FREMS as a Novel Therapy for treatment of DFU

Conway T. McLean, DPM Director of Podiatric Surgery Cottage Clinics Chicago, IL

A diabetic patient presented to the office with a common presenting complaint, a non-healing wound. Like so many individuals with diabetes, this particular patient’s level of self-care (as well as their understanding of the disease) was somewhat lacking. A limb-threatening infection had developed of the left foot, due, at least in part, to inappropriate care. Relevant medical history included a five year history of a charcot foot deformity of the right tarsus.

The motor changes associated with this patient’s neuropathy manifested in hammertoe deformities, which predictably led to a distal digit ulceration. A better informed diabetic would have sought care sooner, well before the ulcer had developed into osteomyelitis. Thus, a primary causative agent, it might be argued, was a lack of education.

The patient presented to the office three weeks after the development of the digital ulceration. He had received minimal care prior to his arrival, consisting of simple wet-to-dry guaze dressing changes.

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Ulceration at first post-op check following debridement of infected bone and non-viable soft tissue, appropriate wound care.

Physical Exam

Initial assessment naturally included evaluation of the wound, vascular status and neurological function, and radiographs. Arterial doppler studies revealed patent pedal vessels, although skin perfusion was reduced, likely due in part to excessive edema with induration of soft tissues. The ulceration itself was fairly typical for the clinical situation, with surrounding hyperkeratosis, the presence of mild amounts of purulence, and gross enlargment of the digit. No actual pain was reported by the patient secondary to neuropathy, nor were systemic signs of infection evident, as is so often the case with a localized diabetic infection.

Musculoskeletal exam revealed contracture of the lesser digits with increased pressures to the distal aspect of the 3rd digit left. As is the pathogenesis of this condition, mild, non-infectious erythema led to the development of hyperkeratosis. The insensate patient will experience minimal to no symptoms, and only attuned health care specialists will be aware of impending events.

Plain film radiographs revealed osseous changes consistent with osteomyelitis, including cystic changes, fragmentation and osteolysis.

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Digit after debridement and excision of osteomyelitic bone and one FREMS treatment.

Treatment Considerations

Unfortunately for many diabetics, the terrible triad of immunopathy, neuropathy and vasculopathy combine to create very real and formidable obstacles to healing. “We are held captive by the blood flow” is a very apt saying, and though this individual had sufficient large vessel flow, signs of inadequate perfusion due to microvasculopathy were noted, included hair loss and atrophic epithelium.. The most obvious and accepted therapies, which were utilized here, include debridement of necrotic bone and soft tissue, moist wound healing, and appropriate antibiosis.

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Ulcerated digit demonstrating progressive healing following seven FREMS treatments

Unique Treatment

Utilized in this case was a very new, unique form of electrical stimulation, which employs high negative potential, single-phase electric current pulses, with suitably modulated frequencies and very short durations. These pulses are regulated in frequency, intensity, duration and potential, and act on the surface as well as the deep tissues. FREMS (Frequency Rhythmic Electrically Modulated Stimulation) was designed to take advantage of the belief that the summation of sub-threshold electrical stimuli, conveyed through the skin proximal to a motor nerve in a non-invasive system, would induce composite motor action potentials in excitable tissues.

This is in stark contrast to a single, low-intensity impulse of brief duration, such as the one delivered by TENS. This is unable to overcome the dielectric skin barrier and thus will not excite the underlying nervous and/or muscle to elicit a recordable motor action potential (MAP). The signal of the FREMS is quite different. Through a specific sequence of weak impulses, with a rapid increase and decrease in pulse frequency and duration, there is a gradual recruitment of MAP in the stimulated tissues.

The patient’s wound closed quickly and progressively, without interruption. An additional benefit to this patient was the associated improvement in sensorium. Because the therapy was utilized to treat the ulceration, it was performed unilaterally. The increase in sensation, as compared to the untreated side, was reported by the patient with signs including improved two point discrimination, vibratory sensation, monofilament detection. Also importantly, this benefit continued, with minimal loss, for eleven months.

The science and art of wound care has developed rapidly as a field of study in the last few decades. This is evidenced by the explosion of new products and materials now available. Many adjunctive treatments have been developed, with more recent advances including negative pressure wound therapy, hyperbaric oxygen therapy and biological living skin equivalents.

The FREMS device has been shown through numerous double-blind studies to have several significant and important effects. For example, there are changes in the perfusion velocity in the microcirculation, as well as inducing a long-acting increase in vasomotor activity (with significant changes noted at four months post treatment).

Some other effects are an increase in the release of growth factors including VEGF, increased blood flow and capillary density encouraging the formation of new granulation tissue. Additionally, there is a significant increase in nerve conduction velocity(MNCV) and a statistically significant reduction of pain after FREMS. On average, at the end of active treatment, MNCV was increased by almost 5 m/s; vibration perception threshold was reduced by more than 2 V; and the number of foot points insensitive to the Semmes–Weinstein monofilament was decreased.

In this case, healing progressed rapidly upon initiating the FREMS, while the usual armamentarium of antibiosis, appropriate debridement and proper wound care were employed. Osteomyelitic bone was resected during the course of FREMS treatments (typically consists of ten sessions). The presence of infection is not a contraindication to its use, and it seems likely that FREMS aids the process of bacterial eradication by increasing perfusion.

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Osteomyelitic metatarsal head excision site healing via secondary intention.

Immunopathy is an important component of the lower extremity problems experienced so frequently by people with diabetes. Yet vasculopathy and neuropathy may be considered the more devastating mechanisms, which lead so often to limb loss, disability, and a drastic reduction in quality of life. Those studies performed to date appear to indicate that we have a new and powerful tool that may significantly alter the natural history of this condition, leading to morbidity and mortality. No side effects or complications from it’s use have been experienced, and though perhaps not all will experience such dramatic effects as this patient did, it appears certain that this modality has the potential to drastically change the outcomes of diabetic patient care and maintanence.

Sincerely,

REFERENCES:

• Barrella M, Toscano R, Goldoni M, Bevilacqua. Frequency rhythmic electrical modulation system (FREMS) on H-reflex amplitudes in healthy subjects. Eura Medicophys 2007, 43: 37-47.
• Bevilacqua M, Barrella M, Toscano R et al (2004) Disturbances of vasomotion in diabetic (type 2) neuropathy: increase of vascular endothelial growth factor, elicitation of sympathetic efflux and synchronization of vascular flow (vasomotion) during frequency modulated neural stimulation (FREMS). 86th Annual Meeting of the Endocrine Society, p 321, P 2–61 (abstract)
• Bevilacqua M., Baruffaldi L., Foddis L., Toscano R., Vago. Increase of  Vascular Endothelial Growth Factor by Electrical Stimulation with High Varialbility in Frequency and Amplitude: a clinical study in non-insulin dependent diabetics with limb ischemia. 85th International Congress of Endocrine Society, Philadelphia, June 2003
• Bevilacqua M. et al. – Increase of Vascular Endothelial Growth Factor (VEGF) by FREMS. A clinical study in Non-Insulin Dependent Diabetics with Limb Ischemia. Presented at ENDO 2003 – Endocrinology Society’s 85th annual meeting – Philadelphia.
• Bosi E, Conti M, Vermigli C, et al. Effectiveness of a novel frequency modulated electro-magnetic neural stimulation in the treatment of painful diabetic neuropathy. Diabetologia 2005, 48: 817-23
• Ciancia, et al. Diabetic plantar ulcer treated with an innovative thearpy – FREMS (frequency modulated  electro-magnetic neural stimulation).  Italian Society of Gerontology and Geriatics, Florence; Palazzo Congressi 9-13 November 2005
• Combi F. Application of novel neuromodulation for skeletal muscle regeneration following chronic fobrosis process. The Rehabiliation of Sports Muscle and Tendon Injuries-Milano April 2004
• Conti M., Peretti E., Cazzetta G., Folini L., Vermigli C., Galimberti G. Frequency modualted electromagnetic neural stimulation enhances cutaneous microvascular perfusion in patients with diabetic neuropathy. 42nd Annual Meeting of the European Association for the Study of Diabetes, Copenhagen Sept. 2006
• Da Ros R., C. Vitale, R. Assaloni, A. Ceriello  Neuromodulation FREMS in the treatment  of diabetic peripheral arterial disease. 42nd Annual Meeting of the European Association for the Study of Diabetes, Copenhagen Sept. 2006
• Facchini M.G., Mambelli E., Checchia G., Gaggi R., Santoro A., The Lorenz Therapy: a new tool in the treatment of uremic neuropathy. European Dialysis and Transplant Association, Lisbona May 2004.
• Farina S., Casarotto M., Benelle M., Tinazzi M., Fiaschi A., A randomized controlled study on the effect of two different treatments (FREMS and TENS) in myofascial pain syndrome. EUR MED PHYS 2004; 40:293-301
• Guggi S, Cavina U. Experience of a novel transcutaenous neuromaodulation as first approach to muscle injuries. XIV International Congress on Sports Rehabilitation and Traumatology, Bologna 2005
• Kumar D, Marshall HJ (1997) Diabetic peripheral neuropathy: amelioration of pain with transcutaneous electrostimulation. Diabetes Care 20:1702–1705
• Scionti L., Conti M., Vermigli C., Cazzetta G., Galimberti G., Bosi E. A new treatment for painful diabetic neuropathy: the Frequency Modulated Neural Stimulation (FREMS). NEURODIAB, Resensburg, Germany
• Zhao M. Bai H, Wang E, Forrester J.V., McCaig CD. Electrical stimulation directly induces pre-angiogentic responses in vascular endothelial cells by signaling through VEGF receptors. J Cell Sci 2003:117.395-405.

Lorenz NeuroVasc is a Canadian company operating as the exclusive supplier of FREMS™ technology to the North American healthcare industry. FREMS™ technology is the product of Lorenz Biotech S.p.A. of Modena, Italy, and is rapidly being adopted as a preferred treatment option in the European markets.   — Products — FREMS™ is a composition of electrical signals characterized by negative and multi-modulated pulses which mimic different electrophysiological processes. Aptiva™ Ballet is the ideal device for the treatment and clinical research of peripheral nervous and vascular systems diseases. Aptiva™ Move is the portable and flexible choice in rehabilitation.

To learn more about Lorenz Neurovasc and its products and services, visit www.lorenzneurovasc.ca or call toll free at 1.866.443.8567.

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