作者：Allison Gandey
出處：WebMD醫學新聞
January 13, 2010 — 研究者報告指出，一個自動立體像素分類步驟可以分辨難以診斷之病患的不同動作異常。經確認，代謝與多巴胺傳輸子影像圖可以顯示出自發性巴金森氏症、多發性系統退化症、進行性核上眼神經麻痺症等異常，可以幫助醫師區分它們。
領銜研究者、紐約Feinstein醫學研究中心的Chris Tang醫師在新聞稿中表示，這些疾病的病理完全不同，但是初期症狀相當相似。
最初被視為巴金森氏症的病患，約有10%實際上是有其他動作異常。資深研究者、同樣來自Feinstein醫學研究中心的David Eidelberg醫師表示，這對醫師而言是個大問題，巴金森氏症的治療方法對這些病患將會無效，而且還會引起副作用，關鍵在於準確診斷。
該研究團隊對167名不明潛在疾病的病患，使用「氟18螢光去氧葡萄糖正電子射線斷層攝影術」，他們先掃描病患，然後，在做出臨床診斷前，由一個不知情的動作異常症專家評估他們2年以上。
他們報告指出，在最後的臨床診斷前幾年，影像分類就是準確的，當考量難治型巴金森氏症的治療選項時特別相關，因為侵犯性手術方法，如腦深層刺激手術，對於非典型疾病患者一般是無效的。
結果線上登載於1月11日的Lancet Neurology期刊。
義大利米蘭、巴金森研究中心、威尼斯IRCCS San Camillo的Angelo Antonini醫師在編輯評論中表示，不應該低估這些發現的臨床與研究相關性，神經保護與疾病修飾藥物的研究正在增加，而這些結果都需仰賴準確的早期診斷。
醫師解釋，不同於現在的單光子放射電腦斷層攝影機的多巴胺運輸子影像、或正子放射斷層攝影(PET)的氟多巴(fluorodopa)攝取，這個新的代謝影像分析不只可以區別、還可以分類不同的巴金森氏症病患。
Tang醫師與其研究團隊，藉由比較臨床診斷結果來評估最初影像分類的準確度。他們發現，每個異常的陽性預測值超過90%，研究者接著以重複掃描確認影像分類，有9個病患在死後進行驗屍確認。
表. 與臨床診斷有關的影像分類
動作異常 | 敏感度， % | 專一度， % | 陽性預測值， % | 陰性預測值， % |
自發性巴金森氏症 | 84 | 97 | 98 | 82 |
非典型症狀 | 82 | 98 | 97 | 88 |
多發性系統退化症 | 85 | 96 | 97 | 83 |
進行性核上眼神經麻痺症 | 88 | 94 | 91 | 92 |
Antonini醫師指出，如果巴金森氏症的神經元損失依循一個線性或指數模式，早期治療是關鍵，不幸的是，早期治療也意味著較大的診斷不確定性。
最近被用來支持多巴胺傳輸子影像臨床診斷的研究指出，如果病患納入時的疾病期間小於12個月，沒有多巴胺缺乏證據的掃描頻率達15%。
Antonini醫師指出，最近的「Attenuation of Disease Progression with Azilect Given Once-daily (ADAGIO)」研究沒有將影像納入，從其研究結果看來，應該將影像分類方法納入。
ADAGIO研究顯示，兩種劑量的rasagiline (商品名Azilect，Teva Neuroscience藥廠)出現相反的結果。在2006年時，這個選擇性不可逆、第2代單胺氧化酶-B抑制劑獲得美國食品藥物管理局核准用於治療自發性巴金森氏症。
Antonini醫師指出，該試驗中，研究者納入平均罹病期間4.5個月的1,176名病患。根據以前納入類似罹病期間之病患研究的基礎，提出假設認為約有15%的病患並沒有巴金森氏症，這可能會影響ADAGIO研究的結果。
【臨床研究與轉診是重要的】
Antonini醫師認為，這個情況對於多發性系統退化症或進行性核上眼神經麻痺症的早期診斷並沒有比較好，這些異常的病患無法在幾年前被正確診斷，另外，由於這些疾病的病患其平均餘命只有7年，這個時間對於有意義的檢測或運用任何有神經保護作用的製劑都嫌不足。
Antonini醫師表示，鼓勵使用目前有的、容易運用的診斷方法，如代謝與多巴胺傳輸子影像，不過，他強調，這些結果不能取代完整的臨床檢查，病患應轉診給動作異常症的神經專家。
國家健康研究中心以及Feinstein醫學研究中心的一般臨床研究中心資助本研究。Eidelberg醫師擁有審查中的兩個腦部疾病診斷空間模式的美國專利。
Lancet Neurol. 線上發表於2010年1月11日。
Metabolic and Dopamine Imaging Differentiates Forms of Parkinson's
By Allison Gandey
Medscape Medical News
January 13, 2010 — An automated voxel-based classification procedure can distinguish among different movement disorders in difficult-to-diagnose patients, report researchers. Metabolic and dopamine transporter imaging maps and validates pattern abnormalities for idiopathic Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy to help clinicians differentiate among them.
"The pathology is totally different, but the earliest symptoms are so similar," lead investigator Chris Tang, MD, from the Feinstein Institute for Medical Research in Manhasset, New York, said in a news release.
An estimated 10% of patients initially thought to have Parkinson's actually had another movement disorder. "This is a big problem for physicians," senior investigator David Eidelberg, MD, also from the Feinstein Institute, added. "The treatments for Parkinson's will not work for these patients, and they can cause their own side effects," he noted. "Accurate diagnosis is key."
The research team used fluorine-18-labeled-fluorodeoxyglucose positron emission tomography in 167 patients with unclear underlying disease. They scanned patients early, and a blinded movement disorder specialist assessed them for more than 2 years before making a clinical diagnosis.
The clinical and research relevance of these findings should not be underestimated.
"Imaging classification was accurate several years before the final clinical diagnosis," they report. This is especially relevant when considering treatment options for patients with medically refractory Parkinson's, the investigators point out, because invasive surgical approaches, such as deep brain stimulation, are generally ineffective for patients with atypical disease.
The results were published online January 11 in Lancet Neurology.
In an accompanying editorial, Angelo Antonini, MD, from the IRCCS San Camillo, Venice, and Parkinson Institute in Milan, Italy, said, "The clinical and research relevance of these findings should not be underestimated. Neuroprotective and disease-modifying drug research is intensifying, and results mostly rely on accurate early diagnosis."
Unlike currently available imaging of dopamine transporters with single-photon emission computed tomography or fluorodopa uptake with positron emission tomography, Dr. Antonini explained, this metabolic imaging analysis allows not only identification but also categorization of patients with different forms of Parkinson's.
Dr. Tang and his team evaluated the accuracy of the initial image-based classification by comparing those results with the clinical diagnosis. They found the positive predictive value exceeded 90% for each disorder. The investigators further validated the imaging categorization with repeated scans. They confirmed it post mortem in 9 patients.
Table. Imaging Classification Relative to Clinical Diagnosis
| Movement Disorder | Sensitivity, % | Specificity, % | Positive Predictive Value, % | Negative Predictive Value, % |
| Idiopathic Parkinson's | 84 | 97 | 98 | 82 |
| Atypical syndrome | 82 | 98 | 97 | 88 |
| Multiple system atrophy | 85 | 96 | 97 | 83 |
| Progressive supranuclear palsy | 88 | 94 | 91 | 92 |
"If neuronal loss in Parkinson’s disease follows a linear or exponential pattern, early treatment is crucial," Dr. Antonini noted. "Unfortunately, early treatment also means greater diagnostic uncertainty."
Recent studies in which dopamine transporter imaging was used to support clinical diagnosis reported that if patients whose disease duration is less than 12 months are enrolled, the frequency of scans without evidence of dopaminergic defects can reach 15%.
Dr. Antonini points out that the recent Attenuation of Disease Progression with Azilect Given Once-daily (ADAGIO) study did not include imaging. "It is a good example of why this imaging classification method might be important," he notes.
ADAGIO showed opposite outcomes for 2 doses of rasagiline (
Azilect, Teva Neuroscience). The selective, irreversible, second-generation monoamine oxidase-B inhibitor was approved by the US Food and Drug Administration in 2006 for the treatment of idiopathic Parkinson's disease.
In the trial, investigators enrolled 1176 patients with a mean disease duration of 4.5 months, Dr. Antonini points out. "On the basis of previous studies in which patients with a similarly short disease duration were enrolled, the assumption can be made that almost 15% of patients did not have Parkinson's disease," he notes, "which might have affected the results of the ADAGIO study."
Clinical Investigation and Referral Important
Dr. Antonini suggests that the situation is not better for the early diagnosis of multiple system atrophy or progressive supranuclear palsy. Patients with these disorders might not be correctly diagnosed for several years," Dr. Antonini points out. "Because the mean life expectancy of patients with these disorders is only 7 years, this time to diagnosis is far too long for meaningful testing or application of any potential neuroprotective agent."
Dr. Antonini says the availability of easy-to-apply diagnostic procedures, such as metabolic and dopamine transporter imaging, is encouraging. However, he emphasizes, these results are no replacement for thorough clinical investigation, and patients should be referred to movement disorder neurologists.
This study was funded by the National Institutes of Health and General Clinical Research Center at The Feinstein Institute for Medical Research. Dr. Eidelberg has 2 US patents pending on spatial patterns for the diagnosis of brain disease.
Lancet Neurol. Published online January 11, 2010.
