy in last year's Round-up started by stating that “the evidence base that underpins the pharmacological management of the epilepsies is not earth shattering”. During the past 12 months, a few randomised controlled trials (RCTs) have gone some way to address the evidence gap. A double-blind, placebo-controlled, add-on trial has demonstrated that levetiracetam is efficacious in controlling myoclonic seizures in patients with refractory idiopathic generalised epilepsies.¹ Overall, 25% of patients in the levetiracetam group were free from myoclonic seizures during the 12-week assessment period, compared with 5% in the placebo group (p=0·004). This was not only the first RCT to be done in myoclonic seizures, but also the first RCT in a specific idiopathic generalised epilepsy syndrome—juvenile myoclonic epilepsy. The results from this trial are consistent with earlier data that have suggested that levetiracetam is a useful alternative to valproate in the treatment of myoclonic and tonic-clonic seizures associated with idiopathic generalised epilepsies. However, the efficacy of levetiracetam compared with valproate in these and other generalised epilepsies, and in newly diagnosed patients with generalised epilepsies, still needs to be investigated.

European Journal of Neurology:Volume 16(2)February 2009p 212-217

Differences in clinical course between dementia with Lewy bodies and Alzheimer's disease

[Original Articles]

Hanyu, H.; Sato, T.; Hirao, K.; Kanetaka, H.; Sakurai, H.; Iwamoto, T.

Department of Geriatric Medicine, Tokyo Medical University, Tokyo, Japan

Received 31 July 2008

Accepted 17 October 2008

Correspondence: H. Hanyu, MD, Department of Geriatric Medicine, Tokyo Medical University, 6-7-1 Nishishinjuku Shinjuku-ku, Tokyo 160-0023, Japan (tel.: +81-3-3342-6111; fax: +81-3-3342-2305; e-mail: h-hanyu@tokyo-med.ac.jp).

Abstract

Background and purpose:: To investigate whether there may be differences in the clinical course and changes in cognitive progression between dementia with Lewy bodies (DLB) and Alzheimer's disease (AD).

Methods:: We compared the time from the first visit to endpoints (discontinuation of visits because of admission, death, or institutionalization) between 56 patients with DLB and 111 patients with AD. Mini-Mental State Examination (MMSE) scores of patients were every 12 months examined up to 60 months.

Results:: Dementia with Lewy bodies had a significantly shorter time to reaching endpoints than those with AD (median time; 40 months vs. 52 months, P < 0.0001). The proportion of admission (or death) was significantly higher in DLB than in AD (30% vs. 14%, P < 0.05), while the difference in institutionalization in nursing homes did not reach statistical significance (25% vs. 17%). Rates of longitudinal MMSE score decline for DLB and AD groups were equivalent.

Conclusion:: Dementia with Lewy bodies had a greater risk of admission (or death) because of most commonly fall-related injuries and bronchopneumonia than AD, but the two groups did not differ in rate of cognitive decline.

THE LANCET Neurology

Volume 7, Issue 1, January 2008, Pages 18-19

2007 Round-Up

Karen L Roos^a

^aIndiana University School of Medicine, 545 Barnhill Drive, Indianapolis, IN 46202, USA
Article Outline

References

Patients with suspected community-acquired bacterial meningitis are commonly treated with dexamethasone, vancomycin, and a cephalosporin; vancomycin is included in case the meningitis is due to a cephalosporin-resistant strain of Streptococcus pneumoniae. However, because penetration of vancomycin through the blood–brain barrier is enhanced by meningeal inflammation, there has been concern that the anti-inflammatory properties of dexamethasone might limit concentrations of vancomycin in the CSF. In a prospective study, Ricard and colleagues¹measured vancomycin concentrations in the serum and CSF of adults in medical intensive care units who had confirmed pneumococcal meningitis and who were treated with dexamethasone and intravenous antibiotics including vancomycin (60 mg/kg per day after a loading dose of 15 mg/kg). After a few days, the mean concentration of vancomycin in CSF was four to ten times greater than the minimal inhibitory concentration of vancomycin for S pneumoniae. Eight of the 13 patients survived and were discharged from hospital with normal neurological status, and the high dose of vancomycin was well tolerated. This study supports previous reports that intravenous vancomycin can achieve adequate concentrations in the CSF when dexamethasone is used as an adjunctive agent².Ricard and colleagues recommend that vancomycin should be given at 45–60 mg/kg per day in an 8 h dosing interval.

THE LANCETVolume 372, Issue 9648, 25 October 2008-31 October 2008, Pages 1502-1517

Multiple sclerosis

Alastair Compston FRCP^a and Dr Alasdair Coles FRCP^a

^aDepartment of Clinical Neurosciences, University of Cambridge Clinical School, Addenbrooke's Hospital, Cambridge, UK
Summary

Multiple sclerosis is primarily an inflammatory disorder of the brain and spinal cord in which focal lymphocytic infiltration leads to damage of myelin and axons. Initially, inflammation is transient and remyelination occurs but is not durable. Hence, the early course of disease is characterised by episodes of neurological dysfunction that usually recover. However, over time the pathological changes become dominated by widespread microglial activation associated with extensive and chronic neurodegeneration, the clinical correlate of which is progressive accumulation of disability. Paraclinical investigations show abnormalities that indicate the distribution of inflammatory lesions and axonal loss (MRI); interference of conduction in previously myelinated pathways (evoked electrophysiological potentials); and intrathecal synthesis of oligoclonal antibody (examination by lumbar puncture of the cerebrospinal fluid). Multiple sclerosis is triggered by environmental factors in individuals with complex genetic-risk profiles. Licensed disease modifying agents reduce the frequency of new episodes but do not reverse fixed deficits and have questionable effects on the long-term accumulation of disability and disease progression. We anticipate that future studies in multiple sclerosis will provide a new taxonomy on the basis of mechanisms rather than clinical empiricism, and so inform strategies for improved treatment at all stages of the disease.

2009

英文文献摘要09

1、Neurology (R) 2009; 73: 498-503 volume: 73 issue: 7 page: 498-503

Neuropsychological and MRI measures predict short-term evolution in benign multiple sclerosis

Authors: Portaccio E (Portaccio, E.), Stromillo ML (Stromillo, M. L.), Goretti B (Goretti, B.), Zipoli V (Zipoli, V.), Siracusa G (Siracusa, G.), Battaglini M (Battaglini, M.) Giorgio A (Giorgio, A.), Bartolozzi ML (Bartolozzi, M. L.), Guidi L (Guidi, L.), Sorbi S (Sorbi, S.), Federico A (Federico, A.), Amato MP (Amato, M. P.), De Stefano N (De Stefano, N.)

Abstract：Objective: To assess whether neuropsychological tests and MRI measures could be used as predictors of short-term disease evolution in a population of patients with benign multiple sclerosis (B-MS).Background: The definition of B-MS is controversial. Recent data suggest that neuropsychological tests and MRI measures can provide valuable information for a more correct definition and interpretation of B-MS.Methods: Sixty-three patients with B-MS (Expanded Disability Status Scale [EDSS] <= 3.0 and disease duration >= 15 years) underwent neuropsychological assessment using the Rao's Brief Repeatable Neuropsychological Battery and the Stroop Test. At that time, conventional brain MRI and magnetization transfer (MT) imaging was performed. White matter lesion load, global and regional brain volumes, and MT ratio in lesions and normal-appearing brain were measured. After a mean follow-up of 5 years, patients still having an EDSS score <= 3.5 were classified as still benign, whereas patients who had developed a secondary progressive course or who had an EDSS score >= 4.0 were defined as no longer benign (NLB).Results: At end of follow-up, 29% of patients were classified as NLB. Male gender (hazard ratio [HR] = 2.9; 95% confidence interval [CI] 1.2-7.5; p = 0.02), number of neuropsychological tests failed (HR = 1.4; 95% CI 1.1-1.7; p = 0.003), and T1-weighted lesions (HR = 1.3; 95% CI 1.1-1.5; p = 0.002) were related to NLB status. In a model including these 3 variables, the NLB status was predicted with an accuracy of 82%.Conclusions: Cognitive assessment and MRI metrics can predict short-term disease evolution in benign multiple sclerosis (B-MS). This information can be useful to correctly identify patients with B-MS.

KeyWords: BRAIN-DAMAGE; SPIN-ECHO; FOLLOW-UP; DISABILITY; POPULATION; IMPAIRMENT; ATROPHY

2、Neurology (R) 2009; 73: 504-510 volume: 73 issue: 7 page: 504-510

Smoking is associated with increased lesion volumes and brain atrophy in multiple sclerosis

Authors:Zivadinov R (Zivadinov, R.), Weinstock-Guttman B (Weinstock-Guttman, B.), Hashmi K (Hashmi, K.), Abdelrahman N (Abdelrahman, N.), Stosic M (Stosic, M.), Dwyer M (Dwyer, M.), Hussein S (Hussein, S.), Durfee J (Durfee, J.) Ramanathan M (Ramanathan, M.)

Abstract: Background: Cigarette smoking has been linked to higher susceptibility and increased risk of progressive multiple sclerosis (MS). The effects of smoking on MRI characteristics of patients with MS have not been evaluated.Objectives: To compare the MRI characteristics in cigarette smoker and nonsmoker patients with MS.Methods: We studied 368 consecutive patients with MS (age 44.0 +/- SD 10.2 years, disease duration 12.1 +/- 9.1 years) comprising 240 never-smokers and 128 (34.8%) ever-smokers (currently active and former smokers). The average number of packs per day smoked (+/-SD) was 0.95 +/- 0.65, and the mean duration of smoking was 18.0 +/- 9.5 years. All patients obtained full clinical and quantitative MRI evaluation. MRI measures included T1, T2, and gadolinium contrast-enhancing (CE) lesion volumes (LVs) and measures of central, global, and tissue-specific brain atrophy. The associations between smoking status and MRI measurements were assessed in regression analysis.Results: Smoking was associated with increased Expanded Disability Status Scale (EDSS) scores (p = 0.004). The median EDSS scores (interquartile range) in the ever-smoker group and the active-smoker group were both 3.0 (2.0), compared with 2.5 (2.5) in never-smokers. There were adverse associations between smoking and the lesion measures including increased number of CE lesions (p < 0.001), T2 LV (p = 0.009), and T1 LV (p = 0.003). Smoking was associated with decreased brain parenchymal fraction (p = 0.047) and with increases in the lateral ventricle volume (p = 0.001) and third ventricle width (p = 0.023).Conclusions: Smoking is associated with increased blood-brain barrier disruption, higher lesion volumes, and greater atrophy in multiple sclerosis.

KeyWords: ENVIRONMENTAL RISK-FACTORS; EPSTEIN-BARR-VIRUS; C-REACTIVE PROTEIN; CIGARETTE-SMOKING; MATTER ATROPHY; DISEASE; EPIDEMIOLOGY; PROGRESSION; CESSATION; EXPOSURE

3、Neurology (R) 2009;72:2076-2082 volume: 72 issue: 24 page: 2076-2082

Cyclophosphamide therapy in pediatric multiple sclerosis

Authors: Makhani N (Makhani, N.), Gorman MP (Gorman, M. P.) Branson HM (Branson, H. M.), Stazzone L (Stazzone, L.), Banwell BL (Banwell, B. L.) Chitnis T (Chitnis, T.)

Abstract:Objective: To review our multicenter experience with cyclophosphamide in the treatment of children with multiple sclerosis (MS).Methods: Retrospective chart review of children with MS treated with cyclophosphamide. Demographic, clinical, treatment, and MRI parameters were collected.Results: We identified 17 children with MS treated with cyclophosphamide. All but one had worsening of Expanded Disability Status Scale scores or multiple relapses prior to treatment initiation. Children were treated with one of three regimens: 1) induction therapy alone; 2) induction therapy with pulse maintenance therapy; or 3) pulse maintenance therapy alone. Treatment resulted in a reduction in relapse rate and stabilization of disability scores assessed 1 year after treatment initiation in the majority of patients. Longer follow-up was available for most cases. Cyclophosphamide was well tolerated in most patients. However, side effects included vomiting, transient alopecia, osteoporosis, and amenorrhea. One patient developed bladder carcinoma that was successfully treated.Conclusions: Cyclophosphamide is an option for the treatment of children with aggressive multiple sclerosis refractory to first-line therapies. Recommendations regarding patient selection, treatment administration, and monitoring are discussed.

KeyWords:INTENSIVE IMMUNOSUPPRESSION; PLASMA-EXCHANGE; INTERFERON-BETA; FOLLOW-UP; CHILDHOOD; ONSET; CANCER; SAFETY; TOLERABILITY; MITOXANTRONE

4、EPILEPSIA(2009) valume: 50 issue: 1 page: 24-32

Gene therapy in epilepsy

Authors:Riban V (Riban, Veronique), Fitzsimons HL (Fitzsimons, Helen L.), During MJ (During, Matthew J.)

Abstract:Results from animal models suggest gene therapy is a promising new approach for the treatment of epilepsy. Several candidate genes such as neuropeptide Y and galanin have been demonstrated in preclinical studies to have a positive effect on seizure activity. For a successful gene therapy-based treatment, efficient delivery of a transgene to target neurons is also essential. To this end, advances have been made in the areas of cell transplantation and in the development of recombinant viral vectors for gene delivery. Recombinant adeno-associated viral (rAAV) vectors in particular show promise for gene therapy of neurological disorders due to their neuronal tropism, lack of toxicity, and stable persistence in neurons, which results in robust, long-term expression of the transgene. rAAV vectors have been recently used in phase I clinical trials of Parkinson's disease with an excellent safety profile.Prior to commencement of phase I trials for gene therapy of epilepsy, further preclinical studies are ongoing including evaluation of the therapeutic benefit in chronic models of epileptogenesis, as well as assessment of safety in toxicological studies.

KeyWords:Seizures; Transplantation; Adeno-associated viral vector; Neuropeptide Y; Galanin

5、EPILEPSIA(2009) Valume: 50 page: 2-7 增刊: Suppl. 3

The clinical concept of epilepsy

Authors:Reynolds EH (Reynolds, Edward H.), Rodin E (Rodin, Ernst)

Abstract: This article reviews the history of clinical concepts of epilepsy and its classification, especially in the last 100 years. Throughout its recorded history of 3 to 4 millennia, epilepsy has always been defined by its most dramatic symptoms, for example, falling, motor activity or loss of consciousness, but separation from other causes of the same paroxysmal symptoms has always proved challenging. For over a century there has been some semantic confusion whether to call the various paroxysms fits, convulsions, seizures, or epilepsies. Since the middle of the 19th century a great unresolved debate has continued about whether recurrent seizures or epilepsy should be viewed as a separable symptom of underlying brain disease or as one or more idiopathic diseases or syndromes, with an inherent age-related natural history; or indeed viewed as both a symptom and a disease. A major advance in the 20th century is that vascular theories of epilepsy, which reached their peak with Turner in 1907, have been replaced by electromagnetic discharges, based especially on the work of Todd, Jackson, Berger, Lennox, and the Gibbs, culminating eventually in new ILAE classifications of seizures (1981) and epilepsy syndromes (1989). However 21st century uncertainties about symptomatic versus idiopathic or cross-sectional (seizures) versus longitudinal (epilepsy) approaches to the problem very much reflect similar divergences of view a century ago. More attention is now being directed at interseizure events and processes which may lead either to remission or intractability with associated cognitive and psychosocial consequences. The search for the elusive essence, diathesis or predisposition to epilepsy, including seizure threshold, continues.

Keywords: Epilepsy; Seizure; Convulsion; Symptom; Disease; Classification

6、Stroke. 2009;40:e678-e682 Volume: 40 Issue: 12 Page: E678-E682

Baroreflex: A New Therapeutic Target in Human Stroke?

Authors: Sykora M (Sykora, Marek), Diedler J (Diedler, Jennifer), Turcani P (Turcani, Peter), Hacke W (Hacke, Werner), Steiner T (Steiner, Thorsten)

Abstract:Background and Purpose-Autonomic dysfunction, including increased sympathetic drive and blunted baroreflex, has repeatedly been observed in acute stroke. Of clinical importance is that the stroke-related autonomic imbalance seems to be linked to worse outcome after stroke. Here, we discuss the role of baroreflex impairment in acute stroke and its possible pathophysiological and therapeutic relevance.Summary of Review-Possible mechanisms linking baroreflex impairment with unfavorable outcome in stroke may include increased cardiovascular morbidity and mortality, promotion of secondary brain injury due to local inflammation, hyperglycemia, or altered cerebral perfusion.Conclusions-We suggest therefore that the modifying of autonomic functions may have important therapeutic implications in acute ischemic as well as in hemorrhagic stroke. (.)

Keywords:baroreflex sensitivity; acute stroke; heart-brain relations; outcome; therapy

7、Stroke. 2009;40:e683-e693 Volume: 40 Issue: 12 Page: E683-E693

Systematic Review of the Perioperative Risks of Stroke or Death After Carotid Angioplasty and Stenting

Authors: Touze E (Touze, Emmanuel), Trinquart L (Trinquart, Ludovic), Chatellier G (Chatellier, Gilles), Mas JL (Mas, Jean-Louis)

Abstract: Background and Purpose-Carotid angioplasty and stenting (CAS) has not been shown to be as safe as carotid endarterectomy (CEA) with regard to the risks of periprocedural complications, but beyond the perioperative period, the risks are comparable, suggesting that CAS may be an acceptable option in selected patients. However, risk factors for perioperative stroke and death have not been clearly established. We aimed to estimate the 30-day absolute risks of stroke or death after CAS and investigate sources of heterogeneity.Methods-We sought articles published between January 1990 and June 2008 by using MEDLINE, EMBASE, the COCHRANE databases, hand-searching, abstract books from conferences, and official websites. Two reviewers independently and in duplicate selected articles on the risks of CAS, irrespective of the type of treatment, study design, setting, or language. The 2 reviewers abstracted data and assessed the quality of the studies.Results-Two hundred six independent studies (with 54 713 patients) were included. The overall 30-day risk of stroke or death was 4.7% (95% CI, 4.1 to 5.2) with substantial heterogeneity across studies. Symptomatic patients were about twice as likely as those with asymptomatic stenoses to have complications. The 30-day risk of stroke or death was 7.6% (3.6 to 9.1) in symptomatic and 3.3% (2.6 to 4.1) in asymptomatic patients. Risks increased with age, hypertension, and history of coronary artery disease; were unrelated to sex and the presence of contralateral carotid occlusion; and were lower in patients who had carotid restenosis after CEA and in those treated with the use of a cerebral protection device. Risks have also decreased over time.Conclusions-Risks of CAS vary substantially across studies. Risks are overall higher than those of CEA in symptomatic patients. Some factors are likely to help select good candidates for CAS. (.)

KeyWords :stroke; carotid disease; stenting; angioplasty; atherosclerosis; systematic review

8、BRAIN (2009) Volume: 132 Part 7 Page: 1810-1819

Depletion of medullary serotonergic neurons in patients with multiple system atrophy who succumbed to sudden death

Authors:Tada M (Tada, Mari), Kakita A (Kakita, Akiyoshi), Toyoshima Y (Toyoshima, Yasuko), Onodera O (Onodera, Osamu) Ozawa T (Ozawa, Tetsutaro), Morita T (Morita, Takashi), Nishizawa M (Nishizawa, Masatoyo) Takahashi H (Takahashi, Hitoshi)

Abstract:Multiple system atrophy (MSA) is a neurodegenerative disorder characterized by prominent autonomic failure with ataxia and/or parkinsonism. The leading cause of death in MSA is sudden death. We have shown that the early development of autonomic failure is an independent risk factor for sudden death. The depletion of sympathetic preganglionic neurons in the spinal intermediolateral cell column (IML) and its afferent medullary catecholaminergic and serotonergic neurons has been proposed to be partly responsible for autonomic failure in MSA. In this study, we investigated whether the depletion of neurons in any of these autonomic neuron groups contributes to sudden death in MSA. Out of 52 autopsy-proven patients with MSA, we selected 12 individuals who had died within 3.5 years after disease onset to define the accurate levels of slices and identify early neuropathological changes of autonomic nuclei in MSA. Four patients succumbed to sudden death and eight patients died through established causes. Serial 10 mu m sections were obtained from the 8th segment of the thoracic cord and the rostral medulla oblongata. Sections from the medulla oblongata were immunostained for thyrosine hydroxylase and tryptophan hydroxylase. The total cell number in the five sections was computed for comparison. Compared with the control, the MSA group showed a marked depletion of neurons in the IML (38.0 +/- 7.1 versus 75.2 +/- 7.6 cells, P < 0.001), thyrosine hydroxylase-immunoreactive neurons in the ventrolateral medulla (VLM) (17.4 +/- 5.1 versus 72.8 +/- 13.6 cells, P < 0.01) and tryptophan hydroxylase-immunoreactive neurons in the VLM (15.6 +/- 9.2 versus 60.8 +/- 17.0 cells, P < 0.01), nucleus raphe obscurus (19.3 +/- 4.4 versus 75.3 +/- 8.6 cells, P < 0.001), nucleus raphe pallidus (2.1 +/- 2.7 versus 9.0 +/- 3.4 cells, P < 0.03), and arcuate nucleus (0.4 +/- 0.8 versus 2.3 +/- 1.5 cells, P < 0.05). Moreover, in patients who succumbed to sudden death, when compared with patients who had established causes of death, we found a marked depletion of tryptophan hydroxylase-immunoreactive neurons in the VLM (7.3 +/- 3.5 versus 21.8 +/- 6.5 cells, P < 0.02) and nucleus raphe obscurus (15.0 +/- 2.0 versus 22.5 +/- 2.1 cells, P < 0.01). The results indicate that the spinal IML and medullary catecholaminergic and serotonergic systems are involved even in the early stages of MSA, and the dysfunction of the medullary serotonergic system regulating cardiovascular and respiratory systems could be responsible for sudden death in patients with MSA.

KeyWords: multiple system atrophy; sudden death; medulla oblongata; serotonin; catecholamine

9、BRAIN (2009) Volume: 132 Part 11 Page: 2947-2957

A clinico-pathological study of subtypes in Parkinson's disease

Authors: Selikhova M (Selikhova, M.)Williams DR (Williams, D. R.), Kempster PA (Kempster, P. A.) Holton JL (Holton, J. L.) Revesz T (Revesz, T.), Lees AJ (Lees, A. J.)

Abstract:We have carried out a systematic review of the case files of 242 donors with pathologically verified Parkinson's disease at the Queen Square Brain Bank for Neurological Disorders in an attempt to corroborate the data-driven subtype classification proposed by Lewis and colleagues (Heterogeneity of Parkinson's disease in the early clinical stages using a data driven approach. J Neurol Neurosurg Psychiatry 2005; 76: 343-8). Cases were segregated into earlier disease onset (25%), tremor dominant (31%), non-tremor dominant (36%) and rapid disease progression without dementia (8%) subgroups. We found a strong association between a non-tremor dominant disease pattern and cognitive disability. The earlier disease onset group had the longest duration to death, and greatest delay to the onset of falls and cognitive decline. Patients with a tremor dominant disease pattern did not live significantly longer than non-tremor dominant patients and showed no difference in mean time to onset of falls and hallucinations. Rapid disease progression was associated with older age, early depression and early midline motor symptoms, and in 70% of the cases, tremulous onset. The non-tremor dominant subgroup had a significantly higher mean pathological grading of cortical Lewy bodies than all other groupings (P < 0.05) and more cortical amyloid-beta plaque load and cerebral amyloid angiopathy than early disease onset and tremor dominant groups (P = 0.047). An analysis of cases with pathologically defined neocortical Lewy body disease confirmed the link between bradykinetic onset, cognitive decline and Lewy body deposition in the neocortex. Although neuropathological examination failed to distinguish the other subtypes, the classification scheme was supported by an analysis of clinical data that were independent of the basic subgroup definitions.

KeyWords: bradykinesia; Parkinson's disease dementia; Lewy body; tremor dominant phenotype; age of onset

10、EUROPEAN JOURNAL OF NEUROLOGY (2009) Volume: 16 Issue: 11 Page: 1233-1239

A study of F-waves in patients with unilateral lumbosacral radiculopathy

Authors: Pastore-Olmedo C (Pastore-Olmedo, C.), Gonzalez O (Gonzalez, O.), Geijo-Barrientos E (Geijo-Barrientos, E.)

Abstract：Background and purpose:The F wave, a late response of low amplitude, is widely used in the study of peripheral nerve lesions, and its persistence and latencies are the main parameters that are usually considered. The analysis of repeater F-waves, which are commonly observed in association with focal or generalized motor neuropathy, is not always performed as a standard electrodiagnostic protocol.Methods:We recorded and quantified the F waves from 13 healthy subjects and 22 patients with unilateral lumbosacral radiculopathy (ULSR) affecting the L5 or S1 roots.Results:We found differences between the injured and normal sides of patients with ULSR in several F-wave parameters. Taking into consideration the normalized and pooled values of tibial and peroneal nerves in the injured side of patients with ULSR, the minimum and mean latencies were higher (1.05 and 1.04 with respect to 1.00; P < 0.01), the relative amplitude of the F waves was higher (1.95 with respect to 1.00; P < 0.001), and the percentage of repeater F-waves was also higher (4.19 with respect to 1.00; P < 0.001). This latter parameter was the most sensitive to detect lateral differences as indicated by the percentage of change and its high z score.Conclusions:Our results show that the use of F-waves may improve the electrodiagnosis of the ULSR if the number of repeater waves is evaluated given the clear and consistent increase of this variable in patients with lumbosacral root injury.

KeyWords： electromyography; F-waves; nerve conduction studies; repeater F-waves; single fiber electromyography

11、EUROPEAN JOURNAL OF NEUROLOGY（2009） Volume 16 Issue 5 Page: 589-594

Assessment of dementia in patients with multiple system atrophy

Authors: Kitayama M (Kitayama, M.) Wada-Isoe K (Wada-Isoe, K.), Irizawa Y (Irizawa, Y.), Nakashima K (Nakashima, K.)

Abstract： We investigated dementia in patients with multiple system atrophy (MSA) in order to characterize the prevalence and nature of impairments in these patients.

Fifty-eight MSA patients were recruited in our institution between April 1996 and December 2006 and investigated.Of 58 patients, 10 were diagnosed with dementia. There were no significant differences in age at onset, gender, duration of disease, or severity of cerebellar dysfunction between patients with and without dementia. The early and delayed heart to mediastinum (H/M) ratios obtained with I-123-metaidobenylguanidine (MIBG) cardiac scintigraphy were significantly decreased in patients with dementia compared with those without dementia. Of the 10 patients with dementia, three were found to have cognitive decline that preceded onset of motor symptoms. White matter lesions were evident in these patients, whilst frontal atrophy was prominent in patients whose cognitive decline was preceded by onset of motor symptoms.Dementia in patients with MSA may be more common than previously thought, furthermore, we speculate that clinical features of dementia in these patients might be heterogeneous.

Keywords：cognitive impairment; Lewy body disease; MIBG cardiac scintigraphy; multiple system atrophy; alpha-synucleinopathy

13、EUROPEAN JOURNAL OF NEUROLOGY（2009）Volume 16 Issue: 2 Page: 205-211 biomarker profile and diagnostic value in vascular dementia

Authors: Paraskevas GP (Paraskevas, G. P.), Kapaki E (Kapaki, E.), Papageorgiou SG (Papageorgiou, S. G.), Kalfakis N (Kalfakis, N.), Andreadou E (Andreadou, E.), Zalonis I (Zalonis, I.), Vassilopoulos D (Vassilopoulos, D.)

Abstract：The differential diagnosis between vascular dementia (VD) and Alzheimer's disease (AD) or mixed dementia (MD) is not always easy in clinical practice. The purpose of the present study was to evaluate the cerebrospinal fluid (CSF) biomarkers tau protein in its total (tau(T)) or hyperphosphorylated at threonin-181(tau(P-181)) form and beta amyloid peptide 1-42 (A beta 42) alone and their combinations to investigate their diagnostic value in the discrimination between VD and AD or MD.The above CSF biomarkers were determined in duplicate and blind to the clinical diagnosis by double sandwich, enzyme-linked immunosorbent assay (ELISA) commercial kits (Innogenetics, Gent, Belgium) in 92 AD patients, 23 VD patients, 17 patients with MD and 68 controls.Alzheimer's disease and MD showed increased levels of tau(T), tau(P) and reduced levels of A beta 42 as compared with the controls. The best discrimination between VD and AD or MD was achieved by the combination of all three biomarkers, correctly classifying >= 85% of patients, either in the form of a discriminant function or in the form of the tau(T) x tau(P-181)/A beta 42 formula.Cerebrospinal fluid biomarkers may be a useful adjunct for the discrimination between AD/ MD and VD in every day clinical practice.

KeyWords Alzheimer's disease; cerebrospinal fluid; phospho-tau; tau protein; vascular dementia; beta-amyloid

14、NEUROLOGY 2009;73:552-559 volume: 73 issue: 7 page: 552-559

The challenge of follow-on biologics for treatment of multiple sclerosis

Authors: Reingold SC (Reingold, S. C.), Steiner JP (Steiner, J. P.), Polman CH (Polman, C. H.), Cohen JA (Cohen, J. A.), Freedman MS (Freedman, M. S.), Kappos L (Kappos, L.), Thompson AJ (Thompson, A. J.), Wolinsky JS (Wolinsky, J. S.)

Abstract：Intellectual property protections for biologic medicinals for multiple sclerosis ( MS) are beginning to expire, opening the possibility of development, regulatory approval, and marketing of so-called follow-on biologics, biosimilars, or subsequent entry biologics that might be offered at lower price to consumers and third-party payers, as has been the case for generic drugs. Determining the comparability of a follow-on biologic to its innovator product is more difficult than for small-molecule drugs because of the greater complexity of biologics and the possibility that manufacturing differences can introduce differences in biologic activity and immunogenicity that could result in unpredictable differences in safety or efficacy. We provide a perspective on issues surrounding development, regulatory approval, and potential use of follow-on biologics, with an emphasis on disease-modifying agents for MS.

KeyWords:INTERFERON-BETA; ANTIBODIES; IMMUNOGENICITY; GUIDELINES; THERAPIES; IMPACT