Neurology – Page 30 – American ME and CFS Society

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

Corticotropin releasing hormone in the pathophysiology of melancholic and atypical depression and in the mechanism of action of antidepressant drugs

Abstract:

Hypercortisolism in depression seems to preferentially reflect activation of hypothalamic CRH secretion. Although it has been postulated that this hypercortisolism is an epiphenomenon of the pain and stress of major depression, our data showing preferential participation of AVP in the hypercortisolism of chronic inflammatory disease suggest specificity for the pathophysiology of hypercortisolism in depression.

Our findings that imipramine causes a down-regulation of the HPA axis in experimental animals and healthy controls support an intrinsic role for CRH in the pathophysiology of melancholia and in the mechanism of action of psychotropic agents. Our data suggest that hypercortisolism is not the only form of HPA dysregulation in major depression.

In a series of studies, commencing in patients with Cushing’s disease, and extending to hyperimmune fatigue states such as chronic fatigue syndrome and examples of atypical depression such as seasonal affective disorder, we have advanced data suggesting hypofunction of hypothalamic CRH neurons. These data raise the question that the hyperphagia, hypersomnia, and fatigue associated with syndromes of atypical depression could reflect a central deficiency of a potent arousal-producing anorexogenic neuropeptide.

In the light of data presented elsewhere in this symposium regarding the role of a hypofunctioning hypothalamic CRH neuron in susceptibility to inflammatory disease, these data also raise the question of a common pathophysiological mechanism in syndromes associated both with inflammatory manifestations and atypical depressive symptoms. This concept of hypofunctioning of hypothalamic CRH neurons in these disorders also raises the question of novel forms of neuropharmacological intervention in both inflammatory diseases and atypical depressive syndromes.

Source: Gold PW, Licinio J, Wong ML, Chrousos GP. Corticotropin releasing hormone in the pathophysiology of melancholic and atypical depression and in the mechanism of action of antidepressant drugs. Ann N Y Acad Sci. 1995 Dec 29;771:716-29. http://www.ncbi.nlm.nih.gov/pubmed/8597444

Auditory brain stem evoked potentials in the evaluation of chronic fatigue syndrome

Abstract:

The Chronic Fatigue Syndrome (CFS) was formally defined to describe disabling fatigue of multifactorial ethology with depression and immunologic dysfunctions linked to some currently recognized infectious agents. In most cases neurophysiological tests reveal abnormalities.

In this paper the Authors use low (11 pps) and high (51-71 pps) frequency ABR to evaluate the electrophysiological function of auditory brainstem responses. Eighteen patients with suspected CFS, between the ages of 17 and 63, were examined. Eleven subjects had clinically diagnosed “true” CFS (CDC criteria modified by Fukuda). The 11 pps frequency test did not reveal a high number of abnormalities in the patients in question.

However, the high frequency stimulation test (with 51 and 71 pps) which was statistically significant (P = 0.009) revealed numerous aberrations in 7 patients; absence of the first wave in 1 case, in 5 numerous wave gap delays and in 1 patient absence of the first wave and numerous wave gap delays. The high frequency test did not show many abnormalities for the 4 remaining patients. For the 7 “non CFS” subjects, the clinical-audiological comparison showed no statistical significance (P = 0.920).

The Authors hypothesize that the absence of the first wave in the CFS Subject may well indicate a cyto-neural junction disease in the organ of Corti. The combined analysis of clinical and audiological data showed that the described tests are more reliable when employed in dealing with patients with clinically assessed “true” CFS.

Source: Bianchedi M, Croce A, Moretti A, Neri G, Barberio A, Iezzi A, Pizzigallo E. Auditory brain stem evoked potentials in the evaluation of chronic fatigue syndrome. Acta Otorhinolaryngol Ital. 1995 Dec;15(6):403-10. [Article in Italian] http://www.ncbi.nlm.nih.gov/pubmed/8711992

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

The relationship between neurally mediated hypotension and the chronic fatigue syndrome

Abstract:

OBJECTIVE: To compare the clinical symptoms and response evoked by upright tilt-table testing in healthy individuals and in a sample of those satisfying strict criteria for chronic fatigue syndrome.

DESIGN: Case-comparison study with mean (SD) follow-up of 24 (5) weeks.

SETTING: Tertiary care hospital.

PATIENTS AND OTHER PARTICIPANTS: A sample of 23 patients with chronic fatigue syndrome (five men and 18 women; mean age, 34 years), each of whom fulfilled the strict diagnostic criteria of the Centers for Disease Control and Prevention, was recruited from regional chronic fatigue support groups and from the investigators’ clinical practices. There were 14 healthy controls (four men and 10 women; mean age, 36 years).

INTERVENTIONS: Each subject completed a symptom questionnaire and underwent a three-stage upright tilt-table test (stage 1, 45 minutes at 70 degrees tilt; stage 2, 15 minutes at 70 degrees tilt with 1 to 2 micrograms/min of isoproterenol; and stage 3, 10 minutes at 70 degrees with 3 to 4 micrograms/min of isoproterenol). Patients were offered therapy with fludrocortisone, beta-adrenergic blocking agents, and disopyramide, alone or in combination, directed at neurally mediated hypotension.

MAIN OUTCOME MEASURES: Response to upright tilt and scores on symptom questionnaires prior to and during follow-up.

RESULTS: An abnormal response to upright tilt was observed in 22 of 23 patients with chronic fatigue syndrome vs four of 14 controls (P < .001). Seventy percent of chronic fatigue syndrome patients, but no controls, had an abnormal response during stage 1 (P < .001). Nine patients reported complete or nearly complete resolution of chronic fatigue syndrome symptoms after therapy directed at neurally mediated hypotension.

CONCLUSIONS: We conclude that chronic fatigue syndrome is associated with neurally mediated hypotension and that its symptoms may be improved in a subset of patients by therapy directed at this abnormal cardiovascular reflex.

Comment in:

Chronic fatigue syndrome and neurally mediated hypotension. [JAMA. 1996]

Orthostatic hypotension and chronic fatigue syndrome. [JAMA. 2001]

Chronic fatigue syndrome and neurally mediated hypotension. [JAMA. 1996]

Source: Bou-Holaigah I, Rowe PC, Kan J, Calkins H. The relationship between neurally mediated hypotension and the chronic fatigue syndrome. JAMA. 1995 Sep 27;274(12):961-7. http://www.ncbi.nlm.nih.gov/pubmed/7674527

Vagal tone is reduced during paced breathing in patients with the chronic fatigue syndrome

Abstract:

Patients with chronic fatigue syndrome (CFS) often complain of an inability to maintain activity levels and a variety of autonomic-like symptoms that make everyday activity intolerable at times. The purpose of the study was to determine if there were differences in vagal activity at fixed breathing rates in women with CFS.

Twelve women with the diagnosis of CFS between the ages of 32 and 59 years volunteered for the study. Healthy women, who were between the ages of 30 and 49, served as controls. Full signal electrocardiograph and respiratory signals were collected during a paced breathing protocol of three fixed breathing rates (8, 12 and 18 breaths/min) performed in the sitting and standing postures. Vagal activity was analyzed by means of heart rate spectral analysis to determine the subject’s response to specific breathing rates and postures. Heart rate variability was used as a non-invasive method of measuring the parasympathetic component of the autonomic nervous system.

Using this method, although there was significantly less vagal power in the sitting versus the standing postures for both groups, the overall vagal power was significantly lower (p < 0.034) in the CFS group versus healthy controls. Vagal power was also significantly lower (p < 0.01 to p < 0.05) at all breathing rates in both postures except while standing and breathing at 18 breaths/min. Knowledge of the differences in vagal activity for CFS patients may allow stratification for the analysis of other research variables.

Source: Sisto SA, Tapp W, Drastal S, Bergen M, DeMasi I, Cordero D, Natelson B. Vagal tone is reduced during paced breathing in patients with the chronic fatigue syndrome. Clin Auton Res. 1995 Jun;5(3):139-43. http://www.ncbi.nlm.nih.gov/pubmed/7549414

Is neurally mediated hypotension an unrecognised cause of chronic fatigue?

Abstract:

Neurally mediated hypotension is now recognised as a common cause of otherwise unexplained recurrent syncope, but has not been reported in association with chronic fatigue. We describe seven consecutive non-syncopal adolescents with chronic post-exertional fatigue, four of whom satisfied strict criteria for chronic fatigue syndrome. Upright tilt-table testing induced significant hypotension in all seven (median systolic blood pressure 65 mm Hg, range 37-75), consistent with the physiology of neurally mediated hypotension. Four had prompt improvement in their chronic fatigue when treated with atenolol or disopyramide. These observations suggest an overlap in the symptoms of chronic fatigue syndrome and neurally mediated hypotension.

Comment in:

Is neurally mediated hypotension an unrecognised cause of chronic fatigue? [Lancet. 1995]

Source: Rowe PC, Bou-Holaigah I, Kan JS, Calkins H. Is neurally mediated hypotension an unrecognised cause of chronic fatigue? Lancet. 1995 Mar 11;345(8950):623-4. http://www.ncbi.nlm.nih.gov/pubmed/7898182

Fatigue brought on by malfunction of the central and peripheral nervous systems

Abstract:

Increased fatigability necessarily occurs in every patient with muscle weakness, regardless of whether the latter is due to a central or peripheral neurological disorder. The tendency for disuse to increase fatigability, as a secondary phenomenon, must also be considered; disuse affects both motoneuron recruitment and the biochemical and physiological properties of the muscle fibers. In recent studies impaired recruitment has been observed in postpolio patients, while patients with multiple sclerosis or spinal cord injury have shown, in addition, altered neuromuscular function. Findings are also presented in ALS and the chronic fatigue syndrome. In general, the most dramatic increases in fatigability take place in disorders of the peripheral nervous system and almost any cell component can be incriminated. There is a need to study fatigability systematically in neurology and rehabilitation.

Source: McComas AJ, Miller RG, Gandevia SC. Fatigue brought on by malfunction of the central and peripheral nervous systems. Adv Exp Med Biol. 1995;384:495-512. http://www.ncbi.nlm.nih.gov/pubmed/8585475

Sympathetic overactivity in subjects complaining of unexplained fatigue

Abstract:

Theoretical and practical considerations suggest that in subjects complaining of fatigue, in the absence of evident organ dysfunction, an alteration in the autonomic nervous system might be present as a functional correlate.

Autoregressive spectral analysis of R-R interval variability from a surface ECG, was used in healthy control subjects (n = 24, age 45 +/- 4 years) and in subjects complaining of unexplained fatigue (n = 53, age 46 +/- 9 years) to obtain quantitative indices of the state of the sympathovagal balance, both at rest and during a mental stimulus (mental arithmetic), capable of enhancing sympathetic drive. Sympathetic and vagal modulations were inferred from the normalized powers of the low frequency and high frequency spectral components respectively.

We observed in patients, at rest, a prevailing low frequency component of R-R variability (patients low frequency = 73 +/- 11, control subjects 51 +/- 10 normalized units, P < 0.05). The responsiveness to mental arithmetic was reduced in patients as compared with controls. Systolic blood pressure variability did not differ. This suggested a selective imbalance in autonomic control of the sinoatrial node, characterized by sympathetic predominance as well as by vagal withdrawal, at rest.

The possibility of discriminating patients from control subjects on the basis of simple non-invasive functional markers might provide a better understanding of the mechanisms, clinical evolution and outcome of conditions such as the chronic fatigue syndrome, which lack ordinary evidence of disease, but comprise, as physiopathological correlate, a quantitative alteration of autonomic control.

Source: Pagani M, Lucini D, Mela GS, Langewitz W, Malliani A. Sympathetic overactivity in subjects complaining of unexplained fatigue. Clin Sci (Lond). 1994 Dec;87(6):655-61. http://www.ncbi.nlm.nih.gov/pubmed/7874856

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