Book Review: I-Cubed and <i>The Autoimmune Brain</i>, A Five-Step Plan

Abstract

The Autoimmune Brain 1 explains I-Cubed, a shorthand for post-infectious autoimmunity that results from the multiplier effect of infection, immunity and inflammation, when protective immunity becomes the source of autoimmunity, conditioned by applicable environmental and genetic predisposing factors. In keeping with the post-infectious autoimmune nature of I-Cubed, neurologic and psychiatric symptoms evolve beyond a standard of care course of antibiotic therapy. Extensive serologic, electrophysiological and neuroradiographic diagnostic testing provides clues to areas of central, peripheral and autonomic nervous system, and systemic involvement that guide therapy. A multimodality therapeutic approach employing immune modulatory (Ig) therapy that addresses the underlying mechanisms and not just the symptoms of Cubed disorders is most effective. Representative cases of post-infectious autoimmunity associated with Lyme disease and PANDAS are presented.

Post-Acute Sequelae of SARS-Cov-2 Infection Associating Peripheral, Autonomic and Central Nervous System Disturbances: Case Report and Review of the Literature

“…The mechanism of post-infectious immunity, which appears likely in the present patients may be described by the acronym, I-Cubed (I 3 ) that posits the multiplier effect of infection, immunity, and inflammation, which when conditioned by environmental and genetic predisposing factors, can be the source of nervous system autoimmunity [12]. It is unlikely that the designations, Covid Long Hauler and Long Covid [13] are inclusive enough to describe this disorder, however, given the magnitude of those affected, and their congregation and self-selection among mounting Facebook Groups (https://www.facebook.com/groups/359321171725541), they may be useful cohorts for future studies (https://www.davidsyounger.com).…”

Post-acute sequelae of SARS-CoV-2 infection (PASC): peripheral, autonomic, and central nervous system features in a child

“…PASC can be described by the acronym, I-Cubed (I 3 ) that posits a multiplier effect of infection, immunity, and inflammation; which conditioned by environmental and genetic predisposing factors, may be the source of host autoimmunity [ 30 ]. The underlying basis of PASC, especially in the CNS, may not be fully appreciated until controlled clinical and autopsy cohort studies are performed.…”

Preliminary Guidelines for the Use of IVIg during COVID-19

“…veloped in a patient convalescing from COVID-19 illness prompting treatment with IVIg. A mechanism of post-infectious immunity, which appeared likely in this patient and in other LHs, is best described by the acronym, I-Cubed (I 3 ), that posits the multiplier effect of infection, immunity, and inflammation, conditioned by environmental and genetic predisposing factors, as the source of nervous system autoimmunity[27]. While awaiting the results of large-scale cohort studies from the NIH, IVIg is first-line recommended treatment for adults and children with PASC.The MIS-C and COVID-19-Related Hyperinflammation Task Force of the American College of Rheumatology studying MIS-C[28] has addressed treatment of children with COVID-19 related hyperinflammation and MIS-C. MIS-C is a disorder that resembles Kawasaki Disease (KD) both of which have a potentially fatal outcome due to cardiac and nervous system damage related to systemic vasculitis if not treated promptly with IVIg therapy.…”