Category: Treatment

Clinical Profile and Aspects of Differential Diagnosis in Patients with ME/CFS from Latvia

Abstract:

Background and objectives: There is still an uncertainty regarding the clinical symptomatology and the diagnostic criteria in terms of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS), as different diagnostic criteria exist. Our aim is to identify the core symptoms of ME/CFS in the outpatient setting in Riga; to distinguish symptoms in patients with ME/CFS and those with symptoms of fatigue; and to investigate patient thoughts on the onset, symptoms, treatment and effect of ME/CFS.

Materials and methods: Total of 65 Caucasian patients from an ambulatory care setting were included in the study. Questionnaires, specialist evaluation of the patients and visual analogue scale (VAS) measurements were used to objectify the findings.

Results: The study showed that ME/CFS with comorbidities is associated with a more severe disease. A negative correlation was found regarding an increase in age and number of current symptoms, as well as an increase in VAS score and the duration of fatigue and age in the ME/CFS without comorbidities group.

Conclusions: Comorbidities tend to present with a more severe course of ME/CFS. Fatigue, myalgia, arthralgia and sleep disturbances tend to be more prevalent in the ME/CFS patients compared to the non-ME/CFS patients. VAS score has a tendency to decrease with age and duration of fatigue. Nonsteroidal anti-inflammatory drugs are the most commonly used pharmacological drug class that reduces ME/CFS symptoms.

Source: Krumina A, Vecvagare K, Svirskis S, Gravelsina S, Nora-Krukle Z, Gintere S, Murovska M. Clinical Profile and Aspects of Differential Diagnosis in Patients with ME/CFS from Latvia. Medicina (Kaunas). 2021 Sep 11;57(9):958. doi: 10.3390/medicina57090958. PMID: 34577881. https://pubmed.ncbi.nlm.nih.gov/34577881/

Asthenic disorders as a manifestation of chronic fatigue syndrome

Abstract:

The article explains the changes in terminology and diagnostic criteria for asthenic disorders as manifestations of chronic fatigue syndrome CFS (myalgic encephalomyelitis). Chronic fatigue syndrome is defined as neuroimmune endocrine dysfunction with a purely clinical diagnosis. Probably, viral infections can play a leading role in the pathogenesis. Published diagnostic criteria reveal possible correlations between chronic fatigue syndrome and COVID-19 disease. A promising strategy for the therapy and rehabilitation of patients is the use of smart peptides, a representative of which is the drug cortexin.

Source: Putilina MV. Astenicheskie rasstroistva kak proyavlenie sindroma khronicheskoi ustalosti [Asthenic disorders as a manifestation of chronic fatigue syndrome]. Zh Nevrol Psikhiatr Im S S Korsakova. 2021;121(8):125-130. Russian. doi: 10.17116/jnevro2021121081125. PMID: 34481448. [Abstract in English, Russian] https://pubmed.ncbi.nlm.nih.gov/34481448/

Chronic fatigue syndrome and long covid: individualisation, not compartmentalisation

Newman’s investigation of chronic fatigue syndrome and long covid supports the development of specialised multidisciplinary support for patients with long covid.1 But compartmentalisation of a problem like chronic fatigue syndrome can sometimes miss the point.

Dysregulated systems, by their nature, cannot be manipulated into functionality, so the clinical modelling of a system disturbance is often best undertaken by a clinician with dedicated expertise in multisystem assessment who can pull the “hard” and “soft” data together.

Specialised teams, such as the fatigue clinic at the Royal London Hospital for Integrated Medicine, routinely individualise chronic fatigue syndrome cases to a high level of detail. In the absence of objective data, the use of advanced and holistic history taking can explore the factors that perpetuate the clinical state.

The “forensic” part of the inquiry searches for the symptomatic features of pathophysiological change, hypothalamic dysregulation, or ongoing immunological disturbance. The physical and functional inquiry is then contextualised by an empathic and holistic psychosocial survey.

Each patient has a unique combination of perpetuating factors in chronic fatigue syndrome and long covid, so treatment approaches should also be individualised to a high degree. This level of individualisation is not always possible using a compartmentalised method of assessment.

Source: Malcolm R S. Chronic fatigue syndrome and long covid: individualisation, not compartmentalisation. BMJ 2021; 374 :n1863 doi:10.1136/bmj.n1863 https://www.bmj.com/content/374/bmj.n1863

Tolerability and Efficacy of s.c. IgG Self-Treatment in ME/CFS Patients with IgG/IgG Subclass Deficiency: A Proof-of-Concept Study

Abstract:

Background: Chronic fatigue syndrome (ME/CFS) is a complex disease frequently triggered by infections. IgG substitution may have therapeutic effect both by ameliorating susceptibility to infections and due to immunomodulatory effects.

Methods: We conducted a proof of concept open trial with s.c. IgG in 17 ME/CFS patients suffering from recurrent infections and mild IgG or IgG subclass deficiency to assess tolerability and efficacy. Patients received s.c. IgG therapy of 0.8 g/kg/month for 12 months with an initial 2 months dose escalation phase of 0.2 g and 0.4 g/kg/month.

Results: Primary outcome was improvement of fatigue assessed by Chalder Fatigue Scale (CFQ; decrease ≥ 6 points) and of physical functioning assessed by SF-36 (increase ≥ 25 points) at month 12. Of 12 patients receiving treatment per protocol 5 had a clinical response at month 12. Two additional patients had an improvement according to this definition at months 6 and 9. In four patients treatment was ceased due to adverse events and in one patient due to disease worsening. We identified LDH and soluble IL-2 receptor as potential biomarker for response.

Conclusion: Our data indicate that self-administered s.c. IgG treatment is feasible and led to clinical improvement in a subset of ME/CFS patients.

Source: Scheibenbogen C, Sotzny F, Hartwig J, Bauer S, Freitag H, Wittke K, Doehner W, Scherbakov N, Loebel M, Grabowski P. Tolerability and Efficacy of s.c. IgG Self-Treatment in ME/CFS Patients with IgG/IgG Subclass Deficiency: A Proof-of-Concept Study. J Clin Med. 2021 May 29;10(11):2420. doi: 10.3390/jcm10112420. PMID: 34072494. https://pubmed.ncbi.nlm.nih.gov/34072494/

Coenzyme Q 10: Clinical Applications beyond Cardiovascular Diseases

Abstract:

Coenzyme Q10 (CoQ10) is an essential cofactor in oxidative phosphorylation (OXPHOS), present in mitochondria and cell membranes in reduced and oxidized forms. Acting as an energy transfer molecule, it occurs in particularly high levels in the liver, heart, and kidneys. CoQ10 is also an anti-inflammatory and antioxidant agent able to prevent the damage induced by free radicals and the activation of inflammatory signaling pathways. In this context, several studies have shown the possible inverse correlation between the blood levels of CoQ10 and some disease conditions.

Interestingly, beyond cardiovascular diseases, CoQ10 is involved also in neuronal and muscular degenerative diseases, in migraine and in cancer; therefore, the supplementation with CoQ10 could represent a viable option to prevent these and in some cases might be used as an adjuvant to conventional treatments. This review is aimed to summarize the clinical applications regarding the use of CoQ10 in migraine, neurodegenerative diseases (including Parkinson and Alzheimer diseases), cancer, or degenerative muscle disorders (such as multiple sclerosis and chronic fatigue syndrome), analyzing its effect on patients’ health and quality of life.

Source: Testai L, Martelli A, Flori L, Cicero AFG, Colletti A. Coenzyme Q10: Clinical Applications beyond Cardiovascular Diseases. Nutrients. 2021 May 17;13(5):1697. doi: 10.3390/nu13051697. PMID: 34067632. https://pubmed.ncbi.nlm.nih.gov/34067632/

Off label use of Aripiprazole shows promise as a treatment for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): a retrospective study of 101 patients treated with a low dose of Aripiprazole

Note: The ME Association does not recommend that anyone with ME/CFS attempt to obtain or to take this drug, even in small doses, until such time as more appropriate research can better determine safety and efficacy. Read their full statement here. 

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) is a chronic, debilitating illness of unknown etiology. An ME/CFS diagnosis is based solely on symptoms with case definitions made by expert consensus, including the Fukuda (1994), Canadian Consensus Criteria (CCC, 2003), International Consensus Criteria (ICC, 2011), and the Institute of Medicine (IOM, 2015) case criteria. According to the most recent IOM case definition, the core symptoms of ME/CFS include debilitating fatigue, unrefreshing sleep, post-exertional malaise, and either cognitive dysfunction or orthostatic intolerance [1]. Although the cause of the illness is unknown, a growing body of evidence suggests that ME/CFS involves inflammation of the brain. Up to 85% of patients with ME/CFS report symptoms of cognitive impairment also referred to as “brain fog,” which includes difficulty with memory, attention, and information processing. Additional evidence includes changes in inflammatory cytokines in both plasma and cerebrospinal fluid correlated with the severity of symptoms [2]. Other studies using positron emission tomography (PET) show evidence of activated microglia or astrocytes in various regions of the brain in patients with ME/CFS [3].

Source: Crosby, L.D., Kalanidhi, S., Bonilla, A. et al. Off label use of Aripiprazole shows promise as a treatment for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): a retrospective study of 101 patients treated with a low dose of Aripiprazole. J Transl Med 19, 50 (2021). https://doi.org/10.1186/s12967-021-02721-9 https://translational-medicine.biomedcentral.com/articles/10.1186/s12967-021-02721-9 (Full text)

Theory: Treatments for Prolonged ICU Patients May Provide New Therapeutic Avenues for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS)

We here provide an overview of treatment trials for prolonged intensive care unit (ICU) patients and theorize about their relevance for potential treatment of myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Specifically, these treatment trials generally target: (a) the correction of suppressed endocrine axes, notably through a “reactivation” of the pituitary gland’s pulsatile secretion of tropic hormones, or (b) the interruption of the “vicious circle” between inflammation, oxidative and nitrosative stress (O&NS), and low thyroid hormone function. There are significant parallels in the treatment trials for prolonged critical illness and ME/CFS; this is consistent with the hypothesis of an overlap in the mechanisms that prevent recovery in both conditions. Early successes in the simultaneous reactivation of pulsatile pituitary secretions in ICU patients—and the resulting positive metabolic effects—could indicate an avenue for treating ME/CFS. The therapeutic effects of thyroid hormones—including in mitigating O&NS and inflammation and in stimulating the adreno-cortical axis—also merit further studies. Collaborative research projects should further investigate the lessons from treatment trials for prolonged critical illness for solving ME/CFS.

Source: Dominic Stanculescu, Lars Larsson and Jonas Bergquist. Theory: Treatments for Prolonged ICU Patients May Provide New Therapeutic Avenues for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS). Front. Med., 07 May 2021 | https://doi.org/10.3389/fmed.2021.672370 https://www.frontiersin.org/articles/10.3389/fmed.2021.672370/full (Full text)

Possible involvement of the autonomic nervous system in cervical muscles of patients with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS)

Abstract:

Background: Patients with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS) sometimes present with stiffness of the cervical muscles. To investigate the pathophysiology of ME/CFS, this observational study compared patients with versus without recovery from ME/CFS through local modulation of the cervical muscles.

Methods: Over a period of 11 years, a total of 1226 inpatients with ME/CFS who did not respond to outpatient care were enrolled in this study. All patients received daily cervical muscle physical therapy during hospitalization. Self-rated records documenting the presence or absence of ME/CFS, as well as the representative eight symptoms that frequently accompany it at admission and discharge, were compared. Pupil diameter was also measured to examine autonomic nervous system function involvement.

Results: The recovery rate of ME/CFS after local therapy was 55.5%, and did not differ significantly by sex, age strata, and hospitalization period. The recovery rates of the eight symptoms were variable (36.6-86.9%); however, those of ME/CFS in the symptom subpopulations were similar (52.3-55.8%). The recovery rates of all symptoms showed strong associations with that of ME/CFS (p < 0.001). The pupil diameter was more constricted in the ME/CFS-recovered patients than in the ME/CFS-unrecovered patients in the total population and the subpopulations stratified by sex, age, and hospitalization period.

Conclusions: There was a strong association between the recovery of ME/CFS and other related whole-body symptoms. The recovery of ME/CFS may be partly linked to amelioration of the autonomic nervous system in the cervical muscles.

Source: Matsui T, Hara K, Iwata M, Hojo S, Shitara N, Endo Y, Fukuoka H, Matsui M, Kawaguchi H. Possible involvement of the autonomic nervous system in cervical muscles of patients with myalgic encephalomyelitis / chronic fatigue syndrome (ME/CFS). BMC Musculoskelet Disord. 2021 May 5;22(1):419. doi: 10.1186/s12891-021-04293-7. PMID: 33952227. https://pubmed.ncbi.nlm.nih.gov/33952227/

Oral Minocycline Therapy Improves Symptoms of Myalgic Encephalomyelitis, Especially in the Initial Disease Stage

Abstract:

Objective: Central nervous system dysfunction associated with myalgic encephalomyelitis (ME) has been suggested to be the main cause of chronic fatigue syndrome. In animal models of chronic fatigue, minocycline was reported to act as a suppressor of neural inflammation. Minocycline may thus exert favorable therapeutic effects in patients with ME.

Methods: Oral minocycline (100 mg ×2 on the first day, followed by 100 mg/day for 41 days) was administered to 100 patients with ME. The performance status score (0-9), orthostatic intolerance during the 10-min standing test, neurologic disequilibrium, and neuropathic pain were compared before and after treatment.

Results: After therapy completion, favorable effects were observed with a decrease in the performance status score of ≥2 points in 27 patients (27%). Before treatment, 6 of the 27 patients had orthostatic intolerance with an inability to complete the 10-min standing test; after treatment, this symptom resolved in 4 and improved in 2 patients. In addition, after treatment, postural orthostatic tachycardia resolved in five of eight patients, disequilibrium resolved in five of eight patients, and fibromyalgia or neuropathic pain was attenuated in four of five patients. The favorable effects appeared dependent on a shorter disease duration, primarily for a duration of less than three years and most frequently within six months of the disease onset. However, acute adverse effects with nausea and/or dizziness caused 38 patients (38%) to discontinue treatment in the first few days.

Conclusion: Oral minocycline therapy may be an effective treatment option for patients with ME, especially in the initial stage of the disease.

Source: Miwa K. Oral Minocycline Therapy Improves Symptoms of Myalgic Encephalomyelitis, Especially in the Initial Disease Stage. Intern Med. 2021 Apr 26. doi: 10.2169/internalmedicine.6082-20. Epub ahead of print. PMID: 33896862. https://pubmed.ncbi.nlm.nih.gov/33896862/

Off label use of shows promise as a treatment for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): a retrospective study of 101 patients treated with a low dose of Aripiprazole

In a retrospective study, we reviewed the medical records of 101 patients who met the criteria for a ME/CFS diagnosis according to three separate case definitions (Fukuda, CCC, and IOM) and who received off-label aripiprazole (Table ​(Table1).1). Medical records were included for individuals evaluated in the clinic at least twice, representing periods before and after the use of the medication. The age range was from 18 to 84 years old (mean 50 years), with a gender distribution of 67% female and 33% male, and the duration of illness was from 1 to 54 years (median 13 years).

The daily oral dose of aripiprazole ranged from 0.2 to 2.0 mg/day (mean 1.1 mg/day). Dosage started at 0.25 mg/day and titrated up or down based on each patient’s observations and feedback. The duration of aripiprazole therapy ranged from less than one month to 17 months (mean 7.8 months). Patient records were also evaluated for concurrent use of various classes of antidepressants, including selective serotonin reuptake inhibitors (SSRI), serotonin-norepinephrine reuptake inhibitors (SNRI), serotonin modulators, norepinephrine–dopamine reuptake inhibitors (NDRIs), and tri-cyclic antidepressants. The difference in antidepressant use between responders vs. non-responders was not statistically significant (p = 0.145) using the test for proportions, suggesting that antidepressant use does not predict or preclude a clinical response to aripiprazole.

Source: Crosby LD, Kalanidhi S, Bonilla A, Subramanian A, Ballon JS, Bonilla H. Off label use of Aripiprazole shows promise as a treatment for Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS): a retrospective study of 101 patients treated with a low dose of Aripiprazole. J Transl Med. 2021 Feb 3;19(1):50. doi: 10.1186/s12967-021-02721-9. PMID: 33536023; PMCID: PMC7860172. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7860172/ (Full text)