Surgical outcome of motor deficits and neurological status in brainstem cavernous malformations based on preoperative diffusion tensor imaging: a prospective randomized clinical trial

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Surgical management of brainstem lesions is challenging due to the highly compact, eloquent anatomy of the brainstem. This study aimed to evaluate the safety and efficacy of preoperative diffusion tensor imaging (DTI) and diffusion tensor tractography (DTT) in brainstem cavernous malformations (CMs).


A prospective randomized controlled clinical trial was performed by using stratified blocked randomization. The primary eligibility criterion of the study was being a surgical candidate for brainstem CMs (with informed consent). The study enrolled 23 patients who underwent preoperative DTI/DTT and 24 patients who did not (the control group). The pre- and postoperative muscle strength of both limbs and modified Rankin Scale (mRS) scores were evaluated. Muscle strength of any limb at 12 months after surgery at the clinic visit was the primary outcome; worsened muscle strength was considered to be a poor outcome. Outcome assessors were blinded to patient management. This study reports the preliminary results of the interim analysis.


The cohort included 47 patients (22 women) with a mean age of 35.7 years. The clinical baselines between these 2 groups were not significantly different. In the DTI/DTT group, the corticospinal tract was affected in 17 patients (73.9%): it was displaced, deformed/partially interrupted, or completely interrupted in 6, 7, and 4 patients, respectively. The surgical approach and brainstem entry point were adjusted in 3 patients (13.0%) based on DTI/DTT data. The surgical morbidity of the DTI/DTT group (7/23, 30.4%) was significantly lower than that of the control group (19/24, 79.2%, p = 0.001). At 12 months, the mean mRS score (1.1, p = 0.034) and percentage of patients with worsened motor deficits (4.3%, p = 0.006) were significantly lower in the DTI/DTT group than in the control group (1.7% and 37.5%). Multivariate logistic regression identified the absence of preoperative DTI/DTT (OR 0.06, 95% CI 0.01–0.73, p = 0.028) and use of the 2-point method (OR 4.15, 95% CI 1.38–12.49, p = 0.011) as independent adverse factors for a worsened motor deficit. The multivariate model found a significant correlation between poor mRS score and both an increased preoperative mRS score (t = 3.559, p = 0.001) and absence of preoperative DTI/DTT (t = −2.747, p = 0.009).


DTI/DTT noninvasively allowed for visualization of the anatomical relationship between vital tracts and pathologies as well as facilitated the brainstem surgical approach and entry-point decision making. The technique was valuable for complex neurosurgical planning to reduce morbidity. Nonetheless, DTI/DTT data should be interpreted cautiously.

■ CLASSIFICATION OF EVIDENCE Type of question: therapeutic; study design: randomized controlled trial; evidence: class I.

Clinical trial registration no.: NCT01758211 (

ABBREVIATIONS CM = cavernous malformation; CN = cranial nerve; CST = corticospinal tract; DTI = diffusion tensor imaging; DTT = diffusion tensor tractography; DVA = developmental venous anomaly; FA = fractional anisotropy; GTR = gross-total resection; ICP = inferior cerebellar peduncle; MCP = middle cerebellar peduncle; ML = medial lemniscus; MLF = medial longitudinal fasciculus; MRC = Medical Research Council; mRS = modified Rankin Scale; MS = muscle strength; SCP = superior cerebellar peduncle.

Article Information

Correspondence Yong Cao: Beijing Tiantan Hospital, Capital Medical University, Beijing, China.

INCLUDE WHEN CITING Published online March 16, 2018; DOI: 10.3171/2017.8.JNS17854.

D.L. and Y.M.J. contributed equally to this work.

Disclosures The authors report no conflict of interest concerning the materials or methods used in this study or the findings specified in this paper.

© AANS, except where prohibited by US copyright law.



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    Flowchart depicting the trial profile.

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    Case 12. A 41-year-old woman presented with motor deficits of the right limbs (MRC grade 4), mild facial palsy (House-Brackmann scale, grade II), and diplopia due to left CN VI dysfunction. Preoperative DTI (A), DTT (B–D, G, and H), and T1-weighted axial (E) and sagittal (F) MRI scans showed a pons CM with mass effect and ependymal representation to the fourth ventricle (B). The left CST (yellow; C, D, G, and H) was completely interrupted at the pontomedullary sulcus level ventroinferiorly to the lesion (orange), which was not relevant to preoperative motor function, while the lesion was surrounded by bilateral MCP and ML/MLF (A and B). The lesion was completely resected (I and J) via the suboccipital midline approach and suprafacial triangle with the assistance of intraoperative monitoring. Postoperative DTT (K and L) showed the improved left CST (yellow). She experienced immediate improvement of right-limb MS (MRC grade 5). Diplopia and facial palsy were unchanged at discharge, but both recovered to normal at 3 months after surgery. Figure is available in color online only.

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    Case 17. Preoperative T1-weighted axial MR image (A) showed a pons CM deviating to the left side. Preoperative DTI (B) and DTT (C and D) scans revealed the laterally displaced, completely interrupted CST (yellow) and posterolaterally displaced ML/MLF, and both fiber tracts covered the lateral and posterolateral aspect of the lesion. Postoperative T1-weighted axial MR image (E) showed the GTR. The patient did not undergo postoperative DTI/DTT. Figure is available in color online only.

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    Case 8. A 41-year-old woman presented with right-limb weakness (MRC grade 4) and left oculomotor deficit with a preoperative mRS score of 2. Preoperative DTI (A), DTT (B–D, G, and H), and T1-weighted axial (E) and coronal (F) MRI scans showed a left midbrain CM (orange) with rostral and caudal extension. The ipsilateral CST (yellow) was posterolaterally displaced and partially disrupted in a splayed pattern. The contralateral CST (green) was intact and distant from the lesion. The subtemporal transtentorial approach was used with a brainstem entry point shifting from the anterior mesencephalic zone (according to conventional MRI) to the left ventrolateral aspect of the cerebral peduncle based on the DTI/DTT data. Postoperative T1-weighted axial (I) and contrasted coronal (J) MR images revealed GTR. Postoperative DTT (K and L) showed the integrated, but thinner, bilateral CST. At discharge, the patient suffered worsened MS of the right limbs (MRC grade 2), which corresponded to the postoperative DTT findings. After 38.7 months, the right lower limbs recovered MS to the preoperative baseline level (grade 4), but the right upper limb did not (MRC grade 3); nonetheless, she could function independently. Figure is available in color online only.

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    Case 18. Preoperative DTI (A and C), DTT (B), and T1-weighted sagittal MRI (D) scans showed a right pons CM posterolaterally displacing the ipsilateral CST, which was completely disrupted. Postoperative DTT (E) showed recovery of the right CST (green) and the absence of the lesion. The patient experienced complete motor deficit improvement. Figure is available in color online only.

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    Preoperative axial DTI/DTT in 14 patients with morphologically abnormal CSTs. In cases 2 (A), 13 (I), 15 (J), 16 (K), and 20 (N), the CSTs were displaced posteriorly; in cases 4 (C), 5 (D), 7 (F), 11 (G), 12 (H), and 21 (O), the CSTs were displaced anteriorly; and in cases 3 (B), 6 (E), and 19 (L and M), the CST was displaced posteromedially, laterally, and posterolaterally, respectively. The DTT (M) showed the posteromedially displaced CST (yellow). A safe-entry zone was used in all except 3 cases (cases 3, 13, and 20), in which the 2-point method was used. Abbreviations below each panel indicate the brainstem entry zone used in each case. AMZ = anterior mesencephalic zone; IFC = infrafacial collicular; LMS = lateral mesencephalic sulcus; LPZ = lateral pontine zone; PTZ = peritrigeminal zone; SFC = suprafacial collicular; STZ = supratrigeminal zone; TPM = 2-point method. Figure is available in color online only.

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    Box plot illustrating the distribution of the sum of the postoperative MS scores (left) and the postoperative mRS score (right) at 12 months based on preoperative DTI/DTT examination. The dashed line in the left panel indicates the mean value of the sum of the MS scores at 12 months. The dashed line in the right panel indicates the mean value of the overall mRS score at 12 months after surgery.



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