Background: Multiple sclerosis (MS) is a chronic demyelinating neurological disease afflicting young and middle-aged adults, resulting in problems with coordination, strength, cognition, affect, and sensation.Objective: The objective of this study was to determine whether a ginkgo extract (EGb 761) improved functional performance in individuals with MS.Design: This study used a double-blind, placebo-controlled, parallel group design. The end point was change between baseline (ie, preintervention) and follow-up evaluation following a regimen of four tablets per day at 60 mg per tablet for four weeks.Setting: The study was conducted in academic and clinical-based settings.Patients/Participants: Twenty-two individuals with MS were randomly assigned to either the treatment or control condition. Groups did not differ with respect to age, IQ, and education.Intervention: Half of the subjects received 240 mg per day of ginkgo special extract (EGb 761), and the other half received 0 placebo.Main Outcome Measure: The main outcome measures assessed depression (Center for Epidemiologic Studies of Depression Scale [CES-D]), anxiety (State-Trait Anxiety Inventory [STAI]), fatigue (Modified Fatigue Impact Scale [MFIS]); symptom severity (Symptom Inventory [SI]) and functional performance (Functional Assessment of Multiple Sclerosis [FAMS]).Results: The ginkgo group had significantly more individuals showing improvement on four or more measures with improvements associated with significantly larger effect sizes on measures of fatigue, symptom severity, and functionality. The ginkgo group also exhibited less fatigue at follow-up compared with the placebo group.Conclusions: This exploratory pilot study showed that no adverse events or side effects were reported and that ginkgo exerted modest beneficial effects on select functional measures (eg, fatigue) among some individuals with MS.

The longitudinal course of subjective and objective neuropsychological functioning, psychological functioning, disability level, and employment status in chronic fatigue syndrome (CFS) was examined. The relations among several key outcomes at follow-up, as well as the baseline characteristics that predict change (e.g., improvement), were also evaluated. The study sample consisted of 35 individuals who met the 1988 and 1994 CFS case definition criteria of the Centers for Disease Control (CDC) at intake. Participants were evaluated a mean of 41.9 (SEM = 1.7) months following their initial visit (range = 24-63 months). Results indicated that objective and subjective attention abilities, mood, level of fatigue, and disability improve over time in individuals with CFS. Moreover, improvements in these areas were found to be interrelated at follow-up. Finally, psychiatric status, age, and between-test duration were significant predictors of outcome. Overall, the prognosis for CFS appears to be poor, as the majority of participants remained functionally impaired over time and were unemployed at follow-up, despite the noted improvements.

OBJECTIVETo determine whether a course of Feldenkrais bodywork would result in significant improvement in physical, mood symptoms and functioning in multiple sclerosis (MS) patients beyond the effects observed using a sham condition (nontherapeutic bodywork).DESIGNThe bodywork method used was the Feldenkrais method. Subjects were randomly assigned to 1 of 2 groups in a crossover design to control for order effects of treatment. Half of the subjects received 8 weeks of sham sessions followed by 8 weeks of Feldenkrais sessions. The other half of the subjects received Feldenkrais sessions first and then sham. All subjects completed the outcome measures prior to the first course of treatment, in between Feldenkrais and sham, and at study completion.SETTINGParticipants were recruited from a regional MS clinic and were administered bodywork treatment and outcome measures in a bodywork practitioner's office.SUBJECTSTwenty individuals with clinically definite MS and disability status scores between 2.0 and 6.0 participated.OUTCOME MEASURESNine-hole pegboard test of hand dexterity, Hospital Anxiety and Depression Scale, MS self-efficacy scale, MS Symptom Inventory, MS Performance Scales, and the Perceived Stress Scale.RESULTSThe only significant differences were observed for perceived stress and lowered anxiety after Feldenkrais sessions. There were nonsignificant trends toward higher self-efficacy after both Feldenkrais and sham sessions. MS symptoms, levels of functional ability, and upper extremity performance were not affected by Feldenkrais or sham sessions.

Relatively few studies have examined the personality characteristics of patients with chronic fatigue syndrome (CFS). The personality profiles of 38 CFS subjects were compared with 40 healthy controls and 40 subjects with multiple sclerosis (MS), a chronic illness that shares many symptoms with CFS (e.g., fatigue), but has a known neurological substrate. Subjects were examined within Cloninger's biosocial theory of personality, which delineates basic dimensions of temperament. Both illness groups displayed similarly elevated levels of Harm Avoidance, and lower levels of Reward Dependence as compared with healthy controls. The MS group showed a lower level of Persistence than controls and CFS subjects. Implications for the relationship between chronic illness and personality are discussed.

Objectives-To examine the relation between neuropsychological impairment and functional disability in patients with chronic fatigue syndrome, and determine whether the relation is independent of psychiatric factors.Methods-The subjects were 53 patients with chronic fatigue syndrome and 32 healthy controls who did not exercise regularly. Subjects were administered a structured psychiatric interview and completed questionnaires focusing on depression and functional disability. They also completed a battery of standardised neuropsychological tasks focusing on the cognitive domains that patients with chronic fatigue syndrome experience as particularly difficult: memory (verbal and visual), and attention/concentration. A test score was defined as failing when it was greater than or equal to 2 SD below the mean of the healthy controls after controlling for demographic factors.Results-Those patients with chronic fatigue syndrome with higher numbers of failing neuropsychological test scores reported significantly more days of general inactivity in the past month than those with fewer failing scores. This result remained significant even after partialling out the contribution of the presence of a comorbid axis I psychiatric episode and the overall level of depressive symptomology. Patients with failing verbal memory scores were particularly functionally disabled compared with those with passing scores.Conclusion-A relation was found between cognitive impairment and functional disability which could mot be explained entirely on the basis of psychiatric factors.

Objective-To examine the effect of the presence or absence ofpsychiatric disease on cognitive functioning in chronic fatigue syndrome. Methods-Thirty six patients with chronic fatigue syndrome and 31 healthy controls who did not exercise regularly were studied. Subgroups within the chronic fatigue syndrome sample were formed based on the presence or absence of comorbid axis I psychiatric disorders. Patients with psychiatric disorders preceding the onset chronic fatigue syndrome were excluded. Subjects were administered a battery of standardised neuropsychological tests as well as a structured psychiatric interview. Results-Patients with chronic fatigue syndrome without psychiatric comorbidity were impaired relative to controls and patients with chronic fatigue syndrome with concurrent psychiatric disease on tests of memory, attention, and information processing. Conclusion-Impaired cognition in chronic fatigue syndrome cannot be explained solely by the presence of a psychiatric condition. (J Neurol Neurosurg Psychiatry 1997;62:151-155)

To examine the influence of mode of illness onset on psychiatric status and neuropsychological performance, 36 patients with CFS were divided into two groups: sudden vs gradual onset of symptoms. These two CFS subgroups were compared to each other and to sedentary healthy controls on standardized neuropsychological tests of attention/concentration, information processing efficiency, memory, and higher cortical functions. In addition, the distribution of comorbid Axis I psychiatric disease between the two CFS groups was examined. The rate of concurrent psychiatric disease was significantly greater in the CFS-gradual group relative to the CFS-sudden group. While both CFS groups showed a significant reduction in information processing ability relative to controls, impairment in memory was more severe in the CFS-sudden group. Because of the significant heterogeneity of the CFS population, the need for subgroup analysis is discussed.

This study was conducted to examine the rates of somatization disorder (SD) in the chronic fatigue syndrome (CFS) relative to other fatiguing illness groups.It further addressed the arbitrary nature of the judgments made in assigning psychiatric vs. physical etiology to symptoms in controversial illnesses such as CFS. Patients with CFS (N = 42), multiple sclerosis (MS) (N = 18), and depression (N = 21), were compared with healthy individuals (N = 32) on a structured psychiatric interview. The SD section of the Diagnostic Interview Schedule (DIS) III-R was reanalyzed using different criteria sets to diagnose SD. All subjects received a thorough medical history, physical examination, and DIS interview. CFS patients received diagnostic laboratory testing to rule out other causes of fatigue. This study revealed that changing the attribution of SD symptoms from psychiatric to physical dramatically affected the rates of diagnosing SD in the CFS group. Both the CFS and depressed subjects endorsed a higher percentage of SD symptoms than either the MS or healthy groups, but very few met the strict DSM-III-R criteria for SD. The present study illustrates that the terminology used to interpret the symptoms (ie, psychiatric or physical) will determine which category CFS falls into. The diagnosis of SD is of limited use in populations in which the etiology of the illness has not been established.

This study investigated the relative rates of personality disturbance in chronic fatigue syndrome (CFS). Individuals who met the CDC criteria for CFS were compared to two other fatiguing illness groups, mild multiple sclerosis and depression, as well as sedentary healthy controls. Subjects were administered a structured psychiatric interview to determine Axis I psychiatric disorders and two self-report instruments to assess Axis II personality disorders and the personality trait of neuroticism. The depressed group had significantly more personality disorders and elevated neuroticism scores compared with the other three groups. The CFS and MS subjects had intermediary personality scores which were significantly higher than healthy controls. The CFS group with concurrent depressive disorder (34% of the CFS group) was found to account for most of the personality pathology in the CFS sample. The results are discussed in the context of the relationship between personality variables and fatiguing illness.

Because depression is commonly observed in the chronic fatigue syndrome (CFS), the present study sought to determine whether the symptom pattern is similar to that seen in clinically depressed subjects (DEP). Individuals with multiple sclerosis (MS) were chosen as an additional comparison group because MS is a fatiguing illness of known organic etiology. The Beck Depression Inventory (BDI) was used to compare categories of depressive symptomatology. Absolute scores on the BDI were higher for the depressed group on mood and self-reproach symptoms, but were not higher than the CFS group on somatic and vegetative items. Analysis of symptoms as a percentage of total BDI score revealed no significant differences in mood or vegetative items among the three groups. The CFS and MS groups exhibited a significantly lower percentage of self-reproach symptoms than DEP, whereas the DEP group showed a lower percentage of somatic symptoms than the CFS and MS groups.

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.

To examine the degree and nature of cognitive impairments in chronic fatigue syndrome, a comprehensive neuropsychological battery was given to patients with chronic fatigue syndrome, multiple sclerosis, depressed patients, and healthy controls. The battery included tests of attention and concentration, information processing speed, verbal and visual memory, intellectual ability, and concept formation. Measures of depression and anxiety were also obtained. The chronic fatigue syndrome group did not differ from the depressed group in overall neuropsychological performance, but differed from the multiple sclerosis and control groups. The most significant impairment was in information processing speed in the chronic fatigue syndrome group. Depression and anxiety were not related to neuropsychological performance. The influence of reduced information processing on other areas of cognition is discussed.

Chronic fatigue syndrome (CFS) is a heterogeneous illness characterized by a high prevalence of psychiatric problems. We reasoned that we could reduce heterogeneity by excluding patients with psychiatric problems preceding CFS. We compared the functional status, mood, fatigue level, and psychiatric status of this more homogeneous group of CFS patients with the same parameters in patients with mild multiple sclerosis and in patients with major depression or dysthymia. Patients with CFS and those with multiple sclerosis were similar in terms of level of anger, severity of depression, level of anxiety, and frequency of current psychiatric diagnoses. Patients with CFS resembled depressed patients in having impaired vigor and experiencing substantial fatigue and confusion--problems constituting part of the case definition of CFS. The group with CFS was not psychologically vulnerable before the development of this condition and maintained adequate networks of social support despite disabling illness. Stratification to exclude patients with prior psychiatric disease and those with mild CFS allowed us to define a group of patients with CFS who more resembled patients with mild MS than patients with major depression or dysthymia and thus were more likely to have illness with an infectious or immunologic cause. Use of such a stratification strategy should prove important in testing of the viral/immunologic hypothesis of the etiology of CFS.

Chronic fatigue syndrome (CFS) is an illness that results in debilitating fatigue as well as rheumatological, infectious, and neuropsychiatric symptoms. The present paper is a brief overview of the neuropsychological and psychiatric research on CFS. Studies from our laboratory contrasting CFS with patients with multiple sclerosis, depression, and healthy controls are detailed. Our hypothesis of the neuropsychological impairments in CFS is discussed.

OBJECTIVE:To compare the cognitive performance of subjects with chronic fatigue syndrome (CFS), multiple sclerosis (MS), and healthy controls. All subjects were matched for age, education, and verbal intelligence, as previous neuropsychological studies of CFS had not used appropriate control groups.DESIGN:Case-control design. All subjects were given a neuropsychological battery and the test scores were compared among the groups.SETTING:Subjects with CFS and subjects with MS were recruited from private and institutional practice and from the community. Healthy subjects were recruited from the community. PATIENTS/OTHER PARTICIPANTS: Twelve subjects (all female) with CFS participated in the study. Chronic fatigue syndrome was diagnosed in these patients in accordance with the requirements outlined by the Centers for Disease Control as modified subsequently to not exclude patients with concurrent depression and/or anxiety. All subjects with CFS were referred for a neuropsychological examination to assess persistent cognitive complaints. Eleven subjects (10 female, one male) with the diagnosis of clinically stable MS were chosen from clinics and the community because of complaints of mild to moderate cognitive impairment. The subjects with MS and 11 healthy volunteers (10 female, one male) were matched to the group with CFS by age, education, and estimated verbal intelligence (based on the Vocabulary subtest of the Wechsler Adult Intelligence Scale-Revised). The subjects with MS had a mean Kurtzke Expanded Disability Status Scale score of 4.95 (SD, 1.95; range, 2.0 to 7.5). As a result of the matching procedure, there were no differences among the three groups in age (F[2,31] = 0.32), education (F[2,31] = 0.80), and verbal intelligence (F[2,31] = 0.31).INTERVENTIONS:None.MAIN OUTCOME MEASURES:These measures included the Beck Depression Inventory (BDI), the Paced Auditory Serial Addition Test (PASAT), Digit Span Test, and the Similarities Test of Verbal Abstract Reasoning.RESULTS:The mean number of correctly identified responses collapsed across the four PASAT trials was significantly different across groups (F[2,31] = 4.03; P < .05). While the CFS and MS groups did not differ from each other, subjects with CFS (SEM, 124.2 +/- 6.4) and subjects with MS (SEM, 112.9 +/- 10.9) scored significantly below controls (SEM, 146.4 +/- 6.4) (Fisher's Protected Least Significant Difference test; P < .05). There were significant differences among the three groups on mean Digit Span Test performance (F[2,31] = 5.5; P < .01). While the CFS and MS group did not differ significantly from each other, only the CFS group was significantly lower than control (Fisher's Protected Least Significant Difference test; P < .05). Mean performance on the Similarities test did not differ among the three groups (F = 0.58). In addition, there were significant differences among the three groups in mean BDI scores (F[2,31] = 7.6; P < .01). The CFS and MS groups did not differ significantly from each other, and both groups showed a statistically significantly elevated mean BDI score relative to the control group (Fisher's Protected Least Significant Difference test; P < .05). No significant correlations were found between BDI scores and PASAT total scores (CFS, r = -.21; MS, r = .13; control, r = .27), or between BDI and Digit Span Test (CFS, r = -.32; MS, r = -.40; control, r = -.19). Results of the PASAT and Digit Span Test were significantly correlated in the CFS group (r = .71; P < .01), but not in the MS (r = .06) or control groups (r = .49).CONCLUSIONS:These results indicate that subjects with CSF and subjects with MS show significant impairment on a test of complex concentration when compared with appropriate controls. The data suggest that subjects with CFS and subjects with MS have difficulty on tasks that require the simultaneous processing of complex cognitive information. Selective impairment in information processing efficiency may lie at the