Overlapping Illnesses – Page 203 – American ME and CFS Society

Decades of delayed diagnosis in 4 levodopa-responsive young-onset monogenetic parkinsonism patients

Abstract:

BACKGROUND: We report 4 patients with young-onset monogenetic parkinsonism, each of whom was misdiagnosed with either a psychogenic movement disorder or chronic fatigue syndrome for 10 to 23 years after the onset of their first symptoms.

RESULTS: Once the diagnosis was eventually made, they all had a rapid and excellent response to levodopa, albeit with the early appearance of interdose dyskinesias in 3.

CONCLUSIONS: We discuss possible reasons for the missed diagnosis despite the relentless progression of their motor handicap. DAT scanning supported the revised clinical diagnosis of parkinsonism.

Source: Ling H, Braschinsky M, Taba P, Lüüs SM, Doherty K, Hotter A, Poewe W, Lees AJ. Decades of delayed diagnosis in 4 levodopa-responsive young-onset monogenetic parkinsonism patients. Mov Disord. 2011 Jun;26(7):1337-40. doi: 10.1002/mds.23563. Epub 2011 Mar 29. https://www.ncbi.nlm.nih.gov/pubmed/21449012

Chronic widespread musculoskeletal pain, fatigue, depression and disordered sleep in chronic post-SARS syndrome; a case-controlled study

Abstract:

BACKGROUND: The long term adverse effects of Severe Acute Respiratory Syndrome (SARS), a viral disease, are poorly understood.

METHODS: Sleep physiology, somatic and mood symptoms of 22 Toronto subjects, 21 of whom were healthcare workers, (19 females, 3 males, mean age 46.29 yrs.+/- 11.02) who remained unable to return to their former occupation (mean 19.8 months, range: 13 to 36 months following SARS) were compared to 7 healthy female subjects. Because of their clinical similarities to patients with fibromyalgia syndrome (FMS) these post-SARS subjects were similarly compared to 21 drug free female patients, (mean age 42.4 +/- 11.8 yrs.) who fulfilled criteria for fibromyalgia.

RESULTS: Chronic post-SARS is characterized by persistent fatigue, diffuse myalgia, weakness, depression, and nonrestorative sleep with associated REM-related apneas/hypopneas, an elevated sleep EEG cyclical alternating pattern, and alpha EEG sleep anomaly. Post- SARS patients had symptoms of pre and post-sleep fatigue and post sleep sleepiness that were similar to the symptoms of patients with FMS, and similar to symptoms of patients with chronic fatigue syndrome. Both post-SARS and FMS groups had sleep instability as indicated by the high sleep EEG cyclical alternating pattern rate. The post-SARS group had a lower rating of the alpha EEG sleep anomaly as compared to the FMS patients. The post-SARS group also reported less pre-sleep and post-sleep musculoskeletal pain symptoms.

CONCLUSIONS: The clinical and sleep features of chronic post-SARS form a syndrome of chronic fatigue, pain, weakness, depression and sleep disturbance, which overlaps with the clinical and sleep features of FMS and chronic fatigue syndrome.

Source: Moldofsky H, Patcai J. Chronic widespread musculoskeletal pain, fatigue, depression and disordered sleep in chronic post-SARS syndrome; a case-controlled study. BMC Neurol. 2011 Mar 24;11:37. doi: 10.1186/1471-2377-11-37. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3071317/ (Full article)

Relationships among rhinitis, fibromyalgia, and chronic fatigue

Abstract:

New information about the pathophysiology of idiopathic nonallergic rhinopathy indicates a high prevalence in chronic fatigue syndrome (CFS). This article shows the relevance of CFS and allied disorders to allergy practice. CFS has significant overlap with systemic hyperalgesia (fibromyalgia), autonomic dysfunction (irritable bowel syndrome and migraine headaches), sensory hypersensitivity (dyspnea; congestion; rhinorrhea; and appreciation of visceral nociception in the esophagus, gastrointestinal tract, bladder, and other organs), and central nervous system maladaptations (central sensitization) recorded by functional magnetic resonance imaging (fMRI).

Neurological dysfunction may account for the overlap of CFS with idiopathic nonallergic rhinopathy. Scientific advances are in fMRI, nociceptive sensor expression, and, potentially, infection with xenotropic murine leukemia-related virus provide additional insights to novel pathophysiological mechanisms of the “functional” complaints of these patients that are mistakenly interpreted as allergic syndromes. As allergists, we must accept the clinical challenges posed by these complex patients and provide proper diagnoses, assurance, and optimum care even though current treatment algorithms are lacking.

Source: Baraniuk JN, Zheng Y. Relationships among rhinitis, fibromyalgia, and chronic fatigue. Allergy Asthma Proc. 2010 May-Jun;31(3):169-78. doi: 10.2500/aap.2010.31.3311. https://www.ncbi.nlm.nih.gov/pubmed/20615318

An intriguing and hitherto unexplained co-occurrence: Depression and chronic fatigue syndrome are manifestations of shared inflammatory, oxidative and nitrosative (IO&NS) pathways

Abstract:

There is a significant ‘comorbidity’ between depression and myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS). Depressive symptoms frequently occur during the course of ME/CFS. Fatigue and somatic symptoms (F&S), like pain, muscle tension, and a flu-like malaise, are key components of depression. At the same time, depression and ME/CFS show major clinical differences, which allow to discriminate them with a 100% accuracy.

This paper aims to review the shared pathways that underpin both disorders and the pathways that discriminate them. Numerous studies have shown that depression and ME/CFS are characterized by shared aberrations in inflammatory, oxidative and nitrosative (IO&NS) pathways, like systemic inflammation and its long-term sequels, including O&NS-induced damage to fatty acids, proteins and DNA; dysfunctional mitochondria; lowered antioxidant levels, like zinc and coenzyme Q10; autoimmune responses to neoepitopes formed by O&NS; lowered omega-3 polyunsaturated fatty acid levels; and increased translocation of gram-negative bacteria. Some IO&NS-related pathways, like the induction of indoleamine 2-3-dioxygenase, neurodegeneration and decreased neurogenesis, are more specific to depression, whereas other pathways, like the 2′-5′ oligoadenylate synthetase/RNase L pathway, are specific to ME/CFS.

Most current animal models of depression, e.g. those induced by cytokines, are not reminiscent of human depression but reflect a mixture of depressive and F&S symptoms. The latter symptoms, sometimes called sickness behavior, differ from depression and ME/CFS because the former is a (sub)acute response to infection-induced pro-inflammatory cytokines that aims to enhance recovery, whereas the latter are characterized by long-term sequels in multiple IO&NS pathways.

Depression and ME/CFS are not ‘comorbid’ disorders, but should be regarded as ‘co-associated disorders’ that are clinical manifestations of shared pathways.

Source: Maes M. An intriguing and hitherto unexplained co-occurrence: Depression and chronic fatigue syndrome are manifestations of shared inflammatory, oxidative and nitrosative (IO&NS) pathways. Prog Neuropsychopharmacol Biol Psychiatry. 2011 Apr 29;35(3):784-94. doi: 10.1016/j.pnpbp.2010.06.023. Epub 2010 Jul 4. https://www.ncbi.nlm.nih.gov/pubmed/20609377

Cervical spine stenosis as a cause of severe ME/CFS and orthostatic intolerance symptoms

Background: Comparatively little has been published on the clinical features and management of severe forms of ME/CFS.

Objectives: To describe the presenting symptoms and neurological examination findings in three young adult women whose disabling ME/CFS symptoms and orthostatic intolerance improved after the recognition and surgical management of cervical spine stenosis (CSS).

Methods: This retrospective case series includes three consecutive individuals who (1) met the Fukuda and criteria for CFS, (2) had evidence of refractory orthostatic intolerance, (3) were unable to work or attend school, and (4) were minimally responsive to medical and psychiatric management. To investigate pathological reflex findings, all underwent MRI evaluations. CSS was considered present if the AP cervical spinal canal diameter (SCD) was less than 10 mm at any level. Overall function was assessed before and after cervical disc replacement surgery using (1) a clinician-assigned Karnofsky score (range 0 to 100) and (2) the SF-36 physical function (PF) subscale score (range 10-30). Higher scores indicate better function on both measures.

Results: Age at onset of symptoms was 12, 29, and 29 years. The onset of ME/CFS was acute in all three. Neurological exam findings included > 3+ (brisk) deep tendon reflexes (DTR) in 2/3, positive Hoffman sign in 2/3, tremor in 2/3, and absent gag reflex in 1/3. Diagnosis was delayed for 6-9 years after the onset of symptoms. Brain MRIs were normal. The youngest patient had congenital CSS with a single level disc protrusion at C5-6 that caused further ventral cord compression and a SCD of 7 mm. Her mother also has cervical stenosis. A second
patient had two disc protrusions at C5-6 and C6-7 with SCD of 7 and 9 mm, and myelomalacia (this patient has a sibling with Chiari I malformation). The third had acquired CSS due to a single level disc bulge at C5-6 (SCD = 8.5 mm).

Improvements were evident within 2 months of single-level cervical disc replacement surgery (one patient also had fusion at an adjacent level). After 16-40 months of follow-up, all reported improved fatigue, cognitive dysfunction, PEM, lightheadedness, and anxiety. The pre- to post-op SF-36 PF scores improved from 13 to 30, 18 to 30, and 16 to 26, respectively, and the Karnofsky scores improved from 40 to 90, 40 to 90, and 50 to 100, respectively. Standing tests conducted at variable intervals from pre- to post-op showed a reduction in the maximal heart rate (HR) change during 5 minutes of standing from 64 to 22 bpm, 42 to 29 bpm, and 34 to 27 bpm, respectively.

Conclusion: This case series draws attention to the potential for CSS to contribute to ME/CFS and orthostatic symptoms, extending work by Heffez in fibromyalgia (Eur Spine J 2004;13:516). Further work is needed to define indications for surgery. However, the improvements in HR and function following surgery emphasize the importance of detecting and treating CSS, especially in the subset of those with ME/CFS whose severe symptoms are refractory to other interventions.

Peter C. Rowe, M.D.
Professor of Pediatrics
Johns Hopkins University School of Medicine/200 N. Wolfe Street/Room 2077
Baltimore, MD 21287
prowe@jhmi.edu

Dr. Rowe is supported by the Sunshine Natural Wellbeing Foundation Professorship in Chronic Fatigue and Related Disorders. No author has a conflict of interest.

Source: Peter C. Rowe, M.D*, Colleen L. Marden, Scott Heinlein, PT, Charles Edwards II, M.D. Cervical spine stenosis as a cause of severe ME/CFS and orthostatic intolerance symptoms. Poster presentation, IACFS/ME 2016 conference.

EEG findings in burnout patients

Abstract:

The concept of burnout remains enigmatic since it is only determined by behavioral characteristics. Moreover, the differential diagnosis with depression and chronic fatigue syndrome is difficult.

EEG-related variables in 13 patients diagnosed with burnout syndrome were compared with 13 healthy comparison subjects in order to explore the existence of neurobiological markers for burnout.

Burnout patients showed reduced P300 amplitude, a lower alpha peak frequency and reduced beta power. These EEG-related differences in burnout patients differ from those described in the literature in depression and chronic fatigue patients. Our preliminary findings suggest that burnout might be considered as a separate clinical syndrome.

Source: van Luijtelaar G, Verbraak M, van den Bunt M, Keijsers G, Arns M. EEG findings in burnout patients. J Neuropsychiatry Clin Neurosci. 2010 Spring;22(2):208-17. doi: 10.1176/appi.neuropsych.22.2.208. https://www.ncbi.nlm.nih.gov/pubmed/20463115

Functional impairment in chronic fatigue syndrome, fibromyalgia, and multiple chemical sensitivity

Abstract:

OBJECTIVE: To characterize patients diagnosed with multiple chemical sensitivity (MCS), chronic fatigue syndrome (CFS), or fibromyalgia (FM), to compare their level of function with Canadian population average values, and to assess factors associated with function.

DESIGN: Chart review and abstraction of clinical information.

SETTING: The Environmental Health Clinic (EHC) at Women’s College Hospital in Toronto, Ont, which is a provincial referral centre for patients with illnesses with suspected environmental links, especially MCS, CFS, and FM.

PARTICIPANTS: A total of 128 consecutive patients diagnosed with 1 or more of MCS, CFS, or FM, seen between January 2005 and March 2006 at the EHC.

MAIN OUTCOME MEASURES: Demographic and socioeconomic characteristics, comorbid diagnoses, duration of illness, health services usage, life stresses, helpful therapeutic strategies, and functional impairment measured by the Short Form-36, compared with Canadian population average values. Factors significantly associated with function in bivariate analyses were included in multiple linear and logistic regression models.

RESULTS: The patient population was predominantly female (86.7%), with a mean age of 44.6 years. Seventy-eight patients had discrete diagnoses of 1 of MCS, CFS, or FM, while the remainder had 2 or 3 overlapping diagnoses. Most (68.8%) had stopped work, and on average this had occurred 3 years after symptom onset. On every Short Form-36 subscale, patients had markedly lower functional scores than population average values, more so when they had 2 or 3 of these diagnoses. Having FM, younger age at onset, and lower socioeconomic status were most consistently associated with poor function.

CONCLUSION: Patients seen at the EHC demonstrated marked functional impairment, consistent with their reported difficulties working and caring for their homes and families during what should be their peak productive years. Early comprehensive assessment, medical management, and social and financial support might avoid the deterioration of function associated with prolonged illness. Education and information resources are required for health care professionals and the public, along with further etiologic and prognostic research.

Source: Lavergne MR, Cole DC, Kerr K, Marshall LM. Functional impairment in chronic fatigue syndrome, fibromyalgia, and multiple chemical sensitivity. Can Fam Physician. 2010 Feb;56(2):e57-65. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2821254/ (Full article)

Immunological similarities between cancer and chronic fatigue syndrome: the common link to fatigue?

Abstract:

Cancer and chronic fatigue syndrome (CFS) are both characterised by fatigue and severe disability. Besides fatigue, certain aspects of immune dysfunctions appear to be present in both illnesses. In this regard, a literature review of overlapping immune dysfunctions in CFS and cancer is provided.

Special emphasis is given to the relationship between immune dysfunctions and fatigue. Abnormalities in ribonuclease (RNase) L and hyperactivation of nuclear factor kappa beta (NF-kappaB) are present in CFS and in prostate cancer. Malfunctioning of natural killer (NK) cells has long been recognised as an important factor in the development and reoccurrence of cancer, and has been documented repeatedly in CFS patients.

The dysregulation of the RNase L pathway, hyperactive NF-kappaB leading to disturbed apoptotic mechanisms and oxidative stress or excessive nitric oxide, and low NK activity may play a role in the two diseases and in the physiopathology of the common symptom fatigue. However, in cancer the relation between the immune dysfunctions and fatigue has been poorly studied. Immunological abnormalities to such as a dysregulated RNase L pathway, hyperactive NF-kappaB, increased oxidative stress and reduced NK cytotoxicity, among others, are present in both diseases.

These anomalies may be part of the physiopathology of some of the common complaints, such as fatigue. Further studies to confirm the hypotheses given here are warranted.

Source: Meeus M, Mistiaen W, Lambrecht L, Nijs J. Immunological similarities between cancer and chronic fatigue syndrome: the common link to fatigue? Anticancer Res. 2009 Nov;29(11):4717-26. http://ar.iiarjournals.org/content/29/11/4717.long (Full article)

Somatic comorbidities in irritable bowel syndrome: fibromyalgia, chronic fatigue syndrome, and interstitial cystitis

Abstract:

Fibromyalgia, chronic fatigue syndrome, and interstitial cystitis frequently overlap with irritable bowel syndrome (IBS). There is a positive correlation between the incidence of these comorbidities and increased health care seeking, reduction in quality of life, and higher levels of mood disorders, which raises the question of a common underlying pathophysiology. A possible central hypersensitization disorder seems to be particularly involved in the dysfunction of bidirectional neural pathways and viscerovisceral cross-interactions within the CNS, thus explaining these many extraintestinal manifestations in IBS.

Source: Mathieu N.Somatic comorbidities in irritable bowel syndrome: fibromyalgia, chronic fatigue syndrome, and interstitial cystitis. Gastroenterol Clin Biol. 2009 Feb;33 Suppl 1:S17-25. doi: 10.1016/S0399-8320(09)71521-0. [Article in French] https://www.ncbi.nlm.nih.gov/pubmed/19303534

http://www.em-consulte.com/article/206075/alertePM (Full article)

Cardiovascular dysfunction with low cardiac output due to a small heart in patients with chronic fatigue syndrome

Abstract:

OBJECTIVE: Little attention has been paid to possible cardiovascular involvement in patients with chronic fatigue syndrome (CFS), although many of their symptoms and signs suggest cardiovascular dysfunction. Possible cardiovascular symptoms and cardiac function were investigated in CFS patients.

METHODS: Cardiovascular symptoms were intensively investigated and cardiac function was evaluated echocardiographically.

PATIENTS: Fifty-three patients (23 men and 30 women, mean age: 31+/-7 years) with CFS under 50 years were studied.

RESULTS: Slender build (body mass index <20 kg/m(2)) was common (47%). Possible cardiovascular symptoms including shortness of breath (32%), dyspnea on effort (28%), rapid heartbeat (38%), chest pain (43%), fainting (43%), orthostatic dizziness (45%) and coldness of feet (42%), were all frequent complaints. Hypotension (28%) was occasionally noted. Electrocardiograms frequently revealed right axis deviation (21%) and severe sinus arrhythmia (34%) suggesting accentuated parasympathetic nervous activity. Small heart shadow (cardiothoracic ratio <or=42%) was noted on the chest roentgenogram in 32 patients (60%). Echocardiographic examination demonstrated low cardiac indexes (<2 L/min/m(2)) with low stroke volume indexes (<30 mL/m(2)) due to a small left ventricular chamber in 19 (36%, p<0.05 vs. 8% in 36 controls). None had reduced left ventricular ejection fraction.

CONCLUSION: Cardiovascular symptoms are common in CFS patients. Cardiac dysfunction with low cardiac output due to small left ventricular chamber may contribute to the development of chronic fatigue as a constitutional factor in a considerable number of CFS patients.

Source: Miwa K, Fujita M. Cardiovascular dysfunction with low cardiac output due to a small heart in patients with chronic fatigue syndrome. Intern Med. 2009;48(21):1849-54. Epub 2009 Nov 2. https://www.ncbi.nlm.nih.gov/pubmed/19881233