Pain, fatigue, and sleep in eosinophilia-myalgia syndrome: relationship to neuropsychological performance.

Cognitive problems are frequently reported in patients with eosinophilia-myalgia syndrome (EMS). This is the first study to explore, in EMS, the relationship between specific neuropsychological deficits and fatigue and pain. Relationships among depression, sleep disturbance, and neuropsychological deficits in EMS were also examined. Neither fatigue nor pain was correlated with memory impairment. Sleep disturbance was significantly correlated with verbal memory impairment, but not with deficits in visuospatial memory. These results suggest that cognitive loss in EMS cannot be attributed to pain or fatigue. Although some aspects of memory impairment may be associated with disturbed sleep, visual memory deficits are clearly independent of sleep deficits and may result from direct effects of the disease on the central nervous system.

Eosinophilia-myalgia syndrome: selective cognitive impairment, longitudinal effects, and neuroimaging findings.

OBJECTIVE: To identify the specific nature of the neurocognitive impairments of eosinophilia-myalgia syndrome (EMS) in an unselected population, and to present longitudinal patterns. METHODS: A consecutive sample of 23 patients with EMS and 18 age and education matched control subjects were assessed on a comprehensive neuropsychological battery. Longitudinal results were gathered from six patients. RESULTS: Neurocognitive impairments were found which represent a subset of deficits reported in previous group and case study reports. Deficits were limited to complex visual memory, conceptual set shifting, and attention, which suggest a selective dysexecutive syndrome. The motor slowing and verbal memory deficits previously reported were not found. Although depression, fatigue, sleep deprivation, and pain were significant symptoms, they were unassociated with deficits with the exception of an association of depression with one deficit. There was no pattern of overall decline over time in a subset of the group, although considerable heterogeneity in the longitudinal patterns of neurocognitive tests was found. Abnormalities of white matter appeared in the MRI of eight of 12 patients. CONCLUSIONS: The neurocognitive and neuroimaging findings contribute to the evidence which indicates that the neural substrate of EMS is white matter damage.

Cognitive deficits in a murine model of the eosinophilia-myalgia syndrome: a preliminary report.

The described study was to determine the effects of chronic exposure to 1,1'-ethylidenebis[L-tryptophan] (EBT), a tryptophan contaminant, on cognitive behavior of female C57BL/6 (C57) mice. EBT (also designated as "peak E" or "peak 97") is one of several compounds that are suspect in the eosinophilia-myalgia syndrome (EMS). Groups of female C57 mice (12/group) were injected IP with saline (SAL), tryptophan (TRY), EBT, or an EBT + tryptophan combination (EBT + TRY) over a 6-week period. Previous experiments established that the dosing conditions produce several characteristics of EMS, including dermal inflammation and fibrosis, increased dermal mast cells, and increased levels of quinolinic acid. The mice exposed to EBT + TRY were abnormal during the solution of a Morris water maze problem. First, they had a shorter latency to locate the submerged platform goal during the initial day of training compared to SAL or TRY mice; secondly, they did not show the systematic reduction in latency to locate the platform goal across days of training noted for SAL or TRY mice. These abnormalities occurred in the absence of altered body weight or gross motor activity during the treatment procedure, or in the animal's swim speeds at the time of testing, 3 days after termination of treatment. The results suggest that prolonged exposure to EBT + TRY can alter the reaction to a stressful environment and can alter cognitive behavior.

Psychiatric aspects of the eosinophilia-myalgia syndrome.

The eosinophilia-myalgia syndrome (EMS) is a rare systemic disease caused by presumably contaminated L-tryptophan. Thirteen outpatients with EMS were found to have a high degree of depression, anxiety, and difficulty adjusting to illness. Pre-EMS history of major depression but not EMS severity predicted poor adjustment to illness.

Neuropsychological and emotional sequelae of eosinophilia-myalgia syndrome.

In recent years there has been an increasing number of cases presenting with a newly recognized multiple systemic disorder, Eosinophilia-Myalgia Syndrome (EMS), in the United States. This report documents demographic data and scores from intelligence, memory, neuropsychological, and achievement testing from eight patients, and Minnesota Multiphasic Personality Inventory-2 (MMPI-2) profiles obtained by nine patients, all of whom were referred to a doctoral level neuropsychologist in private practice. Intelligence scores revealed a Full Scale Mean IQ of 90.6, with a Verbal IQ Mean of 92.3, and a Performance IQ Mean of 90.9 for the Wechsler Adult Intelligence Scale--Revised. For the Wechsler Memory Scale, the patients earned a mean Memory Quotient of 80.5. On the Halstead-Reitan Neuropsychological Test Battery, the patients earned a mean Impairment Index of .82, and Achievement Test scores on the Wide Range Achievement Test--Revised ranged from a grade level of 4th grade to a grade level of above 12th grade for reading, and from a grade level of 5th grade to a grade level of above 12th grade for arithmetic. Both the modal and mean MMPI-2 profiles had 2-3/3-2 two point codes suggesting feelings of depression, tension, nervousness, fatigue, helplessness, somatic complaints and overcontrol. In all, the neuropsychological, intellectual, memory and achievement test scores suggested a pattern of moderate to severe impairment and the MMPI-2 test scores suggested a pattern of moderate emotional disturbance.

Neurocognitive dysfunction in the eosinophilia-myalgia syndrome.

The eosinophilia-myalgia syndrome (EMS), a multisystem disorder associated with ingestion of L-tryptophan-containing products, causes sclerodermatous skin changes, cardiopulmonary disease, and a range of peripheral neurologic complications. Many EMS patients also report cognitive difficulty in association with the disease. To determine the frequency of objective neurocognitive impairment in EMS patients with subjective complaints of cognitive difficulty and to assess the relationship of neurocognitive loss with demographic features, degree of peripheral eosinophilia, and psychiatric diagnosis, we compared 24 EMS patients with 32 age- and education-matched healthy controls, using a comprehensive neuropsychological test battery. EMS patients additionally underwent a psychiatric interview and rheumatologic evaluation. Sixty-two percent (15 of 24) of the EMS patients demonstrated neurocognitive deficits. Compared with healthy controls, EMS patients demonstrated significant impairment on tests of verbal memory, visual memory, conceptual reasoning, and motor speed. Cognitively impaired EMS patients did not differ from those without cognitive impairment on demographic markers, degree of peripheral eosinophilia, presence of peripheral neuropathy, or frequency of concurrent psychiatric disorder, including major depression. These data support the hypothesis that EMS is associated with an encephalopathy in addition to its previously recognized peripheral neuropathy and other rheumatologic manifestations.

Central nervous system involvement in the eosinophilia-myalgia syndrome.

A patient with eosinophilia-myalgia syndrome developed progressive central nervosa system involvement that did not improve despite discontinuation of L-tryptophan therapy. Neurologic impairment was manifested initially by spastic monoparesis, which was improved by treatment with methyl-prednisolone and hydroxyurea. Recurrence of weakness was accompanied by gait ataxia, dysphagia, and complaints of a gradual decline in memory and concentration. Neuropsychological testing identified a broad pattern of cognitive deficits suggestive of a subcortical dementia, and magnetic resonance imaging demonstrated multiple high-signal lesions in the white matter. Cognitive deficits appear to be underrecognized in patients with the eosinophilia-myalgia syndrome. The response of our patient's initial symptoms to corticosteroid therapy suggests a possible role for autoimmune mechanisms in the pathogenesis of central nervous system involvement in the eosinophilia-myalgia syndrome. Neuropsychological evaluation should be performed in patients with cognitive complaints to delineate the full spectrum of central nervous system impairment associated with the eosinophilia-myalgia syndrome.