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Background Chronic gastrointestinal dysmotility greatly impacts the quality of life. Treatment options are limited and generally symptomatic. Neural autoimmunity is an under-recognized etiology. We evaluated immunotherapy as an aid to diagnosing autoimmune gastrointestinal dysmotility ( AGID). Methods Twenty-three subjects evaluated at the Mayo Clinic for suspected AGID ( August 2006- February 2014) fulfilled the following criteria: (1) prominent symptoms of gastrointestinal dysmotility with abnormalities on scintigraphy-manometry; (2) serological evidence or personal/family history of autoimmune disease; (3) treated by immunotherapy on a trial basis, 6-12 weeks (intravenous immune globulin, 16; or methylprednisolone, 5; or both, 2). Response was defined subjectively (symptomatic improvement) and objectively (gastrointestinal scintigraphy/manometry studies). Key Results Symptoms at presentation: constipation, 18/23; nausea or vomiting, 18/23; weight loss, 17/23; bloating, 13/23; and early satiety, 4/23. Thirteen patients had personal/family history of autoimmunity. Sixteen had neural autoantibodies and 19 had extra-intestinal autonomic testing abnormalities. Cancer was detected in three patients. Preimmunotherapy scintigraphy revealed slowed transit (19/21 evaluated; gastric, 11; small bowel, 12; colonic, 11); manometry studies were abnormal in 7/8. Postimmunotherapy, 17 (74%) had improvement (both symptomatic and scintigraphic, five; symptomatic alone, eight; scintigraphic alone, four). Nine responders re-evaluated had scintigraphic evidence of improvement. The majority of responders who were re-evaluated had improvement in autonomic testing (six of seven) or manometry (two of two). Conclusions & Inferences This proof of principle study illustrates the importance of considering an autoimmune basis for idiopathic gastrointestinal dysmotility and supports the utility of a diagnostic trial of immunotherapy. [ABSTRACT FROM AUTHOR]

Background: The metabolic characteristics of obese Irish children are not well defined. We prospectively examined the relationship between the degree of obesity and glucose metabolism, insulin sensitivity and suspected non-alcoholic steatohepatosis (NASH) in a pilot study of obese Irish children. Methods: We measured height, weight, body mass index (BMI), blood pressure, waist and hip circumference in 18 participants (mean age 15.5 years). Fasting blood glucose, insulin, lipid profile and alanine aminotransferase (ALT) concentrations were also measured. A standard 75 g oral glucose tolerance test was performed and insulin sensitivity was derived from this using a mathematical model – oral glucose insulin sensitivity. Results: There were significant associations between the degree of obesity, insulin sensitivity and markers of liver steatosis. For example, when adjusted for pubertal status, there were significant associations between standardized BMI and insulin sensitivity (regression coefficient, β = -70.1, P = 0.018) and ALT (β = 20.7, P = 0.007) Conclusion: This study suggests that the degree of obesity is associated with lower insulin sensitivity and possible NASH in obese Irish children. [ABSTRACT FROM AUTHOR]

Controversy exists regarding the pathogenic or predictive role of anti-myelin oligodendrocyte glycoprotein (MOG) antibodies in patients with multiple sclerosis (MS). Four immunopathological patterns (IP) have been recognized in early active MS lesions, suggesting heterogeneous pathogenic mechanisms. Whether MOG antibodies contribute to this pathological heterogeneity and potentially serve as biomarkers to identify specific pathological patterns is unknown. Here we report the frequencies of antibodies to human recombinant MOG (identified by Western blot and enzyme-linked immunoabsorbent assay (ELISA)) in patients with pathologically proven demyelinating disease, and investigate whether antibody status is associated with clinical course, HLA-DR2-genotype, IP or treatment response to plasmapheresis. The biopsy cohort consisted of 72 patients: 12 pattern I, 43 pattern II and 17 pattern III. No association was found between MOG antibody status and conversion to clinically definite MS, DR-2 status, IP or response to plasmapheresis. There was poor agreement between Western blot and ELISA (kappa = 0.07 for MOG IgM). Fluctuations in antibody seropositivity were seen for 3/4 patients tested serially by Western blot. This study does not support a pathologic pattern-specific role for MOG-antibodies. Variable MOG-antibody status on serial measurements, coupled with the lack of Western blot and ELISA correlations, raises concern regarding the use of MOG-antibody as an MS biomarker and underscores the need for methodological consensus. [ABSTRACT FROM AUTHOR]

β2-glycoprotein I (β2GPI) is a plasma protein suspected to have a role in inhibition of thrombosis. This suspicion is reinforced by the observation that β2GPI is the major target for autoantibodies in the antiphospholipid syndrome. However, little is known about its circulating levels in common thrombotic diseases or inflammation. We measured β2GPI levels in 344 healthy controls, 58 normal pregnancies, 102 patients with non-haemorrhagic stroke, 121 patients with acute coronary syndrome and 200 patients with elevated C-reactive protein (CRP). In healthy individuals, we found a strong positive correlation between age and β2GPI concentration (r = 0.274, P < 0.001) and that β2GPI levels fall significantly after the eighth week of pregnancy (P = 0.002). We also found significantly reduced levels of β2GPI in patients with stroke and in elderly patients with myocardial syndrome (P = 0.013 and 0.043). However, in neither group did β2GPI levels change in the following six months, suggesting that the reduced levels were not a transient post-event phenomenon. In patients with inflammation, β2GPI levels showed a significant negative correlation with CRP (r = –0.284, P < 0.001) and positively correlated with albumin and transferrin (r = 0.372 and 0.453, respectively with P < 0.001 for both). Furthermore, the largest reduction in β2GPI levels occurred in patients with the highest CRP values (P < 0.001). [ABSTRACT FROM AUTHOR]

Background: A pathological classification has been developed of early active multiple sclerosis (MS) lesions that reveals four patterns of tissue injury: I-T cell/macrophage associated; II-antibody/complement associated; III-distal oligodendrogliopathy, and IV-oligodendrocyte degeneration in the periplaque white matter. Mechanisms of demyelination in early MS may differ among the subgroups. Previous studies on biopsied MS have lacked clinicopathological correlation and follow up. Critics argue that observations are not generalisable to prototypic MS. Objective: To describe the clinicopathological characteristics of the MS Lesion Project biopsy cohort. Methods: Clinical characteristics and disability of patients with pathologically confirmed inflammatory demyelinating disease (excluding ADEM) classified immunopathologically (n = 91) and patients from the Olmsted County MS prevalence cohort (n=218) were determined. Results: Most patients who underwent biopsy and had pathologically proved demyelinating disease ultimately developed definite (n = 70) or probable (n =12) MS (median follow up 4.4 years). Most had a relapsing remitting course and 73% were ambulatory (EDSS ⩽ 4) at last follow up. Nine patients remained classified as having an isolated demyelinating syndrome at last follow up. Patients with different immunopathological patterns had similar clinical characteristics. Although presenting symptoms and sex ratios differed, the clinical course in biopsy patients was similar to the prevalence cohort. Median EDSS was <4.0 in both cohorts when matched for disease duration, sex, and age. Conclusions: Most patients undergoing biopsy, who had pathologically confirmed demyelinating disease, were likely to develop MS and remain ambulatory after a median disease duration of 4.4 years. The immunopathological patterns lacked specific clinical correlations and were not related to the timing of the biopsy. These data suggest that pathogenic implications derived largely from MS biopsy studies may be extrapolated to the general MS population. [ABSTRACT FROM AUTHOR]

Background/Objectives: Calf muscle hypertonicity following stroke may impair walking rehabilitation. The aim of this study was to assess botulinum toxin (Dysport®) in post-stroke calf spasticity. Methods: A prospective, multicentre, double-blind, placebo-controlled, dose-ranging study was performed to evaluate dysport at 500, 1,000 or 1,500 units in 234 stroke patients. They were assessed at 4-week intervals over 12 weeks. Results: The primary outcome measure, 2-min walking distance and stepping rate increased significantly in each group (p < 0.05, paired test), but there was no significant difference between groups (including placebo). Following dysport treatment, there were small but significant (p = 0.0002-0.0188) improvements in calf spasticity, limb pain, and a reduction in the use of walking aids, compared to placebo. Investigators' and patients' assessments of overall benefit suggested an advantage for dysport over placebo, but this was not significant. Sixty-eight patients reported 130 adverse events, with similar numbers in each group. The few severe events recorded were not considered to be treatment-related. Conclusion: Dysport resulted in a significant reduction in muscle tone, limb pain and dependence on walking aids. The greatest benefits were in patients receiving dysport 1,500 units, but 1,000 units also had significant effects. Dysport 500 units resulted in some improvements. Since few adverse events were reported, this therapy is considered safe and may be a useful treatment in post-stroke rehabilitation of the leg. Possible reasons why functional improvements in gait parameters were not observed are also discussed. [ABSTRACT FROM AUTHOR]

Objective. To study the efficacy and safety of botulinum toxin type A (BtxA) in the treatment of upper limb muscle spasticity, caused by stroke. Methods. This was a randomized, controlled trial. Patients received either placebo injections or a total of 1000 IU of BtxA (Dysport) into five muscles of the affected arm. Muscle tone was assessed using the Modified Ashworth Scale (MAS). Other outcome measures were the change in the joint range of motion (ROM), the Barthel index, pain score, goal attainment and the subjective evaluation of benefit by patients and investigators. The patients were assessed blind to randomization at baseline and 4, 8, 12 and 16 weeks after treatment. Results. Fifty nine patients were recruited and received treatment. One patient was lost to follow-up before the last scheduled visit of the study. The group of patients who received BtxA had a significant reduction in the summed MAS score at week 4 compared with the placebo group (P=0.004). The magnitude of benefit over the 16 week follow-up period was significantly reduced for the BtxA group in the wrist (P=0.004) and the finger joints (P=0.001) when compared with the placebo. There was no statistically significant difference between the groups in the joint ROM, muscle pain, goal-attainment or the Barthel index scores at week 4 of the study. At week 16, the BtxA group showed significantly greater improvement in the passive ROM at the elbow (P=0.036). The patients’ global assessment of benefit at the end of the study showed that 16 (50%) patients in the placebo group had ‘much improved’ or had ‘some improvement’ compared with 24 (92.3%) patients in the BtxA group (P=0.007). The investigators’ rating for the same item was 16 (50%) and 23 (88.4%) patients, respectively (P=0.002). Sixteen and twenty patients in the BtxA and placebo groups, respectively, had an adverse event. The most frequently reported adverse events were accidental injury, respiratory and urinary tract infections and muscle pain. Conclusion. The findings of the present study suggest that treatment with BtxA in a dose of 1000 units reduces muscle tone in patients with post-stroke upper limb spasticity. This effect is sustained for at least 16 weeks. BtxA is safe in the dose used in this study. Important note. The authors wish to emphasize that the botulinum toxin preparation used in this study was Dysport (Ipsen Ltd) which has a different therapeutic equivalence from other commercially available product, Botox (Allergan Inc.). [ABSTRACT FROM AUTHOR]

There are few data regarding the standard of stroke care in Ireland. To investigate the level of documentation for 13 key areas of stroke management. Using a validated stroke audit package, this study reviewed the medical records of 100 consecutive patients hospitalised with acute stroke. Documentation of stroke symptoms, risk factors, general examination and investigations (cranial computer tomography [CT] and carotid Dopplers) were satisfactory. Neurological documentation was variable, with power (87%), sensation (70%) and eye movements (63%) being the most frequently recorded features, while cognition (3%), visual fields (13%), gait (7%), incontinence (1%) and swallowing (0%) were infrequently recorded. Diagnostic formulation and an acute management plan were documented in less than half of patients, whereas cranial CT (93%) and carotid Dopplers (93%) were well documented. Secondary preventive measures were documented in two-thirds of patients at follow-up. These results serve as a baseline from which to initiate and monitor improvements in the service at our hospital, including the involvement of neurologists in stroke care, and will also allow assessment of the impact of such changes. [ABSTRACT FROM AUTHOR]

The article discusses a study that addressed the frequency of immunoglobulin G (IgG) autoantibody (NMO-IgG) among adult patients with idiopathic inflammatory demyelinating disorders in Hong Kong, China. The study noted that the high particularity of NMO-IgG for neuromyelitis optica (NMO) and partial formation of the disorder depicted an uncontrollable stage and other patients were tested seropositive. These NMO-IgG seropositive patients had clinical features dissimilar with NMO.

The Irish childhood obesity epidemic, one of the highest ranking internationally, represents a major threat to public health. We sought to perform a retrospective observational study of a clinic based cohort of obese Irish children. Clinical data relating to gender, age, height, weight, body mass index and blood pressure were analysed, from 206 children referred to a paediatric endocrine referral centre over a 15-year period for assessment of obesity. Younger patients tended to have a higher standardised body mass index at initial presentation; 92% of boys and 96% of girls referred were obese (age-related BMI ≥ 95th percentile). Boys (51%) and girls (49%) had initial blood pressure measurements in the hypertensive range. There was a correlation between the degree of obesity and systolic blood pressure, particularly in boys. Obese Irish children present with significant long-term health risks, including hypertension at baseline. [ABSTRACT FROM AUTHOR]

Two patients with large bilateral subdural haematomas with patterns of non-enhanced brain computed tomography (CT) falsely suggesting coexistent subarachnoid haemorrhage are presented. The CT images showed marked effacement of the basal cisterns with hyperdense signal along the tentorium, sylvian fissure, and the perimesencephalic cisterns. In both cases, the suspicion of subarachnoid haemorrhage led to the performance of angiographic studies to rule out vascular lesions. Thus, recognition of this radiological feature is important to avoid unnecessary testing and treatment delay. [ABSTRACT FROM AUTHOR]

An abstract of the article "Chronic Relapsing Inflammatory optic Neuropathy: An Extension of the Neuromyelitis Optica Spectrun Disorder," by A. Petzold, S. Pittock, V. Lennon, A. Gale, A. Wanijha, R. Caulkin, B.G. Weinshenker, and G.T. Plant is presented.

Comments on the rapid clinical and CFS response to intravenous gamma globulin in acute disseminated encephalomyelitis. Complaints on the usage of intravenous gamma globulin (IVIG) in multiple sclerosis; Absence of serum antibodies to common viral and mycoplasma antigens and rheumatological diseases; Effectivity of IVIG treatment in normalizing blood-brain barrier disruption.