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Brain & Heart Neurologic manifestations of IBD

polyneuropathy after undergoing fecal transplantation. and pathological evidence supports the notion that a
This finding supports the theory of a cross-reaction hypercoagulable state in IBD patients markedly increases
of pathogenic anti-gut antibodies with neural surface their risk of cerebrovascular complications such as strokes.
antigens and provides evidence regarding the process of Notably, deep vein thrombosis and pulmonary embolism
molecular mimicry. The gut-brain axis concept integrates remain prevalent, yet the incidence of cerebral venous
a diverse range of signals, including neural, endocrine, thrombosis (CVT) and ischemic arterial strokes suggests
nutrient, and immunological signals between the CNS these complications are likely underreported. CVT, in
and the GI system, emphasizing a bidirectional interaction particular, poses a severe threat, manifesting as fatal
with multiple mechanisms guiding each direction. Other extraintestinal complications of IBD with high morbidity
19
studies have shown clinical responses to immunotherapy and mortality rates. Symptoms such as persistent headaches,
in IBD patients with both axonal and demyelinating which appear in approximately 90% of CVT cases, along
polyneuropathy, highlighting the involvement of T cells in with increased intracranial pressure leading to neurological
the pathogenesis of demyelinating neuropathies, although deficits, highlight the acute dangers of this condition. 26,27
the role of the immune system in axonal damage remains In terms of diagnostic practices, MRI and venography
less clear despite being supported by clinical improvements are considered definitive for identifying CVT, by virtue of
observed with immunomodulatory therapies. their direct visualization of thrombi predominantly in the
28
In Brazil, 33 patients with IBD-related peripheral sagittal and transverse sinuses. The pro-coagulative activity
neuropathy, including 18 with CD and 15 with UC, associated with IBD is further complicated by an array of
were treated with immunomodulatory therapy. Various factors including impaired fibrinolysis, thrombocytosis,
agents such as intravenous immunoglobulin, prednisone, and endothelial dysfunction. Interestingly, while IBD is
fludarabine, cyclophosphamide, azathioprine, etanercept, associated with higher thromboembolism rates compared
and plasmapheresis have been used in the management of to other autoimmune disorders, genetic factors such as
20
peripheral neuropathy. It has been observed that among factor V Leiden and prothrombin mutations have not been
UC patients with peripheral neuropathy, 11% showed major conclusively linked to these thrombotic manifestations. 29,30
improvement, 56% moderate improvement, and 33% mild Moreover, the role of intestinal barrier dysfunction in
improvement. Discrepancies in clinical response across promoting a prothrombotic state has garnered attention.
studies may stem from the different immune processes This is illustrated by elevated levels of lipopolysaccharides
involved in neuropathy, which could be primarily related (LPS) and the activation of Toll-like receptors in IBD, which
to IBD, secondary to gut microbiota, or coincidental with correlate poorly with clinical disease activity but strongly
autoimmune polyneuropathy. CIDP cases have also been with intestinal permeability. Such findings offer insights
20
reported, but symptom development during CD treatment into the complex interplay between IBD pathophysiology
complicates determinations of whether the neuropathy is and thrombotic risk, emphasizing the need for heightened
primarily due to CD or a secondary iatrogenic complication. 21 vigilance and tailored therapeutic strategies in managing

Furthermore, improvement in the neurological these patients. 30,31
symptoms and abnormal electrophysiologic findings Both TLR2 and TLR4 are crucially expressed by
after surgical removal of the peri-appendiceal abscess platelets and endothelial cells, with their ligands initiating
has been reported, which is possibly attributed to the procoagulant activities within these cells. The interaction
immunomodulatory properties of the appendix. 22 between TLR2 and its ligands triggers thrombo-
inflammatory responses in platelets through mechanisms
3.2. Cerebrovascular diseases
involving phosphoinositide 3-kinase, cyclooxygenase, and
Extensive research has illuminated a discernible link the activation of purinergic receptors P2Y1 and P2Y12,
between IBD and prothrombotic state, with studies citing alongside the release of alpha-granules. Conversely, the
a prevalence of thrombosis ranging from 1% to 39% in binding of LPS to TLR4 enhances traditional agonist-
this patient population. 23,24 Specifically, the incidence of induced aggregation of platelets. 32,33
arterial and venous thrombosis is notably elevated in IBD Furthermore, the activation of nuclear factor-κB in
cases, as evidenced by both clinical studies and autopsy endothelial cells by TLR2 and TLR4 signaling plays a pivotal
findings. Schneiderman et al. have contributed to this role in the production of proinflammatory mediators,
26
25
understanding by identifying thrombus formations in which are instrumental in initiating the coagulation
cerebral small vessels during post-mortem examinations of cascade. This process is particularly significant in the
IBD patients who experienced cerebrovascular incidents. context of atherosclerosis, where activated macrophages
Further, a constellation of clinical, hematological, within plaques respond robustly to TLR stimulation,

Volume 2 Issue 4 (2024) 4 doi: 10.36922/bh.3486