Despite being the most common spinal vascular malformation, spinal arteriovenous fistula (AVF) is often

Introduction

Despite being the most common spinal vascular malformation, spinal arteriovenous fistula (AVF) is often

underdiagnosed. Diagnosis of this disease is difficult because symptoms are nonspecific and similar to other radiculopathy related to spinal stenosis. However, with delay in diagnosis and treatment, symptoms slowly progress and become more severe. Jellema et al. ¹ reported a 15­month median delay in diagnosis for 62 of 80 patients with AVF. Here we report an unusual case wherein a spinal AVF patient with progressive weakness in the bilateral lower limbs had been incorrectly diagnosed due to his symptoms and medical

항암치료를 시행한 환자의 척수 경막 동정맥루에 의한 흉부 척수병증에 대한 증례보고

전소연

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¹

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가톨릭대학교 성빈센트병원 ¹재활의학과, ²영상의학과

A Rare Case of Thoracic Myelopathy Caused by

Spinal Dural Arteriovenous Fistula in Chemotherapy Treated Patient

So Yeon Jun ¹ , Leechan Jo ¹ , Seong Hoon Lim ¹ , Bo Young Hong ¹ , Yon Kwon Ihn ² , Joon-Sung Kim ¹

Departments of

Rehabilitation Medicine and

Radiology, St. Vincent's Hospital, College of Medicine, The Catholic University of Korea, Suwon, Korea

Received January 2, 2017

Revised (1st) February 11, 2017, (2nd) March 31, 2017 Accepted April 5, 2017

Corresponding Author: Joon-Sung Kim

Department of Rehabilitation Medicine, St. Vincent’s Hospital, College of Medicine, The Catholic University of Korea, 93 Jung-bu-daero, Paldal-gu, Suwon 16247, Korea

Tel: 82-31-249-7650, Fax: 82-31-249-4481, E-mail: svpmr@chol.com

Spinal arteriovenous fistula is the most common vascular malformation of the spinal cord and causes progressive impairment like paraplegia or tetraplegia. Diagnosis of the disease is often challenging because its heterogeneous presentation mimics those of other neurological disorders, such as lumbosacral radiculopathy or peripheral polyneuropathy. Here we report a case of thoracic myelopathy resulting from spinal arteriovenous fistula in a patient treated with chemotherapy. In our clinic, he was diagnosed with spinal arteriovenous fistulas through magnetic resonance imaging and spinal angiography. Electromyography was used to evaluate the clinical features of the patient.

Subsequently, he underwent surgery and was transferred to our outpatient department to continue rehabilitation therapy. Eventually, the motor power grade in his lower extremities improved from poor to fair and he was able to walk independently with a wheel walker.

Key Words: paraplegia, spinal arteriovenous fistula, thoracic myelopathy

Copyright © by Korean Association of EMG Electrodiagnostic Medicine

This is an Open Ac cess article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

ISSN 1229-6066 https://doi.org/10.18214/jkaem.2017.19.1.29 J Korean Assoc EMG Electrodiagn Med 19(1):29-35, 2017

J Korean Assoc

Electrodiagn Med EMG

history. Using magnetic resonance imaging (MRI) and

spinal angiography, we correctly diagnosed him with spinal AVF. In addition, electromyography (EMG) was used to understand the patient’s symptoms.

Case Report

A 74­year­old man visited the Department of Rehabilitation Medicine at our hospital in March 2015.

He had been diagnosed with hepatocellular carcinoma in July 2013 and had a medical history of hepatitis B virus infection. The patient had been treated for hepatocellular carcinoma with surgical resection in December 2013 as well as chemotherapy and transhepatic arterial chemoembolization (TACE) from 2013 to 2014. In June 2014, the patient first experienced bilateral lower limb weakness, constipation, increased urinary frequency, and residual urine sensation. These symptoms had slowly progressed since then. On his spinal MRI taken in April 2014 at a local clinic, there was cord signal change at the thoracic level and lumbar spinal stenosis at the L1~L2 level. Considering his medical history of cancer treated with chemotherapy, weakness of the lower extremities had been considered complications of chemotherapy. However, even after his chemotherapy

ended, the paraplegia continued to progress and his symptoms worsened.

When the patient came to our outpatient clinic the first time, we suggested his disease might be related to radiculopathy with spinal stenosis. Another possibility was cancer induced myelopathy with peripheral polyneuropathy caused by chemotherapy because he received chemotherapy for almost 3 months with TACE and doxorubicin before his symptoms began. He first experienced a tingling sensation and numbness, which slightly improved with methylcobalamine. Motor power in his bilateral lower limbs was grossly poor grade. He also had difficulty walking and used a walker for indoor gait and a wheelchair for outdoor activities.

Light touch and pain sensations were impaired below both knees. He frequently had voiding, approximately 100~200 cc each time, and post-voiding residual urine was approximately 200 cc. He also had decreased deep tendon reflexes on both knees and ankle jerks, but no pathologic reflex was apparent.

On the follow­up lumbar spinal MRI in March 2015, previous lower thoracic myelopathy and spinal stenosis of L1~L2 were still noticeable, and the diameter of the spinal canal on L1~L2 was 6.0 mm. EMG was conducted to evaluate lumbosacral radiculopathy in

Table 1. Nerve Conduction Studies (Performed on 2015.03.20)

Nerve Stimulation site Recording site Latency (ms) Amplitude (mV) CV (m/s)

Rt Lt Rt Lt Rt Lt

Sensory nerve conduction

Superficial peroneal Ankle Lateral ankle 3.10 3.10 3.80 7.70 45 45

Sural Lower leg Posterior ankle 3.90 3.80 5.40 9.50 36 37

LFC Above inguinal ligament Anterior thigh 2.80 3.00 7.50 7.20 42 40

Median Wrist 3rd digit 3.20 - 29.7 - 44 -

Ulnar Wrist 5th digit 3.10 - 20.9 - 45 -

Radial Wrist 1st digit 2.20 - 30.1 45

Motor nerve conduction

Peroneal Ankle EDB NR NR NR NR - -

Fibula NR NR NR NR - -

Peroneal Fibula TA 1.9 1.5 3.5 4.2

Popliteal fossa 3.8 3.3 3.4 4.1 52.6 55.5

Tibial Ankle AH 4.7 4.3 4.4 6.9

Popliteal fossa 12.9 12.9 4.4 4.0 45.7 44.1

Femoral Above inguinal ligament RF 4.0 4.3 1.0 0.9

All motor latencies are onset latencies and all sensory latencies are peak latencies

CV: Conduction velocity, EDB: Extensor digitorumbrevis, TA: Tibialis anterior, AH: Abductor hallucis, RF: Rectus femoris, NR: No response, mV: millivolts, ms:

milliseconds, m/s: meters per second

March 2015. The EMG showed diffuse denervation potentials in the lumbar paraspinalis and bilateral lower limb muscles below the L2 myotomes. This finding was compatible with diffuse bilateral lumbosacral radiculopathy below the L4 level. Furthermore, there was a finding of peripheral polyneuropathy involving the lower extremities, possibly due to the chemotherapy he had previously received (Table 1, 3). Considering these observations, we performed thoracic spinal MRI in March 2015 to evaluate thoracic myelopathy and the enhanced image showed a serpentine pattern signal on the posterior region of the spinal cord, suggesting spinal AVF (Fig. 1A). This was

the first MRI to suggest the existence of spinal dural AVF. In the subsequent computed tomography (CT) image of the abdominal aorta with enhancement, there were tortuous elongated vascular lesions on the right side of the posterior region of the thoracic spinal cord (Fig. 2A, B). Finally, we performed spinal angiography to investigate the specific site of the lesions. From the spinal subtraction angiography, we could confirm the lesion was related to the right T7 intercostal artery with a perimedullary vein (Fig. 2C). Surgical clipping of the radicular artery feeding the dural AVF was performed in April 2015 in the neurosurgery department of our hospital. On postoperative follow­up MRI, there was

Table 3. Electromyography

Initial (2015.03.20) Follow-up (2015.07.15)

Spon. activity MUPs

Interfer. Spon. activity MUPs

Interfer.

Fibs PSW Poly Amp Dur Fibs PSW Poly Amp Dur

Muscle (right)

L1-L2 psp Not sampled 1+ 1+

L2-L3 psp Not sampled None 1+

L3-L4 psp None 1+ None None

L4-L5 psp None 2+ None 1+

L5-S1 psp None 1+ Not sampled

G Max None 1+ NL NL NL Discrete

G Med None 1+ NL NL NL Discrete

Iliopsoas None None NL NL NL Reduced None None NL NL NL Full

Add L None None NL NL NL Reduced Not sampled

VM None None NL NL NL Reduced Not sampled

TA None None NL NL NL Discrete Not sampled

PL None 2+ NL NL NL Discrete Not sampled

GCM None 2+ NL NL NL Discrete Not sampled

EAS None None NL NL NL Discrete Not sampled

Muscle (left)

L1-L2 psp Not sampled None 2+

L2-L3 psp Not sampled None 1+

L3-L4 psp None 2+ None 1+

L4-L5 psp None 1+ None 1+

L5-S1 psp None 1+ Not sampled

G Max None None NL NL NL Discrete Not sampled

G Med None None NL NL NL Discrete Not sampled

Iliopsoas None None NL NL NL Reduced None None NL NL NL Full

Add L Not sampled Poor resting NL NL NL Full

VM None None NL NL NL Reduced None None NL NL NL Full

TA None 1+ NL NL NL Discrete None None NL NL NL Full

PL None 2+ NL NL NL Discrete Not sampled

GCM None 2+ NL NL NL Discrete Uncheckable due to muscle twitching

EAS None None NL NL NL Discrete Not sampled

Spon.: spontaneous, MUPs: motor unit potentials, Interfer.: interference pattern, Fibs: fibrillation potentials, PSW: positive sharp waves, Poly: polyphasia,

Amp: amplitude, Dur: duration, NL: normal, psp: paraspinal, G Max: Gluteus maximus, G Med: Gluteus medius, Add L: Adductor longus, VM: Vastusmedialis,

TA: Tibialis anterior, PL: Peroneus longus, GCM: Gastrocnemius, EAS: External anal sphincter

no evidence of residual tortuous signal voids along the

posterior region of the spinal cord (Fig. 1B). After the surgery, the patient received rehabilitation treatment for 2 years and showed some degree of motor power gain. He also reported an improvement in the tingling

sensation in the bilateral lower limbs. Importantly, his symptoms did not progress any further. When he was discharged from our hospital in May 2015, the motor power grades for his lower extremities were grossly fair or good grade, although he walked using a wheel walker with maximal support. His voiding problems eased with the administration of drugs such as bethanechol chloride.

In July 2016, we re­examined his EMG. There were some improvements including interferential patterns on maximal muscle volition in the bilateral lower limbs compared with the previous examination in March 2015 (Table 2, 3). Sixteen months after the surgery, he was able to walk independently using bilateral quad canes for 100 m.

Discussion

This case report describes a 74­year­old male patient who experienced paraplegia, voiding difficulties, and urinary frequency. Even after visiting multiple hospitals, his symptoms progressed as his medical history of cancer and chemotherapy complicated early diagnosis.

This case study demonstrates that heavily relying on a patient’s medical history could delay timely and accurate diagnosis.

A B C

Fig. 2. (A, B) The abdominal aorta angio computed tomography images showed tortous elongated vascular lesions (arrow and open arrow) at right side posterior aspect of spinal thoracic cord (T7- T10) level suggesting spinal dural AVF (A is axial view and B is coronal view). (C) The angiography image showed dural AVF arising from thoracic spinal level. Early phase angiographic film of intercostal artery injection at right T7 level. Spinal dural AVF (open arrow) fills from T7 intercostal artery (arrows) with early arteriovenous shunting into the perimedullary vein.

A B

Fig. 1. (A) The T2-weighted magnetic resonance image on pre-

operative state in March 2015, demonstrated enlarged pial vein

(arrows) along the dorsal surface of the cord. Diffuse swelling of

spinal cord was seen from T6 to T12 level. (B) The T2-weighted

magnetic resonance image on post-operative state. Operation was

done to clip AVF feeder with T6-7-8 laminectomy. There was no

residual tortuous, dilated signal voids along the posterior region of

the spinal cord after surgery. When compared to initial magnetic

resonance image (A), the extent decreased of residual T2-weighted

high signal intensity swelling from T8 to T12 level.

Based on the MRI and spinal angiography results, we successfully diagnosed him with spinal dural AVF and accordingly performed surgery. We also performed EMG to better comprehend his symptoms. He has followed a rehabilitation program for 16 months since the surgery and his symptoms have ameliorated.

Spinal dural AVF is an abnormal connection of a dural artery with a radicular medullary vein, characterized by a subacute state of necrotizing myelopathy. ² This disease can be categorized based on its pathophysiology, neuroimaging characteristics, or neuroanatomy, which are helpful to guide the treatment. ³ AVFs are subdivided into extradural and intradural; intradural lesions are categorized as either dorsal or ventral. ³ In our case, the lesion in the patient was intradural and dorsal. Spinal AVF commonly occurs in males older than 60 years and can result in paralysis and loss of bowel, bladder, and sexual functions. ⁴ Spinal dural AVF patients show progressive weakness in both limbs related to myelopathy if not treated in a timely manner. There could be a time lag between the onset of symptoms and diagnosis of spinal AVF because the disease is rarely encountered by clinicians and its symptoms mimic those of other common neurological deficits. ⁵ By the time the disease is diagnosed, many patients already have one or more signs or symptoms related to the sacral segments of the spinal cord. Because our patient was previously treated with TACE with doxorubicin, we also considered the possibility of chemotherapy­

induced myelopathy. However, there are only a few

reports of myelopathy or radiculopathy related to this chemo regimen. Chemotherapy­induced myelopathy is a very rare complication of chemotherapy, particularly with intrathecal administration. The disease often leads to severe neurological sequelae. ⁶ As an example, there was a case report of a patient with L2 complete paraplegia following the intrathecal administration of doxorubicin with incomplete neurological recovery. ⁶ Additionally, MRI scans of patients with chemotherapy­

induced myelopathy characteristically show high signal intensity in the posterolateral columns. ⁷ In contrast, only some characteristics of AVF are conspicuous in T2 MRI. For instance, intramedullary enhancement in T2 images and abnormal, dilated, and engorged perimedullary veins can be seen. However, MRI is not sufficient for spinal AVF diagnosis, ² so additional diagnostic tools, such as spinal angiography, are often required. In our case, thoracic MRI performed in 2015 showed several features including dilated perimedullary veins that provided enough clues for diagnosis.

Common symptoms at the early stage of spinal dural AVF, such as walking disturbance, paresthesia, and sensory changes, are also seen in patients diagnosed with spinal stenosis, radiculopathy, or peripheral polyneuropathy. ^1,4 After a certain period, spinal dural AVF patients develop bladder and bowel problems such as incontinence related to dysfunction of the anal sphincter or a feeling of paraparesis. ⁸ In their study with 80 spinal AVF patients, Jellema et al. ¹ reported that the most common symptoms at the initial and

Table 2. Nerve Conduction Studies (Performed on 2015.07.15)

Nerve Stimulation site Recording site Latency (ms) Amplitude (mV) CV (m/s)

Rt Lt Rt Lt Rt Lt

Sensory nerve conduction

Superficial peroneal Ankle Lateral ankle 3.10 3.00 4.80 3.60 45 47

Sural Lower leg Posterior ankle 4.00 3.90 8.00 7.10 35 36

Motor nerve conduction

Peroneal Ankle EDB 5.7 4.6 0.4 1.4 - -

Fibula 14.7 12.6 0.3 1.2 34.4 40.0

Tibial Ankle AH 5.8 4.3 5.7 8.3

Popliteal fossa 15.1 13.9 3.4 4.6 40.5 40.7

All motor latencies are onset latencies and all sensory latencies are peak latencies

CV: Conduction velocity, EDB: Extensor digitorumbrevis, AH: Abductor hallucis, mV: millivolts, ms: milliseconds, m/s: meters per second

later stages were walking disturbances and micturition

problems, respectively. Although there are many features of AVF similar to those of other neurological diseases, some symptoms are specific to AVF patients.

Paralysis involving the upper limbs is rare in AVF but is possible in polyneuropathies. In contrast, micturition symptoms are common in AVF. ¹ These patterns were also present in our patient.

To treat spinal AVF, most neurosurgeons have two options: surgical clipping or endovascular embolization.

These treatments are aimed at occluding the shunting vessels by either embolization with an embolic agent or surgery. ⁹ In a meta­analysis by Steinmetz et al. ¹⁰ 98%

of patients treated with surgery showed successful obliteration, but only 46% of patients treated with embolization achieved such success. The procedures involved in embolization cannot be performed when the AVF artery is also feeding another spinal artery, and recurrence is possible after the procedures. ^4,10 After treatment, 67% of patients showed motor power improvement. The patient described in this report complained of paraplegia, voiding difficulties, and urinary frequency before surgery. He underwent surgical clipping and his symptoms stopped progressing.

In the rehabilitation department, there are many paraplegic patients with various causes and different medical histories. Physicians should seriously consider the medical histories of patients before diagnosis, but previous history sometimes leads to confusion regarding the cause of some symptoms. In this case, the patient visited multiple hospitals and different departments (e.g., internal medicine for hepatology, urology, and neurosurgery departments). Nevertheless, clinicians thought his symptoms were simply related to his history of cancer treatment or lumbar spinal stenosis. When we examined the patient, the fact that his symptoms progressed even after the suspected etiology, namely chemotherapy, was removed led us to search for other explanations for his symptoms. On EMG, he showed bilateral lumbosacral radiculopathy.

Hence, clinically, we could have also considered

cauda equina syndrome. Other possibilities were that his symptoms were due to either AVF or lumbosacral radiculopathy. His symptoms did not progress further after surgery for AVF, not for radiculopathy, which convinced us that the patient had received the proper treatment. The correct diagnosis followed by surgery stabilized his symptoms. Almost 2 years after the onset of his symptoms, he is continuously undergoing rehabilitation at our department’s outpatient clinic, and his conditions have improved to the extent that he can walk with bilateral quad canes without additional support.

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