脊髄造影CT 検査を用いたサラブレッドの頸椎狭窄性脊髄症の形態学的解明

• Material Type: 博士論文
• Title: 脊髄造影CT 検査を用いたサラブレッドの頸椎狭窄性脊髄症の形態学的解明
• Author/Editor: 近藤, 太郎
• Author Heading: 近藤, 太郎
• Publication Date: 2023-03-15
• Publication Date (W3CDTF): 2023-03-15
• Alternative Title: Investigation of the morphological factors of cervical vertebral stenotic myelopathy on computed tomographic myelography in Thoroughbred horses
• Degree grantor/type: 麻布大学
• Date Granted: 2023-03-15
• Date Granted (W3CDTF): 2023-03-15
• Dissertation Number: 甲第176号
• Degree Type: 博士(獣医学)
• Text Language Code: jpn
• Target Audience: 一般
• Note (General): サラブレッドの頸椎狭窄性脊髄症（Cervical Vertebral Stenotic Myelopathy；CVSM）は、脊柱管の狭窄による神経損傷で、後肢の不全麻痺を主徴とする疾患である。本疾患は成長期整形外科的疾患の一つに分類されるが、発症要因は明らかになっていない。これまでCVSMは脊髄造影X線検査で診断されてきた。脊髄造影X線画像は頸椎の配列不整箇所や頸髄の背腹方向の圧迫箇所の特定が可能である。しかし、頸椎の関節突起の骨病変の分布や背外側方向からの頸髄圧迫の特定は困難であった。近年、馬では全身麻酔下による脊髄造影CT検査が頸髄疾患の診断に用いられるようになっている。脊髄造影CT検査は断層画像であるため、頸椎の前関節突起と後関節突起をそれぞれ観察することや、背外側方向からの頸髄圧迫を詳細に評価することができる。しかし、脊髄造影CT検査を用いたCVSMによる頸髄圧迫の客観的指標は確立していなかった。そこで本研究では、サラブレッドの脊髄造影CT検査を用いたCVSMの形態学的解明を行った。はじめに、CVSMの特徴的画像所見を収集した（第1章）。続いて、頸椎体積を用いたCVSMの発症要因を検討した。（第2章）。さらに、頸髄体積と脊柱管体積を用いたCVSMの発症要因を検討した（第3章）。加えて、頸髄圧迫の客観的指標を検討した（第4章）。本研究では、2013年6月から2019年10月までに帯広畜産大学で頸部CT検査を実施したサラブレッドの画像データ（合計41検体）を用いた。本研究で用いた検体は、生体または屠体を含み、検査時または生前に跛行や後肢の不全麻痺といった神経症状が観察されていた。本研究は帯広畜産大学実験動物委員会の承認を得て実施した（承認番号：27-127）。脊髄造影とCT検査は全身麻酔下で行った。全ての検体は麻酔前投与薬としてmedetomidine hydrochloride（5 μg/kg，Domitor，Nippon Zenyaku Kogyo，Tokyo）を静脈内投与した。麻酔導入は、midazolam（0.03 μg/kg，Dormicum，Maruishi Pharmaceutical，Osaka）とthiamylal（4 mg/kg，Isozol，Nichi-Iko Pharmaceutical，Toyama）を投与した後、guaifenesin（25 mg/kg，Guaifenesin，Shinyo Pure Chemicals，Osaka）を倒馬するまで急速静脈内投与した。なお、倒馬後は速やかに気管挿管を実施し、酸素吸入を開始した。麻酔維持は、guaifenesin（200 mg/kg/hr）とxylazine（1 mg/kg/hr，Celactar，Bayer，Tokyo）、ketamine（2 mg/kg/hr，Ketalar，Daiichi-Sankyo，Tokyo）を混合したトリプルドリップ法を用いて行った。脊髄造影手技は、はじめに全身麻酔下にて21G脊髄針を大槽へ刺入した。脳脊髄液はクモ膜下腔から2分間かけて抜き、その後、抜けた脳脊髄液と同量の造影剤（脊髄造影X線検査時：300 mgI/ml，iohexol，Daiichi Sankyo Company，Tokyo；脊髄造影CT検査時：140 mgI/ml，iohexol，Teva Pharmaceutical Industries，Tokyo）をクモ膜下腔内に注入した。造影剤を注入した後、注入部位から造影剤を尾側に移動させるため、5分間、頭部を挙上した。CT装置は、ガントリー径72 cmの4列マルチスライスCT（Asteion Super4，Canon Medical，Ohtawara）およびガントリー径90 cmの16列マルチスライスCT（Aquilion LB，Canon Medical）を使用した。撮影条件はそれぞれ、管電圧135 kV、管電流150 mA、スライス厚2.0 mmまたは管電圧135 kV、管電流300 mA、スライス厚0.5 mmとした。第1章では、サラブレッドの脊髄造影CT画像解析を行い、CVSMの特徴的画像所見を収集した。対象は、41検体のうち、歩様異常の臨床症状からCVSMが疑われ、第7頸椎まで観察可能であった23検体の脊髄造影CTデータを抽出した。頸髄圧迫の分布は、各頸椎間の腹側または背側からの頸髄圧迫の割合と頸椎間の箇所で、回帰分析を行った。骨病変の分布は、各頸椎の前関節突起または後関節突起の骨病変の割合と頸椎の箇所で、回帰分析を行った。それぞれの解析の有意水準（P値）は0.05と設定した。頸髄圧迫の分布は、腹側からの頸髄圧迫は頸部頭側で、背側からの頸髄圧迫は頸部尾側で多く観察された（R2 = 0.85，P < 0.05）。馬の頸椎はS字状に配列しており、第3–4頸椎間は荷重点となっている。てこの原理の観点から、第3–4頸椎間は支点、頭部は作用点として機能している。襲歩による競走時、馬の頭部の上下運動は第3–4頸椎間で背腹方向に負荷がかかり、頸部頭側の頸椎はこの動きに耐えることができない。このため、第2–3頸椎間と第3–4頸椎間は頸椎の配列不整が起きやすい。骨病変の分布は、後関節突起が前関節突起と比較して観察される割合が高かった（R2 = 0.71，P < 0.05）。解剖学的観点から後関節突起は前関節突起よりも外側に位置している。それ故、後関節突起は転倒や闘争といった外的要因による影響を受けやすいと考えられた。これらの所見はCVSMを発症したサラブレッドに特徴的な脊髄造影CT画像所見であった。サラブレッドにおける脊髄造影CT検査はCVSMによる変化を検出する有用な方法であった。第2章では、サラブレッドの頸椎の大きさの不均衡とCVSMの発症要因の関係を検討するために、頸椎の骨体積測定を行った。対象は、41検体のうち、CVSM発症群17検体とCVSM非発症群4検体の雄のみの頸部CTデータを抽出した。骨体積の測定範囲は第2頸椎から第6頸椎とした。頸椎体積の統計学的解析は、各頸椎体積の測定値と日齢の散布図を作成し、CVSM発症群とCVSM非発症群それぞれの頸椎体積の予測値を算出した。2つの頸椎体積を比較する場合はWelch’s t検定を用いた。また、それぞれの頸椎体積を他の2つの頸椎体積と比較する場合は一元配置分散分析を用いた。それぞれの解析の有意水準（P値）は0.05と設定した。CVSM発症群の第3頸椎は第2頸椎や第4頸椎と比較して体積が有意に小さかった（P < 0.05）。従って、第2–3頸椎間と第3–4頸椎間は関節が不安定であったと考えられた。加えて、頸部頭側の靭帯は強度が弱いことが報告されている。そのため、頸部頭側の不均衡な頸椎の大きさは本疾患の発症要因である可能性が示唆された。第3章では、頸髄に対する脊柱管の大きさの不均衡とCVSMの発症要因の関係を検討するために、頸髄と脊柱管の体積測定を行った。対象は、41検体のうち、CVSMが疑われた雄20検体と雌9検体の脊髄造影CTデータを抽出した。頸髄体積と脊柱管体積の測定範囲は、第3頸椎頭側端から第6頸椎尾側端までとした。また、頸髄体積を脊柱管体積で除して頸髄体積・脊柱管体積比を算出した。頸髄体積、脊柱管体積および頸髄体積・脊柱管体積比の性差の統計学的解析では、雄と雌の頸髄体積の測定値と日齢から散布図を作成し、予測値を算出した。同様に脊柱管体積と頸髄体積・脊柱管体積比の予測値も算出した。雌雄の予測値はStudent’s t検定を用いて比較した。それぞれの解析の有意水準（P値）は0.05と設定した。頸髄体積は雄が雌よりも有意に大きかった（P < 0.05）。一方、脊柱管体積に性差は観察されなかった（P = 0.19）。また、頸髄体積・脊柱管体積比は雄が雌より有意に高かったが（P < 0.05）、約1,400日齢で性差は観察されなくなった。そのため、若齢の雄の頸髄体積に対して十分な空間ではない脊柱管体積は、頸椎の配列不整や骨病変による頸髄圧迫を引き起こしやすく、CVSMの発症要因の一つである可能性が示唆された。第4章では、脊髄造影CT検査を用いたサラブレッドの頸髄圧迫の客観的指標を検討した。対象は、41検体のうち、CVSMが疑われ、第7頸椎まで観察可能であった23検体の脊髄造影CTデータを抽出した。頸髄高測定は、curved multi-planar reformationで作成した矢状断像で1検体につき6箇所行った。頸髄高のカットオフ値はReceiver Operating Characteristic（ROC）曲線から算出した。また、頸髄高測定が頸髄圧迫を反映していることを証明するために、従来法である頸髄面積をクモ膜下腔面積で除して頸髄狭窄率を算出し、回帰分析を行った。本解析の有意水準（P値）は0.05と設定した。頸髄高と頸髄狭窄率には弱い有意な負の相関が認められた（R2 = 0.08，P < 0.05）。また、ROC曲線のカットオフ値から頸髄高が7.06 mm以下であった場合、頸髄圧迫の指標となることが明らかとなった。以上、脊髄造影CT検査を用いてサラブレッドの頸椎を解析したところ、CVSMには形態学的な発症要因が存在していることが明らかになった。; Thoroughbred horses appear to be particularly predisposed to cervical vertebral stenotic myelopathy (CVSM), which is a developmental orthopedic disease, and a common cause of cervical spinal cord compression. The primary clinical signs of CVSM include general proprioceptive ataxia and weakness. However, the pathogenic mechanism of CVSM remains poorly understood. Radiographic myelography is a diagnostic tool for CVSM. Findings of radiographic myelograms, including malalignment and dorsal and ventral compression sites, suggest cervical abnormalities. However, it is difficult to distinguish between cranial and caudal articular processes and lateral cervical spinal cord compression sites using radiographic myelography. Recently, computed tomographic (CT) myelography of the cervical spinal cord in living horses, performed under general anesthesia, has become feasible. CT myelography can distinguish between cranial and caudal articular processes and lateral cervical spinal cord compression sites because it uses cross-sectional images. However, quantitative evaluation of cervical spinal cord compression has not been established yet. Thus, this study aimed to investigate the morphological factors of CVSM on CT myelography in Thoroughbred horses. The study structured as follows: In chapter 1, the characteristic CT myelography findings of CVSM lesions in Thoroughbred horses were determined. In chapter 2, a contributing factor for CVSM was investigated for measuring the cervical vertebral volume. In chapter 3, a contributing factor for CVSM was investigated for measuring the cervical spinal cord and spinal canal volumes. In chapter 4, a quantitative index of cervical spinal compression was established.A total of 41 Thoroughbred horses were included in this study. Cervical CT images of all horses were obtained between June 2013 and October 2019 at the Obihiro University of Agriculture and Veterinary Medicine. All horses, both living and cadaveric, were admitted for gait abnormalities involving lameness/neurological signs at the time of examination or while they were alive. This study’s protocol was approved by the Animal Experiment and Welfare Committee of the Obihiro University of Agriculture and Veterinary Medicine (No. 27-127). CT myelography was performed underwent general anesthesia. All horses were premedicated intravenously with medetomidine hydrochloride (5 μg/kg, Domitor, Nippon Zenyaku Kogyo, Tokyo, Japan). Anesthesia was induced using intravenous administration of midazolam (0.03 μg/kg, Dormicum, Maruishi Pharmaceutical, Osaka, Japan) and thiamylal (4 mg/kg, Isozol, Nichi-Iko Pharmaceutical, Toyama, Japan). Guaifenesin (25 mg/kg, Guaifenesin, Shinyo Pure Chemicals, Osaka, Japan) was rapidly infused until the horse became ataxic, and intratracheal intubation was performed. Anesthesia was subsequently maintained using a triple drip mixture of guaifenesin (200 mg/kg/hr), xylazine (1 mg/kg/hr, Celactar, Bayer, Tokyo, Japan) and ketamine (2 mg/kg/hr, Ketalar, Daiichi-Sankyo, Tokyo, Japan). CT myelography procedure was as follows. First, a 21-gage spinal needle was inserted into the subarachnoid space via the atlanto-occipital junction under general anesthesia. Cerebrospinal fluid was allowed to drain out of the subarachnoid space for 2 min, after which the same volume of the contrast agent (140 mgI/ml, iohexol, Teva Pharmaceutical Industries, Tokyo, Japan) as the drained cerebrospinal fluid was injected into the subarachnoid space. The horses’ heads were lifted for 5 min to run the contrast agent toward the caudal region, and then following which the horses underwent myelography. CT myelograms were obtained with a tube voltage of 135 kV, tube current of 150 mA, and slice thickness of 2.0 mm using a 4-row multidetector CT (Asteion Super4, Canon Medical Systems Corporation, Ohtawara, Japan) with a gantry opening of 72 cm and with a tube voltage of 135 kV, tube current of 300 mA, and slice thickness of 0.5 mm using a16-row multidetector CT (Aquilion LB, Canon Medical Systems Corp.) with a gantry opening of 90 cm.In chapter 1, the CT myelograms were analyzed, and the characteristic CT myelography findings of CVSM lesions were determined. The target of analysis for this chapter was 23 Thoroughbred horses, that showed clinical signs such as gait abnormalities and were suspected of CVSM. Regression analysis was performed to analyze the ratio of ventral or dorsal cervical spinal cord compression and the place of cervical spinal compression. The ratio of cervical vertebral osseous lesions of each cervical vertebra was calculated. Additionally, regression analysis was performed to analyze the ratio of cervical vertebral osseous lesions of each cervical vertebra and the place of the cervical vertebra. A P-value of less than 0.05 was considered significant. The cranial cervical vertebrae were observed more frequently in ventral compression than the caudal cervical vertebra, and the caudal cervical vertebrae were observed more frequently in dorsal compression than the cranial cervical vertebrae (R2 = 0.85, P < 0.05). Horse cervical vertebrae were lined up in an S-shaped arrangement, with load-deflection points on C3–C4. Taking into consideration the principle of leverage, the point of C3–C4 serves as the fulcrum point, and the head serves as the application point. The head movement affects dorsoventral stress in C3–C4 due to the up-and-down sequence of motion during galloping. Moreover, the cranial cervical vertebral joint cannot be resistant to this moment. Therefore, malalignment was prone to occur in C2–C3 and C3–C4. Osseous lesions of the caudal articular process were observed more frequently than those of the cranial articular process (R2 = 0.71, P < 0.05). The caudal articular process is located dorsal to the cranial articular process. Thus, the caudal articular process might be more easily affected by external impact involving falls and fights. These were the characteristic CT myelography findings of CVSM in Thoroughbred horses. Therefore, CT myelography in Thoroughbred horses is a useful method for detecting CVSM changes.In chapter 2, cervical vertebral volumes were measured, and it was investigated whether cervical vertebral volume variations can be a contributing factor in CVSM development. The target of analysis for this chapter was 17 CVSM horses and 4 non-CVSM horses. These samples comprised only male horses. The cervical vertebral volume, measured from C2 to C6, was calculated for each vertebra. Scatter plots were created by the measured value of cervical vertebral volume and the horses’ age. After that, the prediction values of the cervical vertebral volume in CVSM or non-CVSM were calculated. The prediction values of each cervical vertebral volume between CVSM and non-CVSM horses were compared using unpaired Welch’s t-test. Each cervical vertebral volume was compared with the next two cervical vertebral volumes using a one-way analysis of variance. A P-value of less than 0.05 was considered significant. C3 in CVSM horses demonstrated a significantly smaller cervical vertebral volume than C2 and C4 (P < 0.05). Consequently, the C2–C3 and C3–C4 joints in CVSM horses were inefficient. Furthermore, the cranial cervical vertebral area (C2–C4) exhibits inefficient strong ligaments. Our findings suggest that variations in cranial cervical vertebral volume in CVSM male horses can be an important contributing factor in CVSM development.In chapter 3, cervical spinal cord and spinal canal volumes were measured, and it was investigated whether size variations between the cervical spinal cord and spinal canal can be a contributing factor in CVSM development. The target of analysis for this chapter was 20 male and 9 female Thoroughbred horses suspected of CVSM. The cervical spinal cord and spinal canal volumes, measured from the cranial top of the C3 to the caudal end of the C6, were calculated. Additionally, the cervical spinal cord-to-spinal canal volume ratios were calculated by dividing the cervical spinal cord volume by the spinal canal volume. Scatter plots were created by the measured value of cervical spinal cord volume and the horses’ age. Thereafter, the male and female prediction values of cervical spinal cord volume were calculated. The prediction values of the spinal canal and cervical spinal cord-to-spinal canal volume ratios were calculated similarly. The prediction values for the male and female horses were compared using unpaired Student’s t-test. A P-value of less than 0.05 was considered significant. Male horses had a significantly larger cervical spinal cord volume than female horses (P < 0.05). Furthermore, no significant difference in the spinal canal volume was observed between male and female horses (P = 0.19). Additionally, male horses had a significantly higher cervical spinal cord-to-spinal canal volume ratio than female horses (P < 0.05). Sex differences in the cervical spinal cord-to-spinal canal volume ratio gradually decreased until around 1,400 days of age. Thus, younger male horses have a narrower interspace between the cervical spinal cord and spinal canal than younger female horses, suggesting that an imbalanced cervical spinal cord and spinal canal volume is one of the causes of CVSM. In chapter 4, a quantitative index of cervical spinal compression was established. The target of analysis for this chapter was 23 Thoroughbred horses suspected of CVSM. The spinal cord height was measured in the sagittal plane reformatted using curved multi-planar reformation. The measurement was performed at the level of each of the six intervertebral spaces. Accordingly, the appropriate cut-off value for spinal cord height was determined using the receiver-operating characteristic (ROC) curve. Furthermore, the cervical spinal cord height was compared with the stenotic ratio (i.e., dividing the area of the spinal cord by that of the subarachnoid space), which was a conventional measurement, using regression analysis. A P-value of less than 0.05 was considered significant. The cut-off value for spinal cord height was determined at 7.06 mm based on the ROC curve analysis. A weak negative correlation was observed between spinal cord height and stenotic ratio (R2 = 0.08, P < 0.05). Thus, 7.06 mm of spinal cord height can be used for quantitative evaluation of spinal cord compression. In conclusion, the investigation of cervical vertebrae using CT myelography in Thoroughbred horses indicated that the morphological factors could cause CVSM development.
• DOI: 10.14944/00005479; https://doi.org/10.14944/00005479
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