Lameness is a pathological change in gait due to dysfunction of one or both lower extremities. Occurs when limb length changes, motor and sensory function is impaired. Lameness in the form of a fall on a shorter leg is observed with congenital underdevelopment of the limb, systemic lesions, curvature and defects of bones, pseudarthrosis of various origins, after improperly healed fractures, as a result of inflammatory diseases (osteomyelitis). Lameness occurs with various defects in the joints (“duck” gait with bilateral hip dislocation), lameness is observed with rachitic or post-traumatic deformities of the femoral neck. Sometimes lameness occurs as a result of pain caused by various pathological processes in soft tissues, bones, joints and nerves. The gait of such patients is characterized by the desire to quickly transfer support to the healthy leg.

Intermittent claudication is caused by acute oxygen starvation of tissues due to insufficient blood supply (see, obliterative). Lameness may be the first symptom of a very serious disease (tuberculous arthritis, bone tumor, etc.).

Treatment of lameness. Elimination of the causes that cause it, which requires clinical, radiological and other studies. Complex surgical treatment methods, orthopedic shoes (see Footwear, orthopedic) and functional orthopedic devices are more often used.

Lameness (claudicatio) is a pathological change in gait due to dysfunction of one or both lower extremities with a change in the length of the limb, its curvature, impaired motor and sensory functions.

A change in limb length, absolute or relative, is observed with micromelia, chondrodystrophy, congenital dislocation of the hip and other congenital diseases, as well as with a number of acquired skeletal lesions: as a result of improperly healed fractures or after various inflammatory processes that led to the destruction of part of the skeleton of the limb or to a violation its enchondral zones in the period of incomplete bone growth, for example, with epiphyseal osteomyelitis in childhood, osteoarticular tuberculosis.

When one of the lower limbs is shortened, lameness is expressed by accentuation of the step, “falling” on the shorter leg. With a bilateral violation of the support of the legs, for example, with a bilateral (usually congenital) dislocation of the hip, the gait takes on the character of swaying from side to side, “duck-like,” which is caused by the alternating sliding of the dislocated heads along the pelvic wing at the moment of stepping on the leg while weakening the tone of the gluteal muscles. A similar lameness is observed with bilateral varus curvature of the femoral-cervical angle (rachitic or traumatic origin). Lameness also occurs with contractures, dislocations, false joints, varus, valgus curvatures of the thigh and lower leg, also due to shortening of the deformed leg. Lameness as a result of motor disorders occurs with paresis and paralysis of the lower extremities. Depending on the type of paralysis (flaccid, spastic), the degree of its prevalence, the combination of affected muscles, one- or two-sided lesions, the nature of lameness is very diverse, especially since paralysis is often combined with shortening of the affected leg, for example after polio. Disorders of the sensitive sphere that cause lameness are of two kinds: less often due to the disappearance of sensitivity (anesthesia) and very often due to its pathological increase - pain. Anesthesia of a limb develops due to a traumatic or inflammatory interruption of the centripetal nerve pathways; the gait of such patients is shuffling, ataxic in nature.

Pain that causes lameness occurs as a result of damage to nerve conductors, when they are irritated by foreign bodies (after injuries), scars, which is often accompanied by trophic disorders (chronic ulcers and osteoporosis). Most often, lameness is caused by pain caused by various pathological processes in soft tissues, bones and joints: myositis, neuritis, osteomyelitis, arthritis, fragile callus after a fracture, sprain, flat feet, etc. The gait of such patients is characterized by careful stepping on the sore leg and the desire to transfer support to the healthy leg as quickly as possible, which is why, in contrast to lameness with simple shortening of the leg, the patient begins to limp when stepping not on the affected leg, but on the healthy leg.

A special type of lameness develops with pain caused by oxygen starvation of the tissues of the limb due to the onset of obliterating endarteritis; pain occurs acutely when walking, often with spasm of the calf muscle; after a short stop they calm down, but when they resume, the movements are repeated. This is the so-called intermittent claudication (see).

It should be borne in mind that lameness is often the first symptom of a very serious disease, for example tuberculous arthritis, bone sarcoma, etc.

Radical treatment of lameness consists in eliminating the cause that causes it, which requires careful clinical, radiological and other studies. For small degrees of anatomical shortening, it is often enough to put an insert (cork, linden, felt, plastic) into the shoe.

With a more significant shortening, special orthopedic shoes are required (see) or an operation to lengthen the shortened leg, sometimes in combination with shortening the healthy one. For lameness caused by paralysis, various plastic surgeries are indicated (muscle transplantation, tenodesis, arthrodesis, arthrorrhiza), and if their effectiveness is insufficient, functional orthopedic devices are indicated. For lameness due to contractures, bone curvatures, false joints - surgical treatment (redressation, myotomy, osteotomy, etc.). For lameness of painful origin - immobilization of the limb, blockade of the painful focus (for arthrosis, some forms of chronic arthritis) and the main treatment of the underlying disease accompanied by lameness.

This year, 2013, a new revision of the National Guidelines for the Management of Patients with Peripheral Artery Diseases was published. An important place in it is given to diseases of the blood vessels of the legs. Despite the lack of comprehensive statistical data, it can be stated that the estimated number of people suffering from this disease based on the prevalence (0.9-7% of the population depending on the age group) in Russia is at least 1.5 million, which means that 100,000 citizens are diagnosed with terminal (critical) form of the disease; which annually leads to 20,000-40,000 amputations for this indication alone.

Intermittent claudication (IC) is the main clinical syndrome of atherosclerotic lesions of the arteries of the lower extremities. Unfortunately, most specialists forget about the relevance of this disease; Perhaps, against the backdrop of the dramatic course of other manifestations of atherosclerosis, this form undeservedly does not attract close attention. However, the prevalence of PC, depending on age, ranges from 0.9% to 7.0%. According to authoritative publications and large population studies (SAGE Group, 2010; Russian Consensus Document, 2013; PANDORA Study, 2012), the prevalence of peripheral arterial disease is high, ranging from 5.8% in the USA and 7% in Russia to 12.2% and 22.9% in France and Italy respectively. It is important that up to 50% of patients with PC have never consulted a doctor about these symptoms, but they still experience discomfort due to leg pain. Medical specialists, when examining such patients if they contact medical institutions for other complaints, do not ask them for the presence of ischemic pain in the legs when walking.

It has been established that atherosclerosis is the cause of damage to peripheral arteries in 80-90% of cases, the rest is “pure” diabetic angiopathy (without background significant atherosclerosis of the vessels of the lower extremities) and vascular damage of autoimmune origin. It has long been known that patients with PC have a high risk of developing myocardial infarction (MI) and acute cerebrovascular accident. Thus, compared to the normal population, their risk of MI is increased from 20% to 60%, and the risk of death from coronary pathology is increased from 2 to 6 times. With PC, the risk of developing acute cerebrovascular accident increases by 40%.

In more than half of patients with peripheral artery diseases, already at the time of treatment, stage IIB (surgical) of the disease is registered according to the classification of A.V. Pokrovsky-Fontaine, which corresponds to intermittent claudication that occurs when walking 50-200 m. Such patients are candidates for endovascular open or hybrid surgical treatment. However, the high level of development of modern reconstructive surgery of the arteries of the lower extremities cannot solve all the problems in this group of patients. The success of reconstructive interventions directly depends on the condition of the so-called. outflow tracts - vessels located below the inguinal fold. According to some data, up to 40% of patients requiring surgical treatment cannot undergo arterial reconstruction due to distal or widespread multifocal lesions of the arterial bed.

The appearance of rest pain and ulcerative-necrotic changes in the skin up to gangrene in patients with PC indicates the development of critical lower limb ischemia (CLI), a state of decompensation of arterial blood flow. Treatment of CLI requires a more active approach, both in terms of pharmacotherapy and surgical interventions. The dynamics and statistics of CLI are such that during the first 6 months after diagnosing CLI, the limb can be saved only in 40% of cases, since 20% of patients will die, and the rest will undergo major amputation. As a result, by the end of the first year after verification of the diagnosis, only 45% of patients have a chance of saving a limb, about 30% continue to live after amputation of the thigh or lower leg, and a quarter of patients will not survive this time period (Fig. 1).

It is recognized (A.V. Gavrilenko et al., 2010) that when a diagnosis of peripheral arterial disease is made in a patient with PC or CLI, conservative therapy is indicated regardless of the location and extent of the vascular lesion and is prescribed for life. After endovascular or surgical interventions on the arteries, the need for conservative treatment also remains. In cases where it is not possible to achieve adequate compensation of blood circulation by surgical methods, the isolated use of therapeutic treatment remains the only therapeutic tactic of the doctor.

Modern approaches to conservative therapy

According to the guidelines of the American Heart Association (2005), the main goal of conservative therapy in patients with PC and CLI is to improve quality of life and reduce the risk of fatal cardiovascular events. To achieve this, the doctor’s treatment tactics must include both the correction of risk factors and the prescription of effective medications. One of the leading areas of risk factor correction is smoking cessation, which includes behavior modification, nicotine replacement therapy, bupropion therapy) (evidence class I) (Fig. 2).

All patients with PC are shown effective physical activity - dosed walking, that is, walking until almost maximum ischemic pain appears (evidence class I). An exercise therapy program is recommended as the initial form of treatment for patients with intermittent claudication as the primary manifestation of chronic lower limb ischemia (CLI) (Evidence Level A). The duration of physical therapy classes is from 30 to 45 minutes minimum, classes are held 3 times a week, the minimum course is 12 weeks. The maximum effectiveness of dosed walking appears after 1-2 months and persists after 3 or more months. The beneficial effect is explained by an improvement in the metabolism of skeletal muscles, an increase in muscle mass, as well as an improvement in endothelial function and, to a lesser extent, the formation of collateral circulation.

In addition to the modification of risk factors and dosed walking, targeted conservative treatment has the following main vectors: prevention of thrombotic and cardiovascular complications (MI, stroke, death due to cardiovascular events) through long-term administration of antiplatelet agents, administration of pharmaceutical drugs with complex and metabolic effects . Long-term, often life-long, use of medications requires strict adherence to the dosing and administration regimen, implementation of non-pharmacological treatment measures, as well as regular monitoring by a doctor. Patient “adherence to therapy” is a key factor in achieving high treatment effectiveness.

An important area is monitoring blood lipid levels. Treatment with hydroxymethylglutaryl-acetyl-coenzyme A reductase inhibitors (statins) is indicated in all patients with peripheral artery disease (PAD) to achieve a target low-density lipoprotein (LDL) level of less than 100 mg/dL (Class I evidence). Treatment of dyslipidemia reduces the risk of adverse cardiovascular events in patients with atherosclerosis. However, the clinical picture of severe damage to the arterial bed of the lower extremities does not always strictly correlate with changes in the lipid spectrum of the blood and the level of cholesterol and LDL.

All patients with PAD, both with PC and CLI, are advised to control blood glucose levels (reducing the level of glycosylated hemoglobin to 7%), and in the presence of diabetes mellitus, intensive therapy with antihyperglycemic drugs or insulin, as well as careful care of the skin of the feet and legs (class of evidence I) .

In addition to glucose control, an important direction in the correction of PAD risk factors is blood pressure (BP) control. In patients without concomitant pathology, a blood pressure level of less than 140/90 mm Hg should be considered optimal. Art., while the presence of conditions such as arterial hypertension, coronary heart disease, chronic heart failure, diabetes mellitus and renal failure necessitate maintaining blood pressure levels below 130/80 mm Hg. Art. (class of evidence I). The targeted drugs are angiotensin-converting enzyme (ACE) inhibitors, which significantly reduce the risk of MI, stroke, and death due to cardiovascular events in patients with PAD.

Antiplatelet (antiplatelet) therapy in the form of Aspirin at a dosage of 75-325 mg/day or clopidogrel 75 mg/day is indicated for patients with atherosclerosis of the arteries of the lower extremities to reduce the risk of cardiovascular events (evidence class I). The practitioner should remember that in patients with PAD, oral anticoagulants should not be used to prevent adverse cardiovascular ischemic events.

It is advisable to prescribe a phosphodiesterase III inhibitor, cilostazol, which has a vasodilating, metabolic and disaggregant effect to patients with HP (evidence class I). At a dosage of 100 mg twice daily, the drug increased pain-free walking distance (PDW) by 40-60% compared with placebo after 12-24 weeks of treatment. Cilostazol, however, is not registered in the Russian Federation. Another obstacle to its widespread use is the need for the patient to have no concomitant pathology in the form of chronic heart failure of any class according to the New York Heart Association (NYHA) classification, as well as restrictions imposed by the European Medicines Agency on its use in 2013 due to the high likelihood of side effects.

Pentoxifylline at a dose of 1200 mg per day can be considered as one of the main drugs for increasing the maximum walking distance (MTD) in patients with PC (evidence class IIB). Pentoxifylline improves microcirculation and rheological properties of blood, has a vasodilating effect, blocks phosphodiesterase and promotes the accumulation of cyclic adenosine monophosphate in cells, which leads to a minimal but statistically significant increase in DBC by 21-29 meters and the maximum distance traveled by 43-48 meters.

Sulodexide (250 LE orally 2 times a day), previously recommended for use in patients with CLI, is currently recommended for patients with PC. In this cohort of patients, sulodexide increases DBC by up to 95% when used in a course in combination with parenteral administration (evidence class IIA). The effectiveness of the drug is explained by its complex effect on the main links in the pathogenesis of the disease: correction of endothelial dysfunction, normalization of blood rheology and microvasculature, increased fibrinolytic activity.

A promising direction in the complex treatment of patients with PC of atherosclerotic etiology is the correction of endothelial dysfunction, aimed at stimulating the synthesis of nitric oxide (NO) by endothelial cells. Endothelial dysfunction is expressed in increased permeability and adhesiveness, as well as in increased secretion of procoagulant and vasoconstrictor factors, which can be considered as an early stage in the development of vascular damage. NO is an important regulator of cell metabolism and plays an important role in the pathogenesis of endothelial dysfunction. Intermittent pneumocompression can have a positive effect aimed at correcting endothelial dysfunction, including in patients with critical ischemia of the lower extremities. Another vector for correcting endothelial dysfunction is the use of drugs from the group of angiotensin-converting enzyme inhibitors, mainly perindopril, angiotensin II receptor blockers, mainly losartan, as well as beta-blockers, mainly nebivolol. This is especially important given the high prevalence of arterial hypertension, as well as coronary heart disease and chronic heart failure in patients with CLI. Beta-blockers are effective antihypertensive drugs and are not contraindicated in patients with lower extremity arterial disease, as most practitioners believe.

Correction of endothelial dysfunction is also possible by stimulating NO secretion by exogenous factors of the L-arginine - NO - guanylate cyclase system, in particular, when using the nitric oxide precursor L-arginine. Therapy aimed at correcting endothelial dysfunction is extremely promising, but is currently mostly at the stage of clinical trials.

As stated in the National Guidelines (2013), high class of evidence IIA includes the use of gene therapy drugs. This group of drugs has been actively studied over the past two decades. They are agents of the so-called. “therapeutic angiogenesis” is a new therapeutic tactic designed to induce the development of a microvascular network by introducing gene therapeutic drugs encoding the synthesis of various short-lived and short-distance molecules (growth factors, transcription factors), and subsequently lead to the formation of collaterals. It is believed that the development of the microvasculature in the ischemic muscle mass of the lower extremities promotes tissue oxygenation, reduces overall peripheral vascular resistance, and new vessels formed at the level of occlusion are able to evolve into functional collaterals. Plasmid and adenoviral gene constructs that do not integrate into the genome are being tested as potential drugs. A large number of clinical studies have shown their safety, including oncological ones. At the level of phase II clinical trials, significant results in increasing pain-free walking distance were obtained with genes encoding vascular endothelial growth factor (VEGF165), basic fibroblast growth factor (bFGF), hepatocyte growth factor growth factor, HGF), etc. However, treatment efficacy was not established for all designs in phase III. In particular, the use of a drug based on the bFGF gene in patients with stage IV of the disease (according to A.V. Pokrovsky-Fontaine) did not affect life expectancy and limb safety. At the same time, a plasmid construct with the HGF gene, used for the same indications, significantly reduced the severity of pain, had a positive effect on the quality of life, and promoted the healing of ulcers, which was the basis for recognizing its effectiveness.

Currently, the gene therapy drug Neovasculgen, the active substance of which is a supercoiled plasmid with the VEGF165 gene, is included in the State Register of Medicines of Russia. Its safety and effectiveness were studied in multicenter controlled randomized studies, which showed a significant increase in pain-free walking distance, as well as a number of other effects, including an increase in tissue oxygen tension, to some extent, linear blood flow velocity, and ankle-brachial index. The drug is intended for inclusion in the complex therapy of patients with IIa-III degrees of PC (according to Pokrovsky-Fontaine) of atherosclerotic origin. The drug is administered at a dose of 1.2 mg locally intramuscularly twice with an interval of 14 days. The capabilities of the drug are realized as part of complex therapy. As part of clinical studies, the effectiveness of the drug was assessed in patients who did not undergo surgical revascularization methods and who were not prescribed therapy with prostaglandin drugs. It was found that within six months, patients experienced an increase in pain-free walking distance by an average of 110.4%, and after a year by 167.2%. Patients with a more severe stage of the process - III - responded to therapy to a greater extent; for them, increases were established at 231.2 and 547.5%, respectively. Also, statistically significant shifts are recorded when monitoring transcutaneously determined oxygen tension. Indicators of macrohemodynamics—the ankle-brachial index and linear blood flow velocity—change to a lesser extent. It is important that when assessing the quality of life in such patients, a significant increase was established on the “physical component of health” scale (p = 0.001).

In the treatment of CLI, if it is impossible to perform endovascular or open arterial reconstruction, the therapeutic approach differs from the treatment of PC. Prostanoids, the drugs prostaglandin E1 (PGE1) and prostacyclin I2 (PGI2), have been the most studied in the treatment of CLI. Numerous studies have shown that their parenteral administration for 7-28 days can reduce rest pain and promote healing of trophic ulcers and, in some cases, avoid or delay limb amputation (class of evidence IIB, level of evidence A).

Gene therapeutic angiogenic drugs recommended for use in the treatment of PC are considered potentially effective in the treatment of patients with CLI. Their role in the complex treatment of patients with CLI is shown in terms of improving long-term results of reconstructive interventions. The first data are emerging (I. N. Brodsky, 2013) on the successful combination of prostacyclin drugs with the induction of microvascular development by Neovasculgen in severe patients with CLI.

Data on the effectiveness of hyperbaric oxygenation, spinal neurostimulation, as well as traditional types of physiotherapy (laser therapy, magnetic therapy) used in Russia in the treatment of CLI are contradictory, and therefore there are no clear recommendations regarding their use. Encouraging data have been obtained regarding the use of regional catheter thrombolysis in the complex therapy of CLI in diabetic angiopathy. The purpose of local thrombolysis in this cohort of patients is the treatment and prevention of microthrombosis, stabilization of blood coagulation properties.

Effective treatment of patients with intermittent claudication and its dangerous complication in the form of critical ischemia of the lower extremities is an urgent problem in practical medicine due to insufficient attention, high morbidity, and treatment difficulties. The authors of the article hope that the material presented in the work will be useful in the work of not only angiosurgeons, but also doctors of other medical specialties.

Literature

1. Pokrovsky A.V. Clinical angiology: manual: in 2 volumes. M.: Medicine, 2004. T. 1-3.
2. National recommendations for the management of patients with pathology of the arteries of the lower extremities: angiology and vascular surgery. Application. 2013. T. 19, No. 2. P. 1-67.
3. Obolensky V. N., Yanshin D. V., Isaev G. A., Plotnikov A. A. Chronic obliterating diseases of the arteries of the lower extremities - diagnosis and treatment tactics // Russian Medical Journal. 2010. No. 17. P. 1049-1054.
4. Savelyev V. S., Koshkin V. M., Kunizhev A. S. Critical ischemia as a consequence of inadequate treatment of patients with chronic obliterating diseases of the arteries of the lower extremities at the outpatient stage. Angiology and Vascular Surgery. 2004. No. 1. P. 7-10.
5. Burger D.H., Kappetein, Van Bockel J.H. Breslau A prospective randomized trial comparing vein with A. P. polytetrafluoroethylene in P. J. above-knee femoropopliteal bypass grafting // Vasc. Surg. 2000. Vol. 32. R. 278-283.
6. Cacoub P., Cambou J. P., Kawnator S. et al. Prevalence of peripheral arterial disease in high-risk patients using ankle-brachial index in general practice: a cross-sectional study // Int. J. Clin. Pract. 2009. Vol. 63. No. 1. P. 63-70.
7. Shaginyan A. R. Long-term results of surgical treatment of Leriche syndrome // Thoracic and cardiovascular surgery. 2007. No. 1. P. 53-59.
8. Norgren L., Hiatt W. R., Dormandy J. A. et al. Inter-Society Consensus for the Management of Peripheral Arterial Disease (TASC II) // Eur. J.Vasc. Endovasc. Surg. 2007. No. 33. R. 1-70.
9. Gavrilenko A.V., Kotov A.E., Muravyova Ya.Yu. The influence of tactical errors on the results of surgical treatment of patients with critical ischemia of the lower extremities. Angiology and Vascular Surgery. 2010. No. 1. P. 138-143.
10. Hirsch A. T., Haskal Z. J., Hertzer N. R. et al. ACC/AHA guidelines for the management of patients with peripheral arterial disease // J. Am. Coll. Cardiol. 2006. No. 6. P. 1239-1312.
11. Savelyev V. S., Koshkin V. M., Karalkin A. V. Pathogenesis and conservative treatment of severe stages of obliterating atherosclerosis of the arteries of the lower extremities. M.: MIA, 2010. 214 p.
12. Cilostazol: cilostazol prescribing information. http://www.drugs.com/pro/cilostazol.html.
13. European Medicines Agency recommends restricting use of cilostazol-containing medicines. http://www.ema.europa.eu/docs/en_GB/document_library/Press_release/2013/03/WC50014067.pdf.
14. Girolami B., Bernardi E., Prins M. et al. Treatment of intermittent claudication with physical training, smoking cessation, pentoxifylline, or nafronyl: a meta-analysis // Arch. Intern. Med. 1999. No. 4. P. 337-345.
15. Hood S. C., Moher D., Barber G. G. Management of intermittent claudication with pentoxifylline: meta-analysis of randomized controlled trials // Cmaj. 1996. No. 8. P. 1053-1059.
16. Kalinin R. E. Correction of endothelial dysfunction. Saarbrucken, Germany: LAP Lambert Academic Publishing, 2012.128 pp.
17. Kirichuk V. F., Glybochko P. V., Ponomareva A. I. Endothelial dysfunction. Saratov: Saratov Medical Publishing House. Univ., 2008. 129 p.
18. Shvalb P. G., Kalinin R. E., Pshennikov A. S., Suchkov I. A. The influence of intermittent pneumocompression on the production of nitric oxide as the main marker of endothelial dysfunction in patients with obliterating atherosclerosis of the arteries of the lower extremities // News of surgery. 2011. No. 3. P. 77-81.
19. Lipnitsky E. M., Amosov G. G., Morozov K. M. The use of rhythmic pneumocompression for the treatment of patients with chronic obliterating diseases of the arteries of the lower extremities. Angiology and Vascular Surgery. 2007. No. 3. P. 22-26.
20. Haro J., Acin F., Florez A. et al. A prospective randomized controlled study with intermittent mechanical compression of the calf in patients with claudication // J. Vasc. and Endovasc. Surg. 2010. No. 4. P. 857-862.
21. Kalinin R. E., Pshennikov A. S. Methods for stimulating the secretion of nitric oxide in patients with obliterating atherosclerosis of the arteries of the lower extremities from the perspective of correction of endothelial dysfunction // Bulletin of the National Medical and Surgical Center named after. N.I. Pirogova. 2011. No. 3. P. 12-16.
22. Belenkov Yu. N., Mareev V. Yu., Ageev F. T. Angiotensin-converting enzyme inhibitors in the treatment of cardiovascular diseases (Quinapril and endothelial dysfunction). M., 2002. 86 p.
23. Grigoriev N. B., Granik V. G. Nitric oxide (NO). A new path to drug discovery. M.: University Book, 2004. 360 p.
24. Flu W. J., van Kuijk J. P., Chonchol et al. Timing of pre-operative beta-blocker treatment in vascular surgery patients // J. M. Am. Coll. Cardiol. 2010. No. 23. R. 1922-1929.
25. Uhlir O., Dvorak I., Gregor P. et al. Nebivolol in the treatment of cardiac failure: a double-blind controlled clinical trial // J. Card. Fail. 1997. No. 4. R. 271-276.
26. Gao Y. S., Nagao T., Bond R. A. et al. Nebivolol inducesendothelium-dependent relaxations of canine coronary arteries // J. Cardiovasc. Pharmacol. 1991. No. 6. R. 964-969.
27. Mishalov V. G., Chernyak V. A. Peripheral artery occlusive disease: what can we do for the patient today? // Practical angiology. 2011. No. 1. P. 12-19.
28. Drexler H., Zeiher A. M., Meinzer K., Just H. Correction of endothelial dysfunction in coronary microcirculation of hypercholesterolemic patients by L-arginine // Lancet. 1991. Vol. 338. R. 1546-1550.
29. Walker H. A., McGing E., Fisher I. et al. Endothelium-dependent vasodilation is independent of the plasma L-arginine/ADMA ratio in men with stable angina: lack of effect of oral L-arginine on endothelial function, oxidative stress and exercise performance // J Am Col Cardiol. 2001. Vol. 38. R. 499-505.
30. Gupta R., Tongers J., Losordo D. W. Human Studies of Angiogenic Gene Therapy // Circ. Res. 2009. Vol. 105. P. 724-736.
31. Deev R.V., Grigoryan A.S., Potapov I.V. and others. World experience of gene therapy for ischemic diseases // Angiology and vascular surgery. 2011. No. 2. P. 145-154.
32. Baumgartner I., Chronos N., Comerota A. Local gene transfer and expression following intramuscular administration of FGF-1 plasmid DNA in patients with critical limb ischemia // Mol. Ther. 2009. No. 5. P. 914-921.
33. Nikol S., Baumgartner I., Van Belle E. Therapeutic angiogenesis with intramuscular NV1 FGF improves amputation-free survival in patients with critical limb ischemia // Mol. Ther. 2008. No. 5. P. 972-978.
34. Rajagopalan S., Mohler E. R. III, Lederman R. J. Regional angiogenesis with vascular endothelial growth factor in peripheral arterial disease: a phase II randomized, double-blind, controlled study of adenoviral delivery of vascular endothelial growth factor 121 in patients with disabling intermittent claudication // Circulation. 2003. Vol. 108. P. 1933-1938.
35. Belch J., Hiatt W. R., Baumgartner I. Effect of fibroblast growth factor NV1 FGF on amputation and death: a randomized placebo-controlled trial of gene therapy in critical limb ischemia // Lancet. 2011. No. 9781. P. 1929-1937.
36. Shigematsu H., Yasuda K., Iwai T. Randomized, double-blind, placebo-controlled clinical trial of hepatocyte growth factor plasmid for critical limb ischemia // Gene Ther. 2010. No. 9. P. 1152-1161.
37. Shvalb P. G., Gavrilenko A. V., Kalinin R. E. and others. Efficacy and safety of using the drug “Neovasculgen” in complex therapy of patients with chronic ischemia of the lower extremities (phase 2-3 of clinical trials) // KTTI. 2011. No. 3. P. 76-83.
38. Chervyakov Yu. V., Staroverov I. N., Nersesyan E. G. and others. Therapeutic angiogenesis in the treatment of patients with chronic obliterating diseases of the arteries of the lower extremities. Short-term and long-term results // Angiology and vascular surgery. 2012. No. 3. P. 19-27.
39. Gavrilenko A. V., Voronov D. A., Konstantinov B. A., Bochkov N. P. Combination of reconstructive vascular operations with genetic engineering technologies for stimulating angiogenesis: a modern strategy for improving long-term results of treatment of patients with chronic ischemia of the lower extremities. Angiology and Vascular Surgery. 2008. No. 4. P. 49-53.

R. E. Kalinin*, 1 , Doctor of Medical Sciences, Professor
N. D. Mzhavanadze*
R. V. Deev**, Candidate of Medical Sciences

The good old days, when there were few doctors and self-medication was extremely common, truly amazing ones were found among folk remedies. For example, in case of intermittent claudication, or rather a symptom of pain in the leg, one was supposed to rub it with turpentine and sit in front of the fire until it began to tingle. One can only hope that the patients who received such dubious treatment did not burn alive. In our article we will talk about the signs of intermittent claudication and treatment of intermittent claudication.

Treatment of intermittent claudication

Yes, the same exercise that leads to leg pain is also one of the best treatments for intermittent claudication. “When I tell patients that they need to go out more, they look at me like I’m crazy. People want pills for treatment. But we don't really have a pill that works better for claudication than walking," says Dr. Jay Coffman, chief of vascular pathology at Boston University Medical Center. “Regularly exercising the muscles during claudication symptoms increases their ability to extract oxygen from the blood,” explains Dr. Santilli. Therefore, if you walk more, the leg muscles will learn to use the limited amount of it more efficiently and will suffer less from oxygen starvation, and therefore from pain and cramps.

He recommends that patients with signs of intermittent claudication walk for an hour a day, 5 times a week, for treatment. While walking, if symptoms of pain appear, it is better not to stop immediately, but despite its intensification, set a goal for yourself, say, the next bench, try to get there and only after that give yourself a break. Then move on. At the next attack of pain, it is advisable to set yourself a more ambitious task, for example, to reach the second bench, etc. And such small feats must be accomplished within the entire hour.

"It doesn't matter how many times you have to stop or how fast you go," Dr. Santilli says. Some people rest every 2-3 minutes at first. This is fine. If a person maintains this type of training for several weeks, the symptom of pain from intermittent claudication will subside and stoppages will become less frequent. In fact, studies show that using this method can double the pain-free distance you can walk in just 2-3 months.

Antioxidants for the treatment of intermittent claudication

Usually, the symptoms of intermittent claudication become easier if you take antioxidants for treatment, in particular vitamins E and C, which inhibit the development of atherosclerosis, especially in its early stages. Vitamin E is prescribed in the treatment of intermittent claudication, one might say traditionally. One study in Sweden showed that signs of intermittent claudication were reduced when treated with 300 IU per day.

However, for smokers with signs of intermittent claudication, vitamin E does not seem to help. In all likelihood, according to Dr. Weiss, its antioxidant effect is not able to neutralize the damage caused to the cardiovascular system by tobacco smoke. The first step is to give up this bad habit to treat the symptoms of intermittent claudication. By the way, for many who quit smoking, intermittent claudication goes away on its own over time.

Typically, Dr. Weiss prescribes 400-800 IU of vitamin E and 1,000-3,000 mg of vitamin C daily for patients with signs of atherosclerosis for treatment. The first of them prevents the oxidation of “bad cholesterol” (low-density lipoproteins) - a process that directly leads to the formation and growth of atherosclerotic plaques in the vascular walls. Vitamin C, in the treatment of intermittent claudication, restores the active form of vitamin E, and also promotes the release of nitric oxide by the endothelium, which, as already mentioned, dilates the arteries. The most effective vitamin E preparations for the treatment of intermittent claudication are O-alpha tocopherol and a mixture of tocopherols.

Folk remedies for intermittent claudication

Ginkgo - a folk remedy for the treatment of intermittent claudication

“We tend to think of this folk remedy as being good for the brain, but it actually improves overall circulation,” says Boulder, Colorado-based herbalist Mindy Green. Much research has been devoted to the effect of ginkgo on intermittent claudication during treatment. Some of them achieved statistically significant and clinically significant increases in pain-free walking distance. Have your relative take standardized ginkgo extract tablets or capsules according to the package directions.

Garlic for treating intermittent claudication

It's not clear why, but garlic seems to improve blood circulation in all parts of the body. The most convenient (and least odoriferous) form of this medication is capsules. Let your patient with signs of intermittent claudication take two pieces two to three times a day for 2-6 months until symptoms disappear.

Foot cocktail for the treatment of intermittent claudication

The amino acid arginine is needed to produce nitric oxide to treat intermittent claudication. It is secreted by the endothelium (the lining of the arteries) and helps them relax and widen, increasing blood flow, explains Decker Weiss, a naturopath at the Arizona Heart Institute in Phoenix. The standard dose of treatment is 1 capsule with 500 mg of arginine up to three times a day.

Magnesium for the treatment of intermittent claudication

Along with arginine, Dr. Weiss recommends taking one of the most important metals for the treatment of intermittent claudication - magnesium. It promotes relaxation of the muscles of the arterial walls, i.e. expansion of blood vessels, the lumen of which is narrowed by atherosclerotic deposits. It is possible that your relative may have a general magnesium deficiency, for example, if he takes medications commonly prescribed for heart patients such as diuretics (diuretics) and digitalis glycosides - digitoxin (Christodigine) or digoxin (Aanicor). Signs of this deficiency are general muscle weakness, nausea, irritability. For most people, a safe daily dose of magnesium supplement for treatment is 350 mg. Dr. Weiss recommends taking orotate or glycinate of this metal.

Signs of intermittent claudication

The natural remedies available these days for the symptoms of intermittent claudication are much safer. We are talking about a chronic pathology, also known as Charcot's syndrome, the symptoms of which affect almost every tenth person over 70 years of age. signs of intermittent claudication are caused by atherosclerosis - hardening of the walls and narrowing of the lumen of the peripheral arteries that carry blood with oxygen and nutrients to the legs. Predisposing signs of intermittent claudication are hypertension, diabetes, smoking, and high cholesterol—the same factors that risk coronary heart disease. In this case, signs of ischemia also appear, i.e. oxygen starvation, but not of the myocardium, but of the muscles of the foot, lower leg, thigh, and sometimes even buttocks. As a result, a burning, cramping pain occurs in these parts of the body.

Symptoms of claudication usually begin to occur after a person has walked a short distance, often less than a city block. The patient stops, rests for a few minutes, and symptomatic pain stops. He sets off again, stops again from pain, etc. Over time, the signs of atherosclerosis and ischemia progress, and as a result, the distance traveled between breaks is increasingly reduced.

“Signs of intermittent claudication certainly reduce quality of life. However, up to 90% of people suffering from this pathology never see a doctor about it. Most consider it an inevitable accompaniment of aging. They just think, “What can you do, the years are taking their toll,” says Dr. Steven Santilli, a vascular surgery specialist in Minneapolis. - Such fatalism is not justified in any way. Lifestyle changes, such as quitting smoking and regular exercise, can significantly improve the condition of your feet. Medicine sees no reason to put up with intermittent claudication.” Here are some effective ways to treat intermittent claudication.

Prevention of intermittent claudication

Smoking cessation as a way to prevent intermittent claudication

According to Dr. Santilli, smokers have twice the risk of intermittent claudication as non-smokers. Tobacco smoke narrows the arteries and makes it difficult for muscles to work, including in the legs, and in addition, contributes to the development of atherosclerosis. Even if a person has smoked for many years, quitting this bad habit will improve his blood circulation and relieve pain.

Fat reduction to prevent intermittent claudication

“Fatty foods lead to the progression of intermittent claudication,” warns Dr. Santilli, “because they promote the development of atherosclerosis.” Have your sick relative snack on 4 grams of fruit, vegetables, legumes, or whole grains for every gram of meat. This will help him transition to a leaner - and healthier - lifestyle. If he just can't do without fatty foods, you can treat him to fried chicken, bacon or meat gravy once a month.

Intermittent claudication (IC) or intermittent claudication is one of the names of the disease of the arteries of the lower extremities, the cause of which, in most cases, is atherosclerosis.

Causes of PC syndrome

Occurs both in the aorta and in medium and small arteries. When blood vessels are blocked, the legs do not receive sufficient blood and oxygen, especially during exercise. This lack of oxygen is called ischemia, which causes pain. In severe cases, ischemic ulcers can develop, as well as gangrene, which can lead to amputation of the leg.
Due to its slow progression, the disease is initially asymptomatic for many years. But later, during physical activity, when the muscles in the legs require more oxygen, and the arteries are narrowed and do not allow increased blood flow to the muscles, pain occurs - this is the main symptom that characterizes intermittent claudication.

If a person, after walking a short distance, is forced to stop due to severe pain in the calf muscles, then this condition is called intermittent claudication.

Other conditions in which intermittent claudication may be a symptom include:

• thromboangio-obliterating arteritis (Buerger's disease),
• coarctation of the aorta,
• Takayasu disease (so-called “pulseless disease”),
• radiation damage to arteries,
• peripheral blood clots,
• narrowing of the artery caused by pressure through a Baker's cyst (popliteal cyst),
• popliteal artery stenosis,
• popliteal artery aneurysm,
• hip syndrome that occurs in cyclists,
• vascular spasms (periodic arterial spasms, manifested by a temporary absence of pulse in the periphery and the appearance of symptoms of lameness),
• anemia (especially in the presence of atherosclerotic stenoses).

Among the causes of lameness, lumbar discopathy and spinal canal narrowing syndrome are also mentioned.

Symptoms of intermittent claudication

• depending on the location of the narrowing of the vessel, pain appears in the lower leg, under the knee or around the buttocks, which forces the patient to often stop while walking; as the disease progresses and blood flow deteriorates, the patient may walk shorter and shorter distances,
• decreased muscle mass in the legs, which is due to the fact that the supply of oxygen and nutrients to the muscles is reduced due to insufficient blood flow; slow muscle degeneration and atrophy occurs, leading to muscle weakness,
• weak pulse in the extremities, caused by stiffness and calcification of the walls of blood vessels,
• the skin on the legs becomes thinner, paler and hair begins to fall out,
• skin ulcers that appear in further stages of the disease,
• necrosis, which is the result of prolonged ischemia; impaired mobility and soreness are also annoying during rest; necrosis may involve part of the limb, and in extreme cases there are extensive necrotic changes that sometimes require surgery or amputation.

The first symptoms of PH are pain when climbing stairs or uphill, as well as when walking a long distance. Over time, the disease progresses and the person needs frequent stops when walking.

Pain in the legs that appears when walking stops immediately, even when stopping for a minute, but reappears as soon as movement begins, causing the patient to limp. Depending on the location of the narrowing or blockage, pain occurs in the legs, thighs, or toes.

In some patients, intermittent claudication remains stable for many years. Sometimes there may be a sudden deterioration in health, associated, for example, with the appearance of a new stenosis. In many cases, prolonged ischemia of the bloodstream activates adaptation mechanisms in the form of new connections between vessels - this provides improved blood supply and can manifest itself in the form of relief of symptoms.

Other signs of the disease

Over time, the nutrition of the legs deteriorates, and trophic changes in the skin occur - dryness, peeling, discoloration, pallor. Hair falls out, the color and quality of nails changes. Ischemic changes are also associated with deterioration of blood flow, nutrition and oxygen flow - the formation of ulcers, necrosis, even gangrene. Long-term intermittent claudication usually forms collaterals - bypass vessels that fully or partially compensate for the disease. But sometimes a complete blockage of the vessel occurs. In such cases, emergency surgery is necessary, otherwise gangrene may occur.

Pain and cramping in the legs is the main symptom of intermittent claudication. It can be sharp or dull, aching, throbbing and burning.

The severity of peripheral artery disease, the location of the blockage, and muscle activity determine the severity of symptoms and location. Atherosclerotic plaques often begin in the arteries farthest from the heart. If the blockage goes further up the leg, the pain from the limp may be in the hip. If there is a blockage in the aorta (the main arterial vessel that carries blood from the heart to the legs), intermittent claudication may include tenderness in the buttocks, groin, or symptoms of erectile dysfunction (Leriche syndrome).

Degrees and stages of ischemia

To determine the indications for surgery and prognosis, the degree of ischemia is assessed, usually according to four classification levels:

• I degree - no symptoms;
• II degree - intermittent claudication;
• III degree - the occurrence of pain even at rest;
• IV degree - necrosis, gangrene.

For some people, the only symptom of the developing condition is numbness in the foot so severe that it is impossible to stand safely. When the patient stops and rests, the numbness and discomfort disappear, but they return after traveling a distance close to the previous one.

Intermittent claudication - diagnosis

Although the signs of intermittent claudication are very typical, sometimes differentiation is required from other diseases in which pain in the extremities is also associated with tension. That is why it is very important to collect a detailed history, in which you need to clarify:

• - the location of the pain,
• - the distance at which pain appears or causes the patient to stop,
• - pain occurs constantly after walking a given distance,
• - the time required for the pain to subside after the end of the load,
• - a specific position or type of rest that brings the most rapid relief.

Such a survey in most cases makes it possible to make a diagnosis. However, attention should be paid to diseases with a similar clinical picture.

For example, intermittent lower leg claudication is most often confused with venous claudication, in which pain results from chronic venous insufficiency, usually a consequence of venous thrombosis and insufficient vascular recanalization. In this case, walking causes increased blood flow to the arteries and then to the narrowed veins, where the pressure increases, causing severe pain. Rapid relief after lifting the limb upward is characteristic of venous claudication. It goes away more slowly after you stop trying.

In most cases, intermittent claudication can be diagnosed during the initial examination. This is evidenced by symptoms and absence of pulse in the lower extremities. Additional examination methods include: ultrasound examination of vascular patency (Dopplerography) and angiography. Ultrasound examination - Dopplerography, allows you to determine the degree of circulatory disturbance in the lower parts of the leg. A Doppler examination is a non-invasive test that evaluates blood flow through the arteries and the vessels themselves, as well as the presence of any atherosclerotic plaques or blood clots.

The main method of studying patients with vascular blockage and serious circulatory disorders is radiocontrast angiography. This method allows you to accurately determine the location and extent of the blockage.

Additional methods for assessing the vascular system are spiral computed tomography and magnetic resonance angiography.

Treatment of intermittent claudication

Conservative treatment

The following medications are used:

• Medicines to prevent excessive blood clotting (aspirin or medicines with a similar effect - so-called anticoagulants);
• Vasodilators;
• Medicines that reduce blood fat and cholesterol (only in combination with a proper diet);
• Medicines that improve blood flow through capillaries;
• Multi-acting drugs that combine the above modes of action - and prostaglandins, which are used in repeated series of injections (the exact determination of their effectiveness requires further research);
• Drugs used to treat diabetes, hypertension, heart disease.

Drug treatment of circulatory disorders is common to other vascular diseases. Medicines that improve blood circulation are prescribed, such as aspirin and pentoxifylline (trental, oxopurine). Products that improve fat metabolism and lower cholesterol levels are also added.

Quitting smoking is the most important condition for treatment. Diabetes, which is a common condition in patients, needs to follow a diet and maintain normal blood sugar levels. It is very important to maintain foot hygiene, avoid skin damage and cracks, and use soft, comfortable shoes.

However, the main method of conservative treatment of circulatory failure of the lower extremities is dosed walking.

This is a kind of physiotherapeutic treatment that promotes the development of collateral circulation and thus improves blood supply to tissues. Walking should be daily and for as long as possible until pain appears that prevents you from continuing to move. After a short rest and cessation of pain, you must continue walking. And so on repeatedly for an hour or more. Many months of daily hard training with the help of dosed walking allow many patients with PC to significantly increase the distance they can walk without stopping.

Treatment of lower limb ischemia requires great physical effort. Therefore, it is recommended to ride both a regular and a stationary bicycle (you can install it in front of the TV). Instead of a stationary bicycle, you can use a treadmill, that is, a device that allows you to walk in place. Walking is recommended even for patients in the third stage of intermittent claudication. Very good results are achieved by training on a treadmill under the supervision of an experienced physiotherapist. Performed 3 times a week for 30 minutes for at least several weeks, it is the most effective treatment for intermittent claudication.

Surgical treatment

The procedures are usually performed in vascular surgery units and the type depends on the location and extent of changes in the vessels, as well as the age and general condition of the patient. This:

• Removal of atherosclerotic plaques from the lumen of blood vessels;
• Bypassing (creating bypass routes) of vascular sections using grafts from one’s own venous vessels or artificial vascular prostheses;
• Sympathectomy - division of the nerves responsible for vascular spasm in the area affected by lameness;
• Destroying atherosclerotic plaque and vasodilating using a balloon catheter inserted into the artery (called percutaneous angioplasty). To prevent re-stenosis, you can leave a stent in it, that is, a pipe made of a metal mesh adjacent to the walls of the vessel;
• In difficult cases - surgical treatment of ulcers and supplying them with skin grafts - plastic surgery;
• In case of failure of treatment and extensive necrosis, amputation of the limbs is performed.

Prevention

When talking about preventing intermittent claudication, we should address its cause, that is, chronic limb ischemia. In addition to factors that increase the risk of ischemia but are not modified in any way (age, sex), there are a number of factors that can be effectively controlled. They include.

Atherosclerosis, complicated by serious pathologies of the heart and blood vessels, also has a number of less noticeable concomitant diseases. One of them is intermittent claudication, which develops against the background of the underlying disease and often remains undeservedly ignored.

Damage to the veins is an invariable accompaniment, and the veins of the lower extremities suffer the most. Unfortunately, pain in the legs when walking is not a symptom with which people go to the doctor. Therefore, intermittent claudication has enough time to progress uninterruptedly, covering increasingly larger areas of influence.

Such neglect leads to the fact that patients can lose the affected limb within the first six months after diagnosis of critical ischemia of intermittent claudication. In addition, twice as often as other patients diagnosed with atherosclerosis, they experience various exacerbations of the pathological condition of the blood vessels.

Reasons

It is believed that the main cause of intermittent claudication is atherosclerotic vascular disease, however, there are other causes:

• Traumatic effects on the legs;
• Transferred;
• Deposition of toxins in the vessels of the legs;
• Gout;
• Frostbite.

The above-mentioned sources of PC disease account for about ten percent of the provoking factors of the total number of calls to medical help.

Vascular atherosclerosis, like all diseases associated with disorders of the cardiovascular system, preferentially affects the male body. With the weakening of hormonal protection, that is, by the age of 65, the susceptibility to this pathology increases in women, but the percentage of this statistic will still be approximately 70:30 in the male-female ratio.

The first thing people pay attention to, although this is not the initial stage of the disease, is pain when walking at any intensity. Even before this main sign of intermittent claudication, the attention of patients is attracted by minor phenomena of discomfort, such as fatigue of the legs, partial loss of sensitivity of the skin of the calves and ankles, “goose bumps”.

But the real concern begins to be caused by the inability to walk without pain, even relatively short distances. This is due to the fact that the lack of arterial blood is approaching a critical level and the vessels of the legs begin to starve.

The patient covers a certain distance quite tolerably, however, if the person does not take a break after the onset of fatigue, fatigue quickly gives way to pain and uneven gait (limping). In this case, the patient needs to sit down with his legs (or one leg) stretched out, otherwise the discomfort will be replaced by burning pain.

Over time, depending on how quickly the disease develops, the symptoms of intermittent claudication will worsen with the following symptoms:

• Possible appearance;
• The temperature of the legs will become significantly lower relative to the general body temperature;
• An increasing pallor of the skin will be noted;
• in the area of ​​the foot it can no longer be felt.

At approximately the level of damage to the legs when trophic ulcers are discovered by the patient, walking more than 150 meters will border on unbearable suffering for him. At this stage, frequent pauses and rest no longer play any role - the pain takes on the appearance of unabating.

Diagnostics

Diagnosis of intermittent claudication does not take long and rarely needs confirmation. This is especially true already at those stages when palpating the pulse in the foot is almost impossible, and the appearance of the diseased limb differs significantly from the healthy one in appearance. All these features of intermittent claudication speak for themselves.

Sometimes, to get an overall picture and to identify the stage at which the disease is located, a set of diagnostic measures is required, including:

• in the ankle and shoulder areas (they should be of equal importance);
• Antiographic study;

Treatment of intermittent claudication, with full confirmation of the diagnosis, is carried out mainly within the framework of drug support, although in special cases, surgery is prescribed.

Treatment

Even an operation to restore normal blood flow does not cancel subsequent therapeutic measures. Lameness treatment prescribed after rehabilitation should accompany the patient throughout his life.

Physical activity therapy:

• Most medication measures will lose their significance if they do not have support in the form of constant, dosing physical stress. The most accessible means of doing this is walking. You need to walk for at least half an hour every day, but if this time on your feet borders on severe pain, it is reduced to 10, 15 minutes and then gradually increases.
• Complete smoking cessation is very important during the treatment period.

Conservative treatment:

• Treatment with medications is designed to normalize lost functions, correct lipid metabolism, regulate blood pressure and accelerate metabolic processes in the body.
• To normalize the functioning of the lipid spectrum, medications are prescribed. They should be used in the treatment of intermittent claudication at any stage;
• To control blood sugar levels (if there is no history of diabetes), you need to monitor the glucometer readings and adhere to a diet that excludes simple carbohydrates;
• If the normal pressure is above 140/90 mm Hg. Art., in the absence of pronounced heart diseases (diabetes,), then treatment is prescribed with medications such as lisinopril and perindopril, which prevent the occurrence of strokes and heart attacks;
• Responsible for sulodexide, recommended for intravenous administration

Operation

The technique of performing the surgical procedure can be;

• Minimally invasive;
• Amputation;

Amputation, as the most drastic method, is carried out only in cases of extreme neglect of the condition. Minimally invasive methods include: thrombectomy, endarterectomy, and angioplasty. The latter is sometimes complicated by the introduction of a stent.

Bypass surgery is indicated when there is a possibility of saving the leg from amputation if the use of other methods is inappropriate. In this case, both the patient’s own vessel and a flexible prosthesis are used as a shunt.

Surgical intervention is justified when intermittent claudication no longer responds to drug effects, and the patient’s quality of life decreases progressively.