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Cerebrospinal fluid levels of chromogranin A and phosphorylated neurofilament heavy chain are elevated in amyotrophic lateral sclerosis
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M. Kaiserova Z. Grambalova P. Otruba D. Stejskal H. Prikrylova Vranova J. Mares K. Mensikova P. Kanovsky 《Acta neurologica Scandinavica》2017,136(4):360-364
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L. Fialová J. Švarcová A. Bartos P. Ridzoň I. Malbohan O. Keller R. Rusina 《European journal of neurology》2010,17(4):562-566
Background: The aim of the study was to assess autoimmune involvement in amyotrophic lateral sclerosis (ALS). Methods: We measured IgG antibodies against light (NFL) and medium (NFM) subunits of neurofilaments using ELISA in paired cerebrospinal fluid (CSF) and serum samples from 38 ALS patients and 20 controls. Results: Serum levels of anti‐NFL were higher in ALS patients than in controls (P < 0.005). Serum anti‐NFL antibodies and intrathecal anti‐NFM antibodies were related to patient disability (serum anti‐NFL: P < 0.05; intrathecal anti‐NFM: P < 0.05). Anti‐NFL levels were significantly correlated with anti‐NFM levels in ALS (P < 0.001) and the control group (P < 0.0001) in the CSF, but not in serum. Anti‐NFL and anti‐NFM antibodies significantly correlated between serum and CSF in the ALS group (anti‐NFL: P < 0.0001; anti‐NFM: P < 0.001) and in the control group (anti‐NFL: P < 0.05; anti‐NFM: P < 0.05). Conclusions: Autoimmune humoral response to neurocytoskeletal proteins is associated with ALS. 相似文献
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P. Paladino F. Valentino T. Piccoli F. Piccoli V. La Bella 《European journal of neurology》2009,16(2):257-261
Background: Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder leading to progressive motor neuron cell death. Etiopathogenesis is still imperfectly known and much effort have been undertaken to find a biological marker that could help in the early diagnosis and in the monitoring of disease progression. Cerebrospinal fluid (CSF) concentrations of tau , an axonal microtubule-associated protein, have been measured in ALS with levels found increased in some studies and unchanged in others.
Methods: Total CSF tau level was assayed in a population of ALS patients ( n = 57) and controls ( n = 110) using a specific ELISA method.
Results: No significant differences in the median CSF tau levels between ALS cases and controls were found [ALS: 126 pg/ml (78–222); controls: 112 pg/ml (71–188), P = ns]. In the ALS group, the bulbar-onset patients showed increased CSF tau levels as compared with the spinal-onset cases. These differences might be related to the higher age of the bulbar-onset patients. Further, no correlations were found between CSF tau concentrations and the rate of progression of the disease.
Conclusions: These results do not support the hypothesis that total CSF tau protein is a reliable biological marker for ALS. 相似文献
Methods: Total CSF tau level was assayed in a population of ALS patients ( n = 57) and controls ( n = 110) using a specific ELISA method.
Results: No significant differences in the median CSF tau levels between ALS cases and controls were found [ALS: 126 pg/ml (78–222); controls: 112 pg/ml (71–188), P = ns]. In the ALS group, the bulbar-onset patients showed increased CSF tau levels as compared with the spinal-onset cases. These differences might be related to the higher age of the bulbar-onset patients. Further, no correlations were found between CSF tau concentrations and the rate of progression of the disease.
Conclusions: These results do not support the hypothesis that total CSF tau protein is a reliable biological marker for ALS. 相似文献
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Kawajiri M Mogi M Higaki N Tateishi T Ohyagi Y Horiuchi M Miki T Kira JI 《Acta neurologica Scandinavica》2009,119(5):341-344
Background – Recent studies suggest that angiotensin II, a major substrate in the renin–angiotensin system, protects neurons through stimulation of its type 2 receptors. However, quite a few clinical studies of angiotensin II levels have shown their relation to disease severity in neurodegenerative disorders, including amyotrophic lateral sclerosis (ALS). Aims of the study – To clarify the significance of angiotensin II in ALS. Methods – We assayed angiotensin II concentrations in cerebrospinal fluid (CSF) samples from 23 patients with ALS, nine patients with spinocerebellar degeneration (SCD) and 24 control individuals. We evaluated the disability levels of patients with ALS using the Revised ALS Functional Rating Scale (ALSFRS‐R) and calculated the disease progression rate (DPR). Results – CSF angiotensin II levels were significantly lower in the ALS group compared with that in the control group (P = 0.00864), and showed a significant positive correlation with scores on the ALSFRS‐R, and a significant negative correlation with the DPR. Conclusions – In the present study, we reveal for the first time that angiotensin II levels in the CSF from patients with ALS are significantly reduced and significantly associated with disease severity and progression rate. These findings suggest that reduced levels of intrathecal angiotensin II may play a role in ALS. 相似文献
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肌萎缩侧索硬化症是一种慢性进展性疾病,目前病因及发病机制不明,尚无有效的生物标志物协助疾病诊断、判断疾病进展及预后。生物标记物研究通过对病理生理机制的探索可以加深对疾病的理解,有助于疾病诊断、分类、药效学检测,及识别新的药物靶点,为新疗法实施提供方向。 [引用格式:国际神经病学神经外科学杂志, 2021, 48(4): 392-395.] 相似文献
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Iłzecka J 《Acta neurologica Scandinavica》2006,114(3):205-209
OBJECTIVES: The Flt3 ligand (FL) is a cytokine with a neurotrophic and antiapoptotic activity in the central nervous system that induces the survival of neurons. The aim of the study was to measure levels of FL in amyotrophic lateral sclerosis (ALS) patients. MATERIALS AND METHODS: The study involved 23 ALS patients and 23 people in the control group. The measurement of FL in the cerebrospinal fluid (CSF) and serum was performed by the enzyme-linked immunosorbent method. RESULTS: Results showed that CSF FL levels were significantly increased in ALS patients compared with the controls (P < 0.05) but the serum levels of this cytokine did not differ from the controls (P > 0.05). There was no significant correlation between CSF and serum FL levels and clinical parameters of ALS (P > 0.05). The difference in CSF/serum ratio of FL between ALS patients and controls was not statistically significant (P > 0.05). CONCLUSION: An increase in CSF FL levels in ALS patients, observed in this study, could be a compensative response for neurodegeneration but may also reflect increased diffusion of this cytokine into the central nervous system caused by blood-CSF barrier dysfunction. 相似文献
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F. de Bustos F. J. Jiménez-Jiménez J. A. Molina J. Esteban A. Guerrero-Sola M. Zurdo M. Ortí-Pareja A. Tallón-Barranco C. Gómez-Escalonilla C. Ramírez-Ramos J. Arenas R. Enríquez de Salamanca 《Journal of neural transmission (Vienna, Austria : 1996)》1998,105(6-7):703-708
Summary. We compared CSF and serum levels, and the CSF/serum ratio of alpha-tocopherol (vitamin E), measured by HPLC, in 30 patients
with sporadic amyotrophic lateral sclerosis (SALS) and 78 matched controls. The mean CSF and serum vitamin E levels did not
differ significantly between the 2 study groups. These values were not influenced by the clinical form (spinal versus bulbar)
of SALS. CSF alpha-tocopherol levels did not correlate with age, age at onset, and duration of the disease. These results
suggest that CSF and serum alpha-tocopherol concentrations are unrelated with the risk for ALS.
Received February 25, 1998; accepted April 23, 1998 相似文献
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Siciliano G Piazza S Carlesi C Del Corona A Franzini M Pompella A Malvaldi G Mancuso M Paolicchi A Murri L 《Journal of neurology》2007,254(5):575-580
Abstract
Background
The causes of Amyotrophic Lateral Sclerosis (ALS) are unknown. A bulk of evidence supports the hypothesis that oxidative stress
and mitochondrial dysfunction can be implicated in ALS pathogenesis.
Methods
We assessed, in cerebrospinal fluid (CSF) and in plasma of 49 ALS patients and 8 controls, the amount of oxidized proteins
(AOPP, advanced oxidation protein products), the total antioxidant capacity (FRA, the ferric reducing ability), and, in CSF,
two oxidation products, the 4-hydroxynonenal and the sum of nitrites plus nitrates.
Results
The FRA was decreased (p = 0.003) in CSF, and AOPP were increased in both CSF (p = 0.0039) and plasma (p = 0.001) of ALS patients.
The content of AOPP was differently represented in CSF of ALS clinical subsets, resulting in increase in the common and pseudopolyneuropathic
forms (p < 0.001) and nearly undetectable in the bulbar form, as in controls. The sum of nitrites plus nitrates and 4-hydroxynonenal
were unchanged in ALS patients compared with controls.
Conclusion
Our results, while confirming the occurrence of oxidative stress in ALS, indicate how its effects can be stratified and therefore
implicated differently in the pathogenesis of different clinical forms of ALS. 相似文献
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目的探讨肌萎缩侧索硬化(ALS)患者的脑脊液蛋白、髓鞘碱性蛋白(MBP)水平及脑脊液蛋白与临床特征之间的关系。方法回顾性研究行腰穿查脑脊液的29例确诊ALS患者,检测其脑脊液蛋白及MBP水平,并按性别、年龄、病程、起病部位及临床功能评分〔肌萎缩侧索硬化功能分级量表(ALS-FRS)评分〕等不同临床特征分组,分析不同临床特征对脑脊液蛋白水平的影响。结果 29例ALS患者脑脊液蛋白水平为(0.43±0.15)g/L,其中脑脊液蛋白轻度增高患者9例(31%),最高为0.89g/L;不同性别〔男(0.42±0.15)g/L,女(0.45±0.18)g/L,t=0.501,P=0.620〕、年龄〔60岁组(0.43±0.17)g/L,≥60岁(0.44±0.13)g/L,t=0.141,P=0.889〕、病程〔1年组(0.37±0.11)g/L,≥1年(0.49±0.17)g/L,t=-2.23,P=0.054〕、起病部位〔球部起病组(0.38±0.11),肢体起病组(0.45±0.17),t=0.330,P=0.743〕、ALS-FRS评分〔30分组(0.42±0.16)g/L,≤30分组(0.44±0.16)g/L,t=0.092,P=0.928〕分组间比较,脑脊液蛋白水平差异均无统计学意义。29例患者中13例进行了脑脊液MBP检测,MBP水平(1.66±0.78)nmol/L,13例患者MBP水平均增高,最高达3.39nmol/L。MBP水平与脑脊液蛋白水平无相关性(R=0.198,P=0.517)。结论 ALS患者脑脊液蛋白增高多见。部分ALS患者脑脊液MBP水平增高,但与脑脊液蛋白水平无相关性。 相似文献
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Familial amyotrophic lateral sclerosis with an I104F mutation in the SOD1 gene: Multisystem degeneration with neurofilamentous aggregates and SOD1 inclusions
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Haishan Jiang Hiroshi Shimizu Atsushi Shiga Masami Tanaka Osamu Onodera Akiyoshi Kakita Hitoshi Takahashi 《Neuropathology》2017,37(1):69-77
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By means of a randomized, controlled and open study the authors wanted to find out if cerebrospinal (CSF)-filtration was of substantial benefit to patients with sporadic amyotrophic lateral sclerosis (SALS). Five SALS patients, aged 51-75 years, being treated with riluzole underwent CSF-filtration daily over five days (group A). Five other SALS patients, aged 52-70 years, were treated only with riluzole (group B). Although all five patients in the first group reported a subjective benefit following CSF- filtration, the Norris score, the Frenchay score, the vital capacity, the ulnar nerve F-wave persistence and the peak-ratio of the brachial biceps and anterior tibial muscles did not change significantly after five days of therapy, either in group A or in group B. In conclusion, filtration of 200-250 ml CSF daily, over five days, does not seem to have a substantial therapeutic effect in patients with SALS. Copyright Lippincott Williams & Wilkins 相似文献
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Jiménez-Jiménez FJ Hernánz A Medina-Acebrón S de Bustos F Zurdo JM Alonso H Puertas I Barcenilla B Sayed Y Cabrera-Valdivia F 《Acta neurologica Scandinavica》2005,111(2):114-117
OBJECTIVE: To elucidate whether cerebrospinal fluid (CSF) concentrations of the microtubule-associated tau protein are related to the risk for sporadic amyotrophic lateral sclerosis (SALS). PATIENTS/METHODS: We measured tau concentrations in the CSF of 18 patients with SALS and 75 age- and sex-matched controls, using a specific ELISA method. RESULTS: The mean CSF concentrations of tau protein did not differ significantly between SALS patient and control groups, were not influenced by the clinical form (spinal vs bulbar) of ALS, and were not correlated with age, age at onset, and duration of the disease. CONCLUSIONS: CSF tau concentrations are not a biochemical marker of ALS. 相似文献
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The concentrations of 23 amino acids (AA) were measured in CSF of patients with Amyotrophic Lateral Sclerosis (ALS). A micro-method with picomole sensitivity was used. Compared with healthy controls no significant alterations of single or total AA concentrations were found. These results contrast with data published in a previous study and will be discussed in detail. 相似文献
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J. Kuhle R. L. P. Lindberg A. Regeniter M. Mehling A. J. Steck L. Kappos A. Czaplinski 《European journal of neurology》2009,16(6):771-774
Background and purpose: Amyotrophic lateral sclerosis (ALS) is classically assumed to be a neurodegenerative disorder. Inflammation has been observed in CNS tissue in ALS patients. We investigated the expression and prognostic relevance of proinflammatory chemokines in ALS.
Methods: We analyzed nine chemokines, eotaxin, eotaxin-3, IL-8, IP-10, MCP-1, MCP-4, macrophage derived chemokine (MDC), macrophage inflammatory protein-1β (MIP-1β), and serum thymus and activation- regulated chemokine (TARC) in serum and cerebrospinal fluid (CSF) of 20 ALS- and 20 non-inflammatory neurological disease (NIND)-patients.
Results: MCP-1 and IL-8 levels in CSF in ALS were significantly higher than in NIND (1304 pg/ml vs. 1055 pg/ml, P = 0.013 and 22.7 pg/ml vs. 18.6 pg/ml, P = 0.035). The expression of MCP-1 and IL-8 were higher in CSF than in serum ( P < 0.001). There was a trend towards higher MCP-1 CSF levels in ALS patients with shorter time between first symptoms and diagnosis ( r = −0.407; P = 0.075).
Conclusions: We confirmed previous findings of increased MCP-1 levels in CSF of ALS patients. Furthermore, increased levels of IL-8 in CSF suggest a stimulation of a proinflammatory cytokine cascade after microglia activation. We found a tendency for higher MCP-1 values in patients with a shorter diagnostic delay, who are known to have also a shorter survival. This may suggest an association of higher MCP-1 levels with rapidly progressing disease. 相似文献
Methods: We analyzed nine chemokines, eotaxin, eotaxin-3, IL-8, IP-10, MCP-1, MCP-4, macrophage derived chemokine (MDC), macrophage inflammatory protein-1β (MIP-1β), and serum thymus and activation- regulated chemokine (TARC) in serum and cerebrospinal fluid (CSF) of 20 ALS- and 20 non-inflammatory neurological disease (NIND)-patients.
Results: MCP-1 and IL-8 levels in CSF in ALS were significantly higher than in NIND (1304 pg/ml vs. 1055 pg/ml, P = 0.013 and 22.7 pg/ml vs. 18.6 pg/ml, P = 0.035). The expression of MCP-1 and IL-8 were higher in CSF than in serum ( P < 0.001). There was a trend towards higher MCP-1 CSF levels in ALS patients with shorter time between first symptoms and diagnosis ( r = −0.407; P = 0.075).
Conclusions: We confirmed previous findings of increased MCP-1 levels in CSF of ALS patients. Furthermore, increased levels of IL-8 in CSF suggest a stimulation of a proinflammatory cytokine cascade after microglia activation. We found a tendency for higher MCP-1 values in patients with a shorter diagnostic delay, who are known to have also a shorter survival. This may suggest an association of higher MCP-1 levels with rapidly progressing disease. 相似文献
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I. Niebroj-Dobosz A. Mickielewicz K. Rowiñska-Marciñska H. Kwieciñski 《European journal of neurology》2000,7(6):679-683
Glycoproteins in cerebrospinal fluid of 55 patients with amyotrophic lateral sclerosis (ALS), six disease controls (multifocal motor neuropathy, sensorimotor neuropathy, Guillain-Barré syndrome, spinal muscular atrophy type II, motor neuropathy with monoclonal gammopathy) and 20 healthy controls were separated by PAGE electrophoresis and then detected immunochemically with peanut agglutinin (PNA). In 36 amyotrophic lateral sclerosis patients the 262 kDa glycoprotein was significantly increased (over the normal mean +/- SD x 2), which was associated with a decrease in the 114 kDa fraction. In the remaining patients, both fractions were either equal in concentration or the 114 kDa glycoprotein predominated. In normal cerebrospinal fluid, the 114 kDa glycoprotein predominated over the other glycoproteins. The total amount of separated glycoproteins was increased in 15 amyotrophic lateral sclerosis patients. In 12 of them it was followed by an increase in the percentage of the 262 kDa glycoprotein. There was no correlation between the content of the peanut agglutinin-labelled glycoproteins and the patients' age, duration and severity of the disease. There was a correlation between the 262 kDa glycoprotein being increased in cerebrospinal fluid and the electrophysiological pattern of denervation seen in electromyographic study. The glycoproteins change, similar to that occurring in amyotrophic lateral sclerosis patients, was also observed in one case of multifocal motor neuropathy (MMN). We suggest that in amyotrophic lateral sclerosis and multifocal motor neuropathy, the peanut agglutinin-labelled glycoproteins are released in excess from the nervous tissues into the cerebrospinal fluid as a result of neuronal degeneration. The question to be answered is, whether the released glycoproteins are becoming targets for auto-antibodies. 相似文献