Brain Scans & Neuroinflammation Tests - Hypo-perfusion and Lesions on the brain, Neuroinflammation, EEG markers, NMDA activity


Scientific and Medical Evidence
- Listing of Research conducted worldwide section :

Serious Brain and nervous system abnormalities
Spinal Fluids & Proteomic Markers
Inability to metabolise glucose and sugar
Lowered oxygen consumption in ME patients

Abnormal red blood cell structure

Research Report into brain abnormalities in ME
Dr. Paul Cheney has successfully treated hundreds of CFS patients in the USA.
Lecture by Dr. Paul Cheney who has successfully treated hundreds of CFS patients in the USA
Summary of the above lecture by Dr. Paul Cheney

 

ME, like most neurological illnesses involves injuries to deep brain structures. In ME this typically includes injuries to some or all of the following: Hypothalmus, the dorsal root ganglia, basal ganglia, brain stem, frontal lobes and sub-cortical areas, Pineal and Pituitary glands, vagus nerve, frontal and anterior left parietal lobe, spinal cord, cervical and lumbar nerve roots and peripheral nerves, one side or both sides of the cortex, and either one or all of the posterior chamber organs, the Pons and Cerebellum. Reductions in grey matter and reductions in white midbrain matter. These injuries may differ slightly between subgroups. It is believed that toxins, infections and prolonged / chronic inflammatory immune system damage can cause these deep brain injuries.

Infection(s), chronically activated Immune system and Neuroinflammation & Oxidative and Nitrosative stress and damage in Neurological illnesses
Activated immune pathways and inflammatory cytokines and inflammatory markers, and neuroinflammation, and high oxidative and nitrosative stress and damage, and mitochondria damage, with or without infection(s) has been found in neurodegenerative diseases such as Parkinsons, Alzheimers, MS and many others. This causes extreme fatigue and tiredness. This is also found in autoimmune diseases. And they are also found in ME and CFS, a neurological illness according to WHO, with immune system dysfunctions. Click here to view important research findings

Tests

  • PET scan
    Check for decreased glucose metabolism in the right mediofrontal cortex, and significant hypoperfusion and hypometabolism in the brain stem. Also lesions and reductions in grey matter. Impaired glucose metabolism in the brain is consistently found in ME/CFS. Check for decreased glucose metabolism in the prefrontal and orbitofrontal cortex. Also Check for Basal Ganglia and Pre Frontal Cortex injury and for frontal and anterior left parietal lobe injury (Dr. Byron Hyde).
    Test areas of brain and nervous system for evidence of immune system activation in the brain and Neuroinflammation. Inflammation in limbic regions (cingulate cortex, hippocampus, amygdala, thalamus, midbrain, and pon) of the brain.

      • Neuroinflammation in Patients with Chronic Fatigue Syndrome/Myalgic Encephalomyelitis: An 11C-(R)-PK11195 PET Study. Nakatomi Y, Mizuno K, Ishii A, Wada Y, Tanaka M, Tazawa S, Onoe K, Fukuda S, Kawabe J, Takahashi K, Kataoka Y, Shiomi S, Yamaguti K, Inaba M, Kuratsune H, Watanabe Y.  J Nucl Med. 2014 Mar 24.
        Results
        The BPND values of 11C-(R)-PK11195 in the cingulate cortex, hippocampus, amygdala, thalamus, midbrain, and pons were 45%-199% higher in CFS/ME patients than in healthy controls. In CFS/ME patients, the BPND values of 11C-(R)-PK11195 in the amygdala, thalamus, and midbrain positively correlated with cognitive impairment score, the BPND values in the cingulate cortex and thalamus positively correlated with pain score, and the BPND value in the hippocampus positively correlated with depression score. See picture below.


        Representative PET scans showing activated microglia in a CFS/ME patient.

        Key to brain regions: AMY, amygdala; CC, cingulate cortex; HIP, hippocampus; MID, midbrain; THA, thalamus; and PON: pons. Photo credit: Image courtesy of RIKEN
      • Neuroscience of Fatigue and CFS/ME by Using PET Molecular Imaging and Functional Neuroimaging
        Yasuyoshi Watanabe, Masaski Tanaka, Kei Mizuno, Akira Ishii, Emi Yamano, Sanae Fukuda, Yasuhito Nakatomi, Kouzi Yamaguti, and Hirohiko Kuratsune. IACFS/ME Conference. Translating Science into Clinical Care. March 20-23, 2014 • San Francisco, California, USA


    • Test blood, spinal fluids, and inflamed samples from brain, dorsal root ganglia, basal ganglia, brain stem, vagus nerve, spinal cord, cervical and lumbar nerve roots and peripheral nerves for the following:
      • Measure levels of neopterin, indoleamine 2,3-dioxygenase, L-kynurenine, kynurenic acid and quinolinic acid. Also measure levels of tryptophan. And test for brain lesions consistent with edema, inflammatory destruction and demyelination

    • Reduced cortical blood flow, Reduced glutamate Reduced serotonin transporter, Increased dopamine biosynthesis
      • S. Yamamoto, Y. Ouchi, H. Onoe, E. Yoshikawa, H. Tsukada, H. Takahashi, et al., "Reduction of Serotonin Transporters of Patients with Chronic Fatigue Syndrome," Brain Imaging, Vol. 15, No. 17, 2004, pp. 2571-2574.
      • A. J. Cleare, C. Messa, E. A. Rabiner and P. M. Grasby, "Brain 5-HT1A Receptor Binding in Chronic Fatigue Syndrome Measured Using Positron Emission Tomography and [11C]WAY-100635," Biological Psychiatry, Vol. 57, No. 3, 2005, pp. 239-246.
      • Neuroscience of Fatigue and CFS/ME by Using PET Molecular Imaging and Functional Neuroimaging
        Yasuyoshi Watanabe, Masaski Tanaka, Kei Mizuno, Akira Ishii, Emi Yamano, Sanae Fukuda, Yasuhito Nakatomi, Kouzi Yamaguti, and Hirohiko Kuratsune. IACFS/ME Conference. Translating Science into Clinical Care. March 20-23, 2014 • San Francisco, California, USA

      Check for Basal Ganglia and Pre Frontal Cortex dysfunctions, inflammation and abnormalities. Also check for Dopamine deficiency and reduced dopaminergic drive.
      - Decreased basal ganglia activation in subjects with chronic fatigue syndrome: association with symptoms of fatigue. Miller AH, Jones JF, Drake DF, Tian H, Unger ER, Pagnoni G. PLoS One. 2014 May 23;9(5):e98156.
      - Fatigue in neurological disorders. Chaudhuri A, Behan PO. Lancet. 2004 Mar 20;363(9413):978-88.
      - Fatigue and basal ganglia. Chaudhuri A, Behan PO. J Neurol Sci. 2000 Oct 1;179(S 1-2):34-42.
      - Further Research results & listings

  • Autopsy Reports
    A coroner's report of ME patient Sophia Mirza revealed that 4 out of 5 dorsal root ganglia were abnormal and showed disease. The coroner had not been able to find exactly what had caused this but the result was dorsal root ganglionitis – an inflammation. This suggests an infection of this area. An MRI scan or MRS scan or samples of this area would have revealed abnormalities, infections and inflammation while she was alive, but unfortunately this was never done. She was refused these tests by some doctors.
    These neurological abnormalities and extensive damage to the brain and nervous system were confirmed in another autopsy of a dead ME / CFS patient in 2017.

    'Chronic fatigue syndrome (CFS) is characterized as a persistent, debilitating complex disorder of unknown etiology, whereby patients suffer from extreme fatigue, which often presents with symptoms that include chronic pain, depression, weakness, mood disturbances, and neuropsychological impairment. In this mini review and case report, we address central nervous system (CNS) involvement of CFS and present neuropathological autopsy findings from a patient who died with a prior diagnosis of CFS. Among the most remarkable pathological features of the case are focal areas of white matter loss, neurite beading, and neuritic pathology of axons in the white matter with axonal spheroids. Atypical neurons displaying aberrant sprouting processes in response to injury are observed throughout cortical gray and white matter. Abundant amyloid deposits identical to AD plaques with accompanying intracellular granular structures are observed as well. Neurofibrillary tangles are also present in the white matter of the frontal cortex, thalamus and basal ganglia. Taken together, these neuropathological findings warrant further studies into CNS disease associated with CFS.'
    CNS findings in chronic fatigue syndrome and a neuropathological case report. Kimberly Ferrero, Mitchell Silver, Alan Cocchetto, Eliezer Masliah, Dianne Langford DOI: 10.1136/jim-2016-000390 Published 6 April 2017

    There is a lot of evidence of viral and bacteria infections in ME / CFS, see Scientific Evidence and these may account for the damage to the brain and nervous system.

  • Neuroinflammation Tests
    Test blood, spinal fluids, and inflamed samples from dorsal root ganglia, basal ganglia, brain stem, vagus nerve, autonomic ganglia, peripheral ganglia, anterior and posterior horns of the spinal cord, cervical and lumbar nerve roots and peripheral nerves and sites of brain lesions for the following:


    • Test for activation and upregulation of Toll like receptors (TLR2/4)
    • Test for the activation and upregulation of IL-1β, NF-kappaB, TNF-a, IL-6, IL-8, IL-10, IFNα, COX-2, IDO levels and pro inflammatory cytokines, activation of microglia and astrocytes, inflammatory markers and oxidative and nitrosative stress. Also test for astrocyte abnormalities such as reduced numbers and function.
    • Test for high Glutamate levels, Quinolinic acid levels, ROS levels, IDO levels, 3-Hydroxykynurenine levels, Neopterin and Substance P.
    • Measure levels of Isoprostanes. These are raised in ME and are a good biomarker.
    • General Inflammation Markers in spinal fluids, nerve tissues: high-sensitivity c-reactive protein (hs-CRP), white blood cell count (WBC) , IL-6. prostaglandins E2 and C3A . (Psychoneuroendocrinology 2008:33:18-29)
    • Elevated homocysteine in the cerebrospinal fluid (Regland B, Andersson M, Abrahamsson L, et al. Increased concentrations of homocysteine in the cerebrospinal fluid in patients with fibromyalgia and chronic fatigue syndrome. Scand J Rheumatol 1997;26:301-307)
    • Test for high Histidine levels, and high trans-urocanate levels and high Histamine levels
    • Test for peripheral immune activation and neuroinflammation using FLAIR magnetic resonance imaging (MRI)
    • Test for several inflammatory markers in spinal fluids and the nervous system
    • Test for peripheral immune activation and neuro inflammation using FLAIR magnetic resonance imaging (MRI)
  • Tryptophan destruction in ME
    Tryptophan the precursor of serotonin which is involved in sleep and many other functions is being depleted by high levels of neopterin and indoleamine 2,3-dioxygenase. Test blood, spinal fluids, and inflamed samples from brain, dorsal root ganglia, basal ganglia, brain stem, vagus nerve, spinal cord, cervical and lumbar nerve roots and peripheral nerves and blood for
    the following:
    Measure levels of neopterin, indoleamine 2,3-dioxygenase, L-kynurenine, kynurenic acid and quinolinic acid. Also measure levels of tryptophan. Test for brain lesions consistent with edema, inflammatory destruction and demyelination.


Specific Brain Scans

  • SPECT scan :  Hypoperfusion in the brain is consistently found in ME/CFS patients. Check for lower cortical/cerebellar regional cerebral blood flow in the frontal, parietal, occipital and temporal lobes, basal ganglia, brain stem, insula cortex, and throughout the cerebral cortex. Hypoperfusion in the brain stem (Dr. John Richardson). Decreased basal ganglia activation - Unger ER, Miller AH, Jones JF, Drake DF, Tian H, Pagnoni G: Decreased basal ganglia activation in chronic fatigue syndrome subjects is associated with increased fatigue. FASEB J 2012, 26:1035.20.

    'All patients within this study displayed hypoperfusion in some brain area as shown by their SPECT scans (see Appendix, Table 1.1). *Thirty-five (90%) showed hypoperfusion in the regions comprising: *Twenty-four (62%) in the Brain Stem *Twenty (51%) in the Caudate Nuclei *Nine (23%) showed hypoperfusion in both Brain Stem and Caudate Nuclei regions *Thirty (77%) cases demonstrated hypoperfusion in the regions comprising: *Twenty-four (62%) in the Temporal Lobes *Twelve (31%) in the Parietal Lobes *Nine (23%) in the Frontal Lobes"
    Relationship Between SPECT Scans and Buspirone Tests in Patients with ME John Richardson, MB, BS, Durval Campos Costa, MD, MSc, PhD Journal of Chronic Fatigue Syndrome, Vol. 4(3) 1998

    Cerebral blood flow is reduced in chronic fatigue syndrome as assessed by arterial spin labeling. Biswal B, Kunwar P, Natelson BH. J Neurol Sci. 2011 Feb 15;301(1-2):9-11. 
    Also check for evidence and signs of basal ganglia injury and for frontal and anterior left parietal lobe injury (Dr. Byron Hyde).
    Johnson and DeLuca (2005) concluded that functional neuroimaging studies among patients with ME/CFS generally show hypometabolism in the frontal lobes and ganglia
    J. P. Neary, A. D. W. Roberts, N. Leavins, M. F. Harrison, J. C. Croll and J.R. Sexsmith, "Prefrontal Cortex Oxygenation During Incremental Exercise in Chronic Fatigue Syndrome," Clinical Physiology and Functional Imaging, 2008.

    Check for Basal Ganglia and Pre Frontal Cortex dysfunctions, inflammation and abnormalities. Also check for Dopamine deficiency and reduced dopaminergic drive.
    - Decreased basal ganglia activation in subjects with chronic fatigue syndrome: association with symptoms of fatigue. Miller AH, Jones JF, Drake DF, Tian H, Unger ER, Pagnoni G. PLoS One. 2014 May 23;9(5):e98156.
    - Fatigue in neurological disorders. Chaudhuri A, Behan PO. Lancet. 2004 Mar 20;363(9413):978-88.
    - Fatigue and basal ganglia. Chaudhuri A, Behan PO. J Neurol Sci. 2000 Oct 1;179(S 1-2):34-42.
    - Further Research results & listings
  • EEG
    Zinn et al. show that there is excessive delta wave activity and depleted alpha wave activity in the brains of ME / CFS patients during the day time. This is a good marker.
    qEEG brain topograpy:  Elevated EEG activity in theta and beta frequencies and increased intracerebral electrical sources in left frontal region delta and beta frequencies in eyes closed condition may be identified. Reduced sources in right hemisphere (beta) may be noted during verbal cognitive processing.
    • EEG spectral coherence data distinguish chronic fatigue syndrome patients from healthy controls and depressed patients-A case control study. Frank H Duffy, Gloria B McAnulty, Michelle C McCreary, George J Cuchural and Anthony L Komaroff. (2011). See diagram below:



    • F. Donati, L. Fagioli, A. L. Komaroff and F. H. Duffy, "Quantified EEG Findings in Patients with Chronic Fatigue Syndrome," Paper Presented at the American Association for Chronic Fatigue Syndrome, Ft. Lauderdale, Florida, 1994. (Several important findings relating to ME/CFS).
    • F. H. Duffy, G. B. McAnulty, M. McCreary, M. S. Albert, G. Cucharal, A. Shatzberg, et al., "Electroencephalographic Data Distinguish Patients with CFS from Healthy and Depressed Controls," Paper Presented at the 9th International Association of CFS/ME, Reno, NV, March, 2009.
    • K. M. Billiot, T. H. Budzynski and F. Andrasik, "EEG Patterns and Chronic Fatigue Syndrome," Journal of Neurotherapy, Vol. 2, 1997, pp. 20-30. http://www.snrjnt.org/JournalNT/JNT(22)4.html.8004844
    • L. Sherlin, T. Budzynski, H. Kogan-Budzynski, M. Congedo, M. E. Fischer and D. Buchwald, "Low-Resolution Brain Tomography (LORETA) of Monozygotic Twins Disconcordant for Chronic Fatigue Syndrome," Neuro-Image, Vol. 34, No. 4, 2006, pp. 1438-1442.
    • P. Flor-Henry, J. C. Lind and Z. J. Koles, "EEG Source Analysis of Chronic Fatigue Syndrome," Psychiatric Research, 2009. PMID: 20006474.
    • Cortical Hypoactivation During Resting EEG suggests Subcortical Pathophysiology in Chronic Fatigue Syndrome as Revealed by Exact Low Resolution Electromagnetic Tomography
      Mark A Zinn , Marcie L Zinn, Jose R Maldonado Jane L Norris, Ian Valencia, Jose G Montoya
      EEG Peak Alpha Frequency is Associated with Chronic Fatigue Syndrome: A Case-Control Observational Study 
      Marcie Zinn, Ph.D., Mark Zinn, MM, Jose Maldonado, MD, FAPM, Jane Norris, PA-C, Ian Valencia, BS
      .IACFS/ME Conference. Translating Science into Clinical Care. March 20-23, 2014 • San Francisco, California, USA
      Findings:
      • 50 CFS patients vs. 50 matched controls
      • Peak alpha wave frequency (PAF) significantly reduced over 58% of the cerebral cortex (P=0.006), and delta wave frequency increased, particularly in frontal and limbic areas
      • Both abnormalities highly correlated with the degree of fatigue, as assessed by two validated fatigue instruments (for PAF R2=0.90, P< 0.0001)
      • Indicating likely disruptions of information transfer across cortical networks , & inhibition of ascending arousal systems
      • They are the sorts of things that you see in a whole host of well-documented neurologic diseases and you don’t see in healthy people.
  • MRI scan :  Check for number of lesions in the frontal lobes and sub-cortical areas, pre frontal cortex, basal ganglia, motor cortex, dorsal root ganglia and brain stem suggestive of demyelination or edema. Lesions in any other areas of the brain. Check for reductions in grey matter. Do spinal MRI for disc herneation and minor stenosis.
    • Right Arcuate Fasciculus Abnormality in Chronic Fatigue Syndrome RADIOLOGY Zeineh, M. M., Kang, J., Atlas, S. W., Raman, M. M., Reiss, A. L., Norris, J. L., Valencia, I., Montoya, J. G.Hide2015; 274 (2): 517-526
      • CFS patients had an overall reduction in brain white matter than healthy controls.
      • CFS patients showed a consistent abnormality in the right arcuate fasciculus, a particular part of a nerve tract that connects the frontal lobe and temporal lobe.
      • CFS patients had thickened gray matter at the two areas of the brain connected by the right arcuate fasciculus, compared to the controls.
      Stanford study finds brain abnormalities in chronic fatigue patients . MRI showed that overall white-matter content of CFS patients' brains, compared with that of healthy subjects' brains, was reduced. The tract, which connects two parts of the brain called the frontal lobe and temporal lobe, called the right arcuate fasciculus has an abnormal appearance in CFS patients. a thickening of the gray matter at the two areas of the brain connected by the right arcuate fasciculus in CFS patients, compared with controls.
    • In the paper A chronic illness characterized by fatigue, neurologic and immunologic disorders, and active Human Herpesvirus Type 6 Infection. Annals of Internal Medicine 1116: 103-13 "Magnetic resonance scans of the brain showed punctate, subcortical areas of high signal intensity consistent with oedema or demyelination in 78% of patients"
    • MRI involving voxel-based morphometry in patients with ME/CFS has revealed significant lateral prefrontal cortex gray matter volume reduction. And Significant reductions in gray matter volume located primarily in the prefrontal cortex. Okada T, Tanaka M, Kuratsune H, Watanabe Y, Sadato N (2004) Mechanisms underlying fatigue: a voxel-based morphometric study of chronic fatigue syndrome. BMC Neurol 4(1):14
    • Progressive brain changes in patients with chronic fatigue syndrome: A longitudinal MRI study. Shan ZY, Kwiatek R, Burnet R, Del Fante P, Staines DR1, Marshall-Gradisnik SM, Barnden LR. J Magn Reson Imaging. 2016 Apr 28. doi: 10.1002/jmri.25283. [Epub ahead of print].
    • Check for Basal Ganglia and Pre Frontal Cortex injury and for frontal and anterior left parietal lobe injury (Dr. Byron Hyde).
    •  Barden et al.  using 3 T MRI-based morphometric analysis reported evidence of astrocyte dysfunction and failure of autoregulatory mechanisms in patients 
    • 3-T voxel-based morphometry MRI showing reduced occipital lobe gray and white matter volume
    • A coroner's report of ME patient Sophia Mirza revealed that 4 out of 5 dorsal root ganglia were abnormal and showed disease. He had not been able to find exactly what had caused this but the result was dorsal root ganglionitis – an inflammation. This suggests an infection of this area. An MRI scan of this area may reveal abnormalities, infections, inflammation.
    • "Magnetic resonance scans of the brain showed punctate, subcortical areas of high signal intensity consistent with edema or demyelination in 78% of patients (95% Cl, 72% to 86%)"
      Johnson and DeLuca (2005) concluded that functional neuroimaging studies among patients with ME/CFS generally show hypometabolism in the frontal lobes and ganglia
    • Check the anterior and posterior horns of the spinal cord for infection and inflammation and organic damage
      Myalgic Encephalomyelitis: Guidelines for Doctors John Richardson. Journal: J of Chronic Fatigue Syndrome, Vol. 10(1) 2002, pp. 65-80.

      Brain stem Dysfunction Test. "A strong correlation in CFS between brainstem GM volume and pulse pressure suggested impaired cerebrovascular autoregulation. It can be argued that at least some of these changes could arise from astrocyte dysfunction. These results are consistent with an insult to the midbrain at fatigue onset that affects multiple feedback control loops to suppress cerebral motor and cognitive activity and disrupt local CNS homeostasis, including resetting of some elements of the autonomic nervous system (ANS)."
      A brain MRI study of chronic fatigue syndrome: evidence of brainstem dysfunction and altered homeostasis. Leighton R. Barnden, Benjamin Crouch, Richard Kwiatek, Richard Burnet, Anacleto Mernone, Steve Chryssidis, Garry Scroop, Peter Del Fante. NMR in Biomedicine. Volume 24, Issue 10, pages 1302–1312December 2011

      Buchwald, D., Cheney, P., Peterson, D., Henry, B., Wormsley, S., Geiger, A., Ablashi, D., Komaroff, D.etc. 1992. A chronic illness characterized by fatigue, neurologic and immunologic disorders, and active Human Herpesvirus Type 6 Infection. Annals of Internal Medicine 1116: 103-13. (The seminal scientific research paper on the Lake Tahoe epidemic in the USA in the mid 1980's and the origin of the term CFS)

      A. R. Spitzer and M. Broadman, "Treatment of the Narcoleptiform Sleep Disorder in Chronic Fatigue Syndrome and Fibromyalgia with Sodium Oxybate," Pain Practice, Vol. 10, No. 1, 2010, pp. 54-59.
      Spitzer and Broadman believe that many patients with ME/CFS and FM have a lesion in the ventral-lateral preoptic nucleus of hypothalamus, which is critical to initiating and maintaining sleep. This explains the sleep abnormalities in these illnesses.

      Check for Basal Ganglia and Pre Frontal Cortex dysfunctions, inflammation and abnormalities. Also check for Dopamine deficiency and reduced dopaminergic drive.
      - Decreased basal ganglia activation in subjects with chronic fatigue syndrome: association with symptoms of fatigue. Miller AH, Jones JF, Drake DF, Tian H, Unger ER, Pagnoni G. PLoS One. 2014 May 23;9(5):e98156.
      - Fatigue in neurological disorders. Chaudhuri A, Behan PO. Lancet. 2004 Mar 20;363(9413):978-88.
      - Fatigue and basal ganglia. Chaudhuri A, Behan PO. J Neurol Sci. 2000 Oct 1;179(S 1-2):34-42.
      - Further Research results & listings

  • Increased Ventricular Lactate using NMR spectroscopy
    • Murrough, J. W. et al. Increased ventricular lactate in chronic fatigue syndrome measured by 1H MRS imaging at 3.0 T. II: comparison with major depressive disorder. NMR in biomedicine 23, 643–50 (2010).
    • Shungu, D. C. et al. Increased ventricular lactate in chronic fatigue syndrome. III. Relationships to cortical glutathione and clinical symptoms implicate oxidative stress in disorder pathophysiology. NMR in biomedicine 25, 1073–87 (2012).
    • Mathew SJ, Mao X, Keegan KA, Levine SM, Smith EL, Heier LA, et al. Ventricular cerebrospinal fluid lactate is increased in chronic fatigue syndrome compared with generalized anxiety disorder: an in vivo 3.0 T (1)H MRS imaging study. NMR Biomed. 2009;22:251–8.
  • High‐resolution structural 3‐T cerebral MRI scanning - check for "Significant voxels depicting reduced grey matter volume in the CFS group in the occipital lobes (right and left occipital poles; left lateral occipital cortex, superior division; and left supracalcrine cortex), the right angular gyrus and the posterior division of the left parahippocampal gyrus. Significant voxels depicting reduced white matter volume in the CFS group were also noted in the left occipital lobe."
    Source: Puri BK, Jakeman PM, Agour M, Gunatilake KD, Fernando KA, Gurusinghe A I, et al. Regional grey and white matter volumetric changes in myalgic encephalomyelitis (chronic fatigue syndrome): a voxel - based morphometry 3 T MRI study. Br J Radiol ( 2012 ) 85 : e270 - e273.

    Astrocyte malfunction
    "In patients with ME/CFS, Barnden et al. reported that the volume of white matter, as measured using 3 T MRI, correlates significantly and positively with the severity of fatigue experienced by the patients. The authors noted hemodynamic abnormalities in the brainstem, deep frontal white matter, the caudal basal pons and hypothalamus, suggestive of impaired cerebrovascular autoregulation. When taken as a whole, the evidence pointed to astrocyte dysfunction and resetting of homeostatic norms. Astrocyte activity regulates cerebrovascular autoregulation and cerebral blood flow " (Gerwyn Morris and Michael Maes. Myalgic encephalomyelitis/chronic fatigue syndrome and encephalomyelitis disseminata/multiple sclerosis show remarkable levels of similarity in phenomenology and neuroimmune characteristics. Morris and Maes BMC Medicine 2013 11:205   doi:10.1186/1741-7015-11-205.).
    Also Check for Basal Ganglia and Pre Frontal Cortex injury and for frontal and anterior left parietal lobe injury (Dr. Byron Hyde).

    Check for Basal Ganglia and Pre Frontal Cortex dysfunctions, inflammation and abnormalities. Also check for Dopamine deficiency and reduced dopaminergic drive.
    - Decreased basal ganglia activation in subjects with chronic fatigue syndrome: association with symptoms of fatigue. Miller AH, Jones JF, Drake DF, Tian H, Unger ER, Pagnoni G. PLoS One. 2014 May 23;9(5):e98156.
    - Fatigue in neurological disorders. Chaudhuri A, Behan PO. Lancet. 2004 Mar 20;363(9413):978-88.
    - Fatigue and basal ganglia. Chaudhuri A, Behan PO. J Neurol Sci. 2000 Oct 1;179(S 1-2):34-42.
    - Further Research results & listings
  • fMRI scans.
    • Caseras X, Mataix-Cols D, Rimes KA, Giampietro V, Brammer M, Zelaya F, et al. The neural correlates of fatigue: an exploratory imaginal fatigue provocation study in chronic fatigue syndrome. Psychol Med. 2008;38:941–51.

      Check for Basal Ganglia and Pre Frontal Cortex dysfunctions, inflammation and abnormalities. Also check for Dopamine deficiency and reduced dopaminergic drive.
      - Decreased basal ganglia activation in subjects with chronic fatigue syndrome: association with symptoms of fatigue. Miller AH, Jones JF, Drake DF, Tian H, Unger ER, Pagnoni G. PLoS One. 2014 May 23;9(5):e98156.
      - Fatigue in neurological disorders. Chaudhuri A, Behan PO. Lancet. 2004 Mar 20;363(9413):978-88.
      - Fatigue and basal ganglia. Chaudhuri A, Behan PO. J Neurol Sci. 2000 Oct 1;179(S 1-2):34-42.
      - Further Research results & listings
  • Choline abnormalities in the brain
    'Magnetic resonance spectroscopy identified increased levels of free choline in the brain, which is consistent with a response to an infection resulting in increased breakdown of cell membranes that would cause loss of function.'
    Myalgic encephalomyelitis: a review with emphasis on key findings in biomedical research. M Hooper. J Clin Pathol. 2007 May; 60(5): 466–471. doi: 10.1136/jcp.2006.042408
    Also check for increased levels of free choline in the brain, which is consistent with a response to an infection resulting in increased breakdown of cell membranes that would cause loss of function. Also Check for Basal Ganglia and Pre Frontal Cortex injury and for frontal and anterior left parietal lobe injury (Dr. Byron Hyde).
    Puri B K, Counsell S J, Zaman R. et al Relative increase in choline in the occipital cortex in chronic fatigue syndrome. Acta Psychiatr Scand 2002. 106224–226.226. [PubMed]
    Puri BK, Counsell SJ, Zaman R, Main J, Collins AG, Hajnal JV, Davey NJ: Relative increase in choline in the occipital cortex in chronic fatigue syndrome.Acta Psychiatr Scand 2002, 106:224-226.
    A. Chaudhuri, T. Majeed, T. Dinan and P. O. Behan, "Chronic Fatigue Syndrome: A Disorder of Central Cholinergic Transmission," Journal of Chronic Fatigue Syndrome, Vol. 3, 1997, pp. 3-16.
    Chaudhuri A, Condon B R, Gow J W. et al Proton magnetic resonance spectroscopy of basal ganglia in chronic fatigue syndrome. Brain Imaging Neuroreport 200314225–228.228 Chaudhuri A, Behan P O. In vivo magnetic resonance spectroscopy in chronic fatigue syndrome. Prostaglandins Leukot Essent Fat Acids 200471181–183.183 [PubMed]
  • Homocysteine levels
    Test Homocysteine levels. Homocysteine levels are abnormally high in most neurological illnesses and cardiac and vascular illnesses. This is a good measure of inflammation damage to the nervous system and vascular system.
  • Small Fibre Neuropathy (SFN)
    This has been found in ME / CFS and Fibromyalgia. It is believed to be the main contributing factor to severe pain in ME / CFS and Fibromyalgia patients. A neurologist can carry out tests for Small Fibre Neuropathy (SFN). Dr. Gupta advises that physicians carry out a skin biopsy.
  • Test for Erythrocyte sedimentation rate. The rate is usually very low or zero in ME patients. Canadian clinician Byron Hyde reported in the fall 1989 issue of his newsletter to sufferers, “To my knowledge, there are only five diseases that have a pathological low sedimentation level: myalgic encephalomyelitis (ME also called CFS), sickle-cell anemia, hereditary sperocytosis, hyper-gammaglobulinemia, hyper-fibrogenemia.”
  • CENTRAL NERVOUS SYSTEM
    "Because the effects of this illness are primarily due to AFFERENT tracked pathology, examination must be related to this. In poliomyelitis and other syndromes primarily affecting the efferent pathways, attention to reflexes, etc., is appropriate but in these cases a more detailed approach is necessary to define the adverse signs resulting from the AFFERENT track involvement. Thus the 12 cranial nerves need to be considered first as certain abnormal sensations relating to the cranial nerves are found in these patients. These include abnormal response to olfaction (1st), varying abnormal optic responses (2nd, 3rd, 4th and 6th), facial/motor and sensory responses are through the trigeminal (5th) and the facial (7th) nerves, auditory (8th), valtal (10th). Afferent and efferent responses will be found." Dr. John Richardson, Myalgic Encephalomyelitis/Chronic Fatigue Syndrome: Guidelines for Doctors
  • Test for mast cell dysfunctions and abnormalities. This is linked to inflammation, pain, and blood vessel abnormalities. Some research findings listed on this link - http://phoenixrising.me/archives/13083 and at this link http://mastcellmaster.com/research.php
    Test for:
    • Tryptase, histamine, heparin blood
    • Eosinophilia, basophilia, monocytosis activity
    • Serum chromagranin A
    • Serum and urinary leukotriene and prostaglandin isoforms
    • Urine methylhistamine after exercise
    • Also test for abnormal levels of neuropeptide Y as this directly affects mast cell functions
  • Test for levels of elastase in spinal fluids, nerve tissues, and blood
  • Test for mast cell activation in brain tissue and nerve tissue. This is a good marker for inflammation.
  • Romberg Test. Many ME patients have abnormal results on this test.
  • Activated Microglia
    This has been found in several studies. Test for activated Microglia in the brain and nervous system.
  • Depletion of vital neurotransmitters, hormones  & signalling systems
    Tests for depletion of the following:
    • Cortisol
    • DHEA
    • CRH
    • ACTH
    • GH
    • Oxytocin
    • Melatonin
    • Serotonin
    • Dopamine
    • T3
    • Acetylcholine
    • EPA
    • GABA

    Test for Excessive NMDA and Excessive Reverse T3

  • Dr. Byron Hyde one of the top ME doctors in the world recommends several neurological and brain tests for ME

    • Testable Brain Changes: This second phase becomes chronic and is characterized by various measurable and clinical dysfunctions of the cortical or cortical and subcortical brain. If the patient's illness is not persistently measurable using SPECT, PET or QEEG and / or Neuropsychologicalchanges then it is not M.E. These changes can be roughly characterized as to severity:
      • Type 1:where one side of the cortex is involved. These patients have the best chance of spontaneous recovery.
      • Type 2 where both sides of the cortex are involved: These patients have the least chance of spontaneous recovery.
      • Type 3: where both sides of the cortex, and either one or all of the posterior chamber organs, the Pons and Cerebellum,
        the subcortical and brain stem structures are involved. Type 3 are the most severely affected patients and the most likely to be progressive or see little or no improvement with time.
        Source: A Brief History of Myalgic Encephalomyelitis by Dr. Byron Hyde

    • Check for diffuse inflammatory injury of the capillaries at the level of the basement membrane of the brain.

    • Brain and Neurological Diagnostic Tests
  • Excerpt from The Complexities of Diagnosis By Dr. Byron Hyde, Chairman, Nightingale Research Foundation, Chapter 3 in
    Handbook of Chronic Fatigue Syndrome. Leonard A. Jason, Patricia A. Fennell, Renée R. Taylor
    ' Dr. John Richardson from Newcastle upon Tyne has followed ME patients in Durham and Northumberland counties of the United Kingdom for three to four generations. I am aware of no other physician in the world with such a historic view of ME patients. He has repeatedly demonstrated that many ME patients go on to develop structural heart injury. The injury is usually valvular or related to pericardial effusion, and although most settle down, some do not and may develop myopathy. So I started to look at the hearts of these patients.

    I have found that during the first year of acute onset ME/CFS disability, the incidence of pericardial effusion is unusually high. This seems to settle down with no apparent short-term problem, and after a year, the cases of pericardial fluid decrease considerably. However, the incidence of valvular disease in people in their 30s and 40s appears to be higher than in the normal population. When I find a significant valvular injury, I then repeat the echocardiogram yearly, and more frequently if the patient develops shortness of breath. I have observed several cases of elevated right heart pressure, significant septal defects, and increased myocardial wall thickening. Some who have had the injured valve replaced have miraculously returned to normal health. Are these incidental findings? I do not know, but Dr. Richardson has identified more than several hundred cardiopathies in his ME practice. I had two heart valve replacements in this group in the past year out of a total of 50 new patients.

    Carotid and Transcranial Doppler: Few physicians investigating ME/CFS employ the visual carotid and transcranial Doppler. This is a major error. It is a relatively inexpensive and totally safe procedure that does things no other type of test can do. On rare occasions, you will find aneurysms and subclavian steal anomaly with this test. Carotid atherosclerosis – sometimes substantial – is often found in patients with lipid dysfunction. This is a treatable condition and can be part of the cause of a CNS fatigue syndrome. You may say that any internist or cardiologist can pick up carotid pathology with a stethoscope, but few do who do not have an office Doppler. The carotid scan is also essential if you wish to do a transcranial Doppler. I examined a patient from the United States who had been diagnosed as having CFS in two major U.S. CFS clinics. She was given alternative medications and told to return in one year. She had complete obstruction of the vertebral basilar arteries and approximately 80% and 90% obstruction in either carotid. I was amazed that she was still alive. She was successfully operated on in Boston and her CFS has significantly improved.

    The transcranial Doppler is not a perfect test. Patients with small foramen magnum space are difficult to visualize. But it will demonstrate high level internal carotid and other arterial obstruction that is beyond the normal range of a stethoscope. Only rarely do I get the chance to investigate posttraumatic mitral valve area (MVA) patients who develop an acute fatigue syndrome where personality or intellectual change has given rise to the diagnosis of CFS. In two of the past four such patients, I have demonstrated small subcortical arterial blowouts that had been missed by neurologists and that were possibly the cause of their pathophysiology.
    In patients with ME/CFS, it is possible to demonstrate spasmodic disease of both major and smaller arteries with no typical evidence of migraine. This arterial pathology may be the end organ underlying cause of some ME patients' illness.

    Often MRls and MRAs miss such arterial physiological pathology. Why? The technology of the MRA consists of a receiving computer revolving around the brain that may only give a picture of the maximum arterial diameter. In other words, what you see on the MRA is not reality but one view of reality. With the transcranial Doppler, the operator actually watches and films the kinetic movement of the arteries within the brain and can measure the velocity of the blood flow. Not only can you see these arteries move; if they are in spasm, you can observe this as well. Like ME/CFS muscles, ME brains are sometimes in significant pathological spasm. This knowledge may lead to more effective treatments of ME/CFS disease. Arterial spasm may account for some, but not all, of the SPECT changes that are routinely seen in ME patients.
    I often find partial or complete vertebral or basilar artery obstruction. Frequently, I find left middle cerebral artery spasm or obstruction and, less frequently, frontal artery spasm in ME/CFS patients who do not report a migraine history. Left middle cerebral arterial field hypoperfusion is typical of
  • MRI / PET / SPET / CAT / MRS scans
    Check for evidence of damage to and inflammation in (a) upper spinal motor and sensory nerve roots and (b) the spinal nerve networks traversing the adjacent brain stem, and (c) the brain stem.
  • Infectious Venulitis affecting the brain and nervous system
    Dr. Erich Ryll who is a medical doctor and Professor of Medicine at the University of California, Davis, closely studied Infectious Venulitis since the 1970's and he found many similarities between this illness and ME and CFS. He also studied and examined cases in other countries and found similar results. He believes that a virus is responsible for systemic damage to the body and in particular the vascular system and veins.

Diagnostics - Inflammation of veins, including deep veins. Small haemorrhages around blood vessels in the cerebral cortex extending into the mid-brain, and other areas of the brain. Diffuse micro-haemorrhagic injury of the brain and this occurring around the small blood vessels. Diffuse inflammatory injury of the capillaries at the level of the basement membrane of the brain. Signs of slight vein breakages, minor haemmorhages in different body areas. Easy bruising. Some minor dy-myelination in the brain. Brain hypo-perfusion. Excess pro-inflammatory TH2 cytokines. Difficulty sleeping, unrefreshing sleep. Diffuse pain, headaches, dizziness, brain fog. Poor circulation and feeling cold.

The following articles provide information about this condition

.- Infectious Venulitis, Dr. Erich Ryll

- Simialrities between ME and Infectious Venulitis

- Numerous small haemorrhages around blood vessels in the cerebral cortex extending into the mid-brain (post-mortem of English ME patient Andrew Wallis in 1955)

- Vasculitis involving the skin was recorded during outbreaks in Cumberland, Durham and North West London in 1955. A maculopapular rash may appear during the return of features of the initial illness such as flu-like symptoms and enlargement of lymph glands and liver.
  • Doctors Jay Goldstein and Ismael Mena (USA), using Zenon SPECT brain scans, demonstrated that the physiological brain function of an M.E. patient rapidly deteriorates after exercise. They also demonstrated that this physiological dysfunction could persist for several days following any of several stressors.
  • Deep restorative sleep is vital in all neurological and immune system related illnesses. The following NIH funded research outlines the importance of sleep to many body systems. Sleep deprivation leads to toxin build up in the brain which may contribute to brain lesions and brain hypoperfusion.
  • Measure NMDA activity in the brain. This measures neuro-excitability in the brain. Also measure GABA activity in the brain.


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