Category: Case Study

Longitudinal Cytokine and Multi-Modal Health Data of an Extremely Severe ME/CFS Patient with HSD Reveals Insights into Immunopathology, and Disease Severity

Abstract:

Myalgic Encephalomyelitis/Chronic Fatigue Syndrome (ME/CFS) presents significant challenges in patient care due to its intricate multisystem nature, comorbidities, and global prevalence. To address these complexities, we employed a comprehensive approach, integrating longitudinal cytokine profiling with extensive clinical, health, textual, pharmaceutical, and nutraceutical data, and performed personalized analyses using AI.

Focusing on an exceptionally severe ME/CFS patient with hypermobility spectrum disorder (HSD) and marginal symptom improvements, our study highlights the dynamic nature of symptoms, severity, triggers, and modifying factors. As part of this study, we introduced an updated platform and two applications, ME-CFSTrackerApp, and LexiTime, facilitating real-time symptom tracking and enhancing physician-patient communication.

Our longitudinal cytokine profiling underscores the significance of Th2-type cytokines and synergistic activities between mast cells and eosinophils, leading to skewing of Th1 toward Th2 immune responses in ME/CFS pathogenesis, especially in cognitive impairment and sensorial intolerance. This suggests a potentially shared underlying mechanism with major comorbidities.

Additionally, our data reveal potential roles of BCL6 and TP53 pathways in ME/CFS etiology and emphasize the importance of investigating low-dose drugs with partial agonist activity in ME/CFS treatment. Our analyses underscore the patient-centered care approach for better healthcare management.

Source: Fereshteh Jahanbani1, Justin C. Sing, Rajan D. Maynard, Shaghayegh Jahanbani, Janet Dafoe, Whitney Dafoe, Nathan Jones, Kelvin J. Wallace, Azuravesta Rastan, Hannes Rost, Holden Maecker, Michael P. Snyder, Ronald W. Davis. Longitudinal Cytokine and Multi-Modal Health Data of an Extremely Severe ME/CFS Patient with HSD Reveals Insights into Immunopathology, and Disease Severity. Front. Immunol. Sec. Autoimmune and Autoinflammatory Disorders: Autoinflammatory Disorders. Volume 15 – 2024 | doi: 10.3389/fimmu.2024.1369295 https://www.frontiersin.org/journals/immunology/articles/10.3389/fimmu.2024.1369295/abstract

Electroencephalographic Abnormalities in a Patient Suffering from Long-Term Neuropsychological Complications following SARS-CoV-2 Infection

Abstract:

Introduction: Emotional apathy has recently been identified as a common symptom of long COVID. While recent meta-analyses have demonstrated generalized EEG slowing with the emergence of delta rhythms in patients hospitalized for severe SARS-CoV-2 infection, no EEG study or dopamine transporter scintigraphy (DaTSCAN) has been performed in patients with long COVID presenting with apathy. The objective of this case report was to explore the pathophysiology of neuropsychological symptoms in long COVID.

Case presentation: A 47-year-old patient who developed a long COVID with prominent apathy following an initially clinically mild SARS-CoV-2 infection underwent neuropsychological assessment, cerebral MRI, DaTSCAN, and resting-state high-density EEG 7 months after SARS-CoV-2 infection. The EEG data were compared to those of 21 healthy participants. The patient presented with apathy, cognitive difficulties with dysexecutive syndrome, moderate attentional and verbal episodic memory disturbances, and resolution of premorbid mild gaming disorder, mild mood disturbances, and sleep disturbances. His MRI and DaTSCAN were unremarkable. EEG revealed a complex pattern of oscillatory abnormalities compared to the control group, with a strong increase in whole-scalp delta and beta band activity, as well as a decrease in alpha band activity. Overall, these effects were more prominent in the frontal-central-temporal region.

Conclusion: These results suggest widespread changes in EEG oscillatory patterns in a patient with long COVID characterized by neuropsychological complications with prominent apathy. Despite the inherent limitations of a case report, these results suggest dysfunction in the cortical networks involved in motivation and emotion.

Source: Benis D, Voruz P, Chiuve SC, Garibotto V, Assal F, Krack P, Péron J, Fleury V. Electroencephalographic Abnormalities in a Patient Suffering from Long-Term Neuropsychological Complications following SARS-CoV-2 Infection. Case Rep Neurol. 2023 Dec 5;16(1):6-17. doi: 10.1159/000535241. PMID: 38179211; PMCID: PMC10764086. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10764086/ (Full text)

Case report: Recurrent cervical spinal stenosis masquerading as myalgic encephalomyelitis/chronic fatigue syndrome with orthostatic intolerance

Abstract:

Introduction: Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is a complex, chronic, multi-system disorder that is characterized by a substantial impairment in the activities that were well tolerated before the illness.

In an earlier report, we had described three adult women who met criteria for ME/CFS and orthostatic intolerance, and had congenital or acquired cervical spinal stenosis. All three experienced substantial global improvements in their ME/CFS and orthostatic intolerance symptoms after recognition and surgical treatment of the cervical stenosis. After a several year period of improvement, one of the individuals in that series experienced a return of ME/CFS and orthostatic intolerance symptoms.

Main Symptoms and Clinical Findings: Radiologic investigation confirmed a recurrence of the ventral compression of the spinal cord due to a shift of the disc replacement implant at the involved cervical spinal level.

Therapeutic Intervention: Decompression of the spinal cord with removal of the implant and fusion at the original C5-C6 level was once again followed by a similar degree of improvement in function as had been observed after the first operation.

This recapitulation of the outcomes after surgical management of cervical stenosis provides further evidence in support of the hypothesis that cervical spinal stenosis can exacerbate pre-existing or cause new orthostatic intolerance and ME/CFS. Especially for those with refractory symptoms and neurological signs, surgical interventions may offer relief for selected patients with this complex condition.

Source: Charles C. Edwards III, Charles C. Edwards II, Scott Heinlein, Peter C. Rowe. Case report: Recurrent cervical spinal stenosis masquerading as myalgic encephalomyelitis/chronic fatigue syndrome with orthostatic intolerance. Frontiers in Neurology, Volume-14- 2023. https://www.frontiersin.org/articles/10.3389/fneur.2023.1284062/abstract

Successful treatment of myalgic encephalomyelitis/chronic fatigue syndrome using hydrogen gas: four case reports

Myalgic encephalomyelitis/chronic fatigue syndrome (ME/CFS) is characterized by unexplained fatigue and malaise that persist for more than 6 months with neuropsychiatric symptoms, including slight fever, headache, weakness, impaired thinking, and depression.[1,2] The onset and severity of these symptoms vary and reduce the quality of life as well as social, occupational, and personal activities of those affected, with some becoming bedridden.[1,2] The number of ME/CFS patients in the United States is estimated to be between 836,000 and 2.5 million.[3]

Although it currently remains unclear whether there are objective and biological abnormalities in ME/CFS, recent neuroimaging, blood marker analyses, and energy metabolism and mitochondrial studies detected these abnormalities in ME/CFS patients.[4] ME/CFS may be caused by the activation of the immune system, both within and outside the brain, which induces the release of inflammatory cytokines. ME/CFS is presumed to cause abnormalities in the central and autonomic nervous systems, systemic energy metabolism, and immune system and also involve oxidative and nitrosative stress.[4,5,6] Dysfunctions in systemic energy metabolism may be related to abnormalities in the structure and function of mitochondria.[7,8,9,10]

Molecular hydrogen (H2) is a gaseous molecule that selectively scavenges reactive oxygen and nitrogen species with strong oxidizing power, namely, hydroxyl radicals (·OH) and peroxynitrite, respectively.[11,12] H2 easily crosses the blood-brain barrier and biological membranes, reaches mitochondria, and protects cells from ·OH-induced cell damage.[11,12] A recent literature review revealed that H2 attenuated acute or chronic fatigue in animals and healthy subjects.[13] We also reported that the anti-fatigue effects of H2 involved the protection of mitochondria, which may also ameliorate the pathogenesis of ME/CFS.[13] Therefore, we conducted this case study to test this hypothesis by examining the efficacy of H2 gas inhalation in four patients with ME/CFS.

Source: Hirano, Shin-ichi*; Ichikawa, Yusuke; Sato, Bunpei; Takefuji, Yoshiyasu; Satoh, Fumitake. Successful treatment of myalgic encephalomyelitis/chronic fatigue syndrome using hydrogen gas: four case reports. Medical Gas Research 14(2):p 84-86, June 2024. | DOI: 10.4103/2045-9912.385441 https://journals.lww.com/mgar/fulltext/2024/14020/successful_treatment_of_myalgic.7.aspx (Full text)

Case Report: Rapid and partially persistent, improvements of anorexia nervosa and probable myalgic encephalo-myelitis/chronic fatigue syndrome upon metreleptin treatment during two dosing episodes

Abstract

A comorbidity of anorexia nervosa (AN) and myalgic encephalomyelitis (ME/CSF) is uncommon. A 17-year-old male adolescent with possible onset of ME/CFS after an Epstein Barr Virus infection (EBV) and later onset of AN during a second period of weight loss was twice treated off-label with metreleptin for 15 and 11 days, respectively.

As in previous cases, eating disorder specific cognitions and mood improved. Interestingly, fatigue and post-exertional muscle pain (P-EMP) improved, too. We discuss potential mechanisms. Treatment with metreleptin may prove beneficial in AN and in ME/CSF associated with substantial weight loss.

Source: Jochen Antel, Johannes Hebebrand, Linda Von Piechowski, Cordula Kiewert, Burkhard Stüve, Gertraud Gradl-Dietsch. Rapid and partially persistent, improvements of anorexia nervosa and probable myalgic encephalo-myelitis/chronic fatigue syndrome upon metreleptin treatment during two dosing episodes. Front. Psychiatry, Sec. Adolescent and Young Adult Psychiatry, Volume 14 – 2023. https://www.frontiersin.org/articles/10.3389/fpsyt.2023.1267495/abstract

Chronic Fatigue Syndrome and Multiple Sclerosis have Reduced Craniospinal Compliance and Dilated Pressurized Bridging Cortical Veins: A Hypothesis Illustrated with Two Case Studies

Abstract:

Chronic fatigue syndrome (CFS) and multiple sclerosis (MS) share similarities regarding their epidemiology, symptomatology and craniospinal physiology. Indeed, the cardinal feature of CFS, fatigue, is also a major factor in the symptomatology of the majority of MS patients.

Recently, we have found that there is a significant reduction in the craniospinal compliance in MS which affects both the stiffness of the walls of the spinal canal and the walls of the cerebral venous system. This change in compliance brings about an alteration in the effectiveness of the pulse wave dampening in the craniospinal system. The result is an impedance mismatch between the cortical veins and their draining sinuses, leading to dilatation of these upstream veins.

We deduce this dilatation can only be brought about by an increase in the pressure gradient between the vein lumen and the subarachnoid space (i.e. the transmural pressure gradient). We hypothesise that given the similarities between MS and CFS, a similar mechanism underlies the physiology of CFS. We present two case studies to highlight the expected findings in CFS patients if this hypothesis were proven to be correct.

Source: Bateman, G.; Bateman, A. Chronic Fatigue Syndrome and Multiple Sclerosis have Reduced Craniospinal Compliance and Dilated Pressurized Bridging Cortical Veins: A Hypothesis Illustrated with Two Case Studies. Preprints.org 2023, 2023052264. https://doi.org/10.20944/preprints202305.2264.v1 https://www.preprints.org/manuscript/202305.2264/v1 (Full text available as PDF file)

Management of Post-Viral Postural Orthostatic Tachycardia Syndrome With Craniosacral Therapy

Abstract:

Postural Orthostatic Tachycardia Syndrome (POTS) is a rare disorder of the autonomic nervous system. The number of people afflicted with this dysautonomia has increased dramatically in recent years due to the long-term effects of coronavirus disease (COVID-19); however, it is largely underdiagnosed.

This case report is about a patient with post-viral neuropathic POTS.

Neuropathic POTS is believed to be due to the damage of small nerve fibers that regulate the constriction of the blood vessels in the limb and abdomen, which leads to interference with vasoconstriction, and therefore causes tachycardia.

Current literature emphasizes a treatment that is based on lifestyle modifications, such as increasing water and salt intake, and symptomatic pharmacological treatment.

In this case, the 39-year-old male patient was treated with osteopathic manipulative treatment (OMT), specifically the compression of the fourth ventricle (CV4), which has been associated with the production of hyperparasympathetic and anti-inflammatory effects and, hence, helps overcome the small-fiber neuropathy caused by the viral illness.

We found that the CV4 technique led to the successful remission of the patient’s symptoms. Therefore, we propose craniosacral therapy as a successful single management modality in patients with POTS.

Source: Tafler L, Chaudry A, Cho H, Garcia A. Management of Post-Viral Postural Orthostatic Tachycardia Syndrome With Craniosacral Therapy. Cureus. 2023 Feb 15;15(2):e35009. doi: 10.7759/cureus.35009. PMID: 36938206; PMCID: PMC10021347. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10021347/ (Full text)

Hyperbaric oxygen treatment for long coronavirus disease-19: a case report

Abstract:

Background: The coronavirus disease 2019 pandemic has resulted in a growing population of individuals who experience a wide range of persistent symptoms referred to as “long COVID.” Symptoms include neurocognitive impairment and fatigue. Two potential mechanisms could be responsible for these long-term unremitting symptoms: hypercoagulability, which increases the risk of blood vessel occlusion, and an uncontrolled continuous inflammatory response. Currently, no known treatment is available for long COVID. One of the options to reverse hypoxia, reduce neuroinflammation, and induce neuroplasticity is hyperbaric oxygen therapy. In this article, we present the first case report of a previously healthy athletic individual who suffered from long COVID syndrome treated successfully with hyperbaric oxygen therapy.

Case presentation: A previously healthy 55-year-old Caucasian man presented 3 months after severe coronavirus disease 2019 infection with long COVID syndrome. His symptoms included a decline in memory, multitasking abilities, energy, breathing, and physical fitness. After evaluation that included brain perfusion magnetic resonance imaging, diffusion tensor imaging, computerized cognitive tests, and cardiopulmonary test, he was treated with hyperbaric oxygen therapy. Each session included exposure to 90 minutes of 100% oxygen at 2 atmosphere absolute pressure with 5-minute air breaks every 20 minutes for 60 sessions, 5 days per week. Evaluation after completing the treatment showed significant improvements in brain perfusion and microstructure by magnetic resonance imaging and significant improvement in memory with the most dominant effect being on nonverbal memory, executive functions, attention, information procession speed, cognitive flexibility, and multitasking. The improved cognitive functions correlated with the increased cerebral blood flow in brain regions as measured by perfusion magnetic resonance imaging. With regard to physical capacity, there was a 34% increase in the maximum rate of oxygen consumed during exercise and a 44% improvement in forced vital capacity. The improved physical measurements correlated with the regain of his pre-COVID physical capacity.

Conclusions: We report the first case of successfully treated long COVID symptoms with hyperbaric oxygen therapy with improvements in cognition and cardiopulmonary function. The beneficial effects of hyperbaric oxygen shed additional light on the pathophysiology of long COVID. As this is a single case report, further prospective randomized control studies are needed.

Source: Bhaiyat AM, Sasson E, Wang Z, Khairy S, Ginzarly M, Qureshi U, Fikree M, Efrati S. Hyperbaric oxygen treatment for long coronavirus disease-19: a case report. J Med Case Rep. 2022 Feb 15;16(1):80. doi: 10.1186/s13256-022-03287-w. PMID: 35168680; PMCID: PMC8848789. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8848789/ (Full text)

Stellate Ganglion Block for Long COVID Symptom Management: A Case Report

Abstract:

Stellate ganglion block (SGB) is gaining increasing acceptance as a treatment modality for various medical conditions. It works by blocking neuronal transmissions which in turn alleviates sympathetically-driven disease processes. Many of the prolonged sequelae of long COVID are thought to be mediated by dysregulation of the autonomic nervous system, and SGB is being investigated as a potential option for symptomatic management of long COVID. This case report demonstrates the efficacy of SGB in a previously healthy patient for the management of long COVID symptoms including fatigue, post-exertional malaise, shortness of breath, and gastrointestinal symptoms.

Source: Khan M H, Kirkpatrick K P, Deng Y, et al. (December 07, 2022) Stellate Ganglion Block for Long COVID Symptom Management: A Case Report. Cureus 14(12): e32295. doi:10.7759/cureus.32295 https://www.cureus.com/articles/127985-stellate-ganglion-block-for-long-covid-symptom-management-a-case-report (Full text)

Post-COVID-19 Syndrome: A Novel Diagnosis

Abstract:

Patients with post-COVID-19 syndrome have reported a wide array of symptoms that include autonomic dysfunction. It is hypothesized that this may be secondary to interruption of baroreflex pathways in the carotid arteries or nucleus tractus solitarius, however, confirming studies have yet to be performed. A limited number of studies have highlighted the presence of an exaggerated baroreflex response in patients with a post-COVID-19 syndrome that mirror other chronic autonomic dysfunction-related conditions.

Source: Kalia R, Kalia R, Musih J, Cubelo M, Popat J. Post-COVID-19 Syndrome: A Novel Diagnosis. Cureus. 2022 Aug 22;14(8):e28266. doi: 10.7759/cureus.28266. PMID: 36158335; PMCID: PMC9491485. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9491485/ (Full text)