For those of you who live in the UK what follows is the draft Guidance from NICE. There are a couple of glaring factual mistakes in it and there are a few misconceptions also. Some of us are preparing a list of points to address that I will publish shortly but in the mean time read this and see what you think.
Draft Guidance for
Percutaneous venoplasty for chronic cerebrospinal venous insuf?ciency in multiple sclerosis
Improving blood flow to the brain in patients with multiple sclerosis
It is possible that there is a link between blocked veins in the neck and/or trunk and progression of multiple sclerosis. This procedure aims to open blocked veins by inflating a small balloon in the vein, allowing for better blood flow and a reduction in the symptoms of multiple sclerosis.
The National Institute for Health and Clinical Excellence (NICE) is examining percutaneous venoplasty for chronic cerebrospinal venous insuf?ciency (CCSVI) in multiple sclerosis and will publish guidance on its safety and efficacy to the NHS in England, Wales, Scotland and Northern Ireland. NICE’s Interventional Procedures Advisory Committee has considered the available evidence and the views of Specialist Advisers, who are consultants with knowledge of the procedure. The Advisory Committee has made provisional recommendations about percutaneous venoplasty for chronic cerebrospinal venous insuf?ciency (CCSVI) in multiple sclerosis.
This document summarises the procedure and sets out the provisional recommendations made by the Advisory Committee. It has been prepared for public consultation. The Advisory Committee particularly welcomes:
- comments on the provisional recommendations
- the identification of factual inaccuracies
- additional relevant evidence, with bibliographic references where possible.
Note that this document is not NICE’s formal guidance on this procedure. The recommendations are provisional and may change after consultation.
The process that NICE will follow after the consultation period ends is as follows.
- The Advisory Committee will meet again to consider the original evidence and its provisional recommendations in the light of the comments received during consultation.
- The Advisory Committee will then prepare draft guidance which will be the basis for NICE’s guidance on the use of the procedure in the NHS in England, Wales, Scotland and Northern Ireland.
For further details, see the Interventional Procedures Programme manual, which is available from the NICE website (www.nice.org.uk/ipprogrammemanual).
Through its guidance NICE is committed to promoting race and disability equality, equality between men and women, and to eliminating all forms of discrimination. One of the ways we do this is by trying to involve as wide a range of people and interest groups as possible in the development of our interventional procedures guidance. In particular, we aim to encourage people and organisations from groups who might not normally comment on our guidance to do so.
In order to help us promote equality through our guidance, we should be grateful if you would consider the following question:
Are there any issues that require special attention in light of NICE’s duties to have due regard to the need to eliminate unlawful discrimination and promote equality and foster good relations between people with a characteristic protected by the equalities legislation and others?
Please note that NICE reserves the right to summarise and edit comments received during consultations or not to publish them at all where in the reasonable opinion of NICE, the comments are voluminous, publication would be unlawful or publication would otherwise be inappropriate.
Closing date for comments: 21 September 2011
Target date for publication of guidance: December 2011
1 Provisional recommendations
1.1 Current evidence on the efficacy and safety of percutaneous venoplasty for chronic cerebrospinal venous insuf?ciency (CCSVI) in multiple sclerosis (MS) is inadequate in quality and quantity. Therefore, this procedure should only be used in the context of research.
1.2 NICE encourages further research on venoplasty for CCSVI in MS. Clinical trials should be controlled, ideally comparing venoplasty against sham. Technical success should be clearly defined and should include measurement of pressure gradients across treated vein segments before and after venoplasty. Outcomes should include clinical and quality of life measures.
Comment on Section 1: Provisional recommendations (maximum 1200 characters)
2 The procedure
2.1 Indications and current treatments
2.1.1 MS is a disease of the central nervous system which usually starts in early adult life. It is characterised by neurological symptoms caused by episodes of inflammation and scarring in the white matter of the brain or spinal cord. The three most common patterns of MS are: relapsing–remitting MS (RRMS), in which periods of good health or remission are followed by sudden onset of symptoms or relapses; secondary progressive MS (SPMS), in which symptoms gradually worsen and there are fewer remissions; and primary progressive MS (PPMS), which involves a gradual continuous worsening of symptoms from disease onset. Patients suffer a wide range of symptoms and some become profoundly disabled.
2.1.2 Current treatment for MS includes specialist neurological rehabilitation and medication aimed at symptom control and prevention of disease progression.
Comment on Section 2.1: Indications and current treatments(maximum 1200 characters)
2.2 Outline of the procedure
2.2.1 The aim of CCSVI is to relieve MS symptoms by improving cerebrospinal venous drainage, although the relationships between MS, impaired cerebrospinal fluid drainage, lesions in the veins of the head and neck, and their treatment by venoplasty are not well understood.
2.2.2 With the patient under local anaesthesia, a guidewire is advanced into the superior vena cava under fluoroscopic control using a standard needle, guidewire and catheter technique. Selective venography, and sometimes intravascular ultrasound of the internal jugular and azygous veins, is used to identify stenoses. Where stenoses are found, the veins are dilated with a standard angioplasty balloon; if the result is inadequate, a stent may be inserted. Various devices can be used for this procedure.
Comment on Section 2.2: Outline of the procedure(maximum 1200 characters)
2.2.3 Further venography or ultrasound, or both, is used to assess the outcome of each venoplasty. The puncture site is compressed manually.
Sections 2.3 and 2.4 describe efficacy and safety outcomes from the published literature that the Committee considered as part of the evidence about this procedure. For more detailed information on the evidence, see the overview, available at www.nice.org.uk/guidance/IP/891/overview
2.3 Efficacy
2.3.1 A case series of 65 patients reported a significant reduction in MS Functional Composite (MSFC) score in patients with RRMS (n = 35) at 18 months compared with baseline (0.65 versus 5.5e-18, p = 0.008). There was no significant change in MSFC score at 18 months in patients with PPMS (n = 10) or SPMS (n = 20).
2.3.2 A case series of 24 patients reported that 6 patients had a relapse of clinical symptoms within 1 to 2 months of the procedure, although it was reported that they felt better than they did before the procedure.
2.3.3 The case series of 65 patients reported a significant improvement from baseline to 18-month follow-up in physical health (66 versus 84, p = 0.0097) and mental health (61 versus 82, p = 0.003), as measured by the MS Quality of Life instrument (lower scores indicate lower quality of life) among patients with RRMS (n = 35).
2.3.4 The Specialist Advisers listed key efficacy outcomes as venography and/or ultrasound evidence of improved venous appearance, a significant change in number and character of MS lesions on MRI, a reduction in relapse rate, improvement in function and quality of life.
Comment on Section 2.3: Efficacy (maximum 1200 characters)
2.4 Safety
2.4.1 A report of 2 cases described the death of 1 patient due to a brainstem haemorrhage after insertion of 2 self-expanding stents into the right internal jugular vein (timing not stated); and another patient who required emergency open heart surgery to remove a stent that migrated to the right ventricle from the internal jugular vein.
2.4.2 A series of 18 patients reported 1 case of rupture of the internal jugular vein during balloon angioplasty. This was treated with balloon tamponade and a bare metal stent.
2.4.3 A case series of 495 procedures in 461 patients reported acute in-stent or in-segment thrombosis in 2% (8/495) of procedures. All were treated by selective fibrinolysis, mechanical thromboaspiration and additional balloon angioplasty.
2.4.4 The case series of 495 procedures reported vein dissection in 15 procedures and vein rupture (resolved by prolonged balloon dilatation and stenting) in 2.
2.4.5 The case series of 495 procedures reported cardiac arrhythmias in 1% (6/495) of procedures. These included atrial fibrillation in 4 patients (2 resolved spontaneously and 2 resolved following treatment with amiodarone) and ventricular fibrillation (successfully treated) and ventricular tachycardia (timing not reported) in 1 patient each.
2.4.6 A case series of 331 patients (344 procedures) reported local bleeding from the groin requiring readmission to hospital in 4 patients. Two of these patients had pseudoaneurysms, which were successfully treated with thrombin injection.
2.4.7 The case series of 231 patients reported transient headache after 9% (21/247) of procedures. This persisted beyond 30 days in 1 patient. The same study also reported transient neck pain after 16% (39/247) of procedures.
2.4.8 The Specialist Advisers listed theoretical adverse events as infection, venous occlusion, air embolism, arterio-venous fistula and contrast reaction.
Comment on Section 2.4: Safety(maximum 1200 characters)
2.5 Other comments
2.5.1 The Committee was mindful of the distress and disability caused to patients by MS and the lack of effective treatments. The potential benefit of any efficacious new treatment could be substantial and this consideration underpinned the Committee’s wish to encourage controlled research into venoplasty for CCSVI in MS.
2.5.2 The Committee noted uncertainties about the incidence of cerebrospinal venous stenoses in patients with MS compared with the general population, about whether such stenoses cause CCSVI, and about the relationship between CCSVI and MS. It considered that research to resolve these uncertainties would be useful.
Comment on Section 2.5 Other comments (maximum 1200 characters)
Bruce Campbell
Chairman, Interventional Procedures Advisory Committee
July 2011