Spinal dural arteriovenous fistula and multiple sclerosisHossein zahirmirdamadi 1, Abootorab Shahmohammadi, Elnaz Asadollahzadeh 1, Sareh shahmohammadi 1, Vahid Shahmaei 2, Babak Rafiee 31-Multiple Sclerosis Research Center, Neuroscience Institute, Tehran University of Medical Sciences,Tehran, Iran2- MAHAK Hematology Oncology Research Center (MAHAK-HORC), MAHAK Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran3- Babak Rafiee, MD, Radiologist New century university, Private Gaziosmanpasa hospital, Radiology department Istanbul, TurkeyFirst author: Hossein zahirmirdamadiE-mail: [email protected]*Corresponding author: Abootorab ShahmohammadiMultiple Sclerosis (MS) Research Center, Neuroscience Institute, Tehran University ofMedical Sciences, Tehran, Iran.E-mail: [email protected]: +98 21 66348571Fax: +98 21 66348571Key clinical message:if red flags are present with new symptoms in an MS patient, we should re-evaluate our diagnosis. involvement of more than three segments of the thoracic spinal cord and the severity of the patient’s motor and sphincter symptoms were red flags in diagnosis of MS. misdiagnosis can lead to irreversible complications and disability.Keywords:Mri, Arteriovenous Fistula, Multiple Sclerosis, Spinal CordIntroduction:Arteriovenous shunts in the spinal cord are classified into two general categories: arteriovenous malformation (a network of abnormal vessels with nidus) and arteriovenous fistulas (a direct shunt between the artery and vein ((1). SDAVFs constitute the most common type of spinal vascular malformations. Clinical symptoms are usually progressive gait disturbance with sensory loss or paresthesia and sphincter dysfunctions. Delays in diagnosis and treatment result in poor clinical outcomes and more disabilities after surgery(2).Indeed, the overlapping clinical symptoms between the DAVFs with other neurological conditions such as myelitis secondary to inflammatory or demyelinating diseases such as multiple sclerosis (MS) can often complicate the diagnostic process. Thus, accurate diagnosis and differentiation of these disorders is of utmost importance in ensuring appropriate treatment and management(3).A thorough understanding of the unique clinical and characteristic MRI features, as well as the use of advanced imaging techniques can aid clinicians making a timely precise diagnosis and prevent unnecessary medications or invasive procedures(3, 4).Herein, we describe a 33-year-old male patient with a history of multiple sclerosis (MS), WHO experienced a delayed diagnosis of spinal dural arteriovenous fistula (SDAVF) presented with Back pain and Urinary retention and sub-acute paraparesis.Case report:A 33-year-old male was admitted to the hospital, with a history of blurred vision in his left eye and mild vertigo. The patient’s MRI scan revealed the presence of typical Multiple Sclerosis (MS) lesions of the brain. Fig-1After three days of 16 mg intramuscular injections of dexamethasone, the patient’s symptoms have been resolved. A diagnosis of multiple sclerosis (MS) was established based on the patient’s clinical presentation of typical optic neuritis and diagnostic MRI findings. Treatment with Interferon B-1A s/c was initiated.After 7 months the patient developed low back pain with urinary retention, followed by lower extremities weakness of 3/5 accompanied by numbness in the extremities and perineum. These symptoms progressively worsened over the course of two days.Methods:Brain, cervical and thoracic MRI was performed, and Sagittal T2-weighted and Short-Tau Inversion Recovery (STIR) MRI sequences of the spine show an abnormal hyperintense T2 signal extending from the T6 to T10 vertebral level (Fig-2). We administered 7 grams of methylprednisolone pulse therapy. After that, dramatic improvement in the patient’s symptoms was observed.After reviewing the patient’s MRI result, which revealed demyelinating lesions, because of LETM in the thoracic cord with an H-sign view on the axial cut of the cord lesion without gadolinium enhancement (Fig-2), we suspected that the patient’s diagnosis might be myelin oligodendrocyte glycoprotein antibody associated disease (MOG-AD) regarding the presentation of severe sphincteric dysfunction that the patient needed a catheter and mentioned the radiological findings. However, subsequent laboratory testing for AQP4 & MOG antibodies returned negative results, indicating that the patient’s condition may not be associated with either of these diseases.Following that the patient was treated with Rituximab 1gr every six months as severe myelitis of multiple sclerosis.A follow-up MRI performed three months later showed flow void sign and dilated cortical veins without parenchymal nidus (Fig-3). These findings prompted further research to confirm the presence of spinal DAVF and determine its impact on the patient’s condition.We performed time-resolved contrast kinetics imaging (TRICKS) MRI to determine the likely location of SDAVF because TRICKS could detect the exact level of SDAVF with high accuracy(5).tricks show SDAVF at the level of T9 in this patient (Fig-4).In digital subtraction angiography, a bilateral and complete spinal examination was performed after transfemoral catheterization. First, the aortic arch and then all radiculomedullary, cervical, thoracic, and lumbosacral vessels were examined bilaterally. During angiography, an image of DAVF was observed with a left arterial T9 feeder and successfully retrieved using a microcatheter. The procedure was well embolized with a mixture of glue and lipiodol (Fig-5).CONCLUSIONS:In patients with MS or other demyelinating diseases, we should again look for other differential diagnoses when we encounter red flags on clinical or MRI findings.Discussion:Spinal vascular malformations are 5 to 9% of all CNS vascular malformations and Spinal dural arteriovenous fistulas (DAVFs) are most common type of spinal vascular abnormalities(4). Prevalence of DAVFs are generally rare (5-10 per million in the general population) but constitute about 70% of all cases of spinal arteriovenous shunts(2) which cause various clinical manifestations of myelopathy in the involved person, depending on the location of the spinal cord involvement, the type of arterial and venous connection and whether it is an impairment of arterial blood supply or venous drainage(1, 3, 4).The direct connection of the shunt on the dorsal surface of dural root sleeves between the radicolomeningeal arteries and the radicular vein can cause symptoms. Blood supply insufficiency and ischemia secondary to venous hypertension, thrombosis or compression of dilated veins(6, 7) is the main reason of these symptoms.The clinical symptoms can appear usually as chronic progressive myelopathy or sometimes as an acute or sub-acute vascular events of spinal cord(6) that make diagnosis of DAVFs more difficult.Progressive myelopathy is secondary to venous hypertension due to dysfunction of venous drainage which usually causes congestive myelopathy in the case of drainage into the intradullar veins and compressive myelopathy because of dilated veins in the case of extradural venous drainage(6, 7).Cord ischemia could be acute or subacute due to venous thrombosis or compressive myelopathy(6).Canal stenosis, Demyelinating processes, neoplasm, infarction are the differential diagnosis with SDAVF(3).Our patient presented with low back pain, urinary retention, subacute paraparesis. Because of the underlying MS disease, the first diagnosis was considered as myelitis, and the patient was treated with steroid pulse. About two weeks after the treatment, the patient’s symptoms clearly improved.In the reported cases with acute paraparesis, the symptoms were also transient(3), but in patients who were treated with steroid pulses, the prognosis was usually worse. This worsening can be explained by the increased venous congestion and decreased capillary permeability caused by steroids(8) and fortunately, this complication did not occur in our patient.The incidence of SDAVF peaks in the 5th and 6th decades and males are more commonly affected than females(2).The most common anatomic sites that are involved are the thoracic, thoracolumbar, and cervical and sacral regions, respectively(2, 4, 9).Delay in diagnosis and treatment causes a poor final prognosis in some studies. Of course, the severity of the initial clinical symptoms is also considered to be effective in the patient’s prognosis(3, 9).Analysis of retrospective data from 40 patients diagnosed with Spinal DAVFs shows that thirty-one patients (78%) were initially misdiagnosed with lumbar spinal stenosis or other diseases. The average delay in diagnosis was 11 months and the average time of walking disturbances requiring crutches or a wheelchair was 10 months in these patients and within 6 months of the onset of the disease, 9 patients (23%) required a cane and 6 (15%) required a wheelchair(3).The diagnosis is suspected with MRI, and the definitive diagnosis is made with spinal cord angiography, and MRA is a guide for performing angiography(2).In MRI findings, the following information was observed that pointed out the diagnosis of Spinal DAVFs:Diffuse multilevel intermedullary hyperintensity in T2 weighted and Short-Tau Inversion Recovery (STIR) technique extended more than 3 levels (around 90%) is most sensitive finding than occurs in the context of vasogenic edema(3, 9, 10) the lower thoracic and conus medullaris are mostly involved anatomic location of this signal change. The location of the signal change does not necessarily correlate to the location of Spinal DAVFs(10).Rim of T2 hypo intensity in the periphery of the cord, because of dilated capillaries containing deoxyhemoglobin secondary to venous hypertension is one of the characteristic imaging features(10). Our patient MRI has these findings. (Fig-2, B, C)Another specific finding suggestive of SDAVF is the flow void sign on T2-weighted images, which indicates the presence of dilated veins at the surface of the spinal cord(2, 3). that shows serpentine enhancing veins after gadolinium injection (Fig-2 A, C) High-resolution 3-dimensional T2-weighted sequences or turbo spin echo enhance flow void sign detection(2, 9).Sometimes dilated veins may be so large to give the surface of the cord a scalloped appearance and conversely in other cases cord swelling may compress the dilated vein and prevent flow void appearance in MRI(3, 9).In our patient, in addition to the low accuracy of the initial MRI, maybe the inflammation of the cord also played a role in hiding the appearance of the flow void sign when the patient was symptomatic.Chronic venous congestion increases capillary permeability, so diffuse enhancement of the spinal cord may lead to misdiagnosis of myelitis. Missing-piece sign pattern of enhancement is an anatomic location with better venous drainage in tissues with venous congestion could be differentiate DAVFs from other cause of cord inflammation(10, 11).For localizing SDAVF, time-resolved contrast kinetics imaging (TRICKS) MRI can be useful due to its high accuracy in predicting the precise level of ±1 level(5).MRA with contrast is actually a way to find the appropriate catheterization site for detecting the segmental level of possible arterial feeder of the fistula in angiography(2, 3). We performed catheter spinal angiography as the gold standard method for definite diagnosis(1, 2, 9) and SDAVF was observed with a left arterial T9 feeder.Author Contribution statement:All authors made contributions in equal parts to this manuscript in terms of acquisition and interpretation of data, conception and design, and drafting the manuscript. All authors were involved in the therapeutic management of the patient. All authors were involved in revising the manuscript. All authors read and approved the final version of the manuscript.Patient consentThe patient involved in the study have signed informed con-sent and have authorized the use of aspects of their cases andimaging for research and educational purposes. Consent wasobtained from all patients involved in this study and a recordof this consent is kept with the authors and where possiblehas been documented in the electronic records of the patient’sconcerned. All patients have been de-identified in the paperpresented.1. Patsalides A, Knopman J, Santillan A, Tsiouris A, Riina H, Gobin Y. Endovascular treatment of spinal arteriovenous lesions: beyond the dural fistula. American journal of neuroradiology. 2011;32(5):798-808.2. Krings T, Geibprasert S. Spinal dural arteriovenous fistulas. American journal of neuroradiology. 2009;30(4):639-48.3. Takai K, Taniguchi M. Clinical and neuroimaging findings of spinal dural arteriovenous fistulas: How to avoid misdiagnosis of this disease. Journal of Orthopaedic Science. 2019;24(6):1027-32.4. Bhimani AD, Rosinski CL, Patel S, Chaudhry NS, Denyer S, Behbahani M, et al. Adult Spinal Arteriovenous Malformations: Natural History and a Multicenter Study of Short-Term Surgical Outcomes. World Neurosurgery. 2019;132:e290-e6.5. El Naamani K, Abbas R, Tartaglino L, Sweid A, Herial NA, Tjoumakaris S, et al. The accuracy of the TRICKS MRI in diagnosing and localizing a spinal dural arteriovenous fistula: a feasibility study. World Neurosurgery. 2022;158:e592-e7.6. Da Ros V, Picchi E, Ferrazzoli V, Schirinzi T, Sabuzi F, Grillo P, et al. Spinal vascular lesions: anatomy, imaging techniques and treatment. European Journal of Radiology Open. 2021;8:100369.7. Saito A, Yajima N, Nakamura K, Fujii Y. 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