The demographic characteristics of the 9 included patients (5 men and 4 women) are summarized in Table 1. The mean age of the patients (± standard deviation) was 61 ± 12.2 years (range, 41 to 78 years). The interval between initial diagnosis and hospitalization ranged from 10 days to 4 years (average, 10.7 months). All patients experienced a gradual onset of symptoms and showed a slowly progressive clinical course; no patient experienced an acute onset of symptoms. The clinical manifestations included limb motor deficits causing poor muscle power and weakness in 5 patients (55.6%), sphincter disturbances resulting in urinary dysfunction and abdominal distension in 2 patients (22.2%), and sensory dysfunction triggering paresthesia and/or hypoesthesia in 7 patients (77.8%). Myelopathic signs were noted in 8 patients (88.9%), and radicular symptoms were recorded in 3 patients (33.3%).

All patients underwent preoperative MRI with and without contrast (Table 2, Figures 1–4). Eight lesions were identified in the dorsal spinal canals (88.9%), and 1 lesion was located on the right of the spinal cord (11.11%; Figure 2). In 7 cases, the lesions extended into the intervertebral foramen (77.8%); Figuress 1E, 2B, 3E, and 4F), and vertebral destruction was observed in 3 cases (33.3%; arrow marks in Figures 2B and 4E). In 4 cases, abnormal intramedullary signals were observed (44.4%; Figures 1C and 3B). On T1WI, 6 lesions appeared isointense (66.7%) and 3 were hypointense (33.3%). On T2WI, 8 lesions exhibited hyperintense signals (88.9%) and 1 appeared heterogeneously intense (11.1%; Figure 2B). On fat-saturated T2WI, 8 lesions showed hyperintense signals and 1 lesion showed hypo- and hyperintense signal because of intralesional hemorrhage (Figure 4D). Following gadolinium administration, 5 lesions appeared homogeneous with significant enhancement (55.6%), 3 appeared homogeneous with mild enhancement (33.3%), and 1 appeared heterogeneous with significant enhancement (Case 2; 11.1%). In both Cases 1 and 5, a lesion was detected in the 8^th thoracic vertebra, with mild hyperintense signals on T1WI and hyperintense signals on T2WI (arrow; Figure 4B). After gadolinium enhancement, the lesion presented significant enhancement in Case 1 (Figure 1G); however, Case 5 did not show any enhancement (Figure 4D). Imaging diagnosis confirmed vertebral hemangioma in both cases.

The preoperative diagnosis indicated schwannomas in 5 cases (55.6%), ECH in 3 cases (33.3%), and meningioma in 1 case (11.1%).

All patients underwent early microsurgery under neuronavigation and electrophysiological monitoring. All microsurgeries were performed in the lateral position via the posterior midline approach. Five patients underwent total laminectomy (55.6%), and 4 underwent hemilaminectomy (44.4%). The lesions were always well-circumscribed, reddish, dark reddish, or purplish-red in color, and of a soft consistency. The blood supply was moderate to rich. Anatomically, abnormal proliferation of vascular malformation was usually detected, and prominent small feeding arteries and draining veins were visible. Notably, bleeding on contact with the instrument was a predominant characteristic of lesions. The surface of the lesions was coagulated to cause shrinkage of lesions, which facilitated the careful resection of the lesion. Complete lesion resection was achieved in all cases.

In this case series, the lesions comprised of mature thin-walled blood vessels and sinuses were filled with blood and thrombi in varying degrees (Figure 5). In Case 2, further immunohistochemical examination revealed positive immunostaining for CD34 (Figure 5E) and D2-40 (Figure 5F). CD34, as an endothelial cell marker, is usually used in the diagnosis of tumors derived from vascular endothelial cells. D2-40 is expressed on the surface of lymphatic endothelial cells and mesothelial cells to identify whether there are lymphatic vessels in the lesion.

Postoperative follow-up was achieved in all 9 patients, with an average follow-up duration of 55.1 months (range, 10–123 months; Table 3). Periodical follow-up MRI revealed no recurrence in any patient. Frankel Grade C was observed in 1 case, Grade D in 6 cases, and Grade E in 2 cases, postoperatively. In addition, all cases recovered to Frankel Grade E until the last follow-up in May 2020. Furthermore, limb motor functions returned to normal, resulting in improvements in activities of daily living.

Although the pathogenesis of ECH remains elusive, the development and progression of these entities can be aggravated by the presence of certain predisposing conditions, including pregnancy (2, 7), trauma (18), excessive exercise (16), use of anticoagulants (15), and irradiation (16). In the present study, only Case 8 had a history of falls, and the symptoms gradually intensified within a month. However, in other patients, no such predisposing factors were observed. Thus, various different hypotheses have been proposed to explain the formation of ECHs; however, the specific pathogenesis remains unclear. The blood vessel progenitor dysplasia theory suggested the involvement of progenitor cells in the pathogenesis of these vascular entities (23, 24). Some studies speculated that these lesions originate from the dysplasia vessel-forming mesoderm (23). According to this hypothesis, when the embryonic primordial vessels cannot completely differentiate, ECH may occur (23, 25). Furthermore, the telangiectasia theory assumed that a vascular malformation develops from telangiectasia, which gradually increases in size (26). The third hypothesis is the hereditary theory. The familial occurrences and inheritance studies of these lesions have indicated that ECH might be a hereditary disease with a possible genetic association (23, 27), and some studies have postulated that it is inherited as an autosomal dominant trait with variable expression (10). In our study, we observed two cases of pure ECH combined with vertebral hemangioma, which further support this hypothesis.

In addition, to some extent, pregnancy may explain the female predisposition as pregnancy is considered to be a significant risk factor for the development of neurological signs and symptoms in cases with dormant hemangiomas. Conceivably, gravid uterus impedes the blood flow from the paravertebral veins into the inferior vena cava. The increasing venous pressure can cause the distension of the vascular channels in epidural hemangiomas, leading to a rapid increase in their sizes (3, 7). This is the most critical phenomena contributing to the clinical manifestation of pregnancy-induced symptoms. Furthermore, it can also explain the relatively acute onset of symptoms in the third trimester, as the rapidly enlarging uterus increases the intraabdominal and intrathoracic pressure (28). Symptoms may resolve in the early postpartum period, as a result of the rapid decrease in the pressure caused by the gravid uterus and the correction of the venous blood flow reversal (28). In contrast, the overexpression of angiogenic factors during embryogenesis enhances the occurrence of ECH (29). Estrogen has also been well-recognized to play a crucial role in the development of these lesions by directly acting upon the endothelium of the vascular channels (30, 31). No gestational women were reported to have ECH in our case series; however, ECH during pregnancy has been reported in 8 cases previously (2, 7, 21, 28–32).

The clinical presentations are primarily determined by the localization, growth rate, and intra- or extra-lesion hemorrhage of the malformation (10, 33). Generally, ECHs present with chronic progressive myelopathy and/or radiculopathy (1, 10, 11, 17), and the myelopathy seems more frequent than the radiculopathy (15). This might be attributable to a better capacity of nerve roots, contrary to the spinal cord, to tolerate long-term soft compression (2, 15). Myelopathy was observed in 8 cases (except Case 2), and radiculopathy was noted in 3 cases (Case 3, 5, and 9) in our study. Moreover, an acute presentation (11% to 21% of cases) could always be observed presenting with a sudden onset of severe local pain, followed by the rapid development of paralysis, sensory level, and urinary/fecal incontinence (3, 15, 21). The sudden onset of symptoms is always secondary to the significant enlargement of the lesion by intralesional hemorrhage, thrombosis, increased vascularization caused by hormonal effects, or mechanical venous occlusion (18, 23, 34, 35), and the resulting motor deficits are severe (8, 10, 36). Notably, acute hemorrhage often leads to severe cord damage, requiring emergency surgery to decompress and stabilize the spine; nevertheless, in these cases, even complete lesion resection cannot reverse all preoperative myelopathic symptoms, and the prognosis remains poor (4, 15, 19, 37). However, no acute course was found in our study, and early surgery resulted in a significant improvement in all patients. Sphincter dysfunction has also been cited as a late clinical finding in ECHs (9, 38), which was present in 2 cases in our study (Case 1 and 8). Kuytu et al. also presented that in cases with thoracal and lumbar ECHs, a gradual incidence of neurological deficits is more common, whereas in cases with cervical ECHs, a sudden deficit is more frequent (11).

MRI is an extremely valuable and accurate preoperative investigation tool for assessing ECHs, and helps assess the location and the relationship of the lesion with the surrounding anatomical structures; thus, it is crucial for surgical planning (11, 18). Computed tomography (CT) is also useful for delineating the connections with the surrounding bone or extension into vertebral foramina (1, 18). ECHs always present characteristic lobulated-shaped or spindle-shaped masses filling the epidural space around the spinal cord, with two tapered ends (19, 39). Furthermore, the lesions most often involve multiple vertebral segments, in contrast to arteriovenous malformations, which typically occur at one vertebral segment and usually exhibit a flow void signal on MRI because of high blood velocity (16, 40). In our study, all lesions involved two or more segments. Intervertebral foramen extension is observed frequently and is usually isolated (36), which might be because of the loose tissue structure inside the neural foramina (15, 16, 41); however, pure foraminal and extraforaminal ECH are extremely rare (16). Seven cases presented with intervertebral foramen extension in our study; however, no case of pure foraminal ECH was observed. In addition, pure ECHs rarely cause vertebral destruction (16), which is an occasional observation in cases of recurrence (15). However, in this study, vertebral destruction was observed in 3 cases (Case 2, 5, and 7). In previous studies, homogeneous hypo- to isointensity signals were usually observed in the spinal cord on T1WI with hyperintense signals on T2WI, because of slow blood flow, together with an intense homogeneous signal on contrast enhancement (1, 3, 11, 22, 35). Besides, lesions with hemorrhage, liquefaction of a hematoma, or intravascular thrombosis can always show heterogeneous enhancement (9, 16). In this study, 5 cases exhibited homogeneous enhancement, and 4 cases showed heterogeneous enhancement. For hemorrhagic ECHs, hyperintense signals are seen on both T1WI and T2WI in the acute stage (18, 23). ECHs extending through the intervertebral foramen into the extraspinal region assume an “hourglass” or “dumbbell” shape on axial MRI (Figure 2C) (3, 36), and are almost always misdiagnosed as schwannomas, which was the most common preoperative differential diagnosis in this study (5 cases, 55.6%). However, notably, schwannomas exhibit heterogeneous signal intensity, particularly on enhanced MRI (3), and are frequently associated with cystic changes (15). Furthermore, schwannomas always present with an enlarged foramen because of the compression of the adjacent bone (3, 15). Meningioma is another common differential diagnosis, which typically shows as isointense to the cortex on T1WI and T2WI and shows strong homogeneous enhancement with a dura tail sign on post-contrast imaging (16). Peripheral fat tissue is another characteristic finding for differentiating ECHs from the epidural hemorrhagic mass, which is an acute entity and lacks peripheral fat tissue (arrow in Figures 1A and B) (3). Also, intramedullary hemangiomas always exhibit a mixed signal with a hyperintense hemosiderin ring on T2WI because of repeated bleeding, which is usually not observed in ECHs (16, 17, 19). This might be attributed to the easier elimination of peripheral hemosiderin outside the blood–brain barrier given a richer vascularity of epidural lesions (7, 15, 42).

Previous reports have described a wide-ranging differential diagnosis for ECH, including meningiomas, neurinomas, neurofibromas, schwannomas, metastases, angiolipomas, lymphomas, and also disc herniation, synovial cyst, granulomatous infection, pure epidural hematoma, extramedullary hematopoiesis, and spinal canal stenosis (1, 2, 11, 18, 39, 43). In this review, we do not intend to discuss these diagnoses in detail. Lymphoma usually presents with an isointense signal on T2WI and exhibits less frequent paravertebral extension and intervertebral neural foraminal widening (15). Angiolipoma is typically hyperintense on T1WI because of its fat content, whereas the fat in ECH is usually absent and located at the periphery (15, 44). Angiography does not usually detect ECHs (36), and digital subtraction angiography (DSA) has no role in the management of ECHs as these lesions fail to show up on angiography because of their slow blood flow and cannot be embolized (1, 12, 18, 45). However, DSA can be performed in patients with acute symptom onset caused by hemorrhage to rule out other vascular malformations if the patient’s condition allows for imaging and the patient shows nontypical imaging characteristics (21). Arteriovenous malformations always present with flow void signal on MRI because of high-velocity blood flow (15). Notably, an urgent exploratory laminectomy/decompression should be performed on the appearance of acute paraplegia, and DSA should not delay the surgery (33). However, no spinal CT or DSA was performed in our study.

Histopathologically, the lesions were comprised of mature thin-walled vessels lined with endothelium and intervening loose connective and adipose tissue (12, 23, 34, 36, 40). The walls of vessels are predominantly lined with single layers of flattened endothelial cells in collagenous tissue without elastic and muscular tissue or neurons (12, 18, 23, 34, 36). Thrombosis and previous residual hemorrhages could also be observed within cavernous hemangioma, particularly in more extensive lesions (18, 30, 37).

The prognosis of patients with ECH is generally good, with a recovery rate of up to 92% (48). In our study, the median follow-up duration was 47 months, with seven of the nine cases having a follow-up period of more than 3 years, and no recurrence was observed during follow-up MRI. All patients experienced gradual neurological improvement and a good outcome. These results indicated that surgical intervention was effective (9, 16). Notably, the severity of preoperative neurologic condition appears to be the most significant prognostic factor (1), and severe cord damage resulting from acute hemorrhage may correlate with a poor functional prognosis or adversely influence the outcome (1, 15). Therefore, early surgical treatment is recommended to prevent irreversible neurological damage (17). However, it is also worthwhile to further evaluate surgical opportunities in asymptomatic patients with large epidural cavernous hemangiomas (15). Thus far, the potential for malignant transformation of ECHs has not been reported in the literature (48).