Spinal fluid proteins distinguish Lyme disease from chronic fatigue syndrome

Patients who suffer from Neurologic Post Treatment Lyme disease (nPTLS) and those with the chronic fatigue syndrome report similar symptoms. However unique proteins discovered in spinal fluid can distinguish those two groups from one another and also from people in normal health, according to new research conducted by a team led by Steven E. Schutzer, MD, of the University of Medicine and Dentistry of New Jersey — New Jersey Medical School, and Richard D. Smith, Ph.D., of Pacific Northwest National Laboratory.

This finding, published in the journal PLoS ONE, also suggests that both conditions involve the central nervous system and that protein abnormalities in the central nervous system are causes and/or effects of both conditions.

The investigators analyzed spinal fluid from three groups of people. One group consisted of 43 patients who fulfilled the clinical criteria for chronic fatigue syndrome (CFS). The second group consisted of 25 patients who had been diagnosed with, and treated for, Lyme disease but did not completely recover. The third group consisted of 11 healthy control subjects. “Spinal fluid is like a liquid window to the brain,” says Dr. Schutzer. By studying the spinal fluid, the research team hoped to find abnormalities that could be used as markers of each condition and could lead to improvements in diagnosis and treatment.

Taking advantage of previously unavailable methods for detailed analysis of spinal fluid, the investigators analyzed the fluid by means of high powered mass spectrometry and special protein separation techniques. They found that each group had more than 2,500 detectable proteins. The research team discovered that there were 738 proteins that were identified only in CFS but not in either healthy normal controls or patients with nPTLS and 692 proteins found only in the nPTLS patients. Previously there had been no available candidate biomarkers to distinguish between the two syndromes, nor even strong evidence that the central nervous system is involved in those conditions.

This research represents the most comprehensive analysis of the complete CSF proteome (collection of proteins) to date for both Chronic Fatigue Syndrome and Neurologic Post Treatment Lyme disease (nPTLS). Prior to this study, many scientists believed that CFS was an umbrella category that included nPTLS. However these results call those previous suppositions into question.

According to Dr. Schutzer, spinal fluid proteins can likely be used as a marker of disease, and this study provides a starting point for research in that area. “One next step will be to find the best biomarkers that will give conclusive diagnostic results,” he says. “In addition, if a protein pathway is found to influence either disease, scientists could then develop treatments to target that particular pathway.”

“Newer techniques that are being developed by the team will allow researchers to dig even deeper and get more information for these and other neurologic diseases,” says Dr. Smith. “These exciting findings are the tip of our research iceberg”

Journal Reference: Steven E Schutzer, Thomas E Angel, Tao Liu, Athena A Schepmoes, Therese R Clauss, Joshua N Adkins, David G Camp, Bart K Holland, Jonas Bergquist, Patricia K Coyle, Richard D Smith, Brian A Fallon, Benjamin H Natelson. Distinct Cerebrospinal Fluid Proteomes Differentiate Post-Treatment Lyme Disease from Chronic Fatigue Syndrome. PLoS ONE, 23 Feb 2011 DOI: 10.1371/journal.pone.0017287

 

Source: Public Library of Science. “Spinal fluid proteins distinguish Lyme disease from chronic fatigue syndrome.” ScienceDaily. ScienceDaily, 23 February 2011. https://www.sciencedaily.com/releases/2011/02/110223171235.htm

 

Do anorexia, irritable bowel syndrome, chronic fatigues share a common cause?

Irritable bowel syndrome, chronic fatigue syndrome and anorexia nervosa may all have a common origin according to researchers.

They speculate that all three disorders may be caused by antibodies to the body’s own nerve cells because of a mistake by the immune system following infection.

At the moment, the ultimate cause of these illnesses remains a mystery.

Writing in Medical Hypotheses, Dr Jim Morris from the University Hospitals of Morecambe Bay NHS Trust, Dr Sue Broughton and Dr Quenton Wessels from Lancaster University say current explanations are unsatisfactory.

“Psychological factors might be important, but are unconvincing as the primary or major cause.

“There might, for instance, be an increased incidence of physical and sexual abuse in childhood in those who go on to manifest functional disorders. It is easy to see how this could influence symptoms in adults but it stretches credulity to imagine abuse as the sole and sufficient cause of the functional disorder.”

It is already well known that women are more at increased risk of autoimmune disease especially ones in which antibodies to the body’s own cells are thought to play a role, like thyroid disease, pernicious anemia and myasthenia gravis.

The researchers said: “The female to male ratio in these conditions is of the order of 10. The female excess in Irritable Bowel Syndrome, Chronic Fatigue Syndrome and Anorexia Nervosa is equally extreme and therefore this fits with the idea that auto-antibodies to nerve cells could be part of the pathogenesis of these conditions.”

The formation of auto-antibodies is found mostly among women and increases with age, which could be why these disorders are more common in midlife. Even with anorexia, which reaches a peak at the age of 30, auto-antibodies have been found in the bodies of patients.

There are also links with infection in that the onset of IBS commonly follows an episode of infectious diarrhea while chronic fatigue syndrome can be triggered by infectious mononucleosis and viral hepatitis.

Even anorexia could be influenced by secretions from bacteria affecting the brain, triggering the production of antibodies which affect mood and motivation.

“Auto-antibodies acting on the (brain’s) limbic system could induce extremes of emotion including disgust and fear. These then become linked, in the minds of adolescent girls, to culturally determined ideas of what is, and what is not, the ideal body shape and size. It is then a small step for disgust and fear to be directed to food and obesity which the fashion industry currently demonizes.”

If their idea is proven, the researchers suggest that these disorders may be amenable to treatment using pooled immunoglobulin from the blood of healthy people, especially in severe cases of anorexia where life is threatened. It should also be possible to identify and eliminate from the gut the bacteria which are triggering auto-antibodies.

Journal Reference: J.A. Morris, S.J. Broughton, Q. Wessels. Microbes, molecular mimicry and molecules of mood and motivation. Medical Hypotheses, 2016; 87: 40 DOI:10.1016/j.mehy.2015.12.011

 

Source: Lancaster University. “Do anorexia, irritable bowel syndrome, chronic fatigues share a common cause?.” ScienceDaily. ScienceDaily, 25 April 2016. https://www.sciencedaily.com/releases/2016/04/160425100204.htm

 

Diagnosing Chronic Fatigue? Check For Sinusitis

Washington, D.C. – A new study published in the August 11 issue of the Archives of Internal Medicine demonstrates a possible link between unexplained chronic fatigue and sinusitis, two conditions previously not associated with each other. Also newly noted was a relationship between sinusitis and unexplained body pain. These findings offer new hope to patients lacking a diagnosis and treatment for fatigue and pain.

Sinus disease is seldom considered as a cause of unexplained chronic fatigue or pain, despite recent ear, nose, and throat (otolaryngology) studies documenting significant fatigue and pain in patients with sinusitis and dramatic improvement after sinus surgery. A Harvard study showed that fatigue and pain scores of sinusitis patients were similar or worse than a group 20 years older with congestive heart failure, lung disease, or back pain.

“Chronic fatigue is a condition that frustrates both doctors and their patients since treatments directed at just the symptoms without knowing the cause are typically ineffective,” said Alexander C. Chester, M.D., clinical professor of medicine at Georgetown University Medical Center and principal investigator of the pilot study. “While sinusitis will not be the answer for everyone who comes to an internist with unexplained fatigue or pain, this study does suggest that it should be considered as part of a patient’s medical evaluation.”

Through his private internal medicine practice, Chester questioned 297 patients, noting unexplained chronic fatigue in 22%, unexplained chronic pain in 11%, and both in 9%. While these numbers are consistent with previous studies, Chester observed an unusual connection between patients with chronic pain or fatigue: prevalent sinus symptoms. Sinus symptoms were nine times more common on average in patients with unexplained chronic fatigue than the control group, and six times more common in patients with unexplained chronic pain. In addition, sinus symptoms were more common in patients with unexplained fatigue than in patients with fatigue explained by a mental or physical illness, suggesting the syndrome of unexplained fatigue is more closely associated with sinusitis than are other types of fatigue.

The CDC approximates that sinusitis affects 32 million Americans. Rates are highest among women and people living in the South. Women comprised 46% of the participants in this study, but represented 60% of the group with fatigue, predominance also noted in most prior studies.

15 out of the 65 patients in Chester’s study met criteria for chronic fatigue syndrome (CFS), a severe form of unexplained chronic fatigue associated with body pains and other symptoms. Most CFS patients had sinus symptoms and many noted a sudden onset of their illness, similar to people with sinusitis.

“We clearly need to do more research to see if sinus treatments alleviate fatigue and pain. This study does, however, offer hope for possible help in the future.” said Chester.

Georgetown University Medical Center is an internationally recognized academic medical center with a three-part mission of research, teaching and patient care (through our partnership with MedStar Health). Our mission is carried out with a strong emphasis on public service and a dedication to the Catholic, Jesuit principle of cura personalis–or “care of the whole person.” The Medical Center includes the School of Medicine and the School of Nursing and Health Studies, both nationally ranked, and the world renowned Lombardi Cancer Center.

 

Source: Georgetown University Medical Center. (2003, August 14). Diagnosing Chronic Fatigue? Check For Sinusitis. ScienceDaily. Retrieved March 4, 2017 from  https://www.sciencedaily.com/releases/2003/08/030814072847.htm

Chronic fatigue in Ehlers-Danlos syndrome-hypermobile type

Abstract:

Chronic fatigue is an important contributor to impaired health-related quality of life in Ehlers-Danlos syndrome. There is overlap in the symptoms and findings of EDS and chronic fatigue syndrome. A proportion of those with CFS likely have EDS that has not been identified.

The evaluation of chronic fatigue in EDS needs to include a careful clinical examination and laboratory testing to exclude common causes of fatigue including anemia, hypothyroidisim, and chronic infection, as well as dysfunction of major physiological or organ systems.

Other problems that commonly contribute to fatigue in EDS include sleep disorders, chronic pain, deconditioning, cardiovascular autonomic dysfunction, bowel and bladder dysfunction, psychological issues, and nutritional deficiencies.

While there is no specific pharmacological treatment for fatigue, many medications are effective for specific symptoms (such as headache, menstrual dysfunction, or myalgia) and for co-morbid conditions that result in fatigue, including orthostatic intolerance and insomnia.

Comprehensive treatment of fatigue needs to also evaluate for biomechanical problems that are common in EDS, and usually involves skilled physical therapy and attention to methods to prevent deconditioning.

In addition to managing specific symptoms, treatment of fatigue in EDS also needs to focus on maintaining function and providing social, physical, and nutritional support, as well as providing on-going medical evaluation of new problems and review of new evidence about proposed treatments.

© 2017 Wiley Periodicals, Inc.

 

Source: Hakim A, De Wandele I, O’Callaghan C, Pocinki A, Rowe P. Chronic fatigue in Ehlers-Danlos syndrome-hypermobile type. Am J Med Genet C Semin Med Genet. 2017 Feb 10. doi: 10.1002/ajmg.c.31542. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28186393

 

Chronic Fatigue Syndrome and Chronic Widespread Pain in Adolescence: Population Birth Cohort Study

Abstract:

Although many studies have investigated the overlap between pain phenotypes and chronic fatigue syndrome (CFS) in adults, little is known about the relationship between these conditions in adolescents. The study’s aim was therefore to identify whether a relationship exists between chronic widespread pain (CWP) and CFS in adolescents and investigate whether the two share common associations with a set of covariates.

A questionnaire was administered to offspring of the Avon Longitudinal Study of Parents and Children (ALSPAC) at age 17, asking about site, duration, and pain intensity, from which participants with CWP were identified. At the same research clinic, a computer-based Revised Clinical Interview Schedule was filled out, from which a classification of CFS was obtained. The relationship between selected covariates and CFS and CWP was investigated using a variety of logistic, ordinal logistic, and multinomial regressions.

We identified 3,214 adolescents with complete data for all outcomes and covariates. There were 82 (2.6%) individuals classified as CFS and 145 (4.5%) as CWP. A classification of CFS resulted in an increased likelihood of having CWP (odds ratio = 3.87; 95% confidence interval, 2.05-7.31). Female adolescents were approximately twice as likely to have CFS or CWP, with multinomial regression revealing a greater sex effect for CWP compared with CFS.

Those with exclusive CFS were more likely to report higher levels of pain and greater effect of pain compared with those without CFS, although associations attenuated to the null after adjustment for covariates, which did not occur in those with exclusive CWP. Multinomial regression revealed that relative to having neither CFS nor CWP, a 1-unit increase in the depression and anxiety scales increased the risk of having exclusive CFS and, to a greater extent, the risk of having comorbid CFS and CWP, but not exclusive CWP, which was only related to anxiety.

PERSPECTIVE: In this cohort, 14.6% of adolescents with CFS have comorbid CWP. The likely greater proportion of more mild cases observed in this epidemiological study means that prevalence of overlap may be underestimated compared with those attending specialist services. Clinicians should be aware of the overlap between the 2 conditions and carefully consider treatment options offered.

Copyright © 2016 The Authors. Published by Elsevier Inc. All rights reserved.

 

Source: Norris T, Deere K, Tobias JH, Crawley E. Chronic Fatigue Syndrome and Chronic Widespread Pain in Adolescence: Population Birth Cohort Study. J Pain. 2016 Nov 12. pii: S1526-5900(16)30308-X. doi: 10.1016/j.jpain.2016.10.016. [Epub ahead of print] http://www.jpain.org/article/S1526-5900(16)30308-X/fulltext (Full article)

 

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.

© 2015 John Wiley & Sons Ltd.

 

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)