Aside from well-characterized immune-mediated ataxias with a clear trigger and/or association with specific neuronal antibodies, a large number of idiopathic ataxias are suspected to be immune ...mediated but remain undiagnosed due to lack of diagnostic biomarkers. Primary autoimmune cerebellar ataxia (PACA) is the term used to describe this later group. An International Task Force comprising experts in the field of immune ataxias was commissioned by the Society for Research on the Cerebellum and Ataxias (SRCA) in order to devise diagnostic criteria aiming to improve the diagnosis of PACA. The proposed diagnostic criteria for PACA are based on clinical (mode of onset, pattern of cerebellar involvement, presence of other autoimmune diseases), imaging findings (MRI and if available MR spectroscopy showing preferential, but not exclusive involvement of vermis) and laboratory investigations (CSF pleocytosis and/or CSF-restricted IgG oligoclonal bands) parameters. The aim is to enable clinicians to consider PACA when encountering a patient with progressive ataxia and no other diagnosis given that such consideration might have important therapeutic implications.
An expanding body of literature is examining connections between Autism Spectrum Disorder (ASD) and dietary interventions. While a number of specialist diets have been suggested as beneficial in ASD, ...gluten has received particularly close attention as a potentially exacerbating factor. Reports exist suggesting a beneficial effect of the gluten-free diet (GFD) in ameliorating behavioural and intellectual problems associated with ASD, while epidemiological research has also shown a comorbidity between ASD and coeliac disease. However, both caregivers and clinicians have expressed an uncertainty of the value of people with ASD going gluten-free, and as the GFD otherwise receives considerable public attention a discussion which focuses specifically on the interaction between ASD and gluten is warranted. In this review we discuss the historical context of ASD and gluten-related studies, and expand this to include an overview of epidemiological links, hypotheses of shared pathological mechanisms, and ultimately the evidence around the use and adoption of the GFD in people with ASD.
Summary Background Acute demyelinating optic neuritis, a common feature of multiple sclerosis, can damage vision through neurodegeneration in the optic nerve and in its fibres in the retina. ...Inhibition of voltage-gated sodium channels is neuroprotective in preclinical models. In this study we aimed to establish whether sodium-channel inhibition with phenytoin is neuroprotective in patient with acute optic neuritis. Methods We did a randomised, placebo-controlled, double-blind phase 2 trial at two UK academic hospitals in London and Sheffield. Patients with acute optic neuritis aged 18–60 years, presenting within 2 weeks of onset, with visual acuity of 6/9 or worse, were randomly assigned (1:1) by minimisation via a web-based service to oral phenytoin (maintenance dose 4 mg/kg per day if randomised before or on July 16, 2013, and 6 mg/kg per day if randomised on or after July 17, 2013) or placebo for 3 months, stratified by time from onset, centre, previous multiple sclerosis diagnosis, use of disease-modifying treatment, and use of corticosteroids for acute optic neuritis. Participants and treating and assessing physicians were masked to group assignment. The primary outcome was retinal nerve fibre layer (RNFL) thickness in the affected eye at 6 months, adjusted for fellow-eye RNFL thickness at baseline, analysed in a modified intention-to-treat population of all randomised participants who were followed up at 6 months. Safety was analysed in the entire population, including those who were lost to follow-up. The trial is registered with ClinicalTrials.gov , number NCT 01451593. Findings We recruited 86 participants between Feb 3, 2012, and May 22, 2014 (42 assigned to phenytoin and 44 to placebo). 29 were assigned to phenytoin 4 mg/kg and 13 to phenytoin 6 mg/kg. Five participants were lost to follow-up, so the primary analysis included 81 participants (39 assigned to phenytoin and 42 to placebo). Mean 6-month RNFL thickness in the affected eye at 6 months was 81·46 μm (SD 16·27) in the phenytoin group (a mean decrease of 16·69 μm SD 13·73 from baseline) versus 74·29 μm (15·14) in the placebo group (a mean decrease of 23·79 μm 13·97 since baseline; adjusted 6-month difference of 7·15 μm 95% CI 1·08–13·22; p=0·021), corresponding to a 30% reduction in the extent of RNFL loss with phenytoin compared with placebo. Treatment was well tolerated, with five (12%) of 42 patients having a serious adverse event in the phenytoin group (only one, severe rash, was attributable to phenytoin) compared with two (5%) of 44 in the placebo group. Interpretation These findings support the concept of neuroprotection with phenytoin in patients with acute optic neuritis at concentrations at which it blocks voltage-gated sodium channels selectively. Further investigation in larger clinical trials in optic neuritis and in relapsing multiple sclerosis is warranted. Funding US National Multiple Sclerosis Society, Multiple Sclerosis Society of Great Britain and Northern Ireland, Novartis, UK National Institute for Health Research (NIHR), and NIHR UCLH/UCL Biomedical Research Centre.
We report on a group of patients with gluten sensitivity with and without coeliac disease presenting with unexplained sensory symptoms in the absence of structural pathology.
The patients were ...selected from the gluten neurology clinic based at the Royal Hallamshire Hospital, Sheffield, UK, on the basis of sensory symptoms but normal neuroaxis imaging and peripheral nerve evaluation.
A total of 30 patients were identified with a mean age at presentation of 47 years. The prevalence of enteropathy was 78%. The sensory disturbance was characterised by tingling at 50%, numbness at 27%, pain at 20%, burning at 13% and "buzzing" feeling at 7%. The distribution of the sensory symptoms included hands and feet in 27% of the patients, torso in 27%, legs only in 23%, face in 17% and arms only in 10%. For five patients, the sensory disturbance was migratory and affected different parts of the body at any given time. After the introduction of a gluten-free diet, 77% of patients noted significant improvement in their sensory symptoms. In one-third of the patients, there was a complete resolution of the sensory symptoms.
Unexplained sensory symptoms can be seen in patients with gluten sensitivity and respond to strict adherence to a gluten-free diet.
Superficial siderosis describes haemosiderin deposition on the surface of the brain. When present on infratentorial structures, it can cause ataxia, sensorineural hearing loss and pyramidal signs. ...There is no proven treatment and patients experience slow progression of symptoms. Iron-chelating agents have been suggested as a therapeutic option and deferiprone is suited as it crosses the blood-brain barrier. However, deferiprone is reported to have a 1–2% risk of agranulocytosis. We performed a systematic review on treatment of infratentorial superficial siderosis with deferiprone based on PRISMA guidelines. Studies were included if in English or an English language translation was available, were about human subjects and referred to patients with ataxia. Studies were excluded if they did not possess an English translation, included animal studies or did not have ataxia. Studies were excluded if they discussed cerebral amyloid angiopathy or siderosis of other regions. Eleven papers were included. We identified 69 patients. Seventeen patients (25%) discontinued the drug. The most encountered adverse effect was anaemia (21.7%). Neutropaenia was observed in 8.7% and agranulocytosis in 5.8% of patients. Clinically, response varied, and stability or improvement was seen across neurological domains in 6 studies while 5 showed a mixed response. On imaging, 13 (28.9%) patients improved, 24 (53.3%) stabilised and 8 (17.8%) deteriorated. A prospective international centralised register of patients should be developed to inform the design and conduct of a multicentre, placebo-controlled, randomised clinical trial to evaluate the efficacy of deferiprone. The evidence from this systematic review is that deferiprone is a promising intervention.
High-fat (HF) diet-induced obesity and insulin insensitivity are associated with inflammation, particularly in white adipose tissue (WAT). However, insulin insensitivity is apparent within days of HF ...feeding when gains in adiposity and changes in markers of inflammation are relatively minor. To investigate further the effects of HF diet, C57Bl/6J mice were fed either a low (LF) or HF diet for 3 days to 16 weeks, or fed the HF-diet matched to the caloric intake of the LF diet (PF) for 3 days or 1 week, with the time course of glucose tolerance and inflammatory gene expression measured in liver, muscle and WAT. HF fed mice gained adiposity and liver lipid steadily over 16 weeks, but developed glucose intolerance, assessed by intraperitoneal glucose tolerance tests (IPGTT), in two phases. The first phase, after 3 days, resulted in a 50% increase in area under the curve (AUC) for HF and PF mice, which improved to 30% after 1 week and remained stable until 12 weeks. Between 12 and 16 weeks the difference in AUC increased to 60%, when gene markers of inflammation appeared in WAT and muscle but not in liver. Plasma proteomics were used to reveal an acute phase response at day 3. Data from PF mice reveals that glucose intolerance and the acute phase response are the result of the HF composition of the diet and increased caloric intake respectively. Thus, the initial increase in glucose intolerance due to a HF diet occurs concurrently with an acute phase response but these effects are caused by different properties of the diet. The second increase in glucose intolerance occurs between 12-16 weeks of HF diet and is correlated with WAT and muscle inflammation. Between these times glucose tolerance remains stable and markers of inflammation are undetectable.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Non-Coeliac Gluten Sensitivity (NCGS) is poorly understood, particularly in terms of its neurological outcomes. We initially conducted a prospective postal survey to investigate its neurological ...presentation and symptom course. Results from this then motivated a follow-up pilot study utilising brain MRI to characterise potential diagnostic biomarkers for future research.
Patients with NCGS were recruited from a specialist centre and completed a prospective postal questionnaire (N = 125). This summarised symptoms experienced, their severity and their course. Onset time was compared by Chi-squared analysis to data from the same centre concerning coeliac disease patients (N = 224). Five respondents on a strict gluten-free diet who self-reported brain fog then attended a pilot study, completing MR brain imaging/questionnaires before/after a gluten challenge. "Baseline" data were assessed for abnormalities, while symptom severity and cerebral blood flow (CBF) were compared before/after challenge.
Survey participants were aged 47 (85% female). Prevalence of neurological symptoms were: headaches (51%), brain fog (48%), balance issues (31%), tingling (19%). Median symptom resolution time was 48 hours, while onset was 90 minutes; onset pattern was not significantly different compared to CD patients (p = 0.322). Extra-intestinal symptoms worsened by 37%(±28) during a typical reaction. Predominantly non-statistical observations from the brain imaging study are discussed.
Neurological symptoms in NCGS are common, and onset time is comparable to that in CD. Brain imaging may be a useful future means of investigating physiological injury and responses to gluten in further study.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Intervention with fruit extracts may lower glucose and lipid levels, as well as blood pressure. We reviewed the efficacy of bilberry and grape seed extracts to affect these outcomes across ...populations with varying health status, age and ethnicity, across intervention doses and durations, in 24 intervention studies with bilberry and blackcurrant (n = 4) and grape seed extract (n = 20). Bilberry and blackcurrant extract lowered average levels of glycated hemoglobin (HbA1c), at least in Chinese subjects, especially in those who were older, who were diagnosed with Type 2 Diabetes Mellitus (T2DM) and who were participating in longer-term studies. We also found good evidence that across studies and in subjects with hypercholesterolemia, T2DM or metabolic syndrome, intervention with bilberry and blackcurrant extract, and to some extent grape seed extract, significantly lowered total and low density lipoprotein (LDL) cholesterol levels after four weeks. Intervention with grape seed extract may reduce systolic and diastolic blood pressure in subjects with hypertension or metabolic syndrome. Differential responsiveness in cholesterol and blood pressure outcomes between stratified populations could not be explained by age, dose or study duration. In conclusion, bilberry and blackcurrant extract appears effective in lowering HbA1c and total and LDL cholesterol, whereas grape seed extract may lower total and LDL cholesterol, and blood pressure, in specific population groups.
Background
Myelin-associated glycoprotein (MAG) is a glycoprotein specific to Schwann cells. Schwann cells produce myelin for nerve cells in the peripheral nervous system. MAG also plays a role in ...the central nervous system (CNS) by maintaining myelin integrity and inhibiting axonal regeneration from cerebellar neurons. There is a well-established link between distal demyelinating neuropathy and anti-MAG antibodies in patients with monoclonal gammopathy of unknown significance. We describe a series of five patients with anti-MAG antibodies with evidence of cerebellar rather than just sensory ataxia and our experience of treatment with rituximab.
Methods
Cerebellar ataxia was clinically suspected and confirmed using magnetic resonance spectroscopy (MRS) of the cerebellum. All patients underwent detailed nerve conduction studies.
Results
Four patients were males. The ages ranged from 64 to 82 years. All patients were anti-MAG positive and also had IgM monoclonal gammopathy. Four patients had neuropathy, whilst one had no evidence of neuropathy. All patients were treated with rituximab and showed improvement in the MRS parameters of the cerebellum.
Conclusion
Anti-MAG antibodies might be involved in the pathogenesis of idiopathic sporadic ataxias, even in the absence of peripheral neuropathy. Rituximab seems to be a promising therapeutic intervention for those cases.
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•This study investigated the effect of a three week supplementation of concentrated bilberry extract on glucose metabolism to determine what the initial mechanisms are causing the ...improvement in glucose homeostasis.•This study demonstrates that the ingestion of a concentrated bilberry extract over a three week intervention period reduces postprandial glycaemia without changes in insulin.•We show that the mechanism for the early decreased glycaemic response involves reduced rates of carbohydrate digestion/absorption.•There was no change in anti-inflammatory markers (hsCRP, MCP-1, leptin), markers of vascular health (Apo A1, sVCAM-1, sICAM-1) in the plasma, reducing potential and radical scavenging capacity (as assayed through use of electron transfer ET and ET/hydrogen atom transfer based assays FRAP and TEAC respectively (Huang, Ou, & Prior, 2005; Apak et al., 2016) in plasma or change in the faecal bacterial microbiota measured between the volunteers receiving the bilberry extract and the placebo.
This study investigated the effect of a three week supplementation of bilberry extract on glucose metabolism. Overweight volunteers (n = 16; BMI 31) were given three capsules of either 0.47 g bilberry extract (36% (w/w) anthocyanins) or placebo per day for three weeks in a double blinded cross over intervention.
The ingestion of the bilberry extract decreased the OGTT AUCi for glucose (20%; p = 0.008) but not for insulin compared with the placebo. There was no change in anti-inflammatory markers (hsCRP, MCP-1, leptin), vascular health markers (Apo A1, sVCAM-1, sICAM-1), reducing potential/ radical scavenging capacity or faecal bacterial microbiota. In vitro studies showed that the bilberry extract decreased α-amylase activity (p < 0.0001), α-glucosidase activity (p < 0.0001) and glucose uptake (p < 0.0001).
This study demonstrates that the ingestion of a bilberry extract over a three week intervention period reduces postprandial glycaemia without changes in insulin. This is probably due to reduced rates of carbohydrate digestion and/or absorption.
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