Neuropathy experts make case for infrared light therapy

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Biomechanics Magazine July 2007

Neuropathy experts make case for infrared light therapy

Research suggests treatment improves sensation, but decision makers

question the evidence

By: Jordana Bieze

http://www.biomech.com/showArticle.jhtml?articleID=201000606

A. Arnall, PT, PhD, is not what one would call an early

adopter. A self-proclaimed professional skeptic, he is a believer in

evidence-based medicine who, under most circumstances, puts no stock

in fledgling therapies until their efficacy has been validated

through rigorous scientific study.

The use of infrared light therapy for peripheral neuropathy is not

what one would call evidence-based medicine-certainly not if one

works for the Centers for Medicare and Medicaid Services. In an

October decision memorandum, CMS ruled that the handful of studies

were sufficient to conclude that the therapy was neither reasonable

nor necessary for that indication. Most of the studies were

retrospective or had other limitations; the single well-designed

randomized, controlled trial found no significant benefit.

And yet Arnall, the skeptic, will tell anyone who will listen that

he believes infrared light therapy can restore sensation and reduce

pain in patients with diabetic peripheral neuropathy.

Indeed, this opinion has something to do with scientific evidence:

Arnall conducted a 22-patient study in 2004 in Spain that found

protective sensation significantly improved in neuropathic feet

treated with pulsed infrared light therapy (PILT) compared with

nonsignificant improvements or deterioration in untreated feet. In

lieu of a placebo treatment in the study, one of each patient's feet

was left untreated as a within-subject control. The results were

published in the May 2006 issue of the European journal Acta

Diabetologica.

But Arnall's opinion is also grounded in personal experience. Having

lived with diabetes for 20 years, he had tried every available

therapeutic option, including decompression surgery, to relieve his

peripheral neuropathy with no luck. Infrared light therapy, he says,

succeeded where all the other treatments had failed.

'My neuropathies were resolved,' said Arnall, who is a professor and

chair of physical therapy at East Tennessee State University in

City. 'Now I'm a believer, not only because of the positive

outcomes of the Spanish diabetes patients, but also because of my

own case. This is one modality that is spectacular.'

Arnall isn't alone in having had a positive experience with infrared

light therapy for peripheral neuropathy. The CMS memo authors

received 1315 comments during the initial public comment period, and

all but three supported the use of the therapy. Five of those

supporters were, like Arnall, clinicians who had seen positive

effects on their own symptoms as well as those of their patients.

Although the scientific evidence supporting the use of infrared

light therapy for peripheral neuropathy has thus far failed to

convince CMS decision makers of its merits, the number of anecdotal

success stories has kept the technology from dropping completely off

practitioners' radar.

Given the severe consequences of untreated neuropathy-ulceration

and, ultimately, amputation-and the lack of effective therapeutic

alternatives, even some skeptics remain willing to believe that

better research on infrared light therapy might conclusively

document a positive effect. Also, a stimulated discussion at the

American Physical Therapy Association's annual Combined Sections

Meeting in February, when additional positive outcomes from a study

were reported, served notice that the CMS memo may not be the final

word on the therapy's potential efficacy.

Confusion about infrared light therapy, advocates say, begins with a

lack of knowledge.

'Physicians are not exposed to light therapy during their training,

so at least part of the reluctance of clinicians to look favorably

on it is because they don't understand it well,' said J.

Burke, PhD, director of research and clinical affairs for Anodyne

Therapy and a coauthor of published studies on the company's

infrared therapy technology. 'It's a novel field that will take

time, especially in American medicine where everything is focused on

pharmaceutical treatments, for physicians to get a handle on it.'

Even its strongest advocates, however, remain unsure of the exact

mechanism by which the treatment works. Animal studies have shown

that low-level laser irradiation improves microcirculation through

vasodilation, and researchers believe that infrared light therapy

triggers a similar mechanism, possibly involving the release of

nitric oxide from hemoglobin. Restoring microcirculation is thought

to improve sensation and reduce pain.

Further adding to the confusion about infrared light therapy are

subtle, but possibly significant, differences that exist between

devices used to deliver the therapy. The majority of studies have

used monochromatic infrared energy (MIRE) devices (Anodyne Therapy,

Tampa, FL) that deliver pulsed photoenergy at a wavelength of 890 nm

via arrays of diodes contained in flexible pads strapped to the

skin. Arnall's study involved PILT delivered by a RevitaMed

(LymphaCare Healthlight Therapy, New York, NY) device. In this

device, each therapy pad contains six rows of diodes emitting pulsed

photoenergy at a wavelength of 880 nm (infrared light) alternated

with five rows of diodes emitting light at 650 nm (visible red

light).

The FDA has not cleared any phototherapy devices for treatment of

peripheral neuropathy. Many devices have received approval for the

temporary relief of muscle and/or joint pain and the temporary

increase of local blood circulation, similar to the effects of an

electric heating pad, but the agency has indicated that those

approvals do not extend to the treatment of neuropathic pain.

The outpouring of impassioned but anecdotal evidence in support of

infrared light therapy will likely carry as little weight with the

FDA as it did with the CMS decision makers, whose opinions were

based largely on the scientific strength of the evidence against it.

Scientific findings

The only well-designed randomized, placebo-controlled trial of

infrared light therapy, published in the December 2005 issue of

Diabetes Care, found no significant difference in symptom

improvement between patients with peripheral neuropathy whose feet

were treated for four weeks with an active therapy device and those

who were treated with a sham device.

In that study, researchers from the University of Tennessee in

Memphis and Pulaski Physical Therapy in Pulaski, TN, tested the

sensitivity of 39 subjects to 5.07 Semmes-Weinstein monofilaments at

four sites on each lower extremity. After 12 treatment sessions

administered over four weeks, the mean number of sites sensitive to

the 5.07 monofilament improved from 0.57 (out of five) to 0.94 in

the 35 lower extremities randomized to receive active MIRE treatment

and from 0.86 to 1.42 in the 35 lower extremities that received

placebo treatment. The change from baseline for each group was

statistically significant, but the difference between groups was not.

An earlier study of infrared light therapy for peripheral neuropathy

at the Joslin Center for Diabetes in Clearwater, FL, also involved a

randomized, placebo-controlled design but the sham therapy was

administered for only six of 12 treatment sessions, thus limiting

the conclusions that can be drawn from the study's findings. During

the first six sessions, each of 27 subjects received active MIRE

treatment on one leg and a sham treatment on the other leg. All

subjects were insensate to 5.07 monofilaments in at least two of

five sites on the plantar surface of each foot, but were also

subgrouped according to the subjects' ability to sense a 6.65

monofilament.

Interestingly, the researchers found that six sessions of MIRE

treatment were associated with a significant decrease in the mean

number of test sites insensate to a 5.07 monofilament, but only in

those with less severe neuropathy at baseline. In those who could

sense the 6.65 monofilament at all five test sites at baseline, mean

number of sites insensate to a 5.07 monofilament decreased from 2.4

to 1.9 (a statistically significant change) in those who received

active treatment and from 3.0 to 2.3 (not statistically significant)

in those who received sham treatment. However, in those who were

insensate to the 6.65 monofilament at baseline, the number of sites

insensate to the 5.07 monofilament did not change significantly in

either treatment group.

Those findings, published in the January 2004 issue of Diabetes

Care, seemed to suggest that the efficacy of infrared light therapy

is inversely related to the severity of a subject's peripheral

neuropathy. The findings of other researchers, however, suggest that

even those with very severe loss of sensation at baseline can

benefit from the therapy.

Rather than reporting numbers of sites sensate or insensate to 5.07

monofilaments, Arnall et al documented sensation at each site in

terms of the smallest monofilament that could be felt. In feet that

received eight weeks (24 sessions) of PILT, mean peripheral

protective sensation improved significantly at all four tested sites-

the first, third, and fifth metatarsals, and the great toe-whereas

mean sensation in the contralateral, untreated limbs did not change

significantly from baseline (Table 1).

In contrast to the Florida findings, however, Arnall and colleagues

found that subjects with severe baseline neuropathy did experience

significant positive effects; in fact, improvement was more likely

to be statistically significant at sites where subjects were

insensate to 10 g of force (the amount required for a 5.07

monofilament to buckle) at baseline than in those with less severe

neuropathy (Table 2).

Severity of neuropathy also did not appear to preclude a positive

outcome in a 2006 retrospective review of medical records for 2239

subjects with peripheral neuropathy who had been treated with MIRE

and physical therapy. The multicenter study, led by researchers from

the University of Texas Health Sciences Center in San , found

that the number of sites on both feet that were insensate to a 5.07

monofilament decreased significantly following treatment of varying

durations, from a mean of 7.2 (out of 10) to a mean of 2.4.

Significant improvement was also seen in the nearly 800 subjects who

were insensate to 5.07 monofilaments at all 10 sites at baseline;

following treatment, they were able to sense a mean of 6.2 sites.

Those findings, published in the March-April 2006 issue of the

Journal of Diabetes and Its Complications, were consistent with

those of an earlier retrospective study published in the March-April

2005 issue of the Journal of the American Podiatric Medical

Association by three of the same authors.

The March-April 2006 findings also suggest that MIRE can help reduce

the pain experienced by some patients with peripheral neuropathy. In

1563 subjects with neuropathic pain at baseline, initial mean pain

levels of 7.2 on an 11-point visual analog scale were reduced to

2.4, a statistically significant improvement of 67%. Etiology of a

subject's peripheral neuropathy did not significantly affect

outcomes for either sensation or pain.

These data raise the possibility that the subjects in the Tennessee

randomized controlled study may not have received enough treatments

to see a significant between-group difference in outcomes. Although

the 12 treatments administered were consistent with the

manufacturer's guidelines, Burke said treatment durations in the two

retrospective studies did vary depending on severity of symptoms.

A smaller-scale retrospective analysis of the medical charts of 30

patients with peripheral neuropathy, presented at the Combined

Sections Meeting, also reported that the average number of MIRE

treatments was 14. That study, conducted at Louisiana State

University in Baton Rouge, found that the treatment was associated

with significant reductions in pain and improvements in bilateral

lower extremity sensation and balance.

The possibility of a placebo effect, however, also cannot be ruled

out. All subjects in the Tennessee study had access to pamphlets on

diabetic foot care, which may have resulted in lifestyle changes

that could have positively affected sensation. Because the study did

not include an untreated control group, this premise remains unclear.

'In our placebo group, they improved,' said T. Newton, PT,

DPT, owner of three physical therapy centers, including Pulaski

Physical Therapy, and a coauthor of the Tennessee study. 'A lot of

them swore they were on the active units and were very surprised to

learn that they were not in the treatment group.'

Future research

Fortunately, more answers may be forthcoming. Researchers at the

Mayo Clinic in sdale, AZ, are currently recruiting patients

with painful peripheral neuropathy for a randomized, placebo-

controlled clinical trial of monochromatic near-infrared photoenergy

therapy. Although the primary end point will be pain reduction as

measured by a visual analog scale after four weeks of treatment, the

researchers also plan to measure sensation using great toe vibration

detection and to measure function using the Short-Form-8 Health

Survey and Neuropathic Impairment Score.

In addition, Arnall has been in discussions with Judy Clifft, PT,

the lead author of the Tennessee study, about a project that will

combine aspects of each researcher's previous work.

All parties involved seem to agree that the needs of patients with

peripheral neuropathy are too dire for infrared light therapy to be

ruled out completely at this point. Even Newton, who chose not to

purchase a MIRE device for his practice following the conclusion of

the Tennessee study, plans to refer interested patients (who are

willing to pay out of pocket) to other area therapists who offer the

service.