hypoperfusion – Page 2 – American ME and CFS Society

Chronic fatigue syndrome and depression

Comment on: Cerebral perfusion in chronic fatigue syndrome and depression. [Br J Psychiatry. 2000]

I found MacHale et al’s (2000) discussion of their results confusing. According to the abstract and methods, they screened their patients with chronic fatigue syndrome (CFS) to exclude those with depression. Then they examined this group further using a standardised psychiatric interview (Schedule for Affective Disorders and Schizophrenia), in order to “ exclude subjects with current psychiatric illness, with a particular emphasis on depression”. The data from the Hamilton Rating Scale for Depression are difficult to interpret given the number of illnessrated items, but the scores did not indicate a significant degree of depression either. So, having excluded “subjects with depression or anxiety”, why did the authors claim in their discussion that “the main limitation of the present study is that our CFS subjects had high levels of depression”?

You can read the rest of this comment here: http://bjp.rcpsych.org/content/177/5/470.long

Source: Goudsmit E. Chronic fatigue syndrome and depression. Br J Psychiatry. 2000 Nov;177:470. http://bjp.rcpsych.org/content/177/5/470.long

Cerebral perfusion in chronic fatigue syndrome and depression

Abstract:

BACKGROUND: Patients with chronic fatigue syndrome (CFS) and depressive illness share many, but not all, features.

AIMS: To test the hypothesis that patients with CFS have abnormal cerebral perfusion, that differs from that in patients with depressive illness.

METHOD: We recruited 30 patients with CFS who were not depressed, 12 depressed patients and 15 healthy volunteers. Regional cerebral perfusion at rest was assessed using region of interest (ROI) and voxel-based statistical parametric mapping (SPM) techniques.

RESULTS: On SPM analysis there was increased perfusion in the right thalamus, pallidum and putamen in patients with CFS and in those with depressive illness. CFS patients also had increased perfusion in the left thalamus. Depressed patients differed from those with CFS in having relatively less perfusion of the left prefrontal cortex. The results were similar on ROI analysis.

CONCLUSIONS: Abnormal cerebral perfusion patterns in CFS subjects who are not depressed are similar but not identical to those in patients with depressive illness. Thalamic overactivity may be a correlate of increased attention to activity in CFS and depression; reduced prefrontal perfusion in depression may be associated with the greater neuropsychological deficits in that disorder.

Comment in: Chronic fatigue syndrome and depression. [Br J Psychiatry. 2000]

Source: MacHale SM, Lawŕie SM, Cavanagh JT, Glabus MF, Murray CL, Goodwin GM, Ebmeier KP. Cerebral perfusion in chronic fatigue syndrome and depression. Br J Psychiatry. 2000 Jun;176:550-6. http://bjp.rcpsych.org/content/176/6/550.long (Full article)

Brain positron emission tomography (PET) in chronic fatigue syndrome: preliminary data

Abstract:

Chronic fatigue syndrome (CFS) has been widely studied by neuroimaging techniques in recent years with conflicting results. In particular, using single-photon emission computed tomography (SPECT) and perfusion tracers, hypoperfusion has been found in several brain regions, although the findings vary across research centers. The objective of this study was to investigate brain metabolism of patients affected by CFS, using [18F]fluorine-deoxyglucose (18FDG) positron emission tomography (PET).

We performed 18FDG PET in 18 patients who fulfilled the criteria of the working case definition of CFS. Twelve of the 18 patients were females; the mean age was 34 +/- 15 years (range, 15-68) and the median time from CFS diagnosis was 16 months (range, 9-138). Psychiatric diseases and anxiety/neurosis were excluded in all CFS patients.

CFS patients were compared with a group of 6 patients affected by depression (according to DSM IV-R) and 6 age-matched healthy controls. The CFS patients were not taking any medication at the time of PET, and depressed patients were drug-free for at least 1 week before the PET examination. The PET images examined 22 cortical and subcortical areas.

CFS patients showed a significant hypometabolism in right mediofrontal cortex (P = 0.010) and brainstem (P = 0.013) in comparison with the healthy controls. Moreover, comparing patients affected by CFS and depression, the latter group showed a significant and severe hypometabolism of the medial and upper frontal regions bilaterally (P = 0.037-0.001), whereas the metabolism of brain stem was normal.

Brain 18FDG PET showed specific metabolism abnormalities in patients with CFS in comparison with both healthy controls and depressed patients. The most relevant result of our study is the brain stem hypometabolism which, as reported in a perfusion SPECT study, seems to be a marker for the in vivo diagnosis of CFS.

Source: Tirelli U, Chierichetti F, Tavio M, Simonelli C, Bianchin G, Zanco P, Ferlin G. Brain positron emission tomography (PET) in chronic fatigue syndrome: preliminary data. Am J Med. 1998 Sep 28;105(3A):54S-58S. http://www.ncbi.nlm.nih.gov/pubmed/9790483

Chronic fatigue syndrome–aetiological aspects

Abstract:

The chronic fatigue syndrome (CFS) has been intensively studied over the last 40 years, but no conclusions have yet been agreed as to its cause. Most cases nowadays are sporadic. In the established chronic condition there are no consistently abnormal physical signs or abnormalities on laboratory investigation.

Many physicians remain convinced that the symptoms are psychological rather than physical in origin. This view is reinforced by the emotional way in which many patients present themselves. The overlap of symptoms between CFS and depression remains a source of confusion and difficulty. But even if all CFS patients were rediagnosed as depressives, this would not negate the possibility of an underlying organic cause for the condition, in view of the growing evidence that depression itself has a physical cause and responds best to physical treatments.

There is some evidence both for active viral infection and for an immunological disorder in the CFS. Many observations suggest that the syndrome could derive from residual damage to the reticular activating system (RAS) of the upper brain stem and/or to its cortical projections. Such damage could be produced by a previous viral infection, leaving functional defects unaccompanied by any gross histological changes.

In animal experiments activation of the RAS can change sleep state and activate or stimulate cortical functions. RAS lesions can produce somnolence and apathy. Studies by modern imaging techniques have not been entirely consistent, but many magnetic resonance imaging (MRI) studies already suggest that small discrete patchy brain stem and subcortical lesions can often be seen in CFS.

Regional blood flow studies by single photon-emission computerized tomography (SPECT) have been more consistent. They have revealed blood flow reductions in many regions, especially in the hind brain. Similar lesions have been reported after poliomyelitis and in multiple sclerosis–in both of which conditions chronic fatigue is characteristically present. In the well-known post-polio fatigue syndrome, lesions predominate in the RAS of the brain stem. If similar underlying lesions in the RAS can eventually be identified in CFS, the therapeutic target for CFS would be better defined than it is at present. A number of logical approaches to treatment can already be envisaged.

Comment in:

Chronic fatigue syndrome. [Eur J Clin Invest. 1997]

Source: Dickinson CJ. Chronic fatigue syndrome–aetiological aspects. Eur J Clin Invest. 1997 Apr;27(4):257-67. http://www.ncbi.nlm.nih.gov/pubmed/9134372

Fibromyalgia, chronic fatigue syndrome, and myofascial pain

Abstract:

The prevalence of fibromyalgia in the general population was found to be 2% and increased with age. Multiple traumatic factors, including sexual and physical abuse, may be important initiating events. The most important pathophysiologic studies in fibromyalgia included evidence of altered blood flow to the brain and hypothalamic-pituitary-adrenal dysfunction. The prevalence of chronic fatigue syndrome is much less than that of fibromyalgia. Epidemiologic studies demonstrated that chronic fatigue and symptoms of fibromyalgia are distributed as continuous variables in the general population. No association between chronic fatigue and initial infections was seen in primary care practices.

Source: Goldenberg DL. Fibromyalgia, chronic fatigue syndrome, and myofascial pain. Curr Opin Rheumatol. 1996 Mar;8(2):113-23. http://www.ncbi.nlm.nih.gov/pubmed/8732795

Brainstem hypoperfusion in CFS

Comment on: Brainstem perfusion is impaired in chronic fatigue syndrome. [QJM. 1995]

Sir, Costa and his colleagues {QJ Med 1995; 88:767-73) are to be congratulated for providing more information about chronic fatigue syndrome. Hypocapnia is a powerful and readily available cerebral vasoconstrictor.1

The ‘cerebral vasoconstriction, and reduction in cerebral blood flow, are initiated when the arterial pCO2 has fallen 2 mmHg below normal. When the pCO2 has fallen by 25 mmHg, cerebral blood flow is decreased by about one third … the maximum possible reduction of blood flow that can be achieved by respiratory alkalaemia is of the order of 40 per cent’.2

You can read the rest of this comment here: http://qjmed.oxfordjournals.org/content/89/2/163.1.long

Source: Nixon PG. Brainstem hypoperfusion in CFS. QJM. 1996 Feb;89(2):163-4. http://qjmed.oxfordjournals.org/content/89/2/163.1.long

Comparison of 99m Tc HMPAO SPECT scan between chronic fatigue syndrome, major depression and healthy controls: an exploratory study of clinical correlates of regional cerebral blood flow

Abstract:

An explorative analysis of the relationship between symptomatology and cerebral blood flow in the chronic fatigue syndrome (CFS) as assessed with 99mTc HMPAO SPECT scan reveals statistically significant positive correlations between frontal blood flow on the one hand and objectively and subjectively assessed cognitive impairment, self-rating of physical activity limitations and total score on Hamilton Depression Rating Scale on the other. A pathophysiological role of frontal blood flow in the cognitive impairment and physical activity limitations in CFS is hypothesized.

A comparison of cerebral blood flow between CFS, major depression (MD) and healthy controls (HC) has been performed. A lower superofrontal perfusion index is demonstrated in MD as compared with both CFS and HC. There is neither a global nor a marked regional hypoperfusion in CFS compared with HC. Asymmetry (R > L) of tracer uptake at parietotemporal level is demonstrated in CFS as compared with MD.

Source: Fischler B, D’Haenen H, Cluydts R, Michiels V, Demets K, Bossuyt A, Kaufman L, De Meirleir K. Comparison of 99m Tc HMPAO SPECT scan between chronic fatigue syndrome, major depression and healthy controls: an exploratory study of clinical correlates of regional cerebral blood flow. Neuropsychobiology. 1996;34(4):175-83. http://www.ncbi.nlm.nih.gov/pubmed/9121617

Brainstem perfusion is impaired in chronic fatigue syndrome

Abstract:

We looked for brain perfusion abnormalities in patients with myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). An initial pilot study revealed widespread reduction of regional brain perfusion in 24 ME/CFS patients, compared with 24 normal volunteers. Hypoperfusion of the brainstem (0.72 +/- 0.05 vs. 0.80 +/- 0.04, p < 0.0001) was marked and constant. We then tested whether perfusion to the brainstem in ME/CFS patients differs from that in normals, patients with major depression, and others with epilepsy.

Data from a total of 146 subjects were included in the present study: 40 normal volunteers, 67 patients with ME/CFS (24 in the pilot study, 16 with no psychiatric disorders, 13 with ME/CFS and depression, 14 with ME/CFS and other psychiatric disorders), 10 epileptics, 20 young depressed patients and 9 elderly depressed individuals.

Brain perfusion ratios were calculated using 99Tcm-hexamethylpropylene amine oxime (99Tcm-HMPAO) and single-photon emission tomography (SPET) with a dedicated three-detector gamma camera computer/system (GE Neurocam).

Brain-stem hypoperfusion was confirmed in all ME/CFS patients. Furthermore, the 16 ME/CFS patients with no psychiatric disorders and the initial 24 patients in the pilot study showed significantly lower brainstem perfusion (0.71 +/- 0.03) than did depressed patients (0.77 +/- 0.03; ANOVA, p < 0.0001).

Patients with ME/CFS have a generalized reduction of brain perfusion, with a particular pattern of hypoperfusion of the brainstem.

Comment in: Brainstem hypoperfusion in CFS. [QJM. 1996]

Source: Costa DC, Tannock C, Brostoff J. Brainstem perfusion is impaired in chronic fatigue syndrome. QJM. 1995 Nov;88(11):767-73. http://www.ncbi.nlm.nih.gov/pubmed/8542261

Chronic fatigue syndrome–a review of the literature

Abstract:

Chronic fatigue syndrome is a clinical condition characterized by abnormal fatigue, subfebrile body temperature, sore throat, lymphadenopathy, arthralgia, myalgia and neuropsychiatric symptoms. Typically, the syndrome develops after a flu-like illness and is markedly exacerbated by exercise. The etiology is unknown and there is no single diagnostic test. The patients may have cognitive dysfunction, immunological and endocrinological abnormalities and abnormal mitochondria. Magnetic resonance imaging scans may show increased uptake of signals in the brain, and single photon emission computerized tomography reveals regional hypoperfusion of the brain. The author discusses similarities and distinctions between the syndrome and depression.

Source: Hamre HJ. Chronic fatigue syndrome–a review of the literature. Tidsskr Nor Laegeforen. 1995 Oct 10;115(24):3042-5. [Article in Norwegian] http://www.ncbi.nlm.nih.gov/pubmed/7570537

Chronic fatigue syndrome update. Findings now point to CNS involvement

Abstract:

Neither Epstein-Barr virus nor human herpesvirus 6 appears to play a causative role in chronic fatigue syndrome. The possibility that a novel human retrovirus may be present in patients with the syndrome needs further study. A number of abnormalities found in patients with chronic fatigue syndrome point to central nervous system (CNS) involvement. These include immunologic abnormalities, indications of pituitary and hypothalamic involvement, abnormal basal plasma levels of certain neurotransmitter metabolites, and cerebral perfusion abnormalities. The symptom pattern of chronic fatigue syndrome may eventually be explainable in terms of CNS dysfunction.

Source: Bell DS. Chronic fatigue syndrome update. Findings now point to CNS involvement. Postgrad Med. 1994 Nov 1;96(6):73-6, 79-81. http://www.ncbi.nlm.nih.gov/pubmed/7971614