Peripheral vestibular dysfunction in chronic fatigue syndrome

Abstract:

OBJECTIVE: To report left-sided peripheral vestibular failure as the cause of dizziness in a 12-year-old boy diagnosed as having chronic fatigue syndrome (CFS).

DESIGN: Retrospective case report with review of literature and discussion.

SETTING: Tertiary children’s hospital.

CONCLUSION: We recommend proper vestibular assessment for CFS patients presenting with dizziness, as effective treatment for peripheral vestibular disorder exists in the form of balance rehabilitation exercises.

 

Source: Palaniappan R, Sirimanna T. Peripheral vestibular dysfunction in chronic fatigue syndrome. Int J Pediatr Otorhinolaryngol. 2002 May 31;64(1):69-72. http://www.ncbi.nlm.nih.gov/pubmed/12020917

 

Impaired postural cerebral hemodynamics in young patients with chronic fatigue with and without orthostatic intolerance

Abstract:

OBJECTIVES: To measure postural changes in cerebral hemodynamics in young patients with chronic fatigue with and without orthostatic intolerance.

STUDY DESIGN: We studied 28 patients (age, 10 to 22 years) and 20 healthy control subjects (age, 6 to 27 years). Cerebral oxygenated hemoglobin (oxy-Hb) and deoxygenated Hb were noninvasively and continuously measured with near infrared spectroscopy during active standing. Beat-to-beat arterial pressure was monitored by Finapres.

RESULTS: Orthostatic intolerance determined by cardiovascular responses to standing was observed in 16 of 28 patients: instantaneous orthostatic hypotension in 8, delayed orthostatic hypotension in 2, and postural orthostatic tachycardia in 6. A rapid recovery of oxy-Hb by near infrared spectroscopy at the onset of active standing was not found in 15 of 16 patients with chronic fatigue and orthostatic intolerance and in 6 of 12 patients with chronic fatigue without orthostatic intolerance but only in 2 of 20 control subjects. Thirteen of 16 patients with orthostatic intolerance showed prolonged reduction in oxy-Hb during standing.

CONCLUSIONS: Impaired cerebral hemodynamics in patients with chronic fatigue syndrome and postural orthostatic tachycardia suggest a link between impaired cerebral oxygenation and chronic fatigue. However, this cannot explain the symptoms in patients meeting the criteria of chronic fatigue without orthostatic intolerance.

Comment in:

Chronic fatigue syndrome and Addison’s disease. [J Pediatr. 2003]

Orthostatic intolerance and chronic fatigue syndrome: new light on an old problem. [J Pediatr. 2002]

 

Source: Tanaka H, Matsushima R, Tamai H, Kajimoto Y. Impaired postural cerebral hemodynamics in young patients with chronic fatigue with and without orthostatic intolerance. J Pediatr. 2002 Apr;140(4):412-7. http://www.ncbi.nlm.nih.gov/pubmed/12006954

 

Elevated nitric oxide/peroxynitrite mechanism for the common etiology of multiple chemical sensitivity,chronic fatigue syndrome, and posttraumatic stress disorder

Abstract:

Various types of evidence implicate nitric oxide and an oxidant, possibly peroxynitrite, in MCS and chemical intolerance (CI). The positive feedback loops proposed earlier for CFS may explain the chronic nature of MCS (CI) as well as several of its other reported properties. These observations raise the possibility that this proposed elevated nitric oxide/peroxynitrite mechanism may be the mechanism of a new disease paradigm, answering the question raised by Miller earlier: “Are we on the threshold of a new theory of disease?”

 

Source: Pall ML, Satterlee JD. Elevated nitric oxide/peroxynitrite mechanism for the common etiology of multiple chemical sensitivity,chronic fatigue syndrome, and posttraumatic stress disorder.  Ann N Y Acad Sci. 2001 Mar;933:323-9. http://www.ncbi.nlm.nih.gov/pubmed/12000033

 

Controlled exposures to volatile organic compounds in sensitive groups

Abstract:

Sensitivities to chemicals are characterized by symptoms in multiple organ systems in response to low-level chemical exposures. This paper reviews studies of controlled exposures to odorants and to mixtures of volatile organic compounds. Sensitive subgroups include subjects who met Cullen’s 1987 criteria for multiple chemical sensitivity (MCS), Gulf War veterans with chronic fatigue syndrome and chemical sensitivity (CFS/CS), and subjects with specific self-reported sensitivities to methyl terbutyl ether (MTBE) in gasoline (MTBE-sensitive). All studies include comparison of age- and sex-matched healthy controls.

Studies of olfaction did not support unusual sensitivity, defined as lower odor thresholds, among MCS subjects; however, a dose-response pattern of symptoms was observed in response to suprathreshold concentrations of phenyl ethyl alcohol. In blinded, controlled exposures to clean air, gasoline, gasoline/11% MTBE, and gasoline/15% MTBE, a threshold effect was observed with MTBE-sensitive subjects reporting significantly increased symptoms to gasoline/15% MTBE exposure. Autonomic arousal (heart and respiration rate; end-tidal CO2) in response to odor of chemical mixtures may mediate symptoms for subjects with generalized chemical sensitivities, but not for those whose sensitivities are confined to specific chemicals.

For example, Gulf War veterans with CFS/CS experienced reduced end-tidal CO2 when exposed to diesel fumes, while exposure to MTBE did not produce any psychophysiologic changes in MTBE-sensitive subjects. Controlled olfactory and exposure studies reveal that significant responses can be observed in chemically sensitive subjects even when de-adaptation has not occurred. However, these studies suggest that symptoms are not necessarily accompanied by changes in physiologic arousal. Subject characteristics play a critical role in outcomes.

 

Source: Fiedler N, Kipen HM. Controlled exposures to volatile organic compounds in sensitive groups. Ann N Y Acad Sci. 2001 Mar;933:24-37. http://www.ncbi.nlm.nih.gov/pubmed/12000025

 

Potential mechanisms in chemical intolerance and related conditions

Abstract:

The symptom of chemical intolerance may occur in isolation, but often occurs in conjunction with other chronic symptoms such as pain, fatigue, memory disturbances, etc. This frequent clustering of symptoms in individuals has led to the definition of several chronic multisymptom syndromes, such as multiple chemical sensitivity, fibromyalgia, chronic fatigue syndrome, and Gulf War illnesses. The aggregate research into these syndromes has suggested some unifying mechanisms that contribute to symptomatology. Multiple lines of evidence suggest that there is aberrant function of numerous efferent neural pathways, such as the autonomic nervous system and hypothalamic-pituitary axes, in subsets of individuals with these conditions.

There is perhaps the greatest evidence for abnormal sensory processing in these syndromes, with a low “unpleasantness threshold” for multiple types of sensory stimuli. Psychological and behavioral factors are known to play a significant role in initiating or perpetuating symptoms in some persons with these illnesses. In the field of pain research, the interrelationship between physiologic and psychologic factors in symptom expression has been well studied. Using both established and novel methodologies, studies have suggested that psychologic factors such as hypervigilance and expectancy are playing a relatively minor role in most individuals with fibromyalgia and that clear evidence exists of physiologic amplification of sensory stimuli.

These studies need to be extended to more sensory tasks and to larger numbers of subjects with related conditions. It is of note, though, that existing data on this spectrum of illnesses would suggest that there may be greater psychologic contributions to symptomatology if an illness is defined in part by behavior (e.g., avoidance of chemical exposures) rather than on the basis of symptoms alone.

 

Source: Clauw DJ. Potential mechanisms in chemical intolerance and related conditions.  Ann N Y Acad Sci. 2001 Mar;933:235-53. http://www.ncbi.nlm.nih.gov/pubmed/12000024

 

Mediators of inflammation and their interaction with sleep: relevance for chronic fatigue syndrome and related conditions

Abstract:

In humans, activation of the primary host defense system leads to increased or decreased NREM sleep quality, depending on the degree of early immune activation. Modest elevations of certain inflammatory cytokines are found during experimental sleep loss in humans and, in addition, relatively small elevations of cytokines are seen following commencement of pharmacological treatments with clozapine, a CNS active antipsychotic agent, known to have immunomodulatory properties. Cytokines such as TNF-alpha, its soluble receptors, and IL-6, present in the periphery and the CNS, comprise a link between peripheral immune stimulation and CNS-mediated behaviors and experiences such as sleep, sleepiness, and fatigue. The debilitating fatigue experienced in chronic fatigue syndrome and related diseases may also be related to altered cytokine profiles.

 

Source: Mullington JM, Hinze-Selch D, Pollmächer T. Mediators of inflammation and their interaction with sleep: relevance for chronic fatigue syndrome and related conditions.  Ann N Y Acad Sci. 2001 Mar;933:201-10. http://www.ncbi.nlm.nih.gov/pubmed/12000021

 

Cytokines and chronic fatigue syndrome

Abstract:

Chronic fatigue syndrome (CFS) patients show evidence of immune activation, as demonstrated by increased numbers of activated T lymphocytes, including cytotoxic T cells, as well as elevated levels of circulating cytokines. Nevertheless, immune cell function of CFS patients is poor, with low natural killer cell cytotoxicity (NKCC), poor lymphocyte response to mitogens in culture, and frequent immunoglobulin deficiencies, most often IgG1 and IgG3.

Immune dysfunction in CFS, with predominance of so-called T-helper type 2 and proinflammatory cytokines, can be episodic and associated with either cause or effect of the physiological and psychological function derangement and/or activation of latent viruses or other pathogens. The interplay of these factors can account for the perpetuation of disease with remission/exacerbation cycles. A T-helper type 2 predominance has been seen among Gulf War syndrome patients and this feature may also be present in other related disorders, such as multiple chemical sensitivity. Therapeutic intervention aimed at induction of a more favorable cytokine expression pattern and immune status appears promising.

 

Source: Patarca R. Cytokines and chronic fatigue syndrome.  Ann N Y Acad Sci. 2001 Mar;933:185-200. http://www.ncbi.nlm.nih.gov/pubmed/12000020

 

Review: behavioural interventions show the most promise for chronic fatigue syndrome

Comment on: Interventions for the treatment and management of chronic fatigue syndrome: a systematic review. [JAMA. 2001]

 

QUESTION: In patients with chronic fatigue syndrome (CFS), what is the effectiveness of evaluated interventions?

Data sources: Published and unpublished studies in any language were identified by searching 19 databases, including Medline, EMBASE/Excerpta Medica, PsycLIT, ERIC, Current Contents, and the Cochrane Library (to 2000); the internet was searched using a meta-search engine; references of retrieved articles were scanned; and individuals and organisations were contacted through a website dedicated to this review and through members of 2 advisory panels.

Study selection: Studies were selected if they were randomised controlled trials (RCTs) or controlled clinical trials of any intervention used in the treatment or management of CFS in adults or children. Studies in which diagnoses were based on another syndrome with criteria similar to CFS, such as myalgic encephalomyelitis, chronic fatigue immune deficiency syndrome, or chronic Epstein-Barr virus infection, were included, but studies of fibromyalgia were not.

Data extraction: Data were extracted on study validity (randomisation and allocation concealment [RCTs], control group appropriateness and adjustment for confounders [controlled studies], baseline comparability of groups, blinding, follow up, drop outs, objectivity of outcome assessment, analysis, sample size, and cointerventions); intervention; diagnostic criteria; duration of follow up; and outcomes (psychological, physical, quality of life and health status, physiological, and resource use).

Main results: 44 studies (n=2801; age range 11–87 y, 71% women) were included (32 studies of adults, 1 of children, and 2 of adults and children; 9 studies did not give age information). 31 different interventions were grouped by type of intervention (behavioural, immunological, pharmacological, supplements, complementary or alternative, and other interventions). 36 studies were RCTs. 18 trials (41%) showed an overall beneficial effect of the intervention (≥1 clinical outcome improved). The results from the RCTs are shown in the table. Cognitive behavioural therapy (CBT) and graded exercise therapy (GET) had beneficial effects. Overall evidence from the other interventions was inconclusive.

 

Source: Kinsella P. Review: behavioural interventions show the most promise for chronic fatigue syndrome. Evid Based Nurs. 2002 Apr;5(2):46. http://ebn.bmj.com/content/5/2/46.long (Full article)

 

 

Caring for a relative with chronic fatigue syndrome: difficulties, cognition and acceptance over time

Abstract:

The present study explored the difficulties experienced by carers of chronic fatigue syndrome (CFS) sufferers, their cognitions, and their efforts to accept the illness. Semi-structured interviews were conducted with 17 carers to study these issues, retrospectively, over three stages: before the diagnosis of CFS, shortly after the diagnosis, and at present.

Surprisingly, the results suggested that carers, several of them absent from home during the day, felt that their lives were only minimally constrained by the illness. Nevertheless, all carers reported specific coping efforts to manage both the illness and their own distress, and indicated that they learned to accept the illness over time. However, acceptance appeared to be a form of resignation rather than a positive appreciation of the illness.

In light of the uncertainties surrounding the origin of CFS and carers’ apparent confusion, the results obtained in the present study are significant in that they increase our understanding of CFS carers’ quality of life, their efforts to cope with the illness, and the physical and emotional help they may provide to the sufferer. Such information can be usefully employed in the increasing development of counselling interventions and instrumental support networks that involve both sufferers and their carers.

 

Source:  Ax S, Gregg VH, Jones D.  Caring for a relative with chronic fatigue syndrome: difficulties, cognition and acceptance over time. J R Soc Promot Health. 2002 Mar;122(1):35-42. http://www.ncbi.nlm.nih.gov/pubmed/11989141

 

Antiviral pathway activation in chronic fatigue syndrome and acute infection

Comment on: Antiviral pathway activation in patients with chronic fatigue syndrome and acute infection. [Clin Infect Dis. 2001]

 

SIR—We read the very engaging report by Gow et al. [1] with the utmost interest. However, we feel that this article raises more questions than clear-cut answers regarding the hypothesis that motivated the study—that is, that the previously reported activation of the antiviral pathway in chronic fatigue syndrome (CFS) might be linked to infection rather than to CFS specifically. To verify their hypothesis, Gow and colleagues used PCR to measure the genetic expression of 3 IFN-regulated genes—namely, the latent ribonuclease (RNase L), RNA-regulated protein kinase (PKR), 2,5 synthetase, and the RNase L inhibitor (RLI)—in patients with acute infection (in their study, severe gastroenteritis; group 1), patients with CFS (group 2), and healthy control subjects (group 3).

First, surprisingly enough, although they recognized that acute infection is supposed to induce the expression of the genes selected for their study (see figure 1 of [1]), Gow and colleagues failed to find any significant increase in the expression of 2 major genes (RNase L and 2,5 synthetase) in group 1, as compared with groups 2 and 3; they observed only increased mRNA for PKR and RLI. Although it is recognized that genetic expression of PKR, RNase L, and 2,5 synthetase is under the control of interferon, RLI is definitely not [2]. Upregulation of RLI genetic expression with a normal genetic expression of both 2,5 synthetase and RNase L (although PKR is overexpressed!) during acute infection, as was observed in the study of Gow et al. [1], would indicate not only that RNase L is not activated (normal expression of RNase L and, more importantly, of 2,5 synthetase), but that it is further inhibited by an overexpressed RLI [2]. Such a scenario, if verified, would be in complete disagreement with the current understanding of the IFN pathway [3]. Therefore, we cannot help but wonder how Gow and colleagues reconcile their observations with the acute infection status of study group 1. In our view, this inconsistency severely undermines their conclusions.

You can read the rest of this comment here:  http://cid.oxfordjournals.org/content/34/10/1420.long

 

Source: De Meirleir K, Suhadolnik RJ, Lebleu B, Englebienne P. Antiviral pathway activation in chronic fatigue syndrome and acute infection. Clin Infect Dis. 2002 May 15;34(10):1420-1; author reply 1421-2. http://cid.oxfordjournals.org/content/34/10/1420.long (Full article)