Pediatr Radiol (2010) 40:118130 DOI 10.

1007/s00247-009-1406-3

ORIGINAL ARTICLE

Utility of MRI in the follow-up of pyogenic spinal infection in children

Qiuyan Wang & Paul Babyn & Helen Branson & Dat Tran & Jorge Davila & Edrise L. Mueller

Received: 5 June 2009 / Revised: 6 August 2009 / Accepted: 27 August 2009 / Published online: 10 September 2009 # Springer-Verlag 2009

Abstract Background MRI is used at an increasing rate in evaluation of pediatric spinal infections both at the time of diagnosis and in follow-up. However, the impact of MRI in follow-up has been rarely evaluated to date. Objective To evaluate serial follow-up spinal MRI changes compared to clinical outcome and assess their impact on clinical management. Materials and methods All pediatric (<18 years) patients with pyogenic spinal infection over a 9-year period with at least one follow-up after treatment were included. Atypical infections were excluded. Results We examined 35 whole-spine and 16 localized spinal scans from 17 patients (2 months to 16 years, 9F:8 M) who had 51 follow-ups done 2 weeks to 4.75 years after baseline. Seven children (41%) younger than 3 years underwent 33 follow-ups (65%); most required GA or sedation. Short-term follow-up scans demonstrated epidural and/or paraspinal soft-tissue changes correlating with clinical status and laboratory findings in all cases. However, MRI showed that bone and/or disc abnormalities continued and progressed in some cases despite clinical improvement. Long-term follow-up scans showed bone, disc and softtissue changes 13 years after baseline, despite children
Q. Wang (*) : P. Babyn : H. Branson : J. Davila : E. L. Mueller Department of Diagnostic Imaging, The Hospital for Sick Children, 555 University Ave., Toronto M5G 1X8 ON, Canada e-mail: wangqiuyan8888@yahoo.com.cn D. Tran Infectious Disease Department, The Hospital for Sick Children, 555 University Ave., Toronto M5G 1X8 ON, Canada

being symptom free. Extension of antibiotics occurred in 47% of children partly based on follow-up MRI. Conclusion Epidural and paraspinal soft-tissue changes correlated with childrens clinical symptoms. Progression of bone and disc changes can manifest despite adequate clinical response. Long-term or serial routine follow-ups were not necessary. Management should be made based on clinical response. Keywords Spinal infection . Pyogenic . MRI . Follow-up . Children

Introduction Pyogenic spinal infection can affect any component of the spinal column, often with involvement of the adjacent soft tissue, epidural space or spinal canal [1, 2]. Although uncommon in children, it can cause severe neurologic deficits if diagnosis or treatment is delayed. Imaging, especially MRI, plays an important role in the diagnosis of these conditions, as the clinical and laboratory findings are often ambiguous and nonspecific. The value of MRI in the diagnosis and differential diagnosis of pediatric spinal infection is well established [3]. Diagnostic MRI findings of spinal infection include bone marrow edema, destruction of the affected vertebrae, abnormal signal intensity of the contiguous disc, and paraspinal or epidural extension of infection. Assessment of the spread of infection to the spinal canal with epidural and/or paraspinal abscess formation is an important advantage of MRI. Presence of intervertebral disc involvement and paraspinal soft-tissue infection support the diagnosis of infection and help differentiate it from malignancy. Early use of MRI has

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reduced diagnostic delay, aided recovery and helped avoid lengthy hospitalizations [4]. With the shift in contemporary management from surgical therapy to primary medical therapy [57], MRI is increasingly used in follow-up to assess treatment response. However, the value of MRI in the follow-up of pediatric spinal infection has not been fully established. Several adult studies have shown that no single MRI finding correlates well with clinical status and that some MRI features may persist or even worsen initially despite clinical improvement on antibiotic treatment [810]. Given the differences in vascular supply and immaturity of the pediatric spine, we wished to determine the utility of follow-up MRI in children. Our objectives were to assess the correlation between serial MRI features of spinal infection with clinical outcome and the impact of followup MRI on clinical management for children with pyogenic spinal infection.

Image acquisition All MRI exams were acquired on a GE Signa 1.5-T MRI scanner at software level 9.1 (GE Medical Systems, Milwaukee, WI, USA) except for one case with an outside hospital baseline MRI. The scan protocol at baseline and follow-up MRI consisted of: sagittal T1-W, sagittal FSE T2-W images with fat saturation, axial T1-W and T2-W images of the region of interest, and post-contrast T1-W sagittal, axial and coronal scans with fat saturation. Image review All available MR imaging was reviewed electronically on PACS by two staff radiologists one with more than 20 years of experience in musculoskeletal diseases and a neuroradiologist both blinded to all patients clinical information. MRI features were recorded, specifically bone marrow edema, bone enhancement, bone destruction and vertebral body height loss, abnormal T2-W disc signal and enhancement, epidural enhancement and abscess, canal compromise, and paraspinal soft-tissue enhancement and abscess. Qualitative assessment of interval changes of individual MRI findings on the first follow-up compared with baseline MRI was rated independently by the two radiologists as normal, better, same or worse. The time and anatomic extent of all follow-up exams were recorded. MRIs done less than 4 months after baseline were considered shortterm follow-up, while those conducted after 4 months were considered long-term follow-up. Statistical analysis Inter-observer agreement on interval changes for each MRI feature was evaluated by kappa value.

Materials and methods This is a single-center retrospective cohort study. Institutional Review Board approval was obtained and waiver of consent was granted. Patient population All children diagnosed with pyogenic spinal infection, spondylodiscitis, or localized vertebral osteomyelitis during a 9-year period (January 2000 to September 2008) were identified from a search of our radiology reporting database and health record database using the international classification of disease coding (ICD). Ninety-seven cases of spinal infection were identified. All children with pyogenic spinal infection and available baseline MRI exam before treatment and at least 1 follow-up MRI after initiation of treatment were included in this study. Children with atypical infections including tuberculous or blastomycotic spondylodiscitis, and spondylodiscitis secondary to direct spinal trauma, spinal surgery or instrumentation were excluded. A total of 17 children met our criteria. Clinical information including childrens age, gender, initial presentation and length of symptoms prior to diagnosis was collected. Main laboratory tests included erythrocyte sedimentation rate (ESR), white blood cell (WBC), polymorphonuclear leukocytes (PMN) and C-reactive protein (CRP). The treatment used and response to therapy were recorded. The impact of follow-up MRI on clinical decision making was assessed retrospectively through review of the medical records by an infectious disease physician using a pre-designed data collection form.

Results Clinical and laboratory characteristics Pyogenic spinal infection was found in nine girls and eight boys, ranging in age from 2 months to 16 years. Seven of the 17 children were younger than 3 years, median 16 months. The remaining 10 children were between 9 and 16 years of age, median 12 years. Back or neck pain was the predominant clinical presentation in 13/17 cases, with fever in 11/17 cases. Torticollis, buttock/hip pain, and constipation were encountered in one case each. In the younger age group, the presentation was more nonspecific and included fever, tachypnea, abdominal distension, irritability with movement, and refusal to bear weight.

120 Fig. 1 Time and frequency of follow-up MRI

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Time and frequency of follow-up MRI in 17 cases

60 50 40 Time (month) 30 20 10 0 1 2 3 4 5 6 7 8 9 1011 121314151617 Cases 1st F/U 2nd F/U 3rd F/U 4th F/U 5th F/U 6th F/U 7th F/U

Sixteen cases (94%) had elevated ESR, with 10 cases (59%) showing leukocytosis. Blood cultures were positive in 9/17 cases, including six with Staphylococcus aureus and one case each of Streptococcus pyogenes group A, Salmonella typhimurium, and Pseudomonas species. No other causative infectious lesions for these children were found. Bone biopsies were available in two cases and grew S. aureus and Salmonella typhimurium. Two of three paraspinal soft-tissue biopsies were positive (both for S. aureus). Predisposing conditions were seen in four patients (24%), including one case each of patent ductus arteriosus, hereditary spherocytosis, trisomy 6, and psoriasis. Management All children were treated with intravenous antibiotics based on susceptibility profiles when available. Two underwent laminectomy for extensive epidural abscess. All children except one had satisfactory clinical improvement within 1 month of initiating treatment. Follow-up MRI data Fifty-one follow-up MRIs were done, ranging from 2 weeks to nearly 5 years after the baseline MRI. Mean follow-up number of exams was three per patient, range 17 exams
Table 1 Comparison of MRI findings at baseline and shortterm or long-term follow-up MRI features 2 vertebra involvement Marrow edema Bony enhancement Body height loss Disc T2-W signalb Disc enhancementb Epidural enhancement Epidural abscess Canal compromise Paraspinal enhancement Paraspinal abscess

(Fig. 1). The first follow-up MRI exams were completed 2 17 weeks after baseline MRI, mean 8 weeks. Thirty-five whole spine scans and 16 localized spine scans were performed in follow-up. In those seven patients younger than 3 years, 33 follow-up MRIs were performed, in which 17 exams utilized general anesthesia and 10 required sedation. Short-term follow-up MRIs were performed in all children, while long-term follow-up was done in 10 patients. Stated clinical indications for follow-up MRI exams included: routine follow-up in 37 exams (73%), assess response to antibiotic treatment in six exams (12%), assess spinal cord compression in two exams (4%), assess residual back pain in two exams (4%), assess potential differential diagnosis in two exams (4%), establish length of antibiotic treatment in one exam and evaluate necessity for urgent surgery in one exam. Initial and follow-up MRI features Location The distribution of affected vertebral segments in our patients was as follows: two cervical, five thoracic, five lumbar, three sacral and one each with thoracolumbar and lumbrosacral segment involvement. Specific MRI features noted at baseline and follow-up are tabulated in Table 1.
Baseline MRI (n=17 patients) 12 17 17 3 9 4 13 5 11 15 7 Short-term follow-up (n=17 patients)a 13 16 16 5 10 8 9 1 6 12 4 Long-term follow-up (n=10 patients) 1 7 7 3 7 4 3 1 3 7 1

1 follow-up MRI without contrast

b There is no disc applicable in a C1-2 case

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Fig. 2 A 2-month-old girl with blood culture positive for Staphylococcus aureus. Sagittal T2-W image shows hyperintense T7 spinal process (arrow) with epidural abscess extending from C7 to T11 level. Normal signal intensity is preserved in vertebral bodies and discs

Bone abnormalities At baseline MRI, bone marrow edema (hypointense on T1W and hyperintense on STIR/T2-W images) appeared in all 17 children. Single vertebra involvement was seen initially in five children, while involvement of two or more vertebrae was found in 12 children. No skip lesions were

seen. Bone marrow edema affected the vertebral body in 14 children, while involvement of the posterior elements alone without vertebral body involvement was seen in three children (Fig. 2). The causative organisms were S. aureus in two cases and Pseudomonas species in the other. On follow-up MRI for the five children with single vertebra involvement, bone marrow edema completely resolved in one child, remained as single vertebra involvement in two children and progressed to involve adjacent disc and vertebra in the two other children (Fig. 3). For the 12 children with two or more vertebrae involvement, marrow edema improved in seven, remained static in three, and extended to involve more of the spine in two. Bone enhancement was seen in all 17 children at baseline. On follow-up, abnormal enhancement resolved completely in one child, improved in three and remained static in eight. Worsening of bone enhancement was seen in four cases. The remaining one had no contrast agent study available. Loss of vertebral body height was seen in 3/17 children (17%) on baseline and 5/17 (29%) on follow-up. Sagittal view showed irregularity or erosion of low T2-W signal vertebral end plate (Fig. 4). Bone destruction and nearcomplete collapse of the vertebra was seen in one child on baseline and two on follow-up MRI. At baseline, facet joint involvement was noted in three children, including one with unilateral and two with bilateral involvement. On T2-W images, the affected joints appeared hyperintense with adjacent paraspinal soft-tissue abnormality and slight joint effusion (Fig. 5). There was obvious enhancement after contrast administration.

Fig. 3 A 13-year-old boy. a Diffuse L4 vertebral body shows increased signal intensity on sagittal T2-W image and b enhancement after contrast administration. Normal high signal disc and linear low signal central cleft is preserved in the L4-5 disc. c Two months later

there is improvement in the degree of vertebral body marrow edema in the L4 body with new involvement of the L5 and L4-5 discs. The boy was clinically improved at the time of this follow-up

122 Fig. 4 A 2-month-old girl with biopsy positive culture of Staphylococcus aureus. a Sagittal T2-W image shows destruction of T8, T9 and intervertebral disc with loss of vertebral body height, more so on T9. There is absence of the normal linear hypointensity of the adjacent endplates of T8 and T9. Lobulated paravertebral soft-tissue abscess is present anteriorly. b One month later sagittal T2-W image shows more extensive bone destruction with almost complete vertebral height loss in T8 and T9. Retrolisthesis and kyphosis caused canal compromise and cord compression. The girl was clinically improved at the time

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Disc abnormalities At baseline, discs adjacent to the affected bone were normal on T2-W images in 10 children (59%). Seven children

(41%) showed abnormal signal intensity on T2-W imaging, including four cases that were hypointense, two with mixed signal intensity and one with complete destruction of the interval disc. Among the seven children with abnormal T2-

Fig. 5 A 3-year-old girl with blood positive culture of a Pseudomonas species. a Axial T2-W image shows marrow edema involving the left L5 pedicle, lamina and facet joint. Joint shows irregularity. b Postcontrast axial T1-W image of the baseline MRI shows enhancement in the left posterior element of L5 and paravertebral soft tissue. There is an epidural abscess with thick-walled peripheral enhancement and

right deviation of the dural sac. c Follow-up at 2 months. Post-contrast axial T1-W image shows improvement of paraspinal and epidural enhancement without abscess. d Axial post-contrast T1-W image scanned 18 months after baseline MRI shows persistent epidural enhancement with a possible small abscess (arrow). The girl was symptom-free at the follow-up MRI

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Fig. 6 A 2-year-old girl with spondylodiscitis at L1-2 level. a Initial sagittal T2-W imaging shows diffuse marrow edema of L1-2 vertebral bodies and heterogeneity in disc signal with overall loss of disc hyperintensity and joint space. b There is no disc enhancement post-

contrast administration. c six weeks later T2-W image shows increased endplate and disc destruction with new central disc enhancement d. The girl was clinically improved at the time of follow-up

W signal intensity, five cases showed enhancement after administration of contrast agent. New disc involvement was seen in two children on follow-up MRI (Fig. 6). Disc abscess formation was seen in one child on baseline and two on follow-up MRI; they appeared as a fluid-like T2-W hyperintensity without enhancement (Fig. 7).

Epidural involvement At baseline, 13/17 children (76%) had epidural thickening or mass-like soft-tissue intensity on T1-W/T2-W imaging. Avid enhancement with thickening after contrast administration measured 219.8 mm, mean 6.1 mm. Eight children

Fig. 7 A 12-year-old girl with negative blood culture. a Sagittal T2W image shows decreased T7-8 disc space and signal intensity accompanied by adjacent endplate irregularity. b One month later sagittal T2-W image shows interruption of low signal end plates of

T7-8 and minimal body height loss. c T7-8 disc abscess appears hyperintense without enhancement on post-contrast image. The girl was clinically improved at the time. Note a syrinx at the same level of thoracic spinal cord posteriorly

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Fig. 8 A 9-year-old boy with blood culture of Staphylococcus aureus. a Baseline MRI post-contrast axial T1-W fat-saturated image shows increased enhancement in the posterior element of L4 and paravertebral soft tissue with an irregular central hypointense area

suggesting a small abscess. b Two months later post-contrast axial T1-W image shows improvement of paraspinal soft-tissue infection with complete resolution of abscess. Note involvement of bilateral facet joints

had varying degrees of spinal canal compression. Five children had epidural abscess formation ranging from 3 mm to 11.8 mm, mean 9.2 mm; they were centrally hypointense with rim enhancement on post-contrast sequences (Fig. 5). On short-term follow-up, only a 4-mm epidural abscess remained, in one child. Extent of epidural enhancement decreased, range 212.9 mm, mean 3.8 mm. Paraspinal soft-tissue involvement At baseline, 15/17 children (88%) had paraspinal soft-tissue involvement. The thickness of enhancing paraspinal soft tissue ranged from 4 mm to 60 mm, mean 16.2 mm, which enhanced intensely after contrast administration. Seven children had paraspinal abscess formation, range 2 43 mm, mean 15.6 mm (Fig. 8). Three paraspinal abscesses remained on short-term follow-up MRI; two were smaller

while the other enlarged. Paraspinal soft-tissue enhancement on follow-up MRI improved in all but one case, range 1.420 mm, mean 6.7 mm. Overall follow-up changes compared with baseline MRI Short-term (<4 months) follow-up after starting antibiotic treatment Table 2 presents the independent qualitative assessments of interval changes of individual MRI findings on the first follow-up compared with baseline MRI. Inter-observer reliability, assessed by kappa value, for each MRI finding is detailed in Table 3. The mean kappa value for all MRI findings was 0.72 (range 0.491.0). In short-term follow-up, three patterns of MR appearance were noted: (1) improvement of bone, disc and soft-tissue

Table 2 Assessment of individual MR feature changes on follow-up compared with baseline MRI Normal Case (%) Involved segment (n=17) Marrow edema (n=17) Bony enhancement (n=16)a Body height loss (n=17) Disc T2W abnormal signal (n=16)a Disc enhancement (n=15)a,b Epidural enhancement (n=16)a Epidural abscess (n=17) Canal compromise (n=17) Paraspinal enhancement (n=16)a Paraspinal abscess (n=17)
a b

Better Case (%) 4 (24) 8 (47) 4 (25) 0 1 (6) 0 12 (75) 5 (88) 7 (41) 13 (81) 6 (35)

Same Case (%) 11 (66) 5 (29) 8 (50) 2 (12) 2 (13) 0 0 0 0 0 0

Worse Case (%) 2 4 4 3 6 8 1 0 2 1 1 (12) (24) (25) (17) (38) (53) (6) (12) (6) (6)

0 0 0 12 (71) 7 (44) 7 (47) 3 (19) 12 (71) 8 (47) 2 (13) 10 (59)

1 follow-up MRI without contrast There is no disc applicable in a C1-2 case

Pediatr Radiol (2010) 40:118130 Table 3 Inter-rater comparison about changes on follow-up MR compared with baseline MR n=17a Better Rater1 Involved segment Marrow edema Bony enhancement Body height loss Disc T2-W abnormal signal Disc enhancement Epidural enhancement Epidural abscess Canal compromise Paraspinal enhancement Paraspinal abscess 4 8 5 0 1 0 12 5 7 13 6 Rater2 3 10 8 0 0 1 10 5 7 12 8 Same Rater1 11 5 8 14 10 8 3 12 8 2 10 Rater2 12 3 4 14 12 9 5 12 9 3 7 Worse Rater1 2 4 4 3 6 8 1 0 2 1 1 Rater2 2 4 4 3 5 6 1 0 1 1 2

125 Kappa

1 follow-up MRI without contrast so n=16 for bony, disc, epidural and paraspinal enhancement

0.64 0.71 0.53 1 0.53 0.76 0.73 1 0.49 0.83 0.69

appearance; (2) improvement of soft-tissue appearance but more extensive involvement of bone and/or disc; and (3) worsening of bone, disc and soft-tissue appearance. 1. Improvement of bone, disc and soft-tissue appearance In follow-up MRI, 8/17 (47%) children showed improvement including decrease in or disappearance of: (1) abnormal signal intensity and enhancement within bone marrow and disc, (2) epidural thickening and/or (3) paraspinal soft-tissue

infective changes. Clinical and laboratory results were also improved in these children. Two of these eight children had initial laminectomy for extensive epidural abscess. 2. Improvement of soft-tissue appearance but more extensive involvement of bone and/or disc In follow-up MRI, 8/17 (47%) children showed more bone and/or disc abnormalities such as increased bone marrow edema, vertebral segment involvement, end plate

Fig. 9 A 14-year-old girl with Staphylococcus aureus septicemia. Axial and sagittal postcontrast T1-W images with fat saturation in baseline MRI (a, b) and follow-up 2.5 months later (c, d) show interval improvement of paravertebral soft tissue (black arrows in a) and epidural involvement (white arrow in a). Interval irregularity of the L1-2 end plates and L1-2 disc changes are noted at follow-up with new disc enhancement (arrow in d). Clinically the girl was asymptomatic at this time

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Fig. 10 A 16-year-old boy with biopsy culture of Salmonella typhimurium. Sagittal T2-W and post-contrast axial T1-W images from baseline MRI (a, b) and short-term follow-up 1 month later (c, d) show progressive vertebral end plates of L3 and L4, and L3-4 disc destruction (c). d Increased epidural and paravertebral soft-tissue involvement with paraspinal abscess formation is present at 1-month follow-up. The boy was still febrile and had severe back pain

necessitating analgesics at the time. e At 6-month follow-up, sagittal T1-W image shows hyperintense L3-4 vertebral bodies, isointense on T2-W fat-saturation imaging (f), suggesting healing fat deposit. g Post-contrast axial T1-W image at 6 months post-treatment shows residual paraspinal soft-tissue enhancement (arrow) but complete resolution of epidural infection. The boy was asymptomatic at that time

destruction, vertebral body height loss, disc destruction, and bone and/or disc enhancement after administration of contrast agent. The epidural and paraspinal soft-tissue involvement showed variable improvement with either

disappearance or decrease of epidural and/or paraspinal abscesses (Fig. 9). Clinical and laboratory results (WBC, PMN, ESR and CRP) demonstrated improvement in these children.

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3. Worsening of bone, disc and soft-tissue appearance There was progression in epidural and paraspinal softtissue infection along with further bone and disc destruction in one child (Fig. 10). The interval time of follow-up for this child was 1 month after baseline MRI. Clinically there was no improvement, as the child remained febrile with severe back pain, necessitating analgesics at follow-up MRI. Laboratory results showed increased WBC, PMN and ESR. Long-term (>4 months) follow-up after starting antibiotic treatment Ten children (59%) had follow-up MRI greater than 4 months after baseline. In long-term follow-up, there was overall improvement in bone and soft-tissue involvement in all children. However, some residual bone, disc or soft-tissue changes were evident in some children. Marrow edema, bone enhancement and T2-W disc abnormal signal were persistently seen in seven children, range 733 months, mean 15 months, after baseline MRI. Four of these seven children demonstrated persistent disc enhancement. Loss of vertebral body height was seen in three children at 12, 15 and 33 months after baseline MRI. The near-complete destruction of vertebrae in two children with longlasting spinal misalignment required internal fixation. Three children showed patchy hyperintensity around the region of former bone destruction on T1-W imaging and isointensity on T2-W fat saturated imaging, suggestive of healing fat deposits (Fig. 10). Epidural enhancement was seen in three children, ranging from 6 to 18 months after baseline MRI. A possible small abscess and slight canal compromise was seen in one child by the time of his last follow-up MRI at 18 months after baseline (Fig. 5). The child was symptom-free at that time. Paraspinal soft-tissue enhancement was seen in seven children between 6 and 33 months, mean 14 months, after baseline MRI. A small possible abscess remained in a symptom-free child at 6 months after baseline MRI (Fig. 10). Impact on clinical treatment Extension of antibiotic treatment occurred in 8/17 (47%) children, based in part on abnormal findings on follow-up MRI including prolonged bone, disc or soft-tissue enhancement, despite the children being clinically asymptomatic. The elongation of antibiotic treatment ranged from 2 weeks to 8 months, mean 3.6 months.

Discussion Spondylodiscitis accounts for 24% of all infectious bone diseases [11, 12]. It is even less common in children. However, pediatric pyogenic spinal infection can cause severe and long-lasting neurologic complications. Tuberculosis used to be the predominant form of spondylodiscitis, but nontuberculous pyogenic spine infections have been increasingly noted [13] and are responsible for approximately 2% of all juvenile bone infections [14]. Our study demonstrated a bimodal age distribution for spinal infection (<3 years of age and 916 years of age), consistent with results from a previous study [15]. Predisposing conditions were not uncommon and included patent ductus arteriosus, hereditary spherocytosis, trisomy 6 and psoriasis. Other risk factors include long-term steroid treatment, immunosuppression, sickle cell disease, infection elsewhere and spinal instrumentation [16]. Lumbar spine is most commonly affected, followed by the thoracic segment. Staphylococcus aureus is the most common bacterium to cause spondylodiscitis [11, 12]. It accounted for 67% of our culture-positive cases. It is also most likely to be responsible for epidural abscesses [17]. MRI is the modality of choice, with a sensitivity of 96%, specificity of 92%, and accuracy of 94% in the assessment of vertebral osteomyelitis [18]. MRI is particularly useful in the detection of epidural abscess as compared to bone scan and/or radiograph. For the younger patient whose clinical presentation is nonspecific, MRI can hasten correct diagnosis and treatment by detecting infection and its extent. Contrast enhancement has been recommended at baseline and in follow-up to better delineate soft-tissue changes. Our study showed the typical MRI features of spinal infection at baseline exam as described in the literature [15, 16]: bone marrow edema, end plate irregularity, bone and adjacent disc destruction, and epidural and paraspinal soft-tissue infection. These imaging features are usually diagnostic, especially with disc involvement and paraspinal and/or epidural abscess. Paraspinal and/or epidural soft-tissue inflammatory changes have a 98% sensitivity for infection [19]. Post-contrast fat-saturated T1-W imaging is helpful in delineating epidural abscess formation. Spinal infection can involve only one vertebral body early on and later extend to involve its adjacent disc and nearby vertebral bodies. We saw this in two children. Sometimes the affected bone structure is confined to the posterior element only, without any vertebral body involvement. This phenomenon appeared in 3/17 of our cases. Unilateral or bilateral facet joints can be affected along with paraspinal soft-tissue infection.

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Epidural and/or paraspinal soft-tissue involvement Follow-up MRI can help in monitoring the response to treatment. Our study showed that reduction of epidural and/ or paraspinal soft-tissue inflammation is the earliest sign of improvement compared to bone and/or disc changes after initiation of antibiotic treatment. This concurs with adult studies. Veillard et al. [20] pointed out in a prospective study of 16 cases that the reduction in paravertebral and in epidural abscesses were the only two features that improved on follow-up MRI 1 month after the start of antimicrobial therapy. Similarly, Kowalski et al.s study [9] used associated soft-tissue changes only as the single grading scale to assess the risk of treatment failure on follow-up MRI for patients with spinal infection. Further, epidural and/or paraspinal soft-tissue infection correlated better with our patients clinical status than with bone and/or disc destruction. Most of our patients demonstrated quick reduction of epidural and paraspinal soft-tissue change. However, three children had residual epidural enhancement and seven children had prolonged residual paraspinal soft-tissue enhancement ranging from 6 to 33 months after baseline MRI. Chart review at the time of MRI follow-up showed no fever, pain or any movement limitation. This suggests granulation tissue formation post-infection rather than an active infectious process. Our only case with clinical deterioration at the time of 1month follow-up MRI demonstrated worsening of soft-tissue infection, with abscess formation and further destruction of the vertebral body and intervertebral disc. His subsequent follow-up MRIs at 12 and 14 months showed overall improvement although marrow edema, bone enhancement and abnormal T2-W disc signal were still present. The epidural and paraspinal soft-tissue infection had disappeared and the child was asymptomatic. Bone and disc involvement Our study showed that bone and disc MRI abnormalities can persist or show short-term worsening despite clinical and laboratory improvement in response to antibiotics. This is supported by Zarrouk et al.s [21] prospective study in adults wherein 94% of follow-up MRIs at 3 months after onset of disease had vertebral destruction, with 39% showing worse vertebral destruction compared to baseline MRI. Bone destruction was still present in all of their 22 cases at 6-month follow-up MRI. Where follow-up MRI is not necessary Although MRI is essential for initial diagnosis, our study demonstrates that serial routine follow-up MRIs to assess

treatment response are not necessary for the vast majority of cases. Follow-up MRI is not needed for patients with good clinical response. These patients should be followed clinically and/or with laboratory tests. Ultimately, decisions about treatment should be based on clinical status and not MRI findings. A potential negative impact of follow-up MRI on management in our study was the extension of antibiotic treatment. In 47% of our cases, antibiotic treatment was extended at least in part because the follow-up MRI showed prolonged bone, disc or soft-tissue enhancement despite the patients being clinically symptom free. Roblot et al. [7] reported that short-duration ( 6 weeks) antibiotic therapy does not enhance the risk of spinal infection relapse compared to 3 months or longer duration. In other words, the patients clinical presentation and illness course, rather than the follow-up MRI, should be considered when deciding the length of antibiotic treatment. Indications for follow-up MRI For patients with unsatisfactory clinical response to antibiotics, MRI can help reevaluate the extent of infection, in particular to delineate the presence and extent of epidural abscess and spinal cord or canal compression (Fig. 4). Prompt diagnosis and combined antibiotic and/or surgical treatment help to prevent adverse outcomes, so follow-up MRI is essential in cases with poor clinical response. In the pediatric population, especially for younger children, MRI often needs to be done under general anesthesia or sedation. In our study, 33 of the 51 followup MRI exams were performed on seven children younger than 3 years with multiple general anesthesia and/or sedation. Except for one follow-up MRI exam requested to evaluate spinal cord compression caused by misalignment of the spine, the remaining MRIs were routine followups to assess the response to treatment. Therefore, 41% of our patients accounted for 65% of the follow-up MRIs. This disproportionate number of follow-up MRIs performed on children <3 years of age might be a result of the fact that these children are too young to articulate their symptoms, which makes it difficult for the treating physician to make a clinical judgment about treatment response. In these cases, follow-up MRI is recommended. Timing of MRI follow-up The appearance of spinal infection will vary depending on the timing of follow-up MRI. Kowalski et al. [9] showed that imaging studies performed less than 4 weeks after diagnosis and initial treatment are more likely to show unimproved or worse bone involvement and thus might overestimate the risk of treatment failure. The follow-up

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MRI for the only child in our study with clinical deterioration also had deteriorating bone involvement. However, he also had deteriorating disc and soft-tissue involvement at 1 month after baseline MRI. His subsequent long-term follow-up MRIs showed continuous improvement in bone, disc and soft-tissue changes. Our study shows that long-term (>4 months) follow-up MRI should not be used to determine response to treatment. Neither residual bone nor soft-tissue changes correlated with clinical symptoms in long-term follow-up. The most useful follow-up MRI is conducted between 1 and 4 months, with emphasis on soft-tissue involvement. One should be cautious not to over-interpret progressive bone changes with improving soft-tissue involvement as disease progression. Such inappropriate interpretation of follow-up MRI findings can cause overestimation of the severity of the disease and precipitate unnecessary treatment. Limited follow-up MRI Whole spine MRI can rule out multifocal spinal involvement, which is helpful to distinguish other infectious or inflammatory spondylitis, and should be performed at baseline. For follow-up, however, the value of whole spine MRI is less certain. None of the 35 whole spine scans in our follow-up study showed any additional lesions. Therefore, limited spine MRI is recommended at follow-up to the region of interest, when indicated, to reduce the time of scan and general anesthesia, unless disease progression is suspected. Limitations of our study

to examine the value, indications, timing and frequency of follow-up MRI in the management of children with spinal infection.

Conclusion Epidural and paravertebral soft-tissue changes on shortterm follow-up MRI correlated better with patients clinical symptoms compared to bone and disc destruction. Bone and disc changes can appear to progress more so than softtissue infection despite adequate clinical response to therapy. Although MRI is essential for initial diagnosis, serial routine follow-up MRIs were not necessary for the vast majority of cases. Follow-up MRI is not needed for patients with good clinical response; these patients should be followed clinically and/or with laboratory markers of inflammation. The segment of the pediatric population that might benefit from follow-up MRI includes those who deteriorate clinically and those too young for clinical response to be accurately assessed. If follow-up MRI is indicated, localized spine rather than whole spine scan is recommended unless disease extension beyond the original focus is suspected. Further, for follow-up MRIs conducted between 1 and 4 months, soft-tissue involvement should be the focus rather than bone changes. Long-term follow-up MRI is not necessary. Treatment decisions, including elongation of antibiotic course, should be made based on initial presentation and clinical response rather than on long-term follow-up MRI findings.

References The main limitations of this study are its retrospective nature and small sample size. The imaging analysis was based on the data available at the time of study. The time of follow-up MRI exam was variable based on access to MR imaging and decision making of the treating physicians. The inter-observer agreement was calculated by means of kappa statistics. The interpretation of kappa value for individual MRI features varied from 0.49 to 1, or from moderate agreement, substantial agreement to almost perfect agreement according to Landis and Koch [22]. Assessment for vertebral body height loss and epidural abscess had perfect agreement while assessment for canal compromise had moderate agreement. Although the median kappa value was acceptable, our inter-observer agreement could have likely been improved if readers had a pretest to reach consensus before independent case review. Although the sample size of our study is small, it reflects the largest single institution sample to date. Further prospective and multidisciplinary studies can be undertaken
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