Category: Pathophysiology

Are attention deficit hyperactivity disorder and chronic fatigue syndrome allergy related? What is fibromyalgia?

Abstract:

Despite the progress made in the field of allergy-immunology in recent years, there are a group of diseases that the allergist-immunologist may be called on to manage in which their precise etiologies have not been identified but that appear to be initiated or exacerbated by allergic mechanisms. Attention deficit hyperactivity disorder (ADHD), chronic fatigue syndrome (CFS), and fibromyalgia (FM) fall into this category of disorders.

Although the precise etiology of ADHD still remains unknown, the most prevalent theory is that it represents a neurobiologically based developmental disability leading to inadequate production of the neurotransmitter dopamine.

In patients with CFS, there appears to be a fundamental dysfunction of the neuroendocrine-immunological system with deficiencies of immunological and neurological function, which, together with chronic viral infection, may lead to a sequence of events responsible for the symptoms of this disorder.

FM appears to be a variant of CFS with a predominance of hypothalamic pituitary axis dysfunction. The disorder is characterized by chronic widespread pain and the finding of 11/18 tender points on examination.

Now, there is emerging evidence to suggest that adverse reactions to foods or food components also may be associated with behavioral disturbances that may play a role in each of these disorders. An understanding of the interactive responses involved in the neuroendocrine-immunological network is essential for a comprehension of the pathophysiology of ADHD, CFS, and FM and the role of allergies appears to be an important triggering event in each of the disorders.

 

Source: Bellanti JA, Sabra A, Castro HJ, Chavez JR, Malka-Rais J, de Inocencio JM. Are attention deficit hyperactivity disorder and chronic fatigue syndrome allergy related? What is fibromyalgia? Allergy Asthma Proc. 2005 Jan-Feb;26(1):19-28. http://www.ncbi.nlm.nih.gov/pubmed/15813284

 

 

Brain 5-HT1A receptor binding in chronic fatigue syndrome measured using positron emission tomography and [11C]WAY-100635

Abstract:

BACKGROUND: Research from neuroendocrine challenge and other indirect studies has suggested increased central 5-HT function in chronic fatigue syndrome (CFS) and increased 5-HT1A receptor sensitivity. We assessed brain 5-HT1A receptor binding potential directly using the specific radioligand [11C]WAY-100635 and positron emission tomography (PET).

METHODS: We selected 10 patients from a tertiary referral clinic who fulfilled the CDC consensus criteria for CFS. To assemble a homogenous group and avoid confounding effects, we enrolled only subjects who were completely medication-free and did not have current comorbid psychiatric illness. We also scanned 10 healthy control subjects.

RESULTS: There was a widespread reduction in 5-HT1A receptor binding potential in CFS relative to control subjects. This was particularly marked in the hippocampus bilaterally, where a 23% reduction was observed.

CONCLUSIONS: There is evidence of decreased 5-HT1A receptor number or affinity in CFS. This may be a primary feature of CFS, related to the underlying pathophysiology, or a finding secondary to other processes, such as previous depression, other biological changes or the behavioral consequences of CFS.

 

Source: Cleare AJ, Messa C, Rabiner EA, Grasby PM. Brain 5-HT1A receptor binding in chronic fatigue syndrome measured using positron emission tomography and [11C]WAY-100635. Biol Psychiatry. 2005 Feb 1;57(3):239-46. http://www.ncbi.nlm.nih.gov/pubmed/15691524

 

Do vasoactive neuropeptides and heat shock proteins mediate fatigue-related autoimmune disorders?

Abstract:

Autoimmune dysfunction of certain vasoactive neuropeptides may be implicated in a range of disorders associated with fatigue like states (chronic fatigue syndrome, Gulf War syndrome) and even sudden infant death syndrome. These substances have neurotrophic, neuroregulatory, and neurotransmission functions, as well as that of immune modulators and hormones. They exert significant control over carbohydrate and lipid metabolism.

The hypothesis is that because these substances have vital and indispensable roles in cellular processes, loss or compromise of these roles would lead to predictable and severe cellular and systemic effects. The important roles of certain VNs make them a vulnerable target for autoimmune dysfunction. They are known to be associated with heat shock proteins for intracellular functioning with which they may form immunostimulating complexes. While peptide-HSP complexes are a relatively new area for research, this paper asserts that attention could be focused on these substances and complexes in an effort to elucidate a number of perplexing fatigue-associated disorders.

 

Source: Staines DR. Do vasoactive neuropeptides and heat shock proteins mediate fatigue-related autoimmune disorders? Med Hypotheses. 2005;64(3):539-42. http://www.ncbi.nlm.nih.gov/pubmed/15617862

 

Reduction of serotonin transporters of patients with chronic fatigue syndrome

Abstract:

To assess the involvement of serotonin in the symptoms of chronic fatigue syndrome, we investigated the serotonergic neurotransmitter system of chronic fatigue syndrome patients by the positron emission tomography (PET).

Here we show that the density of serotonin transporters (5-HTTs) in the brain, as determined by using a radiotracer, [C](+)McN5652, was significantly reduced in the rostral subdivision of the anterior cingulate as compared with that in normal volunteers. This subdivision is different from that in the dorsal anterior cingulate in which binding potential values of individual patient showed a weak negative correlation with self-reported pain score of the patients.

Therefore, an alteration of serotonergic system in the rostral anterior cingulate plays a key role in pathophysiology of chronic fatigue syndrome.

 

Source: Yamamoto S, Ouchi Y, Onoe H, Yoshikawa E, Tsukada H, Takahashi H, Iwase M, Yamaguti K, Kuratsune H, Watanabe Y. Reduction of serotonin transporters of patients with chronic fatigue syndrome. Neuroreport. 2004 Dec 3;15(17):2571-4. http://www.ncbi.nlm.nih.gov/pubmed/15570154

 

Diminished central activation during maximal voluntary contraction in chronic fatigue syndrome

Abstract:

OBJECTIVE: We have investigated whether central activation failure (CAF) is increased during local muscle fatigue in chronic fatigue syndrome (CFS).

METHODS: Fourteen female CFS patients and 14 age-matched healthy female controls made a 2 min sustained maximal voluntary contraction (MVC) of the biceps brachii muscle. Before, during, and after sustained MVC, electrical endplate stimulation was applied. Force and 5 channel surface EMG (sEMG) were registered.

RESULTS: Although force responses upon stimulation during rest did not differ between patients and controls, MVC was significantly lower in patients. Already at the beginning of sustained MVC, CFS patients showed significantly larger CAF than controls (36.5+/-17.0% and 12.9+/-13.3%, respectively). For all individual patients mean CAF over the first 45 s was higher than 30%, while it was below 30% for all controls. Less peripheral fatigue in patients was demonstrated by the changes in muscle fibre conduction velocity and the differences between force responses before and after contraction.

CONCLUSIONS: Central activation is diminished in CFS patients. Possible causes include changed perception, impaired concentration, reduced effort and physiologically defined changes, e.g. in the corticospinal excitability or the concentration of neurotransmitters. As a consequence, demands on the muscle are lower, resulting in less peripheral fatigue.

SIGNIFICANCE: CFS patients show reduced central activation during MVC. The underlying pathophysiological processes remain still to be determined.

 

Source: Schillings ML, Kalkman JS, van der Werf SP, van Engelen BG, Bleijenberg G, Zwarts MJ. Diminished central activation during maximal voluntary contraction in chronic fatigue syndrome. Clin Neurophysiol. 2004 Nov;115(11):2518-24. http://www.ncbi.nlm.nih.gov/pubmed/15465441

 

Chronic fatigue syndrome impairs circadian rhythm of activity level

Abstract:

Some of the symptoms of chronic fatigue syndrome (CFS) are the same as for disrupted circadian rhythm. Activity level is frequently used to study circadian rhythm. Continuous waist activity measurements taken every minute 24 h/day for from 5 to 7 days in 10 controls and from 2 to 7 days in 8 patients with CFS yielded two primary findings: (a) lower daytime activity and (b) less regular activity-rest cycles in persons with CFS than in controls.

 

Source: Tryon WW, Jason L, Frankenberry E, Torres-Harding S. Chronic fatigue syndrome impairs circadian rhythm of activity level. Physiol Behav. 2004 Oct 15;82(5):849-53. http://www.ncbi.nlm.nih.gov/pubmed/15451649

 

In vivo magnetic resonance spectroscopy in chronic fatigue syndrome

Abstract:

The pathogenic mechanisms of chronic fatigue syndrome (CFS) are not clearly known. Fatigue, poor short-term memory and muscle pain are the most disabling symptoms in CFS. Research data on magnetic resonance spectroscopy (MRS) of muscles and brain in CFS patients suggest a cellular metabolic abnormality in some cases.

31P MRS of skeletal muscles in a subset of patients indicate early intracellular acidosis in the exercising muscles. 1H MRS of the regional brain areas in CFS have shown increased peaks of choline derived from the cell membrane phospholipids.

Cell membrane oxidative stress may offer a common explanation for the observed MRS changes in the muscles and brain of CFS patients and this may have important therapeutic implications. As a research tool, MRS may be used as an objective outcome measure in the intervention studies. In addition, regional brain 1H MRS has the potential for wider use to substantiate a clinical diagnosis of CFS from other disorders of unexplained chronic fatigue.

 

Source: Chaudhuri A, Behan PO. In vivo magnetic resonance spectroscopy in chronic fatigue syndrome. Prostaglandins Leukot Essent Fatty Acids. 2004 Sep;71(3):181-3. http://www.ncbi.nlm.nih.gov/pubmed/15253888

 

Neural correlates of the chronic fatigue syndrome–an fMRI study

Abstract:

Chronic fatigue syndrome (CFS) is characterized by a debilitating fatigue of unknown aetiology. Patients who suffer from CFS report a variety of physical complaints as well as neuropsychological complaints. Therefore, it is conceivable that the CNS plays a role in the pathophysiology of CFS. The purpose of this study was to investigate neural correlates of CFS, and specifically whether there exists a linkage between disturbances in the motor system and CFS.

We measured behavioural performance and cerebral activity using rapid event-related functional MRI in 16 CFS patients and 16 matched healthy controls while they were engaged in a motor imagery task and a control visual imagery task. CFS patients were considerably slower on performance of both tasks, but the increase in reaction time with increasing task load was similar between the groups.

Both groups used largely overlapping neural resources. However, during the motor imagery task, CFS patients evoked stronger responses in visually related structures. Furthermore, there was a marked between-groups difference during erroneous performance. In both groups, dorsal anterior cingulate cortex was specifically activated during error trials. Conversely, ventral anterior cingulate cortex was active when healthy controls made an error, but remained inactive when CFS patients made an error.

Our results support the notion that CFS may be associated with dysfunctional motor planning. Furthermore, the between-groups differences observed during erroneous performance point to motivational disturbances as a crucial component of CFS.

 

Source: de Lange FP, Kalkman JS, Bleijenberg G, Hagoort P, van der Werf SP, van der Meer JW, Toni I. Neural correlates of the chronic fatigue syndrome–an fMRI study. Brain. 2004 Sep;127(Pt 9):1948-57. Epub 2004 Jul 7. http://brain.oxfordjournals.org/content/127/9/1948.long (Full article)

 

Midodrine treatment for chronic fatigue syndrome

Abstract:

The long term results of midodrine treatment in a patient having debilitating chronic fatigue syndrome (CFS) are reported. Midodrine treatment, directed at the autonomic nervous system, resulted in correction of the dysautonomia followed by improvement of fatigue. This finding is consistent with the hypothesis that dysautonomia plays a major part in the pathophysiology of CFS and that therapies directed at the autonomic nervous system may be effective in the treatment of CFS.

 

Source: Naschitz J, Dreyfuss D, Yeshurun D, Rosner I. Midodrine treatment for chronic fatigue syndrome. Postgrad Med J. 2004 Apr;80(942):230-2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1742969/pdf/v080p00230.pdf (Full article)

 

Alcohol use in chronic fatigue syndrome

Abstract:

OBJECTIVE: To examine the anecdotal observation that patients with chronic fatigue syndrome develop alcohol intolerance.

METHODS: A consecutive case series of 114 patients fulfilling UK criteria for chronic fatigue syndrome referred to a specialist clinic. Self-reported alcohol use pre- and postdiagnosis, fatigue symptoms and comorbidity measures were collected.

RESULTS: Two-thirds reduced alcohol intake. The most common reasons were increased tiredness after drinking (67%), increased nausea (33%), exacerbated hangovers (23%) and sleep disturbance (24%). One-third of the subjects also stopped drinking because “it seemed sensible.” Some had been advised to avoid alcohol, but the majority (66%) did so on the basis of personal experience.

CONCLUSION: Our data supports the anecdotal belief that chronic fatigue syndrome patients reduce or cease alcohol intake. This is associated with greater impairment in employment, leisure and social domains of function, and may hint at psycho-pathophysiological processes in common with other conditions that result in alcohol intolerance.

 

Source: Woolley J, Allen R, Wessely S. Alcohol use in chronic fatigue syndrome. J Psychosom Res. 2004 Feb;56(2):203-6. http://www.ncbi.nlm.nih.gov/pubmed/15016579