Exposure-response relationship between K. brevis blooms and reporting of upper respiratory and neurotoxin-associated symptoms

Abstract:

In southwest Florida, Karenia brevis (K. brevis) blooms occur frequently, can be very intense and persist over several years. Individuals living in coastal communities around the Gulf of Mexico are particularly vulnerable to brevetoxins released by K. brevis in seawater and carried inland within marine aerosol. Exposure to K. brevis occurs during residential, recreational, and occupational activities and has been associated with upper respiratory tract (URT) symptoms in healthy and medically vulnerable individuals. Additionally, ingestion of brevetoxin-contaminated seafood causes neurotoxic shellfish poisoning (NSP), and severe headaches prompting emergency department visits which occur in excess during K. brevis blooms.

The current study examined a dose-response relationship between K. brevis in coastal waters and URT and NSP-like symptoms and headaches among southwest Florida residents. Data on past medical history (PMH) and medical symptoms were collected from the participants (n = 258) in five southwest Florida counties between June 2019 to August 2021. A dose-response relationship was observed between K. brevis blooms and reporting of URT and NSP-like symptoms and headaches. Reporting of NSP-like symptoms was higher among participants with a PMH of migraines, chronic fatigue syndrome (CFS) and mild memory loss, while the association of headaches with K. brevis blooms was accentuated among individuals with a PMH of migraines.

These results suggest further investigations into the threshold of aerosolized brevetoxin dose required to elicit URT, headaches and/or NSP-like symptoms. These symptoms ultimately cause significant public health safety concerns, primarily among vulnerable populations with preexisting neurological conditions.

Source: Abdullah L, Ferguson S, Niedospial D, Patterson D, Oberlin S, Nkiliza A, Bartenfelder G, Hahn-Townsend C, Parks M, Crawford F, Reich A, Keegan A, Kirkpatrick B, Mullan M. Exposure-response relationship between K. brevis blooms and reporting of upper respiratory and neurotoxin-associated symptoms. Harmful Algae. 2022 Aug;117:102286. doi: 10.1016/j.hal.2022.102286. Epub 2022 Jul 12. PMID: 35944953. https://pubmed.ncbi.nlm.nih.gov/35944953/

The link between idiopathic intracranial hypertension, fibromyalgia, and chronic fatigue syndrome: exploration of a shared pathophysiology

Abstract:

PURPOSE: Idiopathic intracranial hypertension (IICH) is a condition characterized by raised intracranial pressure (ICP), and its diagnosis is established when the opening pressure measured during a lumbar puncture is elevated >20 cm H2O in nonobese patients or >25 cm H2O in obese patients. Papilledema is caused by forced filling of the optic nerve sheath with cerebrospinal fluid (CSF). Other common but underappreciated symptoms of IICH are neck pain, back pain, and radicular pain in the arms and legs resulting from associated increased spinal pressure and forced filling of the spinal nerves with CSF. Widespread pain and also several other characteristics of IICH share notable similarities with characteristics of fibromyalgia (FM) and chronic fatigue syndrome (CFS), two overlapping chronic pain conditions. The aim of this review was to compare literature data regarding the characteristics of IICH, FM, and CFS and to link the shared data to an apparent underlying physiopathology, that is, increased ICP.

METHODS: Data in the literature regarding these three conditions were compared and linked to the hypothesis of the shared underlying physiopathology of increased cerebrospinal pressure.

RESULTS: The shared characteristics of IICH, FM, and CFS that can be caused by increased ICP include headaches, fatigue, cognitive impairment, loss of gray matter, involvement of cranial nerves, and overload of the lymphatic olfactory pathway. Increased pressure in the spinal canal and in peripheral nerve root sheaths causes widespread pain, weakness in the arms and legs, walking difficulties (ataxia), and bladder, bowel, and sphincter symptoms. Additionally, IICH, FM, and CFS are frequently associated with sympathetic overactivity symptoms and obesity. These conditions share a strong female predominance and are frequently associated with Ehlers-Danlos syndrome.

CONCLUSION: IICH, FM, and CFS share a large variety of symptoms that might all be explained by the same pathophysiology of increased cerebrospinal pressure.

Source: Hulens M, Rasschaert R, Vansant G, Stalmans I, Bruyninckx F, Dankaerts. The link between idiopathic intracranial hypertension, fibromyalgia, and chronic fatigue syndrome: exploration of a shared pathophysiology. J Pain Res. 2018 Dec 10;11:3129-3140. doi: 10.2147/JPR.S186878. eCollection 2018. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6292399/ (Full article)

The putative glymphatic signature of chronic fatigue syndrome: A new view on the disease pathogenesis and therapy

Abstract:

The underlying pathophysiology of chronic fatigue syndrome remains incompletely understood and there are no curative treatments for this disorder at present. However, increasing neuroimaging evidence indicates that functional and structural abnormalities exist in the brains of chronic fatigue syndrome patients, suggesting that the central nervous system is involved in this disorder and that at least some chronic fatigue syndrome patients may have an underlying neurological basis for their illness.

In the present paper, we speculate that glymphatic dysfunction, causing toxic build up within the central nervous system, may be responsible for at least some cases of chronic fatigue syndrome. We further postulate that cerebrospinal fluid diversion such as lumboperitoneal shunting may be beneficial to this subgroup of patients by restoring glymphatic transport and waste removal from the brain.

Although recent evidence indicates that at least some chronic fatigue syndrome patients may benefit from cerebrospinal fluid drainage, further studies are needed to confirm this finding and to determine whether this can be attributed to enhancement of glymphatic fluid flow and interstitial fluid clearance. If confirmed, this could offer promising avenues for the future treatment of chronic fatigue syndrome. Clearly, given the relative invasive nature of cerebrospinal fluid diversion, such procedures should be reserved for chronic fatigue syndrome patients who are severely debilitated, or for those with severe headaches. Anyhow, it seems worthwhile to make every effort to identify new therapies for patients who suffer from this devastating disease, especially given that there are currently no effective treatments for this condition.

Source: Wostyn P, De Deyn PP. The putative glymphatic signature of chronic fatigue syndrome: A new view on the disease pathogenesis and therapy. Med Hypotheses. 2018 Sep;118:142-145. doi: 10.1016/j.mehy.2018.07.007. Epub 2018 Jul 6. https://www.ncbi.nlm.nih.gov/pubmed/30037603

Chronic fatigue syndrome and idiopathic intracranial hypertension: Different manifestations of the same disorder of intracranial pressure?

Abstract:

Though not discussed in the medical literature or considered in clinical practice, there are similarities between chronic fatigue syndrome and idiopathic intracranial hypertension (IIH) which ought to encourage exploration of a link between them. The cardinal symptoms of each – fatigue and headache – are common in the other and their multiple other symptoms are frequently seen in both.

The single discriminating factor is raised intracranial pressure, evidenced in IIH usually by the sign of papilloedema, regarded as responsible for the visual symptoms which can lead to blindness. Some patients with IIH, however, do not have papilloedema and these patients may be clinically indistinguishable from patients with chronic fatigue syndrome. Yet IIH is rare, IIH without papilloedema (IIHWOP) seems rarer still, while chronic fatigue syndrome is common. So are the clinical parallels spurious or is there a way to reconcile these conflicting observations?

We suggest that it is a quirk of clinical measurement that has created this discrepancy. Specifically, that the criteria put in place to define IIH have led to a failure to appreciate the existence, clinical significance or numerical importance of patients with lower level disturbances of intracranial pressure. We argue that this has led to a grossly implausible distortion of the epidemiology of IIH such that the milder form of the illness (IIHWOP) is seen as less common than the more severe and that this would be resolved by recognising a connection with chronic fatigue syndrome.

We hypothesise, therefore, that IIH, IIHWOP, lesser forms of IIH and an undetermined proportion of chronic fatigue cases are all manifestations of the same disorder of intracranial pressure across a spectrum of disease severity, in which this subset of chronic fatigue syndrome would represent the most common and least severe and IIH the least common and most extreme.

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

Source: Higgins JNP, Pickard JD, Lever AML. Chronic fatigue syndrome and idiopathic intracranial hypertension: Different manifestations of the same disorder of intracranial pressure? Med Hypotheses. 2017 Aug;105:6-9. doi: 10.1016/j.mehy.2017.06.014. Epub 2017 Jun 24. https://www.ncbi.nlm.nih.gov/pubmed/28735654 

Lumbar puncture, chronic fatigue syndrome and idiopathic intracranial hypertension: a cross-sectional study

Abstract:

OBJECTIVE: Unsuspected idiopathic intracranial hypertension (IIH) is found in a significant minority of patients attending clinics with named headache syndromes, if it is specifically sought out. Chronic fatigue syndrome is frequently associated with headache. Could the same be true of chronic fatigue? Moreover, there are striking similarities between the two conditions. Could they be related? Attempting to answer these questions, we describe the results of a change in clinical practice aimed at capturing patients with chronic fatigue who might have IIH.

DESIGN: Cross-sectional.

SETTING: Hospital outpatient and radiology departments.

PARTICIPANTS: Patients attending a specialist clinic with chronic fatigue syndrome and headache who had lumbar puncture to exclude raised intracranial pressure.

MAIN OUTCOME MEASURES: Intracranial pressure measured at lumbar puncture and the effect on headache of cerebrospinal fluid drainage.

RESULTS: Mean cerebrospinal fluid pressure was 19 cm H2O (range 12-41 cm H2O). Four patients fulfilled the criteria for IIH. Thirteen others did not have pressures high enough to diagnose IIH but still reported an improvement in headache after drainage of cerebrospinal fluid. Some patients also volunteered an improvement in other symptoms, including fatigue. No patient had any clinical signs of raised intracranial pressure.

CONCLUSIONS: An unknown, but possibly substantial, minority of patients with chronic fatigue syndrome may actually have IIH. An unknown, but much larger, proportion of patients with chronic fatigue syndrome do not have IIH by current criteria but respond to lumbar puncture in the same way as patients who do. This suggests that the two conditions may be related.

 

Source: Higgins N, Pickard J, Lever A. Lumbar puncture, chronic fatigue syndrome and idiopathic intracranial hypertension: a cross-sectional study. JRSM Short Rep. 2013 Nov 21;4(12):2042533313507920. doi: 10.1177/2042533313507920. eCollection 2013. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3899735/ (Full article)

 

Migraine in gulf war illness and chronic fatigue syndrome: prevalence, potential mechanisms, and evaluation

Abstract:

OBJECTIVE: To assess the prevalence of headache subtypes in Gulf War Illness (GWI) and Chronic Fatigue Syndrome (CFS) compared to controls.

BACKGROUND: Approximately, 25% of the military personnel who served in the 1990-1991 Persian Gulf War have developed GWI. Symptoms of GWI and CFS have considerable overlap, including headache complaints. Migraines are reported in CFS. The type and prevalence of headaches in GWI have not been adequately assessed.

METHODS: 50 GWI, 39 CFS and 45 controls had structured headache evaluations based on the 2004 International Headache Society criteria. All subjects had history and physical examinations, fatigue and symptom related questionnaires, measurements of systemic hyperalgesia (dolorimetry), and assessments for exclusionary conditions.

RESULTS: Migraines were detected in 64% of GWI (odds ratio = 11.6 [4.1-32.5]) (mean [±95% CI]) and 82% of CFS subjects (odds ratio = 22.5 [7.8-64.8]) compared to only 13% of controls. There was a predominance of females in the CFS compared to GWI and controls. However, migraine status was independent of gender in GWI and CFS groups (x (2) = 2.7; P = 0.101). Measures of fatigue, pain, and other ancillary criteria were comparable between GWI and CFS subjects with and without headache.

CONCLUSION: The high prevalence of migraine in CFS was confirmed and extended to GWI subjects. GWI and CFS may share dysfunctional central pathophysiological pathways that contribute to migraine and subjective symptoms. The high migraine prevalence warrants the inclusion of a structured headache evaluation in GWI and CFS subjects, and treatment when present.

 

Source: Rayhan RU, Ravindran MK, Baraniuk JN. Migraine in gulf war illness and chronic fatigue syndrome: prevalence, potential mechanisms, and evaluation. Front Physiol. 2013 Jul 24;4:181. doi: 10.3389/fphys.2013.00181. ECollection 2013. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3721020/ (Full article)

 

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)

 

Migraine headaches in chronic fatigue syndrome (CFS): comparison of two prospective cross-sectional studies

Abstract:

BACKGROUND: Headaches are more frequent in Chronic Fatigue Syndrome (CFS) than healthy control (HC) subjects. The 2004 International Headache Society (IHS) criteria were used to define CFS headache phenotypes.

METHODS: Subjects in Cohort 1 (HC = 368; CFS = 203) completed questionnaires about many diverse symptoms by giving nominal (yes/no) answers. Cohort 2 (HC = 21; CFS = 67) had more focused evaluations. They scored symptom severities on 0 to 4 anchored ordinal scales, and had structured headache evaluations. All subjects had history and physical examinations; assessments for exclusion criteria; questionnaires about CFS related symptoms (0 to 4 scale), Multidimensional Fatigue Inventory (MFI) and Medical Outcome Survey Short Form 36 (MOS SF-36).

RESULTS: Demographics, trends for the number of diffuse “functional” symptoms present, and severity of CFS case designation criteria symptoms were equivalent between CFS subjects in Cohorts 1 and 2. HC had significantly fewer symptoms, lower MFI and higher SF-36 domain scores than CFS in both cohorts. Migraine headaches were found in 84%, and tension-type headaches in 81% of Cohort 2 CFS. This compared to 5% and 45%, respectively, in HC. The CFS group had migraine without aura (60%; MO; CFS+MO), with aura (24%; CFS+MA), tension headaches only (12%), or no headaches (4%). Co-morbid tension and migraine headaches were found in 67% of CFS. CFS+MA had higher severity scores than CFS+MO for the sum of scores for poor memory, dizziness, balance, and numbness (“Neuro-construct”, p = 0.002) and perceived heart rhythm disturbances, palpitations and noncardiac chest pain (“Cardio-construct”; p = 0.045, t-tests after Bonferroni corrections). CFS+MO subjects had lower pressure-induced pain thresholds (2.36 kg [1.95-2.78; 95% C.I.] n = 40) and a higher prevalence of fibromyalgia (47%; 1990 criteria) compared to HC (5.23 kg [3.95-6.52] n = 20; and 0%, respectively). Sumatriptan was beneficial for 13 out of 14 newly diagnosed CFS migraine subjects.

CONCLUSIONS: CFS subjects had higher prevalences of MO and MA than HC, suggesting that mechanisms of migraine pathogenesis such as central sensitization may contribute to CFS pathophysiology.

CLINICAL TRIAL REGISTRATION: Georgetown University IRB # 2006-481

TRIAL REGISTRATION: ClinicalTrials.gov NCT00810329 NCT00810329.

 

Source: Ravindran MK, Zheng Y, Timbol C, Merck SJ, Baraniuk JN. Migraine headaches in chronic fatigue syndrome (CFS): comparison of two prospective cross-sectional studies. BMC Neurol. 2011 Mar 5;11:30. doi: 10.1186/1471-2377-11-30. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3058027/ (Full article)

 

Overlapping conditions among patients with chronic fatigue syndrome, fibromyalgia, and temporomandibular disorder

Abstract:

BACKGROUND: Patients with chronic fatigue syndrome (CFS), fibromyalgia (FM), and temporomandibular disorder (TMD) share many clinical illness features such as myalgia, fatigue, sleep disturbances, and impairment in ability to perform activities of daily living as a consequence of these symptoms. A growing literature suggests that a variety of comorbid illnesses also may commonly coexist in these patients, including irritable bowel syndrome, chronic tension-type headache, and interstitial cystitis.

OBJECTIVE: To describe the frequency of 10 clinical conditions among patients with CFS, FM, and TMD compared with healthy controls with respect to past diagnoses, degree to which they manifested symptoms for each condition as determined by expert-based criteria, and published diagnostic criteria.

METHODS: Patients diagnosed as having CFS, FM, and TMD by their physicians were recruited from hospital-based clinics. Healthy control subjects from a dermatology clinic were enrolled as a comparison group. All subjects completed a 138-item symptom checklist and underwent a brief physical examination performed by the project physicians.

RESULTS: With little exception, patients reported few past diagnoses of the 10 clinical conditions beyond their referring diagnosis of CFS, FM, or TMD. In contrast, patients were more likely than controls to meet lifetime symptom and diagnostic criteria for many of the conditions, including CFS, FM, irritable bowel syndrome, multiple chemical sensitivities, and headache. Lifetime rates of irritable bowel syndrome were particularly striking in the patient groups (CFS, 92%; FM, 77%; TMD, 64%) compared with controls (18%) (P<.001). Individual symptom analysis revealed that patients with CFS, FM, and TMD share common symptoms, including generalized pain sensitivity, sleep and concentration difficulties, bowel complaints, and headache. However, several symptoms also distinguished the patient groups.

CONCLUSIONS: This study provides preliminary evidence that patients with CFS, FM, and TMD share key symptoms. It also is apparent that other localized and systemic conditions may frequently co-occur with CFS, FM, and TMD. Future research that seeks to identify the temporal relationships and other pathophysiologic mechanism(s) linking CFS, FM, and TMD will likely advance our understanding and treatment of these chronic, recurrent conditions.

Comment in: Tobacco use and chronic fatigue syndrome, fibromyalgia, and temporomandibular disorder. [Arch Intern Med. 2000]

 

Source: Aaron LA, Burke MM, Buchwald D. Overlapping conditions among patients with chronic fatigue syndrome, fibromyalgia, and temporomandibular disorder. Arch Intern Med. 2000 Jan 24;160(2):221-7. http://www.ncbi.nlm.nih.gov/pubmed/10647761

 

A controlled study of brain magnetic resonance imaging in patients with the chronic fatigue syndrome

Abstract:

Two neuroradiologists compared the brain MR scans of 52 patients with the CDC criteria for the chronic fatigue syndrome (CFS) with those of 52 age and sex matched controls who had undergone imaging because of histories of head trauma or headache.

CFS patients had significantly more abnormal scans than controls–27% vs 2%. Abnormalities seen were foci of increased white matter T2 signal in 9 CFS patients and one control and ventricular or sulcal enlargement in 5 CFS patients. Follow up of patients with subcortical signal hyperintensities revealed 3 who had symptoms suggestive of other known medical causes of what appeared to be CFS.

The data indicate that some CFS patients have some organic problem manifesting itself on neuroimaging. But, finding MR abnormalities should warn the physician that the patient’s symptoms may be secondary to some other medical illness and not simply primary CFS.

 

Source: Natelson BH, Cohen JM, Brassloff I, Lee HJ. A controlled study of brain magnetic resonance imaging in patients with the chronic fatigue syndrome. J Neurol Sci. 1993 Dec 15;120(2):213-7. http://www.ncbi.nlm.nih.gov/pubmed/8138812