Muscle injections with lidocaine improve resting fatigue and pain in patients with chronic fatigue syndrome

Abstract:

OBJECTIVE: Patients with chronic fatigue syndrome (CFS) complain of long-lasting fatigue and pain which are not relieved by rest and worsened by physical exertion. Previous research has implicated metaboreceptors of muscles to play an important role for chronic fatigue and pain. Therefore, we hypothesized that blocking impulse input from deep tissues with intramuscular lidocaine injections would improve not only the pain but also fatigue of CFS patients.

METHODS: In a double-blind, placebo-controlled study, 58 CFS patients received 20 mL of 1% lidocaine (200 mg) or normal saline once into both trapezius and gluteal muscles. Study outcomes included clinical fatigue and pain, depression, and anxiety. In addition, mechanical and heat hyperalgesia were assessed and serum levels of lidocaine were obtained after the injections.

RESULTS: Fatigue ratings of CFS patients decreased significantly more after lidocaine compared to saline injections (p = 0.03). In contrast, muscle injections reduced pain, depression, and anxiety (p < 0.001), but these changes were not statistically different between lidocaine and saline (p > 0.05). Lidocaine injections increased mechanical pain thresholds of CFS patients (p= 0.04) but did not affect their heat hyperalgesia. Importantly, mood changes or lidocaine serum levels did not significantly predict fatigue reductions.

CONCLUSION: These results demonstrate that lidocaine injections reduce clinical fatigue of CFS patients significantly more than placebo, suggesting an important role of peripheral tissues for chronic fatigue. Future investigations will be necessary to evaluate the clinical benefits of such interventions.

Source: Staud R, Kizer T, Robinson ME. Muscle injections with lidocaine improve resting fatigue and pain in patients with chronic fatigue syndrome. J Pain Res. 2017 Jun 26;10:1477-1486. doi: 10.2147/JPR.S139466. ECollection 2017. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5499959/ (Full article)

Incidence rates of Guillain Barré (GBS), chronic fatigue/systemic exertion intolerance disease (CFS/SEID) and postural orthostatic tachycardia syndrome (POTS) prior to introduction of human papilloma virus (HPV) vaccination among adolescent girls in Finland, 2002-2012

Abstract:

BACKGROUND: In Finland a vaccination programme against human papillomavirus (HPV) was introduced in November 2013 for girls aged 11-12 years with a catchup for girls 13-15 years. Allegations that HPV vaccine is causing Guillain Barré syndrome (GBS) and non-specific diagnostic entities, such as chronic fatigue syndrome/systemic exertion intolerance disease (CFS/SEID) and postural orthostatic tachycardia syndrome (POTS), continue to surface. We examined population register-based incidence rates of CFS/SEID, GBS and POTS to provide baseline data for future HPV vaccine safety evaluations.

METHODS: First diagnosis of CFS/SEID, GBS and POTS in girls aged 11-15 years were obtained from the National Hospital Discharge Register during 2002-2012. We considered the following ICD-10 codes: G93.3 for CFS; G61.0 for GBS and G90.9, G90.8, G93.3, I49.8 for POTS. We calculated incidence rates per 100,000 person-years with 95% confidence intervals (CI).

RESULTS: In total, 9 CFS/SEID, 19 GBS and 72 POTS cases were identified. The overall incidence rate was 0.53/100,000 (95% CI; 0.27-1.01) for CFS/SEID, 1.11 (95% CI; 0.71-1.74) for GBS and 4.21 (95%CI; 3.34-5.30) for POTS. Significant relative increase in annual incidence rate with a peak in 2012 was observed in CFS/SEID (33% (95% CI; 3.0-70.3: p=0.029) and POTS (16.5% (95% CI; 7.8-25.9: p<0.05), but not in GBS (5.4% (95% CI; -8.4-21.3: p=0.460).

CONCLUSIONS: Our findings provide baseline estimates of CFS/SEID, GBS and POTS incidences in Finland. However, rates based on register data should be interpreted with caution, especially for non-specific diagnostic entities for which internationally and even nationally agreed criteria are still being discussed. To assess the associations with HPV vaccine, methods using register linkage for cohort and self-controlled case series should be explored in addition to factors contributing to patients seeking care, treating physicians setting the diagnoses, and their preference of using of codes for these clinical entities.

Copyright © 2017 The Authors. Published by Elsevier B.V. All rights reserved.

Source: Skufca J, Ollgren J, Ruokokoski E, Lyytikäinen O, Nohynek H. Incidence rates of Guillain Barré (GBS), chronic fatigue/systemic exertion intolerance disease (CFS/SEID) and postural orthostatic tachycardia syndrome (POTS) prior to introduction of human papilloma virus (HPV) vaccination among adolescent girls in Finland, 2002-2012. Papillomavirus Res. 2017 Jun;3:91-96. doi: 10.1016/j.pvr.2017.03.001. Epub 2017 Mar 16. http://www.sciencedirect.com/science/article/pii/S2405852116300696?via%3Dihub (Full article)

A Prospective Study of Infectious Mononucleosis in College Students

Abstract:

BACKGROUND: The present study aims to prospectively investigate possible biological and psychological factors present in college students who will go on to develop chronic fatigue syndrome (CFS) following Infectious Mononucleosis (IM). Identification of risk factors predisposing patients towards developing CFS may help to understand the underlying mechanisms and ultimately prevent its occurrence. Our study is enrolling healthy college students over the age of 18. Enrollment began in March of 2013 and is ongoing.

METHODS: Biological and psychological data are collected when students are well (Stage 1), when they develop IM (Stage 2), and approximately 6 months after IM diagnosis (Stage 3).

RESULTS: Two case studies demonstrate the progression of student symptomology across all three stages.

CONCLUSION: The Case Studies presented illustrate the usefulness of a prospective research design that tracks healthy students, following their trajectory of IM illness to either a) full recovery or b) diagnosis with CFS.

Source: Jason LA, Katz B, Gleason K, McManimen S, Sunnquist M, Thorpe T. A Prospective Study of Infectious Mononucleosis in College Students. Int J Psychiatry (Overl Park). 2017;1(2). pii: http://www.opastonline.com/wp-content/uploads/2017/01/a-prospective-study-of-infectious-mononucleosis-in-college-students-IJP-17-016.pdf. Epub 2017 Jan 20. (Full article)

Increase in the Regional Cerebral Blood Flow following Waon Therapy in Patients with Chronic Fatigue Syndrome: A Pilot Study

Abstract:

Objective Chronic fatigue syndrome (CFS) is a complex disorder, with no consensus on therapeutic options. However, Waon therapy has been reported to be an effective treatment. The purpose of this study was to evaluate changes in the cerebral blood flow (CBF) before and after Waon therapy in CFS patients and to investigate the correlation between such changes and the therapeutic efficacy of Waon therapy.

Methods Eleven patients (2 men and 9 women, mean age 27 years old) diagnosed with CFS participated in the study. The disease duration was 8-129 months, and the performance status was 5-8 (on a scale of 0-9). All patients underwent CBF scintigraphy using brain single-photon emission computed tomography (SPECT) with technetium-99m ethyl cysteinate dimer (99mTc-ECD) before and after Waon therapy. CBF changes after Waon therapy were evaluated using a statistical analysis of imaging data, which was performed with a statistical parametric mapping software program (SPM5).

Results Waon therapy reduced symptoms in all 11 patients. We also observed an increase in the CBF within the prefrontal region, orbitofrontal region, and right temporal lobe. These results indicated that an improvement in clinical symptoms was linked to an increase in the CBF.

Conclusion The results indicated abnormalities of the cerebral function in the prefrontal region, orbitofrontal region, and right temporal lobe in CFS patients and that Waon therapy improved the cerebral function and symptoms in CFS patients by increasing the regional CBF. To our knowledge, this is the first report to clarify the CBF changes in CFS patients before and after Waon therapy.

Source: Munemoto T, Soejima Y, Masuda A, Nakabeppu Y, Tei C. Increase in the Regional Cerebral Blood Flow following Waon Therapy in Patients with Chronic Fatigue Syndrome: A Pilot Study. Intern Med. 2017;56(14):1817-1824. doi: 10.2169/internalmedicine.56.8001. Epub 2017 Jul 15. https://www.jstage.jst.go.jp/article/internalmedicine/56/14/56_56.8001/_article (Full article)

Access to Medical Care for Individuals with Myalgic Encephalomyelitis and Chronic Fatigue Syndrome: A Call for Centers of Excellence

Abstract:

The current study sought to better understand the experience of individuals with myalgic encephalomyelitis (ME) and chronic fatigue syndrome (CFS) in accessing care for their debilitating illness. Of 898 participants, less than half had ever seen an ME or CFS specialist, though 99% of participants were interested in specialist care. Participants cited geographic and financial barriers as most frequently precluding access to specialists. Furthermore, satisfaction with specialist care greatly exceeded satisfaction with non-specialist care. These findings suggested that individuals with ME and CFS represent a medically-underserved population, due to lack of available care. The CFS Advisory Committee and NIH Pathways to Prevention Working Group recommended the creation of ME and CFS Centers of Excellence to improve the healthcare access of patients with ME and CFS. The current study documents the need for these centers, as they would ameliorate geographic and financial barriers to quality care.

Source: Sunnquist M, Nicholson L, Jason LA, Friedman KJ. Access to Medical Care for Individuals with Myalgic Encephalomyelitis and Chronic Fatigue Syndrome: A Call for Centers of Excellence. Mod Clin Med Res. 2017 Apr;1(1):28-35. doi: 10.22606/mcmr.2017.11005. Epub 2017 Apr 13. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5510655/ (Full article)

Unperturbed Cytotoxic Lymphocyte Phenotype and Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients

Abstract:

Myalgic encephalomyelitis or chronic fatigue syndrome (ME/CFS) is a debilitating disorder linked to diverse intracellular infections as well as physiological stress. Cytotoxic lymphocytes combat intracellular infections. Their function is attenuated by stress. Despite numerous studies, the role of cytotoxic lymphocytes in ME/CFS remains unclear. Prompted by advances in the understanding of defects in lymphocyte cytotoxicity, the discovery of adaptive natural killer (NK) cell subsets associated with certain viral infections, and compelling links between stress, adrenaline, and cytotoxic lymphocyte function, we reassessed the role of cytotoxic lymphocytes in ME/CFS.

Forty-eight patients from two independent cohorts fulfilling the Canada 2003 criteria for ME/CFS were evaluated with respect to cytotoxic lymphocyte phenotype and function. Results were compared to values from matched healthy controls. Reproducible differences between patients and controls were not found in cytotoxic lymphocyte numbers, cytotoxic granule content, activation status, exocytotic capacity, target cell killing, or cytokine production. One patient expressed low levels of perforin, explained by homozygosity for the PRF1 p.A91V variant. However, overall, this variant was present in a heterozygous state at the expected population frequency among ME/CFS patients.

No single patient displayed any pathological patterns of cellular responses. Increased expansions of adaptive NK cells or deviant cytotoxic lymphocyte adrenaline-mediated inhibition were not observed. In addition, supervised dimensionality reduction analyses of the full, multidimensional datasets did not reveal any reproducible patient/control discriminators.

In summary, employing sensitive assays and analyses for quantification of cytotoxic lymphocyte differentiation and function, cytotoxicity lymphocyte aberrances were not found among ME/CFS patients. These assessments of cytotoxic lymphocytes therefore do not provide useful biomarkers for the diagnosis of ME/CFS.

Source: Theorell J, Bileviciute-Ljungar I, Tesi B, Schlums H, Johnsgaard MS, Asadi-Azarbaijani B, Bolle Strand E, Bryceson YT. Unperturbed Cytotoxic Lymphocyte Phenotype and Function in Myalgic Encephalomyelitis/Chronic Fatigue Syndrome Patients. Front Immunol. 2017 Jun 26;8:723. doi: 10.3389/fimmu.2017.00723. eCollection 2017. http://journal.frontiersin.org/article/10.3389/fimmu.2017.00723/full (Full article)

Subtyping Patients with Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS) By Course of Illness

Abstract:
Past research has subtyped patients with Myalgic Encephalolyelitis (ME) and Chronic Fatigue Syndrome (CFS) according to factors related to illness onset, illness duration, and age. However, no classification system fully accounts for the wide range of symptom severity, functional disability, progression, and prognosis seen among patients. This study examined whether illness trajectories among individuals with CFS were predictive of different levels of symptomology, functional disability, and energy expenditure.
Of the participants (N=541), the majority described their illness as Fluctuating (59.7%), with 15.9% Constantly Getting Worse, 14.1% Persisting, 8.5% Relapsing and Remitting, and 1.9% Constantly Getting Better. The illness courses were associated with significant differences in symptomology on select domains of the DSQ, functioning on select subscales of the SF-36, and on overall levels of energy expenditure.
The significant symptomatic and functional differences between groups suggest that subtyping patients with CFS according to illness course is a promising method for creating more homogeneous groups of patients.
Source:  Jamie Stoothoff, Kristen Gleason, Stephanie McManimen, Taylor Thorpe and Leonard A. Jason.  Subtyping Patients with Myalgic Encephalomyelitis (ME) and Chronic Fatigue Syndrome (CFS) By Course of Illness. Symbiosis, June 26, 2017. https://symbiosisonlinepublishing.com/biosensors-biomarkers-diagnostics/biosensors-biomarkers-diagnostics13.pdf (Full article)

Cognition In Young People With ME/CFS

By Dr R. Vallings

One of the main reasons that young people with ME/CFS struggle with school is associated with cognition. Mental confusion, memory problems and difficulties with concentration are all described and may relate to abnormal neurological pathology, sluggish cerebral circulation and generalised fatigue.

Cognitive effort leads to fatigue in the same way that exercise will lead to muscle fatigue and post-exertional malaise. Headaches are frequently a prominent and persistent symptom, and they too will interfere with the student’s cognitive ability. There can be aggravation of symptoms associated with trying to focus and learn from a computer screen. Many will describe visual symptoms with blurring of text or eye fatigue.

A noisy classroom situation may not be conducive to mental effort, and students are often moving from room to room carrying heavy books, this all adding to the burden which the illness poses.

The young person may have problems with sleep, waking feeling unrefreshed, and again cognitive effort may thus be limited. He/she may arrive at school feeling already exhausted due to lack of restorative sleep and having to get up early, and then issues such as travelling, and the anxiety associated with what may lie ahead that day.

Too much exercise, standing for long periods, heat and poor nutrition can all compromise cognition. The student will be motivated to keep up with peers, and push him/herself mentally, physically and socially beyond the comfort zone, and suffer the consequences cognitively.

The teacher may have minimal understanding of the illness and its sequelae, and even the efforts of parents to explain can be brushed aside as “fussiness”. Attention span may be very short and the labels of laziness, attention deficit or learning disorders can be appended inappropriately.

Those with ME/CFS are usually highly motivated to achieve and will be disappointed by failures and lack of encouragement. Ridicule is often reported.

Parents and medical personnel need to communicate with the teachers to enhance their understanding of ME/CFS. To ensure that the student has the best possible opportunities to achieve appropriate education and a feeling of success. This will mean allowing the student to work at their own pace with adequate rest periods.

Management of the Cognitive Difficulties by the Primary Care Physician

Once a firm diagnosis has been made, the young person will feel relieved that there is an explanation for their problems, particularly those experienced by attempts to participate in regular schooling.

Parents need to be involved in this discussion, which should be addressed principally to the patient, so that he/she is also involved in decision making, and feels part of the team approach. Only the young person knows how they feel, and should be encouraged to verbalise their fears and needs. Teenagers will often need opportunity for discussion without a parent present.

Many young people fear getting behind their peers academically. There is a fear of never being able to catch up and consequently losing friends who move on. There needs to be encouragement to participate in ongoing education, however minimally, but without undue pressure.

This may mean limited attendance at school, or if available, correspondence education or home-schooling. The student can then work at their own pace. They should be encouraged to work for short periods with adequate rest periods, recognising when they are ready to rest. Some sort of structure for the days is helpful.

This may be difficult, if at home with parents needing to work. Particular difficulties need to be discussed, such as aggravation from computer screens, and difficulty focusing on written text (sometimes a ruler placed across the page can help with maintaining focus). Aggravating factors such as noise, bright lights, temperature and unpleasant odours may need to be adjusted. Snacks and drinks need to be available and allowed.

If well enough, some gentle outdoor exercise during breaks between cognitive effort should be suggested, and for younger children playing with siblings or friends after school or at weekends should be encouraged.

Focus on symptom control is important, and this may be achieved with attention to sleep difficulties and efficient pain management. Learning good relaxation strategies with the use of music, visualisation, and teaching self hypnosis all have a role. Having their own private space means that these things are more likely to be done, and rest will be undisturbed. Regular snacking with plenty of salt can help overcome symptoms associated with orthostatic intolerance.

Medication such as very low-dose tricyclics or melatonin to help with sleep may be useful. Some young people benefit from use of stimulants such as methylphenidate, but there is a risk of a false sense of wellbeing, leading to overdoing things. If the child is depressed or unduly anxious, this should be addressed and there should be opportunity to talk things through privately with a trusted professional, who has understanding of this illness.

The young person needs to understand the issues that can aggravate cognition, such as overdoing things mentally and physically, learning m to pace carefully, and avoiding situations which have proved detrimental. Planning time carefully and incorporating rewards can all help to ensure a better outcome.

Attention to achieving a regular body clock will mean that a good routine that fits in with family and school is possible. Standing for long periods, getting overheated or dehydrated and not eating adequately should all be avoided.

Above all there needs to be a sense of achievement, (however small), progress and normality if at all possible. Only the young person him/herself know how they really feel, and gaining a sense of control over this illness, rather than letting the illness control them entirely will achieve a growing sense of personal achievement and freedom from stress.

Reprinted with permission from Meeting Place – Autumn 2016 – Number 123: The official quarterly journal of ANZEMS Inc.

Impact of Rantes from jawbone on Chronic Fatigue Syndrome

Abstract:

This study elucidates the question of whether chronic inflammation in the jawbone contributes to the development of Chronic Fatigue Syndrome (CFS). Fatty degenerative osteonecrosis in jawbone (FDOJ) may contribute to CFS by induction of inflammatory mediators.

We examined seven cytokines by multiplex analysis in jawbone samples from two groups of patients. In order to clarify neurological interrelations, specimens from 21 CFS patients were analyzed from areas of previous surgery in the retromolar wisdom tooth area. Each of the retromolar jawbone samples showed clinically fatty degenerated and osteonecrotic medullary changes. As control, healthy jawbone specimens from 19 healthy patients were analyzed. All fatty necrotic and osteolytic jawbone (FDOJ) samples showed high expression of RANTES and fibroblast growth factor (FGF)-2. FDOJ cohorts showed a 30-fold mean overexpression of RANTES and a 20-fold overexpressed level of FGF-2 when compared to healthy controls. As RANTES is discussed in the literature as a possible contributor to inflammatory diseases, we hypothesize that FDOJ in areas of improper and incomplete wound healing in the jawbone may hyperactivate signaling pathways.

Constituting a hidden source of “silent inflammation” FDOJ may represent a hitherto unknown cause for the development of CFS.

Source: Lechner J, Huesker K, Von Baehr V. Impact of Rantes from jawbone on Chronic Fatigue Syndrome. J Biol Regul Homeost Agents. 2017 Apr-Jun;31(2):321-327. https://www.ncbi.nlm.nih.gov/pubmed/28685531

NLRP3 inflammasome activation mediates fatigue-like behaviours in mice via neuroinflammation

Abstract:

Numerous experimental and clinical studies have suggested that the interaction between the immune system and the brain plays an important role in the pathophysiology of chronic fatigue syndrome (CFS). The NLRP3 inflammasome is an important part of the innate immune system. This complex regulates proinflammatory cytokine interleukin-1β (IL-1β) maturation, which triggers different kinds of immune-inflammatory reactions.

We employed repeated forced swims to establish a model of CFS in mice. NLRP3 knockout (KO) mice were also used to explore NLRP3 inflammasome activation in the mechanisms of CFS, using the same treatment. After completing repeated swim tests, the mice displayed fatigue-like behaviours, including locomotor activity and reduced fall-off time on the rota-rod test, which was accompanied by significantly higher mature IL-1β level in the prefrontal cortex (PFC) and malondialdehyde (MDA) level in serum. We also found increased NLRP3 protein expression, NLRP3 inflammasome formation and increased mature IL-1β production in the PFC, relative to untreated mice. The NLRP3 KO mice displayed significantly moderated fatigue behaviours along with decreased PFC and serum IL-1β levels under the same treatment.

These findings demonstrated the involvement of NLRP3 inflammasome activation in the mechanism of swimming-induced fatigue. Future therapies targeting the NLRP3/IL-1β pathway may have significant potential for fatigue prevention and treatment.

Copyright © 2017. Published by Elsevier Ltd.

Source: Zhang Z, Ma X, Xia Z, Chen J, Liu Y, Chen Y, Zhu J, Li J, Yu H, Zong Y, Lu G. NLRP3 inflammasome activation mediates fatigue-like behaviours in mice via neuroinflammation. Neuroscience. 2017 Jul 3. pii: S0306-4522(17)30453-0. doi: 10.1016/j.neuroscience.2017.06.048. [Epub ahead of print] https://www.ncbi.nlm.nih.gov/pubmed/28684277