今日の臨床サポート

ランバート・イートン(Lambert-Eaton)型筋無力症候群

著者: 中馬越清隆 筑波大学 医学医療系神経内科学

監修: 庄司進一 筑波大学

著者校正済:2021/11/17
現在監修レビュー中
患者向け説明資料

概要・推奨   

  1. Lambert-Eaton型筋無力症候群には肺小細胞癌の合併頻度が高く、Lambert-Eaton型筋無力症候群を疑ったら肺癌検索を行うべきである(推奨度1)
  1. 肺小細胞癌合併Lambert-Eaton型筋無力症候群の治療は癌の根治的治療が優先される(推奨度1)
  1. Lambert-Eaton型筋無力症候群の診断には誘発筋電図検査が重要である(推奨度1)
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となりま
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  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要と
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧には
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧には
  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となり
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  1. 閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必要となります。閲覧にはご契約が必
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薬剤監修について:
オーダー内の薬剤用量は日本医科大学付属病院 薬剤部 部長 伊勢雄也 以下、林太祐、渡邉裕次、井ノ口岳洋、梅田将光による疑義照会のプロセスを実施、疑義照会の対象については著者の方による再確認を実施しております。
※薬剤中分類、用法、同効薬、診療報酬は、エルゼビアが独自に作成した薬剤情報であり、
著者により作成された情報ではありません。
尚、用法は添付文書より、同効薬は、薬剤師監修のもとで作成しております。
※薬剤情報の(適外/適内/⽤量内/⽤量外/㊜)等の表記は、エルゼビアジャパン編集部によって記載日時にレセプトチェックソフトなどで確認し作成しております。ただし、これらの記載は、実際の保険適用の査定において保険適用及び保険適用外と判断されることを保証するものではありません。また、検査薬、輸液、血液製剤、全身麻酔薬、抗癌剤等の薬剤は保険適用の記載の一部を割愛させていただいています。
(詳細はこちらを参照)
著者のCOI(Conflicts of Interest)開示:
中馬越清隆 : 特に申告事項無し[2021年]
監修:庄司進一 : 特に申告事項無し[2021年]

改訂のポイント:
  1. Lambert-Eaton型筋無力症候群と疾患特異性の高い自己抗体である抗P/Q型VGCC抗体が2021年9月から保険適用となった。
  1. 近年、高頻度反復神経刺激検査より実用的な安静時複合筋活動電位(CMAP)振幅低下と強収縮後の手筋で測定したCMAPの増大所見が診断で用いられる。

病態・疫学・診察

疾患情報(疫学・病態)  
  1. Lambert-Eaton型筋無力症候群(Lambert-Eaton myasthenic syndrome、LEMS)は、悪性腫瘍に合併あるいは腫瘍の発症に先行する自己免疫機序が関与する傍腫瘍性症候群の1つである。約60%以上に腫瘍、特に肺小細胞癌を合併するため、LEMSと診断された場合には肺癌などの悪性腫瘍検索が必須である。
  1. 臨床症状は、四肢近位筋の易疲労性と筋力低下を主徴とする。これらの症状に眼瞼下垂や眼筋麻痺などの重症筋無力症類似の眼症状、自律神経症状、小脳失調を合併することがある。
  1. 誘発筋電図検査所見が確定診断および重症筋無力症との鑑別診断上重要である。複合筋活動電位振幅の著明低下、低頻度刺激では漸減(waning)現象、高頻度刺激または短時間運動後では漸増(waxing)現象といった特徴的な所見を認める。
  1. 電位依存性カルシウムチャンネル(voltage-gated Ca2+ channel、VGCC)の機能を阻害する自己抗体が主な原因物質と考えられている。抗P/Q型VGCC抗体は、LEMSの約85%の症例で陽性となり、残り15%のLEMSの症例には検出されない。
 
  1. LEMSには肺小細胞癌の合併頻度が高く、LEMSを疑ったら肺癌検索を行うべきである(推奨度1)
  1. わが国におけるLEMSの臨床像をまとめた論文がある[1]
  1. わが国の110例をまとめたもので、LEMS患者の61%に肺小細胞癌を合併し、残り31%が癌非合併例である。
  1. LEMSを疑ったら、まずは胸部CTを施行すべきである。
 
  1. 胸部X線写真は、肺癌検出を目的として、最初に行うよう勧められる。また胸部X線CTは、肺癌検出を目的として、あるいは胸部X線写真で異常がある場合に、行うよう勧められる(推奨度1)
  1. 肺癌の検出に関する胸部X線および胸部X線CTの有用性に関する論文が数多くある[2][3][4][5]
  1. 胸部X線写真は、簡便で広く普及した検査法である。日常診療において、胸部X線写真による肺癌の検出感度は、80%程度と報告されている。胸部X線CTは、臨床的に問題となる大きさの肺癌を検出する形態診断法として、現時点で最も有力な検査である。病変の有無を検索する従来型CTでは、肺野結節の検出能は病変の大きさに依存し、6mm以上の大きさの結節では95%の検出能が得られるが、6mm以下の結節では70%程度に低下し、特に3mm以下では検出能が低下する。
  1. 肺癌検索のためには胸部X線および胸部X線CTが必須である。
 
  1. 腫瘍マーカーおよびPET/CTは、肺癌検出の目的としては、行うよう勧められない(推奨度2)
  1. 肺癌検出に関する腫瘍マーカーおよびPET/CTの有用性に関する論文がある[6][7][8][9][10][11][12][13][14][15]
  1. 腫瘍マーカーを用いた肺癌検出率は、対象集団の事前確率に影響されるため、一般集団を対象に感度と特異度の優れた腫瘍マーカーを検査しても肺癌検出率は向上しないことが示されている。小細胞癌症例に対する検出感度はNSEが47%、ProGRPが45%程度である。CEA、CYFRA21-1、ProGRP、NSEなどの腫瘍マーカーの変動は腫瘍の病期あるいは治療効果と良好に相関することが報告されている。したがって、腫瘍マーカーは肺癌検出の目的ではなく、肺癌の質的診断の補助、治療効果のモニタリング、再発診断の補助として行うよう勧められる。
  1. 胸部X線CTで検出可能な肺悪性結節のPET/CTによる検出感度は約70%であり、直径10mm未満や低い組織学的gradeの肺悪性結節はPET/CTで偽陰性を呈しやすいことが示されている。一方、肺結節の良悪性鑑別に対するPET/CTの正診率は、メタアナリシスの結果、有意差はないもののPET/CTが胸部X線CTよりも優れる傾向性が認められた。したがって、PET/CTは肺癌検出の目的ではなく、肺癌の質的診断の補助として行うよう勧められる。
  1. 腫瘍マーカーおよびPET/CTは、肺癌検出には胸部X線および胸部X線CTに劣るが、肺癌の質的診断の補助や治療効果のモニタリング、再発診断の補助には利用価値がある。
病歴・診察のポイント  
  1. 筋力低下の主訴に対し、筋炎や重症筋無力症、運動ニューロン疾患など他の神経・筋疾患のみならずLEMSも念頭に置くことが早期診断には重要である。

これより先の閲覧には個人契約のトライアルまたはお申込みが必要です。

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文献 

著者: Y K Nakao, M Motomura, T Fukudome, T Fukuda, H Shiraishi, T Yoshimura, M Tsujihata, K Eguchi
雑誌名: Neurology. 2002 Dec 10;59(11):1773-5.
Abstract/Text The authors characterized the clinical and immunologic features of 110 patients with Lambert-Eaton myasthenic syndrome (LEMS). Anti-P/Q-type voltage-gated calcium channels (VGCC) antibodies were detected in 85% of the patients (seropositive) but not in the rest (seronegative). Except for the indication that small cell lung carcinoma is less common in seronegative patients, no significant differences were found in the clinical characteristics of patients who had or did not have anti-P/Q-type VGCC antibodies. The results of passive transfer experiments suggest that seronegative LEMS is also an autoantibody-mediated disorder.

PMID 12473768  Neurology. 2002 Dec 10;59(11):1773-5.
著者: L G Quekel, A G Kessels, R Goei, J M van Engelshoven
雑誌名: Chest. 1999 Mar;115(3):720-4.
Abstract/Text STUDY OBJECTIVES: To investigate the miss rate of non-small cell lung cancer (NSCLC) on the chest radiograph. In addition, the characteristics, the delay in diagnosis, and the change in prognosis of the missed lesions were studied.
DESIGN: A retrospective study on patients with histopathologically proven NSCLC during the years 1992 through 1995 in a large community hospital.
SETTING: Department of Radiology, Atrium Medical Center, Heerlen, the Netherlands.
PATIENTS: During the study period, 495 patients presented with NSCLC. Of these patients, the complete set of chest radiographs was available for analysis in 396; there were 300 men and 96 women, with a mean age of 68 years.
MAIN OUTCOME MEASURES: The main outcome measures included the miss rate of NSCLC presenting as nodular lesions. Location, diameter, superposing structures, and delay of missed and detected lesions and the change of prognosis as a consequence of the delay in diagnosis were other measures.
RESULTS: In 49 (19%) of 259 patients with NSCLC presenting as a nodular lesion on the chest radiographs, the lesions were missed. The miss rate was not dependent on location. Superposing structures were more often present in the group of missed lesions than in the group of detected lesions, respectively, 71% and 2%. The median diameter of the missed lesions was 16 mm and of the detected lesions it was 40 mm. The median delay of the missed lesions was 472 days and of the detected lesions it was 29 days. Twenty-two (45%) patients with missed lesions remained in stage T1, 6 (12%) remained in stage T2 and in 21 patients (43%), the tumor stage changed from stage T1 into T2.
CONCLUSION: The miss rate of 19% in our study is low compared with the rate in the literature but it has a definitive impact on prognosis.

PMID 10084482  Chest. 1999 Mar;115(3):720-4.
著者: M Peuchot, H I Libshitz
雑誌名: Radiology. 1987 Sep;164(3):719-22. doi: 10.1148/radiology.164.3.3615867.
Abstract/Text Radiologic-surgical correlative studies were performed for new pulmonary parenchymal nodules in 100 lungs of 84 patients with previously treated extrathoracic malignancies. Ten patients with radiographically typical bronchogenic carcinomas were excluded from analysis. Of 237 nodules resected, 173 (73%) were identified with computed tomography (CT) and 64 (27%) were not. Two hundred seven (87%) were of metastatic origin, 21 (9%) were benign, and nine (4%) were bronchogenic carcinomas. Of those nodules seen with CT and not with radiography of the chest, 84% were of metastatic origin. Between patients with carcinoma and those with sarcoma or melanoma, there was little difference in the percentage of nodules found with CT. More resected nodules were metastases in the sarcoma-melanoma group (93%) than in the carcinoma group (77%). New bronchogenic carcinomas and benign lesions were more common in the carcinoma group. Chest radiography disclosed all nodules resected in 44% of cases, whereas CT disclosed 78%. Of 65 nodules detected as solitary nodules with chest radiography, only 35 (54%) proved to be truly solitary, whereas 35 of 44 (80%) detected with CT were truly solitary.

PMID 3615867  Radiology. 1987 Sep;164(3):719-22. doi: 10.1148/radiolo・・・
著者: N Altorki, M Kent, M Pasmantier
雑誌名: J Thorac Cardiovasc Surg. 2001 Jun;121(6):1053-7. doi: 10.1067/mtc.2001.112827.
Abstract/Text OBJECTIVE: Computed tomography has recently been proposed as a useful method for the early detection of lung cancer. In this study we compared the stage distribution of lung cancers detected by a computed tomographic scan with that of lung cancers detected by a routine chest x-ray film.
METHODS: Two groups of patients with biopsy-proven non-small cell lung cancer were reviewed. In the first group of 32 patients, the tumors were detected by a computed tomographic scan. In a second group (n = 101), the lung cancers were detected on routine chest x-ray films. Patients with pulmonary symptoms or a history of cancer were excluded.
RESULTS: There was no difference in age, sex, or cell-type distribution between the 2 groups. A significantly greater number of patients undergoing a computed tomographic scan had stage IA disease compared with those having an x-ray film. Of the 32 patients in the group having a scan, 10 had tumors 1 cm or less in size versus 6 of 101 in the group having a chest radiograph. Additionally, there was a significant reduction in advanced stage disease in the group having a scan.
CONCLUSIONS: In this retrospective study, a higher incidence of stage IA lung cancers and significantly fewer cases of more advanced disease were observed in patients screened with computed tomography than in those having a chest radiograph. These data suggest that computed tomographic screening may be of value in improving the survival of patients with non-small cell lung cancer.

PMID 11385370  J Thorac Cardiovasc Surg. 2001 Jun;121(6):1053-7. doi: ・・・
著者: S Diederich, M Semik, M G Lentschig, F Winter, H H Scheld, N Roos, G Bongartz
雑誌名: AJR Am J Roentgenol. 1999 Feb;172(2):353-60. doi: 10.2214/ajr.172.2.9930781.
Abstract/Text OBJECTIVE: Our aim was to assess the sensitivity of helical CT for revealing pulmonary nodules. Thoracotomy with palpation of the deflated lung, resection, and histologic examination of palpable nodules was used as the gold standard.
SUBJECTS AND METHODS: Thirteen patients underwent helical CT (slice thickness, 5 mm; reconstruction intervals, 3 mm and 5 mm; interpreted by two independent observers). Subsequently, patients underwent unilateral (n = 6) or bilateral (n = 7) surgical exploration, and CT-surgical correlation of 20 lungs was performed.
RESULTS: Ninety nodules were resected (61 were smaller than 6 mm; 13 were 6-10 mm; 11 were larger than 10 mm; in five nodules, the size was not recorded at surgery). Sixty-nine nodules were located in the pulmonary parenchyma and 21 in the visceral pleura. Of the 90 lesions, 43 (48%) were found on histology to represent metastases. For lesions detected by at least one observer, the sensitivity of helical CT was 69% for intrapulmonary nodules smaller than 6 mm, 95% for intrapulmonary nodules larger than or equal to 6 mm, and 100% for histologically proven intrapulmonary metastases larger than or equal to 6 mm. For lesions smaller than or equal to 10 mm, sensitivity was better using a reconstruction interval of 3 mm rather than of 5 mm.
CONCLUSION: In this study, the sensitivity of helical CT exceeded the sensitivity of conventional CT in previous reports. However, because of limitations in the detection of intrapulmonary nodules smaller than 6 mm and of pleural lesions, complete surgical exploration should remain the procedure of choice in patients undergoing pulmonary metastasectomy. Preoperative helical CT should be used to guide the surgeon to lesions that are difficult to palpate.

PMID 9930781  AJR Am J Roentgenol. 1999 Feb;172(2):353-60. doi: 10.22・・・
著者: S E Bates
雑誌名: Ann Intern Med. 1991 Oct 15;115(8):623-38.
Abstract/Text The pursuit of the ideal tumor marker has generated many tests for use in the diagnosis and management of cancer, several of which are now widely available. Tumor markers have five potential uses in patient care: They can be used for screening, for diagnosis, for establishing prognosis, for monitoring treatment, and for detecting relapse. The value of a marker in a given setting depends on two marker-related characteristics--sensitivity and specificity. The value of a marker in a particular malignancy also depends on the effectiveness of therapy for the malignancy. Tumor markers have been used to screen for occult cancer but have proved to be valuable only in selected cancers. As diagnostic tools, tumor markers have limitations: Nearly all markers can be elevated in benign disorders, and most markers are not elevated in the early stages of malignancy. Extreme marker elevation often indicates a poor prognosis and in some malignancies can indicate the need for more aggressive treatment. Tumor markers have their greatest value when used to monitor therapy in patients with widespread cancer. Nearly all markers show some correlation with the clinical course of disease, with marker elevation in any stage declining to normal after a curative intervention. Recurrent disease can be accompanied by increased marker levels, but markers can detect an occult recurrence in only a few diseases, thereby facilitating a second attempt at cure. Although it seems unlikely that an ideal tumor marker will be identified for every malignancy, several workable markers are already available. Increasing our knowledge about the capabilities and limitations of existing markers will enable us to use them judiciously in the treatment of cancer.

PMID 1716430  Ann Intern Med. 1991 Oct 15;115(8):623-38.
著者: P Stieber, H Dienemann, A Schalhorn, U M Schmitt, J Reinmiedl, K Hofmann, K Yamaguchi
雑誌名: Anticancer Res. 1999 Jul-Aug;19(4A):2673-8.
Abstract/Text Gastrin-releasing-peptide (GRP), the mammalian counterpart of amphibian bombesin, has been reported to be produced by cells of SCLC. Using recombinant ProGRP Yamaguchi et al developed an enzyme immunoassay for the measurement of this more stable precursor of GRP. We focused our interest on the comparability of ProGRP to neuron specific enolase (NSE), CYFRA 21-1 and CEA. For this purpose we investigated the sera of 272 patients with histologically proven carcinomas of the lung (87 SCLC, 185 NSCLC). The sera of 74 patients with benign diseases of the lung and smokers served as a reference group. At a specificity of 95% ProGRP and NSE possessed comparable sensitivities (47% versus 45%) in small cell lung carcinomas. ProGRP showed only a few more positive test results than NSE, but reached much higher value levels than NSE. ProGRP and NSE showed a clear additive sensitivity of about 20%. In NSCLC CYFRA 21-1 was the leading marker with 63% sensitivity, whereas ProGRP seldom showed a "false positive" test result. ProGRP proved a very high specificity and good sensitivity for small cell lung carcinomas and therefore enables diagnosis of small cell lung carcinoma in patients with lung tumours of unknown origin as well as good control of efficiency of therapy.

PMID 10470218  Anticancer Res. 1999 Jul-Aug;19(4A):2673-8.
著者: W Ebert, M Hoppe, T Muley, P Drings
雑誌名: Anticancer Res. 1997 Jul-Aug;17(4B):2875-8.
Abstract/Text In a series of 381 consecutive patients with lung tumors and benign pulmonary diseases, we examined whether tumor markers CYFRA 21-1 (EIA, Boehringer, Mannheim), TPA-M (IRMA AB Sangtec Medical, Bromma, Sweden), TPS (IRMA, Beki Diagnostics AB, Bromma, Sweden), CEA and NSE (EIA, Roche, Basel) have the potential to contribute to clinical decision-making processes with respect to diagnosis and assessment of response to therapy. The sensitivity values of the marker tests in NSCLC (CYFRA 21-1: 44.4% > 3.9 ng/ml, TPA-M: 39.4% > 200 U/ml, TPS: 13.2% > 230 U/ml, CEA: 37.5% > 8.6 ng/ml), in SCLC (NSE: 61.9% > 14.0 ng/ml) and in pleural mesothelioma (CYFRA 21-1 and TPS: 36.4%) were found to be clearly inferior to the yield of standard cytopathological examinations (85-98%) when using the 95% specificity versus the group with benign pulmonary disease as cut-off values. Therefore, currently available tumor markers are of minor value in the primary diagnosis of lung tumors. After curative surgery (Ro) of NSCLC only CYFRA 21-1 levels dropped to the normal range within one week. The other markers simulated residual tumor mass by displaying elevated marker levels after surgery. During the monitoring of response to chemo-/radiotherapy the changes in marker levels were compared to the clinical assessment according to standard criteria of the WHO. The criteria defined for marker response were a 65% decrease for a partial response and a 40% increase of the marker levels for progressive disease. Concordant results were obtained in 59.4% of the cases for CYFRA 21-1 (TPA-M: 63.3%, TPS: 65.5%, CEA: 54.8%, NSE: 68.9%). Most discordant results were obtained in tumor remission due to an insufficient decrease in the markers. Progressive disease was most effectively indicated by CYFRA 21-1 in NSCLC 60%) and by NSE in SCLC (70.0%). It is concluded that increasing marker levels may contribute to clinical decision making, at least in helping to decide which patients should no longer treated by ineffective and toxic drugs.

PMID 9329552  Anticancer Res. 1997 Jul-Aug;17(4B):2875-8.
著者: L G Jørgensen, K Osterlind, J Genollá, S A Gomm, J R Hernández, P W Johnson, J Løber, T A Splinter, M Szturmowicz
雑誌名: Br J Cancer. 1996 Aug;74(3):463-7.
Abstract/Text The influence of pretreatment serum neuron-specific enolase (S-NSE) in addition to more conventional prognostic factors on survival duration in small-cell lung cancer (SCLC) was investigated in 770 patients from nine centres in six countries. The other variables included stage of disease, performance status (PS), age, sex, serum lactate dehydrogenase (S-LDH), serum alkaline phosphatase (S-AP), and serum carcinoembryonic antigen (S-CEA). Increased values of S-NSE (> 12.5 micrograms-1 l) were observed in 81% of the patients, whereas S-LDH, S-AP and S-CEA were elevated in only half of the patients or less. Multivariable analysis by Cox's proportional hazard model disclosed S-NSE as the most powerful prognostic factor followed by poor PS and extensive stage disease. If PS was ignored, S-LDH came up as a significant prognostic factor. S-AP, S-CEA, age and sex had no significant influence on the prognosis. The three prognostic factors, S-NSE, PS and stage of disease, enabled establishment of a prognostic index (PI) based on a simple algorithm PI = zNSE + z(stage) + 2zPS. This segregated the patients into four groups with clearly different prognosis. The median survival and 95% confidence intervals of the four groups were: 468 days (540-408), 362 days (405-328), 256 days (270-241) and 125 days (179-58). Based on the present results we recommend S-NSE and PS, in addition to stage, for prognostic stratification in treatment trials on SCLC.

PMID 8695366  Br J Cancer. 1996 Aug;74(3):463-7.
著者: R Salgia, D Harpole, J E Herndon, E Pisick, A Elias, A T Skarin
雑誌名: Anticancer Res. 2001 Mar-Apr;21(2B):1241-6.
Abstract/Text BACKGROUND: CA 125 and CEA are valuable serum tumor markers that can be used to monitor response to therapy in patients with various solid tumors. Systemic studies of CA125 and CEA have not been evaluated in lung cancer. In this study, we report the serum levels of CA 125 and compared it to CEA in newly diagnosed lung cancer and analyzed the serum levels of these markers pre- and post-therapy.
MATERIALS AND METHODS: Two hundred and sixteen patients with newly diagnosed non-small lung cancer were evaluated. CA 125 and CEA levels were correlated with stage and histopathology.
RESULTS: CA 125 levels and CEA levels were shown to be lower in patients with early stage disease as compared to patients with unresectable or metastatic disease. CEA levels were significantly higher among patients with adenocarcinoma, while there was no statistically significant relationship between histology and CA 125. There was a statistically significant difference in the CEA and CA 125 levels dependent on tumor size. Thirty-seven patients were analyzed for responses to chemotherapy and responders are more likely to have decreases in CA 125 or CEA.
CONCLUSION: When abnormally elevated inpatients witlrlung cancer, CA 125 and CEA are useful indicators of disease extent, a useful clinical therapeutic marker, and may potentially have important prognostic value.

PMID 11396194  Anticancer Res. 2001 Mar-Apr;21(2B):1241-6.
著者: H Satoh, H Ishikawa, H Kamma, Y T Yamashita, H Takahashi, M Ohtsuka, S Hasegawa
雑誌名: Clin Cancer Res. 1997 Apr;3(4):495-9.
Abstract/Text To evaluate the correlation between serum levels of sialyl Lewis X-i antigen and distant metastasis and survival in patients with non-small cell lung cancer (NSCLC), we measured the serum levels of the tumor marker in 371 patients with untreated NSCLC. The sialyl Lewis X-i antigen level was measured using a RIA kit. In patients with adenocarcinoma or other NSCLC subtypes, there was a correlation between serum sialyl Lewis X-i antigen and stage of the disease (P = 0.0001 and P = 0.0015, respectively). Levels of the marker varied significantly depending on the number of metastatic organs in adenocarcinoma (P = 0.0089) and in other NSCLC subtypes (P = 0.002). Univariate analysis showed that survival of NSCLC patients with high (more than 100 units/ml) sialyl Lewis X-i antigen levels was significantly poorer than that of patients with low antigen levels (P = 0.0001). Multivariate analysis using Cox's proportional hazard model showed that high sialyl Lewis X-i antigen levels correlated significantly with poor survival (P = 0.004). Our data suggest that a high serum level of sialyl Lewis X-i antigen seems to be an indicator of the presence of metastasis and might indicate the need for a careful investigation of all putative metastatic sites. The serum levels of sialyl Lewis X-i antigen may reflect the extension of metastasis and would be helpful in considering treatment options.

PMID 9815711  Clin Cancer Res. 1997 Apr;3(4):495-9.
著者: Rebecca M Lindell, Thomas E Hartman, Stephen J Swensen, James R Jett, David E Midthun, Mark A Nathan, Val J Lowe
雑誌名: AJR Am J Roentgenol. 2005 Jul;185(1):126-31. doi: 10.2214/ajr.185.1.01850126.
Abstract/Text OBJECTIVE: The objective of our study was to retrospectively review the PET results of non-small cell lung carcinomas detected on screening chest CT in a high-risk population.
CONCLUSION: PET findings were negative in 32% of the cases of non-small cell carcinomas that were detected on screening CT in a high-risk patient population. These tumors were small, low-grade, or both. The most common histology was bronchioloalveolar cell carcinoma. The role of PET in evaluating screening-detected indeterminate nodules in a high-risk population may be more limited than in a general population.

PMID 15972412  AJR Am J Roentgenol. 2005 Jul;185(1):126-31. doi: 10.22・・・
著者: Daniel L Fortes, Mark S Allen, Val J Lowe, Keh-Hsien Robert Shen, Dennis A Wigle, Stephen D Cassivi, Francis C Nichols, Claude Deschamps
雑誌名: Eur J Cardiothorac Surg. 2008 Dec;34(6):1223-7. doi: 10.1016/j.ejcts.2008.09.007. Epub 2008 Oct 9.
Abstract/Text OBJECTIVE: Pulmonary metastasectomy is beneficial in select patients. The sensitivity of (18)F-fluorodeoxyglucose positron emission tomography (FDG-PET) for pulmonary metastasis is unknown. The aims of the study were to determine the accuracy of FDG-PET in detecting pulmonary metastasis and identify factors affecting sensitivity.
METHODS: All patients undergoing metastasectomy from September 2002 through December 2006 who had both chest computed tomography (CT) and FDG-PET scans or a fused CT/FDG-PET within 6 weeks prior to surgery were reviewed. Univariate and multivariate analysis were performed to determine predictors of positivity.
RESULTS: There were 83 patients (41 men, 42 women) who had 104 resections. Median age was 61 years (range, 32-87). In total 154 nodules were resected; 1 nodule in 47 patients and multiple in 36. Histopathology was adenocarcinoma in 94 nodules, sarcoma in 18, squamous cell carcinoma in 15, renal cell carcinoma in 7 and other in 20. At least one nodule was FDG-PET positive in 68 patients (81.9%). True positive FDG-PET was found in 104 nodules (67.5%) while 50 were false negative (32.5%). Multivariate analysis revealed tumor diameter and grade correlated with increased sensitivity of FDG-PET.
CONCLUSION: FDG-PET is positive in only 67.5% of metastatic pulmonary nodules. Nodule size and grade affect the sensitivity of FDG-PET for metastatic pulmonary nodules. FDG-PET is not a sensitive test in the evaluation of patients considered for pulmonary metastasectomy. Moreover, a negative FDG-PET should not be used to rule out metastatic disease.

PMID 18848459  Eur J Cardiothorac Surg. 2008 Dec;34(6):1223-7. doi: 10・・・
著者: Paul Cronin, Ben A Dwamena, Aine Marie Kelly, Steven J Bernstein, Ruth C Carlos
雑誌名: Eur Radiol. 2008 Sep;18(9):1840-56. doi: 10.1007/s00330-008-0970-5. Epub 2008 Jul 8.
Abstract/Text The purpose was to assess the clinical utility of diagnostic tests for identifying malignancy within a solitary pulmonary nodule (SPN), and to create a nomogram or "look-up" table using clinical data and non-invasive radiology (positive) test results to estimate post-test probability of malignancy. Studies that examined computed tomography (CT), magnetic resonance imaging (MRI), positron emission tomography (PET) and single photon emission computed tomography (SPECT) for the evaluation of SPN. Two reviewers independently abstracted data and assessed study quality. Study-specific and overall positive likelihood ratios (LRs) for each diagnostic test confirming a diagnosis of malignancy and negative LR for each diagnostic test excluding a diagnosis of malignancy within an SPN were calculated. Forty-four of 242 articles were included. Positive LRs for diagnostic tests were: CT 3.91 (95% confidence interval 2.42, 5.40), MRI 4.57 (3.03, 6.1), PET 5.44 (3.56, 7.32) and SPECT 5.16 (4.03, 6.30). Negative LRs were: CT 0.10 (0.03, 0.16), MRI 0.08 (0.03, 0.12), PET 0.06 (0.02, 0.09) and SPECT 0.06 (0.04, 0.08). Differences in performance for all tests were negligible; therefore, the clinician may confidently use any of the four tests presented in further evaluating an SPN. Given the low cost and prevalence of the technology, SPECT appears to be the leading choice for additional testing in SPN evaluation.

PMID 18607593  Eur Radiol. 2008 Sep;18(9):1840-56. doi: 10.1007/s00330・・・
著者: Paul Cronin, Ben A Dwamena, Aine Marie Kelly, Ruth C Carlos
雑誌名: Radiology. 2008 Mar;246(3):772-82. doi: 10.1148/radiol.2463062148. Epub 2008 Jan 30.
Abstract/Text PURPOSE: To perform a meta-analysis to estimate the diagnostic accuracy of dynamic contrast material-enhanced computed tomography (CT) and magnetic resonance (MR) imaging, fluorine 18 fluorodeoxyglucose (FDG) positron emission tomography (PET), and technetium 99m ((99m)Tc) depreotide single photon emission computed tomography (SPECT) for evaluation of solitary pulmonary nodules (SPNs).
MATERIALS AND METHODS: Data sources were studies published in PubMed between January 1990 and December 2005. The selected investigations were comparative and noncomparative diagnostic cohort studies to examine the operating characteristics of the four imaging modalities for evaluation of SPNs, involving at least 10 enrolled participants with histologic confirmation and having sufficient data to calculate contingency tables. A random coefficient binary regression model with disease probability conditioned on test results was used to summarize test performance and construct summary receiver operating characteristic (ROC) curves. Sensitivities, specificities, predictive values, diagnostic odds ratios, and areas under the ROC curve were calculated.
RESULTS: Forty-four studies--10 dynamic CT, six dynamic MR, 22 FDG PET, and seven (99m)Tc-depreotide SPECT--met the inclusion criteria. (One study was included in both the FDG PET and SPECT groups.) Sensitivities, specificities, positive predictive values, negative predictive values, diagnostic odds ratios, and areas under the ROC curve were, respectively, 0.93 (95% confidence interval [CI]: 0.88, 0.97), 0.76 (95% CI: 0.68, 0.97), 0.80 (95% CI: 0.74, 0.86), 0.95 (95% CI: 0.93, 0.98), 39.91 (95% CI: 1.21, 81.04), and 0.93 (95% CI: 0.81, 0.97) for dynamic CT; 0.94 (95% CI: 0.91, 0.97), 0.79 (95% CI: 0.73, 0.86), 0.86 (95% CI: 0.83, 0.89), 0.93 (95% CI: 0.90, 0.96), 60.59 (95% CI: 5.56, 115.62), and 0.94 (95% CI: 0.83, 0.98) for dynamic MR; 0.95 (95% CI: 0.93, 0.98), 0.82 (95% CI: 0.77, 0.88), 0.91 (95% CI: 0.88, 0.93), 0.90 (95% CI: 0.85, 0.94), 97.31 (95% CI: 6.26, 188.37), and 0.94 (95% CI: 0.83, 0.98) for FDG PET; and 0.95 (95% CI: 0.93, 0.97), 0.82 (95% CI: 0.78, 0.85), 0.90 (95% CI: 0.83, 0.97), 0.91 (95% CI: 0.84, 0.98), 84.50 (95% CI: 34.28, 134.73), and 0.94 (95% CI: 0.83, 0.98) for (99m)Tc-depreotide SPECT.
CONCLUSION: Dynamic CT and MR, FDG PET, and (99m)Tc-depreotide SPECT are noninvasive and accurate in distinguishing malignant from benign SPNs; differences among these tests are nonsignificant.

(c) RSNA, 2008.
PMID 18235105  Radiology. 2008 Mar;246(3):772-82. doi: 10.1148/radiol.・・・
著者: M J Titulaer, P W Wirtz, J B M Kuks, H J Schelhaas, A J van der Kooi, C G Faber, W L van der Pol, M de Visser, P A E Sillevis Smitt, J J G M Verschuuren
雑誌名: J Neuroimmunol. 2008 Sep 15;201-202:153-8. doi: 10.1016/j.jneuroim.2008.05.025. Epub 2008 Jul 21.
Abstract/Text BACKGROUND: Neuromuscular symptoms in patients with Lambert-Eaton myasthenic syndrome (LEMS) and a small cell lung cancer (SCLC) develop more rapidly than in LEMS patients without a SCLC. We studied how this clinical information, which is readily available at the first consultation, can be used to predict the presence of SCLC.
PATIENTS AND METHODS: In our study we included 52 LEMS patients with SCLC and 45 non-tumor patients (NT-LEMS). We interviewed patients using a structured checklist and reviewed their clinical records. We compared frequency and onset of symptoms during the course of LEMS.
RESULTS: In the first six months, over half the SCLC-LEMS patients had developed seven separate symptoms, while NT-LEMS patients developed only two symptoms. Proximal leg weakness and dry mouth were early symptoms in both groups. Rapid involvement of proximal arm muscles (p=0.0001), distal arm muscles (p=0.0037), distal leg muscles (p=0.0002), dysartria (p=0.0091) and the presence of erectile dysfunction (p=0.007) were found significantly more often in SCLC-LEMS patients in both cohorts. Cerebellar symptoms, although present in 9% of LEMS patients, were almost exclusively related to SCLC-LEMS.
CONCLUSION: A rapidly progressive course of disease from onset in LEMS patients should raise a high suspicion of SCLC. Special attention should be paid to involvement of upper extremities, involvement of distal arm and distal leg muscles, to erectile dysfunction and probably ataxia in order to discriminate between SCLC-LEMS and NT-LEMS.

PMID 18644631  J Neuroimmunol. 2008 Sep 15;201-202:153-8. doi: 10.1016・・・
著者: P D Clouston, C B Saper, T Arbizu, I Johnston, B Lang, J Newsom-Davis, J B Posner
雑誌名: Neurology. 1992 Oct;42(10):1944-50.
Abstract/Text We studied nine patients with a subacute onset of a pancerebellar syndrome. Six had known cancer (three small-cell carcinoma of the lung [SCLC], one metastatic small-cell carcinoma, one small-cell carcinoma of the prostate, and one non-Hodgkin's lymphoma). Six of eight who had neurophysiologic testing, including the three patients without detectable cancer, had coexistent Lambert-Eaton myasthenic syndrome (LEMS). In two of the patients, LEMS was discovered only by neurophysiologic testing. We looked for anti-Purkinje cell autoantibodies in all patient's sera and in four patients' CSF. We also looked for autoantibodies to voltage-gated calcium channels (VGCCs) in seven patients' sera and two patients' CSF, using the 125I-omega-conotoxin radioimmunoassay. We were unable to detect anti-Purkinje cell autoantibodies in any patients' serum or CSF. However, there were raised titers of anti-VGCC autoantibodies in five of seven patients' serum, including one patient with SCLC who did not have LEMS, and in the CSF of one of two patients. We conclude that the frequency of presentation of a pancerebellar syndrome with LEMS is higher than expected by chance and is usually associated with cancer. In some of these patients, LEMS may be clinically occult. The presence of LEMS and raised titers of anti-VGCC autoantibodies in some patients with subacute cerebellar degeneration is suggestive of an autoimmune etiology even though anti-Purkinje cell antibodies could not be detected. Anti-VGCC autoantibodies are not confined to LEMS. They may be found at high titer in CSF as well as serum.

PMID 1407577  Neurology. 1992 Oct;42(10):1944-50.
著者: W P Mason, F Graus, B Lang, J Honnorat, J Y Delattre, F Valldeoriola, J C Antoine, M K Rosenblum, M R Rosenfeld, J Newsom-Davis, J B Posner, J Dalmau
雑誌名: Brain. 1997 Aug;120 ( Pt 8):1279-300.
Abstract/Text Several cancers, especially lung, ovarian and breast, can cause paraneoplastic cerebellar degeneration. The presence of different antineuronal antibodies associated with different cancers and paraneoplastic cerebellar degeneration suggests that several immunological mechanisms may result in the same neurological disorder. In patients with small-cell lung cancer, paraneoplastic cerebellar degeneration may occur with or without Hu antineuronal antibodies (HuAb), indicating that patients with the same tumour can develop paraneoplastic cerebellar degeneration by different immunological mechanisms. Furthermore, paraneoplastic cerebellar degeneration sometimes occurs in association with the Lambert-Eaton myasthenic syndrome. In order to try to understand the clinical implication of antineuronal antibodies in patients with small-cell lung cancer, we examined the serum of 57 patients with presenting symptoms of paraneoplastic cerebellar degeneration for the presence of HuAb and P/Q- and N-type voltage-gated calcium channel antibodies. Patients with paraneoplastic cerebellar degeneration who were HuAb positive were compared with HuAb negative patients with respect to neurological symptoms, course of the neurological disorder, response to treatment, tumour prognosis, pathological findings, and cause of death. The tumour outcome and serological findings of these patients were also compared with those of 109 small-cell lung cancer patients without paraneoplastic syndromes of the CNS. Titres of HuAb were classified as 'high' (immunoblot titre > 1:10,000) or 'low' (< 1:10,000), the latter similar to the antibody titres detected in some small-cell lung cancer patients without paraneoplastic symptoms. Twenty-five patients with paraneoplastic cerebellar degeneration (44%) had high titres of HuAb, four (7%) had low titres of HuAb, and 28 (49%) were HuAb negative; for clinical comparisons with the patients with high titres of HuAb, the four patients with low antibody titres were included in the HuAb negative cohort. None of the 109 small-cell lung cancer patients without paraneoplastic symptoms had high titres of HuAb. The presence of high titres of HuAb defined a subset of patients who differed from the HuAb negative paraneoplastic cerebellar degeneration cohort, HuAb positive patients were more likely to be female (P < 0.01), to have multifocal neurological disease (brainstem encephalopathy and sensory neuropathy being common extracerebellar manifestations) (P < 0.002), and be severely disabled (P < 0.005). A total of nine patients (16%) from both paraneoplastic cerebellar degeneration groups developed electrophysiologically confirmed Lambert-Eaton myasthenic syndrome. Seven of these nine patients had serum available for P/Q-type voltage-gated calcium channel antibody testing and all seven were positive. In addition, 20% of HuAb negative paraneoplastic cerebellar degeneration patients without clinically identified Lambert-Eaton myasthenic syndrome had P/Q-type voltage-gated calcium channel antibodies, while only 2% of small-cell lung cancer patients without paraneoplastic symptoms had these antibodies. Treatment of the tumour and/or immunomodulation did not alter the course of paraneoplastic cerebellar degeneration, but improved Lambert-Eaton myasthenic syndrome symptoms. At the time of death, in 60% of HuAb positive and 20% of HuAb negative paraneoplastic cerebellar degeneration patients, the tumour was either not evident or localized to the chest (P < 0.007); neurological disease was the cause of death of 65% HuAb positive paraneoplastic cerebellar degeneration and 10% HuAb negative paraneoplastic cerebellar degeneration patients (P < 0.001). (ABSTRACT TRUNCATED)

PMID 9278623  Brain. 1997 Aug;120 ( Pt 8):1279-300.
著者: R Voltz, A F Carpentier, M R Rosenfeld, J B Posner, J Dalmau
雑誌名: Muscle Nerve. 1999 Jan;22(1):119-22.
Abstract/Text Whether P/Q-type voltage-gated calcium channel (VGCC) antibodies are present in the serum of patients with paraneoplastic syndromes other than the Lambert-Eaton myasthenic syndrome (LEMS) and tumors other than small-cell lung cancer (SCLC) is controversial. Using a commercially available radioimmunoprecipitation assay kit, we examined the sera of 93 patients with paraneoplastic syndromes of the central nervous system (CNS), including 27 patients with paraneoplastic cerebellar degeneration (PCD) associated with tumors other than SCLC and 66 SCLC patients with paraneoplastic encephalomyelitis and sensory neuronopathy (PEM/SN). All PCD sera from patients with tumors other than SCLC were negative for P/Q-type VGCC antibodies. Eight of 66 (12%) SCLC patients with PEM/SN had P/Q-type VGCC antibodies; 4 had LEMS and the other 4 had no symptoms of LEMS or they were overlooked and, therefore, not examined electrophysiologically. In patients with paraneoplastic syndromes of the CNS, the detection of P/Q-type VGCC antibodies supports the diagnosis of LEMS; in our series, only 6% of patients with SCLC and PEM/SN may have had a false positive antibody result, or undiagnosed LEMS.

PMID 9883867  Muscle Nerve. 1999 Jan;22(1):119-22.
著者: F Graus, B Lang, P Pozo-Rosich, A Saiz, R Casamitjana, A Vincent
雑誌名: Neurology. 2002 Sep 10;59(5):764-6.
Abstract/Text Raised levels of P/Q type voltage-gated calcium-channel (VGCC) antibodies were found in 16 (41%) of 39 patients with paraneoplastic cerebellar degeneration (PCD) and Hu antibodies were found in nine (23%). Seven of the 16 VGCC antibody-positive patients had Lambert-Eaton myasthenic syndrome (LEMS). Seven of 15 CSF samples had VGCC antibodies, with evidence of intrathecal synthesis in four. VGCC antibodies should be looked for in PCD, even if there are no symptoms of LEMS, and may be related to the cerebellar dysfunction.

PMID 12221175  Neurology. 2002 Sep 10;59(5):764-6.
著者: J H O'Neill, N M Murray, J Newsom-Davis
雑誌名: Brain. 1988 Jun;111 ( Pt 3):577-96.
Abstract/Text The clinical and electrophysiological features of 50 consecutive patients with the Lambert-Eaton myasthenic syndrome (LEMS) have been analysed. Carcinoma was detected (CD group) in 25, of whom 21 had small cell lung cancer (SCLC). SCLC was evident within 2 yrs of onset of LEMS symptoms in 20/21 cases, and at 3.8 yrs in 1/21. In the cases in whom no carcinoma was detected (NCD group), 14/25 had a history of LEMS greater than 5 yrs. The dominant neurological features were similar in the CD and NCD groups, and consisted of proximal lower limb weakness (100%), depressed tendon reflexes (92%) with posttetanic potentiation (78%), autonomic features, especially dryness of the mouth (74%) and mild/moderate ptosis (54%). The compound evoked muscle action potential amplitude in abductor digiti minimi was below the lower limit of control values in 48/50, and the increment following maximum voluntary contraction above the upper limit of control values in 48/50. Single fibre electromyographic abnormalities were found in 29/29 cases. The analysis indicates that a patient presenting with LEMS has a 62% risk of an underlying SCLC, and that this risk declines sharply after 2 yrs, becoming very low at 4 to 5 yrs. It is argued that in SCLC cases antigenic determinants on tumour cells initiate the autoimmune response, often early in the course of the malignancy, but that the association of LEMS with tumours other than SCLC may be fortuitous. In the latter, and in NCD patients, the initiating factor(s) are unknown.

PMID 2838124  Brain. 1988 Jun;111 ( Pt 3):577-96.
著者: R W Tim, J M Massey, D B Sanders
雑誌名: Neurology. 2000 Jun 13;54(11):2176-8.
Abstract/Text The authors reviewed the incidence of cancer, repetitive nerve stimulation findings, and response to treatment in 73 patients with Lambert-Eaton myasthenic syndrome. Thirty-one patients (42%) had lung cancer, 29 small cell. Doubling of the compound motor action potential amplitude in three tested distal muscles was seen in only 41% of patients. Treatment with 3, 4-diaminopyridine produced moderate to marked self-reported functional improvement in 79% of the 53 treated patients.

PMID 10851390  Neurology. 2000 Jun 13;54(11):2176-8.
著者: Shin J Oh, Katsumi Kurokawa, Gwen C Claussen, Hewitt F Ryan
雑誌名: Muscle Nerve. 2005 Oct;32(4):515-20. doi: 10.1002/mus.20389.
Abstract/Text Various parameters of the repetitive nerve stimulation (RNS) test of the abductor digiti quinti muscle were analyzed statistically in 34 patients with Lambert-Eaton myasthenic syndrome (LEMS). The sensitivity and specificity of the increments after exercise and after 50-HZ stimulation for the diagnosis of LEMS were compared with reference values in 40 normal subjects and data from 538 tests in patients with myasthenia gravis (MG). When we used a 100% increment (the "gold standard") as the normal limit for the postexercise facilitation (PEF) or the high-rate stimulation (HRS) test, the diagnosis of LEMS was confirmed in 29 (85%) cases. When a 60% increment was used as the normal limit, the diagnosis of LEMS was made in 97% of cases. In MG, a 60% increment was observed in only 4 of 538 cases by HRS and in none by the exercise test. Thus, the use of a 60% increment showed a sensitivity of 97% for the diagnosis of LEMS and a specificity of 99% in excluding MG. A 60% increment in either the PEF or HRS test for the diagnosis of LEMS is a desirable alternative to the 100% increment previously considered to be the gold standard for this diagnosis.

Muscle Nerve, 2005.
PMID 16003742  Muscle Nerve. 2005 Oct;32(4):515-20. doi: 10.1002/mus.2・・・
著者: Yuki Hatanaka, Shin J Oh
雑誌名: Muscle Nerve. 2008 May;37(5):572-5. doi: 10.1002/mus.20979.
Abstract/Text An incremental response after brief exercise or high-rate stimulation on the repetitive nerve stimulation (RNS) test is a critical diagnostic criterion for Lambert-Eaton myasthenic syndrome (LEMS). This prospective study was performed to determine what duration of exercise shows the highest diagnostic sensitivity for LEMS. The compound muscle action potential amplitude in the abductor digiti quinti muscle was obtained at rest and after 5 s, 10 s, 15 s, 20 s, 25 s, and 30 s of exercise. Incremental responses were compared for the different exercise durations in 24 studies performed in nine LEMS patients. The increment was highest with 5-s and 10-s exercises (244%-243%) and lowest with 30-s exercise (84%). A gradual decrease in the increment was noted from 5- to 30-s exercise. A significant difference in the increment was noted between 5- to 10-s and 20-s to 30-s exercise. There was significantly higher diagnostic sensitivity with the 10-s exercise compared with 30-s exercise at 100% increment and 60% increment levels. Higher increment and diagnostic sensitivity were achieved with 10-s exercise than with 30-s exercise. Thus, 10-s exercise should be the standard protocol for the RNS test for LEMS.

PMID 18288711  Muscle Nerve. 2008 May;37(5):572-5. doi: 10.1002/mus.20・・・
著者: P O'Suilleabhain, P A Low, V A Lennon
雑誌名: Neurology. 1998 Jan;50(1):88-93.
Abstract/Text Autonomic dysfunction is a recognized feature of the Lambert-Eaton myasthenic syndrome (LES). However, the characteristic pattern of dysautonomia has not been clearly documented and its pathophysiologic basis is not known. We therefore abstracted autonomic symptomatology and results of quantitative tests for salivation, and vasomotor, cardiovagal, and sudomotor reflexes from records of 30 LES patients. Dry mouth (77%) and impotence (45% of men) were the most common symptoms. Composite Autonomic Scoring Scale results were abnormal in 93% of patients, and autonomic failure was severe in 20%. The frequency of specific test abnormalities were the following: sudomotor function, 83%; cardiovagal reflexes, 75%; salivation, 44%; and adrenergic function, 37%. Although voltage-gated N-type calcium (Ca2+) channels are implicated in autonomic transmission, the low frequency of serum antibodies to N-type Ca2+ channels found in the patients of this study (31% positive) argues against a pathogenic role in mediating LES-related dysautonomia. In contrast, 93% of the patients were seropositive for P/Q-type Ca2+ channel antibodies. A subset of these antibodies is thought to impair neuromuscular transmission. Autoantibodies of thyrogastric or glutamic acid decarboxylase specificity (markers of predisposition to type 1 diabetes mellitus) were found in 45% of patients, and type 1 antineuronal nuclear antibody (or anti-Hu, a marker of autoimmune neuropathy associated with small-cell lung carcinoma) was found in 3%. No autoantibody correlated with autonomic dysfunction severity. Sensorimotor neuropathy was documented in five patients, and was not significantly associated with autonomic neuropathy. Autonomic failure was most severe in older subjects with cancer (p = 0.02, age by cancer interaction).

PMID 9443463  Neurology. 1998 Jan;50(1):88-93.
著者: S A Waterman
雑誌名: Clin Auton Res. 2001 Jun;11(3):145-54.
Abstract/Text Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder characterized by muscle weakness and autonomic dysfunction. Recent ex vivo and in vitro studies demonstrate that autoantibodies to the P/Q-subtype of voltage-gated calcium channel inhibit transmitter release from parasympathetic, sympathetic, and enteric neurons, a mechanism likely to underlie the widespread autonomic dysfunction in LEMS. This review summarizes clinical studies characterizing the autonomic symptoms and signs in LEMS and the effectiveness of treatment in alleviating these symptoms. Serological assays and in vitro pharmacologic and electrophysiologic studies are also discussed.

PMID 11605819  Clin Auton Res. 2001 Jun;11(3):145-54.
著者: AAEM Quality Assurance Committee. American Association of Electrodiagnostic Medicine
雑誌名: Muscle Nerve. 2001 Sep;24(9):1239-47.
Abstract/Text A retrospective literature review of the electrodiagnosis of myasthenia gravis (MG) and Lambert--Eaton myasthenic syndrome (LEMS) through July 1998 was performed for the purpose of generating evidence-based practice parameters. There were 545 articles identified, of which 13 articles met at least three of the six criteria set previously by the American Association of Electrodiagnostic Medicine (AAEM). An additional 21 articles were identified from review articles or the references of these first 13 articles leading to a total of 34 articles. Results of studies utilizing repetitive nerve stimulation (RNS) showed that a 10% decrement in amplitude from the first to fourth or fifth intravolley waveform while stimulating at 2--5 HZ is valid for the diagnosis of MG. The degree of increment needed for the diagnosis of LEMS is at least 25% but most accurate when greater than 100%. Abnormal jitter or impulse blocking are the appropriate criteria for diagnosis of neuromuscular junction (NMJ) disorders when using single fiber electromyography (SFEMG). SFEMG is more sensitive than RNS for the diagnosis of disorders of neuromuscular transmission, but may be less specific and may not be available. Therefore, RNS remains the preferred initial test for MG and LEMS.

Copyright 2001 American Association of Electrodiagnostic Medicine
PMID 11494281  Muscle Nerve. 2001 Sep;24(9):1239-47.
著者: L F Dell'Osso, D R Ayyar, R B Daroff, L A Abel
雑誌名: Neurology. 1983 Sep;33(9):1157-63.
Abstract/Text Accurate ocular motility recordings were made of the saccadic responses of five patients with Eaton-Lambert syndrome (ELS). It was found that, contrary to common belief, the ocular motor system is affected. The saccades of ELS patients mimicked those of patients with myasthenia gravis (MG). Both groups exhibited hypometria and multiple, closely spaced saccades. Two patients demonstrated both saccadic facilitation and positive edrophonium tests. The ELS patients had slow or normal saccadic velocities, not the "super-fast" velocities found in patients with ocular MG.

PMID 6684251  Neurology. 1983 Sep;33(9):1157-63.
著者: C H Chalk, N M Murray, J Newsom-Davis, J H O'Neill, S G Spiro
雑誌名: Neurology. 1990 Oct;40(10):1552-6.
Abstract/Text We evaluated the outcome in 16 patients with Lambert-Eaton myasthenic syndrome (LEMS) associated with histologically verified small-cell carcinoma (SCC). Thirteen patients received specific tumor therapy (chemotherapy, radiation therapy, or resection) and most also received pharmacologic and immunologic treatment for LEMS. Seven of 11 patients surviving for more than 2 months after tumor therapy showed substantial neurologic improvement (1 patient being in complete remission at 7 years); in 3 of 11 improvement was transient. An EMG index of disease severity (compound muscle action potential amplitude in abductor digiti minimi) was significantly increased at final follow-up (p less than 0.01; n = 11). A pretreatment amplitude greater than 3.0 mV was a good prognostic sign. We conclude that a combined treatment approach in SCC-LEMS usually results in neurologic improvement.

PMID 2170866  Neurology. 1990 Oct;40(10):1552-6.
著者: H Lundh, O Nilsson, I Rosén
雑誌名: Neurology. 1984 Oct;34(10):1324-30.
Abstract/Text We used a new drug, 3,4-diaminopyridine, to treat five patients with the Lambert-Eaton syndrome, one with a carcinoma and four cryptogenic. The effects of intravenous, oral, and rectal administration were evaluated clinically and electrophysiologically after single doses and during continuous treatment for up to 21 months. 3,4-Diaminopyridine effectively ameliorated the neuromuscular and autonomic nervous system disorders without severe side effects. Anticholinesterase drugs strongly potentiated the benefit of 3,4-diaminopyridine.

PMID 6541305  Neurology. 1984 Oct;34(10):1324-30.
著者: K M McEvoy, A J Windebank, J R Daube, P A Low
雑誌名: N Engl J Med. 1989 Dec 7;321(23):1567-71. doi: 10.1056/NEJM198912073212303.
Abstract/Text Lambert-Eaton myasthenic syndrome is characterized by muscle weakness, hyporeflexia, and autonomic dysfunction, which result from impaired release of acetylcholine from cholinergic nerve terminals. It is frequently associated with cancer, it is autoimmune-mediated, and treatment has been unsatisfactory. 3,4-Diaminopyridine enhances the release of acetylcholine. In this prospective, double-blind, placebo-controlled crossover study of 12 patients with Lambert-Eaton myasthenic syndrome (7 of whom had cancer), 3,4-diaminopyridine in doses up to 100 mg per day was effective in treating both the motor and the autonomic deficits of the syndrome. Muscle strength increased from an average of 70 percent of normal to 81 percent of normal in the upper extremities, and from 45 to 65 percent of normal in the lower extremities. The amplitudes of compound-muscle-action potentials nearly doubled, increasing from an average of 2.9 mV to 5.0 mV in the arm and from 1.6 mV to 3.1 mV in the leg. Autonomic symptoms were relieved. One patient had a seizure after 10 months of treatment, but other side effects from the drug were minimal and dose-related. We conclude that 3,4-diaminopyridine, either alone or in conjunction with other therapies, may be useful in the treatment of Lambert-Eaton myasthenic syndrome.

PMID 2555713  N Engl J Med. 1989 Dec 7;321(23):1567-71. doi: 10.1056/・・・
著者: H Lundh, O Nilsson, I Rosén, S Johansson
雑誌名: Acta Neurol Scand. 1993 Aug;88(2):136-40.
Abstract/Text 3,4-Diaminopyridine (3,4-DAP) given alone or combined with pyridostigmine is the recommended basic therapy in the Lambert-Eaton myasthenic syndrome (LEMS). We present and exemplify our routine test protocol for monitoring drug introduction and treatment regimen of cholinergic drugs in LEMS. The individual drug responses vary and no recommended standard doses exist. Routine electrophysiological repetitive nerve stimulation studies recording amplitude of initial compound muscle action potential (CMAP) in thenar muscles correlate excellently with clinical myasthenic muscle power tests in clinically affected muscle groups. Therefore repetitive clinical muscle power tests, that often are complicated by painful myalgia and activation potentiation, can be replaced by recordings of CMAP in the introduction and clinical follow up of cholinergic drug treatment in LEMS. Also, adverse effects and other treatment problems from the experience of continuous treatment of 19 LEMS patients with 3,4-DAP for up to 10 years are presented.

PMID 8213058  Acta Neurol Scand. 1993 Aug;88(2):136-40.
著者: D B Sanders, J M Massey, L L Sanders, L J Edwards
雑誌名: Neurology. 2000 Feb 8;54(3):603-7.
Abstract/Text OBJECTIVES: The authors report the results of a prospective, placebo-controlled, randomized study to evaluate the effectiveness of 3,4-diaminopyridine (DAP) in patients with Lambert-Eaton myasthenic syndrome (LEMS) and to determine the acute and long-term side effects of DAP.
METHODS: Twenty-six patients with LEMS completed a two-arm parallel treatment protocol in which DAP, 20 mg three times daily, or placebo was given blindly for 6 days, and a quantitative examination of muscle strength (the quantitative myasthenia gravis [QMG] score) was used as the primary measure of efficacy. After the blinded study, patients were given open-label DAP and monitored for side effects as long as there was symptomatic improvement.
RESULTS: Twelve patients took DAP, and 14 took placebo. There was no difference in the age of LEMS onset, gender distribution, incidence of lung cancer, or baseline muscle strength between the patients who were randomly assigned to receive placebo and those randomly assigned to DAP. Statistical analysis using the Wilcoxon's rank sum test demonstrated that patients who received DAP had a significantly greater improvement in the QMG score and in the summated amplitude of compound muscle action potentials recorded from three sentinel limb muscles. All but one LEMS patient had significant symptomatic improvement from subsequent open-label DAP. Side effects of DAP were negligible, consisting of perioral and digital paresthesia. Laboratory measurements demonstrated no evidence of toxicity affecting liver, renal, hematologic, endocrinologic, encephalographic, or electrocardiologic function acutely or after 6 months of open-label DAP.
CONCLUSIONS: This study corroborates previous studies and many years of clinical experience showing that DAP is an effective and safe treatment for LEMS.

PMID 10680790  Neurology. 2000 Feb 8;54(3):603-7.
著者: P W Wirtz, J J Verschuuren, J G van Dijk, M L de Kam, R C Schoemaker, J G C van Hasselt, M J Titulaer, U R Tjaden, J den Hartigh, J M A van Gerven
雑誌名: Clin Pharmacol Ther. 2009 Jul;86(1):44-8. doi: 10.1038/clpt.2009.35. Epub 2009 Apr 8.
Abstract/Text 3,4-Diaminopyridine and pyridostigmine are widely used to treat Lambert-Eaton myasthenic syndrome (LEMS), either alone or in combination. 3,4-Diaminopyridine enhances the release of acetylcholine at the neuromuscular synapse, and pyridostigmine inhibits the degradation of this neurotransmitter. Although this could lead to a synergistic effect on neuromuscular transmission, no studies have compared the effects of these drugs in patients with LEMS. Therefore, we performed a placebo-controlled, double-dummy, double-blind, randomized, crossover study in nine patients with LEMS.

PMID 19357643  Clin Pharmacol Ther. 2009 Jul;86(1):44-8. doi: 10.1038/・・・
著者: P Maddison, J Newsom-Davis
雑誌名: Cochrane Database Syst Rev. 2005 Apr 18;(2):CD003279. doi: 10.1002/14651858.CD003279.pub2. Epub 2005 Apr 18.
Abstract/Text BACKGROUND: Lambert-Eaton myasthenic syndrome is an autoimmune presynaptic disorder of neuromuscular transmission. Treatments attempt to overcome the harmful autoimmune process, or to improve residual neuromuscular transmission, in order to reverse muscle weakness.
OBJECTIVES: The objective was to examine the efficacy of treatment in Lambert-Eaton myasthenic syndrome.
SEARCH STRATEGY: We searched the Cochrane Neuromuscular Disease Group trials register (December 2004), MEDLINE (January 1966 to December 2004) and EMBASE (January 1980 to December 2004), and checked bibliographies and contacted authors to identify additional published or unpublished data.
SELECTION CRITERIA: All randomised or quasi-randomised trials of adults and children with a diagnosis of Lambert-Eaton myasthenic syndrome, with or without small-cell lung cancer, receiving any form of pharmacological or physical treatment. The primary outcome measure was change in muscle strength scale score (Quantitative Myasthenia Gravis score), or limb muscle strength measured by myometry. The secondary outcome measure was improvement in the mean amplitude of the resting compound muscle action potentials. The mean amplitude used was the mean of all muscles tested.
DATA COLLECTION AND ANALYSIS: We identified three randomised controlled trials.
MAIN RESULTS: Two controlled trials of the effects of 3,4-diaminopyridine compared with placebo in a total of 38 patients with Lambert-Eaton myasthenic syndrome were eligible, one of which was of crossover design. A third crossover trial compared intravenous immunoglobulin treatment to placebo in nine patients. Two trials of 3,4-diaminopyridine reported a significant improvement in muscle strength score, or myometric limb measurement following treatment, and a significant improvement in resting compound muscle action potential amplitude following 3,4-diaminopyridine, compared with placebo.A meta-analysis of the primary endpoint results was not possible because of marked differences in primary outcome measures. However, a meta-analysis of the secondary endpoint was possible. The overall weighted mean difference was 1.80 mV (95% confidence interval 0.82 to 2.78), favouring treatment.A crossover trial reported a significant improvement in myometric limb strength and a non-significant improvement in change in the mean resting compound muscle action potential amplitude when patients received intravenous immunoglobulin compared to placebo infusions. Clinical improvement lasted for up to eight weeks.
AUTHORS' CONCLUSIONS: Limited evidence from randomised controlled trials showed that either 3,4-diaminopyridine or intravenous immunoglobulin improved muscle strength scores and compound muscle action potential amplitudes in patients with Lambert-Eaton myasthenic syndrome. There are insufficient data at present to quantify this treatment effect. Other possible treatments have not been tested in randomised controlled trials.

PMID 15846654  Cochrane Database Syst Rev. 2005 Apr 18;(2):CD003279. d・・・
著者:
雑誌名: 1998 May 13;841:817-22.
Abstract/Text
PMID 9668335  1998 May 13;841:817-22.
著者: S J Oh, D S Kim, T C Head, G C Claussen
雑誌名: Muscle Nerve. 1997 Sep;20(9):1146-52.
Abstract/Text Guanidine hydrochloride is known to be highly effective in the symptomatic treatment of the Lambert-Eaton myasthenic syndrome (LEMS). However, because of its potentially dangerous side reactions of hematologic abnormalities and renal insufficiency, 3,4-diaminopyridine, which is not readily available in the United States, is recommended as the preferred drug for LEMS. We used low-dose guanidine and pyridostigmine combination therapy in 9 patients with LEMS and analyzed its long-term safety and effectiveness. In all patients, a liberal amount of pyridostigmine was used, while daily guanidine dose was kept below 1000 mg a day, and guanidine was given between pyridostigmine dosings. This combination therapy was used for 3-102 months (mean: 34.1 months) and improved clinical status in all patients. Although guanidine had to be discontinued due to severe gastrointestinal symptoms in 3 cases, no serious side reactions such as bone marrow suppressions or signs of renal insufficiency developed in any case. Thus, we conclude that low-dose guanidine therapy is relatively safe and effective for long-term symptomatic treatment of LEMS when it is combined with pyridostigmine.

PMID 9270671  Muscle Nerve. 1997 Sep;20(9):1146-52.
著者: P Maddison, B Lang, K Mills, J Newsom-Davis
雑誌名: J Neurol Neurosurg Psychiatry. 2001 Feb;70(2):212-7.
Abstract/Text OBJECTIVES: To determine the prognosis in patients with Lambert-Eaton myasthenic syndrome (LEMS) without small cell lung cancer (SCLC), and to analyse longitudinal clinical, electrophysiological, and immunological data on each patient to establish prognostic factors for long term outcome.
METHODS: The retrospective and part prospective study of 47 patients with LEMS was undertaken from data recorded during visits to a specialist neuromuscular clinic. Serial measurements of muscle strength score in shoulder abduction, elbow extension and hip flexion, compound muscle action potential (CMAP) amplitude, and postcontraction increment in abductor digiti minimi (ADM), and anti-P/Q-type voltage gated calcium channel (VGCC) antibody titre were made at each visit.
RESULTS: Muscle strength scores were improved in 88% of patients after a median duration of immunosuppressive treatment of 6 years (range 1.3 to 17 years); anti-VGCC antibody titres fell in 52% after treatment; and mean resting CMAP amplitude improved from 2.7 mV initially to 8.8 mV after 2 years of treatment p<0.001). Initial pretreatment anti-VGCC antibody titre did not correlate significantly with either CMAP amplitude, CMAP increment, or clinical score: from serial measurements made during follow up, significant correlation between antibody titre and CMAP amplitude was seen in only two patients. Sustained clinical remission was achieved by 20 (43%) of whom only four remained in remission without the need for immunosuppression. Using a Cox proportional hazards model, the only independent predictor of sustained clinical remission was initial pretreatment clinical score (p=0.03). Lymphoma presented in three patients during the study.
CONCLUSIONS: The prognosis in patients with LEMS without SCLC is favourable, although patients often need significant doses of immunosuppressive treatment to remain clinically stable. Only initial clinical muscle strength measurements and not anti-VGCC antibody titres or electrophysiological recordings are predictive of long term outcome.

PMID 11160470  J Neurol Neurosurg Psychiatry. 2001 Feb;70(2):212-7.
著者: P G Bain, M Motomura, J Newsom-Davis, S A Misbah, H M Chapel, M L Lee, A Vincent, B Lang
雑誌名: Neurology. 1996 Sep;47(3):678-83.
Abstract/Text Intravenous immunoglobulin improves many antibody-mediated autoimmune disorders, but its mode of action is unknown. We investigated its effects on muscle strength and on the serum titer of the calcium-channel autoantibodies that are likely to be pathogenic in the Lambert-Eaton myasthenic syndrome (LEMS). In a randomized, double-blind, placebo-controlled crossover trial, serial indices of limb, respiratory, and bulbar muscle strength and the serum titer of calcium-channel antibodies in nine patients were compared over an 8-week period, using the area-under-the-curve approach, following infusion on two consecutive days of immunoglobulin at 1 g/kg body weight/day (total dose 2.0 g/kg body weight) or placebo (equivalent volume of 0.3% albumin). Calcium-channel antibodies were measured by radioimmunoassay using 125I-omega-conotoxin MVIIC. Direct anti-idiotypic actions of immunoglobulin were tested in this assay. Immunoglobulin infusion was followed by significant improvements in the three strength measures (p = 0.017 to 0.038) associated with a significant decline in serum calcium-channel antibody titers (p = 0.028). Improvement peaked at 2 to 4 weeks and was declining by 8 weeks. Mean serum titers were unchanged at 1 week, however, and direct anti-idiotypic neutralization by immunoglobulin was not demonstrable in vitro. We conclude that immunoglobulin causes a short-term improvement in muscle strength in LEMS that probably results from the induced reduction in calcium-channel autoantibodies. The reduction is not due to a direct neutralizing action of the immunoglobulin, but a delayed anti-idiotypic action cannot be excluded. Improvement following intravenous immunoglobulin in other autoantibody-mediated disorders may similarly be associated with decline in levels of pathogenic autoantibodies.

PMID 8797464  Neurology. 1996 Sep;47(3):678-83.
著者: M Motomura, S Hamasaki, S Nakane, T Fukuda, Y K Nakao
雑誌名: Ther Apher. 2000 Aug;4(4):287-90.
Abstract/Text The Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disorder of peripheral cholinergic transmission in which autoantibodies decrease the presynaptic release of acetylcholine at the neuromuscular junction and autonomic system. Recent results suggest that the antibodies to P/Q-type calcium channels are the principal pathogenic factors in LEMS. Here, we present our experience with cases of LEMS who are noncarcinomatous. We studied the efficacy of plasmapheresis, analyzing the clinical score, electrophysiological finding, and the titer of anti-P/Q-type voltage-gated calcium channel (P/Q-VGCC) antibody. The first case, a 72-year-old female presenting with leg weakness, was treated by plasma exchange (PE). However, clinical improvement was transient; intravenous immunoglobulin (IVIg) therapy was followed by additional PE. She had a clinical and electromyologic improvement, and her P/Q-VGCC antibody titers decreased. Her clinical status and CMAP amplitude correlated closely with the anti-P/Q-VGCC antibody titers. The second case, a 73-year-old male presenting with leg weakness, was treated by PE and double-filtration plasmapheresis. The P/Q-VGCC antibody titres decreased immediately after these aphereses, but recovered to the pretreatment levels 1 week after them. After the immunosuppressive drugs prednisolone and azathioprine were started, his clinical symptoms improved. His antibody titers decreased gradually after immunosuppressive therapy. It is speculated that no sufficient efficacious improvement could be obtained by apheresis alone because of a high rate of P/Q-VGCC antibody production. Considering our experiences and other literature, we discuss the indication of apheresis treatment of LEMS.

PMID 10975475  Ther Apher. 2000 Aug;4(4):287-90.
著者: Hannah L Pellkofer, Raymond Voltz, Tania Kuempfel
雑誌名: Muscle Nerve. 2009 Aug;40(2):305-8. doi: 10.1002/mus.21315.
Abstract/Text Lambert-Eaton myasthenic syndrome (LEMS) is an autoimmune disease that is characterized by impaired transmission across the neuromuscular junction due to autoantibodies directed against the presynaptic voltage-gated calcium channels (VGCC-ab). Clinical symptoms are usually characterized by proximal muscle weakness and mild dysautonomia. In some patients there are signs of cerebellar dysfunction as well, usually associated with cancer. Here we report the long-term follow-up of a patient with VGCC-ab-positive LEMS and a severe cerebellar syndrome but without evidence of cancer over 5 years. While conventional immunosuppressive therapy (steroids, azathioprine) failed, he improved with plasma exchange and consecutive treatment with rituximab. Muscle Nerve 40: 305-308, 2009.

PMID 19609921  Muscle Nerve. 2009 Aug;40(2):305-8. doi: 10.1002/mus.21・・・

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