Parkinson's disease is associated with low striated esophagus contractility potentially contributing to the development of dysphagia.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder, and more than 80% of PD patients will develop oropharyngeal dysphagia. Despite its striated histology, proximity to airway, and potential negative impact of its dysfunction on bolus transport and airway safety, the contractile function of the striated esophagus in PD patients has not been systematically studied. METHODS: Using our repository of clinical manometry and the Milwaukee ManoBank, we analyzed high-resolution manometry (HRM) studies of 20 PD patients, mean age 69.1 (range 38-87 years); 30 non-PD patients with dysphagia, mean age 64.0 (44-86 years); and 32 healthy volunteers, mean age 65.3 (39-86 years). Patients with abnormal findings based on Chicago Classification 4.0 were identified. Repeat analysis was performed in 20% of the manometric tracings by a different investigator with inter-rater concordance between 0.91 and 0.99. KEY RESULTS: The striated esophageal contractile integral in PD patients was significantly lower than that in non-PD dysphagic patients and healthy controls (p = 0.03 and <0.01, respectively). This significant difference persisted after excluding patients with concurrent Chicago Classification motility disorders (p = 0.02 and 0.01, respectively). In both analyses, the distal esophageal contractile integral did not show any significant difference between groups (p = 0.58 and 0.93, respectively). CONCLUSIONS & INFERENCES: PD is associated with a significant decrease in striated esophagus contractility compared to non-PD and healthy controls. This finding may play a pathophysiologic role in development of dysphagia in this patient population.

Prevalence of Undiagnosed Acute Hepatic Porphyria in Cyclic Vomiting Syndrome and Overlap in Clinical Symptoms.

BACKGROUND AND AIMS: Acute hepatic porphyria (AHP) presents with nausea and vomiting and can mimic cyclic vomiting syndrome (CVS). The prevalence of AHP in CVS and overlap in clinical symptomatology is not known. We thus sought to determine the prevalence of pathogenic variants for AHP and characterize symptom overlap between CVS and AHP. METHODS: We conducted a cross-sectional study of 234 CVS patients using Rome criteria. Patients were eligible for AHP genetic testing if they had recurrent episodes of severe, diffuse abdominal pain with ≥ 2 of the following-peripheral nervous system (muscle weakness/aching, numbness, tingling), central nervous system (confusion, anxiety, seizures, hallucinations), autonomic nervous system (hyponatremia, tachycardia, hypertension, constipation) symptoms, red/brownish urine, or blistering skin lesions on sun-exposed areas. A family history of AHP or elevated urinary porphobilinogen (PBG)/aminolaevulinic acid (ALA) were also criteria for genetic testing and was performed using a 4-gene panel. RESULTS: Mean age was 38.7 ± 14.5 years, 180 (76.9%) were female and 200 (85.5%) were Caucasian. During a CVS attack, 173 (92%) reported abdominal pain, 166 (87.2%) had peripheral nervous system, 164 (86.8%) had central nervous system and 173 (92) % had autonomic symptoms. Ninety-one eligible patients completed genetic testing. None were positive for AHP but two had variants of uncertain significance (VUS) in the HMBS gene. CONCLUSIONS: There is a high prevalence of non-gastrointestinal symptoms in CVS, like AHP, which is important for clinicians to recognize. AHP was not detected in this study and larger studies are warranted to ascertain its prevalence.

Differences in fatigability of muscles involved in fecal continence: Potential clinical ramifications.

INTRODUCTION: Fatigue of the anal sphincter complex has been demonstrated using high-resolution anorectal manometry (HRAM). However, the fatigability of individual muscles such as the external anal sphincter (EAS) and puborectalis muscles (PRM) has not been described. Vaginal manometry has been used to study contractile activity of the PRM. By applying both modalities, we attempted to differentiate the fatigability between the PRM and the EAS under different exercise conditions. METHODS: We studied two groups: group 1, 12 healthy women (21 ± 2.7 years) with HRAM and group 2, 10 healthy (20 ± 3 years) women with vaginal manometry. All subjects performed 40 repetitive contractions with and without an intra-anal resistive load. In group 1, areas under the curve (AUC) of the anal canal high-pressure zone (HPZ) including the caudal and rostral halves were compared. In group 2, the maximum and mean pressures of the vaginal HPZ were compared. RESULTS: The AUC decreased significantly only after repetitive contractions against a resistive load (462 ± 129 vs. 390 ± 131 mmHg-cm, p = 0.02), indicating fatigue. The caudal half (EAS) decreased significantly after contractions against a load (288 ± 75 vs. 239 ± 82 mmHg-cm, p = 0.02), while the rostral half (PRM) did not. The vaginal pressures (PRM) also decreased only after repetitive contractions against a load (maximum pressures, 358 ± 171 vs. 239 ± 109 mmHg, p = 0.02). CONCLUSIONS: The EAS and PRM both exhibit fatigue with contractions only against a resistive load. These findings may guide the development of appropriate exercise regimens to target specific muscles involved in fecal continence.

Acute Pancreatitis Masquerading as Inferior Wall Myocardial Infarction: A Review.

A rare presentation of acute pancreatitis is with electrocardiographic (ECG) changes that mimic myocardial ischemia. We present a report of a patient that presented with hemodynamic instability and new ECG changes of ST segment elevations in contiguous leads II, III, and aVF mimicking an inferior wall myocardial infarction. Emergent coronary angiography showed no significant coronary obstruction, but it was followed by a left-sided hemiplegia with radiographic evidence of diffuse embolic stroke. The patient was later found to have an underlying diagnosis of pancreatitis. Additional history that later became available indicated a history of severe acute pancreatitis treated elsewhere a few months prior to the current admission. We present the first comprehensive review of the literature comprising 36 total cases with pancreatitis masquerading as acute myocardial infarction, with inferior wall STEMI pattern being the most frequent. We present this case to highlight the diagnostic dilemma posed by this masquerade of a high acuity myocardial infarction and to highlight alternative diagnoses to be considered in such clinical circumstances.

Migraine, Cyclic Vomiting Syndrome, and Other Gastrointestinal Disorders.

PURPOSE OF REVIEW: Cyclic vomiting syndrome (CVS) is a chronic functional gastrointestinal disorder characterized by episodic nausea and vomiting and is diagnosed using Rome IV criteria. CVS is being recognized more frequently in adults with a prevalence of 2%. It is associated with several functional disorders like autonomic dysfunction, anxiety, and depression, but the strongest association is with migraine. We will elucidate the close relationship between migraine and CVS and briefly discuss its association with other gastrointestinal disorders. RECENT FINDINGS: We highlight similarities in pathophysiology, clinical presentation, and response to medications between CVS and migraine (tricyclic antidepressants, triptans, antiepileptics). We also discuss novel therapies like CGRP inhibitors which are effective in migraine and have potential for adaptation in patients with CVS. Using migraine as a template should enable investigators to elucidate the mechanisms underlying this disorder, develop novel therapies, and direct future research in CVS.

AID dysregulation in lupus-prone MRL/Fas(lpr/lpr) mice increases class switch DNA recombination and promotes interchromosomal c-Myc/IgH loci translocations: modulation by HoxC4.

Immunoglobulin gene somatic hypermutation (SHM) and class switch DNA recombination (CSR) play important roles in the generation of autoantibodies in systemic lupus erythematosus. Systemic lupus is characterized by the production of an array of pathogenic high-affinity mutated and class-switched, mainly IgG, antibodies to a variety of self-antigens, including nuclear components, such as dsDNA, histones, and chromatin. We previously found that MRL/Fas(lpr/lpr) mice, which develop a systemic autoimmune syndrome sharing many features with human lupus, display greatly upregulated CSR, particularly to IgG2a, in B cells of the spleen, lymph nodes, and Peyer's patches. In MRL/Fas(lpr/lpr) mice, the significant upregulation of CSR is associated with increased expression of activation-induced cytidine deaminase (AID), which is critical for CSR and SHM. We also found that HoxC4 directly activates the promoter of the AID gene to induce AID expression, CSR and SHM. Here, we show that in both lupus patients and lupus-prone MRL/Fas(lpr/lpr) mice, the expression of HoxC4 and AID is significantly upregulated. To further analyze the role of HoxC4 in lupus, we generated HoxC4(-/-) MRL/Fas(lpr/lpr) mice. In these mice, HoxC4-deficiency resulted in reduced AID expression, impaired CSR, and decreased serum anti-dsDNA IgG, particularly IgG2a, autoantibodies, which were associated with a reduction in IgG deposition in kidney glomeruli. In addition, consistent with our previous findings in MRL/Fas(lpr/lpr) mice that upregulated AID expression is associated with extensive DNA lesions, comprising deletions and insertions in the IgH locus, we found that c-Myc to IgH (c-Myc/IgH) translocations occur frequently in B cells of MRL/Fas(lpr/lpr) mice. The frequency of such translocations was significantly reduced in HoxC4(-/-) MRL/Fas(lpr/lpr) mice. These findings suggest that in lupus B cells, upregulation of HoxC4 plays a major role in dysregulation of AID expression, thereby increasing CSR and autoantibody production and promoting c-Myc/IgH translocations.