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Spinal Arteriovenous Malformation Associated with Parkes Weber Syndrome: Report of Two Cases and Literature Review
Accepted Manuscript Spinal arteriovenous malformation associated with Parkes Weber syndrome: Report of two cases and literature review Zi-Fu Li, M.D., Qiang Li, M.D., Yi Xu, M.D., Bo Hong, M.D., Qing-Hai Huang, M.D., Jian-Min Liu, M.D PII:
S1878-8750(17)30972-5
DOI:
10.1016/j.wneu.2017.06.080
Reference:
WNEU 5951
To appear in:
World Neurosurgery
Received Date: 1 April 2017 Revised Date:
10 June 2017
Accepted Date: 13 June 2017
Please cite this article as: Li Z-F, Li Q, Xu Y, Hong B, Huang Q-H, Liu J-M, Spinal arteriovenous malformation associated with Parkes Weber syndrome: Report of two cases and literature review, World Neurosurgery (2017), doi: 10.1016/j.wneu.2017.06.080. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Spinal arteriovenous malformation associated with Parkes Weber syndrome: Report of two cases and literature review
[email protected]
Qiang Li, M.D.
[email protected]
Yi Xu, M.D.
[email protected]
Bo Hong, M.D.
[email protected]
Qing-Hai Huang, M.D.
[email protected]
Jian-Min Liu, M.D
[email protected]
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Zi-Fu Li, M.D.
Department of Neurosurgery, Changhai Hospital, Second Military Medical University,
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Shanghai, China
Corresponding to: Qing-Hai Huang or Jian-Min Liu
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Department of Neurosurgery, Changhai Hospital, Second Military Medical University,
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Shanghai 200433, China，
E-mail: [email protected] Telephone: +86 21-31161784; Fax: +86 21-31161784
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Acknowledgements: None
ACCEPTED MANUSCRIPT Spinal arteriovenous malformation associated with Parkes Weber syndrome: Report of two cases and literature review ABSTRACT To present two cases of Parkes Weber syndrome (PWS) with spinal
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Objective
arteriovenous malformation(AVM), and discuss the radiological features and clinical treatment with literature review.
Clinical data on two PWS patients with spinal AVM was acquired in a
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Methods
prospective follow-up investigation. Clinical manifestations, radiographic features,
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procedural results and follow-up outcome were collected and reviewed together with literature review. Results
The first patient presented with limb weakness and urinary dysfunction and
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the second with repetitive subarachnoid hemorrhage followed by paraplegia. Limb hypertrophy, skin ulceration and extensive microfistulas in the affected limb were observed in both patients. Spinal AVM was confirmed by digital subtraction
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angiography and endovascular embolization was performed for them. The first patient
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experienced limb amputation at 6-year follow up due to chronic ulceration and the second did not have neurological improvement. After literature review, 15 cases (male: female=5:10; mean age: 22±10.4 years) were included. The presentations mainly include subarachnoid hemorrhage in 6, radicular pain in 5, myelopathy in 4 and asymptomatic in one. Embolization was performed in 9 cases, solitary surgery in 2 and combined therapy in 4. Among 10 cases with known follow up results, 6 achieved neurological recovery after surgery and one died after solitary surgery.
ACCEPTED MANUSCRIPT Conclusions
Awareness of the association between spinal AVM and PWS is
essential for radiographic screening of spinal lesions with myelopathy or intracranial subarachnoid hemorrhage. Clinical therapeutic strategy should be multidisciplinary
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and individualized on the basis of vasculature and lesion behavior. Key Words Parkes Weber syndrome; myelopathy; spine; arteriovenous malformation;
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subarachnoid hemorrhage
ACCEPTED MANUSCRIPT Introduction Parkes Weber syndrome (PWS) is rare congenital vascular malformation which consists arteriovenous shunts
venous
capillary and lymphatic malformation
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presenting with limb hypertrophy, cutaneous stain and skin ulceration.(4) It is characterized by fast-flow fistulas or shunts, resulting in multisystematic impairment with poor prognosis. The disorder is easily misdiagnosed as Klippel-Trenaunay
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syndrome (KTS), and is clinically and radiologically different from other slow-flow
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vascular malformations.(2)
Spinal arteriovenous malformation (AVM) associated with PWS is a rare condition. Various forms of spinal AVM were reported, mainly including intramedullary, intradural, epidural and paravertebral type. These spinal lesions may
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cause acute myelopathy or subarachnoid hemorrhage (SAH) at a young age, and potentially result in serious neurological sequalae and threaten their quality of life. Here, in order to systematically review the similar cases and promote awareness of the
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association with spinal lesions, we first presented two additional cases, and then
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discuss the radiographic features and clinical treatment with literature review.
Case reports Case 1
A 12-year-old girl complained of low back pain, numbness and weakness of left leg and urinary retention two weeks before admission, with a history of hypertrophy and warmth in the left lower extremity since five months after birth, and a history of
ACCEPTED MANUSCRIPT repetitive ulceration in her left ankle and length discrepancy between two legs at 3 years old. Neurological examination showed reduced muscle strength of 2/5 and
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hypoesthesia in the left lower extremity and negative Babinski sign. Physical examination showed hypertrophy, faint capillary stain on her waist, varicosity in her left leg with higher temperature, ulceration in her left foot. Auscultation revealed bruit
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along the whole left leg and accentuated cardiac sounds in the precordial region.
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Brain natrium protein level (130 pg/ml) was mildly elevated. The RASA1 gene mutation was negative. Magnetic Resonance Imaging (MRI) showed osseous change in the femoral bone. Magnetic Resonance Angiography (MRA) showed enlarged iliac and femoral artery with early appearance of draining vein. Chest X ray showed
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scoliosis.
Digital subtraction angiography (DSA) demonstrated intramedullary spinal AVM with moderate flow fed by anterior spinal artery arised from the left L1 intercostal
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artery. Selective angiograms showed two aneurysms perched on the branches of ASA
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feeding arteries and venous pouch within the nidus. Angiogram in the lower limbs reveals extensive fistulas and shunts in the left thigh, knee and tibial region (Figure 1). Endovascular treatment was performed for the patient in order to eliminate the intranidal aneurysms. The intercostal artery was then selectively catheterized with Cobra catheter (Cook, Indiana, USA). Using a triaxial system, a microcatheter (Marathon, Covidien, CA, USA) was advanced into the ASA branches. After angiographic confirmation of the aneurysm location, 25% Glubran (GEM, Viareggio,
ACCEPTED MANUSCRIPT Italy) was slowly injected into the aneurysm and 16.7% Glubran into the other. Control angiography immediately after embolization demonstrated elimination of the two aneurysms and partial embolization was achieved.
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After endovascular treatment, urinary dysfunction disappeared. The muscle strength of left leg returned to normal at discharge. Embolization of fistulas in the left leg was subsequently embolized with platinum coils for four times in department of
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vascular surgery at the following 3 years of follow up. At 3-year follow-up,
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Ultrasound Doppler showed enlargement of the left ventricle and CT angiography showed pulmonary hypertension. At 5-year follow-up, the girl underwent amputation of the left foot due to chronic skin ulceration and gangrene. At 6-year follow-up, the patient remained neurologically intact and was fully ambulatory with a prosthesis.
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Case 2
A 24-year-old man with a history of congenital overgrown right leg and varicosities experienced subarachnoid hemorrhage (SAH) for three times presenting with severe
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headache within three years. DSA performed in an outside institution showed negative
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findings of intracranial vessels. Two weeks before admission, the patient experienced sudden onset of paraplegia and urinary dysfunction and was transferred to our center. Physical examination showed loss of motor and sensory under the L1 level, and
right leg hypertrophy with varicosities. Significant bruit and temperature difference were noticed along the right low limb. The result of RASA1 gene mutation test was negative. MRI showed a intramedullary spinal AVM at the level of T8-L4. CT angiography showed extensive
ACCEPTED MANUSCRIPT fistulas in the iliac region and early appearance of enlarged superficial veins in the right lower limb and DSA demonstrated that spinal AVM was mainly fed by ASA and posterior spinal artery (PSA) arose from the T9 intercostal artery, and by PSA from
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the T12 intercostal artery. Angiograms also showed multiple fistulous were visualized along the right leg (Figure 2).
Endovascular embolization was performed for the patient due to repetitive SAH
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related to spinal AVM. Supported by Cobra catheter, a triaxial system including
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Marathon microcatheter and microwire initially failed to be advanced into the ASA branches due to a sharp turn at the ostium of radicular medullary artery. Embolization with 20% Glubran was then performed via feeding branches of the PSA that originate from T9 and T12 intercostal arteries. After third injection, reflux of Glubran was
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noticed and then microcatheter was withdrawn from PSA. At this time, contrast extravasation was seen and rapid embolization of rupture point and feeding arteries with Glubran was done to stop the hemorrhage. Finally, partial embolization of the
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spinal AVM was achieved. Ventricular and lumbar drainage was subsequently
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performed. Two weeks later, the patient was discharged with slight improvement on sensory function but paraplegia was not improved. After hyperbaric treatment, urinary dysfunction and motor complete paraplegia were not improved. At 6-year follow-up, no episodes of rebleeding occurred and the neurological status was the same. Review strategy Using Pubmed database, published papers between 1975 and 2015 were searched to identify the PWS patients with spinal AVM. Because the confusion of nomenclature,
ACCEPTED MANUSCRIPT the search was done with combination of keywords: “Klippel-Trenaunay-Weber”, “Parkes Weber”, and “spinal arteriovenous malformation”. The cases with the nomenclature of Klippel-Trenaunay syndrome were excluded. The reported cases of
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Klippel-Trenaunay-Weber syndrome with microfistulas were recognized as PWS. Search results
In the review, 15 cases (5, male; 10; female) were included, with a mean age of 22±
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10.4 years (rang: 9-48 years). The presentations related to spinal AVM mainly include
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subarachnoid hemorrhage in 6, back or neck pain in 5, myelopathy in 4 and asymptomatic in 1. The reported cases were summarized in Table 1. The spinal lesions located in intramedullary portion in 8, intradural in 3, intradural extramedullary in 2
and epidural in 2, and paravertebral in 1. Among 12 cases with
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reported treatment embolization was performed in 6 cases, solitary surgery in 2 case, and combined therapy of embolization and surgery in 4. Among 10 cases with known follow up results, 6 achieved neurological recovery after surgery and one died after
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solitary surgery.
Discussion
The two cases demonstrated the spinal AVM presenting with acute myelopathy and SAH was associated with PWS. The radiological findings showed the fast-flow nature of vascular malformation in the affected limb and spinal lesions. Multisystematic impairment was observed including cardiovascular system and bone. Differential Diagnosis
ACCEPTED MANUSCRIPT Among all the vascular anomalies, PWS is easily misdiagnosed as other vascular malformations, especially KTS, and the overlapping feature of cutaneous stain is also confusing. The slow-flow feature and the relatively good clinical outcome of KTS
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patients differ from PWS clinically and radiologically.(14,22) PWS shares the common feature of fast-flow arteriovenous fistulas along the affected extremity with capillary malformation–arteriovenous malformation (CM-AVM). Similar with PWS,
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several vascular anomalies share the overlapping features of cutaneous stain, such as
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KTS, CM-AVM, Cobb syndrome and Sturge-Weber syndrome.(7,10,15,16,18,27) However, limb overgrowth is not observed in CM-AVM, Cobb syndrome and Sturge-Weber syndrome.(6,10,21) Different genes were reported to be associated with these congenital vascular malformation, and only RASA1 mutation was reported in
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familial cases of PWS and CM-AVM but not in our two cases.(31) The clinical and radiographic characteristics are differentiated and summarized in Table 2. Multisystematic Impairment
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Multisystematic impairment was usually present, as observed in the first case at the
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long-term follow-up. These systems included limb hypertrophy, skin ulceration and pigmentation, cardiac failure and skeletal change.(1,8,11,12,17,24,26,28) The elevated level of brain natrium protein and enlargement of the left ventricle indicate the cardiac impairment. The high-output cardiac failure is attributed to the multiple fistulas or shunts in the affected limbs.(24) At the same time, these microfistulas also cause peripheral microcirculation compromise due to blood steal phenomena, resulting in chronic ulceration or gangrene in the distal area of extremity. The long bone in the
ACCEPTED MANUSCRIPT affected extremity also endure morphological and pathological change, which secondarily leads to scoliosis. The high blood flow, high temperature and enhanced oxygenation caused by the fistulas stimulate the osteoblasts to produce bone
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overgrowth. (19,25) Mechanism of Concomitant Spinal AVM
The mechanism of association of spinal AVM and PWS is not clear. Both of spinal
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AVM and PWS are rare diseases, the coincidence rate is extremely low. We presumed
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that an underlying mechanism responsible for the association. In all the reviewed cases including ours, the location of hypertrophic lower limb mostly corresponds to the level of the spinal AVM at the nearly same level from T12 to L1, we considered that the association may be attributed to the same metamere. However, it can not
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explain the spinal AVM beyond these locations.(30) The RASA1 mutation identified in familial cases of PWS patients can explain the capillary malformation but not the
association.
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spinal AVM instead. More cases with genetic investigation was needed to uncover the
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Characteristics of Concomitant Spinal AVM Many forms of spinal AVM was reported to be associated with PWS, including intramedullary,
intradural,
epidural,
intradural
extramedullary
and
paravertebral.(17,26) In our cases, the intramedullary spinal AVM carries the risky structure of intranidal aneurysms. The flow is relatively high and characterized by multiple enlarged feeding arteries, shunting and multiple enlarged draining veins. Intranidal aneurysms, high-flow shunt and venous pouch increased the architectural
ACCEPTED MANUSCRIPT risks of the spinal AVM, which potentially cause SAH, intramedullary hemorrhage and venous hypertension. The concomitant spinal AVM reminded us that screening of spinal lesions should be paid attention to for PWS patients with SAH and without
Treatment Options for Concomitant Spinal AVM
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intracranial findings.
The optimal approach of treating spinal AVM in PWS patient depends on risk-benefit
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analysis according to the vasculature and lesion behavior. The risky structure of
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intranidal aneurysms and high-flow fistulas potentially cause hemorrhage and venous hypertension, respectively. Embolization of these lesions was necessary. However, complete embolization or resection will increase the risk of spine cord injury due to complexity of the vasculature and easy reflux of embolization materials to the trunk
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of ASA or PSA. Kojima et al.(20) reported a solitary resection for intradural spinal AVM on dorsal side from T11 to L2 and new symptom of bladder dysfunction and weakness in both legs developed after surgery. It suggests that the solitary resection
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probably increased the risks of complication. Rohany et al(26) reported the feasibility
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of surgical removal after preoperative embolization in two cases with multiplicity of pial fistulas on the dorsal side and mass effect, and achieved complete elimination of the spinal AVM and the good clinical outcome. They think that the objective of surgery is to decompress the spinal cord rather than resect the spinal AVM. Alexander et al.(1) performed embolization, partial resection and spinal cord decompression for a case with extensive involvement of the AVM, and considered this palliative strategy benefited the symptoms and gross total resection would increase the risks of
ACCEPTED MANUSCRIPT complication. From our viewpoint, the aim of embolization is to eliminate the risky structure and maximally reduce the microfistulas in order to alleviate the venous hypertension. After adopting partial embolization, no recurrence of bleeding occurred
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at the long-term follow-up in our two cases. Multidisciplinary Treatment
Owing to the multisystematic impairment, multidisciplinary approach is essential to
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treat the involved systems. The strategy included treatment plans for hypertrophic
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tissue, cardiac failure, elongation of the long bone, capillary malformation and fistulas in the involved extremity.(8,13,24,26) Therefore a multidisciplinary team is required, including neurosurgeon, cardiologist, radiologist, orthopedist, plastic and vascular surgeons, geneticist
and the physical therapy physician. With regard to the first case,
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spinal AVM was embolized and the following embolization of microfistulas was performed in multiple sessions in the department of vascular surgery to reduce the hyperkinetic circulation and steal phenomena. However, pulmonary hypertension and
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ventricle enlargement still develop due to the remaining fistulas and shunts. The
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ischemia in her left footwas also worsened, resulting in gangrene and amputation of her left foot. Therefore, maximal embolization of fistulas was vital to reduce the long-term insult to the multiple systems. The cardiac failure is the most common complication for PWS patient due to high-output burden(24), surveillance of cardiac function and balanced fluid management is necessary. For scoliosis caused by bone elongation, life quality can be improved by plastic and orthopedic surgery. Multidisciplinary collaboration and individualized therapy were essential to provide
ACCEPTED MANUSCRIPT needed supports for their return to normal life. Conclusion The two cases demonstrated the association of spinal AVM and PWS. It reminded us
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that the complicated spinal AVM may cause potential myelopathy or SAH. Awareness of radiological screening of spinal AVM was essential to track the source of intracranial SAH in PWS patients. Multidisciplinary approach was essential to deal
1.
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ACCEPTED MANUSCRIPT Table 1. Summary of reported cases of spinal AVM associated with Parkes Weber syndrome Age(years
Reference
Symptoms
Type, location
spinal AVM treatment/Results
Follow up/Outcome
13 /M
SAH
Intramedullary, T9–T12
No treatment
No data provided
22 /F
Repetitive SAH
Intramedullary, T5–T6
No data provided
No data provided
28 /M
SAH
Intramedullary, T9–L2
No data provided
No data provided
13 /F
Repetitive SAH
Intramedullary, L1–L2
Embolization/partial embolization
No data provided
15 /M
SAH
Intramedullary, L1–L2
Embolization with Gelfoam and
No data provided
)/Sex Djindjian et
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al(9), 1977
dura mater/partial embolization 9/F
Back, neck and
28 / F
Low limbs
Intradural extramedullary,
Surgical resection/complete
6 months/ Bladder
weakness
T11-L2.
resection
dysfunction
1989
19/M
Tan et al(30),1990 Nakstad et
13 / F
al(23), 1993 Szajner et al(29),
48 / F
Embolization with
Die
Gelfoam/complete
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low limbs pain
x et al(5), 1985 Kojima et al(20),
Intramedullary, T11-T12
complicated
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Benhaiem-Sigau
Thoracic pain
Intramedullary, T2–T6
Surgical resection
Slight improvement
and paraplegia
and T10–T12
Back pain,
Intradural extramedullary
Embolization with platinum fibre
3
myelopathy
sAVF, T11-T12
coils/complete embolization
Recovery
Asymptomatic
Paravertebral, C4- T1
Embolization with
6 months/Recovery
months
/
NBCA/complete embolization
1999 Alexander et
30 /M
(1)
bilateral lower
Epidural, T3-T4
al , 2002
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limbs weakness, and numbness 37 / F
2007
29 / F
Radicular pain
surgery/partial embolization and
worsened and
pain
complete resection
subsequently
Bagherpour et al(3),2016
SAH
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2008
24 / F
Present cases
14 /F
12 / F
excision/partial resection
and perineal
Epidural, C5-T2
SAH
Back pain,
improved Multiple embolization and
4 years/
surgery/ complete resection
Recovery
Conus medullaris
Endovascular embolization with
6 years /
NBCA/partial embolization
Recovery
Conus medullaris
Bilateral
myelopathy
Iizuka et al(17),
Recovery
3 months / Initially
Neck pain,
Intradural, T12-L2
6 months /
NBCA and then surgical
Embolization with NBCA and
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Rohany et al(26),
Embolization with PVA and
laminectomies
surgical
ligation
followed
by
of
and
2 years/ Recovery
fistulas
endovascular
embolization with NBCA Intramedullary, T12-L4
myelopathy
Embolization with Glubran
6 years/ Ambulatory
/partial embolization
with amputation of her left foot
24 /M
Repetitive SAH,
Intramedullary, T8-L4
myelopathy
Embolization with Glubran / partial embolization
F, female; M, male; SAH, subarachnoid hemorrhage, C, cervical; T, thoracic; L, lumbar; spinal AVM, spinal arteriovenous malformation; NBCA, N-butyl cyanoacrylate.
5 years/Paraplegia
ACCEPTED MANUSCRIPT Table 2. Clinical and radiological characteristics of vascular anomalies KTS
CM-AVM
Cobb
Sturge-Weber
Limb
Limb
Multifocal
Vascular skin
Brain atrophy,
hypertrophy,
hypertrophy,
cutaneous stain,
nevus
seizure, glaucoma
cardiac
Venous
cardiac failure,
failure
varicosities
Radiographic
Extensive
Absence of
High flow
Spinal canal
Subcortical
findings
fistulas in
fistulas in
vascular AVM of
angioma at the
calcification, pial
involved
involved limb
fistulas
same metamere
angiomatosis
Large; pink to red
Multifocal,
Pink to red
Pink to red nevus on
angiomas on the
the head or neck
limb
Arteriovenous
large;
or red to
atypical, small;
pink to red
violaceous
pink-red macules
back
Usually
Always
Usually
None
Always
Absent
fistulas
Overgrowth
Usually the
Usually the lower
feature
lower limb
limb
Lymphatic
Rare
Rarefied,
Always
None
fistula of the spinal canal None
Common
Rare
Lymphangioma
None
Rarefied,
Rarefied,
Kyphoscoliosis
None
None
leptomeningeal
osteoporosis
osteoporosis
Brain
Intracranial
Not reported
Intracranial AVM
involvement
AVM or AVF
Spinal vascular
Extradural
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malformation
None
osteoporosis
disorders
Arteriovenous
Venules
None
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malformation Bone alteration
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Venous varicose
Typically,
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Cutaneous stain
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PWS Main presentation
None
or AVF
Spinal AVM
and spinal
malformations
Spinal AVM or
None
cavernomas
AVM
RASA1
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Involved gene
AGGF1 PIK3CA
RASA1
Not clear
GNAQ
mutation
AVM, arteriovenous malformation; AVF, arteriovenous fistula; PWS, Parkes Weber syndrome; KTS, Klippel-Trenaunay syndrome; CM-AVM, capillary malformation–arteriovenous malformation.
ACCEPTED MANUSCRIPT Figure legends Figure 1 Radiographic findings in a 12-year-old girl with spinal arteriovenous malformation associated with Parkes Weber syndrome. A: MR angiography shows enlarged iliac and femoral artery with early appearance of draining vein. B:
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Angiogram shows fistulas fed by branches of the iliac artery. C: angiograms shows vascular malformation with microfistulas in the ankle region. D: Spinal arteriovenous
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malformation with intranidal aneurysms (asterisk) and venous pouch (arrow) was fed by anterior spinal artery originating from the left L1 intercostal artery. E: After partial
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embolization with Glubran intranidal aneurysm were eliminated and the volume was reduced.
Figure 2 Radiographic findings in a 24-year-old male patient with spinal arteriovenous malformation associated with Parkes Weber syndrome. A-C: CT
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angiography shows vascular malformation fed by enlarged feeding arteries in the iliac, knee (B) and tibial (C) region and varicosed draining veins early appeared in the tibial
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region (C). D: Reconstructed angiogram shows spinal vascular malformation fed by enlarged anterior spinal artery and posterior spinal artery originating from T9
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intercostal artery. E: Multiple enlarged draining veins was observed. F: During the embolization procedure, contrast leakage was noticed. G: Glubran cast in the malformation. H: After partial embolization, the volume of spinal malformation was markedly reduced.
ACCEPTED MANUSCRIPT Table 1. Summary of reported cases of spinal AVM associated with Parkes Weber syndrome Age(years
Reference
Symptoms
Type, location
spinal AVM treatment/Results
Follow up/Outcome
13 /M
SAH
Intramedullary, T9–T12
No treatment
No data provided
22 /F
Repetitive SAH
Intramedullary, T5–T6
No data provided
No data provided
28 /M
SAH
Intramedullary, T9–L2
No data provided
No data provided
13 /F
Repetitive SAH
Intramedullary, L1–L2
Embolization/partial embolization
No data provided
15 /M
SAH
Intramedullary, L1–L2
Embolization with Gelfoam and
No data provided
)/Sex Djindjian et
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al(9), 1977
dura mater/partial embolization 9/F
19/M
al(30),1990 Nakstad et
13 / F
al(23), 1993 Szajner et al(29),
48 / F
Embolization with
Die
Gelfoam/complete
Low limbs
Intradural extramedullary,
weakness
T11-L2.
Surgical resection/complete
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28 / F
1989
Tan et
Intramedullary, T11-T12
low limbs pain
x et al(5), 1985 Kojima et al(20),
Back, neck and
resection
6 months/ Bladder dysfunction complicated
Thoracic pain
Intramedullary, T2–T6
Surgical resection
Slight improvement
and paraplegia
and T10–T12
Back pain,
Intradural extramedullary
Embolization with platinum fibre
3
myelopathy
sAVF, T11-T12
coils/complete embolization
Recovery
Asymptomatic
Paravertebral, C4- T1
Embolization with
6 months/Recovery
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Benhaiem-Sigau
months
/
NBCA/complete embolization
1999 Alexander et
30 /M
(1)
bilateral lower limbs weakness,
al , 2002
Epidural, T3-T4
37 / F
2007
29 / F
Radicular pain
24 / F
and perineal
surgery/partial embolization and
worsened and
pain
complete resection
subsequently
Bagherpour et al(3),2016
SAH
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2008
Present cases
14 /F
12 / F
Recovery
3 months / Initially
Neck pain,
Intradural, T12-L2
Epidural, C5-T2
myelopathy
Iizuka et al(17),
NBCA and then surgical
Embolization with NBCA and
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Rohany et al(26),
6 months /
excision/partial resection
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and numbness
Embolization with PVA and
SAH
Back pain,
Conus medullaris
Conus medullaris
improved Multiple embolization and
4 years/
surgery/ complete resection
Recovery
Endovascular embolization with
6 years /
NBCA/partial embolization
Recovery
Bilateral
laminectomies
surgical
ligation
followed
by
of
and
2 years/ Recovery
fistulas
endovascular
embolization with NBCA Intramedullary, T12-L4
myelopathy
Embolization with Glubran
6 years/ Ambulatory
/partial embolization
with amputation of her left foot
24 /M
Repetitive SAH,
Intramedullary, T8-L4
myelopathy
Embolization with Glubran / partial embolization
F, female; M, male; SAH, subarachnoid hemorrhage, C, cervical; T, thoracic; L, lumbar; spinal AVM, spinal arteriovenous malformation; NBCA, N-butyl cyanoacrylate.
5 years/Paraplegia
ACCEPTED MANUSCRIPT Table 2. Clinical and radiological characteristics of vascular anomalies KTS
CM-AVM
Cobb
Sturge-Weber
Limb
Limb
Multifocal
Vascular skin
Brain atrophy,
hypertrophy,
hypertrophy,
cutaneous stain,
nevus
seizure, glaucoma
cardiac
Venous
cardiac failure,
failure
varicosities
Radiographic
Extensive
Absence of
High flow
Spinal canal
Subcortical
findings
fistulas in
fistulas in
vascular AVM of
angioma at the
calcification, pial
involved
involved limb
fistulas
same metamere
angiomatosis
Large; pink to red
Multifocal,
Pink to red
Pink to red nevus on
angiomas on the
the head or neck
limb
Arteriovenous
large;
or red to
atypical, small;
pink to red
violaceous
pink-red macules
back
Usually
Always
Usually
None
Always
Absent
fistulas
Overgrowth
Usually the
Usually the lower
feature
lower limb
limb
Lymphatic
Rare
Rarefied,
Always
None
fistula of the spinal canal None
Common
Rare
Lymphangioma
None
Rarefied,
Rarefied,
Kyphoscoliosis
None
None
leptomeningeal
osteoporosis
osteoporosis
Brain
Intracranial
Not reported
Intracranial AVM
involvement
AVM or AVF
Spinal vascular
Extradural
EP
malformation
None
osteoporosis
disorders
Arteriovenous
Venules
None
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malformation Bone alteration
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Venous varicose
Typically,
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Cutaneous stain
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PWS Main presentation
None
or AVF
Spinal AVM
and spinal
malformations
Spinal AVM or
None
cavernomas
AVM
RASA1
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Involved gene
AGGF1，PIK3CA
RASA1
Not clear
GNAQ
mutation
AVM, arteriovenous malformation; AVF, arteriovenous fistula; PWS, Parkes Weber syndrome; KTS, Klippel-Trenaunay syndrome; CM-AVM, capillary malformation–arteriovenous malformation.
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EP
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ACCEPTED MANUSCRIPT
ACCEPTED MANUSCRIPT
Highlights 1. Two illustrative cases of Park Weber Syndrome with genetic testing 2. Two illustrative cases of Park Weber Syndrome with long-term follow-up
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3. A summary table of case reports of Parkes-Weber Syndrome in the literature 4. A key table comparing clinical and radiological characteristics of PWS as
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compared to other major vascular syndromes.
ACCEPTED MANUSCRIPT Abbreviations and Acronyms
PWS: Parkes Weber syndrome
MRI: Magnetic Resonance Imaging DSA: Digital subtraction angiography
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SAH: Subarachnoid hemorrhage
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MRA: Magnetic Resonance Angiography
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AVM: Arteriovenous malformation
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KTS: Klippel-Trenaunay syndrome
S1878-8750(17)30972-5
DOI:
10.1016/j.wneu.2017.06.080
Reference:
WNEU 5951
To appear in:
World Neurosurgery
Received Date: 1 April 2017 Revised Date:
10 June 2017
Accepted Date: 13 June 2017
Please cite this article as: Li Z-F, Li Q, Xu Y, Hong B, Huang Q-H, Liu J-M, Spinal arteriovenous malformation associated with Parkes Weber syndrome: Report of two cases and literature review, World Neurosurgery (2017), doi: 10.1016/j.wneu.2017.06.080. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
ACCEPTED MANUSCRIPT Spinal arteriovenous malformation associated with Parkes Weber syndrome: Report of two cases and literature review
[email protected]
Qiang Li, M.D.
[email protected]
Yi Xu, M.D.
[email protected]
Bo Hong, M.D.
[email protected]
Qing-Hai Huang, M.D.
[email protected]
Jian-Min Liu, M.D
[email protected]
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Zi-Fu Li, M.D.
Department of Neurosurgery, Changhai Hospital, Second Military Medical University,
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Shanghai, China
Corresponding to: Qing-Hai Huang or Jian-Min Liu
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Department of Neurosurgery, Changhai Hospital, Second Military Medical University,
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Shanghai 200433, China，
E-mail: [email protected] Telephone: +86 21-31161784; Fax: +86 21-31161784
This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors. Acknowledgements: None
ACCEPTED MANUSCRIPT Spinal arteriovenous malformation associated with Parkes Weber syndrome: Report of two cases and literature review ABSTRACT To present two cases of Parkes Weber syndrome (PWS) with spinal
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Objective
arteriovenous malformation(AVM), and discuss the radiological features and clinical treatment with literature review.
Clinical data on two PWS patients with spinal AVM was acquired in a
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Methods
prospective follow-up investigation. Clinical manifestations, radiographic features,
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procedural results and follow-up outcome were collected and reviewed together with literature review. Results
The first patient presented with limb weakness and urinary dysfunction and
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the second with repetitive subarachnoid hemorrhage followed by paraplegia. Limb hypertrophy, skin ulceration and extensive microfistulas in the affected limb were observed in both patients. Spinal AVM was confirmed by digital subtraction
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angiography and endovascular embolization was performed for them. The first patient
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experienced limb amputation at 6-year follow up due to chronic ulceration and the second did not have neurological improvement. After literature review, 15 cases (male: female=5:10; mean age: 22±10.4 years) were included. The presentations mainly include subarachnoid hemorrhage in 6, radicular pain in 5, myelopathy in 4 and asymptomatic in one. Embolization was performed in 9 cases, solitary surgery in 2 and combined therapy in 4. Among 10 cases with known follow up results, 6 achieved neurological recovery after surgery and one died after solitary surgery.
ACCEPTED MANUSCRIPT Conclusions
Awareness of the association between spinal AVM and PWS is
essential for radiographic screening of spinal lesions with myelopathy or intracranial subarachnoid hemorrhage. Clinical therapeutic strategy should be multidisciplinary
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and individualized on the basis of vasculature and lesion behavior. Key Words Parkes Weber syndrome; myelopathy; spine; arteriovenous malformation;
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subarachnoid hemorrhage
ACCEPTED MANUSCRIPT Introduction Parkes Weber syndrome (PWS) is rare congenital vascular malformation which consists arteriovenous shunts
venous
capillary and lymphatic malformation
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presenting with limb hypertrophy, cutaneous stain and skin ulceration.(4) It is characterized by fast-flow fistulas or shunts, resulting in multisystematic impairment with poor prognosis. The disorder is easily misdiagnosed as Klippel-Trenaunay
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syndrome (KTS), and is clinically and radiologically different from other slow-flow
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vascular malformations.(2)
Spinal arteriovenous malformation (AVM) associated with PWS is a rare condition. Various forms of spinal AVM were reported, mainly including intramedullary, intradural, epidural and paravertebral type. These spinal lesions may
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cause acute myelopathy or subarachnoid hemorrhage (SAH) at a young age, and potentially result in serious neurological sequalae and threaten their quality of life. Here, in order to systematically review the similar cases and promote awareness of the
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association with spinal lesions, we first presented two additional cases, and then
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discuss the radiographic features and clinical treatment with literature review.
Case reports Case 1
A 12-year-old girl complained of low back pain, numbness and weakness of left leg and urinary retention two weeks before admission, with a history of hypertrophy and warmth in the left lower extremity since five months after birth, and a history of
ACCEPTED MANUSCRIPT repetitive ulceration in her left ankle and length discrepancy between two legs at 3 years old. Neurological examination showed reduced muscle strength of 2/5 and
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hypoesthesia in the left lower extremity and negative Babinski sign. Physical examination showed hypertrophy, faint capillary stain on her waist, varicosity in her left leg with higher temperature, ulceration in her left foot. Auscultation revealed bruit
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along the whole left leg and accentuated cardiac sounds in the precordial region.
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Brain natrium protein level (130 pg/ml) was mildly elevated. The RASA1 gene mutation was negative. Magnetic Resonance Imaging (MRI) showed osseous change in the femoral bone. Magnetic Resonance Angiography (MRA) showed enlarged iliac and femoral artery with early appearance of draining vein. Chest X ray showed
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scoliosis.
Digital subtraction angiography (DSA) demonstrated intramedullary spinal AVM with moderate flow fed by anterior spinal artery arised from the left L1 intercostal
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artery. Selective angiograms showed two aneurysms perched on the branches of ASA
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feeding arteries and venous pouch within the nidus. Angiogram in the lower limbs reveals extensive fistulas and shunts in the left thigh, knee and tibial region (Figure 1). Endovascular treatment was performed for the patient in order to eliminate the intranidal aneurysms. The intercostal artery was then selectively catheterized with Cobra catheter (Cook, Indiana, USA). Using a triaxial system, a microcatheter (Marathon, Covidien, CA, USA) was advanced into the ASA branches. After angiographic confirmation of the aneurysm location, 25% Glubran (GEM, Viareggio,
ACCEPTED MANUSCRIPT Italy) was slowly injected into the aneurysm and 16.7% Glubran into the other. Control angiography immediately after embolization demonstrated elimination of the two aneurysms and partial embolization was achieved.
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After endovascular treatment, urinary dysfunction disappeared. The muscle strength of left leg returned to normal at discharge. Embolization of fistulas in the left leg was subsequently embolized with platinum coils for four times in department of
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vascular surgery at the following 3 years of follow up. At 3-year follow-up,
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Ultrasound Doppler showed enlargement of the left ventricle and CT angiography showed pulmonary hypertension. At 5-year follow-up, the girl underwent amputation of the left foot due to chronic skin ulceration and gangrene. At 6-year follow-up, the patient remained neurologically intact and was fully ambulatory with a prosthesis.
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Case 2
A 24-year-old man with a history of congenital overgrown right leg and varicosities experienced subarachnoid hemorrhage (SAH) for three times presenting with severe
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headache within three years. DSA performed in an outside institution showed negative
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findings of intracranial vessels. Two weeks before admission, the patient experienced sudden onset of paraplegia and urinary dysfunction and was transferred to our center. Physical examination showed loss of motor and sensory under the L1 level, and
right leg hypertrophy with varicosities. Significant bruit and temperature difference were noticed along the right low limb. The result of RASA1 gene mutation test was negative. MRI showed a intramedullary spinal AVM at the level of T8-L4. CT angiography showed extensive
ACCEPTED MANUSCRIPT fistulas in the iliac region and early appearance of enlarged superficial veins in the right lower limb and DSA demonstrated that spinal AVM was mainly fed by ASA and posterior spinal artery (PSA) arose from the T9 intercostal artery, and by PSA from
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the T12 intercostal artery. Angiograms also showed multiple fistulous were visualized along the right leg (Figure 2).
Endovascular embolization was performed for the patient due to repetitive SAH
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related to spinal AVM. Supported by Cobra catheter, a triaxial system including
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Marathon microcatheter and microwire initially failed to be advanced into the ASA branches due to a sharp turn at the ostium of radicular medullary artery. Embolization with 20% Glubran was then performed via feeding branches of the PSA that originate from T9 and T12 intercostal arteries. After third injection, reflux of Glubran was
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noticed and then microcatheter was withdrawn from PSA. At this time, contrast extravasation was seen and rapid embolization of rupture point and feeding arteries with Glubran was done to stop the hemorrhage. Finally, partial embolization of the
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spinal AVM was achieved. Ventricular and lumbar drainage was subsequently
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performed. Two weeks later, the patient was discharged with slight improvement on sensory function but paraplegia was not improved. After hyperbaric treatment, urinary dysfunction and motor complete paraplegia were not improved. At 6-year follow-up, no episodes of rebleeding occurred and the neurological status was the same. Review strategy Using Pubmed database, published papers between 1975 and 2015 were searched to identify the PWS patients with spinal AVM. Because the confusion of nomenclature,
ACCEPTED MANUSCRIPT the search was done with combination of keywords: “Klippel-Trenaunay-Weber”, “Parkes Weber”, and “spinal arteriovenous malformation”. The cases with the nomenclature of Klippel-Trenaunay syndrome were excluded. The reported cases of
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Klippel-Trenaunay-Weber syndrome with microfistulas were recognized as PWS. Search results
In the review, 15 cases (5, male; 10; female) were included, with a mean age of 22±
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10.4 years (rang: 9-48 years). The presentations related to spinal AVM mainly include
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subarachnoid hemorrhage in 6, back or neck pain in 5, myelopathy in 4 and asymptomatic in 1. The reported cases were summarized in Table 1. The spinal lesions located in intramedullary portion in 8, intradural in 3, intradural extramedullary in 2
and epidural in 2, and paravertebral in 1. Among 12 cases with
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reported treatment embolization was performed in 6 cases, solitary surgery in 2 case, and combined therapy of embolization and surgery in 4. Among 10 cases with known follow up results, 6 achieved neurological recovery after surgery and one died after
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solitary surgery.
Discussion
The two cases demonstrated the spinal AVM presenting with acute myelopathy and SAH was associated with PWS. The radiological findings showed the fast-flow nature of vascular malformation in the affected limb and spinal lesions. Multisystematic impairment was observed including cardiovascular system and bone. Differential Diagnosis
ACCEPTED MANUSCRIPT Among all the vascular anomalies, PWS is easily misdiagnosed as other vascular malformations, especially KTS, and the overlapping feature of cutaneous stain is also confusing. The slow-flow feature and the relatively good clinical outcome of KTS
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patients differ from PWS clinically and radiologically.(14,22) PWS shares the common feature of fast-flow arteriovenous fistulas along the affected extremity with capillary malformation–arteriovenous malformation (CM-AVM). Similar with PWS,
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several vascular anomalies share the overlapping features of cutaneous stain, such as
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KTS, CM-AVM, Cobb syndrome and Sturge-Weber syndrome.(7,10,15,16,18,27) However, limb overgrowth is not observed in CM-AVM, Cobb syndrome and Sturge-Weber syndrome.(6,10,21) Different genes were reported to be associated with these congenital vascular malformation, and only RASA1 mutation was reported in
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familial cases of PWS and CM-AVM but not in our two cases.(31) The clinical and radiographic characteristics are differentiated and summarized in Table 2. Multisystematic Impairment
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Multisystematic impairment was usually present, as observed in the first case at the
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long-term follow-up. These systems included limb hypertrophy, skin ulceration and pigmentation, cardiac failure and skeletal change.(1,8,11,12,17,24,26,28) The elevated level of brain natrium protein and enlargement of the left ventricle indicate the cardiac impairment. The high-output cardiac failure is attributed to the multiple fistulas or shunts in the affected limbs.(24) At the same time, these microfistulas also cause peripheral microcirculation compromise due to blood steal phenomena, resulting in chronic ulceration or gangrene in the distal area of extremity. The long bone in the
ACCEPTED MANUSCRIPT affected extremity also endure morphological and pathological change, which secondarily leads to scoliosis. The high blood flow, high temperature and enhanced oxygenation caused by the fistulas stimulate the osteoblasts to produce bone
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overgrowth. (19,25) Mechanism of Concomitant Spinal AVM
The mechanism of association of spinal AVM and PWS is not clear. Both of spinal
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AVM and PWS are rare diseases, the coincidence rate is extremely low. We presumed
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that an underlying mechanism responsible for the association. In all the reviewed cases including ours, the location of hypertrophic lower limb mostly corresponds to the level of the spinal AVM at the nearly same level from T12 to L1, we considered that the association may be attributed to the same metamere. However, it can not
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explain the spinal AVM beyond these locations.(30) The RASA1 mutation identified in familial cases of PWS patients can explain the capillary malformation but not the
association.
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spinal AVM instead. More cases with genetic investigation was needed to uncover the
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Characteristics of Concomitant Spinal AVM Many forms of spinal AVM was reported to be associated with PWS, including intramedullary,
intradural,
epidural,
intradural
extramedullary
and
paravertebral.(17,26) In our cases, the intramedullary spinal AVM carries the risky structure of intranidal aneurysms. The flow is relatively high and characterized by multiple enlarged feeding arteries, shunting and multiple enlarged draining veins. Intranidal aneurysms, high-flow shunt and venous pouch increased the architectural
ACCEPTED MANUSCRIPT risks of the spinal AVM, which potentially cause SAH, intramedullary hemorrhage and venous hypertension. The concomitant spinal AVM reminded us that screening of spinal lesions should be paid attention to for PWS patients with SAH and without
Treatment Options for Concomitant Spinal AVM
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intracranial findings.
The optimal approach of treating spinal AVM in PWS patient depends on risk-benefit
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analysis according to the vasculature and lesion behavior. The risky structure of
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intranidal aneurysms and high-flow fistulas potentially cause hemorrhage and venous hypertension, respectively. Embolization of these lesions was necessary. However, complete embolization or resection will increase the risk of spine cord injury due to complexity of the vasculature and easy reflux of embolization materials to the trunk
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of ASA or PSA. Kojima et al.(20) reported a solitary resection for intradural spinal AVM on dorsal side from T11 to L2 and new symptom of bladder dysfunction and weakness in both legs developed after surgery. It suggests that the solitary resection
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probably increased the risks of complication. Rohany et al(26) reported the feasibility
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of surgical removal after preoperative embolization in two cases with multiplicity of pial fistulas on the dorsal side and mass effect, and achieved complete elimination of the spinal AVM and the good clinical outcome. They think that the objective of surgery is to decompress the spinal cord rather than resect the spinal AVM. Alexander et al.(1) performed embolization, partial resection and spinal cord decompression for a case with extensive involvement of the AVM, and considered this palliative strategy benefited the symptoms and gross total resection would increase the risks of
ACCEPTED MANUSCRIPT complication. From our viewpoint, the aim of embolization is to eliminate the risky structure and maximally reduce the microfistulas in order to alleviate the venous hypertension. After adopting partial embolization, no recurrence of bleeding occurred
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at the long-term follow-up in our two cases. Multidisciplinary Treatment
Owing to the multisystematic impairment, multidisciplinary approach is essential to
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treat the involved systems. The strategy included treatment plans for hypertrophic
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tissue, cardiac failure, elongation of the long bone, capillary malformation and fistulas in the involved extremity.(8,13,24,26) Therefore a multidisciplinary team is required, including neurosurgeon, cardiologist, radiologist, orthopedist, plastic and vascular surgeons, geneticist
and the physical therapy physician. With regard to the first case,
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spinal AVM was embolized and the following embolization of microfistulas was performed in multiple sessions in the department of vascular surgery to reduce the hyperkinetic circulation and steal phenomena. However, pulmonary hypertension and
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ventricle enlargement still develop due to the remaining fistulas and shunts. The
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ischemia in her left footwas also worsened, resulting in gangrene and amputation of her left foot. Therefore, maximal embolization of fistulas was vital to reduce the long-term insult to the multiple systems. The cardiac failure is the most common complication for PWS patient due to high-output burden(24), surveillance of cardiac function and balanced fluid management is necessary. For scoliosis caused by bone elongation, life quality can be improved by plastic and orthopedic surgery. Multidisciplinary collaboration and individualized therapy were essential to provide
ACCEPTED MANUSCRIPT needed supports for their return to normal life. Conclusion The two cases demonstrated the association of spinal AVM and PWS. It reminded us
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that the complicated spinal AVM may cause potential myelopathy or SAH. Awareness of radiological screening of spinal AVM was essential to track the source of intracranial SAH in PWS patients. Multidisciplinary approach was essential to deal
1.
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Garzon MC, Huang JT, Enjolras O, Frieden IJ: Vascular malformations. Part II: associated
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Gloviczki P, Driscoll DJ: Klippel-Trenaunay syndrome: current management. Phlebology
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syndromes. J Am Acad Dermatol 56:541-564,2007. 22:291-298,2007. 15.
Hershkovitz D, Bercovich D, Sprecher E, Lapidot M: RASA1 mutations may cause hereditary capillary malformations without arteriovenous malformations. British Journal of Dermatology 158:1035-1040,2008.
Hu Y, Li L, Seidelmann SB, Timur AA, Shen PH, Driscoll DJ, Wang QK: Identification of
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association of common AGGF1 variants with susceptibility for Klippel-Trenaunay syndrome using the structure association program. Annals of Human Genetics 72:636-643,2008. Iizuka Y, Suzuki M, Komura S, Takada T, Shimoji K: Conus medullaris spinal arteriovenous
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Johnson WD, Petrie MM: Variety of spinal vascular pathology seen in adult Cobb syndrome. Journal of Neurosurgery: Spine 10:430-435,2009.
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PH,
Hald
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Bakke
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Multiple
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in
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ACCEPTED MANUSCRIPT Table 1. Summary of reported cases of spinal AVM associated with Parkes Weber syndrome Age(years
Reference
Symptoms
Type, location
spinal AVM treatment/Results
Follow up/Outcome
13 /M
SAH
Intramedullary, T9–T12
No treatment
No data provided
22 /F
Repetitive SAH
Intramedullary, T5–T6
No data provided
No data provided
28 /M
SAH
Intramedullary, T9–L2
No data provided
No data provided
13 /F
Repetitive SAH
Intramedullary, L1–L2
Embolization/partial embolization
No data provided
15 /M
SAH
Intramedullary, L1–L2
Embolization with Gelfoam and
No data provided
)/Sex Djindjian et
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al(9), 1977
dura mater/partial embolization 9/F
Back, neck and
28 / F
Low limbs
Intradural extramedullary,
Surgical resection/complete
6 months/ Bladder
weakness
T11-L2.
resection
dysfunction
1989
19/M
Tan et al(30),1990 Nakstad et
13 / F
al(23), 1993 Szajner et al(29),
48 / F
Embolization with
Die
Gelfoam/complete
SC
low limbs pain
x et al(5), 1985 Kojima et al(20),
Intramedullary, T11-T12
complicated
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Benhaiem-Sigau
Thoracic pain
Intramedullary, T2–T6
Surgical resection
Slight improvement
and paraplegia
and T10–T12
Back pain,
Intradural extramedullary
Embolization with platinum fibre
3
myelopathy
sAVF, T11-T12
coils/complete embolization
Recovery
Asymptomatic
Paravertebral, C4- T1
Embolization with
6 months/Recovery
months
/
NBCA/complete embolization
1999 Alexander et
30 /M
(1)
bilateral lower
Epidural, T3-T4
al , 2002
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limbs weakness, and numbness 37 / F
2007
29 / F
Radicular pain
surgery/partial embolization and
worsened and
pain
complete resection
subsequently
Bagherpour et al(3),2016
SAH
AC C
2008
24 / F
Present cases
14 /F
12 / F
excision/partial resection
and perineal
Epidural, C5-T2
SAH
Back pain,
improved Multiple embolization and
4 years/
surgery/ complete resection
Recovery
Conus medullaris
Endovascular embolization with
6 years /
NBCA/partial embolization
Recovery
Conus medullaris
Bilateral
myelopathy
Iizuka et al(17),
Recovery
3 months / Initially
Neck pain,
Intradural, T12-L2
6 months /
NBCA and then surgical
Embolization with NBCA and
EP
Rohany et al(26),
Embolization with PVA and
laminectomies
surgical
ligation
followed
by
of
and
2 years/ Recovery
fistulas
endovascular
embolization with NBCA Intramedullary, T12-L4
myelopathy
Embolization with Glubran
6 years/ Ambulatory
/partial embolization
with amputation of her left foot
24 /M
Repetitive SAH,
Intramedullary, T8-L4
myelopathy
Embolization with Glubran / partial embolization
F, female; M, male; SAH, subarachnoid hemorrhage, C, cervical; T, thoracic; L, lumbar; spinal AVM, spinal arteriovenous malformation; NBCA, N-butyl cyanoacrylate.
5 years/Paraplegia
ACCEPTED MANUSCRIPT Table 2. Clinical and radiological characteristics of vascular anomalies KTS
CM-AVM
Cobb
Sturge-Weber
Limb
Limb
Multifocal
Vascular skin
Brain atrophy,
hypertrophy,
hypertrophy,
cutaneous stain,
nevus
seizure, glaucoma
cardiac
Venous
cardiac failure,
failure
varicosities
Radiographic
Extensive
Absence of
High flow
Spinal canal
Subcortical
findings
fistulas in
fistulas in
vascular AVM of
angioma at the
calcification, pial
involved
involved limb
fistulas
same metamere
angiomatosis
Large; pink to red
Multifocal,
Pink to red
Pink to red nevus on
angiomas on the
the head or neck
limb
Arteriovenous
large;
or red to
atypical, small;
pink to red
violaceous
pink-red macules
back
Usually
Always
Usually
None
Always
Absent
fistulas
Overgrowth
Usually the
Usually the lower
feature
lower limb
limb
Lymphatic
Rare
Rarefied,
Always
None
fistula of the spinal canal None
Common
Rare
Lymphangioma
None
Rarefied,
Rarefied,
Kyphoscoliosis
None
None
leptomeningeal
osteoporosis
osteoporosis
Brain
Intracranial
Not reported
Intracranial AVM
involvement
AVM or AVF
Spinal vascular
Extradural
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malformation
None
osteoporosis
disorders
Arteriovenous
Venules
None
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malformation Bone alteration
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Venous varicose
Typically,
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Cutaneous stain
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PWS Main presentation
None
or AVF
Spinal AVM
and spinal
malformations
Spinal AVM or
None
cavernomas
AVM
RASA1
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Involved gene
AGGF1 PIK3CA
RASA1
Not clear
GNAQ
mutation
AVM, arteriovenous malformation; AVF, arteriovenous fistula; PWS, Parkes Weber syndrome; KTS, Klippel-Trenaunay syndrome; CM-AVM, capillary malformation–arteriovenous malformation.
ACCEPTED MANUSCRIPT Figure legends Figure 1 Radiographic findings in a 12-year-old girl with spinal arteriovenous malformation associated with Parkes Weber syndrome. A: MR angiography shows enlarged iliac and femoral artery with early appearance of draining vein. B:
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Angiogram shows fistulas fed by branches of the iliac artery. C: angiograms shows vascular malformation with microfistulas in the ankle region. D: Spinal arteriovenous
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malformation with intranidal aneurysms (asterisk) and venous pouch (arrow) was fed by anterior spinal artery originating from the left L1 intercostal artery. E: After partial
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embolization with Glubran intranidal aneurysm were eliminated and the volume was reduced.
Figure 2 Radiographic findings in a 24-year-old male patient with spinal arteriovenous malformation associated with Parkes Weber syndrome. A-C: CT
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region (C). D: Reconstructed angiogram shows spinal vascular malformation fed by enlarged anterior spinal artery and posterior spinal artery originating from T9
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intercostal artery. E: Multiple enlarged draining veins was observed. F: During the embolization procedure, contrast leakage was noticed. G: Glubran cast in the malformation. H: After partial embolization, the volume of spinal malformation was markedly reduced.
ACCEPTED MANUSCRIPT Table 1. Summary of reported cases of spinal AVM associated with Parkes Weber syndrome Age(years
Reference
Symptoms
Type, location
spinal AVM treatment/Results
Follow up/Outcome
13 /M
SAH
Intramedullary, T9–T12
No treatment
No data provided
22 /F
Repetitive SAH
Intramedullary, T5–T6
No data provided
No data provided
28 /M
SAH
Intramedullary, T9–L2
No data provided
No data provided
13 /F
Repetitive SAH
Intramedullary, L1–L2
Embolization/partial embolization
No data provided
15 /M
SAH
Intramedullary, L1–L2
Embolization with Gelfoam and
No data provided
)/Sex Djindjian et
RI PT
al(9), 1977
dura mater/partial embolization 9/F
19/M
al(30),1990 Nakstad et
13 / F
al(23), 1993 Szajner et al(29),
48 / F
Embolization with
Die
Gelfoam/complete
Low limbs
Intradural extramedullary,
weakness
T11-L2.
Surgical resection/complete
SC
28 / F
1989
Tan et
Intramedullary, T11-T12
low limbs pain
x et al(5), 1985 Kojima et al(20),
Back, neck and
resection
6 months/ Bladder dysfunction complicated
Thoracic pain
Intramedullary, T2–T6
Surgical resection
Slight improvement
and paraplegia
and T10–T12
Back pain,
Intradural extramedullary
Embolization with platinum fibre
3
myelopathy
sAVF, T11-T12
coils/complete embolization
Recovery
Asymptomatic
Paravertebral, C4- T1
Embolization with
6 months/Recovery
M AN U
Benhaiem-Sigau
months
/
NBCA/complete embolization
1999 Alexander et
30 /M
(1)
bilateral lower limbs weakness,
al , 2002
Epidural, T3-T4
37 / F
2007
29 / F
Radicular pain
24 / F
and perineal
surgery/partial embolization and
worsened and
pain
complete resection
subsequently
Bagherpour et al(3),2016
SAH
AC C
2008
Present cases
14 /F
12 / F
Recovery
3 months / Initially
Neck pain,
Intradural, T12-L2
Epidural, C5-T2
myelopathy
Iizuka et al(17),
NBCA and then surgical
Embolization with NBCA and
EP
Rohany et al(26),
6 months /
excision/partial resection
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and numbness
Embolization with PVA and
SAH
Back pain,
Conus medullaris
Conus medullaris
improved Multiple embolization and
4 years/
surgery/ complete resection
Recovery
Endovascular embolization with
6 years /
NBCA/partial embolization
Recovery
Bilateral
laminectomies
surgical
ligation
followed
by
of
and
2 years/ Recovery
fistulas
endovascular
embolization with NBCA Intramedullary, T12-L4
myelopathy
Embolization with Glubran
6 years/ Ambulatory
/partial embolization
with amputation of her left foot
24 /M
Repetitive SAH,
Intramedullary, T8-L4
myelopathy
Embolization with Glubran / partial embolization
F, female; M, male; SAH, subarachnoid hemorrhage, C, cervical; T, thoracic; L, lumbar; spinal AVM, spinal arteriovenous malformation; NBCA, N-butyl cyanoacrylate.
5 years/Paraplegia
ACCEPTED MANUSCRIPT Table 2. Clinical and radiological characteristics of vascular anomalies KTS
CM-AVM
Cobb
Sturge-Weber
Limb
Limb
Multifocal
Vascular skin
Brain atrophy,
hypertrophy,
hypertrophy,
cutaneous stain,
nevus
seizure, glaucoma
cardiac
Venous
cardiac failure,
failure
varicosities
Radiographic
Extensive
Absence of
High flow
Spinal canal
Subcortical
findings
fistulas in
fistulas in
vascular AVM of
angioma at the
calcification, pial
involved
involved limb
fistulas
same metamere
angiomatosis
Large; pink to red
Multifocal,
Pink to red
Pink to red nevus on
angiomas on the
the head or neck
limb
Arteriovenous
large;
or red to
atypical, small;
pink to red
violaceous
pink-red macules
back
Usually
Always
Usually
None
Always
Absent
fistulas
Overgrowth
Usually the
Usually the lower
feature
lower limb
limb
Lymphatic
Rare
Rarefied,
Always
None
fistula of the spinal canal None
Common
Rare
Lymphangioma
None
Rarefied,
Rarefied,
Kyphoscoliosis
None
None
leptomeningeal
osteoporosis
osteoporosis
Brain
Intracranial
Not reported
Intracranial AVM
involvement
AVM or AVF
Spinal vascular
Extradural
EP
malformation
None
osteoporosis
disorders
Arteriovenous
Venules
None
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malformation Bone alteration
SC
Venous varicose
Typically,
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Cutaneous stain
RI PT
PWS Main presentation
None
or AVF
Spinal AVM
and spinal
malformations
Spinal AVM or
None
cavernomas
AVM
RASA1
AC C
Involved gene
AGGF1，PIK3CA
RASA1
Not clear
GNAQ
mutation
AVM, arteriovenous malformation; AVF, arteriovenous fistula; PWS, Parkes Weber syndrome; KTS, Klippel-Trenaunay syndrome; CM-AVM, capillary malformation–arteriovenous malformation.
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Highlights 1. Two illustrative cases of Park Weber Syndrome with genetic testing 2. Two illustrative cases of Park Weber Syndrome with long-term follow-up
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3. A summary table of case reports of Parkes-Weber Syndrome in the literature 4. A key table comparing clinical and radiological characteristics of PWS as
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compared to other major vascular syndromes.
ACCEPTED MANUSCRIPT Abbreviations and Acronyms
PWS: Parkes Weber syndrome
MRI: Magnetic Resonance Imaging DSA: Digital subtraction angiography
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SAH: Subarachnoid hemorrhage
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MRA: Magnetic Resonance Angiography
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AVM: Arteriovenous malformation
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KTS: Klippel-Trenaunay syndrome