Perspective TE. Davenport, PT, DPT, OCS, is Assistant Professor, Department of Physical Therapy, Thomas J. Long School of Pharmacy and Health Sciences, University ofthe Pacific, 3601 Pacific Ave, Stockton, CA 95211 (USA). Address all corre- spondence ta Or Davenport al Idavenportepacificedu. SR, Stevens, MA, Is Executive OF rector, Pacific Fatigue Laboratory, Department of Sport Sciences, Univesity ofthe Pacific MJ. VanNess, PhD, Is Associate Professor, Department of Sport Sciences, University ofthe Pactc ‘A. Snell, PHD, is Professor and Chair, Department of Sport Sci- ences, University ofthe Pacific T. ltl, PT, EdD, DMT, FAAOMPT, Is Assodate Professor, Department of Physleal Therapy, ‘Thomas J. Long School of Phar- macy and Health Sciences, Univer= sity of the Pacific, [Davenport TE, Stevens SR, VanNoss ML, etal. Conceptual mode! for physical therapist management of ‘chronic fatigue syndrometmyalgic ‘encephalomyelits. Phys Ther. 2010; '90:602-614) (© 2010 American Physical Therapy Assocation Post a Rapid Response oF find The Bottom Line: we ptfourna.org Conceptual Model for Physical Therapist Management of Chronic Fatigue Syndrome/ Myalgic Encephalomyelitis ‘Todd E. Davenport, Staci R. Stevens, Mark J. VanNess, Christopher R. Snell, Tamara Little Fatigue is one of the most common reasons why people consult health care provid- crs. Chronic fatigue syndrome/myalaic encephalomyeltis (CFS/ME) is one cause of inically debilitating fatigue. The underdiagnosis of CPS/ME, along with the spectrum ‘of symptoms that represent multiple reasons for entry into physical therapy settings, places physical therapists in a unique position to identify this health condition and rect its appropriate management. The diagnosis and clinieal correlates of CS/ME are becoming better understood, although the optimal clinical management of this condition remains controversial. The 4 aims of this perspective article are: (1) to summarize the is of CFS/ME with the goal of promoting the optimal recog- nition of this condition by physical therapists; (2) to discuss aerobic system and cognitive deficits that may lead to the clinical presentation of CFS/ME; (3) to review the evidence for graded exercise with the goal of addressing limitations in body structures and functions, activity, and participation in people with CFS/ME; and G40 presenta conceptual model for the clinical management of CFS/ME by physical therapists 602 M Physical Therapy Volume 90. Number 4 April 2010 1 wioy pepeouNeG uo th UePICw a a y g 2202 seqwoides #1 uo se8n | ownerManagement of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Presse ee css, hormona disorder and ince ns and tivated with poorer hea outcomes and high deere ot recidivism inte gener popu ont Most heath conions that arto devout eace, and Ors tae stb to spec patos hat may respond oe {hy woranousfome often enton ment Toner some people nay th remain nce Recent studies have begun to prove the collective understanding, of chronic fatigue syndrome/myalgic ‘encephalomyelitis (CFS/ME) as one ‘cause of clinically debilitating fatigue. Chronic fatigue syndrome/myalgic cencephalomyelitis affects 1 to 4 mil. ion adults in the United States,9 with women accounting for up to 75% of ccases.' Prevalence in the United States ranges from 230 to 420 per 100,000 adults? with the mean age at onset ranging from 29 to 35 years." Up to 85% of CFS/ME cases may be undiagnosed, and the actual preva- Ience of CFS/ME may be 6 to 10 ‘times higher than presently under. stood,® suggesting that a vast major- ity of CFS/ME cases are untreated and unaccounted for by epidemio- logical studies.” The large number of, ‘cases that may remain undiagnosed places premium on the recognition and management of CFS/ME and CFS/MElike conditions by physical therapists, ‘The purpose of this analysis was ‘fold. First, we summarize the diag- nosis of CFS/ME with the goal of pro moting the optimal recognition of this condition by physical therapists, Second, we discuss aerobic system and cognitive deficits that may lead to the clinical presentation of CFS/ ME. Third, we review the evidence for graded exercise with the goal of addressing limitations in body struc- tures and functions, activity, and par ticipation in people with CFS/ME. We conclude by presenting con- cceptual model, based on current sci entific evidence, for the clinical ma agement of CFS/ME by physical therapists, Characteristic Clinical Findings of CFS/ME That Guide Diagnosis Chronic fatigue syndrome/myatgic encephalomyelts is not a new health condition. The neurologists Beard and Goetz? were among the first to characterize a health condition that they called newrasthenia in the lac ter half of the 19th century; neuras thenia was described as a combina tion of fatigue, anxiety, headache, impotence, and neuralgia. Inthe early 20th century, Gilliam" docu mented an outbreak in Los Angeles, California, of a health condition that resembled poliomyelitis and that he called atypical poliomyelitis. Vari ous outbreaks of health conditions resembling CFS/ME were recorded in the United States and elsewhere throughout the 20th century." Each of these outbreaks was described by its own regionspeciic and some- times pejorative terminology. The term epidemic myatgie encepbato- iyelitis was coined as a result of a Royal Society of Medicine sympo- sium in 1978.12 This development twas notable because it represented the medical community's first-ac: knowledgement that CFS/ME was a distinct disease process rather than a bchavioral disorder, Chronic fatigue syndrome/myalgic “encephalomycti tis reached the popular conscious nes in the United States after an out break in the RenoLake Tahoe, Nevada, region in the 1980s. Re. search involving this outbreak re sulted in the name chronic fatigue syndrome.!* This term is considered to be most representative of the cli ical features of the health condition by many clinicians and researc! rs," although the term myalgic e cephatomyelitis continues to find common usage in the clinical com- munity secondary to popular sup- port from people with CFS/ME.'9 ‘Therefore, both terms were adopted for the purposes of this analysis. Various attempts to characterize CFS/ME were made in the late 20th and early 21st centuries.!* The most current and common case definition was created when the Centers for Disease Control and Prevention con- vened an international working group in 1994, To meet the case def inition criteria for CFS/ME, an ine vidual must report persistent or re~ lapsing, debilitating fatigue for which a preexisting illness. or psychiatric comorbidity cannot be found as an explanation, According to the 1994 case definition of Fukuda and col. leagues, to meet the criteria for (CFS/ME, an individual must have per- sistent or relapsing fatigue for greater than 6 months (Fig. 1). The fatigue of CFS/ME may be character- ized by either gradual or sudden on- sets, and it may be progressive or relapsing and remitting during the course of the condition. In addition to the specific crite for fatigue, CFS/ME is characterized by a broad spectrum of nonspecific physical examination findings. There- fore, to meet the case definition cri- teria for the diagnosis of CFS/ME, an individual concurrently must exhibit roan Sees Ertan et ei) + Audio Abstracts Podcast This article was published ahead of print on February 25, 2010, at pljournal.apta.org. April 2010 Volume 90 Number 4 Physical Therapy 603 3 é 5 gManagement of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Relative Magnitude Figure 1. Pacing Selimanagement Exercise Time ‘Conceptual model for clinical management of people with chronic fatigue syndrome/myalgic encephalomyeltis (CFS/ME). (A) The first presentation of symptoms in people with CFS/ME hypothetically occurs when the intensity of physical activity (solid line) exceeds the tolerance for physical activity (bars). (B) In response to symptoms, people with CFS/ME adapt their behaviors by either activity and symptom avoidance (dashed line) or activity and symptom fluctuation (dotted line). (C) The initiation of a pacing self-management program is hypothesized to stabilize activity levels within the tolerance for physica activity, such as that inlcated by heart rate biofeedback below the anaerobic threshold. (D) Alter symptoms and function are stabilized, progression of anaerobic exercise to graded aerobic ‘exercise may be used to increase tolerance for physical activity at least 4 additional symptoms, such as postexertion malaise (PEM) for at Teast 24 hours after exercise, im- aired memory or concentration, nonrefteshing sleep, muscle pain, pain in multiple joints without signs of inflammation, headaches of a new type or severity, sore throat, and ten- der cervical or axillary Iymph nodes. Secondary symptoms of joint pain and headaches may facilitate entry into physical therapy settings for people with CRYME. Perhaps the ‘most prominent feature of CFS/ME is DEM, which is usually defined as a general feeling of discomfort oF un- ‘ease after even minimal physical ac- tivity." Indeed, among the various health conditions that are associated ‘with fatigue, increased PEM that can alter daily activities for up to 2 weeks!” appears to be unique to CS/ME1 Other diagnostic systems that have been described in the literature are the Oxford criteria2” and the Canadian Consensus Document. The Cana dian Consensus Document case defini tion for CRS/ME# (Tab. 1) may be use- ful because it displays. significantly greater power than the criteria estab- lished by Fukuda and colleagues!# to differentiate people with CFS/ME from people with fitigue related to psychiatric health conditions. Across all definitions, it is important to em- phasize that the fatigue of CFS/ME must be unexplained by another so- ‘matic or psychiatric health condition, making CFS/ME a diagnosis of exclu sion. Given the prominence of pain and fatigue in the symptomatology of CRS/ME,"°2* physical therapists may be among the first health care provid: crs to recognize this health condition and direct appropriate management. Aerobic System and Cognitive Changes Contributing to the Clinical Presentation of CFS/ME A growing body of research confirms the presence of oxidative impair ments in CFS/ME. Our research group** and others! have identified Glinical evidence of oxidative meta- bolic impairments during graded exercise tests, VanNess and. cok leagues identified a range of oxi- dative impairments during graded exercise testing in participants meet- ing the case definition criteria of Fukuda and colleagtes" for CFS/ME. Although the maximum oxygen con- sumption (Vo,max) for participants in that study?" ranged from 36% to 76% of the Vo,max predicted for matched sedentary participants, in only half of the participants. were 608 ml Physical Therapy Volume 90. Number 4 April 2010 1 wioy pepeouNeG uo th UePICw a a y g 2202 seqwoides #1 uo se8n | ownerManagement of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis on Criteria for Identification of Chronie Fatigue Syndrome/Myalgic Encephalopathy + Coes a substantia redition | ‘occupations, personal, soda, or cational cts + Unraived th cst 1 Other medical or + imped memory ot «+ Nonrefreshing sep Muscle pain + Pan in matpe join without signs | ppchiatic conditions | + Headaches of now ached ‘ype or seventy + Sore throat 1 Tender ceria or allay ph nodes (Care Definition of Fulda et al ontord rr Care Definition of Canadian Consensus Document?! Requires the ‘of Severe Disabling Presence of Also Requires 4 or | Fatigue as the Main ‘Also Requires at Least 1 Profound Fatigue, ‘More of the symptom and Further | Requires the Presence of | Symptom From 2 of the Defined as Follows: | Following Features: | Defined as Follows: | the Following Features:_| Following Categories! * Symptom duration of | » Postexertion malae | » Symptom duration of | Symptom duration of | * Autonomic manfxtations mo losing 24m mo mo for adults and (9, orbstate nokeance, | = atlets both physical and rental fnetons| + Symptoms are present 250% ofthe te Bisel or mental fatigue 1s | « Defiate onset apd not | that substantaly reduces song acti eels + Other medical or + Postexertion malaise Poctiatic conditions | + other medial or cided psychi cndtions fxched 3 mo for eidren + New onset of unoxpsined, pesstet, or ecurent Iighcheadednes extreme pallor, noes, tabe Dowel syndem, unary frequency, badder ‘sunaton, plptatons ‘th or witht care nly, exertions yen) + Netroenderne rmantesatons (9, los ot thermostat stably, Intolerance of extremes of teat and cold, marked weight change, ku of ‘septa, esr of Symons ith ses) + Immune manestatons (6g, tender mph nodes recurent soe toa ‘ecuent fle symptoms; ‘ental malas; nw Sent to fod, medications, chemical) American Medical Association guide- lines for moderate to severe aerobic impairments met. This finding sug: gests that a spectrum of aerobic en ‘ergy system impairments may be re- sponsible for the reduced tolerance ‘of physical activity observed in peo- ple with CFS/ME despite their com- mon medical diagnosis Evidence suggests that disruption of the aerobic energy system may be associated with a combination of ge- netic, cellular, and systemic mete bolic deficits.2°-2" Investigators also have found evidence at the cellular level of mitochondrial dysfuncti and impaired energy metabolism oxidative damage (o mitochondrial deoxyribonucleic acid, and poor recovery of adenosine triphosphate after exercise, which may be re- sponsible for the observed deficits in repeated graded exercise test perfor mances, These cellular and systemic npairments in the aerobic energy system lead fo a reduced functional capacity that limits an individual's ability to sustain and repeat func tional activities. Aerobic system im- pairments appear (0 be related to ‘maladaptive sympathetic autonomic responses,*? perhaps in response to a triggering event, such as an injury orillness, in people with an apparent genetic predisposition.’ Over time, these maladaptive responses are sus pected of causing dysregulation of the normal hypothalamuspituitary axis and sympathet sponses? and aan overall reduction in tolerance for physical effort.%* Auto: nomic dysregulation is thought to be responsible for the orthostatic intot erince and abnormal heart rate GR) responses to exercise” exhib- ited by some people with CFS/ME. \utonomic fe In addition to aerobic system impair- ments, people with CFS/ME exhibit centrally mediated disturbances in attention, perception, and affect.*> On avetage, people with CFS/ME rate their effort during physical tasks significantly higher than do people who are healthy; this factor ma lead (0 an overall decrease in maxi- mal exertion. Paradoxically, how- ever, anecdotal observations. from various sources***? indicate that be- havioral responses to symptom exac> erbations in people with CFS/ME range from the maintenance ofa sed entary lifestyle to abrupt increases activity during periods of symptom remission that serve to exacerbate symptoms (Fig. 1). Patient-reported mental fatigue! and maladaptive overactivity are cognitive and psy chological correlates of morbidity in people with CFS/ME, Some authors have suggested that comorbid kine siophobia'! or depressive symptoms!? also may be responsible for these disablements in CFS/ME; however, these findings are inconsistent," and functional deficits remain even after these variables are controlled for."8 April 2010 Volume 90 Number 4 Physical Therapy 605 3 é 5 gManagement of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Arguably, the cognitive effects of CES/ME may serve as the greatest barrier to optimal research, diagno- sis, and effective management of this health condition. Early attempts to ‘characterize CFS/ME involved the as. sumption that it was primarily a psy- chiatric disorder.? Our experience suggests that some clinicians. still seem to view CFS/ME through this lens; this belief could be a source of stigma for people with CFS/ME, Clinical Outcomes Associated With Graded Exercise in People With CFS/ME Graded aerobic exercise as an inter: vention for people with CFS/ME has been the focus of several studies, ‘even though, as a general rule, de conditioning, may not play a role in clsablements secondary t0 C To assess the clinical effect cercise in people with conducted a literature search with the scarch terms “exercise” AND “chronic fatigue syndrome” OR “my~ algic encephalomycitis” in the Cocky rane Database of Systematic Reviews and the EMBASE, ERIC, MEDLINE, PEDro, Ovid Healthstar, Ovid Global Health, and PSYCHINFO databases ‘The initial search yielded 694 dis: tinct citations. The abstracts ofthese citations were scanned for refer fences to treatment responses in peo- ple with chronic fatigue, yielding 94 Citations. These citations were then analyzed for observational, compari son, or randomized studies that rc ported on the effects of an exercise tervention in adults with CRS/ME according to existing diagnostic eri teria, yiekling 9 citations for consid ration in this analysis. These studies are summarized in Table 2 Body structure and function deficits (eg, fatigue, muscle strength [force- generating capacity], cognitive pro- ‘cessing, maximal and submaximal ‘exercise test variables) and personal factors (eg, mood) in people with CFS/ME appeared to improve consi tently with graded aerobic exercise (Fab. 2). Fulcher and White"* found a Significantly lower mean HR du. ng treadmill testing in participants in a graded exercise group than in participants in a flexibility exerc group, as well as significantly lower ratings of perceived exertion (RPEs) in participants who received graded exercise than in participants who re- ceived flexibility exercise. Physiologic improvements were maintained at the month follow-up in the graded exercise group. MossMorris et al reported significant improvements in physical, mental, and total fatigue in the exercise group compared with the control group. Pardaens and col leagues identified si provements in duration, peak power Gbility to perform work over time), and peak respiratory exchange ratio, as well asa significant improvement in isokinetic hamstring muscle strength, response to a graded exercise in- behavioral therapy. Wearden and cok Jeagues* found significantly greater functional work capacity in people who received graded exercise than in people in comparison groups, but fatigue ratings did not differ among the groups. Wallman et al"? noted significant improvements in resting HR, resting blood pressure, power, peak oxygen consumption, respira. tory exchange ratio, and net blood lactate production in participants who received graded exercise com- pared with participants who te. ceived flexibility and relaxation ex ercises. Significant improvements also were documented in depression anxiety, physical fatigue, and mental fatigue in participants who received ‘graded exercise compared with par: ticipants who received flexibility and relaxation exercises. Modified Stroop word color identification test performance was significantly better icipants who received graded exercise. Despite the consistent im- provements in body structure and function deficits in response to graded exercise across studies, Pardaens and colleagues” reported that these im: provements were weakly correlated with of were not significantly corre lated with functional improvements. Although there seemed to be a qual. itative trend toward improvement, observations of qualitative and q tative improvements at the levels of activity and participation were more mixed (Tab, 2). Fulcher and White? and Pardaens et al” found that scores fon subscales of the Medical Out. comes Study 36tem Health Survey Questionnaire (SF-36) were signifi- cantly higher in participants who re- ceived graded exercise than in par ticipants who received a comparison intervention, Powell and colleagues identified significantly higher SF-36 physical functioning subscale scores in the intervention groups than in the control group. At the 2year follow up”, all groups maintained significant improvements, and no significant di ferences persisted among the groups. ‘Moss-Morris etal documented no sig nificant differences in SF36 physical functioning subscale scores among the groups, and Wallman et al did not identify significant changes in tivity. It is notable that many studies conducted to examine the effective. ness of gricled exercise had high drop- ‘out rates, suggesting the presence of a subpopulation for whom graded exer. cise interventions may be ineffective at the levels of body structure and funetion, activity, and participation. Additional research seems to be nec- essary to clarify the effects of different exercise volumes on activity and pa ticipation in people with CFS/ME A major challenge of research and clinical practice related to exercise prescription for people with CES/ME is the phenomenon that increased self-reported activity levels during i tervention may be a direct result of the exercise program at the expense 606 mM Physical Therapy Volume 90. Number 4 April 2010 3 é 5 gManagement of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Table 2. Studies of Comparative Effectiveness Involving Graded Aerobic Exercise in People With Chronic Fatigue Syndrome/Myalgic Encephalomyelitis” study Intervention Program Participants ‘Outcome Measures ‘Main study Findings Pardaens et a” | Evite the eet of m0 | 116 paripans meeting |» S36 > Serica improvement a rogram of cearitve behavioral | theres proposed |» Symptom Checls-20, S36 uta scores cept Itewenton(conssing of graup | By Fukuda etal | Coutal Atuibaton ust ‘rotiona imation dscussions relation and 4m ofthe amplehad | + Saeticay Seale + Soputcant improvement in treating exerci, and ‘an addtional, 1 Graded execs esting on |” Causal atbution List psyehatic and medial Sdagnoss of Statenary bic with onphyscal subscale core eorftatons, a ned) ftromjalga Anaya of exped gases | Sepia improvements embined with graded eect on exec apc eases, Intervention was proved nh {tester sexo te pe eck forthe et month and oe per ‘weaker the ext 5 mo. + Toksnete dynamamety of the ight and et aquadeceps and hamstring tusces dtaion, peak pomes, and pesto exchange ratio Irth graded eee text, Slouteansmprowement it iota hamsting uc ‘tenth ogre was nt comet ‘who as weakly cole Tah changes in quay ie Fulcher and Tested the fet af a 12 graded ‘seobic eerie program wha home execs component roid woe sesons on elk mye of Suge in be complete at ea 5 th ital ssn of 5-15 min aa Intensy of 4055 of Vo.mas. The dhly prescription was creased ‘oman th the sje 0 ‘masa of 30 mil ane 60% of Voumax. Conta lennon Comite of relaeation and fesity execs. {66 partcpas meting ‘he Odd rea (¢9 women) * teil glbalimpeeson ot change + Graded tread waking test ath arabs of expt ones + Prceued exertion on sxcrche testing + omatte quseicops muscle testing + 5h36 1 Val analog sae for Pisa mental, and total fatigue Signcany more partpants inthe exec group (5159) than in the conte ou. (27%) rated thoes uch ble” 0 “wry muh beter” Signa lower mean het tao dong trend testing the aed sere group than inthe exbilty exer group Sipitcanty lower rains of perce exertion inthe {jaded execs grup than the leity exer group 5-36 ta, phys ‘unetoning aed general health subscale scores were Sinan higher in he ‘faded exes goup than in the ledbity exer group Posto improwerents ‘were mahtaned at mo Tollowsup in the graded ‘eure eu uate, ager proportions ot prtpans in Ue faded ‘eerse group than in the ‘enbity exercise group rated theses at Ty flows a Improved, were woking ot studying at least parte, and ‘consdored theres egy ‘Mow Mow a Trvetignted the fective and nechankone of change atte {o goed exercise. rtervenion \goup parted in 12 wheat (Fade walking, staring a 40% Soe of Voy, 45 Umeivke Specie intent vs set at a vel Unley to exacerbate symptoms, ‘tdetrinedncallaboration ‘ad the sujet. Exetel dation ras inerease 3-5 mini, th Fina gol of 30min ane 70% of Vo,max. Conta group reeves sStandaced medial fre an sce, 1 portcpms meeting ‘the itera proposed by Fuk eal + Teva glbal impeeson change + Sh36 1 tem fatigue aqusstionaie + Croded tread exerci testing + Berend exertion on rere tating + Mes Pereptons Questonnate-Revsed + Hines Management Questionnaire Sigcanty more partpants| inthe graded exacie gfoup (4886) than the conta ‘foup 21%) rated themsees SSmuch beter o "ry uch Teter” the ed of 2 0k ane at the fll Signcant improvements in ysl, mental and total {augue inthe execle gru compared with te conta ‘reup No sigitcant erences teen groups in S36 phys fonetionng sabe (Conte) April 2010 Volume 90 Number 4 Physical Therapy 607 sin wow papeowuNog uo th Pe a a y g 2202 soquwaidas #1 uo 19sn | euiner iManagement of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Table 2. Continued study Intervention Program Participants ‘Outcome Measures ‘Main study Findings Powell al | Documented the ect of paycho- | 148 partkipats mesting | + SF36 + Significantly more participants ‘slucaona tereton to ‘he Oxford citer | » Hoyptal Ansety and in the mervention groups lencourge graded oxerse a by Depression G1AD) Seale | (84%) than i the contro fol. Ierventon groups item seep problem ‘10up (12%) ated themselves receved madcl ase and questionnae 23 “uch beter” oe “very than evidence-based explanations + Indvidial global impression | much beter of symptoms to encourage ot enange + Sgnicanty higher F-36 ‘graded activity. Interventions physical functioning subscale ined minima intervention ore inthe intervention (@nperon sees), tephone (groups than in the conto Intention (mir ‘soup Intervention seven 30.20 + Signy tower aque telephone contac), and Sores inthe intervention ‘maxinum iterertion ‘groups than in the conta (rium interverion + seven ‘soup ‘rh impeson contacts). Cond group Fes standardized adil cae condsing of medial assesment adie, and reformation bookie that ‘planed symptoms to encourage graded at. Powel et ab | Measired the eect ofa paycho- | 114 parcpants meeting [+ S36 Al groups maintained ‘sestiona nterention the Odor eteaa and | © HAD Sale Significant improverents rcourge graded exercise at 2y | _papating nthe | item sip problem ‘compared with baseline folowp.Itanenton groups” | orighal ul of Powel |” questonnave measurement, and no received meal assent and then evidence-based explanations of symptoms to encourage ‘gad activity. erverions Inetded minimum intervention Girpen me hoe Intention + seven 30-0 telephone contac) and ‘maximum stevention (eimai intention + seven “rh inperson contacts). Corte group Feed Standaraed medial care, condsing of redial asiesment adie, and tveformation book that explained symptoms to reourage graded at Snacant ferences a pyseal functioning and Fatgue scores parted mong the groups Stniicant improvements in physical hnetioning ane Fatgue scores over tne in ‘contol qroup partpants tao were alowed t0 cos ‘ve ino treatment groups siter the conekason othe Fist sty period Woliman eta Tested the fective ofa Tonk rogram of graded execs wt pacing on physiological, Pythologal, and cognitive felon. ttervanton group pateipated in 5-15 mi of exec for lige muscles, Intesty was based onthe mean eat ate ring eer esting, Parpants were stcte to exerci vey ether day, unless they hada symptom reps. that case, subsequent exercise sense were redced to rth ssssd bythe patpants to be ‘manageable. Contol goup received relaxation ane Hex rect 61 participants meeting the tera proposed by Fulda ota + Submaximl bey cexercle teting with analysis of expred gases bad periodic blood saming| eccved erin on exer testing + Older Act Exerc Status Inventory 1 1tem fatigue ating sale SHAD scale + Modis! troop word color ‘denteaton ext Significant improvements resting heat fate, resting bod presaite, power, ogi, espratey exchange rao, and net bod lactate prodoction in patcpans| to rceve pale exercise Compared with participants ta received ebay and Felmation exercies Siniicant improvements in ‘epresion, aay, ysl faligue, and rental fatigue a partipants whe recived ‘rade exerci compared vith partiipans wie receied leit nd Felinatlon exercies (Contract) 608 mI Physical Therapy Volume 90. Number 4 April 2010 fadnoo'dne owopece;rsdnw wou pepeojunod 2202 soqwiaidas +1 uo s98n | ewer yeusionUN Ka sezsBez/e0RrHI06/O.NNManagement of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Table 2. Continued study Intervention Program | Participants ‘Outcome Measures ‘Main study Findings ‘Waliman et * Activity levels among grows Contes) were not igolfeanty erent + Sgaieane improvements in moa stoop word clot ‘dentcation text, perormance in patipans to received graded enerse Compared with patipants ‘en receive lb and {elation exercises status, physical work Capacity, and mood Partipants were randomized among 4 ‘groups Muosetine + placebo + graded toni, uoretin + 20mg. ‘ceived foxetine whe recehed graced ‘or exceeding 75% of ‘apable butt not cave specie ‘sessed the act ofa 26- ‘wk regen of fuoxetine and graded exercise on faigue, general heats ‘taded exetese uoxetine ‘graded exercise placebo, and fvoxetine placebo + ‘faded excl placebo. ‘he fhoxetine dose was ipa who placebo recehed an inert Substance Parcpants fxercie were encouraged toexercte 3 timedink for 20 minat an intensity at Yuma. Partipant who received graded exercie placebo were instructed to fexercie whan they felt n=156 meeting Oxord| + HAD Scale 7 Graded exec eting wih ana of expres tem fatigue rating sale + Medial Outcomes Survey + Signticant improvement in smaod in pariapants who received Huoxatine at 12 We «+ Futons wor capac was Significantly increased at week 12 anc week 26 the exeee groups «Nether intervention wat Slonticanty associated uth edced fatigue ings, although a qualitative trend toward improvement the excrete groups was noted + Drepouns were sigicanty mote quent inthe extese ‘groups than inthe onererce groups © ll sods were controlled sue, ones otherwie noted, One obwevatonal uy" war excided because the description ofthe exrce intervention ‘was incomplete. Two contrled suche: were eacaded because the eters or nchason were imcear.Sf-6-Meceol Oueomes Study 36-em Health Survey Questonnat, Voymax=maximum oxygen consumption "Observational studs, of actual increases in daily activities. For example, Black and colleagues*! studied the effectiveness of advice to \crease physical activity on daily physical activity, fatigue, mood, and pain in participants who were diag nosed with CFS/ME by a physician and in matched sedentary control partici pants. Participants were requested to increase their physical activity during the first 2 weeks of the program in an incremental manner, Intervention in- cluded a Gweek walking program consisting of an inerease in daily walk ing time to a total of 30% more than pretreatment levels. The authors doc. "umented a significant increase in phys- ical activity in participants with CES ME by use of an accelerometer, lead ing to their conclusion that the inter vention was a feasible and effective ‘way to facilitate increased physical tivity in this population, However, sl reported mood became significantly worse in. participants with CFYME than in control participants overtime. Ratings of fatigue and pain, which were already significantly different be tween groups throughout the study, increased over time in participants with CPS/ME. A secondary analysis of the data revealed that participants ‘with CFS/ME could actually maintain the increase in physical activity for the first 4 to 10 days of the study, exercis ing for a mean of 23 minutes? In contrast, during the final 3 weeks of the studly, physical activity time fell t0 approximately 8 minutes per day. The April 2010 Volume 90 Number 4 Physical Therapy 609 1 wioy pepeouNeG puscc dn Loew a a y g 2202 seqwoides #1 uo se8n | ownerManagement of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Decreased Risk for ‘Aggravation of Funetional impairment Increased Risk for Aggravation of Functional Impairment ee Le Relative Contributions of Metabolic Pathways 2min ‘S min Activity Duration Figure 2. Hypothetical relationship among duration pathways, and functional impairments in ‘of functional activity, metabolic energy people with chronic fatigue syndromey Imyalgic encephalomyelitis (CFS/ME). The creatine phosphate-adenosine triphosphate immediate (teal line) and anaerobic short-term (redline) energy systems predominate ‘during the fist 2 minutes of activity (dashed blackline). Activities longer than 2 minutes in duration are characterized by a rapid decrease in the contributions of these short- term energy systems and an exponential increase in the contiibution of the aerobic long-term energy system (blue line) It has been hypothesized that activities longer than 2 minutes in duration aggravate symptoms and functional deficits in people with CCFS/ME because they have aerobic system impairments. decrease in physical activity appeared tobe coincident with the timing of the ‘worsening mood and increased symp- toms. It is possible that a similar trend has been observed in studies docu- menting significant increases in fune- tioning in association with graded ex- cercise in people with CFS/ME, but the ‘use of quantitative measurements to document daily physical activity and secondary analyses of existing studies Model for Clinical Management of CFS/ME ‘The goal for the clinical management of CFS/ME should include an individ val’s return to an optimal level of function, Disablement attributable to CFS/ME results from maladaptive physiologic responses that Iead to overloaded body systems (Fig. 1. This assertion is consistent with the predictions of physical stress theo: 8 which suggests that changes in relative stress in tissues result in pre- dictable tissue adaptations ringing from decreased stress toler maintenance to increased stress tol ernce. Therefore, consistent with physical stress theory>* and other models for the clinical management of CFS/ME,*° optimal functioning for people with CRS/ME first de- pends on the achievement of a level Of tissue stress that corresponds t0 symptom and functional m nance, This objective will require the implementation of strategies that focus on pacing selfmanagement to promote energy conservation and rest. After maintenance is achieved, physical stress must be provided in a ‘manner that results in improved stress tolerance. As mentioned before, ear lier models encouraged the use of graded exercise to achieve increased tissue stress tolerance. ° However, our experience has been that an ap- proach beginning with therapeutic activities and exercises that avoid ex- cessive use of the impaired aerobic system also is promising because it may mitigate the subsequent fune tional impairments associated with PEM. This approach involves short duration exercises that are con pleted at intensities below an esti mated anaerobic threshold (AT). Alter anaerobic activities are initi ated without symptom exacerbation, progression to graded aerobic exer: cise can be undertaken. Finally, the chronic and episodic nature of this health condition’ requires physical therapists to ensure that people with (CFS/ME demonstrate adequate devel ‘opment of the cognitive and physical skills necessary to facilitate Tong. term symptom selfmanagement and optimal functioning inte- Pacing Self-Management: Criteria and Strategies Strategies to promote energy conser- vation appear to be important in peo- ple with CFS/ME. To date, recommen: dations for pacing selfmanagement in people with CPS/ME have been made fon the basis of symptom acuity and irvitability.°5" Although these criteria seem to be intuitive, they may fail to account for the rapid changes in fanc- tion that are characteristic of CRS/ ME. An impaired perception of effort in people with CFS/ME may interfere with the optimal maintenance of symptomfree activity levels if pac 610. Ml Physical Therapy Volume 90. Number 4 April 2010 nroo‘dho ope; 3 e 2202 seqwoides #1 uo se8n | ownerManagement of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis selfimanagement criteria that are based solely on symptomatology are used ‘Also, the ability 10 predict when ac tivities might cause a flare-up of symp- ‘toms and functional deficits would be most helpful, The metabolic impair ments observed in people with CFS ME suggest the need to limit the tensity of activity to avoid exces. sive use of the aerobic energy sys tem (Fig, 2). Therefore, we suggest that AT may be a critical objective limit for ensuring that physical ac- tivity is maintained at an appropriate level to facilitate optimal pacing selfmanagement. ‘The use of criteria based on HR bio- feedback for pacing seltmanagement may be helpful in people with CFS/ ME.%! We assert that HR biofeedback should be used to ensure that activ. ities are conducted at intensities be- low the AT. The gold standard for hing the HR at the AT is a graded exercise test with periodic blood sampling. However, even in «clinical settings in which graded ex- ercise and blood sampling proce- dures are prohibitive in terms of ‘cost, time, or expertise, the need 10 index activity pacing recommenda tions (0 quantitative data. remains. ‘Therefore, the HR at the AT may be estimated indirectly. from Vo,max measurements obtained during sub- maximal exercise testing; tively, the HR corresponding to RPEs ‘of 13 (0 15 during submaximal exer cise testing may be used. Clinicians should bear in mind that although submaximal exercise testing demon- strates good. discriminative validity for people with CFS/ME versus peo- ple without CFS/ME,> such testing also demonstrates high withinsubject variability.% Frequent reassessment will be necessary to maintain conti- dence in the AT estimates obtained from submaximal testing, In untrained people, the AT has been approxi mated at 55% Voumax.” Thus, we suggest that clinicians may approxi mate the HR at the AT by calculating 595% of the HR at the Voymax as a starting point, although specific es tablishment of the HR at the AT in this population requires additional research, We suggest that people's RPEs dur- may be used to approximate the threshold for pacing selfmanagement, in which ratings below 13 to 15 rep: ity at an intensity below the AT.* Although exercise testing important clinical tool for guid ing the clinical management of CFS/ ME, we emphasize that it should be conducted with extra care second: ary to the risk for orthostatic impair- ‘ments and the high likelihood of symptom exacerbation, Extra care cludes adequate individual educs- tion regarding expected outcomes, with the goal of achieving appropri fate consent for testing, as well as close symptom and physiologic mon- itoring to determine the need for test cessation or modification, In line with earlier models for the clinical management of CFS/ME,* the importance of energy conser tion in reducing symptom exacerba- ‘ion and promoting optimal function- ing in people with CFS/ME indicates, that pacing. selfmanagement_strate- fies should be provided in the con- text of a comprehensive psycho: educational program. The 5 A's construct, originally proposed by the Canadian Task Force on Preventive Health Care," has been. applied to individual education 2s part of clini | management programs for other chronic health conditions.» The com: ponents of the 5 A’s construct®*— sess, advise, agree, assist, and ar range—also may be applied {© peo- ple with CFS/ME. This construct contains a leaming needs assessment, which includes determining the presence of behaviors that may ex: acerbate symptoms as well as the individual's preferred behavior change ‘goals, methods, and constraints. An individual's level of knowledge re- lated to CFS/ME and overall health literacy also should be ned. Advice for people with CFS/ME i cludes specific and personalized be- havior change counseling based on the learning needs assessment and centered on maintaining physical ex ertion below the HR at the AT. Peo- ple should be encouraged to wear an HR monitor for this purpose. Given the variability inherent in the use of many tests for establishing the HR at the AT, we suggest that a 10% margin below the estimated HR should be used as the critical threshold for pac ing selfmanagement to account for variability and ensure that an indivi ual’s exertion remains below the AT. ‘Therefore, the monitor's alarm should be set to sound if the HR exceeds 10% below the HR at the AT. Fre- quent breaks. including diaphra ‘matic breathing, alternate positions, and adaptive equipment should be prescribed to assist people in main: taining the target level of physical exertion. Further identification of ac- tivities that exacerbate symptoms and, as a result, necessitate attention may be aided by the use of activity logs, in which an individual with CFS/ME records the time of day, type and duration of activity, and symp- toms for systematic analysis by the individual and the physi People with CFS/ME and their a tending physical therapists should agree on the goals and methods of psychoeducational interventions for behaviors. The behavior change plan should be a collaborative effort be- tween the individual and the attend: ing physical therapist. People with CFS/ME may require assistance plementing the behavior change plan; physical therapists may provide such assistance during both clinic visits and distance consultations. Finally. arrangement of follow-up contacts allows for additional assistance and alteration of the behavior change phin and reinforces the importance of behavior change to the individual April 2010 Volume 90 Number 4 Physical Therapy ml 611 3 é 5 gManagement of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis Physical therapists are in a unique position to follow up with clinical brief counseling strategies because of their relatively frequent contact with people (compared with that of other health care providers) Exercise Interventions Exercise interventions for people with CFS/ME must be carefully cus: tomized to reflect the unique needs of each individual. The existing liter- ature mentions 2 critical issues in prescribing physical activity for peo- ple with CFS/ME. First, clear commu- nication between the individual and the physical therapist about the ef fects of the exercise program is crit- ical to avoid the perception that physi y has heen increased because of increased physical capac ity instead of the selffulfiling proph- ecy associated with starting an exer cise program. Second, aerobic system impairments associated with CFS/ME result in functional impairments that may not be amenable to training in people with CFS/ME compared with people who are sedentary. We assert that exercise interventions for people with CFS/ME require a combination of compensation and rehabilitation approaches to physical training in which training begins with activities that provide stress to the unimpaired anaerobic energy system before the impaired aerobic energy system is stressed, Therefore, we ad vocate a training approach in which initial therapeutic activities are short duration, low intensity, and directed toward specific contributing impair- ments in body structures and fune tions, Because oxidative phosphory- lation serves as the primary metabolic pa ies lasting longer than 2 minutes (Fig. 2), aerobic sys- tem impairments in people with CS/ME would seem to limit activities Jonger than 2 minutes because of the risk of developing symptoms and func- peutic activities that last less than 2 minutes and are conducted at an in- tensity consistent with an HR that is 10% below the HR at the AT or RPEs below 13 to 15. Previous studies demonstrated that reducing exerci time and intensity is effective in re- ducing symptoms of PEM in people with CRS/ME. These recommends. tions regarding duration and inten: sity are flexible: eli should be guided by the individual's immediate and latent responses to therapeutic activities to determine appropriate exercise volume, We recommend that activities ini tially consist of stretching and active- range-ofmotion (AROM) exercises to improve regionspecific strength and flexibility, because deficits in strength and flexibility may be the source of increased energy expendi ture through suboptimal movement mechanics. The specific exercises in- corporated into the flexibility and AROM program depend on the clini- Gian’s thorough examination and evaluation of potentially contributing pathomechanics. After participating in a stretching and AROM program that docs not reproduce symptoms of PEM, people may advance to strength training in which the focus. on short duration, low-intensity strengthening swith maintenance of adequate rest in- tervals, Clinicians should use caution during the creation and progression of, cause the safety and effectiveness of these interventions in people with CRS/ME require additional research. Finally, people with CFS/ME may ad- vance to shortduration, low-intensity interval training. As starting criteria, the duration of the intervals should not exceed 2 minutes, and the inten: sity should not exceed an HR that és 10% below the HR at the AT. Pro- ‘gression of interval trtining should volve increasing the number and in- tensity of intervals while maintaining tem in people with CFS/ME. Interval training should involve functional re- training whenever possible, according, to the physical therapist's evaluation of the individual's disablement. When shortduration interval training can be completed successfully, clink. cians should consider initiating short- duration aerobic interval training, which can be advanced in an incre: ‘mental manner according to people's symptoms, as described elsewhere.” Despite the importance of exercise to address physical conditioning in some people with CFS/ME, the health- related quality of life of people with CES/ME is only weakly correlated with exercise capacity measurements. This fact underlines the of multimodal treatment, including individual education and pacing self: ‘management, to address the activity and participation limitations in peo- ple with CFS/ME. Summary The prevalence of CFS/ME emph sizes the importance of the recog tion and management of CFS/ME and CRSMEtike conditions by physical therapists, The prominent features of CFS/ME inchude aerobic system ime pairment and centrally mediated dix furbances in attention, perception, andaffect. Pacing selfmanigement ci teri based on HR biofeedback may be helpful in ensuring that activities are conducted at an intensity below the AT in people with CFS/ME. The mode and intensity of exercisebased inter ‘ventions for people with CFYME mist be carefully customized to reflect the unique needs of cach individual. Fir ture studies should continue to cay the roles of pacing selfmanagement and exercise in the context of a com- prehensive clinical management pro- fm for people with CFS/MTE All authors provided concept/idea/project design. Or Davenport, Dr Snel, and Dr Little tional deficits associated with PEM. a taining range that prevents exces provided vmiting. Dr VanNess and Dr Snell ‘Therefore, we recommend. thera sive use of the impaired aerobic sys provided data collection andi analyss, fund 612. M Physical Therapy Volume 90. Number 4 April 2010 3 é 5 gManagement of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis procurement, and _facilties/equipment. Dr Davenport and Dr Snell provided project management and institutional aisons. Dr Davenport provided clerical. support. Dr Davenport, Ms Stevens, Dr Snell, and Dr Little provided consultation (including re- view of manuscript before submission). This article wos received February 16, 2009, and was accepted November 15, 2008. ok: 10.2522/pt1.20090047 References van der Winde DA, Dunn KM, Spice Dorgelo MNo etal Impact of physical ‘smptoms on perceived heath in the com Iomiy. J Pajebosom Ree, 28042 a Naor, van der Horst H, van der Wind D. Prognosis of fatigue, 4 systematic re View. Pavchoson Res. 2008°61:385-349, 3 Centers for Disease Control and Preven tion. Chronic fatigue syadrome- Available at itp eww ede gov. Accessed De ‘Sember 12,2008 4 Cairns R, Hotopt M. A systematic review deschbing the prognosis of crotch lugue syacrome. Deeup Med (Lond). 2008, 5820-41 45 Jason LA, Richman JA, Rademaker AW. (eal A community-based study of chronic Fate syncrome Arc Intent Med 1999; tso2129-2157 6 Reeves WC, Jones JF, Maloney E, ta Prevalence of chtonic fate sprdrome it metropolitan. urban, ane fur Gens. Popul Heath Meir 20075 7 Prins JB, van der Meet JW. Blejenbers 6. ‘Chronic fii syndrome Lameet. 2006, S07 16-355 8 Beard G, Neurasthenia, or nervous exhaus- thom The Boston Medical md Surgical Journ 18698217-221 9 Goets CG. Poor Beard! Charco’s inter Iatonalizaion of neurathenis, the "American disease.” Neurology. 200157 siossia 10 Gilliam AG. Epidemiological Study on an Epidemic, Diagnosed. as: Polioneliti Occurring Among the Personnel of Las Angeles County General Hospital During be Suomen of 1951 Washington, DEUS ‘Goveenment Printing Otic 1934 111 Ramsay AM, Postiral Fatigue Syndrome: ‘The Saga of Regu Free Diss. New York, NY: Gower Medial Pubishings 1986 12 Epidemic nwvalgic encephalomyeiti Br Med f 1978 1436-143 13 Holmes GP, Kaplan JE, Gantz NM, ett ‘Chronic fatigoe syniome 4 working case Aefiition sb Diter Med. 1988108 ss 389, 14 Evengard B, Schacterle RS, Komaroll AL ‘Chronic atigue syndfome! new insights and old ignorance. J Intern Med. 1999; Beh55- 400. 15 Jason LA, Hisele H, Taylor RR. Asessing fatigue syndrome. Fal Heals Prof. 2001; Dandi 438, 16 Fokws K, Straus SE, Mickie 1, etl, The chronic fie syndrome: 4 comprehen Sve approuch to ts defition and stu International Chronic Fatigoe Syndrome Soule Group. sn Intern Med. 1ODL2T 953-959. 17 Sisto SA, Tapp WN, LaManea J, et al Phys teal activigy before and after exercise in ‘women wid chronic fatigue syndrome (OFM 1998914684753, 48 Cook DB. Nagelkisk PR, Peckerman A, etal, Exercise and cognitive performance in chronte fatigue syndrome Med ‘So Shorts Exerc 2008:37 1100-167 19 Sorensen B, Sec IE, Stra! M ea Cm plement aeunation st a model of chronic fatigue syidrome. J Allergy Cle Tina hol 2003112339740, 20 sharpe MC, Archard LC, Banavala JE, a A report=ehtonic. hte syndeome: guidelines for research. JR Soc Med. 1991 Siiis-120 21 Carruthers BM, Jain AK, DeMeiteir KL, eal. MYalgie ‘encepbalomyetiis/ehronic fauigoe syndrome: chinieal Working case Mdennition, diagnostic and treatment proto. ols (a consensus document). Journal of Chronic Fatigue Syndrome 20811-7113. 22 Jason LA, TornesHanting SR, Jungens A. Helgerson |. Comparing the Fukida et a fester and the Canadian ease deiiton for chronic fatigue syndrome Journal of Chronte Fatigue Syndrome 2004 1247-53. 23 Mecus M, Nis}, Meisler KD. Chronic mus ‘loskcletal pin in anvils with the ‘rome fitighe syle: systematic Fo Mew Bur Pain. 200711377386, 24 VanNess JM. Snell CR, Stayer DR. eta Shclssiying chronic fatigue syndrome Uhroush exercise testing Med Ser Sports rove 2008:38 908-915 25 De Hocker P, Rocykens J. Reynders M tal, Exercise capacity in chronic faige fndnome. Arc Inter Med 2000 0: Seon. 26 Tins W. Treating chronic fig states asa disease of the regulation of energy metabo lism: Med Hypoibeses. 2008 71181-188 27 Sorensen B, Jones P, Vernon SD, Rajeevan MS. Transceipional contol of comple: ‘ment activation in an exercise model of {hronic fatigue syndrome: Mo! Med. 2009 sara 28 Whistler Jones JF. Unger ER, Veron SD. Exercise responsive genes measured in pe ripheral blood af women with chronic tie syncrome and matted control sab jects BMC Physiol 200555, 29 Whistler T, Taylor R, Craddock RC, ea Gene expression correlates of "unex: Plaine gic Muermaceenonis, 200% Fs305-405, 30 Fulle S, Mecocei P, Fano G, eta. Specie DOsitive alterations. in vastus. laterals tnncl of indidale withthe diagnosis of homie fatigue syndrome Free adie Biol Med 2000,29"1252-1239, 31 Wong R, Lopasehuk G, Zhu G, eta. Shel. ca muscle metabolism the chronic Tigue symdronve:n vivo assessment by" nuclear magnetic esonance spectre De Chest 1992 102 1716-1722 {32 Conero DI. Sisto SA, Tapp WN, eta. De creased Vagal power ting” ead ‘kins invias with chronic fate ‘pdrome Clin Anton ee 19366 229-385 38 Fang H, Xie Q, Boneva R. etal. Gene ex pression profie exploration ofa lage dat ‘Scton cheonie tage syndrome, Pharma eagenomtes. 20067 29-440, 34 Van Den Bede F. Mootkens G, Van Howden. hove Beal. Hypothalamic pittar aden {xis function i chronic atigoe syodeome: Newropycobrodogy 2007:98:1 12-120. 35 Van Houdentove B, Verheyen L, Pardaens Kretal.Rehabvltation of decreased motor performance i indiiials with chronic {ugue syndrome: should we teat low el fot capacty or reduced effort tolerance? (Gin Reba, 20072111 21-1142, 36 NaschitzJF, Rosner I, Rozenlbaum M, ea ‘The head pti test with haemodynamic instability score in diaunosing chronic fa tigue syadrome. QM 2003:96133-142 37 Broderick G, Craddock RC Whistler T, cal, Identifying illness parameters inf Tigliag syndromes Using classical projec: tion methods. Pharmacogenomics. 2006; 0. £38 Wallman KE, Sacco P. Sense of effort due Ing fatiguing exetese protocol in chronic Titigue syndrome Res Sports Med. 200" 15a 39) 39 Nijs J, Paul L, Wallman K. Chronie fatigue sytdrome: aa approach combining. se Management with grided exerese” 00 void exicerbations J Rebabil Med 2008: quiz 40 Van Houdenhove B, Bruyninckx K, Luyten Din search of pew balance: can high “action proneness” in iniviuals Wwith chronic Ete syndrome be changed by 4 multipart J Pa Chosonm Res. 2006180628" 625, 41 NijsJ, De Meier K, Duquet W. Kinesio- phobis in chronic fate syndrome: ae EtSsment and associations with daaity Areb Pls Med Rehabil 200438:1586— 1592 42 Wallman KE, Morton AR, Goodman C ral Randomised controlled tal of graded ‘exercse in chromic Latigue syndrome Mee Stist 2004: 180:414— 8 43 tackwood SK, MacHlae SM, Power MI Cal. Effects of exereise on cognitive and ‘motor function ia chron fatigue sy ‘rome and depresion J Neurol Neuro Surg Peebianry 1OSS'SA1 546, 44 Razelmans F,Bleienberg G, Van Der Meer IW, Folgering H. Is physical deconditi Ing petpetating facor in chronic Luge ‘Snide A controlled study on inal ‘Geer perormance ad telaions with tigve impairment and physica actiy. Py dol Med. 20031-10711 45 Fulcher KY, White PD. Randomised con ‘wolled tral of graded exerese in individ Tals with the Chronic fugue syndrome BM 1997 314.1647-1652. April 2010 Volume 90 Number 4 Physical Therapy 613 fadnoo'dne owopece;rsdnw wou pepeojunod 2202 soqwiaidas +1 uo s98n | ewer yeusionUN Ka sezsBez/e0RrHI06/O.NNManagement of Chronic Fatigue Syndrome/Myalgic Encephalomyelitis 46 MoseMorsis R, Sharon C, Tobin R, Bal Je A randomized controled graded exer ‘ice ial for chronic tise syndrome ‘outcomes and mechanisms of THtely Psebol. 2008:10:245-259. 47 Parco, Hagonen Van Wambeke Pia How stn aw cncrose cops i mewures for aleting treatment ef {cctrim hone ae ee” Resale one ty lin Rebubil 2006 20°56 - 0. 448 Weanden AJ Morris RK, Malis Bet al. Ran omised, doubting, placeho-ontraled Payebiatry W972 A89= 190 449 Powell ,Hentall RP. Nyc FJ, Edwards RH Randomised controled tal of individ ‘editeation to encourage graded exerci ‘Chronic fatigue syndrome. BU. 2001;322: 587-390. 50 PowellP, Beta RP. Nye FJ, Edwards RH. Individal education to encounige uraded ‘exercise. in chronic. fatigue syndrome year followap of randomised controlled Anal Be] Paychiatry. 2004 194 142-146 51 Black CD, O'Connor PJ. MeCully KK. te fressed daly physical activity aa faige SSmptoms in chronic fatigue syndome. Dyn Med. 2005-4 52 Mack CD, McCully KK. Time course of txercise indice alterations in daly ati layin conic fatigue syndrome, Dy Med. 200810, 53 Muciler Mf, Maluf KS. Tissue adaptation to physical tress a proposed “phgstea sess theory” to guile pinsieal therapist prac ‘ce, education, and research. PDys Iber bones Sa3- 403 454 NijsJ, Almond F, De Becker P, etal. Can exeicice limits prevent = postexcrtional false in chronic fatigue svadrome? An mmcontrolied clinical thal Clin Reba 108.225126-185 55 Waltman KE, Morton AR, Goodman €, Grove It Physiologiealrespoases during a Stibmasimal eycte test in chronic fate Syndrome, Med Sci Sports Exerc. 2004:36: Toss i688 156 NijsJ, DemolS, Wallman K, Can submax: tal exerci variables predict pesk exer: {se performance in women with chronic fatigbe syndrome? sre Me! Rex. 2007-38 Ss0c353. 57 Demello I, Cucton KJ, Boincau RE, Singh MAI Ratings of percenied exertion at the Jaetate threshold in trained and untrained zen and women. Med Sei Sports Ever Teo 19.354 362 ‘58 Whitlock EP, Orleans CT, Pender N. Allan J-Bualuating primary care behavioral coun ‘Sling interventions an evidence based ‘roach iJ Prev Med, 2002:28:267- 288 59 Davenport TE, KuligK, Matharu Y, Blanco CE. The bat Reb model for nonsurgical ‘anagement of tendinopathy. Phys Ther 2008355 1093-1103. 660 Clapp LL Richardson MF. smith JF eta ‘Seite effects of tasty minutes Of lit: (61 Sader M, Evans JR Philips €, Broad A.A. preliminary study so the effetiveness of mnult-convergentcherapy in the treatment ffheterogeneous incviduals with chronic higue syndrome. Journal of Chronic Fa. tigine Spndronne. 0007 95-100 614m Physical Therapy Volume 90. Number 4 April 2010 sin wow papeowuNog uo th Pe a a y g 2202 soquwaidas #1 uo 19sn | euiner i