Overlapping Illnesses – Page 198 – American ME and CFS Society

Mitochondrial Myopathy in Follow-up of a Patient With Chronic Fatigue Syndrome

Abstract:

Introduction. Symptoms of mitochondrial diseases and chronic fatigue syndrome (CFS) frequently overlap and can easily be mistaken.

Methods. We report the case of a patient diagnosed with CFS and during follow-up was finally diagnosed with mitochondrial myopathy by histochemical study of muscle biopsy, spectrophotometric analysis of the complexes of the mitochondrial respiratory chain, and genetic studies.

Results. The results revealed 3% fiber-ragged blue and a severe deficiency of complexes I and IV and several mtDNA variants. Mother, sisters, and nephews showed similar symptoms, which strongly suggests a possible maternal inheritance. The patient and his family responded to treatment with high doses of riboflavin and thiamine with a remarkable and sustained fatigue and muscle symptoms improvement.

Conclusions. This case illustrates that initial symptoms of mitochondrial disease in adults can easily be mistaken with CFS, and in these patients a regular reassessment and monitoring of symptoms is recommended to reconfirm or change the diagnosis.

Source: Galán F, de Lavera I, Cotán D, Sánchez-Alcázar JA. Mitochondrial Myopathy in Follow-up of a Patient With Chronic Fatigue Syndrome. J Investig Med High Impact Case Rep. 2015 Sep 24;3(3):2324709615607908. doi: 10.1177/2324709615607908. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4748504/ (Full article)

Borderline Intracranial Hypertension Manifesting as Chronic Fatigue Syndrome Treated by Venous Sinus Stenting

Abstract:

Chronic fatigue syndrome and cases of idiopathic intracranial hypertension without signs of raised intracranial pressure can be impossible to distinguish without direct measurement of intracranial pressure. Moreover, lumbar puncture, the usual method of measuring intracranial pressure, can produce a similar respite from symptoms in patients with chronic fatigue as it does in idiopathic intracranial hypertension. This suggests a connection between them, with chronic fatigue syndrome representing a forme fruste variant of idiopathic intracranial hypertension. If this were the case, then treatments available for idiopathic intracranial hypertension might be appropriate for chronic fatigue.

We describe a 49-year-old woman with a long and debilitating history of chronic fatigue syndrome who was targeted for investigation of intracranial pressure because of headache, then diagnosed with borderline idiopathic intracranial hypertension after lumbar puncture and cerebrospinal fluid drainage. Further investigation showed narrowings at the anterior ends of the transverse sinuses, typical of those seen in idiopathic intracranial hypertension and associated with pressure gradients.

Stenting of both transverse sinuses brought about a life-changing remission of symptoms with no regression in 2 years of follow-up. This result invites study of an alternative approach to the investigation and management of chronic fatigue.

Source: Higgins N, Pickard J, Lever A. Borderline Intracranial Hypertension Manifesting as Chronic Fatigue Syndrome Treated by Venous Sinus Stenting. J Neurol Surg Rep. 2015 Nov;76(2):e244-7. doi: 10.1055/s-0035-1564060. Epub 2015 Sep 14. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4648738/ (Full article)

A systematic review of the comorbidity between Temporomandibular Disorders and Chronic Fatigue Syndrome

Abstract:

The most common cause of chronic oro-facial pain is a group of disorders collectively termed temporomandibular disorders (TMDs). Chronic painful TMD is thought to be a ‘central sensitivity syndrome’ related to hypersensitivity of the nervous system, but the cause is unknown. A similar understanding is proposed for other unexplained conditions, including chronic fatigue syndrome (CFS). Exploring the comorbidity of the two conditions is a valuable first step in identifying potential common aetiological mechanisms or treatment targets.

METHOD: Systematic literature review. Studies were included if they recruited community or control samples and identified how many reported having both TMD and CFS, or if they recruited a sample of patients with either TMD or CFS and measured the presence of the other condition.

RESULTS: Six papers met inclusion criteria. In studies of patients with CFS (n = 3), 21-32% reported having TMD. In a sample of people with CFS and fibromyalgia, 50% reported having TMD. Studies in people with TMD (n = 3) reported 0-43% having CFS. Studies in samples recruited from oro-facial pain clinics (n = 2) reported a lower comorbidity with CFS (0-10%) than a study that recruited individuals from a TMD self-help organisation (43%).

CONCLUSION: The review highlights the limited standard of evidence addressing the comorbidity between oro-facial pain and CFS. There is a valuable signal that the potential overlap in these two conditions could be high; however, studies employing more rigorous methodology including standardised clinical assessments rather than self-report of prior diagnosis are needed.

Source: Robinson LJ, Durham J, Newton JL. A systematic review of the comorbidity between Temporomandibular Disorders and Chronic Fatigue Syndrome. J Oral Rehabil. 2016 Apr;43(4):306-16. doi: 10.1111/joor.12367. Epub 2015 Nov 9. https://www.ncbi.nlm.nih.gov/pubmed/26549386

The many roads to mitochondrial dysfunction in neuroimmune and neuropsychiatric disorders

Abstract:

BACKGROUND: Mitochondrial dysfunction and defects in oxidative metabolism are a characteristic feature of many chronic illnesses not currently classified as mitochondrial diseases. Examples of such illnesses include bipolar disorder, multiple sclerosis, Parkinson’s disease, schizophrenia, depression, autism, and chronic fatigue syndrome.

DISCUSSION: While the majority of patients with multiple sclerosis appear to have widespread mitochondrial dysfunction and impaired ATP production, the findings in patients diagnosed with Parkinson’s disease, autism, depression, bipolar disorder schizophrenia and chronic fatigue syndrome are less consistent, likely reflecting the fact that these diagnoses do not represent a disease with a unitary pathogenesis and pathophysiology. However, investigations have revealed the presence of chronic oxidative stress to be an almost invariant finding in study cohorts of patients afforded each diagnosis. This state is characterized by elevated reactive oxygen and nitrogen species and/or reduced levels of glutathione, and goes hand in hand with chronic systemic inflammation with elevated levels of pro-inflammatory cytokines.

SUMMARY: This paper details mechanisms by which elevated levels of reactive oxygen and nitrogen species together with elevated pro-inflammatory cytokines could conspire to pave a major road to the development of mitochondrial dysfunction and impaired oxidative metabolism seen in many patients diagnosed with these disorders.

Source: Morris G, Berk M. The many roads to mitochondrial dysfunction in neuroimmune and neuropsychiatric disorders. BMC Med. 2015 Apr 1;13:68. doi: 10.1186/s12916-015-0310-y. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4382850/ (Full article)

Chronic fatigue syndrome and fibromyalgia in diagnosed sleep disorders: a further test of the ‘unitary’ hypothesis

Abstract:

BACKGROUND: Since chronic fatigue syndrome (CFS) and fibromyalgia (FM) often co-exist, some believe they reflect the same process, somatization. Against that hypothesis are data suggesting FM but not CFS was common in patients with sleep-disordered breathing (SDB). The presence of discrete case definitions for CFS and FM allowed us to explore rates of CFS alone, CFS with FM, and FM alone in SDB patients compared to those with sleep complaints that fulfilled criteria for insomnia.

METHODS: Participants were 175 sequential patients with sleep-related symptoms (122 had SDB and 21 had insomnia) and 39 healthy controls. Diagnoses were made by questionnaires, tender point count, and rule out labs; sleepiness was assessed with Epworth Sleepiness Scale and mood with Beck Depression Inventory.

RESULTS: Rates of CFS, FM or CFS + FM were high: 13% in SDB and 48% in insomnia. CFS occurred frequently in SDB and insomnia, but FM occurred frequently only in insomnia. SDB patients with CFS and/or FM had higher daytime sleepiness than those without these disorders.

CONCLUSION: CFS patients should complete Epworth scales, and sleep evaluation should be considered for those with scores ≥ 16 before receiving the diagnosis of CFS; the coexistence of depressed mood in these patients suggests some may be helped by treatment of their depression. That FM was underrepresented in SDB suggests FM and CFS may have different underlying pathophysiological causes.

Source: Pejovic S, Natelson BH, Basta M, Fernandez-Mendoza J, Mahr F, Vgontzas AN. Chronic fatigue syndrome and fibromyalgia in diagnosed sleep disorders: a further test of the ‘unitary’ hypothesis. BMC Neurol. 2015 Apr 12;15:53. doi: 10.1186/s12883-015-0308-2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4405866/ (Full article)

Anti-neural antibody response in patients with post-treatment Lyme disease symptoms versus those with myalgic encephalomyelitis/chronic fatigue syndrome

Post-treatment Lyme disease symptoms (PTLDS) and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) have several clinical features in common, including fatigue, musculoskeletal pain, and cognitive difficulties (Gaudino et al., 1997). Immunologic mechanisms have been suspected to play a role in both PTLDS and ME/CFS. However, biomarkers for the two conditions are currently lacking, creating a barrier to better understand them. In a previous study published in BBI, we developed a semi-quantitative immunoblot assay to compare antibody reactivity to neural antigens in a group of PTLDS patients and controls (Chandra et al., 2010).

You can read the rest of this study here: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4638178/

Source: Ajamian M, Cooperstock M, Wormser GP, Vernon SD, Alaedini A. Anti-neural antibody response in patients with post-treatment Lyme disease symptoms versus those with myalgic encephalomyelitis/chronic fatigue syndrome. Brain Behav Immun. 2015 Aug;48:354-5. doi: 10.1016/j.bbi.2015.04.006. Epub 2015 Apr 10. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4638178/ (Full article)

Central pathways causing fatigue in neuro-inflammatory and autoimmune illnesses

Abstract:

BACKGROUND: The genesis of severe fatigue and disability in people following acute pathogen invasion involves the activation of Toll-like receptors followed by the upregulation of proinflammatory cytokines and the activation of microglia and astrocytes. Many patients suffering from neuroinflammatory and autoimmune diseases, such as multiple sclerosis, Parkinson’s disease and systemic lupus erythematosus, also commonly suffer from severe disabling fatigue.

Such patients also present with chronic peripheral immune activation and systemic inflammation in the guise of elevated proinflammtory cytokines, oxidative stress and activated Toll-like receptors. This is also true of many patients presenting with severe, apparently idiopathic, fatigue accompanied by profound levels of physical and cognitive disability often afforded the non-specific diagnosis of chronic fatigue syndrome.

DISCUSSION: Multiple lines of evidence demonstrate a positive association between the degree of peripheral immune activation, inflammation and oxidative stress, gray matter atrophy, glucose hypometabolism and cerebral hypoperfusion in illness, such as multiple sclerosis, Parkinson’s disease and chronic fatigue syndrome. Most, if not all, of these abnormalities can be explained by a reduction in the numbers and function of astrocytes secondary to peripheral immune activation and inflammation.

This is also true of the widespread mitochondrial dysfunction seen in otherwise normal tissue in neuroinflammatory, neurodegenerative and autoimmune diseases and in many patients with disabling, apparently idiopathic, fatigue. Given the strong association between peripheral immune activation and neuroinflammation with the genesis of fatigue the latter group of patients should be examined using FLAIR magnetic resonance imaging (MRI) and tested for the presence of peripheral immune activation.

SUMMARY: It is concluded that peripheral inflammation and immune activation, together with the subsequent activation of glial cells and mitochondrial damage, likely account for the severe levels of intractable fatigue and disability seen in many patients with neuroimmune and autoimmune diseases.This would also appear to be the case for many patients afforded a diagnosis of Chronic Fatigue Syndrome.

Source: Morris G, Berk M, Walder K, Maes M. Central pathways causing fatigue in neuro-inflammatory and autoimmune illnesses. BMC Med. 2015 Feb 6;13:28. doi: 10.1186/s12916-014-0259-2. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4320458/ (Full article)

The inflammatory hypothesis of mood spectrum broadened to fibromyalgia and chronic fatigue syndrome

Abstract:

OBJECTIVES: The present paper aimed at reviewing literature data on the inflammatory hypothesis of mood spectrum, as well as the overlapping features with some chronic rheumatologic disorders, in particular fibromyalgia and chronic fatigue syndrome.

METHODS: A literature search was carried out for English papers published in the years 2000-2014, while using the following words: mood spectrum, depression, bipolar disorders, fibromyalgia, chronic fatigue syndrome, neurotransmitters, inflammation, neuroinflammation, cytokines.

RESULTS: Overlapping features were highlighted between mood spectrum, fibromyalgia and chronic fatigue syndrome suggesting common underlying mechanisms at pathophysiological level involving both central nervous and the immune systems.

CONCLUSIONS: Taken together, the literature would suggest that the borders between different medical domains should be reconsidered in the light of common processes linking them.

Source: Dell’Osso L, Bazzichi L, Baroni S, Falaschi V, Conversano C, Carmassi C, Marazziti D. The inflammatory hypothesis of mood spectrum broadened to fibromyalgia and chronic fatigue syndrome. Clin Exp Rheumatol. 2015 Jan-Feb;33(1 Suppl 88):S109-16. Epub 2015 Mar 18. https://www.ncbi.nlm.nih.gov/pubmed/25786052

Early menopause and other gynecologic risk indicators for chronic fatigue syndrome in women

Abstract:

OBJECTIVE: This study aims to examine whether gynecologic conditions are associated with chronic fatigue syndrome (CFS).

METHODS: This study includes a subset of 157 women from a population-based case-control study in Georgia, United States, conducted in 2004-2009. Gynecologic history was collected using a self-administered questionnaire. Crude odds ratios (ORs) with 95% CIs and ORs adjusted for body mass index and other covariates, where relevant, were estimated for gynecologic conditions between 84 CFS cases and 73 healthy controls.

RESULTS: Cases and controls were of similar age. Women with CFS reported significantly more gynecologic conditions and surgical operations than controls: menopause status (61.9% vs 37.0%; OR, 2.37; 95% CI, 1.21-4.66), earlier mean age at menopause onset (37.6 vs 48.6 y; adjusted OR, 1.22; 95% CI, 1.09-1.36), excessive menstrual bleeding (73.8% vs 42.5%; adjusted OR, 3.33; 95% CI, 1.66-6.70), bleeding between periods (48.8% vs 23.3%; adjusted OR, 3.31; 95% CI, 1.60-6.86), endometriosis (29.8% vs 12.3%; adjusted OR, 3.67; 95% CI, 1.53-8.84), use of noncontraceptive hormonal preparations (57.1% vs 26.0%; adjusted OR, 2.95; 95% CI, 1.36-6.38), nonmenstrual pelvic pain (26.2% vs 2.7%; adjusted OR, 11.98; 95% CI, 2.57-55.81), and gynecologic surgical operation (65.5% vs 31.5%; adjusted OR, 3.33; 95% CI, 1.66-6.67), especially hysterectomy (54.8% vs 19.2%; adjusted OR, 3.23; 95% CI, 1.46-7.17). Hysterectomy and oophorectomy occurred at a significantly younger mean age in the CFS group than in controls and occurred before CFS onset in 71% of women with records of date of surgical operation and date of CFS onset.

CONCLUSIONS: Menstrual abnormalities, endometriosis, pelvic pain, hysterectomy, and early/surgical menopause are all associated with CFS. Clinicians should be aware of the association between common gynecologic problems and CFS in women. Further work is warranted to determine whether these conditions contribute to the development and/or perpetuation of CFS in some women.

Source: Boneva RS, Lin JM, Unger ER. Early menopause and other gynecologic risk indicators for chronic fatigue syndrome in women. Menopause. 2015 Aug;22(8):826-34. doi: 10.1097/GME.0000000000000411. https://www.ncbi.nlm.nih.gov/pubmed/25647777

Cytokine expression provides clues to the pathophysiology of Gulf War illness and myalgic encephalomyelitis

Abstract:

Gulf War illness (GWI) is a chronic disease of unknown etiology characterized by persistent symptoms such as cognitive impairment, unexplained fatigue, pervasive pain, headaches, and gastrointestinal abnormalities. Current reports suggest that as many as 200,000 veterans who served in the 1990-1991 Persian Gulf War were afflicted. Several potential triggers of GWI have been proposed including chemical exposure, toxins, vaccines, and unknown infectious agents. However, a definitive cause of GWI has not been identified and a specific biological marker that can consistently delineate the disease has not been defined.

Myalgic encephalomyelitis (ME) is a disease with similar and overlapping symptomology, and subjects diagnosed with GWI typically fit the diagnostic criteria for ME. For these reasons, GWI is often considered a subgroup of ME.

To explore this possibility and identify immune parameters that may help to understand GWI pathophysiology, we measured 77 serum cytokines in subjects with GWI and compared these data to that of subjects with ME as well as healthy controls.

Our analysis identified a group of cytokines that identified ME and GWI cases with sensitivities of 92.5% and 64.9%, respectively. The five most significant cytokines in decreasing order of importance were IL-7, IL-4, TNF-α, IL-13, and IL-17F. When delineating GWI and ME cases from healthy controls, the observed specificity was only 33.3%, suggesting that with respect to cytokine expression, GWI cases resemble control subjects to a greater extent than ME cases across a number of parameters. These results imply that serum cytokines are representative of ME pathology to a greater extent than GWI and further suggest that the two diseases have distinct immune profiles despite their overlapping symptomology.

Source: Khaiboullina SF, DeMeirleir KL, Rawat S, Berk GS, Gaynor-Berk RS, Mijatovic T, Blatt N, Rizvanov AA, Young SG, Lombardi VC. Cytokine expression provides clues to the pathophysiology of Gulf War illness and myalgic encephalomyelitis. Cytokine. 2015 Mar;72(1):1-8. doi: 10.1016/j.cyto.2014.11.019. Epub 2014 Dec 13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4410698/ (Full article)