神经生长因子经鼻给药治疗有机溶剂中毒性脑病临床分析
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摘要
目的分析有机溶剂中毒性脑病的临床诊治特点,并探索神经生长因子经鼻给药方法的可行性和安全性。方法回顾性分析15例经鼻给予神经生长因子治疗的有机溶剂中毒性脑病患者的临床特点,比较分析给药前后的实验室检验指标,同时记录不良事件。结果有机溶剂中毒性脑病患者症状表现为头晕、乏力等非特异性症状,以及记忆力下降、计算力下降等认知障碍。15例患者经鼻给药平均时间为14(9~31)d,治疗后2例有鼻黏膜轻微不适,其余未见异常。给药前后实验室指标比较,差异无统计学意义(P>0.05)。结论有机溶剂中毒性脑病的诊断主要依据暴露史、临床表现及影像学检查综合判断,经鼻给予神经生长因子治疗有机溶剂中毒性脑病是一种安全、可行的方法。
Objective To study the clinical characteristics of diagnosis and treatment for solvent-induced toxic encephalopathy and explore the feasibility and safety of intranasal administration with nerve growth factor(NGF)for the treatment of toxic encephalopathy.Methods The retrospective analysis was performed to analyze the clinical characteristics of 15 patients diagnosed with solvent-induced toxic encephalopathy and treated with NGF by intranasal administration.Then the comparative analysis was made to compare the laboratory test indexes before and after treatment,and the adverse events were also recorded.Results The main clinical manifestation in the patients with solvent-induced toxic encephalopathy involved the non-specific symptoms such as headache and fatigue and the cognitive disorders such as the deterioration of memory and computing power.The mean time of intranasal administration with NGF was 14 days with the range of 9 to 31 days.Only two patients felt slight discomfort of nasal mucosa.No significant differences were found in the laboratory test indexes between before and after treatment(P>0.05).Conclusion The diagnosis of solvent-induced toxic encephalopathy was mainly based on the exposure history,clinical manifestation and comprehensive judgement of neuroimaging examination.The intranasal administration with NGF is feasible and safe in treating the patients with toxic encephalopathy.
Objective To study the clinical characteristics of diagnosis and treatment for solvent-induced toxic encephalopathy and explore the feasibility and safety of intranasal administration with nerve growth factor(NGF)for the treatment of toxic encephalopathy.Methods The retrospective analysis was performed to analyze the clinical characteristics of 15 patients diagnosed with solvent-induced toxic encephalopathy and treated with NGF by intranasal administration.Then the comparative analysis was made to compare the laboratory test indexes before and after treatment,and the adverse events were also recorded.Results The main clinical manifestation in the patients with solvent-induced toxic encephalopathy involved the non-specific symptoms such as headache and fatigue and the cognitive disorders such as the deterioration of memory and computing power.The mean time of intranasal administration with NGF was 14 days with the range of 9 to 31 days.Only two patients felt slight discomfort of nasal mucosa.No significant differences were found in the laboratory test indexes between before and after treatment(P>0.05).Conclusion The diagnosis of solvent-induced toxic encephalopathy was mainly based on the exposure history,clinical manifestation and comprehensive judgement of neuroimaging examination.The intranasal administration with NGF is feasible and safe in treating the patients with toxic encephalopathy.
引文
[1]Filley C M.Occupation and the risk of chronic toxic leukoencephalopathy[J].Handb Clin Neurol,2015,131:73-91.
[2]Rimkus Cde M,Andrade C S,Leite Cda C,et al.Toxic leukoencephalopathies,including drug,medication,environmental,and radiation-induced encephalopathic syndromes[J].Semin Ultrasound CT MR,2014,35(2):97-117.
[3]Kim Y,Kim J W.Toxic encephalopathy[J].Saf Health Work,2012,3(4):243-256.
[4]Ip N Y,Yancopoulos G D.Neurotrophic factors and their receptors[J].Ann Neurol,1994,35(Suppl):S13-S16.
[5]Jiang Y,Wei N,Zhu J,et al.A new approach with less damage:intranasal delivery of tetracycline-inducible replication-defective herpes simplex virus type-1 vector to brain[J].Neuroscience,2012,201:96-104.
[6]Grasso P.Neurotoxic and neurobehavioral effects of organic solvents on the nervous system[J].Occup Med,1988,3(3):525-539.
[7]Baker E L,Sepplinen A M.Proceedings of the Workshop on Neurobehavioral Effects of Solvents.October 13-16,1985,Raleigh,North Carolina,U.S.A[J].Neurotoxicology,1986,7(4):1-95.
[8]Dick F D.Solvent neurotoxicity[J].Occup Environ Med,2006,63(3):221-226.
[9]Sainio M A Sr.Neurotoxicity of solvents[J].Handb Clin Neurol,2015,131:93-110.
[10]Mi T,Han C,Wang Y,et al.Acute toxic leukoencephalopathy in migrant workers exposed to organic solvents in construction materials[J].Occup Environ Med,2013,70(6):435-436.
[11]White R F,Proctor S P.Solvents and neurotoxicity[J].Lancet,1997,349(9060):1239-1243.
[12]Dobbs M R.Toxic encephalopathy[J].Semin Neurol,2011,31(2):184-193.
[13]Filley C M,Halliday W,Kleinschmidt-DeMasters B K.The effects of toluene on the central nervous system[J].J Neuropathol Exp Neurol,2004,63(1):1-12.
[14]Feldman R G.Occupational neurology[J].Yale J Biol Med,1987,60(2):179-186.
[15]van Hout M,Hageman G,van Valen E.Pitfalls in clinical assessment of neurotoxic diseases:Negative effects of repeated diagnostic evaluation,illustrated by a clinical case[J].NeuroToxicology,2014,45:247-252.
[16]Visser I,Wekking E M,de Boer A G,et al.Prevalence of psychiatric disorders in patients with chronic solvent induced encephalopathy(CSE)[J].Neurotoxicology,2011,32(6):916-922.
[17]Filley C M,Kleinschmidt-DeMasters B K.Toxic leukoencephalopathy[J].N Engl J Med,2001,345(6):425-432.
[18]van der Laan G,Sainio M,van Valen E.Solvent-induced encephalopathy in the Netherlands and Finland[J].Occup Med(Lond),2015,65(8):609-611.
[19]Spee T,van Valen E,van Duivenbooden C,et al.A screening programme on chronic solvent-induced encephalopathy among Dutch painters[J].Neurotoxicology,2012,33(4):727-733.
[20]Verberk M M,van der Hoek J A,van Valen E,et al.Decision rules for assessment of chronic solvent-induced encephalopathy:Results in 2370 patients[J].Neurotoxicology,2012,33(4):742-752.
[21]Kao H W,Pare L,Kim R,et al.Toxic leukoencephalopathy with atypical MRI features following a lacquer thinner fire[J].J Clin Neurosci,2014,21(5):878-880.
[22]Dietemann J L,Botelho C,Nogueira T,et al.Imaging in acute toxic encephalopathy[J].J Neuroradiol,2004,31(4):313-326.
[23]刘力学,樊双义,夏学林.60例一氧化碳中毒患者脑电图分析及对迟发性脑病的预测价值[J].成都医学院学报,2015,10(5):567-570.
[24]Guégan C,Ceballos-Picot I,Chevalier E,et al.Reduction of ischemic damage in NGF-transgenic mice:correlation with enhancement of antioxidant enzyme activities[J].Neurobiol Dis,1999,6(3):180-189.
[25]Zassler B,Humpel C.Transplantation of NGF secreting primary monocytes counteracts NMDA-induced cell death of rat cholinergic neurons in vivo[J].Exp Neurol,2006,198(2):391-400.
[26]Zhao M,Li X Y,Xu C Y,et al.Efficacy and safety of nerve growth factor for the treatment of neurological diseases:a meta-analysis of 64randomized controlled trials involving 6,297patients[J].Neural Regen Res,2015,10(5):819-828.
[27]Lochhead J J,Wolak D J,Pizzo M E,et al.Rapid transport within cerebral perivascular spaces underlies widespread tracer distribution in the brain after intranasal administration[J].J Cereb Blood Flow Metab,2015,35(3):371-381.
[28]樊新颖,李芸,马敏敏,等.神经生长因子鼻腔给药对有机磷酸酯类化合物中毒大鼠纹状体损伤的影响[J].中华医学杂志,2012,92(33):2366-2369.
[29]樊新颖,朱武生,杨龙,等.经鼻给予神经生长因子对沙林染毒大鼠梨状皮质神经元的影响[J].中华神经科杂志,2007,40(9):634-636.
[30]Finger E C,MacKinley J,Blair M,et al.Oxytocin for frontotemporal dementia:a rando mized dose-finding study of safety and tolerability[J].Neurology,2015,84(2):174-181.
[31]Claxton A,Baker L D,Hanson A,et al.Long-acting intranasal insulin detemir improves cognition for adults with mild cognitive impairment or early-stage Alzheimer's disease dementia[J].J Alzheimers Dis,2015,44(3):897-906.
[2]Rimkus Cde M,Andrade C S,Leite Cda C,et al.Toxic leukoencephalopathies,including drug,medication,environmental,and radiation-induced encephalopathic syndromes[J].Semin Ultrasound CT MR,2014,35(2):97-117.
[3]Kim Y,Kim J W.Toxic encephalopathy[J].Saf Health Work,2012,3(4):243-256.
[4]Ip N Y,Yancopoulos G D.Neurotrophic factors and their receptors[J].Ann Neurol,1994,35(Suppl):S13-S16.
[5]Jiang Y,Wei N,Zhu J,et al.A new approach with less damage:intranasal delivery of tetracycline-inducible replication-defective herpes simplex virus type-1 vector to brain[J].Neuroscience,2012,201:96-104.
[6]Grasso P.Neurotoxic and neurobehavioral effects of organic solvents on the nervous system[J].Occup Med,1988,3(3):525-539.
[7]Baker E L,Sepplinen A M.Proceedings of the Workshop on Neurobehavioral Effects of Solvents.October 13-16,1985,Raleigh,North Carolina,U.S.A[J].Neurotoxicology,1986,7(4):1-95.
[8]Dick F D.Solvent neurotoxicity[J].Occup Environ Med,2006,63(3):221-226.
[9]Sainio M A Sr.Neurotoxicity of solvents[J].Handb Clin Neurol,2015,131:93-110.
[10]Mi T,Han C,Wang Y,et al.Acute toxic leukoencephalopathy in migrant workers exposed to organic solvents in construction materials[J].Occup Environ Med,2013,70(6):435-436.
[11]White R F,Proctor S P.Solvents and neurotoxicity[J].Lancet,1997,349(9060):1239-1243.
[12]Dobbs M R.Toxic encephalopathy[J].Semin Neurol,2011,31(2):184-193.
[13]Filley C M,Halliday W,Kleinschmidt-DeMasters B K.The effects of toluene on the central nervous system[J].J Neuropathol Exp Neurol,2004,63(1):1-12.
[14]Feldman R G.Occupational neurology[J].Yale J Biol Med,1987,60(2):179-186.
[15]van Hout M,Hageman G,van Valen E.Pitfalls in clinical assessment of neurotoxic diseases:Negative effects of repeated diagnostic evaluation,illustrated by a clinical case[J].NeuroToxicology,2014,45:247-252.
[16]Visser I,Wekking E M,de Boer A G,et al.Prevalence of psychiatric disorders in patients with chronic solvent induced encephalopathy(CSE)[J].Neurotoxicology,2011,32(6):916-922.
[17]Filley C M,Kleinschmidt-DeMasters B K.Toxic leukoencephalopathy[J].N Engl J Med,2001,345(6):425-432.
[18]van der Laan G,Sainio M,van Valen E.Solvent-induced encephalopathy in the Netherlands and Finland[J].Occup Med(Lond),2015,65(8):609-611.
[19]Spee T,van Valen E,van Duivenbooden C,et al.A screening programme on chronic solvent-induced encephalopathy among Dutch painters[J].Neurotoxicology,2012,33(4):727-733.
[20]Verberk M M,van der Hoek J A,van Valen E,et al.Decision rules for assessment of chronic solvent-induced encephalopathy:Results in 2370 patients[J].Neurotoxicology,2012,33(4):742-752.
[21]Kao H W,Pare L,Kim R,et al.Toxic leukoencephalopathy with atypical MRI features following a lacquer thinner fire[J].J Clin Neurosci,2014,21(5):878-880.
[22]Dietemann J L,Botelho C,Nogueira T,et al.Imaging in acute toxic encephalopathy[J].J Neuroradiol,2004,31(4):313-326.
[23]刘力学,樊双义,夏学林.60例一氧化碳中毒患者脑电图分析及对迟发性脑病的预测价值[J].成都医学院学报,2015,10(5):567-570.
[24]Guégan C,Ceballos-Picot I,Chevalier E,et al.Reduction of ischemic damage in NGF-transgenic mice:correlation with enhancement of antioxidant enzyme activities[J].Neurobiol Dis,1999,6(3):180-189.
[25]Zassler B,Humpel C.Transplantation of NGF secreting primary monocytes counteracts NMDA-induced cell death of rat cholinergic neurons in vivo[J].Exp Neurol,2006,198(2):391-400.
[26]Zhao M,Li X Y,Xu C Y,et al.Efficacy and safety of nerve growth factor for the treatment of neurological diseases:a meta-analysis of 64randomized controlled trials involving 6,297patients[J].Neural Regen Res,2015,10(5):819-828.
[27]Lochhead J J,Wolak D J,Pizzo M E,et al.Rapid transport within cerebral perivascular spaces underlies widespread tracer distribution in the brain after intranasal administration[J].J Cereb Blood Flow Metab,2015,35(3):371-381.
[28]樊新颖,李芸,马敏敏,等.神经生长因子鼻腔给药对有机磷酸酯类化合物中毒大鼠纹状体损伤的影响[J].中华医学杂志,2012,92(33):2366-2369.
[29]樊新颖,朱武生,杨龙,等.经鼻给予神经生长因子对沙林染毒大鼠梨状皮质神经元的影响[J].中华神经科杂志,2007,40(9):634-636.
[30]Finger E C,MacKinley J,Blair M,et al.Oxytocin for frontotemporal dementia:a rando mized dose-finding study of safety and tolerability[J].Neurology,2015,84(2):174-181.
[31]Claxton A,Baker L D,Hanson A,et al.Long-acting intranasal insulin detemir improves cognition for adults with mild cognitive impairment or early-stage Alzheimer's disease dementia[J].J Alzheimers Dis,2015,44(3):897-906.