Neurology – Page 25 – American ME and CFS Society

Unconscious amygdalar fear conditioning in a subset of chronic fatigue syndrome patients

Abstract:

Here, a novel hypothesis for chronic fatigue syndrome (CFS) is proposed. CFS may be a neurophysiological disorder focussing on the amygdala. During a ‘traumatic’ neurological event often involving acute psychological stress combined with a viral infection or other chemical or physiological stressor, a conditioned network or ‘cell assembly’ may be created in the amygdala. The unconscious amygdala may become conditioned to be chronically sensitised to negative symptoms arising from the body. Negative signals from the viscera or physiological, chemical and dietary stressors, become conditioned stimuli and the conditioned response is a chronic sympathetic outpouring from the amygdala via various brain pathways including the hypothalamus.

This cell assembly then produces the CFS vicious circle, where an unconscious negative reaction to symptoms causes immune reactivation/dysfunction, chronic sympathetic stimulation, leading to sympathetic dysfunction, mental and physical exhaustion, and a host of other distressing symptoms and secondary complications. And these are exactly the symptoms that the amygdala and associated limbic structures are trained to monitor and respond to, perpetuating a vicious circle. Recovery from CFS may involve projections from the medial prefrontal cortex to the amygdala, to control the amygdala’s expressions. I shall firstly discuss predisposing, precipitating, and perpetuating factors involved in the possible etiology of chronic fatigue syndrome (CFS), followed by the patient’s experience of the illness. Finally, I shall look at a suggested explanation for the symptoms of CFS.

Source: Gupta A. Unconscious amygdalar fear conditioning in a subset of chronic fatigue syndrome patients. Med Hypotheses. 2002 Dec;59(6):727-35. http://www.ncbi.nlm.nih.gov/pubmed/12445517

Dysautonomias: clinical disorders of the autonomic nervous system

Abstract:

The term dysautonomia refers to a change in autonomic nervous system function that adversely affects health. The changes range from transient, occasional episodes of neurally mediated hypotension to progressive neurodegenerative diseases; from disorders in which altered autonomic function plays a primary pathophysiologic role to disorders in which it worsens an independent pathologic state; and from mechanistically straightforward to mysterious and controversial entities.

In chronic autonomic failure (pure autonomic failure, multiple system atrophy, or autonomic failure in Parkinson disease), orthostatic hypotension reflects sympathetic neurocirculatory failure from sympathetic denervation or deranged reflexive regulation of sympathetic outflows. Chronic orthostatic intolerance associated with postural tachycardia can arise from cardiac sympathetic activation after “patchy” autonomic impairment or blood volume depletion or, as highlighted in this discussion, from a primary abnormality that augments delivery of the sympathetic neurotransmitter norepinephrine to its receptors in the heart. Increased sympathetic nerve traffic to the heart and kidneys seems to occur as essential hypertension develops.

Acute panic can evoke coronary spasm that is associated with sympathoneural and adrenomedullary excitation. In congestive heart failure, compensatory cardiac sympathetic activation may chronically worsen myocardial function, which rationalizes treatment with beta-adrenoceptor blockers. A high frequency of positive results on tilt-table testing has confirmed an association between the chronic fatigue syndrome and orthostatic intolerance; however, treatment with the salt-retaining steroid fludrocortisone, which is usually beneficial in primary chronic autonomic failure, does not seem to be beneficial in the chronic fatigue syndrome. Dysautonomias are an important subject in clinical neurocardiology.

Source: Goldstein DS, Robertson D, Esler M, Straus SE, Eisenhofer G. Dysautonomias: clinical disorders of the autonomic nervous system. Ann Intern Med. 2002 Nov 5;137(9):753-63. http://www.ncbi.nlm.nih.gov/pubmed/12416949

Brain regions involved in fatigue sensation: reduced acetylcarnitine uptake into the brain

Abstract:

Fatigue is an indispensable sense for ordering rest. However, the neuronal and molecular mechanisms of fatigue remain unclear. Chronic fatigue syndrome (CFS) with long-lasting fatigue sensation seems to be a good model for studying these mechanisms underlying fatigue sensation.

Recently, we found that most patients with CFS showed a low level of serum acetylcarnitine, which well correlated with the rating score of fatigue, and that a considerable amount of acetyl moiety of serum acetylcarnitine is taken up into the brain. Here we show by metabolite analysis of the mouse brain that an acetyl moiety taken up into the brain through acetylcarnitine is mainly utilized for the biosynthesis of glutamate.

When we studied the cerebral uptake of acetylcarnitine by using [2-(11)C]acetyl-L-carnitine in 8 patients with CFS and in 8 normal age- and sex-matched controls, a significant decrease was found in several regions of the brains of the patient group, namely, in the prefrontal (Brodmann’s area 9/46d) and temporal (BA21 and 41) cortices, anterior cingulate (BA24 and 33), and cerebellum.

These findings suggest that the levels of biosynthesis of neurotransmitters through acetylcarnitine might be reduced in some brain regions of chronic fatigue patients and that this abnormality might be one of the keys to unveiling the mechanisms of the chronic fatigue sensation.

Source: Kuratsune H, Yamaguti K, Lindh G, Evengård B, Hagberg G, Matsumura K, Iwase M, Onoe H, Takahashi M, Machii T, Kanakura Y, Kitani T, Långström B, Watanabe Y. Brain regions involved in fatigue sensation: reduced acetylcarnitine uptake into the brain. Neuroimage. 2002 Nov;17(3):1256-65. http://www.ncbi.nlm.nih.gov/pubmed/12414265

Relative increase in choline in the occipital cortex in chronic fatigue syndrome

Abstract:

OBJECTIVE: To test the hypothesis that chronic fatigue syndrome (CFS) is associated with altered cerebral metabolites in the frontal and occipital cortices.

METHOD: Cerebral proton magnetic resonance spectroscopy (1H MRS) was carried out in eight CFS patients and eight age- and sex-matched healthy control subjects. Spectra were obtained from 20 x 20 x 20 mm3 voxels in the dominant motor and occipital cortices using a point-resolved spectroscopy pulse sequence.

RESULTS: The mean ratio of choline (Cho) to creatine (Cr) in the occipital cortex in CFS (0.97) was significantly higher than in the controls (0.76; P=0.008). No other metabolite ratios were significantly different between the two groups in either the frontal or occipital cortex. In addition, there was a loss of the normal spatial variation of Cho in CFS.

CONCLUSION: Our results suggest that there may be an abnormality of phospholipid metabolism in the brain in CFS.

Source: Puri BK, Counsell SJ, Zaman R, Main J, Collins AG, Hajnal JV, Davey NJ. Relative increase in choline in the occipital cortex in chronic fatigue syndrome. Acta Psychiatr Scand. 2002 Sep;106(3):224-6. http://www.ncbi.nlm.nih.gov/pubmed/12197861

Brainstem conundrum: the Chiari I malformation

Abstract:

PURPOSE: To describe the Chairi I Malformation in relation to the anatomy of the brain and spinal cord, the common manifestations of the condition, diagnostic considerations, and management for the primary care provider.

DATA SOURCES: Extensive review of the world-wide scientific literature on the condition, supplemented with actual case studies.

CONCLUSIONS: The adult Chairi I Malformation is an insidious congenital brainstem anomaly that consists of caudal displacement of the cerebellar tonsils, brainstem and fourth ventricle into the upper cervical space, resulting in overcrowding of the posterior fossa.

IMPLICATIONS FOR PRACTICE: Due to the vague, and often ambiguous presenting symptoms of Chiari I Malformation, many patients are misdiagnosed with conditions such as multiple sclerosis, fibromyalgia, chronic fatigue syndrome, or psychiatric disorders. Patients frequently experience symptoms months to years prior to accurate diagnosis and often incur irreversible neurologic deficits.

Source: Mueller D. Brainstem conundrum: the Chiari I malformation. J Am Acad Nurse Pract. 2001 Apr;13(4):154-9. http://www.ncbi.nlm.nih.gov/pubmed/11930527

Neuroendocrine mechanisms in fibromyalgia-chronic fatigue

Abstract:

Fibromyalgia and chronic fatigue syndrome are poorly understood disorders that share similar demographic and clinical characteristics. Because of the clinical similarities between both disorders it was suggested that they share a common pathophysiological mechanism, namely, central nervous system dysfunction.

This chapter presents data demonstrating neurohormonal abnormalities, abnormal pain processing and autonomic nervous system dysfunction in fibromyalgia and chronic fatigue syndrome. The possible contribution of the central nervous system dysfunction to the development and symptomatology of these conditions is discussed. The chapter concludes by reviewing the effect of current treatments and emerging therapeutic modalities in fibromyalgia and chronic fatigue syndrome.

Source: Buskila D, Press J. Neuroendocrine mechanisms in fibromyalgia-chronic fatigue. Best Pract Res Clin Rheumatol. 2001 Dec;15(5):747-58. http://www.ncbi.nlm.nih.gov/pubmed/11812019

Hemodynamic instability in chronic fatigue syndrome: indices and diagnostic significance

Abstract:

OBJECTIVES: To evaluate the cardiovascular response to postural challenge in patients with chronic fatigue syndrome (CFS) and to determine whether the degree of instability of the cardiovascular response may aid in diagnosing CFS.

METHODS: Patients with CFS (n = 25) and their age- and gender-matched healthy controls (n = 37), patients with fibromyalgia (n = 30), generalized anxiety disorder (n = 15), and essential hypertension (n = 20) were evaluated with the aid of a standardized tilt test. The blood pressure (BP) and heart rate (HR) were recorded during 10 minutes of recumbence and 30 minutes of head-up tilt. We designated BP changes as the differences between successive BP values and the last recumbent BP. The average and standard deviation (SD) were calculated. Time curves of BP differences were loaded into a computerized image analyzer, and their outline ratios and fractal dimensions were measured. HR changes were determined similarly. The average and SD of the parameters were calculated, and intergroup comparisons were performed.

RESULTS: On multivariate analysis, the independent predictors of CFS patients versus healthy controls were the fractal dimension of absolute values of the systolic BP changes (SYST-FD.abs), the standard deviation of the current values of the systolic BP changes (SYST-SD.cur), and the standard deviation of the current values of the heart rate changes (HR-SD.cur). The following equation was deduced to calculate the hemodynamic instability score (HIS) in the individual patient: HIS = 64.3303 + (SYST-FD.abs x -68.0135) + (SYST-SD.cur x 111.3726) + (HR-SD.cur x 60.4164). The best cutoff differentiating CFS from the healthy controls was -0.98. HIS values >-0.98 were associated with CFS (sensitivity 97%, specificity 97%). The HIS differed significantly between CFS and other groups (P <.0001) except for generalized anxiety disorder. Group averages (SD) of HIS were CFS = +3.72 (5.02), healthy = -4.62 (2.26), fibromyalgia = -3.27 (2.63), hypertension = -5.53 (2.24), and generalized anxiety disorder = +1.08 (5.2).

CONCLUSION: The HIS adds objective criteria confirming the diagnosis of CFS.

Source: Naschitz JE, Sabo E, Naschitz S, Shaviv N, Rosner I, Rozenbaum M, Gaitini L, Ahdoot A, Ahdoot M, Priselac RM, Eldar S, Zukerman E, Yeshurun D. Hemodynamic instability in chronic fatigue syndrome: indices and diagnostic significance. Semin Arthritis Rheum. 2001 Dec;31(3):199-208. http://www.ncbi.nlm.nih.gov/pubmed/11740800

Autonomic nervous system derangement in fibromyalgia syndrome and related disorders

Abstract:

Fibromyalgia syndrome is a chronic, painful musculoskeletal disorder of unknown etiology and/or pathophysiology. During the last decade many studies have suggested autonomic nervous system involvement in this syndrome, although contradictory results have been reported. This review focuses on studies of the autonomic nervous system in fibromyalgia syndrome and related disorders, such as chronic fatigue syndrome and irritable bowel syndrome on the one hand and anxiety disorder on the other, and highlights techniques of dynamic assessment of heart rate variability. It raises the potentially important prognostic implications of protracted autonomic dysfunction in patient populations with fibromyalgia and related disorders, especially for cardiovascular morbidity and mortality.

Source: Cohen H, Neumann L, Kotler M, Buskila D. Autonomic nervous system derangement in fibromyalgia syndrome and related disorders. Isr Med Assoc J. 2001 Oct;3(10):755-60. http://www.ncbi.nlm.nih.gov/pubmed/11692551

LPS-induced IL-10 production in whole blood cultures from chronic fatigue syndrome patients is increased but supersensitive to inhibition by dexamethasone

Abstract:

Several causes have been held responsible for the chronic fatigue syndrome (CFS), including an altered hypothalamus-pituitary-adrenal gland (HPA)-axis activity, viral infections and a reduced Th1 activity. Therefore, it was investigated whether the regulation of IL-10 is different in CFS.

LPS-induced cytokine secretion in whole blood cultures showed a significant increase in IL-10 and a trend towards a decrease in IL-12 as compared with healthy controls. In patients and controls, IL-12 secretion was equally sensitive to suppression by dexamethasone, whereas IL-10 secretion appeared more sensitive in CFS-patients. In controls, IL-10 and IL-12 secretion were inversely correlated with free serum cortisol (r=-0.492, p<0.02 and r=-0.434, p<0.05, respectively). In CFS, such an inverse correlation was found for IL-12 (r=-0.611, p<0.02) but not for IL-10 (r=-0.341, ns).

These data are suggestive for a disturbed glucocorticoid regulation of IL-10 in CFS.

Source: Visser J, Graffelman W, Blauw B, Haspels I, Lentjes E, de Kloet ER, Nagelkerken L. LPS-induced IL-10 production in whole blood cultures from chronic fatigue syndrome patients is increased but supersensitive to inhibition by dexamethasone. J Neuroimmunol. 2001 Oct 1;119(2):343-9. http://www.ncbi.nlm.nih.gov/pubmed/11585638

Corticospinal inhibition appears normal in patients with chronic fatigue syndrome

Abstract:

The pathogenesis of chronic fatigue syndrome (CFS) remains unknown. Thresholds and latencies of motor evoked potentials (MEPs) in response to transcranial magnetic stimulation (TMS) are normal but intracortical inhibition has not been investigated.

Eleven patients with CFS were compared with 11 control subjects. Each patient completed a questionnaire using visual analogue indices of pain, fatigue, anxiety and depression. Subjects released a button to initiate simple (SRTs) and choice reaction time (CRTs) tasks; for each task, movement times were measured between release of the initiation button and depression of a second button 15 cm away. Subjects held a 10 % maximum voluntary contraction in the thenar muscles of their dominant hand while TMS was applied to the motor cortex; the duration and extent of inhibition of surface electromyographic (EMG) activity were assessed at stimulus strengths above and below the threshold for MEPs.

Patients had significantly (P < 0.05) higher mean indices of fatigue than of pain, anxiety or depression. Mean (+/- S.E.M.) SRTs (but not CRTs) were longer in patients (309 +/- 45 ms) than in controls (218 +/- 9 ms). Movement times were longer in patients for both SRTs and CRTs. TMS thresholds, expressed as a percentage of the maximum stimulator output, were not significantly (P > 0.05) different in both groups for both MEPs (patients, 34 +/- 3%; controls, 36 +/- 3%) and inhibition of voluntary contraction (patients, 29 +/- 2%; controls, 34 +/- 4%). The duration and extent of inhibition did not differ significantly between groups at any stimulus strength. The pattern of change in duration and extent of inhibition with increasing stimulus intensity was no different in the two groups. The duration and extent of corticospinal inhibition in patients with CFS did not differ from controls, adding further evidence to the notion that the feeling of fatigue and the slowness of movement seen in CFS is not manifest in corticospinal output pathways.

Source: Zaman R, Puri BK, Main J, Nowicky AV, Davey NJ. Corticospinal inhibition appears normal in patients with chronic fatigue syndrome. Exp Physiol. 2001 Sep;86(5):547-50. http://www.ncbi.nlm.nih.gov/pubmed/11571481