1998 Boston AACFS Conference
Dr Rosamund Vallings
I was privileged to attend the AACFS conference in Cambridge, Massachussets from 10th-12th October 1998. People had come from all over the world for this event and it was really good to be able to put faces to the names one had corresponded with over the Internet. The conference was spread over three days and divided into 3 main segments: Research, Clinical and Patients. The programme was intense with very little free time, so that by the end one felt overwhelmed with all the new information. I have tried to sort it out into sections representing the various disciplines involved, and I have included notes on some of the excellent poster presentations.
The prevalence of CFS was discussed by L. Jason (Chicago). The general population had been surveyed rather than looking at just those seeking treatment. Prolonged fatigue was found to occur in 5 -7.7% of individuals and Chronic Fatigue in 2.6 - 4.1%. This represents a higher number of likely sufferers than previously noted. K.Jordan (Chicago) had found the prevalence rate of CFS-like illness in children 2.1%. Females were more frequently affected in the group of 4000 5 - 17 year olds surveyed. The girls tended to suffer more from headaches, the boys from impaired cognition. H.Kang (Washington) presented work on the prevalence of CFS in Gulf War veterans. 5.1% had an illness fitting the criteria for CFS, compared to a rate of 1.2% in controls. High rates of post-traumatic stress disorder and multiple chemical sensitivity were also noted, with considerable overlap of symptoms.
A.Hartz (Iowa) reviewed the prognostic factors and noted that interrupted sleep, lack of income and single status were main factors interfering with recovery. Psychological factors such as low self-confidence, depression and a relative with psychological problems worsened prognosis. Also if the fatigue was viewed as totally physical prognosis was adversely affected. The severity of the fatigue, lack of social support and psychological problems also had a negative effect slowing recovery.
P.Manu (New York) had reviewed 112 patients with a diagnosis of CFS and found that 37.5% did not match the criteria. 8 people had other medical conditions, 18 had had insufficient investigation, 10 did not have enough of the criteria for diagnosis, and 1 was not even fatigued. One patient was described who had thought he was suffering from "toxic exposure" and was found to have a serious liver disorder. All those who genuinely did have CFS had cognitive difficulties and exercise intolerance. He stressed that we need to distinguish between CFS and Idiopathic CF in clinical practice.
The fluctuation and outcome of the illness over time in severely ill patients was discussed by L.Tiersky (NJ). She had looked at 23 people over 3.5 years who had a 50% reduction in activity. 1 had recovered, 9 had improved and 13 (57%) remained severely affected.
The diagnosis of CFS in NE Brazil (L.Nacul) is uncommon, probably because most doctors are ignorant of the condition. Diagnosis is often of a more psychological nature with psychological intervention. It is thought likely that the incidence is similar to that in developed countries. Work from Italy (D.Raciatti) concluded that CFS is a heterogeneous illness with several different pathogenic mechanisms.
B.Evengard (Sweden) showed that most in her study from a large CFS clinic had had an infective onset, and there was improvement in fatigue and functional capacity over 3 years. A.Chester (Washington) pointed out that we need to be aware of sinusitis as a risk factor in CFS. A.Donnay (Baltimore) noted considerable overlap between CFS, fibromyalgia and multiple chemical sensitivity and suggested we should screen all patients for all 3 disorders.
L.Jason (Chicago) described 4 phases of recovery in CFS:
- Crisis - the onset with a feeling of urgent need for treatment with a sense of ambiguity ie an external locus of control but felt self responsible for the illness.
- Stabilisation - recognising symptom patterns and beginning to feel a sense of control over the illness. Alternative sources of support and treatment often sought at this time.
- Coming to terms with illness - grieving. A time of creative construction of the meaning of the illness experience.
- Integration of pre and post crisis lives. He stressed that we need to recognise these phases when making diagnosis as the phase can impact on stress, fatigue and activity.
S.Schwarz (Tulsa) expressed the importance of using validated measures to determine the benefit and impact of treatment in CFS. T.Walker (Michigan) had looked at outcome from a nursing perspective and found that 75% of 40 patients were considerably better after 14 months, and those that had improved felt they had been most helped by psychotherapy, medication or a combination of both.
Various clinical research papers were presented which opened up some exciting possibilities for the future. N.Klimas (Miami) had used immunomodulatory therapy in 14 CFS patients. Lymph nodes were removed, modified and expended in the laboratory and the altered cells were reintroduced to the patients. No adverse events were reported and the expansions were successful. Those patients followed up showed improvement in T cell parameters and positive improvement particularly in cognitive symptoms. These results are only interim and ongoing follow up continues.
Bellanti (Washington) had measured urinary 5-HIAA (a serotonin metabolite) as a marker of the efficacy of NADH in 26 patients. 5-HIAA is a possible predictive marker of neurocognitive dysfunction and has been shown to be elevated in 50% CFS patients. NADH was given in a single dose before breakfast. 31% had significant improvement in symptoms and 70% had normalised 5-HIAA, which equated with less breakdown of serotonin. NADH (nicotinamide adenine dinucleotide) is a natural substance, which triggers ATP and alleviates depression.
G.Moorkens (Belgium) had researched the effects of Growth Hormone in CFS. 20 patients with peak GH levels of <10ug/L were given GH (1.7ug/Kg) for 3 months. 17 followed up and reported feeling better, but were not significantly improved on questionnaires. A number of changes however occurred in body chemistry with normalisation of amino acid levels. All hormonal parameters remained normal although weight tended to increase and fluid retention was noted. Long term risk of cancer of the prostate needs to be borne in mind.
200 patients were followed by D.Strayer (Philadelphia) trialling the drug Ampligen. The drug was administered IV twice weekly over 6 months. Karnofsky scales increased over the 6 months, as did treadmill performance and cognition. Progression was slow and steady. No abnormalities developed in blood chemistry and the drug seems safe. Rnase-L activity decreased towards normal. There was no correlation on placebo.
D.Klonoff (San Francisco) studied the rehabilitation of 35 patients with CFS. He found that those with work disability of <4 months and age <30 years were the most likely to recover. 26% were able to return to work after a generalised approach encompassing exercise, stress management, diet (to prevent hypoglycaemia), attendance at monthly support group and individual psychotherapy. Pharmacological intervention was also deemed important addressing symptomatic relief and the use of tricyclics, SSRIs and non-steroidal anti-inflammatory drugs.
A.Lloyd and his team in Sydney are following a cohort of 75 subjects with post-infective states. They have found that resolution of the prolonged fatigue is associated with improvement in cell-mediated immunity. They plan to continue to follow this group long-term. The likely aetiology of CFS seems to be a genetic predisposition coupled with a tendency to psychological disorders, a persistent infection (with heterogeneity of micro-organisms) and abnormal cytokine activity.
Clinical Studies Posters
D.Berg (Phoenix) postulated that CFS maybe due to a hypercoagulable state because of immune activation of coagulation, and that anticoagulants maybe useful. High rates of abnormalities were found in CFS/FM patients at a rheumatology clinic. 16 were treated with heparin and the patients felt somewhat improved 48-96 hours later. This was described as an intriguing study, but needing to be replicated using double blind placebo controlled approach.
P.Cheney (NC) had tried secretagogue therapy in 14 patients to promote increases in Growth Hormone. This is a plant derived cheaper alternative to GH with the ability to raise IGF-1 levels. 57% reported benefit with a 35% drop in symptom scores, particularly fatigue and muscle pain. The IGF-1 levels changed significantly particularly in those reporting an "excellent" response.
C.Lapp (NC) overviewed his use of Ampligen in CFS, describing it as a useful antiviral, immunomodulatory drug. (Later in the day several of these patients described their positive experiences with the drug).
A 5 year follow up on the young people treated with IV gamma-globulin in Melbourne was presented by K.Rowe to see if the initial improvement was sustained. There was no deterioration overall function and most had continued to improve, though some remained severely disabled.
R.Vallings (Auckland) presented results of an initial pilot study of the use of serine supplements in 10 patients with low urinary serine excretion. Some improvement was noted in cognition, emotional lability, vision, gastrointestinal and respiratory systems. This was however a brief study needing double-blinded, controlled replication.
An overview of immune function in relation to the sleep-wake cycle was presented by H.Moldofsky (Toronto). He noted that CFS patients have altered diurnal patterns in cortisol, prolactin and NK cell production. There was an association with a specific sleep disorder as shown by EEG, and this was associated with daytime sleepiness, fatigue and pain. Cortisol production and NK decline were shown to be phase-advanced in CFS occurring *-3/4 hour earlier in CFS. He explained the close relationship between biological rhythms, the immune system, temperature control, the endocrine system and the sleep-wake cycle.
E.Tan (California) found that CFS patients have auto-antibody responses which target epitope or epitopes in the N-terminal region of lamin B1. Immune-slot blot assay comparing reactivities between N-terminal fragment and full length lamin B1 appears to be the best discriminant to identify this antibody.
A.Vojdani (CA) discussed enhancement of the interferon-induced enzyme PKR at the mRNA and protein level, along with elevated apoptotic cell population in those with CFS. This may contribute to the pathogenesis and symptoms of fatigue.
S.Wagner (Miami) found that the immunologic status correlates with the severity of the illness and physical symptoms in CFS. Elevations in T-helper/inducer cells, activated T-cells, activated cytotoxic/suppressor T-cells and CD4/CD8 ratio are associated with greater disease severity. Reductions in T-suppressor/cytotoxic cells appears related to greater severity of CFS-related physical symptoms suggesting greater symptoms are associated with lower availability of regulatory T-cells.
Q.Zhang (NJ) Confirmed that veterans suffering from CFS (GWS) had a similar altered immune status. He mentioned that added likely stressors in these people were multiple vaccinations and the stress of the situation.
The whole issue of the altered immune responses in CFS was presented in a number of posters. L.Helder (Miami) confirmed the aforementioned strong relationships between severity of illness and immune functioning. There was a high level of immune activation associated with psychological distress. The same team, headed by N.Klimas (Miami) confirmed the hypothesis re-the immunopathogenesis of this syndrome. J.Visser (Netherlands) had done some preliminary studies on altered cytokine production in CFS and de Meirleir (Brussels) had cultured human lymphocytes and found a greater degree of cell damage during cell division in CFS patients. Cell division was also adversely affected by alcohol. The findings point to abnormalities in intracellular protein metabolism with increased sensitivity to alcohol. Interestingly however, LaManca (NJ) did not find a significant difference in immune responses after exhaustive exercise when compared to controls.
2 studies on sensitivity/allergy were displayed. One from Sweden by G.Lindh showed an increase in nickel allergy in CFS. Other metals such as mercury, tin, gold, potassium, lead and silver were also tested and allergy tendency was not found to be increased. M.Cichon (Florida) had reviewed those with silicon breast implants who had clinical illness. He describes this as a probable auto-immune condition producing atypical symptoms not fitting the criteria for any known condition, and this should probably be considered a new entity.
An important preliminary study by R.Patarca (Miami) stressed the need for additional research on the biological correlates of unexplained multiple somatic symptoms. He had found that chemical intolerance had a strongly positive correlation between serum neopterin levels and all of the scales measuring somatization.
This session was concerned with the psychological and social aspects of the illness. N.Endicott (New York) studied patients from a psychiatric practice, and found that those who had developed CFS had a significantly great number of premorbid anomalous conditions of brain organisation than other patients. Conditions such as learning disorders, speech disorders, migraine etc. were cited as likely conditions, which may predispose one to CFS. D.Fairhurst from Leeds found that the CFS group in his study performed more slowly than controls in tests with a higher conceptual processing load. The cognitive fatigue with CFS may therefore be due to the processing activity causing slowing down.
Looking at the psychological differences in CFS, chronic pain syndrome and fibromyalgia, R.Marlin (Ontario) found no increased evidence of psychopathology. He did however note that these people are "suffering" and that the "mind/body" connection is an important consideration to be addressed. B.Evangard (Sweden) found that 67% of patients had a negative life event in the year preceding the illness. She also found that in the 3 months preceding the onset, there had been a dramatic rise in fatigue in CFS patients with a tendency to fatigue and tendency to infections in the year leading up to the illness. She concluded that the increased tendency to infections may predispose one to CFS should negative life events occur.
N.Ware (Boston) gave much food for thought in her presentation regarding the difficulties many with CFS experience in the workplace, and stressed the need for employers to be much more aware of the needs of the disabled person particularly with an illness such as CFS. The unpredictable symptom flare-ups interfere with ability to commit to a work schedule. Memory and concentration problems impede job learning and communication and fatigue reduces effort and productivity. There is a need for elimination of unnecessary physical demands and provision of flexible work hours. 50% of those with CFS become unemployed and the aim should be to reduce the financial burden on society by helping those who want to work.
A large number of posters were presented in this session. L.Tiersky (NJ) found that those with psychiatric illness preceding onset were at an increased risk of experiencing negative life events after becoming ill. M.Di Giannantonio (Italy) also found a high prevalence of psychiatric disorders often preceding the CFS and stressed the importance of psychological evaluation. Personality variables in CFS were discussed by S.Johnson (NJ) who found that MS and CFS shared many similarities. Both were experiencing the demoralising effects of coping with chronic illness marked by uncertainty.
E.Bazelmans (Netherlands) looked at the issue of whether the woman's double role put her more at risk, but although he found that women with children had a poorer prognosis, there was no evidence that women were more prone to CFS because of the double role. Another of his studies showed that doctors in the Netherlands have a limited knowledge of CFS, and there are often problems experienced in the doctor/patient relationship, with doctors needing encouragement to increase their knowledge of CFS.
The issue of fatigue was covered in several posters. G.Bleigenberg (Netherlands) found that those who were bedridden were much more easily fatigued, with more physical complaints and had a higher number of psychological disorders. He also showed that years after illness those who had had cancer experienced the same level of fatigue as CFS patients. C.Christodoulou (NJ) found that those with CFS were more mentally fatigued than those with MS, who generally had more physical fatigue.
Short-term group therapy was found to be helpful by B.Evengard (Sweden) though she felt that longer-term therapy or individual therapy was likely to be more helpful. P.Madill (CA) found reduction in fatigue scores after group rehabilitation with cognitive behavioural therapy and felt this had cost cutting implications.
Cognitive brain potentials as looked at by R.Gordon (CA) showed that patients do have good and bad days, which were different from controls, and there were differences according to whether patient felt fatigued or rested. G.Lange (NJ) had studied the abnormalities of auditory working memory and found that this is probably affected in CFS by changes in the posterior brain regions.
The work of R.Suhadolnik (Philadelphia) was furthered with a multicentre study showing that biochemical dysregulation of the 2-5A synthetase/Rnase L antiviral defence pathway is associated with the characteristic clinical signs and symptoms of CFS. 209 assays have now been completed on 90 subjects with a further 75 in the pipeline. Results confirm the previous findings. Evidence shows that the Rnase L dysfunction in CFS is more profound and complex than previously reported. The pathway normally destroys viruses that infect humans, and the more abnormal, the worse the patient feels.
De Meirleir (Brussels) had studied Rnase L function in 57 patients, and 50 were found to have the abnormality, as did 4 out of the 18 controls. He is hopeful that a biochemical assay for this abnormality in CFS will be developed.
2 studies looked at Human Herpes viruses. D.V.Ablashi (Columbia) found that HHV-6 reactivation or persistent latent infection was higher in CFS than in controls, suggesting its role in pathogenesis. HHV-7 & 8 do not appear to be associated. K.Knox (Wisconsin) found that up to 70% of their patients had active persistent infection with HHV-6, which may account for the clinical manifestations of the disease. HHV-6 is neuro-invasive with prominence of neuro-cognitive symptoms. 27%showed associated changes on MRI. It was considered necessary to do repeat testing as the incidence was much increased at the second test. HHV-6 infects all white cells during the acute phase and causes the common childhood illness exanthum subitum (roseola).
Various possible infective agents were considered in this section. P.Cheney (NC) presented interesting work regarding the possibility that root canal-filled teeth frequently harbour infection which is a potential source of xenobiotic toxicity. However this may not be the only source of toxicity and extraction may not lead to improvement. P.Choppa (LA) found significant involvement of mycoplasma organisms in those suffering from CFS, rheumatoid arthritis and GWS. He used multiple PCR for detection, a rapid, cost-efficient procedure.
S.Levine (NY) found that samples taken from CFS patients raised the possibility of Bornavirus infection and one should consider their potential role if the clinical picture supports a viral infection. B.Evengard (Sweden) however found no evidence of bornavirus infection in 169 patients studied. K.Simpson (Glasgow) noted that 18% of patients with CFS had evidence of viral infection, and suggested it is possible that other patients maybe suffering undiagnosed latent conditions.
L.Klapow (CA) had found decayed specimens of a suspected roundworm, cryptostrongylus pulmoni in the sputum of 39% CFS patients but not in any controls. Roundworm infestations can give rise to immune abnormalities similar to those in CFS including low cortisol, altered antiviral responses and altered cholinergic processes.
W.Behan (Glasgow) gave an overview of ion channel function particularly looking at the hypothesis that symptoms of CFS are related to this. 70% of energy expenditure relates to keeping cells going including 30% to maintain the sodium/potassium gradient. In CFS there maybe loss of potassium with a subsequent need for increased energy to maintain the pump. There will therefore be less energy in reserve. Those with CFS have higher energy expenditure as was shown by large differences in those with CFS after exercise leading to lasting muscle fatigue. In this study irregularities were shown in the handling of potassium by the heart muscle in CFS, but the ECG was normal. Intracellular potassium was decreased in a number of patients suggesting a channelopathy. This hypothesis will only apply to a subset of patients and is comparable to ciguatoxin which is directed against the sodium channels causing an illness indistinguishable from CFS.
The levels of fatigue after extreme exercise in CFS were studied by E.Bazelmans (Netherlands). He found that patients did not suffer from physical deconditioning, and by keeping diaries, in actual terms no decrease in activity was noted by those with CFS on the days following extreme exercise. He felt therefore that the extreme fatigue reported by patients after exercise maybe a cognitive-behavioural problem, and CBT may therefore be useful. G.Bleijenberg (Netherlands) used an actometer to subtype physical activity patterns in CFS. He found that in CBT changing the activity pattern should be an important aim. Initially the activity should be lowered, the limits recognised and then gradually the activity could be increased. The very inactive patients benefit less from CBT than the active and may need a different approach.
Gait was the subject of work by L.Paul (Glasgow) who found a number of gait parameters were altered in CFS. Gait analysis could be a valid outcome measure for treatment intervention analysis.
Cardiovascular issues were addressed by several researchers. S.Sisto (NJ) found that because CFS patients have lower systolic blood pressure and heart rate responses they may not be able to exhibit the expected range of responses to a cognitive or exercise stressor. For example they cannot bring the BP up with exercise. Peckerman (NJ) reported that the most severe patients had the lowest stroke volume. Those with cognitive problems maybe more affected by mental stress, which may indicate a defect in the higher cortical modulation of cardiovascular autonomic control, leading to decrement of function. J.Stewart (NY) confirmed earlier findings that CFS in adolescence is highly related to orthostatic intolerance. This is consistent with partial autonomic defect and may contribute to symptomatology.
Postural orthostatic tachycardia and chronic fatigue in adolescence was also addressed by M.Alexander (CA). He found a distinct response to orthostatic stress with excessive tachycardia and decreased cerebral artery bloodflow velocity early in head-up tilt. A.Sisto (Italy) showed that the tilt table is a useful system for evaluation of neurally mediated hypotension in patients with normal hearts. He postulated NMH as a possible aetiological factor in CFS. Postural stability in CFS was found by L.Paul (Glasgow) to be unaffected by exercise unless the eyes are then closed, when those with CFS had greater instability than controls.
Further studies on ion channels were presented by J.Gow (Glasgow) with data suggesting that abnormal calcium flux is present in skeletal muscle and this warrants further investigation. In the presence of an ion disorder the muscle has to work hard to compensate.
P.de Becker (Belgium) showed that the work capacity in CFS and fibromyalgia is 40% lower than controls, and postulates that this is due to severe muscle weakness and not deconditioning. He also found a significant decrease in lung vital capacity due to significant increase in residual volume. Bronchial hyper-responsiveness was high which may provide some explanation for symptoms.
B.Evangard (Sweden) found no evidence for elevated substance P in the cerebrospinal fluid in CFS, whereas this is elevated in fibromyalgia, and this showed in her study that they are distinct disorders.
N.McGregor (Australia) presented an overview of the work of his team in Newcastle showing the heterogeneity of symptom onset and biochemical profiles in CFS. They conclude that we are looking at various subsets of this disorder with different chemical profiles depending on host responses, infectious responses and type of onset which match the different symptoms and biochemical constellations. These objective measurements and the ability to group patients into subsets represents a major advance. Urinary amino acids, organic acids and plasma fatty acid profiles were all discussed. The major lipid profiles distinguishing CFS patients from controls appear to be of genetic or acquired origin. Multiple regression and clustering techniques revealed 5 different types of CFS lipid profiles, while the control group had a high degree of homogeneity.
Further work on acetyl-carnitine was presented by H.Kuratsune (Japan). Serum acetyl-carnitine (ACR) has an important physiological role in the brain. Regional cerebral blood flow was found to be abnormal on PET scan in several regions. An association was found between ACR uptake and regional cerebral blood flow in CFS. The intracranial abnormalities of ACR metabolism maybe related to the pathogenesis of CFS. Cerebral perfusion was also found to be abnormal on PET by D.Racciatti (Italy) and this could allow comparison with psychiatric disorders. M.Preston (NC) also showed that EEG can be used to differentiate CFS patients from controls - abnormalities previously noted were validated by blind review.
2 case histories were reviewed by J.Montalvan (MD) indicating that exercise overtraining may contribute to the risk of infection and susceptibility to developing CFS. It was proposed that a more systematic study be done.
This was the smaller part of the conference and rather than presentation of individual research papers, the format was a series of overviews of clinical issues by the leading players in the field of CFS. The conference opened with some moving experiences on "Living with CFS" from several patients who were high profile people in the American CFIDS Association. This gave us much food for thought and certainly set the scene for what was to follow.
Biological Aspects of CFS
3 presentations were give summarising some aspects of the current biological knowledge of the illness. T.Dinan (Dublin) covered the endocrine issues and told us there are problems at all levels of the HPA axis in CFS. There is a poor response to CRH with blunted release of ACTH and cortisol. The synacthen test is also blunted and the size of the adrenal glands is reduced. (In depression the adrenal size is enhanced).
J.deLuca (NJ) covered neuropsychological function, and has found that CFS patients do poorly on simultaneous memory tests, and the more complex the test the slower the speed of reaction. Impairment rating showed those with CFS slower than controls, but similar to those with depression. He had reviewed those with CFS with psychological problems compared with those with CFS who were non-psychological. The latter were the greatest impaired, while those with psychological problems performed more like normals. The non-psychological group were also more likely to have abnormalities on MRI. A functional MRI showed changes with cognitive activity, probably because more cerebral resources are needed with cognitive work in CFS. He feels SPECT scans are not a diagnostic marker for CFS and have very little significance in this condition.
N.Klimas (Miami) reviewed the immunological factors involved. There is probably some genetic predisposition with infection as a triggering event in up to 80% of cases. (cf fibromyalgia, where infection is only implicated in 18%). There follows chronic immune activation and immune dysfunction. The causes of immune activation can be viral, autoimmune, allergic or "super" antigenic (e.g. silicon implant). There maybe viral persistence (eg HHV-6). There is interplay between the neuro-endocrine-immune systems which never stand alone and operate via chemical messages. She cited as an example the effects of Hurricane Andrew when cytokine activity increased associated with stress and led to serious persisting relapse in those with CFS.
Children and Adolescents
The next segment was on CFS in children and adolescents. There are as yet no defined criteria for CFS in childhood. J.Jones (Denver) raised the question whether we should consider the diagnosis in prepubertal children. They cannot participate fully in the diagnostic process, they cannot define their fatigue and fatiguing illness with no identifying aetiology is not reported commonly in children. He posed the question "How can we diagnose children accurately?" Adolescents, however can be studied without modification of the definition. Adolescents do complain of fatigue frequently, but the onset of CFS per se is usually acute and although the course of the illness can be variable, they do tend to recover within 2 years. The illness will fit the adult CFS criteria and the young person is able to participate in the diagnostic process. Failure to recover can usually be predicted. D.Bell (NY) however has found that 67% young people take more than 3 years to recover with many still remaining ill after 15 years. He stressed the need for proper research definitions for children. One problem noted was that the literature does not always distinguish between CFS and chronic fatigue.
C.Lapp (NC) echoed some of these thoughts. He has felt the difficulties of the lack of criteria for children, the lack of a biological marker and the confounding psycho-social factors. He has found the condition less prevalent in children than adults and uncommon under the age of 11. The onset seems more gradual under 12 and more acute over 12. The main symptoms in children are fatigue, cognitive difficulties, abdominal complaints, headaches, myalgias and arthralgias.
Fatigue in childhood had been investigated by K.Jordan (MD) using postal survey and the final prevalence of significant fatigue with symptoms suggestive of CFS and effects on learning and cognition was 2.6% (1.9% under 12, 2.91% over 12). Girls were found to be more likely suffering from headaches, lymph gland pain and sore throats, while there were more memory and learning difficulties in the boys. The difficulties with a survey such as this are the likelihood of a high rate of false positives and the fact there was an adult 'gatekeeper' giving the information.
A.Gurwitt (Boston) gave the perspective of the child psychiatrist. He studied 21 cases in the 11-24 year age group. These young people were usually high achievers when they became ill. 75% had no prior psychiatric disorder, 30% had no post-illness psychiatric problem. Others had adjustment reactions. He stressed the need for both parents to be present at interview. Medication is needed to deal with sleep difficulties and depression. Adaptation and coping strategies need to be given with reinforcement by both parents. Parents need ongoing support and modified psychotherapy maybe helpful for the child. Because of the illness, developmental phenomena maybe time-distorted/delayed.
Diagnostic Test Strategies
Each of the presenters in this session summarised the diagnostic approach undertaken. J.Jones (Denver) used a stepwise approach, which helped decide the necessary tests to follow. Type of onset (acute or gradual), time of year and location are important issues to confirm in the history. Direct testing should be done focused on particular patient complaints. Follow-on serological testing maybe appropriate. If no specific illness is detected, check for ongoing inflammation or infection should be undertaken. (WBC, ESR, protein electrophoresis, immunoglobulins, complement, ANA and iron studies). If onset was gradual, hormones, renal function etc. need checking. Autonomic NS testing maybe useful (eg tilt table) and sleep studies to detect non-restorative sleep are important. A home actimeter maybe useful if a specialist sleep clinic is not available. Those with muscle weakness may need more in depth neuro-muscular workup, and those with respiratory symptoms should have allergy tests and possible CT scan of sinuses. Specialised scanning (CT, MRI, SPECT) should only be done if specifically indicated.
D.Klonoff (CA) felt it was vital to evaluate the fatigue itself accurately. He described 3 types of fatigue:
- Neuromuscular (checked by tests of endurance and force),
- Neuropsychological fatigue (cognitive testing),
- Tiredness - affected by mood, personality and motivation (immeasurable).
Fatigue is the 7th most common symptom in general medical practice with 6 million doctor visits annually for this in the USA. Up to 30% of the community are fatigued. The causes of fatigue include every medical and psychological disease, chronic fatigue syndrome and idiopathic chronic fatigue. The latter maybe a milder version of CFS. Medical history needs to include the symptom criteria for CFS, the sleep pattern and the effects of stress. Physical examination should include temperature, inspection of the throat and nodes and postural BP and pulse. Initially blood chemistry, CBC, ESR, TSH and MSU should be done together with psychological tests for stress levels. His 3 messages for management were to be optimistic, aim for gradual improvement and recognise the mind/body connection.
K.de Meirleir (Brussels) used a similar approach to the others, but would include questions about effects of exercise, history of allergies prior to onset and any history of blood transfusion. On physical examination he looked for tender points and checked for mitral valve prolapse. He uses a range of immunological tests but these are only done on those that strictly fit the CFS criteria. Other more specialised tests he would include are pulmonary function, chest Xray, exercise testing for aerobic capacity, polysomnogram and ECG. (The presence of a 'u' wave is associated with an intracellular ion abnormality). Occasionally he uses lumbar puncture, SPECTscan and echocardiogram if indicated for differential diagnosis.
7 well-known CFS clinicians gave a brief overview of the approaches to treatment each considered important and this was followed by panel discussion. D.Bell (NY) focused on the issue of decreased blood volume. In the patients he had studied the haematocrit was normal but the overall volume decreased. There was reduced pulse pressure on standing despite the raised pulse rate. Strategies to increase blood volume include additional salt and fluid intake and use if fludrocortisone, but symptoms do not necessarily improve. However symptoms do improve remarkably following saline infusion, though improvement is only short term. This is a contradiction which he still does not understand.
N.Gantz (PA) described an 8 billion a year industry in natural products and found CFS patients used many therapies. Most interventions are of no help. As well as routine management measures, the use of galantamine could be considered. This is a cholinesterase inhibitor, which should improve cognitive function, neuromuscular transmission and promote earlier onset of REM sleep. It is also an analgesic and increases both cortisol and ACTH levels. Further study is underway.
P.Cheney (NC) presented his pyramid to discuss his treatment plan starting from the bottom and progressively moving upward:
- Liver-gut detoxification
- B vitamins including high dose B12 injections
- Neuro-protection (klonapin, magnesium)
- Limit setting, elimination diet, exercise
He mentioned also that B12 is a detox agent and was used in a cyanide explosion in the UK. Added to this plan he may consider use of hormones too.
C.Lapp (NC) in his brief 10-minute slot listed his 10 top treatments - not in any particular order and not to be all used at once!
- Clonazepam (0.5 - 1.5 mg) for sleep, particularly useful for 'restless legs'
- B12 injections (+folate supplement) - He uses 3000ug twice weekly, sometimes more to a maximum of 11000ug weekly. Acne and CNS hyperactivity can occasionally occur.
- Stimulants. Slow wave brain activity in CFS is speeded up by amphetamines similar to in ADD. Ritalin (5-10mg twice daily) can be very useful. Adverse effects include tremor, increased BP and increase in tics.
- Treatment of NMH with sodium, fluids, florinef and adrenergic blockade. Midodrine and Ritalin may also help this. It maybe 2-3 months before the therapy is effective.
- SSRIs, MAOIs and dopamine agonists such as Wellbutrin.
- Diamox (125-500mg twice daily) - a diuretic which reduces intracranial pressure and may relieve headaches.
- Neurontin (100-300mg 3 times daily to a maximum of 2400mg daily). (GABA-like action).
- Estradiol (0.5-2mg daily) or testosterone (1.25-2.5mg daily)
- Allergy treatment
- Ampligen (He has a small number on this)
Pitfalls in management of CFS were outlined by D.Peterson (NV). He concluded that we should prioritise treatment according to patient requirement. One agent should be used at a time and we should try to measure outcome. We should 'prescribe' strategies for energy conservation. Cognitive Behavioural Therapy was outlined by M.Sharpe (Edinburgh). The therapy is an approach to treatment of CFS which should be focused and time-limited. It is based on the formulation of the 'problem' and focuses collaboratively on changing behaviour if unhelpful or inaccurate. Cognitive restructuring, homework and problem solving are involved. Sharpe's trial showed health improvement over a year. He also discussed the White trial on exercise therapy. Exercise was found to be better than flexibility treatment. However compliance tended to be poor. One needs to integrate with medical treatment to gain acceptance.
Disability and Rehabilitation
Again panel discussion and individual presentation was the format for this session. The patient perspective was well voiced by M.Grambs (CA) and legal issues in the US were discussed by M.Bronstein (Boston).
S.Sisto (NJ) described her physical management of those with CFS. She feels postural approaches are important, as for example, symptoms such as hyperventilation and NMH maybe adversely affected by poor rib cage muscle function. The goals are restoration of muscle length, improvement in mobility and posture, decrease in pain, increase in sleep and increase in daily activity. Areas focused on are:
- BP and heart rate.
- Muscle and fascial integrity eg massage
- Sleep posture/comfort patterns
- Pain management
- Functional capacity
The principles of exercise should acknowledge the patient's fear of exercise and understand the natural history of the illness. Progress should be no faster than weekly increments. Relapses may occur but will gradually be less severe. Other extra activities may mean decreasing the level of exercise.
F.Friedberg (NY) critically reviewed CBT intervetions and noted that often the activities were avoided for fear of symptom flare-ups. He agreed that graded activity however has a role in reducing symptoms.
A panel of experts working in psychological medicine in relation to CFS outlined their management of the condition. A.Gurwitt (Boston) finds that psychiatric problems are often identified and he questioned whether the primary physician has time for detailed evaluation. He stressed the importance of distinguishing between CFS and chronic fatigue. A good psychological history must be taken but not necessarily by a psychiatrist. There is no reason to feel shame about the illness or shame in seeing a psychiatrist if need be. Psychiatric referral in CFS should not be routine and should be for a good reason.
I.Hickie (Sydney) takes a broad-spectrum approach to management involving where possible a multidisciplinary team. He noted there maybe a genetic predisposition for fatigue.
L.Jason (Chicago) discussed the criteria for CFS and pointed out that there is a lot of overlap with depression. Also our questions can be interpreted very differently by our own perspective and by the many different backgrounds of our patients.
M.Sharpe (Edinburgh) posed the question "What is wrong with psychiatrists?' He finds that often the psychiatrist faces difficulties with CFS patients, often feeling quite threatened himself!! CFS should be viewed as a medical disease with accompanying psychiatric disorder, as many do fit the criteria for a psychiatric diagnosis. To treat the condition properly, the patient does need the benefit of a psychological assessment. Various stigma are attached to psychological implications, such as 'its all in the mind', one is to blame for the illness or one is 'weak'. The role of the psychiatrist should be constructive adding a psychosocial dimension to management and to perhaps pronounce that this patient is non-psychiatric. He felt strongly that psychiatry has let these patients down. We need to listen to our patients, combine diagnoses with the psychiatric fraternity and thus clarify the implications for treatment.
Alison Hunter Memorial Foundation
PO Box 6132 North Sydney 2059 Australia
Phone/Fax +61 2 9958 6285
All material on the site © AHMF | Sitemap