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Positive frequency of autoantibodies in multiple sclerosis patients Are they associated with therapy?

Neural Regeneration Research 2010年第4期5卷 257-260页

作者： Gerardo Iuliano Luigi Cinquanta Anna Maria Ferruzzi Rosa Napoletano Azienda Ospedaliera Ospedali Riuniti di SalernoU.O.NeurologiaCentro Provinciale Sclerosi Multipla Azienda Ospedaliera Ospedali Riuniti di SalernoU.O.Laboratorio Patologia Clinica Azienda Ospedaliera Ospedali Riuniti di Salerno

BACKGROUND： Humoral autoimmunity in patients with multiple sclerosis is often asymptomatic and transient during interferon therapy. OBJECTIVE： To analyze the frequency of positivity to autoantibodies in multiple sclerosis patients and to clarify whether it is modified by immunomodulating therapy. DESIGN： A retrospective *** AND SE＇rrlNG： The study was performed at the Multiple Sclerosis Center, Department of Neurosciences, Salerno Hospital, Italy, between 2005 and 2007. PARTICIPANTS： A total of 169 multiple sclerosis patients were included, 57 males and 112 females Individuals were mainly outpatients and were usually tested yearly for autoantibodies. Patients with previous immunological diseases were excluded from statistical evaluation. METHODS： The frequency of positivity was calculated in patients grouped for gender, multiple sclerosis clinical parameters, magnetic resonance imaging features and disease modifying therapy. A total of 113 patients were treated with beta interferons. MAIN OUTCOME MEASURES： Frequency of positivity to any autoantibody. Prevalences and incidences were ***： The overall prevalence of autoantibodies within 3 years was 47.3%. In multiple sclerosis patients who were untreated or treated with drugs other than interferons, the prevalence was higher, and greater positivity to autoantibodies was seen in patients treated with interferons [odds ratio （95% confidence interval）, 2.87 （1.5 - 5.2）, P 〈 0.05 - 0.01]. Multiple regression analysis showed a significant association of the positivity to autoantibodies with interferon therapy, rather than gender, relapse or magnetic resonance imaging. CONCLUSION： Interferon therapy is associated with significantly higher frequency of autoantibodies in patients with multiple sclerosis. The differences among the therapies are not influenced by other variables such as gender or clinical pattern.

关键词： multiple sclerosis autoimmunity autoantibodies immunomodulation interferon

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帕金森病患者的疼痛和运动并发症

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世界核心医学期刊文摘(神经病学分册) 2006年第11期 31-32页

作者： Tinazzi M Del Vesco C Fincati E 郭俊 unità operativa di neurologia OC Borgo Trento Piazzale Stefani 1 37100 Verona Italy Dr.

Aims: To study the association of pain with motor complications in 117 patients with Parkinson’s disease. Methods: Patients were asked to refer any pain they experienced at the time of study and lasting since at least 2 months. Basic parkinsonian signs and motor complications (including motor fluctuations and dyskinesia) were assessed and Unified Parkinson’s disease Rating Scale (UPDRS) motor score part III (during on) and part IV were calculated. Information on age, sex, duration of disease, use of dopamine agonists and levodopa, years of levodopa treatment and current levodopa dosage, medical conditions possibly associated with pain, and depression were collected. Single and multiple explanatory variable logistic regression models were used to check the association of pain with the investigated variables. Results: Pain was described by 47 patients (40%) and could be classified into dystonic (n=19) and non dystonic pain (n=16); in 12 patients both types coexisted. Multiple explanatory variable logistic regression models indicated a significant association of pain with motor complications (adjusted OR, 5.7; 95%CI, 2 to 16.5; P = 0.001). No association was found between pain, dystonic or non dystonic, and the other investigated variables including medical conditions known to be associated to pain in the general population. There was a significant correlation (r = 0.31, p disease frequently associated with motor complications. The association is independent of a number of potentially relevant demographic and clinical variables.

关键词：运动并发症帕金森病疼痛患者

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急性非腔隙性脑半球梗死发病3h内开始静脉注射肝素治疗

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世界核心医学期刊文摘（神经病学分册） 2006年第3期2卷 53-54页

作者： Camerlingo M. Salvi P. Belloni G. 刘凯 unità operativa di neurologia Policlinico San Marco Corso Europa 7 I-24040 Osio Sotto (Bergamo) Italy

Background and Purpose -Heparin is widely used for acute stroke to prevent thrombus propagation and/or multiple emboli generation, although there is, as yet, no demonstrated efficacy. However, all of the available clinical studies allowed long intervals from stroke to treatment. The purpose of this study was to try an intravenous regimen of unfractionated heparin the acute cerebral infarction starting treatment within the first 3 hours of the onset of symptoms. Methods -The study was an outcome evaluator-blind design trial. Patients had to display signs of a nonlacunar hemispheric infarction. Selected patients were randomly allocated to receive intravenous heparin sodium or saline. Heparin was infused at a rate to maintain activated partial thromboplastin time ratio 2.0 to 2.5 ×control for 5 days. The primary end point was recovery of a modified Rankin score zero to 2 at 90 days of stroke at phone interview by a single physician blind to treatment. Safety end points were death, symptomatic intracranial hemorrhages, and major extracranial bleedings by 90 days of stroke. Results -A total of 418 stroke patients were included. In the heparin group, there were more self-independent patients (38.9%versus 28.6%; P=0.025). In addition, in the same group, there were fewer deaths (16.8%versus 21.9%; P=0.189), more symptomatic brain hemorrhages (6.2%versus 1.4%; P=0.008), and more major extracerebral bleedings (2.9%versus 1.4%; P=0.491). Conclusions -Intravenous heparin sodium could be of help in the earliest treatment of acute nonlacunar hemispheric cerebral infarction, even keeping into account an increased frequency of intracranial symptomatic brain hemorrhages.

关键词：肝素钠急性卒中症状性出血脑内出血急性脑梗死大脑半球普通肝素凝血活酶血栓形成电话访谈

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Depressive symptoms in neurodegenerative diseases

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World Journal of Clinical Cases 2015年第8期3卷 682-693页

作者： Miquel Baquero Nuria Martín Servei de neurologia Hospital Universitari i Politècnic La Fe

Depressive symptoms are very common in chronic conditions. This is true so for neurodegenerative diseases. A number of patients with cognitive decline and dementia due to Alzheimer's disease and related conditions like Parkinson's disease, Lewy body disease, vascular dementia, frontotemporal degeneration amongst other entities, experience depressive symptoms in greater or lesser grade at some point during the course of the illness. Depressive symptoms have aparticular significance in neurological disorders, specially in neurodegenerative diseases, because brain, mind, behavior and mood relationship. A number of patients may develop depressive symptoms in early stages of the neurologic disease, occurring without clear presence of cognitive decline with only mild cognitive deterioration. Classically, depression constitutes a reliable diagnostic challenge in this setting. However, actually we can recognize and evaluate depressive, cognitive or motor symptoms of neurodegenerative disease in order to establish their clinical significance and to plan some therapeutic strategies. Depressive symptoms can appear also lately, when the neurodegenerative disease is fully developed. The presence of depression and other neuropsychiatric symptoms have a negative impact on the quality-of-life of patients and caregivers. Besides, patients with depressive symptoms also tend to further decrease function and reduce cognitive abilities and also uses to present more affected clinical status, compared with patients without depression. Depressive symptoms are treatable. Early detection of depressive symptoms is very important in patients with neurodegenerative disorders, in order to initiate the most adequate treatment. We review in this paper the main neurodegenerative diseases, focusing in depressive symptoms of each other entities and current recommendations of management and treatment.

关键词： Neurodegenerative diseases Alzheimer Depressive symptoms Frontotemporal degeneration Vascular dementia Lewy body disease Depression Dementia

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Stroke and depression: A bidirectional link

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World Journal of Meta-Analysis 2014年第3期2卷 49-63页

作者： Elisabetta Del Zotto Paolo Costa Andrea Morotti Loris Poli Valeria de Giuli Alessia Giossi Irene Volonghi Antonio Callea Alessandro Padovani Alessandro Pezzini U.O. di Recupero e Rieducazione Funzionale IRCCS Fondazione Don Gnocchi dipartimento di Scienze Cliniche e Sperimentali Clinica NeurologicaUniversità degli Studi di Brescia U.O neurologia Istituto Clinico "S. Anna" dipartimento Fisiopatologia Medico-Chirurgica e dei Trapianti Sezione di NeuroscienzeUniversità degli Studi di Milano

A number of studies have assessed the influence of depression on the risk of cardiovascular disease. A growing literature indicates a link between depression and cerebrovascular events, although the direction of this association remains unclear. Numerous data have emerged suggesting an association between depressive symptoms and subsequent risk of stroke, thus leading to the hypothesis that a direct causality between depression and stroke exists. Notwithstanding, how depression may act as a risk factor for stroke is still unclear. Depression might be linked to stroke via neuroendocrine and inflammation effects, through correlation with major comorbidities such as hypertensionand diabetes or by intervention of lifestyle behavioral mediators. Finally, antidepressant medications have recently drawn attention for a possible association with increased risk of stroke, although such findings remain uncertain. Depression has been also established as an important consequence after stroke, exerting a significant adverse impact on the course of motor recovery, social functioning and, overall, on quality of life. Post stroke depression occurs in nearly one third of stroke cases, but the exact mechanism leading to depression after stroke is still incompletely understood. In this article, we will review contemporary epidemiologic studies, discuss potential mechanisms and specific aspects of the complex relation between depression and stroke.

关键词： Depression Mood disorders Stroke Poststroke depression Antidepressant medications Cerebrovascular disease

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散发性Mbius综合征的面部运动损伤定位

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世界核心医学期刊文摘(神经病学分册) 2006年第12期 6-7页

作者： Cattaneo L. Chierici E. Bianchi B. 牛亚利 Dr.Sezione di neurologia Dipartimento di NeuroscienzeUniversitàdi ParmaVia Gramsci 1443100 ParmaItaly

OBJECTIVE:To investigate the neurophysiologic aspects of facial motor control in patients with sporadic Mbius syndrome defined as nonprogressive congenital facial and abducens ***:The authors assessed 24 patients with sporadic Mbius syndrome by performing a complete clinical examination and neurophysiologic tests including facial nerve conduction studies,needle electromyography examination of facial muscles,and recording of the blink reflex and of the trigeminofacial inhibitory ***:Two distinct groups of patients were identified according to neurophysiologic *** first group was characterized by increased facial distal motor latencies(DMLs)and poor recruitment of small and polyphasic motor unit action potentials(MUAPs).The second group was characterized by normal facial DMLs and neuropathic *** is hypothesized that in the first group,the disorder is due to a rhombencephalic maldevelopment with selective sparing of small-size MUs,and in the second group,the disorder is related to an acquired nervous injury during intrauterine life,with subsequent neurogenic remodeling of *** trigeminofacial reflexes showed that in most subjects of both groups,the functional impairment of facial movements was caused by a nuclear or peripheral site of lesion,with little evidence of brainstem interneuronal ***:Two different neurophysiologically defined phenotypes can be distinguished in sporadic Mbius syndrome,with different pathogenetic implications.

关键词：散发性面部 bius 综合征综合病症

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原发性高血压肾素-血管紧张素-醛固酮系统基因多态性和肾功能不全之间的关系

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世界核心医学期刊文摘（心脏病学分册） 2005年第8期1卷 59-60页

作者： Fabris B. Bortoletto M. Candido R. 杜媛 University of Trieste Dipto. di Med. Clinica e Neurologia c/o Ospedale di Cattinara Strada di Fiume 447 34149 Trieste Italy

Objective: The renin- angiotensin- aldosterone system(RAAS)plays an important role in the control of renal function both in physiological and pathological conditions. The aim of the present study was to evaluate the relation between four genetic polymorphisms of the RAAS and renal insufficiency in a population of patients with essential hypertension living in north- east Italy. Design and methods: Eighty- six hypertensive patients with renal insufficiency and 172 hypertensive patients without renal damage matched for age and hypertension duration to within 2 years were evaluated. Genotyping for insertion/deletion of angiotensin- converting enzyme(ACE I/D), angiotensinogen(AGT) M235T, angiotensin II type 1 receptor(AT1R)A1166C and aldosterone synthase(CYP11B2)- 344C/T polymorphisms were performed using polymerase chain reaction, with further restriction analysis when required. Results: Each of the genetic polymorphisms of the RAAS genes was associated with renal failure; the adjusted odds ratios were 1.47 and 1.89 for ACE D allele, assuming a co dominant and a recessive mode of inheritance, respectively; 1.51 for AGT T235 allele assuming a co dominant, and 1.98 assuming a recessive, pattern of inheritance; 1.79 for AT1R C1166 allele considering a dominant pattern; and 3.89 for CYP11B2- 344C allele as a recessive effect. However, CYP11B2 genotypes were not in Hardy- Weinberg equilibrium among controls. The associations AGT TT- AT1R AC and CYP11B2 CC- ACE DD showed a possible positive interaction in the development of renal insufficiency among hypertensive subjects. The association AGT MM- AT1R AA and AGT MM- AT1R AA- CYP11B2 TT or TC combinations were associated with a reduced risk for renal failure. Conclusions: Our findings suggest that in patients with essential hypertension an unfavorable genetic pattern of RAAS may contribute to the increased risk for the development of renal failure.

关键词：原发性高血压肾功能不全基因多态性高血压病程血管紧张素原 RAAS 肾功能衰竭肾功能受损比值比 Weinberg

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Hakim-Adams syndrome secondary to syphilis

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Case Reports in Clinical Medicine 2013年第6期2卷 377-379页

作者： Ricardo Krause Martinez de Souza Alexandre Zatera Fernanda Leal Suzano Flavia de Oliveira Braga Samanta Fabrício Blattes da Rocha Ricardo Ramina Pedro Andre Kowacs Ambulatorio de Desordens da Memoria e do Comportamento Instituto de Neurologia de CuritibaCuritibaBrazil Instituto de Psiquiatria do Parana CuritibaBrazil Servico de neurologia e Neurocirurgia CuritibaBrazil

Normal pressure hydrocephalus (NPH) secondary to syphilis is an atypical form of neurosyphilis with an unusual clinical presentation and uncommon neuroimaging findings. A case of Syndrome de Hakim-Adams occurring in a 79-year-old male was admitted for investigation of a dementia syndrome. The patient presented with clinical features and neuroimaging compatible with NPH. Syphilis serology was reactive and compatible with active disease. The patient was treated with crystalline penicillin (4 million units every 4 hours for 21 days) and was assessed again after three months, when his cognition and gait had improved and the urinary incontinence had resolved. According to this information, we describe a case of syphilis mimicking normal pressure hydrocephalus, making clear the importance of the investigation of sexually transmitted diseases in the differential diagnosis of dementia, even in patients without established risk supposedly.

关键词： Neurosyphilis Hakim-Adams Syndrome Syphilis Normal Pressure Hydrocephalus

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抗-MAG抗体阳性和阴性的慢性免疫异常脱髓鞘性多神经病的鉴别诊断

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世界核心医学期刊文摘（神经病学分册） 2005年第5期1卷 24-25页

作者： Isoardo G. Migliaretti G. Ciaramitaro P. 江山 divisione di neurologia Ospedale Civile Via Botallo 4 14100 Asti Italy Dr.

The distinction between chronic demyelinating polyneuropathies associated wit h IgM paraproteinemia and anti-myelin-associated glycoprotein (MAG) antibodi es (MAG- PN) and chronic inflammatory demyelinating polyneuropathies (CIDPs) r elies on the anti-MAG antibodies assay. The aim of the study was to identify c linical and electrophysiological features suggesting a diagnosis of MAG-PN. Fo urteen patients with MAG-PN and 35 with CIDP were included, and a discriminant analysis was performed to identify the clinical and electrophysiological featur es suggestive of MAG-PN. Pure sensory clinical phenotype, low median and ulnar terminal latency index, and absence of M responses in the lower limbs were sign ificantly associated with the diagnosis of MAG-PN, and indicate a moderate to large increase in probability of this diagnosis in patients with chronic dysimmu ne demyelinating polyneuropathies.

关键词：脱髓鞘性 MAG抗体鉴别诊断多神经病免疫异常慢性炎性电生理学临床表型正中神经尺神经

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S-adenosyl-methionine decreases ethanol-induced apoptosis in primary hepatocyte cultures by a c-Jun N-terminal kinase activity-independent mechanism

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World Journal of Gastroenterology 2006年第12期12卷 1895-1904页

作者： Maria del Pilar Cabrales-Romero Lucrecia Márquez-Rosado Samia FatteI-Fazenda Cristina Trejo-Solis Evelia Arce-Popoca Leticia Alemán-Lazarini Saúl Villa-Trevineo Department of Cell Biology Centro de Investigacién y Estudios Avanzados IPN Av. IPN No. 2508 México DF México Department of Neuroimmunology Instituto National de Neurologia y Neurocirugia MVS Insurgentes Sur 3877 Col La Fama DF México

AIM： To determine the role of c-Jun N-terminal kinase （JNK） activity in ethanol-induced apoptosis and the modulation of this signaling cascade by S-Adenosylmethionine （AdoMet）. METHODS： Primary hepatocyte cultures were pretreated with 100 IJmol/L SP600125, a selective JNK inhibitor, 1 mL/L DMSO or 4 mmol/L AdoMet and then exposed to 100 mmo/L ethanol. Hepatocyte apoptosis was determined by the TUNEL and DNA ladder assays. JNK activity and its inhibition by SP600125 and AdoMet were determined by Western blot analysis of c-jun phosphorylation and Bid fragmentation. SP600125 and AdoMet effects on the apoptotic signaling pathway were determined by Western blot analysis of cytochrome c release and pro-caspase 3 fragmentation. The AdoMet effect on glutathione levels was measured by EIIman＇s method and reactive oxygen species （ROS） generation by cell cytometry. RESULTS： The exposure of hepatocytes to ethanol induced JNK activation, c-jun phosphorylation, Bid fragmentation, cytochrome c release and pro-caspase 3 cleavage; these effects were diminished by SP600125, and caused a significant decrease in ethanol-induced apoptosis （P〈 0.05）. AdoMet exerted an antioxidant effect maintaining glutathione levels and decreasing ROS generation, without a significant effect on JNK activity, and prevented cytochrome c release and pro-caspase 3 cleavage.CONCLUSION： The JNK signaling cascade is a key component of the proapoptotic signaling pathway induced by ethanol. JNK activation may be independent from ROS generation, since AdoMet which exerted antioxidant properties did not have a significant effect on JNK activity. JNK pathway modulator agents and AdoMet may be components of promising therapies for alcoholic liver disease （ALD） treatment.

关键词： Alcoholic liver disease c-Jun N-terminal kinase Apoptosis SP600125 S-Adenosyl methionine Bid Reactive oxygen species

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