When the Main Vein from the Brain Won't Drain, Rooke Thinks It Might

4/14/2016

30 min When the Main Vein from the Venous obstruction / reflux Brain Won’t Drain, Rooke thinks has predictable effects … it Might Cause Pain … Acute … Is he Insane?

Thom Rooke Krehbiel Professor of Vascular Medicine Renal vein Mayo Clinic (“nutcracker”) with gonadal Sioux Falls 2016 Chronic vein reflux

The head and neck can … including intracranial … The head and neck can Volume 4, Issue 7, July 2005, Pages 437–444 be affected, too … Cerebral Sinus Thrombosis be affected, too … Other effects Transient global amnesia (TGA) is one of the most striking syndromes in clinical neurology … Studies with … venous duplex … confirmed the importance of jugular-vein-valve insufficiency.

… headache probably results from stretching of the … veins that drain into the sinuses, although elevated ICP may also play a role. In

Cerebral Venous Sinus Thrombosis (CVST) addition to headache, clouding of Posted by Rathachai Kaewlai, M.D consciousness and seizures are common … http://radiologyinthai.blogspot.com/2011/06/cerebral-venous-sinus-thrombosis-cvst.html https://www.dartmouth.edu/~dons/part_2/chapter_18.html

Why not still more effects? First in 2008 J Neurol Neurosurg Psychiatry 2009;80:392-399 MS Chronic cerebrospinal venous insufficiency in patients Plaques with multiple sclerosis P Zamboni, et. al. Veins

http://www.nature.com/nri/journal/v3/n6/fig_tab/nri1108_F1.html http://missinglink.ucsf.edu/lm/ids_104_demyelination/didactic/msmicropath.htm

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Chronic Cerebro-Spinal Venous Insufficiency (CCSVI) Multiple Sclerosis Venous Ulcer Venous Ultrasound … venous outflow anomalies were dramatically associated (with MS) (OR 43, p<0.0001).

“… MS is strongly Journal of Cerebral Blood Flow & Metabolism Alamelu V. Is chronic venous associated with (2009) 29, 1867–1878; 2 September 2009 ulcer curable? A sample survey Anomalous venous blood flow and iron CCSVI, a scenario that of a plastic surgeon. Indian J J Neurol Neurosurg deposition in multiple sclerosis has not previously Psychiatry 1 2 Plast Surg 2011;44:104-9 Ajay Vikram Singh and Paolo Zamboni been described …” 2009;80:392-399

Focus on Obstruction Meta-Analysis of the Correlation Between Chronic Cerebrospinal Venous Insufficiency 2013 The “Liberation Procedure” and Multiple Sclerosis Vascular and Endovascular Surgery 47(8) 620-624

“… CCSVI endovascular treatment Looks very promising! significantly improved MS clinical outcome measures … the rate of relapse-free patients changed from 27% to 50% postoperatively …

“The results of this pilot study (65 pts) warrant a subsequent Odds Ratio = 2.6 randomized control study.” This triggered an effusive world-wide response. Zamboni, J Vasc Surg. 2009 Dec;50(6):1348-58. For example …

CardioVascular and The silent treatment: How Canada has failed Cardiovascular and Interventional Radiological Interventional MS sufferers: Internal documents show why Society of Europe Commentary on the Treatment Radiology of Chronic Cerebrospinal Venous Insufficiency Feb 2011, Volume Canada has not kept its promise to accelerate 34, Issue 1, pp 1-2 contentious clinical trials for MS Anne Kingston June 25, 2012 “… there is increasing worldwide acceptance of CCSVI … even though there is no supporting scientific evidence. “Canada has one of the highest per capita MS … most of the information we have comes from one populations: three people are diagnosed every day. source only. … it stirred rare hope among the … 75,000 Canadians The treatment is called “liberation treatment,” and the suffering from the incurable, degenerative condition.” results of the treatment can be watched on YouTube.

“By June 2010, many were travelling out of country, The current forum for the reporting of success … seems paying upwards of $10,000 for CCSVI … The issue had to be the Internet. become a flashpoint. … CCSVI was up for debate in the There are … testimonies by MS patients who have House of Commons.” gained improvement … (but not) …from patients who “… the Ministry of Health … was under pressure to act.” underwent unsuccessful treatments …”

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Neurology. 2011 Aug 30;77(9):844-50. Italy Progressive MS is not associated with chronic Mult Scler October 2013 vol. 19 no. 11 1508-1517 multicenter Italy cerebrospinal venous insufficiency. Observational case-control study of the prevalence of chronic cerebrospinal venous insufficiency in multiple … CCSVI is not … associated with disability. sclerosis: results from the CoSMo study PLoS One. 2013;8(2) Italy 1874 subjects aged 18–55. Chronic cerebrospinal venous insufficiency is not associated with MS and its severity: a blind-verified study. Color … duplex sonography

… CCSVI was not associated with MS … nor its severity. The primary (goal) is to compare the

BMC Med. 2013 Jul 18;11:167 Buffalo, NY prevalence of CCSVI in patients with Chronic cerebrospinal venous insufficiency is not associated MS versus patients affected by other with cognitive impairment in MS. neurodegenerative diseases (OND)

… We find no evidence of an association between the and healthy volunteers. presence and severity of CCSVI … in patients with MS Conclusions: CCSVI is not associated with MS.

Neurology Lancet. 2014 Jan 11;383(9912):138-45. Canada Volume 83, Issue 5, 29 July 2014, Pages 441-449 USA

Prevalence of extracranial venous narrowing on Prospective randomized trial of catheter venography in people with multiple sclerosis, venous angioplasty in MS (PREMiSe) their siblings, and unrelated healthy controls: a … sham-controlled, randomized, and double- blinded, case-control study. blind (10 sham procedure, 9 treated). Extracranial venous narrowing > 50% is a frequent finding in patients with MS … … endpoints included changes in disability, brain volume, cognitive tests, and quality of life. (and) controls. Conclusion: Venous angioplasty is The significance of venous not an effective treatment for narrowing to MS symptomatology MS … and may exacerbate underlying remains unknown … disease activity.

FDA NEWS RELEASE Mult Scler October 2013 vol. 19 no. 11 1508-1517 Observational case-control study of the

prevalence of chronic cerebrospinal For Immediate Release: May 10, 2012 venous insufficiency in multiple

sclerosis: results from the CoSMo study FDA issues alert on potential dangers of unproven treatment for multiple sclerosis Conclusions: CCSVI is not associated with MS. The U.S. Food and Drug Administration is alerting health care professionals and patients about injuries Nobody wants to and death associated with the use of an be associated with experimental procedure sometimes called “liberation therapy” or the “liberation procedure” to treat CCSVI anymore chronic cerebrospinal venous insufficiency (CCSVI). – it’s embarrassing

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But … could venous insufficiency These are Very Common Problems (obstruction) produce other (non-MS) neurological/head symptoms? # of migraine sufferers … in the US = 12 million

What about?: Lipton RB, Stewart WF, Diamond S, et al. Prevalence and burden of migraine in the United States: data from the American Migraine Study II. Headache. 2001;41(7):646-657. • Headache • Visual changes • Speech difficulties Prevalence of tension-type headache = 78%.

Rasmussen BK, et. al. Epidemiology of headache in a general population — a prevalence study. J Clin • Imbalance Epidemiol 1991;44:1147-1157. • Cognitive issues • Elevated IC pressure How often does venous impairment • Others play a role?

#1 Problem -- How do we determine if a Mechanism of “Venous” HA ? If the venous patient has CCSVI? blockage is not Very Complicated Intracranial “severe” … blood flow increases

Non- Compliant

Reflux

Vasodilators

More on this later … Simpler?

Validity of the diagnostic criteria for chronic cerebrospinal Variants of “normal” causing venous insufficiency and association with multiple sclerosis venous compression (often CMAJ June 2, 2014 asymptomatic) are common 120 patients with multiple sclerosis and 60 healthy controls. Normal?

“… We detected no differences in the proportion of Normal? venous outflow abnormalities between patients with multiple sclerosis and healthy controls.”

"Perhaps the most striking finding in our study was the range of venous outflow anomalies Normal? detected that did not reflect pathology, but instead demonstrated the large natural variance in intracranial and extra-cranial venous anatomy …” Popliteal vein entrapment Vasc Med. 2006 Nov;11(4):278-9. Thoracic outlet syndrome

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Movement of the neck is much more complicated Normal?

Pinched FINDINGS: “MR venography the cervical and intracranial vasculature is negative. The Open dural venous sinuses are widely patent. No evidence of obstruction of the internal jugular veins in the neck.”

Case #1 “Pathology?” Or just a “Variant?” Case #2 78 year-old woman with chronic, severe Dilemma headache Decisions based “No Dx” Collateral entirely on “Nothing to do” vein? Or anatomical congenital appearance +/- Gradient 2-3 mmHg variant? catheter-assessed Dilatation of jugular pressure gradient stenosis X 3 sessions. Each helped … for 3-6 Is this weeks. Then congenitally symptoms – and “small” • Stenosis? stenosis – returned. transverse sinus “too small?” Is • Compression? Finally treated with stent. Complete flow obstructed? • Normal variant? resolution of symptoms. No recurrence.

Case #3 38 year old male. Chronic visual “fatigue,” Case #4 68 year-old man. DVT (Factor V positive). Subdural headache, “brain fog.” hematoma on Coumadin. MRV findings may have Hematoma evacuated X 2. Still unstable. He’s worried he may have MS been positional? Did we miss something? Or “overcall?” Clot

Nothing!

No Stenosis stenosis No Bleeding Small transverse sinus. gradient Collaterals Shift Possible obstruction?

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It gets worse … Do you attempt to What we need is a “functional test …” open the jugular? MRV X 2 – findings consistent Ultrasound seems like a good place to start. It’s the basis for many other hemodynamic / functional vascular tests …

Collateral Dominant jugular is occluded?

… But can we see the area of interest with Duplex?

“Normal”

How to Test? • Increase inflow (vasodilator)

• Outflow obstructed (Limits overall flow)

This produces:

• Symptoms?

• Increased venous velocity

• Increased ICP

“Abormal?” • Brain “stiffness”?

• EEG / PET scan?

• Other changes?

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Case Example? Work-up = negative MRV – Venous obstruction? Attempted dobutamine 78 year old female echo (to assess possible

CAD) – stopped because Worsening “myoclonus” of severe exacerbation

of myoclonus. (Most often, myoclonus occurs as a result of a nervous system (neurological) disorder, Does she have such as epilepsy, or of a metabolic physiologically condition, or as a reaction to a medication. significant venous

obstruction? The cause of essential myoclonus is often unexplained (idiopathic) or, in some cases, Is it contributing to her hereditary.) http://www.mayoclinic.org/diseases- myoclonus? conditions/myoclonus/basics/definition/con-20027364

Chronic (Cervical) Venous Occlusive Disease:

• Probably exists and is under-recognized

• Does not appear to cause MS?

• May cause HA and other CNS symptoms

However …

• Diagnostic criteria are lacking (And thus all the controversy)

• There is a need for better anatomic / hemodynamic / functional testing