This study was designed as a cross-sectional study to investigate the incidence of CVD among patients with leg pain visiting a spine center and to compare it with lumbar spinal disease. It was approved by the local ethics committee (PSSH 0475-202207-HR-10) of the Pohang Strokes and Spine Hospital in July 2022. All methods were carried out in accordance with relevant guidelines and regulations and informed consent was obtained from all subjects and/or their legal guardians.
The inclusion criteria were based on patients’ symptoms and history of illness. Patients were included if they experienced leg pain combined with common clinical features of CVD, such as atypical radiculopathy mismatching dermatome level, cutaneous changes like telangiectasia, reticular veins or varicose changes, cramping, coldness, morning heaviness, nocturnal aggravation of symptoms, and chronic leg pain persisting over years.
The exclusion criteria were applied to patients presenting with definite radiculopathy symptoms and root irritation signs examined by straight leg raising test and femoral nerve stretching test, along with corresponding motor weakness. Cases with a history or diagnosis of arterial occlusion or deep vein thrombosis in the lower extremities were also excluded.
A total of 196 patients were recruited and underwent lower extremity ultrasound examinations from January to December 2021. All ultrasound examinations were performed by the first author, who had more than six months of experience in CVD ultrasound diagnosis.
The sample size of 196 patients was smaller than the calculated value for a 95% confidence level and a 5% margin of error. However, it was deemed to sufficient to provide initial insights into the study objectives.
The CEAP grade is a well-known clinical grade system for CVD that classifies it as follows: C0: no visible or palpable signs, C1: telangiectasias (veins less than < 1mm), reticular veins (1–3 mm in diameter), C2: varicose veins (> 3mm), C3: edema, C4: secondary skin alterations. C4a: pigmentation and eczema, C4b: lipodermatosclerosis or white atrophy, C5: healed ulcer, and C6: open ulcer 5. All patients’ CEAP grades were recorded and classified.
The areas of symptom complaints were classified as low back, buttock, thigh, knee, calf, and foot. The types of symptoms were classified as pain, tingling-paresthesia, hypoesthesia, cramping, coldness, heat, swelling, and weakness. Each patient could have more than one symptom area and type of symptom manifestation.
The CVD diagnosis groups were classified according to the ultrasound findings, which were classified as follows: VD0 for no CVD finding, VD1 for venous reflux only in tributaries and perforators, VD2 for venous reflux in major veins such as GSV or SSV and varicose vein, and VD3 for venous reflux in major veins, tributaries, and perforators.
The lumbar disc herniation and the lumbar spinal stenosis were included in the lumbar spinal disease diagnosis group based on magnetic resonance imaging (MRI) findings. The lumbar disc herniation was categorized according to the degree of disc protrusion. The lumbar spinal stenosis was graded based on the presence of cerebrospinal fluid (CSF) signal as follow: Grade A for clearly visible CSF inside the dural sac, Grade B for individualized rootlets occupying the entire dural sac, Grade C for homogeneous gray signal dural sac with no visible CSF signal and unrecognizable rootlets, and Grade D for the absence of posterior epidural fat 6. The lumbar spinal disease groups were classified by combining severities of two diseases as follows: LD0 for no definite disc protrusion or spinal canal narrowing, LD1 for mild disc bulging or stenosis grade A and B which unlikely to cause any leg symptoms, LD2 for moderate disc protrusion or stenosis grade C which potentially to cause leg pain, and LD3 for ruptured disc or stenosis grade D.
None of cases had any history or diagnosis of arterial occlusion or deep vein thrombosis in the lower extremities.
CVD-diagnosed cases (VD123) were divided into two groups for comparison analysis based on the severity of lumbar spinal disease. The first group, CVD-dominant group (VDG), had a lower degree of lumbar spinal disease and symptoms were believed to be caused by CVD. The second group, lumbar spinal disease-dominant group (LDG), had a higher degree of lumbar spinal disease, and patients’ symptoms were thought to be influenced by the lumbar spinal diseases.
Vasoactive medications were provided to the cases diagnosed with CVD, but surgical management for CVD was not performed, which could be a limitation in improving symptoms, especially in severe cases of CVD. To compensate for this limitation, the trends of symptom improvement graphs were compared between the two groups.
Symptom improvements were assessed at the first follow-up visits within a two-month period and were categorized as excellent, good, or poor based on the patients’ own descriptions of their symptoms. The visual analog scale (VAS) or numeric rating scale (NRS) was irrelevant and not used because CVD symptoms include pain as well as a variety of other symptoms. It was hypothesized that if there was significant difference in vasoactive medication effect between the VDG and LDG, it could provide indirect evidence for the existence of venous pain in patients presenting to the spine center with leg pain.
The estimation of vasoactive medication effect could be affected by several factors such as pain medication, neuropathic medication, pain block, and lumbar surgery. Pain medications (PM) were graded according to its strength as follows: PM0 for no pain medication, PM1 for NSAIDs (non-steroidal anti-inflammatory drugs), PM2 for weak opioids (combination of codeine, acetaminophen, and ibuprofen or combination of tramadol and acetaminophen), and PM3 for strong opioids. Neuropathic medications (NM) were graded as follows: NM0 for no neuropathic medication and NM1 for gabapentin or pregabalin. These factors were included in the group comparisons to estimate the effect of vasoactive medication.
The ultrasound examinations were conducted in an erect position along the pathway of the great saphenous vein (GSV), small saphenous vein (SSV) and their major tributaries from the inguinal to the lower medial calf, posterior knee to posterior calf, and lateral knee to calf. The B mode ultrasound examinations were started to find the proximal junction of the saphenous vein at the inguinal area for GSV and the posterior knee for SSV. Venous refluxes were assessed using a manual compression-and-release maneuver. An assistant made an upward venous flow by manually compressing and releasing more distal leg from the test site. Upward flow and following venous flow were examined by real-time simultaneous Color and Pulsed Wave Doppler mode. A positive finding was defined as the presence of reflux flow for more than one second of reflux flow in major saphenous veins, and for at least half a second of reflux in tributaries and perforators. The examination was carried out using both a linear probe (12L, 4.5–13 MHz, GE Healthcare) and a hockey-stick probe (8L-18i, 8–18 MHz, GE Healthcare).
The frequency data were displayed without statistical comparison. Chi-square tests were used for comparing categorical variables, and a p-value of < 0.05 was considered statistically significant. The analyses were performed using the IBM SPSS Statistics software, version 25.