Category: Neurology

A comparative review of systemic and neurological symptomatology in 12 outbreaks collectively described as chronic fatigue syndrome, epidemic neuromyasthenia, and myalgic encephalomyelitis

Abstract:

Outbreaks of illnesses of unknown etiology typified by a chronic relapsing course of constitutional symptoms and nervous system involvement have collectively been referred to as chronic fatigue syndrome, epidemic neuromyasthenia, and myalgic encephalomyelitis. To examine heterogeneity of clinical presentation, a comparative review was undertaken for 12 well-documented outbreaks reported since 1934.

A systemic syndrome characterized by excessive fatigue, myalgias, headache, low-grade fever, and other constitutional symptoms was common to cases in all outbreaks. However, marked heterogeneity in the range of neurological features was apparent.

On the basis of predominant neurological manifestations, outbreaks could be grouped into four levels of increasing neurological involvement: affective neuropsychological changes (level I); prominent cutaneous sensory symptoms with both affective and cognitive neuropsychological changes (level II); marked objective paresis with cutaneous sensory as well as affective and cognitive neuropsychological changes (level III); and cutaneous sensory, affective and cognitive neuropsychological, posterior column, cranial nerve, and mixed upper and lower motor neuron changes (level IV). Groups with the most prominent objective neurological findings (levels III and IV) comprised exclusively outbreaks reported between the 1930s and 1950s. All but one outbreak in groups with less prominent neurological findings (levels I and II) were reported between the 1960s and 1980s; a range of neurological features was observed for these groups.

Because a complete neurological examination is not emphasized as part of the diagnostic workup in current outbreaks, it is possible that less obvious neurological findings may be overlooked. Careful evaluation of neurological features in epidemic and endemic cases of what is now called chronic fatigue syndrome may be one approach to distinguishing subtypes of what has been described in the past as a nosological entity.

 

Source: Briggs NC, Levine PH. A comparative review of systemic and neurological symptomatology in 12 outbreaks collectively described as chronic fatigue syndrome, epidemic neuromyasthenia, and myalgic encephalomyelitis. Clin Infect Dis. 1994 Jan;18 Suppl 1:S32-42. http://www.ncbi.nlm.nih.gov/pubmed/8148451

 

A controlled study of brain magnetic resonance imaging in patients with the chronic fatigue syndrome

Abstract:

Two neuroradiologists compared the brain MR scans of 52 patients with the CDC criteria for the chronic fatigue syndrome (CFS) with those of 52 age and sex matched controls who had undergone imaging because of histories of head trauma or headache.

CFS patients had significantly more abnormal scans than controls–27% vs 2%. Abnormalities seen were foci of increased white matter T2 signal in 9 CFS patients and one control and ventricular or sulcal enlargement in 5 CFS patients. Follow up of patients with subcortical signal hyperintensities revealed 3 who had symptoms suggestive of other known medical causes of what appeared to be CFS.

The data indicate that some CFS patients have some organic problem manifesting itself on neuroimaging. But, finding MR abnormalities should warn the physician that the patient’s symptoms may be secondary to some other medical illness and not simply primary CFS.

 

Source: Natelson BH, Cohen JM, Brassloff I, Lee HJ. A controlled study of brain magnetic resonance imaging in patients with the chronic fatigue syndrome. J Neurol Sci. 1993 Dec 15;120(2):213-7. http://www.ncbi.nlm.nih.gov/pubmed/8138812

 

Behavioural problems associated with the chronic fatigue syndrome

Abstract:

Disturbances of memory, concentration and motor function are often reported by patients with the chronic fatigue syndrome (CFS). The present study objectively evaluated these behavioural problems using a computerized test battery measuring memory, attention and motor skills.

Fifty-seven CFS patients were compared with 19 matched controls and all subjects completed the performance test battery and filled in questionnaires measuring psychopathology and mood. The patients reported significantly higher levels of depression, anxiety, physical symptoms and cognitive failures than the controls. Similarly, they reported more negative affect at the time of testing.

The patients were slower on psychomotor tasks, showed increased visual sensitivity and impaired attention. Digit span and free recall were not impaired but retrieval from semantic memory and logical reasoning were slower. None of the performance differences between patients and controls could be attributed to differences in psychopathology. These results agree with recent findings from other laboratories, and it is now time to consider the nature of the neurological dysfunction underlying these effects.

 

Source: Smith AP, Behan PO, Bell W, Millar K, Bakheit M. Behavioural problems associated with the chronic fatigue syndrome. Br J Psychol. 1993 Aug;84 ( Pt 3):411-23. http://www.ncbi.nlm.nih.gov/pubmed/8401992

 

Memory deficits associated with chronic fatigue immune dysfunction syndrome

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.

 

Source: Sandman CA, Barron JL, Nackoul K, Goldstein J, Fidler F. Memory deficits associated with chronic fatigue immune dysfunction syndrome. Biol Psychiatry. 1993 Apr 15-May 1;33(8-9):618-23. http://www.ncbi.nlm.nih.gov/pubmed/8329493

 

Abnormal arginine-vasopressin secretion and water metabolism in patients with postviral fatigue syndrome

Abstract:

Water metabolism and the responses of the neurohypophysis to changes in plasma osmolality during the water loading and water deprivation tests were studied in nine patients with postviral fatigue syndrome (PVFS) and eight age and six-matched healthy control subjects. Secretion of arginine-vasopressin (AVP) was erratic in these patients as shown by lack of correlation between serum and urine osmolality and the corresponding plasma AVP levels. Patients with PVFS had significantly low baseline arginine-vasopressin levels when compared with healthy subjects. Patients with PVFS as a group also showed evidence of increased total body water content. These results may be indicative of hypothalamic dysfunction in patients with PVFS.

 

Source: Bakheit AM, Behan PO, Watson WS, Morton JJ. Abnormal arginine-vasopressin secretion and water metabolism in patients with postviral fatigue syndrome. Acta Neurol Scand. 1993 Mar;87(3):234-8. http://www.ncbi.nlm.nih.gov/pubmed/8475696

 

The neuropsychiatry of chronic fatigue syndrome

Abstract:

This paper explores the relationship between chronic fatigue syndrome (CFS) and psychiatric disorder, with special reference to neuropsychiatry, Topics reviewed include (1) epidemiological evidence of central disorder in CFS; (2) evidence from longitudinal studies of an interaction between vulnerability to CFS and psychiatric disorder; and (3) evidence from neuroimaging, neuropsychology, neurophysiology and neuroendocrinology of disordered CNS function in CFS. The most impressive evidence of CNS disturbance comes from neuroendocrinological studies, which suggest a role of hypothalamic disorder as a final common pathway for CFS. It is concluded that the equal and opposite tendencies of psychiatry to be ‘brainless’ and neurology to be ‘mindless’ have led to needless controversy over the nature of CFS. Now that the contributions of psychiatric disorder to CFS, and of neurobiological dysfunction to psychiatric disorder, are both established, it will be possible to make real advances in understanding the nature of CFS.

 

Source: Wessely S. The neuropsychiatry of chronic fatigue syndrome. Ciba Found Symp. 1993;173:212-29; discussion 229-37. http://www.ncbi.nlm.nih.gov/pubmed/8491099

 

Enteroviruses and postviral fatigue syndrome

Abstract:

Postviral fatigue syndrome (PFS) occurs both in epidemics and sporadically. Many of the original epidemics were related to poliomyelitis outbreaks which either preceded or followed them.

The core clinical symptoms are always the same: severe fatigue made worse by exercise, myalgia, night sweats, atypical depression and excessive sleep. The other common symptoms include dysequilibrium disorders and irritable bowel syndrome.

We have detected enteroviral genome sequences in muscle biopsies from cases of PFS, using specific enteroviral oligonucleotide primers in the polymerase chain reaction (PCR). In addition, whole virus particles can be demonstrated in PCR-positive muscle, using solid-phase immuno-electron microscopy.

An increase in the number and size of muscle mitochondria was found in 70% of PFS cases, suggesting an abnormality in metabolic function. Evidence of hypothalamic dysfunction was present, particularly involving 5-hydroxytryptamine metabolism.

A putative model of PFS, based on persistent enteroviral infection in laboratory mice, revealed resolving inflammatory lesions in muscle with, however, a marked increase in the production of certain cytokines in the brain. This model may help to explain the pathogenesis of PFS.

 

Source: Behan PO, Behan WM, Gow JW, Cavanagh H, Gillespie S. Ciba Found Symp. 1993;173:146-54; discussion 154-9. http://www.ncbi.nlm.nih.gov/pubmed/8387908

 

Neuro-psychiatric aspects of chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is easily differentiated from various neurological organic disorders by conventional clinical examinations. The most important disease for distinguishment from CFS is fibromyalgia syndrome, in which the prominent and cardinal feature is a deprivation of stage 4 slow wave sleep.

Experimentally, the sleep disturbance in controls can induce general myalgia, muscle tender points, severe fatigue and stiffness on awakening. The EEG abnormality is slow alpha wave contaminants on slow wave background, which is identical to EEG of CFS. The results clearly imply that CFS is not a hysterical or psychogenic disease, and that fibromyalgia may be a central fundamental of CFS.

Fibromyalgia, however, has distinct features such as no antecedent inflammatory process and no endemics. Therefore, the syndrome has features distinct from, in addition to common features to CFS. It is also very difficult to distinguish CFS from depression. The above-mentioned features can be observed in depression. Now, study of brain blood flow or metabolism by PET or SPECT can be a possible tool for establishment of the CFS identity.

 

Source: Shimizu T. Neuro-psychiatric aspects of chronic fatigue syndrome. Nihon Rinsho. 1992 Nov;50(11):2630-4. [Article in Japanese] http://www.ncbi.nlm.nih.gov/pubmed/1287239

 

Assessment of regional cerebral perfusion by 99Tcm-HMPAO SPECT in chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) is a severely disabling illness of uncertain aetiology. It is characterized by a chronic, sustained or fluctuating sense of debilitating fatigue without any other known underlying medical conditions. It is also associated with both somatic and neuropsychological symptoms. Both physical and laboratory findings are usually unremarkable.

Regional cerebral blood flow (rCBF) was assessed in 60 clinically defined CFS patients and 14 normal control (NC) subjects using 99Tcm-hexamethylpropyleneamine oxime (99Tcm-HMPAO) single photon emission computed tomography (SPECT). Compared with the NC group, the CFS group showed significantly lower cortical/cerebellar rCBF ratios, throughout multiple brain regions (P < 0.05). Forty-eight CFS subjects (80%) showed at least one or more rCBF ratios significantly less than normal values.

The major cerebral regions involved were frontal (38 cases, 63%), temporal (21 cases, 35%), parietal (32 cases, 53%) and occipital lobes (23 cases, 38%). The rCBF ratios of basal ganglia (24 cases, 40%) were also reduced. 99Tcm-HMPAO brain SPECT provided objective evidence for functional impairment of the brain in the majority of the CFS subjects. The findings may not be diagnostic of CFS but 99Tcm-HMPAO SPECT may play an important role in clarifying the pathoaetiology of CFS. Further studies are warranted.

 

Source: Ichise M, Salit IE, Abbey SE, Chung DG, Gray B, Kirsh JC, Freedman M. Assessment of regional cerebral perfusion by 99Tcm-HMPAO SPECT in chronic fatigue syndrome. Nucl Med Commun. 1992 Oct;13(10):767-72. http://www.ncbi.nlm.nih.gov/pubmed/1491843

 

Attention and short-term memory in chronic fatigue syndrome patients: an event-related potential analysis

Abstract:

We recorded event-related brain potentials (ERPs) from 13 patients with chronic fatigue syndrome (CFS) and 13 matched normal controls. To assess attentional and memory deficits in CFS patients, we used a short-term memory task in which events occurred in different spatial locations and the patients made a rapid-response (RT) when a letter in a relevant location matched a letter in the prememorized set (Attention paradigm).

Time-on-task effects on the ERP and behavioral measures were assessed over the 2 1/4-hour duration of this task. Both groups also performed a visual Oddball paradigm, with an RT, before and after the Attention paradigm. The patients’ RTs were much more variable and, in nine of 13 cases, slower than the mean RT of the controls in both paradigms.

The patients’ memory performance was not significantly different from that of the controls and there were no group differences in the overall amplitude, latency, or scalp distribution of the N1, P2, N2, or P300 components of the ERP in either paradigm. The ERP and performance data from both paradigms suggest that perceptual, attentional, and short-term memory processes were unaffected in CFS patients and that the differences were limited to response-related processes.

 

Source: Scheffers MK, Johnson R Jr, Grafman J, Dale JK, Straus SE. Attention and short-term memory in chronic fatigue syndrome patients: an event-related potential analysis. Neurology. 1992 Sep;42(9):1667-75. http://www.ncbi.nlm.nih.gov/pubmed/1513453