Category: Neurology

Decreased immunoreactive beta-endorphin in mononuclear leucocytes from patients with chronic fatigue syndrome

Abstract:

OBJECTIVE: To investigate beta-endorphin concentrations in the peripheral blood mononuclear cells (PBMC) of patients with chronic fatigue syndrome (CFS).

METHODS: Sixteen patients with CFS were enrolled in this study. Ten healthy subjects were studied as controls. Beta-endorphin concentrations were measured in PBMC by radioimmunoassay performed with antibodies specific for the C-terminal portion of human beta-endorphin.

RESULTS: Beta-endorphin concentrations in the PBMC of chronic fatigue patients were significantly lower (p < 0.001) than in healthy subjects (mean +/- SD: 8.5 +/- 7.0 vs. 42.6 +/- 22.6).

CONCLUSION: Patients with CFS were found to have low levels of PBMC beta-endorphin. This finding may reflect the condition of chronic immune activation in CFS that has been reported in previous investigations. Beta-endorphin concentrations in PBMC seem to mirror the central nervous system homeostasis of the opioid. Therefore, we would postulate that the fatigue and weakness typical of CFS could be related to low beta-endorphin concentrations at the central nervous system level.

 

Source: Conti F, Pittoni V, Sacerdote P, Priori R, Meroni PL, Valesini G. Decreased immunoreactive beta-endorphin in mononuclear leucocytes from patients with chronic fatigue syndrome. Clin Exp Rheumatol. 1998 Nov-Dec;16(6):729-32. http://www.ncbi.nlm.nih.gov/pubmed/9844768

 

Neurally mediated hypotension and autonomic dysfunction measured by heart rate variability during head-up tilt testing in children with chronic fatigue syndrome

Abstract:

Recent investigations suggest a role for neurally mediated hypotension (NMH) in the symptomatology of chronic fatigue syndrome (CFS) in adults. Our previous observations in children with NMH and syncope (S) unrelated to CFS indicate that the modulation of sympathetic and parasympathetic tone measured by indices of heart rate variability (HRV) is abnormal in children who faint during head-up tilt (HUT). In order to determine the effects of autonomic tone on HUT in children with CFS we performed measurements of HRV during HUT in 16 patients aged 11-19 with CFS.

Data were compared to 26 patients evaluated for syncope and with 13 normal control subjects. After 30 minutes supine, patients were tilted to 80 degrees for 40 minutes or until syncope occurred. Time domain indices included RR interval, SDNN, RMSSD, and pNN50. An autoregressive model was used to calculate power spectra. LFP (.04-.15 Hz), HFP (.15-.40Hz), and TP (.01-.40Hz). Data were obtained supine (baseline) and after HUT.

Thirteen CFS patients fainted (CFS+, 5/13 pure vasodepressor syncope) and three patients did not (CFS-). Sixteen syncope patients fainted (S+, all mixed vasodepressor-cardioinhibitory) and 10 did not (S-). Four control patients fainted (Control+, all mixed vasodepressor-cardioinhibitory) and nine did not (Control-). Baseline indices of HRV were not different between Control+ and S+, and between Control- and S-, but were depressed in S+ compared to S-. HRV indices were strikingly decreased in CFS patients compared to all other groups.

With tilt, SDNN, RMSSD, and pNN50 and spectral indices decreased in all groups, remaining much depressed in CFS compared to S or control subjects. With HUT, sympathovagal indices (LFP/HFP, nLFP, and nHFP) were relatively unchanged in CFS, which contrasts with the increase in nLFP with HUT in all other groups. With syncope RMSSD, SDNN, LFP, TP, and HFP increased in S+ (and Control+), suggesting enhanced vagal heart rate regulation. These increases were not observed in CFS+ patients.

CFS is associated with NMH during HUT in children. All indices of HRV are markedly depressed in CFS patients, even when compared with already low HRV in S+ or Control+ patients. Sympathovagal balance does not shift toward enhanced sympathetic modulation of heart rate with HUT and there is blunting in the overall HRV response with syncope during HUT. Taken together these data may indicate autonomic impairment in patients with CFS.

 

Source: Stewart J, Weldon A, Arlievsky N, Li K, Munoz J. Neurally mediated hypotension and autonomic dysfunction measured by heart rate variability during head-up tilt testing in children with chronic fatigue syndrome. Clin Auton Res. 1998 Aug;8(4):221-30. http://www.ncbi.nlm.nih.gov/pubmed/9791743

 

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

 

Neuroimaging in chronic fatigue syndrome

Abstract:

The diagnosis of chronic fatigue syndrome (CFS) is made difficult by the absence of specific biomedical markers, and depends primarily on determining whether subjective information provided by the patient meets the clinical case definition of this syndrome. Reported cognitive difficulties and/or complaints of headache may instigate referral for brain imaging.

This article will discuss the value of neuroimaging in evaluating CFS, specifically reviewing studies that (1) used static magnetic resonance imaging (MRI) to assess structural abnormalities; and (2) assessed regional cerebral blood flow (rCBF) via detection of Tc-99m hexamethylpropyl-eneamine oxime distribution by single-photon emission computed tomography (SPECT). Future research design considerations are explored including (1) the utilization of positron emission tomography (PET) and other emerging neuroimaging technologies; and (2) methodological concerns, i.e., the influence of psychopathology (such as depression) and neurologic disease (such as multiple sclerosis) as possible confounding factors.

 

Source: Lange G, Wang S, DeLuca J, Natelson BH. Neuroimaging in chronic fatigue syndrome. Am J Med. 1998 Sep 28;105(3A):50S-53S. http://www.ncbi.nlm.nih.gov/pubmed/9790482

 

Autonomic testing in patients with chronic fatigue syndrome

Abstract:

The purpose of this study was to determine whether chronic fatigue syndrome (CFS) patients show autonomic dysfunction at the cardiac level and if so, to discover whether these abnormalities explain the fatiguability and/or other symptoms in CFS.

The study population consisted of 21 CFS patients (Centers for Disease Control and Prevention [CDC] criteria, 1988) and 13 age- and sex-matched healthy controls. The autonomic testing consisted of: (1) postural challenge: registration of heart rate and blood pressure (BP) and heart rate variability in supine and in upright position (tilted to 70 degrees); (2) Valsalva maneuver; (3) handgrip test; (4) cold pressor test; and (5) heart rate response to deep breathing. Statistical analysis was performed using the Mann Whitney rank sum test; results of the test were considered significant at the 0.05 level. After tilting heart rate was significantly higher in CFS patients compared with healthy controls (mean CFS = 88.9 beats/min vs control = 77.9 beats/min; P <0.01).

Low frequency power after tilting was significantly higher in CFS patients compared with controls (mean CFS = 0.603 vs control = 0.428; P = 0.02). There was a trend toward an increased heart rate during the cold pressor test. Other parameters did not differ between the CFS and control populations.

The observed changes point toward a sympathetic overactivity in CFS patients when they are exposed to stress. Parasympathetic abnormalities could not be observed. Therefore, our findings provide no real explanation for the fatigue and intolerance to physical exertion in these patients.

 

Source: De Becker P, Dendale P, De Meirleir K, Campine I, Vandenborne K, Hagers Y. Autonomic testing in patients with chronic fatigue syndrome. Am J Med. 1998 Sep 28;105(3A):22S-26S. http://www.ncbi.nlm.nih.gov/pubmed/9790478

 

Neurally mediated hypotension and chronic fatigue syndrome

Abstract:

 

A substantial body of clinical evidence now supports an association between various forms of hypotension and both idiopathic chronic fatigue and the chronic fatigue syndrome (CFS). Patients with CFS have a high prevalence of neurally mediated hypotension, and open treatment of this autonomic dysfunction has been associated with improvements in CFS symptoms. Randomized trials are now in progress to evaluate the efficacy of treatments directed at neurally mediated hypotension in those with CFS patients, and the results of these trials should help guide more basic inquiries into the mechanisms of orthostatic intolerance in affected individuals.

 

Source: Rowe PC, Calkins H. Neurally mediated hypotension and chronic fatigue syndrome. Am J Med. 1998 Sep 28;105(3A):15S-21S. http://www.ncbi.nlm.nih.gov/pubmed/9790477

 

No strong evidence of disturbed regulation of blood pressure in chronic fatigue syndrome

Abstract:

Recent medical publications postulate a connection between the Chronic Fatigue Syndrome (CFS) and disturbed regulation of the circulation, manifesting itself during orthostatic stress testing.

Four studies were published on the circulatory response on prolonged head up tilt testing. Numerous CFS patients displayed postural tachycardia or syncope during the test. However, many CFS patients examined had had orthostatic symptoms prior to the examination.

It is not certain that cardiovascular dysregulation is present in CFS patients without orthostatic symptoms. It is also not clear whether such a dysregulation would be the effect of physical inactivity or a manifestation of a subtle form of autonomic neuropathy.

 

Source: Smit AA, Bolweg NM, Lenders JW, Wieling W. No strong evidence of disturbed regulation of blood pressure in chronic fatigue syndrome. Ned Tijdschr Geneeskd. 1998 Mar 21;142(12):625-8.[Article in Dutch] http://www.ncbi.nlm.nih.gov/pubmed/9623125

 

The role of delayed orthostatic hypotension in the pathogenesis of chronic fatigue

Abstract:

Past studies have shown that severe fatigue was the presenting symptom in six of seven patients with delayed orthostatic hypotension and that tilt table-induced hypotension was found in 22 of 23 patients with the chronic fatigue syndrome. We have determined the prevalence of fatigue, volunteered in response to a nonspecific pre-examination questionnaire used in 431 patients, each subsequently diagnosed as having one of eight neurological or endocrine disorders.

The results show that fatigue is a very common symptom in patients with delayed orthostatic hypotension (n = 21), as well as both primary (n = 30) and secondary (n = 106) hypocortisolism: 70-83% in all groups. In contrast, fatigue was an uncommon complaint in patients with multiple system atrophy (MSA) (n = 30), pituitary disorders without hypocortisolism (n = 106) or idiopathic hirsutism (n = 96): 7-33% in all groups, and was intermediate in prevalence in patients with acute hyperadrenergic orthostatic hypotension (n = 32): 41%.

It is concluded that fatigue commonly results from delayed orthostatic hypotension and all forms of hypocortisolism but is less common in patients with acute orthostatic hypotension, both idiopathic and due to MSA, which more commonly present with lightheadedness or syncope.

 

Source: Streeten DH, Anderson GH Jr. The role of delayed orthostatic hypotension in the pathogenesis of chronic fatigue. Clin Auton Res. 1998 Apr;8(2):119-24. http://www.ncbi.nlm.nih.gov/pubmed/9613802

 

Impaired associative learning in chronic fatigue syndrome

Abstract:

Patients with chronic fatigue syndrome (CFS) report cognitive difficulties (impaired attention, memory and reasoning). Neuropsychological tests have failed to consistently find cognitive impairments to the degree reported by CFS patients.

We tested patients with CFS and sedentary controls in protocols designed to measure sensory reactivity and acquisition of the classically conditioned eyeblink response. Patients with CFS exhibited normal sensitivity and responsivity to acoustic stimuli.

However, CFS patients displayed impaired acquisition of the eyeblink response using a delayed-type conditioning paradigm. Sensitivity and responsivity to the airpuff stimulus were normal.

In the absence of sensory/motor abnormalities, impaired acquisition of the classically conditioned eyeblink response indicates an associative deficit. These data suggest organic brain dysfunction within a defined neural substrate in CFS patients.

 

Source: Servatius RJ, Tapp WN, Bergen MT, Pollet CA, Drastal SD, Tiersky LA, Desai P, Natelson BH. Impaired associative learning in chronic fatigue syndrome. Neuroreport. 1998 Apr 20;9(6):1153-7. http://www.ncbi.nlm.nih.gov/pubmed/9601685

 

The connection between chronic fatigue syndrome and neurally mediated hypotension

Abstract:

Research from several groups of investigators indicates that some patients with chronic fatigue syndrome have abnormal vasovagal or vasodepressor responses to upright posture. If confirmed, these findings may explain some of the symptoms of chronic fatigue syndrome. There is also speculation that neurally mediated hypotension may be present in fibromyalgia. This article discusses the original research in this area, the results of follow-up studies, and the current approach to treating patients with chronic fatigue syndrome in whom neurally mediated hypotension is suspected.

 

Source: Wilke WS, Fouad-Tarazi FM, Cash JM, Calabrese LH. The connection between chronic fatigue syndrome and neurally mediated hypotension. Cleve Clin J Med. 1998 May;65(5):261-6. http://www.ncbi.nlm.nih.gov/pubmed/9599909