The etiologies and prognosis associated with spinal cord infarction

Study design and patient population

We retrospectively analyzed the clinical presentations, initial neurological examinations, MRI features, and CSF profiles of a total of 38 patients with SCI enrolled from 2002 to 2018. The study protocol was approved by the institutional review board of the Chang Gung Memorial Hospital (IRB number: 201800769B0). All methods were performed in accordance with the relevant guidelines and regulations. Seven patients were excluded from this study due to a lack of complete clinical information or imaging data, leaving a final total of 31 patients in the analyses. We recorded demographic characteristics, medical histories, and information on clinical presentations, including temporal profiles, initial symptoms, the presence of acute focal pain adjacent to the spinal cord lesion, and neurologic examinations. CSF and MRI features, including the topography of the lesions at the initial assessment, were analyzed. The diagnosis of SCI was rendered based on the diagnostic criteria proposed by Zalewski et al.12 Briefly, acute nontraumatic myelopathy defined by onset to the nadir of clinical presentations within 12 h or less was mandatory and was combined with the corresponding MRI and/or CSF findings. Finally, three levels of diagnostic confidence in SCI were made: definite, probable, and possible SCI.

The temporal profiles covering the time from the initial symptom onset to the nadir of neurologic dysfunction were classified as sudden (<30 min), acute (30 min – 4 h), and subacute (>4 h) patterns. The nadir was defined as the point of the worst neurologic function before improvement or plateau was achieved and was based on the patient’s history and neurologic examinations. For each limb, a Medical Research Council (MRC) score (range, 0 to 5) was assigned to represent the muscle power in that limb. The muscle power values in the upper and lower limbs were measured by averaging the MRC scores of both sides. The total muscle power in all four limbs was calculated by summing the four-limb MRC scores. Associated medial history information, such as vascular risk factors (hypertension, diabetes mellitus, and dyslipidemia), previous trauma, and prior fever or upper respiratory tract infections, was also recorded. CSF profiles, including pleocytosis, sugar and protein levels, immunoglobulin G index, and oligoclonal band (OCB) measurements, were documented. Serum anti-aquaporin-4 (AQP4) antibody testing was performed by enzyme-linked immunosorbent assay (ELISA).13 We used modified Rankin scale (mRS) scores to compare the 1-month outcomes of patients with SCI.14 We classified outcomes with grades 0–3 as good prognoses and those with grades of 4–5 as a bad prognosis.

Evaluation of MRI parameters

MRIs of the spine obtained within 2 weeks of admission were reviewed by a board-certified neuroradiologist who was blinded to the clinical diagnosis. All studies included axial and sagittal T1- and T2-weighted sequences of spine images. The length of each lesion was measured by the sagittal extension of T2-hyperintense areas using the number of vertebral body spans. We defined long-segment lesions as longitudinal extension of lesions covering ≥ 3vertebral body spans and short-segment lesions as longitudinal extension of lesions covering < 3 vertebral body spans. The location of each lesion was recorded according to the vertebral body level (e.g., cervical, thoracic, or lumbar). Owl’s eyes sign and adjacent vertebral body infarction were also recorded.6, 15 Gadolinium enhancement [Gd+] on T1-weighted images was recorded as present or absent. The midpoint of each lesion was characterized using axial T2-weighted images. The distribution of the lesions in cross-sections of the spinal cord was classified as anterior, posterior, lateral, and central. In addition, the vascular territory of the spinal cord was used as a fit for the artery infarction observed in patients with SCI (e.g., ASA, PSA, spinal sulcal artery (SSA), or both ASA and PSA).10

Statistical analyses

All statistical analyses were performed using SPSS (version 21.0; IBM). Continuous variables are expressed as the means ± standard deviations. Categorical variables are presented as numbers and ratios. Independent t-tests were performed to compare mean ages between groups. Chi-squared tests, Fisher’s exact tests, and Mann–Whitney U tests were used to compare patients with and without vessel dissection in terms of sex, clinical presentations, 1-month outcomes, and imaging characteristics. Logistic regression was used to study the associations between 1-month outcomes and MRI features. Statistical significance was defined as P < 0.05.

Clinical and imaging features in SCI patients with vessel dissection

Table 2 shows the detailed comparisons between these two groups. The age of onset was significantly younger in SCI patients with vessel dissection than in those without (P < 0.05). The timing of performing MRI from the onset was longer in SCI patients with vessel dissection group (P = 0.03). There were no significant differences in sex, vascular risk factors, temporal profiles, focal pain adjacent to the lesion, muscle power in all limbs, and clinical outcomes after 1 month. A borderline difference in sphincter incontinence was noted between the groups (P = 0.05). Table 3 shows the differences in MRI features between SCI patients with and without vessel dissection. The mean value of the longitudinal extension of lesions in SCI patients with vessel dissection was 4.3 (range 3–10) vertebral body spans, while that in those without vessel dissection was 3.3 (range 1–8) vertebral body spans. Although the Mann–Whitney U test showed no significant group difference in the lengths of lesions based on the number of vertebral body spans (P = 0.06), we found that the proportion of patients with long-segment lesions was significantly higher in the vessel dissection group than in the nondissection group (Fisher’s exact test P = 0.03). In addition, the proportion of patients with an axial posterior pattern was significantly higher in the vessel dissection group (Fisher’s exact test P < 0.05), indicating the involvement of the PSA territory. Figure 2 demonstrates the number of cases and the ratio of lesions at the different vertebral body levels in SCI patients with a history of vessel dissection. In the vessel dissection group, patients frequently had lesions involving the upper cervical (C1–C4) and lower thoracic (T10–T12) vertebral body levels. In contrast, patients without vessel dissection more frequently had lesions distributed in the cervical regions (C5–T7) than in the thoraco-lumbar regions (Fig. 2B).

Clinical and imaging features of SCI without vessel dissection

Compared with SCI patients with vessel dissection, in those without, the longitudinal extension of lesions covered a broader range of vertebral body spans (range, 1–8). We divided these patients into short- and long-segment lesion groups and compared their clinical and imaging presentations. In the whole group, there was a significant association between the lengths of lesions and 1-month outcomes (a binary measure) in a logistic regression (P = 0.03). There was a trend toward a higher proportion of patients reporting focal pain adjacent to the lesion (Fisher’s exact test P = 0.05) and significantly poorer 1-month outcomes (Mann–Whitney U tests P = 0.04) in the long-segment group than in the short-segment group. The etiologies of the SCI observed in the long-segment group were very heterogeneous. Two cases had postoperative abdominal aortic aneurysms, two had coagulopathy related to bladder cancer or liver cirrhosis, four had diabetes mellitus, one had systemic lupus erythematosus, and one had pulmonary emboli. Only 12 patients with SCI underwent CSF studies, and all of these were in the nondissection group. The median cell count was one lymphocyte without red blood cells. The median values for CSF glucose levels and protein were 76 mg/dL and 49 mg/dL, respectively. There was no significant difference in CSF parameters between the two groups. Two cases received serum anti-AQP4 antibody testing, and the results were within a normal range.

Vessel dissection disrupts the longitudinal and axial blood supply

Our findings suggest that vessel dissection can directly disrupt the blood supply in both the horizontal and longitudinal axes. Figure 3A illustrates the anatomy of the cord, vertebrae, and major vessels under normal conditions.9 The radicular arteries originate from the vertebral artery or posterior intercostal arteries of the aorta and enter the spinal foramen before branching off to form the anterior and posterior radicular arteries, which anastomose to the ASA and PSAs, respectively. After parent vessel dissection, the orifices of the radicular arteries can become blocked, interrupting the blood supply to the spinal cord from the anterior to posterior aspects. In cases with longitudinal extension of the vessel dissection, both the upper and lower segments of the radicular arteries could be involved, leading to the breakdown of the longitudinal blood supply in the spinal cord (Fig. 3B).

The timing of performing an MRI may be associated with the lesion length. Early imaging may reveal a normal MRI or a short lesion before evolving to a long lesion. Our results showed a longer time between performing an MRI and the onset of SCI in the dissection group, which might be due to the fact that four patients with aortic dissection immediately received surgery, thus delaying the time of the MRI scan. After excluding these four patients, there was no significant group difference in the time between performing an MRI and onset (SCI with vessel dissection: SCI without vessel dissection = 4.5 ± 6.4: 3.0 ± 1.0 days, P = 0.43).

PSA infarction in SCI

Pure PSA infarction in SCI is relatively rare based on previous case studies.16-18 Multiple etiologies of PSA infarction have been previously reported; these include atherosclerosis,17, 19 fibrocartilaginous embolization,20 head injury,21 or mitral valve strands22. In a recent study that comprised the largest series of PSA infarctions (133 patients with SCI), 15 (11%), patients had a spontaneous PSA infarction.23 This figure suggests that the diagnosis of PSA infarction might be underrecognized in SCI.17 In the current study, acute onset large-fiber sensory impairment was found in all cases and was associated with weakness in 73% of the patients; this finding may have been related to the heterogeneous spinal arterial territories or initial coexisting ASA ischemia. Fourteen patients (93%) had vascular risk factors, such as dyslipidemia, hypertension, smoking, and diabetes mellitus. Approximately, 60% of the patients had long segments of vertebral body spans in the cervical or thoracic regions. The prognoses of these patient were good, and 93% of them were ambulatory. In our study, the only pure PSA infarction case (3.2%) in SCI was a 37-year-old male with left-side vertebral artery dissection demonstrated by angiography. The lesion extended from the occipital to the C2 vertebral body level. The 1-month outcome of this patient was good (grade 3 mRS score). Other patients with PSA involvement were associated with ASA infarction.

Possible etiologies are related to longitudinal extension of SCI

Numerous etiologies have been implicated in SCI; these include aortic disease,24 vertebral dissection,25 arterial or cardiac embolism,26 fibrocartilaginous embolism,20, 27 hypercoagulopathy,28 decompression sickness, vasculitis,29 systemic hypotension or global hypoperfusion from cardiac arrest,30 and radicular artery compression from a disc.31 Local or global hypoperfusion in the border zone area between the intrinsic and extrinsic spinal artery systems is often manifested in the anterior horns because of the gray matter and because motoneurons are notably more vulnerable to anoxia. Thus, the typical MRI features of SCI show bilateral hyperintense lesions on the axial T2-weighted sequence in the region of the anterior horns, illustrating the owl’s eyes configuration.10 Findings from previous studies indicated that the average length of SCI was approximately three vertebral body spans and that long cord lesions were associated with poorer outcomes.11, 25, 32 Approximately, 50–60% of SCI cases had lesions longer than three vertebral body spans.5, 11 In our study, we also found a similar proportion of long-segment lesions in patients with SCI without vessel dissection (58%). Worse 1-month outcomes were associated with long-segment lesions in patients without vessel dissection. Although vessel dissection may explain the longitudinal extension of SCI, other factors may also be present in SCI. We explored factors potentially associated with the longitudinal extension of SCI in our group. Thromboembolism (atheromatous plaque in the aorta or pulmonary emboli), coagulopathy (malignancy, liver cirrhosis, and hemodialysis), and diabetes mellitus contributed to 61% of our SCI patients in the no-dissection group with long-segment lesions. Interestingly, all of these patients were ASA infarction patients. In the short-segment group, the most common etiology of SCI was hypertension.

Vessel dissection can be recognized by modern imaging tools

Dissection has often been considered a single entity in previous reports, and the diagnosis is typically made by various imaging findings, including the absence of vertebral flow; stenosis of the vertebral artery; or the presence of a dissection flap, an intraluminal thrombus, a pseudoaneurysm, or an intramural hematoma.33 Using conventional MRI and MR angiography to study vertebral artery dissection, it was shown that the sensitivity ranged from 95% to 100%, and the specificity ranged from 67% to 99%. The CT angiography also showed a sensitivity ranging from 64% to 100%, and the specificity ranged from 82% to 95%.34 Both CT angiography and MR angiography can effectively visualize vertebral artery dissection; however, CT angiography can be performed rapidly, and it allows simple reconstruction of the dissection artery in an acute setting.35 Recently, it was shown that using the heavily T1-weighted sequence on MRI could increase the reliability of detection of intramural hematoma compared with using the T1-fat saturation method, which could improve the accuracy of vertebral artery dissection diagnosis.36 In aortic dissection, multi-detector row CT is the modality of choice for imaging acute aortic syndrome with a sensitivity and specificity approaching 100%.37