Literature Review

Spinal Diffusion Tensor Imaging in Evaluation of Preoperative and Postoperative Severity

of Cervical Spondylotic Myelopathy: Systematic Review of Literature

Rima S. Rindler1, Falgun H. Chokshi2, James G. Malcolm1, Sheila R. Eshraghi1, Mahmud Mossa-Basha3, Jason K. Chu1,Shekar N. Kurpad4, Faiz U. Ahmad1

-BACKGROUND: Diffusion tensor imaging (DTI) is increasingly investigated asa potential diagnostic and prognostic tool for symptomatic degenerative cervicalpathology; however, it is yet to be validated for this purpose.

-OBJECTIVE: To investigate the association of preoperative DTI signal changesand postoperative outcomes in patients with cervical spondylotic myelopathy(CSM).

-METHODS: We performed a systematic literature review using PubMed forclinical studies using DTI in adults undergoing operative management for CSM.Data on preoperative clinical status, preoperative DTI metrics, and postoperativeclinical outcomes were abstracted. Preoperative DTI parameters were corre-lated with preoperative severity and postoperative outcomes and pooled acrossstudies.

-RESULTS: Nine studies met inclusion criteria for 238 patients who underwentoperative management with mean follow-up time 310 days. Higher preoperativefractional anisotropy (FA) at the level of maximal compression correlates stronglywith a higher preoperative modified Japanese Orthopaedic Association (mJOA)score (n [ 192 patients, rho [ 0.62, P < 0.001). Higher preoperative FA is asso-ciated with less postoperative mJOA change (n[ 27, rho[L0.42, P[ 0.02) buta greater recovery rate (n[ 93, rho[ 0.32, P < 0.001). Preoperative FA correlatedwith lower Neck Disability Index (n [ 15, rho [ L0.61, P [ 0.04). Preoperativefiber tract ratio had a large positive correlation with a postoperative recovery rate(n [ 20, rho [ 0.61, P [ 0.005). When reported, an apparent diffusion coefficientshowed an inverse correlation compared with FA.

-CONCLUSION: DTI is associated with preoperative severity and post-operative outcomes in CSM patients, suggesting that DTI may become useful inidentifying those most likely to benefit from operative intervention (Level 3 Ev-idence). Prospective trials with standardized DTI acquisition techniques andpatient selection are required for higher-level evidence.

Key words- Cervical spondylotic myelopathy- Diffusion tensor imaging- Modified Japanese Orthopaedic Score- Neck Disability Index- Spinal cord

Abbreviations and AcronymsADC: Apparent diffusion coefficientAUC: Area under the curveCSM: Cervical spondylotic myelopathyDTI: Diffusion tensor imagingFA: Fractional anisotropyFTR: Fiber tract ratioLMC: Level of maximal compressionmJOA: modified Japanese Orthopaedic AssociationMRI: Magnetic resonance imagingNDI: Neck Disability IndexOCEBM: Oxford Center for Evidence-Based MedicinePRISMA: Preferred Reporting Items for SystematicReviews and Meta-AnalysesT2W: T2-weighted

From the Departments of 1Neurological Surgery and2Radiology and Imaging Sciences, Emory University School ofMedicine, Atlanta, Georgia; 3Department of Radiology,University of Washington, Seattle, Washington; and4Department of Neurosurgery, Medical College of Wisconsin,Milwaukee, Wisconsin, USA

To whom correspondence should be addressed:Faiz U. Ahmad M.D.[E-mail: faiz.ahmad@emory.edu]

Citation: World Neurosurg. (2017) 99:150-158.http://dx.doi.org/10.1016/j.wneu.2016.11.141

Journal homepage: www.WORLDNEUROSURGERY.org

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INTRODUCTION

Cervical spondylotic myelopathy (CSM) isa clinical entity of cervical spinal cordcompression resulting from degenerationof bone, ligament, and intervertebraldisks.1 The clinical manifestation ofmyelopathy results from directcompression or ischemia.2 Noncontrastmagnetic resonance imaging (MRI) haslong been the gold-standard imagingtechnique in evaluating and diagnosingcervical degeneration and its effects on thespinal canal and cord.3 This is done

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typically with anatomic measurements ofcanal size, cord-to-canal ratios, or dy-namic observation of canal size reductionwith movement. Presence of T2-weighted(T2W) changes in cord parenchyma arealso highly associated with advancedmyelopathy.4-6 Conventional MRI, howev-er, is limited in predicting symptomseverity, as patients may have avarying tolerance of spinal cord compres-sion.7 Patients may be significantlysymptomatic with only “mild” cervicalstenosis and no T2W hyperintensity,

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while others may have “severe” stenosiswith myelomalacia and minimal, if any,symptoms. Furthermore, T2W changesare often a late finding and may predictworse outcome despite decompression.8

These exceptions present diagnostic andtherapeutic uncertainty to clinicians.Diffusion tensor imaging (DTI) is being

increasingly investigated as a potentialdiagnostic and prognostic tool for patientspresenting with symptomatic cervicaldegenerative disease. DTI is thought todetect microstructural changes in tissue by

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LITERATURE REVIEW

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measuring the presence, strength, anddirectionality of water particles,9 which aredisrupted in cervical compression states. Arecent systematic review and meta-analysisby Guan et al10 noted significantdifferences in DTI parameters whencomparing patients with CSM andhealthy controls, specifically decreasedfractional anisotropy (FA) and increasedapparent diffusion coefficient (ADC) inpatients. This suggested that DTI mightbe a useful tool in differentiating patientswith symptomatic cervical stenosis fromminimally or asymptomatic patients andassist in identifying candidates foroperative intervention.Therefore the purpose of this systematic

review is to evaluate the association ofDTI-related cord changes with preopera-tive severity and postoperative outcomesin patients with CSM.

*Pooled variance (sp2) is estimated as the weighted average

of sample variances (si2) and counts (ni): sp

2 ¼ S([ni-1]*si2)/

S(ni-1).

MATERIALS AND METHODS

Data SourcesThis retrospective investigation entails asystematic literature search that was per-formed following Preferred ReportingItems for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.11 TheMeSh database system in PubMed wasused to search for articles discussing therole of DTI in diagnosing and guidingtreatment of cervical degenerativepathology in 3 separate searches. Thefirst was (“Diffusion TensorImaging”[Mesh]) AND (“SpinalCord”[Mesh]). The second was “diffusiontensor imaging” ([All Fields] and “spinalcord” [Title/Abstract]). The third was“DTI spine myelopathy.” References ofreview articles were carefully evaluatedfor additional qualifying articles notidentified in the first 3 searches.

Selection CriteriaArticles were limited to English languagecase reports, case series, and retrospectiveor prospective cohort studies of human pa-tients published between January 1990 andOctober 2016. Only articles describingoperative management of adult patientswith CSM and use of DTI were included.Cervical degenerative pathology includedany process causing symptomatic cervicalstenosis or myelopathy, including spondy-losis, ossification of the posterior

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longitudinal ligament, or intervertebral diskherniation. Specifically, articles detailinguse of DTI in these patients and evaluatingpostoperative outcomes were included.Expert comments or general reviews wereexcluded. Articles that did not detail patientdemographics or operative outcomes or thatincluded nondegenerative cervical spinepathology (e.g., tumor) were excluded. Tworeviewers (RSR and JGM) independentlyselected qualifying studies for inclusion tominimize the risk of selection bias. Dis-agreements were resolved by consensus.Duplicate studies were eliminated.Study quality was assessed using the

Oxford Centre for Evidence-Based Medi-cine (OCEBM) Levels of Evidence catego-rization.12 Risk of bias for cohort studieswas assessed by the Newcastle-OttawaScale, which is a 3-category, 9-point scaleassessing case selection, comparability ofgroups, and exposure, with a higher gradeindicating higher study quality.13

Data ExtractionThe following data were extracted fromeach article according to inclusion criteria:patient demographics (age and gender),clinical pathology; radiographic dataincluding DTI measures of interest, MRIprotocols; use of other standardized clin-ical or radiographic measures; details ofoperative interventions, postoperativeoutcomes, and time to follow-up. Corre-sponding authors were contacted foradditional information and missing data.

Statistical MethodsTo estimate follow-up, the pooled meanand variance were calculated from studiesonly for patients who underwent operativemanagement.* Correlations between DTIparameters (FA and ADC) and themodified Japanese OrthopaedicAssociation (mJOA)14 score in Lee et al15

(2011) were calculated by the authorsusing the Spearman rank correlationcoefficient (rho) to measure themonotonic relationship betweenvariables. Where possible, correlationsbetween DTI parameters and clinicalassessments were pooled. For thesecalculations, the correlation coefficientswere first transformed to normal

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distributions using the Fisher Z-Transform(z ¼ ln[(1þr)/(1�r)]/2) with knownstandard error (1/sqrt[n�3]). These werethen pooled using the Mantel-Haenszelmethod with a fixed-effects model, unlessChi2 and I2 indicated significant heteroge-neity, in which case a random-effects modelwas used.16 Confidence intervals (CIs)are at 95%. A P value <0.05 wasconsidered statistically significant in allanalyses.

RESULTS

Study SelectionA PRISMA flow chart of the screened ar-ticles is shown in Figure 1. The 3 PubMedqueries resulted in 945 nonduplicatedstudies for screening according todescribed parameters. Seven additionalstudies were identified from a carefulbibliography review. Thirty-seven studiesfrom this initial screen underwent full textreview. Twenty-five articles were excludedbecause no operative intervention wasperformed, 2 were review articles,10,17 and1 included other compressive cervicalspine pathologies in averaged data.18 Theremaining 9 articles were included in thisreview (7 of these included preoperativeassessment; 6 included postoperativeoutcome). One of these studies reportedonly 2 patients and was therefore notincluded in the pooled calculations.19

Study CharacteristicsTable 1 provides characteristics of all 9included studies. All studies were eithercase series (i.e., included >3 patientswith detailed clinical and radiographicinformation, n ¼ 5) or cohort studies(i.e., included both patients and healthyvolunteers, n ¼ 4). There were 276patients with CSM, ossification of theposterior ligament, or combination, and81 healthy controls. All studies reported amean age and variably reported standarddeviation and range, which only allowedfor a pooled mean calculation. Twohundred thirty-eight patients (86%) un-derwent operative management and had amean follow-up time of 310 days.

Risk of Bias of Individual Studies andStudy QualityUsing the OCEBM criteria, the 4 cohortstudies were Level of Evidence 3 and the

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Figure 1. PRISMA flow diagram.

LITERATURE REVIEW

RIMA S. RINDLER ET AL. SPINAL DIFFUSION TENSOR IMAGING IN CERVICAL SPONDYLOTIC MYELOPATHY

remaining 5 case series were Level of Evi-dence 4. The Newcastle-Ottawa Scalerevealed a range of cohort study quality,from poor24 to excellent.15 Few of thecohort studies included well-matchedcontrols. Other possible sources of biasinclude selection bias for patientsincluded in case series and publicationbias for studies reporting only on patientswith good surgical outcome.

DTI Data Acquisition TechniquesThe specific preoperative DTI measures ob-tained (e.g., FA, ADC, fiber tractography ra-tio [FTR]) and the reported cervical levels arelisted in Table 2. All studies obtained raw FAdata, but it was not reported by Nakamuraet al21 due to distortion artifact. ADC wasreported in 3 articles.15,22,25 Tractographydata were qualitatively reported in one15 andquantitatively in another using the FTR(FTR ¼ number of fibers at compressedlevel/number of fibers at C2 level� 100%).21

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The spinal cord cross-section at the levelof maximum compression was included as aregion-of-interest for DTI parameters in allbut 2 studies, which reported lateral, poste-rior and anterior regions of interest in theaxial cervical spinal cord.24,25 For thesestudies, the lateral ROI was used in the an-alyses as it encompassed the corticospinaltracts. Some studies also analyzed the cer-vical cord level by level, averaged acrossmultiple levels, or performed a combination.This study focused on DTI results obtainedat the level of maximum compression,because itwas themost commonly evaluatedlevel across studies. Other important find-ings from levels other than level ofmaximum compression were noted.

Clinical Assessments and OperativeInterventionSeveral clinical tools were used to assesspreoperative and postoperative clinicalstatus. The mJOA14 and Nurick clinicalscale27 were used to assess myelopathy

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severity. Both are obtained fromphysical examination. A higher mJOAscore (0e17) or Nurick grade (0e5)indicates worse myelopathy. The ShortForm-36 (SF-36)28-30 and Neck DisabilityIndex (NDI)31 are self-completed ques-tionnaires that assess pain and function.Lower SF-36 scores and higher NDIscores (0e50) indicate worse symptoms,function, and sense of well-being. TheOswestry Disability Index,32 anadditional patient questionnaire, wasused by one article (data not shown).19

All studies reported correlation valuesbetween preoperative DTI with raw scoresfor preoperative clinical assessments.Studies varied in how they accounted forclinical change from the patient’s ownbaseline status postoperatively. One studyinstead reported correlation with changebetween preoperative and postoperativevalues.33 Another study transformed thischange into a recovery rate equalto (postoperative � preoperative)/(17 � preoperative) � 100%, where 17 isthe maximum mJOA score,25 whichessentially quantifies how much deficit apatient has recovered.34

Operative management was discusseddifferently in each study. Three studiesreserved operations for patients with pro-gressive or moderate-to-severe myelopathyand/or severe cord compression,19,20,26

whereas the remaining 3 did not detailoperative criteria.15,21,24 Surgical decom-pression techniques included multilevelanterior cervical discectomy and fusion,19,26

laminoplasty,21,26 or were not described.15,24

Relationship of DTI Measures andPreoperative Clinical AssessmentsFive studies used mJOA as a clinicalassessment tool.15,19,20,23,25,26 One did notspecify whether the JOA tool that was usedwas the “modified” version; it was pre-sumed to be “mJOA” for the purposes ofthis study.21 Among the studies, 2included SF-36,20,24 2 used NDI,20,23 and2 used Nurick.20,22

Pooled calculations revealed a strongpositive correlation between FA and pre-operative mJOA scores at the level ofmaximal compression (LMC) (n ¼ 5studies; rho ¼ 0.62, 95% CI 0.53e0.71, P <0.001) (Table 3A).15,20,23,25,26 FA at the levelof maximum compression did not correlatewith the Nurick assessment (rho ¼ �0.25,P ¼ 0.18) but moderately correlated at the

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Table 1. Demographics and Characteristics of Diffusion Tensor Imaging Studies Investigating Operative Outcomes in CervicalSpondylotic Myelopathy

StudyStudyDesign

OCEBM Levelof Evidence

Newcastle-OttawaScale

Patients (NumberFemale)

Mean Age (Rangeor � SD), Year

Pathology

OperativeInterventionNumber (%)

Follow-Up(Mean � SD, days)Cases Controls Cases Controls

Jones 201119 Ca 4 NA 3 (1) 0 63.7 (52e82) NA OPLL 2 (66.7%) 105 � 21.2

Jones 201320 Ca 4 NA 30 (16) 0 61.9 (�12.4) NA CSM 15 (50%) 180.7 � 103.4

Lee 201115 Co 3 8 20 (7) 20 (7) 49.6 (22e67) “Matched” CCM* 20 (100%) 90

Nakamura 201221 Ca 4 NA 20 (5) 0 64.6 (44e82) NA CSM, OPLL 20 (100%) 401.5 � 45

Rajasekaran 201622 Ca 4 NA 35 (2) 0y 48 (35e82) NA CSM, OPLL 35 (100%) 365

Vedantam 201723 Ca 4 NA 27 (15) 0 54.5 (�1.9) NA CSM 27 (100%) 90

Wang 201524 Co 3 3 4 (0) 5 (2) 61.25 (53e73) 48 (39e53) CSM 4 (100%) 180

Wang 201625 Co 3 7 93 (45) 36 (14) 57.2 (42e69) 51.3 (20e77) CSM 93 (100%) 365

Wen 201426 Co 3 7 45 (19) 20 (10) 64 (43e86) 52 (41e62) CSM 22 (48.9%) 455 � 137.5

Totals 5 Ca4 Co

276 (110) 81 57.0 (n/a) 238 (86%) 310.1

OCEBM, Oxford Center for Evidence-Based Medicine; SD, standard deviation; Ca, case series; NA, not applicable; OPLL, ossification of posterior longitudinal ligamen; CSM, cervical spondyloticmyelopathy; Co, cohort study; CCM, cervical compressive myelopathy.

*Includes CSM, OPLL, os odontoideum.yControls were included in 1 table but never defined.

LITERATURE REVIEW

RIMA S. RINDLER ET AL. SPINAL DIFFUSION TENSOR IMAGING IN CERVICAL SPONDYLOTIC MYELOPATHY

C2-3 (rho ¼ �0.46, P ¼ 0.01) and C7-T1(rho ¼ �0.38, P ¼ 0.04) levels.20 FA alsodid not correlate with NDI (rho ¼ 0.19,P ¼ 0.35) or SF-36 [Physical ComponentScore; pooled rho¼ 0.17, 95% (CI �0.20 to0.49), P ¼ 0.3820,24]. Within the CSMcohort, FA was also significantly lower inpatients with a worse neurologic status in 2of the studies20,26; however, these datacould not be quantitatively pooled (data notshown).Preoperative ADC in CSM had a strong

negative correlation with mJOA(rho ¼ �0.62, P < 0.001, see Table 3A).15

Preoperative FTR had a weak, nonsig-nificant correlation with mJOA (rho ¼ 0.03,P ¼ 0.90, see Table 3A).21 There was nodifference in the number of interrupted orintact fibers on tractography in patientswith better (interrupted, n ¼ 5; intact,n ¼ 5) versus worse (interrupted, n ¼ 3;intact, n ¼ 7) symptoms.15

Predictive Ability for OperativeInterventionFA (area under the curve [AUC] 0.831) andmJOA (AUC 0.7578) were strongly accuratein identifying patients who underwent

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operative management in a single study;however, these values were not statisticallydifferent.20

Relationship of DTI Measures withPostoperative OutcomeSix studies reported correlation analysesbetween DTI measures and postoperativeclinical outcome20-25 in 194 patients withCSM. Differences in preoperative andpostoperative clinical scores were not re-ported in 2 studies15,20,26 or not calcu-lated.19,24 The remaining 3 studies werenot incorporated in pooled analysis for thefollowing reasons. Jones et al19 reportedonly 2 patients, which precludedpostoperative correlation calculations.Lee et al15 reported a dichotomouspostoperative outcome of “better orworse,” defined as a �3-point increase inpreoperative to postoperative mJOA score,but no raw mJOA scores that would allowfor correlation with FA or ADC values.Similarly, Wen et al26 reporteddichotomous postoperative outcomes of“good or bad,” defined as a recovery rateof >50% or �2 point mJOAimprovement for good outcome. Raw

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postoperative mJOA scores were notavailable for calculating correlation.Table 3B indicates some correlation

between DTI and postoperative outcome.Three studies calculated the correlationbetween FA and postoperativemJOA.20,23,25 One study correlated FAwith raw mJOA scores and found nosignificant correlation (rho ¼ 0.06,P ¼ 0.84).20 The second correlated withchange from preoperative baselinefinding that greater preoperative FAcorrelated with less postoperativeimprovement (rho ¼ �0.42, P ¼ 0.02).23

The third study found that greaterpreoperative FA correlated with greaterpercent of recovered function(rho ¼ 0.32, P < 0.001).25 These variedcorrelation tactics precluded pooling.For NDI, FA at the level of maximum

compression had a strong negative corre-lation with postoperative NDI scores, withhigher FA associated with improved levelof function (rho ¼ �0.61, P ¼ 0.04)20.Preoperative FTR had a strong positivecorrelation with postoperative recoveryrate (rho ¼ 0.61, P ¼ 0.005), wherepatients with FTR <60% correlated with

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Table 2. Technical Details of Diffusion Tensor Imaging (DTI) Studies on Cervical Spondylotic Myelopathy; in Systematic Review

Study

DTI Measures

ScannerMake

FieldStrength

(T)DTI

DirectionsVoxel

Size (mm) FOV (mm) b (mm2/s) TR (ms) TE (ms)

SliceThickness

(mm) Acquisition ROI

C-SpineLevels

ExaminedDTI

ProcessingFA ADC MD Tr FTR

Jones 201119 U NA NA NA NA NA NA NA NA NA Axial NA C2/C3, C7/T1 NA

Jones 201320 U GeneralElectric

3 6 NA 180*180 1000 8100 94.1 4 Axial Axial LMC, C2/C3,C7/T1

GE Advantage

Lee 201115 U U U PhilipsAchieva

3 15 1.95*1.95 250*224 600 3380 56 2 Sagittal Axial C1, C7, LMC PRIDE(Philips)

Nakamura 201221 U U U U NA 1.5 7 NA 300*300 1000 9000 84.9 4 Axial Axial C2, LMC Volume-One

Rajasekaran201622

U U SiemensMagnetom

1.5 12 NA 220*220 500 6000 85 4 Axial NA NA NA

Vedantam 201723 U GE SignaExcite

1.5 15 3*3 128*128 600 5000 98.2 3 Axial Axial C1-2, LMC FunctionalNeuroImages

Wang 201524 U U SiemensTim Trio

3 10 (EachSag & Ax)

NA 200*200(Each Sag &

Ax)

750 3200 (Sag),2500 (Ax)

73 (Sag),90 (Ax)

2.5 (Sag),5 (Ax)

Axial,Sagittal

Axial,Sagittal

C2-T1 (Axial),Lateral/Anterior/Posterior

Margins of Cord(Sag)

Neuro 3D(Siemens)

Wang 201625 U U GeneralElectric

3 15 NA 180*180 1000 8000 87.6 4 Axial Axial C1/C2reference, C3-

C7 LMC

GE Functool

Wen 201426 U PhilipsAchieva

3 15 80*80 600 NA NA 7.5 Axial Axial C1-T1 (Axial) DTI Studio

T, Tesla; FOV, field of view; TR, repetition time; TE, echo time; ROI, region of interest; FA, fractional anisotropy; ADC, apparent diffusion coefficient; MD, mean diffusivity; Tr, tractography; FTR, fiber tractography ratio; NA, not available; Sag,sagittal; Ax, axial; LMC, level of maximum compression.

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REVIEW

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IMAGIN

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CERVIC

ALSPONDYLOTIC

MYELOPATHY

Table 3. Relationship of Clinical Assessments and Radiographic Measures at Level of Maximal Compression

Study

FA ADC FTR/Tractography

mJOA NDI Nurick SF-36 mJOA mJOA

A. Preoperative Diffusion Tensor Imaging (DTI) and Preoperative Clinical Assessment (Spearman Rank Correlation, rho)

Jones 201320 0.47, P < 0.01 0.19, P ¼ 0.35 �0.25, P ¼ 0.18 PCS: 0.21, P ¼ 0.29

Lee 201115 0.03, P ¼ 0.90* 0.08, P ¼ 0.75*

Nakamura 201221 NS (P ¼ 0.95)

Vedantam 201723 0.65, P < 0.001 NS NS

Wang 201524 PCS: �0.80, P > 0.60yWang 2016z,25 0.763, P < 0.001 L0.703, P < 0.001

Wen 201426 0.327, P < 0.016

Pooled results [CI] 0.62 [0.53e0.71],P < 0.001

0.16 [�0.20 to 0.49], P ¼ 0.38 L0.62 [L0.72, L0.49], P < 0.001

Study Patients

FA ADC FTR/Tractography

mJOA NDI Nurick SF-36 mJOA Nurick mJOA

B. Preoperative DTI and Postoperative Clinical Assessment (Spearman Rank Correlation, rho)

Jones 201320 15 0.06, P ¼ 0.84 L0.61;P [ 0.04

�0.22, P ¼ 0.44 0.52, P ¼ 0.51

Nakamura 201221 20 0.61,P < 0.005

Rajasekaran 201622 35 �0.036, P ¼ 0.863 �0.325,P ¼ 0.106

Vedantam 201723 27 L0.42, P [ 0.02(change)

NS NS

Wang 201524 4 �0.40, P > 0.60yWang 2016z,25 93 0.32, P < 0.001

(recovery rate)L0.293, P < 0.01(recovery rate)

Pooled results [CI] 194 NA �0.09 [�0.37, 0.21],P ¼ 0.56

0.46 [�0.04, 0.78],P ¼ 0.07

Bold values represents statistical significance at P < 0.05. Italics were the pooled results on the bottom row.FA, fractional anisotropy; ADC, apparent diffusion coefficient; FTR, fiber tracking ratio (# fibers at compressed level/number of fibers at C2 level �100%); mJOA, modified Japanese Outcome

Assessment; NDI, Neck Disability Index; SF-36, Short Form-36; NA, not applicable, see text; NS, reported no significant difference but not quantified, unable to pool.*Recalculated from reported data.yObtained from author correspondence.zAveraged over all regions, see text.

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a recovery rate of <40%.21 Of note, therewas a trend for postoperative FTR tocorrelate with postoperative mJOAscores, but this did not reachsignificance (rho ¼ 0.37, P ¼ 0.05).21

Only 1 study directly evaluated the pre-dictive ability of DTI measures at level of

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maximum compression in identifying pa-tients with good postoperative outcome,reporting an AUC ¼ 0.648 in a logisticregression model.26 In this study,however, mean FA at C3-7 (AUC 0.743)and FA at C2 (AUC 0.781) independentlypredicted good surgical outcome (defined

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as recovery rate >50% or at least 2 pointsmJOA improvement) better than FA at theLMC and level of lowest FA value (AUC0.648). In Lee et al15 2011, 80% of patientswith intact fibers on tractography at LMCin the neurologically “worse” groupimproved at least 3 points on the mJOA

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score postoperatively, compared with only20% of patients with destroyed fibers;however, further sensitivity andspecificity calculations were notperformed.

DISCUSSION

This review found that FA values correlatewith preoperative clinical severity andpostoperative outcome in adult patientswith cervical spondylotic myelopathy,suggesting that DTI measures may beuseful tools in determining symptomseverity and identifying operativecandidates.

Relationship of DTI Measures andPreoperative Clinical AssessmentsSome measures, particularly FA, corre-lated with preoperative clinical assessmenttools measuring severity of myelopathy insome studies. FA at the level of maximumcompression had a strong correlation witha single preoperative assessment (mJOA).ADC was found to have a similar inversecorrelation.15 Tractography (using FTR)21

did not correlate with preoperativeclinical assessment in a single study,which limits interpretation. Our reviewsupports the findings reported in 2015 byGuan et al,10 in their systematic review,that FA at LMC may be a usefuldiagnostic tool for identifying severity ofmyelopathy in patients with cervicalspondylosis.Although FA correlated strongly with

mJOA across many studies, other clinicaltools showed varied results. Several factorsneed to be considered when interpretingthese results. The largest effects ofcompression on DTI may not occur at theLMC, especially in patients with multileveldisease.26 FA values at other levels (e.g.,C2-3, C7-T1) either more strongly corre-lated with mJOA or correlated better withother clinical assessments in somestudies. FA (at C2-3) trended toward beingthe most accurate in identifying the needfor operative intervention over other pa-rameters.20 Multilevel disease may havemore complex effects on FA and DTIparameters than single-level disease,potentially increasing the variability ofvalues at the level of maximum compres-sion and therefore its diagnostic ability.Even when patients with “better” and“worse” symptoms were separated,

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significant differences in DTI between the2 groups were inconsistent, particularly forFA. For example, FA (at LMC) wassignificantly lower in patients with moresevere symptoms within the CSM cohortin some, but not all, studies. Additionally,DTI values vary by level even in healthycontrols, with lower FA values found inlower cervical levels.35 FA may alsodecrease with age,36,37 though this is nota consistent finding.38 One study foundthat using the ratio of LMC to C1-C2 hada stronger correlation with pathology andwas robust to the effect of age.25 Thesefactors may complicate the diagnosticability of DTI and FA across cervicallevels and age groups. Although thesedata support the potential of FA as abiomarker or diagnostic tool for CSMseverity, future studies are required todetermine the optimal DTI measure andanatomic level of acquisition that bestcorrelates with symptom severity.

Relationship of DTI Measures withPostoperative OutcomeThe 2 studies that found moderate corre-lations with preoperative FA and post-operative mJOA each used a uniqueapproach to incorporating mJOA usingeither change from baseline or recoveryrate.23,25 Since each patient has his or herown preoperative baseline score, it isimportant to predict on the basis of that,so more work should be done to explorethese and similar approaches. Patientswho improve postoperatively may havenormalizing clinical assessment scoresand may no longer correlate with preop-erative DTI values. A more appropriatemeasure of postoperative outcome mightbe recovery rate or mean difference inassessment scores. This change mightlead to a more accurate relationship be-tween DTI measures and postoperativeoutcome. Additionally, as previouslystated, the relationship may change ac-cording to the cervical level assessed,which should be further explored in futurestudies. Variable DTI acquisition tech-niques may also account for interstudyvariability in defining a relationship be-tween DTI and postoperative outcome.It is important to note that post-

operative improvement rates in this serieswere highly variable (20%e93%) and likelyvaried in accordance with symptomseverity. There was a wide range of

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definitions for “improvement,” which maycertainly impact the predictive ability ofDTI measures across the entire cohort ofCSM patients. This variability is consistentwith recovery rates reported in the litera-ture, ranging from 54.5%e99.5% in thepast 2 decades, not accounting for pro-cedure type or definition of improve-ment.39,40 This variability should certainlybe taken into account in future studies byperforming subgroup analyses accordingto myelopathy severity and operativeapproach, as well as providing consistentdefinitions for clinical improvement.One future consideration is investi-

gating the utility of DTI in the post-operative setting and the effect thatsurgical decompression might have onDTI measures and correlation with recov-ery. Only one study in this review per-formed postoperative DTI, which showeda trend in FA improvement post-operatively.24 Imaging in this setting may,however, be significantly altered by highartifact from operative instrumentation,thus affecting accuracy of DTI measures.

Strengths and LimitationsThis study reviewed a small number ofqualifying articles, each of which had aunique study design, DTI acquisitiontechniques, and primary outcomes. Allstudies were Level of Evidence 3 or 4 andvaried widely in quality, given that only 4studies had a comparative control group(of varying quality) regarding initial DTIscores, and none had a comparative groupfor outcome. These factors make com-parison across studies challenging.Furthermore, not all relevant data werereported for review and inclusion in ameta-analysis. Despite these limitations,periodic systematic reviews such as thishelp to evaluate the current state of newdiagnostic techniques, exploring theirpotential clinical applications andproviding guidance for future prospectivestudies.

CONCLUSION

DTI of the cervical spinal cord maybecome useful in predicting postoperativeoutcomes in patients with cervical spon-dylotic myelopathy. FA may play a partic-ular role as a biomarker in predictingpostoperative outcome, with a Level ofEvidence 3 recommendation. Large,

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controlled, prospective studies, however,are required for establishing standardizedMRI acquisition protocols with appro-priate DTI parameters, anatomic level ofacquisition, and cut-off values for pre-dicting need for operative intervention.Standardized clinical assessment tools,such as mJOA, should be used for detailedassessment of postoperative outcome inthe context of considering preoperativebaseline.41

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Conflict of interest statement: Faiz U. Ahmad M.D, M.Ch.,has consulting agreements with Depuy-Synthes andMedtronic, Inc. All authors report no conflict of interestconcerning the materials or methods used in this study orthe findings specified in this paper.

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Received 21 August 2016; accepted 28 November 2016

Citation: World Neurosurg. (2017) 99:150-158.http://dx.doi.org/10.1016/j.wneu.2016.11.141

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