Wednesday, February 3, 2010

I cannot help it, I am full of hope...

One of the numerous feeds to which I subscribe channels news about CRPS -- that's not likely a shock to you!

What probably is news is that whenever I prepare to click on the summarizing email, my lungs, my mind, my heart, all fill with hope. Once I see what news awaits, that hope normally fizzles and fades, losing all its precious buoyancy.

I have an appointment with Dr. PainDude in a little under two hours. It has been a long while since I showed up with papers in hand, with hope. I just printed the following article, and almost miss the days of toner smell, mimeograph fumes. Today, the paper gives nothing away.

It blurs my eyes, these words: The team at the Pain Research Institute discovered that a single, low dose infusion of intravenous immunoglobin (IVIG) significantly reduced pain in just under 50 per cent of patients treated, with few adverse effects. The pain relief lasted on average 5 weeks.

O Christ, O God Almighty: Let it be true.

The text in its entirety below. I will do further research this afternoon.

Scientists at the University of Liverpool have discovered that treating the immune system of patients with Complex Regional Pain Syndrome (CPRS) leads to a significant reduction in pain.

CRPS is an unexplained chronic pain condition that usually develops after an injury or trauma to a limb, and continues after the injury has healed. CPRS I - formerly called Reflex Sympathetic Dystrophy - can arise after any type of injury. CRPS II, previously called causalgia (a term coined in the American Civil War when it was first diagnosed), follows partial damage to a nerve. In some cases the pain can be so severe that patients request amputation, only to find that the pain returns in the stump.

CRPS pain can improve within one year after the injury, but if it is still unchanged after 12 months (longstanding CRPS), then it will often not improve at all. Longstanding CRPS affects about 1 in 5,000 people in the UK.

The team at the Pain Research Institute discovered that a single, low dose infusion of intravenous immunoglobin (IVIG) significantly reduced pain in just under 50 per cent of patients treated, with few adverse effects. The pain relief lasted on average 5 weeks. The results of this study may change the future treatment of patients with CRPS, and have an impact on research in other severe chronic pain areas. Intravenous immunoglobulin treatment for CRPS is currently not available on the NHS.

Although the cause of the syndrome is unknown, precipitating factors include injury or damage to the body's tissue. Changes in the way nerves send messages to the brain about pain may occur at the injury site. These changes may then lead to more changes in the nerves of the spinal chord and brain. All these changes are thought to play a role in causing and prolonging the condition. Conventional pain drugs either don't work, or have considerable side effects.

Dr Goebel, Senior Lecturer in Pain Medicine, explains: "In CRPS, the real effect of this treatment in clinic may turn out to be even greater than what we have already seen, because IVIG can be given in higher doses, and repeated treatment may have additional effects. IVIG is normally repeated every four weeks and we are working to develop ways which would allow patients to administer the treatment in their own home."

"The discovery is expected to have a real impact on the treatment of other unexplained chronic pain conditions; if one pain condition can be effectively treated with an immune drug, then it is possible that other types will also respond."

The research is published in the journal Annals of Internal Medicine.

Notes: [....]
The research was carried out in collaboration with University College London.
Research activities on the role of the immune system in chronic pain are the focus of the newly created 'Centre for Immune Studies in Pain' (CISP) at the University of Liverpool, led by Dr. Goebel. For further details visit Support for these and other research activities aimed at relieving chronic pain comes from the Pain Relief Foundation in Liverpool.

Sarah Stamper
University of Liverpool

Aha! A better article,* of course, is available at -- from The Annals of Internal Medicine (cutting to the chase, "results... limitation... conclusion"):

Results: 13 eligible participants were randomly assigned between
November 2005 and May 2008; 12 completed the trial. The average
pain intensity was 1.55 units lower after IVIG treatment than
after saline (95% CI, 1.29 to 1.82; P 0.001). In 3 patients, pain
intensity after IVIG was less than after saline by 50% or more. No
serious adverse reactions were reported.

Limitation: The trial was small, and recruitment bias and chance
variation could have influenced results and their interpretation.

Conclusion: IVIG, 0.5 g/kg, can reduce pain in refractory CRPS.
Studies are required to determine the best immunoglobulin dose,
the duration of effect, and when repeated treatments are needed.

*yes, it is a bit of cold water... damn it.

later... in an email to my sister-in-law, this brief but exciting episode was summarized thusly:

i got all excited this morning by a news report that i.v. immunoglobulin had been found to "significantly" reduce pain in CRPS. an hour later, i found out that the big study had all of 13 people in it, one of whom dropped out. "just under 50%" of the participants had positive results. let's see. putting on my thinking cap. half of 12, six. okay, "just under" must mean... FIVE. then hank did his "statistics" speech: there must be at least a cohort of 30 to be statistically relevant... sometimes, i wish he would keep all that book learnin' to himself. i should have known that when something sounds too good to be true, it probably is.


Friday, 5 February 2010:

Further tidbits keep popping up. An editorial accompanied the published research. It sought to temper impulsive enthusiasm as a response to this study, emphasizing caution and the tremendous need for more work. In case you've not kept up with the exciting times in CRPS/RSD research, the authors give a quick gloss at the beginning of their editorial -- and I am resolved to place my hope in that steady progress. It's just that when severe chronic pain and disability roll on unabated for eight years? Well, it can be difficult to be positive. So I tend to grab and latch on to any research that makes sense. I don't mean to mislead anyone by these occasional bursts of unwarranted optimism; Please pardon me if I inadvertently played upon your heartstrings. Also, my case of CRPS is pretty awful and I sometimes forget that most cases are not this bad. I shouldn't be dragging you into my freak show!

Editorial: Intravenous Immunoglobulin to Fight Complex Regional Pain Syndromes: Hopes and Doubts
Frank Birklein, MD, PhD; and Claudia Sommer, MD, PhD

From University of Mainz, Mainz 55131, Germany; and University of Würzburg, Würzburg 97080, Germany.

Chronic pain is multifaceted. It involves changes in somatosensory processing from the primary afferent neurons to the brain; it induces negative emotions, such as fear and depression; and it often entails serious consequences for working ability and personal life. Long-standing complex regional pain syndrome (CRPS) has all of these features and may be associated with substantial reduction of limb function, leading to physical impairment.

In recent years, we have made progress in understanding CRPS. Studies of the acute phase of posttraumatic CRPS show the importance of cytokines and growth factors for pain and hyperalgesia; the involvement of peptides in changes in skin perfusion, edema, and sweating; and the effect of sympathetic neurotransmission on pain in selected patients. We have learned that in long-standing CRPS, cortical reorganization of sensory, motor, and autonomic function might underlie the profound disturbances of the body reference scheme. Although acute CRPS can be challenging to treat, the outcome is often favorable. Treatment of chronic CRPS, when central neuroplastic changes are fully established, is especially difficult.

And so concludes a pretty accurate, if embarrassing, example of my emotional ups-and-downs as I follow the thread of medical news, in real time [as real as it gets at Marlinspike Hall, deep, deep in the Tête de Hergé (très décédé, d'ailleurs)]. Despite my initial over-reaction, all the subsequent information did not cause too much grief -- it simply served as a reminder that this is serious business, for serious people, and that one mustn't let hope get out of hand.


2/15/2010: I was definitively told, via bullhorn, to "step away from the study... toss your hope on the ground and step away from ridiculous hope." Yes, the Hope Police came down on me like the proverbial ton of bricks. My case is extreme; My case is refractory; My course is "complicated." And then there was this surprise statement from Dr. Go-To Guy: "Bianca, ma belle, this is old news."

As soon as I get my breath back, lobbying will begin for a little offlabel use of immunoglobulin. Shhhhh!

photo credit

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