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Manifestations of axonal excitability in patients with neurofibromatosis type 1
No full text神經系統疾病神經纖維瘤第一型 (neurofibromatosis type1，NF1)的發生率約1/3000-4000為常見單一基因的體染色體顯性遺傳疾病。其外顯率100%，是一種進行性、持續性、變異性相當高的遺傳疾病。NF1約有1.3-2.3%神經病變症狀，且常有疼痛問題主訴。傳統的神經傳導檢查及肌電圖，對於膜電位的改變及神經的興奮性而言，無法提供相關的資訊。因此本實驗在於利用新的神經興奮傳導檢查儀器，來比較NF1與一般人臨床上神經膜電位的改變，及神經的興奮性變化，相關之研究。
神經興奮傳導檢查結果可分出(1) 刺激-反應曲線、(2) 強度 - 持續時間、(3) 閾值電緊張 、(4) 電流 - 電壓曲線 (5) 恢復週期。
在這項研究中，我們共收集神經纖維瘤第一型患者75人，正常對照組共計70 人。每位受試者評估5個項目，部位為正中神經，尺神經的感覺及運動神經及脛骨神經之運動神經。
我們發現在刺激-反應曲線和強度 - 持續時間實驗結果中，NF1與健康正常人相比正中神經之運動及感覺軸索及尺神經感覺神經軸索在(1)Stimulus for 50% max response所需電流量偏高，(2) Rheobase實驗結果中偏高。代表NF1病人的動作電位需要更大的刺激。可能推測的原因是NF1，有些神經束密度不同；又許旺細胞腫瘤的異常增生，導致髓鞘減少或是在某些區域髓鞘消失。 因此可能對paranode的快速鉀離子通道造成影響。
在閾值電緊張實驗結果中，尺神經之感覺神經在過極化方面有許多顯著差異，包含TEh(overshoot)偏低等。可能表示在此區域慢速K+增加，這個結果可能是因為Na+/K+ pump失去功能，造成傳導被抑制 。
在電流 - 電壓曲線實驗結果中，NF1與健康正常人的比較，正中神經之運動神經、尺神經之運動神經、脛骨神經之運動神經Hyperpolarization I/V slope皆向上偏，為外向整流(outward rectification) 的電流出現。NF1許旺細胞瘤的增生引起鉀通道被阻斷，導致NF1過極化現象比一般人明顯。
在恢復週期實驗結果中，NF1病人感覺神經Latency時間較短，是由時NF1產物neurofibromin易造成感覺神經元敏感，在神經傳導上可能導致發射間隔時間變少，可能讓神經纖維瘤第一型病人較容易感受到疼痛的感覺。
Refractoriness at 2.5ms尺神經之運動神經及正中神經之感覺神經閾值的改變百分比偏少，意謂著再產生動作電位的閾值較低。NF1在相對不反應期所需的刺激閾值較低，表示鈉離子通道的復活較一般人快。
神經纖維瘤第一型之神經病變的神經興奮性改變，仍未被仔細研究過，故經由神經興奮傳導檢查所得到的結果，提供給我們更多的訊息，在遺傳諮詢方面，可用來解釋為何神經纖維瘤第一型病患易感到疼痛麻刺感的有力證明，並期能提供未來臨床上的參考。Neurofibromatosis type 1 (NF1) is a common autosomal dominant disorder, affecting approximately one in every 4000 individuals. Although the penetrance rate for NF1 is 100%, the clinical features are highly variable among families as well as intra-family. It has been estimated that 1.3~2.3% of NF1 patients has neuropathic symptoms, and neuropathic pain is one of the common complaints. Traditional nerve conduction test and electromyography which is usually unremarkable in NF1 patients, cannot provide information such as changes in membrane potentials and nerve excitability. This study employed the newly developed nerve excitability test (NET) to compare the parameters of nerve membrane potential and axonal excitability between NF1 and healthy individuals.
In this study, we have recruited 75 NF1 patients and 70 healthy individuals as normal controls. Every subject is evaluated in 5 individual nerves: median motor and sensory nerve, ulnar motor and sensory nerve, and tibial motor nerve. The results of the NET can be divided into 5 main categories: (1) SR, stimulation-response curve; (2) Strength-duration curve; (3) Threshold electrotonus; (4) Current-voltage curve; and (5) Recovery cycle.
In the stimulation-response curve test, NF1 subjects had higher rheobase and higher current in stimulus for 50% max response in the motor axons of median nerve and the sensory one in both median and ulnar nerves. The reason might be due to different density of the nerve fascicles and dysmyelation of some nerve areas in NF1 patients, which could cause inactivation of the fast K+ channels at the paranodal region.
In the threshold electrotonus test, NF1 subjects had lower TEh (overshoot) in the sensory axons of the ulnar nerve. This indicates an increase in slow K+ current and keep the axonal membrane in a hyperpolarization state which possibly reasults from the dysfunction of the Na+/K+ pump in the conduction block region.
In the current-voltage curve test, the NF1 subjects had significantly higher Hyperpolarization I/V slope in the motor axons of the median, ulnar and tibial nerves compared to that of the controls. This might due to the increase of the outward rectification of the K+ current causing a slow polarizating effect. Proliferation of schwannoma cells in NF1 will cause increasing of K+ outward current and result in a more obvious hyperpolarization than healthy subjects.
In the Recovery cycle test, compared to controls, the latency of the sensory axons in NF1 patients is conspicuously short rendering the high frequency of neuropathic pain in NF1 patients. The refractoriness at 2.5ms showed a significant low threshold in the motor axons of the ulnar and sensory ones in the median nerves of the NF1 subjects, indicating that the threshold to generate a new action potential is reduced. Concerning the threshold in RRP (relative refractory periods), NF1 patients had a significant low threshold comparing to that of controls suggesting the reactivation of the nodal Na+ channel is faster in NF1 patients than in healthy subjects.
The nerve excitability change in NF1 neuropathy has not yet being well studied. The results from our study provide more information about the changes of the electrophysiological parameters in NF1 which will facilitate our understanding of the neuropathic pain in NF1.總目 錄
頁次
口試委員會審定書……………………………………………………………… i
誌謝………………………………………………………………………………. ii
中文摘要………………………………………………………………………… iii
英文摘要…………………………………………………………………………. v
目 錄…………………………………………………………………………………I
表目錄………………………………………………………………………………III
圖目錄……………………………………………………………………………….V
第一章、導論
1.1神經纖維瘤疾病簡………………………………………………………………1
1.2神經纖維瘤臨床表現……………………………………………………………3
1.3本論文研究重點…………………………………………………………………6
1.4電生理概論……………………………………………………………………....8
1.5閾值跟蹤方法…………………………………………………………………...12
第二章、研究方法
2.1測試者選擇………………………………………………………………………19
2.2實驗設計…………………………………………………………………………19
2.3實驗儀器及器材…………………………………………………………………20
2.4實驗步驟………………………………………………………………………... 21
2.5資料之蒐集處理評估及統計分析方法………………………………………... 23
第三章、結果
3.1神經纖維瘤第一型與對照組正中神經、尺神經及脛骨神經之運動神經的
神經興奮性檢查結較…………………………………………………………….…26
3.2神經纖維瘤第一型與對照組正中神經及尺神經之感覺神經的
神經興奮性檢查結果比較………………………………………………………….32
第四章、討論……………………………………………………………………….37
第五章、參考文獻…………………………………………………………………..43
表 目 錄
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表 1、 神經纖維瘤的各項臨床表徵………………………………………………55
表2、神經興奮性檢查分類人數統整…………...…………………………………56
表3、神經纖維瘤第一型共計75人臨床症狀統計.................................................57
表4、ID Pain中文版………………………………………………………………..58
表5A、ID Pain分析-神經纖維瘤第一型除了頭痛和偏頭痛外有疼痛經驗者…..59
表5B、ID Pain疼痛項目分析………………………………………………………59
表6A正中神經之運動神經刺激反應參數…………………………………………60
表6B尺神經之運動神經刺激反應參數……………………………………………60
表6C脛骨神經之運動神經刺激反應參數…………………………………………60
表7A正中神經之運動神經的閾值電緊張參數……………………………………61
表7B尺神經之運動神經的閾值電緊張參數………………………………………62
表7C脛骨神經之運動神經的閾值電緊張參數…………………………………....63
表8A正中神經之運動神經的電流 - 電壓曲線參數…………..……………….…64
表8B尺神經之運動神經的電流 - 電壓曲線參數…………..………………….…64
表8C脛骨神經之運動神經的電流 - 電壓曲線參數……………………….……..64
表9A正中神經之運動神經的恢復週期參數……………………………………....65
表9B尺神經之運動神經的恢復週期參數…………………………………………65
表9C脛骨神經之運動神經的恢復週期參數………………………………………66
表10A正中神經之感覺神經刺激反應參數………………………………………..67
表10B尺神經之感覺神經刺激反應參數…………………………………………..67
表11A正中神經之感覺神經的閾值電緊張參數……………………………….….68
表11B尺神經之感覺神經的閾值電緊張參數……………………………………..69
表12A正中神經之感覺神經的電流 - 電壓曲線參數…………………………….70
表12B尺神經之感覺神經的電流 - 電壓曲線參數……………………………….70
表13A正中神經之感覺神經的恢復週期參數……………………………………..71
表13B尺神經之感覺神經的恢復週期參數………………………………………..71
表14 Hyperpol. I/V slope…………………………………………………………….72
圖 目 錄
頁次
圖1、動作電位……………………………………………………………………....73
圖2、軸突的離子分布………………………………………………………………74
圖3、神經性肌強直及肌肉萎縮實驗結果…………………………………………75
圖4、Chemotherapy-induced neurotoxicity………………………………………....76
圖5、 Diabetic neuropathy……………………………………….………………….77
圖6、神經興奮性檢查過程記錄…………………………………………………....78
圖7、刺激-反應曲線…………………………………………………………………79
圖8、強度 - 持續時間曲線……………………………………………..…………..80
圖9、閾值電緊張…………………………………………………………………….81
圖10、電流 - 電壓曲線……………………………………………………………..82
圖11、恢復週期………………………………………………………………….…..83
圖12、實驗儀器……………………………………………………………………...84
圖13、實驗衛材……………………………………………………………….….….85
圖14、檢查環境……………………………………………………………….……..86
圖15A、正中神經之運動神經……………………………………………………….87
圖15B、正中神經之感覺神經………………………………………………………87
圖16A、尺神經之運動神經………………………………………………………….88
圖16B、尺之感覺神經………………………………………………………………88
圖17、脛骨神經之運動神經………………………………………………………..89
圖18、找出正極貼片最合適位置…………………………………………………..90
圖19A、正中神經之運動神經的刺激-反應曲線比較……………………………..91
圖19B、尺神經之運動神經的刺激-反應曲線比較………………………………..99
圖19C、脛骨神經神經之運動神經的刺激-反應曲線比較…………………….….92
圖20A、正中神經之運動神經的強度 - 持續時間曲線比較……………….…….93
圖20B、尺神經之運動神經的強度 - 持續時間曲線比較………………….…….94
圖20C、脛骨神經神經之運動神經的強度 - 持續時間曲線比較…….………….95
圖21A、正中神經之運動神經的閾值電緊張比較…………………………….…..96
圖21B、尺神經之運動神經的閾值電緊張比較…………………………………...96
圖21C、脛骨神經之運動神經的閾值電緊張比較………………………….…….97
圖22A、正中神經之運動神經的電流 - 電壓曲線比較………………………….98
圖22B、尺神經之運動神經的電流 - 電壓曲線比較…………………………….98
圖22C、脛骨神經之運動神經的電流 - 電壓曲線比較…………………………99
圖23A、正中神經之運動神經的恢復週期曲線比較…………………………….100
圖23B、尺神經之運動神經的恢復週期曲線比較……………………………….100
圖23C、脛骨神經之運動神經的恢復週期曲線比較…………………………...101
圖24A、正中神經之感覺神經的刺激-反應曲線比較…………………………..102
圖24B、尺神經之感覺神經的刺激-反應曲線比較……………………………..102
圖25A、正中神經之感覺神經的強度 - 持續時間曲線比較…………………..103
圖25B、尺神經之感覺神經的強度 - 持續時間曲線比較………………….….104
圖26A、正中神經之感覺神經的閾值電緊張比較……………………………..105
圖26B、尺神經之感覺神經的閾值電緊張比較………………………………..105
圖27A、正中神經之感覺神經的電流 - 電壓曲線比較……………………….106
圖27B、尺神經之感覺神經的電流 - 電壓曲線比較………………………….106
圖28A、正中神經之感覺神經的恢復週期曲線比較…………………………..107
圖28B、尺神經之感覺神經的恢復週期曲線比較……………………………..107
圖29 、Multifocal motor neuropathy………………………………………….…108
圖30、運動及感覺軸突興奮比較……………………………………………….10
Motor and Sensory Axon Excitability Properties From the Median and Ulnar Nerves and the Effects of Age on These Properties
No full textPurpose:Threshold tracking is a new noninvasive approach for detecting axonal excitability changes in vivo. In this study, the authors compared the excitability indices of motor and sensory axons of median and ulnar nerves to determine whether the two nerves behave in a similar or a noninterchangeable way. They also examined whether age affects these indices.Methods:Seventy normal subjects aged 22-70 years (mean, 36.7 12.5 years) were recruited. Multiple excitability indices were measured in both motor and sensory axons from median and ulnar nerves.Results:The threshold and rheobase were significantly higher for the ulnar motor axons recorded at the first dorsal interosseous muscle than for the median motor axons at the abductor pollicis brevis muscle. In contrast, the strength-duration time constant was decreased, threshold electrotonus reduction (in both depolarizing and hyperpolarizing directions) was significantly smaller, I/V slope was decreased, and subexcitability was reduced for the ulnar motor axons. Excitability indices measured in the sensory axons of both nerves were not overtly different. In R-square analysis, age had a homogeneous influence on sensory axon excitability but heterogeneous influence on motor axon excitability.Conclusions:The excitability indices may be interchangeable for sensory axons but not motor axons. The authors therefore recommend recording motor axonal excitability in various muscle groups rather than a single muscle group
Going Beyond Counting First Authors in Author Co-citation Analysis
Get PDFThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Variations on the Author
Get PDF“Variations on the Author” discusses two of Eduardo Coutinho’s recent films (Um Dia na Vida, from 2010, and Últimas Conversas, posthumously released in 2015) and their contribution to the general question of documentary authorship. The director’s filmography is characterized by a consistent yet self-effacing form of authorial self-inscription: Coutinho often features as an interviewer that rather than express opinions propels discourses; an interviewer that is good at listening. This mode of self-inscription characterizes him as an author who is not expressive but who is nonetheless markedly present on the screen. In Um Dia na Vida, however, Coutinho is completely absent form the image, while Últimas Conversas, on the contrary, includes a confessional prologue that moves the director from the margins to the center of his films. This article examines the ways in which these works stand out in the filmography of a director who offers new insights into the notion of cinematic authorship
Appropriate Similarity Measures for Author Cocitation Analysis
Get PDFWe provide a number of new insights into the methodological discussion about author cocitation analysis. We first argue that the use of the Pearson correlation for measuring the similarity between authors’ cocitation profiles is not very satisfactory. We then discuss what kind of similarity measures may be used as an alternative to the Pearson correlation. We consider three similarity measures in particular. One is the well-known cosine. The other two similarity measures have not been used before in the bibliometric literature. Finally, we show by means of an example that our findings have a high practical relevance.information science;Pearson correlation;cosine;similarity measure;author cocitation analysis
Dispelling the Myths Behind First-author Citation Counts
Get PDFWe conducted a full-scale evaluative citation analysis study of scholars in the XML research field to explore just how different from each other author rankings resulting from different citation counting methods actually are, and to demonstrate the capability of emerging data and tools on the Web in supporting more realistic citation counting methods. Our results contest some common arguments for the continued
use of first-author citation counts in the evaluation of scholars, such as high correlations between author rankings by first-author citation counts and other citation
counting methods, and high costs of using more realistic citation counting methods that are not well-supported by the ISI databases. It is argued that increasingly available digital full text research papers make it possible for citation analysis studies to go beyond what the ISI databases have directly supported and to employ more
sophisticated methods
koamabayili/VECTRON-author-checklist: VECTRON author checklist
No full textWe have done our best to complete the author checklist relating to the use of animals in the hut study. Note that the objective for the hut study was to evaluate the IRS treatment applications for residual efficacy against Anopheles mosquitoes, including the local An. coluzzii mosquito population. Cows were only used to attract mosquitoes into the huts and no tests were carried out directly on the cows. The author checklist is intended for use with studies where experiments are carried out on animals, which is why we have had such difficulty in completing this for the hut study, as many of the questions do not relate to how the cows were used
Author-wise bibliometric analysis based on entropy.
No full textAuthor-wise bibliometric analysis based on entropy.</p
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