Motor cortex electrical stimulation: a promising therapy when all else has failed
 

We are all too aware of the suffering of everyone who has exhausted every therapy and remains in intractable pain, or worse, so I've been looking to see what may be available on the short-to-medium-term horizon.

One of the things that the landmark study, Abnormal thalamocortical activity in patients with Complex Regional Pain Syndrome (CRPS) Type I, Walton KD, Dubois M, Llinás RR, Pain 2010 Jul; 150(1):41-51, Epub 2010 Mar 24, FULL ONLINE TEXT @ http://www.rsds.org/2/library/articl..._Pain_2010.pdf explained rather nicely was why and how it is that Deep Brain Stimulation (DBS) has been effective in CRPS. Unfortunately (or not in light of possible SERIOUS side effects) DBS for the treatment of pain was banned outside of experimental studies by the FDA in the mid-1980's. Nevertheless, it is approved from the treatment of dystonia and other movement disorders, there it is. And because it's approved for dystonia, etc., it can be done on an "off-label" basis: good luck getting insurance companies to pay for off-label neurosurgery!

Further, the same underlying mechanism, also explains for the first time why electro-shock from various sources actually works in CRPS, right down to the cellular level. For one of the many articles chronicalling the effectiveness of ECT, despite the fact that it's mechanism was "unknown," see, e.g., Treatment of CRPS with ECT, Wolanin MW, Gulevski V, Schwartzman R, Pain Phys. 2007;10:573-578 FULL ONLINE TEXT @ http://www.rsds.org/2/library/articl...chwartzman.pdf

But with ECT, the problem is that, even with the newer and safer "high dosage RUL ECT delivered with an ultra-brief stimulus" (The Cognitive Effects of Electroconvulsive Therapy in Community Settings, Sackeim HA, Prudic J, Fuller R, et al., Neuropsychopharmacology 2007; 32:244-254), the fact remains that there is no money to pay for the large scale studies necessary to obtain FDA approval of RUL ECT for CRPS. Quite simply because, to the medical device industry, having a few thousand CRPS patients using its ECT equipment would be a drop in the bucket, not worthy of investing in new studies. And as a result, without a "co-morbid" Dx of otherwise untreatable depression, insurance carriers won't pick that one up either.

I am however pleased to announce that a new contender has entered the building, if not the arena:

Motor cortex electrical stimulation applied to patients with complex regional pain syndrome, Velasco F, Carrillo-Ruiz JD, Castro G, Argüelles C, Velasco AL, Kassian A, Guevara U, Pain. 2009 Dec 15;147(1-3):91-8, Epub 2009 Sep 29, FULL ONLINE TEXT @ http://www.rsds.org/2/library/articl...uiz_Castro.pdf

Unit for Stereotactic, Functional Neurosurgery and Radiosurgery of the Service of Neurology and Neurosurgery and Pain Clinic, General Hospital of Mexico, Mexico City, Mexico. slanfe@prodigy.net.mx

Abstract
Motor cortex stimulation (MCS) is useful to treat patients with neuropathic pain syndromes, unresponsive to medical treatment. Complex regional pain syndrome (CRPS) is a segmentary disease treated successfully by spinal cord stimulation (SCS). However, CRPS often affects large body segments difficult to cover by SCS. This study analyzed the MCS efficacy in patients with CRPS affecting them. Five patients with CRPS of different etiologies underwent a small craniotomy for unilateral 20-grid-contact implantation on MC, guided by craniometric landmarks. Neurophysiological and clinical tests were performed to identify the contacts position and the best analgesic responses to MCS. The grid was replaced by a definitive 4-contacts-electrode connected to an internalized system. Pain was evaluated by international scales. Changes in sympathetic symptoms, including temperature, perspiration, color and swelling were evaluated. Pre-operative and post-operative monthly evaluations were performed during one year. A double-blind maneuver was introduced assigning two groups. One had stimulators turned OFF from day 30-60 and the other from day 60-90. Four patients showed important decrease in pain, sensory and sympathetic changes during the therapeutic trial, while one patient did not have any improvement and was rejected for implantation. VAS and McGill pain scales diminished significantly (p<0.01) throughout the follow-up, accompanied by disappearance of the sensory (allodynea and hyperalgesia) and sympathetic signs. MCS is effective not only to treat pain, but also improve the sympathetic changes in CPRS. Mechanism of action is actually unclear, but seems to involve sensory input at the level of the spinal cord.

PMID: 19793621 [PubMed - indexed for MEDLINE] [Emphasis added: the point is huge!]

http://www.ncbi.nlm.nih.gov/pubmed/19793621 (And note how they can do double blinding simply by turning electrodes off and on, which is a neat trick.)

Finally, for a nice article explaining both MCS and DBS in clear language, check out, Intracranial Neurostimulation for Pain Control: A Review, Robert Levy, Timothy R. Deer and Jaimie Henderson, Pain Physician 2010; 13:157-165, FULL ONLINE TEXT @ http://www.painphysicianjournal.com/...13;157-165.pdf (And for any unknown term, just Google/bing/yahoo the word in question, preceded by "definition.")

That said, it's too bad that Levy et al missed the 2009 article from Velasco et al, when they go on to say:

While many case series have been published on the use of MCS or DBS for pain, no randomized, controlled trials exist to confirm the therapies’ effectiveness. This lack of class I data may cause some observers to view the therapies skeptically in spite of their considerable history of clinical use. MCS is probably better suited to such studies than other forms of neurostimulation, in that effective stimulation evokes no perception on the part of the patient save for pain relief. This presents researchers with a unique opportunity to perform blinded studies in which placebo effects can be assessed. Such studies could employ crossover designs to encourage enrollment and address ethical concerns related to the implantation of leads into control patients.

The lack of randomized controlled trials may be due, in part, to the challenges of patient recruitment and monitoring and the need to assign patients to control groups, which by definition means subjecting patients to treatments that have already been unsuccessful in managing their pain. However, the risk of not performing these studies is great, because it means that both physicians and patients lack definitive information about the efficacy of intracranial neurostimulation therapies. This then will slow the further development of the therapies and limit the access of patients to them in the future.

Little did they know that, in the case of MCS, it was simply a matter of flipping the switches every so often!

Hopefully, industry has now gotten the message and large scale studies (if performed in only a few select locations) will soon be underway.

Mike

I'm new to this chat Neurostimulation
 

Hello, My name is Mike. My Pain Mangement Doctor has suggested that I consider Neurostimulation Theraphy and have the device surgically implanted. I have been dealing with low back pain traveling through my left leg. I have this pain 24/7 and at times is very difficult to even preform my ADL's. I have been taking pain pills like Morphine for 3 years, done the physical therapy, injections and still live in this pain.

Does someone have any information you would share with me regarding your experience.

Thank you in advance for your time.

Mike

Dear Mike -

Hi there. First, I should say that I've never been offered a SCS because it was thought the pain was too diffuse in my body, where both legs were often in almost total spasm and I had bilateral CRPS in both feet and ankles following an injury at the gym.

Two quick points.First, Neurotalk maintains a "sub-forum" on SCS & Pumps at http://neurotalk.psychcentral.com/forum118.html that I would urge you to check out.

Secondly, I have just come across an article stating that while SCS may provide pain relief from anywhere from 2 - 20 years, it will not otherwise stop the progress of the disease. AAPM: Spine Stimulation Leads to Durable Pain Relief, February 07, 2010, reporting on presentation of Krishna Kumar, MB, BS, of Regina Qu'appelle Health Region in Regina, Saskatchewan, said at the American Academy of Pain Medicine meeting. "All patients in this series experienced a gradual enlargement in the area affected over time. Stimulation does not appear to retard disease spread."

http://www.medpagetoday.com/tbprint.cfm?tbid=18344

Mike

ty
 

thanks for the article Mike...How do I sign up??

Debbie

Hi all, I have been lurking for about a year and must now post to share the success of a deep brain stimulation treatment that I recently had. Writing is extremely difficult for me due to cognitive impairment by CRPS so please bear with me. After the frustration of one more physician suggesting I see a psychiatrist for what I, through my own research knew was autonomic and limbic dysfunction directly related to CRPS, I did what I have done for two years, my own research to help myself. Since I am already doing mirror therapy and graded motor imagery to address cortical reorganization, I began looking at ECT and related treatments. I came upon a clinical trial on tCDS (transcranial Cortical Deep Stimulation. Since I was too late to join the clinical trial I requested to receive the treatment on an outpatient basis. I went to Beth Israel in New Your City the first week in February and received the treatment for five days. The down side is that my health insurance did not cover it because it is experimental). The up side is that I had a dramatic positive response to the treatment: Increased mental clarity, decrease in daily pain range from 5 to 8 out of ten to 2 to 6 out of ten, increased range of motion, improvement in balance and coordination, decrease in ice cold limb, elimination of tremors, bladder problems returned to normal and many more subtle improvements. This treatment is non-invasive, painless and there are only minimal side effects (fatique, headache) which quickly vanish after treatment. There are no long term side effects and the treatment may be repeated indefinitely. I was cautioned that this treatment, like ketamine and blocks, wears off over time. I jokingly told Drs. Knotkova and Cruciani that I should get a 9 volt battery, some electrodes, sponges and saline solution and treat myself. My plan now is to either convince my PM physician to become trained and offer the treatment in his practice (in my dreams) or purchase the equipment and treat myself. The Research conducted by Dr Helena Knotkova and Dr. Ricardo Cruciani is due to be published in March. When I asked how soon this treatment would be routinely available to patients I was told 5-10 years. That's not good enough for me.

Getting very tired so I must go. Will post other non traditional and experimental treatments that have greatly help me. Many thanks to the useful info I have received from this community. I feel like I already know mike and greatly miss the input of Vic who is deceased. Hope this helps!!!!!

Dear Debbie -

Looks like we missed the boat, at least for now. Running a search through ClinicalTrials.gov - maintained by the NIH at http://www.clinicaltrials.gov/ct2/home - as well as the WHO's International Clinical Trials Registry Platform (ICTRP) http://www.who.int/ictrp/en/ shows only a single study on point The Efficacy of Motor Cortex Stimulation for Pain Control, under the direction of Robert M. Brownstone, MD, PhD, a neurosurgeon at the Neuroscience Institute, Dalhousie University, Halifax, Nova Scotia, who has some 38 highly sophisticated neuroscience and neurosurgery articles coming up on PubMed, many of which are freely downloadable. And that study apparently completed its final data collection in July, 2010. So publication is hopefully imminent.

And the "Detailed Description" of the study is encouraging:

This is a prospective, blinded randomized crossover study comparing two stimulation paradigms in three different groups of patients receiving motor cortex stimulation. The aim of this study is to examine the effectiveness of this modality in a controlled blinded manner, which has not been done in previous studies. There are two primary purposes of this study. The first is to compare two different stimulation paradigms: "high" level stimulation (i.e. stimulator activated 'on' for 10 minutes, 'off' for 2 hours; presumed therapeutic dose); versus "low" stimulation ('on' for 1 minute, 'off' for 6 hours; presumed subtherapeutic dose), in a prospective blinded crossover study design.

The second purpose of this study, is to examine the outcome of MCS in three different pain groups. These are:

1. Unilateral upper extremity neuropathic pain such as brachial plexus avulsion, stump pain or phantom limb pain
2. Neuropathic deafferentation facial pain
3. Upper extremity complex regional pain syndrome (CRPS)

Measurements of the effects of motor cortex stimulation will include a visual analogue scale (VAS) of perceived pain, the McGill Pain Questionnaire, SF-36 quality of life questionnaire, Beck Depression Inventory-II, the standard 7-point patient global impression of change (PGIC), medications log (verified by pharmacy records) and an employment status questionnaire. Adverse events will be recorded at each visit. . . . [Emphasis added.]

http://www.clinicaltrials.gov/ct2/sh...0462566&rank=1

http://www.nhs.uk/Conditions/Complex...n=5&Rec=0&CT=0

I suppose what really gets my attention is that researchers are now calibrating dosages!

Mike

study
 

I see one criteria was upper extremity RSD- mine started as lower and not body wide..:(

Debbie -

Not to worry, they were doing a study with a combination of TOS patients.

Trust me, the CRPS results - if statistically robust - will be FULLY GENERALIZABLE: the only difference being in where the electrodes are placed following an fMRI.

Mike

Dear Ballerina -

My goodness, you have been hanging around for a while! So how far back do we do go, as in, does the name John Lester mean anything to you? In any event, we are honored by your (re?)emergence.

You raise the matter of cognitive impairment by CRPS. In that spirit please forgive me for having literally overlooked your post Monday afternoon. I swear, I didn't see it earlier, which is too bad because it is a very small world. In late 2007, I was working on an article on the use of RUL ECT for CRPS when Jim Broach suggested that I speak to Dr. Knotkova about her work on tCDS. She was very kind and provided me with some articles on the subject - please see the attached - but to which I made only passing reference in my piece, which Jim was kind enough to arrange to have published. Right Unilateral Electroconvulsive Therapy Treatment for CRPS, Michaels F Jr., Pract Pain Manage. 2008 March, ONLINE TEXT @ http://www.rsds.org/2/library/articl...haels_CRPS.pdf

Smaller world still, over the last few months I’ve been trying to get an fMRI to fully access the neurocognitive hit of nearly 10 years of CRPS, which I perceive as an almost complete loss of executive functioning - on top of preexisting "pure" ADD - and a lot of short term and working memory loss. See, Neuropsychological deficits associated with Complex Regional Pain Syndrome, Libon DJ, Schwartzman RJ, Eppig J, et al, J Int Neuropsychol Soc. 2010 May;16(3):566-73, Epub 2010 Mar 19, ONLINE TEXT @ http://www.rsds.org/2/library/articl...ychol_2010.pdf So, my doctor suggested a radiology practice affiliated with a local neurologist who is now using a T-3 fMRI to calibrate his rTMS treatments: repetitive transcranial magnetic stimulation. http://en.wikipedia.org/wiki/Transcr...ic_stimulation Unfortunately, because their fMRI “protocols” were designed to locate only areas of pain activity, as opposed to cognition, the radiology practice told me that it would be unable to perform any functional analysis of cognition. And where they claimed only that 60% of those undertaking the (experimental and uninsurable, except for depression) rTMS treatments received a 50% reduction in pain lasting approximately 14 months, I took a pass where I had once been quoted better odds on a 5 – day Lidocaine infusion that did nothing for me. And note that, at least, based upon the attached correspondence to the British Journal of Psychiatry from Fregni et al (2005), TMS is significantly more expensive than tCDS.

I have no idea whether the rTMS would have had cognitive effects, where the magnetic force would have been precisely “aimed” only at those cortical areas associated with pain. Maybe I made the wrong call. As it is, I’m attempting to have the fMRI set up at UCLA instead.

And of course, I’m thrilled by your report, as well as knowing that after at least five years of effort, Drs. Knotkova and Cruciani’s work will be published next month. That’s really great, especially with the promise of affordable care in tCDS. Good times!

It’s funny, I’ve gotten more mileage out of some recent “stretching” PT with an emphasis on “nerve gliding” than anything else I can recall in the last few years. [If anyone in LA wants a reference, drop me a PM.] Sometimes it’s the subtle tweak that makes all the difference. And as interesting as it to speculate that one day we will be able to harness the Large Halcyon Collider in the pursuit of the ultimate mysteries of CRPS, it is so much more comforting when something on a human scale can make all the difference. (Suddenly, I am reminded of watching Nureyev from a distant balcony, thirty years ago and then past his prime, holding the hall spellbound with a perfect turn of his ankle.)

Mike

Hi Mike,
Small world indeed! I have had CRPS since a fall while teaching classical dance in November 2008. My horror stories regarding delayed diagnosis and treatment mirror those of others in this community, thus need no further comment.

Most everything that has been helpful to me is the result of my own research and includes reviewing all past RSD/CRPS posts on Neurotalk. I am so sorry you struggle with cognitive problems and I was saddened to learn through your earlier posts that your long battle with CPS forced you to give up what had to have been your passion, being an attorney.

My success with tCDS was quite encouraging to me since the treatment improved my short term memory problems, word finding problems and sequential processing problems. Although I have a doctorate is is extremely difficult to organize my thoughts and write. Like you, I also have a preexisting brain dysfunction, severe dyslexia. It took me an hour just to register on this site and my first post was lost and I couldn't figure out how.

I learned through my own efforts that my new cognitive problems were not the result of a psychiatric problem as had been suggested by numerous physicians. Thanks for the article by Libon et. al. Prior to my tCDS treatment I tried to get a form of magnetic brain stimulation offered locally (Maryland) through a psychiatrist. I was rejected, however, because I do not have clinical depression. The good news about tCDS is that it seems to be effective for folks with intractable long standing CRPS. Additionally it does not carry the rTMS risk for seizure.

For me, the loss of executive function has been every bit as bad as the pain and other symptoms. I took a chance given the odds of success for me was about 70% and I am convinced that cortical reorganization is the key for me. I expect this will wear off in a month to 9 months. I am using this time to push the limits in PT. I am having good results with mirror therapy and graded motor imagery as well as exercises for stretching and balance.

Who is John Lester? That name does not ring a bell but neither do many names from the past two years.

Hi
 

Do you have touble with muscle wasting...that is a big problem for my and was wondering if this tx helped with that?


TY

Debbie

Dear Ballerina -

I totally get what you're saying about the significance of neurocognitive losses. Funny thing is, when I told my pain doc a couple of months ago that if given the chance, I'd keep my wits and take the pain at full bore, his jaw came close to hitting the floor. He had obviously never heard that expressed before. But it's such an easy call, I'm now starting to work with pain patients, teaching mindfulness techniques for experiencing but not identifying with physical pain. And it's really just a matter of paying close attention to that from which you would otherwise run and flee, until it's no longer an issue.

Granted, it's a lot easier to this on retreat than when you are subject to the social demands of others in a big city, etc. But that's just a matter of making the same problem a little more complicated. Only there your immediate attention has to be on the emotional responses arising within, before they are acted upon.

That said, I'm told that having equanimity with loss of cognitive function is a a strong practice in it's own right. And where we're not exactly in a position to bargain as to the curves that are sent our way, I best keep attending to all phenomena as it arises and stop being picky about what's on the menu.

Right?

Mike


PS John Lester ran a host site called Brain Talk, where this forum had been in its most recent previous incarnation, before the server crashed c. 2006 - 2008, taking with it an unusually rich body of threads and posts. But the place definitely had its quirks . . .

Hi Debbie,

Your question regarding muscle wasting is hard for me to answer in an objective manner. Given my prior profession, teaching classical dance, my body worked like a well oiled machine. On Saturdays alone I taught from 9:00 am until 7:00 pm with no breaks and felt fresh and energized when I finished. Since May of 2010 I have been unable to work and I now occupy an alien body that has difficulty even walking without balance problems, sometimes resulting in falls. Although I have extremely poor muscle tone and some atrophy in my right hand I have done hand to hand combat to maintain range of motion and severe atrophy of my right arm.

When diagnosed in February of 2010 I immediately began to educate myself. I stumbled upon Hoosmand's website and have used much of what I learned there to do what I could to prevent atrophy. I follow Hooshmand's protocol of 20 minutes of exercise and twenty minutes of rest from 7:00 am until bed. It has been exhaustive but I believe it is the reason I am not much worse now.

My recent tCDS treatment has enabled me to increase what I am able to do. Since I am very attuned to subtle changes in my body due to a dance background the improvement in my muscle tone to me is of the atomic bomb variety. Although I still cannot do more than twenty minutes of exercise at a time, and I am still quite limited in terms of the types of exercise I do, I push the limit of what I can do during periods of exercise.

So, yes, the tCDS has improved my muscle tone and atrophy.

Hope this helps!

Teri

That said, I'm told that having equanimity with loss of cognitive function is a a strong practice in it's own right. And where we're not exactly in a position to bargain as to the curves that are sent our way, I best keep attending to all phenomena as it arises and stop being picky about what's on the menu.

Right?

Mike

Hi Mike,

Ah, the ever changing menu of CRPS.

When I began rapidly deteriorating both physically and cognitively I persuaded my neurologist to prescribe Namenda for pain management. As a bonus I saw an improvement in my cognitive problems. I recall in an earlier post that you also tried Namedna at one time. Did it help you in the area of executive functioning?

You sound like you are coping very well in this area. If you need more help I strongly recommend tCDS. The mental clarity it has provided me has greatly improved my quality of life.

Teri

Knotkova and Cruciani
 

Ballerina -

I just found this abstract on PubMed:

Non-invasive transcranial direct current stimulation for the study and treatment of neuropathic pain, Knotkova H, Cruciani RA, Methods Mol Biol. 2010;617:505-15.

Department of Pain Medicine and Palliative Care, Beth Israel Medical Center, Institute for Non-Invasive Brain Stimulation of New York, New York, NY, USA. HKnotkov@chpnet.org

Abstract
In the last decade, radiological neuroimaging techniques have enhanced the study of mechanisms involved in the development and maintenance of neuropathic pain. Recent findings suggest that neuropathic pain in certain pain syndromes (e.g., complex regional pain syndrome/reflex sympathic dystrophy, phantom-limb pain) is associated with a functional reorganization and hyperexitability of the somatosensory and motor cortex. Studies showing that the reversal of cortical reorganization in patients with spontaneous or provoked pain is accompanied by pain relief stimulated the search for novel alternatives how to modulate the cortical excitability as a strategy to relieve pain. Recently, non-invasive brain stimulation techniques such as transcranial magnetic stimulation (TMS) and transcranial direct current stimulation (tDCS) were proposed as suitable methods for modulation of cortical excitability. Both techniques (TMS and tDCS) have been clinically investigated in healthy volunteers as well as in patients with various clinical pathologies and variety of pain syndromes. Although there is less evidence on tDCS as compared with TMS, the findings on tDCS in patients with pain are promising, showing an analgesic effect of tDCS, and observations up to date justify the use of tDCS for the treatment of pain in selected patient populations. tDCS has been shown to be very safe if utilized within the current protocols. In addition, tDCS has been proven to be easy to apply, portable and not expensive, which further enhances great clinical potential of this technique.

PMID: 20336445 [PubMed - indexed for MEDLINE]

http://www.ncbi.nlm.nih.gov/pubmed/20336445

Do you have an understanding as to what more is to be published next month? Read: I am all eyes/ears, etc.


Mike

Done
 

I had this treatment about 2 years ago...it did absolutely nothing for me (as usual)

Dear Teri -

Forgive me once again, I had started my last past to you before your's was on the board, and didn't catch it until now, in case my last came across as a little sterile.

Truth is, I've been on Namenda since it was prescribed on a prophylactic basis (30 mg/day) in 2003 (later joined by Razadyne) and while I was initially aware of greater clarity of thought in coversations with others, sense of alertness, etc. on the days I had taken my Namenda, ALL of the deterioration of executive fuctioning, as well as the loss of my short term and working memory, has occurred on Namenda's watch.

And yes, you have sufficiently engaged my attention in tCDS, to the point that I (truly) await the publication of the study to which we have referred with baited breath.

Mike

Do you have an understanding as to what more is to be published next month? Read: I am all eyes/ears, etc.


Mike[/QUOTE]

Hi Mike,

I believe the abstract you found is not the published CRPS/tCDS study. I will get the article you referred to.

While I was at Beth Israel in early February Helena Dr. Knotkova told me that she did not expect the CRPS/tCDS study to be published before March, maybe later. She indicated that the group of CRPS patients originally enrolled in the tCDS study were continuing in phase two of the study. Phase two is studying among other variables, the number of repeated treatments needed to maintain pain relief. Knotkova is also conducting several additional tCDS clinical trials including fibromyalgia and cancer patients.

I will keep you posted!

Teri

A correction
 

It was just brought to my attention that one of our members with extensive CRPS/RSD has been in touch with a neurosurgeon at Columbia University, who investigated using MCS but reported back that "MCS works best with unilateral pain," and declined to proceed. (I gather there are as of yet unpublished reports of poor results in patients with generalized CRPS/RSD.)

On hearing this, I double checked Motor cortex electrical stimulation applied to patients with complex regional pain syndrome, Velasco F, et al, Pain 2009, and yes, although not specifically commented on by the authors, when you go through the individual case histories of the study participants, their CRPS was indeed confined to a single upper-extremity: possibly including including the shoulder.

I apologize for not catching this, as well for raising hopes that do not appear to be supported by all of the evidence, even if some of it is not yet published.

Hopefully, there will be better results with tDCS for patients with generalized CRPS, but what little I've heard so far on that score isn't all that promising.

Mike