Increased concentrations of homocysteine in the cerebrospinal fluid in patients with fibromyalgia and chronic fatigue syndrome

Abstract:

Twelve outpatients, all women, who fulfilled the criteria for both fibromyalgia and chronic fatigue syndrome were rated on 15 items of the Comprehensive Psychopathological Rating Scale (CPRS-15). These items were chosen to constitute a proper neurasthenic subscale.

Blood laboratory levels were generally normal. The most obvious finding was that, in all the patients, the homocysteine (HCY) levels were increased in the cerebrospinal fluid (CSF). There was a significant positive correlation between CSF-HCY levels and fatiguability, and the levels of CSF-B12 correlated significantly with the item of fatiguability and with CPRS-15.

The correlations between vitamin B12 and clinical variables of the CPRS-scale in this study indicate that low CSF-B12 values are of clinical importance. Vitamin B12 deficiency causes a deficient remethylation of HCY and is therefore probably contributing to the increased homocysteine levels found in our patient group.

We conclude that increased homocysteine levels in the central nervous system characterize patients fulfilling the criteria for both fibromyalgia and chronic fatigue syndrome.

 

Source: Regland B, Andersson M, Abrahamsson L, Bagby J, Dyrehag LE, Gottfries CG. Increased concentrations of homocysteine in the cerebrospinal fluid in patients with fibromyalgia and chronic fatigue syndrome. Scand J Rheumatol. 1997;26(4):301-7. http://www.ncbi.nlm.nih.gov/pubmed/9310111

 

Somatomedin C (insulin-like growth factor I) levels in patients with chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome is a disorder clinically quite similar to fibromyalgia syndrome, and it is of interest to examine if these two syndromes have pathogenetic as well as clinical features in common. Somatomedin C levels have been found to be lower in patients with fibromyalgia syndrome than in healthy controls. An attractive hypothesis relating sleep disturbance, altered somatotropic neuroendocrine function and fibromyalgia symptoms has been put forward as a plausible pathogenic mechanism for fibromyalgia syndrome. We therefore sought to investigate the level of somatomedin C in patients with chronic fatigue syndrome.

Somatomedin C levels were determined by radioimmunoassay in frozen serum specimens from 49 patients with CFS and 30 healthy blood donor control subjects of similar age and gender. Somatomedin C levels were higher in patients with CFS than in healthy control subjects (255.3 +/- 68.5 vs 211.9 +/- 76.2, P = 0.01). There was no effect of gender, use of nonsteroidal anti-inflammatory drugs or tricyclic drugs on levels of somatomedin C. There was a tendency for somatomedin C levels to fall with age.

In contrast to patients with fibromyalgia, in whom levels of somatomedin C have been found to be reduced, levels in patients with CFS were found to be elevated. Thus, despite the clinical similarities between these two conditions, they may be associated with different abnormalities of sleep and/or of the somatotropic neuroendocrine axis.

 

Source: Bennett AL, Mayes DM, Fagioli LR, Guerriero R, Komaroff AL. Somatomedin C (insulin-like growth factor I) levels in patients with chronic fatigue syndrome. J Psychiatr Res. 1997 Jan-Feb;31(1):91-6. http://www.ncbi.nlm.nih.gov/pubmed/9201651

 

Cognitive slowing and working memory difficulties in chronic fatigue syndrome

Abstract:

OBJECTIVE: Patients with chronic fatigue syndrome (CFS) commonly report problems with attention, memory, learning, and speed of cognitive processing. This study attempted to evaluate these complaints using objective test criteria.

METHOD: A test battery composed of six tests assessing these cognitive functions was given on two consecutive days. Twenty CFS patients were compared with 20 healthy control subjects and 14 patients with a history of major depression or dysthymia matched by age, intelligence, education level, and sex.

RESULTS: Compared with control subjects, CFS patients consistently scored lower on tests in which motor and cognitive processing speeds were a critical factor, eg, reaction-time tasks. They also had more difficulty on working-memory tests in which rapid cognitive processing speed is also an important factor. The effort made on the first day of testing did not result in a decline in cognitive function on the following day. CFS patients did not qualify as having affective disorder by several different diagnostic criteria. Nonetheless, CFS patients’ test performances did not differ from patients with a history of major depression or dysthymia.

CONCLUSIONS: It is concluded that, although CFS and major depression and dysthymia have distinct clinical features, these disorders have slowed motor and cognitive processing speed in common.

Comment in: Cognitive slowing in chronic fatigue syndrome (CFS) [Psychosom Med. 1997]

 

Source: Marshall PS, Forstot M, Callies A, Peterson PK, Schenck CH. Cognitive slowing and working memory difficulties in chronic fatigue syndrome. Psychosom Med. 1997 Jan-Feb;59(1):58-66. http://www.ncbi.nlm.nih.gov/pubmed/9021867

 

Decreased postexercise facilitation of motor evoked potentials in patients with chronic fatigue syndrome or depression

Abstract:

We studied the effects of exercise on motor evoked potentials (MEPs) elicited by transcranial magnetic stimulation (TMS) in 18 normal (control) subjects, 12 patients with chronic fatigue syndrome, and 10 depressed patients. Subjects performed repeated sets of isometric exercise of the extensor carpi radialis muscle until they were unable to maintain half maximal force.

MEPs were recorded before and after each exercise set and for up to 30 minutes after the last set. The mean amplitude of MEPs recorded from the resting muscle immediately after each exercise set was 218% of the mean pre-exercise MEP amplitude in normal subjects, 126% in chronic fatigue patients, and 155% in depressed patients, indicating postexercise MEP facilitation in all three groups. The increases in the patient groups, however, were significantly lower than normal.

The mean amplitudes of MEPs recorded within the first few minutes after the last exercise sets in all three groups were approximately half their mean pre-exercise MEP amplitudes. This postexercise MEP depression was similar in all groups. We conclude that postexercise cortical excitability is significantly reduced in patients with chronic fatigue syndrome and in depressed patients compared with that of normal subjects.

 

Source: Samii A, Wassermann EM, Ikoma K, Mercuri B, George MS, O’Fallon A, Dale JK, Straus SE, Hallett M. Decreased postexercise facilitation of motor evoked potentials in patients with chronic fatigue syndrome or depression. Neurology. 1996 Dec;47(6):1410-4. http://www.ncbi.nlm.nih.gov/pubmed/8960719

 

Functional status in patients with chronic fatigue syndrome, other fatiguing illnesses, and healthy individuals

Abstract:

BACKGROUND: Chronic fatigue syndrome (CFS) is a condition that may be associated with substantial disability. The Medical Outcomes Study Short-Form General Health Survey (SF-36) is an instrument that has been widely used in outpatient populations to determine functional status. Our objectives were to describe the usefulness of the SF-36 in CFS patients and to determine if subscale scores could distinguish patients with CFS from subjects with unexplained chronic fatigue (CF), major depression (MD), or acute infectious mononucleosis (AIM), and from healthy control subjects (HC). An additional goal was to ascertain if subscale scores correlated with the signs and symptoms of CFS or the presence of psychiatric disorders and fibromyalgia.

DESIGN: Prospectively collected case series.

SETTING: Patients with CFS and CF were seen in a university-based referral clinic and had undergone a complete medical and psychiatric evaluation. Other study subjects were recruited from the community to participate in research studies.

PARTICIPANTS: The study included 185 patients with CFS, 246 with CF, 111 with AIM, and 25 with MD. There were 99 HC subjects.

MEASURES: The SF-36 and a structured psychiatric interview were used. The SF-36 contains 8 subscales: physical, emotional, social, and role functioning, body pain, mental health, vitality, and general health- and a structured psychiatric interview.

RESULTS: Performance characteristics (internal reliability coefficients, convergent validity) of the SF-36 were excellent. A strikingly consistent pattern was found for the physical functioning, role functioning, social functioning, general health, and body pain subscales, with the lowest scores in CFS patients, intermediate scores in AIM patients, and the highest scores in the HC subjects. The CFS patients had significantly lower scores than patients with CF alone on the physical functioning (P < or = 0.01), role functioning (P < or = 0.01), and body pain (P < or = 0.001) subscales. The emotional functioning and mental health scores were worst among those with MD. The presence of fibromyalgia, being unemployed, and increasing fatigue severity all were associated with additional functional limitations across multiple functional domains, with increasing fatigue appearing to have the greatest effect.

CONCLUSIONS: The SF-36 is useful in assessing functional status in patients with fatiguing illnesses. Patients with CFS and CF have marked impairment of their functional status. The severity and pattern of impairment as documented by the SF-36 distinguishes patients with CFS and CF from those with MD and AIM, and from HC, but does not discriminate between CF and CFS.

 

Source: Buchwald D, Pearlman T, Umali J, Schmaling K, Katon W. Functional status in patients with chronic fatigue syndrome, other fatiguing illnesses, and healthy individuals. Am J Med. 1996 Oct;101(4):364-70. http://www.ncbi.nlm.nih.gov/pubmed/8873506

 

Research on cognitive complaints and cognitive functioning in patients with chronic fatigue syndrome (CFS): What conclusions can we draw?

Abstract:

People with chronic fatigue syndrome (CFS) complain of difficulties with concentration and memory yet studies suggest that they do not suffer gross deficits in cognitive functioning. Depressed patients make similar cognitive complaints, and there is symptomatic overlap between CFS and depression.

Cognitive complaints and depressed mood are positively correlated in CFS patients but, except on tasks which are particularly sensitive to depression, cognitive performance and depression are not.

The inconsistency between cognitive complaints and results of tests of cognitive functioning resembles that found in other subject groups and may be due in part to the inappropriate use of laboratory memory tests for assessing “everyday” cognitive functioning.

Even when cognitive capacity is intact, cognitive performance may be affected by factors such as arousal, mood, and strategy. In CFS patients, everyday cognitive tasks may require excessive processing resources leaving patients with diminished spare attentional capacity or flexibility.

 

Source: Wearden AJ, Appleby L. Research on cognitive complaints and cognitive functioning in patients with chronic fatigue syndrome (CFS): What conclusions can we draw? J Psychosom Res. 1996 Sep;41(3):197-211. http://www.ncbi.nlm.nih.gov/pubmed/8910243

 

Viral serologies in patients with chronic fatigue and chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is an illness characterized by disabling fatigue associated with complaints of fevers, sore throat, myalgia, lymphadenopathy, sleep disturbances, neurocognitive difficulties, and depression. A striking feature of CFS is its sudden onset following an acute, presumably viral, illness and the subsequent recurrent “flu-like” symptoms. It has been speculated that both CFS and debilitating chronic fatigue (CF) that does not meet strict criteria for CFS may be the direct or indirect result of viral infections.

We therefore tested 548 chronically fatigued patients who underwent a comprehensive medical and psychiatric evaluation for antibodies to 13 viruses. Our objectives were to compare the seroprevalence and/or geometric mean titer (GMT) of antibodies to herpes simplex virus 1 and 2, rubella, adenovirus, human herpesvirus 6, Epstein-Barr virus, cytomegalovirus, and Cox-sackie B virus, types 1-6 in patients with CF to healthy control subjects. Other goals were to determine if greater rates of seropositivity or higher GMTs occurred among subsets of patients with CFS, fibromyalgia, psychiatric disorders, a self-reported illness onset with a viral syndrome, and a documented temperature > 37 degrees C on physical examination.

Differences in the seroprevalence or GMTs of antibodies to 13 viruses were not consistently found in those with CF compared with control subjects, or in any subsets of patients including those with CFS, an acute onset of illness, or a documented fever. These particular viral serologies were not useful in evaluating patients presenting with CF.

 

Source: Buchwald D, Ashley RL, Pearlman T, Kith P, Komaroff AL. Viral serologies in patients with chronic fatigue and chronic fatigue syndrome. J Med Virol. 1996 Sep;50(1):25-30. http://www.ncbi.nlm.nih.gov/pubmed/8890037

 

Health status in patients with chronic fatigue syndrome and in general population and disease comparison groups

Abstract:

PURPOSE: To measure the functional status and well-being of patients with chronic fatigue syndrome (CFS), and compare them with those of a general population group and six disease comparison groups.

PATIENTS AND METHODS: The subjects of the study were patients with CFS (n = 223) from a CFS clinic, a population-based control sample (n = 2,474), and disease comparison groups with hypertension (n = 2,089), congestive heart failure (n = 216), type II diabetes mellitus (n = 163), acute myocardial infarction (n = 107), multiple sclerosis (n = 25), and depression (n = 502). We measured functional status and well-being using the Medical Outcomes Study 36-Item Short-Form Health Survey (SF-36), which is a self-administered questionnaire in which lower scores are indicative of greater impairment.

RESULTS: Patients with CFS had far lower mean scores than the general population control subjects on all eight SF-36 scales. They also scored significantly lower than patients in all the disease comparison groups other than depression on virtually all the scales. When compared with patients with depression, they scored significantly lower on all the scales except for scales measuring mental health and role disability due to emotional problems, on which they scored significantly higher. The two SF-36 scales reflecting mental health were not correlated with any of the symptoms of CFS except for irritability and depression.

CONCLUSION: Patients with CFS had marked impairment, in comparison with the general population and disease comparison groups. Moreover, the degree and pattern of impairment was different from that seen in patients with depression.

 

Source: Komaroff AL, Fagioli LR, Doolittle TH, Gandek B, Gleit MA, Guerriero RT, Kornish RJ 2nd, Ware NC, Ware JE Jr, Bates DW. Health status in patients with chronic fatigue syndrome and in general population and disease comparison groups. Am J Med. 1996 Sep;101(3):281-90. http://www.ncbi.nlm.nih.gov/pubmed/8873490

 

Selective impairment of auditory processing in chronic fatigue syndrome: a comparison with multiple sclerosis and healthy controls

Abstract:

The most consistent deficit observed in individuals with Chronic Fatigue Syndrome has been in efficiency of information processing. To examine the possibility of a modality-specific impairment, the present study examined subjects with Chronic Fatigue Syndrome, multiple sclerosis, and healthy controls on an auditory-versus visual-paced serial-addition test. 20 subjects with Chronic Fatigue Syndrome, 20 subjects with clinically definite Multiple Sclerosis, and 20 sedentary healthy controls were compared.

One-half of the subjects in each group were administered the Paced Auditory Serial Addition Test and the other half were administered the Paced Visual Serial Addition Test. The group with Chronic Fatigue Syndrome was differentially impaired on the auditory relative to the visual processing task. The group with Multiple Sclerosis was equally impaired on both versions of the task. The results are discussed within the framework of Baddeley’s model of working memory.

 

Source: Johnson SK, DeLuca J, Diamond BJ, Natelson BH. Selective impairment of auditory processing in chronic fatigue syndrome: a comparison with multiple sclerosis and healthy controls. Percept Mot Skills. 1996 Aug;83(1):51-62. http://www.ncbi.nlm.nih.gov/pubmed/8873173

 

The measurement of fatigue in patients with multiple sclerosis. A multidimensional comparison with patients with chronic fatigue syndrome and healthy subjects

Abstract:

OBJECTIVE: To provide a multidimensional characterization of fatigue in patients with multiple sclerosis (MS).

DESIGN: Cross-sectional design. Fifty patients with clinically definite MS were compared on the dimensions of fatigue with 51 patients with chronic fatigue syndrome (CFS) and 53 healthy subjects.

RESULTS: Fourty-six percent of the patients with MS reported fatigue to be present at least once a week. Patients with MS and patients with CFS had significantly higher subjective fatigue severity scores than healthy subjects. Patients with MS and patients with CFS had significantly higher scores on measures of psychological well-being than healthy subjects. Patients with MS had scores similar to those of patients with CFS, except that patients with CFS had significantly higher somatization scores. High somatization scores reflect strong focusing on bodily sensations. Both groups of patients were significantly less active than the healthy subjects. The Kurtzke Expanded Disability Status Scale (EDSS) and the Beck Depression Inventory scores were not related to subjective fatigue severity. In patients with MS and in patients with CFS, subjective fatigue severity was related to impairment in daily life, low sense of control over symptoms, and strong focusing on bodily sensations. In CFS, but not in MS, evidence was found for a relationship between low levels of physical activity and attributing symptoms to a physical cause and between subjective fatigue severity and physical activity.

CONCLUSIONS: Patients with MS experienced significant fatigue, which had a significant impact on daily functioning and was not related to depression on Expanded Disability Status Scale score. Psychological factors, such as focusing on bodily sensations and low sense of control play a role in the experience of fatigue in MS and CFS.

 

Source: Vercoulen JH, Hommes OR, Swanink CM, Jongen PJ, Fennis JF, Galama JM, van der Meer JW, Bleijenberg G. The measurement of fatigue in patients with multiple sclerosis. A multidimensional comparison with patients with chronic fatigue syndrome and healthy subjects. Arch Neurol. 1996 Jul;53(7):642-9. http://www.ncbi.nlm.nih.gov/pubmed/8929171