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.

Cognitive functioning of patients with chronic fatigue syndrome. Johnson SK, DeLuca J, Fiedler N, Natelson BH. Clinical Infectious Diseases 1994; 18(Supp 1): S84-5.

Abstract: Neuropsychological problems are a distressing and frequent component of the symptom complex associated with chronic fatigue syndrome. Objective assessment of these difficulties is essential to understanding the nature of this illness. Results of the studies discussed in this paper suggest that impaired information processing, rather than primary memory dysfunction, may be at the root of the cognitive problems that afflict so many patients with CFS.

Relationships of cognitive difficulties to immune measures, depression and illness burden in CFS. Lutgendorf S, Klimas NG, Antoni M, Brickman A, Fletcher MA. Journal of Chronic Fatigue Syndrome 1995; 1(2): 23-41.

Abstract: OBJECTIVE. We related the subjective assessment of cognitive difficulties with lymphocyte phenotypes, cell-mediated immunity (CMI), cytokine and neopterin levels in patients with chronic fatigue syndrome (CFS), in order to determine if CFS patients complaining of greater cognitive difficulties would show greater impairments in cell-mediated immunity and a greater degree of immune system dysregulation, and to determine if these cognitive difficulties would correlate with the other non-affective measures of CFS-associated illness burden. We also assessed whether these relationships would hold independent of depression in two ways, by statistically covarying depression severity scores and by comparing subsets of CFS patients with and without a concurrent diagnosis of major depressive disorder. DESIGN. A case series of CFS patients. SETTING. Outpatient tertiary referral clinic at the Unversity of Miami School of Medicine, Miami, FL. PATIENTS. Consecutive sample of 65 patients who were referred as CFS to the University of Miami Diagnostic Immunology Clinic, who met the Centers for Disease Control and Prevention (CDC) criteria for diagnosis of CFS and consented to participate. MAIN MEASURES. Self-assessment of cognitive difficulties, depression and illness burden, clinician-assessed depression and CFS symptoms, lymphocyte phenotype, proliferative response to mitogens, serum levels of cytokines and neopterin. RESULTS. Among CFS patients, high Cognitive Difficulty Scale (CDS) scores were significantly related to lower lymphocyte proliferative responses to mitogens, higher neopterin levels, and higher CD4 and lower CD8 lymphocyte counts. These relationships, with the exception of T cell subset percentages, were maintained when depression severity was used as a co-variate. High CDS scores were also significantly related to lower Karnofsky scores, and greater illness burden as measured by the Sickness Impact Profile. Evidence is presented that CFS patients with higher cognitive difficulty scores have more immune and clinical dysfunction than those with less cognitive difficulty, and that these relationships are independent of depression. These observations provide support for the concept that although both cognitive difficulties and immunologic abnormalities, such as immune activation and impaired cell-mediated immunity, may represent secondary sequelae to the same event(s), they are not likey to be secondary sequelae to depression.

Cognitive deficits in patients with chronic fatigue syndrome. Marcel B, Komaroff AL, Fagioli LR, Kornish RJ, Albert MS. Biological Psychiatry 1996; 40(6): 535-41.

Abstract: Twenty-nine subjects with chronic fatigue syndrome (CFS) and 25 healthy control subjects were administered a lengthy neuropsychological battery that included standard neuropsychological tests and a computerized set of tasks that spanned the same areas of ability. The primary significant differences between patients and controls were found on tests of learning and memory. These differences remained when the degree of psychiatric symptomatology in the subjects was covaried. Patients on and off psychoactive medications did not differ in their performance on these tasks. These results suggest that at least a subset of CFS patients may experience significant impairments in learning and memory.

Cognitive functioning in patients with chronic fatigue syndrome. Michiels V. Cluydts R, Fischler B, Hoffman G, LeBon O, De Meirleir K. Journal of Clinical and Experimental Neuropsychology 1996; 18(5): 666-677.

Abstract: A comprehensive battery of neuropsychological tests was administered to 35 outpatients suffering from Chronic Fatigue Syndrome (CFS). They were compared to 33 normal controls matched for age, gender, intelligence, and education. The patients displayed psychomotor slowing and impaired attention. The learning rate of verbal and visual material for patients with CFS was slower, and delayed recall of verbal and visual information was impaired. Because there was a high variability in cognitive impairment within the CFS group, it would be inappropriate to generalize results to the entire CFS population. Two neuropsychological variables indicating aspects of psychomotor performance and verbal memory were found to discriminate best between patients and controls.

Sensory and cognitive event-related potentials in myalgic encephalomyelitis. Prasher D, Smith A, Findley L. Journal of Neurology Neurosurgery and Psychiatry 1990; 53: 247-53.

Abstract: Myalgic Encephalomyelitis (ME) is a form of post viral fatigue syndrome resulting in myalgia and fluctuating fatiguability. Symptoms reflecting central nervous system dysfunction are common and include muscle weakness, headache, sensory disturbances, poor short term memory and impairment of concentration. In view of the fact that sensory and cognitive disturbances are experienced by many patients objective evidence was sought with multi-modality sensory evoked potentials and auditory event-related cognitive potentials in a group of ME patients both with and without the enteroviral antigen, VP1 test positive. The auditory brainstem, median nerve somatosensory and pattern reversal checkerboard visual potentials were normal for all 37 patients tested. In contrast to the sensory potentials significant differences in the mean latencies of the cognitive potential N2 and P3 were found. Reaction times were also significantly prolonged but the performance in terms of error was not significantly affected. No significant difference emerged in any of the parameters for the VP1 test. P3 was abnormal in latency or amplitude in 36% of the VP1 positive patients for the frequency discrimination task and 48% for the more difficult duration discrimination task. The abnormalities indicate attentional deficits in some patients and slower speed of information processing in others. The prolonged latencies observed in these patients have not been observed in patients with depression in many other studies.

Memory deficits associated with chronic fatigue immune dysfunction syndrome. Sandman CA, Barron JL, Nackoul K, Goldstein J, Fidler F. Biological Psychiatry 1993; 33(8-9): 618-23.

Abstract: Performance on tests of memory in 39 patients who met Center for Disease Control (CDC) criteria for chronic fatigue immune dysfunction syndrome (CFIDS) was compared with 23 depressed patients (DSM-III-R) and 129 healthy controls. Although the CFIDS patients had normal neuropsychological profiles, they significantly overestimated their ability (metamemory), performed significantly worse on tests of recall as context increased (e.g., recognition), made more errors when rehearsal was prevented, and had delayed mental scanning as memory load increased. The overall pattern indicated that CFIDS patients had a significant memory deficit, far worse than implied by CDC criteria. The pattern for CFIDS patients was consistent with temporal-limbic dysfunction and significantly different than depressed patients and control subjects.

The psychiatric status of patients with the chronic fatigue syndrome. Hickie I, Lloyd A, Wakefield D, Parker G. British Journal of Psychiatry 1990; 156: 534-40.

Abstract: The prevalence of psychiatric disorder in 48 patients with chronic fatigue syndrome (CFS) was determined. Twenty-two had had a major depressive (non-endogenous) episode during the course of their illness, while seven had a current major (non-endogenous) depression. The pre-morbid prevalence of major depression (12.5%) and of total psychiatric disorder (24.5%) was no higher than general community estimates. The pattern of psychiatric symptoms in the CFS patients was significantly different to that of 48 patients with non-endogenous depression, but was comparable with that observed in other medical disorders. Patients with CFS were not excessively hypochondriacal. We conclude that psychological disturbance is likely to be a consequence of, rather than an antecedent risk factor to the syndrome.

The role of mitochondria in the pathogenesis of neurodegenerative diseases. Manfredi G, Beal MF Department of Neurology and Neuroscience, Weill Medical College of Cornell University and the New York Hospital, Cornell Medical Center, New York 10021, USA. gim2004@mail.med.cornell.edu Brain Pathol 2000 Jul;10(3):462-72

A growing body of evidence indicates that mitochondrial dysfunction may play an important role in the pathogenesis of many neurodegenerative disorders. Because mitochondrial metabolism is not only the principal source of high energy intermediates, but also of free radicals, it has been suggested that inherited or acquired mitochondrial defects could be the cause of neuronal degeneration as a consequence of energy defects and oxidative damage. Mitochondrial respiratory chain dysfunction has been reported in association with primary mitochondrial DNA abnormalities, and also as a consequence of mutations in nuclear genes directly involved in mitochondrial functions, such as SURF1, frataxin, and paraplegin. Defects of oxidative phosphorylation and increased free radical production have also been observed in diseases that are not due to primary mitochondrial abnormalities. In these cases, the mitochondrial dysfunction is likely to be an epiphenomenon, which, nevertheless, could be of importance in precipitating a cascade of events leading to cell death. In either case, understanding the role of mitochondria in the pathogenesis of neurodegenerative diseases could be important for the development of therapeutic strategies in these disorders.

Politics, science, and the emergence of a new disease. Jason LE, Richman JA, Friedberg F, et al.  American Psychologist 1997; 52(9): 973-983.

Abstract: Chronic fatigue syndrome (CFS) emerged as a diagnostic category during the last decade. Initial research suggested that CFS was a relatively rare disorder with a high level of psychiatric comorbidity. Many physicians minimized the seriousness of this disorder and also interpreted the syndrome as being equivalent to a psychiatric disorder. These attitudes had negative consequences for the treatment of CFS. By the mid-1990s, findings from more representative epidemiological studies indicated considerably higher CFS prevalence rates. However, the use of the revised CFS case definition might have produced heterogeneous patient groups, possibly including some patients with pure psychiatric disorders. Social scientists have the expertise to more precisely define this syndrome and to develop appropriate and sensitive research strategies for understanding this disease.

In honour of International ME Awareness day An article lists the symptoms of brain injury noting how many of them are seen in ME/ICD-CFS also.

Brain SPECT Abstracts (Choose CFS on the pull down menu)

Detection of intracranial abnormalities in patients with chronic fatigue syndrome: comparison of MR imaging and SPECT. Schwartz RB, Garada BM, Komaroff AL, Tice HM, Gleit M, Jolesz FA, Holman BL. American Journal of Roentgenology 1994; 162(4): 935-41.

Abstract: OBJECTIVE. Chronic fatigue syndrome is a recently characterized condition of unknown origin that is manifested by fatigue, flulike complaints, and neurologic signs and symptoms, including persistent headache, impaired cognitive abilities, mood disorders, and sensorimotor disturbances. This syndrome can be difficult to diagnose clinically or by standard neuroradiologic tests. We performed MR imaging and single-photon emission computed tomography (SPECT) in patients with chronic fatigue syndrome to compare the usefulness of functional and anatomic imaging in the detection of intracranial abnormalities. SUBJECTS AND METHODS. Sixteen patients who fulfilled the Centers for Disease Control, British, and/or Australian criteria for chronic fatigue syndrome had MR and SPECT examinations within a 10-week period. Axial MR and SPECT scans were analyzed as to the number and location of focal abnormalities by using analysis of variance with the Student-Newman-Keuls option. MR imaging findings in patients with chronic fatigue syndrome were compared with those in 15 age-matched control subjects, and SPECT findings in the patients with chronic fatigue syndrome were compared with those in 14 age-matched control subjects by using Fisher's exact test. The findings on MR and SPECT scans in the same patients were compared by using the Wilcoxon matched-pairs signed-ranks test. RESULTS. MR abnormalities consisted of foci of T2-bright signal in the periventricular and subcortical white matter and in the centrum semiovale; there were 2.06 foci per patient, vs 0.80 foci per control subject. MR abnormalities were present in eight (50%) of 16 patients, compared with three (20%) of 15 age-matched control subjects. Neither of these differences reached significance, although the power of the study to detect differences between groups was small. Patients with chronic fatigue syndrome had significantly more defects throughout the cerebral cortex on SPECT scans than did normal subjects (7.31 vs 0.43 defects per subject, p <.001). SPECT abnormalities were present in 13 (81%) of 16 patients, vs three (21%) of 14 control subjects (p < .01). SPECT scans showed significantly more abnormalities than did MR scans in patients with chronic fatigue syndrome (p < .025). In the few patients who had repeat SPECT and MR studies, the number of SPECT abnormalities appeared to correlate with clinical status, whereas MR changes were irreversible. CONCLUSION. SPECT abnormalities occur more frequently and in greater numbers than MR abnormalities do in patients with chronic fatigue syndrome. SPECT may prove to be useful in following the clinical progress of patients with this syndrome.