Neuroimage in patients with Breast Implant Illness (BII), an explorative pilot fMRI-study

In 2018, over 1.8 million breast augmentations were performed worldwide. An
estimated 3 percent of the Dutch women between 20 and 70 years has breast
implants1. Some of these women report a pattern of systemic health complaints
with varying severity, such as myalgia, arthralgia, fever, fatigue, dry eyes
and mouth, as well as cognitive impairment2, 3. In 1994, Shoaib and Patten
described an adjuvant breast neurological disease in patients with silicone
breast implants with symptoms of a multiple sclerosis (MS)-like syndrome and/or
atypical motor neuron disease4, 5. It is characterized by a collection of
neurological symptoms and/or demyelination supposedly caused by silicone breast
implants6. In 2011, Shoenfeld et al. introduced ASIA syndrome: an Autoimmune
Syndrome Induced by Adjuvants, e.g. breast implants7. Many studies have
investigated the possible health effects of silicone breast implants, however,
a clear association between breast implants and systemic diseases or autoimmune
diseases remains uncertain8-10.
Colaris et al. described a Dutch cohort of ASIA-syndrome patients. Of these
women, 98 suffered from fatigue, 91 from arthralgia, 54 from myalgia, 73 from
sicca complaints and 20 from severe neurological manifestations. Interestingly,
54 patients underwent removal of their silicone implants, after which 50% of
the patients experienced improvement of complaints3.

The explanation of complaints in these patients is probably multi-factorial. In
addition to the symptoms that would have occurred in the same person even if no
implants were placed, immunogenetic factors, such as pre-existing allergies,
and environmental aspects, such as smoking, may play a role in the development
of SBI-induced health complaints, also referred to as breast implant illness
(BII)11, 12. Furthermore, there is a remarkable overlap with fibromyalgia and
it cannot be excluded that it concerns the same disease13-15.

For several decades, fibromyalgia has been recognized as a chronic, centrally
mediated, widespread, chronic pain syndrome that affects approximately 2*4% of
the population16 17, 18. Ceko et al. also reported that additional to chronic
pain, many patients with fibromyalgia complain of problems with memory and
concentration19. These cognitive difficulties associated with chronic pain are
especially so-called *fibro-fog* in fibromyalgia16, 20. Many fibromyalgia
patients experience the cognitive symptoms as more disabling than their chronic
pain21.

Previous (functional) MRI studies in chronic pain patients and fibromyalgia
patients demonstrated altered brain activity and even structural changes in
particular the pain matrix (thalamus, insular cortex, primary somatosensory
cortex, secondary somatosensory cortex, anterior cingulate cortex, prefrontal
cortex)22-24.

Functional magnetic resonance imaging (fMRI) provides an indirect measurement
of brain activity via the blood oxygen level-dependent (BOLD) response, which
is a measure of the amount of deoxygenated blood and blood volume in brain
regions involved in the response to a stimulus 26. Resting-state functional
magnetic resonance imaging (rs-fMRI) examines intrinsic connectivity of the
brain in the resting basal state. This technique detects change in terms of the
relative levels of oxyhemoglobin and deoxyhemoglobin due to activation of
neurons which causes a hemodynamic response27.

DTI (diffusion tensor imaging) is used to map white matter tracts as well as
imaging functionally localized brain regions to increase understanding of brain
networks and their connectivity. In FM patients, DTI shows decreases in FA
(fractional anisotropy) in thalamus and insula and increases in the postcentral
gyrus (S1) suggesting more and less effective information transfer,
respectively22.
Structural MRI is used for detailed information about gray and white matter.
Changes in gray matter volume are often seen in chronic pain/FM (abnormality in
PFC, insula, and ACC)22, 23, 25.
In fibromyalgia, connectivity between the insula to the default mode network
(DMN) is associated with spontaneous pain ( = PFC, ACC and posterior parietal
cortex)24.
In FM, increased activation of the insula correlated with pain intensity,
decreased activation of DLPFC correlated with poor coping during pain22, 25.

Shoaib and Patten reported 100 women with silicone breast implants from which
84 patients underwent a Magnetic resonance imaging (MRI) of the brain4.
Nineteen of these 84 women, of whom nine were clinically diagnosed with
multiple sclerosis-like syndrome or brains disease, showed multiple white
matter lesions and thirteen women showed multiple small ischemic lesions. At
present, it is unknown whether BII patients have altered fMRI scans as well.

The aim of this pilot study is to explore the structure and function of brain
regions associated with the pain matrix in Breast Implant Illness (BII). This
pilot study will be the foundation for grant application for future research.

This study will be an exploratory pilot functional MRI study to generate a
proof-of-evidence that substantiates an idea and increases the likelihood of
further grant funding for follow-up research. Therefore, we want to examine 24
women diagnosed with Breast Implant Illness, of which 12 women with breast
implants (group 1) and 12 women who already had their implant removed (group
2), and a group of 12 healthy controles with silicone breast implants (group 3)
by means of a functional MRI scan with the same protocol, to investigate
functional or structural differences between the groups.

No major or minor risks are known to be associated with this study. Subjects
can experience the MRI scan as uncomfortable. The scan will take about 45
minutes. Furthermore patients are being asked several questions and an MMSE is
conducted. This is no difficult test.