Acquired intestinal aganglionosis and circulating autoantibodies without neoplasia or other neural involvement
Abstract
The clinical course, diagnosis, and treatment of 2 patients with acquired intestinal aganglionosis without other neurological involvement or neoplasia are described. They initially presented with constipation and abdominal pain in late childhood. They were found to have enteric ganglionitis with a loss of neurons together with vacuolated nerve cells surrounded by CD3- and CD4-positive T lymphocytes. This process initially affected only the colon but later the entire gastrointestinal tract was involved in 1 patient. Associated with this process there were circulating immunoglobulin G class enteric neuronal antibodies in high titer (1:5000-8000). The staining of central nervous system neuronal nuclei and Western blotting indicated the presence of antineuronal nuclear protein antibodies of the ANNA-1 (anti-Hu) type usually associated with paraneoplastic sensory neuropathy. However, the reaction pattern in enteric neurons was quite different with strong reaction to perikarya and only weak staining of nuclear antigens. (Gastroenterology 1997 Apr;112(4):1366-71)
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Long lasting trigeminal neuropathy, limbic encephalitis and abdominal ganglionitis without primary cancer: An atypical case of Hu-antibody syndrome
2020, Clinical Neurology and NeurosurgeryAnti-Hu antibodies (Hu-Abs) are the most frequent onconeural antibodies associated with paraneoplastic neurologic syndromes (PNS). PNS include a variety of neurological syndromes, affecting less than 1/10,000 patients with cancer. In the majority of cases, PNS will manifest before the malignancy is diagnosed. We found a case in which PNS was diagnosed without finding a primary malignancy after extensive work-up and even post-mortem autopsy.
We present a case report of a 58-year-old man. This article includes extensive clinical work-up, full-body autopsy and brain autopsy with classical histochemical and myelin stainings and immunohistochemistry was performed.
The patient developed a progressive trigeminal neuropathy over a period of 5 years, in combination with cerebellar degeneration, asymmetrical brainstem and limbic encephalitis. Serum showed repeatedly high anti-Hu antibodies. Comprehensive cancer screening could not demonstrate any primary malignancy. Therapy with corticosteroids, plasma exchange, cyclophosphamide and rituximab showed no beneficial effect. He died from the complications of enteric ganglionitis 5 years after onset of the first symptoms. A postmortem autopsy could not detect a primary malignancy either. Brain morphology is described in detail.
Paraneoplastic anti-Hu encephalitis cases associated with SCLC or other primary neoplasms are well known. An adult with a progressive multifocal neurological syndrome in the presence of positive anti-Hu antibodies, but without any primary neoplasm after a follow-up over 5 years is unusual.
Idiopathic gastroparesis
2020, Gastroparesis: Pathophysiology, Clinical Presentation, Diagnosis and TreatmentIdiopathic gastroparesis (IG) is a motility disorder characterized by delayed gastric emptying without a detectable primary underlying etiology and manifesting as postprandial fullness, early satiety, fullness, nausea, vomiting, and abdominal pain. IG is the most common etiology of gastroparesis accounting for as many as 60% of cases. However, figures suggesting an increasing incidence, prevalence, and hospitalization rates for IG may need to be balanced by some confusion with the entity of cyclic vomiting syndrome and hyperemesis cannabis. Several studies from the NIH-funded Gastroparesis Clinical Research Consortium (GpCRC) concluded that IG primarily affects women (up to 88%), 46% are overweight, 50% have acute onset of symptoms, 19% have a documented infectious prodrome, and the average age of onset is 41 years.IG is associated with significant morbidity, particularly related to abdominal pain. In addition, symptomatology can overlap with other diagnoses that may inaccurately be labeled as IG. Long term follow up suggests that many IG patients may eventually normalize their gastric emptying and also experience symptom improvement. This chapter will provide updates on the current understanding of IG as well as review the clinical characteristics and diagnostic requirements required to be labeled as “idiopathic gastroparesis.”
Gastrointestinal Pathology
2020, Pediatric Gastrointestinal and Liver Disease, Sixth EditionInterpretation of endoscopic gastrointestinal biopsy specimens requires adequate clinical information including medication history and illnesses that may have associated gastrointestinal findings. The clinical history can guide additional studies in addition to the standard hematoxylin and eosin staining. Precise identification of the biopsy site enables the most accurate and definitive diagnosis. The endoscopist should attempt to obtain the largest possible piece of tissue. Multiple biopsies for each site often provide the best information. If special studies such as culture for microorganisms, electron microscopy, or flow cytometry are required, communication with the laboratory before biopsy is recommended. Standard histopathologic evaluation is best performed on tissue immediately placed in fixative. The resulting “final diagnosis” may require re-review if additional clinical findings are obtained.
Oesophageal motor function in chronic intestinal idiopathic pseudo-obstruction: A study with high-resolution manometry
2018, Digestive and Liver DiseaseChronic intestinal idiopathic pseudo-obstruction (idiopathic CIPO) is a rare heterogeneous condition for which the different phenotypes are difficult to be established. Oesophageal motility has shown to be impaired in patients with idiopathic CIPO at traditional manometry, whereas no studies have assessed it by high resolution manometry (HRM).
To evaluate oesophageal motility by HRM in patients with idiopathic CIPO.
14 patients with idiopathic CIPO underwent oesophageal HRM. Multiple rapid swallows (MRS) were performed in order to evaluate contraction reserve. The Chicago Classification 3.0 was used to classify the oesophageal motility disorders.
One idiopathic CIPO patient had type-II achalasia, one aperistalsis and 12 had minor disorder of peristalsis (11 ineffective oesophageal motility and one fragmented peristalsis). These minor disorders were not significantly different from those of 50 other consecutive patients who underwent HRM for dysphagia or GERD and received the diagnosis of ineffective oesophageal motility. Three of the 12 idiopathic CIPO patients with minor disorder of peristalsis had no contraction reserve after MRS.
HRM is able to identify different grades of oesophageal motor impairment in patients with idiopathic CIPO. Presence of major oesophageal dismotility or absent contraction reserve suggest a more severe and widespread motor disorder.
Neuropathophysiology of the Irritable Bowel Syndrome
2018, Physiology of the Gastrointestinal Tract, Sixth EditionThe irritable bowel syndrome (IBS) may well reflect a neurological problem emerging from disordered neurophysiology in the enteric nervous system (ENS), the central nervous system (CNS), or in both simultaneously. A normally functioning ENS is essential for a symptom-free gut: the gut does not work at all when the ENS is absent (e.g., Hirschsprung’s disease). This chapter deals mainly with enteric neuroimmune pathophysiology to the exclusion of multiple other explanations, hypotheses and theories, such as small intestinal bacterial overgrowth, gas generating foods, fructose malabsorption, maladjustment to life circumstances, among others that speak to IBS.
Concepts for the neuropathophysiology of the hallmark symptoms of IBS, which include abdominal pain, defecation urgency, bloating, and alterations in stool consistency, emerge in this chapter. Emphasis is focused on gaining acquaintance with the neurophysiology of visceral pain, ENS control of intestinal motility, and ENS control of mucosal secretion as a requirement for productive basic and translational interpretation of the hallmark symptoms.
Mastocytotic enteritis is explored as a biomarker in the context of the diarrhea-predominant form of IBS. This involves release by enteric mast cells of multiple inflammatory mediators that act in paracrine signaling manner at receptors expressed by ENS neurons and intramural sensory afferent terminals. Afferent sensitization amplifies nociceptive input to the CNS and becomes a factor in IBS-related pain.
Enteric mast cells use immunological memory to detect specific foreign antigens as they appear and reappear inside the gut lumen throughout the lifetime of an individual. Paracrine signaling relays the information on foreign antigen identity to the ENS. Paracrine signals, coming from mast cells, are interpreted in turn by the ENS as a labeled code for the presence of an antigenic threat in the intestinal lumen. The ENS interprets the signal as a potential threat to homeostatic integrity and “calls up,” from its program library, secretory and propulsive motor behavior organized for rapid and effectively expulsion of the menace. Commonalty of symptoms between postinfectious IBS and acute psychogenic stress in IBS are likely reflections of neuroimmune communication that includes degranulation of enteric mast cells.
Autoimmune-related enteric neuropathy underlies symptoms in disorders that include lower esophageal sphincter achalasia, intestinal pseudoobstruction, small-cell carcinoma in the lungs, and IBS. Functional symptoms in a subset of IBS patients reflect enteric neuronal damage or ablation related to circulating antienteric autoimmune antibodies.
Chronic intestinal pseudo-obstruction as an expression of inflammatory enteric neuropathy
2014, GE Portuguese Journal of GastroenterologyChronic intestinal pseudo-obstruction (CIPO) is characterised by inadequate digestive tract motility and can lead to severely disordered motility. CIPO manifests as recurrent episodes of intestinal sub-occlusion without an anatomical obstruction. We present the case of a 41-year-old female, with severe chronic constipation and several episodes of intestinal sub-occlusion. Investigation revealed colonic inertia and marked distension of the small bowel and colon with no evidence of stenosis or obstructive lesions, compatible with CIPO. After several treatments were tried (domperidone, erythromycin, cisapride, octreotide, total enteral nutrition), with partial or no response, further work-up was done trying to identify an etiology. Gastrointestinal manometry showed neuropathic type abnormalities, transmural biopsy of the jejunum revealed degenerative enteric neuropathy and anti-HU antineuronal antibody screen was positive, suggesting an autoimmune type neuropathy with diffuse involvement of the digestive tract. Corticosteroids showed partial improvement of short duration and azathioprine was also tried but discontinued due to intolerance. Marked dietary intolerance and malnutrition lead to total parenteral nutrition (TPN) at home since October 2011. Since then, symptoms and nutritional status improved, with rare episodes of pseudo-obstruction, not requiring hospitalisation.
Pseudo-obstrução intestinal crónica (POIC) caracteriza-se por motilidade inadequada do tubo digestivo, frequentemente com dismotilidade severa. Manifesta-se por episódios recorrentes de suboclusão intestinal, sem obstrução anatómica. Apresentamos o caso de uma mulher de 41 anos, com obstipação crónica severa e episódios de suboclusão intestinal. A investigação inicial revelou inércia cólica e distensão marcada do intestino delgado e cólon, sem lesões obstrutivas, compatível com POIC. Após diversas terapêuticas (domperidona, eritromicina, cisapride, octreótido, nutrição entérica total),com eficácia parcial ou nula, progrediu-se na investigação tentando esclarecer a etiologia. A manometria gastrointestinal revelou alterações neuropáticas e uma biopsia transmural jejunal demonstrou alterações degenerativas entéricas. Estes achados, associados á presença de anticorpos antineuronais anti-HU, sugeriam uma neuropatia entérica autoimune atingindo difusamente o tubo digestivo. Com corticoterapia obteve-se melhoria parcial e de curta duração e azatioprina foi tentada mas com intolerância a obrigar á sua descontinuação. Devido ao desenvolvimento de intolerância alimentar marcada, associada a desnutrição, a doente está sob nutrição parentérica total domiciliária desde 10/2011, com melhoria significativa dos sintomas e estado nutricional, raros episódios de pseudo-obstrução, sem necessidade de internamentos.