Neurological autoimmune disorders with prominent gastrointestinal manifestations: A review of presentation, evaluation, and treatment

Abstract

Background The identification of autoantibodies directed against neuronal antigens has led to the recognition of a wide spectrum of neurological autoimmune disorders (NAD). With timely recognition and treatment, many patients with NAD see rapid improvement. Symptoms associated with NAD can be diverse and are determined by the regions of the nervous system affected. In addition to neurological symptoms, a number of these disorders present with prominent gastrointestinal (GI) manifestations such as nausea, diarrhea, weight loss, and gastroparesis prompting an initial evaluation by gastroenterologists. Purpose This review provides a general overview of autoantibodies within the nervous system, focusing on three scenarios in which nervous system autoimmunity may initially present with gut symptoms. A general approach to evaluation and treatment, including antibody testing, will be reviewed.

Autoimmune encephalitis and gastrointestinal dysmotility: achalasia, gastroparesis, and slow transit constipation

“…The antibody-triggered autoimmune inflammation may disturb all levels of the gut-brain axis including brain, spinal cord, peripheral, and, particularly, the enteric nervous system. This has been shown by immunohistochemical staining of neurons and glia cells within the enteric nervous system of the gut [2,[10][11][12]. Furthermore, a direct excitatory action of ANNA-1, in particular anti-HuD IgGs on human and guinea pig enteric neurons as well as on mouse visceral afferents, which involves nicotinic and P2X receptors, could be demonstrated recently [10].…”

“…Group II antibodies (N-methyl D-aspartate receptor, voltage-gated potassium channel, voltage-gated calcium channel, gamma-aminobutyric acid receptor, alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor) target cell surface neuronal antigens, are less likely to be associated with an underlying malignancy, and use more "restricted" humoral immune mechanisms of neurotoxicity that typically respond better to early immunomodulatory therapy [3][4][5][6]. In addition, typical NAD with gastrointestinal manifestation include the area postrema syndrome in neuromyelitis optica, the dipeptidyl-peptidase-like protein 6-associated encephalitis, and the autoimmune autonomic and enteric neuropathies [2,4,7]. Among these AA, ANNA-1 targeting intracellular neuronal antigens as part of the immune response is most frequently seen in paraneoplastic syndromes [3][4][5][6].…”

“…Because of the complexity of neural gastrointestinal regulation, neurological autoimmunity may present with symptoms that do not necessarily point to the disturbed level within the gut-brain axis. For example, antibodies targeting chemoreceptors (such as the area postrema) or enteric neurons may result in severe vomiting, early satiety, dysphagia, or diarrhea [2]. The autoantibodies (AA) in autoimmune encephalitis affect not only CNS structures but also gastrointestinal functions [3][4][5][6][7].…”

DPPX autoimmune encephalitis: A short report on two patients presenting with classic features of this rare but treatable disease

“…Both patients initially had prominent GI symptoms and weight loss which are well-described clinical features of the disease and often precede the neurologic symptoms by months (Boronat et al, 2013;Hara et al, 2017). GI symptoms have been attributed to the widespread expression of Kv4.2 channels in the myenteric plexus (Blackburn et al, 2019). Dysautonomia resulting from antibody mediated dysfunction of the GI autonomic nervous fibers also likely contributes to dysmotility.…”

Gastrointestinal motility disorders in neurologic disease

“…There are circulating IgG antibodies (e.g., ANNA-1 or anti-Hu) directed against enteric neuronal nuclei, suggesting that the enteric plexus is the major target of this paraneoplastic phenomenon (123,124). Other autoantibodies (anti-CRMP-5 [also known as anti-CV-2] and anti-ganglionic acetylcholine receptor) (125) associated with lung cancer or thymoma result in gastroparesis or constipation. Several patients have shown evidence of a more extensive neuropathologic process (126).…”