Biomarkers of intestinal barrier function in multiple sclerosis are associated with disease activity.

BACKGROUND: Recent evidence suggests a role for the gut-brain axis in the pathophysiology of multiple sclerosis (MS). MATERIALS AND METHODS: We studied biomarkers of intestinal permeability in 126 people with MS (57 relapsing-remitting multiple sclerosis (RRMS) and 69 progressive MS) and in a group of healthy controls for comparison. Serum/plasma concentrations of zonulin (a regulator of enterocyte tight junctions), tight junction proteins (ZO-1 and occludin), intestinal fatty acid binding protein (IFABP)/ileal bile acid binding protein (IBABP), D-lactate, and lipopolysaccharide (LPS) binding protein were measured. RESULTS: Zonulin concentrations were significantly higher when a concurrent magnetic resonance imaging (MRI) confirmed the presence of blood-brain barrier (BBB) disruption (Gad+ RRMS) and were correlated with tight junction proteins. IBABP and D-lactate were elevated in people with RRMS compared to controls, but did not discriminate between Gad+ and Gad- subgroups. Baseline zonulin concentrations were associated with 1-year disease progression in progressive MS. CONCLUSIONS: People with MS have altered biomarkers of intestinal barrier integrity. Zonulin concentrations are associated with 1-year disease progression in progressive MS and closely mirror BBB breakdown in RRMS. Zonulin may mediate breakdown of both the intestinal barrier and the BBB in gut dysbiosis through the regulation of tight junctions. This could explain how the gut-brain axis modulates neuroinflammation in MS.

Area postrema syndrome: A short history of a pearl in demyelinating diseases.

In this topical review, we discuss the history of the area postrema syndrome, with special attention given to early studies aimed at identifying the area postrema and its function, possible early cases of the syndrome and its current relevance in neuroimmunology and demyelinating diseases. In 1896, Retzius named a structure in the posterior medulla oblongata as the area postrema. The work of Borison in the middle of the 20th century led to the elucidation of its function as a "vomiting center." The historical medical literature is filled with excellent examples that could be described as "area postrema syndrome." While severe and bilateral optic neuritis and transverse myelitis still constitute the classic components of neuromyelitis optica spectrum disorder (NMOSD), intractable vomiting and hiccups due to area postrema involvement is now recognized as essentially pathognomonic, indeed a shiny pearl in neuroimmunology and demyelinating diseases.

The intestinal barrier in multiple sclerosis: implications for pathophysiology and therapeutics.

Biological barriers are essential for the maintenance of homeostasis in health and disease. Breakdown of the intestinal barrier is an essential aspect of the pathophysiology of gastrointestinal inflammatory diseases, such as inflammatory bowel disease. A wealth of recent studies has shown that the intestinal microbiome, part of the brain-gut axis, could play a role in the pathophysiology of multiple sclerosis. However, an essential component of this axis, the intestinal barrier, has received much less attention. In this review, we describe the intestinal barrier as the physical and functional zone of interaction between the luminal microbiome and the host. Besides its essential role in the regulation of homeostatic processes, the intestinal barrier contains the gut mucosal immune system, a guardian of the integrity of the intestinal tract and the whole organism. Gastrointestinal disorders with intestinal barrier breakdown show evidence of CNS demyelination, and content of the intestinal microbiome entering into the circulation can impact the functions of CNS microglia. We highlight currently available studies suggesting that there is intestinal barrier dysfunction in multiple sclerosis. Finally, we address the mechanisms by which commonly used disease-modifying drugs in multiple sclerosis could alter the intestinal barrier and the microbiome, and we discuss the potential of barrier-stabilizing strategies, including probiotics and stabilization of tight junctions, as novel therapeutic avenues in multiple sclerosis.

Severe hypertriglyceridemia associated with teriflunomide in a patient with multiple sclerosis: A case report.

OBJECTIVE: To describe a case of severe hypertriglyceridemia in a patient receiving teriflunomide. METHODS: This is a case study. RESULTS: Our patient developed severe hypertriglyceridemia (>5000 mg/dL) while on teriflunomide. The drug was withdrawn. Resolution began over 3 weeks later. CONCLUSION: We describe the first probable case of teriflunomide-associated severe hypertriglyceridemia in a patient with multiple sclerosis, an adverse event previously associated with leflunomide in patients with rheumatologic diseases. Clinicians should be aware of this rare but potentially dangerous adverse event.

Alterations in balance and mobility in people with epilepsy.

PURPOSE: People with epilepsy (PWE) are burdened by physical disability and side effects of antiepileptic drugs (AED) such as drowsiness and blurred vision. These factors place them at risk for reduced mobility and falls. The purpose of this study was to evaluate mobility and balance in PWE. METHODS: This was a cross-sectional study of PWE and age- and sex-matched controls. We evaluated mobility and balance using the Timed Up and Go Test (TUG) and the Tinetti Mobility Test (TMT). Self-reported confidence in balance was assessed using the Activities-Specific Balance Confidence Scale (ABC). Clinical and demographic characteristics and particularly epilepsy-related variables were recorded. RESULTS: We included 33 PWE and 33 controls. PWE had a mean age of 36.7years, and 61% were male. They had a mean of 1.52 of seizures per month and used a mean of 1.6 anti-epileptic drugs (AEDs). PWE scored significantly worse in all measures (TUG, TMT, ABC) when compared with controls. PWE had poor performance in 60.6% of cases in the TUG and in 48.5% of cases in the TMT, compared to none in the control group. There was good correlation between the three instruments. TUG scores were correlated with epilepsy duration, but not age, seizure control or AED use. On multivariate logistic regression, poor performance TMT was significantly associated with poor confidence in balance, according to the ABC. CONCLUSIONS: PWE have significant alterations in balance and mobility, independently of AED use or seizure control. These alterations are reflected in a poor self-reported confidence in carrying out daily activities.

Acute toxic leukoencephalopathy associated with a non-prescription weight loss supplement: a report of two cases.

Weight loss dietary supplements are used with some frequency by an increasingly overweight population. Some products are not adequately regulated and may pose potential health risks. We report two new cases of acute toxic leukoencephalopathy (ATL) due to the use of a supplement marketed as a thermogenic weight loss aid. ATL is a heterogeneous clinic-radiological entity that has been associated with various compounds, such as chemotherapeutic drugs and immunomodulators. It is characterized by an often reversible periventricular and infratentorial demyelination. The commercialization of non-regulated weight loss products continues to be a health risk in our population.

Affective symptoms and determinants of health-related quality of life in Mexican people with epilepsy.

Epilepsy is known to be associated with multiple psychiatric comorbidities, such as depression, sleep-disorders, and anxiety. The objective of this study was to determine the prevalence and impact of affective symptoms over health-related quality of life (QOL) in Mexican people with epilepsy (PWE). We performed a cross-sectional observational study on 73 consecutive PWE and corresponding age- and sex-matched controls. HrQOL was assessed using the QOLIE-10 (QOL in Epilepsy-10) instrument. Clinical and demographic characteristics were recorded, and instruments evaluating depressive/anxiety symptoms, sleep quality, and insomnia were completed. PWE had more depressive/anxiety symptoms when compared with controls. QOLIE-10 scores were significantly inversely correlated with poor sleep quality, insomnia symptoms, depressive/anxiety symptoms, and number of anti-epileptic drugs used, but not with seizure type or number of seizures per month. A poor QOL was independently associated only with anti-epileptic drug polytherapy. PWE are burdened with depressive/anxiety symptoms at alarming rates. The presence of depressive symptoms along with sleep disturbances and more significantly, anti-epileptic drug polytherapy, appears to negatively impact QOL, to a greater degree than short-term seizure control.

Abdominal Aortic Dissection and Cold-Intolerance After Whole-Body Cryotherapy: A Case Report.

Whole-body cryotherapy (WBC) involves short exposures to air temperatures below -100°C and is purported to enhance recovery after exercise and accelerate rehabilitation after injury. It is generally considered a procedure with few side effects, but there are no large studies that have established its safety profile. We present the case of a 56-year-old patient who developed an abdominal aortic dissection after receiving 15 sessions of WBC. The patient had no other strong risk factors for aortic dissection. Exposure to cold temperatures, including WBC, has multiple hemodynamic effects, including increases in blood pressure, heart rate, and an adrenergic response. We suggest that these changes could act as a trigger for the onset of aortic dissections. This could be the first reported cardiovascular complication associated with WBC.

Prevalence and impact of irritable bowel syndrome in people with epilepsy.

PURPOSE: Epilepsy is known to be associated with affective disorders and sleep alterations, as well as with gastrointestinal conditions such as peptic ulcers and inflammatory bowel disease. There is comparatively little evidence linking epilepsy and gastrointestinal functional disorders. The objective of this study was to determine the prevalence and impact of irritable bowel syndrome (IBS) in patients with epilepsy. METHODS: We carried out a cross-sectional observational study on 65 consecutive people with epilepsy (PWE) and age- and sex-matched controls. Irritable bowel syndrome and functional dyspepsia (FD) diagnosis were based on Rome III criteria. Clinical and demographic characteristics were recorded, and instruments evaluating sleep quality, depressive/anxiety symptoms, insomnia, and health-related quality of life were also completed. RESULTS: Irritable bowel syndrome prevalence was significantly different between groups (3% in controls and 16% in patients with epilepsy; p=0.04), while no difference was found in FD (2% vs. 6%, respectively). People with epilepsy with IBS had significantly more insomnia and depressive and anxiety symptoms. No demographic or clinical characteristics were significantly different between groups. The presence of IBS did not affect health-related quality of life in PWE. On multivariate analysis, insomnia and depressive and anxiety symptoms did not independently predict IBS diagnosis. CONCLUSION: Irritable bowel syndrome was more frequent in PWE compared with that in healthy controls. Irritable bowel syndrome does not appear to affect health-related quality of life but is associated with a greater burden of affective symptoms and insomnia.

Pituitary apoplexy presenting as diabetic ketoacidosis: A great simulator?

Pituitary apoplexy is a life-threatening illness due to acute infarction of the pituitary gland. The most common symptoms associated with pituitary apoplexy are headache, nausea, vomiting, visual impairment, hypopituitarism, and altered mental status. Diabetic ketoacidosis is a common acute complication of diabetes mellitus and is itself associated with similar symptoms. We present the case of a 38 year old woman, who presented with altered mental status and biochemical alterations suggestive of diabetic ketoacidosis who was found to have a pituitary apoplexy. The low frequency of this condition coupled with an acute and usually dramatic presentation that includes non-specific symptoms makes it a diagnostic challenge. Pituitary apoplexy can simulate a wide range of neurological conditions.

Cutaneous amyloidosis associated with autoimmune hepatitis-primary biliary cirrhosis overlap syndrome.

Cutaneous amyloidosis is a rare disease characterized by the deposition of amyloid in the dermis. It can be primary or secondary, depending on associated diseases. It has been linked to various autoimmune diseases, including primary biliary cirrhosis. We present the case of a patient with an autoimmune hepatitis-primary biliary cirrhosis overlap syndrome with concomitant cutaneous amyloidosis, a very unusual association, and discuss similar cases and possible pathophysiological implications.