In the 1990s, French clinicians and researchers began noticing and reporting on a mysterious inflammatory muscle disorder with a distinctive pathological pattern that later earned the name “macrophagic myofasciitis” or MMF.¹ Myofasciitis refers to inflammation of muscles and their connective tissue (fascia). 

Initially, the cause and features of MMF were unknown. Subsequent research by French investigators elucidated that the deltoid muscle lesions characteristic of MMF were secondary to intramuscular injection with vaccines containing aluminum hydroxide adjuvants.² The lesions revealed both an ongoing local immune reaction along with long-term persistence of aluminum hydroxide at the injection site.²

An ongoing series of admirably methodical studies also have confirmed a number of other post-vaccination clinical symptoms associated with MMF.³ These disabling health problems include not just muscle pain but joint pain, chronic fatigue, autonomic nervous system dysfunction, autoimmunity, and cognitive dysfunction.⁴ The cognitive deficiencies experienced by MMF patients mirror the cognitive impairments that have been observed to result from chronic exposure to aluminum particles.⁵ Together, all of these dysfunctions are “paradigmatic” of an emerging aluminum-adjuvant-related syndrome that has come to be known as ASIA (autoimmune/inflammatory syndrome induced by adjuvants).⁶

 MMF brain abnormalities visualized

Experimental evidence indicates that injected aluminum particles can “translocate” into brain tissue.⁷ A new MMF study reports on the brain metabolic abnormalities that result from this translocation, describing both the extent and location of the irregularities.⁵ Led by a research team at Paris-Est Créteil University (the largest multidisciplinary university in the Paris region), the study retrospectively assessed 100 consecutive MMF patients with varying degrees of neuropsychological alteration. The study site formerly had obtained brain images from all 100 patients (2012–2015) using a noninvasive three-dimensional imaging technology called 18-fluoro-deooxyglucose positron emission tomography/computed tomography (FDG-PET/CT). The patients also previously had undergone a series of neuropsychological tests assessing executive functions (working memory, flexibility, inhibition, and planning); attention; visual and verbal memory; total and delayed recall; and interhemispheric connection.

The researchers used the test results to delineate four distinct subgroups of MMF patients:

Individuals were considered to have no significant cognitive dysfunction (42%) if all of their tests remained below the pathological threshold.

1. Patients were designated as having frontal subcortical (FSC) dysfunction (29%) if their executive function tests produced pathological results.
2. Patients with papezian dysfunction (22%) were the same as subgroup #2 and also had pathological test results for the episodic memory and total and delayed recall tests.
3. The small subgroup of individuals with callosal disconnection (7%) were the same as subgroups #2 and #3, but with additional pathological results for interhemispheric connection (assessed via dichotic listening).

Next, the researchers examined cerebral glucose metabolism patterns in each MMF subgroup and compared them to brain images from 44 healthy controls with normal brain scans. Disruptions in brain glucose metabolism make it difficult for neurons to function efficiently, and this is linked to numerous neuropsychiatric disorders.⁸ The research team used a statistical technique called analysis of covariance (ANCOVA) that tests the significance of differences among group means. ANCOVA improves statistical precision by adjusting for factors such as (in this instance) age and gender.

The study’s results, expressed in terms of voxels (short for volume elements, the three-dimensional equivalent of pixels) were unambiguous for subgroups 1 through 3. (The small size [n=7] of the “callosal disconnection” subgroup precluded meaningful statistical testing.)

Patients in subgroup 2 (FSC dysfunction) exhibited the most severe (hypometabolic) brain abnormalities (35,223 voxels).

• Patients in subgroup 3 (papezian dysfunction) also showed significant abnormalities (13,680 voxels).
• Interestingly, even subgroup 1 (the group without discernable cognitive impairment) showed low brain metabolism (5,453 voxels), displaying a “less intense” but abnormal spatial pattern “that could represent a presymptomatic state.”

These observed patterns of hypometabolism, as depicted in the article’s visually stunning figures, involved multiple brain regions corresponding to specific neuropsychological impairments, including the occipital cortex (visuospatial impairment), the cerebellum (motor and executive functions), and the limbic system (long-term memory storage).

 Magnified threat from nanoparticles

A second just-released study (involving two of the same lead investigators as the first study) zeros in on the “insidious” nature of the nano-sized aluminum oxyhydroxide particles contained in Alhydrogel^®, the immuno-potentiating adjuvant added to over half a dozen widely used vaccines.⁴ Sharing a similar focus on MMF and ASIA, the researchers affirm the particles’ “striking biopersistence” and ability to migrate to and remain in the brain.

To assess the potential for a dose-response relationship between Alhydrogel^® and neurotoxicity, the researchers evaluated brain function and long-term aluminum concentration six months after administering three spaced injections of the adjuvant (either 200, 400, or 800 micrograms per kilogram of body weight) to three different subgroups of adult female mice.⁴ The three dosage levels represented the “mouse equivalent” of two, four, and eight human doses of aluminum-containing vaccine. At 180 days post-injection, the researchers subjected the three experimental groups of mice (as well as a fourth control group) to a battery of tests focused on behavioral and/or physical measures such as locomotor activity and coordination, muscular strength, anxiety level, and pain sensitivity.

The eight tests identified a number of significant effects of exposure to the aluminum adjuvant, including decreased locomotor activity levels, aversion to open spaces, microglial activation, and significantly increased cerebral levels of aluminum—but these effects appeared solely in the mice who had received the lowest dose of adjuvant. Conversely, the mice injected with the two higher doses showed “neither neurobehavioral changes nor microglial reaction.” The authors offer an intriguing explanation for this non-linear dose-response curve (a pattern that is not unprecedented in the field of aluminum toxicology), proposing a model of “particle toxicology” whereby particle size plays a pivotal role in cellular uptake and distribution of aluminum in the body. Specifically, the study’s results suggest that “the injected suspensions corresponding to the lowest dose, but not to the highest doses, exclusively contained small agglomerates in the bacteria-size range known to favor capture and…transportation” by innate immune cells.⁴

 More than skin deep

Taken together, the two studies underscore the urgent need to reevaluate aluminum adjuvant safety, despite assurances by the World Health Organization (WHO)’s Global Advisory Committee on Vaccine Safety that “there is no reason to conclude that a health risk exists as a result of administration of aluminium-containing vaccines.”⁹ In fact, while WHO concedes that MMF is “a lesion containing aluminium salts, identified by histopathological examination, [and] found at the site of previous vaccination with an aluminium-containing vaccine,” it continues to deny any possibility of clinical illness resulting from injection of toxic aluminum compounds.⁹ Instead, WHO benevolently likens MMF lesions to “a residual ‘tattoo’”⁹ on its MMF webpage (which has not been updated for nearly ten years). This lax attitude suggests that WHO’s close and increasingly controversial ties to the pharmaceutical industry¹⁰ have created a captured agency incapable of seizing on the implications of these two excellent studies.

 REFERENCES

1. Gherardi RK, Coquet M, Chérin P, Authier F-J, Laforêt P, Bélec L, et al. Macrophagic myofasciitis: an emerging entity. The Lancet. 1998;352(9125):347-352.
2. Gherardi RK, Coquet M, Chérin P, Bélec L, Moretto P, Dreyfus PA, et al. Macrophagic myofasciitis lesions assess long-term persistence of vaccine-derived aluminium hydroxide in muscle. 2001;124(Pt 9):1821-1831.
3. Passeri E, Villa C, Couette M, Itti E, Brugieres P, Cesaro P, et al. Long-term follow-up of cognitive dysfunction in patients with aluminum hydroxide-induced macrophagic myofasciitis (MMF). Journal of Inorganic Biochemistry. 2011;105(11):1457-1463.
4. Crépeaux G, Eidi H, David MO, Baba-Amer Y, Tzavara E, Giros B, et al. Non-linear dose-response of aluminium hydroxide adjuvant particles: selective low dose neurotoxicity. 2017;375:48-57.
5. Van Der Gucht A, Sebaiti MA, Guedj E, Aouizerate J, Yara S, Gherardi R, et al. Brain FDG-PET metabolic abnormalities in patients with long-lasting macrophagic myofasciitis. Journal of Nuclear Medicine. 2017;58(3):492-498.
6. Gherardi RK, Authier F-J. Macrophagic myofasciitis: characterization and pathophysiology. 2012;21(2):184-19.
7. Khan Z, Combadiere C, Authier F-J, Itier V, Lux F, Exley C, et al. Slow CCL2-dependent translocation of biopersistent particles from muscle to brain. BMC Medicine. 2013;11:99.
8. Kaidanovich-Beilin O, Cha DS, McIntyre RS. Metabolism and the brain. The Scientist, December 1, 2012. http://www.the-scientist.com/?articles.view/articleNo/33338/title/Metabolism-and-the-Brain/.
9. World Health Organization (WHO). Questions and answers about macrophagic myofasciitis (MMF). Last updated October 23, 2008. http://www.who.int/vaccine_safety/committee/topics/aluminium/questions/en/.
10. Neale T and Medpage Today. World Health Organization scientists linked to swine flu vaccine makers. ABC News, June 5, 2010. http://abcnews.go.com/Health/SwineFlu/swine-flu-pandemic-world-health-organization-scientists-linked/story?id=10829940.