XML Template (2014) [30.7.2014–9:35am] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/PHLJ/Vol00000/140097/APPFile/SG-PHLJ140097.3d
(PHL)
[1–3] [PREPRINTER stage]
Phlebology OnlineFirst, published on July 31, 2014 as doi:10.1177/0268355514544782
Short Report
Chronic cerebrospinal venous insufficiency is not associated with chronic venous disorders: A case–control study
Phlebology 0(0) 1–3 ! The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0268355514544782 phl.sagepub.com
Maurizio A Leone1,2, Olga Raymkulova1, Piergiorgio Lochner3, Laura Bolamperti1, Gianandrea Rivadossi4, Alessandro Stecco5, Giuseppe Zaccala6, Maurizio Maggio7, William Liboni4, Marilena Guido8, Lorenzo Coppo1 and Daniele Imperiale8
Abstract Objectives: To evaluate the relationship between chronic cerebrospinal venous insufficiency (CCSVI) and the presence of a Chronic Venous Disorder (CVD). Method: We included 55 subjects with CCSVI aged >18 years, and 186 controls without CCSVI. Each subject was evaluated with color Doppler sonography in accordance with Zamboni’s five criteria, examined by two neurologists and interviewed with an ad-hoc designed form. The neurologists and the sonographers were mutually blinded. CVD were classified according to CEAP. Results: Mean age was 42 years (SD ¼ 9) in cases and 43 years (10) in controls (p ¼ ns). The odds ratios in subjects CCSVI were 0.6 (0.2–2.2) for CEAP 1, 0.9 (0.2–4.5) for CEAP 2, and 1.0 (0.6–1.9) for family history of varicose veins. The prevalence of CVD and, family history of varicose veins, was similar between cases and controls for each Zamboni criterion. Conclusions: We found no association of CCSVI with the presence of CVD or family history of varicose veins.
Keywords CCSVI, multiple sclerosis, veins, CEAP, blinding
Introduction Chronic cerebrospinal venous insufficiency (CCSVI) is a recently described vascular condition that has been weakly associated with some peripheral venous diseases in one study.1 Chronic Venous Disorder (CVD) of the lower extremities are highly frequent in western populations and include a wide spectrum of clinical presentations, ranging from telangectasias to venous ulcerations.2 During two studies of the association of CCSVI with Multiple Sclerosis (MS) conducted in the Novara and Torino hospitals3,4,5 we collected information on the presence of CVD, allowing us to assess the relationship between CCSVI and the presence of CVD.
Methods We enrolled 217 MS patients (age >18 years), 126 healthy subjects (HS), and 49 patients with other
neurodegenerative diseases (OND), matched to MS patients by gender and age (5 years). Exclusion criteria (applied to MS, HS, and OND) were acute or chronic disabling disorders, severe cardiopathies or 1
SCDU Neurologia, Head and Neck Department, AOU ‘‘Maggiore della Carita`’’, Novara, Italy 2 Interdisciplinary Research Center of Autoimmune Diseases, IRCAD, Novara, Italy 3 Department of Neurology, Tappeiner Hospital, Merano, Italy 4 Fondazione ‘‘Un passo insieme’’, Valdellatorre, Italy 5 Istituto di Radiologia Diagnostica e Interventistica, AOU ‘‘Maggiore della Carita`’’, Novara, Italy 6 Department of Medicine, AOU ‘‘Maggiore della Carita`’’, Novara, Italy 7 SC Neurologia, Civile Hospital, Ivrea, Italy 8 SC Neurologia, Maria Vittoria Hospital, Torino, Italy Corresponding author: Maurizio A Leone, Centro Sclerosi Multipla, Ospedale ‘‘Maggiore della Carita`’’, C.so Mazzini 18, Novara 28100, Italy. Email: [email protected]
Downloaded from phl.sagepub.com at Kungl Tekniska Hogskolan / Royal Institute of Technology on November 15, 2015
XML Template (2014) [30.7.2014–9:35am] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/PHLJ/Vol00000/140097/APPFile/SG-PHLJ140097.3d
(PHL)
[1–3] [PREPRINTER stage]
2
Phlebology 0(0)
pulmonary diseases, prior cerebral or extracerebral venous thromboembolism, transient global amnesia, neoplasia, thrombophilic diseases, diabetes, head, and neck surgery, vasculitides, family history of MS, cerebral vascular malformations, congenital vascular malformations, and MS relapse or using steroids during the previous 30 days. Two neurologists blind to the color Doppler sonography (CDS) operators performed a general and neurological examination before the CDS and interviewed all subjects with an ad-hoc designed form. CDS were done with a GE Vivid7 scanner, with a 7.5–10 MHz high-resolution linear array transducer for extracranial measurements and a 2–3 MHz probe for transcranial evaluation of venous drainage (GE Healthcare, Milwaukee, Wisconsin, USA) in Novara, and with a MyLab-Vinco 25 machine (Esaote Biomedica, Genoa, Italy) with a linear LA332 11.3 MHz probe for extracranial measurement and with a phased PA240 2.5 Mhz probe for intracranial measurements in Torino. Several strategies were employed to ensure blinding of the CDS operators.3,4,5 The CDS investigation was carried out in accordance with the five criteria suggested by Zamboni et al.:3 a subject was considered CCSVI positive (CCSVI+) if 2 criteria were met. Subjects considered as borderline in our previous study3 are excluded here. CVD were classified according to the CEAP classification,6 based on clinical visit and ultrasound examination of the limbs when clinically indicated. Comparisons between groups were assessed using Student’s t-test and chisquare test were appropriate, and calculating Odds Ratios (OR) with their 95% confidence limits (CL). The study was approved by the Ethical Committees of the
Novara (# 28/11), and Torino (# 73/12/10) hospitals. Written informed consent was signed by all subjects.
Results Information on the presence of CVD was available for 182 subjects in Novara (79% of the total sample) and 59 in Torino (37%), including 136 MS patients (99 relapsing-remitting, 29 secondary progressive, and 8 primary progressive), 95 HS, and 10 OND (total ¼ 241). Comparison of the subjects with available information with the others did not disclose any statistically significant difference for age, gender, place of birth, type of MS, treatment, age at onset, and disease duration (data not shown). CCSVI was found in 30 MS patients, 24 OND, and 1 HC for a total of 55 CCSVIþ subjects (cases); the other 186 subjects without CCSVI (CCSVI) acted as controls. Women numbered 36 (65%) among CCSVI+ and 120 (65%) among CCSVI subjects (p ¼ ns). Mean age was 42 years (SD=9) in CCSVI+ and 43 years (10) in CCSVI (p=ns). Table 1 shows the prevalence of CVD and of family history of varicose veins among subjects positive and negative for each criterion and for CCSVI as a whole. Neither a single criterion nor CCSVI was associated with CVD. According to the CEAP classification, 19 subjects had primary and 4 secondary postthrombotic CVD. We did not find any association with the anatomic site (superficial vs. deep/perforator veins: 2/4 in CCSVI+ and 6/11 in CCSVI; p ¼ 0.93) and pathophysiology (occlusion/reflux/none ¼ 1/2/3 in CCSVI+ and 3/4/10 in CCSVI; p ¼ 0.89). We also analyzed CVD in subjects with and without MS
Table 1. Prevalence of chronic vascular disorders (according to CEAP classification) and family history of varicose veins in CCSVI positive and negative subjects. CEAP 1 CCSVI Criterion
CEAP 0 N (%)
N (%)
Criterion 1 þ
40 (90.9)
2 (4.6)
178 (90.4)
11 (5.6)
Criterion 2 þ
21 (100.0)
0
Criterion 3 þ
197 (89.6) 109 (91.6)
13 (5.9) 5 (4.2)
109 (89.3)
8 (6.6)
Criterion 4 þ
23 (82.1)
4 (14.3)
195 (91.6)
9 (4.2)
Criterion 5 þ
27 (90.0)
2 (6.7)
191 (90.5)
11 (5.2)
CCSVI
þ
49 (89.1)
4 (7.3)
169 (90.9)
9 (4.9)
CEAP 2 p*
OR (CL)*
0.79
p*
OR (CL)*
1.2
1 (2.3)
0.67
1.6
1 (2.3)
18; 26 (40.9)
(0.3–5.8)
7 (3.6)
(0.2–13.1)
1 (0.5)
73; 124 (37.1)
–
0
0.42
– 1.6
8 (3.6) 5 (4.2)
(0.5–5.0)
3 (2.5)
0.3
1 (3.6)
(0.1–0.9)
7 (3.3)
0.75 0.49
Family history of varicose veins
N (%)
0.24
0.03
CEAP 3–4
0.8
0
(0.2–3.7)
8 (3.8)
0.7
2 (3.6)
(0.2–2.2)
6 (3.2)
0.36 0.49 0.86 0.29 0.87
yes; no (% yes)
–
0
0.6
2 (0.9) 0
82; 138 (37.3) 46; 73 (38.7)
(0.1–2.6)
2 (1.6)
45; 77 (36.9)
0.8
0
12; 16 (42.9)
(0.1–7.0)
2 (0.94)
–
9; 12 (42.9)
1 (3.3)
11; 19 (36.7) 80; 131 (37.9)
0
(0.2–4.5)
2 (1.1)
0.63
21; 34 (38.2) 70; 116 (37.6)
*CEAP ¼ 0 is the reference category. No p-value is significant after Bonferroni’s correction for multiple comparisons.
Downloaded from phl.sagepub.com at Kungl Tekniska Hogskolan / Royal Institute of Technology on November 15, 2015
OR (CL) 1.2 (0.6–2.3)
0.61
1.3
0.78
(0.5–3.1) 1.1 (0.6–1.8)
0.55
79; 134 (37.1)
1 (0.47) 0.9
p
1.3 (0.6–2.8)
0.90
0.9 (0.4–2.1)
0.94
1.0 (0.6–1.9)
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3
separately. In MS patients, the ORs of being CCSVI+ were 1.0 (0.2–4.9) for CEAP 1, 0.6 (0.1–3.2) for CEAP 2, and 0.9 (0.4–2.1) for family history of varicose veins. The correspondent figure for HS and OND subjects were 0.3 (0.1–2.3) for CEAP 1, 1.0 (0.9–1.1) for CEAP 2, and 1.2 (0.5–2.9) for family history of varicose veins.
Discussion We found no association of CCSVI with the presence of CVD or a family history of varicose veins in this blinded study. The only other study that investigated peripheral venous diseases1 found that MS patients positive for CCSVI had an excess of bilateral telangiectasia at the legs, reticular veins, and venous stasis dermatitis. However sample size was very small and the results contradictory, since varicose veins were even more frequent in CCSVI negative subjects. Our study involved 241 patients and did not found an association with either telangectasia (CEAP 1) or varicose veins (CEAP 2). One limitation of our study is its nature of post-hoc analysis; however, the present sample (55 cases; 3.4 controls per case, alpha error ¼ 0.05) has enough power (1-beta ¼ 0.97) to detect an OR of 3.0, assuming a 30% prevalence of exposure (http://www.dceg.cancer.gov/tools/design/ power). Power was 0.35 and 0.70 for an OR of 1.5 and 2.0. The major strengths of our study are its blinded nature and the broad spectrum of the subjects examined.
Funding Dr. Olga Raymkulova is supported by CRT Foundation, Torino.
References 1. Van den Berg PJ, Van den Berg GB, Westerhuis LW, et al. Occurrence of CCSVI in patients with MS and its relation with iron metabolism and varicose veins. Eur J Neurol 2013; 20: 519–526. 2. Meissner MH, Gloviczki P, Bergan J, et al. Primary chronic venous disorders. J Vasc Surg 2007; 46(Suppl): 54–67. 3. Leone MA, Raymkulova O, Naldi P, et al. Chronic cerebrospinal venous insufficiency is not associated with multiple sclerosis and its severity: a blind-verified study. PLoS One 2013; 8: 2. 4. Imperiale D, Melis F, Giaccone C, et al. Chronic cerebrospinal venous insufficiency in multiple sclerosis: a sonographer-blinded case–control study. Clin Neurol Neurosurg 2013; 115: 1394–1398. 5. Leone MA, Raymkulova O, Lucenti A, et al. A reliability study of colour-Doppler sonography for the diagnosis of chronic cerebrospinal venous insufficiency shows low inter-rater agreement. BMJ Open 2013; 3(11): e003508. 6. Eklo¨f B, Rutherford RB, Bergan JJ, et al. American venous forum international ad hoc committee for revision of the CEAP classification. Revision of the CEAP classification for chronic venous disorders: consensus statement. J Vasc Surg 2004; 40: 1248–1252.
Conflict of interest None declared.
Downloaded from phl.sagepub.com at Kungl Tekniska Hogskolan / Royal Institute of Technology on November 15, 2015
(PHL)
[1–3] [PREPRINTER stage]
Phlebology OnlineFirst, published on July 31, 2014 as doi:10.1177/0268355514544782
Short Report
Chronic cerebrospinal venous insufficiency is not associated with chronic venous disorders: A case–control study
Phlebology 0(0) 1–3 ! The Author(s) 2014 Reprints and permissions: sagepub.co.uk/journalsPermissions.nav DOI: 10.1177/0268355514544782 phl.sagepub.com
Maurizio A Leone1,2, Olga Raymkulova1, Piergiorgio Lochner3, Laura Bolamperti1, Gianandrea Rivadossi4, Alessandro Stecco5, Giuseppe Zaccala6, Maurizio Maggio7, William Liboni4, Marilena Guido8, Lorenzo Coppo1 and Daniele Imperiale8
Abstract Objectives: To evaluate the relationship between chronic cerebrospinal venous insufficiency (CCSVI) and the presence of a Chronic Venous Disorder (CVD). Method: We included 55 subjects with CCSVI aged >18 years, and 186 controls without CCSVI. Each subject was evaluated with color Doppler sonography in accordance with Zamboni’s five criteria, examined by two neurologists and interviewed with an ad-hoc designed form. The neurologists and the sonographers were mutually blinded. CVD were classified according to CEAP. Results: Mean age was 42 years (SD ¼ 9) in cases and 43 years (10) in controls (p ¼ ns). The odds ratios in subjects CCSVI were 0.6 (0.2–2.2) for CEAP 1, 0.9 (0.2–4.5) for CEAP 2, and 1.0 (0.6–1.9) for family history of varicose veins. The prevalence of CVD and, family history of varicose veins, was similar between cases and controls for each Zamboni criterion. Conclusions: We found no association of CCSVI with the presence of CVD or family history of varicose veins.
Keywords CCSVI, multiple sclerosis, veins, CEAP, blinding
Introduction Chronic cerebrospinal venous insufficiency (CCSVI) is a recently described vascular condition that has been weakly associated with some peripheral venous diseases in one study.1 Chronic Venous Disorder (CVD) of the lower extremities are highly frequent in western populations and include a wide spectrum of clinical presentations, ranging from telangectasias to venous ulcerations.2 During two studies of the association of CCSVI with Multiple Sclerosis (MS) conducted in the Novara and Torino hospitals3,4,5 we collected information on the presence of CVD, allowing us to assess the relationship between CCSVI and the presence of CVD.
Methods We enrolled 217 MS patients (age >18 years), 126 healthy subjects (HS), and 49 patients with other
neurodegenerative diseases (OND), matched to MS patients by gender and age (5 years). Exclusion criteria (applied to MS, HS, and OND) were acute or chronic disabling disorders, severe cardiopathies or 1
SCDU Neurologia, Head and Neck Department, AOU ‘‘Maggiore della Carita`’’, Novara, Italy 2 Interdisciplinary Research Center of Autoimmune Diseases, IRCAD, Novara, Italy 3 Department of Neurology, Tappeiner Hospital, Merano, Italy 4 Fondazione ‘‘Un passo insieme’’, Valdellatorre, Italy 5 Istituto di Radiologia Diagnostica e Interventistica, AOU ‘‘Maggiore della Carita`’’, Novara, Italy 6 Department of Medicine, AOU ‘‘Maggiore della Carita`’’, Novara, Italy 7 SC Neurologia, Civile Hospital, Ivrea, Italy 8 SC Neurologia, Maria Vittoria Hospital, Torino, Italy Corresponding author: Maurizio A Leone, Centro Sclerosi Multipla, Ospedale ‘‘Maggiore della Carita`’’, C.so Mazzini 18, Novara 28100, Italy. Email: [email protected]
Downloaded from phl.sagepub.com at Kungl Tekniska Hogskolan / Royal Institute of Technology on November 15, 2015
XML Template (2014) [30.7.2014–9:35am] //blrnas3/cenpro/ApplicationFiles/Journals/SAGE/3B2/PHLJ/Vol00000/140097/APPFile/SG-PHLJ140097.3d
(PHL)
[1–3] [PREPRINTER stage]
2
Phlebology 0(0)
pulmonary diseases, prior cerebral or extracerebral venous thromboembolism, transient global amnesia, neoplasia, thrombophilic diseases, diabetes, head, and neck surgery, vasculitides, family history of MS, cerebral vascular malformations, congenital vascular malformations, and MS relapse or using steroids during the previous 30 days. Two neurologists blind to the color Doppler sonography (CDS) operators performed a general and neurological examination before the CDS and interviewed all subjects with an ad-hoc designed form. CDS were done with a GE Vivid7 scanner, with a 7.5–10 MHz high-resolution linear array transducer for extracranial measurements and a 2–3 MHz probe for transcranial evaluation of venous drainage (GE Healthcare, Milwaukee, Wisconsin, USA) in Novara, and with a MyLab-Vinco 25 machine (Esaote Biomedica, Genoa, Italy) with a linear LA332 11.3 MHz probe for extracranial measurement and with a phased PA240 2.5 Mhz probe for intracranial measurements in Torino. Several strategies were employed to ensure blinding of the CDS operators.3,4,5 The CDS investigation was carried out in accordance with the five criteria suggested by Zamboni et al.:3 a subject was considered CCSVI positive (CCSVI+) if 2 criteria were met. Subjects considered as borderline in our previous study3 are excluded here. CVD were classified according to the CEAP classification,6 based on clinical visit and ultrasound examination of the limbs when clinically indicated. Comparisons between groups were assessed using Student’s t-test and chisquare test were appropriate, and calculating Odds Ratios (OR) with their 95% confidence limits (CL). The study was approved by the Ethical Committees of the
Novara (# 28/11), and Torino (# 73/12/10) hospitals. Written informed consent was signed by all subjects.
Results Information on the presence of CVD was available for 182 subjects in Novara (79% of the total sample) and 59 in Torino (37%), including 136 MS patients (99 relapsing-remitting, 29 secondary progressive, and 8 primary progressive), 95 HS, and 10 OND (total ¼ 241). Comparison of the subjects with available information with the others did not disclose any statistically significant difference for age, gender, place of birth, type of MS, treatment, age at onset, and disease duration (data not shown). CCSVI was found in 30 MS patients, 24 OND, and 1 HC for a total of 55 CCSVIþ subjects (cases); the other 186 subjects without CCSVI (CCSVI) acted as controls. Women numbered 36 (65%) among CCSVI+ and 120 (65%) among CCSVI subjects (p ¼ ns). Mean age was 42 years (SD=9) in CCSVI+ and 43 years (10) in CCSVI (p=ns). Table 1 shows the prevalence of CVD and of family history of varicose veins among subjects positive and negative for each criterion and for CCSVI as a whole. Neither a single criterion nor CCSVI was associated with CVD. According to the CEAP classification, 19 subjects had primary and 4 secondary postthrombotic CVD. We did not find any association with the anatomic site (superficial vs. deep/perforator veins: 2/4 in CCSVI+ and 6/11 in CCSVI; p ¼ 0.93) and pathophysiology (occlusion/reflux/none ¼ 1/2/3 in CCSVI+ and 3/4/10 in CCSVI; p ¼ 0.89). We also analyzed CVD in subjects with and without MS
Table 1. Prevalence of chronic vascular disorders (according to CEAP classification) and family history of varicose veins in CCSVI positive and negative subjects. CEAP 1 CCSVI Criterion
CEAP 0 N (%)
N (%)
Criterion 1 þ
40 (90.9)
2 (4.6)
178 (90.4)
11 (5.6)
Criterion 2 þ
21 (100.0)
0
Criterion 3 þ
197 (89.6) 109 (91.6)
13 (5.9) 5 (4.2)
109 (89.3)
8 (6.6)
Criterion 4 þ
23 (82.1)
4 (14.3)
195 (91.6)
9 (4.2)
Criterion 5 þ
27 (90.0)
2 (6.7)
191 (90.5)
11 (5.2)
CCSVI
þ
49 (89.1)
4 (7.3)
169 (90.9)
9 (4.9)
CEAP 2 p*
OR (CL)*
0.79
p*
OR (CL)*
1.2
1 (2.3)
0.67
1.6
1 (2.3)
18; 26 (40.9)
(0.3–5.8)
7 (3.6)
(0.2–13.1)
1 (0.5)
73; 124 (37.1)
–
0
0.42
– 1.6
8 (3.6) 5 (4.2)
(0.5–5.0)
3 (2.5)
0.3
1 (3.6)
(0.1–0.9)
7 (3.3)
0.75 0.49
Family history of varicose veins
N (%)
0.24
0.03
CEAP 3–4
0.8
0
(0.2–3.7)
8 (3.8)
0.7
2 (3.6)
(0.2–2.2)
6 (3.2)
0.36 0.49 0.86 0.29 0.87
yes; no (% yes)
–
0
0.6
2 (0.9) 0
82; 138 (37.3) 46; 73 (38.7)
(0.1–2.6)
2 (1.6)
45; 77 (36.9)
0.8
0
12; 16 (42.9)
(0.1–7.0)
2 (0.94)
–
9; 12 (42.9)
1 (3.3)
11; 19 (36.7) 80; 131 (37.9)
0
(0.2–4.5)
2 (1.1)
0.63
21; 34 (38.2) 70; 116 (37.6)
*CEAP ¼ 0 is the reference category. No p-value is significant after Bonferroni’s correction for multiple comparisons.
Downloaded from phl.sagepub.com at Kungl Tekniska Hogskolan / Royal Institute of Technology on November 15, 2015
OR (CL) 1.2 (0.6–2.3)
0.61
1.3
0.78
(0.5–3.1) 1.1 (0.6–1.8)
0.55
79; 134 (37.1)
1 (0.47) 0.9
p
1.3 (0.6–2.8)
0.90
0.9 (0.4–2.1)
0.94
1.0 (0.6–1.9)
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separately. In MS patients, the ORs of being CCSVI+ were 1.0 (0.2–4.9) for CEAP 1, 0.6 (0.1–3.2) for CEAP 2, and 0.9 (0.4–2.1) for family history of varicose veins. The correspondent figure for HS and OND subjects were 0.3 (0.1–2.3) for CEAP 1, 1.0 (0.9–1.1) for CEAP 2, and 1.2 (0.5–2.9) for family history of varicose veins.
Discussion We found no association of CCSVI with the presence of CVD or a family history of varicose veins in this blinded study. The only other study that investigated peripheral venous diseases1 found that MS patients positive for CCSVI had an excess of bilateral telangiectasia at the legs, reticular veins, and venous stasis dermatitis. However sample size was very small and the results contradictory, since varicose veins were even more frequent in CCSVI negative subjects. Our study involved 241 patients and did not found an association with either telangectasia (CEAP 1) or varicose veins (CEAP 2). One limitation of our study is its nature of post-hoc analysis; however, the present sample (55 cases; 3.4 controls per case, alpha error ¼ 0.05) has enough power (1-beta ¼ 0.97) to detect an OR of 3.0, assuming a 30% prevalence of exposure (http://www.dceg.cancer.gov/tools/design/ power). Power was 0.35 and 0.70 for an OR of 1.5 and 2.0. The major strengths of our study are its blinded nature and the broad spectrum of the subjects examined.
Funding Dr. Olga Raymkulova is supported by CRT Foundation, Torino.
References 1. Van den Berg PJ, Van den Berg GB, Westerhuis LW, et al. Occurrence of CCSVI in patients with MS and its relation with iron metabolism and varicose veins. Eur J Neurol 2013; 20: 519–526. 2. Meissner MH, Gloviczki P, Bergan J, et al. Primary chronic venous disorders. J Vasc Surg 2007; 46(Suppl): 54–67. 3. Leone MA, Raymkulova O, Naldi P, et al. Chronic cerebrospinal venous insufficiency is not associated with multiple sclerosis and its severity: a blind-verified study. PLoS One 2013; 8: 2. 4. Imperiale D, Melis F, Giaccone C, et al. Chronic cerebrospinal venous insufficiency in multiple sclerosis: a sonographer-blinded case–control study. Clin Neurol Neurosurg 2013; 115: 1394–1398. 5. Leone MA, Raymkulova O, Lucenti A, et al. A reliability study of colour-Doppler sonography for the diagnosis of chronic cerebrospinal venous insufficiency shows low inter-rater agreement. BMJ Open 2013; 3(11): e003508. 6. Eklo¨f B, Rutherford RB, Bergan JJ, et al. American venous forum international ad hoc committee for revision of the CEAP classification. Revision of the CEAP classification for chronic venous disorders: consensus statement. J Vasc Surg 2004; 40: 1248–1252.
Conflict of interest None declared.
Downloaded from phl.sagepub.com at Kungl Tekniska Hogskolan / Royal Institute of Technology on November 15, 2015
