急性病毒性脑炎并发癫癎持续状态的临床研究

目的探讨急性病毒性脑炎并发癫癎持续状态和难治性癫癎持续状态的临床特征及预后影响因素。方法回顾分析26例急性病毒性脑炎并发癫癎持续状态患者癫癎持续状态出现的时间,以及脑脊液、影像学、脑电图变化特点和预后相关影响因素。结果26例患者中15例（57．69％）进展为难治性癫癎持续状态,与非难治性癫癎持续状态患者相比,12例（12／15）于急性病毒性脑炎发病后10d内出现癫癎持续状态;14例（14／15）脑脊液压力升高;7例（7／15）急性期呈弥漫性脑水肿;14例（14／15）脑电图检查显示普遍重度异常;7例（7／15）同时应用≥5种抗癫癎药物;15例患者均伴有并发症,其中14例（14／15）需呼吸机辅助呼吸;住院时间明显延长f（446±336）d];5例死亡。6例难治性癫痈持续状态患者随访2～10年,2例呈植物状态生存;3例为难治性癫癎伴智力减退;1例发作终止,遗留轻度记忆力减退。结论急性病毒性脑炎是导致癫癎持续状态的常见原因,其中近半数患者可进展为难治性癫癎持续状态。危险因素包括疾病早期即出现癫癎持续状态、脑脊液压力升高、急性期脑水肿、脑电图异常等。难治性癫癎持续状态患者病死率高,预后不良。     

Relationship between CSF neurotransmitter metabolites and aggressive behavior in Alzheimer's disease

To assess neurochemical correlates of aggressive behavior in Alzheimer's disease (AD) we examined concentrations of homovanillic acid (HVA) and 5-hydroxyindolacetic acid (5-HIAA) in lumbar cerebrospinal fluid (CSF) of 11 clinically diagnosed Alzheimer's disease (AD) patients and 12 non-demented age-equivalent controls. There were no significant differences between AD patients and controls in CSF HVA concentrations. However, the CSF 5-HIAA content was significantly lower in AD patients compared to controls. Patients without aggressive behavior had significantly lower concentrations of HVA and 5-HIAA than those with aggression, in whom concentrations were preserved compared to non-demented controls.     

帕金森氏病患者丘脑腹外侧核毁损术后脑脊液中单胺类递质含量的变化

目的：观察帕金森氏病患者脑立体定向术前、后脑脊液中神经递质水平的变化，这种变化的作用机理如何。方法：对１５例帕金森氏病患者丘脑腹外侧核毁损术前及术后一周脑脊液中单胺类递质水平检测及手术疗效观察。结果：患者术后脑脊液中多巴胺水平与术前无显著差异，而５－羟色胺、去甲肾上腺素、５－羟吲哚乙酸显著减少，术后毁损区对侧上下肢体震颤、肌强直消失，但运动不能症状未能改善。结论：帕金森氏病术后中枢多种神经递质发生改变并在低水平下暂时获得平衡。从中枢神经递质生化变化，脑立体定向术不能彻底治愈帕金森氏病     

A case control study of CSF copper, iron and manganese in Parkinson disease

To elicit possible variations in the CSF concentrations of copper, iron and manganese due to Parkinson disease (PD) or to the stage reached, we tested 11 patients with idiopathic PD, 6 untreated and 5 on long term L-dopa, versus 22 age and sex matched patients with other neurological disorders (control group-CG). The CSF levels of the three metals, measured by electrothermal atomization, did not differ significantly between the PD group and CG or between either of the PD subgroups and CG. Our findings therefore do not support the hypothesis that CSF Cu is a marker of PD.

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Sommario Nell'intento di rilevare possibili variazioni liquorali delle concentrazioni di rame, ferro e manganese dovute al morbo di Parkinson o allo stadio dello stesso, abbiamo esaminato 11 pazienti (10 uomini e 1 donna) di età media 64,9 (età compresa tra 49 e 78 anni) con morbo di Parkinson idiopatico, dopo averne ottenuto il consenso informato. Di essi 6, di età media 63.1, erano de-novo, mentre 5, di età media 67.0 anni erano in terapia da tempo (media 4.5, minimo 2 e massimo di 9 anni). Il gruppo di controllo (CG) era costituito da 22 pazienti con altre patologie neurologiche, di età e sesso comparabili.Il dosaggio di Cu, Fe, Mn è stato eseguito sui campioni di liquor con tecniche ETA-AAS. Nel C.G. il Cu, Fe, Mn erano rispettivamente (medie ±SD g/l) 6.7±19.9, 181.7±75.1 e 5.4±3.9, mentre nei pazienti parkinsoniani i valori erano 64.9±14.4, 275.9±153.6 e 5.7±1.8.Per quanto riguarda i pazienti parkinsoniani, nei pazienti de-novo le concentrazioni di Cu, Fe, Mn erano di 63.2±11.5, 283.8±141.5 e 6.0±1.3 e nei pazienti in trattamento 67.0±18.5, 26.4±183.6 e 5.4±2.4. Sia per quanto riguarda i pazienti de-novo che quelli in terapia, questi risultati non si sono rivelati significativi nei confronti del gruppo di controllo. Quindi i nostri dati non sembrano indicare che il Cu possa costituire un marker per il morbo di Parkinson. Tuttavia è possibile che la concentrazione dei metalli pesanti nel liquor non rifletta la loro concentrazione tissutale.

     

On the relationship between l-DOPA therapy and CSF monoamine metabolites in parkinson's disease

Summary HVA, the main dopamine catabolite, was shown to be decreased in CSF of parkinsonian patients. A significant relationship was also shown between clinical improvement and HVA concentration increase in CSF. It was, however, recently claimed that such increase was not specific.A study on the CSF concentrations of HVA and 5-HIAA (the main serotonin metabolite) was undertaken on 10 parkinsonian patients. The determinations were made before and after l-DOPA therapy, when a satisfactory clinical status was achieved. The results obtained clearly demonstrate that a large increase of HVA was found in CSF during l-DOPA therapy, but no relationship was found between HVA levels and clinical improvement. A decrease of 5-HIAA in CSF during l-DOPA treatment was found.These results are discussed in the light of a relationship between dopamine and serotonin during l-DOPA therapy.     

A partial GDNF depletion leads to earlier age-related deterioration of motor function and tyrosine hydroxylase expression in the substantia nigra

Glial cell line-derived neurotrophic factor (GDNF) is a trophic factor for peripheral organs, spinal cord, and midbrain dopamine (DA) neurons. Levels of GDNF deteriorate in the substantia nigra in Parkinson's disease (PD). A heterozygous mouse model was created to assess whether chronic reductions in this neurotrophic factor impact motor function and the nigrostriatal dopamine system during the aging process. Due to the important role GDNF plays in kidney development, kidney function and histology were assessed and were found to be normal in both wild-type (WT) and GDNF+/- mice up to 22 months of age. Further, the animals of both genotypes had similar weights throughout the experiment. Locomotor activity was assessed for male WT and GDNF+/- mice at 4-month intervals from 4 to 20 months of age. Both GDNF+/- and WT mice exhibited an age-related decline in horizontal activity, although this was found 4 months earlier in GDNF+/- mice, at 12 months of age. Comparison of young (8 month old) and aged (20 month old) GDNF+/- and WT mice on an accelerating rotarod apparatus established a deficiency for aged but not young GDNF+/- mice, while aged WT mice performed as well as young WT mice on this task. Finally, both WT and GDNF+/- mice exhibited an age-related decrease in substantia nigra TH immunostaining, which was accelerated in the GDNF+/- mice. These behavioral and histological alterations suggest that GDNF may be an important factor for maintenance of motor coordination and spontaneous activity as well as DA neuronal function during aging, and further suggest that GDNF+/- mice may serve as a model for neuroprotective or rescue studies.     

Deterioration of dopaminergic pathways and alterations in cognition and motor functions

Degeneration of central dopaminergic neurons is the most characteristic pathological feature of Parkinson's disease. It remains to be established to what extent these lesions explain the motor, cognitive and affective disorders observed in patients, but there are now some interesting clues to a possible solution.     

帕金森病患者和健康对照者的纵向CSF生物标志物对比研究

目的 探讨帕金森病(Parkinson's disease,PD)患者脑脊液(CSF)生物标志物的水平变化及其临床意义。方法 选取本院2018年3月-2019年3月收治的70例PD患者,并根据改良PD综合评分量表(UPDRS量表)及Hoehn-Yahr评分标准将患者分为轻度组(n=38)、中度组(n=18)和重度组(n=14)。另选择同期于本院接受体检健康人员70例作为对照组,检测并比较4组研究对象CSF生物标志物蛋白α-突触核蛋白(α-syn)、磷酸化Tau蛋白(P-Tau)及总Tau蛋白(T-Tau),微小RNA133 b(miR-133b)及C反应蛋白(CRP)、白细胞介素-8(IL-8)水平。结果 各组性别、年龄比较无明显差异(P>0.05); 不同病情严重程度PD患者UPDRS评分比较有明显差异,且均显著高于对照组(P<0.05); PD患者轻度组、中度组及重度组H-Y评分比较有明显差异(P<0.05)。各组α-syn、P-Tau、T-Tau、miR-133b、CRP及IL-8水平比较有明显差异(P<0.05),且随着PD患者病情严重程度加重,α-syn水平显著降低,P-Tau、T-Tau、miR-133b、CRP及IL-8水平显著升高(P<0.05)。Pearson相关分析显示,α-syn与UPDRS评分呈显著正相关,P-Tau、T-Tau、miR-133b、CRP及IL-8与UPDRS呈显著负相关(P<0.05)。受试者工作曲线(ROC)显示α-syn、P-Tau、T-Tau、miR-133b、CRP及IL-8水平诊断PD的曲线下面积(AUC)分别为0.755、0.785、0.742、0.746、0.779、0.755,联合诊断的AUC为0.905。结论 脑脊液生物标志物的水平变化是PD发生与发展的重要参考指标,其对于PD的诊断和病情严重程度判断具有重要价值     

Correlation of apomorphine- and amphetamine-induced turning with nigrostriatal dopamine content in unilateral 6-hydroxydopamine lesioned rats

In the unilateral 6-hydroxydopamine (6-OHDA)-lesioned rat model of Parkinson's disease, controversy exists concerning the use of apomorphine- ord-amphetamine-induced rotations as reliable indicators of nigrostriatal dopamine depletion. Our objective was to evaluate which, if either, drug-induced behavior is more predictive of the extent of nigrostriatal dopamine depletion. Fischer 344 and Sprague-Dawley rats were unilaterally injected with 9μg/4μl/4 min 6-hydroxydopamine into the medial forebrain bundle. The animals were behaviorally tested with apomorphine (0.05 mg/kg, s.c.) andd-amphetamine (5.0 mg/kg, s.c.). Following testing, the brains were removed and the right and left striata, substantia nigra and ventral tegmental area were dissected free and quickly frozen at −70°C for analysis of catecholamine content by high performance liquid chromatography coupled with electrochemical detection. Our results indicate that an animal which has greater than a 90% depletion of dopamine in the striatum might not rotate substantially on apomorphine, without a concomitant depletion of 50% of the DA content in the corresponding substantia nigra. No correlations were seen involving depletions of the ventral tegmental area and the extent of the lesions to the striatum. Submaximally lesioned (75–90% depleted) rats were found to rotate ond-amphetamine but not on apomorphine. In addition, control rats that did not receive lesions were often seen to rotate extensively ond-amphetamine. We therefore conclude that maximal lesions of the striatum and substantia nigra are required to generate rotations demonstrable with low dose apomorphine but not withd-amphetamine. Apomorphine, rather thand-amphetamine, is thus a better predictor of maximal lesions of the striatum produced by 6-OHDA.     

血清和脑脊液中MMPs与TIMP-1在重症手足口合并脑炎患儿中的诊断意义

目的探讨重症手足口合并脑炎患儿血清及脑脊液中MMPs与TIMP-1变化,为重症手足口合并脑炎患儿早期诊断提供依据。方法以2015-01—2018-03于郑州儿童医院就诊确诊为手足口患儿100例为研究对象,其中普通型55例,重型22例,危重型23例,其中重型及危重型HFMD组均为合并神经系统受累的患儿,统称为脑炎组。统计分析患儿脑脊液蛋白、脑脊液细胞数水平及脑脊液和血清中MMP-2、MMP-9、TIMP-1水平。结果(1)重型和危重型HFMD血清和脑脊液MMP-2、MMP-9、TIMP-1水平较普通型和健康对照组显著增高,危重型增高较为显著,差异有统计学意义(P<0.05);(2)脑炎组血清MMP-2、MMP-9、TIMP-1浓度水平较普通型、健康对照组组显著增高(P<0.05);(3)相关性分析结果显示,HFMD患儿血清MMP-2、MMP-9、TIMP-1浓度水平和脑脊液MMP-2、MMP-9、TIMP-1浓度水平显著正相关,相关系数分别为(r=0.719,P=0.001;r=0.638,P=0.000;r=0.704,P=0.000);(4)血清MMP-2、MMP-9和TIMP-1浓度水平预测脑炎ROC分析,曲线下面积分别为0.95695%CI(0.919、0.994)、0.95195%CI(0.906、0.996)、0.88795%CI(0.852、0.949),最佳截断点分别为103.59、96.34、108.64,相应敏感度和特异度分别为84.4%和94.5%、93.3和87.3%、88.9%和72.7%。结论重型和危重型HFMD合并神经系统受累病例血清和脑脊液中MMP-2、MMP-9、TIMP-1水平升高明显,对于重症手足口病合并脑炎的辅助诊断在临床上具有重要的意义。     

肌萎缩侧索硬化症患者血浆和脑脊液谷氨酸含量变化的研究

目的 了解肌萎缩侧索硬化症(ALS)患者血浆、脑脊液谷氨酸浓度的改变,为治疗提供依据。方法应用毛细管电泳-激光诱导荧光检测器,测定ALS患者和对照组的血浆及脑脊液谷氨酸含量,比较两者的不同,并对不同病情ALS患者的谷氨酸浓度进行比较。结果 ALS患者血浆、脑脊液谷氨酸的浓度均较对照组明显升高(P<0.05)。不同病情患者间的谷氨酸浓度也有区别,谷氨酸水平升高程度与病情轻重相关。结论 ALS患者血浆和脑脊液的谷氨酸水平较正常高,脑脊液谷氨酸浓度比血浆浓度敏感,临床病情越重,谷氨酸浓度越高。     

精神分裂症患者脑脊液细胞学对照研究

目的：探讨精神分裂症患者中枢神经系统免疫学改变的细胞学基础。方法：对40例精神分裂症患者治疗前后各进行1次脑脊液细胞学检查,并以9名外科手术腰麻者的脑脊液作为对照.结果：（1）精神分裂症患者淋巴细胞减少,单核细胞增多,出现吞噬细胞,治疗前及治疗后与对照组相比,其差异有非常显著性（P＜0．01）,（2）精神分裂症治疗前青春型的脑脊脑淋巴细胞减少,单核细胞增多比偏执型更为突出（P＜0．01）,与治疗后比较,其差异无显著性,（3）精神分裂症治疗前病程在半年以内者脑脊液淋巴细胞减少比3年以上者突出,两者相比差异显著（P＜0．02）,与治疗后相比,其差异无显著性,结论：提示精神分裂症患者中枢神经系统存在免疫在免疫反应,这种免疫反应可能参与了精神分裂症发病的病理过程。     

Salsolinol,catecholamine metabolites,and visual hallucinations in L-dopa treated patients with Parkinson's disease

Summary We could quantify the tetrahydroisoquinoline derivative salsolinol in urine of patients with Parkinson's disease and normal control subjects by means of high performance liquid chromatography and electrochemical detection. Urine levels of salsolinol were positively related to the homovanillic acid/3-O-methyl-dopa ratio in the cerebrospinal fluid that reflects dopamine metabolism. In the patient group with visual hallucinations, mean salsolinol level was significantly increased to almost the 3-fold of those found in patients without hallucinations. Since the daily L-dopa doses of both patient groups were nearly identical this result is not due to different L-dopa medications. Additionally, either high values of the main serotonin metabolite, 5-hydroxyindole acetic acid (HIAA) or the L-dopa/3-O-methyl-dopa ratio were found in cerebrospinal fluid of patients with hallucinations.The enhanced salsolinol levels in patients with visual hallucinations seem to be due to an overloaded dopaminergic pathway with an imbalance between dopaminergic and serotonergic systems. Thus, salsolinol appears as a predictor for hallucinosis in Parkinson's disease.     

A ferritin tracer study of compensatory spinal CSF outflow pathways in kaolin-induced hydrocephalus

Spinal drainage of cerebrospinal fluid (CSF) into the lymphatic system is important in physiological and pathological conditions in both humans and rodents. However, in hydrocephalus and syringomyelia the exact CSF pathway from the central canal into the lymphatic tissue around the spinal nerves remains obscure. We therefore induced syringomyelia and hydrocephalus in 36 Lewis rats by injection of 0.1 ml kaolin into the cisterna magna. At 2, 4 and 6 weeks later cationized ferritin was stereotactically infused into the cisterna magna of controls and into the lateral ventricles of hydrocephalic animals followed by dissection of brain, spinal cord and spinal nerves. CSF pathway and tracer flow were studied by light and electron microscopy. We found that in rats with kaolin-induced CSF outflow obstruction, CSF passes from central canal syringes through ruptured ependyma and dorsal columns into the spinal subarachnoid space, from where it is absorbed along spinal nerves into extradural lymphatic vessels. Taken into account that spinal hydrostatic pressure in humans differs significantly from pressure in animals due to the upright gait, we conclude that spinal compensatory CSF outflow pathways might be of even greater importance in human hydrocephalus.     

Acetylcholine receptor binding and cholinergic interneuron density are unaltered in a genetic animal model of primary paroxysmal dystonia

The underlying pathophysiological mechanisms of hereditary types of paroxysmal dyskinesias are still unknown, but basal ganglia dysfunctions seem to play a critical role. In fact, numerous pharmacological, neurochemical, immunohistochemical and electrophysiological investigations in the dt(sz) hamsters, a unique rodent model of age-dependent primary paroxysmal dystonia, revealed alterations within the basal ganglia, particularly of the GABAergic and dopaminergic neurotransmitter systems. A deficit in several types of striatal GABAergic interneurons in dt(sz) mutant hamsters seems to play a crucial pathophysiological role, but deficits in other types of striatal interneurons cannot be excluded by previous studies. In view of ameliorating effects of anti-cholinergic drugs in dystonic patients, we therefore investigated the density of striatal cholinergic interneurons in the present study. These interneurons were marked specifically by the enzyme choline acetyltransferase and counted by using a stereological counting method in a blinded fashion. Additionally, acetylcholine receptor binding was determined in mutant and nondystonic control hamsters by autoradiographic analyses with the nonselective muscarinic ligand [(3)H]-quinuclidinyl benzilate (QNB) in 11 brain (sub)regions. There were no significant differences in the density of striatal cholinergic interneurons between dt(sz) mutant hamsters (789 +/- 39 interneurons/mm(3)) and nondystonic controls (807 +/- 36 interneurons/mm(3)). [(3)H]QNB binding was also comparable between mutant and control hamsters. These results point to an unaltered striatal cholinergic neurotransmitter system in dt(sz) hamsters under basal conditions.     

帕金森病患者脑脊液中抗D2受体抗体的检测

目的检测帕金森病(PD)患者脑脊液(CSF)中抗D2受体抗体.方法采用免疫组化和免疫印迹检测30例PD患者CSF,15例正常人CSF中的抗D2受体抗体.结果7例浓缩10倍的PD-CSF存在抗D2受体抗体,18例未浓缩PD-CSF及15例正常人CSF未检测到该抗体.结论部分PD患者CSF中存在抗D2受体抗体.     

帕金森病伴发抑郁的神经递质改变

目的　探讨帕金森病 (PD)伴发抑郁的神经递质改变。方法　用抑郁自评量表 (CESD)和汉密尔顿抑郁量表 (HAMD)评出PD伴发抑郁患者 33例 ,其中轻度抑郁 2 4例 ,中、重度抑郁 9例 :另取阑尾炎、腹股沟疝气、内、外混合痔等 2 5例作为对照组。应用高效液相色谱仪 ,电化学检测器对两组患者进行了脑脊液 (CSF)中单胺类神经递质 5 羟色胺 (5 HT)的代谢产物 5 羟吲哚乙酸 (5 HIAA)和去甲肾上腺素 (NE)的代谢产物 3 甲氧基 4羟基苯乙二醇 (MHPG)的含量测定。结果　患者组CSF中的 5 HIAA和MHPG含量均低于对照组 ,P <0 .0 1,有显著性差异。结论　PD伴发抑郁的患者其CSF中 5 HIAA和MHPG含量显著减少 ,抑郁症状可能与 5 HT和 (或 )NE的缺乏有关。提示PD伴发抑郁有着相应的生化病理基础     

Long-term effects of MPTP on central and peripheral catecholamine and indoleamine concentrations in monkeys

5 Macaca fascicularis monkeys developed a severe parkinsonian syndrome in the days following intravenous administration of the toxin MPTP. One monkey remained untreated while two groups of two animals were treated daily for 5 months with supramaximal oral doses of either Sinemet or bromocriptine. Both drugs relieved the parkinsonian symptoms. Plasma prolactin concentrations were elevated in MPTP-treated monkeys compared to intact monkeys. MPTP caused a rapid decrease of homovanillic acid (HVA) concentrations in the CSF of these monkeys within days of the toxin injection and these values remained low until sacrifice of the animals 5 months later. By contrast, CSF 5-hydroxyindoleacetic acid (5-HIAA) concentrations were elevated a few days after the start of MPTP treatment and these values returned to control levels by 5 months. Five months after the start of MPTP treatment, epinephrine (E) and dopamine (DA) levels were decreased in the adrenal medulla while the norepinephrine (NE) concentration remained unchanged. Catecholamines were assayed in the caudate putamen, nucleus accumbens, amygdala and frontal cortex of these monkeys. NE concentrations were decreased in the frontal cortex of MPTP-treated monkeys while a decrease of E concentrations after MPTP was only observed in the n. accumbens. Dopamine and its metabolites dihydroxyphenylacetic acid (DOPAC) and HVA were reduced in the caudate, putamen, n. accumbens and frontal cortex. Our results show that MPTP treatment in the long-term (5 months) not only affects the dopaminergic system of the caudate-putamen but also has effects on dopaminergic systems in other regions as well as on noradrenergic and adrenergic systems in the brain and the periphery.     

Changes in body temperature markedly affect striatal dopamine release and metabolism: an in vivo study

Summary Dopamine release and metabolism in the corpus striatum increased markedly when the core body temperature of anesthetized rats was increased from 35 ° to 41 °C while temperatures below 34 ° were associated with a marked attenuation of dopamine release. These observations may have clinical relevance in cases where alterations in body temperature are associated with extrapyramidal dysfunction.     

Effects of monoamine oxidase inhibition by selegiline on concentrations of noradrenaline and monoamine metabolites in CSF of patients with Alzheimer's disease

Summary A double-blind, cross-over trial with 12 patients with Alzheimer's disease (AD) was carried out primarily to test the suitability of this design in the investigation of the clinical, effects of selegiline (10 mg/day) in AD. Cerebrospinal fluid (CSF) samples for the determination of concentrations of noradrenaline (NA) and several monoamine metabolites were collected at baseline and at the end of both four-week treatment periods (placebo and selegiline). The severity of dementia was assessed using Ferm's and Gottfries-Bråne-Steen (GBS) dementia scales. The concentrations of the dopamine metabolite, 3,4-dihydroxyphenylacetic acid (DOPAC) and the NA metabolites, 3,4-dihydroxyphenylglycol (DHPG), and 3-methoxy-4-hydroxyphenyl glycol (MHPG) decreased significantly during selegiline treatment. There was a clear trend of reduction in concentrations of homovanillic acid (HVA) during selegiline treatment, whereas the concentrations of NA, 5-hydroxyindoleacetic acid (5-HIAA), and tryptophan did not differ significantly. The study design was not suitable for the analysis of the clinical results as there was a significant carry-over effect in both scales. As only the first period data could be used in the analysis, there were no significant differences in the scores of Ferm's or GBS scales, but clear positive trends could be detected in favour of selegiline.