Reviewing the CCSVI research..

In my role as education person for the local MS Society, I've been called upon to try and figure out a presentation re: CCSVI.  The only problem is that little research has been completed to date.  There are status updates to the research funded by the MS Societies on their pages, but I went wandering through the other research looking for something else that might have been done.
Here are my conclusions:
Anyone associated with Dr.s Zamboni, Haacke, Simka, or their research institute have found that CCSVI has positive results.  Sample sizes are small, and my impression is that the several published papers resulted mainly from the same study set.
Anyone who is a neurologist finds no benefits from the CCSVI procedure. Their study sizes are also small, except for one study that looked for brain ferritin levels (following the iron damage hypothesis) which looked at 1408 patients with brain disorders and normals and found an increased amount of ferritin in people with various forms of MS and brain damage of other sorts.
Interestingly, studies by interventional radiologists also don't find a positive association between CCSVI treatment and MS improvement.
"Improvement" is, as has been said before, stated in terms of fatigue level improvement, some sensory improvement.  As someone who is dead tired all the time and numb from stem to stern, this sounds vaguely appealing, except for the costs. And the transience of the improvement. The study summaries are below.
The small sample sizes are a problem, as so much difference can be explained by random changes, especially in a variable disease like MS.  It's also a problem that most of the studies were unblinded - in other words, the experimenters knew who they were looking at.  This allows for bias and in fact, if you happen to have a vested interest in the results, like the neurologists who have invested years in the autoimmune theory, or the Zamboni group who are currently marketing the only machine capable of detecting the hard to find CCSVI (some conflict of interest there, methinks), bias comes in inevitably.
On the good side, the whole debate has increased interest in MS research.  On the bad side, several people have, for some unknown reason, decided the current researchers are not capable of doing a proper study, and so have stopped sending money to the MS Society.  Instead we should be sending more, and demanding unbiased studies, multisectorial, blinded, and large. We won't know for sure until we get those studies done. Until then, taking a stand is perhaps premature.

Study/date	Blinded?	Number of participants	results
The perfect crime? CCSVI not leaving a trace in MS. J Neurol Neurosurg Psychiatry. 2011 Feb 4. [Epub ahead of print] Mayer CA, Pfeilschifter W, Lorenz MW, et al	Yes ++	20 MS, 20 controls	No retrograde blood flow Conclusions This triple-blinded extra- and transcranial duplex sonographic assessment of cervical and cerebral veins does not provide supportive evidence for the presence of CCSVI in MS patients. The findings cast serious doubt on the concept of CCSVI in MS.
Chronic cerebrospinal venous insufficiency and iron deposition on susceptibility-weighted imaging in patients with multiple sclerosis: a pilot case-control studyInt Angiol. 2010 Apr;29(2):158-75. Zivadinov R, Schirda C, Dwyer MG, Haacke ME, Zamboni P et al	No	16 RRMS 8 controls	All 16 MS patients fulfilled the diagnosis of CCSVI (median VH=4), compared to none of the HC Iron concentration measures were related to longer disease duration and increased disability as measured by EDSS and MSFC, and to increased MRI lesion burden and decreased brain volume.
CSF dynamics and brain volume in multiple sclerosis are associated with extracranial venous flow anomalies: a pilot study. Zamboni P, Menegatti E, Weinstock-Guttman B, , Zivadinov R. et al Int Angiol. 2010 Apr;29(2):140-8.	No	16 MS 8 controls	Vascular Hemodynamic changes occur more frequently in MS patients than controls. Altered VH is associated with abnormal CSF flow dynamics and decreased brain volume.
No Evidence of Chronic Cerebrospinal Venous Insufficiency at Multiple Sclerosis Onset Claudio Baracchini, MD,1 Paola Perini, MD,1,2 Massimiliano Calabrese, MD,1,2 Francesco Causin, MD,3 Francesca Rinaldi, MD,1,2 and Paolo Gallo, MD, PhD1	No	50 MS 60 global amnesia 60 healthy.	Our findings do not support a cause-effect relationship between CCSVI and pMS. Further studies are warranted to clarify whether CCSVI is associated with later disease stages and characterizes the progressive forms of MS.
Intracranial venous pressure is normal in patients with multiple sclerosis. Meyer-Schwickerath R, Haug C, Hacker A, Fink F, Seidel D, Hartung HP, Haupts MR.	No	29 MS 28 Controls 19 patients with increased intracranial pressure	There is no evidence of an increased intracranial venous pressure in MS patients.
Cardiovasc Intervent Radiol. 2011 Feb;34(1):1-2. Epub 2010 Dec 7. Cardiovascular and Interventional Radiological Society of Europe commentary on the treatment of chronic cerebrospinal venous insufficiency. Reekers JA, Lee MJ, Belli AM, Barkhof F.	No	Comment only	Thus far, no trial data are available, and there is currently no randomized controlled trial (RCT) in proress Therefore, the basis for this new treatment rests on anecdotal evidence and successful testimonies by patients on the Internet. CIRSE believes that this is not a sound basis on which to offer a new treatment, which could have possible procedure-related complications, to an often desperate patient population. PMID: 21136256 [PubMed - in process]
Nervenarzt. 2010 Jun;81(6):740-6. ["Chronic cerebrospinal venous insufficiency" and multiple sclerosis: critical analysis and first observation in an unselected cohort of MS patients]. [Article in German] Krogias C, Schröder A, Wiendl H, Hohlfeld R, Gold R.	No	?	The "venous hypothesis" is analyzed and evaluated with regard to the following aspects: first concerning the validity of published data, second with regard to the plausibility in view of the currently approved pathogenetic model of MS, and third with regard to the compatibility with preliminary neurosonological findings in a small but unselected cohort of patients at our department.The authors conclude that the "chronic cerebrospinal venous insufficiency (CCSVI)" cannot represent the exclusive pathogenetic factor in the pathogenesis of MS. In our cohort, only 20% of the patients fulfilled the required neurosonological features of CCSVI. So far, the pathogenetic relevance of these findings remains speculative. Thus, based on the current scientific position we cannot justify invasive "therapeutic" approaches, especially if they are performed outside of clinical trials.
Normal CSF ferritin levels in MS suggest against etiologic role of chronic venous insufficiency. Worthington V, Killestein J, Eikelenboom MJ, Teunissen CE, Barkhof F, Polman CH, Uitdehaag BM, Petzold A. Neurology. 2010 Nov 2;75(18):1617-22. Epub 2010 Sep 29.	No	cross-sectional (n = 1,408) longitudinal (n = 29) patients with MS and a range of neurologic disorders.	Pathologic (>12 ng/mL) CSF ferritin levels were observed in 4% of the control patients (median 4 ng/mL), 91% of patients with superficial siderosis (75 ng/mL), 73% of patients with a subarachnoid hemorrhage (59 ng/mL), 10% of patients with relapsing-remitting MS (5 ng/mL), 11% of patients with primary progressive MS (6 ng/mL), 23% of patients with secondary progressive MS (5 ng/mL), and 23% of patients with meningoencephalitis (5 ng/mL). In MS, there was no significant change of CSF ferritin levels over the 3-year follow-up period. CONCLUSION: These data do not support an etiologic role for CCSVI-related parenchymal iron deposition
No cerebrocervical venous congestion in patients with multiple sclerosis. Doepp F, Paul F, Valdueza JM, Schmierer K, Schreiber SJ. Ann Neurol. 2010 Aug;68(2):173-83.	No	56 MS 20 Controls Sonography study, flow analysis, CCSVI criteria	Our results challenge the hypothesis that cerebral venous congestion plays a significant role in the pathogenesis of MS. Future studies should elucidate the difference between patients and healthy subjects in BVF regulation. No MS patient had >1 CCSVI criterion
Int Angiol. 2010 Apr;29(2):189-92. Chronic cerebro-spinal venous insufficiency: report of transcranial magnetic stimulation follow-up study in a patient with multiple sclerosis. Plasmati R, Pastorelli F, Fini N, Salvi F, Galeotti R, Zamboni P.	No	I patient	The demonstration of a modification of the cerebrovenous function with both clinical manifestation and via TMS suggests that the hampered cerebral venous return may contribute to the clinical course of MS.
Is chronic fatigue the symptom of venous insufficiency associated with multiple sclerosis? A longitudinal pilot study. Malagoni AM, Galeotti R, Menegatti E, Manfredini F, Basaglia N, Salvi F, Zamboni P. Int Angiol. 2010 Apr;29(2):176-82.	No.	31 fatigue testing 1, 6 and 12 mos post-procedure	The reestablishment of cerebral venous return dramatically reduced CF perception in a group of MS patients with associated CCSVI, suggesting that CF is likely the symptom of CCSVI. Note: Patients were identified as having CCSVI and Chronic Fatigue
Chronic cerebrospinal venous insufficiency and multiple sclerosis Omar Khan MD1,*, Massimo Filippi MD2, Mark S. Freedman MD3, et al ANN NEUROL 2010;67:286–290			In this Point of View, we discuss the recent investigations that led to the description of CCSVI as well as the conceptual and technical shortcomings that challenge the potential relationship of this phenomenon to MS. The need for conducting carefully designed and rigorously controlled studies to investigate CCVSI has been recognized by the scientific bodies engaged in MS research. At present, invasive and potentially dangerous endovascular procedures as therapy for patients with MS should be discouraged until such studies have been completed, analyzed, and debated in the scientific arena.
Venous and cerebrospinal fluid flow in multiple sclerosis: A case-control study .    Peter Sundström MD, PhD1,*, Anders Wåhlin MSc2, Khalid et al	No	21 MS 20 control	We found no differences regarding internal jugular venous outflow, aqueductal cerebrospinal fluid flow, or the presence of internal jugular blood reflux. Three of 21 cases had internal jugular vein stenoses. In conclusion, we found no evidence confirming the suggested vascular multiple sclerosis hypothesis. ANN NEUROL 2010;68:255–259
Endovascular treatment for chronic cerebrospinal venous insufficiency: is the procedure safe? T Ludyga *, M Kazibudzki *, M Simka * , M Hartel , M wierad *, J Piegza *, P Latacz *, L Sedlak * and M Tochowicz *	No	564 procedures in 331 MS patients with CCSVI	The procedures appeared to be safe and well tolerated by the patients, regardless of the actual impact of the endovascular treatments for venous pathology on the clinical course of multiple sclerosis, which warrants long-term follow-up.
No association of abnormal cranial venous drainage with multiple sclerosis: a magnetic resonance venography and flow-quantification study Mike P Wattjes1, Bob W van Oosten2, Wolter L de Graaf1, Alexandra Seewann2, et al	Yes	20 MS, 20 control MRV studies (magnetic resonance venography)	A completely normal venous anatomy was observed in 10 MS patients and 12 controls. Anomalies of the venous system (venous stenosis/occlusions) were found in 10 MS patients and eight healthy controls. An anomalous venous system in combination with associated alternative venous drainage was observed in six MS patients and five healthy controls. Flow quantification showed no venous backflow in any MS patient or control. Conclusions Findings suggestive of anomalies of the cranial venous outflow anatomy were frequently observed in both MS patients and healthy controls. Given the normal intracranial venous flow quantification results, it is likely that these findings reflect anatomical variants of venous drainage rather than clinically relevant venous outflow obstructions.
Iron and Neurodegeneration in Multiple Sclerosis Michael Khalil,1, 2 Charlotte Teunissen,2 and Christian Langkammer1 Multiple Sclerosis International Volume 2011, Article ID 606807,			In summary, increased iron deposition has been consistently reported to occur in MS, but its role in pathogenetic processes of this disease has not yet been completely clarified. Quantitative MRI and histopathologic analyses of postmortem MS brains should complement these     [9] studies.

Well, it's one of those days...

Got up, poured my cereal in my coffee mug.
It's gone downhill from there.
I'm trying to get organized for my move to heaven  Nova Scotia (specifically, Dartmouth) and my brain is NOT cooperating. I am mixed up between trying to organize paperwork, throw out items, book movers, change addresses, etc., etc. and my desk is a disaster, my hair is a spectacle, and my dog is becoming surly. It's just about time to take him for a walk and mail a variety of things, but first I have to figure out the byzantine rules for getting money back from the drug support program here in Ontario for my horrendously expensive Copaxone. And other drugs.

Expensive disease, this. And it's only beginning. The pharmacist figures out I spent $16,000 on meds last year - most of it covered by insurance, thank gods, but this year my coverage stops at $2400 (the max available under my insurance). Even the support program only pays for 80%. As my income is about twice my drug total, life is looking a bit grim. Perhaps I will have to just give them up. Or maybe the makers of Copaxone, Teva pharmaceuticals, who were in fact fined for overcharging, could lower their prices a wee bit. I know, overall, it is less costly than the alternative - crippling disease progression - and it seems to have stopped that for me. I know it's expensive to make, and involves years of research - I know they have to charge a hefty fee.  But perhaps a wee bit less hefty would be a big help.

Malingering and MS

Okay, you've all heard it.  About how MSers fake their symptoms so they can be accepted into trials.  About how neurologists have to judge the story and see if they believe it before treating. About how MSers demand more more more all the time and insist on treatment even when their symptoms don't warrant it.
No?
Well I have heard this from three sources in the past two weeks (two live, one on Memorex), and I don't know quite how to react.
Burning down my neuro's office seems extreme.
Yelling in the privacy of my own home seems ineffectual.
Slapping the person who implied I was malingering is chargable.
So I'm settling for the middle road and writing here.

Okay, I'm mad.
Hmm.

So, you get told you have a chronic incurable debilitating disease. You are told you have to take expensive medications for the rest of your life or risk crippling disability. You are told you have lesions and holes in your brain.

Some of us wallow in self-pity.  I did that, for about a year. I figure that's pretty normal. But once I bonded on the idea of a walk in tub, I was fine, really. For the most part, though I can't help grieving some of my losses.
("of all the things I've lost, I miss my mind the most...")

It's hard to be cheerful all the time when you have muscle spasms and numbness and forget where anything is and can no longer do simple math without thinking really hard and have to leave work because few employers would put up with a 2 hour nap every afternoon. But wotthehell, Archie, toujours gai, as Mehitabel the cat would say.

So, if you're me, you give your head a shake and start exercising. You exercise every day.  You ignore the fact that this means the rest of the day is a writeoff because you know that if you don't exercise, your balance gets worse, your muscles atrophy, you feel more pain, you get fat(ter). Exercising means that your muscles are capable of walking the dog.

Exercising means that you still can walk, even if some days it takes more concentration than it really should and your feet cramp up afterwards and you notice that that old left leg just isn't swinging forward the way it should.  But you plunge on and you do your best because you are fighting the disability, damn it, with all the energy you've got.
BUT you're still numb, you can't see properly, you can kiss sexuality goodbye, you still walk like a drunk when tired and a certain amount of your zest for living vanishes along with your energy.

And then you interact with your doctor.
And he treats you like those things, those smallish things that exist and ruin your life, those smallish things that shine most bright because of all your hard work stretching and moving and exercising even when you are beyond tired and your positive thinking and sense of humour about not being able to feel your lips or having them tango dance every time you go to the dentist - those things that still bother you - he treats them as if they are nothing, as if you should be grateful, as if you are wasting his time.

And in a way, you are.  There's nothing that can be done for you in any case. Well, except more drugs. Which cost more money. And have side effects and dubious efficacy.

And then there's the support you need to maintain your status as disabled, that status that means you get an income even though you are too tired to work for one, even though, as an employee, you'd be pretty damn unreliable. And that he holds over your head like a sword of Damocles, in his might, swinging it to and fro, to and fro.

It's no wonder people with MS are telling the tales of their worst days, not their best. Minimize your symptoms at your peril, lest your funding be removed. Minimize your pain, or forget those nights when you couldn't sleep because of spasms, and you get scorn.

It's no wonder people hop on the comet trails of every possible treatment that doesn't involve their neurologist, even if the hope is as ephemeral as those trails, just to avoid that scorn, that feeling of being examined and found wanting as a person and a patient. I'm sure half of the benefits found through CCSVI treatment come from someone listening to the patient, and showing some caring.

I've lived with ongoing pain most of my life.  It's from a variety of causes, probably not all MS, but I've lived with it and dealt with it and moved on. I resent like hell being told I malinger, when I ignored the symptoms of MS until I went blind one day (thank heavens, for a short time only) so that I wouldn't bother the medical establishment. I ignored the symptoms of a kidney stone and coped on my own with it so I wouldn't have to go to emergency. If I am saying now that I CAN'T DO IT, then by god, I CAN'T DO IT.

I am reminded of my favourite patient when I was teaching nurses.  They were going to give her a bath and they had placed her in a bath chair to raise her up and into a huge tub. She was stark naked, up about five feet in the air, and she was hollering, "Come here!  Come here so I can kick you!"

I feel as powerless as she was, and just about as mad.