Overlapping Illnesses – Page 202 – American ME and CFS Society

Attention-deficit hyperactivity disorder in chronic fatigue syndrome patients

Abstract:

Psychopathological disorders are frequent in chronic fatigue syndrome patients. The present study examines the presence of attention-deficit hyperactivity disorder (ADHD) in a sample of adult chronic fatigue syndrome (CFS) patients, and evaluates its clinical consequences in this population. CFS patients were assessed for childhood and adult ADHD by clinical interview and ADHD-specific scales. Psychopathological comorbidities were evaluated by clinical examination and questionnaires.

Forty-seven of 158 CSF patients (29.7%) were diagnosed of childhood ADHD and in 33 (20.9%), the condition persisted into adulthood. CFS patients with adult ADHD had an earlier CSF onset, more severe anxiety and depression symptoms, and a higher risk of suicide than CFS patients without ADHD. Using lineal regression analysis, we found that depressive symptoms and ADHD severity were significant predictors of fatigue intensity. Consequently, ADHD may be common in CFS patients, and is associated with a more severe psychopathologic clinical profile.

Source: Sáez-Francàs N, Alegre J, Calvo N, Antonio Ramos-Quiroga J, Ruiz E, Hernández-Vara J, Casas M. Attention-deficit hyperactivity disorder in chronic fatigue syndrome patients. Psychiatry Res. 2012 Dec 30;200(2-3):748-53. doi: 10.1016/j.psychres.2012.04.041. Epub 2012 May 28. https://www.ncbi.nlm.nih.gov/pubmed/22648008

Biological underpinnings of the commonalities in depression, somatization, and Chronic Fatigue Syndrome

Abstract:

BACKGROUND: Somatization is a multisomatoform disorder characterized by medically unexplained, functional or psychosomatic symptoms. Similar somatic symptoms are key components of depression and Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS).

METHODS: This paper reviews the evidence that such symptoms are organically based. We use the term “physio-somatic” to describe these symptoms.

RESULTS: Inflammation, cell-mediated immune (CMI) activation and alterations in the tryptophan catabolite (TRYCAT) pathway are associated with the physio-somatic symptoms of depression, ME/CFS and/or somatization. Proinflammatory cytokines, decreased tryptophan and aberrations in TRYCATs may cause physio-somatic symptoms, such as fatigue, autonomic symptoms, hyperalgesia and somatic presentations.

CONCLUSIONS: The data suggest co-ordinated and interacting biological pathways driving the occurrence of physio-somatic symptoms across these three disorders, giving a biologically validated “pathway phenotype”. These data have far-reaching implications for DSM-IV diagnostic conceptualizations of somatization (and ME/CFS) suggesting the presence of an emerging organic explanation. Future research should focus on the role of immune regulation, and co-ordination, of neuronal activity and, through larger data sets, ultimately creating new, biologically validated classification rules. These data have implications for the development of novel therapies utilizing these insights, buttressing the role of psychotherapy in psychosomatic presentations.

Source: Anderson G, Maes M, Berk M. Biological underpinnings of the commonalities in depression, somatization, and Chronic Fatigue Syndrome. Med Hypotheses. 2012 Jun;78(6):752-6. doi: 10.1016/j.mehy.2012.02.023. Epub 2012 Mar 23. https://www.ncbi.nlm.nih.gov/pubmed/22445460

Cervical neuro-muscular syndrome: discovery of a new disease group caused by abnormalities in the cervical muscles

Abstract:

Our previous study of whiplash injury found that abnormalities in the cervical muscles cause autonomic dystonia. Further research has found that abnormalities in the cervical muscles cause headache, chronic fatigue syndrome, vertigo, and dizziness. We named this group of diseases cervical neuro-muscular syndrome. Patients treated within a 2-year period from April 1, 2002 to March 31, 2004 reported good outcomes in 83.8% for headache, 88.4% for vertigo and dizziness, 84.5% for chronic fatigue syndrome, 88.0% for autonomic dystonia, and 83.7% for whiplash-associated disorder. A large number of outpatients present with general malaise, including many general physical complaints without identifiable cause. We propose that treatment of the cervical muscle is effective for general malaise.

Source: Matsui T, Ii K, Hojo S, Sano K. Cervical neuro-muscular syndrome: discovery of a new disease group caused by abnormalities in the cervical muscles. Neurol Med Chir (Tokyo). 2012;52(2):75-80. https://www.jstage.jst.go.jp/article/nmc/52/2/52_2_75/_pdf (Full article)

Lyme disease in a British referral clinic

Abstract:

BACKGROUND: Concerns about over-diagnosis and inappropriate management of Lyme disease (LD) are well documented in North America and supported by clinical data. There are few parallel data on the situation in the UK.

AIM: To describe the patterns of referral, investigation, diagnosis and treatment of patients with suspected LD referred to an infectious disease unit in Liverpool, UK. Previous management by National Health Service (NHS) and non-NHS practitioners was reviewed.

DESIGN: Descriptive study conducted by retrospective casenotes review.

METHODS: Retrospective case notes review of adults referred with possible LD to an infectious disease unit in Liverpool, UK, over 5 years (2006-2010).

RESULTS: Of 115 patients, 27 (23%) were diagnosed with LD, 38 (33%) with chronic fatigue syndrome (CFS) and 13 (11%) with other medical conditions. No specific diagnosis could be made in 38 (33%). At least 53 unnecessary antibiotic courses had been given by non-NHS practitioners; 21 unnecessary courses had been prescribed by NHS practitioners. Among 38 patients, 17 (45%) with CFS had been misdiagnosed as having LD by non-NHS practitioners.

CONCLUSION: A minority of referred patients had LD, while a third had CFS. LD is over-diagnosed by non-specialists, reflecting the complexities of clinical and/or laboratory diagnosis. Patients with CFS were susceptible to misdiagnosis in non-NHS settings, reinforcing concerns about missed opportunities for appropriate treatment for this group and about the use of inappropriate diagnostic modalities and anti-microbials in non-NHS settings.

Comment in: [Borreliosis]. [Orthopade. 2013]

Source: Cottle LE, Mekonnen E, Beadsworth MB, Miller AR, Beeching NJ. Lyme disease in a British referral clinic. QJM. 2012 Jun;105(6):537-43. doi: 10.1093/qjmed/hcs003. Epub 2012 Feb 1. http://qjmed.oxfordjournals.org/content/105/6/537.long (Full article)

Adrenal histoplasmosis: a case series and review of the literature

Abstract:

Adrenal histoplasmosis is an uncommon mycotic disease typically caused by Histoplasma capsulatum. The objective was to determine the clinicopathological findings in adrenal histoplasmosis.

Pathological records were searched from the database at the Department of Pathology, Faculty of Medicine Ramathibodi Hospital, Mahidol University from 1993 to 2008 for cases of adrenal histoplasmosis. The keywords were “histoplasmosis” and “adrenal gland”.

Adrenal histoplasmosis was diagnosed by histopathology and Gomori-Grocott methenamine silver staining. Histoplasma capsulatum was confirmed by tissue culture and/or serology. The authors report seven cases of adrenal histoplasmosis in immunocompetent patients. The mean age at diagnosis was 67 years. All patients presented as chronic fatigue syndrome.

The onset of symptoms ranged from one to three months. Addison’s disease was found in adrenal histoplasmosis in one case (14.3%). The computed tomography revealed adrenal nodules measuring 1.2 to 7.8 cm in diameter.

The histopathology showed granulomatous inflammation with caseous necrosis. Culture of adrenal tissue from two patients revealed Histoplasma capsulatum. Serum Histoplasma antibodies were positive in four cases. A cure was accomplished in 6 out of 7 cases (85.7%). The patients were followed up for 2.5 to 16.5 years.

Source: Larbcharoensub N, Boonsakan P, Aroonroch R, Rochanawutanon M, Nitiyanant P, Phongkitkarun S, Poonvutikul S, Watcharananan SP, Ngarmukos C. Adrenal histoplasmosis: a case series and review of the literature. Southeast Asian J Trop Med Public Health. 2011 Jul;42(4):920-5. https://www.ncbi.nlm.nih.gov/pubmed/22299474

Activation of cell-mediated immunity in depression: association with inflammation, melancholia, clinical staging and the fatigue and somatic symptom cluster of depression

Abstract:

BACKGROUND: Depression is characterized by activation of cell-mediated immunity (CMI), including increased neopterin levels, and increased pro-inflammatory cytokines (PICs), such as interleukin-1 (IL-1) and tumor necrosis factor-α (TNFα). These PICs may induce depressive, melancholic and chronic fatigue (CF) symptoms.

METHODS: We examined serum neopterin and plasma PIC levels in depressive subgroups in relation to the depressive subtypes and the melancholic and CF symptoms of depression. Participants were 85 patients with depression and in 26 normal controls. Severity of depression was assessed with the Hamilton Depression Rating Scale (HDRS) and severity of CF with the Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale.

RESULTS: Serum neopterin was significantly higher in depressed patients and in particular in those with melancholia. There were positive correlations between serum neopterin, the plasma PICs and the number of previous depressive episodes. Neopterin and TNFα were associated with melancholia, while both PICs were associated with CF. Melancholia-group membership was predicted by the HDRS and neopterin, and CF group membership by age, the FF score and serum TNFα.

DISCUSSION: Depression and melancholia are accompanied by CMI activation, suggesting that neopterin plays a role in their pathophysiology, e.g. through activation of oxidative and nitrosative stress and apoptosis pathways. The intertwined CMI and inflammatory responses are potentially associated with the onset of depression and with the melancholic and CF symptoms of depression. Exposure to previous depressive episodes may magnify the size of CMI and PIC responses, possibly increasing the likelihood of new depressive episodes. CMI activation and inflammation may contribute to the staging or recurrence of depression.

Source: Maes M, Mihaylova I, Kubera M, Ringel K. Activation of cell-mediated immunity in depression: association with inflammation, melancholia, clinical staging and the fatigue and somatic symptom cluster of depression. Prog Neuropsychopharmacol Biol Psychiatry. 2012 Jan 10;36(1):169-75. doi: 10.1016/j.pnpbp.2011.09.006. Epub 2011 Sep 16. https://www.ncbi.nlm.nih.gov/pubmed/21945535

IgM-mediated autoimmune responses directed against multiple neoepitopes in depression: new pathways that underpin the inflammatory and neuroprogressive pathophysiology

Abstract:

BACKGROUND: There is evidence that depression is accompanied by oxidative and nitrosative stress (O&NS), as indicated by increased free radical levels, lipid peroxidation, and lowered antioxidant levels. The aims of the present study are to examine whether depression is accompanied by autoimmune responses directed against a) neoepitopes that are formed following O&NS damage; and b) the major anchorage molecules, i.e. palmitic and myristic acids and S-farnesyl-L-cysteine.

METHODS: We examined serum IgM antibodies to the conjugated fatty acids, palmitic and myristic acids; acetylcholine; S-farnesyl-L-cysteine; and NO-modified adducts in 26 depressed patients and 17 normal controls. Severity of depression was measured with the Hamilton Depression Rating Scale and severity of fatigue and somatic (F&S) symptoms with the Fibromyalgia and Chronic Fatigue Syndrome (FF) Rating Scale.

RESULTS: The prevalences and mean values for the serum IgM levels directed against conjugated palmitic and myristic acids, acetylcholine, S-farnesyl-L-cysteine; and the conjugated NO adducts, NO-tyrosine, NO-phenylalanine, NO-aspartate, NO-histidine, and NO-creatine were significantly higher in depressed patients than in normal controls. The autoimmune responses were significantly related to FF symptoms, such as fatigue and a flu-like malaise, whereas the indicants of nitrosative stress were related to gastro-intestinal and autonomic symptoms.

DISCUSSION: Depression is characterized by IgM-related autoimmune responses directed against a) neoepitopes that are normally not detected by the immune system but that due to damage by O&NS have become immunogenic; and b) anchorage epitopes, i.e. palmitic and myristic acids, and S-farnesyl-L-cysteine. These autoimmune responses play a role in the inflammatory and O&NS pathophysiology of depression and may mediate the cellular dysfunctions that contribute to neuroprogression, e.g. aberrations in signal transduction, cellular differentiation and apoptosis.

Source: Maes M, Mihaylova I, Kubera M, Leunis JC, Geffard M. IgM-mediated autoimmune responses directed against multiple neoepitopes in depression: new pathways that underpin the inflammatory and neuroprogressive pathophysiology. J Affect Disord. 2011 Dec;135(1-3):414-8. doi: 10.1016/j.jad.2011.08.023. Epub 2011 Sep 17. https://www.ncbi.nlm.nih.gov/pubmed/21930301

Neurohumoral and haemodynamic profile in postural tachycardia and chronic fatigue syndromes

Abstract:

Several studies recognized an overlap between CFS (chronic fatigue syndrome) and POTS (postural tachycardia syndrome). We compared the autonomic and neurohormonal phenotype of POTS patients with CFS (CFS-POTS) to those without CFS (non-CFS-POTS), to determine whether CFS-POTS represents a unique clinical entity with a distinct pathophysiology.

We recruited 58 patients with POTS, of which 47 were eligible to participate. A total of 93% of them reported severe fatigue [CIS (Checklist of Individual Strength), fatigue subscale >36], and 64% (n=30) fulfilled criteria for CFS (CFS-POTS). The prevalence of CFS symptoms (Centers for Disease Control and Prevention criteria) was greater in the CFS-POTS group, but the pattern of symptoms was similar in both groups.

Physical functioning was low in both groups (RAND-36 Health Survey, 40±4 compared with 33±3; P=0.153), despite more severe fatigue in CFS-POTS patients (CIS fatigue subscale 51±1 compared with 43±3; P=0.016). CFS-POTS patients had greater orthostatic tachycardia than the non-CFS-POTS group (51±3 compared with 40±4 beats/min; P=0.030), greater low-frequency variability of BP (blood pressure; 6.3±0.7 compared with 4.8±1.0 mmHg2; P=0.019), greater BP recovery from early to late phase II of the Valsalva manoeuvre (18±3 compared with 11±2 mmHg; P=0.041) and a higher supine (1.5±0.2 compared with 1.0±0.3 ng/ml per·h; P=0.033) and upright (5.4±0.6 compared with 3.5±0.8 ng/ml per h; P=0.032) PRA (plasma renin activity).

In conclusion, fatigue and CFS-defining symptoms are common in POTS patients. The majority of them met criteria for CFS. CFS-POTS patients have higher markers of sympathetic activation, but are part of the spectrum of POTS. Targeting this sympathetic activation should be considered in the treatment of these patients.

Source: Okamoto LE, Raj SR, Peltier A, Gamboa A, Shibao C, Diedrich A, Black BK, Robertson D, Biaggioni I. Neurohumoral and haemodynamic profile in postural tachycardia and chronic fatigue syndromes. Clin Sci (Lond). 2012 Feb;122(4):183-92. doi: 10.1042/CS20110200. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3203411/ (Full article)

Mitochondrial enzymes discriminate between mitochondrial disorders and chronic fatigue syndrome

Abstract:

We studied the extent of mitochondrial involvement in chronic fatigue syndrome (CFS) and investigated whether measurement of mitochondrial respiratory chain complex (RCC) activities discriminates between CFS and mitochondrial disorders.

Mitochondrial content was decreased in CFS compared to healthy controls, whereas RCC activities corrected for mitochondrial content were not. Conversely, mitochondrial content did not discriminate between CFS and two groups of mitochondrial disorders, whereas ATP production rate and complex I, III and IV activity did, all with higher activities in CFS. We conclude that the ATP production rate and RCC activities can reliably discriminate between mitochondrial disorders and CFS.

Source: Smits B, van den Heuvel L, Knoop H, Küsters B, Janssen A, Borm G, Bleijenberg G, Rodenburg R, van Engelen B. Mitochondrial enzymes discriminate between mitochondrial disorders and chronic fatigue syndrome. Mitochondrion. 2011 Sep;11(5):735-8. doi: 10.1016/j.mito.2011.05.005. Epub 2011 Jun 2. https://www.ncbi.nlm.nih.gov/pubmed/21664495

Factors affecting duration of chronic fatigue syndrome in pediatric patients

Abstract:

OBJECTIVE: To determine factors affecting duration of chronic fatigue syndrome (CFS) in pediatric patients.

METHODS: This Retrospective cohort consisted of patients with CFS at the regional referral infectious disease clinic for evaluation of fatigue in children and adolescents. Demographic, clinical, and laboratory data were analyzed to identify the impact on duration and severity of pediatric CFS.

RESULTS: A total number of 53 predominantly white (98.1%) patients with CFS, aged 9-18 years, were included in the study. Other than fatigue, headaches and sleep disturbance were the most common symptoms of pediatric CFS. Seropositive status for Borrelia burgdorferi (B. burgdorferi) and Epstein-Barr virus (EBV) was identified in 66% of the patients with the diagnosis of CFS by CDC criteria. No association was found between the CFS symptoms, gender, or age at diagnosis and duration of fatigue symptoms. Duration of CFS was associated with high Body-Mass Index (BMI) in a regression model after adjustment for patient’s age, gender, and seropositive status for B. burgdorferi and/or EBV (0.34 ± 0.15, P < 0.04).

CONCLUSIONS: BMI is significantly associated with prolonged duration of CFS.

Source: Petrov D, Marchalik D, Sosin M, Bal A. Factors affecting duration of chronic fatigue syndrome in pediatric patients. Indian J Pediatr. 2012 Jan;79(1):52-5. doi: 10.1007/s12098-011-0463-4. Epub 2011 May 27. https://www.ncbi.nlm.nih.gov/pubmed/21617905